Abstract Book Eram-Serin2010

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1 INCIDENCE AND RISK FACTORS OF ACUTE RHINOSINUSITIS IN AN URBAN POPULATION: A GA2LEN STUDY SERIN Symposium 1 - Epidemiology of airway disease in Europe Tomassen P 1, Van Zele T 1, Mahachie J 1, Van Bruaene N 1, Burney P 2, Fokkens W 3, Bachert C 1 Upper Airway Research Laboratory, Dpt. Of Otorhinolaryngology, Ghent University, Ghent, Belgium 2 Respiratory Epidemiology & Public Health, Imperial College, London, United Kingdom3 Department of Otorhinolaryngology, Academic Medical Centre, Amsterdam, Netherlands
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Background: The epidemiology of acute rhinosinusitis (ARS) is largely unknown, due to a lack of comparable studies with standardized diagnostic criteria. The present study, as part of the Galen Survey, aims to characterize the incidence and risk factors ARS in an urban population. Methods: The study was designed as a cross-sectional mail-based survey. A random sample of 5000 inhabitants was sent a questionnaire in up to three attempts. The questionnaire was constructed based on the ECRHS questionnaire for asthma and allergic rhinitis, and on the EP3OS criteria for rhinosinusitis. Additionally, patients were asked the frequency of ARS episodes, if they visited a doctor for ARS, and if antibiotics and nasal steroids were taken. Risk factors and corresponding odds ratios were estimated using binomial and multinomial logistic regression. Results: 1881 subjects (37%) returned the questionnaire, of which 54,1% were female and the median age was 45y. 25.6% of subjects were past smokers, and 23.7% were current smokers. The incidence of at least one episode of ARS was 34,0% (IQR 31,9-35,2%). Of those, 52,3% consulted a doctor, 24,0% had antibiotics, and 32,6% had nasal steroids for ARS. Logistic regression for ARS revealed significant associations with female sex, smoking history, eczema history, chronic plegm coughing, current allergic rhinitis and CRS. With multinomial regression, risk factors were evaluated for the frequency of ARS episodes. Current allergic rhinitis was associated with all frequencies of ARS episodes, and CRS increased the odds of having 2 or more episodes. Age was negatively correlated with up to 3 episodes, and female sex was associated with 2 or 3 episodes. Smoking was associated with 3 or more episodes. Visiting a doctor for ARS was associated with CRS, current allergic rhinitis and age. Age and CRS were associated with antibiotic use. The frequency of ARS episodes, current allergic rhinitis and a healthcare job were associated with nasal steroid use. Discussion: We report a 34% yearly incidence of at least one episode of ARS in an urban population. This number is strikingly higher compared to previously reported incidences, but differences in diagnostic criteria and limitations of mail-based surveys must be considered. Female sex and young age were associated with modest increases in ARS episodes. The association of smoking behavior with high numbers of ARS episodes opens perspectives on the effect of smoke on upper airway defense mechanisms.
2 A COMMUNITY BASED SURVEY ON THE PREVALENCE OF RHINITIS SERIN Symposium 1 - Epidemiology of airway disease in Europe Sami A 1, McComb A 2, Jeffs J 3, Howarth P 3 Royal National Throat, Nose and Ear Hospital, London , United Kingdom 2 Frimley Park Hospital, Frimley Park, United Kingdom 3 Southampton General Hospital, Southampton, United Kingdom
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Background: Rhinitis is an increasingly common condition although there is limited information as to its true prevalence within the community. This study aimed to obtain a current prevalence of rhinitis within the community and to explore its impact on social and emotional functioning. A survey of 2000 adults in the Farnborough area was devised and carried out using the Modified SNOT-20 (MSNOT-20) questionnaire for this study. Method: A postal survey of rhinitis was conducted in the Farnborough area with 2000 MSNOT-20 questionnaires being sent to randomly selected adults from the electoral register. There were 1595 returned (79.8%) of which 1580 were evaluable. 58% of respondents were female and 41.9% male. Results: The population age range was 16.9 to 92.4 years (mean 48.6 years). A score of 01 on a six-point rating scale was taken as normal for each question and a score of 2-5 taken as abnormal. 32.5% of the population had an abnormal score for needing to blow their nose, 31.4% for sneezing, 25.4% for runny nose and 30.1 % for blocked nose. The combined nasal sub-score (sum of 4 questions, max score 20) identified a score of 4 or less in 62.1 % (39.9 % abnormal rhinitis score). Those with rhinitis were more likely to score abnormally on the other domains in comparison to those with normal scores; paranasal (55.5% vs. 28.8%), sleep (41.5% vs. 22.1%), social and emotional (38.9 vs. 19.6%). Conclusion: This study identifies the common prevalence of rhinitis and the associated morbidity, with over 30% of the population experiencing nasal blockage, sneezing and need to blow their nose. A total MSNOT-20 score does not provide information exclusively on ENT disease; due to the wide range of conditions affecting quality of life. Subdivision into separate symptom clusters does, however, permit exploration of disease prevalence. Using symptom clusters, this study identified that there is also a high prevalence of ENT morbidity within the community.
3 IN-DEPTH ANALYSIS OF THE ASSOCIATIONS OF ALLERGIC AND CHRONIC RHINITIS WITH ASTHMA AND LOWER RESPIRATORY SYMPTOMS: DATA FROM LARGE POPULATION SURVEY IN WEST SWEDEN SERIN Symposium 1 - Epidemiology of airway disease in Europe Eriksson J, Bjerg A, Lotvall J, Ronmark E, Toren K, Lundback B Department of Internal Medicine/Krefting Research Centre, Sahlgrenska Academy, Gothenburg, Sweden
Background: Asthma and rhinitis frequently coexist. However, no population study has investigated the impact of nasal comorbidities on risk factors and symptom expression of asthma. Methods: In 2008, a postal questionnaire focused on respiratory health was sent to 30 000 randomly selected subjects aged 16-75 years in West Sweden, 29 218 could be traced and 18 087 (62%) responded. The questionnaire included questions on asthma, rhinitis, respiratory symptoms and possible determinants. Results: Prevalence of allergic rhinitis in asthma was 63.9% and of asthma in allergic rhinitis 19.8%. Asthma in allergic rhinitis was more common in young subjects (physiciandiagnosed asthma: 22.7% in ages 16-35 yrs. vs. 18.1% in ages 56-75 yrs.; pvalue<0.001), while symptoms of bronchitis in allergic rhinitis were more common in the old (chronic productive cough: 6.7% in ages 16-35 yrs. vs. 14.3% in ages 56-75 yrs.; pvalue<0.001).
[fig 1] Asthmatic subjects with chronic rhinitis had significantly more symptoms common in asthma and bronchitis than asthmatics without rhinitis (p<0.001), whereas those with allergic rhinitis had more symptoms common in asthma only. Further, the proportion of current asthmatics with multiple (i.e. four) symptoms was significantly higher when two chronic nasal symptoms were present, than when one or no symptoms were present (two symptoms: 41.9%, no symptoms: 21.1%; p-value<0.001). Conclusion: The considerable comorbidity of asthma and rhinitis decreased by age. Symptom expression and risk factor patterns of asthma varied extensively with different nasal comorbidities, suggesting that nasal comorbidities may be markers of different phenotypes of asthma.
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4 GLUCOCORTICOID RESISTANT AIRWAY DISEASE Oral Presentations 1 Pujols L Respiratory Immunoallergy, IDIBAPS, CIBERes, Hospital Clinic, Barcelona, Spain
Inhaled and intranasal glucocorticoids are the most common and effective drugs for treating inflammatory airway diseases such as allergic rhinitis, chronic rhinosinusitis with/without nasal polyps, and asthma. The main target of glucocorticoid action is the inhibition of inflammatory cell activation and survival, although structural cells such as epithelial cells and fibroblasts, are also targets of glucocorticoid treatment. Glucocorticoid effects are mediated through activation of the isoform of the glucocorticoid receptor (GR), which acts as an hormone-dependent transcription factor. The alternative GR isoform does not bind hormone but it may inhibit GR function when overexpressed with respect to GR . Although glucocorticoid treatment is effective in most of the asthmatic patients, some of them have a poor response to treatment. Similarly, some patients with nasal polyposis do not respond to intranasal glucocorticoids, or to short courses of oral glucocorticoids, ultimately requiring surgery, or even repeated surgeries, to remove nasal polyps. Recent in vitro studies carried out in cells from these non-responsive patients have contributed to the understanding of the molecular mechanisms responsible for this glucocorticoid resistance. These mechanisms encompass alterations in different points of the complex GR signalling pathway, including an imbalance in the GR /GR expression ratio, defects in GR binding to ligand, GR translocation to the cell nucleus, or GR binding to GREs, decreased capacity of GR to transactivate the expression of anti-inflammatory genes and/or to transrepress the expression of pro-inflammatory genes, and/or a defective cross-talk between activated GR and transcription factors, like the activator protein-1. These alterations in GR expression and/or GR action in cells from these glucocorticoid resistant patients appear to be the result of the excessive activation of pro-inflammatory pathways, like the mitogen-activated protein kinase pathways, induced by different pro-inflammatory cytokines. Finally, several of these alterations can coexist in the same patient and can be common in different inflammatory diseases.
5 LACK OF EVIDENCE FOR A MAJOR ROLE OF VEGF AND PlGF IN EDEMA FORMATION AND EXTRAVASATION IN NASAL POLYP TISSUE Oral Presentations 1 Bobic S 1, Hox V 1, Callebaut I 1, Jorissen M 2, Ceuppens J 1, Hellings P2 Laboratory of Experimental Immunology, Catholic University, Leuven, Belgium 2 Department of Otorhinolaryngology, Head and Neck Surgery, Catholic University, Leuven, Belgium
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Background: Edema represents a major feature of nasal polyp (NP) tissue and may be linked to the presence of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). Both are involved in vascular permeability and edema formation in diseases like cancer-associated retinopathy, macular edema and cutaneous inflammation. We evaluated the expression of VEGF, PlGF and their receptors in NP tissue compared to healthy nasal mucosa under baseline and inflammatory conditions and correlated these factors with markers of edema. Methods: Nasal mucosa was taken from healthy donors (n=20) and polyp tissue from NP patients (n=18) and wet/dry ratios were determined. Expression levels of VEGF, PlGF and receptors VEGFR1 and VEGFR2 were measured by real-time RT-PCR. Protein levels of VEGF, PlGF and albumin were measured in the supernatants of homogenized tissue by ELISA. 1x106 cells of suspended nasal mucosa (n=12) and polyp tissue (n=9) were stimulated with IL-1 (10ng/ml) and TNF (10ng/ml) for 24h. Expression of VEGF, PlGF and receptors was determined by ELISA and real-time RT-PCR. Results: Albumin levels and wet/dry ratios were higher in NP tissue compared to healthy nasal mucosa. VEGF expression was lower in NP tissue on both protein (87.0311.49 vs. 55.5510.42 pg/ml, P=0.034) and mRNA level (11.751.994 vs. 6.2761.56, P=0.0229) whereas PlGF showed similar levels. Only inhibitory VEGFR1 was up-regulated in NP tissue (0.94120.2218 vs. 9.8942.41, P=0.0003) whereas VEGFR2 was unaltered. IL-1 induced higher expression of VEGF and PlGF in control tissue and significantly reduced expression of VEGFR2, but had no effect on NP tissue. Expression levels of VEGF, PlGF and their receptors did not correlate with edema markers. Conclusion: Based on the differential expression patterns and in vitro induction of VEGF, PlGF and their receptors, our data point towards a lack of major contribution of these angiogenic factors to the edema formation in NP disease.
6 HERPES SIMPLEX VIRUS-1 INFECTION FACILITATES INVASION OF STAPHYLOCOCCUS AUREUS IN THE NASAL Oral Presentations 1 Wang X 1, Zhang N 2, Glorieux S 3, Holtappels G 2, Vaneechoutte M 4 , Krysko O 2, Zhang L 5, Han D 5, Nauwynck H 3, Bachert C 2 The Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Beijing, China 2 The Department of Otolathe Upper Airway Research Laboratory, University of Ghent, Ghent, Belgium 3 Laboratory of Virology, Faculty of Veterinary Medicine, University of Ghent, Ghent, Belgium 4 Laboratory of Bacteriology Research, University of Ghent, Ghent, Belgium 5 Beijing Institute of Otolaryngology, Beijing, China
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Background: Staphylococcus aureus (S.aureus) plays an important role in the pathogenesis of chronic rhinosinusitis with nasal polyps. However the mechanisms underlying the damage and/or invasion of the nasal mucosa by S.aureus are not clearly understood. The purpose of this study was to investigate the interaction between S.aureus and herpes simplex virus-1(HSV1) in the invasion of the nasal mucosa by S.aureus. Methods: Inferior turbinate samples were collected from 10 patients presenting for nasal surgery and maintained as explant cultures ex-vivo. The explants were infected with HSV1, S.aureus or HSV1+S.aureus and after incubation for 24h and 48h assessed by immunofluorescence- and hematoxylin-staining. Cryosections were evaluated for HSV1/S.aureus invasion and epithelial-damage, respectively, by two independent observers. Non-infected explants were used as controls. Results: HSV1S.aureus-infection led to focal infection of outer epithelial cells after 24 hours and loss or damage of the epithelium and basement membrane and invasion of HSV1 into the lamina propria after 48h. In contrast, S.aureus-infection did not affect the epithelial integrity after 24 hours or 48h, and was not different from control explants incubated for 48h. Invasion scores at 24 and 48h post-infection for HSV1 were significantly increased from baseline (p<0.001) in HSV1S.aureus-infected explants, whereas the invasion scores for S.aureus were significantly increased from baseline (p<0.001) only in HSV1+S.aureusinfected explants. Similarly, epithelium damage scores were significantly higher for HSV1S.aureus-infected explants, compared with control explants or S.aureus-infected explants, and significantly correlated with HSV1-invasion scores (R= 0.63-0.74, P<0.0001). Conclusion: Our results demonstrate that HSV1 leads to significant damage of the nasal epithelium and consequently may facilitate invasion of S.aureus into the nasal mucosa.
7 BIOMARKERS OF INFLAMMATION TO EVALUATE ASTHMA CONTROL Poster Discussion Session 1 Navratil M, Dodig S, Plavec D, Turkalj M Srebrnjak Children's Hospital, Zagreb, Croatia
Aim: The aim was to compare different biomarkers of inflammation in children with controlled and uncontrolled allergic asthma as well as to investigate their value in evaluation of asthma control. Study population and Methods: The study group comprised 43 patients (age 10.92.8, 21 boys) with mild-to-moderate allergic asthma (29 uncontrolled, 14 controlled asthma) all on their regular asthma therapy. We measured pulmonary function and inflammatory biomarkers: spirometry, eosinophilic cationic protein (ECP), exhaled NO (FENO), highsensitivity C-reactive protein (hs-CRP), white blood cells (WBC) and differential leukocyte counts from peripheral blood. Results: FEV1 and lymphocytes were significantly higher in controlled than in uncontrolled asthma (FEV1, 96.59.5% vs. 86.413.6%, P=0.002; and lymphocyte Z-score, 0.220.5 vs. -0.0990.33, P=0.016). FENO, serum hs-CRP and ECP were however higher in uncontrolled asthma but it didnt reach significant difference (FENO, 55.238.6 ppb vs. 3833.3 ppb; hs-CRP, 0.680.74 mg/L vs. -0.290.15 mg/L; ECP 32.719.8 mcg/L vs. 24.519.8 mcg/L). FENO showed closer correlation with peripheral blood markers of eosinophilic inflammation than ECP with the correlation of these 2 markers being mild (r2=0.39). Both of this markers (alone or combined) showed poor predictability of asthma control (P=0.318; PPV 66.7%, NPP 70.0%), compared to the combination of several inflammatory markers (FENO, ECP, IgE, Z-scores for % of eosinophils and basophils and absolute number of lymphocytes and neutrophils) that showed better predictability of asthma control (P=0.011; PPV 85.7%, NPV 93.1%). Conclusion: In children with allergic asthma FEV1 showed moderate predictability of control. Markers of both lung and systemic inflammation showed good predictability but only when used in combination.
8 THE MODIFIED SNOT-20 QUESTIONNAIRE: REPEATABILITY AND APPLICABILITY TO RHINITIS Poster Discussion Session 1 Sami A 1, McComb A 2, Jeffs J 3, Howarth P 3 Royal National Throat, Nose and Ear Hospital, London, United Kingdom 2 Frimley Park Hospital, Frimley Park, United Kingdom Southampton General Hospital, Southampton, United Kingdom
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Background: Rhinitis is a clinically prevalent disease, symptomatically characterised by nasal itch, sneezing and difficulty breathing through the nose. Patients with rhinitis often suffer from associated symptoms related to posterior nasal, sinus and ear disease. Other effects on the psychological well being are also accountable to rhinitis. A number of these features are encompassed in disease specific quality of life (QoL) questionnaires. However, the Modified SNOT-20 (MSNOT-20) questionnaire aims to correspond to the requirements for a complete and comprehensive assessment of rhinitis and its impact. It uses a six-point scale to identify clinical severity (0=no problem, 5=very severe problem). The MSNOT-20 questionnaire was evaluated in a pilot study of disease and non-disease and then used to assess the prevalence of rhinitis and associated features in a community based survey. Method: The pilot study used a group of healthy subject attending an ENT clinic for nasal disease to evaluate the MSNOT-20 questionnaire. Following a successful pilot project, 2000 postal questionnaires were sent to randomly selected adults from the electoral register in Farnborough. Differences in housing, social class and environment were balanced with repeat questionnaires sent for non-respondents. Results: In the pilot study, there were significant differences (p < 0.001) in symptom reporting between rhinitics and non-rhinitics, with 92.67% of the healthy controls responding on all 20 questions either 0=no problem (85.67%) or 1=very mild problems (7%) in comparison to 42.07 % in the rhinitis group (28.7 % of responses no problem, 13 % very mild problems). A score of 0 or 1 was thus taken as normal and 2-5 taken as abnormal. In the community survey in Farnborough, 68% of 1580 evaluable respondents (79.8 % response rate) had a total SNOT-20 score of 0-20 (max 100) with 32% scoring 21 + (max 88). There were significant correlations between the rhinitis domain and the 4 other domains (paranasal [sinus and ear], sleep, social and emotional). The repeatability of these responses was evaluated in a follow-up evaluation in a subpopulation. Conclusion: MSNOT-20 questionnaire is a disease-related QoL rhinitis questionnaire, which is valid for the evaluation of rhinitis and the impact of disease on quality of life. It identified a high prevalence of nasal and paranasal problems within the community with significant co-morbidity caused by rhinitis.
9 EPIDEMIOLOGY OF RHINITIS IN SECONDARY SCHOOL CHILDREN USING MSYPQ (MODIFIED SINO-NASAL OUTCOME TEST-20 YOUNG PERSON QUESTIONNAIRE) AND COMPARISON WITH MODIFIED SNOT-20 USED IN ADULT COMMUNITY BASED SURVEY. Poster Discussion Session 1 Sami A, Scadding G Royal National Throat, Nose and Ear Hospital, London, United Kingdom
Background: Rhinitis is significantly prevalent in the adult community but this research aimed to explore the prevalence of nasal and paranasal symptoms within the age group of 11-16 years while also assessing, within the same student population, the prevalence of impaired sleep, social and emotional function, time off school and visits to the family doctor. The Sino-Nasal Outcome Test -20 (SNOT-20) questionnaire, a valid disease related quality of life instrument, was modified for use on secondary school children for this project. The Modified SNOT-20 for Young Person Questionnaire, MSYPQ was used in secondary school children in east London with the result compared to a similar adult survey. Method: The pilot project tested MSYPQ according to EPOS criteria. EPOS positive showed significantly high score on MSYPQ confirming the presence of the disease (Rhinitis/Rhinosinusitis), while EPOS negative had very low to zero score on MSYPQ. This confirmed that MSYPQ can identify subjects with rhinitic symptoms and is a good instrument to assess the effect on quality of life. The MSYPQ was used in a face-to-face interview and postal survey for children aged between 11-16 years in three large east London schools. The data was collected and analysed for the prevalence of rhinitis, associated symptoms and effects on quality of life. Results: The results showed that over 32% of secondary school children suffered rhinitic symptoms (cough was identified as one of the most significant symptoms). A similar prevalence of 30% was found in adults. More than 21% of secondary school students had their quality of life affected by rhinitis and more than 47% took between 2-15 days off school due to rhinitic symptoms. In adults these values were 25% and 10% respectively. Conclusion: This analysis confirmed that rhinitis is a common problem in the 11-16 year age group. It affects quality of life and performance at school, as students have to take days off from the school and are frustrated by their symptoms. This study also confirms that MSYPQ is a good tool for identifying the prevalence of rhinitis symptoms in 11-16 age group and its effect on quality of life.
10 CROSS REACTIVITY IN THE NOSE, MOUTH AND LUNGS: SURVEY OF PATIENTS Poster Discussion Session 1 Rudenko M 1, Smith H 2, Tarzi M 3, Frew A 1 Brighton and Sussex University Hospitals, Respiratory Medicine, Brighton, United Kingdom 2 University of Sussex, Primary care, Brighton, United Kingdom 3 University of Sussex, Immunology, Brighton, United Kingdom
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Approximately 300 million people in the world currently have allergic rhinitis and asthma, with a progressive increase in prevalence of these conditions in both children and adults over recent decades. Many patients who are allergic to birch pollens report that cross reactivity influences their lifestyle and prevents them from consuming fruits and vegetables. We performed a survey among patients who attended the allergy clinic in Brighton and Sussex University hospitals using a questionnaire that was delivered by freepost or during consultations in the allergy clinic. Statistical analysis performed using statistic software SPSS. 35 patients who reported fruit related symptoms were included: their age ranged from 17 to 75 (mean 375.22) years, 84% of them were female, and mean duration of symptoms was 171.35 years. 20.0% of them have asthma and 24.0% reported one or more episodes of angioedema. According to the results of skin prick testing (SPT) obtained from patients notes each patient was allergic to 2.080.34 airborne allergens, among them Grass pollen 44.0%, Tree pollen (mixture included birch) 100.0%, Cat epithelium 32.0%, House dust mite - D. Pteronyssinus 12.0%, Mould 12.0%. All of them demonstrated negative results of SPT with panel of fruit allergens. On average patients reported symptoms with 3.480.82 different fruits, among them Apples 84.0%, Pears 36.0%, Peaches 52.0%, Plums 56.0%, Nectarines 52.0% and Cherries 68.0%. All of the patients complained of seasonal allergic rhinitis, with some patients symptoms starting in February (40.0%) while others went on until September (32.0%). Patients varied in their degree of concern about their condition: 12.0% said that they were not worried, 28.0% were a little worried, 48.0% were moderately worried, and 12.0% were very worried. 92.0% of respondents were interested in obtaining treatment for their condition if one was available. Conclusion: Oral Allergy Syndrome causes considerable distress to patients. Most of patients with Oral Allergy Syndrome react to multiple fruits and a significant minority also suffer from asthma.
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11 HAPTOGLOBIN POLYMORPHISM IN ASTHMATIC PATIENTS Poster Discussion Session 1 Cortez E Castro M 1, Marinho C 2, Ferreira J 2, Pereira-Barbosa M 1, Bicho M 2
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CHLN-HSM-Allergy Department, Lisbon, Portugal School-Genetic Department, Lisbon, Portugal
Lisbon Medical
Background: Haptoglobin (Hp), a polymorphic protein known to bind free hemoglobin (Hb), has been implicated in modulation of Th1/Th2 response. Hp genotype described as: Hp1-1(homozygous for allele1) Hp2-2(homozygous for allele2) or Hp2-1 (heterozygous). Methods: 116 asthmatics: 70 females, 46 males; 98 atopic, 18 non-atopic; 47 noncontrolled, 69 controlled asthma; 238 healthy volunteers (control group). Hp levels assayed by nephelometry; genotypes by polyacrylamide gel electrophoresis. Results: In asthmatics, Hp levels are not statistical differents between non-controlled vs controlled asthma (p=0.433), allergic vs non-allergic (p=0.158) and between males vs females (p=0.175) but are statistical different between patients >30 vs <30 years (134.2149.70 vs 101.03.48.06, p=0.001). Hp frequencies in asthmatics: Hp 1-1 19.8%, Hp 2-1 47.4%, Hp 2-2 32.8%, are not statistical different between males vs females (p=0.103), uncontrolled vs controlled asthma (p=0.908), allergic vs non-allergic (p=0.235), between patients >30 vs <30 years (0.295). Hp 2-2 presented lower levels of the circulating protein when compared to Hp 2-1 and Hp 1-1 (95.61 vs 135.69 vs 142.52mg/dL) and is statistical different (p=0.000). In patients >30 years Hp levels are different between genotypes (p=0.000): 1-1 and 2-1 differ from 2-2. In patients <30 years Hp levels are not different between genotypes (p=0.129). Hp genotype (p=0.293) and allelic (p=0.970) distribution are not different from the control group. Conclusion: Although no statistical differences were find between Hp genotype and allelic distribution in asthmatics, when compared to control group, these data point to differences among groups that could be related to Hp genotypes: Hp* 1 genotype is associated with the highest levels of Hp and Th2 profile as opposed to Hp * 2 genotype that is associated with lower levels of Hp and Th1 profile.
12 LOCAL IMMUNE CHANGES IN ASTHMA COMORBIDITY WITH RESPIRATORY AND ENT INFECTIONS IN SCHOOLCHILDREN Poster Discussion Session 1 Sciuca S, Selevestru R, Babin A State Medical and Pharmaceutical University, Chisinau, Moldova
Background: Evaluation of secretory IgA concentrations in nasal secretions from students with asthma comorbidity with respiratory infections and ENT. Methods: Our study involved the study group of 46 schoolchildren aged 6-12 years with asthma comorbidity with respiratory and ENT infections and the control group of 40 healthy schoolchildren the same age. The levels of secretory IgA (sIgA) concentration in nasal secretions were performed by immunoenzymatic method (-T, Russia). The nasal secretions were collected after proceeding nasal cavity with 2% saline soil. The material was analyzed by using Microsoft Excel, Epi Info-3.5 and Table EpiMax programmes. Results: SIgA concentration in nasal secretions is 169.516.3 mg/l in children with asthma in comparison with to sIgA concentration 29520.9 mg/l (<0.001) in healthy children. Identify local immune changes depending on the concentration of sIgA in nasal secretions can be assessed by the area lying below the ROC curve (receiver operator characteristics), which in the study was equal to 0.72 and demonstrated the high informativity of this method. The persistence of chronic inflammation in bronchial mucosa induces a local immune deficiency manifested by low concentration of sIgA in nasal secretions in schoolchildren with asthma comorbidity with respiratory infections and ENT and it is not noted in healthy schoolchildren. Conclusion: This study confirmed the local immune changes manifested by low concentration of sIgA in nasal secretions in schoolchildren with asthma comorbidity with respiratory infections and ENT.
13 THE CLINICO-EXPLORATIVE PHENOTYPE OF BRONCHIAL ASTHMA IN SCHOOLCHILDREN Poster Discussion Session 1 Sciuca S, Selevestru R, Babin A State Medical and Pharmaceutical University, Chisinau, Moldova
Background of this study was to evaluate clinical and explorative phenotype of bronchial asthma in schoolchildren. Methods: The study included 122 schoolchildren (6-12 years) with asthma, inclusive 37 children (30.3%) with intermittent asthma, 39 children (32%) with mild persistent asthma, 33 children (27%) with moderate persistent asthma and 13 children (10.7%) with severe persistent asthma. Results: The definition of bronchial asthma phenotype severity in schoolchildren has revealed allergen-induced bronchial asthma in 70,5%: 95%CI, 61,6-78,4 (86 schoolchildren); virus-induced bronchial asthma in 7,4%: 95%CI, 0,3-13,5 (9 schoolchildren); bronchial asthma induced by physical effort in 6,6%: 95%CI, 2,9-12,5 (8 schoolchildren) and unresolved asthma in 15,6%: 95%CI, 9,6-23,2 (19 schoolchildren). Virus-induced asthma was found in 10.8% of schoolchildren with intermittent asthma, in 10.3% children with mild persistent asthma, 3% with moderate persistent asthma and was not identified in children with severe asthma. Exercise-induced asthma is noticed in 8.1% children with intermittent asthma, in 5.1% children with mild persistent asthma, in 9.1% children with moderate persistent asthma and was not seen in children with severe persistent asthma. Unresolved asthma was confirmed in 27% children with intermittent asthma, in 15.4% children with mild persistent asthma, in 6.1% children with moderate persistent asthma and in 7.7% children with severe persistent asthma. The allergen-induced asthma predominates in severe forms of the disease: in 54% children with intermittent asthma, in 69.2% children with mild persistent asthma, 81.8% children with moderate persistent asthma and 92.3% children with severe asthma. Conclusion: The allergen-induced phenotype prevails in severe forms of asthma. The virusinduced asthma, exercise-induced and unresolved phenotypes of asthma are present in mild forms of the disease.
14 ALLERGIC RHINITIS COMORBIDITY WITH BRONCHIAL ASTHMA IN SCHOOLCHILDREN Poster Discussion Session 1 Sciuca S, Selevestru R, Babin A State Medical and Pharmaceutical University, Chisinau, Moldova
Background: The study aims to evaluate the frequency of allergic rhinitis in schoolchildren with bronchial asthma. Methods: The study included 122 schoolchildren (aged 6-12 years). The assessment of severity degrees of asthma identified 37 children (30.3%) with intermittent asthma, 39 children (32%) with mild persistent asthma, 33 children (27%) with moderate persistent asthma and 13 children (10.7%) with severe persistent asthma. Statistical analysis of results was processed by Epi Info method. Results: Personal history analysis in children with asthma showed allergic rhinitis comorbidity in 56.6%: 95% CI, 48.3-66.1 cases. The frequency of allergic rhinitis in children with asthma is directly proportional to the severity of the disease: in intermittent asthma 21.6%: 95% CI, 14.7-28.5, in mild persistent asthma 38.5%: 95% CI, 23.455.4, in moderate persistent asthma 30.5%: 95% CI, 15.6-48.7 and in severe asthma 92.3%: 95% CI, 84.6-99.8. The distribution by sex showed the presence of allergic rhinitis in 42.2%: 95% CI, 29.9-55.2 boys and in 31%: 95% CI, 19.5- 44.5 girls. The age distribution allows grouping children in next categories: I class in 41.4%: 95% CI, 23.561.1 children with allergic rhinitis, II class in 11%: 95% CI, 21.5-59.4 children, III class in 32%: 95% CI, 14.9-53.5 and IV class in 35%: 95% CI, 20.6-51.7. Conclusion: Allergic rhinitis associated in schoolchildren with asthma in manifest forms of the disease is more frequent in boys and has no correlation with children age.
15 PRE-ASTHMA STAGE IN PATIENTS WITH ALLERGIC RHINITIS Poster Discussion Session 1 Bolpacic J, Plavsic A, Bogic M Clinical Center of Serbia, Clinic for Allergology and Immunology, Belgrade, Serbia
Background: Association between the allergic rhinitis and allergic bronchial asthma has been clinically observed long time ago. The aim of our study was to determinate the possible presence of inflammation of the lower airway mucosal tissue in patients with allergic rhinitis who were symptom-free in the lower airways. Methods: A total of 87 patients with allergic rhinitis, 25 patients with allergic bronchial asthma without allergic rhinitis and 25 healthy controls were examined. Based on the results of the non-specific and specific bronhoprovocation tests (NBPT and SBPT), the patients with allergic rhinitis were divided into 4 subgroups: the patients with negative results of both tests (subgroup 1), patients only with positive NBPT results (subgroup 2), patients only with positive SBPT (subgroup 3) and patients with positive results of both tests (subgroup 4). Results: The results of the cytological analysis of the induced sputum from the subgroups of patients with allergic rhinitis were compared to those obtained from the patients with allergic bronchial asthma and healthy controls and confirmed presence of the allergic inflammation in subgroups 3 and 4 of the patients. Conclusions: Absence of lower airway complaints in subgroup 4 patients with allergic rhinitis may be explained by still insufficient degree of the allergic inflammation in comparison to the one in patients with allergic bronchial asthma.
16 THE SIGNIFICANCE OF ALLERGIC INFLAMMATION MARKERS IN CHILDREN WITH ALLERGIC RHINITIS TO EARLY DIAGNOSIS OF BRONCHIAL ASTHMA Poster Discussion Session 1 Bilichenko T, Baldueva M, Vosnesenskiy N, Libedin Y Research Institute of Pulmonology FMBA, Moscow, Russia
Background: Early diagnosis of bronchial asthma (BA) is very important for treatment of children who have allergic rhinitis (AR). The aim of the study was to assess the significance of four allergic inflammation markers in patients with AR for diagnosis of BA. Methods: Three groups of children aged 12-14 years old have been investigated using ISAAC questionnaire: 21 subjects without respiratory symptoms (Group 1), 51 subjects with AR in the last 12 months (Group 2), 66 subjects with AR and wheezing in the last 12 months (Group 3). The eosinophils (E) in the blood, total IgE in serum (Immune enzyme analysis), exhaled NOex and nasal fraction NOnas (Logan Research 2149, England) were studied in children. PEF and PIFin were investigated. Statistical analysis was performed using Statistica (Version 6) software. Results: The mean levels of E were higher in Group 2 patients (4,42,9%; p<0,01 ) and Group 3 (5,14,9%; p<0,03) vs Group 1 (2,51,5%). The levels of total IgE was 5 times higher in Group 2 (281,3286,8; median 153,7 ME/ml; p<0,001) and 9 times higher in Group 3 (487,8617,3; median 300,0 ME/ml; p<0,003) than in Group 1 (57,283,8; median 27,3 ME/ml). The mean levels of NOex were 2 times higher in children of Groups 2 (12,37,9 ppb; median 10,0 ppb; p<0,001) and 3 times higher in group 3 (24,119,4 ppb; median 18,0 ppb; p<0,0004) than in patients of group 1 (5,12,3 ppb; median 5,1 ppb). The mean level of NOex was significantly higher in Group 3 than in Group 2. The mean levels of NOnas were equivalent in Group 2 (818,6288,4 ppb; median 831,5 ppb) and Group 3 (812,8282,0 ppb; median 840,0 ppb) but they were significantly higher compared with the patients of Group 1 (626,6239,7 ppb; median 690,0 ppb; p<0,02). PIFin was lower in Group 2 and PEF together with PIFin were lower in Group 3 vs Group 1. Conclusions: The markers of allergic inflammation such as E, total IgE, NOex and NOnas can all be used for diagnosis AR, while total serum IgE, exhaled NOex can also be used for early diagnosis of BA in children with AR.
17 IKK-2 INHIBITION IN NASAL POLYPS Poster Discussion Session 1 Patou J 1, Holtappels G 1, Afleck K 2, Gevaert P 1, Bachert C 1 Upper Airways Laboratory, ENT Department, Ghent, Belgium GSK, Stevenage, United Kingdom
1 2
Background: Long term therapy with potent intranasal glucocorticosteroids is frequently performed to control nasal polyp inflammation and growth, but the response to this treatment is often only partially successful. Targeting IKK-2 represents a growing area of interest for researchers and pharmaceutical firms, as the last decade, small molecule inhibitors have become available. Nuclear Factor (NF) -kappaB is held inactive in the cytoplasm bound to I-kappaB. The removal of I-kappaB, via the actions of inhibitor of kappaB kinase-2 (IKK-2), allows NF-kappaB to enter the nucleus and regulate the expression of many inflammatory genes, including cytokines, chemokines, and adhesion molecules. Our goal was to determine the impact in the release of inflammatory cytokines when inhibiting IKK-2 in comparison to the topical corticosteroid fluticasone propionate in nasal polyposis. Methods: Surgical samples were collected from patients with nasal polyposis (n=8). Tissue fragments were preincubated for 1 hour with a specific IKK-2 inhibitor and fluticasone propionate in different concentrations and then stimulated with RPMI (negative control) and Staphylococcus aureus enterotoxin B (SEB) for 6 hours. Supernatants were measured by Multiplex for pro-inflammatory cytokines (IL-1, tumor necrosis factor-) and T cell and subset related cytokines (interferon-, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p70, IL-13). Results: Stimulation with SEB for 6 hours gave a significant increase of IL-2, IL-4, IL-5, IL13, IFN-, IL-1 and TNF-. The IKK-2 inhibitor and fluticasone propionate were able to almost completely block the release of IL-4, IL-5 and IL-13. For IL-2 and IFN- fluticasone propionate had less impact than the IKK-2 inhibitor. Furthermore, the IKK-2 inhibitor could completely block the release of TNF- and IL1-, whereas fluticasone propionate had no effect on their release. Conclusion: To conclude, inhibition of IKK-2 results in a general reduction of inflammatory cytokines in nasal polyposis. Our results suggest that the IKK-2 inhibitor seemed, in certain respects, to possess a more comprehensive anti-inflammatory profile to that of fluticasone propionate in nasal polyposis.
18 FLUTICASONE FUROATE NASAL SPRAY REDUCES CONJUNCTIVAL SYMPTOMS AFTER A NASAL GRASS POLLEN PROVOCATION AND DURING THE GRASS POLLEN SEASON Poster Discussion Session 1 Callebaut I 1, Vandewalle E 2, Hox V 1, Bobic S 1, Jorissen M 3, Stalmans I 2, Ceuppens J 4, Hellings P 3 Laboratory of Experimental Immunology, KULeuven, Leuven, Belgium 2 Division of Ophthalmology, University Hospitals Leuven, Leuven, Belgium 3 Division of Otorhinolaryngology, Head and Neck Surgery, UZ Leuven, Leuven, Belgium 4 Division of Clinical Immunology, University Hospitals Leuven, Leuven, Belgium
1
Session: Authors:
Affiliations:
Background: Up to now, it remains unknown to what extent nasal treatment with corticosteroids prevents the induction of conjunctival inflammation by grass pollen provocation (GPP) in allergic rhinitis (AR) patients. The aim of this study is to evaluate the effect of nasal treatment with fluticasone furoate (FF) on the conjunctival symptoms in AR, both during the grass pollen season as well as after nasal GPP. Methods: A double-blinded placebo-controlled study was performed in which 26 grass pollen AR subjects with rhinoconjunctivitis symptoms underwent a selective nasal grass pollen provocation at the start of the grass pollen season and at 2 weeks after the treatment with FF or placebo nasal spray. Nasal and conjunctival symptoms were scored during the season and in relation to GPP using a Visual Analogue Scale (VAS) scoring system. Results: Treatment with FF nasal spray reduced total conjunctival symptoms like lacrimation and pruritus at 15 min (2.78 0.52 vs 4.09 0.50 score, p=0.05) and 1 h (1.23 0.30 vs 2.154 0.35 score, p=0.01) after a nasal GPP compared to placebo treatment, beside reduction of runny nose, itchy nose, blocked nose and sneeze 15 min (2.82 0.36 vs 5.40 0.33 score, p<0.0001), 1h (1.11 0.21 vs 3.46 0.39 score, p<0.0001) and 24h (1.23 0.25 vs 1.93 0.20, p=0.0006). Moreover, total nasal and conjunctival symptoms were significantly reduced after 1 and 2 weeks of FF treatment during the grass pollen season compared to placebo treatment. Conclusion: Fluticasone furoate nasal spray significantly reduced conjunctival and nasal symptoms in grass pollen AR patients after a selective nasal grass pollen provocation and during the grass pollen season.
19 KAEMPFEROL INHIBITS EOTAXIN EXPRESSION AND ATTENUATES AIRWAY INFLAMMATION BY SUPPRESSING STAT OR NUCLEAR FACTOR KAPPAB ACTIVITY IN AIRWAY EPITHELIAL Poster Discussion Session 1 Gong J , Han S, Shin D , Kang Y Hallym University, Chuncheon, Korea
Background: The airway epithelium is thought to play an important role in the pathogenesis of asthmatic disease. Airway epithelial activation may contribute to the inflammatory and airway-remodeling events characteristic of severe asthma. Kaempferol, a flavonoid with anti-oxidative and anti-tumor properties, has been studied as an antiinflammatory agent; however, little is known regarding its effects on allergic asthma. Methods: We used human airway epithelial cell lines BEAS-2B to investigate the effect of kaempferol on allergy-associated airway inflammation. Eotaxin-1 level and intracellular adhesion molecule-1 (ICAM-1) protein expression were analyzed by Western blot. Interleukin-8 (IL-8) release and monocyte chemotactic protein-1 (MCP-1) transcriptional expression were assessed using ELISA and RT-PCR. Results: We found that kaempferol nontoxic at 1-20 M suppressed the endotoxin lipopolysaccharide-induced eotaxin-1 protein expression and IL-8 secretion involved in the chemotaxis for eosinophils. Kaempferol at 1-20 M dose-dependently attenuated the tumor necrosis factor (TNF- )-induced expression of ICAM-1 protein and MCP-1 mRNA with decreasing its monocyte-epithelial adhesion. Furthermore, kaempferol blocked LPStriggered STAT signaling and TNF- -induced nuclear translocation of nuclear factor-B (NFB). Conclusion: Kaempferol may attenuate eotaxin-1 up-regulated possibly by LPS-triggered toll like receptors, which appears to depend on STAT. Kaempferol attenuates inflammatory ICAM-1 and MCP-1 in cooperation with NF-B signaling. Therefore, kaemepferol is effective in ameliorating allergic and inflammatory airway diseases through its inhibitory interaction with STAT or NF-B signaling.
20 ANALYSIS OF CHRONIC COUGH IN 208 CHILDREN FROM ASTHMA CLINIC CENTER TO ENT DEPARTMENT Poster Discussion Session 1 Gu Q 1, Chen Y 2, Cui J
1 3
Department of Otolaryngology, Capital Institute of Pediatrics Affiliated Children's Hospital, Beijing, China 2 Asthma Clinic Center , Capital Institute of Pediatrics Affiliated Children's Hospital, Beijing, China 3 Department of Otolaryngology, Women and Children Hospital, TongZhou, Beijing, China
Background: To disclose the etiological factor and investigate the effect of the therapy on nasal disorders in 208 children with intractable cough. Methods: 208 children with intractable cough were consulted by ENT doctors who got low response after treated in Asthma clinic center. Nasopharyngscope were performed to observe common meatus, middle meatus, olfactory sulcus, nasopharynx and laryngopharynx in all of the children. UACS (chronic upper airway cough syndrome) was diagnosed in those who are full of purulent secretion in nasopharynx, and determined according to the symptom improvement of cough after one week treatment. In addition, those children with nasal disease were treated accordingly. Results: A total of 208 children with median age of 5.32.4 years(range 2-13 ys) were enrolled in Capital institute of pediatrics affiliated childrens hospital from Feb 2008 to Jun 2010, of which clinical course of was 4.41.5 ms ( range 2.0-28.0 ms). Among the children, 166 cases of 208 children had nasal disorders, UACS was diagnosed in 129 (62.0%) cases, 37(17.8%) cases of nasal disorders without UACS,42 (20.2%) cases of no nasal disorders. Clinical symptoms, signs and electric nasopharyngoscope were analyzed in the children with UACS. Among those children with UACS, allergic rhinitis happened in 87 cases, rhino-sinusitis in 46 cases, adenoid hypertrophy in 67 cases, and chronic rhinitis in 11 cases .However, 26 cases with UACS showed no any typical occurrence at regular examination, such as no clinical symptoms and signs of allergic rhinitis, chronic rhinitis , rhino-sinusitis , and no abnormal secretion in pharynges were happened. All of the 26 cases were diagnosed by nasopharyngoscopy due to purulent secretion in nasopharynx, in which only 5 cases occurred adenoid hypertrophy. Among the children with UACS, the results also showed that the regular cough occurred in 74 cases, nasal disease in 81 casessubjective feeling of postnasal discharge in 21 cases, mouse breathing or snoring in 36 cases, purulent secretion in nasal meatus in 75 cagesretropharyngeal folliculosis in 78 casespurulent secretion in pharynges detected in 52 cases, and purulent or viscosity secretion were found in 124 at the first nasopharyngoscopy detectionAfter 14 days treatment, the children with UACS (126/129) had significant higher remission in cough than those who had nasal disorders but without UACS (18/37)( P=0.000 Fisher test). Conclusions: The nasal disorders, especially for UACS, are common in chronic cough children. The therapy to nasal disorders can release the chronic cough symptoms in those who did not acquire the improvement in Asthma clinic center. The electric nasopharyngoscope can improve the accuracy of UACS diagnosis.
21 THE EFFECT OF POOR SANITATION AND ENVIRONMENT ON VILLAGE CHILDREN UNDER SEVEN AND ASTHMA PREVALENCE IN KENYA Poster Discussion Session 2 Nyabade G 1, Oluoch A 2
1
Go Fishnet Youth Project, Kisumu, Kenya Kisumu, Kenya
Africa Inland Church,
Purpose: The purpose of this review is to bring forth a theory of asthma's pathogenesis which reflects its cause through gradual development of strains of RV causing asthma in babies and small children and lack of immunity by antiviral machinaery at infection stages Background: Africa amongst other developing continents suffer the so called "Hygene Hypothesis" within the context of early prevention of astha prevalence among young children of ages 0-7 through infection, especially in infancy, by a respiratory virus, most likely a human rhinovirus (HRV)due to poor sanitation and environment and inadequate personal hygene. Methods: The villages and remote communities with lack of awarenes and sensitization programmes received Community Health Workers (CHWs) with thorough seminars, workshops, roadshows and health education at every local health facilities. Every child out of 120 received received asthma testing and facilitation in and around Kisumu, Kenya. Data was established through Written Questionare rating 54%. Results: High level of community influence such as ignorance, laxity, poverty and lack of asthma technical and health facilities contributed much to the increase of asthma amongst infants due to ignorance and lack of handy medical facilitation and sensitization in the past decate until this studies was carried out with effective measures in the communities in and around Kisumu. The ages 0-7 children responded to hygene, good sanitation and clean environment of their community and death penalties to asthma prevalence! Conclusion: Efficiency of this approach depends on its success in introducing thorough village sensitization and awareness programme of good sanitation and clean environment around where people live and village positive response to hygene! Finally, there is need to train community health worker volunteers with specific mandate of reaching out to asthmatic communities for infants with not only awareness programmes but health facilititations.
22 NON-ALLERGIC RHINITIS Poster Discussion Session 2 Hasham Sattar S 1, M Ishaq S2

1
Aman Hospital, Peshawar, Pakistan Nowshera, Pakistan
Al-Junaid Hospital,
Introduction: The condition rhinitis is characterized by rhinorhea, sneezing, nasal congestion, nasal itch and/or postnasal drip. It is important to make diagnosis in order to exclude or diagnose sensitivity to inhalant allergens. Methods: The non-allergic rhinitis (NAR) include multiple discrete settings that may even co-exist with allergic rhinitis (AR). They may vary in their appearance and treatment. As well, the pathogenesis of NAR is not obviously clarified and possibly diverse. Several conditions can have similar appearances to NAR or AR such as anatomical/mechanical factors nasal polyps, autoimmune diseases, metabolic conditions, genetic conditions and immunodeficiency. Patients may be misdiagnosed and treated allergic rhinitis instead of vasomotor rhinitis with grave outcomes. Results: Several nasal conditions may have similar presentation; still a conclusive diagnosis mandates a thorough knowledge of the relevant conditions. Concusions: Before resorting to aggressive treatment for non-allergic rhinitis, a policy of wait and see in association with identification of the actual condition is essential.
23 ELDERLY AND YOUNG ADULTS HAVE SIMILAR CLINICAL ALLERGIC RESPONSES TO AEROALLERGEN EXPOSURE Poster Discussion Session 2 Lourenco O 1, Fonseca A 1, Taborda-Barata L 2 CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Covilha, Portugal 2 Department of Allergy & Clinical Immunology, Centro Hospitalar Cova da Beira, Covilha, Portugal
1
Background: Aeroallergen exposure conditions sensitisation profiles and is associated with the development of allergic diseases, namely Allergic Rhinitis (AR) and bronchial asthma (BA). The aim of the present study was to compare the pattern of aeroallergen sensitization between elderly and young adults and assess the prevalence and clinical allergic responses in both groups. Method: This was a cross-sectional study using a simple random sample. The population consisted of 2 groups of individuals from Beira Interior recruited from the patients lists of the County Health Care Centre: one of young adults (born between 1973 and 1991) and another of elderly individuals (born before 1945). Skin prick tests (SPT) and a standardized allergy questionnaire were carried out in all volunteers. All patients signed a written informed consent and the study was approved by the Regional Health Authority Ethics Committee. Chi-square test was used for statistical analysis. A p value less than 0.05 was considered statistically significant. Results: Our study sample included 684 randomized volunteers from each group. 99 young adults and 196 elderly agreed to be skin prick tested. Overall, the prevalence of sensitisation was significantly higher in young adults (56.7%) than in elderly (36.8%) volunteers (p=0.001). Differences were observed in the sensitization patterns between the two sensitised groups with the elderly being mostly sensitized to D. pteronyssinus (48.5%), P. judaica (33.8%) and D. farinae (30.9%) and young adults mostly to D. pteronyssinus (76.4%), D. farinae (47.3%), olive tree pollen (41.8%), and cereal pollen (41.8%). Selfreported symptoms associated with BA and AR were not statiscally different between both groups (BA 26.5% vs. 41.8%, p=0.073 and AR 63.2% vs. 67.3%, p= 0.641, for elderly and young adults respectively). Conclusions: Although there may be differences in the profile of sensitization to aeroallergens between young and elderly individuals, the clinical phenotypes of allergic disease are similar.
24 TOPICAL NASAL STEROID THERAPY IMPROVES NASAL MUCOSAL FUNCTION SUPINE IN PATIENTS WITH ASTHMA: A DOUBLE BLIND PLACEBO CONTROLLED CROSS OVER STUDY Poster Discussion Session 2 Hellgren J 1, Rimmer J 2, Bartlett D 2, Greenwood A
1 2
Dept ENT Head & Neck Surgery Sahlgrenska University Hospital, Goteburg, Sweden 2 Woolcock Institute of Medical Research Sydney University, Sydney, Australia
Background: Rhinitis is an independent risk factor for sleep disturbances in asthma but the mechanism is poorly understood. In healthy individuals the nasal patency decreases when changing body position from sitting to supine. This study evaluates if the regulation of nasal patency between sitting and supine is impaired in asthma and if a topical steroid can improve nasal regulation as well as rhinitis related quality of life and sleep. Methods: Nineteen subjects (mean age 40) with mild to moderate asthma (mean duration 24.6 years) and a history of untreated rhinitis were randomized to fluticasone propionate nasal spray (Beconase), 200g daily or placebo (FESS saline nasal spray) for 6 weeks in a double blind, cross over design with 4 week wash-out in between treatments (total 16 weeks). Acoustic rhinometry was measured sitting and supine, peak nasal inspiratory flow (PNIF) and spirometry were measured, and quality of life and sleep were assessed with the Rhinitis Quality of Life Questionnaire (RQLQ), Short Form 36 (SF-36), Epworth Sleeping Scale (ESS), Fatigue Questionnaire, Depression Anxiety Stress Scales (DASS) and Pittsburgh sleep quality index (PSQI). Objective sleep assessment with Actimetry was obtained in a subsample of 9 individuals. Results: At baseline a change in body position from sitting to supine did not affect the minimal cross-sectional area (MCA). After fluticasone treatment, but not after placebo, the MCA sitting increased significantly and a change in posture from sitting to supine resulted in a significant decrease in MCA. After fluticasone there was a significant improvement in RQLQ and in physical functioning and general health on the SF-36 but no significant change in FEV1.0 or difference in asthma symptoms with either treatment. Subjective sleep did not change significant on the ESS, Fatigue Questionnaire or PSQI. Actigraphy from 9 subjects revealed no difference between fluticasone and placebo. Conclusion: This study shows that the regulation of nasal patency when changing body position from sitting to supine is impaired in patients with asthma and that treatment with fluticasone propionate nasal spray restored this function accompanied by an improved quality of life. Impaired regulation of nasal patency supine may be an important marker of poor control of upper airway inflammation in asthma and could play a role rhinitis related sleep disturbances in asthma.
25 ATOPIC RHINITIS: FREQUENCY OF IMMUNOGLOBULINE GENE FAMILIES USING AND CDR/FR REGIONS NUCLEOTIDE COMPOSITION. Poster Discussion Session 2 Stolyarova E, Stolyarova T, Titov L Republican Scientific and Practical Center for Epidemiology and Microbiology, Minsk, Belarus
The basis of atopic rhinitis is a disbalance between Th1-and Th2-cells with increased activity of Th2 stimulating the production of IgE. The basis of atopic rhinitis is a disbalance between Th1-and Th2-cells with increased activity of Th2 stimulating the production of IgE. The interaction of allergen with IgE activation of mast cells occurs with the subsequent release of mediators, causing edema, increased vascular permeability, hypersecretion of mucous glands. The aim of the work is to analyze an immunoglobulin genes families usage and nucleotide replacement in genes, which code of the variable regions of IgE in patients with atopic rhinitis. Materials: as a materials from databases of Gene-Bank were selected nucleotide sequences of 162 fragments of genes of variable regions immunoglobulins E of patients with atopic rhinitis and sequences of IgE VH genes from non-atopic donor (127). Methods: for identification of family genes, the software IMGT-QEST was used. Nucleotides replacement was performed by VVK 3.4 programs. Results: VH genes coding of IgE in non-atopic donor mostly are formed on the basis VH3 and VH4 families (41, 7% and 41, 7%), VH1, VH5 and VH6 families included in the synthesis of IgE in 9, 4%, 3, 2% and 2, 4%. VH genes coding of IgE antibodies in patients with atopic rhinitis mostly are formed on the basis V3 families of genes - 43, 2%, other variable regions are formed on the basis of V3, V1, V4 and V5 families (18, 5%, 17, 3% and 16, 7%). Study of genes germlines showed that the highest ratio of <4>-fold sites to the number of <0>-fold sites of CDR2 region is observed in the V5 family of genes germinal lines (0,219), the third family is characterized by the lowest value of the relationship (0,139). The ratio of synonymous sites to nonsynonymous of CDR2 region V3 family of genes (3, 83) is above this ratio in V4 (3, 1) and V5 (2, 95) families. Conclusion: The results indicate a higher fitness CDR2 region V3 gene family to the emergence nonsynonymous substitutions. Value of frequency changes of GC / AT to AT / GC in the fragments of variable regions of immunoglobulin genes patients with atopic rhinitis is not changed in comparison with sequences of immunoglobulin genes from non-atopic donors. The frequency transitions of GC / AT exceeds the frequency of transversions GC/CG from patients with atopic rhinitis and non-atopic donors. The results show the balance of the repair enzymes in B-cells of patients with atopic rhinitis.
26 BRONCHIAL ASTHMA: FREQUENCY OF IMMUNOGLOBULINE GENE FAMILIES USING AND NUCLEOTIDE COMPOSITION CDR AND FR REGIONS. Poster Discussion Session 2 Titov L, Stolyarova T, Stolyarova E Republican Scientific and Practical Center for Epidemiology and Microbiology, Minsk, Belarus
Background: The prevalence of allergic diseases has increased in the Republic of Belarus. Atopy, which underlies the development of allergic diseases, is characterized by the hyperproduction of IgE allergen-specific immunoglobulins. The induction of IgE synthesis by B-cells requires several distinct signals, including cytokines and cell surface molecules expressed by activated CD4+ T-lymphocytes. The aim of the present work is to investigate the codons composition and mutations in VH CDR and FR fragments of IgE genes in patients with bronchial asthma. Methods: For identification of family genes, the software IMGT-QEST was used. Sequences comparison was done using the Identity method. Nucleotides replacement was performed by VVK 3.4 programs. Materials have been the sequences of IgE VH genes from databases of Gene-Bank patients with bronchial asthma (538) and sequences of IgE VH genes from non-atopic donor (127). Results: VH genes coding of IgE antibodies in non-atopic donor mostly are formed on the basis VH3 and VH4 families (41, 7% and 41, 7%), VH1, VH5 and VH6 families included in the synthesis of IgE antibodies in 9, 4%, 3, 2% and 2, 4%. In patients with bronchial asthma, genes coding IgE mostly were formed on the basis of V3 family (49, 26%). In 18, 03% and 12, 45% they belonged to V5 and V4 families. GC-content CDR1 and CDR2 regions was 0,482 0, 02 and 0,3550,041 for V3 family; 0,4990,043 and 0,4420,044 for V4 family. GC-content in FR1, FR2, FR3 regions was 0,6490, 01, 0,6480,018, 0, 50,012 for V3 family, 0,6250,009, 0,6550,022, 0,5310, 01 for V4 family. Conclusion: Genes germinal lines unevenly saturated guanine and cytosine in the FR and CDR regions: the content of GC and 3GC in the hypervariable CDR regions below the level of saturation GC and 3GC FR-regions. Value of frequency changes of GC / AT to AT / GC in the fragments of variable regions of immunoglobulin genes patients with bronchial asthma is not changed in comparison with sequences of immunoglobulin genes from non-atopic donors. The frequency transitions of GC / AT exceeds the frequency of transversions GC/CG from patients with bronchial asthma and non-atopic donors.
27 PREOPERATIVE TREATMENT WITH TOPICAL CORTICOIDS AND BLEEDING DURING PRIMARY ENDOSCOPIC SINUS SURGERY Poster Discussion Session 2 Gocea A 1, Mitre I 2, Albu S 1 2nd Department of Otolaryngology, University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, Romania 2 Dpt of Maxillofacial Surgery, University of Medicine and Pharmacy Cluj-Napoca, ClujNapoca, Romania
1
Introduction: It is widely recognized that topical corticosteroids (TC) are powerful antiinflammatory agents acknowledged as a cornerstone in the treatment of CRS with and without nasal polyps. TC are capable of reducing eosinophil infiltration, activation and survival within the nasal mucosa; they decrease local tissue infiltration with T lymphocytes, diminish inflammatory mediators release, suppress the local production of cytokines and accordingly vascular permeability is reduced. Other alleged TCs mechanisms responsible for decreasing bleeding are decreased tissue edema and reduction of capillary bleeding. Objective: since significant inflammation of the sinus mucosa is associated with increased degree of vascularity we tried to find out whether the constant preoperative use of a topical corticoid (mometasone furoate - MF) could really improve the operative field quality and decrease bleeding during endoscopic sinus surgery (ESS). Study Design: Double-blind, randomized controlled trial. Setting: Tertiary referral center. Methods: Seventy patients with chronic rhinosinusitis (CRS) with and without polyps underwent ESS under standardized general anesthesia with equal randomization into two groups. During four weeks within the preoperative period, 35 cases were treated with MF, while the other half received placebo matching sprays. Total blood loss, operation time and surgical field quality were recorded. Results: Intraoperative blood loss in the MF-treated group was 142.8 mL, less than in the control group (170.6 mL). The difference between the groups is 27.7 mL (95% confidence interval [CI] 3.5-51.92), statistically significant: P =0.025. Time of surgery was 59 minutes in the MF group and 70 minutes in the control group. The difference was 11.2 minutes (95% CI 2.82-19.51), which is statistically significant: P = 0.009. The quality of the endoscopic surgical field was significantly better for patients treated with MF. Treatment with topical corticoid enables significantly reduced bleeding, decreased operation time and improved endoscopic vision during ESS for CRS. Conclusion: The use of topical corticoid (MF) in the preoperative period can improve endoscopic vision, reduce bleeding and decrease operation time in CRS patients with and without polyps undergoing ESS, but our sample size cannot exclude small, and possibly trivial, group differences.
28 EPIDEMIOLOGY AND DIFFERENCE BETWEEN NONALLERGIC AND ALLERGIC RHINITIS IN CHILDREN Poster Discussion Session 2 Bajraktarevic A 1, Trninic S 1, Sporisevic L 2, Djukic B 2, Selimovic A 3, Resic M 4, Begovic L 5, Katica A 6, Visegradjanin B 6, Lihic Trninic F 6, Frankic T 7, Pahor Kurilic A 7 Public Health Institution of Canton Sarajevo-Pediatrics Department, Sarajevo, Bosnia and Herzegovina 2 First Medical AidPediatrics Department, Sarajevo, Bosnia and Herzegovina 3 Pediatrics Clinic Sarajevo, Sarajevo, Bosnia and Herzegovina 4 Clinical Medical Center Sarajevo-ORL Clinics, Sarajevo, Bosnia and Herzegovina 5 General Hospital Sarajevo- ORL Department, Sarajevo, Bosnia and Herzegovina 6 Public Health Institution of Canton Sarajevo-ORL Department, Sarajevo, Bosnia and Herzegovina 7 Pharmaceutical Faculty Sarajevo, Sarajevo, Bosnia and Herzegovina
1
Session: Authors:
Affiliations:
Background: Nonallergic rhinitis involves chronic sneezing or having a congested, drippy nose with no apparent cause. Rhinitis is defined as inflammation of the membranes lining the nose, characterized by nasal symptoms, including itching, rhinorrhea, and nasal congestion. Methods: A blood test made measures of children immune system's response to common allergens by measuring the amount of certain antibodies in bloodstream, known as immunoglobulin E (IgE) antibodies for establishing right diagnosis and cause of rhinitis.Aims have been alternative hypothesis work is the fact that there were significant, are evident difference between allergic rhinitis and nonallergic rhinitis in children. Results: Authors reported a 19% frequency of nonallergic rhinitis among 1019 children selected for having a history that suggested allergic rhinitis. We determined that nonallergic rhinitis with eosinophilia syndrome (NARES) was found in 13%, blood eosinophilia nonallergic rhinitis syndrome (BENARS) in 3%, and elevated IgE in 11% children. Conclusions: Nasal symptoms characteristic of nonallergic rhinitis are often indistinguishable from those that occur in allergic rhinitis, and, therefore, negative testing for IgE-mediated sensitivity to relevant aeroallergens is necessary to confirm this diagnosis. No specific test is available to diagnose vaso-motor rhinitis. Discussion: First-line treatment should include the safest therapies such as steam inhalation, nasal saline sprays, and an avoidance of irritants. Topical medical therapy is preferred to systemic.
29 DIAGNOSTIC METHODS IN LATEX ALLERGY Poster Discussion Session 2 Juarez-Martinez L, Pavon G, Teran L, Gonzalez M National Institute Of Respiratory Diseases, Mexico D.F., Mexico
Introduction: It is a hypersensitivity reaction predominantly type I, sometimes type IV hypersensitivity caused specifically by the proteins in latex. The high risk populations are the atopic individuals, health workers and children with spina bifida or multiple surgeries. Reactions occur in a short period after exposure (mucosal vasodilation, severe bronchospasm and increased permeability with edema and cardiovascular collapse). Diagnostic methods for latex allergy include skin test with 65-96% sensitivity and 88-94% specificity, glove tests with low sensibility and specificity, rubbing test, determination of specific IgE to latex, and most recently a diagnostic method with nasal challenge to latex. Case Presentation: A Mexican 7 year old girl, with a history of asthma since age 5, treated with Salmeterol/Fluticasone BID and Salbutamol as needed. When she touches balloons, she notes itching in the oral cavity, lips edema, dyspnea, wheezing, coughing, conjunctival erythema, so does eating kiwi, banana and avocado. In the glove test refers mild local itching and examination reveals erythema. The skin tests included avocado, kiwi, banana, potato, apple, apricot, grapes, wheat, tomato and latex; only with the last one she presented erythema of 30 and wheal of 17 mm with a histamine control of 10 and 5 mm respectively. The nasal challenge started with instillation of Latex Sol with 0.9% saline, a nasal flow of 408 ml/s, then latex was instilled with increasing doses until the end of 50 mcg in Latex at which the nasal flow decreases significantly because she couldnt perform rhinomanometry due to nasal obstruction symptoms (sneezing, moderate rhinorrhea and nasal obstruction) that precluded the test. Specific IgE was reported in 3.51-17.5 kU/l (normal 0.35 kU/l). We start specific latex immunotherapy, and recommend eliminating from the diet: avocado, kiwi, bananas, potatoes, apricots, grapes, wheat and tomato. Discussion: Latex allergy is rare, so we present a case in which various diagnostic tests were performed to corroborate the usefulness of nasal challenge to support a diagnosis of latex allergy and to give immunotherapy and dietary support. It is noteworthy that the patient is currently with maintenance SLIT with specific latex vaccine and successful immunotherapy outcomes.
30 EFFECTS OF SEASONAL ALLERGIC RHINITIS ON FATIGUE LEVELS AND MOOD Poster Discussion Session 2 Adwan Z SMA HOSP, Damaskus, Syria
Objective: Many allergy patients complain of fatigue, moodiness, and dysphoria during their allergy seasons. This study evaluated the effect of symptomatic allergic rhinitis on both fatigue level and mood. Methods: Symptomatic ragweed allergic rhinitis patients on no medications and healthy control subjects completed the Multi-Dimensional Fatigue Inventory and the Positive AffectNegative Affect mood rating scales in an in-out-in ragweed season research design. Results: During ragweed seasons, allergic patients reported higher levels of general fatigue and mental fatigue, but not physical fatigue, as well as reduced motivation. Patients described experiencing feelings of greater sadness and reduced pleasurable engagement. Increased anxiety or emotional distress was not reported. Conclusion: These findings suggest that having allergic reactions to ragweed pollen causes significant fatigue and mood changes in at least a subgroup of patients. Psychoneuroimmunology and medical genetics research suggests that allergic reactions engender biochemical changes that directly affect the central nervous system.
31 HYPERRESPONSIVENESS TO METHACHOLINE CHALLENGE IN ASTHMATIC PATIENTS AND A HEALTHY POPULATION IN MEXICO Poster Discussion Session 2 Juarez Martinez L, Gonzalez Galarza M, Teran Juarez L, Garcia Cruz M National Institute Of Respiratory Diseases, Mexico D.F., Mexico
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Background: This is a study to assess the degree of hyperresponsiveness to methacholine challenge in asthmatic and healthy patients. Methods: Experimental study that was performed in the service of Allergy and Clinical Immunology, at the National Institute of Respiratory Diseases in Mexico City, Mexico, in order to determine the degree of bronchial hyperreactivity on methacholine challenge of the Institute population during the period February 2010 to August 2010. Results: We analyzed data on 145 patients referred to the service of Clinical Immunology and Allergy, 58 healthy (40%) and 87 diagnosed with asthma (60%), 64.1% of them were females, the age range were reported under 18 years old: 28 patients (19.3%), between 19 to 25 years 20 patients (20.8%), in the group of 26 to 50 years 83 patients (57.2%) and aged above 50 years 14 patients (9.7%), with 90 testing positive methacholine bronchial challenge (62%), 77 of them had asthma (53.1%) and 13 were considered healthy (9%). They asthmatic patients were categorized according to the Guide to Methacholine Bronchial Challenge of the American Thoracic Society (ATS) such as: Normal (> of 16mg/ml) 6.9%, Borderline (from 6 mg/ml 4) 22.1%, Slight Positive (1-4 mg / ml) 15.9% Moderate Severe (<1 mg / ml) 15.9%. The sensitivity of methacholine bronchial challenge was 88%, specificity of 81%, positive predictive value of 88% and negative predictive value 77%. In the analysis of ROC curve (area under the curve) showed that with the methacholine challenge test, 85% of patients were actually diagnosed with asthma or excluding this diagnosis (p <0.05), 20% of healthy controls with a negative challenge, showed a fall in FEV1 between 10 and 20% Dermatophagoides allergen was the most common (29.8%). Also 66.7% had serum IgE levels greater than 500 UI/ml, we observed a higher rate of atopy in those asthmatics with positive challenge compared to a negative challenge. Conclusions: The sensitivity of methacholine bronchial challenge was 88%, a specificity of 81% positive predictive value of 88% and a negative predictive value of 77%. It is a safe and useful diagnostic method with which we have for HRB.
32 EFFECT OF DHMEQ, A NF-KAPPAB INHIBITOR, ON NASAL CULTURES Poster Discussion Session 2 Valera F 1, Umezawa K 2, Brassesco M 3, Gamero A 3, Tone L 3, Anselmo-Lima W 1 Division of Otolaryngology - School of Medicine of Ribeirao Preto (FMRP-USP), Ribeirao Preto, Brazil 2 Keio University, Yokohoma, Japan3 Department of Pediatrics - School of Medicine of Ribeirao Preto (FMRP-USP), Ribeirao Preto, Brazil
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Background: nasal polyposis is generally treated with glucocorticoids, which mainstay is to reduce the inflammation through inhibiting transcription factors, such as NF-kappaB. NFkappaB inhibitors are being developed, in an attempt to improve anti-inflammatory efficacy and to reduce resistance to glucocorticoids. Our group has previously observed that DHMEQ displays an anti-inflammatory effect on nasal fibroblasts, and this effect is increased when both drugs were superposed. Nevertheless, the security of DHMEQ on nasal polyps viability is unknown, which impairs future in vivo studies. Thus, the objective was to evaluate the effect of DHMEQ, a NF-kappaB inhibitor, on nasal fibroblasts cultures. Methods: cell viability, apoptosis fraction and clonogenic assay were assessed in 5 different concentrations of DHMEQ (10, 100, 1.000, 10.000, 20.000 and 40.000nM), for 24, 48 and 72 hours in 6 samples from patients with nasal polyposis submitted to surgery. Each concentration was statistically compared to control. Results: Cell viability and apoptosis fraction were similar to control for all different concentrations and periods analyzed. Clonogenic assay was significantly lower than control for the concentration of 40.000 nM of DHMEQ, for all the three periods evaluated (24 hours: 12 colonies for 40.000nM vs. 18 for controls, P=0.02); (48 hours: 14 colonies for 40.000nM vs. 28 for controls, P=0.02); (72 hours: 10 colonies for 40.000nM vs. 31 for controls, P<0.0001). Conclusions: the concentration of 40.000nM of DHMEQ significantly inhibited nasal polyps mitosis, without lessen cell viability. This concentration should be tested in futures in vitro studies to establish the anti-inflammatory effect of this drug.
33 PROTECTIVE EFFECT OF PRANLUKAST HYDRATE AGAINST JAPANESE CEDAR POLLEN BASED ON DATA COLLECTED IN A POLLEN-EXPOSURE CHAMBER (THE OHIO CHAMBER) Poster Discussion Session 2 Okubo K 1, Hashiguti K 2, Gotoh M 1, Endo S 3, Suzuki H 4, Masuyama K 3 Department of Otolaryngology, Nippon Medical School, Tokyo, Japan 2 Department of Otolaryngology, Kitasato Institute Hospital, Tokyo, Japan 3 Department of Otorhinolaryngology, Graduate School of Medical Engineering, Kohfu, Japan 4 Department of Pharmacology, Nippon Medical School, Tokyo, Japan
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Background: We previously reported that pranlukast, a leukotriene receptor antagonist, improved the symptoms of Japanese cedar pollinosis in a double-blind crossover controlled study using a pollen-exposure chamber (the OHIO Chamber). It is ideal that the appearance of symptoms can be delayed or be undeveloped. A stratified analysis of data from this study was performed to examine whether pranlukast hydrate is an appropriate drug with a protective effect against symptoms of Japanese cedar pollen Method: A double-blind crossover controlled study was performed to investigate the efficacy of pranlukast in patients with cedar pollinosis who were exposed to a specific amount of cedar pollen (8000/m3) in the OHIO Chamber. The study was performed during a period outside the pollen-scattering season. The subjects underwent two exposures of 3 hours each at a 1-week interval. Pranlukast was administered orally after a meal before and after each exposure. The effect of pranlukast was evaluated based on nasal symptoms. Results: The percentage of patients with nasal congestion in the OHIO Chamber was significantly lower in the pranlukast group compared to the placebo group: 25.6% vs. 53.8% at 60 min after entry; and 35.9% vs. 61.5% at 120 min after entry. Nasal congestion appeared at average times of 77.9 and 51.9 min after entry in the pranlukast and placebo groups, respectively. The percentages of patients with nasal symptoms in the period between exposure in the OHIO Chamber and the following night were lower in the pranlukast group compared to the placebo group. Conclusion: Our results show a protective effect of pranlukast hydrate against symptoms of Japanese cedar pollen exposure using a pollen-exposure chamber, with a particularly strong effect on nasal congestion. Therefore, treatment with pranlukast may improve the quality of life of patients with Japanese cedar pollinosis. We conclude that pranlukast is an appropriate drug with therapeutic and protective effects against symptoms of Japanese cedar pollen
34 CLINICAL FEATURES IN PATIENTS WITH SUBNORMAL SERUM LEVELS OF IMMUNOGLOBULIN A Poster Discussion Session 2 Gonzalez M , Garcia M , Juarez L, Pavon G , Ramirez F , Teran L National Institute Of Respiratory Diseases, Mexico D.F., Mexico
Background: The immunoglobulin A (IgA) is the most abundant antibody in mucous membranes and the second highest concentration in the blood. Its concentration is less than 7 IU / ml is defined as selective IgA deficiency, which can be asymptomatic or have respiratory infections and digestive recurrent or associated with allergic symptoms. There are few reports describing the clinical characteristics of patients with partial deficiency of Ig A (2 SD for age). Objective: To report the frequency of history, symptoms and severity of atopic and nonatopic diseases in patients with subnormal levels of Ig A in a tertiary hospital in Mexico City. Methods: A cross sectional study in children with allergy consultation IgA levels <80UI/ml, the population was stratified by age group, analyzing the frequency of atopic diseases and atopic with 2 p <0.05% with SPSS 16.0. Results: We analyzed 61 patients of which 88.5% have partial IgA deficiency and 11.5% is selective. Reported men 52.3% and women 47.5%. 90% have symptoms suggestive of allergy, elevated IgE 44.3% and 16.4% had positive skin tests. The most common allergen Dermatophagoides pt was 13.1% (p <0.05). The frequency of allergic diseases is: 88.5% allergic rhinitis (59% moderate persistent) asthma 13.1% (62% uncontrolled), 32.1% early wheezing, persistent wheezing 9.8%, 3.3% late wheezing, 19.7% protein allergy milk, atopic dermatitis 4.9%, in relation to non-atopic disease: Gastro esophageal reflux 41% syndrome, obstructive sleep apnea 6.6%. As background, tonsillectomy was 14.8%, 32.8% had a history of pneumonia, the womb was 49.2% and 24.6% whole milk was weaned. Conclusion: IgA has anti-inflammatory activity by preventing adhesion of antigens to mucosal surfaces. This study shows that partial deficiency of IgA is associated with increased frequency and severity of allergic rhinitis and asthma, as well as greater number of respiratory infections which coincides with history of pneumonia by nearly 50% of them. Knowing this condition will help the doctor evaluate other factors exacerbating allergic disease and optimize treatment of the same.
35 NASAL HYPERACTIVITY IN ALLERGIC AND NON-ALLERGIC PATIENTS SERIN Symposium 2 - Phenotyping of chronic airway disease all over the world Segboer C, Holland C, Georgalas C, van Drunen C, Fokkens W Academic Medical Center Amsterdam, Ear Nose Throat Department, Amsterdam, Netherlands
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Background: To assess the prevalence and distribution of nasal hyperreactivity in allergic and non allergic rhinitis patients. To investigate the presence of constant, recurring patterns of sensitivity to specific provoking factors. To assess if nasal hyperreactivity is season-dependent. Methods: 885 non allergic rhinitis patients and 1103 allergic rhinitis patients recorded prospectively regarding their symptoms including nasal hyperreactivity to changes of temperature, tobacco smoke and scents, humidity, exercise and emotional stress. The seasonal variation of their symptoms was also recorded. Comparisons between groups were made using Chi-square test and Fishers exact test. Results: In the allergic and the non allergic patient group prevalence and distribution of provoking factors were the same. In both groups the most common nasal provoking factor was change of temperature, followed by tobacco smoke and scents, exercise, emotional stress and last humidity. Both in the allergic as in the non allergic group there was no clinically significant seasondependency of nasal hyperreactivity. Conclusion: Prevalence and characteristics of nasal hyperreactivity were the same in both the allergic and the non allergic patient groups. No specific pattern or combination of provoking factors were found in either group.
36 CHANGING IMMUNOPHENOTYPES AFTER MULTIPLE SURGERY IN CHRONIC RHINOSINUSITIS WITH NASAL POLYPS SERIN Symposium 2 - Phenotyping of chronic airway disease all over the world Van Zele T, Holtappels G, Bachert C Ghent University, Ghent, Belgium
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Background: Introduction Nasal polyposis (NP) is a disabling chronic inflammatory disease that is frequently operated. It has a high failure rate because of recurrence of disease. We have shown that caucasian NP demonstrate a distinct Th2 cytokine profiles without IL17 but we dont know if this profile predicts recurrence or changes after multiple surgery. Methods: Only NP patients who underwent functional endoscopic sinus surgery for the second time were selected (n=10). Tissue samples were obtained during endonasal surgery and concentrations of IL-1beta, IL-5, IL-6, IL-17 , TGFbeta1, and MPO were measured on tissue homogenates using ELISA, whereas, total and specific IgE to S. Aureus enterotoxins and ECP were measured by CAP system. Results: Absolute concentrations of MPO and IL-1beta were significantly after the second surgery compared to the first surgery, whereas no significant difference could be found for IL-5, IL-6, IL-17, TGFbeta1, IgE, spec IgE and ECP. All patients had a Th2 profile at the first surgery and remained IL-5 positive after the second surgery. However none of the patients had a Th17 signal at the first surgery while after the second surgery 4 of the 10 became IL17 positive. Conclusion: 40% of the NP patients become IL17 positive after multiple polyps. This leads to a combined Th2 Th17 profile and is associated increased MPO concentrations leading to a combined eosinophilic inflammation. These results suggest that the immunophenotype of NP can especially in a group with recurrences. surgery for nasal with significantly and neutrophilic change over time
37 GA2LEN STUDY: PREVALENCE OF CHRONIC RHINOSINUSITIS IN EUROPE BY EP3OS CRITERIA SERIN Symposium 2 - Phenotyping of chronic airway disease all over the world Hastan D 1, Fokkens W 1, Bachert C 2, Toskala E, Hoffmans R 1, Tomassen P 2, Kok J 1, Smulders Y 1, Potts J 3, Newson R 3, van Bruaene N 2, Zuberbier T 4, Bousquet J 5, Jarvis D 3, Burney P 3 Academic Medical Center, Amsterdam, The Netherlands, 2 Ghent University, Ghent, Belgium, 3 Imperial College, London, United Kingdom, 4 Universitatsmedizin Berlin, Berlin, Germany, 5 INSERM, Hopital Arnaud de Villeneuve, Montpellier, France
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Background: Chronic rhinosinusitis (CRS) is a common health problem, with significant direct medical costs and severe impact on lower airway disease and general health outcomes. However, to date there have been no large population based studies conducted across Europe to assess the prevalence and burden of disease. Recently a taskforce endorsed by EAACI and ERS has agreed a definition of chronic rhinosinusitis which can be used for epidemiological research (the EP3OS criteria). Based on these definitions the GA2LEN network of excellence funded by the European Union started a Survey in 19 cities in 12 countries of Europe to evaluate the prevalence of chronic rhinosinusitis. Method: A postal questionnaire was sent to a random sample of 66.549 adults aged 15-75 obtained from a suitable population based sampling frame. The questionnaire asked, amongst others, for symptoms of CRS, age, gender, and smoking history. The definition of CRS was based on the EP3OS criteria being the presence of > 2 of 1) nasal blockage 2) nasal discharge, 3) facial pain/pressure or 4) reduction in sense of smell for > 12 weeks in the past year with at least one symptom being nasal blockage or discharge. Physician diagnosed CRS was considered to be present if the participant reported they had ever been told by a doctor they had CRS. Results: Twenty-five centres in 15 countries took part in the survey. Applying selection criteria 19 centres in 12 countries were left for data analysis concerning a total of 57.128 responders (9.421 non-responders). Applying the EP3OS criteria and adjusting for age and gender by the Standard European Population, the CRS prevalence was estimated at 10.8% (95%CI 10.5-11.0), with geographical variation. This is more than twice the number of physician diagnosed CRS, 5.1%. The odds ratio for CRS in smokers versus non smokers was 1.7 (95%CI 1.6-1.9, p<0.0001). Conclusion: A multicentric survey was conducted on the prevalence of CRS in Europe. Data from 57.128 questionnaires were analysed. A single prevalence estimate for Europe is not possible due to geographical variation, however for the total sample one in ten people have CRS by EP3OS criteria. The prevalence of CRS was moderately associated with smoking.
38 LOCAL VS SYSTEMIC ALLERGIC RHINITIS: NASAL CYTOKINE PATTERN Oral Presentations 2 Rondon C 1, Mayorga C 2, Herrera R 2, Antunez C 2, Campo P 1, Garcia I 1, Blanca-Lopez N 3, Canto G 3, Blanca M 1 Allergy Service, Carlos Haya Hospital, Malaga, Spain 2 Research Laboratory, Carlos Haya Hospital-Fundacion IMABIS, Malaga, Spain 3 Allergy Service Infanta Leonor Hospital, Madrid, Spain
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Background: Local allergic rhinitis (LAR) is a new form of allergic rhinitis (AR) in the absence of systemic atopy. The aim of this study was to compare the nasal production of cytokines and inflammatory mediators in LAR and AR. Methods: Nasal challenge with D. Pteronyssinus was performed in 22 LAR and 16 AR patients. We measured nasal secretion of IFN-gamma, TNF-alpha, TNF-beta, IL-1beta, IL-2, IL-6, IL-4, IL-5, IL-8, IL-12p70, tryptase and ECP at baseline, 15min, 1-2-24 hours after NAPT. Results: After challenge, 16 LAR and 12 AR patients presented an immediate response, and the other, a dual response. We observed a significant increase of IFN-gamma, IL-1beta, IL-2, IL-4, IL-8, IL-12p70, tryptase and ECP in both LAR and AR patients after challenge. Immediate responders had a similar inflammatory pattern with peaks of IL-1beta, IL-12p70 and tryptase at 1h, IL-4 (2h) and ECP (24h); but different peaks of IFN-gamma and IL-2 (LAR=1h, AR=2h), IL-6 (LAR=1h), and IL-8 (LAR=2h). Dual responders exhibit a similar pattern with peaks of IL-8 and tryptase at 2h, and ECP at 24h; and different peaks of IFNgamma (LAR=15m, AR=2h), IL1-beta (LAR=24h, AR=2h), IL-2 (LAR=1h, AR=2h), IL-4 (LAR=1h), IL-6 (LAR=2h), and IL-12p70 (LAR=15m, AR=2h). Conclusions: Nasal exposure to D. Pteronyssinus induces a similar inflammatory response in LAR and AR patients, with significant increase of IFN-gamma, IL-1beta, IL-2, IL-4, IL-8, IL-12p70, tryptase and ECP. A faster secretion of IFG-gamma, IL-2, IL-4, IL-6, IL-8 and IL12p70 was observed in LAR. Further studies are needed to explore the cytokine production during the late response.
39 ROLE OF OCCUPATIONAL EXPOSURE ON THE OUTCOME OF SINUS SURGERY: AN OBSERVATIONAL STUDY. Oral Presentations 2 Delrue S 1, Hox V 1, Scheers H 2, Adams E 4, Keirsbilck S 4, Jorissen M 1, Nemery B 2, Hellings P 1 Department of Otorhinolaryngology, Head and Neck Surgery, University Hospitals, Leuven, Belgium 2 Research Unit of Lungtoxicology, Faculty of Medicine, University of Leuven, Leuven, Belgium 3 Laboratory of Experimental Immunology, University Hospitals, Leuven, Belgium 4 Clinic for Occupational and Environmental Medicine, Department of Pneumology, Leuven, Belgium
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Background: Functional endoscopic sinus surgery (FESS) is the therapy of choice in patients with chronic rhinosinusitis (CRS) that are insufficiently controlled by medical treatment. Several endogenous as well as exogenous factors may be responsible for persistent or recurrent inflammation in the sinonasal cavities postoperatively and hence insufficient symptom control after FESS. The role of occupational and environmental agents in failure after FESS has not been investigated so far. The aim of this large-scale observational study was to evaluate retrospectively exposurelevels to occupational factors in CRS patients undergoing FESS and controls and to relate the exposure to the number of FESS procedures needed to control the symptoms. Methods: Questionnaires were sent to 890 patients who underwent FESS and to 182 control patients. Besides general medical health questions, the questionnaire asked about professional and recreational activities and exposure levels to high molecular weight (HMW) and low molecular weight (LMW) occupational agents. Exposure was assessed as a binary variable. A chi-square test was used to investigate the relationship between number of FESS and exposure state. Odds ratios were calculated by a Proportional Odds Model and a Poisson regression model was worked out. Results: There is a significant relationship between exposure to occupational substances at work and number of FESS (chi2=13.62; p=0.009). The odds ratio for developing surgeryrequiring CRS is 2.15 (p=0.047) when there is professional exposure to occupational agents. The odds ratio for needing a higher number of surgeries is 1.8 (p=0.004) when someone is professionally exposed. Professionally exposed subjects undergo an average number of FESS that is 1.25 times higher than unexposed patients (CI 95% CI 1.06 1.48). Smoking and allergy are no confounding factors. Conclusions: Our data show that the risk for developing surgery-requiring CRS is significantly higher in people exposed to occupational agents. CRS patients who needed revision sinus surgery had a significant higher exposure rate to occupational agents then CRS patients in whom the first operation was successful. Therefore, these data suggest that exposure to occupational and recreational agents may be associated with persistent postoperative sinonasal inflammation and hence be responsible for failure after FESS.
40 NASAL PROVOCATION IN PATIENTS WITH NASAL POLYPOSIS Oral Presentations 2 Devuyst L 1, Gevaert P
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Upper Airway Research Center, UZ Ghent, Ghent, Belgium 2 Ghent University, Otorhinolaryngology, Ghent, Belgium
Background: Nasal polyps are characterized by a high concentration of eosinophils and local IgE. Because the allergic reaction is initiated by binding of an allergen with IgE, which causes stimulation of the mastcell and activates the allergic cascade, we wonder if this locally elevated IgE in the nasal polyps has an influence on the allergic reaction on aeroallergens. Objective: To compare the effect of nasal provocation in patients with or without allergic rhinitis and with or without nasal polpys and to observe the role of IgE in nasal polyps in the allergic reaction. Methods: We included 12 patients in each of the 4 groups. A nasal provocation test was done with 0.1 IR/ml, 1 IR/ml and 10 IR/ml solutions of grass pollen allergen (Stallergnes). The provocation was scored following the German guidelines (including nasal conductance and allergic symptom scores). Before and after the nasal provocation, blood and nasal secretions were collected, a nasal endoscopy and an allergic symptom VAS score were done. Results: In the non polyp patients, the nasal provocation test was negative in all non allergic and positive in all allergic subjects. Almost all nasal polyp patients (allergic and non allergic) had negative test results except 1 allergic subject. The symptoms: nasal obstruction, rhinorrhea, sneezing and nasal itching did increase significantly after nasal provocation in allergic patients. Conclusion: This study shows that exposure to allergens does not increase symptoms in nasal polyp patients. Possible explanations for the inhibition of the IgE- mediated allergic reaction are the polyclonal IgE that saturates mastcell receptors, the blocking activity of IgG4 and a negative regulation of inflammatory processes by IgA. These parameters will be measured in the nasal secretions and serum.
41 GENE EXPRESSION OF MMP-1, MMP-2, MMP-9 AND TIMP-1 IN NASAL POLYPS SERIN Symposium 3 - Nasal and sinus remodelling Anselmo-Lima W, Malinsky R, Milaneze C, Santana J, Tamashiro E, Valera F School of Medicine of Ribeirao Preto - University of Sao Paulo (FMRP-USP), Ribeirao Preto, Brazil
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Background: edema in nasal polyps (NP) is related to extracellular matrix degeneration, which in turn is regulated by MMPs (matrix metalloproteinases) and their inhibitor, TIMP. Several studies relate MMP and TIMP expression to airway inflammatory diseases. The purpose of this study was to evaluate if NP in Brazil are similar to those in Europe regarding MMP and TIMP expression. Methods: NPs were collected during surgery in 30 patients. They were compared to middle turbinate mucosa collected from 19 asymptomatic patients during rhinoplasty surgery. mRNAs were extracted, and gene expression of MMP-1, MMP-2, MMP-9 and TIMP-1 was evaluated by Real-time PCR. Data was analyzed through Student t test. Results: NPs presented significantly higher expression of MMP-1 (9.7912.62 for NP vs. 1.381.21 for middle turbinates, P<0.005), MMP-2 (3.431.86 for NP vs. 0.830.61 for middle turbinates, P<0.0001) and MMP-9 (5.256.12 for NP vs. 0.900.56 for middle turbinates, P<0.05). TIMP-1 expression was detected neither in NP nor in middle turbinates. Conclusions: Brazilian NP presented higher expression of all the 3 studied MMPs (MMP-1, MMP-2 and MMP-9), without the increase of their inhibitor, TIMP-1. Although there is some controversy about this subject, this pattern is very similar to that observed for NP in Europe.
42 MECHANISMS RESPONSIBLE FOR GLUCOCORTICOID INSENSITIVITY IN NASAL MUCOSA AND NASAL POLYPS. SERIN Symposium 3 - Nasal and sinus remodelling Fernandez-Bertolin L 1, Alobid I 2, Mullol J 2, Picado C 3, Pujols L 1 IRCE, IDIBAPS. Hospital Clinic, Barcelona, Spain 2 U. Rinologia i Clinica del Olfacte, Servei Otorrinolaringologia, Hospital Clinic, Barcelona, Spain 3 Servei de Pneumologia i Allergia respiratoria, Hospital Clinic, Barcelona, Spain
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Background: Nasal polyposis (NP) is a chronic inflammatory disease of the sinus mucosa often associated with asthma. Poor response of nasal polyp (NP) to glucocorticoids (GC) may be due to abnormal GC receptor (GR) function. The aim of this study was to evaluate the capacity of dexamethasone (Dex) to induce and regulate the anti-inflammatory target genes MAP kinase phosphatase-1 (MKP-1), glucocorticoid-induced leucine zipper (GILZ) and tristetraprolin (TTP) in fibroblasts from nasal mucosa (NM) and NP samples. Methods: Primary lines of fibroblasts were obtained from control NM (N=10) and NP tissues from asthmatic patients (N=12, 7 Aspirin intolerant asthmatics (AIA)). Fibroblasts were treated with culture media +/- Dex (10-7M), RU486, actinomycin D (Act. D) and cycloheximide (CHX) at different time points to study MKP-1, GILZ and TTP mRNA induction and regulation by Dex (analysed by RT-PCR). Basal GR quantification was analysed by RTPCR and Western blot. GR nuclear translocation was analysed by fluorescent immunocytochemistry and Western blot. Data is shown as median and 25th-75th percentiles. Results: Dex treatment induced the mRNA synthesis of the 3 target genes that was abrogated by RU486. Dex induction was also blocked by act D but not by CHX, suggesting a transcriptional regulatory mechanism of the studied gens. MKP-1, GILZ and TTP induction was significantly higher in NM fibroblasts (5.8;3.4-7.2, 12.3;9.5-14.1 and 1.6.3-2.2 respectively) than in NP fibroblasts from both aspirin tolerant (3.5;1.6-4.3, 10.8;4.6-11.6 and 1.2;1-1.5, p<0.05) and AIA patients (1.5;1.4-2.6, 5.4;3-11.3 and 1;0.8-1.5, p<0.05). Target genes induction was also significantly lower in AIA patients compared to ATA (p<0.05). There were no differences in GR protein and mRNA expression among the studied groups. Similarly, there were no differences in GR nuclear translocation. Conclusions: In our in vitro model we found that fibroblast from nasal polyps are less sensitive to the anti-inflammatory effects of GC. Our data suggest that the poor clinical response of NP to GC, and therefore their surgery requirement, may be due to an impaired ability of GC to induce anti-inflammatory genes. This alteration appears not to be due to alterations in GR number or nuclear translocation.
43 EUROPEAN VIEW ON THE IMMUNOPATHOLOGY OF CHRONIC RHINOSINUSITIS AND NASAL POLYPOSIS: FIRST RESULTS OF THE GA2LEN SINUSITIS COHORT STUDY SERIN Symposium 3 - Nasal and sinus remodelling Tomassen P, Bachert C Upper Airway Research Laboratory, Dpt. Of Otorhinolaryngology, Ghent University, Ghent, Belgium and Global Allergy and Asthma European Network
Background: Chronic rhinosinusitis with nasal polyposis is in Caucasians hallmarked by a Th-2-linked eosinophilic inflammation with polyclonal IgE production. Although evidence for a disease-modifying role of IgE specific to Staphylococcal enterotoxins (SAE-IgE) is well established, there have been variable reports on their prevalence in nasal polyp patients. We aimed to characterize the prevalence of SAE-IgE-positivity and its impact on inflammation in a large pan-European population of chronic rhinosinusitis (CRS) subjects. Methods: The study was designed as a multicenter, non-matched case-control study, and recruited CRS subjects with nasal polyps (CRSwNP), without nasal polyps (CRSsNP), and controls undergoing septoplasty or conchotomy. Surgery was conducted independently from the study. Serum, nasal secretions and tissue were analyzed for a range of cytokines, for total IgE and for SAE-IgE (SEA, SEC and TSST-1). Results: 848 subjects were enrolled, of which 301 were operated. Of these, 90 were controls, 96 had CRSsNP, and 105 had CRSwNP. CRSwNP was characterized by increased concentrations in tissue homogenates of ECP, MPO, IgE, IL-5, IL-6, IL-8 and sIL-2Ra, but not of TGF-beta, and of IgE, sCD23 and sIL-5Ra in nasal secretions, compared to CRSsNP and controls. SAE-IgE was detectable in tissue homogenates of 23,5 % of CRSwNP subjects, with considerable geographic variation. They were not detected in tissue of controls or in CRSsNP. SAE-IgE positive CRSwNP patients had an increased prevalence of asthma but not of atopy or smoking history. Concentrations of ECP, total IgE, IL-5, IL-1-beta, IL-6, IL-8, but not of TNF-alpha, MPO, IFN-gamma, IL-17 or TGF-beta-1, were significantly increased in tissue homogenates of SAE-IgE positive nasal polyps compared to SAE-IgE negative nasal polyps. In nasal secretions, increases in total IgE, sCD23, sIL-5R-alpha, IL-6 and IL-17 were significant. In serum, ECP, and total IgE were increased significantly. Conclusions: In a large European sample, SAE-IgE is detected in CRSwNP to a variable extent, indicating environmental and genetic predisposition to superantigen mediated disease. SAE-IgE is associated with an intense Th2-linked, IL-5 driven eosinophilic inflammation with high IgE production, confirming previous evidence in a broader population. A systemic effect linking CRSwNP with asthma is suggested.
44 INCREASED EXHALED NITRIC OXIDE PREDICTS INCIDENT AND PERSISTENT RHINITIS IN CHILDREN SERIN Symposium 4 - Non allergic rhinitis and polyps Malinovschi A 1, Alving K 2, Kalm-Stephens P 2, Janson C 3, Nordvall L 2 Dept. of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden 2 Dept. of Women's and Children's Health, Uppsala University, Uppsala, Sweden 3 Dept. of Medical Sciences: Respiratory Medicine and Allergology, Uppsala University, Uppsala, Sweden
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Background: The fraction of nitric oxide in exhaled air (FENO) is increased both in subjects with rhinitis and asthma. Recent studies demonstrated that high levels of exhaled NO in asymptomatic subjects can predict later onset of asthma. Little information is available with respect to the predictive value of increased exhaled NO in asymptomatic subjects for later onset of upper airways symptoms. The aim is to investigate in a cohort of schoolchildren if increased exhaled NO levels at the age of 13-14 years predicted new-onset or persistent rhinitis within a 4 years-period. Methods: A total of 959 randomly selected schoolchildren, aged 13-14 years, answered a questionnaire on respiratory symptoms, performed lung function and exhaled NO measurements at baseline. Follow-up was performed four years later and consisted of the same questionnaire. After exclusion of subjects with asthma diagnosis or asthma symptoms at baseline, 661 participants were eligible for the present study. Results: Subjects with new-onset rhinitis had a trend towards higher FENO compared to subjects who did not develop rhinitis (4.8 ppb (4.0, 5.9) vs 4.0 ppb (3.7, 4.3), p=0.06). Increased FENO (p=0.008) and increased BMI (p=0.01) predicted new-onset rhinitis in a multiple logistic regression model. The risk of new-onset rhinitis was 2.4 (1.3, 4.4) higher if FENO > 90th percentile of the group without rhinitis at baseline. Subjects with rhinitis remission had lower levels of FENO than subjects with persistent rhinitis (3.5 ppb (2.6, 4.8) vs 6.2 ppb (4.9, 7.8), p=0.04). Only increased FENO (p=0.03) predicted persistent rhinitis in multiple logistic regression model. The risk of persistent rhinitis was 4.7 (1.3, 17.4) higher if FENO > 90th percentile among the children in the group with rhinitis at baseline. Conclusion: Increased levels of exhaled NO were predictors of incident and persistent rhinitis in this population-based study of schoolchildren. An enhanced Th2 cytokine-driven response in the asymptomatic individuals might be a plausible explanation. The current results suggest that exhaled NO measurements could be used to predict rhinitis even when the patients status of allergic sensitization is not known.
45 EPIDEMIOLOGY OF NASAL POLYPS IN POLAND ACCORDING TO ECAP STUDY SERIN Symposium 4 - Non allergic rhinitis and polyps Wojas O 1, Arcimowicz M 2, Samolinski B 1 Department of Prevention of Environmental Hazards and Allergology, Warsaw, Poland 2 Otolaryngology Department Medical University in Warsaw, Warsaw, Poland
1
Background: Presented part of ECAP project (Epidemiology of Allergic Diseases in Poland) was carried out in Poland between 2006-2008 years. It took advantage of the international standards set forth by the ECRHS II (European Community Respiratory Health Survey II) and ISAAC (International Study of Asthma and Allergy in Childhood) surveys, adapting them for use in Central and Easter Europe. It encompassed 9 regions of Poland, in which 22 703 randomly selected participants (adults and children) underwent questionnaire interviews. One of the given question concerned nasal polyps. So it allowed us to describe the incidence of nasal polyps in studied Polish population and to evaluate the correlation between nasal polyps and such diseases as allergic and nonallergic rhinitis, asthma, allergic dermatitis as well as the influence of age, sex, socioeconomic status and environmental factors on nasal polyps development. Material and methods: Finally 18458 surveys collected passed all stages of quality control. The group consisted of 4473 children (age: 6 7 years); 4675 teenagers (age: 13 14 ys) and 9310 adults (age: 20 44 ys). Among them: 9922 females and 8536 males. To increase the quality of the data and gaining the information that is most reflective of the population being studied, the sample was selected via stratified sampling. The ECAP questionnaire was written on the basis of the original ECRHS II and ISAAC questionnaires. The study took advantage of the CAPI (Computer Assisted Personal Interviewing) system loaded on PDA (Personal Digital Assistant) devices. Taking into account the nature of computerized questionnaires, the amount of open-ended questions was limited to those with a numerical answer. With the goal of maximizing the quality of the data, special quality control procedures were implemented (telephone verification). Results: Nasal polyps were found in 204 subjects (1.1% of all cases); children group 29 (0.6%); teenagers 31 (0.7%); adults 144 (1.5%), more often among the patients suffering from asthma (statistically significant correlation in adults group; odds ratio OR=3.38). Nasal polyps and sex: in children and adults groups the nasal polyps were often in females; in teenagers in males (in all groups not statistically significant). In all groups we found the higher incidence of nasal polyps among people with allergic and nonallergic rhinitis in such cases the risk for developing nasal polyps statisticaslly significant. Also we observed positive correlation (but not statistically significant) between allergic skin diseases and nasal polyps. The socioeconomic status as well as environmental factors had no influence on prevalence of nasal polyps, except at least one-year tobacco smoking (adults group). Conclusions: In presented ECAP project the prevalence of nasal polyps was 1.1% of all investigated subjects. The population studied in ECAP is obviously age-limited, and do not include the subjects for whom the development of nasal polyps is the most typical according to previous epidemiological studies. Although it gives us some direction for further investigation and present the particular epidemiological tools, which could be useful in such studies.
46 CAPSAICIN-INDUCED VASODILATATION IN HUMAN NASAL MUCOSA INVOLVES MODULATION OF COX-2 ACTIVITY AND IS ABROGATED BY EP3 RECEPTOR AGONISM SERIN Symposium 4 - Non allergic rhinitis and polyps Van Crombruggen K 1, Van Nassauw L 2, Timmermans J 2, Holtappels G 1, Hall D 3, Bachert C 1 Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University, Ghent, Belgium 2 Laboratory of Cell Biology & Histology, University of Antwerp, Antwerp, Belgium 3 Respiratory CEDD, GlaxoSmithKline, Stevenage, United Kingdom
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Background: Extensively based on evidence gained from experimental animal models, the TRPV1-activator capsaicin is regarded as a valuable tool in the research on neurogenic inflammation. Although capsaicin-related drugs gained renewed interest as a therapeutic tool, there is also controversy as whether neurogenic inflammation actually takes place in human upper airways diseases. In this study we verified the involvement of capsaicin in nasal vascular responses that are regarded to be implicated in the cascade of neurogenic inflammatory mechanisms. Method: By means of ex-vivo functional tissue bath experiments on human nasal mucosal vascular beds, the effect and mechanism of action of capsaicin was assessed in the absence and presence of various agents that interfere with potentially related transduction pathways. Results: 10 M capsaicin induced vasodilatations that were reduced by the selective EP1 prostanoid receptor antagonist SC19220 (10 M) and almost abolished by the selective COX-2 inhibitor NS398 (1 M) and the EP3 receptor agonist sulprostone (0.1 nM 10 nM), but not affected by the TRPV1-antagonists capsazepine (5 M), the neurokinin NK1 receptor antagonist GR20517A (1 M), and the Calcitonin Gene Related Peptide (CGRP) receptor antagonist CGRP8-37 (100 nM). Spontaneously released PGE2 and PGD2 levels were significantly reduced in the presence of capsaicin. Conclusion: Capsaicin, at concentrations clinically applied or under investigation for diverse disease backgrounds, induces a vasodilatory response in human nasal mucosa via a mechanism involving TRPV1-independent reduction of PGE2 production by modulation of COX-2 enzymatic activity. These capsaicin-vasodilatations can be suppressed by the EP3 receptor agonist sulprostone at subnanomolar concentrations and by selective COX-2 inhibition.
47 LOCAL IGE IS SIGNIFICANTLY CORRELATED WITH SEVERITY OF INFLAMMATION IN CRS WITHOUT NASAL POLYPS SERIN Symposium 5 - Eicosanoids - more than end products
Session:
Rasic I, Pegan A, Vagic D, Bukovec Z, Kalogjera L University Hospital "Sestre milosrdnice", Zagreb, Croatia
Background: It has been demonstrated that local specific and total IgE in nasal polyps (NP) is related to local eosinophilic infiltration. These findings are a hallmark of eosinophilic inflammation in the polyps of patients with asthma and aspirin intolerance. Less data are available in the literature concerning these findings in patients with chronic rhinosinusitis (CRS) without nasal polyps. The aim of the study was to demonstrate the relationship between local IgE, local eosinophilia, and infiltration of inflammatory cells in patients with CRS without nasal polyps, comparing subgroups of patients with and without asthma, measuring IgE and ECP in maxillary sinus lavage, and IgE+ cells, eosinophils, lymphocyte and plasma cells infiltration in maxillary sinus mucosa. Besides comparing data for these 2 subgroups, the relationship between pathohistology and concentrations of IgE and eosinophil activation marker were compared. Patients and methods: The sinus lavages with 5 ccm of saline and mucosal biopsies were taken bilaterally from maxillary sinuses through inferior antrostomy in 17 asthmatic and 36 non-asthmatic adult patients with CRS without NP. The concentrations of IgE and eosinophil cationic protein (ECP) were determined by fluoroenzymeimmunoassay (UniCAP, Pharmacia & Upjohn, Sweden). Biopsy specimens were formalin fixed, routinely processed, paraplast embedded, cut at 3 micrometers, and hemalaun-eosine stained. Additional sections were prepared for immunohistochemical IgE staining (polyclonal rabbit anti-human IgE, DAKO, Denmark). IgE+ cells, eosinophils, lymphocytes and plasma cells counted in 8 randomly selected high power fields (400x) by blinded pathologist. Results: Both IgE and ECP concentrations were significantly higher in the asthmatic subgroup (ECP conentrations 64,61 vs. 19,48 mcg/L respectively; IgE 44,25 vs 7,34 mcg/L respectively). Strong significant correlation was demonstrated between IgE in nasal lavage and number of IgE+ cells, as well as severity of inflammatory cells infiltration, in both subgroups, probability being of similar order of magnitude for asthmatics and nonasthmatics. Although correlations between ECP and these parameters were also significant, correlation coefficents were below 0,5. Conclusions: Local IgE, measured by concentrations in sinus lavage or number of IgE+ cells, is stronger marker of inflammation than ECP, in terms of inflammatory cells infiltration in sinus mucosa of patients with CRS without NP.
48 ASPIRIN DESENSITISATION IN ASTHMA: A DOUBLE-BLIND STUDY
Session:
SERIN Symposium 5 - Eicosanoids - more than end products
Authors:
Swierczynska-Krepa M 1, Nizankowska-Mogilnicka E 1, Swierczynski Z 2, Blicharz R 2, Rybarczyk H 1, Szczeklik A 1 Dept of Medicine, Jagiellonian University Medical College, Krakow, Poland 2 Dept. of Otolaryngology, Private Plastic Surgery Clinic, Bielsko-Biala, Poland
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Background: Beneficial effects of chronic aspirin (ASA) desensitisation in patients with aspirin-induced asthma (AIA) have been shown in many open trials. We aimed to compare these effects on clinical and some biochemical parameters in a double-blind, placebo controlled study in patients with AIA and chronic rhinosinusitis with nasal polyps and in a comparable group of asthmatics tolerating aspirin well (ATA). Method: 34 patients underwent aspirin challenge to confirm or exclude ASA hypersensitivity. Subsequently, 20 AIA patients were randomized to chronic desensitisation with 624 mg of ASA for 6 months (AIA-ASA, n=12) or administration of placebo (AIA-PL, n=6). Similarly, 14 patients with ATA were randomized to ASA desensitisation (ATA-ASA, n=6) or placebo (ATA-PL, n=8). Clinical symptoms of rhinosinusitis (evaluated on visual analogue scale), Sino-Nasal Outcome Test (SNOT20), Asthma Control Questionnaire (ACQ), doses of oral, inhaled and nasal corticosteroids, spirometry parameters, peak expiratory flow rate (PEFR), peak nasal inspiratory flow (PNIF) and blood eosinophilia were recorded on monthly basis for 6 months. Levels of urinary leukotriene E4 (LTE4) were evaluated at baseline (V0) and after 1 (V1), 3 (V3), 5 (V5) and 6 (V6) months of aspirin desensitisation or placebo intake. Results: In AIA-ASA group 6 months of aspirin desensitisation significantly improved sense of smell (p=0.045) and diminished SNOT20 and ACQ scores (p=0.04 and 0.008, respectively) in comparison to baseline parameters. There was also an increase in PNIF (p=0.045). Median doses of inhaled steroids and number of respiratory tract infections tended to be lower (p=0.06 and p=0.065, respectively). Those parameters did not change significantly in any other group studied. Median LTE4 in AIA-ASA group after 6 months of ASA desensitisation increased as compared to AIA-PL group (p=0.06). Conclusion: In this double-blind, placebo controlled study aspirin desensitisation appeared to have a beneficial effect on the course of rhinosinusitis and bronchial asthma in patients with aspirin hypersensitivity. Chronic aspirin intake may sustain and even increase the overproduction of LTE4 in subjects sensitive to aspirin, which possibly does not interfere with clinical improvement.
49 INHIBITORY FACTOR-KAPPAB KINASE(IKK-2) INHIBITOR TPCA REPRESSES CHEMOKINES CXCL1 AND CXCL8 IN NASAL POLYP EPITHELIAL CELLS SERIN Symposium 5 - Eicosanoids - more than end products
Session:
Sachse F 1, Becker K 2, Basel T 1, Weiss D 1, Rudack C 1 Department of Otorhinolaryngology Head and Neck Surgery, University of Muenster, Muenster, Germany 2 Institute of Medical Microbiology, University Hospital Muenster, Muenster, Germany
1
Background: Nasal polyposis (NP) is considered a subgroup within chronic rhinosinusitis. NP can be further subdivided into an aspirin sensitive- and an aspirin tolerant (ASNP/ ATNP) group. Apart from aspirin desensitization glucocorticosteroids are still the drugs of first choice if medical treatment is intended. One of the main effects of glucocorticosteroids is repression of pro-inflammatory mediators by inhibition at the level of nuclear transcription. Alternative targets for anti-inflammatory intervention are cellular kinases such as inhibitory factor-kappaB kinase (IKK-2) that has a key function in the activation of nuclear transcription factor kappaB. Therefore, IKK-2 activity was indirectly quantified by immunohistochemistry and anti-inflammatory potential of IKK-2 inhibitor TPCA-1 was evaluated in nasal polyp epithelial cell culture. Methods: Paraffin sections of ASNP (n=12), ATNP (n=17) and inferior turbinates (n=16) were immunostained using an antibody directed against serines 32 and 36 of the PhosphoInhibitory-kappaB-alpha protein (P-IkappaB-alpha(Ser32/36)). P-IkappaB-alpha(32/36) is a direct product of IKK-2 activity and is only detected following IKK-2 mediated phosphorylation at serines 32 and 36. Intensity of epithelial staining was analyzed semiquantitatively by two independent observers. In cultured NPECs epithelial derived chemokines CXCL1 and CXCL8 were induced by TNF-alpha or staphylococcal supernatants of strain Newman and subsequently repressed by prednisolone or by different concentrations of IKK-2 inhibitor TPCA-1. Quantification of chemokines was performed by ELISA in supernatants after 24 hours. Results: Significant P-IkappaB-alpha(32/36) staining was observed in the nasal epithelium of ASNP compared to ATNP and inferior turbinates suggesting increased IKK-2 activation in patients with ASNP. In cell culture experiments, chemokines CXCL1 and CXCL8 were significantly repressed by prednisolone and TPCA-1. Conclusion: IKK-2 activity was increased in the subgroup of ASNP. Chemokine responses were repressed by IKK-2 inhibitor TPCA-1 in vitro. IKK-2 inhibitors might represent a potential target for anti-inflammatory intervention in ASNP.
50 IMMUNOGLOBULIN FREE LIGHT CHAINS ARE INCREASED IN NASAL POLYPOSIS: POSSIBLE RELEVANCE TO THE PATHOGENESIS? SERIN Symposium 5 - Eicosanoids - more than end products
Session:
Redgeld F 1, Groot Kormelink T 1, Gevaert P 2, Bachert C 2 Div. of Pharmacology, Utrecht Institute f. Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands 2 Upper Airway Research Laboratory, University Hospital Ghent, Ghent, Belgium
1
Nasal polyposis is an inflammatory condition of unknown etiology. Chronic inflammation of the nasal and sinus mucous membranes may be responsible for inducing a reactive hyperplasia of the intranasal mucosal membrane, which results in the formation of polyps. The precise mechanism of polyp formation is incompletely understood. Chronic rhinosinusitis (CRS) with polyps is often accompanied with an accumulation of eosinophils, but increased numbers of T cells and plasma cells (CD138) are also found in nasal polyps. Interestingly, in mature polyps degranulated mast cells and eosinophils are often diffusely distributed in the polyp tissue. Greater mast cell degranulation in CRS inferior turbinate with NP is found compared to healthy inferior turbinate, although the mechanism of mast cell activation is not elucidated (1). In recent studies, we found that immunoglobulin free light chains (FLC) are greatly increased in non-atopic rhinitis with eosinophilic syndrome (NARES) (2). Moreover, crosslinking of FLC can induce mast cell activation (3). In this study, we investigated if this mechanism may be relevant in the pathogenesis of nasal polyps. Serum, merocel isolates and nasal polyp homogenates from CRS patients with polyps were analyzed for kappa and lambda FLC using a sandwich ELISA. Tissue distribution of FLC, plasma cells and mast cells were further analyzed with immunohistochemistry. Both kappa and lambda FLC are significantly increased in merocel isolates and nasal tissue homogenates from patients with CRS with polyps compared to healthy controls. Increased expression of FLC was detected in polyp tissue using immunohistochemistry and this correlated with tissue homogenates FLC levels. Immunofluorescent staining further indicated that the number of FLC positive cells partly correlated with the number of CD138 plasma cells. Interestingly, colocalization of FLC with mast cells was evident. Our study demonstrates that FLCs are increased in nasal polyps and are possibly produced by local plasma cells. The association of FLC with mast cells suggests that FLC could be (in part) responsible for local mast cell activation in nasal polyposis.
1. WJ Fokkens, VJ Lund, J Mullol et al., European Position Paper on Nasal Polyps 2007. Rhinology 45; suppl. 20: 1139. 2. DG Powe, T Groot Kormelink, M Sisson, BR Blokhuis, MF Kramer , NS Jones & FA Redegeld, Evidence for the involvement of free light chain (FLC) immunoglobulins in allergic (IgE) and nonallergic rhinitis, J. Allergy Clin Immunol 125, 139-145, 2010. 3. Redegeld, FA, Van der Heijden, M, Kool, M, Heijdra, BM, Garssen, J, Kraneveld, AD, Van Loveren, H, Roholl, P, Saito, T, Claassen, J, Verbeek, SJ, Koster, AS, and Nijkamp, FP, Ig light chain mediate immediate hypersensitivitylike responses, Nature Medicine 8(7), 694-701, 2002
51 ATOPIC ASTHMA AND RELATED RISK FACTORS Oral Presentations 3 Tomic Spiric V 1, Jankovic S 2, Maksimovic N 2, Delic R 1, Bogic M 1 Clinical Center of Serbia, Clinic for Allergology and Immunology, Belgrade, Serbia 2 Institute for Epidemiology, University School of Medicine, Belgrade, Serbia
1
Background: Numerous factors that increase asthma risk have been identified. The aim of the study was to investigate the factors associated with atopic asthma in adult Serbian population. Method: A case-control study of 134 atopic asthmatics and 134 non-asthmatics was carried out, during the period from March 2002 to June 2003. The cases and controls were matched by sex, age (+ 5 years) and place of residence (urban, rural). A detailed questionnaire based on the latest research results in the field was to obtain information on the known risk factors. Stressful life events were recorded using Paykels Interview for Recent Life Ivents. Results: According to multivariate conditional logistic regression, the following factors were independently significantly associated with the occurrence of atopic asthma: allergic rhinitis (OR = 30.74, 95% CI = 7.62 - 123.98, p < 0.001), sinusitis (OR = 5.06, 95% CI = 1.27 20.17 ), p = 0.022), and lower respiratory tract infections in childhood (OR = 5.72, 95% CI = 1.65 19.87, p = 0.006). Conclusion: Our study indicates potentially important roles of allergic rhinitis, sinusitis and infections of the lower airways in childhood as factors increasing the risk of atopic asthma. Recognizing of the risk factors is important for the diagnosis and prevention of the disase.
52 CONTRIBUTION OF THE TIMOTHY GRASS POLLEN MAJOR ALLERGEN PHL P 1 TO THE GRASS POLLEN EXTRACT INDUCED RESPONSE OF RESPIRATORY EPHITELIUM Oral Presentations 3 Roeschmann K 1, Luiten S 1, Jonker M 2, Breit T 2, Fokkens W 1, Petersen A 3, van Drunen C 1 Department of Otorhinolaryngology, Academic Medical Center, Amsterdam, Netherlands 2 Microarray Department, University of Amsterdam, Amsterdam, Netherlands 3 Division of Molecular and Clinical Allergology, Research Center Borstel, Borstel, Germany
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Type I hypersensitivity reactions are the most common allergic diseases, with current prevalences of up to 30% in industrialized countries. Allergens are otherwise innocuous environmental triggers with the ability to elicit powerful T helper lymphocyte Type 2 responses, culminating in IgE antibody production. Besides the interaction of allergens with well known players such as T-cells and dendritic cells there is a growing awareness of the interaction of airway epithelial cells (AEC) with allergens. Beyond the role of AEC as physical barrier towards invading pathogens it has becoming clear that they also affect the outcome of the immune response by the production of various mediators in response to allergen encounter. We have previously shown that Timothy grass pollen (GP) extract regulates a broad variety of genes and mediators in AEC. In this study we focus on the contribution of the response induced by the purified single allergen Phl p 1 to the response induced by whole GP extract. To this extend we determined the mRNA profiles using a microarray analysis and mediator release by a multiplex enzyme-linked immunosorbent assay. Stimulation of AEC with Phl p 1 resulted in a huge response on gene expression level with 7.200 regulated transcripts in total. The larger GP extract induced response with 11.800 regulated transcripts is likely to result from the GP extract consisting of multiple components. Interestingly, we saw an overlap of only about 3.100 transcripts being regulated by both stimuli, referring to 1.600 regulated genes. K-means clustering of these transcripts revealed 800 transcripts to be regulated in a comparable manner, while around 2.300 transcripts were identified to either be up-regulated by Phl p 1 and down-regulated by GP extract or vice versa, indicating Phl p1 does not just reflect a partial GP extract induced response. Taking this into account, this study might be useful for emphasizing the importance of the consideration of multiple interactions between allergenic components and AEC with regards to the allergic response in general.
53 META-ANALYSIS SUPPORTS THE EFFICACY OF GRASS ALLERGY IMMUNOTHERAPY TABLETS IS COMPARABLE TO SUBCUTANEOUS IMMUNOTHERAPY Oral Presentations 3 Calderon M 1, Strodl Andersen J 2, Lawton S 2 Allergy and Clinical Immunology-NHLI, Imperial College, London, United Kingdom 2 ALK-Abello, Hoersholm, Denmark
1
Background: Both subcutaneous (SCIT) and sublingual immunotherapy (SLIT) have been shown to be effective in the treatment of allergic rhinitis. However, limited data is available comparing the efficacy of the two administration routes. Recent meta-analyses suggest the magnitude of effect is greater with SCIT, but significant heterogeneity calls for careful interpretation of these data. To reduce clinical and methodological heterogeneity we performed meta-analysis on grass immunotherapy trials alone and further separated sublingual treatments into SLIT drops and allergy immunotherapy tablets (AIT). Methods: We conducted a search of MEDLINE, Embase and the Cochrane Library, the search was limited to English language literature published up until August 2010. We only considered randomised double-blind placebo-controlled (RDBPC) trials of commercially available SCIT, SLIT drops and AIT modalities for treatment of grass induced allergic rhinitis/rhinoconjunctivitis. Articles were cross-checked against those identified in recent meta-analyses and reviews. Data regarding rhinitis/rhinoconjunctivitis symptom scores were extracted from the publications and meta-analysis was performed separately for the three respective treatment modalities. Results: Twenty-four RDBPC trials fulfilled selection criteria (6 SCIT, 12 SLIT drops, 6 AIT) and included a total of 3629 subjects (1920 active, 1709 placebo). Main reasons for excluding trials: lack of double-blinding/randomisation, review articles, duplicate trials, utilised multiple unrelated allergens, experimental preparations, and insufficient rhinitis/rhinoconjunctivitis symptom data. Using a fixed-effect model, all three treatment modalities significantly reduced rhinitis/rhinoconjunctivitis symptoms compared with placebo. Nominally the level of efficacy was greater for grass AIT (SMD 0.41, 95% CI 0.51 to -0.31; p < 0.001) and grass SCIT (SMD 0.46, 95% CI 0.62 to 0.31; p < 0.001) than for grass SLIT drops (SMD 0.14, 95% CI 0.25 to 0.02; p = 0.02). Test for heterogeneity was non-significant for AIT and SCIT (p = 0.23 and p = 0.99 respectively) but significant for the SLIT drop analysis (p = 0.002). Results were similar with a randomeffects model. Conclusion: When comparing the level of efficacy from available RDBPC trials, pertaining to the treatment of grass pollen induced rhinitis/rhinoconjunctivitis, AIT and SCIT demonstrate a comparable level of symptom reduction, while findings from trials utilising SLIT drop preparations show great heterogeneity and a lower overall magnitude of effect.
54 CLINICAL OUTCOME AFTER FESS SURGERY IN CHRONIC RHINOSINUSITIS (CRS) BASED ON A MINIMAL 3-YEAR PROSPECTIVE STUDY Poster Discussion Session 3 Vlaminck S Az St-Johns Hospital, Bruges, Belgium
Background: Evidence-based literature (level IV) suggests a benefit from sinus surgery for patients with chronic rhinosinusitis (CRS) with (CRSwNP) and without nasal polyposis (CRSsNP). Overall 10 % revision surgery within 3 years is accepted. The aim of the study was to prospectively gather clinical and pathological findings and evaluate factors which might help in predicting clinical outcome after functional endoscopic sinus surgery (FESS). Material and Methods: We prospectively analysed during a minimum of 3 years (20032005) 231 consecutive CRS patients unresponsive to medical treatment. All were operated by the same surgeon, performing complete ethmoidectomy with maxillary antrostomy and sphenoidotomy on both sides except for 3 cases. Allergy, asthma and aspirin hypersensitivity were noted. Pathologic findings on resected tissue and collected secretions were checked for eosinophils, Charcot-Leyden crystals (Ch-Lc) and fungal hyphae. Results: There were 104 patients with nasal polyposis (CRSwNP) and 127 patients without (CRSsNP). In patients with CRSwNP 78 % showed eosinophilic involvement whereas in CRSsNP only 38%. In the CRSwNP group with eosinophilic substrate 68% showed layers of necrotic eosinophils and Ch-Lc versus 41 % in the CRSsNP group. In the eosinophilic CRSwNP group 14 % showed hyphae on silver staining versus 1,5 % in the CRSsNP group. There seemed to be no influence regarding allergy or asthma in both groups in predicting the clinical outcome. Patients in the CRSwNP group with signs of eosinophilic necrosis and Ch-Lc in their secretions showed objective clinical endoscopic recurrence in 38 % of the cases versus 15 % recurrence of complaints in the CRSsNP group. Moreover if eosinophilic necrosis, Ch-Lc and fungal hyphae were present, success rates dropped dramatically to 30% in the CRSwNP group. Conclusions: Our data on 231 consecutive operated CRS patients with and without polyposis show that the presence of eosinophils, eosinophilic necrosis and hyphae give valuable information regarding the clinical outcome after FESS surgery. The secretions collected for pathology add to this information. Allergy and asthma do not seem to be reliable predictors for clinical outcome. The overall success rate of 90% in sinus surgery - as mentioned in the EPOS guidelines- should thoroughly be questioned especially in the group of CRSwNP patients.
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55 PATTERNS OF NASAL CONGESTION Poster Discussion Session 3 Rennie C 1, Taylor D 2, Doorly D 2, Schroter R 3, Gedroyc W 4, Tolley N1 Department of Otorhinolaryngology, St Mary's Hospital, London, United Kingdom 2 Department of Aeronautics, Imperial College London, London, United Kingdom 3 Department of Bioengineering, Imperial College London, London, United Kingdom, 4 Department of Radiology, St Mary's Hospital, London, United Kingdom
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Background: This study is aimed at investigating the effect of decongestion on nasal airway dimensions in normal subjects using high resolution 3T MRI scans. Localised changes in the nasal mucosa are detailed and their subsequent impact on nasal morphology is studied. Methods: Healthy volunteers were screened to ensure they had no nasal complaints and no obvious rhinoscopic abnormalities. Acoustic rhinometry and nasal peak inspiratory flow measurements were performed on all subjects by a single trained operator in accordance with published protocols. Each subject underwent 2 MRI scans one pre and one post decongestion. Subjects' heads were immobilised in a head coil for their scans. Scans were performed on a 3 Tesla, MRI scanner (Discovery MR750, GE Medical Systems). A series of 120 contiguous 1.2mm thick coronal sections was obtained. Slice spacing was 1.2 mm and each image was 512 x 512 pixels with a pixel size of 0.3516 x 0.3516 mm. All subjects remained immobilised following the scan and were decongested in a standardised way with Xylometazoline. A second MRI scan was taken after 25 minutes allowing time for the decongestant to take effect followed by repeat acoustic rhinometry and NIPF measures. The MRI scans were segmented using Amira (Visage Imaging) and reconstructed in a computer aided design package for analysis.
Results: Decongestion had the greatest effect on the turbinate region of nasal cavity. The maximum change in cross sectional area was seen in the mid turbinate region. The area least effected by decongestion was the region of the nasal vestibule. To highlight mucosal changes the volume of the airways was calculated from 2cm to 5cm along the acoustic rhinometry path length. Good correlation was found between acoustic rhinometry and MRI measurement for minimal cross sectional area anteriorly. Conclusions: The effects of decongestion on nasal airway morphology have been investigated in vivo, in far greater detail than previously studied, and at higher spatial resolution. MRI was found to be an excellent modality to study mucosal changes within the nose as it images the air mucosa interface directly. Regional changes have been quantified throughout the nasal cavity not just anteriorly as seen with acoustic rhinometry. Decongestion has a large effect on nasal area volumes but only a limited effect on the surface area. Surface area to volume ratios are hence significantly decreased with decongestion.
56 siRNA MEDIATED INHIBITION OF RSV REPLICATION Poster Discussion Session 3 Khaitov M, Faizuloev E, Nikonova A, Trofimov D, Alexeev L NRC Institute of Immunology FMBA, Moscow, Russia
Background: Respiratory syncytial virus (RSV) is an important respiratory pathogen. RSV infects almost 100% of children in the first 3 years of life and causes most cases of viral bronchiolitis. Severe infantile RSV infections are associated with recurrent wheezing and asthma development in later life. RSV is also one of the major causes of virus-induced asthma exacerbations in children and adults. Our previous investigations demonstrated high antiviral activity of siRNA against RSV in cell culture. The aim of this study was to investigate siRNA mediated inhibition of RSV in vivo on murine model of RSV infection. Methods: RSV strain Long was concentrated by PEG precipitation. Viral stocks were used at 2106 TCID50/mL. For in vivo experiments 3 different siRNAs targeted to RSV phosphoprotein (P) mRNA were chosen according to their in vitro performance. BALB/C mice were divided into 6 groups. Each group included 6 animals. RSV infection and siRNA treatment were performed via endotracheal catheter. Groups 1-3 were infected by RSV and treated by different siRNAs. Group 4 was infected by RSV and treated by rhinovirus 16 specific siRNAs as a control of siRNA specificity. Groups 5 and 6 were used as a control of infection and as a negative control. Inhibition of RSV replication was assessed on day 6 p. i. by viral titer estimation and viral RNA quantity measured by RT-PCR in culture supernatants. Results: In groups 1 siRNA caused up to 14-fold decrease of viral RNA quantity in comparing with non-specific siRNA (P<0,001). In groups 2 siRNA caused up to 7-fold decrease of viral RNA quantity in comparing with non-specific siRNA (P<0,001). Conclusion: Obtained results correspond with data from in vitro studies. siRNA anti-P caused statistically significant suppression of RSV infection in vivo. RSV-P mRNA is a successful target for siRNA mediated RSV replication inhibition, promising an advance in treatment of RSV infection for preventing and control of asthma exacerbations.
57 CORRELATION OF THE MAIN MARKER OF ATOPY IMMUNOGLOBULIN E WITH SOME ANTI-INFLAMMATORY BLOOD CYTOKINES AT CHILDREN WITH BRONCHIAL ASTHMA Poster Discussion Session 3 Hajiyeva N, Veliyeva S Azerbaijan State Advanced Training Institute for Doctors, Pediatrics Department, Baku, Azerbaijan
Background: To study the correlation of immunoglobulin E (IgE) content with the levels of interleukin-4 (IL-4) and interleukin-1 (IL-1) at children with bronchial asthma (BA). Method: There were 86 children with BA at the age between 3 and 15 under this study. 15 practically healthy children were in the group of comparison. Childrens clinical status displayed classical symptoms of the disease such as strokes of expiratory dyspnea, dry paroxysmal cough and wheezing. Serum content of the interleukins and IgE was defined by the spectrum-colorimetric method with the usage of test-systems for enzyme-linked immunosorbent assay (ELISA). The Wilkokson-Mann-Whitney nonparametric U-criteria was used for statistical analysis of the study in MS EXCEL program. Differences under p<0.05 were considered true. Results: The content of IgE at children with BA constituted 155.67 IU/ml, which is truly higher (p<0.001) than in the comparison group 38.58 IU/ml. Concentration of IL-4 constituted 124.85 pq/ml which is also truly higher than the results which were obtained in the comparison group 32.87 pq/ml (p<0.001); the level of IL-1 226.09 pq/ml was also truly higher (p<0.001) than the control results 46.27 pq/ml. While analyzing correlation between serum content of the indicated cytokines and IgE level, true correlative relation (p<0.01-0.001) was found between IgE level and the content of afore-mentioned interleukins which is also directly proportional to the severity of BA clinical course. Conclusion: This study revealed a number of typical immunological disorders which explain pathogenesis of BA from the point of view of allergic inflammation. Increase of the levels of anti-inflammatory cytokines IL-4 and IL-1 in the blood serum of the sick children indicates the intensity of inflammatory effects in the diseased body. Level of the intensity of immunological disorders has direct relation with the level of control over disease. Disclosure of the direct correlation between levels of IgE and interleukins once more confirms IL-4 indirect hyper-production of IgE. This connection is in direct proportion to the severity of BA clinical course, which indicates that in case of no control under asthma, which is the same as severe clinical course of this disease, immunological disorders are more evident.
58 COMPONET-RESOLVED DIAGNOSIS IN PATIENTS ALLERGIC TO COMMON POLLENS: IN VITRO USE OF NATURAL AND RECOMBINANT ALLERGENS AND CROSS REACTIVITY WITH SOME NATURAL FOODS Poster Discussion Session 3 Postiglione L 1, Spadaro G 2, Di Spigna G 1, Triggianese P 2, Galdiero M 2, Rivellese F 2, Covelli B 1, Rossi G 1 Department of Cellular and Molecular Biology and Pathology L.Califano, University of Naples Federico II, Naples, Italy, 2 Department of Internal Medicine, Cardiovascular and Immunological Sciences, University of Naples Federico II, Naples, Italy
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Background: The diagnosis of Type I allergy is based on the measurement of allergenspecific IgE antibodies and on provocation tests with allergens. Current forms of allergy diagnosis are performed with allergen extracts. The standard in vitro assay for measuring allergen-specific IgE does not permit the identification and measurement of specific IgE to individual allergenic components in the extract. The development of recombinant allergens offers new possibilities to study IgE reactivity profiles. Several studies have demonstrated the advantages of recombinant allergen based diagnosis. Component-Resolved Diagnosis with recombinant allergens reveals the antibody reactivity profile of allergic patients and identifies the disease-eliciting allergen molecules. Methods: The aim of our study was to demonstrate in sera of patients allergic to some common pollens the presence of IgE specific to recombinant molecular components thus enabling the development of new IgE reactivity profiles. In fact using recombinant allergens in in vitro diagnostic devices, a patients individual IgE reactivity profile can be quantitatively established. We focused on allergenic recombinant components of pollen extracts such as Bet v1-v2-v4, Phl p1-p5b-p7-p12, Par j2, Art v1. Blood samples of 50 patients with clinical history of pollen hypersensitivity and/or allergy were collected. We used a panel of purified natural and recombinant allergens to establish the molecular sensitization profiles and natural extracts for some foods. IgE concentrations were determined by ImmunoCAP 250 System (PHADIAItaly). Results: The data indicated a good correlation between clinical history and skin prick test versus specific IgE concentrations in vitro evaluated by a large panel of allergen natural extracts. The use of specific panel of recombinant allergens showed in all patients the presence at different concentrations of specific IgE for some recombinant molecular components; IgE sensitization was also observed against cross-reactive natural extracts for some foods. Conclusion: The identification of sensitization profiles may play a paramount role in the choice of specific allergen-based immunotherapy and in monitoring the success of the treatment. Moreover, the presence of IgE to cross-reactive allergen components can be determined and used to predict clinically relevant sensitization to allergen sources which contain immunologically related allergens.
59 ANALGESIC INTOLERANCE (SAMTERS DISEASE): CHARACTERIZATION OF INCOMPLETE PICTURES Poster Discussion Session 3 Foerster U 1, Strathmann S 1, von Jaschke N 1, Morawietz L 2, Olze H1 ENT Department Charite Campus Virchow Klinikum Berlin, Berlin, Germany 2 Institute of Pathology Charite Berlin, Berlin, Germany
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Background: The complete picture of the Samters triad is characterized by nasal polyps (NP), asthma and a sensitivity of non steroidal inflammatory drugs (NSAIDs). An altered arachidonic acid metabolism of prostaglandins (PG) and leukotrienes (LT) is the underlying pathomechanism. The aim of the study is the examination of PG and LT, endoscopy score, CT score, number of sinus surgeries, degree of eosinophils and the symptoms smell and headache as predictive markers of the development of disease. Methods: A total of 37 patients were included in a prospective study (median age 43 y, follow up 6 y): Chronic rhinosinusitis sine NP n=5 (sNP); Recurrent NP (NP-R) n=11; NP and asthma (NP-A) n=9 and NP, asthma and NSAID sensitivity (NP-AA) n=12. Following parameters were examined: Davos score, Lund CT score, measurement of PGE and LT (functional eicosanoid test FET), sinus surgeries (number of operations, degree of eosinophils), VAS score (smell, headache). Results: The results of FET tests correlated according the clinical symptoms of the groups sNP/NP-R/NP-A/NP-AA (0.9/ 1.2/1.5/1.7). Also Davos score (0/1.2 /1.4 /1.7), Lund score (9/12.4 /14.4 /17.4), number of surgeries (0/2.8 /1.9 /3.1) and degree of eosinophilia (0/1.6/1.8/1.9) correlated with clinical symptoms. Conclusion: FET test, Lund and Davos score, number of surgeries, degree of eosinophils are predictive factors of the development of disease. The diagnosis should be performed before the complete picture of Samters triad is obvious in order to initiate an early therapy.
60 DOES SINUSITIS "CAUSE" ASTHMA OR ASTHMA "CAUSE" SINUSITIS? Poster Discussion Session 3 Ribeiro H, Filipe J, Matos T, Angelo P, Costa T, Nabuco C , Branco C , Dinis B Centro Hospitalar Lisboa Norte-Hospital Pulido Valente, Otorinolaringologia II, Lisbon, Portugal
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Introduction: For many years, anecdotal data and uncontrolled studies have etiopathogenically linked bronchial asthma with rhinosinusitis, implying that nasal symptoms clinically exacerbate concomitant lung disease and that surgery upon the sinuses benefits asthma outcome. These reports remained unchallenged for long time, until recently. Purpose: The purpose of this study is to address how sinusitis and asthma clinically interrelate, where at the moment in their disease process asthmatic subjects are proposed functional endoscopic sinus surgery due to medically recalcitrant nasal symptoms. Method: In a controlled, prospective and retrospective setting, asthmatic and nonasthmatic patients were extensively evaluated before and one year after surgery. Surgical results were analyzed, lung function re-assessed, and patients clinical status addressed. Results: Asthma is clearly a critical factor in sinus disease, negatively affecting sinonasal disease at all times and the objective outcome of sinus surgery. On the other hand, sinus disease extension does not seem to correlate with asthma severity. Sinus surgery, despite being capable of clinically improving asthma in a sub-set of patients with no clear preoperative profile, ultimately fails to produce a significant change in lung function scores. Asthma improvement per se could only correlate to subjective, but not objective, improvement of nasal symptoms after surgery. Conclusion: These results lead us to conclude that the asthma-sinusitis association, more than a causative relationship, more likely reflects a systemic inflammatory process of the whole respiratory mucosa in which the lower airway involvement is a step further towards severity in unified airway inflammation.
61 NASAL RESPONSE TO LYSINE-ASPIRIN CHALLENGE IN HYPERSENSITIVITY REACTIONS TO NSAIDS WITH RESPIRATORY VERSUS CUTANEOUS INVOLVEMENT Poster Discussion Session 3 Campo P 1, Cornejo J 2, Dona I 1, Rondon C 1, Haggeman L 2, Torres M 1, Melendez L 2, Rodriguez-Bada J 2, Canto G 3, Blanca M 1 Hospital Carlos Haya, Allergy Service, Malaga, Spain 2 Fundacion IMABIS, Allergy Research Center, Malaga, Spain 3 Hospital Infanta Leonor, Allergy Service, Madrid, Spain
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Background: Non-steroidal anti-inflammatory drugs (NSAIDs) may cause respiratory (rhinitis and/or asthma), cutaneous (urticaria/angioedema) or anaphylactic reactions. This study is designed to evaluate possible differences in responses to nasal lysine-aspirin challenge test in subjects with hypersensitivity reactions to NSAIDs with respiratory versus cutaneous involvement Methods: We recruited subjects with confirmed history of hypersensitivity to NSAIDs (2 episodes with at least 2 different NSAIDs or positive drug provocation). Clinical evaluation and skin prick testing to aeroallergens were performed. Lysine-aspirin challenge test was done with 100 l of solution per nostril (29 mg lysine) and response was evaluated by means of VAS, symptom score and acoustic rhinometry Results: Thirty-three subjects were evaluated: 10 cutaneous/anaphylaxis, 15 respiratory and 8 controls. Subjects with hypersensitivity with cutaneous involvement (8F/2M, 4 urticaria, 3 angioedema, 3 anaphylaxis) were 57% atopic and had previous history of respiratory disease (rhinitis/asthma) in 43% of cases. Nasal challenge showed 1/10 positive nasal responses (10%). Subjects with hypersensitivity with respiratory involvement (11F/4M, 3 rhinitis, 8 asthma, 4 rhinitis and asthma) were 73% atopic and all but one had previous respiratory disease (93%). Nasal challenge showed positive responses in 12/15 (80%). All four controls (4 atopic rhinitis, 4 non atopic) had negative nasal challenges. Conclusion: Subjects with confirmed history of hypersensitivity to NSAIDs with cutaneous involvement showed a lower rate of positive nasal responses to lysine compared to those with respiratory involvement. Further studies with higher number of subjects are needed to confirm these results and define common and differential features between both entities.
62 RHINITIS AND ASTHMA INCIDENCE IN CHILDREN IN SERBIA Poster Discussion Session 3 Krivokapic T, Radic S, Gvozdenovic B, Calovic O Center for Children's Pulmonology and TB, Belgrade, Serbia
Bronchial asthma and allergic rhinitis often co-exist, and many epidemiologic, pathophysiologic, and clinical studies have strengthened the concept that bronchial asthma and allergic rhinitis are manifestations of a linked inflammatory process within a continuous airway. However, the reported incidence of allergic rhinitis (AR) in asthmatic children varies widely. The aim of this study was to investigate the incidence of allergic rhinitis in children with asthma in Serbia, and the difference in clinical course and lung function test in children with asthma with or without AR. Methods: A cohort of 231 children (ages 5-18, mean age 10.6 years, 49% of boys, at least one SPT positive in 86%) with asthma, treated in or out patiently in our hospital, was evaluated. Objective diagnosis of AR was made by ORL specialist on the basis of questionnaire, rhinoscopy, nasal cytology, positive at least one skin prick test and total IgE. Diagnosis of sinusitis was confirmed by X-ray. The incidence of allergic rhinitis was 67.5% (mean age 11.2 years, 47% of boys), and the incidence of rhino sinusitis was 23.4%. In children with co-morbid asthma and AR total IgE (556: 532 IU/ml, t=4.50, P=0.03), and average number of asthma exacerbations requiring IM/IV/oral short course of corticosteroid therapy in the last 12 months was higher (6.4:4.8; t=2.02, P=0.045). However, asthma started earlier (3.2:3.6 years), diagnose of asthma was established earlier (5.6:5.8 years), and number of hospitalizations was higher (2.8:2.3), but without statistic significance. In children with co-morbid asthma and AR atopic dermatitis (x2=6.4, P=0.009) and other allergies (drugs, cold, exercise, venom) were more prevalent (x2=8.8, P=0.012). Children with co-morbid AR had lower values of VC, FEV1, PEF and MEF75 but with no statistic difference, however, MEF25 was statistically lower (106.10:96.48%, t=2.07, P=0.040), and MEF50 was more than 5% lower (105.87:99.75%). Conclusion: AR is prevalent in 53.9% of Serbian children with asthma. The burden of co-morbid disease in asthmatic children is associated with increased level of total IgE, frequent manifestation of other allergies, more asthma exacerbations treated with short course of IV/IM/oral corticosteroid therapy and lower values of MEF25 and MEF50.
63 INFLUENCE OF SPECIFIC IMMUNOTHERAPY ON SOME PATHOPHYSIOLOGICAL ASPECTS OF BRONCHIAL ASTHMA Poster Discussion Session 3 Filonenko K, Pobedonna T, Budovska L, Gavrylov A Lugansk State Medical University, Lugansk, Ukraine
Background: Bronchial asthma (BA) is a complex disease with clinically well-defined pathogenic components, including recurrent reversible airway obstruction, chronic airway inflammation and development of airway hyperresponsiveness. In BA is observed proliferation of Th2 cells, that results into overproduction of IgE and increased synthesis of IL-4. One of the most effective forms of immunocorrection in BA is the method of specific immunotherapy (SIT), which targets Th2 cells activated by specific allergens. The main purpose of this method is to achieve a reduction of a specific patient's sensitivity to the causal allergen or a group of allergens and to improve clinical course of asthma. Aim of the work: To study the effect of SIT on the cytokines and cellular metabolism condition in asthma patients. Materials and Methods: A total of 74 patients were diagnosed as having intermittent (n=31) and mild persistent (43) BA (55 female, 19 male; mean age 21,1 1,5 yrs). 30 healthy persons aged (25,1 5,6) have been studied to determine the normative parameters. Diagnosis of asthma was based on the international guidelines. Allergy was defined on the basis of anamnestic indications of patients, positive skin prick test and determination of specific IgE. For the SIT allergens were used by subcutaneous injection method. Cellular metabolism condition was investigated by determining total oxidant activity (TOA) and antioxidant activity (TAA) in exhaled breath condensate (EBS), nitric oxide metabolites in blood serum and EBS of the patient. Investigated cytokine composition of blood serum and EBS were determined by immune-enzyme analysis. The laboratory data were evaluated after 2,5 - 4 months from the beginning of treatment, the clinical indicators were studied in 6 month and in 1 year. Results. Of the 74 patients, 38(51%) had domestic allergy, 24(33%) - pollen, 12 (16%) domestic and pollen allergy. Before the treatment TOA was almost 10 times higher than reference standard, TAA in EBC was 16% higher than similar in the control. The coefficient of TOA/TAA was more than reference ratio. After 1 week of the treatment TOA increased and exceeded in 19 times the same in healthy individuals. TAA in EBC tended to increase, and the coefficient of TOA/TAA has somewhat decreased. After 4 months of therapy in EBC TOA decreased in 2.5 times from the initial, but remained elevated. Before the treatment the elevated levels of IL-1b and IL-4 in blood serum and in EBC could be found. The production of IL-1b after the treatment decreased, but did not reach the normal values. The level of IL-4 in the end of the treatment decreased and was almost as high as among healthy people. The majority of patients during the treatment had a satisfactory level of health. Conclusions: On the one hand, our results confirm good efficiency of SIT, on the other hand - maintenance of oxidative stress in the tracheobronchial tree denoted the need for its prolongation. The lack of manifestations of endogenous metabolic intoxication syndrome and elimination of systemic manifestations of oxidative stress when high doses of SIT are achieved, confirm the safety and high efficacy of this method.
64 EOSINOPHIL AND MAST CELL ACTIVATION RELATED TO ENDOSINUSAL TREATMENT OR ENDOSCOPIC SINUS SURGERY IN CHRONIC RHINOSINUSITIS Poster Discussion Session 3 Pegan A, Rasic I, Vagic D, Bukovec Z, Kalogjera L University Hospital " Sestre Milosrdnice", Zagreb, Croatia
Background: It was suggested that different predisposing factors for chronic rhinosinusitis (CRS), like allergy and asthma, may have impact on inflammation pattern and treatment outcomes. As asthma is predisposing for eosinophilic inflammation in CRS with and without nasal polyps, it is expected that steroid treatment would significantly reduce inflammatory response and improve subjective outcomes. The study was performed to compare the effect of topical endosinusal glucocorticoid/antibiotic treatment on eosinophil and mast cell activation in asthmatic and non-asthmatic patients with chronic rhinosinusitis (CRS) without nasal polyposis. Patients and method: Eighteen mild to moderate asthmatics and 19 non-asthmatics with CRS were subjected to antral sinoscopy and endosinusal treatment with 2 mg of dexamethasone and 40 mg of gentamycine per maxillary sinus during 7 days. Sinus lavage and serum samples were taken prior to and after the treatment and eosinophil cationic protein ( ECP ) and tryptase ( try ) were analyzed by fluoroenzymeimmunoassay (UniCAP, Pharmacia & Upjohn, Sweden). Concentrations in antral lavages prior to and after the treatment were compared in both groups. Changes in the serum ECP and try in patients treated endosinusally were compared with the same parameters of operated with endoscopic sinus surgery, including those receiving perioperative systemic glucocorticoid treatment. Results: ECP concentrations in sinus lavages of asthmatics were significantly higher than in non-asthmatics, while there were no differences in sinus tryptase. ECP and tryptase were significantly reduced both in serum and sinus fluid of the asthmatics, but such changes were not observed in patients with CRS without asthma. Tryptase, but not ECP were significantly reduced in sinus lavage of non-asthmatics with CRS. When comparing serum ECP values in asthmatic patients submitted to endoscopic sinus surgery, with or without perioperative systemic steroid treatment, no significant changes were observed. Conclusion: Response to endosinusal treatment with glucocorticoid and antibiotic instillation during 7 days has significantly reduced eosinophil activation in sinus mucosa and serum of the asthmatic patients with CRS, but not in non-asthmatic patients. The activation of mastocytes was significantly affected in sinus mucosa of both groups. Short term effect of endoscopic sinus surgery on eosinophil and mast cell activation in the serum was not observed.
65 CLINICAL AND EPIDEMIOLOGICAL COMPARATIVE STUDY BETWEEN LOCAL AND SYSTEMIC ALLERGIC RHINITIS Poster Discussion Session 3 Rondon C 1, Dona I 2, Garcia R 1, Salas-Cassinello M 1, BlancaLopez N 3, Canto G 3, Blanca M 1 Allergy Service Carlos Haya Hospital, Malaga, Spain 2 Research Laboratory Carlos Haya Hospital-Fundacion IMABIS, Malaga, Spain 3 Allergy Service Infanta Leonor Hospital, Madrid, Spain
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Background: Local allergic rhinitis (LAR) has been detected in more than 45% of patient previously diagnosed by non-allergic rhinitis. The aim of this study was to compare the clinical and epidemiological characteristics of LAR and classical allergic rhinitis with systemic atopy (AR). Methods: We undertook a cross-sectional study in patients attending in allergy service by LAR and AR. Time of evolution, ARIA classification, identification and intensity of nasal symptoms, disturbance of sleep, and the presence of alterations of smell and co-morbidities were evaluated by clinical questionnaires and visual analogue scales (VAS). Results: A total of 20 patients with LAR and 20 with AR were consecutively selected. LAR patients had positive response to nasal allergen provocation test (NAPT) and/or nasal specific IgE. The majority of subjects presented moderate-persistent perennial rhinitis with a median of 6 years of evolution. The most frequent symptoms were: rhinorrhea and nasal itching (85%) in LAR, and nasal itching (90%) and sneezing (85%) in AR. Seventy percent of LAR patients and 75% of AR complained of sleep disturbances. About 40% with LAR and 30% of patients with AR referred intermittent hyposmia for exacerbations of rhinitis. Conjunctivitis (75% LAR and 85% AR) and asthma (40% LAR and 45% AR) were the most frequent co-morbidity. No significant differences were found between groups. Conclusions: Local and classical systemic allergic rhinitis shares the same clinical and epidemiological characteristics. Nasal allergen provocation test and nasal specific IgE determination must be take in count for the diagnosis of LAR in patients with symptoms suggestive of allergic rhinitis and with SPT and/or serum specific IgE negative.
66 EOTAXINS EXPRESSION IN NASAL MUCOSA OF COPD PATIENTS Poster Discussion Session 3 Arcimowicz M 1, Paplinska M 2, Hermanowicz-Salamon J 2, Mazurek J 2, Chazan R 2, Grubek-Jaworska H 2 Otolaryngology Department Medical University in Warsaw, Warsaw, Poland 2 Department of Internal Medicine, Pneumonology and Allergology, Warsaw, Poland
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Background: Eotaxins (eotaxin-1 CCL11, eotaxin-2 CCL24, eotaxin-3 CCL26) are known as the strongest chemotactic agents for eosinophils. They are small CC chemokiens and all act through their specific CCR3 receptor presented on eosinophiles, macrophages, lymphocytes T, basophiles, lung epithelium. In eotaxins expression key players are Th2 cytokines which can act synergistically with TNF . Eotaxin-1 is known as constitutive, present both in healthy and allergic or asthmatic patients. Eotaxin-3 and eotaxin-2 seems to be responsible for long lasting eosinophilia after Late Asthmatic Response. The role, which could play eotaxins in COPD mechanisms are not well recognized yet. The aim of study was to evaluate eotaxins (CCL11, CCL24, CCL26) genes expression in nasal mucosa in patients with COPD. Methods: The studied group consisted of 14 patients with COPD and as control group - 5 healthy volunteers. The nasal mucosa from nasal brushing were collected in RNA later solution. Total RNA was isolated using Machery & Nagel columns kit. 1 ng RNA was taken to quantitative reverse transcription (Super ScriptIII). Quantitative real time PCR was made using standard curve method on Prism 7500 (Applied Biosystem). TaqMan primersand probes were designed using Primer Express Software. Results were expressed as a number of eotaxins gene copies in 1l of cDNA samples after reverse transcription . Preparations for brushing cytology of nasal mucosa was stained according MG-Giemsa method and the percentage of inflammatory and epithelial cells were calculated. Results:
Patient CCL11 Eotaxin-1 107,13 462,24 113,16 461,73 374,03 258,64 355,86 403,15 25,43 322,8 412,66 230,03 185,5 137,76 275,01 38.40 CCL24 Eotaxin-2 4352,85 13035,07 2304,92 5644,98 2980,37 16785,54 4517,19 14703,2 1223,63 1305,15 7053,35 2313,51 4161,42 8678,55 6361,41 1524,7 CCL26 Eotaxin-3 131,49 324,65 281,3 146,55 452,54 447,56 265,56 792,2 131,12 159,72 415,8 49,97 267,96 216,8 291,66 132,8 Nasal cytology Neutrophils (%) 11 19 91 8 99 95 31 18 18 20 28 59 14 5 37 9
1 2 3 4 5 6 7 8 9 10 11 12 13 14 COPD /mean/ Control group /mean/
Conclusions: CCL24 is the main eotaxin expressed in nasal mucosa. All studied eotaxins (CCL11, CCL24, CCL26) were significantly higher in patients with COPD as compared to healthy volunteers. In all cases of COPD subjects the expression of CCL24 was distinctly increased. Marked neutrophilic inflammation is observed in patients with COPD. Nasal brushing seems to be a useful and non-invasive method to obtain specimen not only for nasal cytology, but also for evaluating changes in genes expression in nasal mucosa.
67 EFFECTS OF INHALED CORTICOSTEROIDS ON SERUM INFLAMMATORY MARKERS IN ASTHMATIC PATIENTS IN COMPARISON WITH CONTROL GROUP Poster Discussion Session 4 Tahghighi F, Halvani H, Hadi Nodoshan H Shahid Sadoghi Medical University, Yazd, Iran
Background: Asthma is one of the most common chronic diseases all over the world results from a state of persistent sub acute inflammation of the airways. Beside local inflammation, systemic inflammation is present too shown by increased levels of CRP. One of the most important cells in this inflammation process is eosinophil used in diagnosis and prognosis. The goal of this study was to compare CRP level between asthmatic and control groups to find association between local and systemic inflammation. Method: 61 patients with mild to moderate asthma enrolled according to clinical and spirometric findings, divided into 2 groups at the base of using inhaled steroid or not. Sputum was inducted by ultrasonic nebulizer and then Samples of peripheral venous blood were collected to measures peripheral cell count and CRP by Elisa. 37 healthy subjects were selected and sample of their blood was taken. Result: 30 asthmatic patients in user group (14 female/16 male) with the average of 39.49.37years, 31 asthmatic ones in non user group (13female/18 male) with the average of 35.58.87 years and 37 healthy control (17 female/20 male) were enrolled in our study. The mean of serum concentration of CRP was 2.6 g/ml, 3.32 g/ml and 1.16g/ml user, non user and control group; respectively. Serum concentrations of hs(High Sensitivity)-CRP were significantly increased in the non user group.(P-Value=0.0001) and also user group compared with healthy controls (P-value=0.016). The number of sputum eosinophils and peripheral blood eosinophils were significantly increased in the non users compared with healthy controls (P=0.0001),(p=0.003). In the non user group, serum hs-CRP levels correlated negatively with FEV1 and positively with numbers of sputum eosinophils which was not significant. Atopic status, age and sex did not affect hs-CRP levels in both asthmatic groups. Conclusion: It was found that, in steroid-naive patients, increased sputum eosinophil numbers and decreased pulmonary function were associated with higher serum hs-CRP levels, which suggests serum hs-CRP, could be a surrogate marker, indirectly reflecting the degree of airway inflammation. However, further studies are required in order to better understanding of clinical significance of the association of hs-CRP and asthma, especially its responsiveness to treatment.
68 NASAL NITRIC OXIDE MEASUREMENTS AND OTHER OBJECTIVE METHODS OF ASSESSING NASAL ALLERGEN CHALLENGE Poster Discussion Session 4 Tworek D, Kurmanowska Z, Kuna P Division of Internal Diseases, Asthma and Allergy, Barlicki University Hospital, Lodz, Poland
Background: Several objective methods are used in assessing the result of nasal allergen challenge. The aim of this study was to compare the diagnostic value of nasal nitric oxide (nNO) measurements with peak nasal inspiratory flow (PNIF), nasal lavages -tryptase levels and cell count changes after nasal provocation with grass pollen. Methods: 24 patients allergic to grass pollen and 24 healthy controls were included. All subjects underwent grass allergen challenge preceded by placebo administration. Visual Analogue Scale (VAS), nNO, PNIF were determined and nasal lavages were collected before and 30 minutes after placebo and allergen administration. The study was performed outside the pollen season. Results: Significant changes in nNO, PNIF, nasal lavages -tryptase levels and cell count were observed only in allergic subjects after administration of allergen. The ROC curves were drawn for all methods of assessing the result of allergen challenge. The best diagnostic value characterised PNIF measurements. The cut-off point of -12,5% change in PNIF after the challenge produced sensitivity 82,4%, specificity 100%, negative predictive value 84,6% and positive predictive value 100%. Change in nNO levels of -11,987% was indicated as the best cut-off point discriminating allergic patients from healthy subjects with senstitivity 60,9%, specificity 100% negative predictive value of 71% and positive predictive value of 100%. Comparison of area under ROC curves did not show significant difference between diagnostic value of changes in nNO levels and other objective methods of assessment of the outcome of allergen nasal provocation. Conclusion: The best diagnostic value was observed for measurements of PNIF and tryptase levels in nasal lavages. Changes in nNO levels does not differ significantly from other methods used in objective assessment of nasal challenge outcome. Due to insufficient sensitivity nNO measurements have limited value as a sole diagnostic tool of assessment of the outcome of allergen nasal challenge.
69 INFERIOR NASAL TURBINATE WOUND HEALING AFTER SUBMUCOSAL ULTRASOUND TISSUE REDUCTION AND MONOPOLAR ELECTROCAUTERY IN SHEEP
Session: Authors:
Poster Discussion Session 4 Gouveris H 1, Nousia C 1, Giatromanolaki A 2, Watelet J 3, Riga M 1, Katotomichelakis M 1, Ypsilantis P 4, Van Cauwenberge P 3, Danielides V 1 Dept. of Otorhinolaryngology, University of Thrace Medical School, Alexandroupolis, Greece 2 Dept. of Pathology, University of Thrace Medical School, Alexandroupolis, Greece 3 Dept. of Otorhinolaryngology, Ghent University Medical School, Ghent, Belgium 4 Laboratory of Experimental Surgery, University of Thrace Medical School, Alexandroupolis, Greece
1
Affiliations:
Background: we aimed at studying histopathologic profiles of nasal mucosal remodeling during wound healing of the inferior nasal turbinate (INT) after submucosal ultrasound tissue reduction (UTR) and submucosal monopolar electrocautery (MEC). Methods: randomized controlled experimental study in sheep. In hematoxylin/eosin stained sections, stromal fibrosis and edema, mucosal epithelial cell necrosis, submucosal inflammation and sinusoid engorgement were compared between UTR- and MEC- treated specimens 1, 3 and 8 weeks post-operatively (4 samples at each time point for each technique) and in 5 samples of controls. A four-point semi-quantitative histopathologic grading scale (0=absence, 1=mild, 2=medium, 3=pronounced) was used to asses changes. Comparisons were made using Mann-Whitney U-test and Kruskal-Wallis one-way ANOVA. Results: at week 8 in the UTR-group significantly less submucosal inflammation (p=0.036) and significantly less sinusoid engorgement (p=0.022), more extensive fibrosis (p=0.061), more reduction of stromal edema (p=0.127) and less epithelial cell necrosis (p=0.321) were observed than in the MEC-group. Conclusions: UTR induces less traumatic tissue damages than MEC for INT volume reduction. In MEC-group, nasal mucosal remodeling during wound healing was dominated by more severe inflammation and epithelial cell necrosis than in UTR-group. However, UTR induced a greater reduction in sinusoid engorgement than MEC did.
70 ALLERGIC RHINITIS AND NON-ALLERGIC RHINITIS IN PREGNANCY Poster Discussion Session 4 Alizadeh Korkinejad N 1, Heidarnazhad H 2, Zafarghandi S 3, Rabei 3, Moin M 1 Immunology, Asthma and Allergy Research Institute,Tehran University of Medical Science, Tehran, Iran 2 National Research Institute of Tuberculosis and Lung Disease, Shaheed Beheshti University, Tehran, Iran 3 Zeinab Hospital, Shahed University of Medical Sciences, Tehran, Iran
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Background: Allergic Rhinitis is a frequent allergic disease in pregnancy and also a risk factor for developing asthma in future.It is important to differentiate non-allergic rhinitis in pregnancy from allergic rhinitis and a suitable management for them in pregnancy must be considered.In this study we aimed to evaluate the prevalence of allergic rhinitis and nonallergic rhinitis in pregnant women and also their effects on respiratory function. Methods: In a cross-sectional descriptive study we evaluated 123 pregnant women referred to the prenatal care clinic of Zeinab Hospital through 6 months.The diagnosis of different allergic diseases was done according to medical history and using the ARIA guideline.Non-allergic rhinitis was assessed considering the signs and symptoms of rhinitis such as coryza ,sneezing,nasal stiffness and absence of positive history of allergic diseases in them prior to pregnancy and in their families.Pulmonary Function Test was done for all of the pregnant women with respiratory and allergic rhinitis symptoms. Results: 123 pregnant women with a mean age of 27 years were enrolled in the study.38.2% of the pregnant women suffered from different allergic diseases that 18.7% of them had allergic rhinitis and 61.8% had no atopic disease.There was no case of nonallergic rhinitis.The sinusitis coexisted in 2(8.7%) patients with allergic rhinitis.We performed pulmonary function test for 20 out of 23 patients with allergic rhinitis.3 of them had FEV1less than 80% and other results were normal.All of the FEV1/FVC% were normal.The frequency of small airway disease( defined by FEF7525 less than 60% )was found in 4 (17.39%) of patients with allergic rhinitis.The frequency of respiratory symptoms(dyspnea,cough or wheezing)in pregnant women with allergic rhinitis was 13(56%). Conclusion: All of the pregnant cases complained of rhinitis had allergic rhinitis and allergic rhinitis was the most prevalent allergic diseases in pregnant women(18.7%).High prevalence of allergic rihinitis in pregnant women and specially its coexistence with repiratory symptoms in 56% of them necessitates more attention to this disease in pregnancy.According to the united airway disease hypothesis , allergic rhinitis is an important risk factor for airway hyperresponsiveness in future ,therefore better preventive,diagnostic and therapeutic programs must be designed for pregnant women with allergic rhinitis.
71 RHINOLIGHT TOOLS IN THE TREATMENT OF ALLERGIC RHINITIS Poster Discussion Session 4 Krzych-Falta E, Wojas O, Samolinski B, Szczesnowicz-Dabrowska P Departament of the Prevention of Environmental Hazards, Warsaw, Poland
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Background: The main aim of this study was to evaluate the effectiveness of allergic rhinitis treatment using UV rays (UVA and UVB light below 3%) emitted by a device called Rhinolight. Due to its properties, the phototherapy a beam of variable rays - did not pose any risk of nasal mucous membrane damage, pain or local burns. The sample was a group of 8 patients (5 women and 3 men) diagnosed with seasonal or perennial allergic rhinitis. Method employed in the study was Rhinolight. The spectrum of the light emitted by the device on nasal mucous membrane is visible light (85%), UVA (less than 10%) and UVB (less than 3%). Patients with seasonal allergy received the therapy for 2 weeks and those with perennial allergic rhinitis for 6 weeks (their nasal mucous membranes were irradiated for 2 minutes+ to 3 minutes in the final phase of the therapy, at average intervals of 3-4 days). Additionally, the patients received vitamin A (suspension) to grease their nasal mucous membranes in the event of their excessive dryness. Approval was obtained from the Bioethics Committee, Medical University of Warsaw (Approval No. KB/71/2006). Before and after the phototherapy, the patients underwent the following diagnostic tests: skin prick tests, nasal cytology, acoustic rhinometry and rhinomanometry, followed by an objective assessment of the nasal symptoms reported by each patient (on a 0-3 point scale). Results: The acoustic rhinometry, rhinomanometry and nasal cytology tests revealed no statistically significant changes in all the patients under study. In the objective assessment of nasal symptoms (amount of nasal secretion, number of sneezes, nasal obstruction, nasal itching) rated on a 3 point scale (0 none, 1 weak, 2 medium, 3 strong), a statistically significant correlation (p<0.05) was observed before and after the phototherapy, especially reduced nasal symptoms: a reduction in the number of sneezes, reduced nasal obstruction and a reduction in the amount of nasal secretion, with no statistically significant correlation for nasal itching (p<0.058). Conclusions: In addition to the treatment methods of pharmacotherapy immunotherapy, phototherapy can only help to treat allergic rhinitis. and
72 OMALIZUMAB ADMINISTRATION IN PATIENT WITH NEURO BEHCET SYNDROME Poster Discussion Session 4 Caruso C, Alonzi C, Gaeta F, Valluzzi R, Maggioletti M, Rumi G, Marinella V, Romano A Allergy Unit-Complesso Integrato Columbus, Rome, Italy
Session: Authors:
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Background: Behet disease (BD) is a systemic vasculitic disorder of unknown aetiology characterised by oral and genital ulcers, which may be associated with systemic involvement. The central nervous system involvement in Behet disease is either caused by primary neural parenchymal lesions (neuro-Behet syndrome [NBD]) or is secondary to major vascular involvement. Method: We present the case of a 27-year-old woman with neuro-BD treated with infliximab with a good clinical response to this treatment. The specific cytokine marker activation for NBD persisted elevated [CD3+/CD38+ (27,2%)] despite the treatment. She also had a 7 year history of asthma, difficult to treat despite the use of high-dose inhaled steroid (fluticason 1gr/d), long-acting 2 agonists (salmeterol 200mcg/d) and several courses of oral steroid (prednisone 5mg/d) during 5 years pulse therapy. Result: When she was referred to our Allergy Unit, clinical and laboratory ndings included: normal white blood cell count, mild eosinophilia (absolute eosinophil count, 500/mcgL) and elevated serum IgE (100 IU/mL); spirometry displayed a decrease in FEV1 (75% of predicted) and PEF (3,9 l/min). An ACT (Asthma Control Test) questionnaire was performed (score: 9 points). Skin testing were carried out with a panel of commercial extracts of aeroallergens and were positive for parietaria judaica, confirmed by specific IgE. At that point, on the basis of her initial IgE level (100 IU/mL) and weight, a dose of 375 mg subcutaneously every 4 weeks for 4 months was initiated. Following anti-IgE administration, the patient showed signicant improvement of her asthma. We emphasize that the patient had not received systemic steroids during the 4 months omalizumab treatment, implicating anti-IgE therapy as putative agent for lung inflammation control. At this time of writing the laboratory findings are: normal white blood cell count and eosinophil (130), IgE of 300 IU/mL, and normal T activated cells [CD3+/CD38+ (8,39%)]; spirometry (FEV1 101%, PEF 6,6), and ACT questionnaire score 22 points. Conclusions: Anti-IgE therapy offers the potential to decrease asthma activity, but whether it can also impact the activity of other manifestations of NBD is an open question. In this patient, anti-IgE therapy improved asthma control, decreased eosinophil blood count, and specific marker of inflammation and disease activity. Infliximab and omalizumab cotreatment was associated with a good clinical response without side effects.
73 RHINOPLETHYSMOGRAPHY AND NASAL RESISTANCE MEASUREMENT Poster Discussion Session 4 Khamaktchian M 1, Michel O 2, Bisschop P 1 CHU Brugmann - ENT Departement - University of Brussels (ULB), Brussels, Belgium 2 CHU Brugmann - Immuno-Allergology Departement - University of Brussels (ULB), Brussels, Belgium
1
Background: Nasal resistance (NR) measurement is usually done by anterior rhinomanometry (AR). The weakness of this technique is to not take into consideration a possible concomitant bronchial resistance change after nasal challenge tests. By body pletysmography (BP) technique, it is possible to measure simultaneously nasal and bronchial resistances. We adapted the BP to measure total resistances through a nasal mask. NR was calculated as the differential between total and bronchial resistance. The aim was to assess NR measurement by BP. Methods: Prospective randomized trial in 10 healthy adult volunteers. Approval from the ethic committee and written informed consent from all subjects were obtained. NR were consecutively measured by AR and by BP, in a randomized order at 0, 15 & 30 minutes. Xylometazolin (XMZ) 1mg/ml nasal spray was delivered at the last measurement. Measurements were repeated 14 days after. Nasal reactivity to histamine at increasing doses titrated at 2,4 and 8 mg/mL every 10 minutes was measured, using the two techniques in a randomized order. Results: Population included 5 women and 5 men with an age range of 2355 years. Mean NR measured by BP at time 0; 15; 30 (XMZ) were 2,011,23; 3,21,60; 1,710,96 , respectively, and at day 14 (1) & (2XMZ) 2,451,01; 2,281,58 (XMZ) cmH20/l/s, respectively. Mean NR measured by AR at time 0; 15; 30 (XMZ) were 3,71,79 ; 3,111,39 ; 2,20,99 and at day 14 (1) & (2XMZ) 4,22,7 3,691,8 (XMZ) cm H20/l/s, respectively. The Bland and Altmann reproductibility coefficients were 106,1 % for BP and 64 % for AR. Both techniques showed a statistical increase of NR related to histamine during histamine challenges, but BP significantly increased after a lower dose of histamine compared to AR (BP p=0,0001 and AR p=NS). On the contrary to AR, the dose-responsecurve-study with BP showed a significant raise of the NR related to the histamine concentration. Interestingly, a patient developed an inaugural crisis of asthma during nasal histamine challenge, which was observed by the concomitant measurement of the bronchial resistance together with NR. Conclusion: NR measurement by the BP was a feasible and intra-subject reproducible technique. This technique was more sensitive to detect a change in the NR induced by histamine. The BP technique had the interest to measure simultaneously the changes in bronchial resistances.
74 EMR (ELECTRONIC MEDICAL RECORD) DATES PROVIDE AN INSUFFICIENT TOOL FOR IDENTIFYING ASTHMA Poster Discussion Session 4 Prints S 1, Heimer D 2
1
Clalit Health Services, Beer-Sheba, Israel Soroka Medical Center, Beer-Sheba, Israel
Pulmonary Unit of
Background: The electronic databases used internationally for monitoring different study populations have greatly evolved over the last decade. Israels Program of Quality Indicators for Community Health Care uses the electronic records for tracking anti-asthma medication purchases in order to identify persistent asthma patients. Methods: We have investigated adult asthma patients (18-56 age range) according to the criteria established by the National Program in the Negev District of Leumit Health Fund (Israel). A study group was gathered randomly from this population. We checked their previous pulmonary function tests (PFT) using electronic & paper sources. For patients without or with inconclusive PFT, we performed additional breathing tests until conclusive results could be attained. An experienced pulmonologist reviewed all of PFT & clinical records before we proceeded to draw our final conclusions. Results: The study group was 90 people (55.9% of the all study population). Majority of them (96.1%) had an EMR diagnosis of obstructive pulmonary disease, but only 28 (26.1%) were undergoing previous PFT conclusive with asthma. After additional tests were administrated 50 (56.7%) of the studied patients were identified as asthma patients. Conclusion: Relying on electronic diagnoses and EMR for anti-asthma medicine consumption can lead to the overestimation of the prevalence of asthma. The validation of EMR dates is necessary before them can be used for epidemiological studies.
75 CORRELATION BETWEEN RESULTS OF ACOUSTIC RHINOMETRY AND ANTHROPOMETRIC PARAMETERS IN HEALTHY SUBJECTS Poster Discussion Session 4 Szczesnowicz - Dabrowska P, Samolinski B, Wojas O, Krzych E Department of Prevention of Environmental Hazards, Medical University of Warsaw, Warsaw, Poland
Background: The aim of this study was to evaluate if intranasal dimensions as measured with acoustic rhinometry (AR) correlate with age, height and weight in school children and to establish AR normal values for Caucasian school children. Method: There were examined the group of 638 healthy volunteers (329 female 52% and 188 male subjects 48%) from 6 to 76 years old (mean age: 15,3 y.o.) in this study. 522 children aged 6 to 17 years (252 girls, 270 boys) and 116 adults aged 17 to 76 underwent: AR, weight and height measurements. The following AR parameters were evaluated: CSA-1, reflecting the nasal valve area, CSA F (the maximum CSA anterior to CSA-1), CSA-3cm (mean cross-sectional area at the distance of 3 cm posterior to CSA-1) and distance 0-1 distance between 0 notch (reflecting anterior nostrils) and 1 notch of AR curve (nasal valve). Results: The differences in: distance 0-1 and CSA-F appear in the age over 14 (p<0,00002 0,000001), and the differences in: CSA-1 i CSA-3cm are observed in the group over 17 years old (p<0,01 0,0001). All parameters are significantly depending on the age (p<0,000001). Total increasing of AR parameters according to the average values between age of 7 to 17 y.o. is as follows: CSA-1 (area of nasal valve) in women case till 0,15 cm2 , in men case till 0,24 cm2 , CSA-F (area of nasal vestibule) in women case 0,42 cm2 , in men case 0,68 cm2 , CSA-1m3 (mean cross-sectional areas calculated for the three centimetres distance of AR curve from nasal valve) is in case of measurement before decongestions 0,40 0,50 cm2 , and in case of rhinometric examine after decongestions 0,60 - 0,66 cm2 , distance between CSA-0 (anterior nostrils) and CSA-1 (nasal valve) in women case 0,35 cm, in men case 0,4 cm. Conclusion: After the age of 16 nasal cavities of males were still growing, while in females all measured parameters were nearly stabilized after this age. The AR parameters strongly correlated with age and height.
76 ALLERGIC PHARYNGITIS-A PHENOTYPE OF CHRONIC AIRWAY DISEASE?
Poster Discussion Session 4 Zheng M Shandong Provincial Hospital affiliated to Shandong University, Jinan, China
Background: The allergic rhinitis and bronchial asthma are well known as some kind of phenotypes of chronic airway disease. However, allergic pharyngitis had not been paid great attention, even neglected. In our pharyngolaryngeal clinic, there are patients who has no symptoms and signs in their nose or/and tracheal but mainly in throat. These patients have not been officially identified as a named diagnosis so that they failed to be treated as general pharyngitis with usual medicine or antibiotics. How to diagnose these patients needs to be discussed so that they can be identified and treated effectively. Methods: 39 patients with sting in throat, sometimes have dry cough without sputum or very little sputum in throat. There are 30 female and 9 male. Age is from 21-49 years old. 31 patients without allergic history, have no positive signs in nose and no bronchitis. 8 patients had ever suffered from allergic rhinitis in history over 1 year ago, but not any symptoms at present. Throat mucosa looks as normal or lighter red. Chest x-rays presents no positive signs. However, allergic skin-test resulted in stark positive after they stopped taking any medicine for one week. Patients were diagnosed as allergic pharyngitis and then treated only with antihistamine. Results: All patients are effective with no or very less symptoms after treated against allergy. Conclusion: Allergic pharyngitis should be one of phenotypes of chronic airway diseases.
77 DETERMINATION OF ATOPY FREQUENCY RATE AT A TENDER AGE FOLLOWING TB LATENT INFECTION EMERGED THROUGH CONFIRMED FAMILY CONTACTS Poster Discussion Session 4 Omiadze K V. Gogokhia Allergy and Clinical Immunology Branch, Tbilisi State Medical University, Tbilisi, Georgia
Background: The effects of various infectious agents on allergic diseases have long been a subject of extensive research. Aiming to find connections between the Hygiene Theory (HT) and a real life, investigators are mainly focused on developed country models. Developing countries are poorly studied, post-Soviet republics being a typical example. The HT has become an urgent issue in the post-Soviet countries, due to the high prevalence of tuberculosis (TB) and a dramatic rise in allergic diseases during the last two decades. Georgia is one of the clear examples of such an epidemiologic situation. Methods: The present case-control study involved weekly telephone calls to reveal and monitor allergic reactions. Extensive allergic examinations were conducted, if necessary. The Mantoux test was applied to detect M. tuberculosis infection (PPD-RT23-Apisol, ParkeDavis, Morris Plains, NJ, USA). The LTD Biopharm ELIZA test system was used for specific IgE identification. The research data were statistically analyzed with the Epi-info software (Version 3.3.2., Atlanta, USA). Results: The frequency of atopic diseases in children of different age groups, infected with TB though family contacts, was distributed in the following way: 1998-2006 years: children under 1 year total of 53 cases for 2-7 years of follow-up; diagnosed atopic cases 2. Children of 1-4 years total of 123 cases for 2-7 years of follow-up; diagnosed atopic cases 4. The confirmed frequency detected in the control group (uninfected children) was 10.1 %. The frequency of diagnosed atopic diseases among patients infected through close TB contacts was much lower (3.4 %) than in the uninfected children of the same age (10.1 %). Conclusions: This prospective study showed a statistically significant epidemiological inverse association between the family contact-related latent tuberculosis and the development of atopic diseases in children (0-4 years). Moreover, atopic diseases manifested later in TB-infected population compared to the uninfected community. The above-mentioned indicates that the TB infection in early childhood supresses atopic disease development and delays its clinical onset.
78 THE LEVELS OF IGA, IGM, IGG, IGE AND IL-4, IL-6 AND TNFALPHA IN CHILDREN WITH ASTHMA Poster Discussion Session 4 Matsiushchanka V Vitebsk State Medical University, Vitebsk, Belarus
Chronic inflammation in children with asthma is often caused by immune Th1/Th2 imbalance, accompanied by abnormalities in the system of cytokines. Therefore, the study of immune status in these children makes it possible to determine the activity of disease as well as effectiveness of treatment. The aim of the work was to determine the state of functional activity of B-cell immunity in children with asthma as well as the study of IL-4, IL-6 and TNF- levels. We examined 50 children aged 4 to 14 years diagnosed with allergic asthma. Concentration of Ig, IL, TNF- were studied by ELISA method. Statistical analysis of data was performed with STATISTICA 7.0 software package. As a result of ELISA studies of blood serum of children with asthma, the largest fluctuations occur in the concentration of total IgA and IgG. In relation to the values corresponding accepted norms of age we revealed reduced levels of IgG (n=31; average level 4,27 0,51 g/l) and reduced levels of IgA (n=22; 0,55 0,10 g/l). Within the age norm of IgA (n=27; 1,50 0,17 g/l), IgM (n=35; 1,13 0,13 g/l), IgG (n=16; 9,89 1,08 g/l). The average concentration of serum IgE (n=40) was 313,59 87,42 IU/ml, only 6 children had total IgE level below 100 IU/ml. As for the cytokines levels in serum IL-4 was revealed in the average concentration of 3,39 2,66 pg/ml in all examined children with asthma (n=41), IL-6 was in the usual rate 0-50 pg/ml (n=35; 10,40 3,70 pg/ml) and higher than 50 pg/ml (n=6; 209,66 192,24 pg/ml). The increase of TNF- more than 50 pg/ml was in 11 children (100,16 38,48 pg/ml), its acceptable normal concentration in blood serum had 30 examined children (9,58 4,95 pg/ml). Thus in 44% of examined children with asthma there is a probable lack of local immunity due to some low serum concentrations of total IgA, and 62% of children can be regarded to have a transient immunodeficiency state considering low levels of total IgG, but significant defects in humoral immunity were not found. Concentration of total serum IgE noted above the level of 100 IU/ml in 88% of children with asthma can affect on the severity of atopic diseases, and in conjunction with the hyperproduction of IL-4 indicate the prevailing role of Th2 in children with asthma. Low levels of IL-4 in serum may be due to the period and clinical course of the disease, considering the fact that the majority of children surveyed (n=43) were in the state of complete or partial remission, as well as 80% of them had a diagnosis of mild asthma.
79 ASTHMA CONTROLLER MEDICATIONS ARE NOT OF COMMON USE IN EAST DELTA OF EGYPT, WHY? Poster Discussion Session 4 Taha O, El Behidy R, Mohamed Y, Badawy S Department of Pediatrics, Zagazig University, Zagazig, Egypt
Background: Asthma is the most common chronic disease of childhood, affecting 5-10% of children and resulting in approximately 400,000 hospitalizations annually. Asthma defined as a chronic inflammatory disorder of the airways that involves many different cells, including mast cells, eosinophils, and T lymphocytes. Materials: We aimed to clarify the extent of use of controller drugs by asthmatic children, and if they are not widely used what are the main causes and factors for this although they offer excellent chance for proper asthma control? Observational cross-sectional study done over six month period in Pediatric department, Zagazig University on asthmatic children aged two years and older of both sex regardless socio-economic status attending outpatient clinic, emergency room or inpatient ward. All was submitted to: (1) History: Asthma regarding onset,course,duration of its symptoms, frequency of exacerbations, any associated medical problems, types of medications used and for how long. (2) Chest examination. Results: There was more prevalence in males (56.5%), positive family history of atopy (78.3%), urban areas (60.2%) and low socio-economic levels (52%). False believes about asthma among caregivers (53.3%). About 84.8% not using controller medications properly, 63.5% never used them and 21.3% has used it regularly. Only 13.9% well controlled,while 23.9% partially controlled and 62.2% totally uncontrolled. More than half of studied group (52.2%) was managed by GP. There was significant relationship between age, family history of atopy, high socio-economic level and proper use & adherence to asthma controller medications. Patient education was in 41.7% and only 19.1% had experienced self-induced education. There was highly significant relationship between managing physician as being chest specialist caring for follow up of our outpatient asthma clinic and proper use of asthma controller medications. On the other hand, a highly significant relationship coexist between managing physician as being GP and repeated visits to emergency room and improper use of controller drugs. A highly significant relationship between adherence to asthma controller medications and better control of asthma. The major risk factors affecting proper use of asthma controllers were false believes about asthma, asthma control level, family history of atopy and managing physician specialty. Conclusion: The under-use of asthma controller medications was related to false beliefs, lack of asthma care program, socio-economic level and financial issues. The more the use of controller medications, the better the asthma control.
80 PREVALENCE OF ANXIETY DISORDERS AMONG ALLERGIC ASTHMA AND RHINITIS PATIENTS IN QAZVIN Poster Discussion Session 4 Kianiamin M 1, Fallahzadeh M 2, Esfahani A 1 Qazvin University of Medical Sciences, Pediatric Immunology and Allergy Department, Qazvin, Iran 2 Qazvin University of Medical Sciences, Psychiatry Department, Qazvin, Iran
1
Background: Asthma and Allergic Rhinitis are heterogenous disorders with different ongoing problems. The most important psychologic presentations which has demonstrated are anxiety and depression. Consequens of these psychosomatic problems recently has been shown, causes economic as well as social and medical disadvantages. Objective: This study was performed to assess the abundance of comorbid depression and anxiety in Allergic respiratory adult patients. Methods: In this study 98 patients with respiratory allergy enrolled in three separte groups as Allergic rhinitis asthma and co-existense af asthma and allergic rhinitis(AR).From a total of 98 , 61out of 98(61.3%)had allergic rhinitis,26 out of 98(26.1%) were asthmatic and 11patients(11.2%)identified as both asthma and allergic rhinitis.Prevalence and severity of anxiety disorders in these subgroups identifed by Hamilton questionaire. Results: Our results showed a general prevalence of 27.5% among these allergic patients. Prevalence of allergy revealed 26.2% in AR, 30% in asthma and 27.3% in simultanous AR and asthma. It seems that asthmatic patients are more prone to psychosomatic disorders but severity was detected prominently in patients with AR. Conclusion: Anxiety occurs significantly among allergic disorders and however it is not considered as an important factor, can cause problem in medical treatment or sometimes poor control.
81 DOWNREGULATION OF POLYMERIC IMMUNOGLOBULIN RECEPTOR (pIgR) EXPRESSION IN PATIENTS WITH CHRONIC RHINOSINUSITIS SERIN Symposium 6 - Chronic infection in rhinosinusitis/nasal polyps Hupin C 2, Rombaux P 2, Lecocq M 1, Pilette C 3 Universite Catholique de Louvain (UCL)IREC, Brussels Belgium Cliniques Universitaires Saint-Luc, ENT Department, Brussels, Belgium3 Cliniques Universiatires Saint-Luc, Pneumology Department, Brussels, Belgium
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Background : IgA represents a frontline defense factor in the airways, which is transported across the surface epithelium after binding to the polymeric immunoglobulin receptor (pIgR). We observed that pIgR immunostaining is reduced in patients with severe COPD (Pilette, 2001) and correlated to reduced lung function and neutrophilic infiltration. Whether mechanisms of IgA secretion are affected in chronic rhinosinusitis (CRS) remains poorly known. Method: Surgical sinonasal tissue was obtained from patients with CRS with (CRS-NP, n = 7) or without nasal polyposis (CRS group, n = 11), as compared to patients with allergic rhinitis (AR, n = 8) and control healthy subjects (controls, n = 10). Real-time RT-PCR (SybrGreen) was used for mRNA quantification of pIgR expression, corrected to that of beta-actin used as housekeeping gene. Immunohistochemistry was also carried out for pIgR protein, as well as for immune cell infiltration (CD3/T cells, CD20/ B cells, CD68/macrophages, CD117/mast cells). Results: A significant reduction of pIgR mRNA was observed in the ethmoidal biopsies from CRS (CRS, CRS-NP) patients, when compared to control subjects (mean +/-SD : controls, 5.51 +/-7.54; CRS, 1.29 +/- 1.29; CRS-NP, 1.41 +/- 2.16; p value < 0.05). This pIgR downregulation was not observed in the turbinal mucosa from these CRS patients, and was not correlated to inflammatory cell counts. Immunolocalisation of pIgR was observed in submucosal glands as well as in the surface epithelium, where it was restricted to seroglandular cells (no staining in goblet cells and in basal cells). Conclusion: These data show for the first time that epithelial expression of pIgR is decreased in chronic rhinosinusitis, with or without polyposis. It is also suggested that this pIgR downregulation relates to remodelling of the sinusal epithelium rather than local inflammation.
82 PREVALENCE OF RHINOVIRUS RNA IN NASAL LAVAGE FROM PATIENTS WITH CHRONIC RHINOSINUSITIS SERIN Symposium 6 - Chronic infection in rhinosinusitis/nasal polyps Valera F 1, Paula F 2, Modena J 2, Tamashiro E 1, Souza J 2, Lopes L 2 , Arruda E 2, Anselmo-Lima W 1 Division of Otolaryngology - School of Medicine of Ribeirao Preto (FMRP-USP), Ribeirao Preto, Brazil 2 Division of Virolgy - School of Medicine of Ribeirao Preto (FMRP-USP), Ribeirao Preto, Brazil
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Background: until the present day, the physiopathology of chronic rhinosinusitis (CRSsNP) and nasal polyps (CRSwNP) remains unclear. Some pathogens have been implicated, such as fungi and bacteria, especially S aureus. The real impact of virus infection in this perpetuation of inflammatory process, though, is still to be stablished. The purpose of this study was to evaluate the prevalence of rhinovirus RNA in nasal lavage from patients with CRSwNP and CRSsNP, without acute exacerbations. Methods: nasal and sinusal (maxillary) lavages were collected from a total of 36 patients with CRSwNP and CRSsNP, during ESS procedure, from july 2008 to august 2010. The RNA of human rhinovirus was evaluated through RT-qPCR, using TaqMan primers specific to human rhinovirus sp. Results: Rhinovirus RNAs were found in 19 (51.35%) of the samples. There was correlation between nasal and sinusal lavages of 61%. There was no correlation between rhinovirus prevalence and seasonality. Rhinovirus was present in 6 out of 13 samples of CRSsNP (46%) and 12 out of 23 samples of CRSwNP (52%). Lund Mackay score ranged from 2 to 8 (mean 4.4) among CRSsNP patients and from 8 to 24 (mean 14) among CRSwNP patients. Mean Lund-Mackay score was very similar between CRSwNP patients with or without rhinovirus (16.9 vs. 17.3, respectively). There was a non-significant increase in LundMackay score in patients with CRSsNP and rhinovirus presence (5.4) versus those without rhinovirus (3.5). Conclusions: There is a very high prevalence of rhinovirus RNA in nasal lavages from patients with CRSsNP and CRSwNP.
83 HUMAN RHINOVIRUSES STIMULATE THE PRODUCTION OF LEUKOTRIENES UPON INFECTION OF BRONCHIAL EPITHELIAL CELLS SERIN Symposium 6 - Chronic infection in rhinosinusitis/nasal polyps Trochoutsou A 1, Spyridaki I 1, Skevaki C 1, Tsakris A 2, Papadopoulos N 1 Allergy Research Laboratories, Second Department of Pediatrics, NKUA, Athens, Greece 2 Microbiology Department, School of Medicine, NKUA, Athens, Greece
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Background: Bronchial epithelial cells, among other structural cells, are considered to contribute little to leukotriene (LT) production. These cells were originally thought to lack the 5-lipoxygenase enzyme (5-LO) and thus synthesize LTs only by metabolizing LTA4 produced by leukocytes, the major autonomous LT producers. Nevertheless, studies now indicate that airway epithelium does express 5-LO at low concentrations and may synthesize LTs from arachidonate upon stimulation. Our aim was to examine whether human rhinoviruses (RV), the most common precipitants of asthma exacerbations, may induce LT production upon infection of bronchial epithelial. cells. Method: BEAS-2B, a bronchial epithelial cell line, was cultured and subsequently exposed to minor RV serotypes (RV1b) at 0.5, 1, 3 and 5 multiplicity of infection (MOI) or major RV serotypes (RV16) at 1 and 10 MOI or to control medium (HeLa lysate) for 1 hour. The virus/control solution was then removed, cells were washed twice, replenished with fresh medium and incubated at 33oC thereafter. Supernatants were removed at 8, 24, 48, 72 and 96 hours after infection, clarified by centrifugation and deep-frozen. Cells were stained with crystal violet to assess RV-induced cytotoxicity. Leukotriene release was evaluated with the use of LTB4 and cysteinyl-LT (cys-LT) EIA kits (Cayman Chemical, US). Results: RV1b-infected BEAS-2B cells produced significantly higher levels of LTB4, 48 and 72 hours after infection as compared to control (p<0.01 and p<0.001 for 0.5 MOI at 48 and 72h respectively). Cell treatment with heat-inactivated (hi) or filtered (filt) RV1-b or RV16 did not induce LTB4 release. BEAS-2B cells also produced higher levels of cys-LTs (LTC4, LTD4, LTE4) 72 and 96 hours after infection with RV1b at 1 MOI, compared to non-infected (H) cells (p<0.05 at t=72h, p<0.01 at t=96h), while RV1b infection at 0.5-5 MOI yielded greater release of cysLTs by BEAS-2B cells at 96 hours after infection with all doses tested as compared to control (p<0.05 for 0.5&5 MOI, p<0.01 for 1&3 MOIs). RV infection induced cytotoxicity in a time- and dose-dependent manner, and it was greater after RV1b infection than RV16 infection. Conclusion: Our data support that structural cells, such as bronchial epithelial cells, are able to produce leukotrienes following RV infection. This pathway may contribute to the inflammatory component of virus-induced asthma and may reveal novel therapeutic avenues in the same context.
84 DENDRITIC CELLS IN THE NASAL MUCOSA OF SUBJECTS WITH DIFFERENT ALLERGIC SENSITIZATIONS Oral Presentations 4 Reinartz S, van Tongeren J, van Egmond D, de Groot E, van Drunen C, Fokkens W Department of Otorhinolaryngology, Academic Medical Center, Amsterdam, The Netherlands
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Background: Dendritic cells (DCs) play a pivotal role in several distinct phases of the allergic response. DCs have many functions which are not equally distributed among the different DC subsets. We assessed DC subtypes in the nasal mucosa of allergic rhinitis subjects and healthy controls by use of the specific DC-markers BDCA-1 and BDCA-3 for myeloid DCs, BDCA-2 and BDCA-4 for plasmacytoid DCs, and the Langerhans cell-markers CD1a and langerin. Method: Immunohistochemical staining was performed on nasal mucosal biopsies taken from allergic rhinitis and control subjects before and after nasal allergen provocation (NP). The allergic rhinitis subjects were either monosensitized to house dust mite, monosensitized to grass pollen, or polysensitized. All were challenged with relevant allergen. Results: We found that numbers of myeloid DCs, plasmacytoid DCs and Langerhans cells differ between subjects with different allergic sensitizations. At baseline BDCA-1+ cells were highest in the subjects mono-sensitized to grass pollen. The dynamics after nasal allergen provocation were largest for several DC subsets in the nasal mucosa of house dust mitemonosensitized allergic subjects, while overall the dynamics were very limited for the polysensitized individuals. The median ratio BDCA-1/BDCA-2 cells in the epithelium after NP was significantly higher in the allergic subjects compared to healthy controls (p=0.006). Conclusion: The higher number of BDCA-1+ cells in grass pollen-sensitized subjects may play a role in persistent inflammation despite the absence of allergen outside the season. The differences we found between subjects with different sensitizations hint both to allergen-specific differences in the immune response, and also to an interaction between different allergen sensitizations.
85 ALTERED NASAL FLUID PROTEOME IN RESPIRTORY ALLERGY Oral Presentations 4 Lang-Loidolt D 1, Birner-Gruenbeger R 2, Tomazic P 1, Britta O
1 2
Medical University Graz, Department of Otorhinolaryngology, Graz, Austria 2 Medical University Graz, Proteomics Core Facility, Center f. Medical Research, Graz, Austria
By employing shotgun proteomics and spectral counting, we determined the protein composition of nasal fluids from subjects allergic to pollen (n=11) as compared to healthy subjects (n=19) with the aim to provide new findings for a better understanding of the barrier function and involvement of the nasal fluid in the autoimmune response. 2 g of protein of collected samples were analyzed by nanoHPLC-tandem mass spectrometry after tryptic digestion. Proteins were identified by searching the human UniKProt public database before automatic validation. Spectral counts, i.e. the number of MS-MS spectra of each identified protein in each sample, were compared between groups and subjected to nonparametric statistical testing for determination of significantly changed protein amounts. In total, we identified 199 distinct proteins in the isolated fluids across all groups, the largest published data set of nasal fluid proteins so far. This included proteins involved in innate and adaptive immunity, metabolism, transport, cell communication, cell growth and maintenance and inflammation. The function of about 11% identified proteins was still unknown. No significant differences were found between female and male subjects. Interestingly, 12 proteins were significantly altered in allergic patients as compared to healthy subjects. Although they were of different origin, either secreted from serous or mucous glands, of vascular origin or cellular components, more than half of them were implicated in innate immunity; three harbored potential protease inhibitor activity and one may play a role in calcium regulation. Since extracellular endogenous proteases, as well as exogenous proteases from allergens may react with cell-surface receptors in the airways to generate leukocyte infiltration and amplify the response to allergens, leading to increased intracellular calcium and gene transcription, the identified proteins may have a protective function.
86 THE EPIGENETIC AND AIRWAYS DISEASE Oral Presentations 4 Hasham Sattar S 1, M Ishaq S2
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Aman Hospital, Peshawar, Pakistan Nowshera, Pakistan
Al-Junaid Hospital,
The epigenetic is the idiom employed to depict genetic changes in gene expression that are not coded in the DNA series itself but by post-translational changes in DNA and histone proteins. Such changes include a series of novelties histone acetylation, methylation, ubiquitination, sumoylation and phosphorylation. For generating diversity of cell types during mammalian development, epigenetic regulation is not only critical, but it is also important for preserving the stability and integrity of the expression profiles of different cell types. Until recently, the study of human disease has focused on genetic mechanisms rather than on non-coding events. Nonetheless, it is becoming increasingly clear that interruption of epigenetic developments can lead to several major pathologies, including cancer, syndromes involving chromosomal instabilities, and mental retardation. In addition, the idiom and activity of enzymes that regulate these epigenetic modifications have been documented to be abnormal in the airways of patients with respiratory disease. The progress of new diagnostic tools might disclose other diseases that are caused by epigenetic modifications. Despite being heritable and stably maintained, these changes, are also potentially reversible and there is possibility for the development of 'epigenetic therapies' for disease.
87 MUCOSAL TISSUE POLYCLONAL IGE IS FUNCTIONAL IN RESPONSE TO ALLERGEN AND SEB SERIN Symposium 7 - The superantigen story Zhang N2, Holtappels G1, Gevaert P1, Patou J1, Bachert C1 Upper Airway Research Laboratory (URL), Department of OtoRhino-Laryngology, Gent, Belgium , 2 Department of Oto-RhinoLaryngology, Zhongshan City Peoples Hospital, Zhongshan, China
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Background: Evidence is accumulating that Staphylococcus aureus plays an important role as disease modifier in upper and lower airway disease, specifically severe nasal polyps(NP) and asthma, by stimulating T-cells via classical enterotoxins. Those superantigens also can induce local formation of polyclonal IgE antibodies, the role of which is unknown. Methods: Nasal tissue and serum was obtained from 26 adult patients (12 allergic rhinitis patients and 14 nasal polyp subjects), in who skin prick tests were also performed. Total IgE and specific IgE abs to inhalant allergens and enterotoxins were determined in both, serum and tissue. Tissue fragments were stimulated with either TCM, 10 g/ml -chain specific anti-human IgE antibody, 10 M ionomycin, 0.5 g/mL SEB or grass and house dust mite allergens for 30 minutes. PGD2 was measured to demonstrate mast cell degranulation. Results: In allergic rhinitis(AR) patients, reactivity of tissue mast cells upon allergen exposure and presence of specific IgE abs to inhalant allergens corresponded in 23/24 cases for tissue IgE abs and in 21/24 cases for serum IgE abs. Total IgE in serum and inferior turbinate tissue homogenates highly correlated (r=0.91, p<0.0001). In contrast, in NP patients, reactivity of tissue mast cells upon allergen exposure and presence of specific IgE abs to inhalant allergens or SEB corresponded for tissue, but not for serum IgE abs. In SAE IgE positive polyp tissue, we could demonstrate degranulation of tissue mast cells upon allergens to which these patients did not show any serum specific IgE or skin prick test positivity. Total IgE was significantly higher in tissue compared to serum in these patients; and total IgE in serum and tissue did fail to show a meaningful correlation. Conclusions: We here for the first time demonstrate that SAE-induced local IgE antibodies in NP tissue are functional and able to activate mast cells upon inhalant and non-inhalant allergen challenge; specific IgE antibodies in NP tissue can be found independently of their presence in serum. We postulate that superantigen-induced polyclonal IgE abs, including IgE to SAE, in airway disease contribute to chronic inflammation by continuously activating mast cells
88 STAPHYLOCOCCUS AUREUS INVADES THE EPITHELIUM IN NASAL POLYPOSIS AND INDUCES IL-6 IN NASAL EPITHELIAL CELLS IN VITRO. SERIN Symposium 7 - The superantigen story Rudack C 1, Becker K 2, Metze D 3, Sachse F 1 Dep. ENT Head and Neck Surgery, University Hospital Muenster, Muenster, Germany 2 Dep Microbiology, University Hospital Muenster, Muenster, Germany 3 Dep Dermatology, University Hospital Muenster, Muenster, Germany
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Background: Staphylococcus aureus has been associated with chronic rhinosinusitis with nasal polyps (CRSwNP) pathogenesis but its role is still controversially discussed. Here, we demonstrate S. aureus detection in the mucosa of CRSwNP. In addition, intracellular persistence of S. aureus in nasal polyp epithelial cells (NPECs) and its capability to induce TH-2 cytokines were analyzed in vitro. Methods: Staphylococcus aureus detection in CRSwNP (n = 25), CRS without polyps (CRSsNP, n = 5), and turbinate mucosa (TM, n = 10) was performed by peptide nucleic acid-fluorescence in situ hybridization (PNA-FISH) and microbial cultivation from tissue biopsies. Intracellular residency was examined by intracellular persistence assay and electron microscopy. IL-6 and IL-13 responses to S. aureus infection and supernatants were quantified by ELISA. Results: Peptide nucleic acid-fluorescence in situ hybridization positive bacterial cells were significantly increased in the epithelium of CRSwNP (17/25) compared to CRSsNP (0/5) and TM (1/10). Good concordance of PNA-FISH results and S. aureus cultivation was found applying Cohen's kappa for CRSwNP (kappa = 0.841) and TM (kappa = 1.0). Intracellular persistence assay with S. aureus strain Newman and its corresponding small-colony variant mutant strain III33 demonstrated intracellular survival and replication of S. aureus within NPECs. Both S. aureus strains significantly induced IL-6 but not IL-13 in infected NPECs and in NPECs challenged with corresponding staphylococcal supernatants. Conclusion: Invasion of the epithelium by S. aureus was a phenomenon seen predominantly in CRSwNP. Regardless of an intra- or extracellular localization in the epithelium, S. aureus is capable to induce IL-6 synthesis in vitro and thus may contribute to the TH-2 cytokine pattern in CRSwNP.
89 ALTERNATIVELY ACTIVATED MACROPHAGES AND IMPAIRED PHAGOCYTOSIS OF S.AUREUS IN CHRONIC RHINOSINUSITIS. SERIN Symposium 7 - The superantigen story Krysko O 1, Holtappels G 1, Zhang N 1, Kubica M 2, Deswarte K 4, Derycke L 1, Clayes S 1, Hammad H 4, Brusselle G 5, Vandenabeele P 2 , Krysko D 2, Bachert C 1 The Upper Airway Research Laboratory (URL), Ghent University, Ghent, Belgium 2 Molecular Signaling and Cell Death Unit, DMBR, VIB, Ghent, Belgium 3 DMBR, Ghent University, Ghent, Belgium 4 Laboratory for Immunoregulation, Ghent University, Ghent, Belgium 5 Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium
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Background: Classically (M1) and alternatively (M2) activated macrophages, characterized by expression of specific surface receptors, chemokine production and have different functions in control of infections and development of human diseases. Although extensive evidence on macrophage activation phenotypes has been obtained in in vitro experiments, the data on human upper airway pathology are missing. Chronic inflammatory disease of the upper airways, which is also known as chronic rhinosinusitis (CRS), is reported in 17% of the European population. Methods: In this study we analyzed different macrophage polarization states in 28 healthy and chronic rhinosinusitis patients by immunohistochemistry, FACS analysis and their phagocytosis capacity of S. aureus was studied. Results: We observed significantly more M2 macrophages (CD163+, MMR+) in the CRS with nasal polyps compared to CRS without nasal polyps. Expression of these M2 markers was positively correlated to increased levels of IL-5, ECP and total local IgE. The group of patients with high numbers of M2 macrophages also had low levels of IL-6, IL-1 and INF. FACS analysis on dissociated nasal tissue showed that the number of M2 macrophages (CD206+HLADR+CD14+CD11clowCD16-CD20-) was significantly higher in patients with nasal polyps as compared to controls (3.5% vs 0.7%), while the number of M1 macrophages (CD206-HLADR+CD14+CD11clowCD16+/-CD20-) was not different between the groups of patients. Phagocytosis of S. aureus by human tissue derived macrophages was reduced in CRS with nasal polyps as compared to macrophages from the inferior turbinates of control patients. Next, M1 and M2 macrophages from nasal tissue were sorted out by FACS and the expression levels of TLR2, TLR4, MARCO and NOD1 on these subpopulations of macrophages will be discussed. Conclusion: Decreased phagocytosis of S. aureus and an M2 activation phenotype in CRSwNP could potentially contribute to persistence of chronic inflammation in CRSwNP.
90 T HELPER PLASTICITY IN CHRONIC UPPER AIRWAY DISEASE SERIN Symposium 8 - T-cells and dendritic cells in airway disease Derycke L 1, Eyerich S 2, Holtappels G 1, Deruyck N 1, SchmidtWeber C 2, Bachert C 1 Upper Airways Research Laboratory, Department of Otorhinolaryngology, Ghent, Belgium 2 ZAUM - Zentrum Allergie und Umwelt, Munich, Germany
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Background: Chronic inflammation of the upper airways is affecting 18% (chronic rhinosinusitis, CRS) of the Belgian population and is a significant health problem causing morbidity and loss of quality of life/performance. The airways are in constant contact with viruses, bacteria, and their products (like enterotoxins). These pathogens are activating different antigen presenting cells, for example dendritic cells, which release on their turn different cytokines and are able to activate nave T cells to become T helper cells. Methods and Results: We collected fresh nasal mucosa from healthy individuals and nasal mucosa from patients suffering from chronic rhinosinusitis with or without nasal polyps. From all samples homogenates were prepared to analyze cytokines and IgE status by using Luminex and Unicap instruments. The other part of the mucosa was dispersed to make a single cell suspension and all cells were stimulated for 5 hours with PMA/ Ionomycin. One part of cells were collected for RNA extraction and qPCR analysis was performed for cytokines (IL-4, IL-5, IL-12, IL-13, Interferon-) and transcription factors (GATA3, T-bet, FOXP3). The rest of cells were stained T helper cytokines and processed on FACS CANTO. Increased IL-5, IL-4 and GATA-3 positive CD4 cells were observed in nasal polyps compared with normal nasal mucosa and the cytokines IL-17, IL-10 and interferon- were significantly less produced by CD4 T helper cells. We could not find any difference on the level of CD4 cytokines between normal nasal mucosa and chronic rhinosinusitis without nasal polyps.
Conclusion: We could demonstrate that the T cell cytokine pattern in chronic rhinosinusitis with nasal polyps is severely biased to Th2 compared to normal nasal mucosa, whereas in chronic sinusitis without nasal polyps, no disturbance can be shown.
91 EXPRESSION OF GENES ASSOCIATED WITH ACTIVATION OF T-CELLS, B-CELLS AND ANTIGEN PRESENTING CELLS IN CHRONIC RHINOSINUSITIS SERIN Symposium 8 - T-cells and dendritic cells in airway disease Weiss D, Basel T, Sachse F, Rudack C Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Muenster, Germany
Background: The etiology of chronic rhinosinusitis (CRS) is still unknown. Since some of the patients with CRS develop nasal polyps (CRSwNP) while others do not (CRSsNP), a different underlying pathology may be relevant in both of these entities. Numerous studies have concentrated on gene expression profiles of pro-inflammatory mediators whereas studies characterizing the impact of T-cell, B-cells and antigen presenting cells in CRSwNP and CRSsNP are still limited. Methods: In order to gain insight into the pathomechanisms of CRS we performed Reverse Transcriptase PCR of mRNA of 84 genes in 6 patients with CRSwNP and 6 patients with CRSsNP using a commercially available assay with focus on gene expression of markers associated with antigen-presentation and activation of T- and B-cells. Inferior turbinates of 4 subjects without any history or clinical evidence of allergy, atopy or sinonasal disease served as controls. We only concentrated on genes with Fold Difference in up- or downregulation of 1.5 and significance p < .05. Results: In the assay designed for dendritic cells we could find an up-regulation for CCL13, CD209 and CD44 in CRSwNP compared to normal mucosa while CXCL2, CXCL12, IFNG, IL2, ITGAM and MIF were down-regulated. Comparing CRSsNP and normal mucosa we interestingly only found up-regulated genes (CD4, CD40, CD74, CD80, CD8A, CDC42, CXCR4, ERBB2, FAS, HLA-A, HLA-DPA1, ICAM2, IFIT3, IFNGR1, IL12B, IL16, ITGAM, LRP1, MDK, MIF, NFB2, PDIA3, RELA, STK4, TAP2, TLR1 and TLR2). In the assay for T- and Bcells the following genes showed down-regulation in CRSwNP: CCL4, CCR2, CD27, CD40LG, CXCR4, HDAC4, HDAC7, IFNG, IL2, IRF4, KLF6, NCK2, PRLR, RGS1 and SOCS5. PVRL1, TGF1 and IL4R were up-regulated. If CRSsNP and healthy mucosa were compared only two genes showed significant down-regulation (CCL3 and HDAC7). Conclusion: Both, dendritic and T-/ B-cell-assays, showed that the vast majority of tested genes were down-regulated in CRSwNP, which might suggest a lack of local immune defense mechanisms that may contribute to CRSwNP pathogenesis.
92 A ROLE FOR IL-25 AS 'INITIATOR' IN TH2 DRIVEN INFLAMMATION IS RESTRICTED TO IL-5 HIGH TH2 PATIENTS SERIN Symposium 8 - T-cells and dendritic cells in airway disease Seys S 1, Adriaensen W 1, Dilissen E 1, Grabowski M 2, Decraene A 3, Ceuppens J 1, Dupont L 3, Bullens D 1
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Lab of Clinical Immunology, KU Leuven, Leuven, Belgium 2 Department of Internal Medicine and Allergology, Medical University, Wroclaw, Poland 3 Department of Pneumology, Leuven, Belgium
Background: A Th2 high and a Th2 low asthma population was defined by Woodruff et al based on the expression level of three IL-13 inducible genes. Th2 low asthma represents a significant proportion of patients and responds poorly to current therapies, whereas Th2 high asthma is mostly steroid sensitive. IL-25 might amplify Th2 driven airway inflammation that is associate with allergic disorders. To characterize asthma molecular phenotypes based on sputum cytokine IL-25 levels and to study the association between IL-25 mRNA expression and Th2 cytokine expression in asthmatics. Methods: Cells were obtained by sputum induction in 41 healthy subjects and 54 asthmatic patients as already described. Sputum IL-4, IL-5, IL-25, TNF- and IFN-gamma mRNA levels were measured by quantitative RT-PCR and normalized to -actin. The upper 90percentile value of the cytokine mRNA levels in the healthy population was used as a cut-off value for cytokine positivity. Results: Cut-off values for IL-4, IL-5, IL-25, TNF- and IFN- were respectively 0.1; 1445; 345; 51000 and 7 copy numbers. Thirty asthma patients were identified as having Th2 high asthma (IL-4-high (n=23) and/or IL-5-high) and 24 patients had non-Th2 asthma. Patients with IL-25-high asthma all belong to the IL-5-high but not to the IL-4-high asthma group nor to the non-Th2 group. 11 patients had an elevated IFN--high asthma and 6 patients had TNF--high asthma. The percentage of FEV1 predicted was significantly lower in the Th2 high asthma group when compared to the Th2 low asthma group (p=0.03). Furthermore, both exhaled NO (FeNO) and sputum eosinophils (%) were significantly higher in the Th2 high group (p=0.01; p=0.009). Conclusion: Th2 asthmatics have higher markers of eosinophilic inflammation and poorer lung function when compared to non-Th2 asthmatics. Th2 asthmatics can be subdivided in IL-4-high and IL-5-high asthma. IL-25-high asthma is restricted to the latter. Non-Th2 asthma still has to be further characterized. We hypothesize that patients molecular phenotypes influence their response to classical and new anti-cytokine therapy (e.g. antiIL5, anti-IL4R).
93 INDOLEAMINE 2,3-DIOXYGENASE ACTIVITY AND EXPRESSION IN NASAL POLYPS SERIN Symposium 9 - Innate immunity: PAMPs, DAMPs and others Honkanen T 1, Luukkainen A 2, Lehtonen M 2,3, Paavonen T 1, Karjalainen J 4, Hurme M 5, Myller J 2,6, Huhtala H 7, Rautiainen M 2,3, Toppila-Salmi S 8,9 Department of Pathology, University of Tampere, Tampere, Finland 2 Department of Otorhinolaryngology, University of Tampere, Tampere, Finland 3 Department of Eye, Ear and Oral Diseases, Tampere University Hospital, Tampere, Finland 4 Allergy Centre, Tampere University Hospital, Tampere, Finland 5 Department of Microbiology, University of Tampere, Tampere, Finland 6 Department of Otorhinolaryngology, Paijat-Hame Central Hospital, Lahti, Finland 7 School of Public Health, University of Tampere, Tampere, Finland 8 Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland 9 Department of Otorhinolaryngology, Helsinki University Hospital, Hyvinkaa, Finland
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Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) and without (CRSsNP) are considered to be distinct phenotypes with different pathomechanisms. CRSwNP in aspirin (ASA) intolerant patients might differ from that in ASA tolerant patients. Antrochoanal polyps (ACP) constitute a distinct disease entity. Indoleamine 2,3-dioxygenase (IDO) is an enzyme expressed in many cells involved in the catabolism of the essential amino acid tryptophan to kynurenine. IDO might promote allergic airway inflammation. The aim was to evaluate the IDO activity in asthma patients with or without NP, and the expression of IDO during CRS subgroups and ACP. Methods: The subjects of the first part were participants of a Finnish population-based case-control study. Serum samples of 383 non-asthmatic controls and 238 asthma patients with or without NP were obtained. The serum IDO activity was evaluated by assessing the kyn/trp ratio by liquid chromatography. Secondly, sinonasal specimens were obtained either from healthy volunteers or during surgery. IDO was immunohistochemically analysed in the nasal cavity from 19 control inferior turbinate, 54 CRSwNP, and 10 ACP patients; and in the sinus mucosa of 12 healthy, 41 CRSsNP, and 14 CRSwNP patients. Results: Low IDO activity was associated with NP (P<0.01, OR=0.95, CI=0.91- 0.98). When adjusted to asthma, atopy, and smoking, the result remained the same. Asthma and ASA-intolerance were associated with NP (P<0.001, OR=2.9, CI=1.66-5.08; P<0.05, OR=2.68, CI=0.87-1.07), whereas atopy or smoking were not. Secondly, CRSwNP and antrochoanal polyps had a significantly increased expression of leukocyte and epithelial IDO compared to control inferior turbinate. In the maxillary sinus mucosa, there was not a significant change in epithelial IDO compared to controls. In contrast, the expression of leukocyte IDO increased during CRSsNP and CRSwNP also in maxillary sinus mucosa, if there was additionally microscopical evidence of hypertrophic polypoid sinus mucosa. The presence of ASA intolerance, asthma, allergic rhinitis, smoking and use of medication did not significantly change these results. Conclusions: The low serum IDO activity indicates that patients with NP diagnosis might have systemic changes in the immunoregulation independent of other related factors. Secondly, the differences in the expression of IDO might indicate phenotype-specific differences in the pathomechanisms of CRSsNP, CRSwNP and ACP. Further studies are required.
94 S100A8, S100A9 AND S100A8/9 IN CHRONIC RHINOSINUSITIS WITH NASAL POLYPS SERIN Symposium 9 - Innate immunity: PAMPs, DAMPs and others Van Crombruggen K 1, Holtappels G 1, Vogl T 2, Bachert C 1 Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University, Ghent, Belgium 2 Institute of Immunology, University of Muenster, Muenster, Germany
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Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with a Th2-skewed eosinophilic inflammation with increased interleukin (IL)-5 and eosinophil cationic protein (ECP) concentrations, while the Th1 cytokine interferon (INF)- and the levels of other inflammatory mediators such as tumor necrosis factor (TNF)-, IL1-, IL-10, and IL-17 are not significantly different from those in healthy control tissue. Intracellular housekeeping molecules such as the calcium binding proteins of the S100 family are termed damage-associated molecular-patterns (DAMPs) when released into the extracellular space via a non-classical secretory pathway during inflammation. Although these proteins are described as modulators of inflammatory responses via regulation of immune cells, their exact implication and mechanism of action in CRSwNP is not completely understood. Methods: Homomeric S100A8, S100A9 and heteromeric S100A8/9 protein levels were evaluated in tissue homogenates, serum and nasal secretions of CRSwNP patients and healthy controls (n=18-22) by ELISA and immunohistochemical (IHC) staining. Sinonasal tissue fragments from human nasal polyps of CRSwNP patients were stimulated for 24h with human homodimeric S100A8 and S100A9 and heteromeric S100A8/9 proteins; supernatants were measured for several key cytokines. Results: Tissue homogenate and serum levels of S100A8/A9 are significantly higher in CRSwNP patients versus healthy controls, while S100A9 was only increased in tissue homogenates. No differences in the levels of both proteins were observed in nasal secretions. The majority of the human samples showed levels of S100A8 below detection limit, consequently not yielding statistical significances. IHC staining showed increased deposition of S100A9 proteins on extracellular matrix structures in CRSwNP tissue. Stimulation of nasal polyp tissue fragments with 5 g/ml recombinant S100A8 or S100A9 proteins resulted in clear-cut increased IL1-, IL-10, IL-17, TNF- and INF- levels in the tissue culture supernatants, while IL-5 and ECP were not affected. S100A8/9 did not alter the release of any of the inflammatory mediators measured. Conclusion: S100 proteins are increased in CRSwNP, and the homodimers show the potential to modulate the inflammatory response in CRSwNP tissue by shifting the cytokine pattern away from the typical Th2-skewed inflammation.
95 EXACERBATION OF CIGARETTE-SMOKE-INDUCED PULMONARY INFLAMMATION BY STAPYLOCOCCUS AUREUS ENTEROTOXIN B IN MICE SERIN Symposium 9 - Innate immunity: PAMPs, DAMPs and others Huvenne W 1, Lanckacker E 2, Krysko O 1, Bracke K 2, Demoor T 2, Joos G 2, Brusselle G 2, Maes T 2, Bachert C 1 Upper Airways Research Laboratory (URL), ENT Dept, Ghent Univeristy Hospital, 2 Department of Respiratory Medicine, Ghent University Hospital,
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Background: Cigarette smoke (CS) is a major risk factor for the development of COPD. CS exposure is associated with an increased risk of bacterial colonization and respiratory tract infection, because of suppressed antibacterial activities of the immune system and delayed clearance of microbial agents from the lungs. Colonization with Staphylococcus aureus results in release of virulent enterotoxins, with superantigen activity which causes T cell activation. These staphylococcal enterotoxins are known modulators of airway inflammation, and therefore interesting to study in the pathogenesis of COPD. Objective was to study the effect of S. aureus enterotoxin B (SEB) on CS-induced inflammation, in a mouse model of COPD. Methods: C57/Bl6 mice were exposed to CS or air for 4 weeks (5 cigarettes/exposure, 4x/day, 5 days/week). Endonasal SEB (10g/ml) or saline was concomitantly applied starting from week 3, on alternate days. 24h after the last CS exposure, and 48h after the last SEB application, mice were sacrificed for BAL fluid and lung tissue collection. Results: Combined exposure to CS and SEB has resulted in a raised number of lymphocytes and neutrophils in BAL, as well as increased number of CD8+ T lymphocytes and granulocytes in lung tissue, compared to single CS or SEB exposure. Moreover, concomitant CS/SEB exposure has induced both increased IL-13 mRNA expression in lungs and goblet cells in the airway wall. In addition, SEB has stimulated the formation of dens, organized aggregates of B- and T- lymphocytes in lungs after subacute CS exposure, as well as significant higher CXCL-13 (protein, mRNA) and CCL19 (mRNA) levels in lungs. Conclusions: Combined CS and SEB exposure aggravates CS-induced inflammation in mice. These results suggest that S. aureus might influence the pathogenesis of COPD.
96 PRELIMINARY FINDINGS FROM A WHOLE GENOME EPIGENETIC ANALYSIS OF THE MANCHESTER ASTHMA AND ALLERGY STUDY SERIN Symposium 10 - Genetics and epigenetics of airway diseases Curtin J 1, Custovic A 1, Simpson A 1, Martinez F 2 The University of Manchester, School of Translational Medicine, Manchester, United Kingdom 2 Arizona Respiratory Center, Tuscon, USA
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Background: Mechanisms that underlie the development of asthma are complex and include both heritable and environmental factors. Recent studies suggest that epigenetic modifications may regulate the complex gene-by-environment interactions leading to asthma. These include the reduction of histone deacetylase-2 in people with smoking induced asthma as well as the association of altered methylation of ACSL3 with exposure to polycyclic aromatic hydrocarbons and the subsequent development of asthma symptoms in young children. We are using a genome wide approach to investigate how DNA methylation may alter the risk of asthma and its intermediate phenotypes in a unique population-based birth cohort, the Manchester Asthma and Allergy Study (MAAS). Methods: We used the Illumina Infinium Assay to assess the methylation status of 27,578 CpG dinucleotides spanning 14,495 genes in the genomes of 211 CBMC DNA samples from the MAAS cohort. Data quality control and normalisation were carried out on the Bioconductor package Methylumi. Results: A total of 197 samples passed our quality control measures and could be distinguished as Male or Female with an MDS plot of probes located on the X chromosome. In a preliminary analysis of a sample subset (n=87) we found that 51% of CpG sites were hypomethylated and 16% were hypermethylated. We found that a higher proportion probes located in CpG islands (n=19252) were hypomethylated (68%) and only 6% were hypermethylated, confirming previous observations that CpG islands are generally unmethylated. We found that many genes implicated in asthma were frequently hypomethylated (IL-15, IL4R, TLR2, TLR4, ADRB2, EDN1, IRAK3 and IRAK4) or hypermethylated (IL-4, FCERB, IL-5, IL-13, CCL5, CCL11 and IFNG) with very little variability. Conclusion: Some genes that are commonly associated with asthma in genetic studies appear to be frequently either hyper or hypo methylated and have very little variability indicating that their epignetic status is unlikely to be informative. However the methylation status of over 500 CpG sites are sufficiently variable for further downstream analysis.
97 STAPHYLOCOCCAL AUREUS ENTEROTOXIN P-PROINFLAMMATORY NETWORK IN UPPER AIRWAY DISEASES AND ITS RELATIONSHIP WITH EPIGENETIC CHANGES SERIN Symposium 10 - Genetics and epigenetics of airway diseases Perez Novo C 1, Trooskens G 2, Renard J 2, De Ruyck N 1, Holtappels G 1, Van Criekinge W 2, Bachert C 1 Upper Airways Research Laboratory, Dpt. of Otorhinolaryngology, Ghent University, Ghent, Belgium 2 Laboratory for Bioinformatics and Computational Genomics, Ghent University, Ghent, Belgium
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Background: Diverse cellular functions including the regulation of inflammatory gene expression, DNA repair and cell proliferation are regulated by epigenetic changes. Anergy is an important mechanism of peripheral tolerance in which T cells lose the capacity to produce pro-inflammatory cytokines and it may be associated with epigenetic changes that oppose cytokine gene expression. Viral superantigens may induce T-cell tolerance by enhancing DNA methylation and reducing histone acethylation at the regulatory regions of important pro-inflammatory genes. Based on that we hypothesize is that bacterial superantigens may induce epigenetic changes in the loci of genes regulating inflammatory reactions. Methods: Nasal polyp tissue explants were cultured in presence and absence of staphylococcal enterotoxin B (0.5g/ml) for 24 hours. Genomic DNA was isolated and 1 g was fragmented on a Covaris that was set to have an average fragment size of 200bp's. MBD2 precipitation was performed with the MethylCollector kit from Active Motif according to the manufacturers' protocol starting from 200ng of fragmented gDNA. After MBD2 precipitation captured gDNA was measured with Invitrogen Picogreen kit on ND-3300 and sequenced on the Illumina GAIIx with the gDNA paired end kit (multiplexed) 2 x 40bp and 7bp's index. Results: Data analysis was performed with the Hitchikers Guide to the Genome V1.2 (H2G2, Biobix Ghent Univ.). In the genome search, 198 genes were found to have genomic regions differentially methylated in SEB treated sample compared to control medium. Cluster analysis of these genes revealed 34 clusters and the highest scores included genes involve in maintenance of protein location within the cell, transcription regulation, protein amino acid alkylation and methylation events, positive regulation of cell growth and response to oxidative stress. Methylated regions were found contained in non-coding regions, exons and in some genes in the transcription start site. The score observed for un-methylated genes was much lower than the one obtained for methylated genes after SEB treatment. Conclusions: Nasal polyp tissue explants cultured with SEB showed a different hypermethylated pattern in genes involved in vital cell functions and transcriptional regulation events that may influence its pro-inflammatory effect.
98 ASSOCIATION OF THE TUMOUR NECROSIS FACTOR ALPHA (308 G/A) GENE POLYMORPHISM WITH ASTHMA RELATED PHENOTYPES AMONG CHILDREN IN DURBAN, SOUTH AFRICA SERIN Symposium 10 - Genetics and epigenetics of airway diseases Makamure M 1, Reddy P 2, Chuturgoon A 3, Moodley D 4, Naidoo R 5 Department of Community Health Studies, Durban University of Technology, Durban, South Africa 2 Department of Community Health Studies, Durban University of Technology, Durban, South Africa 3 Department of Medical Biochemistry, University of KwaZulu Natal, Durban, South Africa 4 Department of Medical Biochemistry, University of Kwa-Zulu Natal, Durban, South Africa 5 Department of Occupational and Environmental Health, University of Kwa-Zulu Nata, Durban, South Africa
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Background: Tumour necrosis factor (TNF ) is a proinflammatory cytokine which has been implicated in airway pathology and has been associated with adverse respiratory outcomes and/or the involvement of neutrophils in these processes. However, these findings have not been consistently replicated and there is limited data available with asthma related phenotypes in South Africa. We investigated the frequency of the TNF -308 G/A promoter polymorphism in black South African schoolchildren. We also evaluated if genotype variation influenced TNF expression and whether the polymorphism in the promoter was associated with asthma and bronchial hyperresponsiveness (BHR). Method: The current study is based on data from a sub-sample of the South Durban Health Study (SDHS). Respiratory outcomes were determined by validated questionnaires. Baseline spirometric assessments and methacholine challenge tests were conducted following American Thoracic Society (ATS) guidelines. Genomic DNA was extracted from whole bloods of a sample of 104 schoolchildren aged 9-11 years old and the TNF-308 polymorphism was determined using a PCR restriction method (Wilson et al, 1997). Cytokine levels were measured using the Human TNF- ELISA MAXTM set Deluxe BioLegend kit. Frequency and descriptive analysis was done using STATA version 9. Results: Preliminary results indicate a high proportion of G allele (76%) in our African population. The frequencies of AA, AG and GG genotypes in the population were 7%, 33%, and 60% respectively. The level of TNF- ranged from 0-44pg/ml, with a mean of 11.5pg/ml. There were no significant differences in plasma TNF concentrations when comparing individuals homozygous for the G allele with those homozygous for the A allele. Bivariate tests indicated no statistically significant association between the TNF -308 G/A promoter polymorphism with persistent asthma and BHR. Conclusion: The present study found no association of the TNF -308 G/A polymorphism and serum TNF concentrations with respiratory phenotypes such as persistent asthma and BHR in black South African children. Increased cytokine concentrations are biomarkers of increased inflammation and correlation of environmental factors with the TNF -308 polymorphism are ongoing.
29a THE ASSOCIATION OF CHRONIC RHINOSINUSITIS WITH NASAL POLYPOSIS SEVERITY AND ASTHMA Poster Discussion Session 2 (Replacement) Olszewska-Ziaber A, Kowlaksi M L
Department of Immunology, Rheumatology and Allergy, Medical University of Lodz, Poland
Background: Chronic rhinosinusitis with nasal polyps coexists with asthma in up to 15% of patients. The aim of the study was to compare the intensity of paranasal disease in patients with and without asthma by means of various clinical tools: clinical symptom score, endoscopic examination, computed tomography (CT), presence of atopy and the lung function. Methods: One hundred seventy eight patients with chronic rhinosinusitis and polyps were enrolled and divided into two groups: patients with bronchial asthma (105 patients) and without asthma (73 patients). The symptoms of rhinosinusitis were assessed using a SNOT-20 questionnaire and the size of polyps in the nose was evaluated by rhinoscopy with fiberoscope and graded on a 0-3point scale according to Johansen. The presence of atopy was evaluated in the skin prick tests and the lung function with spirometry. The extent of mucosal hypertrophy in the paranasal sinuses was assessed by computerized tomography (CT) ad graded according to V. Lund-Mackay scale. Results: There was no statistically significant difference in age , mean symptom score (SNOT-20 ) and mean size of polyps assessed by flexible rhinoscopy between the groups(mean 1.71+0,9 in patients without asthma and 1.82+0,8 in asthmatics). The presence of atopy was significantly higher in asthmatic than non-asthmatic patients (p<0.05), although positive skin prick tests showed 46,2% of non-asthmatics. The lung function in spirometry differed in significantly lower FEV1 values in asthmatic patients (mean 0.86+0.34 0.90+0.26 as compared to non-asthmatic ones (0.90+0.26, p<0.002). The extent of hypertrophy in paranasal sinuses assessed on CT scans was significantly higher in patients with asthma (mean score 15,33 + 6.14) as compared to non asthmatic patients ( mean score 11,33 + 6,04 ; P<0.002).
Conclusion: Patients with chronic rhinosinusitis with polyps and coexisting asthma show significantly higher mucosal hypertrophy in the paranasal sinuses although they do not differ in the size of polyps in the nose or symptom score.
31a CHRONIC SINUSITIS: DISEASE DIFFERENTIATION BY INNATE IMMUNITY MARKERS Poster Discussion Session 2 (Replacement) Claeys S University Hospital Ghent, ENT, Ghent, Belgium
Chronic rhinosinusitis (CRS) is a heterogenic disorder with recognized different clinical and inflammatory patterns. Four subgroups can be defined: chronic rhinosinusitis without nasal polyposis (CRSsNP), nasal polyposis without co-morbidity (NP), nasal polyposis with asthma /asperin intolerance (NP-AI), nasal polyposis in cystic fibrosis patients (CF-NP). The exact triggers of onset and differentiation of the CRS subgroups are not established yet, but differences in local bacterial load and toxicity, allergy, genetic markers and polymorphisms explain circumstances in which certain CRS inflammation patterns are induced. The adaptive immune systems clearly shows polarized inflammation CRSsNP exhibits predominant Th1 cytokine profile with increased levels NP is characterized by Th2 skewed eosinophilic inflammation and S.aureus producing enterotoxins (SAEs). In the NP-AI group specific Ig in 60-80 % of the patients and in CF-NP shows a predominant Th1 inflammation. in CRS subgroups: of TGF- and IFN-, has been linked to E to SAEs is present skewed neutrophilic
The pathways by which pathogens or environmental factors trigger the onset of CRS inflammation are not determined yet. Dysfunction of first line defence barriers and innate immune responses play an important role in disease onset and differentiation. On the level of bacterial clearance (S aureaus SHIPS and SCIN, alternative activated macrophages), inducible antimicrobial effect (HBD 2, LL-37), pathogen recognition (MMR, TLR 9) and restoration of mucosal homeostasis innate markers show differences in the different CRS subgroups.

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CHLN-HSM-Allergy Department, Lisbon, Portugal School-Genetic Department, Lisbon, Portugal

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Go Fishnet Youth Project, Kisumu, Kenya Kisumu, Kenya

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22 NON-ALLERGIC RHINITIS Poster Discussion Session 2 Hasham Sattar S 1, M Ishaq S2

Aman Hospital, Peshawar, Pakistan Nowshera, Pakistan

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