Kliegman: Nelson Textbook of Pediatrics, 18th ed.

Copyright 2007 Saunders, An Imprint of Elsevier Chapter 143 Childhood Asthma

Andrew H. Liu Ronina A. Covar Joseph D. Spahn Donald Y.M. Leung

Asthma is a chronic inflammatory condition of the lung airways resulting in episodic airflow obstruction. This chronic inflammation heightens the twitchiness of the airwaysairways hyperresponsiveness (AHR)to provocative exposures. Asthma management is aimed at reducing airways inflammation by minimizing proinflammatory environmental exposures, using daily controller anti-inflammatory medications, and controlling co-morbid conditions that can worsen asthma. Less inflammation typically leads to better asthma control, with fewer exacerbations and decreased need for quick-reliever asthma medications. Exacerbations can, nevertheless, still occur. Early intervention with systemic corticosteroids greatly reduces the severity of such episodes. Advances in asthma management and especially pharmacotherapy enable all but the uncommon child with severe asthma to live normally.
ETIOLOGY.

Although the cause of childhood asthma has not been determined, contemporary research implicates a combination of environmental exposures and inherent biological and genetic vulnerabilities ( Fig. 143-1 ). Respiratory exposures in this causal environment include inhaled allergens, respiratory viral infections, and chemical and biological air pollutants such as environmental tobacco smoke. In the predisposed host, immune responses to these common exposures can be a stimulus for prolonged, pathogenic inflammation and aberrant repair of injured airways tissues. Lung dysfunction (i.e., AHR and reduced airflow) develops. These pathogenic processes in the growing lung during early life adversely affect airways growth and differentiation, leading to altered airways at mature ages. Once asthma has developed, ongoing exposures appear to worsen it, driving disease persistence and increasing the risk of severe exacerbations.

Figure 143-1 Etiology and pathogenesis of asthma. A combination of environmental and genetic factors in early life shape how the immune system develops and responds to ubiquitous environmental exposures. Respiratory microbes, inhaled allergens, and toxins that can injure the lower airways target the disease process to the lungs. Aberrant immune and repair responses to airways injury underlie persistent disease. AHR, airways hyperresponsiveness; ETS, environmental tobacco smoke.

Genetics.

More than 22 loci on 15 autosomal chromosomes have been linked to asthma. Although the genetic linkages to asthma have sometimes differed between cohorts, asthma has been consistently linked with loci containing pro-allergic, proinflammatory genes (the interleukin [IL]4 gene cluster on chromosome 5). Genetic variation in receptors for different asthma medications is associated with variation in biologic response to these medications (polymorphisms in the 2-adrenergic receptor). Other candidate genes include ADAM-33 (member of the metalloproteinase family), the gene for the prostanoid DP receptor, and genes located on chromosome 5q31 (possibly IL-12).

Environment.

Recurrent wheezing episodes in early childhood are associated with common respiratory viruses, including respiratory syncytial virus, rhinovirus, influenza virus, parainfluenza virus, and human metapneumovirus. This implies that host features affecting immunologic host defense, inflammation, and the extent of airways injury from ubiquitous viral pathogens underlie susceptibility to recurrent wheezing in early childhood. Furthermore, injurious viral infections of the airways manifesting as pneumonia or bronchiolitis requiring hospitalization are risk factors for persistent asthma in childhood. Other airways exposures can also exacerbate ongoing airways inflammation, increase disease severity, and drive asthma persistence. Indoor and home allergen exposures in sensitized individuals can initiate airways inflammation and hypersensitivity to other irritant exposures, and are strongly linked to disease severity and persistence. Consequently, eliminating the offending allergen(s) can lead to resolution of asthma symptoms and can sometimes cure asthma. Environmental tobacco smoke and air pollutants (ozone, sulfur dioxide) aggravate airways inflammation and increase asthma severity. Cold dry air and strong odors can trigger bronchoconstriction when airways are irritated, but do not worsen airways inflammation or hyperresponsiveness.
EPIDEMIOLOGY.

Asthma is a common chronic disease, causing considerable morbidity. Based on information collected by the National Center for Health Statistics of the Centers for Disease Control and Prevention, in 2002, 8.9 million children (12.2%) had been diagnosed with asthma in their lifetime, and 4.2 million children (5.8%) had an asthma attack in the preceding 12 mo, indicative of current disease. Boys (14% vs 10% girls) and children in poor families (16% vs 10% not poor) are more likely to have asthma. In the United States, childhood asthma is the most common cause of childhood emergency department visits, hospitalizations, and missed school days, accounting annually for 867,000 emergency department visits, 166,000 hospitalizations, and 10.1 million school days lost. In the United States in 2000, asthma was responsible for 223 childhood deaths. A disparity in asthma outcomes links high rates of asthma hospitalization and death with poverty, ethnic minorities, and urban living. In the past 2 decades, African-American compared to white children had 2 to 4 times more emergency department visits, hospitalizations, and deaths due to asthma. For ethnic minority asthmatics living in U.S. inner-city low-income communities, a combination of biologic, environmental, economic, and psychosocial risk factors is believed to increase the likelihood of severe asthma exacerbations. Although asthma prevalence is higher in black vs non-black U.S. children (in 2002, 17.7% vs 11.1% white and 10.3% Latino), prevalence differences cannot fully account for this disparity in asthma outcomes. Worldwide, childhood asthma appears to be increasing in prevalence, despite considerable improvements in our management and pharmacopeia to treat asthma. Numerous studies conducted in different countries, including the United States, have reported an increase in asthma prevalence of about 50% per decade. Globally, childhood asthma prevalence varies widely in different locales. A large international survey study of childhood asthma prevalence in 56 countries (International Study of Asthma and Allergies in Childhood) found a wide range in asthma prevalence, from 1.6 to 36.8%. Furthermore, asthma prevalence correlated well with reported allergic rhinoconjunctivitis and atopic eczema prevalence. Childhood asthma seems particularly common in modern metropolitan locales and is strongly linked with other allergic conditions. In contrast, children living in rural areas of developing countries and farming communities are less likely to develop asthma and allergy.

Approximately 80% of all asthmatics report disease onset prior to 6 yr of age. Of all young children who experience recurrent wheezing, however, only a minority will go on to have persistent asthma in later childhood. Early childhood risk factors for persistent asthma have been identified ( Table 143-1 ). A modified Asthma Predictive Index ( Table 143-2 ) optimizes risk factor assessments of young children to predict the risk for persistent asthma in later childhood. Allergy in young children has emerged as a major risk factor for the persistence of childhood asthma.

TABLE 143-1 -- Early Childhood Risk Factors for Persistent Asthma Parental asthma Allergy Atopic dermatitis Allergic rhinitis Food allergy Inhalant allergen sensitization Food allergen sensitization Severe lower respiratory tract infection Pneumonia Bronchiolitis requiring hospitalization Wheezing apart from colds Male gender Low birthweight Environmental tobacco smoke exposure
*

Reduced lung function at birth.

TABLE 143-2 -- Asthma Predictive Index for Children

MAJOR CRITERIA Parent asthma Eczema

MINOR CRITERIA Allergic rhinitis Wheezing apart from colds

Inhalant allergen sensitization Eosinophils 4% Food allergen sensitization Modified from Castro-Rodriguez JA, Holberg CH, Wright AL, et al: A clinical index to define risk of asthma in young children with recurrent wheezing. Am J Respir Crit Care 2000;162:14031406; and Guilbert TW, Morgan WJ, Zeiger RS, et al: Atopic characteristics of children with recurrent wheezing at high risk for the development of childhood asthma. J Allergy Clin Immunol 2004;114:12821287.

Through a statistically optimized model for preschool-age children with frequent wheezing in the past year,one major criterion OR two minor criteria provide a high specificity (97%) and positive predictive value (77%) for persistent asthma into later childhood (Tucson Children's Respiratory Study;Tucson, AZ).

Types of Childhood Asthma.

Asthma is considered to be a common clinical presentation of intermittent, recurrent wheezing and/or coughing, resulting from different airways pathologic processes underlying different types of asthma. There are 2 main types of childhood asthma: (1) recurrent wheezing in early childhood, primarily triggered by common viral infections of the respiratory tract; and (2) chronic asthma associated with allergy that persists into later childhood and often adulthood. A 3rd type of childhood asthma typically emerges in females who develop obesity and early-onset puberty (by 11 yr of age). Some children may be hypersensitive to common air pollutants (environmental tobacco smoke, ozone) such that these exposures might not only make existing asthma worse, but they may also have a causal role in the susceptible. Similarly, although asthma mediated by occupational exposures is often not considered in children, some are raised in settings where occupational-type exposures can mediate asthma if they are susceptible (on farms or with animals in the home, with increased endotoxin). Triad asthma, characteristically associated with hyperplastic sinusitis/nasal polyposis and hypersensitivity to aspirin and nonsteroidal anti-inflammatory medications (ibuprofen), rarely has its onset in childhood. The most common persistent form of childhood asthma is that associated with allergy.
PATHOGENESIS.

Airflow obstruction in asthma is the result of numerous pathologic processes. In the small airways, airflow is regulated by smooth muscle encircling the airways lumens; bronchoconstriction of these bronchiolar muscular bands restricts or blocks airflow. A cellular inflammatory infiltrate and exudates distinguished by eosinophils, but also including other inflammatory cell types (neutrophils, monocytes, lymphocytes, mast cells, basophils), can fill

and obstruct the airways and induce epithelial damage and desquamation into the airways lumen. Helper T lymphocytes and other immune cells that produce pro-allergic, proinflammatory cytokines (IL-4, IL-5, IL-13) and chemokines (eotaxin) mediate this inflammatory process. Pathogenic immune responses and inflammation may also result from a breach in normal immune regulatory processes (regulatory T lymphocytes that produce IL-10 and transforming growth factor [TGF]) that dampen effector immunity and inflammation when they are no longer needed. Airways inflammation is linked to AHR or hypersensitivity of airways smooth muscle to numerous provocative exposures that act as triggers ( Table 143-3 ), as well as airways edema, basement membrane thickening, subepithelial collagen deposition, smooth muscle and mucous gland hypertrophy, and mucus hypersecretionall processes that contribute to airflow obstruction (see Chapter 139 ).

TABLE 143-3 -- Asthma Triggers Common viral infections of the respiratory tract Aeroallergens in sensitized asthmatics Animal dander Indoor allergens Dust mites Cockroaches Molds Seasonal aeroallergens Pollens (trees, grasses, weeds) Seasonal molds Environmental tobacco smoke Air pollutants Ozone Sulfur dioxide Particulate matter Wood- or coal-burning smoke Endotoxin, mycotoxins

Dust Strong or noxious odors or fumes Perfumes, hairsprays Cleaning agents Occupational exposures Farm and barn exposures Formaldehydes, cedar, paint fumes Cold air, dry air Exercise Crying, laughter, hyperventilation Co-morbid conditions Rhinitis Sinusitis Gastroesophageal reflux

CLINICAL MANIFESTATIONS AND DIAGNOSIS.

Intermittent dry coughing and/or expiratory wheezing are the most common chronic symptoms of asthma. Older children and adults will report associated shortness of breath and chest tightness; younger children are more likely to report intermittent, nonfocal chest pain. Respiratory symptoms can be worse at night, especially during prolonged exacerbations triggered by respiratory infections or inhalant allergens. Daytime symptoms, often linked with physical activities or play, are reported with greatest frequency in children. Other asthma symptoms in children can be subtle and nonspecific, including self-imposed limitation of physical activities, general fatigue (possibly due to sleep disturbance), and difficulty keeping up with peers in physical activities. Asking about previous experience with asthma medications (bronchodilators) may provide a history of symptomatic improvement with treatment that supports the diagnosis of asthma. Lack of improvement with bronchodilator and corticosteroid therapy is inconsistent with underlying asthma and should prompt more vigorous consideration of asthma-masquerading conditions. Asthma symptoms can be triggered by numerous common events or exposures: physical exertion and hyperventilation (laughing), cold or dry air, and airways irritants (see Table 143-3 ).

Exposures that induce airways inflammation, such as infections (respiratory syncytial virus, metapneumovirus, torquetenovirus, rhinovirus, parainfluenza virus, influenza virus, adenovirus, Mycoplasma pneumonia, Chlamydia pneumoniae), and inhaled allergens, also increase AHR to irritant exposures. Numerous occupational exposures incite asthma in some adults. Similarly, some susceptible children might be chronically exposed to these same airways toxicants in their home or school environments, leading to occupational-type asthma in children. Accordingly, an environmental history is essential for optimal asthma diagnosis and management (see Chapter 140 ). The presence of risk factors, such as a history of other allergic conditions (allergic rhinitis, allergic conjunctivitis, atopic dermatitis, food allergies), parental asthma, and/or symptoms apart from colds, supports the diagnosis of asthma. During routine clinic visits, children with asthma commonly present without abnormal signs, which stresses the importance of the medical history in diagnosing asthma. Some may exhibit a dry, persistent cough. The chest examination is often normal. Deeper breaths can sometimes elicit otherwise undetectable wheezing. In clinic, quick resolution (within 10 min) or convincing improvement in symptoms and signs of asthma with administration of a short-acting inhaled beta-agonist (SABA [albuterol]) is supportive of the diagnosis of asthma. During asthma exacerbations, expiratory wheezing and a prolonged expiratory phase can usually be appreciated by auscultation. Decreased breath sounds in some of the lung fields, commonly the right lower posterior lobe, are consistent with regional hypoventilation owing to airways obstruction. Crackles (or rales) and rhonchi can sometimes be heard, resulting from excess mucus production and inflammatory exudate in the airways. The combination of segmental crackles and poor breath sounds can indicate lung segmental atelectasis that is difficult to distinguish from bronchial pneumonia and can complicate acute asthma management. In severe exacerbations, the greater extent of airways obstruction causes labored breathing and respiratory distress manifested as inspiratory and expiratory wheezing, increased prolongation of exhalation, poor air entry, suprasternal and intercostal retractions, nasal flaring, and accessory respiratory muscle use. In extremis, airflow may be so limited that wheezing cannot be heard.
DIFFERENTIAL DIAGNOSIS.

Many childhood respiratory conditions can present with symptoms and signs similar to asthma ( Table 143-4 ). Besides asthma, other common causes of chronic, intermittent coughing include rhinosinusitis and gastro-esophageal reflux (GER). Both GER and chronic sinusitis can be challenging to diagnose in children. Often, GER is clinically silent in children, and children with chronic sinusitis do not report sinusitis-specific symptoms such as localized sinus pressure or tenderness. In addition, both GER and rhinosinusitis are often co-morbid conditions with childhood asthma and, if not specifically treated, make asthma difficult to manage.

TABLE 143-4 -- Differential Diagnosis of Childhood Asthma UPPER RESPIRATORY TRACT CONDITIONS Allergic rhinitis[*] Chronic rhinitis[*]

Sinusitis[*] Adenoidal or tonsillar hypertrophy Nasal foreign body MIDDLE RESPIRATORY TRACT CONDITIONS Laryngotracheobronchomalacia[*] Laryngotracheobronchitis (e.g., pertussis)[*] Laryngeal web, cyst, or stenosis Vocal cord dysfunction[*] Vocal cord paralysis Tracheoesophageal fistula Vascular ring, sling, or external mass compressing on the airway (e.g., tumor) Foreign body aspiration[*] Chronic bronchitis from environmental tobacco smoke exposure[*] Toxic inhalations LOWER RESPIRATORY TRACT CONDITIONS Bronchopulmonary dysplasia (chronic lung disease of preterm infants) Viral bronchiolitis[*] Gastroesophageal reflux[*] Causes of bronchiectasis: Cystic fibrosis Immune deficiency Allergic bronchopulmonary mycoses (e.g., aspergillosis)

Chronic aspiration Immotile cilia syndrome, primary ciliary dyskinesia Bronchiolitis obliterans Interstitial lung diseases Hypersensitivity pneumonitis Pulmonary eosinophilia, Churg-Strauss vasculitis Pulmonary hemosiderosis Tuberculosis Pneumonia Pulmonary edema (e.g., congestive heart failure) Medications associated with chronic cough Acetylcholinesterase inhibitors -adrenergic antagonists
*

More common asthma masqueraders.

In early life, chronic coughing and wheezing can indicate recurrent aspiration, tracheobronchomalacia, a congenital anatomic abnormality of the airways, foreign body aspiration, cystic fibrosis, or bronchopulmonary dysplasia. In older children and adolescents, vocal cord dysfunction (VCD) can present as intermittent daytime wheezing. In this condition, the vocal cords close inappropriately, during inspiration and sometimes exhalation, producing shortness of breath, coughing, throat tightness, and often audible laryngeal wheezing and/or stridor. In most VCD cases, spirometric lung function testing will reveal truncated and inconsistent inspiratory and expiratory flow-volume loops, a pattern that differs from the reproducible pattern of airflow limitation in asthma that improves with bronchodilators. VCD may also be visualized with laryngoscopy. VCD can coexist with asthma. VCD does not respond to traditional asthma therapy. Speech therapy is the treatment of choice for VCD. In some locales, hypersensitivity pneumonitis (farming communities, homes of bird owners), pulmonary parasitic infestations (rural areas of developing countries), or tuberculosis may be common causes of chronic coughing and/or wheezing. Rare asthma-masquerading conditions in childhood include bronchiolitis obliterans; interstitial lung diseases; primary ciliary dyskinesias; humoral immune deficiencies; allergic bronchopulmonary mycoses; congestive heart failure; mass lesions in or compressing the larynx, trachea, or bronchi; and medication-induced coughing

and/or wheezing as an adverse effect. Chronic pulmonary diseases often produce clubbing; this is a very unusual finding in childhood asthma.
LABORATORY FINDINGS.

Lung function tests can help to confirm the diagnosis of asthma and determine disease severity.
Pulmonary Function Testing.

Forced expiratory airflow measures are helpful in diagnosing and monitoring asthma and in assessing efficacy of therapy. Lung function testing is particularly helpful in children with asthma who are poor perceivers of airflow obstruction or when physical signs of asthma do not occur until airflow obstruction is severe. Many asthma guidelines promote spirometric measures of airflow and lung volumes during forced expiratory maneuvers as standard for asthma assessment. Spirometry is helpful as an objective measure of airflow limitation ( Fig. 143-2 ). Knowledgeable personnel are needed to perform and interpret spirometry tests. Valid spirometric measures are dependent on a patient's ability to perform properly a full, forceful, and prolonged expiratory maneuver, usually feasible in children >6 yr of age (with some younger exceptions). Reproducible spirometric efforts are an indicator of test validity; if, on 3 attempts, the FEV1 (forced expiratory volume in 1 sec) is within 5%, then the highest FEV1 effort of the 3 is used. This standard utilization of the highest of 3 reproducible efforts is indicative of the effort-dependence of reliable spirometric testing.

Figure 143-2 Spirometry. A, Spirometric flow-volume loops. A is an expiratory flow-volume loop of a nonasthmatic, without airflow limitation. B through E are expiratory flow-volume loops in asthmatic patients with increasing degrees of airflow limitation (B is mild; E is severe). Note the scooped or concave appearance of the asthmatic expiratory flow-volume loops; with increasing obstruction, there is greater scooping. B, Spirometric volume-time curves. Subject 1 is a nonasthmatic; subject 2 is an asthmatic. Note how the FEV1 and FVC lung volumes are obtained. The FEV1 is the volume of air exhaled in the 1st sec of a forced expiratory effort. The FVC is the total volume of air exhaled during a forced expiratory effort. Note that subject 2's FEV 1 and FEV1/FVC ratio are smaller than subject 1's, demonstrating airflow limitation. Also, subject 2's FVC is very close to what is expected. FEV 1, forced expiratory volume in 1 sec; FVC, forced vital capacity.

In asthma, airways blockage results in reduced airflow with forced exhalation and smaller partial-expiratory lung volumes (see Fig. 143-2 ). Because asthmatics are typically hyperinflated, FEV1 can be simply adjusted for full expiratory lung volumethe forced vital capacity (FVC) with an FEV1/FVC ratio. Generally, an FEV1/FVC ratio <0.80 indicates significant airflow obstruction ( Table 143-5 ). Normative values for FEV1 have been determined for children, based on height, gender, and ethnicity. Abnormally low FEV1 as a percentage of predicted norms is 1 of 4 criteria used to determine asthma severity in the National Institutes of Health (NIH) sponsored asthma guidelines. The guidelines cutoff criteria of FEV1 <80% and <60% of predicted for moderate and severe asthma, respectively, are controversial for children with asthma, many of whom can have near-normal or even supra-normal airflow despite having the other hallmarks of moderate to severe disease.

TABLE 143-5 -- Lung Function Abnormalities in Asthma Spirometry (in clinic) Airflow limitation Low FEV1 (relative to percentage of predicted norms) FEV1/FVC ratio <0.80 Bronchodilator response (to inhaled -agonist) Improvement in FEV1 12% or 200 mL[*] Exercise challenge Worsening in FEV1 15%[*] Daily peak flow or FEV 1 monitoring: day to day and/or AM-to-PM variation 20%[*]

FEV1, forced expiratory volume in 1 sec; FVC, forced vital capacity.

Main criteria consistent with asthma.

Such measures of airflow alone, however, are not diagnostic of asthma, because numerous other conditions can cause airflow reduction. Bronchodilator response to an inhaled -agonist (e.g., albuterol) is greater in asthmatics vs non-asthmatics; an improvement in FEV1 12% or >200 mL is consistent with asthma. Bronchoprovocation challenges can be helpful in diagnosing asthma and optimizing asthma management. Asthmatic airways are hyperresponsive and

therefore more sensitive to inhaled methacholine, histamine, and cold or dry air. The degree of AHR to these exposures correlates to some extent with asthma severity and airways inflammation. Although bronchoprovocation challenges are carefully dosed and monitored in an investigational setting, their use is rarely practical in a general practice setting. Exercise challenges (aerobic exertion or running for 68 min) can help to identify children with exercise-induced bron chospasm. Although the airflow response of non-asthmatics to exercise is to increase functional lung volumes and improve FEV1 slightly (510%), exercise often provokes airflow obstruction in inadequately treated asthmatics. Accordingly, in asthmatics, FEV1 typically decreases during or after exercise by >15% (see Table 143-5 ). The onset of exercise-induced bronchospasm is usually within 15 min after a vigorous exercise challenge and can spontaneously resolve within 3060 min. Studies of exercise challenges in school-age children typically identify an additional 510% with exercise-induced bronchospasm and previously unrecognized asthma. Exercise challenges can induce severe asthma exacerbations in at-risk patients; careful patient selection for exercise challenges and preparedness for severe asthma exacerbations are required. Measuring exhaled nitric oxide (FENO), a marker of airway inflammation in asthma, can help titrate medications and confirm the diagnosis of asthma. Peak expiratory flow (PEF) monitoring devices provide a simple and inexpensive home-use tool to measure airflow and can be helpful in a number of circumstances ( Fig. 143-3 ). Poor perceivers of airflow obstruction due to asthma can benefit by monitoring PEFs daily to assess objectively airflow as an indicator of asthma control or problems that would be more sensitive than their symptom perception. PEFs vary in their ability to detect airflow obstruction; in some patients, PEFs decline only when airflow obstruction is severe. Therefore, PEF monitoring should be started by measuring morning and evening PEFs (best of 3 attempts) for several weeks for patients to practice the technique, to determine a personal best, and to correlate PEF values with symptoms (and ideally spirometry). PEF variation >20% is consistent with asthma (see Fig. 143-3 and Table 143-5 ).

Figure 143-3 An example of the role of peak flow monitoring in childhood asthma. A, Peak expiratory flows (PEFs) performed and recorded twice daily, in the morning (am) and evening (pm), over 1 mo in an asthmatic child. This child's personal best PEF is 220 L/min; therefore, green zone (>80100% of best) is 175220 L/min; yellow zone (5080%) is 110175 L/min; and red zone (<50%) is <110 L/min. Note that this child's pm PEFs are almost always in the green zone, whereas his am PEFs are often in the yellow or red zone. This illustrates the typical diurnal am-to-pm variation of inadequately controlled asthma. B, PEFs performed twice daily, in the morning (am) and evening (pm), over 1 mo in an asthmatic child who developed an asthma exacerbation from a viral respiratory tract infection. Note that the child's PEF values were initially in the green zone. A viral respiratory tract infection led to asthma worsening, with a decline in PEF to the yellow zone that continued to worsen until PEFs were in the red zone. At that point, a 4-day prednisone course was administered, followed by improvement in PEF back to the green zone.

Radiology.

Chest radiographs (posteroanterior and lateral views) in children with asthma often appear to be normal, aside from subtle and nonspecific findings of hyperinflation (flattening of the diaphragms) and peribronchial thickening ( Fig. 143-4 ). Chest radiographs can be helpful in identifying abnormalities that are hallmarks of asthma masqueraders (aspiration pneumonitis, hyperlucent lung fields in bronchiolitis obliterans), and complications during asthma exacerbations (atelectasis, pneumomediastinum, pneumothorax). Some lung abnormalities can

be better appreciated with high-resolution, thin-section chest CT scans. Bronchiectasis is sometimes difficult to appreciate on chest radiograph, but is clearly seen on CT scan and implicates an asthma masquerader such as cystic fibrosis, allergic bronchopulmonary mycoses (aspergillosis), ciliary dyskinesias, or immune deficiencies.

Figure 143-4 A 4-year-old boy with asthma. Frontal (A) and lateral (B) radiographs show pulmonary hyperinflation and minimal peribronchial thickening. No asthmatic complication is apparent.

Other tests, such as allergy testing to assess sensitization to inhalant allergens, help with the management and prognosis of asthma. In a comprehensive U.S. study of 512 yr old asthmatic children (Childhood Asthma Management Program [CAMP]), 88% had inhalant allergen sensitization by allergy prick skin testing.
TREATMENT.

The key elements to optimal asthma management are well recognized ( Fig. 143-5 ). The NIH National Heart, Lung and Blood Institute (NHLBI) developed current asthma management guidelines. For childhood asthma, a joint publication of the American Academy of Allergy, Asthma and Immunology, the American Academy of Pediatrics, and the NIH, entitled Pediatric Asthma: Promoting Best Practice, has been updated to reflect the 2002 National Asthma Education and Prevention Program (NAEPP) Update. These guidelines describe 4 principle components to optimal asthma management ( Table 143-6 ).

Figure 143-5 The key elements to optimal asthma management.

TABLE 143-6 -- Four Components of Optimal Asthma Management REGULAR ASSESSMENT AND MONITORING Asthma checkups Every 24 wk until good control is achieved 24 per yr to maintain good control

Lung function monitoring CONTROL OF FACTORS CONTRIBUTING TO ASTHMA SEVERITIY Eliminate or reduce problematic environmental exposures Treat co-morbid conditions: rhinitis, sinusitis, gastroesophageal reflux ASTHMA PHARMACOTHERAPY Long-term-control vs quick-relief medications Classification of asthma severity for anti-inflammatory pharmacotherapy Step-up, step-down approach Asthma exacerbation management PATIENT EDUCATION Provide a two-part care plan Daily management Action plan for asthma exacerbations

Regular Assessment and Monitoring.

Asthma management can be optimized through regular clinic visits every 24 wk until good asthma control is achieved. Two to 4 asthma checkups per year are recommended for maintaining good asthma control. During these visits, the optimal goals of asthma control can be assessed by determining the: (1) frequency of asthma symptoms during the day, at night, and with physical exercise; (2) frequency of rescue SABA medication use and refills; (3) number and sever ity of asthma exacerbations since the last visit; and (4) participation in school, sports, and other preferred activities (see Fig. 143-5 ). Lung function testing (spirometry) is recommended at least annually and more often if asthma is inadequately controlled or lung function is abnormally low. PEF monitoring at home can be helpful when assessing asthmatic children with poor symptom perception, other causes of chronic coughing in addition to asthma, moderate to severe asthma, or a history of severe asthma exacerbations. PEF monitoring is feasible in children as young as 4 yr old and who are able to master this skill. Use of a stoplight zone system, tailored to each child's personal best PEFs, can optimize effectiveness and interest (see Fig 143-3 ): The green zone (80100% of personal best) indicates good control; the yellow zone (5080%) indicates less than optimal control and necessitates increased awareness and treatment; whereas the red zone (<50%) indicates poor control and increased likelihood of

an exacerbation, requiring immediate intervention. In actuality, these ranges are approximate and may need to be adjusted for many asthmatic children by raising the ranges that indicate inadequate control (in the yellow zone from 70 to 90%). The NAEPP guidelines recommend at least once-daily PEF monitoring, preferably in the morning when peak flows are typically lower.
Control of Factors Contributing to Asthma Severity.

Controllable factors that can significantly worsen asthma can be generally grouped as (1) environmental exposures and (2) co-morbid conditions ( Table 143-7 ).

Control of Factors Contributing to Asthma Severity.

Controllable factors that can significantly worsen asthma can be generally grouped as (1) environmental exposures and (2) co-morbid conditions ( Table 143-7 ).

TABLE 143-7 -- Control of Factors Contributing to Asthma Severity ELIMINATE OR REDUCE PROBLEMATIC ENVIRONMENTAL EXPOSURES Environmental tobacco smoke elimination or reduction In home and automobiles Allergen exposure elimination or reduction in sensitized asthmatics Animal danders Pets (cats, dogs, rodents, birds) Pests (mice, rats) Dust mites Cockroaches Molds Other airway irritants Wood- or coal-burning smoke Strong chemical odors and perfumes (e.g., household cleaners) Dusts TREAT CO-MORBID CONDITIONS Rhinitis Sinusitis Gastroesophageal reflux ANNUAL INFLUENZA VACCINATION (UNLESS EGG-ALLERGIC)
ELIMINATING AND REDUCING PROBLEMATIC ENVIRONMENTAL EXPOSURES.

The majority of children with asthma have an allergic component to their disease; steps should be taken to investigate and minimize allergen exposures in sensitized asthmatics. For sensitized asthmatics, reduced exposure to perennial allergens in the home decreases asthma symptoms,

medication requirements, AHR, and asthma exacerbations. The important home allergens that are linked to asthma worsening differ between locales and even between homes. Common perennial allergen exposures include furred or feathered animals as pets (cats, dogs, ferrets, birds) or as pests (mice, rats) and occult indoor allergens such as dust mites, cockroaches, and molds. Although some sensitized children may report an increase in asthma symptoms on exposure to the allergen source, improvement from allergen avoidance may not become apparent without a sustained period of days to weeks away from the offending exposure. Tobacco, wood and coal smoke, dusts, strong odors, and noxious fumes can all aggravate asthma. These airways irritants should be eliminated or reduced from the homes and automobiles used by asthmatic children. School classrooms and daycare settings can also be sites of asthma-worsening environmental exposures. Eliminating or minimizing these exposures (furred pets in classrooms with sensitized asthmatic children) can reduce asthma symptoms, disease severity, and the amount of medication needed to achieve good asthma control. Annual influenza vaccination continues to be recommended for all asth matic children (except for those with egg allergy), although influenza is not responsible for the large majority of virus-induced asthma exacerbations experienced by children.
TREAT CO-MORBID CONDITIONS.

Rhinitis, sinusitis, and gastroesophageal reflux often accompany asthma and can mimic asthma symptoms and worsen disease severity. Indeed, these conditions with asthma are the 3 most common causes of chronic coughing. Effective management of these co-morbid conditions can often improve asthma symptoms and disease severity, such that less asthma medication is needed to achieve good asthma control. Gastroesophageal reflux (GER) is common in asthmatics, with a reported incidence of up to 64% with GER-related asthma symptoms. GER may worsen asthma through 2 postulated mechanisms: (1) aspiration of refluxed gastric contents (micro- or macro-aspiration); and (2) vagally-mediated reflex bronchospasm. Occult GER should be suspected in individuals with difficult-to-control asthma, especially patients with prominent asthma symptoms while eating or sleeping (in a horizontal position), or who prop themselves up in bed to reduce nocturnal symptoms. GER can be demonstrated by reflux of barium into the esophagus during a barium swallow procedure or by esophageal pH monitoring. Because radiographic studies lack sufficient sensitivity and specificity, extended esophageal pH monitoring is the method of choice for diagnosing GER. If significant GER is noted, reflux precautions should be instituted (no food 2 hr before bedtime, head of the bed elevated 6 in, avoid caffeinated foods and beverages) and medications such as proton pump inhibitors (omeprazole, lansoprazole) or H2-receptor antagonists (cimetidine, ranitidine) administered for 8 to 12 wk. Rhinitis is usually co-morbid with asthma, detected in 90% of asthmatic children. Rhinitis can be seasonal and/or perennial, with allergic and non-allergic components. Rhinitis complicates and worsens asthma via numerous direct and indirect mechanisms. Nasal breathing may reduce exercise-induced bronchospasm and lower airways dysfunction by humidifying and warming inspired air, and filtering out allergens and irritants that can trigger asthma and increase AHR. Reduction of nasal congestion and obstruction can help the nose to perform these humidifying, warming, and filtering functions. In asthmatics, improvement in rhinitis is also associated with improvement in AHR, lower airways inflammation, asthma symptoms, and asthma medication use. Optimal rhinitis management in children is similar to asthma management in regards to the importance of interventions to reduce nasal inflammation (see Chapter 142 ). Radiographic evidence for sinus disease is common in patients with asthma. There is usually significant improvement in asthma control in patients diagnosed and treated for sinus disease. A

coronal, screening or limited CT scan of the sinuses is the gold standard test for sinus disease and is often helpful if recurrent sinusitis has been suspected and treated without such evidence. If the patient with asthma has clinical and radiographic evidence for sinusitis, topical therapy to include nasal saline irrigations and possibly intranasal corticosteroids should be instituted, and a 23 wk course of antibiotics administered.
Principles of Asthma Pharmacotherapy.

The NAEPP guidelines offer a stepwise approach to management based on asthma severity categorized as mild intermittent, mild persistent, moderate persistent, and severe persistent asthma (Tables 143-8, 143-9, and 143-10 [8] [9] [10]). The classification of asthma severity is based on the following parameters: (1) frequency of daytime and (2) nighttime symptoms, (3) degree of airflow obstruction by spirometry, and/or (4) PEF variability (see Table 143-8 ). For younger children (<5 yr of age), management is primarily based on symptoms since young children cannot perform the maneuvers required for conventional lung function measurements (see Table 143-8 ). A major objective of this approach is to identify and treat all persistent asthma with anti-inflammatory controller medication. The type(s) and amount(s) of daily controller medications to be used are determined by the asthma severity rating. The three strikes rule is a handy memory aid for determining if an asthmatic child should receive controller therapy. Simply put, if an asthmatic child has asthma symptoms or uses quick-relief medication at least 3 times per wk, awakens at night due to asthma at least 3 times per mo, requires a refill for a quick-relief inhaler prescription at least 3 times per yr, experiences asthma exacerbations at least 3 times per yr, or requires short courses of systemic corticosteroids at least 3 times a yr, then that patient should receive daily controller therapy. In addition, according to the NAEPP guidelines, controller therapy can be considered for children who present with frequent exacerbations (at least 2 exacerbations occurring <6 wk apart). Inhaled corticosteroid (ICS) therapy is recommended as preferred therapy for all levels of asthma severity except for the mild intermittent category. Leukotriene pathway modifiers or sustained-release theophylline (only for patients >5 yr of age) are considered alternative controllers for mild persistent asthmatics. Combination therapy of a low-to-medium dose ICS with a long-acting -agonist (LABA; preferred) or a leukotriene modifier or theophylline is a mainstay therapy for moderate persistent asthma in older children and adults. While the use of medium-dose ICS alone is an alternative therapy for older children and adults with moderate persistent severity, for infants and young children, it is considered a preferred treatment for moderate persistent asthma. Severe persistent asthmatics should receive high-dose ICS, a long-acting bronchodilator, and routine oral corticosteroids if needed. Daily controller therapy is not recommended for mild intermittent asthma. SABAs are the recommended quick-reliever medications for symptoms and exercise pretreatment for all asthma severity levels.

TABLE 143-8 -- Classification of Asthma Severity FOR ADULTS AND CHILDREN AGE > 5 YEARS WHO CAN USE A SPIROMETER OR PEAK FLOW METER FEV1 or PEF[*] PEF % Predicted Variability Normal (%) Severe persistent Moderate persistent 4 3 Continual Daily Frequent >1/wk 60 >60<80 >30 >30

NIGHTS DAYS WITH WITH CLASSIFICATION STEP SYMPTOMS SYMPTOMS

NIGHTS DAYS WITH WITH CLASSIFICATION STEP SYMPTOMS SYMPTOMS

FOR ADULTS AND CHILDREN AGE > 5 YEARS WHO CAN USE A SPIROMETER OR PEAK FLOW METER FEV1 or PEF[*] PEF % Predicted Variability Normal (%)

Mild persistent

>2/wk, but <1 time/day

>2/mo

80

2030

Mild intermittent 1 2/wk <2/mo 80 <20 From National Asthma Education and Prevention Program Expert Panel Report. Based on clinical features before treatment; classification is determined by the patient's most severe feature. Guidelines for the Diagnosis and Management of AsthmaUpdate on Selected Topics (2002). NIH publication no: 025075.
* Perecentage of predicted norms for Forced Expiratory Volume in 1 sec (FEV1); percentage of personal best for Peak Expriatory Flow

(PEF).

TABLE 143-9 -- Stepwise Approach for Managing Infants and Young Children (5 Yr of Age) with Acute or Chronic Asthma;Treatment CLASSIFY SEVERITY: CLINICAL MEDICATIONS REQUIRED TO FEATURES BEFORE TREATMENT OR MAINTAIN LONG-TERM CONTROL ADEQUATE CONTROL

Symptoms/Night Step 4 Severe persistent

Daily Medications Preferred treatment High-dose inhaled corticosteroids AND Long-acting inhaled 2agonists AND, if needed, Corticosteroid tablets or syrup long term (2 mg/kg/day, generally do not exceed 60 mg/day).(Make repeat attempts to reduce systemic corticosteroids and maintain control with high-dose inhaled corticosteroids.)

Step 3 Moderate persistent

Preferred treatment Low-dose inhaled

CLASSIFY SEVERITY: CLINICAL FEATURES BEFORE TREATMENT OR ADEQUATE CONTROL

MEDICATIONS REQUIRED TO MAINTAIN LONG-TERM CONTROL

corticosteroids and longacting inhaled 2-agonists OR Medium-dose inhaled corticosteroids. Alternative treatment Low-dose inhaled corticosteroids and either leukotriene receptor antagonist or theophylline. If needed (particularly in patients with recurring severe exacerbations): Preferred treatment Medium-dose inhaled corticosteroids and longacting 2-agonists. Alternative treatment Medium-dose inhaled corticosteroids and either leukotriene receptor antagonist or theophylline. Preferred treatment Low-dose inhaled corticosteroid (with nebulizer or MDI with holding chamber with or without face mask or DPI). Alternative treatment Cromolyn (nebulizer is preferred or MDI with holding chamber) OR leukotriene receptor antagonist. Step 1 Mild intermittent Quick Relief All Patients Relief All Patients No daily medication needed. No daily medication needed.

Step 2 Mild persistent

CLASSIFY SEVERITY: CLINICAL FEATURES BEFORE TREATMENT OR ADEQUATE CONTROL

MEDICATIONS REQUIRED TO MAINTAIN LONG-TERM CONTROL

Bronchodilator as needed for symptoms. Intensity of treatment will depend on severity of exacerbation. Preferred treatment: Short-acting inhaled 2agonists by nebulizer or face mask and space/holding chamber Alternative treatment: Oral 2-agonist

With viral respiratory infection Bronchodilator q 46 hr up to 24 hr (longer with physician consult); in general, repeat no more than once every 6 wk Consider systemic corticosteroid if exacerbation is severe or patient has history of previous severe exacerbations

Use of short-acting 2-agonists >2 times/wk in intermittent asthma (daily, or increasing use in persistent asthma) may indicate the need to initiate (increase) long-term-control therapy. Note The stepwise approach is intended to assist, not replace, the clinical decision-making required to meet individual patient needs.

Step down Review treatment every 1 to 6 mo; a gradual stepwise reduction in treatment may be possible.

Step up If control is not maintained, consider step up. First, review patient medication technique, adherence, and environmental control. Classify severity: assign patient to most severe step in which any feature occurs. There are very few studies on asthma therapy for infants. Gain control as quickly as possible (a course of short systemic corticosteroids may be required); then step down to the least medication necessary to maintain control. Minimize use of short-acting inhaled 2-agonists. Overreliance on short-acting inhaled 2-agonists (e.g., use of approxi-mately one

GOALS OF THERAPY: ASTHMA CONTROL

CLASSIFY SEVERITY: CLINICAL FEATURES BEFORE TREATMENT OR ADEQUATE CONTROL

MEDICATIONS REQUIRED TO MAINTAIN LONG-TERM CONTROL canister/mo even if not using it every day) indicates inadequate control of asthma and the need to initiate or intensify long-termcontrol therapy.

Minimal or no chronic symptoms day or night

Minimal use of short-acting inhaled 2agonist

Provide parent education on asthma management and controlling environmental factors that make asthma worse (e.g., allergies and irritants). Consultation with an asthma specialist is recommended for patients with moderate or severe persistent asthma. Consider consultation for patients with mild persistent asthma.

Minimal or no exacerbations

Minimal or no adverse effects from medications

No limitations on activities; no school/parent's work missed

TABLE 143-10 -- Stepwise Approach for Managing Asthma in Adults and Children >5 Yr of Age: Treatment CLASSIFY SEVERITY: CLINICAL MEDICATIONS REQUIRED TO FEATURES BEFORE TREATMENT OR MAINTAIN LONG-TERM CONTROL ADEQUATE CONTROL Step 4 Severe persistent Daily Medications Preferred treatment High-dose inhaled corticosteroids AND Long-acting inhaled 2-agonists AND, if needed, Corticosteroid tablets or syrup long term (2 mg/kg/day,

CLASSIFY SEVERITY: CLINICAL FEATURES BEFORE TREATMENT OR ADEQUATE CONTROL

MEDICATIONS REQUIRED TO MAINTAIN LONG-TERM CONTROL

generally do not exceed 60 mg/day).(Make repeat attempts to reduce systemic corticosteroids and maintain control with high-dose inhaled corticosteroids.) Step 3 Moderate persistent Preferred treatment Low-to-medium dose inhaled corticosteroids and long-acting inhaled 2-agonists. Alternative treatment Increase inhaled corticosteroids within medium-dose range OR Low-to-medium dose inhaled corticosteroids and either leukotriene modifier or theophylline. If needed (particularly in patients with recurring severe exacerbations): Preferred treatment Increase inhaled corticosteroids with medium-dose range and add long-acting inhaled 2-agonists. Alternative treatment Increase inhaled corticosteroids within medium-dose range and add either leukotriene modifier or theophylline. Preferred treatment Low-dose inhaled

Step 2 Mild persistent

CLASSIFY SEVERITY: CLINICAL FEATURES BEFORE TREATMENT OR ADEQUATE CONTROL

MEDICATIONS REQUIRED TO MAINTAIN LONG-TERM CONTROL

corticosteroid. Alternative treatment (listed alphabetically): cromolyn, leukotriene modifier, nedocromil, OR sustained-release theophylline to serum concentration of 515 /mL. No daily medication needed.

Step 1 Mild intermittent Quick Relief All Patients

Short-acting bronchodilator: 24 puffs short-acting inhaled 2-agonists as needed for symptoms. Intensity of treatment will depend on severity of exacerbation; up to 3 treatments at 20-minute intervals or a single nebulizer treatment as needed. Course of systemic corticosteroids may be needed. Use of short-acting 2-agonists >2 times/wk in intermittent asthma (daily, or increasing use in persistent asthma) may indicate the need to initiate (increase) long-term-control therapy. Note The stepwise approach is meant to assist, not replace, the clinical decisionmaking required to meet individual patient needs.

Step down Review treatment every 1 to 6 mo; a gradual stepwise reduction in treatment may be possible. Step up If control is not maintained, consider step up. First, review patient medication technique, adherence, and environmental control.

Classify severity: assign patient to most severe step in which any feature occurs (PEF is % of personal best; FEV1 is % predicted). Gain control as quickly as possible (consider a short course of systemic corticosteroids); then step down to the least medication necessary to maintain control. Minimize use of short-acting inhaled

GOALS OF THERAPY: ASTHMA CONTROL

2-agonists. Overreliance on short-acting

CLASSIFY SEVERITY: CLINICAL FEATURES BEFORE TREATMENT OR ADEQUATE CONTROL

MEDICATIONS REQUIRED TO MAINTAIN LONG-TERM CONTROL inhaled 2-agonists (e.g., use of one canister/mo even if not using it every day) indicates inadequate control of asthma and the need to initiate or intensify long-term-control therapy.

Minimal or no chronic symptoms day or night Minimal or no exacerbations

Maintain (near) normal pulmonary function Minimal use of shortacting inhaled 2agonist Minimal or no adverse effects from medications

Provide education on self-management and controlling environmental factors that make asthma worse (e.g., allergens and irritants). Refer to an asthma specialist if there are difficulties controlling asthma or if step 4 care is required. Referral may be considered if step 3 care is required.

No limitations on activities; no school/work missed

From National Asthma Education and Prevention Program (NAEPP) Expert Panel Report. Guidelines for the Diagnosis and Management of Asthma-Update on Selected Topics. Washington, DC, NIH, 2002 (NIH publication no: 025075).
STEP-UP, STEP-DOWN APPROACH.

The NAEPP guidelines emphasize initiating higher-level controller therapy at the outset to establish prompt control, with measures to step down therapy once good asthma control is achieved. Initially, airflow limitation and the pathology of asthma may limit the delivery and efficacy of ICS such that stepping up to higher doses and/or combination therapy may be needed to gain asthma control. Fur thermore, ICS requires weeks to months of daily administration for optimal efficacy to occur. Combination pharmacotherapy can provide relatively immediate improvement while also providing daily ICS to improve long-term control. Asthma therapy can be stepped down after good asthma control has been achieved and ICS has had time to achieve optimal efficacy, by determining the least number or dose of daily controller medications that can maintain good control, thereby reducing the potential for medication adverse effects. The NAEPP guidelines recommend decreasing ICS dose by about 25% every 2 to 3 mo, as long as good asthma control is maintained. Other step-down options include reducing the frequency of controller therapy (bid to qd), discontinuing combination therapy while continuing ICS, or reducing the dose of ICS while maintaining combination therapy.
DELIVERY DEVICES AND INHALATION TECHNIQUE.

Inhaled medications are delivered as an aerosolized form in a metered-dose inhaler (MDI), as a dry powder inhaler (DPI) formulation, or in a suspension or solution form delivered via a nebulizer. In the past, MDIs, which require coordination and use of a spacer device, have dominated the market. Spacer devices, recommended for the administration of all MDI medications, are simple and inexpensive tools that: (1) decrease the coordination required to use MDIs, especially in young children; (2) improve the delivery of inhaled drug to the lower

airways; and (3) minimize the risk of propellant-mediated adverse effects (thrush). Optimal inhalation technique for each puff of MDI-delivered medication is a slow (5 sec) inhalation, then a 510 sec breath-hold. No waiting time between puffs of medication is needed. Young pre school-age children cannot perform this inhalation technique; MDI medications can then be delivered with a spacer and mask, using a different technique: each puff administered with regular breathing for about 30 sec or 510 breaths, a tight seal must be maintained, and talking, coughing, or crying will blow the medication out of the spacer. This technique will not deliver as much medication per puff when compared with the optimal MDI technique used by older children and adults. DPI devices (Diskus, Turbuhaler, Autohaler, Aerolizer) are popular because of their simplicity of use, albeit adequate inspiratory flow is needed. They are breath-actuated (the drug comes out only as it is breathed in) and spacers are not needed. Mouth rinsing is recommended after ICS use to rinse out ICS deposited on the oral mucosa and reduce the swallowed ICS and the risk of thrush. Nebulizers have been the mainstay of aerosol treatment for infants and young children. An advantage of using nebulizers is the simple technique required of relaxed breathing. The preferential nasal breathing, small airways, low tidal volume, and high respiratory rate of infants markedly increase the difficulty of inhaled drug targeting to the lung airways. Disadvantages of nebulizers include need for a power source, inconvenience in that treatments take about 5 min, expense, and potential for bacterial contamination.
ADHERENCE.

Asthma is a chronic condition that is often best managed with daily controller medication. Adherence with a daily regimen is commonly suboptimal; ICS are underused 60% of the time. Individuals who require an oral corticosteroid course due to an asthma exacerbation had used their ICS the least (<15% of the time). Adherence is poorer when prescribed frequency of medication administration is greater (34 times/24 hr). Controller formulations for twice- and even once-daily dosing can improve patient adherence. Misconceptions about controller medication efficacy and safety often underlie poor adherence and can be addressed by asking about such concerns at each visit.
Long-Term Controller Medications.

All levels of persistent asthma should be treated with daily medications to improve long-term control (Tables 143-11 and 143-12 [11] [12]). Such medications include ICS, LABAs, leukotriene modifiers, nonsteroidal anti-inflammatory agents, and sustained-release theophylline. An anti-IgE preparation, omalizumab (Xolair), has been approved by the Food and Drug Administration (FDA) for children 12 yr as an add-on therapy for patients with moderate to severe allergic asthma. Corticosteroids are the most potent and effective medications used to treat both the acute (administered systemically) and chronic (administered by inhalation) manifestations of asthma. They are available in inhaled, oral, and parenteral forms (see Table 143-12 ).

TABLE 143-11 -- Usual Dosages for Long-Term-Control Medications DOSAGE MEDICATION FORM ADULT DOSE CHILD DOSE[*] INHALED CORTICOSTEROIDS (SEE TABLE 143-12 ) SYSTEMIC CORTICOSTEROIDS Methylprednisolone 2, 4, 8, 16, 32 7.560 mg daily 0.252 mg/kg

MEDICATION

DOSAGE FORM mg tablets

ADULT DOSE in a single dose in AM or qod as needed for control Short-course burst to achieve control: 4060 mg/day as single or 2 divided doses for 310 days

CHILD DOSE[*] daily in single dose in AM or qod as needed for control Short-course burst: 12 mg/kg/day, maximum 60 mg/day for 310 days

Prednisolone

5 mg tablets, 5 mg/5 cc, 15 mg/5 cc,

Prednisone

1, 2.5, 5, 10, 20, 50 mg tablets; 5 mg/cc, 5 mg/5 cc

LONG-ACTING INHALED 2-AGONISTS (SHOULD NOT BE USED FOR SYMPTOM RELIEF OR FOR EXACERBATIONS. USE WITH INHALED CORTICOSTEROIDS.) Salmeterol MDI 21 g/puff DPI 50 g/blister Formoterol DPI 12 g/single-use capsule DPI 100, 250, or 500 g/50 g 2 puffs q 12 hours 1 blister q 12 hours 1 capsule q 12 hours 12 puffs q 12 hours 1 blister q 12 hours 1 capsule q 12 hours

COMBINED MEDICATION Fluticasone/Salmeterol 1 inhalation bid; dose depends on severity of asthma 1 inhalation bid; dose depends on severity of asthma

CROMOLYN AND NEDOCROMIL Cromolyn MDI 1 mg/puff Nebulizer 20 mg/ampule Nedocromil MDI 1.75 mg/puff 4 or 5 mg chewable tablet 24 puffs tid-qid 1 ampule tid-qid 24 puffs bid-qid 12 puffs tid-qid 1 ampule tid-qid 12 puffs bid-qid

LEUKOTRIENE MODIFIERS Montelukast 10 mg qhs 4 mg qhs (25 yrs)

MEDICATION

DOSAGE FORM 10 mg tablet

ADULT DOSE

CHILD DOSE[*] 5 mg qhs (614 yrs) 10 mg qhs (>14 yrs)

Zafirlukast Zileuton

10 or 20 mg tablet 300 or 600 mg tablet

40 mg daily (20 mg tablet bid) 2,400 mg daily (give tablets qid)

20 mg daily (711 yrs) (10 mg tablet bid)

METHYLXANTHINES (SERUM MONITORING IS IMPORTANT [SERUM CONCENTRATION OF 515 mG/ML AT STEADY STATE]). Theophylline Liquids, sustainedrelease tablets, and capsules Starting dose 10 mg/kg/day up to 300 mg max; usual max 800 mg/day Starting dose 10 mg/kg/day; usual max: <1 year of age: 0.2 (age in wk) +5 = mg/kg/day 1 year of age: 16 mg/kg/day

From National Asthma Education and Prevention Program (NAEPP) Expert Panel Report. Guidelines for the Diagnosis and Management of AsthmaUpdate on Selected Topics. Washington, DC, NIH, 2002. (NIH publication no: 025075).
* Children 12 years of age.

TABLE 143-12 -- Estimated Comparative Daily Dosages for Inhaled Corticosteroids LOW DAILY MEDIUM DAILY HIGH DAILY DOSE DOSE DOSE DRUG Adult Child[*] 84336 g 80160 g Adult 504840 g 240840 g Child[*] 336672 g 160320 g 400800 g 1.0 g 1,000 1,250 g 175440 g 200400 g >2,000 g Adult Child[*] Beclomethasone CFC 42 or 84 168504 g/puff g Beclomethasone HFA 40 or 80 80240 g/puff g Budesonide DPI 200 g/inhalation Inhalation suspension for nebulization (child dose) Flunisolide 250 g/puff Fluticasone MDI: 44, 110, or 220 g/puff DPI: 50, 100, or 250 g/inhalation Triamcinolone acetonide 100 g/puff >840 g >672 g >480 g >320 g >1,200 >800 g g 2.0 g >1,250 g

200600 200400 6001,200 g g g 0.5 g 500 500750 1,000 1,000 g g 2,000 g 88264 g 88176 g 264660 g 300600 g

>660 g >440 g >600 g >400 g >2,000 g >1,200 g

100300 100200 g g 400 400800 1,000 g g

1,000 8001,200 2,000 g g

From National Asthma Education and Prevention Program (NAEPP) Expert Panel Report. Guidelines for the Diagnosis and Management of AsthmaUpdate on Selected Topics. (2002). NIH publication no: 025075.
* Children 12 years of age.

INHALED CORTICOSTEROIDS (ICS).

The NAEPP guidelines recommend daily ICS therapy as the treatment of choice for all patients with persistent asthma (see Table 143-9 ). ICS therapy has been shown to reduce asthma symptoms, improve lung function, reduce AHR, reduce rescue medication use and, most important, reduce urgent care visits, hospitalizations, and prednisone use for asthma exacerbations by about 50%. ICS therapy may lower the risk of death due to asthma. It can achieve all of the goals of asthma management and, as a result, is viewed as first-line treatment for persistent asthma. There are currently 5 ICSs that are approved by the FDA, and the NAEPP guidelines provide an equivalence classification (see Table 143-12 ), although direct comparisons of efficacy and safety outcomes in children are lacking. Newer forms are being developed (mometasone furoate, ciclesonide) that may enhance the efficacy-to-safety profile of ICS therapy while allowing for less frequent dosing. ICSs are available in MDIs, DPIs, or in suspension for nebulization. Fluticasone propionate, mometasone furoate and, to a lesser extent, budesonide are considered 2nd-generation ICSs in that they have increased anti-inflammatory potency and reduced systemic bioavailability for potential adverse effects, owing to extensive first-pass hepatic metabolism. The selection of the initial ICS dose is based on the determination of disease severity. A fraction of the initial ICS dose is often sufficient to maintain good control after this has been achieved. Although ICS therapy has been widely used in adults with persistent asthma, its application in children has lagged due to concerns of the potential for adverse effects with chronic use. Generally, clinically significant adverse effects that occur with chronic systemic corticosteroid therapy have not been seen or have been only very rarely reported in children receiving ICSs in recommended doses. The risk of adverse effects from ICS therapy is related to the dose and frequency with which ICSs are given ( Table 143-13 ). High doses (1,000 g/day in children) and frequent administration (4 times/day) are more likely to cause local and systemic adverse effects. Children who are maintained on higher ICS doses are also likely to require systemic corticosteroid courses for asthma exacerbations, further increasing the risk of corticosteroid adverse effects. TABLE 143-13 -- Risk Assessment for Corticosteroid Adverse Effects CONDITIONS RECOMMENDATIONS Low risk (1 risk factor[*]) Low- to medium-dose ICS (see Table 143-10 ) Monitor blood pressure and weight with each physician visit Measure height annually (stadiometry); monitor periodically for declining growth rate and pubertal developmental delay Encourage regular physical exercise Adequate dietary calcium and vitamin D with additional supplements for daily

CONDITIONS

RECOMMENDATIONS calcium if needed Avoid smoking and alcohol Ensure TSH status if with history of thyroid abnormality As above, plus: Yearly ophthalmologic evaluations to monitor for cataracts or glaucoma Baseline bone densitometry (DEXA scan) Consider at increased risk for adrenal insufficiency, esp. with physiologic stressors (e.g., surgery, accident, significant illness) As above, plus: DEXA scan: if DEXA Z score <-1.0, recommend close monitoring (every 12 mo) Consider referral to a bone or endocrine specialist Bone age Complete blood count Serum calcium, phosphorus, alkaline phosphatase Urine calcium and creatinine Testosterone in males, estradiol in amenorrheic premenopausal women, vitamin D (25-OH and 1,25-OH vitamin D), parathyroid hormone, osteocalcin Urine telopeptides for those on chronic systemic or frequent oral corticosteroid treatment Assume adrenal insufficiency for physiologic stressors (e.g., surgery, accident, significant illness)

Medium risk

(if >1 risk factor,[*] consider evaluating as high risk) High-dose ICS (see Table 143-10 ) At least 4 oral corticosteroid courses/yr

High risk

Chronic systemic corticosteroids (>7.5 mg daily or equivalent for >1 mo) 7 oral corticosteroid bursts/year Very high dose ICS (e.g., fluticasone propionate 800 g/day)

ICS, inhaled corticosteroid; TSH, thyroid-stimulating hormon

Risk factors for osteoporosis: Presence of other chronic illness(es), medications (corticosteroids, anticonvulsants, heparin, diuretics), low body weight, family history of osteoporosis, significant fracture history disproportionate to trauma, recurrent falls, impaired vision, low dietary calcium and vitamin D intake, and lifestyle factors (decreased physical activity, smoking, and alcohol intake).

The most commonly encountered adverse effects from ICSs are local: oral candidiasis (thrush) and dysphonia (hoarse voice). Thrush results from propellant-induced mucosal irritation and local immunosuppression. Dysphonia occurs from vocal cord myopathy. These effects are dose-

dependent and are most common in individuals on high-dose ICS and/or oral cortico-steroid therapy. The incidence of these local effects can be greatly minimized by using a spacer with MDI ICS because spacers reduce oropharyngeal deposition of the drug and propellant. Mouth rinsing using a swish and spit technique after ICS use is also recommended. The potential for growth suppression with long-term ICS use has been a concern. Complicating this issue is the observation that poorly controlled asthma can adversely affect growth. In the long-term, prospective NIH-sponsored CAMP study, after a mean of 4.3 yr of therapy, children with mild to moderate asthma randomized to budesonide (400 g/day) had grown 22.7 cm, whereas those randomized to placebo had grown 23.8 cma 1.1 cm difference. Of importance, this 1.1 cm difference occurred primarily in the 1st year of ICS therapy, indicating that the growth reduction was a transient, not progressive phenomenon. A controlled study found no difference in the measured vs expected adult heights of asthmatic children who received inhaled budesonide (400 g/day) for >9 yr. Transient growth suppression was noted in the 1st few years of therapy, with eventual catch-up growth and no effect on final adult height. Two large pediatric studies that have evaluated the effect of long-term ICS on bone mineral density failed to find a relationship between ICS use and diminished bone mineral density (see Chapter 705 ). Although these studies cannot predict a significant effect of ICS therapy on osteoporosis in later adulthood, improved asthma control may result in less corticosteroid therapy (oral, inhaled) needed over time. These findings were with budesonide at doses of about 400 g/day; higher doses of ICSs, especially those with increased potency, have a greater potential for adverse effects. Hence, corticosteroid adverse effects screening and osteoporosis prevention measures are recommended for patients on higher doses of ICSs, as these patients are also likely to require systemic courses for exacerbations (see Table 143-13 ).
SYSTEMIC CORTICOSTEROIDS.

ICS therapy has allowed the large majority of children with asthma to maintain good disease control without maintenance (qod) oral corticosteroids. Oral corticosteroid therapy is used primarily to treat asthma exacerbations and in rare patients with severe disease who remain symptomatic despite optimal use of other asthma medications. In these severe asthmatics, every attempt should be made to exclude any co-morbid conditions and to keep the oral corticosteroid dose at 20 mg qod. Doses exceeding this amount are associated with numerous adverse effects (see Chapter 578 ). To determine the need for continued oral corticosteroid therapy, a taper of the oral corticosteroid dose (over weeks to several months) should be considered, with close monitoring of the patient's symptoms and lung function. When administered orally, prednisone, prednisolone, and methylprednisolone are rapidly and nearly completely absorbed, with peak plasma concentrations occurring within 12 hr. Prednisone is an inactive pro-drug that requires biotransformation via first-pass hepatic metabolism to prednisolone, its active form. Corticosteroids are metabolized in the liver into inactive compounds, with the rate of metabolism influenced by drug interactions and disease states. Anticonvulsants (phenytoin, phenobarbital, carbamazepine) increase the metabolism of prednisolone, methylprednisolone, and dexamethasone, with methylprednisolone most significantly affected. Rifampin also enhances the clearance of corticosteroids and can result in diminished therapeutic effect. Other medications (ketoconazole, oral contraceptives) can significantly delay corticosteroid metabolism. Macrolide antibiotics (erythromycin, clarithromycin, troleandomycin) delay the clearance of only methylprednisolone. Children who require chronically administered oral cortico-steroids are at risk of developing associated adverse effects over time. Essentially all major organ systems can be adversely

affected by chronically administered oral corticosteroid therapy (see Chapter 578 ). Some of these effects occur immediately (metabolic effects). Others can develop insidiously over several months to years (growth suppression, osteoporosis, cataracts). Most adverse effects occur in a cumulative dose- and duration-dependent manner. Children who require routine or frequent short courses of oral corticosteroids, especially with concurrent high-dose ICSs, should receive corticosteroid adverse effects screening (see Table 143-13 ) and osteoporosis preventive measures (see Chapter 705 ).
LONG-ACTING INHALED -AGONIST (LABA).

Although LABAs (salmeterol, formoterol) are -agonists, they are consid ered to be daily controller medications, not intended for use as rescue medication for acute asthma symptoms or exacerbations, nor as monotherapy for persistent asthma. Salmeterol has a prolonged onset of action, with maximal bronchodilation about 1 hr after administration, whereas formoterol has an onset of action within 510 min. Both medications have a prolonged duration of effect of at least 12 hr. Given their long duration of action, they are well suited for patients with nocturnal asthma and for individuals who require frequent SABA use during the day to prevent exercise-induced bronchospasm. Their major role is as an add-on agent in patients who are suboptimally controlled on ICS therapy alone. For those patients, several studies have found the addition of LABA to ICS to be superior to doubling the dose of ICS, especially on day and nocturnal symptoms. There are also controller formulations that combine ICS with LABA (fluticasone/salmeterol, budesonide/formoterol).
LEUKOTRIENE-MODIFYING AGENTS.

Leukotrienes are potent pro-inflammatory mediators that can induce bronchospasm, mucus secretion, and airways edema. Two classes of leukotriene modifiers have been developed: inhibitors of leukotriene synthesis and leukotriene receptor antagonists (LTRA). Zileuton, the only leukotriene synthesis inhibitor, is not approved for use in children <12 yr of age. Because zileuton requires administration 4 times daily, can result in elevated liver function enzymes in 2 4% of patients, and interacts with medications metabolized via the cytochrome-P450 system, it is rarely prescribed for children with asthma. LTRAs have bronchodilator and targeted anti-inflammatory properties and reduce exercise-, aspirin-, and allergen-induced bronchoconstriction. They are recommended as an alternative treatment for mild persistent asthma and as an add-on medication to ICS for moderate persistent asthma. Two LTRAs are FDA-approved for use in children: montelukast and zafirlukast. Both medications improve asthma symptoms, decrease need for rescue -agonist use, and improve lung function. Montelukast, which is FDA-approved for use in children 1 yr of age, is administered once daily. Zafirlukast is FDA-approved for use in children 5 yr of age and is administered twice daily. Although incompletely studied in children with asthma, LTRAs appear to be less effective than ICSs in patients with moderate persistent asthma. In general, ICS improves lung function by 515%, whereas LTRA improves lung function by 27.5%. LTRAs are not thought to have significant adverse effects, although case reports described a ChurgStrausslike vasculitis (pulmonary infiltrates, eosinophilia, cardiomyopathy) in adults with cortico-steroid-dependent asthma treated with LTRAs. It remains to be determined whether these patients have a primary eosinophilic vasculitis masquerading as asthma, which was unmasked as their oral corticosteroid dose was tapered, or whether the disease is a very rare adverse effect of LTRA.
NONSTEROIDAL ANTI-INFLAMMATORY AGENTS.

Cromolyn and nedocromil are non-corticosteroid anti-inflammatory agents that can inhibit allergen-induced asthmatic responses and reduce exercise-induced bronchospasm. According to the NAEPP guidelines, both drugs are considered alternative anti-inflammatory drugs for children with mild persistent asthma. Although largely devoid of adverse effects, these medications must be administered frequently (24 times/day) and are not nearly as effective daily controller medications as ICSs and leukotriene-modifying agents. Because they inhibit exercise-induced bronchospasm, they can be used in place of SABAs, especially in children who develop unwanted adverse effects with -agonist therapy (tremor and elevated heart rate). They can also be used in addition to a SABA as a combination pretreatment for exercise-induced bronchospasm in patients who continue to experience symptoms despite SABA pretreatment alone.
THEOPHYLLINE.

In addition to its bronchodilator effects, theophylline has anti-inflammatory properties as a phosphodiesterase inhibitor, although the extent of their clinical relevance has not been clearly established. Theophylline, when used chronically, can reduce asthma symptoms and the need for rescue SABA use. Although it is considered an alternative monotherapy controller agent for older children and adults with mild persistent asthma, it is no longer considered a first-line agent for small children in whom there is significant variability in the absorption and metabolism of different theophylline preparations, necessitating frequent dose monitoring (blood levels) and adjustments. Because theophylline may have some corticosteroid-sparing effects in individuals with oral corticosteroid-dependent asthma, it is still sometimes used in this group of asthmatic children. Theophylline has a narrow therapeutic window; therefore, when used, serum theophylline levels need to be routinely monitored especially if the patient has a viral illness associated with a fever or is placed on a medication known to delay theophylline clearance, such as macrolide antibiotics, cimetidine, oral antifungal agents, oral contraceptives, leukotriene synthesis inhibitor, and ciprofloxacin. Theophylline overdosage and elevated theophylline levels have been associated with headaches, vomiting, cardiac arrhythmias, seizures, and death.
ANTI-IgE (OMALIZUMAB).

Omalizumab is a humanized monoclonal antibody that binds IgE, thereby preventing its binding to the high-affinity IgE receptor and blocking IgE-mediated allergic responses and inflammation. Since it is unable to bind IgE that is already bound to high-affinity IgE receptors, the risk of anaphylaxis via direct IgE cross linking by the drug is circumvented. It is FDA-approved for patients >12 yr old with moderate to severe asthma, documented hypersensitivity to a perennial aeroallergen, and inadequate disease control with inhaled and/or oral corticosteroids. It is given every 24 wk subcutaneously based on body weight and serum IgE levels. Its clinical efficacy as an add-on therapy for patients with moderate to severe allergic asthma has been demonstrated in large clinical trials, with asthmatics receiving omalizumab having fewer asthma exacerbations and symptoms while reducing their ICS and/or oral corticosteroid doses. It is generally well tolerated, although local injection site reactions can occur. Hypersensitivity reactions (including anaphylaxis) and malignancies have been very rarely associated with Omalizumab use.
Quick-Reliever Medications.

Quick-relief or rescue medications (short-acting inhaled -agonists, inhaled anticholinergics, and short-course systemic corticosteroids) are used in the management of acute asthma symptoms ( Table 143-14 ).

TABLE 143-14 -- Asthma Exacerbation Management (Status Asthmaticus) RISK ASSESSMENT ON ADMISSION Focused history Onset of current exacerbation Frequency and severity of daytime and nighttime symptoms and activity limitation Frequency of rescue bronchodilator use Current medications and allergies Potential triggers History of systemic steroid courses, emergency department visits, hospitalization, intubation, or lifethreatening episodes Physical examination findings: vital signs, breathlessness, air movement, use of accessory muscles, retractions, anxiety level, alteration in mental status Pulse oximetry Lung function (defer in patients with moderate to severe distress or history of labile disease)

Clinical assessment

Risk factors for asthma morbidity and death TREATMENT DRUG AND TRADE NAME Oxygen (Mask or nasal cannula)

See Table 143-15

MECHANISMS OF ACTION AND DOSING

CAUTIONS AND ADVERSE EFFECTS Monitor pulse oximetry to maintain oxygen saturation >92% Cardiorespiratory monitoring Nebulizer:when giving concentrated

Inhaled shortacting -agonists Bronchodilator

DRUG AND TRADE NAME

MECHANISMS OF ACTION AND DOSING

CAUTIONS AND ADVERSE EFFECTS forms, dilute with saline to 3 mL total nebulized volume

Albuterol nebulizer solution (5 mg/mL concentrate; 2.5 mg/3 mL, 1.25 mg/3 mL, 0.63 mg/3 mL)

Nebulizer: 0.15 mg/kg (minimum: 2.5 mg) as often as every 20 min for 3 doses as needed, then 0.15 0.3 mg/kg up to 10 mg every 14 hr as needed, or up to 0.5 mg/kg/hr by continuous nebulization 28 puffs up to every 20 min for 3 doses as needed, then every 14 hr as needed

For MDI:use spacer/holding chamber

Albuterol MDI (90 g/puff)

During exacerbations, frequent or continuous doses can cause pulmonary vasodilation, V/Q mismatch, and hypoxemia Adverse effects: palpitations, tachycardia, arrhythmias, tremor, hypoxemia

Levalbuterol (Xopenex) nebulizer solution (1.25 mg/0.5 mL concentrate; 0.31 mg/3 mL, 0.63 mg/3 mL, 1.25 mg/3 mL) Systemic Corticosteroids

0.075 mg/kg (minimum: 1.25 mg) every 20 min for 3 doses, then 0.0750.15 mg/kg up to 5 mg every 1 4 hr as needed, or 0.25 mg/kg/hr by continuous nebulization Anti-inflammatory

Levalbuterol 0.63 mg is equivalent to 1.25 mg of standard albuterol for both efficacy and side effects. If exposed to chickenpox or measles, consider passive immunoglobulin prophylaxis. Also, risk of complications with herpes simplex and

Prednisone

0.51 mg/kg every 612 hr for 48 hr, then 12 mg/kg/day bid (maximum: 60 mg/day)

DRUG AND TRADE NAME

MECHANISMS OF ACTION AND DOSING

CAUTIONS AND ADVERSE EFFECTS tuberculosis.

1,2.5,5,10,20,50 mg tablets

For daily dosing, 8 AM administration minimizes adrenal suppression Children may benefit from tapering if course exceeds 7 days Adverse effects monitoring: Frequent bursts risk numerous corticosteroid adverse effects (see Chapter 579 ). See Table 14313 for adverse effects screening recommendations

Methylprednisolone (Medrol)

2,4,8,16,24,32 mg tablets;

Prednisolone 5 mg tablets; 5 mg/5 mL and 15 mg/5 mL solution Depo-Medrol (IM); Short-course burst for Solu-Medrol (IV) exacerbation: 12 mg/kg/day qd or bid for 3 7 days Anticholinergics Mucolytic/bronchodilator Should not be used as first-line therapy; added to 2-agonist therapy

Ipratropium Atrovent (nebulizer Nebulizer: 0.5 mg q68 hr solution 0.5 mg/2.5 (tid-qid) as needed mL;MDI 18 g/inhalation) MDI:2 puffs qid Ipratropium with Nebulizer:may mix ipratropium with albuterol

DRUG AND TRADE NAME albuterol DuoNeb nebulizer solution (0.5 mg ipratropium + 2.5 mg albuterol/3 mL vial)

MECHANISMS OF ACTION AND DOSING 1 vial by nebulizer qid

CAUTIONS AND ADVERSE EFFECTS

Injectable Bronchodilator Sympathomimetic

For extreme circumstances (e.g., impending respiratory failure despite high-dose inhaled SABA, respiratory failure)

Epinephrine Adrenalin 1 mg/mL SC or IM:0.01 mg/kg (max (1 : 1000) dose 0.5 mg); may repeat after 1530 min EpiPen autoinjection device (0.3 mg; EpiPen Jr 0.15 mg) Terbutaline Continuous IV infusion (terbutaline only): 210 g/kg loading dose, followed by Monitoring with continuous infusion: cardiorespiratory monitor, pulse 0.1 0.4 g/kg/min. Titrate in 0.10.2 g/kg/min oximetry, blood pressure, serum potassium increments every 30 min, depending on clinical response. Terbutaline is agonist-selective relative to epinephrine Adverse effects: tremor, tachycardia, palpitations, arrhythmia, hypertension, headaches, nervousness, nausea, vomiting, hypoxemia

Brethine 1 mg/mL

RISK ASSESSMENT FOR

DRUG AND TRADE NAME DISCHARGE Medical Stability

MECHANISMS OF ACTION AND DOSING Discharge to home if sustained improvement in symptoms and bronchodilator treatments are at least 3 hr apart, normal physical findings, PEF > 70% of predicted or personal best, oxygen saturation > 92% on room air

CAUTIONS AND ADVERSE EFFECTS

Home Supervision Capability to administer intervention, and to observe and respond appropriately to clinical deterioration Asthma Education See Table 143-16 IM, intramuscular; MDI, metered dose inhaler; PEF, peak expiratory flow; SABA, short-acting beta-agonist;SC, subcutaneous; V/Q, ventilation-perfusion.

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Benadryl Dosage Chart

By BabyZone Editors The children's Benadryl dosage chart below can help you determine the right amount of antihistamine to give your child.

(*Please check with a clinician before using for the first time, especially for children under age 2) Antihistamine ONLY Flavor Dosing Frequency Under 3 months* 4-11 mos.* 12-17 lbs. 12-23 mos. 18-23 lbs. 2-3 yrs. 24-35 lbs. 4-5 yrs. Benadryl Allergy Liquid 12.5 mg/ 5ml Cherry Every 4-6 hours Benadryl l Dye-free Allergy Liquid 12.5 mg/5ml Bubble Gum Every 4-6 hours Benadryl Allergy Chewables 12.5mg/tab Grape Every 4-6 hours

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Related Articles:

Can You Give Antihistamines to Children to Make Them Feel (and Sleep) Better? Can I Give My Child Benadryl on Long Plane or Car Rides? BabyZone Allergy Guide Look Who's Talking!

Diphenhydramine
Generic Name: Diphenhydramine hydrochloride Dosage Form: elixir
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Rx ONLY

DESCRIPTION:
Diphenhydramine hydrochloride is an antihistamine drug having the chemical name 2(diphenylmethoxy)-N,N -dimethylethylamine hydrochloride and has the molecular formula C17H21NOHCL (molecular weight 291.82). It occurs as a white odorless, crystalline powder and is freely soluble in water and alcohol. The structural formula is as follows:

Each 5 mL contains 12.5 mg of Diphenhydramine hydrochloride and alcohol 14% for oral administration. INACTIVE INGREDIENTS: Citric acid, D&C Red No.33, FD&C Red No.40, flavoring, purified water, sodium citrate, and sucrose.

CLINICAL PHARMACOLOGY:
Diphenhydramine hydrochloride is an antihistamine with anticholinergic (drying) and sedative effects. Antihistamines appear to compete with histamine for cell receptor sites on effector cells. A single oral dose of Diphenhydramine hydrochloride is quickly absorbed with maximum activity occurring in approximately one hour. The duration of activity following an average dose of Diphenhydramine hydrochloride is from four to six hours. Diphenhydramine is widely distributed throughout the body, including the CNS. Little, if any, is excreted unchanged in the urine; most appears as the degradation products of metabolic transformation in the liver, which are almost completely excreted within 24 hours.

INDICATIONS AND USAGE:

Diphenhydramine hydrochloride in the oral form is effective for the following indications:

Antihistaminic:
For allergic conjunctivitis due to foods; mild, uncomplicated allergic skin manifestations of urticaria and angioedema; amelioration of allergic reactions to blood or plasma; dermatographism; as therapy for anaphylactic reactions adjunctive to epinephrine and other standard measures after the acute manifestations have been controlled.

Motion Sickness:
For active and prophylactic treatment of motion sickness.

Antiparkinsonism:
For parkinsonism (including drug-induced) in the elderly unable to tolerate more potent agents; mild cases of parkinsonism (including drug-induced) in other age groups; in other cases of parkinsonism (including drug-induced) in combination with centrally acting anticholinergic agents. Nighttime Sleep-aid.
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CONTRAINDICATIONS:
Use in Newborn or Premature Infants:
This drug should not be used in newborn or premature infants.

Use in Nursing Mothers:

Because of the higher risk of antihistamines for infants generally, and for newborns and prematures in particular, antihistamine therapy is contraindicated in nursing mothers.

Antihistamines are also contraindicated in the following conditions:

Hypersensitivity to Diphenhydramine hydrochloride and other antihistamines of similar chemical structure.

WARNINGS:
Antihistamines should be used with considerable caution in patients with narrow-angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction, symptomatic prostatic hypertrophy, or bladderneck obstruction.

Use in Children:
In infants and children, especially, antihistamines in overdosage may cause hallucinations, convulsions, or death. As in adults, antihistamines may diminish mental alertness in children. In the young child, particularly, they may produce excitation.

Use in the Elderly (approximately 60 years or older):

Antihistamines are most likely to cause dizziness, sedation, and hypotension in elderly patients.

PRECAUTIONS:
General:
Diphenhydramine hydrochloride has an atropine-like action and therefore, should be used with caution in patients with a history of lower respiratory disease including asthma, increased intraocular pressure, hyperthyroidism, cardiovascular disease or hypertension.

Information for Patients:

Patients taking Diphenhydramine hydrochloride should be advised that this drug may cause drowsiness and has an additive effect with alcohol. Patients should be warned about engaging in activities requiring mental alertness such as driving a car or operating appliances, machinery, etc.

Drug Interactions:
Diphenhydramine hydrochloride has additive effects with alcohol and other CNS depressants (hypnotics, sedatives, tranquilizers, etc.). MAO inhibitors prolong and intensify the anticholinergic (drying) effects of antihistamines.

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Long-term studies in animals to determine mutagenic and carcinogenic potential have not been performed.

Pregnancy:
Pregnancy Category B: Reproduction studies have been performed in rats and rabbits at doses up to 5 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to Diphenhydramine hydrochloride. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

ADVERSE REACTIONS:
The most frequent adverse reactions are underscored. 1. General: Urticaria, drug rash, anaphylactic shock, photosensitivity, excessive perspiration, chills, dryness of the mouth, nose and throat. 2. Cardiovascular System: Hypotension, headache, palpitations, tachycardia, extrasystoles. 3. Hematologic System: Hemolytic anemia, thrombocytopenia, agranulocytosis. 4. Nervous System: Sedation, sleepiness, dizziness, disturbed coordination, fatigue, confusion, restlessness, excitation, nervousness, tremor, irritability, insomnia, euphoria, paresthesia, blurred vision, diplopia, vertigo, tinnitus, acute labyrinthitis, neuritis, convulsions. 5. GI System: Epigastric distress, anorexia, nausea, vomiting, diarrhea, constipation. 6. GU System: Urinary frequency, difficult urination, urinary retention, early menses. 7. Respiratory System: Thickening of bronchial secretions, tightness of chest and wheezing, nasal stuffiness.

OVERDOSAGE:
Antihistamine overdosage reactions may vary from central nervous system depression to stimulation. Stimulation is particularly likely in children. Atropine-like signs and symptoms, dry mouth; fixed, dilated pupils; flushing and gastrointestinal symptoms may also occur. If vomiting has not occurred spontaneously, the patient should be induced to vomit. This is best done by having him drink a glass of water or milk after which he should be made to gag. Precaution against aspiration must be taken, especially in infants and children. If vomiting is unsuccessful, gastric lavage is indicated within 3 hours after ingestion and even later if large amounts of milk or cream were given beforehand. Isotonic or 1/2 isotonic saline is the lavage solution of choice. Saline cathartics, as milk of magnesia, by osmosis draw water into the bowel and therefore are valuable for their action in rapid dilution of bowel content.

Stimulants should not be used. Vasopressors may be used to treat hypotension.

DOSAGE AND ADMINISTRATION:

DOSAGE SHOULD BE INDIVIDUALIZED ACCORDING TO THE NEEDS AND THE RESPONSE OF THE PATIENT. A single oral dose of Diphenhydramine hydrochloride is quickly absorbed with maximum activity occurring in approximately one hour. The duration of activity following an average dose of Diphenhydramine hydrochloride is from four to six hours. ADULTS: 25 to 50 mg three or four times daily. The nighttime sleep-aid dosage is 50 mg at bedtime. CHILDREN: (over 20 lbs.): 12.5 to 25 mg three or four times daily. Maximum daily dosage not to exceed 300 mg. For physicians who wish to calculate the dose on the basis of body weight or surface area, the recommended dosage is 5 mg/kg/24 hours or 150 mg/m2/24 hours. Data are not available on the use of Diphenhydramine hydrochloride as a nighttime sleep-aid in children under 12 years. The basis for determining the most effective dosage regimen will be the response of the patient to medication and the condition under treatment. In motion sickness, full dosage is recommended for prophylactic use, the first dose to be given 30 minutes before exposure to motion and similar doses before meals and upon retiring for the duration of exposure. STORAGE: Keep tightly closed. Store at controlled room temperature 15-30C (59-86F). Protect from light.

HOW SUPPLIED:
Diphenhydramine HCL Elixir (colored pink) is supplied in the following oral dosage forms: NDC 0121-0489-05 (unit dose cups of 5 mL, 10 x 10s), NDC 0121-0489-10 (unit dose cups of 10 mL, 10 x 10s), NDC 0121-0489-20 (unit dose cups of 20 mL, 10 x 10s). Each 5 mL of elixir contains 12.5 mg Diphenhydramine HCL with 14% alcohol.