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Rhinitis, sinusitis, and upper airway disease

Efficacy of nasal mometasone for the treatment of chronic


sinonasal disease in patients with inadequately controlled
asthma
American Lung Association–Asthma Clinical Research Centers’ Writing Committee: Anne E. Dixon, MA, BM BCh,a
Mario Castro, MD, MPH,b Rubin I. Cohen, MD,c Lynn B. Gerald, PhD, MPH,d Janet T. Holbrook, PhD,e
Charles G. Irvin, PhD,a Shyam Mohapatra, PhD,f Stephen P. Peters, MD,g Sobharani Rayapudi, MD,h
Elizabeth A. Sugar, PhD,i and Robert A. Wise, MDh Burlington, Vt, St Louis, Mo, New Hyde Park, NY, Tucson, Ariz, Baltimore,
Md, Tampa, Fla, and Winston-Salem, NC

Background: Chronic sinonasal disease is common in asthmatic Objective: We sought to determine whether treatment of chronic
patients and associated with poor asthma control; however, sinonasal disease with nasal corticosteroids improves asthma
there are no long-term trials addressing whether chronic control, as measured by the Childhood Asthma Control Test and
treatment of sinonasal disease improves asthma control. Asthma Control Test in children and adults, respectively.
Methods: A 24-week multicenter, randomized, placebo-controlled,
double-blind trial of placebo versus nasal mometasone in adults and
From athe Department of Medicine, University of Vermont, Burlington; bthe Department children with inadequately controlled asthma was performed.
of Medicine, Washington University School of Medicine, St Louis; cThe Thalheim Treatments were randomly assigned, with concealment of allocation.
Asthma Center Hofstra, North Shore-Long Island Jewish School of Medicine, Results: Two hundred thirty-seven adults and 151 children were
New Hyde Park; dthe Arizona Respiratory Center, Mel and Enid Zuckerman College
randomized to nasal mometasone versus placebo, and 319
of Public Health, University of Arizona, Tucson; the Departments of eEpidemiology,
h
Medicine, and iBiostatistics, Johns Hopkins University, Baltimore; fthe Department participants completed the study. There was no difference in the
of Medicine, University of South Florida, Tampa; and gthe Section on Pulmonary, Crit- Childhood Asthma Control Test score (difference in change with
ical Care, Allergy & Immunologic Diseases, Wake Forest University, Winston-Salem. mometasone 2 change with placebo [DM 2 DP], 20.38; 95% CI,
Supported by grants from the National Heart, Lung, and Blood Institute (UO1HL089464 22.19 to 1.44; P 5 .68; age 6-11 years) or the Asthma Control Test
and U01 HL089510, UL1 TR000448) and the American Lung Association. Study drug
score (DM 2 DP, 0.51; 95% CI, 20.46 to 1.48; P 5 .30; age > _12
and placebo were provided by Merck.
Disclosure of potential conflict of interest: This study was funded by the National Heart, years) in those assigned to mometasone versus placebo. In children
Lung, and Blood Institute and the American Lung Association. Study materials were and adolescents (age 6-17 years) there was no difference in asthma or
provided by Merck. A. E. Dixon’s institution has received funding from the National sinus symptoms but a decrease in episodes of poorly controlled
Institutes of Health (NIH) and Merck; has received consultancy fees from Roche; has
asthma defined by a decrease in peak flow. In adults there was a small
received grants or has grants pending from Pfizer; and receives royalties from Springer.
M. Castro’s institution has received funding from the National Institutes of Health and difference in asthma symptoms measured by using the Asthma
has received grants or has grants pending from Boston Scientific, Amgen, Ception, Symptom Utility Index (DM 2 DP, 0.06; 95% CI, 0.01 to 0.11;
Cephalon, Teva, Genentech, MedImmune, Merck, Novartis, GlaxoSmithKline, Sanofi P < .01) and in nasal symptoms (sinus symptom score DM 2 DP,
Aventis, Vectura, Next Bio, and KalosBios; has received consultancy fees from 23.82; 95% CI, 27.19 to 20.45; P 5.03) but no difference in asthma
Asthmatx/Boston Scientific, Genentech, IPS/Holaira, and Neostem; has received
payment for delivering lectures from GlaxoSmithKline, Genentech, Boston Scientific,
quality of life, lung function, or episodes of poorly controlled asthma
Boehringer Ingelheim, and Teva; receives royalties from Elsevier; and has stock/stock in adults assigned to mometasone versus placebo.
options from Sparo. R. I. Cohen’s institution has received funding from the American Conclusions: Treatment of chronic sinonasal disease with nasal
Lung Association Asthma Clinical Research Centers. C. G. Irvin has received corticosteroids for 24 weeks does not improve asthma control.
consultancy fees from TEVA; has received grants or has grants pending from Hydra
Treatment of sinonasal disease in asthmatic patients should be
Bioscience; and receives royalties from UpToDate. S. P. Peters has received
consultancy fees from the Coordination Center at Johns Hopkins, AstraZeneca, determined by the need to treat sinonasal disease rather than to
Aerocrine, Airsonett AB, Boehringer Ingelheim, GlaxoSmithKline, Merck, Novartis, improve asthma control. (J Allergy Clin Immunol
Ono Pharmaceuticals, Pfizer, Sunovion, Targacept, TEVA, Pharmaceutical Product 2015;135:701-9.)
Development, and Quintiles; has received payment for delivering lectures from
Integrity CE; and receives royalties from UpToDate. R. A. Wise’s institution has Key words: Asthma, rhinitis, sinusitis, sinonasal, asthma control,
received funding from Merck, as well as consultancy fees from AstraZeneca, Merck, lung function, asthma exacerbation
GlaxoSmithKline, Boehringer-Ingelheim, Novartis, Pfizer, Mylan, Roche, Janssen,
Pulmonx, Spiration, Intermune, MedImmune, Sunovion, and Forest and has received
support for travel and other meeting-related expenses from Forest. The rest of the
authors declare that they no relevant conflicts of interest. Poor asthma control is a significant cause of morbidity. One
Received for publication February 12, 2014; revised June 16, 2014; accepted for publi- important factor thought to affect asthma control is disease of the
cation June 25, 2014.
Available online August 28, 2014.
upper airway, such as rhinitis and sinusitis.1-5 Therefore chronic
Corresponding author: Anne E. Dixon, MA, BM BCh, University of Vermont, Pulmonary sinonasal disease is often treated in asthmatic patients in an effort
and Critical Care, 792 College Parkway, MOB 105, Colchester, VT 05446. E-mail: to improve asthma control. However, although acute and severe
anne.dixon@vtmednet.org. sinonasal disease clearly warrant treatment directed toward upper
0091-6749/$36.00
airway disease, it is not clear whether treating chronic sinonasal
Ó 2014 American Academy of Allergy, Asthma & Immunology
http://dx.doi.org/10.1016/j.jaci.2014.06.038 disease improves asthma control.

701

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702 DIXON ET AL J ALLERGY CLIN IMMUNOL
MARCH 2015

June 2010 through February 2013. Randomization was stratified by center and
Abbreviations used age (6-17 years or > _18 years) by using permuted blocks of varying sizes.
ACT: Asthma Control Test Participants aged 12 years and older received 2 sprays of mometasone or
cACT: Childhood Asthma Control Test placebo per nostril daily (50 mg of mometasone per spray vs vehicle control;
DM 2 DP: Change with mometasone 2 change with placebo Merck, Whitehouse Station, NJ); those aged 6 to 11 years received 1 spray per
SNOT-22: Sino Nasal Outcomes Test 22 nostril daily. After a 2-week run-in period, participants were randomized and
followed for 24 weeks while receiving treatment. Allocation concealment was
enforced as follows: clinical center personnel keyed eligibility data into a
centralized Web-based randomization system to receive a study kit number
Rhinitis, sinusitis, and asthma are closely linked. At least 70% that corresponded to the assigned treatment. Unique drug assignment
of asthmatic patients have rhinitis,6,7 and 30% to 40% report numbers were used to distribute and track the study drug. Personnel at the
sinusitis.6 A number of mechanisms link sinonasal disease and data-coordinating center involved in randomization and drug distribution to
asthma, which might represent a common immune disorder the centers had access to the treatment information; no personnel at the clinical
sites had access to the treatment codes. Analysts looked at treatment identity
affecting the whole respiratory system. Allergen challenge in
after data collection was completed and were aware of treatment assignment
one region produces inflammation in the other,8,9 postnasal drip when performing the analyses of the completed data set.
of inflammatory mediators can occur,10 and a nasobronchial
reflex might produce bronchoconstriction.11 Chronic sinonasal
disease is very common in asthmatic patients and might be part Participants
of a common disease process. Participants were aged 6 years and older with a history of physician-
Despite sinonasal disease and asthma being closely related diagnosed asthma and either a positive methacholine challenge result (20%
disease processes, it is not clear whether treatment of sinonasal decrease in FEV1 at <16 mg/mL methacholine) in the previous 2 years or
documentation of at least 12% and 200-mL increase in FEV1 with bronchodi-
disease affects the course of asthma. Treatment of severe and
lator in the previous 2 years. Subjects were required to meet the following
acute sinonasal disease is clearly warranted and might improve inclusion criteria: poor asthma control was defined as a score of 19 or less
asthma control,12,13 but most studies have been observational on the Childhood Asthma Control Test (cACT; age 6-11 years)21 or Asthma
because such sinonasal disease requires treatment regardless Control Test (ACT; age > _12 years22; ACT and cACT scores of 19 or less
of the effect on asthma.12 Some small studies suggest that identify ‘‘not well controlled asthma,’’ which is defined as an asthma
treatment of acute rhinitis improves airway reactivity,14,15 specialist’s rating of not controlled at all/poorly controlled/somewhat
whereas others do not,16,17 and some observational studies report controlled)21,23 and chronic symptoms of rhinitis and sinusitis as measured
that long-term treatment for sinonasal disease improves asthma by a mean score of 1 or greater on the Sino-Nasal Questionnaire.20 Participants
outcomes.18 However, there are no controlled studies suggesting were excluded if they had comorbidities predisposing to complicated
that long-term treatment of chronic sinonasal disease improves rhinosinusitis; chronic illnesses that, in the judgment of the physician, would
interfere with study participation; history of upper airway symptoms for less
asthma control, although this is often done in clinical practice.19
than 8 weeks at the time of randomization; temperature of greater than
One barrier to understanding the interaction between sinonasal 38.38C within the prior 10 days; sinus surgery within the prior 6 months;
disease and asthma is the lack of simple tests to diagnose rhinitis use of systemic or nasal corticosteroids within the prior 4 weeks or antileuko-
and sinusitis in asthmatic patients. We previously developed a triene medication within the prior 2 weeks; FEV1 of less than 50% of predicted
clinical tool to identify chronic rhinitis and sinusitis in patients value before bronchodilator; a greater than 10 pack year smoking history or
with inadequately controlled asthma. This questionnaire, which active smoking within the last 6 months; or cataracts, history of glaucoma,
specifically asks about symptoms experienced over the last 3 or other conditions resulting in increased intraocular pressure. Other exclusion
months, identifies patients with chronic rhinitis and sinusitis, with criteria were nonadherence (<80% completion of daily diaries during the
a sensitivity of 0.90 and specificity of 0.94.20 This questionnaire run-in period); inability to take study medications, perform baseline
accurately diagnoses chronic sinonasal disease in asthmatic measurements, or be contacted by telephone; or pregnancy.
Participants underwent allergen skin testing at baseline. Percutaneous
patients, is inexpensive and simple to use, and therefore facilitates
allergen scratch skin testing was performed with a Multi-Test II device
the study of the relationship between chronic sinonasal disease (Lincoln Diagnostics, Decatur, Ill) and 16 allergens (mite mix, cockroach mix,
and asthma. mouse, rat, Penicillium species, Alternaria species, Aspergillus species,
Chronic sinonasal disease is common in asthmatic patients and Cladosporium species, cat, and dog; 4 local center-specific allergens; and
can be associated with severe disease, but the effect of long-term positive and negative controls; Greer Laboratories, Lenoir, NC). A positive
treatment of sinonasal disease on asthma control is not known. test result was defined as a wheal 3 mm larger than that elicited by the negative
The purpose of this study was to determine the efficacy of treating control.
chronic sinonasal disease in children and adults with inadequately Participants were asked to refrain from taking nonstudy medications (other
controlled asthma, as is common medical practice. There is than topical decongestants or saline) for their nasal symptoms. They were
supportive but inconclusive evidence that such treatment reduces trained to exhale all orally inhaled corticosteroids through the mouth to avoid
any potential benefit of orally inhaled corticosteroids on the nasal mucosa.
asthma morbidity, and therefore this clinical trial addresses an
Participants continued their usual asthma medications during the trial.
important and practical issue that has extensive implications for After randomization, participants kept daily diaries to record morning peak
public health and health care costs. expiratory flow, medication use, and asthma symptoms and returned for
The trial was registered at ClinicalTrials.gov as NCT01118312 assessments at 4, 12, and 24 weeks. Procedures performed at each visit
under the acronym Study of Asthma and Nasal steroids (STAN). included an interval medical history interview, asthma and sinus symptoms
questionnaires, and spirometry (Koko Spirometer; Ferris Respiratory,
Louisville, Colo), according to American Thoracic Society standards.24 At
METHODS baseline and the 24-week follow-up visits, fraction of exhaled nitric oxide
Study design values were measured with the Insight eNO System (Apieron, Menlo Park,
This was a multicenter, randomized, placebo-controlled, double-masked, Calif), and methacholine challenge testing was performed. Allergen skin
parallel-design (allocation ratio 1:1) trial conducted at 19 clinical centers from testing and the sinonasal questionnaire were administered at baseline.

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J ALLERGY CLIN IMMUNOL DIXON ET AL 703
VOLUME 135, NUMBER 3

FIG 1. Eligibility screening, randomization, and follow-up of study participants. All patients were included in
the analysis based on the assigned treatment.

Outcomes Asthma Clinical Research Centers are not bound by any confidentiality
The primary outcome measure was the change in cACT score (for children agreement in respect to the study results.
aged <12 years)21 or the ACT (for those aged > _12 years22) at 24 weeks from
baseline. Secondary outcomes included changes in methacholine reactivity;
asthma symptoms (Asthma Symptom Utility Index)25; asthma-related Statistical approach
quality-of-life questionnaires (Childhood Health Survey for Asthma26 or All analyses were stratified by age (pediatric [6-17 years] and adult [> _18
Marks Asthma Quality of Life Questionnaire27); sinusitis and rhinitis symp- years]). The pediatric age category was further divided into younger children
toms, including a sinus symptom questionnaire28 and sinusitis-related (age 6-11 years) and adolescents (age 12-17 years). The ACT score analysis
quality-of-life questionnaires (Sino-Nasal Survey 529 for those aged 6-17 was stratified by age groups of 6 to 11 years and 12 years and older, the age
years and Sino-Nasal Outcome Test 22 [SNOT-22]30 for those aged > _18 ranges validated for the pediatric cACT and adult ACT instruments,
years); spirometry; and exhaled nitric oxide. Secondary outcomes also respectively. For all other outcomes, the 2 age groups were defined as 6 to
included the rate of acute episodes of poor asthma control defined as a 17 years and age 18 years and older. The randomization was stratified
decrease of greater than 30% in morning peak flow rate from personal best according to the age 18-year cut point.
(assessed during the run-in period) for 2 consecutive days, addition of an The planned sample size of 190 adult participants (95 receiving active and 95
oral corticosteroid to treat asthma symptoms, unscheduled contact with a receiving placebo therapy) had 90% power to detect a difference of 2.8 in the
health care provider for asthma symptoms, or increased use of short-acting change in ACT score from baseline to 24 weeks for the mometasone versus the
b-agonists (>_4 additional puffs of rescue medication or >_2 additional nebulizer placebo group, with a type 1 error rate of 2.5% and an SD of 5 (this SD was based
treatments in 1 day). Participants were also questioned about potential adverse on prior data from studies by this research network and previous publica-
effects of treatment at each visit and rhinitis/sinusitis exacerbations. tions).31,32 Assuming equal recruitment, the same calculation was applied for
pediatric patients, for a total sample size of 380 and a total type 1 error rate
of 5%. However, of the 151 participants less than 18 years of age enrolled in
Study oversight the study, only 86 were between the ages of 6 and 11 years, the age range for
The Steering Committee of the American Lung Association Asthma the cACT questionnaire, and therefore the actual detectable difference,
Clinical Research Centers designed, approved, and oversaw the study was larger for that subgroup (approximately 4.1). The sample size
implementation. Active drug and placebo were supplied by Merck, who had calculations include an increase of 11% to account for missing data and loss
no role in designing, conducting, or approving the study or analyzing the to follow-up.
results. The study was approved by the institutional review board at each The analysis of the primary outcome, change in ACT score, incorporated
center. The participants or their legal guardians signed informed consent the repeated measures through use of linear mixed-effects models, which are
statements. Participants less than 18 years of age signed assent forms, robust to data that are missing at random. Treatment, visit, and the interaction
according to local regulatory policies. The American Lung Association between treatment and visit were included as fixed effects, and an unstructured

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704 DIXON ET AL J ALLERGY CLIN IMMUNOL
MARCH 2015

TABLE I. Characteristics of the study population at variance-covariance matrix was used. Contrasts were used to produce
randomization estimates for the change over 24 weeks.
Analyses of continuous secondary outcomes followed the same analytic
Mometasone Placebo
(n 5 189) (n 5 199)
strategy used for the primary outcome. PC20 (measured at baseline and 24
weeks) was analyzed on the log scale, and results were translated into the
Demographics percentage change. Rates of exacerbations were evaluated by using negative
Age (y), median (IQR) 27 (12-46) 26 (12-43) binomial models.
Age categories, no. (%) All randomized subjects were included in the analysis according to their
Pediatric (6-11 y) 40 (21) 46 (23) assigned treatment group. Robust variance estimates were used for all analytic
Adolescent (12-17 y) 32 (17) 33 (17) models. The primary analyses were performed independently by 2 analysts to
Adult (>_18 y) 117 (62) 120 (60) confirm the accuracy of data filters and analytic routines. Analyses were
Race/ethnicity, no. (%) performed with SAS (SAS/STAT User’s Guide, Version 9.1; SAS, Cary, NC),
White 71 (38) 76 (38) STATA (Stata Statistical Software, Release 13; StataCorp, College Station,
Black 74 (39) 73 (37) Tex), and R (The R Project for Statistical Computing, Version 2.11.1, available
Hispanic 35 (19) 46 (23) at: http://www.r-project.org/) software.
Other 9 (5) 4 (2)
Male sex, no. (%) 84 (44) 93 (47)
RESULTS
Second-hand smoke exposure, no. (%) 50 (26) 42 (21)
Atopy, no. (%) 137 (82)* 149 (84)*
A total of 1567 participants were screened for eligibility
Asthma characteristics (Fig 1). Three hundred eighty-eight participants were random-
Age of asthma onset (y), median 5 (1-13) 4 (1-12) ized, 199 to placebo and 189 to mometasone. A similar number
(IQR) of adults (age > _18 years) and children (age 6-17 years) were
Emergency visits in past 12 mo, 123 (65) 125 (63) randomized to both groups (120 adults and 79 children to placebo
no. (%) and 117 adults and 72 children to mometasone). The loss to
Steroid bursts in past 12 mo, no. (%) 88 (47) 102 (51) follow-up rate was similar in each group; 82% of participants
Using controller medication, no. (%)  134 (71) 144 (72) completed the primary outcome questionnaire at week 24, and
ICS in combination with LABA 81 (43) 85 (43)
90% of all follow-up visits were completed. Baseline characteris-
ICS without LABA 52 (28) 59 (30)
tics of participants completing the study (n 5 319) were similar to
Lung function, median (IQR)
Prebronchodilator FEV1 (% predicted) 85 (76-96) 85 (73-95) those who did not complete the final visit (n 5 69), except for the
Prebronchodilator FVC (% predicted) 96 (86-106) 95 (86-105) fact that controller use was significantly greater in those who
Prebronchodilator FEV1/FVC ratio 0.75 (0.70-0.80) 0.75 (0.68-0.81) completed the study compared with those who did not (74% vs
Peak expiratory flow (L/min) 340 (280-420) 350 (280-430) 61%, P 5 .04; see Table E1 in this article’s Online Repository
PC20 (mg/mL) 2.29 (0.53-6.11) 0.67 (0.20-3.01) at www.jacionline.org). Self-reported adherence to study
Questionnaires, median (IQR) treatments was high (>90% of follow-up days) in both groups
ACT score (range, 5-25)[à 16 (14-19) 17 (14-18) according to diary cards and interviews at study visits. Use of
cACT score (range, 0-27)[à 17 (15-19) 17 (14-18) new sinus and new/increasing asthma medications was similar
Asthma Symptom Utility Index 0.77 (0.69-0.88) 0.79 (0.69-0.88)
in the placebo and mometasone groups (see Table E2 in this
(range, 0-1)[§
Marks Asthma Quality of Life 17 (10-30) 21 (11-31)
article’s Online Repository at www.jacionline.org).
Questionnaire (range, 1-80)Yk
Children’s Health Survey for Characteristics of study participants
Asthma (range, 0-100)[{ Demographics, medication use, and measures of asthma and
Physical health (child) 77 (68-87) 77 (68-87) sinus disease were similar in both groups, although participants
Activities (child) 85 (65-95) 85 (65-100) assigned to mometasone tended to have lower bronchial
Activities (family) 96 (83-100) 92 (83-100) reactivity, as indicated by a higher PC20, at baseline (Table I).
Emotional health (child) 80 (65-95) 80 (55-95) By design, participants had poor asthma control, with an ACT
Emotional health (family) 79 (69-90) 78 (71-90)
score of less than 19 required at enrollment, although some
Sinus symptom score (range, 1-60)Y§ 25 (17-32) 25 (16-34)
SNOT-22 (range, 0-120)Yk 37 (23-54) 36 (21-53)
improved beyond that threshold by randomization. Many
SN-5 (range, 1-7)Y{ 3.3 (2.8-4.0) 3.8 (3.0-4.6) participants (28%) were not taking controller medication for their
asthma; this was not a requirement for study participation.
[, High scores indicate better health; Y, low scores indicate better health; FVC, forced
vital capacity; ICS, inhaled corticosteroid; IQR, interquartile range; LABA, long-acting
b-agonist; SN-5, Sino-Nasal Survey 5.
Effect of treatment on asthma control
*A total of 168 participants in the mometasone arm and 178 participants in the After 24 weeks of study treatment, there was no significant
placebo arm had valid skin testing data available. Thirty did not perform the test, 3 difference in the change in childhood asthma control scores
were missing data, and 9 did not have a valid test (ie, the positive control response was (children aged 6-11 years) between those assigned to mometa-
negative).
sone and those assigned to placebo (difference in change with
 One subject was using long-acting b-agonists without inhaled corticosteroids in the
mometasone arm. mometasone 2 change with placebo [DM 2 DP], 20.38; 95% CI,
àThe ACT was administered to participants aged 12 years and older, and the cACT 22.19 to 1.44; P 5.68; Table II). Asthma control scores tended to
was administered to participants aged 6 to 11 years. improve over the course of the trial in both treatment groups
§The Asthma Symptom Utility Index and sinus symptom score were administered to (range, 1.81-4.53; P < .0001 at all time points; see Fig E1, A, in
all participants.
kThe Marks Asthma Quality of Life Questionnaire and SNOT-22 were administered to
this article’s Online Repository at www.jacionline.org). Similarly,
participants aged 18 years and older. there was no difference in the asthma control test for adults and
{The Children’s Health Survey for Asthma and the Sino-Nasal Survey 5 were adolescents (age > _12 years) for those assigned to mometasone
administered to participants aged 6 to 17 years. versus those assigned to placebo (Table II), and asthma control

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J ALLERGY CLIN IMMUNOL DIXON ET AL 705
VOLUME 135, NUMBER 3

TABLE II. Comparison of the change in asthma control for participants treated with mometasone versus placebo at 4, 12, and 24
weeks
Change from randomization (SE) Difference in change from randomization (95% CI)
No.* Mometasone Placebo Mometasone 2 placebo P value

cACT: Pediatric (age 6-11 y)[


Week 4 82 1.81 (0.58) 2.69 (0.54) 20.88 (22.47 to 0.71) .27
Week 12 75 3.40 (0.61) 3.05 (0.71) 0.34 (21.52 to 2.21) .71
Week 24 71 4.15 (0.64) 4.53 (0.65) 20.38 (22.19 to 1.44) .68
ACT: Adolescent and adult (age >
_12 y)[
Week 4 277 1.89 (0.26) 1.75 (0.31) 0.14 (20.66 to 0.94) .72
Week 12 262 2.69 (0.30) 2.25 (0.32) 0.44 (20.43 to 1.31) .32
Week 24 248 2.95 (0.31) 2.44 (0.38) 0.51 (20.46 to 1.48) .30
Asthma control was measured by using the ACT for adolescent and adult participants (age >
_12 years) and by using the cACT for pediatric participants (age 6-11 years).
[, An increase indicates improved control.
*Number of participants with follow-up at each time point (4, 12, and 24 weeks).

TABLE III. Twenty-four week change in asthma symptoms, lung function, and sinus symptoms in children (age 6-17 years) treated
with mometasone versus placebo
Change from randomization (SE) Difference in change from randomization (95% CI)
No. Mometasone Placebo Mometasone 2 placebo P value

Asthma Symptom Utility Index 126 0.04 (0.02) 0.1 (0.02) 20.06 (20.13 to 0.01) .07
Childhood Health Survey for Asthma
Physical health 123 6.37 (1.63) 7.33 (1.59) 20.95 (25.45 to 3.55) .68
Activities (child) 125 7.41 (2.03) 5.95 (2.38) 1.45 (24.74 to 7.65) .64
Activities (family) 125 2.09 (1.74) 5.35 (1.43) 23.26 (27.72 to 1.20) .15
Emotional health (child) 125 3.87 (2.83) 7.35 (2.46) 23.48 (210.91 to 3.94) .36
Emotional health (family) 123 4.01 (1.61) 3.26 (1.55) 0.76 (23.66 to 5.18) .74
Lung function
Prebronchodilator FEV1 (% predicted) 127 2.62 (1.68) 20.83 (1.1) 3.45 (20.52 to 7.42) .09
Prebronchodilator FVC (% predicted) 127 2.1 (1.24) 20.34 (0.92) 2.44 (20.60 to 5.48) .12
FEV1/FVC ratio 127 0.007 (0.009) 20.007 (0.006) 0.013 (20.009 to 0.035) .23
FENO (ppb)* 123 10.92 (5.34) 5.65 (2.89) 5.28 (26.72 to 17.28) .39
Sinus symptoms
Sinus symptom score 127 27.38 (1.38) 27.38 (1.43) 20.004 (23.94 to 3.93) >.99
SN-5 126 20.76 (0.12) 20.98 (0.14) 0.22 (20.14 to 0.59) .22

FENO, Fraction of exhaled nitric oxide; FVC, forced vital capacity; SN-5, Sino-Nasal Survey 5.
*FENO levels were measured at baseline and 24 weeks.

tended to improve in both treatment groups (range, 1.75-2.95; peak flow for 2 consecutive days (rate ratio, 0.44; P 5 .03).
P < .0001 at all time points; see Fig E1, B). No differences in the other components of episodes of poor asthma
control (ie, urgent care visits, use of systemic steroids, or use of
rescue medications were noted; Table IV). In post hoc analyses
Effect of treatment in children (age 6-17 years) with we did not find any suggestion of a subgroup, as defined by sex,
poorly controlled asthma controller medication use, or atopic status, that benefited from
There was no significant difference in the change in asthma nasal steroids in this 24-week treatment trial.
symptoms, asthma quality of life, sinus symptom scores, or
exhaled nitric oxide at 24 weeks compared with baseline in
children assigned to placebo versus those assigned to mometasone Effect of treatment in adults (age > _18 years) with
(Table III). There was a small difference in improvement in lung poorly controlled asthma
function measured based on FEV1 (DM 2 DP, 3.45; 95% CI, There was a statistically significant improvement in the
20.52 to 7.42) and some evidence of larger improvement in change in Asthma Symptom Utility Index scores at 24 weeks
forced vital capacity in children assigned to mometasone compared with baseline in adults assigned to mometasone
(DM 2 DP, 2.44; 95% CI, 20.60 to 5.48), although neither was versus placebo (DM 2 DP, 0.06; 95% CI, 0.01 to 0.11;
statistically significant (P 5 .09 and .12, respectively). The per- P 5 .0095; Table V). There was no difference in the change
centage improvement in PC20 was similar for both treatments in asthma quality of life, lung function, or exhaled nitric oxide
(test of interaction: P 5.52) at 89% (95% CI, 37% to 159%). There levels in those assigned to mometasone versus placebo. There
was a lower rate of episodes of poor asthma control (rate ratio, was a significantly greater decrease in the sinus symptom score
0.64; P 5.04) in children assigned to mometasone versus placebo. in those assigned to mometasone (DM 2 DP, 23.82; 95% CI,
The effect was primarily driven by lower rates of episodes of 27.19 to 20.45; P 5 .026), as well as the change in the
decreased peak flow, which was defined as a 30% decrease in SNOT-22 score (DM 2 DP, 24.83; 95% CI, 29.86 to 0.21),

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706 DIXON ET AL J ALLERGY CLIN IMMUNOL
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TABLE IV. Episodes of poor asthma control in children (age 6-17 years) treated with mometasone versus placebo
Treatment assignment Rate ratio (95% CI),*
Episodes of poor asthma control Mometasone (n 5 66) Placebo (n 5 75) mometasone/placebo P value*

Overall
Patients with >
_ 1 event, no. (%) 36 (55) 42 (56)
No. of events 73 128
Annual per-person event rate (95% CI) 2.7 (2.1-3.6) 4.2 (3.1-5.8) 0.64 (0.42-0.97) .04
Individual components
Decrease in peak flow of > _30% for 2 consecutive days
Patients with >
_1 event, no. (%) 14 (21) 20 (27)
No. of events 30 73
Annual per-person event rate (95% CI) 1.1 (0.7-1.9) 2.5 (1.5-4.2) 0.44 (0.22-0.90) .03
Urgent asthma care
Patients with >
_1 event, no. (%) 15 (22) 10 (13)
No. of events 18 12
Annual per-person event rate (95% CI) 0.7 (0.4-1.1) 0.4 (0.2-0.7) 1.75 (0.81-3.80) .15
Systemic steroids
Patients with >
_1 event, no. (%) 13 (20) 13 (17)
No. of events 13 13
Annual per-person event rate (95% CI) 0.5 (0.3-0.8) 0.4 (0.3-0.7) 1.17 (0.57-2.36) .67
Increased rescue medications
Patients with >
_1 event, no. (%) 27 (44) 27 (38)
No. of events 47 67
Annual per-person event rate (95% CI) 1.8 (1.3-2.6) 2.3 (1.5-3.4) 0.82 (0.49-1.39) .44

*Rate ratios, 95% CIs, and P values are based on negative binomial regression.

TABLE V. Twenty-four week change in asthma symptoms, lung function, and sinus symptoms in adults (ages 18 and older)
treated with mometasone versus placebo
Difference in change from
Change from randomization (SE) randomization (95% CI)
N Mometasone Placebo Mometasone - placebo P value

Asthma Symptom Utility Index 193 0.09 (0.01) 0.03 (0.02) 0.06 (0.01, 0.11) <.01
Marks Asthma Quality of Life Questionnaire 192 25.26 (1.11) 25.48 (1.06) 0.22 (22.82, 3.26) .89
Lung function
Prebronchodilator FEV1 (% predicted) 193 21.40 (1.07) 0.51 (0.97) 21.91 (24.76, 0.94) .18
Prebronchodilator FVC (% predicted) 193 21.27 (0.95) 0.06 (0.85) 21.33 (23.85, 1.19) .30
FEV1/FVC ratio 193 20.001 (0.004) 0.004 (0.004) 20.005 (20.017, 0.008) .43
FENO (ppb)* 183 20.08 (1.98) 20.02 (2.96) 20.06 (27.08, 6.96) .99
Sinus symptoms
Sinus symptom score 194 29.46 (1.18) 25.64 (1.24) 23.82 (27.19, 20.45) .03
SNOT-22 193 211.2 (1.86) 26.37 (1.75) 24.83 (29.86, 0.21) .06
FENO, Fraction of exhaled nitric oxide; N, number of participants evaluable at 24 weeks.
*FENO was measured at baseline and at 24 weeks.

although the latter did not reach statistical significance or adults with inadequately controlled asthma. This study is
(P 5 .06). Although the PC20 was greater at baseline for those unique in that it included a diverse patient population of adults
treated with mometasone versus those treated with placebo and children with inadequately controlled asthma, and we studied
(geometric mean, 1.64 vs 0.77, a difference that was statistically the effect of nasal corticosteroids over a 24-week time period.
significant [P 5 .004]), there was not a significant difference in The results of this study have important implications for the
the percentage change from baseline for the 2 groups (P 5 .42), treatment of asthmatic patients.
with an overall improvement of 58% (95% CI, 19% to 111%; Sinonasal disease has been associated with severe asthma, and
P 5 .002). There was no difference in the rate of episodes of treatment of sinonasal disease is frequently advocated to improve
poor asthma control in those assigned to mometasone versus asthma control. However, our current study provides important
placebo overall (P 5 .92, Table VI). In post hoc analyses we new insights into our understanding of the relationship between
did not find any suggestion of a subgroup, as defined by sex, sinonasal disease and asthma, significantly expanding on previous
controller medication use, or atopic status, that benefited from studies. There have been many observational and small single-
nasal steroids in this 24-week treatment trial. center studies published on the effectiveness of treatment of
sinonasal disease for the control of asthma in patients with both
DISCUSSION sinonasal disease and asthma. Some small studies suggest that
This study demonstrated that treatment of chronic sinonasal short-term treatment of seasonal and perennial allergic rhinitis
disease for 24 weeks does not improve asthma control in children improves airway reactivity in asthmatic patients,15,33 whereas

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VOLUME 135, NUMBER 3

_18 years) treated with mometasone versus


TABLE VI. Asthma symptoms, lung function, and sinus symptoms in adults (age >
placebo
Treatment assignment Rate ratio (95% CI),*
Mometasone (n 5 111) Placebo (n 5 111) mometasone/placebo P value*

Episodes of poor asthma control, overall


Patients with >
_1 event, no. (%) 45 (41) 48 (43)
No. of events 104 114
Annual per-person event rate (95% CI) 2.5 (1.9-3.5) 2.6 (1.9-3.5) 0.98 (0.64-1.51) .92
Episodes of poor asthma control, components
Decrease in peak flow of >_30% for 2 consecutive days
Patients with >
_1 event, no. (%) 14 (21) 20 (27)
No. of events 38 68
Annual per-person event rate (95% CI) 0.9 (0.5-1.5) 1.7 (1.1-2.6) 0.55 (0.27-1.10) .09
Urgent asthma care
Patients with >
_1 event, no. (%) 6 (5) 11 (9)
No. of events 6 14
Annual per-person event rate (95% CI) 0.1 (0.1-0.3) 0.3 (0.2-0.6) 0.45 (0.16-1.27) .13
Systemic steroids
Patients with >
_1 event, no. (%) 15 (14) 17(15)
No. of events 20 15
Annual per-person event rate (95% CI) 0.3 (0.2-0.5) 0.4 (0.3-0.7) 0.78 (0.40-1.52) .47
Increased rescue medications
Patients with >
_1 event, no. (%) 29 (28) 27 (26)
No. of events 62 49
Annual per-person event rate (95% CI) 1.7 (1.1-2.5) 1.2 (0.8-1.9) 1.42 (0.78-2.59) .25

*Rate ratios, 95% CIs, and P values are based on negative binomial regression.

others do not.34 Recently, there have been a few multicenter trials translate into improved asthma control and was not associated
investigating the short-term effects of treating sinonasal disease in with other more clinically significant markers of asthma
asthmatic patients. Dahl et al16 found no effect of 6 weeks of exacerbations.
nasal corticosteroids on airway reactivity or induced sputum As anticipated, we found that nasal corticosteroids improved
eosinophilia; Katial et al35 and Nathan et al36 found that 4 weeks sinus symptoms and tended to improve quality of life related to
of intranasal corticosteroids improved nasal symptoms but had no sinus disease in adults. We did not see any improvement in sinus
effect on asthma control. These prior trials have studied the disease symptoms in children. The questionnaire we used to
short-term efficacy of nasal corticosteroids in asthmatic patients screen for sinonasal disease was developed in adults, but other
and suggest that the short-term treatment of sinonasal disease measures of sinonasal disease produced scores similar to those
with nasal corticosteroids does not improve asthma outcomes. previously reported for children with chronic rhinosinusitis and
There have been very few prospective controlled studies of perennial rhinitis, suggesting the study group had significant
longer-term treatment of sinonasal disease in asthmatic patients. disease that could respond to intervention.29,38-42 This lack of
In one longer-term (16 week) single-center study, Stelmach improvement was unexpected given that previous studies
et al37 found that patients with allergic rhinitis and asthma had showed nasal mometasone in the dose used in this study was
decreased pulmonary symptoms over the course of the study effective for the treatment of rhinitis in children43 and that nasal
when treated with nasal corticosteroids; however, there was no corticosteroids are considered first-line therapy for the treatment
placebo group, and all patient groups improved over the course of sinonasal disease in children.44 Although we do not know the
of the study, as occurred in our own study. Our trial is unique in reason for the lack of improvement, it is possible that adherence
that we measured the effects of nasal steroids compared with or drug delivery was more challenging in children than adults.
placebo over a longer time period (24 weeks) in both adults and Adherence in this study was monitored from diary cards and
children with chronic disease and poor asthma control. Our study appeared to be the same in adults and children (>90%), but this
shows that chronic nasal corticosteroids do not have a significant was by self-report and therefore might be subject to reporter
effect on asthma control. bias. The fact that we saw some improvement in lung function
We did find a small improvement in lung function in children in children assigned to nasal mometasone would also suggest
assigned to nasal mometasone. This improvement was not simply that the children were using this medication, although it is
in children not using controller medication. It might be that the possible that the drug was not being correctly delivered in
added dose of nasal steroid was beneficial for lung function children compared with adults.
either through systemic effects or perhaps postnasal drip of We included both rhinitis and sinusitis in this trial, rather than
corticosteroids. However, the clinical significance of this small trying to separate out the two. Asthma, rhinitis, and sinusitis share
improvement in lung function is uncertain. a common pathophysiology with common inflammatory media-
We saw fewer episodes of 2 consecutive days with a decrease tors and histopathologic changes apparent in the upper and lower
in peak flow of 30% or greater in children. The reason for this is airways.45 Rhinitis and sinusitis in asthmatic patients represent a
not known, although we speculate this might be related to disease continuum of the upper airway, which might be difficult to
some effect of postnasal drip in the large airways. However, the separate out without invasive testing, and therefore we did not
clinical significance of this is uncertain given that it did not attempt to distinguish the two.

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708 DIXON ET AL J ALLERGY CLIN IMMUNOL
MARCH 2015

The strengths of this study are that it was a large multicenter trial 2. Sazonov Kocevar V, Thomas J 3rd, Jonsson L, Valovirta E, Kristensen F, Yin DD,
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709.e1 DIXON ET AL J ALLERGY CLIN IMMUNOL
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CREDIT ROSTER MD (co-investigators); Stephanie M. Burns (principal clinic


American Lung Association Asthma Clinical coordinator); Kendall Black.
Research Centers Ohio State University Medical Center/Columbus
Baylor College of Medicine, Houston, Tex: Nicola Hanania, Children’s Hospital, Columbus, Ohio: John Mastronarde, MD
MD, FCCP (principal investigator); Marianna Sockrider, (principal investigator); Jonathan Parsons, MD (co-investigator);
MD, DrPH (co-principal investigator); Laura Bertrand, RN, Janice Drake, CCRC (principal clinic coordinator); Joseph
RPFT (principal clinic coordinator); Mustafa A. Atik, MD Santiago, BS (coordinator). Former members: David Cosmar,
(coordinator). Former member: Blanca A. Lopez, LVN. BA; Rachael A. Compton (coordinators).
Columbia University–New York University Consortium, Maria Fareri Children’s Hospital at Westchester Medical
New York, NY: Joan Reibman, MD (principal investigator); Center and New York Medical College, Valhalla, NY: Allen
Emily DiMango, MD, Linda Rogers, MD (co-principal investiga- J. Dozor, MD (principal investigator); Sankaran Krishnan, MD,
tors); Karen Carapetyan, MA (clinic coordinator at New York MPH; Joseph Boyer, MD (co-investigators); Agnes Banquet,
University); Kristina Rivera, MPH; Newel Bryce-Robinson; MD; Elizabeth de la Riva-Velasco, MD; Diana Lowenthal, MD;
Melissa Scheuerman (clinic coordinators at Columbia Univer- Suzette Gjonaj, MD; Y. Cathy Kim, MD; Nadav Traeger, MD;
sity). Former member: Elizabeth Fiorino, MD. John Welter, MD; Marilyn Scharbach, MD; Subhadra Siegel,
Duke University Medical Center, Durham, NC: John Sundy, MD (study physicians); Ingrid Gherson, MPH (lead research
MD, PhD (principal investigator); Brian Vickery, MD; Deanna coordinator); Lisa Monchil, RRT, CCRC; Aliza Goldstein, BA
Green, MD; Eveline Wu, MD (co-principal investigators); (research coordinators); Tara M. Formisano, BS; Patrick H.
Catherine Foss, BS, RRT, CCRC (principal clinic coordinator); Frangos; Jillian Jones, BSN, PNP; Jessica Williams (data entry
Jessica Ghidorzi; Sabrena Mervin-Blake; Elise Pangborn; personnel).
V. Susan Robertson; Nicholas Eberlein; Stephanie Allen St Louis Asthma Clinical Research Center, Washington
(coordinators). Former member: Michael Land, MD. University, St Louis, Mo: Mario Castro, MD, MPH (principal
Illinois Consortium, Chicago, Ill: Lewis Smith, MD investigator); Leonard Bacharier, MD; Kaharu Sumino, MD;
(principal investigator); Ravi Kalhan, MD; James Moy, MD; Raymond Slavin, MD (co-investigators); Jaime J. Tarsi, RN,
Mary Nevin; Edward Naureckas, MD (co-principal investiga- MPH (principal coordinator); Brenda Patterson, MSN, RN,
tors); Jenny Hixon, BS, CCRC (principal clinic coordinator); FNP; Deborah Keaney (coordinators); Terri Montgomery.
Abbi Brees, BA, CCRC; Zenobia Gonsalves; Virginia Zagaja; University of Arizona, Tucson, Ariz: Lynn B. Gerald, PhD,
Jennifer Kustwin; Ben Xu, BS, CCRC; Thomas Matthews, MSPH (principal investigator); James L. Goodwin, PhD; Mark
MPH, RRT; Lucius Robinson; Noopur Singh (coordinators). A. Brown, MD; Kenneth S. Knox, MD (co-principal investiga-
Indiana University, Asthma Clinical Research Center, Indi- tors); Tara F. Carr, MD; Cristine E. Berry, MD, MHS; Fernando
anapolis, Ind: Michael Busk, MD, MPH (principal investigator); D. Martinez, MD; Wayne J. Morgan, MD; Cori L. Daines, MD;
Paula Puntenney, RN, MA (principal clinic coordinator); Nancy Michael O. Daines, MD; Roni Grad, MD; Dima Ezmigna,
Busk, BS, MS; Janet Hutchins, BSN (coordinators). MBBS (study physicians); Monica M. Vasquez, MPH, MEd
Louisiana State University Health Sciences Center, The (principal clinic coordinator); Jesus A. Wences, BS; Silvia S.
Ernest N. Morial Asthma, Allergy and Respiratory Disease Lopez, RN; Janette C. Priefert (coordinators). Former members:
Center, New Orleans, La: Kyle I. Happel, MD (principal inves- Monica T. Varela, LPN; Rosemary J. Weese, RN, RRT (coordina-
tigator); Richard S. Tejedor, MD (co-principal investigator); tors); Katherine Chee; Andrea Paco (data entry personnel).
Marie C. Sandi, RN, MN, FNP-BC (principal clinic coordinator); University of Miami, Miami, Fla–University of South Flor-
Connie Romaine, RN, FNP; Callan J. Burzynski; Jonathan Cruse ida, Tampa, Fla: Adam Wanner, MD (principal investigator,
(coordinators). Former member: Arleen Antoine. Miami); Richard Lockey, MD (principal investigator, Tampa);
National Jewish Health, Denver, Colo: Rohit Katial, MD Michael Campos, MD; Andreas Schmid, MD (co-investigators,
(principal investigator); Flavia C. Hoyte, MD; Dan Searing, Miami); Monroe King (co-investigator, Tampa); Eliana S.
MD (co-principal investigators); Trisha Larson (principal clinic Mendes, MD (principal clinic coordinator for University of
coordinator); Nina Thompson (recruiter); Michael P. White Miami); Patricia D. Rebolledo; Johana Arana; Lilian Cadet;
(coordinator). Former member: Holly Currier, RN. Rebecca McCrery; Sarah M. Croker, BA (coordinators). Former
Nemours Children’s Clinic–University of Florida member: Shirley McCullough, BS, LPN (coordinator).
Consortium, Jacksonville, Fla: John Lima, PharmD (principal University of Missouri, Kansas City School of Medicine,
investigator); Kathryn Blake, PharmD (co-principal investigator); Kansas City, Mo: Gary Salzman, MD (principal investigator);
Jason Lang, MD (co-principal investigator); Deanna Seymour, Chitra Dinakar, MD; Asem Abdeljalil, MD; Dennis Pyszczynski,
RN, BSN (principal coordinator); Nancy Archer, RN, BSN MD; Abid Bhat, MD (co-investigators); Patti Haney, RN, BSN,
(coordinator). CCRC (principal clinic coordinator); Susan Flack, RN, CCRC,
Hofstra North Shore–LIJ School of Medicine, Beth Thal- Donna Horner, LPN, CCRC (coordinators).
heim Asthma Center (formerly North Shore–Long Island University of California San Diego, San Diego, Calif: Ste-
Jewish Health System), New Hyde Park, NY: Rubin Cohen, phen Wasserman, MD (principal investigator); Joe Ramsdell,
MD (principal investigator); Maria Santiago, MD (co-principal MD; Xaiver Soler, MD, PhD (co-principal investigators); Katie
investigator); Ramona Ramdeo, MSN, FNP-C, RN, RT (principal Kinninger, RCP (principal clinic coordinator); Paul Ferguson,
clinic coordinator). MS; Amber Martineau; Samang Ung (coordinators). Former
Vermont Lung Center at the University of Vermont, member: Tonya Greene (clinic coordinator).
Colchester, Vt: Charles Irvin, PhD (principal investigator); University of Virginia, Charlottesville, Va: W. Gerald
Anne E. Dixon, MD; David A. Kaminsky, MD; Thomas Lahiri, Teague, MD (principal investigator); Kristin W. Wavell, BS

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VOLUME 135, NUMBER 3

(principal coordinator). Former members: Donna Wolf, PhD; Shanklin Casper, MA; Marie Daniel, BA; Adante Hart; Andrea
Denise Thompson-Batt, RRT, CRP (coordinators). Lears, BS; Gwen Leatherman, BSN, MS, RN; Deborah Nowa-
Data Coordinating Center, Johns Hopkins University kowski; Nancy Prusakowski, MS; Alexis Rea; Joy Saams, RN;
Center for Clinical Trials, Baltimore, Md: Robert Wise, MD David Shade, JD; Elizabeth Sugar, PhD; April Thurman;
(center director), Janet Holbrook, PhD, MPH (deputy director); Christine Wei, MS; Razan Yasin, MHS. Former members: Ellen
Sobharani Rayapudi, MD, ScM (principal coordinator); Debra Brown, MS; Charlene Levine, BS; Suzanna Roettger, MA;
Amend-Libercci; Anna Adler; Christian Bime, MD, MSc; Anne Paul Chen; Nien-Chun Wu; Lucy Wang; Johnson Ukken, BA.

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709.e3 DIXON ET AL J ALLERGY CLIN IMMUNOL
MARCH 2015

FIG E1. Asthma control during study treatment for participants assigned to mometasone and placebo for
participants aged 6 to 11 years measured by using the cACT (A) and for participants aged 12 years or older
measured by using the ACT (B).

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TABLE E1. Characteristics of the study population at


randomization stratified by availability of the ACT or cACT
questionnaire at 24 weeks
Noncompleters Completers
(n 5 69) (n 5 319)

Therapy, no. (%)


Placebo 35 (18) 164 (82)
Mometasone 34 (18) 155 (82)
Demographics
Age (y), median (IQR) 21 (14-35) 28 (12-45)
Age categories, no. (%)
Pediatric (6-11 y) 15 (22) 71 (22)
Adolescent (12-17 y) 11 (16) 54 (17)
Adult (>_18 y) 43 (62) 194 (61)
Race/ethnicity, no. (%)
White 26 (38) 121 (38)
Black 29 (42) 118 (37)
Hispanic 14 (20) 67 (21)
Other 0 (0) 13 (4)
Male sex, no. (%) 34 (49) 143 (45)
Second-hand smoke exposure, no. (%) 13 (19) 79 (25)
Asthma characteristics
Age of asthma onset (y), median 5 (2-13) 5 (1-13)
(IQR)
Emergency visits in past 12 mo, 53 (77) 195 (61)
no. (%)
Steroid bursts in past 12 mo, no. (%) 39 (57) 151 (47)
Using controller medication, no. (%)* 42 (61) 236 (74)
ICS in combination with 26 (38) 140 (44)
LABA
ICS without LABA 16 (23) 95 (30)
Lung function, median (IQR)
Prebronchodilator FEV1 (% predicted) 86 (76-96) 85 (74-95)
Prebronchodilator FVC (% predicted) 100 (92-108) 95 (84-105)
Prebronchodilator FEV1/FVC ratio 0.74 (0.67-0.77) 0.76 (0.69-0.81)
Peak expiratory flow (L/min) 360 (300-440) 340 (280-420)
PC20 (mg/mL) 0.75 (0.25-3.63) 1.34 (0.29-4.31)
Questionnaires, median (IQR)
ACT score (range, 5-25)[  16 (14-19) 17 (14-19)
cACT score (range, 0-27)[  18 (16-19) 17 (14-19)
Asthma Symptom Utility Index 0.83 (0.71-0.89) 0.77 (0.69-0.88)
(range, 0-1)[à
Marks Asthma Quality of Life 18 (10-39) 19 (11-30)
Questionnaire (range, 1-80)Y§
Children’s Health Survey for
Asthma (range, 0-100)[k
Physical health (child) 75 (67-85) 77 (70-87)
Activities (child) 85 (70-95) 85 (65-100)
Activities (family) 96 (88-100) 92 (83-100)
Emotional health (child) 90 (55-100) 80 (60-95)
Emotional health (family) 76 (71-90) 79 (69-90)
Sinus symptom score (range, 1-60)Yà 26 (17-33) 25 (17-33)
SNOT-22 (range, 0-120)Y§ 37 (18-51) 37 (22-54)
SN-5 (range, 1-7)Yk 3.2 (2.8-4.6) 3.6 (2.8-4.5)

[, High scores indicate better health; Y, low scores indicate better health; FVC, forced
vital capacity; ICS, inhaled corticosteroid; IQR, interquartile range; LABA, long-acting
b-agonist; SN-5, Sino-Nasal Survey 5.
*One subject was using long-acting b-agonists without inhaled corticosteroids.
 The ACT was administered to participants aged 12 years and older, and the cACT
was administered to participants aged 6 to 11 years.
àThe Asthma Symptom Utility Index and sinus symptom score were administered to
all participants.
§The Marks Asthma Quality of Life Questionnaire and the SNOT-22 were
administered to participants aged 18 years and older.
kThe Children’s Health Survey for Asthma and the SN-5, Sino-Nasal Survey 5 were
administered to participants aged 6 to 11 years.

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709.e5 DIXON ET AL J ALLERGY CLIN IMMUNOL
MARCH 2015

TABLE E2. New sinus and new/increasing asthma medication use during treatment period of trial
Mometasone Placebo
No. New users Percentage No. New users Percentage P value*

Children
Started new sinus medication 66 23 35 75 23 31 .60
Started or increased dose of asthma medication 66 12 18 75 9 12 .30
Adults
Started new sinus medication 111 35 32 111 38 34 .67
Started or increased dose of asthma medication 111 6 5 111 9 8 .42
New sinus medication did not include nasal steroids, which were not permitted in this study, but included antihistamines and decongestants, which were permitted.
*P values are based on x2 tests comparing the proportion of participants in each treatment group.

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