Rationale: Reducing asthma exacerbation frequency is an important criterion for approval of asthma therapies, but the clinical features of exacerbation-prone asthma (EPA) remain incompletely defined.Objectives: To describe the clinical, physiologic, inflammatory, and comorbidity factors associated with EPA.Methods: Baseline data from the NHLBI Severe Asthma Research Program (SARP)-3 were analyzed. An exacerbation was defined as a burst of systemic corticosteroids lasting 3 days or more. Patients were classified by their number of exacerbations in the past year: none, few (one to two), or exacerbation prone (>3). Replication of a multivariable model was performed with data from the SARP-1 1 2 cohort.Measurements and Main Results: Of 709 subjects in the SARP-3 cohort, 294 (41%) had no exacerbations and 173 (24%) were exacerbation prone in the prior year. Several factors normally associated with severity (asthma duration, age, sex, race, and socioeconomic status) did not associate with exacerbation frequency in SARP-3; bronchodilator responsiveness also discriminated exacerbation proneness from asthma severity. In the SARP-3 multivariable model, blood eosinophils, body mass index, and bronchodilator responsiveness were positively associated with exacerbation frequency (rate ratios [95% confidence interval],

Background: Previous research has found relationships between specific indoor environmental exposures and exacerbation of asthma.Objectives: In this review we provide an updated summary of knowledge from the scientific literature on indoor exposures and exacerbation of asthma.Methods: Peer-reviewed articles published from 2000 to 2013 on indoor exposures and exacerbation of asthma were identified through PubMed, from reference lists, and from authors’ files. Articles that focused on modifiable indoor exposures in relation to frequency or severity of exacerbation of asthma were selected for review. Research findings were reviewed and summarized with consideration of the strength of the evidence.Results: Sixty-nine eligible articles were included. Major changed conclusions include a causal relationship with exacerbation for indoor dampness or dampness-related agents (in children); associations with exacerbation for dampness or dampness-related agents (in adults), endotoxin, and environmental tobacco smoke (in preschool children); and limited or suggestive evidence for association with exacerbation for indoor culturable Penicillium or total fungi, nitrogen dioxide, rodents (nonoccupational), feather/down pillows (protective relative to synthetic bedding), and (regardless of specific sensitization) dust mite, cockroach, dog, and dampness-related agents.Discussion: This review, incorporating evidence reported since 2000, increases the strength of evidence linking many indoor factors to the exacerbation of asthma. Conclusions should be considered provisional until all available evidence is examined more thoroughly.Conclusion: Multiple indoor exposures, especially dampness-related agents, merit increased attention to prevent exacerbation of asthma, possibly even in nonsensitized individuals. Additional research to establish causality and evaluate interventions is needed for these and other indoor exposures.Citation: Kanchongkittiphon W, Mendell MJ, Gaffin JM, Wang G, Phipatanakul W. 2015. Indoor environmental exposures and exacerbation of asthma: an update to the 2000 review by the Institute of Medicine. Environ Health Perspect 123:6–20; http://dx.doi.org/10.1289/ehp.1307922

IMPORTANCE In asthma and other diseases, vitamin D insufficiency is associated with adverse outcomes. It is not known if supplementing inhaled corticosteroids with oral vitamin D3 improves outcomes in patients with asthma and vitamin D insufficiency. OBJECTIVE To evaluate if vitamin D supplementation would improve the clinical efficacy of inhaled corticosteroids in patients with symptomatic asthma and lower vitamin D levels. DESIGN, SETTING, AND PARTICIPANTS The VIDA (Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness in Asthma) randomized, double-blind, parallel, placebo-controlled trial studying adult patients with symptomatic asthma and a serum 25-hydroxyvitamin D level of less than 30 ng/mL was conducted across 9 academic US medical centers in the National Heart, Lung, and Blood Institute’s AsthmaNet network, with enrollment starting in April 2011 and follow-up complete by January 2014. After a run-in period that included treatment with an inhaled corticosteroid, 408 patients were randomized. INTERVENTIONS Oral vitamin D3 (100 000 IU once, then 4000 IU/d for 28 weeks; n = 201) or placebo (n = 207) was added to inhaled ciclesonide (320 µg/d). If asthma control was achieved after 12 weeks, ciclesonide was tapered to 160 µg/d for 8 weeks, then to 80 µg/d for 8 weeks if asthma control was maintained. MAIN OUTCOMES AND MEASURES The primary outcome was time to first asthma treatment failure (a composite outcome of decline in lung function and increases in use of β-agonists, systemic corticosteroids, and health care). RESULTS Treatment with vitamin D3 did not alter the rate of first treatment failure during 28 weeks (28%[95% CI, 21%-34%] with vitamin D3 vs 29% [95% CI, 23%–35%] with placebo; adjusted hazard ratio, 0.9 [95% CI, 0.6–1.3]). Of 14 prespecified secondary outcomes, 9 were analyzed, including asthma exacerbation; of those 9, the only statistically significant outcome was a small difference in the overall dose of ciclesonide required to maintain asthma control (111.3 µg/d [95% CI, 102.2–120.4 µg/d] in the vitamin D3 group vs 126.2 µg/d [95% CI, 117.2–135.3 µg/d] in the placebo group; difference of 14.9 µg/d [95% CI, 2.1–27.7 µg/d]). CONCLUSIONS AND RELEVANCE Vitamin D3 did not reduce the rate of first treatment failure or exacerbation in adults with persistent asthma and vitamin D insufficiency. These findings do not support a strategy of therapeutic vitamin D3 supplementation in patients with symptomatic asthma. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01248065