Background Short-term targeted treatment can potentially prevent fall asthma exacerbations while limiting therapy exposure. Objective We sought to compare (1) omalizumab with placebo and (2) omalizumab with an inhaled corticosteroid (ICS) boost with regard to fall exacerbation rates when initiated 4 to 6 weeks before return to school. Methods A 3-arm, randomized, double-blind, double placebo-controlled, multicenter clinical trial was conducted among inner-city asthmatic children aged 6 to 17 years with 1 or more recent exacerbations (clincaltrials.gov #NCT01430403). Guidelines-based therapy was continued over a 4- to 9-month run-in phase and a 4-month intervention phase. In a subset the effects of omalizumab on IFN-α responses to rhinovirus in PBMCs were examined. Results Before the falls of 2012 and 2013, 727 children were enrolled, 513 were randomized, and 478 were analyzed. The fall exacerbation rate was significantly lower in the omalizumab versus placebo arms (11.3% vs 21.0%; odds ratio [OR], 0.48; % CI, 0.25–.92), but there was no significant difference between omalizumab and ICS boost (8.4% vs 11.1%; OR, 0.73; 95% CI, 0.33–1.64). In a prespecified subgroup analysis, among participants with an exacerbation during the run-in phase, omalizumab was significantly more efficacious than both placebo (6.4% vs 36.3%; OR, 0.12; 95% CI, 0.02–0.64) and ICS boost (2.0% vs 27.8%; OR, 0.05; 95% CI, 0.002–0.98). Omalizumab improved IFN-α responses to rhinovirus, and within the omalizumab group, greater IFN-α increases were associated with fewer exacerbations (OR, 0.14; 95% CI, 0.01–0.88). Adverse events were rare and similar among arms. Conclusions Adding omalizumab before return to school to ongoing guidelines-based care among inner-city youth reduces fall asthma exacerbations, particularly among those with a recent exacerbation.

Background Treatment levels required to control asthma vary greatly across a population with asthma. The factors that contribute to variability in treatment requirements of inner-city children have not been fully elucidated. Objective To identify the clinical characteristics which distinguish difficult-to-control asthma. Methods Children with asthma aged 6-17 underwent baseline assessment and bimonthly guidelines-based management visits over one year. Difficult- versus easy-to-control asthma were defined as daily therapy with fluticasone ≥500mcg +/-LABA versus ≤100mcg assigned on at least 4 visits. Forty-four baseline variables were used to compare the 2 groups using univariate analyses and identify the most relevant features of difficult-to-control asthma using a variable selection algorithm. Nonlinear seasonal variation in longitudinal measures (symptoms, pulmonary physiology and exacerbations) was examined using generalized additive mixed-effects models. Results Among 619 recruited participants, 40.9% had difficult-to-control asthma, 37.5% had easy-to-control asthma and 21.6% fell into neither group. At baseline, FEV1 bronchodilator responsiveness was the most important characteristic distinguishing difficult- from easy-to-control asthma. Markers of rhinitis severity and atopy were among the other major discriminating features. Over time, difficult-to-control asthma was characterized by high exacerbation rates, particularly in spring and fall, greater day and night symptoms, especially in fall and winter, and compromised pulmonary physiology despite ongoing high dose controller therapy. Conclusions Despite good adherence, difficult-to-control asthma showed little improvement in symptoms, exacerbations or pulmonary physiology over the year. Besides pulmonary physiology measures, rhinitis severity and atopy were associated with high dose asthma controller therapy requirement. Clinical Implications Clinical baseline characteristics related to pulmonary physiology, rhinitis severity, and atopy prospectively distinguish difficult- from easy-to-control asthma.

Most adolescents with asthma in this study used CAM. The prevalence of CAM use in this study population was twice the national average for adults.

BackgroundDevelopment of adult respiratory disease is influenced by events in childhood. The impact of childhood pneumonia on chronic obstructive pulmonary disease (COPD) is not well defined. We hypothesize that childhood pneumonia is a risk factor for reduced lung function and COPD in adult smokers.MethodsCOPD cases and control smokers between 45–80 years old from the United States COPDGene Study were included. Childhood pneumonia was defined by self-report of pneumonia at <16 years. Subjects with lung disease other than COPD or asthma were excluded. Smokers with and without childhood pneumonia were compared on measures of respiratory disease, lung function, and quantitative analysis of chest CT scans.ResultsOf 10,192 adult smokers, 854 (8.4 %) reported pneumonia in childhood. Childhood pneumonia was associated with COPD (OR 1.40; 95 % CI 1.17-1.66), chronic bronchitis, increased COPD exacerbations, and lower lung function: post-bronchodilator FEV1 (69.1 vs. 77.1 % predicted), FVC (82.7 vs. 87.4 % predicted), FEV1/FVC ratio (0.63 vs. 0.67; p < 0.001 for all comparisons). Childhood pneumonia was associated with increased airway wall thickness on CT, without significant difference in emphysema. Having both pneumonia and asthma in childhood further increased the risk of developing COPD (OR 1.85; 95 % CI 1.10-3.18).ConclusionsChildren with pneumonia are at increased risk for future smoking-related lung disease including COPD and decreased lung function. This association is supported by airway changes on chest CT scans. Childhood pneumonia may be an important factor in the early origins of COPD, and the combination of pneumonia and asthma in childhood may pose the greatest risk.Clinical trials registrationClinicalTrials.gov, NCT00608764 (Active since January 28, 2008).Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-015-0273-8) contains supplementary material, which is available to authorized users.

Rationale: Puerto Ricans have the highest prevalence of and morbidity from asthma of all ethnic groups in the United States. One potential contributor to the high burden of asthma in Puerto Rican children is exposure to stress and violence. Objectives: To examine whether exposure to stress and violence is associated with an increased risk of asthma among Puerto Rican children. Methods: This study was a population-based probability sample of children in the San Juan and Caguas metropolitan areas in Puerto Rico. Information was collected in a household survey of 1,213 children and their primary caretakers. Measurements and Main Results: The prevalence of lifetime physiciandiagnosed asthma was 39.6%. In the year before the survey, 14% of children had witnessed an act of violence, 7% had been victims of violence, and 6% had been victims of physical or sexual abuse. Although stressful life events and exposure to neighborhood violence were not associated with asthma, a history of physical or sexual abuse was associated with approximately twice the odds of current asthma (odd ratio [OR], 2.52; 95% confidence interval [CI], 1.27-5.00), health care use for asthma (OR, 1.95; 95% CI, 0.96-3.96), and medication use for asthma (OR, 2.35; 95% CI, 1.05-5.26). Conclusions: Physical or sexual abuse is associated with high asthma morbidity among Puerto Rican children. To our knowledge, this is the first report of an association between childhood abuse and asthma. Our findings highlight the importance of screening for asthma among victims of childhood abuse, and to be aware of the possibility of physical or sexual abuse among children with asthma.