Rationale: For unclear reasons, obese children with asthma have higher morbidity and reduced response to inhaled corticosteroids.Objectives: To assess whether childhood obesity is associated with airway dysanapsis (an incongruence between the growth of the lungs and the airways) and whether dysanapsis is associated with asthma morbidity.Methods: We examined the relationship between obesity and dysanapsis in six cohorts of children with and without asthma, as well as the relationship between dysanapsis and clinical outcomes in children with asthma. Adjusted odds ratios (ORs) were calculated for each cohort and in a combined analysis of all cohorts; longitudinal analyses were also performed for cohorts with available data. Hazard ratios (HRs) for clinical outcomes were calculated for children with asthma in the Childhood Asthma Management Program.Measurements and Main Results: Being overweight or obese was associated with dysanapsis in both the cross-sectional (OR, 1.95; 95% confidence interval [CI], 1.62-2.35 [for overweight/obese compared with normal weight children]) and the longitudinal (OR, 4.31; 95% CI, 2.99-6.22 [for children who were overweight/obese at all visits compared with normal weight children]) analyses. Dysanapsis was associated with greater lung volumes (FVC, vital capacity, and total lung capacity) and lesser flows (FEV 1 and forced expiratory flow, midexpiratory phase), and with indicators of ventilation inhomogeneity and anisotropic lung and airway growth. Among overweight/obese children with asthma, dysanapsis was associated with severe disease exacerbations (HR, 1.95; 95% CI, 1.38-2.75) and use of systemic steroids (HR, 3.22; 95% CI, 2.02-5.14).Conclusions: Obesity is associated with airway dysanapsis in children. Dysanapsis is associated with increased morbidity among obese children with asthma and may partly explain their reduced response to inhaled corticosteroids.

IMPORTANCE Severe asthma exacerbations cause significant morbidity and costs. Whether vitamin D 3 supplementation reduces severe childhood asthma exacerbations is unclear. OBJECTIVE To determine whether vitamin D 3 supplementation improves the time to a severe exacerbation in children with asthma and low vitamin D levels. DESIGN, SETTING, AND PARTICIPANTS The Vitamin D to Prevent Severe Asthma Exacerbations (VDKA) Study was a randomized, double-blind, placebo-controlled clinical trial of vitamin D 3 supplementation to improve the time to severe exacerbations in high-risk children with asthma aged 6 to 16 years taking low-dose inhaled corticosteroids and with serum 25-hydroxyvitamin D levels less than 30 ng/mL. Participants were recruited from 7 US centers. Enrollment started in February 2016, with a goal of 400 participants; the trial was terminated early (March 2019) due to futility, and follow-up ended in September 2019. INTERVENTIONS Participants were randomized to vitamin D 3 , 4000 IU/d (n = 96), or placebo (n = 96) for 48 weeks and maintained with fluticasone propionate, 176 μg/d (6-11 years old), or 220 μg/d (12-16 years old). MAIN OUTCOMES AND MEASURES The primary outcome was the time to a severe asthma exacerbation. Secondary outcomes included the time to a viral-induced severe exacerbation, the proportion of participants in whom the dose of inhaled corticosteroid was reduced halfway through the trial, and the cumulative fluticasone dose during the trial. RESULTS Among 192 randomized participants (mean age, 9.8 years; 77 girls [40%]), 180 (93.8%) completed the trial. A total of 36 participants (37.5%) in the vitamin D 3 group and 33 (34.4%) in the placebo group had 1 or more severe exacerbations. Compared with placebo, vitamin D 3 supplementation did not significantly improve the time to a severe exacerbation: the mean time to exacerbation was 240 days in the vitamin D 3 group vs 253 days in the placebo group (mean group difference, −13.1 days [95% CI, −42.6 to 16.4]; adjusted hazard ratio, 1.13 [95% CI, 0.69 to 1.85]; P = .63). Vitamin D 3 supplementation, compared with placebo, likewise did not significantly improve the time to a viral-induced severe exacerbation, the proportion of participants whose dose of inhaled corticosteroid was reduced, or the cumulative fluticasone dose during the trial. Serious adverse events were similar in both groups (vitamin D 3 group, n = 11; placebo group, n = 9). CONCLUSIONS AND RELEVANCE Among children with persistent asthma and low vitamin D levels, vitamin D 3 supplementation, compared with placebo, did not significantly improve the time to a severe asthma exacerbation. The findings do not support the use of vitamin D 3 supplementation to prevent severe asthma exacerbations in this group of patients.

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Rationale: Women have a higher burden of asthma than men. Although sex hormones may explain sex differences in asthma, their role is unclear.Objectives: To examine sex hormone levels and asthma in adults.Methods: Cross-sectional study of serum levels of free testosterone and estradiol and current asthma in 7,615 adults (3,953 men and 3,662 women) aged 18-79 years who participated in the 2013-2014 and 2015-2016 U.S. National Health and Nutrition Examination Survey. Logistic regression was used for the multivariable analysis of sex hormones and current asthma, which was conducted separately in women and men.Measurements and Main Results: Free testosterone levels in the fourth quartile were associated with lower odds of current asthma in women (odds ratio [OR] for the fourth quartile [Q4] vs. Q1, 0.56; 95% confidence interval [CI], 0.39-0.80). Given an interaction between obesity and sex hormones on current asthma, we stratified the analysis by obesity. In this analysis, elevated free testosterone (OR for Q4 vs. Q1, 0.59; 95% CI, 0.37-0.91) and estradiol (OR for Q4 vs. Q1, 0.43; 95% CI, 0.23-0.78) levels were associated with reduced odds of current asthma in obese women, and an elevated serum estradiol was associated with lower odds of current asthma in nonobese men (OR for Q4 vs. Q1, 0.44; 95% CI, 0.21-0.90).Conclusions: Our findings suggest that sex hormones play a role in known sex differences in asthma in adults. Moreover, our results suggest that obesity modifies the effects of sex hormones on asthma in adults.

SUMMARY Dietary changes may partly explain the high burden of asthma in industrialized nations. Experimental studies have motivated a significant number of observational studies of the relation between vitamins (A, C, D, and E) or nutrients acting as methyl donors (folate, vitamin B12, and choline) and asthma. Because observational studies are susceptible to several sources of bias, well-conducted randomized controlled trials (RCTs) remain the “gold standard” to determine whether a vitamin or nutrient has an effect on asthma. Evidence from observational studies and/or relatively few RCTs most strongly justify ongoing and future RCTs of: 1) vitamin D to prevent or treat asthma, 2) choline supplementation as adjuvant treatment for asthma, and 3) vitamin E to prevent the detrimental effects of air pollution in subjects with asthma. At this time, there is insufficient evidence to recommend supplementation with any vitamin or nutrient acting as a methyl donor to prevent or treat asthma.

Our findings suggest that a proinflammatory diet, assessed by the DII, increases the odds of current wheeze in adults and children with allergic (atopic) wheeze. These results further support testing dietary interventions as part of the management of asthma.

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Background and Objectives Although community violence may influence asthma morbidity by increasing stress, no study has assessed exposure to gun violence and childhood asthma. We examined whether exposure to gun violence is associated with asthma in children, particularly in those reporting fear of leaving their home. Methods Case-control study of 466 children aged 9 to 14 years with (n=234) and without (n=232) asthma in San Juan, Puerto Rico. Lifetime exposure to gun violence was defined as hearing a gunshot more than once. We also assessed whether the child was afraid to leave his/her home because of violence. Asthma was defined as physician-diagnosed asthma and wheeze in the prior year. We used logistic regression for the statistical analysis. All multivariate models were adjusted for age, gender, household income, parental asthma, environmental tobacco smoke, prematurity and residential distance from a major road. Results Cases were more likely to have heard a gunshot more than once than control subjects (n=156 or 67.2% vs. n=122 or 52.1%, P <0.01). In a multivariate analysis, hearing a gunshot more than once was associated with asthma (odds ratio [OR]=1.8, 95% confidence interval [CI]=1.1 to 1.7, P=0.01). Compared with children who had heard a gunshot not more than once and were not afraid to leave their home because of violence, those who had heard a gunshot more than once and were afraid to leave their home due to violence had 3.2 times greater odds of asthma (95% CI for OR=2.2 to 4.4, P <0.01). Conclusions Exposure to gun violence is associated with asthma in Puerto Rican children, particularly in those afraid to leave their home. Stress from such violence may contribute to the high burden of asthma in Puerto Ricans.