Roflumilast May Increase Risk of Exacerbations When Used to Treat Poorly Controlled Asthma in People with Obesity.

Rationale: People with obesity often have severe, difficult-to-control asthma. There is a need to develop better treatments for this population. One potential treatment is roflumilast, a phosphodiesterase 4 inhibitor, as it is reported to have efficacy for the treatment of asthma and can promote weight loss. Objectives: To investigate the potential efficacy of roflumilast for the treatment of poorly controlled asthma in people with obesity. Methods: A randomized, double-masked, placebo-controlled trial of 24 weeks of roflumilast versus placebo for the treatment of poorly controlled asthma in people with obesity (body mass index of 30 kg/m2 or higher). The primary outcome was a change in ACT (Asthma Control Test) score. Results: Twenty-two people were randomized to roflumilast and 16 to placebo. Roflumilast had no effect on change in the ACT (increased by 2.6 [interquartile range (IQR), 0.5-4.4] in those on roflumilast vs. 2.0 [IQR, 0.7-3.3] in those on placebo). Participants assigned to roflumilast had a 3.5-fold (relative risk [RR] 95% confidence interval [CI], 1.3-9.4) increased risk of an episode of poor asthma control and an 8.1-fold (RR 95% CI, 1.01-65.0) increased risk of an urgent care visit for asthma. Ten participants (56%) assigned to roflumilast required a course of oral corticosteroids for asthma exacerbations, and none in the placebo group. Participants losing 5% or more of their body weight experienced a clinically and statistically significant improvement in asthma control (ACT increased by 4.4 [IQR, 2.5-6.3] vs. 1.5 [IQR, 0.0-3.0] in those who lost less than 5%). Conclusions: Roflumilast had no effect on asthma control. Of concern, roflumilast was associated with an increased risk of exacerbation in obese individuals with poorly controlled asthma. These results highlight the importance of studying interventions in different subpopulations of people with asthma, particularly people with obesity and asthma who may respond differently to medications than lean people with asthma. Weight loss of at least 5% was associated with improved asthma control, indicating that interventions other than roflumilast promoting weight loss may have efficacy for the treatment of poorly controlled asthma in people with obesity. Clinical trial registered with www.clinicaltrials.gov (NCT03532490).

An Online Weight Loss Intervention for People With Obesity and Poorly Controlled Asthma.

BACKGROUND: Weight loss might improve asthma control in people with obesity. However, people with asthma might have particular challenges losing weight and the amount of weight loss needed to improve asthma control is not clear. OBJECTIVES: To pilot-test an online weight loss intervention and to estimate the impact of weight loss on asthma control. METHODS: We performed a 6-month, single-arm, futility trial of an online weight loss intervention at 2 centers. To reject the assumption of futility, 9 or more participants had to lose at least 5% of their body weight. We also assessed the association between weight loss (≥5%) and asthma outcomes. RESULTS: Forty-three participants (85% women) started the weight loss intervention. The median and interquartile range for the body mass index was 40.3 kg/m2 (range 34.7-46.8 kg/m2), and 14 (range 12-17 kg/m2) for the Asthma Control Test score. At 6 months, 10 participants (23%; 95% CI 12%-39%) lost at least 5% of their initial weight. Weight loss of at least 5% was associated with a clinically and statistically significant improvements in their Asthma Control Test (median [interquartile range] increase of 3 [1 to 7]; P < .05), Marks Asthma Quality of Life Score (-9.5 [-18 to -3]; P = .008), and their general health-related quality of life score (RAND-36; improved by 9.4 [2.8 to 22.5]; P =.014). CONCLUSIONS: An online weight loss intervention has the potential to meet U.S. Food and Drug Administration guidance for product evaluation (at least a 5% weight loss in 35% of people) for treating obesity, and is associated with a clinically significant improvement in asthma control, quality of life, and overall health-related quality of life.

The challenge of addressing obesity in people with poorly controlled asthma.

OBJECTIVE: There is a high prevalence of obesity in people with asthma, and obesity is associated with poorly controlled asthma. Significant weight loss might improve asthma control: the purpose of this study was to investigate patient characteristics and factors that might affect implementation of a weight loss and/or roflumilast intervention, to target both obesity and asthma. METHODS: A cross-sectional study of people with obesity and poorly controlled asthma performed at 13 sites across the United States. RESULTS: One hundred and two people participated in this study. Median BMI was 37 (IQR 35-42). The majority, 55%, were African American and 76% were female. Fifty two percent had very poorly controlled asthma. Most participants were quite sedentary (70% reported being inactive or participating only in light-intensity activities according to the Stanford Brief Activity Survey). Participants reported significant impairments related to physical function on the Impact of Weight on Quality of Life-Lite questionnaire (median score 67 [IQR 41-84]). Thirty-five percent of participants reported mild, and 2 % moderate, depressive symptoms as assessed by the Patient Health Questionnaire-9. CONCLUSIONS: Poorly controlled asthma and obesity often affect minority populations and are associated with significant impairments in health related to physical function and low levels of physical activity that might complicate efforts to lose weight. Interventions targeted at poorly controlled asthma associated with obesity in the United States need to address factors complicating health in underserved communities, such as increasing opportunities for physical activity, while also managing activity limitations related to the combination of asthma and obesity.

Study protocol for a national cohort of adults focused on respiratory health: the American Lung Association Lung Health Cohort (ALA-LHC) Study.

INTRODUCTION: The current framework for investigating respiratory diseases is based on defining lung health as the absence of lung disease. In order to develop a comprehensive approach to prevent the development of lung disease, there is a need to evaluate the full spectrum of lung health spanning from ideal to impaired lung health. The American Lung Association (ALA) Lung Health Cohort is a new, population-based, cohort study focused primarily on characterising lung health in members of the millennial generation without diagnosed severe respiratory disease. Participants will be enrolled for the baseline study visit starting in 2021, and funding will be sought to support future study exams as part of a longitudinal cohort study. This study will be crucial for developing a novel paradigm of lung health throughout the adult life course. METHODS AND ANALYSIS: This study will leverage the existing infrastructure of the ALA Airways Clinical Research Centers network to enrol 4000 participants between ages 25 and 35 years old at 39 sites across the USA between April 2021 and December 2024. Study procedures will include physical assessment, spirometry, chest CT scan, accelerometry and collection of nasal epithelial lining fluid, nasal epithelial cells, blood and urine. Participants will complete questionnaires about their sociodemographic characteristics, home address histories and exposures, work history and exposure, medical histories, lung health and health behaviours and activity. ETHICS AND DISSEMINATION: The study was approved by the Johns Hopkins Medicine Institutional Review Board. Findings will be disseminated to the scientific community through peer-reviewed journals and at professional conferences. The lay public will receive scientific findings directly through the ALA infrastructure including the official public website. Deidentified datasets will be deposited to BioLINCC, and deidentified biospecimens may be made available to qualified investigators along with a limited-use datasets.