Bronchodilators in Tobacco-Exposed Persons with Symptoms and Preserved Lung Function.

BACKGROUND: Many persons with a history of smoking tobacco have clinically significant respiratory symptoms despite an absence of airflow obstruction as assessed by spirometry. They are often treated with medications for chronic obstructive pulmonary disease (COPD), but supporting evidence for this treatment is lacking. METHODS: We randomly assigned persons who had a tobacco-smoking history of at least 10 pack-years, respiratory symptoms as defined by a COPD Assessment Test score of at least 10 (scores range from 0 to 40, with higher scores indicating worse symptoms), and preserved lung function on spirometry (ratio of forced expiratory volume in 1 second [FEV1] to forced vital capacity [FVC] ≥0.70 and FVC ≥70% of the predicted value after bronchodilator use) to receive either indacaterol (27.5 µg) plus glycopyrrolate (15.6 µg) or placebo twice daily for 12 weeks. The primary outcome was at least a 4-point decrease (i.e., improvement) in the St. George's Respiratory Questionnaire (SGRQ) score (scores range from 0 to 100, with higher scores indicating worse health status) after 12 weeks without treatment failure (defined as an increase in lower respiratory symptoms treated with a long-acting inhaled bronchodilator, glucocorticoid, or antibiotic agent). RESULTS: A total of 535 participants underwent randomization. In the modified intention-to-treat population (471 participants), 128 of 227 participants (56.4%) in the treatment group and 144 of 244 (59.0%) in the placebo group had at least a 4-point decrease in the SGRQ score (difference, -2.6 percentage points; 95% confidence interval [CI], -11.6 to 6.3; adjusted odds ratio, 0.91; 95% CI, 0.60 to 1.37; P = 0.65). The mean change in the percent of predicted FEV1 was 2.48 percentage points (95% CI, 1.49 to 3.47) in the treatment group and -0.09 percentage points (95% CI, -1.06 to 0.89) in the placebo group, and the mean change in the inspiratory capacity was 0.12 liters (95% CI, 0.07 to 0.18) in the treatment group and 0.02 liters (95% CI, -0.03 to 0.08) in the placebo group. Four serious adverse events occurred in the treatment group, and 11 occurred in the placebo group; none were deemed potentially related to the treatment or placebo. CONCLUSIONS: Inhaled dual bronchodilator therapy did not decrease respiratory symptoms in symptomatic, tobacco-exposed persons with preserved lung function as assessed by spirometry. (Funded by the National Heart, Lung, and Blood Institute and others; RETHINC ClinicalTrials.gov number, NCT02867761.).

Impact of the Coronavirus Disease 2019 Pandemic on Physical and Mental Health of Patients With COPD: Results From a Longitudinal Cohort Study Conducted in the United States (2020-2021).

Background: Patients with chronic obstructive pulmonary disease (COPD) are at higher risk for severe coronavirus disease 2019 (COVID-19). From the pandemic's onset there has been concern regarding effects on health and well-being of high-risk patients. Methods: This was an ancillary study to the Losartan Effects on Emphysema Progression (LEEP) Trial and was designed to collect descriptive information longitudinally about the health and wellbeing of COPD patients who were enrolled in a clinical trial. Participants were interviewed by telephone about their health status every 2 weeks and their mental health, knowledge, and behaviors every 8 weeks from June 2020 to April 2021. There were no pre-specified hypotheses. Results: We enrolled 157 of the 220 participants from the parent LEEP trial. Their median age was 69 years, 55% were male, and 82% were White; median forced expiratory volume in 1 second (FEV1)% predicted was 48%. Nine confirmed COVID-19 infections were reported, 2 resulting in hospitalization. Rates of elevated anxiety or depressive symptoms were 8% and 19% respectively in June 2020 and remained relatively stable during follow-up. By April 2021, 85% of participants said they were "very likely" to receive a vaccine; 91% were vaccinated (≥1 dose) by the end of December 2021. Conclusion: Our select cohort of moderate to severe COPD patients who were well integrated into a health care network coped well with the COVID-19 pandemic. Few participants were diagnosed with COVID-19, levels of depression and anxiety were stable, most adopted accepted risk reduction behaviors, and did not become socially isolated; most were vaccinated by the end of 2021.

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.

Losartan Effects on Emphysema Progression Randomized Clinical Trial: Rationale, Design, Recruitment, and Retention.

The Losartan Effects on Emphysema Progression (LEEP) trial was designed to test the hypothesis that losartan slows progression of emphysema in chronic obstructive pulmonary disease (COPD) patients (NCT00720226). It was conducted by the Pulmonary Trials Cooperative consortium, in collaboration with the American Lung Association Airways Clinical Research Centers network. We describe the design of the trial and challenges for recruitment and follow-up of participants. LEEP is a placebo-controlled, parallel randomized trial, allocation ratio of 1:1, with a planned sample size of 220. Primary eligibility criteria were mild emphysema based on high-resolution computed tomography (HRCT) scans with 5% to 35% voxels <-950 Hounsfield units (HU), airway obstruction based on spirometry, and not taking an angiotensin receptor blocker or angiotensin converting enzyme (ACE) inhibitor. Participants received either losartan or placebo for 48 weeks. A total of 2779 individuals were screened to enroll 220 eligible participants at 26 clinical sites, all located in the continental United States. Recruitment took 45% longer than planned (32 months versus 22 months), with an average accrual rate of 6.7 participants per month. Recruitment challenges included identification of eligible participants who were not already taking or who did not have an established clinical indication for an angiotensin receptor blocker or ACE inhibitor drug and recalls of contaminated lots of losartan by the Food and Drug Administration. A number of recruitment initiatives were launched in response. Recruitment was completed in February 2020, just prior to a nationwide shutdown of research activities due to the coronavirus disease 2019 (COVID-19) pandemic.