Bronchodilator response does not associate with asthma control or symptom burden among patients with poorly controlled asthma.

PURPOSE: The purpose of this study was to determine how four different definitions of bronchodilator response (BDR) relate to asthma control and asthma symptom burden in a large population of participants with poorly controlled asthma. PROCEDURES: We examined the baseline change in FEV1 and FVC in response to albuterol among 931 participants with poorly controlled asthma pooled from three clinical trials conducted by the American Lung Association - Airways Clinical Research Centers. We defined BDR based on four definitions and analyzed the association of each with asthma control as measured by the Asthma Control Test or Asthma Control Questionnaire, and asthma symptom burden as measured by the Asthma Symptom Utility Index. MAIN FINDINGS: A BDR was seen in 31-42% of all participants, depending on the definition used. There was good agreement among responses (kappa coefficient 0.73 to 0.87), but only 56% of participants met all four definitions for BDR. A BDR was more common in men than women, in Blacks compared to Whites, in non-smokers compared to smokers, and in non-obese compared to obese participants. Among those with poorly controlled asthma, 35% had a BDR compared to 25% of those with well controlled asthma, and among those with a high symptom burden, 34% had a BDR compared to 28% of those with a low symptom burden. After adjusting for age, sex, height, race, obesity and baseline lung function, none of the four definitions was associated with asthma control or symptom burden. CONCLUSION: A BDR is not associated with asthma control or symptoms in people with poorly controlled asthma, regardless of the definition of BDR used. These findings question the clinical utility of a BDR in assessing asthma control and symptoms.

Cataract Surgery in Patients With Uveitis Treated With Systemic Therapy in the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study: Risk Factors and Outcomes.

PURPOSE: To evaluate the rate of, risk factors for, and outcomes of cataract surgery in patients with intermediate, posterior, and panuveitides treated with systemic corticosteroids and immunosuppression. DESIGN: Cohort study of participants from a randomized clinical trial. METHODS: A multicenter clinical trial with extended follow-up comprised the study setting. From the cohort of participants assigned to systemic therapy in the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study, 125 phakic eyes of 74 patients with intermediate, posterior, or panuveitides treated with systemic therapy were included. The main outcome measures were cataract surgery and visual acuity after cataract surgery. RESULTS: The cumulative incidence of cataract surgery was 43% at 7 years of follow-up, and the risk did not plateau. Risk factors for cataract surgery included age >50 years (hazard ratio [HR] 2.86, 95% CI 1.52, 5.42; P = .001), topical corticosteroid use (time-updated HR 3.13, 95% CI 1.42, 6.94; P = .005), glaucoma medication use (HR 2.75, 95% CI 1.38, 5.47; P = .004), and possibly history of anterior chamber inflammation (HR 1.90, 95% CI 0.95, 3.84; P = .07). Median gain in acuity and median best corrected visual acuity 1 year after cataract surgery were 4.8 lines and 20/25, respectively, among 42 eyes undergoing cataract surgery with 1-year follow-up data. CONCLUSIONS: Among patients with intermediate, posterior, and panuveitides, treated with oral corticosteroids and immunosuppression, there is a substantial long-term risk of cataract surgery. Visual acuity outcomes after cataract surgery are generally good.

Examining the association of habitual e-cigarette use with inflammation and endothelial dysfunction in young adults: The VAPORS-Endothelial function study.

INTRODUCTION: Acute exposure to e-cigarette aerosol has been shown to have potentially deleterious effects on the cardiovascular system. However, the cardiovascular effects of habitual e-cigarette use have not been fully elucidated. Therefore, we aimed to assess the association of habitual e-cigarette use with endothelial dysfunction and inflammation - subclinical markers known to be associated with increased cardiovascular risk. METHODS: In this cross-sectional study, we analyzed data from 46 participants (23 exclusive e-cigarette users; 23 non-users) enrolled in the VAPORS-Endothelial function study. E-cigarette users had used e-cigarettes for ≥6 consecutive months. Non-users had used e-cigarettes <5 times and had a negative urine cotinine test (<30 ng/mL). Flow-mediated dilation (FMD) and reactive hyperemia index (RHI) were used to assess endothelial dysfunction, and we assayed high-sensitivity C-reactive protein, interleukin-6, fibrinogen, p-selectin, and myeloperoxidase as serum measures of inflammation. We used multivariable linear regression to assess the association of e-cigarette use with the markers of endothelial dysfunction and inflammation. RESULTS: Of the 46 participants with mean age of 24.3 ± 4.0 years, the majority were males (78%), non-Hispanic (89%), and White (59%). Among non-users, 6 had cotinine levels <10 ng/mL while 17 had levels 10-30 ng/mL. Conversely, among e-cigarette users, the majority (14 of 23) had cotinine ≥500 ng/mL. At baseline, the systolic blood pressure was higher among e-cigarette users than non-users (p=0.011). The mean FMD was slightly lower among e-cigarette users (6.32%) compared to non-users (6.53%). However, in the adjusted analysis, current e-cigarette users did not differ significantly from non-users in their mean FMD (Coefficient=2.05; 95% CI: -2.52-6.63) or RHI (Coefficient= -0.20; 95% CI: -0.88-0.49). Similarly, the levels of inflammatory markers were generally low and did not differ between e-cigarette users and non-users. CONCLUSIONS: Our findings suggest that e-cigarette use may not be significantly associated with endothelial dysfunction and systemic inflammation in relatively young and healthy individuals. Longer term studies with larger sample sizes are needed to validate these findings.

Intravitreal Therapy for Uveitic Macular Edema-Ranibizumab versus Methotrexate versus the Dexamethasone Implant: The MERIT Trial Results.

PURPOSE: To evaluate the effectiveness of 3 different intravitreal treatments for persistent or recurrent uveitic macular edema (ME): dexamethasone implant, methotrexate, and ranibizumab. DESIGN: Single-masked, randomized controlled clinical trial. PARTICIPANTS: Patients with minimally active or inactive uveitis and persistent or recurrent uveitic ME in one or both eyes. METHODS: Patients at 33 centers were randomized 1:1:1 to receive 1 of the 3 therapies. Patients with bilateral ME received the same treatment in both eyes. MAIN OUTCOME MEASURES: The primary outcome, measured at 12 weeks, was reduction in central subfield thickness (CST) expressed as a proportion of baseline (CST per CST at baseline) assessed with spectral-domain OCT by readers masked to treatment assignment. Secondary outcomes included improvement and resolution of ME, change in best-corrected visual acuity (BCVA), and elevations in intraocular pressure (IOP). RESULTS: One hundred ninety-four participants (225 eligible eyes) were randomized to dexamethasone (n = 65 participants and 77 eyes), methotrexate (n = 65 participants and 79 eyes), or ranibizumab (n = 64 participants and 69 eyes). All received at least 1 injection of the assigned treatment. At the 12-week primary outcome point, each group showed significant reductions in CST relative to baseline: 35%, 11%, and 22% for dexamethasone, methotrexate, and ranibizumab, respectively. Reduction of ME was significantly greater in the dexamethasone group than for either methotrexate (P < 0.01) or ranibizumab (P = 0.018). Only the dexamethasone group showed a statistically significant improvement in BCVA during follow-up (4.86 letters; P < 0.001). Elevations of IOP by 10 mmHg, to 24 mmHg or more, or both were more common in the dexamethasone group; IOP spikes to 30 mmHg or more were uncommon overall and were not significantly different among groups. Reductions in BCVA of 15 letters or more were more common in the methotrexate group and typically were attributable to persistent ME. CONCLUSIONS: At 12 weeks, in eyes with minimally active or inactive uveitis, dexamethasone was significantly better at treating persistent or recurrent ME than methotrexate or ranibizumab. Risk of IOP elevation was greater with dexamethasone, but elevations to levels of 30 mmHg or more were infrequent. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Comprehension by Caregivers and Adolescents of Clinical Trial Information Delivered via Multimedia Video Versus Conventional Practice: Nonrandomized Controlled Trial.

BACKGROUND: Research participants often misunderstand the required elements of informed consent information, whether provided in written or oral format. Informed consent instruments with embedded evidence-based learning theory principles administered in multimedia electronic formats may improve comprehension and retention. OBJECTIVE: This study aims to determine whether study information comprehension and retention using an interactive multimedia video consent process was noninferior to comprehension and retention after an in-person face-to-face interaction with a conventional written consent document for caregivers and adolescents enrolled in a clinical trial. METHODS: Participants were caregivers and children aged 12 to 17 years who were enrolled in a clinical trial of asthma treatment. Consent information was presented as a multimedia web-based video consent interaction or as a conventional written consent document with in-person interaction between the prospective participants and the study staff. The trial used a parallel nonrandomized noninferiority design that compared the 2 consent methods. Caregivers and adolescents completed a 17-item open-ended comprehension questionnaire (score range 17-51) at enrollment and at the end of the study 20 weeks later. Comprehension and retention were compared between the consent formats. Noninferiority was established if the 95% CI upper bound of the difference in scores (conventional format minus web-based) was less than the noninferiority margin of 2.4; superiority was established if the upper bound of the CI was <0. RESULTS: In total, 54 caregiver and adolescent dyads completed the interactive multimedia web-based video consent, and 25 dyads completed the conventional consent. Overall, 33% (26/79) of all adolescents were Black, 57% (45/79) were male, and 61% (48/79) had a household income of

Efficacy and tolerability of zinc acetate for treatment of chronic refractory cough: pilot randomised futility trial.

Background: Cough is the most reported symptom in the United States, with chronic refractory cough representing significant morbidity to patients. Zinc acetate may have beneficial effects in the cough reflex pathway. We sought to assess the safety and efficacy of zinc acetate in the management of chronic refractory cough. Study design and methods: This was a randomised, placebo-controlled, parallel-design pilot trial of individuals with chronic refractory cough. The effects of 6 weeks of zinc acetate versus placebo on quality of life and symptoms as measured by the Cough Quality-of-Life Questionnaire (CQLQ), Leicester Cough Questionnaire (LCQ), cough visual analogue score (C-VAS) and Global Assessment of Change in Cough (GACC) scores were evaluated. A futility analysis plan with a one-sided 80% confidence interval was used to compare treatment effect to published minimum clinically important differences (MCID) for each outcome. Results: 34 participants, 17 in each group, were enrolled and randomised. Participants were primarily white females with moderate-severe cough. Participants assigned to zinc acetate had a significant increase in serum zinc levels after 6 weeks, while those assigned to placebo did not. Both groups showed improvement in CQLQ, LCQ, C-VAS and GACC scores, but the treatment effects of zinc acetate versus placebo were small with confidence intervals that did not include the MCIDs. Interpretation: We observed no benefit of zinc therapy over placebo on cough symptoms or quality of life and conclude that larger trials of zinc for chronic cough are not warranted.

The mediating roles of the oral microbiome in saliva and subgingival sites between e-cigarette smoking and gingival inflammation.

BACKGROUND: Electronic cigarettes (ECs) have been widely used by young individuals in the U.S. while being considered less harmful than conventional tobacco cigarettes. However, ECs have increasingly been regarded as a health risk, producing detrimental chemicals that may cause, combined with poor oral hygiene, substantial inflammation in gingival and subgingival sites. In this paper, we first report that EC smoking significantly increases the odds of gingival inflammation. Then, through mediation analysis, we seek to identify and explain the mechanism that underlies the relationship between EC smoking and gingival inflammation via the oral microbiome. METHODS: We collected saliva and subgingival samples from 75 EC users and 75 non-users between 18 and 34 years in age and profiled their microbial compositions via 16S rRNA amplicon sequencing. We conducted raw sequence data processing, denoising and taxonomic annotations using QIIME2 based on the expanded human oral microbiome database (eHOMD). We then created functional annotations (i.e., KEGG pathways) using PICRUSt2. RESULTS: We found significant increases in α-diversity for EC users and disparities in ß-diversity between EC users and non-users. We also found significant disparities between EC users and non-users in the relative abundance of 36 microbial taxa in the saliva site and 71 microbial taxa in the subgingival site. Finally, we found that 1 microbial taxon in the saliva site and 18 microbial taxa in the subgingival site significantly mediated the effects of EC smoking on gingival inflammation. The mediators on the genus level, for example, include Actinomyces, Rothia, Neisseria, and Enterococcus in the subgingival site. In addition, we report significant disparities between EC users and non-users in the relative abundance of 71 KEGG pathways in the subgingival site. CONCLUSIONS: These findings reveal that continued EC use can further increase microbial dysbiosis that may lead to periodontal disease. Our findings also suggest that continued surveillance for the effect of ECs on the oral microbiome and its transmission to oral diseases is needed.

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).

Subgroup Analysis of a Randomized Trial of the Effects of Positive Messaging on Patient-Reported Outcomes with Asthma - Effect of Obesity.

Objective: Asthma in obese patients represents a specific phenotype that is associated with increased symptoms, more frequent and severe exacerbations, reduced responsiveness to treatment, and decreased quality of life. Marketing and placebos have been shown to alter subjective responses to interventions in both asthma and obesity. We evaluated obesity as a potential treatment effect modifier of the effects enhanced drug messaging or placebos on subjective asthma outcomes. Methods: We conducted a secondary analysis of a multicenter, randomized clinical trial that studied the effect of messaging and placebos on asthma outcomes. A total of 601 participants were randomized (1:1:1:1:1) to one of 5 groups: enhanced messaging with montelukast or placebo, neutral messaging with montelukast or placebo, or usual care and followed for 4 weeks after randomization. We compared baseline characteristics by obesity status for 600 participants with data on body weight. Obesity was evaluated as an effect modifier for enhanced messaging (versus neutral messaging) and on placebo effects (versus usual care) in 362 participants assigned to a placebo group or usual care for three asthma questionnaires: Asthma Control Questionnaire, Asthma Quality of Life Questionnaire and Asthma Symptoms Utility Index. Results: Overall, 227 (37%) of participants were obese. Obese participants were older (mean age 41 vs 34), more likely female (82% vs 67%) and self-identified as Black (44% vs 25%) than non-obese participants. As previously published, enhanced messaging was associated with improvements in patient-reported asthma scores, but there was no evidence for a placebo effect. Obesity status did not influence the message effects nor did it modify responses to placebo. Conclusion: Obesity has been shown to be an important factor associated with asthma outcomes and an effect modifier of drug treatment effects. We conducted a post hoc, subgroup analysis of data from a multicenter randomized trial of enhanced messaging and placebo associated with drug treatment on asthma outcomes. Our findings suggest that observed differences in treatment effects between obese and non-obese patients sometimes seen in trials of asthma treatments are unlikely to be due to different "placebo" effects of treatment and may reflect differential physiologic effects of active agents.

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.

Clinical Trial of Losartan for Pulmonary Emphysema: Pulmonary Trials Cooperative Losartan Effects on Emphysema Progression Clinical Trial.

Rationale: There are no pharmacologic agents that modify emphysema progression in patients with chronic obstructive pulmonary disease (COPD). Objectives: To evaluate the efficacy of losartan, an angiotensin receptor blocker, to reduce emphysema progression. Methods: The trial was a multicenter, randomized, placebo-controlled trial conducted between May 2017 and January 2021. Eligible participants were aged ⩾40 years, had moderate to severe airflow obstruction, ⩾10 pack-years of smoking, mild-moderate emphysema on high-resolution computed tomography, and no medical indication for or intolerance of angiotensin receptor blockers. Treatment with losartan 100 mg daily or matching placebo (1:1) was randomly assigned. The primary outcome was emphysema progression on high-resolution computed tomography over 48 weeks. Secondary outcomes included the St George's Respiratory Questionnaire, the modified Medical Research Council dyspnea scale, the COPD Assessment Test, and the Physical Function-Short Form 20a. Measurements and Main Results: A total of 220 participants were enrolled; 58% were men, 19% were African American, and 24% were current smokers. The medians (interquartile ranges) for age were 65 (61-73) years and 48 (36-59) for percent predicted FEV1 after bronchodilator use. The mean (95% confidence interval) percentage emphysema progression was 1.35% (0.67-2.03) in the losartan group versus 0.66% (0.09-1.23) in the placebo group (P = NS). Conclusions: Losartan did not prevent emphysema progression in people with COPD with mild-moderate emphysema. Clinical trial registered with www.clinicaltrials.gov (NCT02696564).

The Conundrum of Clinical Trials for the Uveitides: Appropriate Outcome Measures for One Treatment Used in Several Diseases.

The uveitides consist of >30 diseases characterized by intraocular inflammation. Noninfectious intermediate, posterior, and panuveitides typically are treated with oral corticosteroids and immunosuppression, with a similar treatment approach for most diseases. Because these uveitides collectively are considered a rare disease, single-disease trials are difficult to impractical to recruit for, and most trials have included several different diseases for a given protocol treatment. However, measures of uveitis activity are disease specific, resulting in challenges for trial outcome measures. Several trials of investigational immunosuppressive drugs or biologic drugs have not demonstrated efficacy, but design problems with the outcome measures have limited the ability to interpret the results. Successful trials have included diseases for which a single uveitis activity measure suffices or a composite measure of uveitis activity is used. One potential solution to this problem is the use of a single, clinically relevant outcome, successful corticosteroid sparing, defined as inactive uveitis with a prednisone dose ≤7.5 mg/day coupled with disease-specific guidelines for determining inactive disease. The clinical relevance of this outcome is that active uveitis is associated with increased risks of visual impairment and blindness, and that prednisone doses ≤7.5 mg/day have a minimal risk of corticosteroid side effects. The consequence of this approach is that trial visits require a core set of measures for all participants and a disease-specific set of measures, both clinical and imaging, to assess uveitis activity. This approach is being used in the Adalimumab Versus Conventional Immunosuppression (ADVISE) Trial.

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.

"It is kind of like a responsibility thing": transitional challenges in asthma medication adherence among adolescents and young adults.

OBJECTIVE: Nonadherence to asthma medications is prevalent among adolescents and young adults (AYAs) with asthma, leading to worsened control of asthma symptoms and more frequent exacerbations. AYAs have unique developmental transitional challenges that may alter medication adherence. We aimed to use a socio-ecological framework to explore the effect of transitional challenges from adolescence to young adulthood on asthma controller medication adherence and to identify possible strategies to promote medication adherence. METHODS: We conducted qualitative semi-structured interviews by phone with 7 adolescents (14 to 17 years), their respective caregivers, and 7 young adults (18 to 30 years). Participants were recruited from a respiratory clinical trial network and pulmonary clinics in 4 states at 6 different sites through convenience sampling. Interviews were audio recorded, transcribed and coded using thematic analyses. RESULTS: Participants identified personal challenges affecting adherence to asthma medications during the transition from adolescence to young adulthood including responsibility for asthma self-management, understanding of asthma condition and severity, embarrassment, and life demands. Health systems factors including medication cost, challenges with insurance, difficulties obtaining refills, and difficulty with access to medications at school also impacted asthma medication adherence. Participants recommended adherence strategies including improved access to inhalers, incorporating asthma medications into daily routines, and using reminders. CONCLUSIONS: Focusing on the transitional challenges of AYAs during the time period from adolescence to young adulthood is necessary for supporting their asthma medication adherence and creating future interventions. Socio-ecological and systems factors should also be targeted for improved asthma medication adherence.Supplemental data for this article can be accessed online at https://doi.org/10.1080/02770903.2021.1897836.

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.

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.

Association of mild cognitive impairment and characteristic of COPD and overall health status in a cohort study.

Introduction: We evaluated risk factors and demographic characteristics of associated with mild cognitive impairment (MCI) in patients with COPD. Methods: 220 individuals with COPD enrolled in a cohort study designed to evaluate anxiety conducted at 16 clinical centers. Cognitive impairment was assessed with the Montreal Cognitive Assessment (MoCA), a cutoff score of <26 defined as MCI. Data were collected including spirometry, 6-minute walk test, symptom burden by COPD Assessment Test and dyspnea by Modified Medical Research Council, anxiety measured by Anxiety Inventory of Respiratory Disease, Generalized Anxiety Disorder-7 and Hospital Anxiety Depression Scale, depression by Patient Health Questionnaire-9 and health status by Patient Reported Outcomes Measurement Information System and sleep quality by the Pittsburg Sleep Quality Index. Results: The median age was 65 years and 54% of participants were male. 119(54%) of participants had MCI as classified by MoCA. In multivariable logistic regression, higher odds ratios (OR) (95% confidence interval) for MCI (MoCA) <26 were associated with increased years of age, 1.06 (1.02 -1-09, p<0.003); African-American race, 3.68(1.67-8.11, p<0.001); persistent phlegm, 2 (1.12-3.57, p<0.01) and sleep disturbance, 1.04(1.01-1.08, p<0.01). Conclusions: COPD patients commonly screen positive for MCI. Characteristics associated with MCI included age, African-American race, sleep disturbance and persistent phlegm.

Visual Acuity Outcome over Time in Non-Infectious Uveitis.

Introduction: We evaluated visual acuity (VA) over 5 years in a subspecialty noninfectious uveitis population.Methods: Retrospective data from 5,530 noninfectious uveitis patients with anterior, intermediate, posterior or panuveitis were abstracted by expert reviewers. Mean VA was calculated using inverse probability of censoring weighting to account for losses to follow-up.Results: Patients were a median of 41 years old, 65% female, and 73% white. Initial mean VA was worse among panuveitis (20/84) than posterior (20/64), intermediate (20/47), and anterior (20/37) uveitides. On average, mean VA improved by 0.62, 0.51, 0.37, and 0.26 logMAR-equivalent lines over 2 years, respectively (each P < .001), then remained stable, except posterior uveitis mean VA worsened to initial levels.Conclusion: Mean VA of uveitic eyes improved and, typically, improvement was sustained under uveitis subspecialty care. Because VA tends to improve under tertiary care, mean VA change appears a better outcome for clinical studies than time-to-loss of VA.

Seven-Year Outcomes of Uveitic Macular Edema: The Multicenter Uveitis Steroid Treatment Trial and Follow-up Study Results.

PURPOSE: To evaluate the long-term outcomes of uveitic macular edema (ME). DESIGN: Longitudinal follow-up of a cohort of participants in a randomized clinical trial. PARTICIPANTS: A total of 248 eyes of 177 participants with uveitic ME enrolled in the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study. METHODS: OCT measurements, taken at baseline and annually, were graded by reading center graders masked to clinical data. Macular edema was defined as a center macular thickness (CMT) ≥240 µm on time-domain OCT or time-domain OCT equivalent. Resolution of ME was defined as normalization of macular thickness on OCT. Relapse of ME was defined as increase in macular thickness to ≥240 µm in an eye that previously had resolution. Visual acuity was measured at each visit with logarithmic visual acuity charts. MAIN OUTCOME MEASURES: Resolution and relapse of ME. Visual acuity. RESULTS: Among 227 eyes with ME followed ≥1 year, the cumulative percent of eyes with ME resolving at any point during 7 years was 94% (95% confidence interval [CI], 89-97). Epiretinal membranes on OCT were associated with a lower likelihood of ME resolution (hazard ratio [HR], 0.74; 95% CI, 0.55-1.01; P = 0.05). Among 177 eyes with resolved ME, the cumulative percent with relapse within 7 years was 43% (95% CI, 32-51). Eyes in which ME resolved gained a mean of 6.24 letters (95% CI, 4.40-8.09; P < 0.001) compared with eyes that remained free from ME during the 1-year follow-up intervals, whereas eyes in which ME did not resolve experienced no gain in vision (mean change -1.30 letters; 95% CI, -2.70 to 0.09; P = 0.065), and eyes that developed ME during the year (incident or relapsed) experienced a mean loss of -8.65 letters (95% CI, -11.5 to -5.84, P < 0.001). CONCLUSIONS: Given sufficient time and treatment, nearly all uveitic ME resolves, but episodes of relapse were common. Visual acuity results were better among eyes with resolved ME, suggesting that control of inflammation and resolution of ME might be visually relevant treatment targets.