Annals of the American Thoracic Society最新文献

Rationale: Inhaled nitric oxide (iNO) has been shown to result in benefits in moderate to vigorous physical activity (MVPA) in patients with fibrotic interstitial lung disease (f-ILD) receiving supplemental oxygen in two independent trials. Objective: This phase III randomized, double-blind, placebo-controlled study sought to validate the benefit of ambulatory iNO in patients with f-ILD requiring supplemental oxygen. Methods: Patients with f-ILD receiving supplemental long-term oxygen were randomized in a 1:1 fashion to iNO at 45 μg/kg ideal body weight per hour or placebo for 16 weeks. The primary outcome was the change from baseline to Week 16 in MVPA assessed by accelerometry. Secondary outcomes included overall activity, 6-minute-walk distance and patient-reported outcomes. Results: 145 patients were enrolled; 75 were assigned to receive iNO and 70 placebo. The changes from baseline in MVPA at 16 weeks were -9.2 min/d (standard error, 3.51) in the iNO45 group and -3.7 min/d (3.76) in the placebo group (difference, 5.5; P = 0.265). No statistically significant differences between the two treatment arms were found for any of the secondary outcomes. A subgroup analysis of patients with an intermediate or high probability of pulmonary hypertension on echocardiography did not demonstrate any benefit. The most common adverse events reported were respiratory tract infections, but the therapy was generally very well tolerated. Conclusions: There was no demonstrable benefit to iNO in patients with f-ILD receiving supplemental oxygen in daily physical activity assessed by actigraphy, a potential novel clinical trial endpoint. Clinical trial registered with www.clinicaltrials.gov (NCT03267108).

Rationale: Patients who are critically ill and require admission to an intensive care unit (ICU) should receive the same quality of care regardless of their sex. Objectives: To determine, using population data from a multicenter database in Ontario, Canada, whether sex is associated with differences in the use of eight best practices and other interventions during the ICU care of mechanically ventilated women and men. Methods: Using a cohort of patients receiving mechanical ventilation in eight ICUs, our coprimary outcomes were differences in compliance with eight evidence-based practices between women and men (opioid administration, use of continuous sedation or opioids, sedation minimization, spontaneous breathing trials, stress ulcer prophylaxis, deep venous thrombosis [DVT] prophylaxis, physical restraint, and mobilization). All analyses were adjusted for confounders using logistic regression and restricted to patients eligible for each best practice Results: We included 19,070 (11,910 men, 7,160 women) patients who were mechanically ventilated for >4 hours. Men and women had similar opioid administration, sedation minimization, stress ulcer prophylaxis, DVT prophylaxis, and mobilization. Women were less likely to receive continuous infusions of sedation or opioids than men (adjusted odds ratio [OR], 0.86; 95% confidence interval [CI], 0.78-0.95) and less likely to be physically restrained (adjusted OR, 0.82; 95% CI, 0.74-0.89). Conclusions: In this cohort of mechanically ventilated patients, the use of evidence-based practices was similar between women and men, except for a higher use of continuous sedative or opioid infusions and physical restraints in men.

Rationale: Chronic obstructive pulmonary disease (COPD) includes respiratory symptoms and chronic airflow limitation (CAL). In some cases, emphysema and impaired diffusing capacity of the lung for carbon monoxide (Dl_CO) are present, but characteristics and symptoms vary with smoking exposure. Objective: To study the prevalence of CAL, emphysema, and impaired Dl_CO in relation to smoking and respiratory symptoms in a middle-aged population. Methods: We investigated 28,746 randomly invited individuals (52% women) aged 50-64 years across six Swedish sites. We performed spirometry, Dl_CO testing, and high-resolution computed tomography and asked for smoking habits and respiratory symptoms. CAL was defined as post-bronchodilator forced expiratory volume in 1 second divided by forced vital capacity (FEV₁/FVC) < 0.7. Results: The overall prevalence was 8.8% for CAL, 5.7% for impaired Dl_CO (Dl_CO < LLN), and 8.8% for emphysema, with a higher prevalence in current smokers than in ex-smokers and never-smokers. The proportion of never-smokers among those with CAL, emphysema, and impaired Dl_CO was 32%, 19%, and 31%, respectively. Regardless of smoking habits, the prevalence of respiratory symptoms was higher among people with CAL and impaired Dl_CO than those with normal lung function. Asthma prevalence in never-smokers with CAL was 14%. In this group, asthma was associated with lower FEV₁ and more respiratory symptoms. Conclusions: In this large population-based study of middle-aged people, CAL and impaired Dl_CO were associated with common respiratory symptoms. Self-reported asthma was not associated with CAL in never-smokers. Our findings suggest that CAL in never-smokers signifies a separate clinical phenotype that may be monitored and, possibly, treated differently from smoking-related COPD.

Rationale: Growing evidence suggests that air pollution exposure is a major risk factor in chronic obstructive pulmonary disease (COPD) that is associated with an increased prothrombotic state and adverse cardiovascular outcomes. However, much of this work is based on observational data or human exposure studies involving younger participants. The biological causality and mechanism of air pollution-induced prothrombotic response in patients with COPD remain to be explored. Objectives: The main aim of this work was to investigate the impact of short-term diesel exhaust (DE) exposure on circulating prothrombotic markers-fibrinogen and plasminogen activator inhibitor-1 (PAI-1)-and urinary eicosanoids in patients with COPD. Methods: Twenty-nine research participants were recruited in this randomized, double-blind, crossover, controlled human exposure study to DE. Participants included former smokers with and without mild or moderate COPD (ex-smokers [ES] and COPD group) and healthy never-smokers without COPD (nonsmoker [NS] group). Each participant was exposed to DE (300 μg/m³ of particulate matter with an aerodynamic diameter ≤2.5 μm) and filtered air for 2 hours on different occasions, in randomized order, separated by a 4-week washout. Blood and urine samples were collected before and 24 hours after each exposure. Plasma fibrinogen and serum PAI-1 concentrations were quantified using enzyme-linked immunosorbent assays. Urinary eicosanoid concentrations were quantified using ultraperformance liquid chromatography coupled to tandem mass spectrometry. Linear mixed-effects models were used for statistical comparisons. Results: Participants with COPD showed an increase in plasma fibrinogen (effect estimate, 1.27 [1.06-1.53]; P = 0.01) after DE relative to filtered air, but no significant DE-associated change in serum PAI-1 (0.95 [0.87-1.04]; P = 0.26). In never-smokers and ex-smokers without COPD, fibrinogen (NS group, 1.10 [0.99-1.23]; P = 0.08; ES group, 0.86 [0.68-1.09]; P = 0.08] and PAI-1 (NS group, 1.12 [0.96-1.32]; P = 0.15; ES group, 0.90 [0.79-1.03]; P = 0.13) were not changed after DE exposure. Participants with COPD showed a DE-attributable increase in urinary thromboxane B2 (TXB₂) metabolite concentrations as follows: 11-dehydro-TXB₂ (1.45 [1.02-2.08]; P = 0.04) and 2,3-dinor-TXB₂ (1.45 [1.05-2.00]; P = 0.03). Conclusions: Participants with COPD had increased plasma fibrinogen and urinary TXB₂ metabolites after short-term DE exposure, suggesting they may be more susceptible to a pollution-attributable prothrombotic response than healthy control subjects or ex-smokers without COPD. Clinical trial registered with www.clinicaltrials.gov (NCT02236039).

Rationale: Pulmonary rehabilitation (PR) is a clinically effective and cost-effective outpatient treatment for chronic obstructive pulmonary disease (COPD) that remains highly underused. Existing analyses of PR use patterns have been focused largely on patient characteristics, but hospital-level analysis is lacking and is needed to inform interventions aimed at improving use after COPD hospitalization. Objectives: To evaluate PR use across hospitals after COPD hospitalization in the state of Michigan, with the goal of characterizing hospital-level variation and identifying the characteristics of high-performing hospitals. Methods: This is a retrospective study of patients with COPD hospitalizations between January 1, 2018, and December 31, 2021, using claims data from the Michigan Value Collaborative and hospital data from the American Hospital Association annual survey. Our primary outcome was the initiation of PR within 30 days of discharge. Chi-square tests and analysis of variance were used to test for differences in patient and hospital covariates. Multilevel logistic regression was used to analyze associations between patient covariates and the primary outcome and to characterize hospital-level variation. Results: A total of 36,389 patients and 99 hospitals were included in the analysis. The majority of patients were older than 65 years of age, female, White, and Medicare fee-for-service insured. The rate of PR initiation within 30 days after hospitalization was 0.8%. Adjusted rates of PR initiation by hospital ranged from 0.4% to 2.0%. Compared with the set reference groups, being female, in the fifth Distressed Community Index quintile, and older than 85 years of age independently decreased the odds of initiating PR. Some variation in initiation rate was attributed to the hospital level (7%; intraclass correlation coefficient = 0.07 [95% confidence interval, 0.03-0.15]). The median odds ratio was 1.6 for PR initiation by hospital. Conclusions: Rates of PR initiation after COPD hospitalization are universally low across all hospitals, though there is some variation. Interventions targeted at patients alone are not sufficient to improve use. Hospital-based strategies to improve PR use after discharge, adapted from those being successfully used with cardiac rehabilitation, should be further explored.

Rationale: Findings from individual trials of physical rehabilitation interventions in critically ill adults have limited potential for meta-analysis and informing clinical decision-making because of the heterogeneity in selection and reporting of outcomes used for evaluation. Objectives: The objective of this study was to determine a core outcome set (COS) for use in all future trials evaluating physical rehabilitation interventions delivered across the critical illness continuum of recovery. Methods: An international, two-round, online, modified Delphi consensus process, following recommended standards, was conducted. Participants (N = 329) comprised three stakeholder groups-researchers, n = 58 (18%); clinicians, n = 247 (75%); and patients and caregivers, n = 24 (7%)-and represented 26 countries and nine healthcare professions. Participants rated the importance of a range of relevant outcomes. Outcomes included in the COS were those prioritized of "critical importance" by all three stakeholder groups. Results: Survey response rates were 88% (Round 1) and 91% (Round 2). From a total of 32 initial outcomes, the following outcomes reached consensus for inclusion in the COS: physical function, activities of daily living, survival, health-related quality of life, exercise capacity, cognitive function, emotional and mental well-being, and frailty. Conclusions: This study developed a consensus-generated COS for future clinical research evaluating physical rehabilitation interventions in critically ill adults across the continuum of recovery. Ascertaining recommended measurement instruments for these core outcomes is now required to facilitate implementation of the COS.

Rationale: Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) are both genetic diseases of mucociliary clearance resulting in progressive lung disease with onset in early life. PCD is often considered to be milder than CF in childhood, based on minimal evidence. Similar to CF, genotype-phenotype associations exist in PCD; pathogenic variants in CCDC39 and CCDC40, causing inner dynein arm/microtubular defects (IDA/MTD), are associated with more severe disease. Objectives: To compare longitudinal outcomes in matched children with PCD and CF. We hypothesized that children with PCD with IDA/MTD defects would have lower lung function but better nutritional indices than matched children with CF with minimal function genotypes (i.e., those associated with pancreatic insufficiency). Methods: Children with PCD enrolled in a prospective, multicenter, observational study were matched with patients with CF from the Cystic Fibrosis Foundation Patient Registry by birth cohort, age, sex, race/ethnicity, and year of study visit. The association of disease group overall and by severity class (PCD-IDA/MTD vs. all other defects and CF-minimal vs. residual function) with longitudinal outcomes up to age 17 was evaluated with cubic spline mixed effects models. Results: Groups included 136 children with PCD (40 IDA/MTD, 96 other) and 476 with CF (446 minimal function, 30 residual function). Below age 14, the PCD group had similar or lower estimated mean forced expiratory volume in 1 second percent predicted compared with CF (e.g., at age 10, -5.4% predicted lower; 95% confidence interval [CI], -7.7, -3.1). Compared with the CF-minimal function (pancreatic insufficient) group, the PCD-IDA/MTD group had similar body mass index; estimated mean forced expiratory volume in 1 second percent predicted was significantly lower by age 10 (mean difference, -10.6%; 95% CI, -14.7, -6.4), increasing at age 14 (mean difference, -15.7%; 95% CI, -20.3, -11.2). The CF cohort had increased prevalence of Pseudomonas aeruginosa cultured on one or more occasions compared with children with PCD (67% vs. 27%; P < 0.001); there was no difference in the prevalence of P. aeruginosa between children with PCD-IDA/MTD and PCD-other. Conclusions: In childhood, average lung function abnormalities in PCD are not milder than CF, particularly for those with IDA/MTD ciliary defects. New guidelines and treatments to improve outcomes in PCD are urgently needed.

Rationale: The slope of decline in forced expiratory volume in 1 second (FEV₁) is commonly used to reflect the rate of disease progression for descriptive studies and therapeutic trials in chronic obstructive pulmonary disease (COPD). The frequency and duration of spirometric testing needed to report the true slope are unknown. Objectives: We sought to define the minimum frequency and follow-up duration needed to accurately describe the annualized rate of FEV₁ change among patients with moderate to very severe COPD. Methods: We performed a post hoc analysis of the annualized rate of FEV₁ change among 4,412 subjects previously enrolled in the 4-year Understanding Potential Long-Term Impacts on Function with Tiotropium-or, UPLIFT-trial of tiotropium versus placebo. Slope estimates were modeled for different iterations of semiannual or annual testing over a variable duration up to 42 months. All models were compared with a reference of semiannual spirometry for 42 months. Results: The overall annual rate of postbronchodilator FEV₁ decline measured semiannually for 42 months (44.6 ml; 95% confidence interval [CI] = 42.5-46.6) did not differ significantly from annual spirometry over the same period (43.7 ml; 95% CI = 41.3-46.1) or semiannual spirometry over the first 2 years (44.3 ml; 95% CI = 41.1-47.5). Agreement was consistent for two follow-up values as far as 24 months apart (43.3 ml; 95% CI = 39.9-46.8). Models that are based on less than two follow-up values or a duration less than 18 months were characterized by relative underestimation of the slope. Conclusions: In a large cohort of patients with moderate to very severe COPD, the annualized rate of change in FEV₁ was accurately represented by a minimum of two annual follow-up measurements over 18 months compared with semiannual testing over 42 months.

Intensive care unit (ICU) strain, characterized by a discrepancy between perceived or actual intensive care resources and demand, significantly impacts patient outcomes and healthcare worker well-being. The coronavirus disease (COVID-19) pandemic exacerbated ICU strain, leading to increased mortality and extended hospital stays, affecting both critically ill patients with and without COVID-19. A systematic review identified 16 leading and lagging indicators of ICU capacity strain, including queuing, premature and after-hours ICU discharge, use of temporary space, length of stay, burnout, staffing and nurse-to-patient ratio, ICU census, acuity and turnover, standardized mortality ratio, readmissions, availability of critical supplies, ventilator use, and surgery cancellation. However, variability in operational definitions and limited evidence regarding the reliability, validity, usability, and feasibility limit the value of single indicators for informed strategic planning and policy guidance. Regional and national policies and programs are essential to enhance real-time monitoring for effective management of critical care resources, and they mitigate the impact of ICU strain, facilitating complex interhospital transfers to reduce strain and ensuring comprehensive strategies for enhancing ICU resilience. Proactive regional cooperation is advocated for policy formulation, knowledge exchange, and resource allocation to anticipate and mitigate ICU strain, ensuring equitable healthcare access during global health crises. The policy implications for future preparedness emphasize the importance of evidence-based triage and adaptable patient management strategies alongside ethical considerations in resource allocation and the role of behavioral economic insights in optimizing resource utilization and collaborative healthcare practices. This multifaceted approach for addressing ICU strain comprehensively and effectively during a pandemic would promote health equity and enhance healthcare system resilience under both routine operations and crisis conditions.