Annals of the American Thoracic Society最新文献

Rationale: In an 8-week, active-controlled, phase 3 study (445-104), elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to be efficacious and safe in participants ≥ 12 years of age with cystic fibrosis (CF) and F508del-gating (F/G) or F508del-residual function (F/RF) genotypes, conferring additional clinical benefits relative to IVA and TEZ/IVA. Participants who completed this 8-week parent study continued to an open-label extension.

Objective: To assess the long-term safety and efficacy of ELX/TEZ/IVA in adolescents and adults with CF and F/G or F/RF genotypes.

Methods: This two-part (Part A [96 weeks] and Part B [48 weeks]) phase 3 open-label extension study enrolled adolescents and adults age ≥ 12 years with CF and F/G or F/RF genotypes who completed study 445-104. Primary endpoint (Part A and B) was safety and tolerability. Secondary endpoints (Part A only) included absolute changes in percent predicted FEV1 (ppFEV1), sweat chloride concentration, CF Questionnaire-Revised (CFQ-R) respiratory domain score, and body mass index (BMI).

Results: A total of 251 participants received ≥ 1 dose of ELX/TEZ/IVA in Part A; 217 (86.5%) completed treatment. In Part A, 96.0% of participants had ≥ 1 adverse event (AE), which for most were mild (32.3%) or moderate (55.0%) in severity. Thirteen participants (5.2%) discontinued due to treatment-emergent AEs. Participants who received ELX/TEZ/IVA in the parent study maintained improvements in ppFEV1, sweat chloride concentration, CFQ-R respiratory domain score, and BMI while participants who received IVA or TEZ/IVA (active controls) in parent study had similar improvements after transitioning to ELX/TEZ/IVA. Eighty-four participants (33.5%) entered Part B, 96.4% of whom discontinued due to commercial drug availability. In Part B, 62 participants (73.8%) had ≥ 1 AE, which for most were mild or moderate in severity and none of which led to discontinuation.

Conclusions: ELX/TEZ/IVA remained generally safe and well-tolerated with no new safety findings. Improvements in lung function, CFTR function, respiratory symptoms, and nutritional status after starting ELX/TEZ/IVA were maintained through 96 weeks of follow-up. These results demonstrate the safety and durable efficacy of ELX/TEZ/IVA in adolescents and adults with F/G or F/RF genotypes.

Climate change, fueled by greenhouse gas (GHG) emissions, is a major threat to human health and demands immediate and decisive action. The effects of climate change directly harm the health of patients cared for by pulmonary, sleep, and critical care health professionals while putting healthcare delivery at risk. Ironically, the healthcare sector itself contributes to GHG emissions. In 2024, an American Thoracic Society workshop convened an international work group of adult and pediatric pulmonologists, intensivists, nurses, researchers, educators, healthcare administrators, and healthcare advocates to identify strategies to decrease pulmonary, sleep, critical care, and research laboratory-related emissions; improve quality; and support sustainability. The workshop prioritized strategies with the highest probability of reducing healthcare sector emissions significantly and urgently while considering the short- and long-term impacts of mitigation strategies on safe healthcare delivery and unintended adverse effects on vulnerable populations. Interventions were identified on micro (individual provider), meso (healthcare organization), and macro (regulatory/government/policy) levels. As trusted voices, health professionals and their professional societies are uniquely positioned to advocate for systemic change, ensuring that healthcare not only adapts to the challenges of climate change but also actively contributes to solutions that promote a healthier, more sustainable future for all.

Rationale/research objective: Sleep-disordered breathing (SDB) is common among hospitalized individuals and may contribute to increased health utilization and mortality after discharge, yet the optimal timing and setting for sleep testing remain unclear. We compared one-year healthcare utilization and mortality among hospitalized individuals undergoing (i) inpatient polysomnography (PSG), (ii) delayed post-discharge PSG within one month of discharge (primary analysis), or (iii) no PSG during hospitalization or within one year after discharge (matched non-PSG controls); secondary analyses examined delayed PSG completed within three and six months post-discharge.

Objectives/methods: We conducted a retrospective province-based study using health administrative databases on all adults aged ≥ 18 years (Ontario, Canada), hospitalized between 2012 and 2018, and followed until the earliest of death, loss to follow-up, or December 31, 2019. Outcomes within one year after hospitalization included all-cause death and healthcare costs. To balance baseline characteristics across study groups, we used overlap propensity score weighting to create similar weighted populations for pairwise comparisons.

Results: We identified 748 individuals in the inpatient PSG group, 9,310 in the delayed PSG group, and 7,480 in the matched non-PSG controls by exact age, sex, health region and calendar year to the inpatient PSG group.In weighted populations, compared to delayed PSG (within the first month), inpatient PSG group was associated with increased one-year mortality (HR: 2.18, 95% CI: 1.68-2.82) and higher cost (Ratio of Means (RoM): 1.82, 95% CI: 1.64-2.03). Compared to non-PSG controls, inpatient PSG was associated with decreased mortality (HR: 0.72, 95% CI: 0.55-0.94) and higher cost (RoM: 1.73, 95% CI: 1.50-1.99). In the secondary analyses, delayed PSG, compared to non-PSG controls, was associated with lower cost when conducted within 3 and 6 months, but not within one month.

Conclusions: In this population-based study of propensity score-weighted hospitalized individuals, inpatient PSG was associated with higher mortality and costs compared to delayed PSG, and with lower mortality, but greater resource use than non-PSG controls. Although weighting reduced measured differences, unmeasured clinical complexity may still influence these associations. Among hospitalized individuals with suspected SDB, delaying PSG until after discharge may achieve similar or better outcomes at lower cost, warranting confirmation in prospective studies.

Rationale: An estimated 14% of Chronic Obstructive Pulmonary Disease (COPD) is caused by occupational exposure to vapor, gas, dust and fumes (VGDF). In collaboration with the Washington State Department of Labor and Industries' Safety and Health Assessment and Research for Prevention Program, we developed a surveillance algorithm for retrospective identification of Occupational COPD using a cohort of Washington workers.

Methods: Potential cases were identified from workers' compensation claims filed in Washington State between 2010-2020 using keywords, disease diagnosis codes, and occupational injury and illness codes. Cases were confirmed for the presence of COPD using post-bronchodilator forced-expiratory-volume-over-1-second/forced-vital-capacity (FEV1/FVC) < 0.7. If spirometry was unavailable, alternate clinical criteria were used. In an iterative process based on review of the first 100 cases and longitudinal studies on Occupational COPD, we developed an algorithm to classify cases as Probable, Possible, Work-Aggravated or Unlikely Occupational COPD. This algorithm incorporated confirmation of COPD diagnosis, total career duration with exposure to medium or high VGDF, and smoking history. Exposure risk was estimated using a COPD-specific, occupation-based Job Exposure Matrix (JEM).

Results: Of 508 potential cases identified in the workers' compensation claims data, 494 had had a COPD diagnosis and were included in the final analysis. Of these, 132 (27%) met criteria for Occupational COPD, including 72 Probable, 4 Possible, and 56 Work-Aggravated cases. There were 362 (73%) cases that did not meet criteria and were classified as Unlikely to have Occupational COPD. Overall, 19 cases with Occupational COPD were never-smokers or had smoked < 10 pack years total, including seventeen classified as Probable and two classified as Work-Aggravated. Occupations ascribed through the JEM to have medium or high exposure to VGDF included construction workers, production workers, maintenance workers and drivers, among others, and there was overlap in occupations and hazards between Occupational COPD classifications.

Conclusions: This comprehensive algorithm provides an approach for Occupational COPD surveillance that can be used to inform and prioritize prevention efforts in an effort to reduce disease burden in high-risk occupations.

Introduction: Guidelines recommend non-surgical biopsy for indeterminate pulmonary lesions > 8 mm. Shape-sensing robotic-assisted bronchoscopy (ssRAB) is growing in use to biopsy small pulmonary nodules; however current literature is limited to single center studies with limited follow-up. This study, PRECIsE, assessed safety and performance of the first ssRAB iteration across multiple sites and nascent users.

Methods: Prospective, multicenter, observational study evaluating ssRAB without cone-beam CT guidance in patients with nodules 10-30 mm located in or beyond the sub-segmental airways. Patients were followed for 2 years; the primary endpoint was sensitivity for malignancy with diagnostic yield, and safety as secondary endpoints. Multilevel logistic regression models were used to control for factors associated with sensitivity and diagnostic yield.

Results: A total of 305 procedures were performed across 6 centers. Median nodule size was 17.0 mm (IQR: 14.0-23.0) with bronchus sign present in 37% of cases. Sensitivity for malignancy through 2 years was 81.3% (95% CI: 75.7, 86.1). Multi-level modelling demonstrated female sex, smaller nodule size, lower lobe location, semi-solid density, and higher body-mass-index were associated with lower sensitivity. Diagnostic yield was 74.1% (95% CI: 68.8, 78.9) according to the ATS/ACCP criteria and 77.5% [95% CI: 72.4, 81.8] according to the intermediate criteria. Multi-level modeling demonstrated a non-significant site/center level effect on ATS/ACCP diagnostic yield (P = .36). Pneumothorax requiring intervention was 1.6% (5/305); bleeding was 1.0% (3/305) with two (2) Nashville grade 2 and one (1) Nashville grade 3 events.

Conclusions: The first iteration of ssRAB demonstrated encouraging performance and a strong safety profile among nascent users for the biopsy of small peripheral nodules.