Annals of the American Thoracic Society最新文献

Rationale: Pulmonary hypertension (PH) is a systemic illness with increasingly subtle disease manifestations, including sleep disruption. Patients with PH are at increased risk for disturbances in circadian biology, although, to date, there are no data on "morningness" or "eveningness" in pulmonary vascular disease.

Objectives: Our group studied circadian rhythms in patients with PH, on the basis of chronotype analysis, to explore whether there is a link between circadian parameters and physiological risk-stratifying factors to inform novel treatment strategies in patients with PH.

Methods: We serially recruited participants from July 2022 to March 2024 by administering the Munich Chronotype Questionnaire in clinic. We then compared free-day sleep measurements in patients with PH and bed-partner control subjects (BPCs), investigating associations with survival predictors. In exploratory analysis, we looked for associations between known single-nucleotide polymorphism (SNP) variants of core clock genes and cardiopulmonary hemodynamics. Finally, we performed circadian analysis of time-stamped heart rate variation from a PH cohort compared with control subjects.

Results: In this pilot study, we recruited 103 patients with PH and 38 BPCs, ages 20 to 86 years. Compared with BPCs, patients with PH had longer sleep duration and less social jet lag (SJL), with no clear difference in chronotype. Within the PH cohort, sleep duration was associated with worse functional class, whereas SJL was associated with a low risk for disease progression and more severe signs of right ventricular dysfunction. However, a later chronotype was associated with a decrease in mean pulmonary artery pressure. In an independent cohort of patients with PH, there was a relationship between functionally distinct core clock gene SNP variants and relevant hemodynamic parameters. Patients with PH exhibited a distinct delayed phase shift in circadian HR variation.

Conclusions: PH in adults is associated with significant changes in sleep duration and SJL, corroborated by both genomic and physiologic data. Dependence between circadian variables, SNP data, and disease characteristics suggest that findings may directly relate to disease pathogenesis through derangement in the molecular core clock.

Rationale: The impact of elexacaftor/tezacaftor/ivacaftor (ETI) on provision of airway samples, chronic infection definitions, and Pseudomonas aeruginosa (Pa) isolation frequency and abundance in those with established chronic Pa infection before ETI is unknown.

Objectives: To retrospectively analyse the impact of ETI on airway sampling and infection in those with chronic Pa at the time of ETI initiation.

Methods: This was a retrospective cohort study of 211 people with cystic fibrosis at Royal Brompton with Leeds-defined chronic Pa infection either -1 or -2 years before ETI. Electronic patient records were analyzed 5 years before (-5 to -1) and 2 years after (+1 and +2) ETI for: number/type of airway samples provided per person per year (pppy), Pa (mucoid/nonmucoid) culture results (to calculate isolation frequency), and Pa abundance (log-transformed median cfu/ml).

Results: A total of 148 patients had complete data; 136 provided one or more airway samples per year. Year -1 coincided with the coronavirus disease (COVID-19) pandemic. Comparisons are made from Year -2 to Years +1 and +2, finding sustained reduction in: samples provided pppy (yr, mean [standard deviation (SD)]: -2, 8.0 [4.5]; +1, 3.0 [2.5]; P < 0.0001; +2, 2.9 [2.2]; P < 0.0001), proportion of people meeting Standards of Care of four or more samples pppy (Year -2, 90%; Year +1, 31%; Year +2; P < 0.0001), proportion of Pa-positive samples (Year -2, 84.1%; Year +1, 66.1%; P < 0.0001; Year +2, 58.3%; P < 0.0001), proportion exhibiting mucoid phenotype (Year -2, 62.1%; Year +1, 48.4%; P < 0.001; Year +2, 43.6%; P < 0.0001), and median mucoid and nonmucoid Pa abundance (1-2 log cfu/ml).

Conclusions: Introduction of ETI coincides with reduced sample provision pppy; a minority of patients now meet Standards of Care (four or more samples pppy), challenging the use of current chronic infection definitions. Use of ETI, even in those with established chronic Pa and mucoid phenotype, coincides with reduced Pa isolation frequency/abundance.

Rationale: The association between firefighting exposure and respiratory injuries remains poorly quantified, despite the inhalational hazards of firefighting.

Objectives: To describe respiratory injury rates among California firefighters between 2000 and 2019 demographically, -temporally, and geographically.

Methods: Using data from the California Workers' Compensation Information System from 2000 to 2019, we analyzed California firefighter workers' compensation claims for respiratory injuries from 2000 to 2019. We identified firefighter -respiratory claims using nature of injury codes, injury description keywords, and International Classification of Diseases, Ninth or Tenth Revision codes. We estimated California firefighter employment totals using the American Community Survey.

Results: We calculated respiratory injury rates, rate ratios, and their associated Confidence Intervals (CI) by age and injury date and location. We identified 3431 respiratory injury claims between 2000 and 2019 (478 respiratory claims/100 000 California career firefighters [90% CI, 432-534]) and the respiratory injury rate remained unchanged. Firefighters aged 50-59 years had a higher risk of respiratory injuries compared to those aged 18-29 years (rate ratio, 1.7 [90% CI, 1.6-1.8]). Firefighters during wildfire season months had significantly more respiratory injuries than during non-wildfire season months. From 2000 to 2019, firefighters' respiratory injury rate in rural and small/medium metro counties increased significantly, while firefighters' respiratory injury rate in large metro counties decreased significantly.

Conclusions: Older firefighters, firefighters during wildfire season, and those in rural and small/medium metro counties may be at higher risk of respiratory injury, based on our large-scale, multiyear surveillance study among career California firefighters.

Rationale: Nontuberculous mycobacterial pulmonary disease (NTM-PD) treatment involves the long-term administration of multiple drugs, often associated with adverse drug reactions (ADRs). However, the incidence and severity of ADRs during treatment are not fully understood.

Objectives: We performed a systematic review and meta-analysis of prospective studies reporting ADRs up to June 11, 2025, to assess the burden of ADRs during NTM-PD treatment.

Methods: We evaluated the incidence rates of ADRs, medication discontinuation, and ADR-related deaths. Secondary outcomes included the clinical manifestations of ADRs and incidence rates according to the causative species.

Results: In total, 8061 studies were identified through database searches, 36 of which were included in the analysis, including 26 nonrandomized prospective studies (1784 patients) and 10 randomized controlled studies (1511 patients). The overall ADR incidence rate was 59% (95% CI, 39%-78%), with ADR-related drug discontinuation and death rates of 15% (95% CI, 10%-20%) and 2% (95% CI, 1%-3%), respectively. The clinical manifestation rates of ADRs ranged from 2% to 65%, with gastrointestinal symptoms being the most common. For the treatment of NTM-PD caused by Mycobacterium avium complex, the ADR incidence rate was 57% (95% CI, 31%-79%), whereas that for Mycobacterium abscessus was 39% (95% CI 15%-70%). The outcomes were similar between randomized and nonrandomized studies.

Conclusions: ADRs during NTM-PD treatment are notably frequent, leading to drug discontinuation and possible mortality. Clinicians should be vigilant of ADRs during NTM-PD management, and further research is required to alleviate their burden and improve outcomes.

Rationale: Increased body mass index (BMI; measured in kilograms per square meter) has been consistently associated with reduced mortality from lung cancer (LC), relative to low BMI, and termed the "obesity paradox." Although the basis of the obesity paradox remains unknown, mediating effects from sex, smoking status, diabetes mellitus (DM), and methodological issues (including bias) have been suggested causes.

Objective: Our aim was to examine whether respiratory comorbidity may contribute to this paradox. Methods: In this secondary analysis of 18,463 high-risk participants in the National Lung Screening Trial, we examined factors contributing to LC mortality (primary endpoint) using stratification analyses and regression models according to baseline demographics and comorbidity; specifically, respiratory-related comorbidity based on lung function and/or clinical history.

Findings: With increasing BMI, both respiratory and LC mortality decreased (P < 0.001), consistent with the obesity paradox. However, increasing BMI was associated with a linear decrease in the prevalence of airflow limitation (halving) and linear increases in both pre-COPD (twofold) and DM (eightfold) across BMI septiles (all Ps < 0.0001). In a sequentially constructed competing risk model for LC death, and after adjustment for smoking, age, sex, BMI, and other comorbidities, we found that airflow limitation, pre-COPD, and DM remained significant predictors of increased LC death (P < 0.01), albeit from opposite ends of the BMI continuum. When subjects with airflow limitation, pre-COPD, and DM were sequentially removed, the obesity paradox for LC mortality was substantially attenuated and almost abolished.

Interpretation: We propose that the obesity paradox in high-risk ever-smokers who develop lung cancer results, in large part, from the stronger deleterious effect of airflow limitation on LC mortality, with a lesser effect associated with DM-pre-COPD, where each predominate at opposite ends of the BMI continuum.

Rationale: Endobronchial ultrasound (EBUS)-guided sampling for evaluation of benign conditions and lymphoma is not standardized. Sampling methods remain under study as new tools become available.

Methods: We performed a single-center study with protocolized sampling and processing to evaluate the diagnostic yield of transbronchial needle aspiration (TBNA), Franseen needle biopsy (transbronchial needle biopsy [TBNB]), and cryobiopsy in patients with mediastinal and hilar abnormality with concern for sarcoid, lymphoma, or undifferentiated lymphadenopathy. Following TBNA, exploratory sampling was performed. A tract was created with a TBNB needle pass followed by cryobiopsy. Sampling was subsequently alternated for a total of 3 passes per tool. The primary outcome was diagnostic yield, using a strict criterion modeled from recent American Thoracic Society/American College of Chest Physicians guidelines. Secondary outcomes included procedural outcomes and pathologic assessment of TBNB and cryobiopsy samples.

Results: Between January and December 2024, 56 nodes were sampled in 51 patients. Diagnostic yield per node was 86% (48/56). Regarding individual tools, the yield was 50% for TBNA, 73% for TBNB, and 82% for cryobiopsy (TBNA vs cryobiopsy, P = .0001; TBNA vs TBNB, P = .006; TBNB vs cryobiopsy, P = .13). In subgroup analysis, TBNB and cryobiopsy enhanced diagnostic yield in benign conditions (TBNA [59%], TBNB [88%], and cryobiopsy [100%]; TBNA vs cryobiopsy, P = .002; TBNA vs TBNB, P = .01; TBNB vs cryobiopsy, P = .11). For lymphoma, the diagnostic yield per node was 3/10 for TBNA, 5/10 for TBNB, and 6/10 for cryobiopsy (TBNA vs cryobiopsy, P = .001; TBNA vs TBNB, P = .1; TBNB vs cryobiopsy, P = .1). Upon pathology review, TBNB provided larger samples compared to cryobiopsy but TBNB samples contained a larger proportion of blood; these differences translated to similar resultant areas of diagnostic tissue for both tools. Sample usage for immunohistochemistry and special staining was higher for cryobiopsy (61%) vs TBNB (33%). Study sampling was feasible in all patients with a 2% complication rate (1 pneumothorax).

Conclusions: Both TBNB and cryobiopsy enhance the diagnostic yield of EBUS-TBNA in benign conditions. Multiple passes with 3 biopsy tools at an individual lymph node is safe and feasible. Cryobiopsy provides superior sample quality relative to TBNB and superior yield vs TBNA in lymphoma.