Annals of the American Thoracic Society最新文献

Rationale: Tuberculosis (TB) is a major worldwide cause of disability, with TB survivors experiencing significant and often under-recognised burden, and approximately half going on to develop post-tuberculosis lung disease (PTLD). Pulmonary rehabilitation may offer effective disease management but there is a lack of evidence in PTLD populations.

Objectives: We aimed to determine the clinical and cost effectiveness of pulmonary rehabilitation for adults living with PTLD in Kyrgyzstan.

Methods: A single-blind randomised controlled trial, conducted March 2021 to June 2022 in Bishkek, Kyrgyzstan, compared supervised PR to usual care for adults living with PTLD. Participants were randomised (1:1) to receive either usual care (control) or culturally adapted pulmonary rehabilitation (intervention), comprising individually prescribed and tailored exercise and self-management education. The primary outcome was change in maximal exercise capacity, measured by the incremental shuttle walking test (ISWT), from baseline to the end of 6-weeks of pulmonary rehabilitation, analysed by intention-to-treat analysis. Secondary outcomes included health-related quality of life (HRQoL) and cost-effectiveness analysis.

Results: 114 participants (mean ± SD 43.3 ± 15.2 years, 57% male) received either supervised pulmonary rehabilitation or usual care. Compared with the control group, changes in exercise capacity and HRQoL from baseline were significantly greater in the intervention group (ISWT: 123.0 m, 95%CI 81.2-164.8, P < .001; EQ-5D-5L VAS: 20.2, 95% CI 15.5-24.9, P < .0001). The intervention group saw a significant increase in quality-adjusted life years (QALYs) over the control group (0.2 [95%CI 0.1-0.2]). We calculated a total programme cost of U.S.$5,686.5 (U.S.$95 per patient who received pulmonary rehabilitation), giving a programme cost, after adjusting for purchasing power, of U.S.$2,143.2 per QALY [95%CI 1,621.9-2,663.9].

Conclusions: In adults with PTLD in Kyrgyzstan, a culturally adapted pulmonary rehabilitation programme significantly improved exercise capacity and HRQoL compared with usual care and was both clinically and cost effective.

Rationale: Interstitial lung abnormalities (ILA) are incidental CT findings that often represent early, subclinical interstitial lung disease. Their prevalence and progression rates vary widely across studies, emphasizing the need to understand the impact of age, sex, and smoking for better risk stratification and management.

Objectives: To evaluate the prevalence and progression rates of ILA by age, sex, and smoking intensity using individual patient-level data from global cohorts, and to analyze progression-free survival (PFS).

Methods: Systematic searches in OVID-MEDLINE and Embase identified eligible original articles reporting ILA prevalence or progression, confirmed through radiologist-reviewed CT scans. Random-effects models were used to pool estimates stratified by age, sex, and smoking intensity. Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). Progression-free survival (PFS) probabilities were calculated using Kaplan-Meier analysis.

Measurements and main results: Data from 14 studies comprising 31,739 individual subjects showed a pooled ILA prevalence of 5.6% (95% CI, 4.3-7.3%), increasing with age from 2.5% (<55 years) to 14.6% (≥80 years). Age was the most influential factor, and it was further amplified in males and heavy smokers. The overall pooled progression was 34%, with fibrotic ILAs exhibiting higher progression, and age did not affect progression. PFS was evaluated in 202 individuals with ILA, with estimated rates of 76% at 3 years and 55% at 5 years.

Conclusions: Age is the strongest determinant of ILA prevalence. ILAs show significant progression on imaging over time, and progression is mainly driven by fibrotic features rather than age once ILA is established. Given the higher prevalence in older adults, targeted screening in aging populations remains appropriate, while follow-up strategies should be guided by fibrotic burden rather than age.

Background: Dehydroepiandrosterone sulfate (DHEA-S) has anti-inflammatory and immune-modulating properties but its role in asthma is unclear.

Objective: To examine serum DHEA-S levels and asthma or asthma exacerbations in a nationwide study of U.S. adults.

Methods: Cross-sectional study of serum DHEA-S and asthma in 4,212 adults (2,334 females and 1,878 males) aged 18-79 years who participated in the 2021-2023 U.S. National Health and Nutrition Examination Survey. Eosinophilic and non-eosinophilic asthma were defined by absolute blood eosinophil counts ≥ 300 and < 300 cells/uL, respectively. An asthma exacerbation was defined as an asthma attack or an emergency room or urgent care visit due to asthma in the previous year. Logistic regression was used for the multivariable analysis of DHEA-S and asthma or asthma exacerbations, which was conducted separately in females and males.

Results: Serum DHEA-S levels decreased with age in male and female participants. In an analysis adjusting for other sex hormones and other covariates, serum DHEA-S levels in the fourth quartile were associated with lower odds of asthma in females (odds ratio [OR] for quartile [Q]4 vs. Q1 = 0.55, 95% confidence interval [CI]=0.30-0.98) and in males (OR for Q4 to Q1 = 0.42 [95% CI = 0.20-0.87]). Similar associations were found for non-eosinophilic asthma but not for eosinophilic asthma. There was a non-significant trend for an association between higher DHEA-S levels and reduced odds of asthma exacerbations in females with asthma (OR for Q4 to Q1 = 0.45 (95% CI = 0.20, 1.01).

Conclusions: Higher serum DHEA-S levels are associated with lower odds of asthma in a representative sample of U.S. adults.

Rationale: Early intolerance to nintedanib may shorten time spent on treatment. Whether initiating treatment at 100 mg vs. 150 mg twice daily improves treatment persistence for 12 months without compromising lung function is uncertain.

Objectives: To estimate the effects of 100 mg vs. 150 mg at initiation on 12-month time on treatment and ∼1-year lung function.

Methods: An observational emulation of an individually randomized target trial in a single-center new-user cohort was conducted. Baseline confounding was addressed using stabilized inverse-probability-of-treatment weighting (IPTW) with 1st-99th percentile trimming. The primary estimand was the difference in the restricted mean time on treatment (RMST) over 12 months. Key secondary estimands were the IPTW-adjusted absolute risk difference (RD) in 12-month treatment discontinuation (accounting for competing death) and the mean difference in change in forced vital capacity (FVC) %predicted at ∼12 months among survivors. Uncertainty was quantified by patient-level bootstrapping.

Measurements and main results: Among 172 initiators (100 mg; n = 94; 150 mg; n = 78), 100-mg initiation extended the 12-month RMST by 52.9 days (95% CI, 11.8-97.1) and decreased the 12-month discontinuation risk (cumulative incidence function 0.135 vs. 0.281; RD 0.146). The ΔFVC %predicted was broadly similar among survivors, but the estimates were imprecise.

Conclusions: In this target-trial emulation, starting at 100 mg twice daily improved 12-month treatment persistence. One-year FVC %predicted estimates among survivors were broadly similar but imprecise and should be interpreted with caution; a start-low, escalate-as-tolerated policy warrants prospective evaluation.

Background: People living with idiopathic pulmonary fibrosis (IPF) often experience rapid disease progression and high burden of distressing symptoms. Timely referral to specialist palliative care for people with IPF is uncommon. This study aims to establish consensus on criteria which would prompt a referral to specialist palliative care for people living with IPF.

Methods: An international Delphi study was conducted over three online rounds between April and July 2025 to identify consensus amongst expert clinicians and researchers on the referral criteria for specialist palliative care for people living with IPF. Consensus was defined a priori as agreement of at least 70%. A focus group of people with lived experience of IPF or specialist palliative care was conducted to provide feedback on the relevance and acceptability of the putative referral criteria.

Results: Up to 46 expert panellists participated in the Delphi. Panellists included physicians (78-83%) and nurses (15-20%) with specialist qualifications in respiratory (80-84%) or palliative medicine (31-35%). Consensus was reached on 17 major criteria and 40 minor criteria relating to 'hospital utilisation', 'respiratory therapies', 'symptom distress', 'comorbidities', 'exacerbation of IPF', 'time-based factors' and 'psychosocial factors'. Focus group participants (n = 6) broadly concurred with the agreement rates from the panellists, albeit often leaning towards earlier indicators than those which reached final consensus as major criteria.

Conclusion: Consensus referral criteria for specialist palliative care referral in ILD are presented, which emphasise comprehensive needs assessment and open communication between clinicians and patients. Future work is needed to examine the implementation of these criteria in clinical respiratory care.

Rationale: How rurality may influence recovery after critical illness is unknown.

Objectives: To examine the association between rurality and disability, cognitive function, and health-related quality of life in ICU survivors and whether it is modified by area-level socioeconomic deprivation.

Methods: We measured rurality using Rural-Urban Commuting Area (RUCA) codes (range: 1 [most urban] to 10 [most rural]). At 3- and 12-months post-discharge, we assessed cognition, basic and instrumental activities of daily living, and quality of life. We measured area-level socioeconomic deprivation using the Area Deprivation Index (ADI). We used multivariable regression with inverse probability of attrition weighting, adjusting for pre-specified covariates including ADI. We conducted pre-specified analyses assessing the interaction between rurality and ADI.

Measurements and main results: We enrolled 1,040 critically ill patients with 781 surviving to hospital discharge. Survivors had a median (IQR) age of 62 (52-71) years and RUCA score of 4 (1-7). At 3-month follow-up, greater rurality was associated with greater odds of disability in basic activities of daily living (aOR: 2.16, 95% CI: 1.27 to 3.67, P = .02). This association remained significant at 12-month follow-up (P = .03). We found no association between rurality and other outcomes. There was no interaction between RUCA and ADI with basic activities of daily living, suggesting that socioeconomic deprivation did not alter these associations.

Conclusions: Among survivors of critical illness, greater rurality was associated with greater disability in basic activities of daily living but not cognitive function or quality of life.

Rationale: While clinical criteria are used to diagnose pneumonia in critically ill patients, rates of concordance between a clinician's suspicion for pneumonia and a diagnosis of lower respiratory tract infection using bronchoalveolar lavage (BAL) results are undefined.

Objective(s): To assess rates of concordance between clinically suspected pneumonia and pneumonia diagnosed by BAL and clinical adjudication in mechanically ventilated patients undergoing BAL for suspected pneumonia, and to identify clinical factors and outcomes associated with diagnostic discordance.

Methods: This was a single-center prospective observational study of intubated, mechanically ventilated patients undergoing BAL for suspected pneumonia. From 2018 to 2022, clinicians were asked to quantify their suspicion for pneumonia on the same day they performed a BAL for the patient with one of the following options: <15%, 30%, 50%, 70% or > 85%. Responses were categorized as low (<15% to 30%), intermediate (50%) or high (70% to > 85%) suspicion for pneumonia and compared to diagnoses of pneumonia based on independent adjudication of clinical data plus BAL results.

Results: Among 659 patients, 84% (553/659) were adjudicated to have pneumonia based on chart review and BAL results. Clinicians assigned a low suspicion for pneumonia to 20% (109/553) of patients with an adjudicated diagnosis of pneumonia. Clinicians assigned a high suspicion for pneumonia in 28% (30/106) of patients without pneumonia based on adjudication. Amongst patients with an adjudicated diagnosis of pneumonia, there were no significant differences in vital signs or laboratory values between those assigned a low suspicion for pneumonia and those assigned a high suspicion for pneumonia. In patients adjudicated to have culture negative pneumonia (n = 117), those assigned a low suspicion for pneumonia, compared to those assigned a high suspicion for pneumonia, had a longer length of stay in the hospital (36 days vs 18 days, p = 0.02) and ICU (21 days vs 9 days, p = 0.01).

Conclusions: Over-diagnosis, rather than a missed diagnosis, is the more frequent cause of diagnostic discordance. A low suspicion for pneumonia in patients with an adjudicated diagnosis of culture-negative pneumonia is associated with longer ICU and hospital lengths of stay. There is a need to improve diagnostic accuracy in critically ill patients with suspected pneumonia.