Annals of the American Thoracic Society最新文献

Rationale: Elexacaftor/tezacaftor/ivacaftor (ETI) has been associated with varied effects on mental health (MH) in people with cystic fibrosis (PwCF). Currently published literature has focused primarily on MH diagnoses/symptoms with ETI as opposed to associated pharmacotherapy.

Objectives: We sought to evaluate the effect of ETI on MH diagnosis and associated pharmacotherapy in both adult and pediatric PwCF.

Methods: We conducted a multicenter retrospective study in PwCF who started ETI at 7 accredited CF centers. Primary outcomes were rate of MH diagnosis and medication use pre- and post-ETI initiation. Secondary outcomes were rate of MH medication changes and dose adjustments pre-and post-ETI.

Measurements and main results: Overall, 1,046 PwCF were included, with 453 in the "MH group" because they had either a MH diagnosis and/or MH medication use at any time point post-ETI. MH medication use and diagnosis both significantly increased from baseline at all time points post-ETI initiation.

Conclusions: The rate of MH medication use increased significantly from baseline at all time points in PwCF not previously prescribed MH medications, while rate of MH medication use remained consistent for those already on medications pre-ETI.

Rationale: There are limited longer-term follow-up data on bronchiolitis obliterans (BOS)- and retransplant-free survival among patients who underwent lung transplantation for coronavirus disease (COVID)-related lung disease.

Objectives: To evaluate overall, retransplant-free, and BOS- and retransplant-free survival in a national cohort of COVID lung transplant recipients (LTR).

Methods: We identified all United States adult LTR in the Scientific Registry of Transplant Recipients who underwent transplant for COVID-related lung disease between 8/2020 and 5/2025. We used propensity score matching (PSM) to construct balanced cohorts of COVID LTR and non-COVID group D (restrictive lung disease) LTR, comparing overall, transplant-free, and BOS- and retransplant-free survival in the two populations.

Results: There were 605 LTR with COVID lung disease and 8,809 with non-COVID group D diagnoses. Among patients with at least three years follow-up time, the COVID LTR survival was 79.1% and 73.7% in non-COVID LTR. In a PSM cohort of 451 matched pairs, overall survival (LTR (HR=0.81, 95% CI=0.60-1.10, p=0.17) and retransplant-free survival ((HR=0.81, 95% CI=0.60-1.09, p=0.16) did not differ between the groups. Among non-COVID LTR, 51 (16.0%) developed BOS and 56 (16.3%) COVID-LTR developed BOS. Overall, 122 (33.7%) non-COVID LTR died, were retransplanted, or developed BOS and 110 (29.1%) COVID LTR died, were retransplanted, or developed BOS. COVID LTR had improved retransplant- and BOS-free survival compared to non-COVID LTR (HR=0.76, 95% CI=0.58-0.98, p=0.04), driven by 8 fewer deaths in the COVID LTR cohort. COVID ARDS LTR had similar overall, retransplant-free, and BOS- and retransplant survival as COVID fibrosis LTR.

Conclusions: In this national cohort study, there was no significant difference in overall and retransplant-free survival for COVID LTR compared to non-COVID, restrictive lung disease LTR at a median follow-up time of 2.5 years. COVID LTR, however, had slightly lower hazard for BOS- and retransplant-free survival.

Rationale: The United States (US) experienced a considerable decline in tuberculosis (TB) incidence in 2020 following the COVID-19 pandemic.

Objectives: While TB rates have since returned to near pre-pandemic levels, analyzing the pandemic's impact offers insight into TB epidemiology in the US.

Methods: Focusing on California, Florida, New York, and Texas - the four states with the highest TB incidence - we explored three potential mechanisms of pandemic-related disruption on TB epidemiology: (i) reduced immigration; (ii) reduced Mtb transmission (through social distancing and other behavior changes); and (iii) delays in care-seeking. We used data on volume of non-immigrant arrivals and new permanent residents, Google mobility and US transit data, and data on volume of emergency department visits and cancer screenings to inform the magnitude of these effects at the state level, adapting previously developed state-specific transmission models. We then estimated the impact of each mechanism and projected future TB incidence through 2032.

Measurements and main results: Disruptions to migration and care-seeking across all four states were considerable but short-lasting, with 70-90% reductions in the first four months of the pandemic that returned to pre-pandemic levels by 2021. In contrast, transmission disruptions were moderate but more prolonged, with mobility still 10-20% lower than pre-pandemic in 2022. No statistical evidence was identified to favor models emphasizing immigration, transmission, versus access to care.

Conclusions: Revised projections for pandemic-related disruptions did not substantially differ from pre-pandemic projections beyond 2024. Future declines in TB incidence in the four states are likely to be small without additional interventions.

Rationale: Excess weight contributes to impaired physical function among individuals with chronic obstructive pulmonary disease (COPD) and sleep apnea. Self-directed lifestyle-based weight management programs are an accessible option to promote weight loss and improve physical function, but their effectiveness has not been clearly demonstrated.

Objective: To test whether a self-directed lifestyle program improves 6-minute walk test (6MWT) distance among individuals with COPD and comorbid sleep apnea.

Study design and methods: We performed a subset analysis of participants previously enrolled in the INSIGHT-COPD randomized clinical trial (low-intensity lifestyle intervention vs. usual care) who self-reported a diagnosis of sleep apnea. Our primary outcome was between-group differences for change in 6MWT distance (minimally important difference [MID] 30 m). Secondary outcomes included between-group differences in weight (a loss of 3% defines meaningful reduction) and quality of life (SF-12 Physical Component Score [PCS], MID 3-3.5 points). We also tested whether sleep apnea modified the effect of the intervention across the entire INSIGHT-COPD population.

Measurements and main results: Among 285 participants with sleep apnea (141 randomly allocated to intervention, 144 to usual care), those randomized to intervention could walk further (difference in 6MWT distance of 25.5 m, 95% CI 8.2 m to 42.9 m; 23.4% vs. 20.1% had a MID increase in 6MWT distance) and had a greater reduction in weight (difference in weight of -2.4 kg, 95% CI -3.9 to -0.9 kg; 36.2% vs 23.6% had a 3% reduction in weight) at 12 months. The intervention group also reported a greater physical-function related quality-of-life (difference in SF-12 PCS of 1.78 pts, 95% CI 0.10 to 3.49) in comparison to usual care at 12 months.

Conclusions: Among patients with COPD and sleep apnea, a self-directed video-based weight management program led to favorable changes 6MWT distance compared to usual care, though this did not meet the threshold of a clinically important improvement. However, fewer participants in the intervention group saw a decline in 6MWT distance, and more achieved meaningful weight loss. To effectively improve function in this population, additional interventions beyond self-directed weight management will be necessary.

Rationale: Pulmonary artery (PA) dilation on CT has been associated with moderate-severe pulmonary hypertension (PH) using outdated diagnostic criteria. The association between PA size and mean PA pressure (mPAP) in mild PH and the prognostic implications of PA dilation remain unclear.

Objectives: To investigate associations between PA size, mPAP, and survival in subjects without significant lung disease aside from PH.

Methods: PA size on CT was measured for individuals with group 1 or 2 PH and matched controls in the Pulmonary Vascular Disease Phenomics cohort. Outcomes included mPAP on right heart catheterization (RHC) and time to heart and/or lung transplantation or death.

Measurements and main results: 691 subjects were included, with 595 undergoing RHC. PA diameter and PA:aorta ratio demonstrated significant association with mPAP (ρ = 0.557 and 0.564, respectively). Size increased incrementally from no PH to mild PH to moderate-severe PH for PA diameter (27.64 [95% CI 17.64-37.64] to 30.65 [18.99-42.31] to 36.00 [22.46-49.54] mm) and PA:aorta (0.89 [0.53-1.24] to 0.99 [0.63-1.35] to 1.19 [0.60-1.78]). PA diameter and PA:aorta demonstrated good discrimination of mPAP > 20 mmHg (AUC 0.834 and 0.816, respectively). Transplant-free survival decreased across the continuum of PA diameter and PA:aorta (p < 0.001). Adjusted hazard ratio of third versus first quartile values was 2.36 [1.58-3.54] for PA diameter and 2.24 [1.52-3.30] for PA:aorta.

Conclusions: In subjects without significant lung disease outside of PH, PA size on CT was associated with increased mPAP and decreased transplant-free survival across the spectrum of PH severity and demonstrated modest diagnostic discriminatory ability using updated hemodynamic criteria. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Rationale: Critically ill lung cancer patients are a growing, high-risk population. However, prognostic tools to guide intensive care unit (ICU) decision-making are limited.

Objective: To identify oncologic and critical illness factors associated with 90-day mortality following ICU admission in patients with lung cancer.

Methods: We conducted a retrospective cohort study of lung cancer patients admitted to the ICU across Mayo Clinic Health System between 2018 and 2024. The primary outcome was 90-day mortality. Two complementary Cox proportional hazards models were developed: a focused model including cancer-specific variables (stage, cause of critical illness, ECOG performance status prior to admission, code status at admission, and time since last systemic therapy) and a full model that added broader clinical factors (age and Sequential Organ Failure Assessment [SOFA] score). We also evaluated discharge disposition and transitions in code status.

Results: Among 528 patients, 90-day mortality was 58.7%. In the focused model (C-index 0.67), independent predictors of mortality included late-stage disease, cancer-specific reason for ICU admission, DNR/DNI status, and ECOG >1. In the full model (C-index 0.95), only age and SOFA score remained significant. Among early-stage patients, recent targeted or combination therapy was associated with higher mortality. Patients who changed code status during admission had high mortality (83%) and a low rate of discharge home (11%).

Conclusions: Lung cancer patients admitted to ICU experience high short-term mortality, with outcomes shaped by both oncologic status and the severity of acute illness. A dual-model approach suggests a risk hierarchy: cancer-specific factors inform baseline mortality risk with an ICU admission, but age and physiologic derangement are the dominant drivers of survival once critical illness develops. These findings support dynamic, multidisciplinary prognostication and underscore the need to integrate oncology and critical care expertise in ICU decision-making. Word count: 310.

Background: Patients with pulmonary hypertension due to interstitial lung disease (PH-ILD) have worse exercise capacity and survival than ILD patients without PH. Vasoreactivity with inhaled nitric oxide (NO) provides prognostic and therapeutic implications in pulmonary arterial hypertension, but little is known on its value in PH-ILD. We evaluated the pulmonary hemodynamic changes following inhaled NO and their association with outcomes in PH-ILD.

Methods: We measured pulmonary hemodynamics in patients with PH-ILD who underwent inhaled NO administration during right heart catheterization. We recorded baseline clinical, echocardiographic, and pulmonary function testing measures; and investigated the use of inhaled treprostinil as well as the rate of hospitalization, death and lung transplantation.

Results: In 120 patients (age 67 ± 11 years, 62% women), the administration of inhaled NO resulted in a median (IQR) decrease in mean pulmonary artery pressure (mPAP) of -3 (-5, -1) mmHg, p<0.001, and PVR of -0.8 (-1.8, -0.2) Wood units, p<0.001. The % change in mPAP and PVR were -6.3 (-10.9, -1.8) % and -16.8 (-27.3, -3.3) %, respectively. Factors associated with the % drop in PVR included baseline PVR (r= 0.30, p<0.001), cardiac output (r= -0.19, p=0.04), and WHO functional class (r=0.25, p=0.01). The median (IQR) follow-up was 14.5 (7, 25) months. During this time, 40 (33%) patients died, 8 (7%) underwent lung transplantation, and 76 (63%) experienced either hospitalization due to respiratory failure, transplantation, or death. The % drop in mPAP and PVR during inhalation of NO had no significant impact on these outcomes and was not associated with clinical response to inhaled treprostinil measured by changes in six-minute walk distance (6MWD) and forced vital capacity (FVC).

Conclusion: Inhaled NO caused a modest reduction in mPAP and PVR in patients with PH-ILD, but the acute hemodynamic response to inhaled NO, in our cohort, was not associated with outcomes or response to inhaled treprostinil therapy.