Annals of the American Thoracic Society最新文献

Rationale: Deployment to the Southwest Asia theater of military operations is associated with new-onset respiratory symptoms, yet commonly used parameters on pulmonary function testing (PFT) are typically reported to be within the normal range for most deployers, referred to here as deployment-exposed veterans with preserved spirometry (DEPS). The relationship between these normal-range PFT parameters and long-term outcomes has not been thoroughly investigated. Objectives: To evaluate the clinical utility of PFT parameters among DEPS and examine associations with baseline respiratory symptoms, functional limitations, healthcare use, and longitudinal trajectories. Methods: We identified veterans in the U.S. Department of Veterans Affairs AHOBPR (Airborne Hazards and Open Burn Pit Registry) who enrolled in the Veterans Health Administration and underwent at least one pulmonary function test after the end of their initial deployment (1990-2019) and before completion of the AHOBPR self-assessment questionnaire (2014-2024). We defined DEPS as having no airflow obstruction (ratio of forced expiratory volume in 1 second to forced vital capacity greater than or equal to the lower limit of normal [LLN]) or restriction (total lung capacity greater than or equal to the LLN). We applied adjusted mixed-effects regression and machine learning to assess the predictive value of PFT parameters for key outcomes. We also examined the longitudinal trajectories of DEPS' PFT patterns using interval-censored Cox proportional-hazards regression. Results: Among eligible veterans with complete data (n = 3,814), 68% reported respiratory symptoms (modified Medical Research Council dyspnea scale score ≥1), but most had preserved spirometry (DEPS, 49%), followed by obstructive (28%), restrictive (21%), and mixed (2%) PFT patterns. Among DEPS (n = 1,879, 37 ± 10 yr of age, 86% men, 15% current smokers and 19% former smokers, 64% with modified Medical Research Council dyspnea scale scores ≥1), several PFT parameters were linked to outcomes, but diffusing capacity of the lung for carbon monoxide (Dl_CO) was the strongest predictor, showing significant relationships with many outcomes (odds ratios ranging from 0.46 to 0.89; P < 0.05 for all). Among the 289 DEPS with follow-up PFT 6 ± 4 years later, those with baseline isolated reduction in Dl_CO (less than the LLN) were more likely to develop restrictive impairments compared with those with normal Dl_CO (33% vs. 19%; P = 0.048). Conclusions: In a national sample of deployed veterans with military environmental exposures, approximately half had preserved spirometry (DEPS), but many endorsed substantial respiratory symptoms and functional limitation. DEPS with reduced Dl_CO appear to be at increased risk for developing lung parenchymal disease over time.

Rationale: Examining lung cancer mortality trends at the county level would better inform our understanding of racial, ethnic, and geographic differences in the United States. Objectives: To analyze lung cancer mortality trends by race and/or ethnicity (American Indian or Alaska Native [AIAN], Asian, Black, Latino, and White), sex, and county. Methods: Data from the National Vital Statistics System and National Center for Health Statistics (2000-2019) were used to estimate age-standardized lung cancer mortality in 3,110 counties, adjusted for misclassification. Results: From 2000 to 2019, lung cancer mortality decreased from 68.3 (95% uncertainty interval, 67.9-68.7) to 42.5 (42.3-42.8) deaths per 100,000. Males experienced a larger decrease (44.8%) than females (29.4%). Similar patterns were observed at the county level, with considerable geographic variation within and across racial and/or ethnic populations. In 2019, higher rates among Black and White populations were observed in the Mississippi River watershed and Appalachia and in AIAN populations in the upper Midwest, Northeast, North Carolina, Oklahoma, and Kansas. From 2000 to 2019, for males and females combined, lung cancer mortality rates increased in 57 counties (12.0%) for the AIAN population, with a median increase of 7.5 deaths per 100,000. Increases in counties were less common among Asian (n = 36, 5.4%), Latino (n = 36, 2.4%), and White (n = 1) populations, whereas no county showed an increase for Black individuals. Conclusions: Despite marked reductions in lung cancer mortality, geographic and racial and/or ethnic differences persist, which emphasizes the need for targeted interventions to further improve lung cancer outcomes for all populations.

Rationale: Clustering of social and environmental risks in low-income neighborhoods is a key factor in racial and ethnic asthma disparities. Integrating school and in-home programs, with treatment tailored to disease risk, is a promising approach for children with high disease burden. Objectives: We evaluated the Rhode Island Asthma Integrated Response (RI-AIR) program in improving asthma outcomes at the individual and community levels. RI-AIR leverages existing community collaborations and technological advances to identify children with asthma at the highest risk for poor outcomes through a system of identification, screening, and intervention. Methods: We conducted a stepped wedge cluster randomized hybrid type II effectiveness-implementation study. School-based catchment areas (N = 32) of high asthma burden were identified using geospatial mapping of asthma-related urgent healthcare use from 2010 through 2018. Families received only school-based interventions if the child's asthma was categorized as "not well controlled" or school- and home-based interventions if the child's asthma was deemed "poorly controlled." Community health workers facilitated communication between families, schools, and healthcare providers. Follow up visits occurred every 3 months to 1 year after the intervention. Results: Individual level: At 3 months, asthma control (primary outcome) improved (d = 0.47; 95% confidence interval, 0.33-0.61) and symptom-free days increased (d = 0.37; 0.24-0.51); both improvements were sustained at 12 months. Community level: healthcare use remained the same or increased (rate ratio, 1.16; 1.00-1.36); however, sensitivity analyses indicated that healthcare use was slightly lower in areas with greater family participation (i.e., penetration; active intervention, 0.93 [0.87-0.99]; postintervention, 0.91 [0.86-0.97]). Conclusions: Intensive, multicomponent interventions and community engagement are needed to improve asthma outcomes in areas of high burden. Clinical trial registered with www.clinicaltrials.gov (NCT03583814).

Rationale: Elexacaftor/tezacaftor/ivacaftor (ETI) provided substantial health benefits to children with cystic fibrosis (CF) in clinical trials; there is less information about its effectiveness in a "real world" setting. Objectives: The aim of the PROMISE (A Prospective Study to Evaluate Biological and Clinical Effects of Significantly Corrected CFTR Function) Pediatric substudy is to determine the long-term (four years) impact of clinically prescribed ETI among children 6-11 years of age at enrollment. The primary outcome measure is the lung clearance index at a 2.5% (LCI_2.5). Methods: The PROMISE Pediatric substudy enrolled children with CF 6 to <12 years of age starting ETI. Outcomes measured at baseline (before ETI) and 1, 3, 6, and 12 months after ETI initiation included LCI_2.5, percentage predicted forced expiratory volume in 1 second, Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain symptom score, height, weight, oropharyngeal cultures, and culture and deoxyribonucleic acid-based analysis of sputum microbiology (when sputum was available). Sweat chloride was assessed at baseline and at 1 and 6 months. Results: One hundred twenty-five participants were enrolled at 20 U.S. CF centers. Lung function improvement after ETI initiation was rapid and sustained through 12 months, with a mean decrease in LCI_2.5 of -0.79 (95% confidence interval [CI], -1.04 to 0.55) and a mean increase in percentage predicted forced expiratory volume in 1 second of 5.6% (95% CI, 3.4% to 7.7%). Respiratory symptoms also diminished significantly (mean change in CFQ-R respiratory domain symptom score, 4.1 [95% CI, 1.94 to 6.24]). Sweat chloride decreased significantly at 6 months (mean change, -47.2 mmol/L [95% CI, -51.99 to -43.8 mmol/L]). Weight, body mass index, and height z-scores were not different from baseline at 12 months. Staphylococcus aureus prevalence in oropharyngeal or sputum cultures did not change, but its density in sputum cultures decreased a mean of 1.47 log₁₀ colony-forming units/g (95% CI, -2.37 to -0.58 colony-forming units/g) at 12 months. Conclusions: Initiation of ETI in a real-world setting was associated with clinically significant improvements in lung function and symptoms and decreased S. aureus sputum density at one year; lung function improvements were smaller than those reported in clinical trials. Clinical trial registered with www.clinicaltrials.gov (NCT04038047).