Annals of the American Thoracic Society最新文献

Chronic obstructive pulmonary disease (COPD) is a highly prevalent and burdensome disease that develops over decades. Treatments for COPD are most commonly prescribed in later stages of the disease, leaving missed opportunities to modify the course of disease at earlier stages. This workshop was conducted to promote progress in the design and conduct of clinical trials of treatments that modify progression to COPD. The aims of the workshop were to provide an operational definition of pre-COPD and to discuss the elements and design of potential clinical trials in pre-COPD. The key focus areas of this workshop included: 1) defining a study population for pre-COPD clinical trials; 2) endpoints in pre-COPD clinical trials; and 3) design considerations for pre-COPD clinical trials.

Rationale: Patients receiving invasive mechanical ventilation (IMV) require accurate assessments of ventilator parameters. Documentation of these parameters in standard practice may fail to capture meaningful variation due to intermittent missingness.

Objectives: To assess variation in continuously-measured ventilator parameters and agreement with measurements documented as part of routine care in the electronic health record (EHR).

Methods: We performed a retrospective cohort study of patients receiving IMV in a medical intensive care unit from November 2024-March 2025. We compared the observed tidal volume, minute ventilation, peak inspiratory pressure, and positive end-expiratory pressure, measured continuously from device waveforms with intermittent EHR documentation. We calculated descriptive statistics and measures of agreement between these sources.

Measurements and main results: For 59 encounters, the median age was 65 (IQR, 59-72), 33 (56%) patients were male and 17 (29%) were Black. 34 (58%) patients died or were discharged to hospice. Among 358 patient-days of data, continuous measurements captured significantly more variation than EHR-documented measurements across all parameters. The largest errors were in observed tidal volume (mean absolute error 69 mL, 95% CI, 62-77 mL; correlation coefficient 0.540). Agreement in tidal volume was worse among patients receiving mandatory modes of ventilation (correlation coefficient 0.454).

Conclusions: Intermittent measurement of ventilator parameters fails to capture large variability observed in continuous, waveform-derived measurements. Poor agreement in parameters like tidal volume, even in mandatory modes of ventilation, highlights the potential for ventilator waveform data to improve care and advance research for patients with acute respiratory distress syndrome and others receiving IMV.

Rationale: Idiopathic pulmonary fibrosis (IPF) is an incurable chronic progressive fibrotic lung disease with median survival of 3-5 years from diagnosis. Estimates of incidence rate and prevalence of IPF are outdated and vary widely due to differences in study methodology and diagnostic definitions.

Objectives: To provide an up-to-date estimate of IPF incidence rates and prevalence and describe the comorbidity burden for people with IPF in the United States.

Methods: This non-interventional retrospective study used claims data from the Optum Clinformatics Data Mart database from 2017 to 2022. Individuals were required to have at least 365-day continuous enrollment in the database to enter the study. Individuals with IPF were identified based on claims with the International Classification of Diseases, Tenth Revision code for IPF (J84.112) following study entry. IPF definitions varied by requirement for 1 or 2 qualifying IPF claims and computed tomography scan of the chest and/or lung biopsy. In this analysis, 3 primary case definitions and 2 sensitivity analysis definitions were used to identify individuals with IPF.

Results: By primary case definitions, the overall crude and age- and sex-adjusted incidence rates (per 100,000 person-years) were 14.5-26.1 and 9.8-18.4, respectively; the crude and adjusted prevalences (per 100,000 persons) were 46.3-88.9 and 34.4-67.1, respectively. Incidence rate and prevalence increased markedly with age and varied with ethnicity and region. The most frequent comorbidities were systemic hypertension, chronic obstructive pulmonary disease, and coronary artery disease.

Conclusions: This study provides an up-to-date summary of the incidence rate and prevalence of IPF in the United States and shows a substantial burden of comorbidities among patients diagnosed with IPF.

Rationale: The clinical characteristics of persistent airflow limitation (PAL) were explored in patients aged ≥12 years with physician-assigned diagnoses of asthma, asthma plus chronic obstructive pulmonary disease (COPD), or COPD in the NOVEL Observational longiTudinal studY (NOVELTY) cohort. The NOVELTY study is a prospective study conducted in primary and secondary care in 18 countries.

Objectives: To determine the proportion of patients with PAL at baseline, their baseline characteristics, and the stability and prognostic utility of PAL during follow-up.

Methods: PAL was defined as post-bronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio less than the lower limit of the normal range (European Respiratory Society [ERS]/American Thoracic Society [ATS]) or as <0.7 (Global Initiative for Chronic Obstructive Lung Disease [GOLD] criteria).

Results: We studied 9081 patients over 3 years (asthma: 4754; asthma + COPD; 1147; COPD: 3180). Baseline prevalence of PAL was 24.2% and 29.2% (asthma), 63.3% and 74.1% (asthma + COPD), and 65.4% and 75.8% (COPD) using ERS/ATS and GOLD criteria, respectively. Patients with PAL had markedly worse symptom burden and a history of more frequent moderate and severe exacerbations. In patients with asthma, PAL was associated with higher blood eosinophils and fractional exhaled nitric oxide (FeNO) values; 60% had never smoked. Of patients with PAL at baseline 84% continued to meet PAL criteria at Year 3. Irrespective of physician diagnosis, PAL was a marker of increased risk of moderate and severe exacerbations and poor symptom control during the 3-year follow-up.

Conclusions: PAL is a stable trait associated with more severe disease and poor outcomes in adults with a physician-assigned diagnosis of asthma and/or COPD.

Clinical trial registration (if any): NOVELTY: NCT02760329.

Rationale: AAT (alpha-1 antitrypsin) deficiency (AATD) is a known but underrecognized genetic cause of chronic obstructive pulmonary disease (COPD) and liver disease. Little is known about the epidemiology and burden of AATD among U.S. veterans.

Objectives: To examine the veteran characteristics and epidemiology of AATD and severe AATD throughout the Veterans Health Administration.

Methods: Data were obtained from the electronic health record to describe demographic, clinical, testing outcomes, and geographic data for veterans between January 1, 2010, and December 31, 2019. Multivariable logistic regression analysis was performed to evaluate veteran characteristics associated with AATD. We defined intermediate AATD as a serum AAT concentration >57 and <100 mg/dl or any allelic combination other than PI*MM, PI*MS, PI*SZ, and PI*ZZ. Severe AATD was defined by PI*ZZ and PI*SZ genotypes as well as any combination with a serum AAT concentration ≤57 mg/dl (≤11 μmol/L).

Results: Among 12 million veterans enrolled during the study period, 175,508 were tested for AATD; 8,832 received diagnoses of intermediate AATD and 3,088 of severe AATD. The positivity rate of AATD varied year to year, ranging from 62 to 76 cases per 1,000 persons tested. AATD occurred in 57 cases per 1,000 persons tested with COPD, and there were 66 cases of AATD per 1,000 persons tested with liver disease; however, testing rates of COPD (4.04%) or liver disease (17.91%) were low. There was a heterogeneous distribution of AATD throughout the United States. Factors associated with detection and diagnosis of AATD included younger age, White race, and no history of tobacco use.

Conclusions: This study represents a national analysis of AATD in the Veterans Health Administration. Although the annual positivity rates of AATD among those tested varied over the decade, it confirmed AATD is prevalent in veterans. However, the number of eligible veterans tested is low, which highlights the need for increased awareness of this condition.