Annals of the American Thoracic Society最新文献

Rationale: Some patients with interstitial lung disease (ILD) have a high mortality rate or experience acute exacerbation of ILD (AE-ILD) that results in increased mortality. Early identification of these high-risk patients and accurate prediction of the onset of these important events is important to determine treatment strategies. Although various factors that affect disease behavior among patients with ILD hinder the accurate prediction of these events, the use of longitudinal information may enable better prediction.

Objectives: To develop a deep-learning (DL) model to predict composite outcomes defined as the first occurrence of AE-ILD and mortality using longitudinal data.

Methods: Longitudinal clinical and environmental data were retrospectively collected from consecutive patients with ILD at two specialty centers between January 2008 and December 2015. A DL model was developed to predict composite outcomes using longitudinal data from 80% of patients from the first center, which was then validated using data from the remaining 20% patients and second center. The developed model was compared with the univariate Cox proportional hazard (CPH) model using the ILD gender-age-physiology (ILD-GAP) score and multivariate CPH model at the time of ILD diagnosis.

Measurements and main results: AE-ILD was reported in 218 patients among the 1,175 patients enrolled, whereas 380 died without developing AE-ILD. The truncated concordance index (C-index) values of univariate/multivariate CPH models for composite outcomes within 12, 24, and 36 months after prediction were 0.789/0.843, 0.788/0.853, and 0.787/0.853 in internal validation, and 0.650/0.718, 0.652/0.756, and 0.640/0.756 in external validation, respectively. At 12 months after ILD diagnosis, the DL model outperformed the univariate CPH model and multivariate CPH model for composite outcomes within 12 months, with C-index values of 0.842, 0.840, and 0.839 in internal validation, and 0.803, 0.744, and 0.746 in external validation, respectively. Neutrophils, C-reactive protein, ILD-GAP score, and exposure to suspended particulate matter were strongly associated with the composite outcomes.

Conclusions: The DL model can accurately predict the incidence of AE-ILD or mortality using longitudinal data.

Rationale: Incidence rates for pulmonary hypertension using diagnostic data in patients with cardiopulmonary disease are not known.

Objectives: To determine incidence rates of, risk factors for, and mortality hazard associated with pulmonary hypertension among patients referred for transthoracic echocardiography.

Methods: Retrospective cohort study using data from the Veterans Health Administration (1999-2020) and Vanderbilt University Medical Center (1994-2020). Pulmonary hypertension was defined as pulmonary artery systolic pressure >35mmHg with prevalent cases excluded. Heart failure and chronic obstructive pulmonary disease were the primary exposures of interest. The primary outcome was incident pulmonary hypertension. Secondarily, we examined mortality rate following incident diagnosis.

Measurements and main results: We identified 245,067 VA patients (94% male, 20% Black) and 117,526 Vanderbilt patients (46% male, 11% Black) without pulmonary hypertension, of whom 38,882 VA patients and 8,061 Vanderbilt patients developed pulmonary hypertension. Only 18-19% of patients with echo-based pulmonary hypertension also had a diagnostic code. Hazard of pulmonary hypertension was 4-fold higher in patients with heart failure and chronic obstructive pulmonary disease compared to patients without either. Mortality rates increased from pulmonary artery systolic pressure of 35mmHg to 45mmHg then plateaued. Independent risk factors for incident pulmonary hypertension included older age, male sex, black race, and cardiometabolic comorbidities.

Conclusions: Pulmonary hypertension incidence rates estimated by diagnostic data are higher than code-based rates. Heart failure and chronic obstructive pulmonary disease strongly associate with incident pulmonary hypertension. Pulmonary artery systolic pressure >45mmHg at diagnosis is associated with high mortality. New pulmonary hypertension on echocardiography is an important prognostic sign.

Rationale: Older adults make up the majority of patients with advanced non-small cell lung cancer (NSCLC) and often carry multiple other comorbidities (multimorbidity) when initiating treatment. The nature and impact of multimorbidity remain largely unknown, given the limitations of standard count-based comorbidity indices in aging patients and their exclusion from clinical trials.

Objective: Our objective is to identify and define multimorbidity patterns in older U.S. veterans newly treated for advanced NSCLC in the national VA healthcare system between 2002 to 2020, and whether they are associated with mortality and healthcare utilization.

Methods: We measured 63 chronic conditions in 10,160 veterans age ≥ 65 years newly treated for NSCLC in the national Veterans Affairs healthcare system from 2002 to 2020. Latent class analysis (LCA) was used to identify patterns of multimorbidity among these conditions, with final patterns determined based on model fit and clinical meaningfulness. Kaplan-Meier and Cox proportional hazards regression analyses were used to evaluate the association of multimorbidity patterns with overall survival (primary outcome), and with emergency department visits and unplanned hospitalizations (secondary outcomes).

Results: Five multimorbidity patterns arose from the LCA, with overall survival varying across patterns (log-rank 2-sided P<0.001). Veterans with metabolic diseases (24.7% of all patients; HR [95% CI], 1.10 [1.04 -1.16]), psychiatric and substance use disorders (16.0%; HR [95% CI], 1.17 [1.10-1.24]), cardiovascular disease (14.4%; HR [95% CI], 1.22 [1.15-1.30]), and multisystem impairment (10.7%; HR [95% CI], 1.36 [1.26 -1.46]) had a higher hazard of death compared to veterans with common conditions of aging beyond their NSCLC (34.2%, reference), controlling for age, gender, race, days between diagnosis and treatment, date of diagnosis, and NSCLC stage and histology. Associations held after adjusting for the count-based Charlson Comorbidity Index. Multimorbidity patterns were also independently associated with emergency department visits and unplanned hospitalizations.

Conclusion: Our findings reveal that the numerous chronic conditions present in older veterans with late-stage NSCLC cluster together into distinct multimorbidity patterns; the nature of conditions in these patterns carry value beyond their number.

Rationale: Multiple clinical practice guidelines lack recommendations pertaining to non-invasive ventilation (NIV) in acute asthma exacerbations due to a paucity of evidence. However, the evidence syntheses for these guidelines were performed years ago and more recent randomized controlled trials (RCTs) and observational studies have been published.

Objective: Update the evidence syntheses from previous guidelines to further clarify the effects of NIV in acute asthma exacerbations.

Methods: A systematic search of Medline, Embase and the Cochrane Library was conducted, studies comparing NIV plus standard medical therapy to standard medical therapy alone in adults with acute asthma exacerbation were selected using a priori selection criteria, and relevant data were extracted. Weighted aggregation (meta-analysis) was performed to summarize effects, which were appraised using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach.

Results: Eight RCTs and five observational studies were selected. NIV was associated with a reduced intubation rate (RCTs RR 0.46, CI 0.16-1.29 and observational studies RR 0.55, CI 0.45-0.68), admission rate (RR 0.57, CI 0.34-0.98), and time to improvement in accessory muscle use (Mean difference -1.13 hours, CI -1.28 - -0.99). Additional outcomes favored NIV plus standard medical therapy but didn't reach statistical significance including dyspnea measures and spirometry measures. There were too few deaths to reliably assess mortality. The quality of evidence ranged from low to very low for all outcomes.

Conclusion: All statistically significant outcomes favored NIV plus standard medical therapy over standard medical therapy alone in adults with acute asthma exacerbation. Our aggregate data suggests that intubation rate may be reduced with NIV plus SMT, though the overall quality of the evidence is low. If this is a true effect, it may be clinically important because intubation has been shown to correlate with mortality in multiple observational trials. Given these findings, patients with acute asthma exacerbations may benefit from a trial of NIV in addition to standard medical therapy.

Rationale: Sleep-related hypoventilation disorder (SHD) is common among obese patients with obstructive sleep apnea (OSA), but the pathological endotypes associated with obesity and SHD remain unclear.

Objectives: To investigate relationship between endotypes with body mass index (BMI) among patients with OSA, and to explore endotypic traits of patients with comorbid SHD.

Methods: We prospectively collected polysomnographic studies of 1364 patients with OSA, and overnight transcutaneous CO2 (TcCO2) measurements among 420 obese patients. Endotypic traits were estimated using polysomnographic signals. SHD was determined using TcCO2 >55 mm Hg for ≥ 10 min. We illustrated the non-linear relationship between BMI and endotypic traits. Differences in endotypic traits between non-obese patients with OSA, obese patients with simple OSA, and obese patients with comorbid OSA and SHD were examined using Kruskal-Wallis tests and multiple regression analysis.

Results: A unit increase in BMI was associated with a 1.02 %eupnea increase in arousal threshold, 1.16 %eupnea increase in collapsibility, 0.01 increase in loop gain, and 0.48%eupnea increase in compensation with a ceiling effect. SHD was observed in 18%-36% of obese patients with OSA, depending on the criteria. Among obese patients with OSA, those with SHD exhibited a 0.06 higher loop gain than those with simple OSA, after adjusting for BMI.

Conclusions: A ceiling effect of upper airway compensation function coupled with worse collapsibility and high loop gain characterizes pathological endotypes of obese patients with OSA. Patients with SHD exhibited a more sensitive respiratory pattern, indicated by increased loop gain.