Annals of the American Thoracic Society最新文献

Rationale: Idiopathic pulmonary fibrosis (IPF) is a complex and heterogeneous disease. Given this, we reasoned that differences in genetic profiles may be associated with unique clinical and radiologic features. Computational image analysis, sometimes referred to as radiomics, provides objective, quantitative assessments of radiologic features in subjects with pulmonary fibrosis. Objectives: To determine if the genetic risk profile of patients with IPF identifies unique computational imaging phenotypes. Methods: Participants with IPF were included in this study if they had genotype data and computed tomography (CT) scans of the chest available for computational image analysis. The extent of lung fibrosis and the likelihood of a usual interstitial pneumonia (UIP) pattern were scored automatically using two separate, previously validated deep learning techniques for CT analysis. UIP pattern was also classified visually by radiologists according to established criteria. Results: Among 329 participants with IPF, MUC5B and ZKSCAN1 were independently associated with the deep learning-based UIP score. None of the common variants were associated with fibrosis extent by computational imaging. We did not find an association between MUC5B or ZKSCAN1 and visually assessed UIP pattern. Conclusions: Select genetic variants are associated with computer-based classification of UIP on CT in this IPF cohort. Analysis of radiologic features using deep learning may enhance our ability to identify important genotype-phenotype associations in fibrotic lung diseases.

Rationale: Hispanic/Latino adults commonly experience high psychosocial stress; yet, little is known about the pathways linking sociocultural stressors and asthma in this population. Objectives: To study whether and how sociocultural stressors are associated with asthma in Hispanic/Latino adults. Methods: We conducted a cross-sectional study of 4,759 adults aged 18 to 74 years who participated in the Sociocultural Ancillary Study of the Hispanic Community Health Study/Study of Latinos. All participants completed a sociocultural assessment, including acculturative stress, perceived ethnic discrimination, neighborhood problems, neighborhood social cohesion, and a cumulative measure of all sociocultural stressors. Weighted multivariable logistic regression accounting for sampling design was used for the analysis of sociocultural stressors and current asthma or current asthma symptoms. A mediation analysis was conducted to estimate the contributions of depressive symptoms and anxiety to the cumulative sociocultural stressors-asthma association. Results: Acculturative stress and neighborhood problems were associated with 1.4 to 2.1 times higher odds of current asthma or current asthma symptoms, and perceived ethnic discrimination was associated with 1.4 times higher odds of current asthma symptoms. Neighborhood social cohesion was associated with 0.6 times lower odds of asthma. Cumulative sociocultural stressors were associated with 1.6 times higher odds of current asthma symptoms (odds ratio for below the median versus greater than or equal to the median value, 1.60; 95% confidence interval, 1.29, 1.99). Depressive symptoms and anxiety explained 26% and 22%, respectively, of the association between cumulative sociocultural stressors and asthma symptoms. Conclusions: Among Hispanic/Latino adults, sociocultural stressors were associated with current asthma or asthma symptoms. Depressive symptoms and anxiety partly mediated this association. Clinicians caring for Hispanic/Latino adults with asthma should be aware of potential stressors and comorbidities such as depression and anxiety.

Rationale: In the United States, ambulatory oxygen is recommended for patients with idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) who experience symptomatic exertional hypoxemia. Ambulatory oxygen need is often determined by submaximal hall walk testing; however, this may fail to accurately characterize exertional hypoxemia in some patients. Objectives: Assess for differences in ambulatory oxygen needs between patients with IPF and COPD who completed a ramped treadmill protocol exercise test (RTPET) and correlate oxygen flow rates determined at highest-level (HL) exertion with lung function and exercise parameters. Oxygen need is defined as the flow rate needed to maintain oxygen saturation ⩾90% in patients who desaturate to ⩽88%. Methods: We conducted a retrospective review of RTPET results for patients with IPF and COPD who also recently completed spirometry. The RTPET has three phases: rest, submaximal usual pace (UP) walking at 0% treadmill grade for 3 minutes, and HL walking at the UP walk speed with increasing treadmill grade by 2% every 2 minutes. Patients with IPF were part of a clinical registry, whereas patients with COPD were identified based on diagnosis coding and spirometry (forced expiratory volume in 1 s/forced vital capacity < 0.70). The RTPET for both groups was completed based on a pulmonologist's referral. Results: We included 329 patients with IPF and 2,343 patients with COPD. A greater proportion of patients with IPF required ambulatory oxygen to maintain saturation ⩾90% at HL exertion. After adjusting for demographic covariates and exercise parameters, patients with IPF required higher ambulatory oxygen flow rates than subjects with COPD with similar diffusion capacity of carbon monoxide values. Of patients who did not require oxygen with submaximal UP testing, 49% with IPF and 24% with COPD required oxygen at HL exertion. Conclusions: The RTPET identified higher oxygen flow needs at HL exertion in patients with IPF versus patients with COPD; however, in both diseases, there was a significant proportion of patients who were only found to have exertional desaturation at HL exertion. Reliance on submaximal testing may fail to meet the needs of patients with IPF and COPD. Further studies are needed to determine if oxygen prescriptions targeting the highest level of desaturation improve clinical outcomes, symptoms, or quality of life.

Rationale: Despite advancements in screening, lung cancer remains the leading cause of cancer-related mortality globally. Objectives: To investigate respiratory function as a prognostic factor for survival in the UK Biobank, a population-based cohort of more than 500,000 participants, and the NLST (National Lung Screening Trial), a high-risk screening population of more than 50,000 screenees. Methods: Participants with an incident lung cancer diagnosis and spirometry-assessed lung function were included. Lung cancer was measured as the ratio of forced expiratory volume in 1 second (FEV₁) and forced vital capacity and percentage of predicted FEV₁. Multivariable Cox proportional hazards models were fitted to estimate the impact of lung function on 5-year overall survival in populations with different baseline lung cancer risks. Results: A total of 2,690 and 609 patients were included in the analysis from the UK Biobank and the NLST, respectively. In the UK Biobank, a higher percentage of predicted FEV₁ and ratio were associated with better survival after lung cancer diagnosis, with hazard ratios of 0.97 (95% confidence interval [CI], 0.95-1.00 per 10% increase) and 0.95 (95% CI, 0.90-1.00 per 10% increase), respectively. No statistically significant results were found when assessing the data from the NLST study. Conclusions: Impaired lung function was associated with poorer survival for patients with lung cancer in the general population, although this was less clear in a high-risk, screening-eligible population. This highlights the potential clinical importance of respiratory function as a prognostic factor in lung cancer in the general population and presents a possibility for personalized cancer management.

Rationale: Patients with sepsis and/or acute respiratory failure are at high risk for death or long hospital stays, yet limited evidence exists to guide triage to intensive care units (ICUs) or general medical wards for the majority of these patients who do not initially require life support. Objectives: To identify factors that influence how hospitals triage patients with capacity-sensitive conditions and those factors that may account for observed ICU relative to ward, or ward relative to ICU, benefits for such patients. Methods: We conducted an explanatory sequential mixed-methods study. As part of a 27-hospital, two-health system retrospective cohort study, we calculated hospital-specific measurements of ICU net benefit for patients with sepsis and/or acute respiratory failure. Hospitals among the highest ICU net benefit and lowest ICU net benefit (or highest ward net benefit) from each study health system were selected for in-depth qualitative study. At each hospital, interviews were conducted with emergency department, ward, and ICU clinicians and administrators. Interview transcripts were analyzed using flexible coding and the framework method. Results: Interviews were conducted with 118 respondents (46 physicians, 43 nurses, 5 advanced practice providers, and 24 administrators) from four hospitals. Respondents across hospitals agreed that the prediction of patient trajectory is central to triage decisions, but there was variation in opinion across work locations about optimal pretriage emergency department interventions in terms of intensity, repetition, clinical reassessment, and observation duration. The main difference observed between high and low ICU net benefit hospitals related to the way respondents working in the ICU and ward described their responses to patients who experience rapid clinical deviations from triage-expected trajectories, including sustained lack of critical care needs after admission to the ICU and acute critical care needs after admission to the ward. Hospitals with low ICU net benefit (or high ward net benefit) had particularly robust and proactive rapid response and clinical decompensation surveillance practices for ward-admitted patients. Conclusions: Particularly proactive rapid response programs that deliver on-location critical care may quantitatively increase ward net benefit by bringing ICU benefits without ICU-associated harms to ward patients who become critically ill.

Rationale: Cystic fibrosis (CF) is characterized by bronchiectasis on imaging, while functionally evolving toward obstructive impairment. Despite its assumed importance in CF, small airway remodeling and its relation to bronchiectasis remains poorly understood. Objectives: The aim of our study was to explore both large and small airway disease morphometrically, by using detailed imaging techniques, such as ex vivo high-resolution computed tomography (HRCT) and micro-computed tomography (μCT), and histological analysis in advanced CF. Methods: On HRCT (600 μm; CF, n = 21; control, n = 6) and μCT (150 μm; CF, n = 3; control, n = 1) scans of inflated explanted lungs, the ratio of visible airway volume to total lung volume (AV%) was calculated as a marker of bronchiectasis, while airway segmentation was used for generation analysis. Clinical data were retrospectively collected. On μCT (8.5 μm) images of lung cores (±2.8 cm³), extracted randomly from each lobe (three per lobe), distal airway (DA) diameter, number of airway collapses, and number of open terminal bronchioles per milliliter were analyzed. Morphometric analysis was supplemented with histological analysis of DA collapse. Results: AV% on HRCT was heterogeneous among CF lungs (0.7-4.6%), overlapping with controls (0.4-1.2%). However, the pattern of airway loss on μCT was homogeneous among CF lungs and most pronounced from generations 9-16. AV% did not correlate with the number of open terminal bronchioles per milliliter or percentage predicted forced expiratory volume in 1 second, which correlated with each other. Open DAs in CF lungs were narrowed compared with DA in controls. On the other hand, collapsed DAs in CF lungs showed varying degrees of proximal dilation, with DA diameter correlating with AV%. On histology, collapsed CF DAs showed constrictive bronchiolitis. Conclusions: Airway remodeling in end-stage CF is heterogeneous, ranging from minimal bronchiectasis, overlapping with control lungs, to extensive bronchiectasis with small airway dilation. However, the degree of bronchiectasis is unrelated to functional impairment or the amount of small airway loss, underscoring the importance of small airway disease.