American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · May 2024
Multicenter StudyProteomic Biomarkers of Quantitative Interstitial Abnormalities in COPDGene and CARDIA Lung Study.
Rationale: Quantitative interstitial abnormalities (QIAs) are early measures of lung injury automatically detected on chest computed tomography scans. QIAs are associated with impaired respiratory health and share features with advanced lung diseases, but their biological underpinnings are not well understood. Objectives: To identify novel protein biomarkers of QIAs using high-throughput plasma proteomic panels within two multicenter cohorts. ⋯ These proteins were enriched for 49 Gene Ontology pathways, including biological processes in inflammatory response, cell adhesion, immune response, ERK1/2 regulation, and signaling; cellular components in extracellular regions; and molecular functions including calcium ion and heparin binding. Conclusions: We identified the proteomic biomarkers of QIAs in an older, smoking population with a higher prevalence of pulmonary disease and in a younger, healthier community cohort. These proteomics features may be markers of early precursors of advanced lung diseases.
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Am. J. Respir. Crit. Care Med. · May 2024
Multicenter StudyAmbient Ultrafine Particulate Matter and Clinical Outcomes in Fibrotic Interstitial Lung Disease.
Rationale: Particulate matter with an aerodynamic diameter ⩽2.5 μm is associated with adverse outcomes in fibrotic interstitial lung disease (fILD), but the impact of ultrafine particulates (UFPs; aerodynamic diameter ⩽100 nm) remains unknown. Objective: To evaluate UFP associations with clinical outcomes in fILD. Methods: We conducted a multicenter, prospective cohort study enrolling patients with fILD from the University of Pittsburgh Dorothy P. and Richard P. ⋯ Higher UFP exposure was associated with lower baseline FVC and more rapid FVC decline in the Simmons registry. Conclusions: Increased UFP exposure was associated with transplantation-free survival and lung function in the cohort with precise residential location linkage. This work highlights the need for more robust regulatory networks to study the health effects of UFPs nationwide.
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Am. J. Respir. Crit. Care Med. · May 2024
Multicenter StudyCommensal Oral Microbiota, Disease Severity and Mortality in Fibrotic Lung Disease.
Rationale: Oral microbiota associate with diseases of the mouth and serve as a source of lung microbiota. However, the role of oral microbiota in lung disease is unknown. Objectives: To determine associations between oral microbiota and disease severity and death in idiopathic pulmonary fibrosis (IPF). ⋯ The Streptococcus genus was mainly composed of Streptococcus mitis species. Conclusions: Increasing buccal microbial diversity predicts disease severity and death in IPF. The oral commensal S. mitis spp associates with preserved lung function and improved survival.
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Am. J. Respir. Crit. Care Med. · Mar 2024
Multicenter StudyCell-Free DNA Maps Tissue Injury and Correlates with Disease Severity in Lung Transplant Candidates.
Rationale: Plasma cell-free DNA levels correlate with disease severity in many conditions. Pretransplant cell-free DNA may risk stratify lung transplant candidates for post-transplant complications. Objectives: To evaluate if pretransplant cell-free DNA levels and tissue sources identify patients at high risk of primary graft dysfunction and other pre- and post-transplant outcomes. ⋯ High pretransplant cell-free DNA increased the risk of primary graft dysfunction (odds ratio, 1.60; 95% confidence interval [CI], 1.09-2.46; P = 0.0220), and death (hazard ratio, 1.43; 95% CI, 1.07-1.92; P = 0.0171) but not chronic lung allograft dysfunction (hazard ratio, 1.37; 95% CI, 0.97-1.94; P = 0.0767). Conclusions: Lung transplant candidates demonstrate a heightened degree of tissue injury with elevated cell-free DNA, primarily originating from innate immune cells. Pretransplant plasma cell-free DNA levels predict post-transplant complications.
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Am. J. Respir. Crit. Care Med. · Mar 2024
Multicenter StudyLung Injury Prediction Model in Bone Marrow Transplantation: A Multicenter Cohort Study.
Rationale: Pulmonary complications contribute significantly to nonrelapse mortality following hematopoietic stem cell transplantation (HCT). Identifying patients at high risk can help enroll such patients into clinical studies to better understand, prevent, and treat posttransplantation respiratory failure syndromes. Objectives: To develop and validate a prediction model to identify those at increased risk of acute respiratory failure after HCT. ⋯ The test cohort differed markedly in demographic, medical, and hematologic characteristics. The model also performed well in this setting in predicting ARDS (C-statistic, 0.841; 95% CI, 0.782-0.900) and the need for IMV and/or NIV (C-statistic, 0.872; 95% CI, 0.831-0.914). Conclusions: A novel prediction model incorporating data elements from the pretransplantation, posttransplantation, and early in-hospital domains can reliably predict the development of post-HCT acute respiratory failure.