American Journal of Respiratory and Critical Care Medicine

Abstract Rationale During tumorigenesis, approximately 20% of EGFR-mutant LUADs progress rapidly to aggressive subtypes. Multi-omics analyses of stage-I LUAD cohorts have revealed that centrally located lesions exhibit enhanced tumorigenic potential compared with peripheral counterparts, whereas the underlying mechanisms remain elusive. Objectives To define the spatial-clinical determinants of ea…

Abstract Rationale Positive end-expiratory pressure (PEEP) balances recruitment against over-inflation in ARDS. The early response to a PEEP step-down remains under-characterized. Four-dimensional computed tomography (4D-CT) can quantify within-breath mechanics with anatomy-specific resolution. Objectives Using 4D-CT to characterize the early (3-5 min) effects of PEEP step-down (15 to 5 cmH2O) on…

Abstract Rationale Information is missing on the tissue cell expression patterns of interleukin IL-33 (IL-33) and splice variants of the IL-33 receptor ST2 in normal and COPD lungs. Objectives To characterize the expression patterns of IL-33, the soluble ST2 (sST2) and membrane-bound ST2 (ST2L) splice variants in the poorly studied small airway and distal lung compartments in COPD and controls. M…

Abstract Rationale As the global population ages, identifying risk factors for age-related diseases, such as COPD, is crucial for public health. Mosaic loss of Y chromosome (mLOY) in blood cells is an age-related somatic mosaicism event, but its relationship with pulmonary health remains undercharacterized. Objectives To examine the association between mLOY and pulmonary outcomes in men. Methods …

Abstract Rationale No recommended therapy exists for chronic fibrosing interstitial lung diseases (CF-ILD) with disease progression despite ongoing treatment with nintedanib or pirfenidone. Pamufetinib (also known as TAS-115) is a novel oral antifibrotic tyrosine kinase inhibitor in development for CF-ILD with a progressive phenotype. Objective We sought to evaluate the dose-response of pamufetin…