American journal of respiratory and critical care medicine
-
Am. J. Respir. Crit. Care Med. · Oct 2024
Efficacy and Safety of Admilparant, an LPA1 Antagonist in Pulmonary Fibrosis: A Phase 2 Randomized Clinical Trial.
Idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) have high morbidity and mortality; thus, novel treatments are needed. ⋯ gov, ID: NCT04308681.
-
Am. J. Respir. Crit. Care Med. · Oct 2024
Sex-specific Genetic Determinants of Right Ventricular Structure and Function.
While sex differences in right heart phenotypes have been observed, the molecular drivers remain unknown. ⋯ BMPR1A has emerged as a biologically plausible candidate gene for female-specific genetic determination of RV function, showing associations with cardiac performance under chronically increased afterload in female patients with PAH.
-
Am. J. Respir. Crit. Care Med. · Oct 2024
Genetically Predicted Body Mass Index and Mortality in COPD.
Rationale: Body mass index (BMI) is associated with chronic obstructive pulmonary disease (COPD) mortality, but the underlying mechanisms are unclear. The effect of genetic variants aggregated into a polygenic score may elucidate the causal mechanisms and predict risk. Objectives: To examine the associations of genetically predicted BMI with all-cause and cause-specific mortality in COPD. ⋯ Compared with participants with concordant measured and genetically predicted BMI, those with discordantly low BMI had higher risks for all-cause mortality (HR, 1.57; 95% CI, 1.41-1.74) and respiratory death (HR, 2.01; 95% CI, 1.61-2.51). Conclusions: In people with COPD, a higher genetically predicted BMI is associated with higher cardiovascular mortality but not respiratory mortality. Individuals with a discordantly low BMI have higher all-cause and respiratory mortality rates than those with a concordant BMI.
-
Am. J. Respir. Crit. Care Med. · Oct 2024
Discovery of Two Novel Immunoepitopes and Development of Peptide-based Sarcoidosis Immunoassay.
Rationale: Sarcoidosis is a systemic granulomatous disorder associated with hypergammaglobulinemia and the presence of autoantibodies. The specific antigens initiating granulomatous inflammation in sarcoidosis are unknown, and there is no specific test available to diagnose sarcoidosis. To discover novel sarcoidosis antigens, we developed a high-throughput T7 phage display library derived from the sarcoidosis cDNA and identified numerous clones differentiating sarcoidosis from other respiratory diseases. ⋯ Combining both biomarkers improved the area under the curve, sensitivity, specificity, and positive and negative predictive value. Conclusions: These results provide a novel immunoassay for sarcoidosis. The discovery of two neoantigens facilitates the development of biospecific drug discovery and the sarcoidosis-specific model.