The pathogenesis of pulmonary diseases is often complex and characterized by multiple cellular events, including inflammation, cell death, and cell proliferation. The mechanisms by which these events are regulated in pulmonary diseases remain poorly understood. Autophagy is an essential process for cellular homeostasis and stress adaptation in eukaryotic cells. This highly conserved cellular process involves the sequestration of cytoplasmic components in double-membrane autophagosomes, which are delivered to lysosomes for degradation. The critical roles of autophagy have been demonstrated in a wide range of pathophysiological conditions. Emerging studies have identified that autophagy plays important roles in the pathogenesis of various lung diseases. In addition, autophagy has been shown to selectively degrade subcellular targets, including proteins, organelles, and pathogens. Here, we highlight the recent advances in the molecular regulation and function of autophagy in lung diseases.

CNS is an inventor on patents related to resolvins and other pro-resolving mediators (both composition of matter and use of) that are licensed by Partners-Brigham and Women's Hospital (Partners-BWH) for clinical development. BTT has served as a consultant on ARDS clinical trial design for Bayer, Boehringer Ingelheim, and GlaxoSmithKline. AMKC is a cofounder of and SAB member for Proterris Inc. and served as a consultant for Teva Pharmaceuticals. AMKC has a use patent on CO, which belongs to

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Introduction: Women with heart failure with reduced ejection fraction (HFrEF) are undertreated with guideline recommended therapy and experience worse quality of life compared with men. Low enrollment of women in HFrEF outcomes trials has limited inferences about drug efficacy in women. We investigated sex-differences in baseline characteristics, clinical outcomes, and response to omecamtiv mecarbil in the GALACTIC-HF trial. Methods: The GALACTIC-HF trial randomized patients with symptomatic HFrEF with EF of 35% or less to omecamtiv mecarbil or placebo. Baseline characteristics for male and female participants were compared using parametric or non-parametric tests. Risk of the primary endpoint, heart failure event or cardiovascular death, was compared between sexes using Kaplan-Meier curves and Cox regression adjusted for 13 relevant clinical covariates. Treatment effect heterogeneity was evaluated by the sex*treatment interaction term. Results: Of the 8,232 patients enrolled, 1749 (21.2%) were women. Women had lower total Kansas City Cardiomyopathy score (59.1 vs 65.8, P<0.001) and were less likely to be treated with ARNI (17.5% vs 20.0%, P=0.02), SGLT2 inhibitor (1.5% vs 2.9% P=0.001), ICD (24.5% vs 33.7%, P<0.001) or CRT (11.5% vs 14.7%, P<0.001). Compared to men, women had lower rates of the primary end point (hazard ratio [HR] 0.89 95% CI 0.81-0.97, p=0.01), which persisted after covariate adjustment (HR 0.85 [95% CI 0.77-0.92], p=0.001). Sex did not significantly modify treatment effect of omecamtiv mecarbil on the primary endpoint (p-interaction = 0.37). Women had higher rates of any reported adverse event but lower risk of serious adverse event leading to treatment discontinuation. Conclusions: Women with HFrEF had worse quality of life, were less likely to be treated with guideline-based therapies and had 15% lower risk of HF event or cardiovascular death compared with men. The effect of omecamtiv mecarbil did not significantly differ by sex.