American journal of respiratory and critical care medicine
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The biological functions of cholesterol are diverse, ranging from cell membrane integrity, cell membrane signaling, and immunity to the synthesis of steroid and sex hormones, vitamin D, bile acids, and oxysterols. Multiple studies have demonstrated hypocholesterolemia in sepsis, the degree of which is an excellent prognosticator of poor outcomes. However, the clinical significance of hypocholesterolemia has been largely unrecognized. ⋯ Hypocholesterolemia is a frequent condition in sepsis and an important early prognosticator. Low plasma concentrations are associated with wider changes in cholesterol metabolism and its functional roles, and these appear to play a significant role in sepsis pathophysiology. The therapeutic impact of cholesterol elevation warrants further investigation.
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Am. J. Respir. Crit. Care Med. · Feb 2022
ReviewTreatment Trials in Young Patients with COPD and Pre-COPD Patients: Time to Move Forward.
Chronic obstructive pulmonary disease (COPD) is the end result of a series of dynamic and cumulative gene-environment interactions over a lifetime. The evolving understanding of COPD biology provides novel opportunities for prevention, early diagnosis, and intervention. To advance these concepts, we propose therapeutic trials in two major groups of subjects: "young" individuals with COPD and those with pre-COPD. ⋯ We detail approaches to RCT design, including potential outcomes such as lung function, patient-reported outcomes, exacerbations, lung imaging, mortality, and composite endpoints. We critically review study design components such as statistical powering and analysis, duration of study treatment, and formats to trial structure, including platform, basket, and umbrella trials. We provide a call to action for treatment RCTs in 1) young adults with COPD and 2) those with pre-COPD at any age.