American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Nov 2023
Association of GLP-1 Receptor Agonists with COPD Exacerbations Among Patients with Type 2 Diabetes.
Rationale: Patients with chronic obstructive pulmonary disease (COPD) and type 2 diabetes (T2D) have worse clinical outcomes compared with patients without metabolic dysregulation. GLP-1 (glucagon-like peptide 1) receptor agonists (GLP-1RAs) reduce asthma exacerbation risk and improve FVC in patients with COPD. Objectives: To determine whether GLP-1RA use is associated with reduced COPD exacerbation rates, and severe and moderate exacerbation risk, compared with other T2D therapies. ⋯ No statistically significant difference in exacerbation outcomes was seen between GLP-1RA and SGLT2 inhibitor users. Conclusions: Prospective studies of COPD exacerbations in patients with comorbid T2D are warranted. Additional research may elucidate the mechanisms underlying these observed associations with T2D medications.
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Am. J. Respir. Crit. Care Med. · Nov 2023
Lower Airway Dysbiosis Augments Lung Inflammatory Injury in Mild-to-Moderate COPD.
Rationale: Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and healthcare costs. Cigarette smoke is a causative factor; however, not all heavy smokers develop COPD. Microbial colonization and infections are contributing factors to disease progression in advanced stages. ⋯ Finally, in a preclinical murine model exposed to cigarette smoke, lower airway dysbiosis with common oral commensals augments the inflammatory injury, revealing transcriptomic signatures similar to those observed in human subjects with COPD. Conclusions: Lower airway dysbiosis in the setting of smoke exposure contributes to inflammatory injury early in COPD. Targeting the lower airway microbiome in combination with smoking cessation may be of potential therapeutic relevance.
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Am. J. Respir. Crit. Care Med. · Nov 2023
IL-33 Expression Is Lower in Current Smokers at Both Transcriptomic and Protein Level.
Rationale: IL-33 is a proinflammatory cytokine thought to play a role in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD). A recent clinical trial using an anti-IL-33 antibody showed a reduction in exacerbation and improved lung function in ex-smokers but not current smokers with COPD. Objectives: This study aimed to understand the effects of smoking status on IL-33. ⋯ Protein analysis demonstrated lower IL-33 levels in lung tissue from current versus former smokers with COPD and a lower proportion of IL-33-positive basal cells in current versus ex-smoking controls. Conclusions: We provide strong evidence that cigarette smoke leads to an overall reduction in IL-33 expression in transcriptomic and protein level, and this may be due to the decrease in resting basal cells. Together, these findings may explain the clinical observation that a recent antibody-based anti-IL-33 treatment is more effective in former than current smokers with COPD.