American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Apr 2022
Cigarette Smoke Exposure and ARDS in Sepsis: Epidemiology, Clinical Features, and Biologic Markers.
Rationale: Cigarette smoke exposure is associated with an increased risk of developing acute respiratory distress syndrome (ARDS) in trauma, transfusion, and nonpulmonary sepsis. It is unknown whether this relationship exists in the general sepsis population. Furthermore, it is unknown if patients with ARDS have differences in underlying biology based on smoking status. ⋯ Similar biomarker patterns were observed in blunt trauma patients with ARDS. Conclusions: Passive and active smoking are associated with an increased risk of developing ARDS in patients with pulmonary and nonpulmonary sepsis. Among patients with ARDS, those with cigarette smoke exposure have less systemic inflammation, while active smokers also have lower severity of illness compared with nonsmokers, suggesting that smoking contributes to biological heterogeneity in ARDS.
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Am. J. Respir. Crit. Care Med. · Apr 2022
Meta AnalysisThree-Month FVC Change: A Trial Endpoint for IPF Based on Individual Participant Data Meta-Analysis.
Rationale: Novel therapies for idiopathic pulmonary fibrosis (IPF) are in development, but there remains uncertainty about the optimal trial endpoint. An earlier endpoint would enable assessment of a greater number of therapies in adaptive trial designs. Objectives: To determine whether short-term changes in FVC, DlCO, and six-minute-walk distance could act as surrogate endpoints to accelerate early-phase trials in IPF. ⋯ An FVC change treatment effect was observed between treatment and placebo arms at 3 months (difference in FVC change of 42.9 ml; 95% CI, 24.0-61.8 ml; P < 0.001). Conclusions: IPD meta-analysis demonstrated that 3-month changes in physiological variables, particularly FVC, were associated with mortality among individuals with IPF. FVC change over 3 months may hold potential as a surrogate endpoint in IPF adaptive trials.
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Am. J. Respir. Crit. Care Med. · Apr 2022
Clinical TrialDaily Exposure to Mild Intermittent Hypoxia Reduces Blood Pressure in Male OSA Patients with Hypertension.
Rationale: Daily exposure to mild intermittent hypoxia (MIH) may elicit beneficial cardiovascular outcomes. Objectives: To determine the effect of 15 days of MIH and in-home continuous positive airway pressure treatment on blood pressure in participants with obstructive sleep apnea and hypertension. Methods: We administered MIH during wakefulness 5 days/week for 3 weeks. ⋯ No detrimental neurocognitive and metabolic outcomes were evident following MIH. Conclusions: MIH elicits beneficial cardiovascular and autonomic outcomes in males with OSA and concurrent hypertension. Clinical trial registered with www.clinicaltrials.gov (NCT03736382).
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Am. J. Respir. Crit. Care Med. · Apr 2022
Modelling Wheezing Spells Identifies Phenotypes with Different Outcomes and Genetic Associates.
Rationale: Longitudinal modeling of current wheezing identified similar phenotypes, but their characteristics often differ between studies. Objectives: We propose that a more comprehensive description of wheeze may better describe trajectories than binary information on the presence/absence of wheezing. Methods: We derived six multidimensional variables of wheezing spells from birth to adolescence (including duration, temporal sequencing, and the extent of persistence/recurrence). ⋯ The spell-based approach was much more robust in dealing with missing data, and the derived clusters were more stable and internally homogeneous. Conclusions: Modeling of spell variables identified a novel intermittent wheeze phenotype associated with lung function decline to early adulthood. Using multidimensional spell variables may better capture wheeze development and provide a more robust input for phenotype derivation.