American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Aug 2022
Multicenter StudyExtracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.
Rationale: Whether patients with coronavirus disease (COVID-19) may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. Objectives: To estimate the effect of ECMO on 90-day mortality versus IMV only. Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO versus no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 < 80 or PaCO2 ⩾ 60 mm Hg). ⋯ However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand and when initiated within the first 4 days of IMV and in patients who are profoundly hypoxemic. Conclusions: In an emulated trial on the basis of a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and regions with ECMO capacities specifically organized to handle high demand.
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Am. J. Respir. Crit. Care Med. · Aug 2022
CD38 Mediates Lung Fibrosis by Promoting Alveolar Epithelial Cell Aging.
Rationale: A prevailing paradigm recognizes idiopathic pulmonary fibrosis (IPF) originating from various alveolar epithelial cell (AEC) injuries, and there is a growing appreciation of AEC aging as a key driver of the pathogenesis. Despite this progress, it is incompletely understood what main factor(s) contribute to the worsened alveolar epithelial aging in lung fibrosis. It remains a challenge how to dampen AEC aging and thereby mitigate the disease progression. ⋯ Mechanistically, we found that CD38 elevation downregulated intracellular NAD, which likely led to the aging promoting impairment of the NAD-dependent cellular and molecular activities. Furthermore, we demonstrated that genetic and pharmacological inactivation of CD38 improved these NAD dependent events and ameliorated bleomycin-induced lung fibrosis. Conclusions: Our study suggests targeting alveolar CD38 as a novel and effective therapeutic strategy to treat this pathology.
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Am. J. Respir. Crit. Care Med. · Aug 2022
Meta AnalysisPulmonary Function and Blood DNA Methylation: A Multi-Ancestry Epigenome-Wide Association Meta-Analysis.
Rationale: Methylation integrates factors present at birth and modifiable across the lifespan that can influence pulmonary function. Studies are limited in scope and replication. Objectives: To conduct large-scale epigenome-wide meta-analyses of blood DNA methylation and pulmonary function. ⋯ Conclusions: We identified numerous novel loci differentially methylated in relation to pulmonary function; few were detected in large genome-wide association studies. Integrative analyses highlight functional relevance and potential therapeutic targets. This comprehensive discovery of potentially modifiable, novel lung function loci expands knowledge gained from genetic studies, providing insights into lung pathogenesis.
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Am. J. Respir. Crit. Care Med. · Aug 2022
Lung Microbiota and Metabolites Collectively Associate with Clinical Outcomes in Milder Stage COPD.
Rationale: Chronic obstructive pulmonary disease (COPD) is variable in its development. Lung microbiota and metabolites collectively may impact COPD pathophysiology, but relationships to clinical outcomes in milder disease are unclear. Objectives: Identify components of the lung microbiome and metabolome collectively associated with clinical markers in milder stage COPD. ⋯ In contrast, several Prevotella members, together with adenosine, 5'-methylthioadenosine, sialic acid, tyrosine, and glutathione, associated with better lung function, absence of COPD, or less symptoms. Significant correlations were observed between specific metabolites and bacteria (Padj < 0.05). Conclusions: Components of the lung microbiome and metabolome in combination relate to outcome measures in milder COPD, highlighting their potential collaborative roles in disease pathogenesis.
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Am. J. Respir. Crit. Care Med. · Aug 2022
Multicenter Study Observational StudyPeri-intubation Cardiovascular Collapse in Critically Ill Patients: Insights from the INTUBE Study.
Rationale: Cardiovascular instability/collapse is a common peri-intubation event in patients who are critically ill. Objectives: To identify potentially modifiable variables associated with peri-intubation cardiovascular instability/collapse (i.e., systolic arterial pressure <65 mm Hg [once] or <90 mm Hg for >30 minutes; new/increased vasopressor requirement; fluid bolus >15 ml/kg, or cardiac arrest). Methods: INTUBE (International Observational Study to Understand the Impact and Best Practices of Airway Management In Critically Ill Patients) was a multicenter prospective cohort study of patients who were critically ill and undergoing tracheal intubation in a convenience sample of 197 sites from 29 countries across five continents from October 1, 2018, to July 31, 2019. ⋯ Conclusions: Peri-intubation cardiovascular instability/collapse was associated with an increased risk of both ICU and 28-day mortality. The use of propofol for induction was identified as a modifiable intervention significantly associated with cardiovascular instability/collapse. Clinical trial registered with clinicaltrials.gov (NCT03616054).