American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Nov 2024
Comparative StudyEvaluation of Etomidate Use and Association with Mortality Compared with Ketamine Among Critically Ill Patients.
Rationale: Uncertainty remains regarding the risks associated with single-dose use of etomidate. Objectives: To assess the use of etomidate in critically ill patients and compare outcomes for patients who received etomidate versus ketamine. Methods: We assessed patients who received invasive mechanical ventilation (IMV) and were admitted to an ICU in the Premier Healthcare Database between 2008 and 2021. ⋯ We found no attenuation of the association with mortality with receipt of corticosteroids in the days after etomidate use. Conclusions: Use of etomidate on the day of IMV initiation is common and associated with a higher odds of hospital mortality than use of ketamine. This finding is independent of subsequent treatment with corticosteroids.
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Am. J. Respir. Crit. Care Med. · Nov 2024
ReviewObesity-related Asthma: A Pathobiology-based Overview of Existing and Emerging Treatment Approaches.
Although obesity-related asthma is associated with worse asthma outcomes, optimal treatment approaches for this complex phenotype are still largely unavailable. This state-of-the-art review article synthesizes evidence for existing and emerging treatment approaches for obesity-related asthma and highlights pathways that offer potential targets for novel therapeutics. Existing treatments targeting insulin resistance and obesity, including metformin and GLP-1 (glucagon-like-peptide 1) receptor agonists, have been associated with improved asthma outcomes, although GLP-1R agonist data in asthma are limited to individuals with comorbid obesity. ⋯ Potential therapeutic targets include adipose tissue eosinophils and the GLP-1-arginine-advanced glycation end products axis, although data in humans are still needed. Finally, transcriptomic and epigenetic studies of "obese asthma" demonstrate enrichment of IFN-related signaling pathways, Rho-GTPase pathways, and integrins, suggesting that these too could represent future treatment targets. We advocate for further study of these potential therapeutic mechanisms and continued investigation of the distinct inflammatory pathways characteristic of obesity-related asthma, to facilitate effective treatment development for this unique asthma phenotype.
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Am. J. Respir. Crit. Care Med. · Nov 2024
Observational StudyThe Effect of Chronic Altitude Exposure on COPD Outcomes in the SPIROMICS Cohort.
Rationale: Individuals with chronic obstructive pulmonary disease (COPD) have airflow obstruction and maldistribution of ventilation. For those living at high altitude, any gas exchange abnormality is compounded by reduced partial pressures of inspired oxygen. Objectives: Does residence at higher altitude exposure affect COPD outcomes, including lung function, imaging characteristics, symptoms, health status, functional exercise capacity, exacerbations, and mortality? Methods: From the SPIROMICS (Subpopulation and Intermediate Outcome Measures in COPD Study) cohort, we identified individuals with COPD living below 1,000 ft (305 m) elevation (n = 1,367) versus above 4,000 ft (1,219 m) elevation (n = 288). ⋯ Conclusions: Long-term altitude exposure is associated with reduced functional exercise capacity in individuals with COPD, but this did not translate into differences in symptoms or health status. In addition, long-term high-altitude exposure did not affect progression of disease as defined by longitudinal changes in spirometry. Clinical trial registered with www.clinicaltrials.gov (NCT01969344).
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Am. J. Respir. Crit. Care Med. · Nov 2024
The Legacy of Redlining: Increasing Childhood Asthma Disparities Through Neighborhood Poverty.
Rationale: Identifying the root causes of racial disparities in childhood asthma is critical for health equity. Objectives: To determine whether the racist policy of redlining in the 1930s led to present-day disparities in childhood asthma by increasing community-level poverty and decreasing neighborhood socioeconomic position (SEP). Methods: We categorized census tracts at the birth address of participants from the Children's Respiratory and Environmental Workgroup birth cohort consortium into categories A, B, C, and D as defined by the Home Owners Loan Corporation, with D being the highest perceived risk. ⋯ In mediation analyses, residing in Grade-D tracts (adjusted odds ratio = 1.03 [95% confidence interval = 1.01, 1.05]) was significantly associated with childhood asthma, with 79% of this increased risk mediated by percentage of low-income households; results were similar for the Social Vulnerability Index and other tract-level variables. Conclusions: The historical structural racist policy of redlining led to present-day asthma disparities in part through decreased neighborhood SEP. Policies aimed at reversing the effects of structural racism should be considered to create more just, equitable, and healthy communities.