American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Sep 2019
Comparative StudyAlveolar Macrophage Transcriptional Programs Are Associated with Outcomes in Acute Respiratory Distress Syndrome.
Rationale: Serial measurements of alveolar macrophage (AM) transcriptional changes in patients with acute respiratory distress syndrome (ARDS) could identify cell-specific biological programs that are associated with clinical outcomes. Objectives: To determine whether AM transcriptional programs are associated with prolonged mechanical ventilation and 28-day mortality in individuals with ARDS. Methods: We performed genome-wide transcriptional profiling of AMs purified from BAL fluid collected from 35 subjects with ARDS. ⋯ Dead/intubatedDay28 subjects exhibited an opposite pattern, characterized by progressive upregulation of proinflammatory programs over the course of ARDS. The relationship between AM expression profiles and 28-day clinical status was distinct in subjects with direct (pulmonary) versus indirect (extrapulmonary) ARDS. Conclusions: Clinical outcomes in ARDS are associated with highly distinct AM transcriptional programs.
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Am. J. Respir. Crit. Care Med. · Sep 2019
A Genetic Risk Score Associated with COPD Susceptibility and Lung Structure on Computed Tomography.
Rationale: Chronic obstructive pulmonary disease (COPD) has been associated with numerous genetic variants, yet the extent to which its genetic risk is mediated by variation in lung structure remains unknown. Objectives: To characterize associations between a genetic risk score (GRS) associated with COPD susceptibility and lung structure on computed tomography (CT). Methods: We analyzed data from MESA Lung (Multi-Ethnic Study of Atherosclerosis Lung Study), a U. ⋯ Lung structure (P < 0.0001), but not the GRS (P > 0.10), improved discrimination of moderate-to-severe COPD cases relative to clinical factors alone. Conclusions: A GRS associated with COPD susceptibility was associated with CT lung structure. Lung structure may be an important mediator of heritability and determinant of personalized COPD risk.
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Am. J. Respir. Crit. Care Med. · Sep 2019
Unique Effect of Aspirin Therapy on Biomarkers in Aspirin-exacerbated Respiratory Disease. A Prospective Trial.
Rationale: Daily high-dose aspirin therapy benefits many patients with aspirin-exacerbated respiratory disease but provides no benefit for aspirin-tolerant patients with asthma. Type 2 inflammation characterizes aspirin-exacerbated respiratory disease. Objectives: To determine whether high-dose aspirin therapy changes biomarkers of type 2 inflammation in aspirin-exacerbated respiratory disease. ⋯ Aspirin had no effect on platelet-leukocyte aggregates, platelet activation markers, or plasma cytokines in either group. Conclusions: High-dose aspirin therapy for 8 weeks paradoxically increases markers of type 2 inflammation in subjects with aspirin-exacerbated respiratory disease, despite reducing nasal symptoms. This effect of aspirin is unique to aspirin-exacerbated respiratory disease and not observed in subjects with aspirin-tolerant asthma.
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Am. J. Respir. Crit. Care Med. · Sep 2019
The Diagnosis of Bronchopulmonary Dysplasia in Very Preterm Infants: An Evidence-Based Approach.
Rationale: Current diagnostic criteria for bronchopulmonary dysplasia rely heavily on the level and duration of oxygen therapy, do not reflect contemporary neonatal care, and do not adequately predict childhood morbidity. Objectives: To determine which of 18 prespecified, revised definitions of bronchopulmonary dysplasia that variably define disease severity according to the level of respiratory support and supplemental oxygen administered at 36 weeks' postmenstrual age best predicts death or serious respiratory morbidity through 18-26 months' corrected age. Methods: We assessed infants born at less than 32 weeks of gestation between 2011 and 2015 at 18 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. ⋯ Rates of this outcome increased stepwise from 10% among infants without bronchopulmonary dysplasia to 77% among those with grade 3 disease. A similar gradient (33-79%) was observed for death or neurodevelopmental impairment. Conclusions: The definition of bronchopulmonary dysplasia that best predicted early childhood morbidity categorized disease severity according to the mode of respiratory support administered at 36 weeks' postmenstrual age, regardless of supplemental oxygen use.
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Am. J. Respir. Crit. Care Med. · Sep 2019
Synergistic Association of House Endotoxin Exposure and Ambient Air Pollution with Asthma Outcomes.
Rationale: House endotoxin and ambient air pollution are risk factors for asthma; however, the effects of their coexposure on asthma are not well characterized. Objectives: To examine potential synergistic associations of coexposure to house dust endotoxin and ambient air pollutants with asthma outcomes. Methods: We analyzed data of 6,488 participants in the National Health and Nutrition Examination Survey 2005-2006. ⋯ A synergistic association was also found for coexposure to higher concentrations of endotoxin and NO2 in children (OR, 3.45; 95% CI, 1.65-7.18). Conclusions: Coexposure to elevated concentrations of residential endotoxin and ambient PM2.5 in all participants and NO2 in children is synergistically associated with increased emergency room visits for asthma. Therefore, decreasing exposure to both endotoxin and air pollution may help reduce asthma morbidity.