American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Jun 2020
RSV Infection Promotes Necroptosis and HMGB1 Release by Airway Epithelial Cells.
Rationale: Respiratory syncytial virus (RSV) bronchiolitis causes significant infant mortality. Bronchiolitis is characterized by airway epithelial cell (AEC) death; however, the mode of death remains unknown. Objectives: To determine whether necroptosis contributes to RSV bronchiolitis pathogenesis via HMGB1 (high mobility group box 1) release. ⋯ Necroptosis inhibition in early life ameliorated asthma progression induced by viral or allergen challenge in later life. Conclusions: Pneumovirus infection induces AEC necroptosis. Inhibition of necroptosis may be a viable strategy to limit the severity of viral bronchiolitis and break its nexus with asthma.
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Am. J. Respir. Crit. Care Med. · Jun 2020
Comparative StudyGenetic Admixture and Survival in Diverse Populations with Pulmonary Arterial Hypertension.
Rationale: Limited information is available on racial/ethnic differences in pulmonary arterial hypertension (PAH). Objectives: Determine effects of race/ethnicity and ancestry on mortality and disease outcomes in diverse patients with PAH. Methods: Patients with Group 1 PAH were included from two national registries with genome-wide data and two local cohorts, and further incorporated in a global meta-analysis. ⋯ An inpatient mortality benefit was observed for Native American patients (n = 185; OR, 0.38 [95% CI, 0.15-0.93]; P = 0.034). Conclusions: This study demonstrates a reproducible survival benefit for Hispanic patients with Group 1 PAH in multiple clinical settings. Our results implicate contributions of genetic ancestry to differential survival in PAH.