American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Sep 2022
Observational StudyReversible Airflow Obstruction Predicts Future COPD Development in the SPIROMICS Cohort.
Rationale: Chronic obstructive pulmonary disease (COPD) is defined by fixed spirometric ratio, FEV1/FVC < 0.70 after inhaled bronchodilators. However, the implications of variable obstruction (VO), in which the prebronchodilator FEV1/FVC ratio is less than 0.70 but increases to 0.70 or more after inhaled bronchodilators, have not been determined. Objectives: We explored differences in physiology, exacerbations, and health status in participants with VO compared with reference participants without obstruction. ⋯ Conclusions: Significant risk for future COPD development exists for those with pre- but not post-BD airflow obstruction. These findings support consideration of expanding spirometric criteria defining COPD to include pre-BD obstruction. Clinical trial registered with www.clinicaltrials.gov (NCT01969344).
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Am. J. Respir. Crit. Care Med. · Sep 2022
COVID-19 in Patients with Pulmonary Hypertension: A National Prospective Cohort Study.
Rationale: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with pulmonary endothelial dysfunction. There are limited data available on the outcomes of coronavirus disease (COVID-19) in patients with pulmonary hypertension (PH), a disease characterized by pulmonary endothelial dysfunction. Objectives: To describe characteristics and outcomes of patients with precapillary PH and COVID-19. ⋯ Use of pulmonary arterial hypertension therapy was similar between survivors and nonsurvivors. Conclusions: COVID-19 in patients with precapillary PH was associated with a high in-hospital mortality. The typical risk factors for severe COVID-19 and severity of PH were associated with mortality in this population.
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Am. J. Respir. Crit. Care Med. · Sep 2022
Tacrolimus Prevents Mechanical and Humoral Alterations in Brain Death-Induced Lung Injury in Pigs.
Rationale: Donor brain death-induced lung injury may compromise graft function after transplantation. Establishing strategies to attenuate lung damage remains a challenge because the underlying mechanisms remain uncertain. Objectives: The effects of tacrolimus pretreatment were evaluated in an experimental model of brain death-induced lung injury. ⋯ Tacrolimus pretreatment prevented increases in the ratio of IL-6 to IL-10, VCAM1 (vascular cell adhesion molecule 1), circulating concentrations of IL-1β, and glycocalyx-derived molecules. Tacrolimus partially decreased apoptosis (Bax [Bcl2-associated X apoptosis regulator]-to-Bcl2 [B-cell lymphoma-2] ratio [P = 0.07] and number of apoptotic cells in the lungs [P < 0.05]) but failed to improve LIS. Conclusions: Immunomodulation through tacrolimus pretreatment prevented pulmonary capillary hypertension as well as the activation of inflammatory and apoptotic processes in the lungs after brain death; however, LIS did not improve.
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Am. J. Respir. Crit. Care Med. · Sep 2022
Thromboxane-Prostanoid Receptor Signaling Drives Persistent Fibroblast Activation in Pulmonary Fibrosis.
Rationale: Although persistent fibroblast activation is a hallmark of idiopathic pulmonary fibrosis (IPF), mechanisms regulating persistent fibroblast activation in the lungs have not been fully elucidated. Objectives: On the basis of our observation that lung fibroblasts express TBXA2R (thromboxane-prostanoid receptor) during fibrosis, we investigated the role of TBXA2R signaling in fibrotic remodeling. Methods: We identified TBXA2R expression in lungs of patients with IPF and mice and studied primary mouse and human lung fibroblasts to determine the impact of TBXA2R signaling on fibroblast activation. ⋯ In vivo treatment with the TBXA2R antagonist ifetroban reduced profibrotic signaling in the lungs, protected mice from lung fibrosis in three preclinical models (bleomycin, Hermansky-Pudlak mice, and radiation-induced fibrosis), and markedly enhanced fibrotic resolution after bleomycin treatment. Conclusions: TBXA2R links oxidative stress to fibroblast activation during lung fibrosis. TBXA2R antagonists could have utility in treating pulmonary fibrosis.