American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Mar 2021
Senescence of Alveolar Type 2 Cells Drives Progressive Pulmonary Fibrosis.
Rationale: Idiopathic pulmonary fibrosis (IPF) is an insidious and fatal interstitial lung disease associated with declining pulmonary function. Accelerated aging, loss of epithelial progenitor cell function and/or numbers, and cellular senescence are implicated in the pathogenies of IPF. Objectives: We sought to investigate the role of alveolar type 2 (AT2) cellular senescence in initiation and/or progression of pulmonary fibrosis and therapeutic potential of targeting senescence-related pathways and senescent cells. ⋯ We establish that senescence rather than loss of AT2 cells promotes progressive fibrosis and show that either genetic or pharmacologic interventions targeting p53 activation or senescence block fibrogenesis. Conclusions: Senescence of AT2 cells is sufficient to drive progressive pulmonary fibrosis. Early attenuation of senescence-related pathways and elimination of senescent cells are promising therapeutic approaches to prevent pulmonary fibrosis.
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Am. J. Respir. Crit. Care Med. · Mar 2021
Comparative StudyEndotypic Mechanisms of Successful Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea.
Rationale: Approximately one-third of patients with obstructive sleep apnea (OSA) treated with hypoglossal nerve stimulation (HGNS) therapy are incomplete responders, despite careful patient selection based on baseline characteristics and drug-induced sleep endoscopy. Objectives: Here we use polysomnographic endotyping to assess the pathophysiological mechanisms underlying favorable versus incomplete responses to HGNS therapy. Methods: Baseline polysomnography data of the STAR (Stimulation Therapy for Apnea Reduction) trial were included. ⋯ Conclusions: Favorable responses to HGNS therapy are associated with the pathophysiological traits causing OSA, particularly a higher arousal threshold. Along with established criteria, individuals with favorable traits could potentially be prioritized for precision HGNS therapy. This analysis was a secondary analysis of the STAR trial registered with clinicaltrials.gov (NCT01161420).