American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Feb 2023
Randomized Controlled TrialA Randomized Trial of Mesenchymal Stromal Cells for Moderate to Severe ARDS From COVID-19.
Rationale: There are limited therapeutic options for patients with coronavirus disease (COVID-19)-related acute respiratory distress syndrome with inflammation-mediated lung injury. Mesenchymal stromal cells offer promise as immunomodulatory agents. Objectives: Evaluation of efficacy and safety of allogeneic mesenchymal cells in mechanically-ventilated patients with moderate or severe COVID-19-induced respiratory failure. ⋯ Resolution or improvement of acute respiratory distress syndrome at 30 days was observed in 51/104 (49.0%) cell recipients and 46/106 (43.4%) control patients (odds ratio, 1.36; 95% confidence interval, 0.57-3.21). There were no infusion-related toxicities and overall serious adverse events over 30 days were similar. Conclusions: Mesenchymal cells, while safe, did not improve 30-day survival or 60-day ventilator-free days in patients with moderate and/or severe COVID-19-related acute respiratory distress syndrome.
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Am. J. Respir. Crit. Care Med. · Feb 2023
Moving toward Equitable Care for Sleep Apnea in the United States: Positive Airway Pressure Adherence Thresholds: An Official American Thoracic Society Policy Statement.
Background: Positive airway pressure (PAP) is a highly effective treatment for obstructive sleep apnea (OSA), but adherence limits its efficacy. In addition, coverage of PAP by CMS (Centers for Medicare & Medicaid Services) and other insurers in the United States depends on adherence. This leaves many beneficiaries without PAP, disproportionally impacting non-white and low socioeconomic position patients with OSA and exacerbating sleep health disparities. ⋯ Results: In this position paper, we advocate for policy change to CMS PAP coverage requirements to reduce inequities and align with patient-centered goals. We specifically call for eradicating repeat polysomnography, eliminating the 4-hour rule, and focusing on patient-oriented outcomes such as improved sleepiness and sleep quality. Conclusions: Modifications to the current policies for PAP insurance coverage could improve health disparities.
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Am. J. Respir. Crit. Care Med. · Feb 2023
The Lung Allocation Score Remains Inequitable for Patients with PAH, Even After the 2015 Revision.
Rationale: The lung allocation score (LAS) was revised in 2015 to improve waiting list mortality and rate of transplant for patients with pulmonary arterial hypertension (PAH). Objectives: We sought to determine if the 2015 revision achieved its intended goals. Methods: Using the Standard Transplant Analysis and Research file, we assessed the impact of the 2015 LAS revision by comparing the pre- and postrevision eras. ⋯ After the 2015 revision, registrants with PAH still had the highest risk of death, now similar to those with interstitial lung disease, and the lowest rate of transplant, now similar to those with chronic obstructive pulmonary disease. Conclusions: Although the 2015 LAS revision improved access to transplant and reduced the risk of waitlist death for patients with PAH, it did not go far enough. Significant differences in waitlist mortality and likelihood of transplant persist.
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Am. J. Respir. Crit. Care Med. · Feb 2023
Notch1 Induces Defective Epithelial Surfactant Processing and Pulmonary Fibrosis.
Rationale: Although type II alveolar epithelial cells (AEC2s) are chronically injured in idiopathic pulmonary fibrosis (IPF), they contribute to epithelial regeneration in IPF. Objectives: We hypothesized that Notch signaling may contribute to AEC2 proliferation, dedifferentiation characterized by loss of surfactant processing machinery, and lung fibrosis in IPF. Methods: We applied microarray analysis, kinome profiling, flow cytometry, immunofluorescence analysis, western blotting, quantitative PCR, and proliferation and surface activity analysis to study epithelial differentiation, proliferation, and matrix deposition in vitro (AEC2 lines, primary murine/human AEC2s), ex vivo (human IPF-derived precision-cut lung slices), and in vivo (bleomycin and pepstatin application, Notch1 [Notch receptor 1] intracellular domain overexpression). ⋯ Conversely, inhibition of Notch signaling in IPF-derived precision-cut lung slices improved the surfactant processing capacity of AEC2s and reversed fibrosis. Conclusions: Notch1 is a central regulator of AEC2 fate in IPF. It induces alveolar epithelial proliferation and loss of Napsin A and of surfactant proprotein processing, and it contributes to fibroproliferation.