Publications by authors named "P H S Sporn"
Hypercapnia, elevation of the partial pressure of CO2 in blood and tissues, is a risk factor for mortality in patients with severe acute and chronic lung diseases. We previously showed that hypercapnia inhibits multiple macrophage and neutrophil antimicrobial functions and that elevated CO2 increases the mortality of bacterial and viral pneumonia in mice. Here, we show that normoxic hypercapnia downregulates innate immune and antiviral gene programs in alveolar macrophages (AMØs).
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- Patients with chronic lung disease, obesity, and other co-existing health issues are at higher risk for severe COVID-19 illness, with hypercapnia (elevated CO levels) linked to increased viral replication and mortality.
- The study found that hypercapnia boosts ACE2 expression and enhances the entry of SARS-CoV-2 pseudovirus into airway epithelial cells, particularly involving increased cholesterol levels in those cells.
- Factors like cigarette smoke also raise ACE2 and SARS-CoV-2 entry, suggesting that hypercapnia and smoking jointly worsen COVID-19 outcomes, while cholesterol synthesis inhibitors may counter these effects.
Hypercapnia, elevation of the partial pressure of CO in blood and tissues, is a risk factor for mortality in patients with severe acute and chronic lung diseases. We previously showed that hypercapnia inhibits multiple macrophage and neutrophil antimicrobial functions, and that elevated CO increases the mortality of bacterial and viral pneumonia in mice. Here, we show that normoxic hypercapnia downregulates innate immune and antiviral gene programs in alveolar macrophages (AMØs).
View Article and Find Full Text PDFBackground: Pulmonary sarcoidosis is characterized by the accumulation of immune cells that form granulomas affecting the lungs. Efzofitimod (ATYR1923), a novel immunomodulator, selectively binds neuropilin 2, which is upregulated on immune cells in response to lung inflammation.
Research Question: What is the tolerability, safety, and effect on outcomes of efzofitimod in pulmonary sarcoidosis?
Study Design And Methods: In this randomized, double-blind, placebo-controlled study evaluating multiple ascending doses of efzofitimod administered intravenously every 4 weeks for 24 weeks, randomized patients (2:1) underwent a steroid taper to 5 mg/d by week 8 or < 5 mg/d after week 16.