Publications by authors named "P Sporn"
Background: In a phase 1b/2a clinical trial of efzofitimod in patients with corticosteroid-requiring pulmonary sarcoidosis, treatment resulted in dose-dependent improvement in key end-points. We undertook a analysis pooling dose arms that achieved therapeutic concentrations of efzofitimod (Therapeutic group) those that did not (Subtherapeutic group).
Methods: Peripheral blood mononuclear cells incubated with tuberculin-coated beads were exposed to varying concentrations of efzofitimod in an assay to determine concentrations that inhibited granuloma formation.
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).
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