Jian Luo

and 9 more

Background: A significant portion of COVID-19 sufferers have asthma. The impacts of asthma on COVID-19 progression are still unclear but a modifying effect is plausible as respiratory viruses are acknowledged to be an important trigger for asthma exacerbations and a different, potentially type-2 biased, immune response might occur. In this study, we compared the blood circulating cytokine response to COVID-19 infection in patients with and without asthma. Methods: Plasma samples and clinical information were collected from 80 patients with mild (25), severe (36) or critical (19) COVID-19 and 29 healthy subjects at the John Radcliffe Hospital, Oxford, UK. The concentrations of 51 circulating proteins in the plasma samples were measured with Luminex and compared between groups. Results: Total 16 pre-existing asthma patients were found (3 in mild, 10 in severe, and 3 in critical COVID-19). The prevalence of asthma in COVID-19 severity groups did not suggest a clear correlation between asthma and COVID-19 severity. Within the same COVID-19 severity group, no differences were observed between patients with or without asthma on oxygen saturation, CRP, neutrophil counts, and length of hospital stay. The mortality in the COVID-19 patients with asthma (12.5%) was not higher than that in patients without asthma (17.2%). No significant difference was found between asthmatic and non-asthmatic in circulating cytokine response in different COVID-19 severity groups, including the cytokines strongly implicated in COVID-19 such as CXCL10, IL-6, CCL2, and IL-8. Conclusions: Pre-existing asthma was not associated with an enhanced cytokine response after COVID-19 infection, disease severity or mortality.

Ian Pavord

and 13 more

Background: Dupilumab, a human monoclonal antibody, blocks the shared receptor component for interleukins 4/13, key and central drivers of type 2 inflammation. The LIBERTY ASTHMA TRAVERSE (NCT02134028) open-label extension study demonstrated the long-term safety and efficacy of dupilumab in patients ≥12 years who had participated in a previous dupilumab asthma study. The safety profile was consistent with that observed in the parent studies. Methods: This analysis includes patients from phase 2b (NCT01854047) or phase 3 (QUEST; NCT02414854) studies receiving high- or medium-dose inhaled corticosteroids (ICS) at parent study baseline (PSBL) and enrolled in TRAVERSE. We analyzed unadjusted annualized severe exacerbation rates, change from PSBL in pre-bronchodilator (pre-BD) FEV 1 (L), asthma control (5-item asthma control questionnaire), and type 2 biomarkers in patients with type 2 asthma at baseline (blood eosinophils ≥150 cells/µL or fractional exhaled nitric oxide [FeNO] ≥25 ppb), and subgroups defined by baseline blood eosinophils or FeNO. Results: Of patients with type 2 asthma (n=1,666) in this analysis, 891 (53.5%) were receiving high‑dose ICS at PSBL. In this subgroup, unadjusted exacerbation rates for dupilumab vs placebo were 0.517 vs. 1.883 (phase 2b) and 0.571 vs. 1.300 (QUEST) over 52 weeks of the parent study, and remained low throughout TRAVERSE (0.313–0.494). Improvements in pre-BD FEV 1 from PSBL were sustained throughout TRAVERSE. Similar clinical efficacy was observed among patients receiving medium-dose ICS at PSBL and biomarker subgroups. Conclusions: Dupilumab showed sustained efficacy for up to 3 years in patients with uncontrolled, moderate-to-severe type 2 asthma on high- or medium-dose ICS.