Abstract
Background: Severe asthma patients are more susceptible to infections with the respiratory syncytial-virus (RSV) than healthy subjects. This implicates defects in immune responses and could explain frequent exacerbations.
Hypothesis: Cytokine production of leukocytes in response to RSV is impaired in severe asthma and is influenced by type2 inflammation.
Methods: Peripheral blood mononuclear cells from 18 healthy never-smokers (NS) and 39 non-smokers with severe asthma (SA) were ex vivo infected with RSV A2 at MOIs 0.1 and 1.0. After 24h and 7d, cytokines were measured in cell culture supernatants by ELISA. Data were normalized to baseline and compared between NS and SA. They were analyzed for correlation with total IgE (n=35 SA) and with the type2 inflammation markers blood eosinophils (n=36 SA), FeNO (n=28 SA) and serum-periostin (n=33 SA).
Results: Baseline IL1β, IL6, TNFα, and CCL2 were reduced, IFNα and CCL5 were increased in SA vs. NS. RSV-induced IL1β, IL6, CCL2, and CCL5 after 24h and 7d, TNFα after 24h and IFNα, IFNγ and IL8 after 7d in NS. IL6, IL8, CCL2, and CCL5 responses were increased in SA compared to NS. The CCL2 response was lower in SA with <300 vs. ≥300 eosinophils/µl blood. The IL1β response was lower in SA with <76 vs. ≥76 IgE IU/ml serum. IFNα, IL6, IL8, CCL5, and IFNγ was higher in SA with ≤25 vs. >25 ppb FeNO. IFNα correlated negatively to eosinophils; IFNα, IFNγ, CCL5, IL6, and IL8 negatively to FeNO; IFNα, IL1β, and CCL2 negatively to periostin.
Conclusion: The impaired activation of circulating leukocytes in response to acute RSV infections may explain the increased susceptibility to RSV in asthma and could be influenced by the severity of type2 inflammation.
Footnotes
Cite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA835.
This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2021