Alcohol Hypersensitivity In Crswnp And Polyphenols

Alcohol sensitivity is reported in up to 74-86.5% of patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) and especially in those with aspirin-exacerbated respiratory disease (AERD). These patients typically report sensitivity to beverages fermented in wood casks, with fruit skins, or with hops, but not to other alcohol-containing drinks. We speculated that alcohol sensitivity in AERD/CRSwNP could result from activation of basophils by polyphenols derived from the aging of fermented beverages. We collected whole blood samples from controls and alcohol sensitive subjects with AERD/CRSwNP. We exposed these cells to red wine extract, various bioactive polyphenols known to be present in red wine, and ethanol, as well as positive activation controls. We evaluated basophil activation via flow cytometry using CD63. Basophils were defined in these whole blood samples as cells within a side scatterlow CCR3high flow cytometry gate. We demonstrated robust basophil activation in alcohol sensitive subjects (increased CD63 expression from 0.72%±0.21 to 25.97%±5.35;n=4; p<0.018) in response to components within red wine extract. No significant changes were observed in control subjects. No activation was observed with ethanol. However, we could not ascribe activation to known immune active polyphenols including either (+)-catechin or resveratrol. Up to 74-86.5% of patients with AERD/CRSwNP report sensitivity to alcoholic beverages, primarily those associated with aging in wooden casks. We demonstrated that components in red wine – but not alcohol itself – can directly activate basophils. We were not able to define the specific bioactive substance(s) in these aged beverages that produce these hypersensitivity reactions.