Polyphenolic Activation of Basophils Explains Alcohol Hypersensitivity in AERD

Alcohol hypersensitivity (AH), an exacerbation of respiratory symptoms in response to alcohol consumption, is common in aspirin-exacerbated respiratory disease (AERD) and other forms of chronic rhinosinusitis (CRS). The mechanism of this is unknown. This study investigates the ability of polyphenolic compounds in alcoholic beverages to activate innate immune cells as a means of explaining AH in AERD.

Data were collected from 478 consecutive adults presenting to a tertiary care sinonasal clinic in whom the presence of AH and their CRS phenotype was determined. A subset of these individuals was invited to provide whole blood samples on which the effects of ethanol, red wine extract (RWE), and individual polyphenolic compounds were explored. Granulocyte activation was quantified by flow cytometry as upregulation of CD63 during the Basophil Activation Test (BAT). Additionally, secretion of lipid metabolites was measured by enzyme immunoassays (EIAs).

Twelve patients with CRSwNP were compared to age and sex-matched healthy controls. A dose-dependent stimulation of basophil degranulation was noted with RWE and epigallocatechin (p < 0.05). No activation was noted in healthy controls or subjects to ethanol. Catechin demonstrated a dose-dependent, but only near-significant difference (p = 0.07) in basophil degranulation compared to controls.

Polyphenolic compounds, and not ethanol, can trigger the activation and degranulation of eosinophils and basophils, and this may explain the sensitivity to alcoholic beverages seen in patients with AERD and CRSwNP.

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