151st Regular Meeting of the Medical Society of Toho University Professor Special Lecture Investigating the Mechanisms of Alcohol-induced Asthma

Introduction: The purpose of the present study was to determine the mechanisms of alcohol-induced asthma. Methods: Oral ethanol provocation test was performed in Japanese asthmatics to measure pulmonary function, blood ethanol, acetaldehyde and histamine. Acetaldehyde dehydrogenase 2 (ALDH2) genotype was determined by polymerase chain reaction (PCR) and ethanol patch test. Human bronchi and mast cells were stimulated with acetaldehyde in vitro. Pure ethanol was orally administered to ALDH2-deficient mice to determine the plasma concentrations of ethanol, acetaldehyde, histamine, and enhanced pause (Penh) values. Mite allergen-sensitized mice were inoculated with intranasal acetaldehyde. Results: Approximately half asthmatic subjects developed bronchoconstriction with concomitant increases in blood acetaldehyde and histamine, which was associated with genetically reduced ALDH2 activities. In vitro acetaldehyde stimulation induces bronchoconstriction and degranulation of human mast cells. ALDH2-deficient mice caused bronchoconstriction following oral ethanol provocation. Acetaldehyde also induced granulocytes macrophage colony stimulating factor (GM-CSF) production and nuclear factor (NF)-κB activation in human bronchi and deteriorated mite allergen-sensitized inflammation in a murine model of asthma. Conclusions: Acetaldehyde has potential effects on human airway by two distinct mechanisms. As a metabolite of alcohol, its elevation following alcohol consumption induces airway mast cells to release histamine, which results in exacerbation of asthma in susceptible populations. As an air pollutant contained in products such as cigarette smoke, its inhalation potentially exacerbates airway inflammation.