ArticleThe Journal of allergy and clinical immunology2025
Reduced aldehyde dehydrogenase 2 in respiratory tract associates with dysregulated alcohol metabolism and respiratory reactions in aspirin-exacerbated respiratory disease.
Article in The Journal of allergy and clinical immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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Who cites it
3 citing papers in PubMed.
- More than a drink: The behavioral impact of alcohol sensitivity in AERD.The journal of allergy and clinical immunology. In practice · 2026Article
- Integrated Immune, Epithelial and Lipid Pathways in NSAID-Exacerbated Respiratory Disease.Clinical and translational allergy · 2026Review
- The relationship of chemokine levels and the type of symptoms caused by NSAIDs or alcohol in patients with NSAIDs-exacerbated respiratory disease.Frontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
backgroundPatients with aspirin-exacerbated respiratory disease (AERD) frequently experience alcohol-induced respiratory reactions, the immunologic mechanism of which remains unknown. Many East Asian patients experience intense alcohol-induced skin flushing, which is due to an alcohol dehydrogenase 2 (ALDH2) polymorphism that leads to impaired alcohol metabolism and acetaldehyde buildup.
objectiveWe sought to determine whether AERD-related alcohol reactions are attributable to ALDH2 deficiency in the respiratory tract.
methodsAERD patients (N = 600) completed a survey to assess alcohol-induced symptoms and disease severity; urinary leukotriene E
resultsAlcohol-induced upper respiratory, lower respiratory, and skin-flushing symptoms were reported by, respectively, 79.6%, 45.1%, and 38.8% of AERD patients. Patients who experienced alcohol-induced respiratory reactions had faster postoperative polyp regrowth, worse baseline sinus disease and asthma control, and higher urinary eicosanoids than did those without alcohol reaction. Treatment with dupilumab or daily aspirin improved alcohol-induced symptoms for most patients. Nasal polyp ALDH2 protein and nasal EpC ALDH2 transcripts were lower in AERD patients than in aspirin-tolerant controls. In vitro stimulation with IL-4/IL-13 decreased ALDH2 expression in EpC cultures. In vivo inhibition of IL-4Rα with dupilumab increased nasal ALDH2 transcript.
conclusionAcquired ALDH2 enzyme deficiency within the respiratory tract in AERD, likely as a result of high local levels of IL-4 and IL-13, may prevent the degradation of alcohol-derived acetaldehyde, leading to mast cell activation and alcohol-induced respiratory reactions.
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