AbstractBackgroundLettuce‐associated respiratory allergy has never been reported before. The aim of this study was to clarify the clinical condition of lettuce‐associated respiratory allergy and to identify the lettuce antigen which induces allergic symptoms.MethodsWe distributed questionnaires to 1168 lettuce farmers and performed medical examinations in those who exhibited respiratory symptoms related to occupational exposure to lettuce. We analysed specific IgE‐binding proteins in the sera of patients through immunoblotting analysis and determined molecular characterization of the IgE‐binding bands using liquid chromatography‐mass spectrometry.ResultsA total of 932 farmers (80%) responded to the questionnaire. Of those, 7% exhibited lettuce‐associated respiratory symptoms, during harvesting and packaging. Thirteen patients were diagnosed with allergy to lettuce and agreed to undergo further examinations. The percentage of activated basophils in these patients was significantly higher compared with that reported in negative controls (P < .05). Lettuce‐specific IgE (ImmunoCAP®) and skin prick testing was positive in 46% and 62% of patients, respectively. Notably, occupational lettuce‐allergic asthma was detected in one patient through specific bronchial provocation testing. The IgE‐binding bands recognized in the sera of >50% of patients were identified as epidermis‐specific secreted glycoprotein EP1‐like (51 kDa).ConclusionThe present analysis identified a novel lettuce allergen. This allergen may have clinically useful applications, such as specific IgE testing and allergen‐specific immunotherapy.