Clinical implication of the serum periostin level for differentiating phenotypes of NSAID hypersensitivity

Nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity is a common drug allergy, inwhich 2major phenotypes, respiratory (aspirin-exacerbated respiratory disease [AERD]) and cutaneous (aspirin-exacerbated cutaneous disease [AECD] or aspirinintolerant acute urticaria [AIAU]) types, are noted.1 Typical symptoms of the respiratory type of NSAID hypersensitivity are dyspnea, cough, and rhinorrhea, while those of the cutaneous type are urticaria and angioedema. However, it is sometimes confused to establish in patients with chest tightness or dyspnea after ingestion of NSAIDs because the symptoms may originated from bronchoconstriction of AERD or from angioedema of AIAU.2 Periostin is an extracellular matrix protein and structurally homologous with fasciclin I, an insect adhesion molecule. The serum periostin level correlates well with eosinophilic airway inflammation and considered a prognostic factor for the treatment of lebrikizumab (amonoclonal antibody to IL-13).3 Recent studies have shown that periostin contributes to tissue remodeling and is increased in the serum or the lesional tissue of allergic rhinitis/chronic rhinosinusitis, atopic dermatitis, and asthma.4e7 In addition, the serum periostin level is significantly higher in AERD patients than in aspirin-tolerant asthmatic patients because AERD shares Th2-mediated pathogenesis with eosinophilic asthma.8 We hypothesized that the serum periostin level would differ between respiratory and cutaneous types of NSAID hypersensitivity because remodeling occurs in the respiratory type of hypersensitivity, but not in the cutaneous type. In the present study, we compared serum periostin levels between respiratory and cutaneous types of NSAID hypersensitivity to evaluate the serum periostin level as a biomarker for differentiating between phenotypes of NSAID hypersensitivity. A total of 326 adult patients with NSAID hypersensitivity and 87 healthy normal control (NC) subjects were included in the study. Serum samples were obtained with written informed consent. The samples were frozen at 70 C after collection and thawed immediately before use. Clinical data were obtained from the registry database and electronic medical records reviewed by the allergy specialists. The protocols used in this study were approved by the Institute Review Board of Ajou University Hospital. According to clinical data, NSAID hypersensitivity was classified into AERD, AECD, and AIAU by the clinicians at the Department of Allergy and Clinical Immunology. AERD was defined by the presence of recurrent typical clinical history (development of respiratory