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Identification of phenotypic clusters of nonsteroidal anti-inflammatory drugs exacerbated respiratory disease

Lee, HY; Ye, YM; Kim, SH; Ban, GY; Kim, SC; Kim, JH; Shin, YS; Park, HS
Allergy, 72(4):616-626, 2017
Journal Title
BACKGROUND: Clinical presentation of nonsteroidal anti-inflammatory drugs exacerbated respiratory disease (NERD) is found to be heterogeneous. This study classified phenotypic clusters to determine NERD subtypes.
METHODS: We performed two-step cluster analysis using urticaria, chronic rhinosinusitis (CRS), and atopy, in a NERD cohort comprising 302 patients. Asthma exacerbation was defined as receiving at least one burst of intravenous steroid treatment and/or at least two bursts of oral steroid use (>/= 45 mg/3 days) per year. The possession rate of anti-asthmatic medications was estimated during the follow-up period.
RESULTS: There were four subtypes: subtype 1 (NERD with CRS/atopy and no urticaria), subtype 2 (NERD with CRS and no urticaria/atopy), subtype 3 (NERD without CRS/urticaria), and subtype 4 (NERD with urticaria). Significant differences were found between the four subtypes in the female proportion, baseline FEV1%, serum total IgE level, and sputum/peripheral eosinophil count. A higher frequency of asthma exacerbations was noted in subtype 1 compared to subtype 3. The possession rates of medium- to high-dose inhaled corticosteroids/long-acting beta2 -agonists showed significant differences among the four subtypes. Metabolomic analysis showed that the four subtypes of NERD had a higher serum leukotriene E4 (LTE4) level than those with aspirin-tolerant asthma. The patients with subtypes 1 and 3 had a higher urine LTE4 level than those with subtype 2.
CONCLUSION: We found four distinct subtypes with different clinical/biochemical findings and asthma exacerbations in a NERD cohort. These findings suggest that stratified strategies by applying subtype classification may help achieve better outcomes in the management of NERD.
MeSH terms
AdultAge of OnsetAnti-Inflammatory Agents, Non-Steroidal/adverse effects*Anti-Inflammatory Agents, Non-Steroidal/therapeutic useAsthma/diagnosisAsthma/epidemiologyAsthma/etiologyAsthma/metabolismBiomarkersCluster AnalysisDisease ProgressionFemaleFollow-Up StudiesHumansInflammation Mediators/metabolismLeukocyte CountLeukotriene E4/bloodLeukotriene E4/urineMaleMetabolomeMetabolomics/methodsMiddle AgedPhenotype*Respiratory Function TestsRespiratory Tract Diseases/diagnosis*Respiratory Tract Diseases/epidemiologyRespiratory Tract Diseases/etiology*Respiratory Tract Diseases/metabolism
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
Journal Papers > Research Organization > Regional Clinical Trial Center
AJOU Authors
예, 영민김, 승현반, 가영신, 유섭박, 해심
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