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


CONCLUSIONS
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.
Department of Statistics, Clinical Trial Center, Ajou University Medical Center, Suwon, Korea.
H Y
HY
Lee
Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
Y M
YM
Ye
Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
S H
SH
Kim
Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
G Y
GY
Ban
Department of Statistics, Clinical Trial Center, Ajou University Medical Center, Suwon, Korea.
S C
SC
Kim
Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
J H
JH
Kim
Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
Y S
YS
Shin
Department of Statistics, Clinical Trial Center, Ajou University Medical Center, Suwon, Korea.|Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
H S
HS
Park
D000328:Adult; D017668:Age of Onset; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D001249:Asthma / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology / Q000378:metabolism; D015415:Biomarkers; D016000:Cluster Analysis; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007958:Leukocyte Count; D017999:Leukotriene E4 / Q000097:blood / Q000652:urine; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D010641:Phenotype; D012129:Respiratory Function Tests; D012140:Respiratory Tract Diseases / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D018836:Inflammation Mediators; D017999:Leukotriene E4
cluster; nonsteroidal anti-inflammatory drugs exacerbated respiratory disease; stratified medicine