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Allergy. 2019 Dec 5. doi: 10.1111/all.14141. [Epub ahead of print]

Subphenotypes of NSAID-exacerbated respiratory disease identified by latent class analysis.

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II Department of Internal Medicine, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland.
Department of Applied Mathematics, AGH University of Science and Technology, Cracow, Poland.



Induced sputum (IS) allows to measure mediators of asthmatic inflammation in bronchial secretions. NSAID-exacerbated respiratory disease (NERD) is recognized as a distinct asthma phenotype, usually with a severe course, eosinophilic airway inflammation and increased production of proinflammatory eicosanoids. A more insightful analysis of NERD patients has shown this phenotype to be nonhomogeneous.


We aimed to identify possible subphenotypes in a cohort of NERD patients with the means of latent class analysis (LCA).


95 asthma patients with aspirin hypersensitivity underwent sputum induction. High-performance liquid chromatography or gas chromatography coupled with mass spectrometry were used to profile eicosanoids in induced sputum supernatant (ISS). 16 variables covering clinical characteristics, IS inflammatory cells and eicosanoids were considered in the LCA.


Three classes (subphenotypes) were distinguished within the NERD cohort. Class 1 subjects had mild to moderate asthma, an almost equal distribution of inflammatory cell patterns, the lowest concentrations of eicosanoids and logLTE4 /logPGE2 ratio. Class 2 represented severe asthma with impaired lung function despite high doses of steroids. High sputum eosinophilia was in line with higher proinflammatory LTE4 in ISS and the highest logLTE4 /logPGE2 ratio. Class 3 subjects had mild to moderate asthma and were also characterized by eosinophilic airway inflammation, yet increased production of pro (LTE4 , PGD2 and 11-dehydro-TBX2 ) was balanced by anti-inflammatory PGE2 . The value of logLTE4 /logPGE2 was between values calculated for class 1 and 3, similarly to disease control and severity.


LCA revealed three distinct NERD subphenotypes. Our results support a more complex pathobiology of aspirin hypersensitivity. Considering NERD heterogeneity, the relationship between inflammatory pathways and clinical manifestations of asthma may lead to more individualized treatment in difficult to treat patients in the future.


NSAID - exacerbated respiratory disease; eicosanoids; induced sputum; latent class analysis; phenotype


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