Subphenotypes of nonsteroidal antiinflammatory disease‐exacerbated respiratory disease identified by latent class analysis

Abstract

Background: 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 pro-inflammatory eicosanoids. A more insightful analysis of NERD patients has shown this phenotype to be nonhomogeneous. Objective:We aimed to identify possible subphenotypes in a cohort of NERD patients with the means of latent class analysis (LCA).Methods: A total of 95 asthma patients with aspirin hypersensitivity underwent sputum induction. High-performance liquid chromatography or gas chromatography coupled with mass spectrometry was used to profile eicosanoids in induced sputum supernatant (ISS). Sixteen variables covering clinical characteristics, IS inflammatory cells, and eicosanoids were considered in the LCA.Results: 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 logLTE 4 /logPGE 2 ratio. Class 2 represented severe asthma with impaired lung function despite high doses of steroids. High sputum eosinophilia was in line with higher pro-inflammatory LTE 4 in ISS and the highest logLTE 4 /logPGE 2 ratio. Class 3 subjects had mild-to-moderate asthma and were also characterized by eosinophilic airway inflammation, yet increased production of pro-(LTE 4 , PGD 2 and 11-dehydro-TBX 2 ) was balanced by

Advances and recent developments in asthma in 2020

“…Although no absolute/consistent cutoff values have been established, subanalyses show an overall better response in patients with more inflammation, defined by higher blood eosinophil levels 115 . Recently, Celejewska‐Wójcik et al demonstrated that three distinct NERD subphenotypes reflect differences in inflammatory response measured by airway eosinophils and the ratio of logLTE 4 /logPGE 2 in induced sputum 116 . Mastalerz et al 117 studied airways PGE2 in induced sputum and reported that NERD subjects had higher levels of PGE2 before aspirin challenge compared to controls.…”

Adult‐onset eosinophilic airway diseases

“…Cysteinyl leukotriene (cysLT) and prostaglandin (PG) D 2 overproduction, especially in NPs, is associated with the pathological condition 73 . Chronic reduction of PGE 2 synthesis due to cyclooxygenase (COX)‐2 and EP2 receptor dysfunction leads to the overproduction of cysLT, 74,75 reduction of anti‐inflammatory mediators such as lipoxin 76 and activation of mast cells and ILC2s 74,77,78 . Pre‐inhalation of PGE 2 79 or cigarette smoking 80 suppresses N‐ERD, supporting that COX‐2 hypofunction and PGE 2 loss are essential pathogenesis of N‐ERD.…”

Platelet-Adherent Leukocytes Associated With Cutaneous Cross-Reactive Hypersensitivity to Nonsteroidal Anti-Inflammatory Drugs

“…Blended reactions represent a heterogeneous group of entities which include cutaneous (urticaria/angioedema) and respiratory symptoms (rhinitis/asthma with or without nasal polyposis); cutaneous symptoms and glottis edema; cutaneous and respiratory symptoms accompanied with glottis edema; and a combination of cutaneous, respiratory and gastrointestinal symptoms (abdominal pain, diarrhea, nausea, vomiting) ( Dona et al, 2018 ). Moreover, we cannot rule out that other phenotypes could be further included in this category ( Dona et al, 2020 ), as described for asthma ( Mastalerz et al, 2015 ) and NERD ( Celejewska-Wojcik et al, 2020 ).…”