The Journal of allergy and clinical immunology · 2020
Heterogeneity of lower airway inflammation in patients with NSAID-exacerbated respiratory disease.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Jakiela Bogdan, Soja Jerzy, Sladek Krzysztof, Przybyszowski Marek, Plutecka Hanna, Gielicz Anna, Rebane Ana, Bochenek Grazyna
Аннотация
BACKGROUND: Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) asthma is characterized by chronic rhinosinusitis and intolerance of aspirin and other COX1 inhibitors. Clinical data point to a heterogeneity within the N-ERD phenotype.
OBJECTIVE: Our aim was to investigate immune mediator profiles in the lower airways of patients with N-ERD.
METHODS: Levels of cytokines (determined by using Luminex assay) and eicosanoids (determined by using mass spectrometry) were measured in bronchoalveolar lavage fluid (BALF) from patients with N-ERD (n = 22), patients with NSAID-tolerant asthma (n = 21), and control subjects (n = 11). mRNA expression in BALF cells was quantified by using TaqMan low-density arrays.
RESULTS: Lower airway eosinophilia was more frequent in N-ERD (54.5%) than in NSAID-tolerant asthma (9.5% [P = .009]). The type-2 (T2) immune signature of BALF cells was more pronounced in the eosinophilic subphenotype of N-ERD. Similarly, BALF concentrations of periostin and CCL26 were significantly increased in eosinophilic N-ERD and correlated with T2 signature in BALF cells. Multiparameter analysis of BALF mediators of all patients with asthma revealed the presence of 2 immune endotypes: T2-like (with an elevated level of periostin in BALF) and non-T2/proinflammatory (with higher levels of matrix metalloproteinases and inflammatory cytokines). Patients with N-ERD were classified mostly as having the T2 endotype (68%). Changes in eicosanoid profile (eg, increased leukotriene E4 level) were limited to patients with N-ERD with airway eosinophilia. Blood eosinophilia appeared to be a useful predictor of airway T2 signature (area under the curve [AUC] = 0.83); however, surrogate biomarkers had moderate performance in distinguishing eosinophilic N-ERD (for blood eosinophils, AUC = 0.72; for periostin, AUC = 0.75).
CONCLUSIONS: Lower airway immune profiles show considerable heterogeneity of N-ERD, with skewing toward T2 response and eosinophilic inflammation. Increased production of leukotriene E4 was restricted to a subgroup of patients with eosinophilia in the lower airway.
OBJECTIVE: Our aim was to investigate immune mediator profiles in the lower airways of patients with N-ERD.
METHODS: Levels of cytokines (determined by using Luminex assay) and eicosanoids (determined by using mass spectrometry) were measured in bronchoalveolar lavage fluid (BALF) from patients with N-ERD (n = 22), patients with NSAID-tolerant asthma (n = 21), and control subjects (n = 11). mRNA expression in BALF cells was quantified by using TaqMan low-density arrays.
RESULTS: Lower airway eosinophilia was more frequent in N-ERD (54.5%) than in NSAID-tolerant asthma (9.5% [P = .009]). The type-2 (T2) immune signature of BALF cells was more pronounced in the eosinophilic subphenotype of N-ERD. Similarly, BALF concentrations of periostin and CCL26 were significantly increased in eosinophilic N-ERD and correlated with T2 signature in BALF cells. Multiparameter analysis of BALF mediators of all patients with asthma revealed the presence of 2 immune endotypes: T2-like (with an elevated level of periostin in BALF) and non-T2/proinflammatory (with higher levels of matrix metalloproteinases and inflammatory cytokines). Patients with N-ERD were classified mostly as having the T2 endotype (68%). Changes in eicosanoid profile (eg, increased leukotriene E4 level) were limited to patients with N-ERD with airway eosinophilia. Blood eosinophilia appeared to be a useful predictor of airway T2 signature (area under the curve [AUC] = 0.83); however, surrogate biomarkers had moderate performance in distinguishing eosinophilic N-ERD (for blood eosinophils, AUC = 0.72; for periostin, AUC = 0.75).
CONCLUSIONS: Lower airway immune profiles show considerable heterogeneity of N-ERD, with skewing toward T2 response and eosinophilic inflammation. Increased production of leukotriene E4 was restricted to a subgroup of patients with eosinophilia in the lower airway.