Occupational asthma and work-exacerbated asthma: do they differ in terms of endotype at diagnosis?

Abstract

Work-related asthma (WRA) comprises occupational asthma (OA) and work-exacerbated asthma (WEA). It is unknown whether the inflammatory pathways activated in WRA are mostly of type 2 (T2) or non-type 2 (non-T2). The aim of the study was to determine whether OA and WEA differ at diagnosis in terms of inflammatory endotype based on T2 or non-T2 circulating biomarkers. We collected clinical data of 40 asthmatics with a diagnosis of OA (n=25) or WEA (n=15) due to various agents (80% isocyanates) confirmed by a positive or negative Specific Inhalation Challenge (SIC) between 2008 and 2018. All the patients had been free from corticosteroid treatment for the last 2 weeks. Blood samples were collected before SIC and sera were stored at -80°C until used. Serum periostin, IL-2, IL-3, IL-5, IL-8, IL-9, IL12p70, IL-17, IL-33, TNFα, IFNγ levels were assessed by ELISA (periostin) and Luminex xMAP Technologies. At diagnosis OA and WEA patients did not differ in terms of age, gender, atopy, eosinophil and neutrophil count in blood, latency and months of symptomatic exposure. OA patients exhibited higher bronchial hyperreactivity (PD20FEV1: median 431 vs 865 mcg), higher levels of fractional exhaled NO (50 vs 29 ppb) and of total IgE (95.9 vs 45.5 kUa/L) than WEA patients. All cytokines were detected in sera. OA patients exhibited higher levels of periostin (31.87 vs 21.98 pg/ml) and IL-33 (4.4 vs 0.7 pg/ml), than WEA subjects. No differences between OA and WEA subjects were found in the expression profiles of the other cytokines. At diagnosis OA is characterized by a more pronounced T2 endotype than WEA. Higher serum IgE, periostin and IL-33 levels might represent potential serologic markers of OA.