Association of Airway Inflammation and Smoking Status with IL-33 expression in Sputum of Patients with Asthma or COPD

<bold>Rationale:</bold> IL-33 expression might be affected by smoking status and the nature of airway inflammation. We investigate the association of smoking status and airway inflammatory phenotypes with IL-33 expression in patients with asthma or COPD <bold>Methods:</bold> This analysis includes patients with COPD of all severity stages, severe asthma patients and healthy controls. Cutoffs of ≥2% eosinophils and ≥50% neutrophils were used to define airway eosinophilia and neutrophilia, respectively. IL-33-concentration was quantified in sputum supernatants by digital Single-Molecule-Assay (SIMOA®, Quanterix) <bold>Results:</bold> IL-33 was higher in patients with COPD (median [IQR]: 38.7 [16-80] pg/mL) or severe asthma (32 [18-77] pg/mL) than in controls (14.1[8-37] pg/mL), (p values < 0.05). In COPD, IL-33 was higher in former smokers (64 [32-108] pg/mL) than in active smokers (23 [11-53] pg/mL), p= 0.002. A post-hoc analysis indicated that only former smokers with pre or mild-moderate COPD (GOLD I-II) had higher IL-33 than controls. However, both former and active smokers with severe COPD had higher IL-33 than control or former smokers with pre or mild-moderate COPD, all p <0.05. In patients with severe asthma, IL-33 levels did not differ between former and never-smokers, p=0.56, and were also similar between those with high and low T2-markers. Patients with a mixed granulocytic, rather than only eosinophilic asthma, had higher IL-33 than control (32 [24-150] pg/mL), (p=0.014). <bold>Conclusion:</bold> Targeting IL-33 might be auspicious in former smokers with COPD. However, in severe COPD the impact of smoking might be outplayed by COPD severity. In asthma, it might be a treatment option irrespective of T2-status