Exploring the roles of airway dipeptidyl peptidase 1 in obstructive airway disease.

Background: Dipeptidyl peptidase 1 (DPP1) exacerbates airway neutrophilic inflammation in bronchiectasis, which is characterised by airway dysfunction and dilation and chronic bacterial infection. However, little is known about the pathogenetic roles of DPP1 in obstructive airway diseases, including COPD, asthma and asthma-COPD overlap (ACO). Here, we tested the hypothesis that airway DPP1 could enhance neutrophilic inflammation and affect mucus plugging, airway dilation and the airway microbiome in patients with these diseases. Methods: Sputum DPP1, cell differential count and microbiome were cross-sectionally evaluated in patients with COPD, asthma with airflow limitation and ACO. Sputum high mobility group box 1 (HMGB1) was measured to estimate airway epithelial damage. Chest computed tomography was also performed to visually assess mucus plugs and airway dilation with the Reiff score and quantify the total airway count and wall area percentage. Results: 68 patients were classified into high-DPP1/high-neutrophil (n=17), low-DPP1/high-neutrophil (n=37) and low-neutrophil (n=14) groups based on sputum DPP1 levels and neutrophil percentages. The rate of mucus plugging and the relative abundance of the phylum Firmicutes were significantly lower and the level of sputum HMGB1 was significantly greater in the high-DPP1/high-neutrophil group than in the low-DPP1/high-neutrophil group. Moreover, airway dilation without mucus plugging was observed only in the high-DPP1/high-neutrophil group (prevalence 29%). Conclusions: High sputum DPP1 levels may reduce colonisation by the phylum Firmicutes and mucus plugging, but increase airway epithelial damage, which could induce airway dilation without mucus plugging in patients with obstructive airway disease with neutrophilic inflammation.