Smoking induces activation of the complement system in the small airways in a sex-specific manner

The role of complement activation in the pathogenesis of COPD is emerging. Several complement proteins are synthesized locally in the lungs, providing a basis for local complement activation. We aimed to explore the effects of smoking on the complement system in small airways from samples obtained by the collection of exhaled particles. Exhaled particles were obtained from 38 current smokers (CS), 47 former smokers (FS) and 22 healthy never smokers (NS) with the PExA® method. Samples were analyzed with SOMAscan proteomics platform. General linear model-based statistics was used and the analysis was stratified by sex. Several proteins involved in the complement system were identified in PExA samples. All were less abundant in female CS compared to NS, however, the majority of these changes were not observed in males (Table 1). The abundance of proteins involved in the complement system in FS was similar as in NS. These findings suggest smoking causes dysregulation of the proteins regulating the complement system, resulting in excessive activation of the complement system and depletion of the complement factors, which may represent an important initiating step in the small airway inflammation.