Activation of the cascade-system in small airways- a pilot study in asthma with small airway involvement

Abstract

The interactions between innate and acquired immune system seem important in the patho-physiology of asthma, but has so far only been explored to a limited extent. The cascade system (complement-, coagulation- and kallekrein systems) constitute an important part of the innate host-defense system. We hypothesize that proteins belonging to cascade system in the lining fluid from small airways, are activated in asthma.

Methods: 10 subjects with asthma and small airway dysfunction (SAD), as indicated by lung-clearance index LCI z-score >3, 10 subjects with asthma with normal LCI , and 10 healthy controls were examined with PExA® method which is based on the sampling of droplets in exhaled air, endogenously formed when small airways close and re-open. 240 ng of undiluted lining fluid were sampled and analyzed using the Somascan platform (SomaLogic Inc). Results are based on GLM statistics using Qlucore Omics Explorer software, the signal from each protein is centered around zero.

Results: 38 proteins belonging to the cascade system were identified in the PEx samples. The relative abundance of five of those proteins differed between healthy and those with SAD, see examples in Figure 1.

Fig 1. Box scatter plots; levels of a) Complement 1q receptor, b) Complement 4, c) Factor IX and d) Factor X.

Conclusion: The cascade system in the lining fluid from small airways seem of high importance in asthma with small airway involvement.