Relationship of airway structural changes and lung function abnormalities with blood and BAL biomarkers in asthma

Airway structural changes are important in asthma pathology and require investigations. In 105 adult asthmatics (53 with fixed obstruction) we determined the airway cross-sectional geometry of two distal and two peripheral bronchi and quantified the low-attenuation lung area (LAA%). We also performed bronchoscopy with BAL and endobronchial biopsy with histological examination. We assessed blood and BAL biomarkers, including IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-17A, IL-23, INFγ and periostin, together with circulating ADAM33, and investigated interplays between analyzed variables with cluster analyses. Results: Patients with fixed airflow limitation had lower lumen area, higher airway area, increased wall area and wall thickness ratios of peripheral airways, accompanied by raised LAA%. They had also increased blood neutrophils and eosinophils, BAL eosinophilia, higher circulating fibrinogen, INFγ, periostin, and ADAM33. Blood neutrophilia, increased serum HDL, TSH, urea, and shorter APTT were determinants of thicker reticular basement membrane (RBM) of bronchial mucosa. BAL eosinophilia was the only positive predictor of collagen I accumulation. We observed a negative correlation between RBM thickness and collagen I deposit. A cluster analysis revealed three well-separated clusters, characterized by different lung function, biomarkers, collagen I deposit and RBM thickness. Conclusions: Unfavourable airway structural changes are related to the Th2 immunity, higher ADAM33, INFγ, and neutrophil count in blood. Thicker RBM might play a protective role against collagen I accumulation and mucosa fibrosis. Funding: National Science Centre, decision No DEC-2013/09/B/NZ5/00758