Structure-function relationship between extracellular matrix in airway smooth muscle and dynamics of lung function in asthma

Rationale: Asthma is characterized by an increased deposition of extracellular matrix (ECM) within the airway smooth muscle (ASM) [Panettieri 2008, Araujo 2008]. We hypothesized that ECM composition within ASM is associated with the dynamics of lung function. Aim: To investigate the fractional areas of collagen I and III within ASM, and their association with spirometry and respiratory resistance R rs and reactance X rs in asthmatics and controls. Methods: Atopic mild asthmatics (n=10, no ICS) and controls (n=17) were included in this cross-sectional study. Spirometry, PC 20 , R rs and X rs (forced oscillation technique during tidal breathing and deep inspiration) were measured. Paraffin sections from endobronchial biopsies were stained for collagen I and III by immunohistochemistry, and fractional areas were obtained by image analysis. Results: There was no difference in fractional areas collagen I and III within ASM between asthmatics and controls (p>0.05). However, ASM collagen III was correlated with the change in R rs after deep inspiration in asthmatics (r=0.74, p=0.015, Fig.1). ASM collagen I and III were not associated with spirometry or PC 20 . Conclusion: These data show that collagen III composition within ASM is correlated with the dynamics of R rs after deep inspiration in asthmatics in vivo . This suggests that ECM within ASM is positively associated with impaired airway mechanics in asthma.