The volume fraction of extracellular matrix within the airway smooth muscle layer is related to fixed airflow obstruction in asthma

Abstract

<b>Introduction:</b> We have previously observed an inverse relationship between FEV₁ and the volume fraction of extracellular matrix (V_VECM) within the layer of airway smooth muscle (ASM) in smokers with airflow obstruction. Many patients with asthma have a degree of fixed airflow obstruction. We hypothesized that fixed and variable obstruction may differ with regard to V_VECM within the ASM layer. <b>Aim:</b> To compare the V_VECM within the ASM layer in asthmatic subjects with (n=7, FEV₁&lt;80% predicted) or without (n=8, FEV₁&gt;80% predicted) fixed airflow obstruction. <b>Methods:</b> The FEV₁, measured pre-operatively in patients undergoing lobectomy (n=12), or obtained from medical records from post-mortem cases (n=3), was recorded. Airways were paraffin embedded and thin (0.5µm) transverse sections were cut and stained using the Masson’s trichrome technique. Point counts were made within the ASM layer to estimate the V_VECM and the correlation between FEV₁ and V_VECM was estimated using Spearman’s correlation coefficient. <b>Results:</b> Mean ± SD, *=p&lt;0.001. V_VECM negatively correlated with FEV₁ (r=0.62, p=0.02) but not in non-smoking asthma cases analyzed separately (r=0.81, p=0.09). <b>Conclusion:</b> The V_VECM within the ASM layer negatively correlated with FEV₁ in asthmatic subjects, with a similar trend seen in non-smoking asthma subjects. These data suggest that, as seen in smokers, fixed airflow obstruction in asthma is related to increased ECM within the ASM layer.