Extracellular matrix within the airway smooth muscle layer correlates with age but not in cases of asthma

Abstract

Introduction/Aim: In patients with asthma, the airway smooth muscle (ASM) layer is thicker and is stable with age. Within the ASM layer, extracellular matrix (ECM) represents less than 20% of its total volume fraction (V V ). Departure from normal development of the ASM layer may alter V V ECM and result in airway hyperresponsiveness and asthma or contribute to fixed airflow obstruction later in life. The aim of this study was to compare the volume fractions of ECM, ASM and “Other” (space between ASM cells) within the ASM layer from infancy to adulthood in subjects with (n=84, age range 4-59yrs) and without (n=59, 0.2-57yrs) asthma. Methods: On transverse airways taken from formalin-fixed, post-mortem lungs, sections were cut from paraffin-embedded tissue blocks at 0.5microns and stained using the Masson9s trichrome technique. Volume fractions of ECM, ASM and Other within the ASM layer were measured (x1000) by point counting and then related to age in cases with and without asthma. Results: Cases of asthma had decreased V V ECM (17±5%, mean ± SD) compared with control subjects (19±4%, p=0.02) and no difference in V V ASM or V V Other. V V ECM and V V ASM positively correlated with age in control subjects (r 2 =0.13, p=0.005 and r 2 =0.11, p=0.01), but not in cases of asthma (r 2 =0.04, p=0.07 and r 2 =0.03, p=0.1). V V ASM and V V Other did not correlate with age. Discussion: These data suggest that the ASM layer normally undergoes structural change from infancy to adulthood and this involves changes in V V ECM. However in asthma, the ASM layer may not follow the same developmental trajectory as control subjects, possibly due to the confounding effect of early structural changes in the layer of ASM.