Directional preference of airway smooth muscle mass increase in human asthmatic airways

Airway smooth muscle (ASM) orientation and morphology determine the ability of the muscle to constrict the airway. In asthma, ASM mass is increased, but it is unknown whether ASM orientation and morphology are altered as well or whether the remodeling at the source of the mass increase is ongoing. We dissected human airway trees from asthmatic and control lungs. Stained, intact airway sections were imaged in axial projection to show ASM bundle orientation, whereas cross-sectional histological slides were used to assess ASM area, bundle thickness, and ASM bundle-to-basement membrane distance. We also used these slides to assess cell size, proliferation, and apoptosis. We showed that ASM mass increase in cartilaginous airways is primarily the result of an increase of ASM bundle thickness (as measured radially in an airway cross section) and coincides with an increased distance of the ASM bundles to the airway perimeter. ASM orientation was unchanged in all airways. Apoptosis markers and cell size did not show differences between asthmatics and controls. Our findings show that ASM mass increase likely contributes to the airway-constricting capacity of the muscle. Both the increased bundle thickness and increased thickness of the airway wall inwards of the ASM bundles could further enhance this capacity. Turnover of ASM appears to be the same in airways and biopsies, but the lack of correlation between different markers of proliferation casts doubt on the specificity of markers generally used to assess proliferation.