Airway smooth muscle remodeling is dynamic in severe asthma
MedWire News: A sensitive marker of proliferating cells suggests that airway remodeling is a dynamic process in patients with severe asthma, results from a Canadian study show.
The marker, known as proliferating cell nuclear antigen (PCNA), is highly correlated with the increase of airway smooth muscle cells.
The results indicate that "remodeling is not an end-stage phenomenon but remains an active process even in longstanding asthma," write James Martin (McGill University, Montreal, Quebec) and colleagues in the Journal of Allergy and Clinical Immunology.
Airway remodeling, particularly the change in smooth muscle mass, is believed to account for many features of asthma. The origin of the excess airway smooth muscle in asthma, however, as well as when it is acquired, is uncertain.
In this study, the researchers assessed the relative sensitivities of two known biomarkers of proliferation, PCNA and Ki67, in airway smooth muscle, and then quantified muscle remodeling by measuring the rate and area of proliferation.
Results showed that both PCNA and Ki67 were highly correlated, but regression equations showed that PCNA had a significantly greater sensitivity than Ki67.
Assessing muscle mass, analyses showed that the normalized area of airway smooth muscle was a significant 3.4-fold greater in subjects with severe asthma than in controls.
"There was also evidence that this remodeling was ongoing," report Martin and colleagues.
For example, the percentage of PCNA positive nuclei in airway smooth muscle compared with total nuclei was approximately 5-fold greater in severe asthma patients compared with controls, and almost 3-fold that of patients with moderate asthma.
The researchers also showed that heparin-binding epidermal growth factor (HB-EGF) was upregulated in proliferating muscle cells in culture and in airway smooth muscle in severe asthmatic tissues.
"These results demonstrate ongoing airway smooth muscle cell hyperplasia in asthma and suggest that HB-EGF is a potential biomarker of active remodeling of airway smooth muscle," write the researchers.
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