Airway smooth muscle proliferation and inflammation in asthma

Author:

James Alan L.12,Noble Peter B.34,Drew Su-Ann13,Mauad Thais5ORCID,Bai Tony R.6,Abramson Michael J.7,McKay Karen O.8,Green Francis H. Y.9,Elliot John G.1

Affiliation:

1. West Australian Sleep Disorders Research Institute, Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, Nedlands, WA, Australia

2. School of Medicine and Pharmacology, University of Western Australia, Nedlands, WA, Australia

3. School of Human Sciences, University of Western Australia, Nedlands, WA, Australia

4. Centre for Neonatal Research and Education, School of Paediatrics and Child Health, University of Western Australia, Perth, WA, Australia

5. University Medical School, Sao Paulo, Brazil

6. University of British Columbia, Vancouver, BC, Canada

7. Department of Epidemiology & Preventive Medicine, Monash University, Melbourne, VIC, Australia

8. Children’s Hospital at Westmead, Sydney, NSW, Australia

9. Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada

Abstract

In asthma, it is unclear if the airway smooth muscle cells proliferate more or are increased at the onset of asthma and remain stable. This study aimed to compare smooth muscle cell proliferation in individuals with and without asthma and correlate proliferation rates with cell size and number and with granulocytic airway inflammation. Postmortem airway sections were labeled with proliferating cell nuclear antigen (PCNA) and percent positive muscle cells calculated. On the same sections, smooth muscle cell size and number and the number of eosinophils and neutrophils were estimated and compared in cases of nonfatal ( n = 15) and fatal ( n = 15) asthma and control subjects ( n = 15). The %PCNA+ muscle cells was not significantly different in fatal (29.4 ± 7.7%, mean ± SD), nonfatal asthma (28.6 ± 8.3%), or control subjects (24.6 ± 6.7%) and not related to mean muscle cell size ( r = 0.09), number ( r = 0.36), thickness of the muscle layer ( r = 0.05), or eosinophil numbers ( r = 0.04) in the asthma cases. These data support the hypothesis that in asthma the increased thickness of the smooth muscle layer may be present before or at the onset of asthma and independent of concurrent granulocytic inflammation or exacerbation. NEW & NOTEWORTHY There is debate regarding the origins of the increased airway smooth muscle in asthma. It may be independent of inflammation or arise as a proliferative response to inflammation. The present study found no increase in the proportion of proliferating smooth muscle cells in asthma and no relation of proliferation to numbers of airway smooth muscle cells or inflammation. These results support a stable increase in smooth muscle in asthma that is independent of airway inflammation.

Funder

Department of Health, Australian Government | National Health and Medical Research Council (NHMRC)

Brazilian Research Council

Alberta Lung Association

Gouvernement du Canada | Health Canada (Santé Canada)

Publisher

American Physiological Society

Subject

Physiology (medical),Physiology

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