ASTHMA

Relationship of airway wall thickening to an imbalance between matrix metalloproteinase-9 and its inhibitor in asthma

H Matsumoto¹, A Niimi¹, M Takemura¹, T Ueda¹, M Minakuchi^1,4, R Tabuena¹, K Chin², T Mio¹, Y Ito¹, S Muro¹, T Hirai¹, S Morita³, S Fukuhara³, M Mishima¹

¹ Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
² Department of Physiotherapy, Kyoto University Graduate School of Medicine, Kyoto, Japan
³ Department of Epidemiology and Health Care Research, Kyoto University Graduate School of Medicine, Kyoto, Japan
⁴ Department of Respiratory Medicine, Tenri Hospital, Nara, Japan

Correspondence to:
Correspondence to:
Dr A Niimi
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan; niimi{at}kuhp.kyoto-u.ac.jp

Background: The balance between matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) may be critical in extracellular matrix remodelling, a characteristic of asthmatic airways. An excess of TIMP-1 over MMP-9 has been associated with chronic airflow obstruction but the mechanisms underlying this association remain unknown. Recent computed tomographic (CT) studies indicate that airway wall thickening is associated with chronic airflow obstruction.

Methods: Sputum levels of MMP-9, TIMP-1, and their molar ratio were examined in 26 patients with stable asthma and their relationship with pulmonary function and airway wall thickness, assessed by a validated CT technique which measured wall area corrected by body surface area (WA/BSA), the ratio of WA to outer wall area (WA%), and the absolute wall thickness corrected by BSA of a segmental bronchus (T/BSA), was examined.

Results: Sputum MMP-9 levels were inversely correlated with WA% and TIMP-1 levels were positively correlated with WA/BSA and T/BSA. The MMP-9/TIMP-1 molar ratio was inversely correlated with WA% and T/BSA and positively correlated with post-bronchodilator values of mid-forced expiratory flow and maximum expiratory flow at the quartile of lung volume.

Conclusion: Excess TIMP-1 may have a pathogenetic role in airway wall thickening in asthmatic patients which may result in chronic airflow obstruction.

Abbreviations: Ao, outer area of the bronchus; BSA, body surface area; ECM, extracellular matrix; FEF_25–75%, mid forced expiratory flow; FEV₁, forced expiratory volume in 1 second; MMP-9, matrix metalloproteinase-9; SBM, subepithelial basement membrane; T, absolute airway thickness; TIMP-1, tissue inhibitor of metalloproteinase-1; WA, airway wall area

Keywords: asthma; airway wall thickening; computed tomography; matrix metalloproteinase-9; tissue inhibitor of metalloproteinase-1

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