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Updated: Apr 27, 2026

Methodology for Sputum Induction and Laboratory Processing
Published on: December 17, 2017
Low sputum MMP-9/TIMP ratio is associated with airway narrowing in smokers with asthma
Rekha Chaudhuri1, Charles McSharry2, Jeffrey Brady3
1Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK rekhachaudhuri@yahoo.com.
Abstract:
Asthmatic smokers have poor symptom control and accelerated decline in lung function. A reduced ratio of matrix metalloproteinase (MMP)-9/tissue inhibitors of metalloproteinases (TIMPs) in nonsmokers with asthma has been implicated in airway remodelling. We tested the hypothesis that sputum MMP-9 activity/TIMPs ratios are reduced in smokers compared with never-smokers with asthma and are associated with reduced lung function and altered computed tomography (CT) measures of airway wall dimensions. Lung function, airway dimensions by CT, and induced sputum concentrations (and activity) of MMP-9 and TIMP-1 and -2 were measured in 81 asthmatics and 43 healthy subjects (smokers and never-smokers). Respiratory epithelial MMP9 and TIMP mRNA was quantified in 31 severe asthmatics and 32 healthy controls. Sputum MMP-9 activity/TIMP-1 and TIMP-2 ratios, and nasal epithelial MMP9/TIMP1 and MMP9/TIMP2 expression ratios were reduced in smokers with asthma compared with never-smokers with asthma. Low sputum ratios in asthmatic smokers were associated with reduced post-bronchodilator forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity ratio and segmental airway lumen area. The association of a low sputum MMP-9 activity/TIMP-1 ratio with persistent airflow obstruction and reduced CT airway lumen area in smokers with asthma may indicate that an imbalance of MMP-9 and TIMPs contributes to structural changes to the airways in this group.
Insights
Asthmatic smokers show lower matrix metalloproteinase (MMP)-9 to tissue inhibitors of metalloproteinases (TIMPs) ratios. This imbalance is linked to reduced lung function and airway remodeling in asthma patients who smoke.
Area of Science:
- Pulmonary Medicine
- Biochemistry
- Respiratory Physiology
Background:
- Asthma patients who smoke experience worse symptom control and faster lung function decline.
- A decreased ratio of matrix metalloproteinase (MMP)-9 to tissue inhibitors of metalloproteinases (TIMPs) is linked to airway remodeling in non-smoking asthma patients.
Purpose of the Study:
- To investigate if sputum MMP-9 activity/TIMP ratios are reduced in smokers with asthma compared to never-smokers.
- To determine if these ratios correlate with reduced lung function and altered airway dimensions measured by CT scan.
Main Methods:
- Measured lung function, CT-based airway dimensions, and sputum MMP-9 and TIMP levels in 81 asthmatics and 43 healthy controls.
- Quantified respiratory epithelial MMP9 and TIMP mRNA in 31 severe asthmatics and 32 healthy controls.
Main Results:
- Sputum MMP-9/TIMP-1 and MMP-9/TIMP-2 ratios were lower in asthmatic smokers versus never-smokers.
- Nasal epithelial MMP9/TIMP1 and MMP9/TIMP2 expression ratios were also reduced in asthmatic smokers.
- Low sputum ratios correlated with reduced FEV1, FEV1/FVC ratio, and airway lumen area.
Conclusions:
- Reduced sputum MMP-9 activity/TIMP ratios in asthmatic smokers are associated with airflow obstruction and airway structural changes.
- An imbalance of MMP-9 and TIMPs may contribute to airway remodeling in smokers with asthma.
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