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.

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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