Persistent airway inflammation and emphysema progression on CT scan in ex-smokers observed for 4 years

Abstract

Background: Tobacco smoking is a principal cause of COPD-emphysema (COPD-E). Whether discontinuing smoking for at least 4 years halts airway inflammation and progression of COPD-E in prior smokers is unknown. In this study we investigated whether discontinuing smoking for approximately 4 years in ex-smokers with GOLD (Global Initiative for Chronic Lung Disease) stage IIb (moderately severe) COPD-E stopped airway inflammation (ie, sputum biomarkers) and halted the progression of COPD-E on chest CT scan.

Methods: Ten ex-smokers with COPD-E who had quit smoking underwent chest CT scans to document the extent of COPD-E, assessment of lung function (FEV(1) and diffusing capacity of lung for carbon monoxide), sputum induction for biomarkers of inflammation (measured by enzyme-linked immunosorbent assay), and blood cotinine levels at baseline and approximately 4 years later. Normal healthy subjects (n = 7) and normal current smokers with no CT scan evidence of COPD-E (n = 8) served as sputum biomarker comparison groups.

Results: After approximately 4 years of not smoking (documented by cotinine levels), ex-smokers with COPD-E had persistent increased levels of mediators of inflammation in sputum (myeloperoxidase, leukotriene B4, IL-8, monocyte chemoattractant protein-1, matrix metalloprotease-9), which was associated with significant progression of COPD-E on chest CT scan.

Conclusions: Cessation of tobacco smoking in heavy smokers with moderately severe COPD-E is associated with evidence of persistent airway inflammation and progression of COPD-E on CT scan 4 years later. Discontinuing smoking may slow the rate of progression of moderate severity COPD-E, but it does not prevent persistent airway inflammation and significant progression of COPD-E on CT scan.

Figure 1.

Subjects with COPD-E (n = 10) had baseline (year 0) and repeat chest CT scans (year 4). Normal current smokers without COPD-E (n = 8), and healthy nonsmokers (n = 7) had baseline chest CT scans. The percent of voxels with density < −910 Hounsfield unit (HU) was recorded in each subject and reported as the chest CT scan %. COPD-E = COPD-emphysema.

Figure 2.

Subjects with COPD-E (n = 10) had baseline (year 0) and repeat FEV₁ (year 4) measurements. Normal current smokers without COPD-E (n = 8) and healthy nonsmokers (n = 7) had baseline FEV₁ measurements. See Figure 1 legend for expansion of abbreviation.

Figure 3.

Subjects with COPD-E (n = 10) had baseline (year 0) and repeat Dlco/VA measurements (year 4). Normal current smokers without COPD-E (n = 8) and healthy nonsmokers (n = 7) had baseline Dlco/VA measurements. Dlco/VA = volume-adjusted diffusing capacity of the lung for carbon monoxide. See Figure 1 legend for expansion of other abbreviation.

Figure 4.

A, Subjects with COPD-E (n = 10) had baseline (year 0) and repeat (year 4) MPO assessed by ELISA. B, Subjects with COPD-E (n = 10) had baseline (year 0) and repeat (year 4) LTB4 levels assessed by ELISA. C, Subjects with COPD-E (n = 10) had baseline (year 0) and repeat (year 4) sputum IL-8 levels assessed by ELISA. Normal current smokers without COPD-E (n = 8) and healthy nonsmokers (n = 7) had baseline sputum MPO, LTB4, and IL-8 measurements. ELISA = enzyme-linked immunosorbent assay; LTB4 = leukotriene B4; MPO = myeloperoxidase. See Figure 1 legend for expansion of other abbreviation.

Figure 5.

A, Subjects with COPD-E (n = 10) had baseline (year 0) and repeat (year 4) sputum MCP-1 levels assessed by ELISA. B, Subjects with COPD-E (n = 10) had baseline (year 0) and repeat (year 4) sputum MMP-9 levels assessed by ELISA. Normal current smokers without COPD-E (n = 8) and healthy nonsmokers (n = 7) had baseline sputum MCP-1 and MMP-9 measurements. MCP-1 = monocyte chemoattractant protein-1; MMP-9 = matrix metalloprotease-9. See Figure 1 and 4 legends for expansion of other abbreviations.

Figure 6.

A, The annual change in CT scan in COPD-E (n = 10) correlated with the annual change in sputum MPO level. B, The annual change in CT scan in COPD-E (n = 10) correlated with the annual change in sputum MCP-1 level. C, The annual change in volume-adjusted Dlco correlated with the baseline sputum MPO level. D, The annual change in volume-adjusted Dlco correlated with the baseline sputum MCP-1 level. See Figures 1, 3, 4, and 5 legends for expansion of abbreviations.