Persistence of oxidant and protease burden in the airways after smoking cessation

Abstract

Background: Oxidative stress is associated with the pathogenesis of cigarette smoke related lung diseases, but longitudinal effects of smoking cessation on oxidant markers in the airways are unknown.

Methods: This study included 61 smokers; 21 with chronic bronchitis or COPD, 15 asthmatics and 25 asymptomatic smokers followed up for 3 months after smoking cessation. Fractional exhaled nitric oxide (FeNO), sputum neutrophil counts, sputum 8-isoprostane, nitrotyrosine and matrix metalloproteinase-8 (MMP-8) were investigated at baseline and 1 and 3 months after smoking cessation.

Results: After 3 months 15 subjects had succeeded in quitting of smoking and in these subjects symptoms improved significantly. Unexpectedly, however, sputum neutrophils increased (p = 0.046) after smoking cessation in patients with chronic bronchitis/COPD. At baseline, the other markers did not differ between the three groups so these results were combined for further analysis. Sputum 8-isoprostane declined significantly during the follow-up at 3 months (p = 0.035), but levels still remained significantly higher than in non-smokers. The levels of FeNO, nitrotyrosine and MMP-8 did not change significantly during the 3 months after smoking cessation.

Conclusion: Whilst symptoms improve after smoking cessation, the oxidant and protease burden in the airways continues for months.

Figure 1

Sputum neutrophils (%) in the induced sputum of the subjects with bronchitis and COPD. P-value was calculated with Wilcoxon signed rank test. P = 0.046.

Figure 2

Fractional exhaled nitric oxide (FeNO) in bronchitis and COPD patients (COPD), asthmatics (A) and asymptomatic smokers (S) at the beginning of the study. The values of non smokers (NS) have been gathered from previously published materials where non-smokers were combined from two groups of subjects i.e. never smokers and ex smokers who had quitted smoking over 20 years ago. The levels of each marker in these two groups of non-smokers have been found to be very similar [8,9,15,20]. P-value was calculated with Kruskall-Wallis test.

Figure 3

Levels of sputum 8-isoprostane in bronchitis and COPD patients (COPD), asthmatics (A) and asymptomatic smokers (S) at the beginning of the study. The values of non smokers (NS) have been gathered from previously published materials where non smokers were combined from two groups of subjects i.e. never smokers and ex smokers who had quitted smoking over 20 years ago. The levels of each marker in these two groups of non-smokers have been found to be very similar [8,9,15,20]. P-value was calculated with Kruskall-Wallis test.

Figure 4

Levels of sputum nitrotyrosine (% of positive cells) in bronchitis and COPD patients (COPD), asthmatics (A) and asymptomatic smokers (S) at the beginning of the study. The values of non smokers (NS) have been gathered from previously published materials where non-smokers were combined from two groups of subjects i.e. never smokers and ex smokers who had quitted smoking over 20 years ago. The levels of each marker in these two groups of non-smokers have been found to be very similar [8,9,15,20]. P-value was calculated with Kruskall-Wallis test.

Figure 5

Levels of sputum MMP-8 in bronchitis and COPD patients (COPD), asthmatics (A) and asymptomatic smokers (S) at the beginning of the study. The values of non smokers (NS) have been gathered from previously published materials where non smokers were combined from two groups of subjects i.e. never smokers and ex smokers who had quitted smoking over 20 years ago. The levels of each marker in these two groups of non-smokers have been found to be very similar [8,9,15,20]. P-value was calculated with Kruskall-Wallis test.

Figure 6

Levels of sputum 8-isoprostane in the combined groups of chronic bronchitis and COPD (COPD), asthma (A) and asymptomatic smokers (S). Individual subgroups are presented as corresponding symbols and shown in the panels. Only 8-isoprostane in the combined group showed a significant decline (p = 0.035) after smoking cessation calculated with Wilcoxon signed rank test. The number of the analyses was lower than the total number of subjects who succeeded in smoking cessation due to unrepresentative sputum specimen during the control visit.

Figure 7

Exhaled fractional nitric oxide (FeNO) in the combined groups of chronic bronchitis and COPD (COPD), asthma (A) and asymptomatic smokers (S). Individual subgroups are presented as corresponding symbols and shown in the panels. Only 8-isoprostane in the combined group showed a significant decline (p = 0.035) after smoking cessation calculated with Wilcoxon signed rank test. The number of the analyses was lower than the total number of subjects who succeeded in smoking cessation due to unrepresentative sputum specimen during the control visit.

Figure 8

Percentage of nitrotyrosine positive cells in the combined groups of chronic bronchitis and COPD (COPD), asthma (A) and asymptomatic smokers (S). Individual subgroups are presented as corresponding symbols and shown in the panels. Only 8-isoprostane in the combined group showed a significant decline (p = 0.035) after smoking cessation calculated with Wilcoxon signed rank test. The number of the analyses was lower than the total number of subjects who succeeded in smoking cessation due to unrepresentative sputum specimen during the control visit.

Figure 9

Levels of sputum MMP-8 in the combined groups of chronic bronchitis and COPD (COPD), asthma (A) and asymptomatic smokers (S). Individual subgroups are presented as corresponding symbols and shown in the panels. Only 8-isoprostane in the combined group showed a significant decline (p = 0.035) after smoking cessation calculated with Wilcoxon signed rank test. The number of the analyses was lower than the total number of subjects who succeeded in smoking cessation due to unrepresentative sputum specimen during the control visit.