Airway inflammation and peribronchiolar attachments in the lungs of nonsmokers, current and ex-smokers

Abstract

To determine the effect of smoking cessation on the number and type of inflammatory cells in the walls of the small airways, we examined the lungs of 13 lifetime nonsmokers, 25 patients who had stopped smoking for at least 6 months, and 49 current smokers. We found that, compared to nonsmokers, both ex-smokers and current smokers had significantly increased numbers of total inflammatory cells and polymorphonuclear leukocytes in the walls of the membranous, but not the respiratory bronchioles. These differences were found even when there was no emphysema present in the gross lung specimen, and current and ex-smokers were matched with the nonsmokers for age. The current and ex-smokers had similar numbers and types of inflammatory cells in the airway wall, and in both current and ex-smokers there was no difference in inflammatory cell number or type when the groups were subdivided based on emphysema score less than or greater than 5. Analysis of peribronchiolar alveolar attachments showed an increase in percentage of alveoli destroyed associated with an increased interalveolar distance in both the current and ex-smokers, which did not change with the presence of emphysema. Pulmonary function was similar in the current and ex-smokers, and the group with emphysema showed greater functional abnormalities compared to the group with little or no emphysema. We conclude that the cigarette smoking habit induces a stereotypical inflammatory response in the small airways. This inflammatory response does not abate after smoking cessation, and in this cross-sectional study, appears to be independent of the presence or absence of emphysema, but related to destruction of the peribronchiolar alveolar attachments.

Smoking is associated with an age-related decline in exhaled nitric oxide

“…Many of these changes persist after subjects quit smoking, including persistence of neutrophil inflammation [16,17]. The hypothesis that long-term cigarette smoking is associated with permanent reductions in FeNO is supported by studies on older smokers who quit smoking [2,6].…”

“…Tobacco-smoke exposure is associated with airway epithelial hyperplasia, mucus cell hyperplasia, airway metaplasia, epithelial damage and airway neutrophil infiltration [16,17]. Many of these changes persist after subjects quit smoking, including persistence of neutrophil inflammation [16,17].…”

“…FeNO levels increase after smoking cessation but not to normal levels [2,6,10], which suggests that smoking-related declines in FeNO may be associated with permanent lung damage. As respiratory epithelium is the likely source of most FeNO [11][12][13][14][15] and is damaged by chronic smoke exposure [16][17][18][19][20], smoking-related declines in FeNO may be a marker of airway epithelial damage.…”

Persistent Airway Inflammation and Emphysema Progression on CT Scan in Ex-Smokers Observed for 4 Years

“…A P value , .05 was considered statistically signifi cant. resected lungs, 8,9 bronchial biopsies, [10][11][12] or induced sputum. [13][14][15] For example, there was no difference in the intensity of infl ammation in central and peripheral airways in studies of the resected lungs of smokers and ex-smokers undergoing surgery for a lung tumor.…”

“…[13][14][15] For example, there was no difference in the intensity of infl ammation in central and peripheral airways in studies of the resected lungs of smokers and ex-smokers undergoing surgery for a lung tumor. 8,9 Studies of bronchial biopsy specimens of smokers and ex-smokers with moderate to severe COPD have also demonstrated no difference in mediators of infl ammation associated with neutrophil and mononuclear cell recruitment, such as IL-8 and monocyte chemoattractant protein (MCP)-1, as well as the MCP-1 chemokine receptor 2, in the lung tissue. 10 Although cross-sectional studies of lung tissue in COPD demonstrate more consistent fi ndings of persistent infl ammation in ex-smokers, 3,[8][9][10][11] cross-sectional studies of sputum, blood, or BAL generally demonstrate reductions in biomarkers of infl ammation 3 or no difference in ex-smokers vs smokers.…”