Relation between duration of smoking cessation and bronchial inflammation in COPD

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is associated with airway inflammation. Although smoking cessation improves symptoms and the decline in lung function in COPD, it is unknown whether bronchial inflammation in patients with established COPD varies with the duration of smoking cessation. Methods: 114 patients (99 men) with COPD of mean (SD) age 62 (8) years, a median (IQR) smoking history of 42 (31-55) pack years, no inhaled or oral corticosteroids, all current or ex-smokers (n = 42, quit .1 month, median cessation duration 3.5 years), post-bronchodilator FEV 1 63 (9)% predicted, and FEV 1 /IVC 48 (9)% were studied cross sectionally. The numbers of subepithelial T lymphocytes (CD3, CD4, CD8), neutrophils, macrophages, eosinophils, mast cells, and plasma cells were measured in bronchial biopsy specimens (median (IQR)/0.1 mm 2 ) using fully automated image analysis. Results: Ex-smokers with COPD had higher CD3+, CD4+, and plasma cell numbers than current smokers with COPD (149 (88-225) v 108 (61-164), p = 0.036; 58 (32-90) v 40 (25-66), p = 0.023; and 9.0 (5.5-20) v 7.5 (3.1-14), p = 0.044, respectively), but no difference in other inflammatory cells. Short term ex-smokers (,3.5 years) had higher CD4+ and CD8+ cell numbers than current smokers (p = 0.017, p = 0.023; respectively). Conversely, long term ex-smokers (quit >3.5 years) had lower CD8+ cell numbers than short term ex-smokers (p = 0.009), lower CD8/CD3 ratios than both current smokers and short-term ex-smokers (p = 0.012, p = 0.003; respectively), and higher plasma cell numbers than current smokers (p = 0.003). Conclusions: With longer duration of smoking cessation, CD8 cell numbers decrease and plasma cell numbers increase. This indicates that bronchial T lymphocyte and plasma cell counts, but not other inflammatory cells, are related to duration of smoking cessation in patients with COPD.

Pathobiology of Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease

“…Whether inflammatory cells play a similar role (i.e., protective or destructive) early versus late in the disease also remains unknown. The finding that ex-smokers have persistent inflammation despite discontinuation of smoking argues for a proinflammatory environment set by cigarette smoke-induced chronic lung damage (176). Recent ground-breaking studies indicate that parenchymal inflammation in advanced emphysema contains oligoclones of CD4ϩ and CD8ϩ T cells, perhaps the first indication in support of a potential autoimmune attack (161,305).…”

NRF2 targeting: a promising therapeutic strategy in chronic obstructive pulmonary disease

“…CS-induced oxidative stress is involved in the pathophysiology of COPD through the amplification of inflammation. The proinflammatory transcription factor nuclear factorkB (NF-kB) is activated in COPD lungs, particularly in alveolar macrophages and airway epithelial cells, and further activates multiple inflammatory genes that contribute to persistent inflammation and oxidative stress [13,14], even after the discontinuation of smoking. Moreover, oxidative and nitrative stress mediate a reduction in nuclear histone deacetylase 2 (HDAC2) expression and activity in the peripheral lungs of COPD patients' airways and alveolar macrophages [15].…”

Aberrant neutrophil functions in stable chronic obstructive pulmonary disease: The neutrophil as an immunotherapeutic target

“…However, while the most common risk factor is chronic tobacco smoke inhalation [44], only one fifth of smokers develop the disease [9] and the characteristic neutrophilic accumulation is not present in smokers without airflow obstruction (so called "healthy smokers"). Furthermore, the airway neutrophilia persists in patients with COPD following smoking cessation, in contrast with smoking controls [45][46][47]. Smoking alone appears insufficient to initiate and sustain disease without the presence of other, as yet undefined susceptibility factors.…”