Relation between duration of smoking cessation and bronchial inflammation in COPD

Thérèse S. Lapperre ^1*, Dirkje S. Postma ², Margot M.E. Gosman ², Jiska B. Snoeck-Stroband ¹, Nick H.T. ten Hacken ², Pieter S. Hiemstra ¹, Wim Timens ², Peter J. Sterk ¹, Thais Mauad ³ and The GLUCOLD Study Group ⁴

¹ Leiden University Medical Center, Netherlands
² Groningen University Medical Center, Netherlands
³ Sao Paulo University, Brazil
⁴ Groningen Leiden Universities, Netherlands

^* To whom correspondence should be addressed. E-mail: t.s.lapperre{at}lumc.nl.

Accepted 17 July 2005

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is associated with airway inflammation. Although smoking cessation improves symptoms and lung function decline in COPD, it is unknown whether bronchial inflammation in patients with established COPD varies with the duration of smoking cessation.

Methods: 114 COPD patients were studied cross- sectionally: 99 males, age 62±8 years, median 42 (IQR: 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), postbronchodilator FEV₁ 63±9% predicted, FEV₁/IVC 48±9%. Subepithelial T-lymphocyte (CD3, CD4, CD8), neutrophil, macrophage, eosinophil, mast cell, and plasma cell numbers were measured in bronchial biopsies (median [IQR] /0.1 mm²), 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] vs. 108 [61-164], p=0.036; 58 [32-90] vs. 40 [25-66], p=0.023; 9.0 [5.5-20] vs. 7.5 [3.1-14], p=0.044, respectively), but no difference in other inflammatory cells. Short-term ex-smokers (<3.5 years) had significantly 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 significantly 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.

Keywords: COPD, bronchial biopsies, inflammation, smoking cessation

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