title: CD8(+) T cells characterize early smoking-related airway pathology in patients with asthma.
abstract: BACKGROUND
  Smoking in asthma occurs frequently and is associated with increased symptom severity, an impaired response to corticosteroids, and accelerated lung function decline. Airway pathology in smoking asthmatics is characterized by neutrophilia and epithelial changes such as goblet cell hyperplasia and increased proliferation. Bronchial CD8(+) T cells are implicated in lung function decline in asthma and COPD. We hypothesized that smoking modifies airway inflammation in asthma by increasing the number of CD8(+) T cells at an early stage.
  
  
  OBJECTIVE
  To study effects of smoking on airway pathology in bronchial biopsies from atopic patients with controlled intermittent or mild persistent asthma (12 smokers, 9.7 py and 11 never-smokers, 0.0 py; 20-50 yrs; FEV1 > 70% predicted; PC20MCh < 8 mg/mL, no ICS) using immunohistochemistry.
  
  
  RESULTS
  Smoking asthmatics showed higher numbers of bronchial CD8(+) T cells (55.8 vs 23.9 cells/0.1 mm(2); p = 0.001) and CD68(+) macrophages (7.5 vs 4.6 cells/0.1 mm(2), p = 0.012), and a lower CD4(+)/CD8(+) cell ratio (0.16 vs 0.40; p = 0.007) compared with non-smoking asthmatics, but no difference in neutrophils. Furthermore, the % intact epithelium was higher in smoking asthmatics (49.3 vs 23.3, p = 0.001).
  
  
  CONCLUSIONS
  Smoking asthmatics with a limited smoking history show a distinct pattern of airway pathology characterized by a bronchial infiltrate of CD8(+) T cells and CD68(+) macrophages, and epithelial remodelling resembling COPD-like features. This raises the hypothesis that early presence of CD8(+) T cells contributes to disease progression in smoking asthmatics.
authors: Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands. jra@rrc.nl
authors: A Janneke
authors: AJ
authors: Ravensberg
authors: Annelies M
authors: AM
authors: Slats
authors: Sandra
authors: S
authors: van Wetering
authors: Kirsten
authors: K
authors: Janssen
authors: Simone
authors: S
authors: van Wijngaarden
authors: Ronald
authors: R
authors: de Jeu
authors: Klaus F
authors: KF
authors: Rabe
authors: Peter J
authors: PJ
authors: Sterk
authors: Pieter S
authors: PS
authors: Hiemstra
mesh_terms: D000328:Adult; D001249:Asthma / Q000209:etiology* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D001706:Biopsy; D001980:Bronchi / Q000276:immunology / Q000473:pathology; D001991:Bronchitis / Q000209:etiology / Q000276:immunology / Q000473:pathology; D001999:Bronchoscopy / Q000379:methods; D016516:CD4-CD8 Ratio; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology*; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D020545:Respiratory Mucosa / Q000276:immunology / Q000473:pathology; D012907:Smoking / Q000009:adverse effects* / Q000276:immunology / Q000503:physiopathology; D055815:Young Adult