Cigarette smoking alters bronchial mucosal immunity in asthma.
BACKGROUND
Cigarette smoking worsens asthma and is associated with reduced response to corticosteroid therapy. As cigarette smoke is known to have immunomodulatory effects, we hypothesized that one mechanism by which smoking mediates its adverse effect is by reduction of the numbers of bronchial mucosal dendritic cells (DCs), which control B-cell growth and T-cell responses.


OBJECTIVE
We set out to sample the bronchial mucosa in smoking and never-smoking patients with asthma and to count DCs, B cells, and cells expressing genes for two key T-lymphocyte regulatory cytokines.


METHODS
Twenty-one never-smoker patients with asthma (6 steroid naive), 24 smoker patients with asthma (9 steroid naive), and 10 healthy never-smokers (control subjects) were recruited and their endobronchial biopsy samples were immunostained for detection of mature DCs (CD83(+)), Langerhans cells (CD1a(+)), B lymphocytes (CD20(+)), and helper T-cell type 1 (IFN-gamma) and helper T-cell type 2 (IL-4) cytokine-expressing cells.


RESULTS
The number (per square millimeter) of CD83(+) mature DCs was significantly lower in smoker patients with asthma (median [range]: 37 [0, 131]) in comparison with never-smoker steroid-naive and steroid-treated patients with asthma (76 [24, 464]; p = 0.006) or control subjects (85 [40, 294]; p = 0.004). Moreover, B cells were fewer in smoker (26 [4, 234]) versus never-smoker steroid-naive and steroid-treated patients with asthma (45 [10, 447]; p = 0.01) and in smoker steroid-naive patients with asthma (23 [4, 111]) versus control subjects (34 [10, 130]; p = 0.05). The number of cells expressing IFN-gamma showed a trend toward fewer in smoker (70 [6, 24]) versus never-smoker steroid-naive patients with asthma (144 [44, 323]; p = 0.10).


CONCLUSIONS
There are important and statistically significant differences in the number of CD83(+) mature DCs and B cells in the large airways of smokers with asthma. We speculate that their reductions may render patients with asthma less responsive to corticosteroids and more susceptible to infection.
Tsoumakidou
Maria
M
Lung Pathology Unit, Department of Gene Therapy, Imperial College London, London, UK.
Elston
William
W
Zhu
Jie
J
Wang
Zhuo
Z
Gamble
Elizabeth
E
Siafakas
Nikos M
NM
Barnes
Neil C
NC
Jeffery
Peter K
PK
D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D001249:Asthma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001980:Bronchi / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D003713:Dendritic Cells / Q000502:physiology; D005260:Female; D006801:Humans; D018928:Immunity, Mucosal / Q000502:physiology*; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012907:Smoking / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D015703:Antigens, CD; C508598:IL4 protein, human; D015847:Interleukin-4; D007371:Interferon-gamma