In order to determine whether the airway inflammatory cells of chronic obstructive pulmonary disease (COPD) are different from those seen in asthma, we have studied a subepithelial zone, 100 microns deep to the epithelial reticular basement membrane in bronchial biopsies taken from five normal nonsmoking subjects without chronic bronchitis or asthma (FEV1 percentage of predicted [mean +/- SD] 105.7 +/- 25.3), 11 subjects with chronic bronchitis alone (FEV1 percentage of predicted 98.5 +/- 12.9), and 13 subjects with chronic bronchitis in whom there was also evidence of airflow limitation (i.e., COPD; FEV1 percentage of predicted 59.7 +/- 10.0). Using immunohistochemical markers, we counted distinct types of inflammatory cell and expressed them as [median and range] per mm basement membrane. When there was airflow limitation we found significantly increased numbers of CD3+ T lymphocytes (COPD 22.3 [2.6 to 68.2] versus normal 3.7 [1.5 to 16.3]; p < 0.05), an increased number of CD8+ cells (COPD 19.3 [1.8 to 45.5] versus normal 2.3 [0.9 to 4.2]; p < 0.01), and increased expression of HLA-DR (COPD versus normal; p = 0.01). There was also an increased number of CD68+ cells (i.e., macrophages) (COPD 7.4 [0.4 to 16.9] versus normal 0.7 [0 to 2.6]; p < 0.01; COPD versus chronic bronchitis alone 2.7 [0 to 12.8]; p < 0.05). There were no significant differences between the groups in the numbers of subepithelial neutrophils, mast cells, eosinophils or B lymphocytes. There were weak but significant negative associations between the CD8+ T-cell subset (r = -0.42), neutrophils (r = -0.46), and eosinophils (r = -0.53) and FEV1 percentage of predicted in all the chronic bronchitic smokers (p < 0.05). The data confirm the involvement of subepithelial T lymphocytes and macrophages in smoking-induced airflow limitation and provide novel data which support the view that COPD is distinct from asthma with respect to the predominance of the CD8+ T-cell subset in this smoking-related condition.

Bronchial biopsy specimens from chronic obstructive pulmonary disease (COPD) patients demonstrate increased numbers of CD8+ T-lymphocytes, macrophages and, in some studies, neutrophils and eosinophils. Smoking cessation affects the rate of forced expiratory volume in one second (FEV1) decline in COPD, but the effect on inflammation is uncertain. Bronchial biopsy inflammatory cell counts were compared in current and ex-smokers with COPD.A pooled analysis of subepithelial inflammatory cell count data from three bronchial biopsy studies that included COPD patients who were either current or ex-smokers was performed.Cell count data from 101 subjects, 65 current smokers and 36 ex-smokers, were analysed for the following cell types: CD4+ and CD8+ T-lymphocytes, CD68+ (monocytes/macrophages), neutrophil elastase+ (neutrophils), EG2+ (eosinophils), mast cell tryptase+ and cells mRNApositive for tumour necrosis factor-a. Current smokers and ex-smokers were similar in terms of lung function, as measured by FEV1 (% predicted), forced vital capacity (FVC) and FEV1/FVC. The results demonstrate that there were no significant differences between smokers and ex-smokers in the numbers of any of the inflammatory cell types or markers analysed.It is concluded that, in established chronic obstructive pulmonary disease, the bronchial mucosal inflammatory cell infiltrate is similar in ex-smokers and those that continue to smoke.

No abstract

No abstract

Abstractresponsiveness, and airway inflammation. During the past decade a growing body of Background -There is increasing evidence to show that leukotrienes are important evidence has shown that leukotrienes play an important part in the pathogenesis of asthma. mediators in asthma. Leukotriene receptor antagonists protect against antigen Moreover, the cysteinyl leukotrienes LTC 4 , LTD 4 , and LTE 4 have been shown potently to and exercise challenges in patients with chronic asthma. A study was undertaken constrict bronchial smooth muscle, stimulate mucous secretions, mediate inflammation, to investigate the activity of the leukotriene receptor antagonist pranlukast (SB and possibly induce bronchial hyperresponsiveness. 1-3205312, ONO-1078) in blocking bronchoconstriction induced by leukotriene D 4 The cysteinyl leukotrienes are released in response to immunological and non-immuno-(LTD 4 ) inhalation. The selectivity of pranlukast was evaluated using histamine chal-logical stimuli from mast cells, eosinophils, macrophages, and other inflammatory cells that lenge. Methods -Pranlukast, 450 mg twice daily, are implicated in asthma. Bronchoconstriction is stimulated directly through leukotriene rewas given to eight healthy non-smoking men for five days in a randomised, double ceptors found on bronchial smooth muscle and other cells. 4-7blind, placebo controlled, crossover study. The specific airways conductance (sGaw) Urinary levels of the leukotriene metabolite LTE 4 are increased in several subpopulations was measured before and after bronchial provocation with inhaled LTD 4 at 3.5 hours of patients who have asthma -namely, aspirinsensitive patients in the resting state and after after the first dose and at 3.5 and 9.5 hours after the last dose of pranlukast on the aspirin challenge, wheezing patients, and patients who have atopic asthma after allergen morning of day 5. The concentration of LTD 4 required to produce a fall in sGaw challenge. 4 8-12 Leukotrienes are also found in 450 mg daily oral dosing in normal subjects.