Chronic bronchitis is a common airway disease, characterized by persistent productive cough. The most important aetiological factor is tobacco smoke. Some smokers with chronic bronchitis also acquire chronic obstructive pulmonary disease (COPD), characterized by irreversible airway obstruction [1]. Smokers with chronic bronchitis have been shown to have damaged ciliated columnar epithelium, an increased number of goblet cells in their major and minor airways [2][3][4][5], and a change in the chemical composition of the mucus [6]. The functional result is impaired mucociliary clearance and productive cough.About one third of the patients with chronic bronchitis are prone to recurrent infectious exacerbations, characterized by pronounced cough, increased sputum production and sputum purulence. Several studies have shown that oral N-acetylcysteine medication can reduce the rate of infectious exacerbations in patients with chronic bronchitis [7][8][9][10][11]. The mechanism for this is unknown.Eur Respir J, 1994, 7, 94-101 DOI: 10.1183 Printed in UK -all rights reserved Our results confirm that chronic bronchitis in smokers leads to increased intrabronchial bacterial colonization. We could also confirm that 1,000 cfu·ml -1 is an adequate cut-off level for significant bacterial growth when using the protected specimen brush. NAC medication was associated with low bacterial numbers. Eur Respir J., 1994, 7, 94-101

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Acute rejection of the transplanted lung is a clinical problem, since it decreases graft survival and predisposes the patient to chronic rejection and obliterative bronchiolitis (OB). In an earlier study, we had indications that eosinophil cationic protein (ECP) from activated eosinophils and hyaluronan (HYA) from fibroblasts were associated with acute pulmonary rejection. This prospective longitudinal study was designed to investigate whether molecules from activated inflammatory cells in bronchoalveolar lavage (BAL) fluid could serve as clinically useful diagnostic markers for acute rejection.BAL fluid from 138 bronchoscopies performed in 10 single lung, four bilateral lung and five heart-lung transplant recipients were analysed. Nine patients were studied for a period of more than 1 yr (mean 13.4 months) after surgery. Differential cell counts were made from the BAL fluid. ECP, myeloperoxidase (MPO), HYA and interleukin-8 (IL-8) were used as indirect markers for activation and attraction of eosinophils, neutrophils and fibroblasts, respectively.Fifty four episodes of acute rejection were diagnosed. Two patients developed OB. Nine episodes of bacterial infection, 13 episodes of cytomegalovirus (CMV) pneumonitis, three of Pneumocystis carinii infection and one of respiratory syncytial virus (RSV) infection were diagnosed. The mean levels of ECP, MPO, HYA and IL-8 were all higher during rejection episodes, but differences were not statistically significant compared to no rejection, when the confounding factors of time, concomitant infection, and repeated measures in the same individual had been accounted for.We could not confirm that measurements of eosinophil cationic protein, myeloperoxidase, hyaluronan and interleukin-8 in bronchoalveolar lavage fluid can be used as diagnostic markers for acute rejection in the postoperative follow-up of lung transplant recipients.

SUMMARY CD4+ and CD8 + lymphocytes are mobilized in severe chronic obstructive pulmonary disease (COPD) and the CD8 + cytokine interleukin (IL)-16 is believed to be important in regulating the recruitment and activity of CD4 + lymphocytes. In the current study, we examined whether tobacco smoke exerts an impact not only on IL-16 in the lower airways but also in CD4 + or CD8 + lymphocytes or in lymphoid tissue. The concentration of IL-16 protein was measured by enzyme-linked immunosorbent assay (ELISA) in concentrated bronchoalveolar lavage fluid (BALF) collected from 33 smokers with chronic bronchitis (CB), eight asymptomatic smokers (AS) and seven healthy never-smokers (NS). The concentrations of IL-16 and soluble IL-2 receptor alpha (sIL-2R a ) protein were also measured in conditioned medium from human blood CD4+ and CD8 + lymphocytes stimulated with tobacco smoke extract (TSE) in vitro . IL-16 mRNA was assessed in vitro as well, using reverse transcription-polymerase chain reaction (RT-PCR). Finally, the intracellular immunoreactivity for IL-16 protein (IL-16IR) was assessed in six matched pairs of palatine tonsils from smokers and non-smokers. BALF IL-16 was higher in CB and AS than in NS. TSE substantially increased the concentration of IL-16 but not sIL-2R a in conditioned medium from CD4 + and CD8 + lymphocytes. There was no corresponding effect on IL-16 mRNA. IL-16IR in tonsils was lower in smokers than in non-smokers. The current findings demonstrate that tobacco smoke exerts a wide impact on the CD8 + cytokine IL-16, in the airway lumen, in blood CD4 + and CD8 + lymphocytes and in lymphoid tissue. The effect on IL-16 release may be selective for preformed IL-16 in CD4 + lymphocytes. New clinical studies are required to evaluate whether tobacco smoke mobilizes T lymphocytes via IL-16 in the lower airways and whether this mechanism can be targeted in COPD.

Tobacco smoking induces profound immunological and inflammatory changes, both in the airways and systemically. Smoking impairs host defences and increases susceptibility to infection [1,2].The literature on the effects of smoking on the immune system is extensive and has been reviewed by several authors [2][3][4]. Evidence of a considerable influence on both humoral and cell-mediated immunity has been presented. Decreased serum immunoglobulin (Ig) levels, mainly IgG, have been reported in smokers [5,6]. Data concerning immediate skin reactivity to common allergens [7,8] as well as specific antibody responses to inhaled antigens [9] and vaccinations [10], indicate depressed immune responses in smokers. There are several reports of decreased activity of natural killer (NK-) cells, both from peripheral blood [11,12] and the lung [13]. Results from functional studies of circulating T-lymphocytes are conflicting, with reports of increased [14], unchanged [15] and decreased [16,17] responses to mitogenic stimulation in vitro. Alterations in immunoregulatory T-lymphocyte subsets with a decreased fraction of helper/inducer and an increased fraction of cytotoxic/suppressor cells have been reported, both locally in the lung [18], and in the peripheral circulation [19,20].Bronchial infections are common in smokers [2], but why only some smokers develop problems with repeated bronchial infections is largely unknown. Hypothetically, smokers prone to bronchial infections might differ immunologically from smokers without this disposition. To our knowledge, there are no studies addressing this issue in which smoking habits of study and control groups have been taken fully into account.Since the disposition for bronchial infections in smokers seems to be related to the presence of chronic bronchitis (CB) [21], a state of chronic mucus hypersecretion [22], and appear in the form of recurrent infectious exacerbations, patients with CB prone to infectious exacerbations were chosen for the study group. We decided to analyse most of the immunological parameters known or thought A significantly (p<0.05) lower level of IgG 3 was found in the CB group, and a significantly (p<0.01) higher proliferative response of PBMCs was found in the CB group after stimulation with diphtheria toxoid. Detectable levels of interleukin (IL)-6, tumour necrosis factor-α (TNF-α) and interferon-γ, but not of IL-2, IL-4 or transforming growth factor-β2, were found in supernatants from cultured cells in both study groups. Stimulated TNF-α production was significantly (p<0.05) higher in the CB group. NK-cell activity did not differ significantly between the study groups. There were no major differences between the groups in lymphocyte subpopulations in blood or BAL.In conclusion, no major alterations in the analysed indices of cell-mediated and humoral immunity were found in patients with chronic bronchitis prone to recurrent infectious exacerbations when compared with asymptomatic smoking controls. Eur Respir J 1998; 11: 46-54.