Cutaneous delayed-type hypersensitivity reactions in smokers with chronic bronchitis and recurrent exacerbations: comparison with asymptomatic smokers and never-smokers.

The aim of the present study was to investigate whether smoking patients with chronic bronchitis (CB) and recurrent exacerbations show signs of depressed cell-mediated immunity (CMI), as reflected in the cutaneous delayed-type hypersensitivity (DTH) reaction, in comparison with asymptomatic smokers and healthy never-smokers. The study was a comparative clinical study performed at a university hospital center of respiratory medicine. Sixteen smokers with stable CB and recurrent exacerbations, five of whom had mild airflow obstruction, 18 asymptomatic smokers and 18 healthy never-smokers, all aged between 35 and 64 years, participated. No subjects treated with corticosteroids or N-acetylcysteine were included. Cutaneous DTH-reactions to seven recall antigens were assessed with Multitest, a standardized in vivo test of clinical CMI. Reactions were assessed 48 h after application by measurement of skin induration. A score (sum in mm of positive reactions) was created to assess overall reactivity. Neither the score nor the number of positive reactions differed significantly between the three study groups. Men had a significantly higher reactivity than women (P < 0.05) irrespective of group affiliation. No influence of smoking status on DTH reactivity could be seen. In the CB group no correlation was found between DTH reactivity and number of exacerbations the past 2 years. Patients with chronic bronchitis and recurrent exacerbations did not differ from asymptomatic smokers or healthy never-smokers with respect to cutaneous DTH reactions. Depression of CMI, as measured in this study, does not seem to be a primary factor behind recurrent exacerbations in smokers with CB.

Immunological findings in blood and bronchoalveolar lavage fluid in chronic bronchitis patients with recurrent infectious exacerbations.

Bronchial infections are common in smokers and seem to be related to the presence of chronic bronchitis (CB). Why only some smokers develop repeated bronchial infections is not known. The aim of this study was to screen for immunological changes associated with disease in patients with CB and recurrent infectious exacerbations compared to asymptomatic smokers. Sixteen smokers with stable CB and recurrent infectious exacerbations, and 18 asymptomatic smokers, all without any immunomodulating treatment, underwent bronchoscopy and bronchoalveolar lavage (BAL). Smoking history and current smoking status were comparable. Serum levels of immunoglobulin (Ig)A, IgM, IgG and IgG subclasses were measured. Blood and BAL lymphocyte phenotypes and proliferative responses of peripheral blood mononuclear cells (PBMCs) to various stimulators were analysed. Unstimulated and tetanus toxoid-stimulated production of cytokines in PBMC cultures was measured. Natural killer (NK-) cell activity was analysed. A significantly (p<0.05) lower level of IgG3 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-alpha (TNF-alpha) and interferon-gamma, but not of IL-2, IL-4 or transforming growth factor-beta2, were found in supernatants from cultured cells in both study groups. Stimulated TNF-alpha 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.

Discrimination between rival dosing histories.

PURPOSE: In population pharmacokinetic studies, the dosing history is sometimes recorded in more than one way. The purpose of this study was to develop and evaluate a procedure for discriminating between rival dosing histories, i.e., for each individual in a data set, identify the dosing history that is the most plausible. METHODS: The procedure consists of four steps. In the first step we identify individuals whose dosing histories produce predictions that are consistent. In the second step these individuals are used to build a population pharmacokinetic model which is used, in step three, to select the dosing history for the individuals not identified in step one. In step four the population model is refined using the best available dosing histories for all individuals. The proposed procedure was evaluated using both simulations and a real data set, in which two dosing histories, based on patient diaries and electronic monitoring devices (MEMS) were available. RESULTS: In the real data set, estimated variabilities were almost always lower when the selected dosing histories were used compared to when no selection procedure was used. The diary dosing histories were selected more often than the MEMS dosing histories. In the simulations, the parameter estimates obtained using the selection procedure were closer to the true parameter values compared to when only one of the dosing histories was used. CONCLUSIONS: The proposed procedure appears to be robust and should be beneficial in at least two respects: improved parameter estimation of population pharmacokinetic and PK/PD models and objective information by which dosage recording methodologies can be compared and patient dose recording behavior can be assessed.