Aktuelle Abstracts 13.07.01

IgG subclasses in smokers with chronic bronchitis and recurrent exacerbations.

Qvarfordt I, Riise GC, Andersson BA, Larsson S
Department of Respiratory Medicine and Allergology, Sahlgrenska University Hospital, S-413 45 Goteborg, Sweden. ingemar.qvarfordt@medfak.gu.se

BACKGROUND: Tobacco smokers have lower serum levels of IgG than non-smokers. IgG subclass deficiency is common in patients with recurrent respiratory infections. Recurrent bronchial infections are common in smokers with chronic bronchitis (CB). We have investigated whether susceptibility to recurrent exacerbations in smokers with CB is associated with altered IgG subclass levels or IgG subclass deficiency. METHODS: Serum levels of IgG, IgA, IgM, and IgG subclasses 1-4 were determined by radial immunodiffusion in 100 subjects: 33 smokers with stable CB and recurrent exacerbations, 24 asymptomatic smokers, and 43 healthy never smokers. Systemic tobacco exposure was verified and excluded using a serum cotinine ELISA. Immunoglobulin data were log transformed to enable use of parametric statistical methods. RESULTS: Compared with never smokers, both patients with CB and asymptomatic smokers had significantly lower levels of IgG (median 9.7 g/l (range 5.6-15.2) and 9.9 (6.1-12.1) g/l v 12.0 (6.9-18.5) g/l) and IgG2 (2.8 (0.9-5.9) g/l and 2.5 (1.0-6.3) g/l v 4.0 (1.7-10.2) g/l). The estimated ratio of median values between the patients with CB and never smokers was 0.78 (95% confidence interval (CI) 0.69 to 0.89) for IgG and 0.65 (95% CI 0.50 to 0.83) for IgG2. The corresponding ratios between asymptomatic smokers and never smokers were 0.79 (95% CI 0.69 to 0.91) and 0.60 (95% CI 0.50 to 0.83), respectively. There were no significant differences between the smoking groups. CONCLUSIONS: Susceptibility to recurrent exacerbations in smokers with CB is not associated with lower levels of IgG subclasses than can be accounted for by smoking per se.

Thorax 2001 Jun;56(6):438-44

Effect of manually assisted cough and mechanical insufflation on cough flow of normal subjects, patients with chronic obstructive pulmonary disease (COPD), and patients with respiratory muscle weakness.

Sivasothy P, Brown L, Smith IE, Shneerson JM
Respiratory Support and Sleep Centre, Papworth Hospital, Papworth Everard, Cambridge CB3 8RE, UK. ps247@cus.cam.ac.uk

BACKGROUND: It has been suggested that cough effectiveness can be improved by assisted techniques. The effects of manually assisted cough and mechanical insufflation on cough flow physiology are reported in this study. METHODS: The physiological actions and patient self-assessment of manually assisted cough and mechanical insufflation were investigated in 29 subjects (nine normal subjects, eight patients with chronic obstructive pulmonary disease (COPD), four subjects with respiratory muscle weakness (RMW) with scoliosis, and eight subjects with RMW without scoliosis). RESULTS: The peak cough expiratory flow rate and cough expiratory volume were not improved by manually assisted cough and mechanical insufflation alone or in combination in normal subjects. The median increase in peak cough expiratory flow in subjects with RMW without scoliosis with manually assisted cough alone or in combination with mechanical insufflation of 84 l/min (95% confidence interval (CI) 19 to 122) and 144 l/min (95% CI 14 to 195), respectively, reflects improvement in the expulsive phase of coughing by these techniques. Manually assisted cough and mechanical insufflation in combination raised peak expiratory flow rate more than either technique alone in this group. The abnormal chest shape in scoliotic subjects and the fixed inspiratory pressure used made effective manually assisted cough and mechanical insufflation difficult in this group and no improvements were found. In patients with COPD manually assisted cough alone and in combination with mechanical insufflation decreased peak expiratory flow rate by 144 l/min (95% CI 25 to 259) and 135 l/min (95% CI 30 to 312), respectively. CONCLUSIONS: Manually assisted cough and mechanical insufflation should be considered to assist expectoration of secretions in patients with RMW without scoliosis but not in those with scoliosis.

Thorax 2001 Jun;56(6):432-7

Enhanced neutrophil response in chronic obstructive pulmonary disease.

Noguera A, Batle S, Miralles C, Iglesias J, Busquets X, MacNee W, Agusti AG
Serveis de Analisis Cliniques, Hospital Universitari Son Dureta, Palma de Mallorca, Spain.

BACKGROUND: Neutrophils are likely to play a major role in the inflammatory response seen in chronic obstructive pulmonary disease (COPD). This study sought to address the hypothesis that an enhanced neutrophil response to proinflammatory agents in COPD may contribute to their recruitment and activation in the lungs. METHODS: Circulating neutrophils were obtained from 10 patients with COPD, eight long term smokers with normal lung function, and eight healthy never smoking controls. The in vitro production of reactive oxygen species (ROS) was measured by the NADPH oxidase method (respiratory burst) and the surface expression of several adhesion molecules (Mac-1, LFA-1 and L-selectin) was measured by flow cytometry. Measurements were obtained under basal conditions and after stimulation with phorbol myristate acetate (PMA) and tumour necrosis factor alpha (TNFalpha). mRNA levels of p22-phox (a subunit of NADPH oxidase) and Mac-1 (CD11b) were also determined by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Patients with COPD showed enhanced respiratory burst compared with smokers with normal lung function, both under basal conditions (mean (SE) fluorescence intensity (MFI) 15.1 (0.5) v 11.6 (0.5); mean difference -3.4 (95% CI of the difference -5.1 to -1.8), p<0.01) and after PMA stimulation (MFI 210 (7) v 133 (10); mean difference -77 (95% CI of the difference -102 to -52), p<0.01). Mac-1 surface expression was also enhanced in patients with COPD, both under basal conditions (MFI 91 (5) v 45 (3); mean difference -46 (95% CI of the difference -61 to -31), p<0.001) and after stimulation with TNFalpha (MFI 340 (15) v 263 (11); mean difference -77 (95% CI of the difference -119 to -34), p=0.001). These differences were also apparent when patients with COPD were compared with non-smokers (p<0.05). The mRNA levels of p22-phox and Mac-1 (CD11b) were similar in patients with COPD and smokers with normal lung function, suggesting that the observed differences were due to post-transcriptional regulation. CONCLUSIONS: These results demonstrate an enhanced neutrophil response to proinflammatory agents in patients with COPD which may contribute to their enhanced recruitment and activation in the lungs of these patients. These findings support those of other studies which have indicated that the neutrophil is likely to play a major role in the pathogenesis of this disease.