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      Randomised, controlled trial of N-acetylcysteine for treatment of acute exacerbations of chronic obstructive pulmonary disease [ISRCTN21676344]


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          Prophylactic treatment with N-acetylcysteine (NAC) for 3 months or more is associated with a reduction in the frequency of exacerbations of chronic obstructive pulmonary disease (COPD). This raises the question of whether treatment with NAC during an acute exacerbation will hasten recovery from the exacerbation.


          We have examined this in a randomised, double-blind, placebo controlled trial. Subjects, admitted to hospital with an acute exacerbation of COPD, were randomised within 24 h of admission to treatment with NAC 600 mg b.d. (n = 25) or matching placebo (n = 25). Treatment continued for 7 days or until discharge (whichever occurred first). To be eligible subjects had to be ≥ 50 years, have an FEV 1 ≤ 60% predicted, FEV 1/VC ≤ 70% and ≥ 10 pack year smoking history. Subjects with asthma, heart failure, pneumonia and other respiratory diseases were excluded. All subjects received concurrent treatment with prednisone 40 mg/day, nebulised salbutamol 5 mg q.i.d and where appropriate antibiotics. FEV 1, VC, SaO 2 and breathlessness were measured 2 hours after a dose of nebulised salbutamol, at the same time each day. Breathlessness was measured on a seven point Likert scale.


          At baseline FEV 1 (% predicted) was 22% in the NAC group and 24% in the control group. There was no difference between the groups in the rate of change of FEV 1, VC, SaO 2 or breathlessness. Nor did the groups differ in the median length of stay in hospital (6 days for both groups).


          Addition of NAC to treatment with corticosteroids and bronchodilators does not modify the outcome in acute exacerbations of COPD.

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          Airway eosinophilia in chronic bronchitis during exacerbations.

          To examine the nature and the degree of airway inflammation in chronic bronchitis during exacerbations, bronchial biopsies and sputum were obtained in 11 subjects with chronic bronchitis examined during an exacerbation, and in 12 subjects with chronic bronchitis examined under baseline conditions. All subjects were nonatopic. Lobar bronchial biopsies were assessed using histochemical and immunohistochemical techniques, and sputum was examined for differential cell counts of leukocytes. Subjects with bronchitis during exacerbations had, on average, 30-fold more eosinophils in their bronchial biopsies than did those examined under baseline conditions (p < 0.001). Although to a lesser extent, the numbers of neutrophils (p < 0.01), T-lymphocytes (CD3) (p < 0.05), VLA-1-positive cells (p < 0.01), and TNF-alpha positive cells (p < 0.05) were also increased during exacerbations. By contrast, the T-lymphocyte subpopulations (CD4 and CD8) and the numbers of macrophages, mast cells, IL-2R-positive cells, and IL-1 beta-positive cells were similar in the two groups of subjects, as well as the percentages of ICAM-1- and E-selectin-positive vessels. Eosinophils were also increased in sputum of subjects with exacerbations when compared with those examined under baseline conditions (p < 0.05). In conclusion, exacerbations of chronic bronchitis are associated with a marked airway eosinophilia and with a milder increase in the number of neutrophils, activated T-lymphocytes, and TNF-alpha-positive cells in the bronchial mucosa.
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            Oral corticosteroids in patients admitted to hospital with exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial.

            The role of oral corticosteroids in treating patients with exacerbations of chronic obstructive pulmonary disease (COPD) remains contentious. We assessed in a prospective, randomised, double-blind, placebo-controlled trial the effects of oral corticosteroid therapy in patients with exacerbations of COPD requiring hospital admission. We recruited patients with non-acidotic exacerbations of COPD who were randomly assigned oral prednisolone 30 mg once daily (n=29) or identical placebo (n=27) for 14 days, in addition to standard treatment with nebulised bronchodilators, antibiotics, and oxygen. We did spirometry and recorded symptom scores daily in inpatients. Time to discharge and withdrawals were noted in each group. We recalled patients at 6 weeks to repeat spirometry and collect data on subsequent exacerbations and treatment. Hospital stay was analysed by intention to treat and forced expiratory volume in 1 s (FEV1) according to protocol. FEV1 after bronchodilation increased more rapidly and to a greater extent in the corticosteroid-treated group: percentage predicted FEV1 after bronchodilation rose from 25.7% (95% CI 21.0-30.4) to 32.2% (27.3-27.1) in the placebo group (p<0.0001) compared with 28.2% (23.5-32.9) to 41.5% (35.8-47.2) in the corticosteroid-treated group (p<0.0001). Up to day 5 of hospital stay, FEV1 after bronchodilation increased by 90 mL daily (50.8-129.2) and by 30 mL daily (10.4-49.6) in the placebo group (p=0.039). Hospital stays were shorter in the corticosteroid-treated group. Groups did not differ at 6-week follow-up. These data provide evidence to support the current practice of prescribing low-dose oral corticosteroids to all patients with non-acidotic exacerbations of COPD requiring hospital admission.
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              Increased exhalation of hydrogen peroxide in patients with stable and unstable chronic obstructive pulmonary disease.

              An imbalance between oxidative stress and antioxidative capacity is thought to play an important role in the development and progression of chronic obstructive pulmonary disease (COPD). To assess the lung oxidative status in patients with COPD, we studied whether exhaled hydrogen peroxide (H2O2) is increased in breath condensate of patients with stable COPD (n = 12, mean FEV1 51% pred) and in patients with exacerbated COPD (n = 19, actual FEV1 36% pred) compared with a healthy control group (n = 10, FEV1 108% pred). Expired breath condensate during 15 min of tidal breathing was collected by cooling. The concentration of H2O2 was measured spectrophotometrically by means of horse radish peroxidase-catalyzed oxidation of tetramethylbenzidine. Concentrations of H2O2 (mean +/- SEM) were significantly elevated at 0.205 +/- 0.054 microM in patients with stable COPD compared with 0.029 +/- 0.012 microM in the control group (p < 0.05) and were further increased to 0.600 +/- 0.075 microM in patients with acutely exacerbated COPD (p < 0.001 compared with patients with stable COPD). Patients with pulmonary infiltrates on chest radiograph showed similar values compared with patients without obvious infiltrates. These findings demonstrate that patients with stable COPD exhibit increased oxidant production in the airways and that oxidant production increases further during exacerbations.

                Author and article information

                BMC Pulm Med
                BMC Pulmonary Medicine
                BioMed Central (London )
                6 December 2004
                : 4
                : 13
                [1 ]Department of Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand
                Copyright © 2004 Black et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Research Article

                Respiratory medicine


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