There are little data describing noncellular changes in bronchial inflammation during exacerbations of chronic bronchitis. The relationship between sputum colour and airway inflammation at presentation has been assessed during an exacerbation in patients with chronic bronchitis and a primary care diagnosis of chronic obstructive pulmonary disease.Sputum myeloperoxidase, neutrophil elastase, leukotriene B 4 (LTB 4 ), interleukin-8 (IL-8), sol:serum albumin ratio and serum C-reactive protein were measured in patients presenting with an exacerbation and mucoid (n~27) or purulent sputum (n~42).Mucoid exacerbations were associated with little bronchial or systemic inflammation at presentation, and sputum bacteriology was similar to that obtained in the stable state. Purulent exacerbations were associated with marked bronchial and systemic inflammation (pv0.025 for all features) and positive sputum cultures (90%). Resolution was related to a significant reduction in LTB 4 (pv0.01), but no change in IL-8, suggesting that LTB 4 may be more important in neutrophil recruitment in these mild, purulent exacerbations. In the stable state, IL-8 remained higher in patients who had experienced a purulent exacerbation (2pv0.02).The presented results indicate that exacerbations of chronic bronchitis, defined by sputum colour, differ in the degree of bronchial and systemic inflammation. Purulent exacerbations are related to bacterial infection, and are associated with increased neutrophilic inflammation and increased leukotriene B 4 concentrations.
Background: Recent studies of the role of bacteria in chronic bronchitis have shown that bacterial colonisation is associated with enhanced inflammation and that purulent acute exacerbations of chronic bronchitis (AECB) are associated with bacteria and characterised by increased inflammation. Changes in bronchial inflammation in response to the success or failure of bacterial eradication following AECB were therefore studied. Methods: Bacterial quantitative culture and sputum markers of inflammation (myeloperoxidase (MPO), neutrophil elastase, leukotriene B4 (LTB4), sol:serum albumin ratio, and secretory leukoprotease inhibitor) were measured in patients presenting with culture positive purulent AECB and repeated 10 days and 2 months later. 41 patients provided sputum sufficient for both bacteriology and assessment of inflammation at baseline and day 10, and 46 provided sufficient sample for bacteriology, 40 of which could also be analysed for inflammation at 2 months (when clinically stable). Results: At day 10, 17 of the 41 patient samples had a positive bacterial culture. In the stable state, 18 of the 46 samples had a positive culture, but with a significantly lower bacterial load than at presentation. Although there was no difference between the groups at presentation, the concentration of MPO was lower (p<0.05) in those in whom bacteria were eradicated by day 10 than in those with persisting bacteria. The LTB4 concentration was similarly lower (p<0.001) in those in whom bacteria were eradicated than in those with persistent bacteria. In the stable clinical state the concentrations of both MPO and LTB4 were lower in those in whom bacteria were eradicated than in patients with persisting bacteria. Conclusion: Resolution of bronchial inflammation following AECB is related to bacterial eradication. Those in whom bacteria continue to be cultured in their sputum have partial resolution of inflammation which may reflect continued stimulation by the reduced bacterial load.
Background-Patients with more frequent exacerbations of chronic obstructive pulmonary disease (COPD) may have increased bronchial inflammation. Airway inflammation was measured in patients who had been thoroughly investigated with full pulmonary function testing, thoracic HRCT scanning, and sputum microbiology to examine further the relationship between exacerbation frequency and bronchial inflammation. Conclusions-There are several clinical features that directly influence bronchial inflammation in COPD. When these were carefully controlled for, patients with more frequent reported exacerbations had lower sputum concentrations of SLPI. This important antiproteinase is also known to possess antibacterial and antiviral activity. Further studies are required into the nature of recurrent exacerbations and, in particular, the regulation and role of SLPI in aVected individuals. (Thorax 2001;56:36-41) Keywords: chronic obstructive pulmonary disease; inflammation; secretory leukoprotease inhibitor (SLPI) Chronic obstructive pulmonary disease (COPD) comprises a heterogeneous group of conditions, characterised by varying degrees of expiratory airflow limitation, related to combinations of abnormalities in the large and small airways and to alveolar destruction. The patients have a reduced state of health that is (loosely) related to the degree of physiological abnormality.
IMPORTANCE Chronic obstructive pulmonary disease (COPD) is a major global health issue and theophylline is used extensively. Preclinical investigations have demonstrated that low plasma concentrations (1-5 mg/L) of theophylline enhance antiinflammatory effects of corticosteroids in COPD. OBJECTIVE To investigate the effectiveness of adding low-dose theophylline to inhaled corticosteroids in COPD. DESIGN, SETTING, AND PARTICIPANTS The TWICS (theophylline with inhaled corticosteroids) trial was a pragmatic, double-blind, placebo-controlled, randomized clinical trial that enrolled patients with COPD between February 6, 2014, and August 31, 2016. Final follow-up ended on August 31, 2017. Participants had a ratio of forced expiratory volume in the first second to forced vital capacity (FEV 1 /FVC) of less than 0.7 with at least 2 exacerbations (treated with antibiotics, oral corticosteroids, or both) in the previous year and were using an inhaled corticosteroid. This study included 1578 participants in 121 UK primary and secondary care sites. INTERVENTIONS Participants were randomized to receive low-dose theophylline (200 mg once or twice per day) to provide plasma concentrations of 1 to 5 mg/L (determined by ideal body weight and smoking status) (n = 791) or placebo (n = 787). MAIN OUTCOMES AND MEASURES The number of participant-reported moderate or severe exacerbations treated with antibiotics, oral corticosteroids, or both over the 1-year treatment period. RESULTS Of the 1567 participants analyzed, mean (SD) age was 68.4 (8.4) years and 54% (843) were men. Data for evaluation of the primary outcome were available for 1536 participants (98%) (772 in the theophylline group; 764 in the placebo group). In total, there were 3430 exacerbations: 1727 in the theophylline group (mean, 2.24 [95% CI, 2.10-2.38] exacerbations per year) vs 1703 in the placebo group (mean, 2.23 [95% CI, 2.09-2.37] exacerbations per year); unadjusted mean difference, 0.01 (95% CI, −0.19 to 0.21) and adjusted incidence rate ratio, 0.99 (95% CI, 0.91-1.08). Serious adverse events in the theophylline and placebo groups included cardiac, 2.4% vs 3.4%; gastrointestinal, 2.7% vs 1.3%; and adverse reactions such as nausea (10.9% vs 7.9%) and headaches (9.0% vs 7.9%). CONCLUSIONS AND RELEVANCE Among adults with COPD at high risk of exacerbation treated with inhaled corticosteroids, the addition of low-dose theophylline, compared with placebo, did not reduce the number COPD exacerbations over a 1-year period. The findings do not support the use of low-dose theophylline as adjunctive therapy to inhaled corticosteroids for the prevention of COPD exacerbations.
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