Objective To investigate the effects of methylprednisolone on airway inflammation of chronic bronchitis in rats, and to explore its possible mechanism. Methods Forty SD rats were randomly divided into five groups, ie. a blank control group, amethylprednisolone control group, a model group, and two methylprednisolone intervention groups. Chronic bronchitis model was established by cigarette inhalation in the model group and two intervention groups. Methylprednisolone was injected intraperitoneally in the two intervention groups before exposing to cigarette smog ( at the dose of 1 mg/ kg and 10 mg/ kg, qd,respectively) . The protein expression of phosphodiesterase 4D ( PDE4D ) in trachea and lung samples was determined by immunohistochemical staining. The average optical density of positive staining of PDE4D was determined by image analysis technique and gray scale scanning. Bronchoalveolar lavage fluid ( BALF) was collected for total and differential cell counts, and the concentrations of TNF-αand interleukin-8 ( IL-8) in BALF were detected by ELISA. Results Cigarette smoking induced obvious airway inflammation in themodel group, and the inflammation was alleviated in the two methylprednisolone intervention groups.Compared with the two control groups, the expression of PDE4D was obviously elevated in tracheal and lungs in the model group( P lt; 0. 05) . Moreover, the increased expression of PDE4D was positively related with theincreased release of TNF-αand IL-8 in BALF. The expression of PDE4D and the release of TNF-αand IL-8 in BALF were decreased after the treatment with methylprednisolone in a dose-dependent manner ( P lt;0. 05) . Compare with the low dose intervention group, there was no markedly difference related to PMNnumber and TNF-α release in the high dose intervention group ( P gt; 0.05) . Conclusions Methylprednisolone may alleviate airway inflammation of chronic bronchitis by inhibiting the expression of PDE4D in rats. Inhibition of PDE4D may down-regulate TNF-αactivity, which may further reduce IL-8 release and alleviate airway inflammation.
Objective To evaluate and select essential medicine for acute exacerbation of chronic bronchitis (AECB) using evidence-based methods based on the burden of disease. Methods By means of the approaches, criteria, and workflow set up in the second article of this series, we referred to the recommendations of evidence-based or authority guidelines from inside and outside China, collected relevant evidence from domestic clinical studies, and recommended essential medicine based on evidence-based evaluation. Data were analyzed by Review Manager (RevMan) 5.1 and GRADE profiler 3.6 to evaluate quality of evidence. Results (1) Five guidelines were included (four foreign guidelines, one domestic guideline; three based on evidence, two based on expert consensus). (2) Medicines recommended at least twice by the National Essential Medicine List (NEML, 2009 version) and Chinese National Formulary (CNF) contained: ipratropium bromide (four times), amoxicillin amp; clavulanate potassium (three times), and corticosteroid (three times), cefuroxime (twice), ciprofloxacin (twice), levofloxacin (twice), salbutamol (twice) and dextromethorphan (twice). (3) As for domestic study evidence, a result of one RCT indicated that amoxicillin amp; clavulanate potassium had efficiencies of 92.3% to 94.7% (n=77, low quality). A result of three RCTs (n=275, low quality) indicated that cefuroxime had efficiencies of 67.6% to 90% and an incidence of 5% as to adverse reaction that mainly included skin rashes, diarrhea, etc. A result of two RCTs (n=120, low quality) indicated that ciprofloxacin had efficiencies of 78.3% to 86.6%, bacterial clearance rates of 72.7% to 86.5% and the incidences of 8.7% to 16.2% as to adverse reaction that mainly included gastrointestinal reaction, skin rashes, etc. A result of seven RCTs (n=523, low quality) indicated that levofloxacin had efficiencies of 72.5% to 94.5%, bacterial clearance rates of 82.1% to 95.8% and the incidences of 5% to 7.5% as to adverse reaction. A result of two RCTs (n=239, low quality) indicated that salbutamol had efficiencies of 85.4% to 96.7%. A result of one RCT (n=95, low quality) indicated that ipratropium bromide had efficiencies of 98%. A result of five RCTs (n=466, low quality) indicated that the combined use of budesonide and bronchodilators had efficiencies of 93.4% to 97.8%. Conclusion (1) We offer a b recommendation for cefuroxime, amoxicillin amp; clavulanate potassium, ciprofloxacin and levofloxacin used in the treatment of AECB. (2) We offer a b recommendation for glucocorticoid (budesonide, aerosol) and anticholinergic bronchodilator (ipratropium bromide) and a weak recommendation for short-acting β2-agonist bronchodilator (salbutamol) and antitussive agent (dextromethorphan) for alleviating symptoms due to AECB. (3) We make a recommendation against mucolytic agents and theophylline as routine use. (4) More large-scale, multi-center, double-blinded RCTs are needed in clinical and pharmacoeconomic studies on AECB and outcome indicator should be improved in order to produce high-quality local evidence.
Objective To evaluate the effectiveness and safety of clarithromycin extended-release and immediate-release formulations in the treatment of patients with acute exacerbation of chronic bronchitis. Methods The randomized controlled trials (RCTs) of clarithromycin extended-release and immediate-release formulations in the treatment of patients with acute exacerbation of chronic bronchitis were searched in the following electronic databases: The Cochrane Library (Issue 1, 2010), PubMed (2000 to Jan. 2010), EMbase (1980 to Dec. 2009), CBM (2000 to Jan. 2010), and WanFang Data (2000 to Jan. 2010). Two reviewers independently screened the included studies, abstracted the data and assessed the quality. The RevMan 5.0 software was used to conduct meta-analyses. Results A total of four RCTs involving 2041 patients were included, and the Jadad scales of all studies were more than five. The results of meta-analyses showed that there was no significant difference between the extended-release formulation group and the immediate-release formulation group in aspects of the clinical cure rate (RR=0.93, 95%CI 0.96 to 1.03), the pathogen eradication rate (RR=0.99, 95%CI 0.94 to 1.04), and the adverse reaction incidence rate (RR=1.06, 95%CI 0.90 to 1.25). Conclusion As the present evidence shows, there is no significant difference in effectiveness and safety between the clarithromycin extended-release and immediate-release formulations in the treatment of patients with acute exacerbation of chronic bronchitis.