Macrolide therapy decreases chronic obstructive pulmonary disease exacerbation: a meta-analysis.

BACKGROUND: Macrolide antibiotics have anti-inflammatory effects, and long-term administration may reduce chronic obstructive pulmonary disease (COPD) exacerbations. OBJECTIVE: To investigate the effects of long-term treatment of macrolide therapy for COPD. METHODS: We searched the PubMed and Embase databases to identify randomized controlled trials that evaluated the effect of macrolide therapy (of at least 2 weeks) for COPD. The primary outcome assessed was the frequency of acute exacerbations during follow-up. RESULTS: Six trials involving 1,485 COPD patients were included in the analysis. Analysis of the pooled data of all 6 trials showed that macrolide administration reduced the frequency of acute exacerbations of COPD [risk ratio (RR) = 0.62; 95% CI 0.43-0.89, p = 0.01]. Subgroup analysis showed that only erythromycin might be associated with decreased COPD exacerbations (erythromycin: p = 0.04, azithromycin: p = 0.22, clarithromycin: p = 0.18). Moreover, macrolide therapy for 3 months did not significantly reduce the number of exacerbations (p = 0.18), whereas a beneficial effect was conclusive in the 6-month (p = 0.009) and 12-month (p = 0.03) treatment subgroups. In addition, nonfatal adverse events were more frequent in the macrolide treatment groups than in the controls (RR = 1.32; 95% CI 1.06-1.64, p = 0.01). However, related clinical factors had no influence on the overall result (p = 0.19). There was no publication bias among the included trials. CONCLUSIONS: Macrolide therapy was effective and safe in decreasing the frequency of exacerbations in patients with COPD. Treatment might provide a significant benefit but only when therapy lasts more than 6 months.

Meta-analysis: Noninvasive ventilation in acute cardiogenic pulmonary edema.

BACKGROUND: Noninvasive ventilation (NIV) is commonly used to treat patients with acute cardiogenic pulmonary edema (ACPE), but the findings of a recent large clinical trial suggest that NIV may be less effective for ACPE than previously thought. PURPOSE: To provide an estimate of the effect of NIV on clinical outcomes in patients with ACPE that incorporates recent trial evidence and explore ways to interpret that evidence in the context of preceding evidence that favors NIV. DATA SOURCES: PubMed and EMBASE from 1966 to December 2009, Cochrane Central Register of Controlled Trials and conference proceedings through December 2009, and reference lists, without language restriction. STUDY SELECTION: Randomized trials that compared continuous positive airway pressure and bilevel ventilation with standard therapy or each other. DATA EXTRACTION: Two independent reviewers extracted data. Outcomes examined were mortality, intubation rate, and incidence of new myocardial infarction (MI). DATA SYNTHESIS: Compared with standard therapy, continuous positive airway pressure reduced mortality (relative risk [RR], 0.64 [95% CI, 0.44 to 0.92]) and need for intubation (RR, 0.44 [CI, 0.32 to 0.60]) but not incidence of new MI (RR, 1.07 [CI, 0.84 to 1.37]). The effect was more prominent in trials in which myocardial ischemia or infarction caused ACPE in higher proportions of patients (RR, 0.92 [CI, 0.76 to 1.10] when 10% of patients had ischemia or MI vs. 0.43 [CI, 0.17 to 1.07] when 50% had ischemia or MI). Bilevel ventilation reduced the need for intubation (RR, 0.54 [CI, 0.33 to 0.86]) but did not reduce mortality or new MI. No differences were detected between continuous positive airway pressure and bilevel ventilation on any clinical outcomes for which they were directly compared. LIMITATIONS: The quality of the evidence base was limited. Definitions, cause, and severity of ACPE differed among the trials, as did patient characteristics and clinical settings. CONCLUSION: Although a recent large trial contradicts results from previous studies, the evidence in aggregate still supports the use of NIV for patients with ACPE. Continuous positive airway pressure reduces mortality more in patients with ACPE secondary to acute myocardial ischemia or infarction. PRIMARY FUNDING SOURCE: None.

[Prevalence of allergic bronchopulmonary aspergillosis in Chinese patients with bronchial asthma].

OBJECTIVE: To evaluate the frequency of sensitization to Aspergillus antigens and the prevalence of allergic bronchopulmonary aspergillosis (ABPA) in asthmatic patients. METHODS: Two hundred consecutive non-smoking outpatients with asthma (≥ 18 years) underwent skin testing with aeroallergens, peripheral eosinophil counting, measurements of total serum IgE level and specific IgE against Aspergillus fumigatus, radiologic investigations and pulmonary function tests. RESULTS: Eleven patients (5.5%) had a positive skin reactivity to Aspergillus antigens. Five of these 11 patients (45.5%) met the diagnostic criteria of ABPA, an overall prevalence of 2.5% (5/200). There were 2 males and 3 females, aging from 19 to 62 years, with a disease duration from 15 to 40 years. All of the patients had asthmatic symptoms such as cough and wheeze. Moderate to severe obstructive ventilatory defect was found in 4 patients. Total serum IgE levels and specific IgE against Aspergillus fumigates were elevated significantly in all the patients, and elevated eosinophil count was found in 3 patients. Three cases were diagnosed as ABPA-CB because of the presence of central bronchiectasis on HRCT. CONCLUSIONS: The prevalence of ABPA in Chinese patients with asthma was underestimated. Clinical features of ABPA were similar to asthma alone, but with longer duration and more severe lung function defect. Sensitization to Aspergillus, increased eosinophils and total serum IgE levels were important indicators for the diagnosis of ABPA.

A meta-analysis of the effects of atrial overdrive pacing on sleep apnea syndrome.

BACKGROUND: Atrial overdrive pacing is a novel method that has been used to treat patients with sleep apnea syndrome (SAS) in many trials. However, the effects of atrial overdrive pacing on SAS are unclear. METHODS: Studies were retrieved from the PubMed and EMBASE databases (1966 to January 2008), the Central Cochrane Controlled Trials Register (January 2008), and reference lists. Randomized controlled trials were selected that compared atrial overdrive pacing with nonpacing in SAS. Information on study design, patient characteristics, the apnea hypopnea index (AHI), and minimum arterial oxygen saturation (SaO2) was extracted. RESULTS: Eight trials that included a total of 129 patients were identified. The analysis showed that atrial overdrive pacing, as compared to nonpacing, reduced the AHI and increased the minimum SaO2 significantly in the subgroup of patients who presented predominantly with central sleep apnea syndrome (CSAS) (for AHI, mean difference [MD]=-17.08, 95% confidence interval [CI]: -23.25 to -10.91; for minimum SaO2, MD=4.00, 95% CI: 2.48 to 5.52, respectively). The AHI (MD=-2.94, 95% CI: -5.33 to -0.54) was also significantly reduced in the subgroup of patients who showed predominant obstructive sleep apnea syndrome (OSAS), but the result of the analysis of AHI in OSAS-predominant trials was not robust to the exclusion of some trials. There was weak evidence of an increase in minimum SaO2 in the subgroup in which OSAS was predominant (MD=0.13, 95% CI: -1.18 to 1.45). CONCLUSIONS: Atrial overdrive pacing appears to be effective in patients with CSAS. The role of atrial overdrive pacing in OSAS remains unclear.

[Study of the role of insulin and insulin receptor in allergic airway inflammation of rats].

OBJECTIVE: To reveal the possible mechanism underlying the inverse relationship between IDDM and asthma and the role of insulin and insulin receptor in allergic airway inflammation. METHODS: Diabetes mellitus was induced in rats by intraperitoneal injection of streptozotocin. Rats were sensitized by subcutaneous injection of ovalbumin (OVA) and challenged with an aerosolized solution of 1% OVA for 20 min 14 days after sensitization to provoke allergic airway inflammation. Sixty-four male Sprague-Dawley rats were divided into 8 groups: group A (asthma), group D (diabetes), group I (insulin treated), group AD (asthma + diabetes), group AI (asthma + insulin treated), group DI (diabetes + insulin treated), group ADI (asthma + diabetes + insulin treated), and group C (control). Blood glucose measurements, total and differential leukocyte counts and serum insulin measurements were carried out. Bronchoalveolar lavage (BAL) were performed, total and differential cell counts were determined. Hematoxylin-eosin stained paraffin section of lung tissue was examined to observe the histological changes. Immunohistochemistry method was used to describe the distribution of insulin receptor, and the expression of insulin receptor mRNA were measured by RT-PCR. RESULTS: All groups of diabetes had higher blood glucose levels than non-diabetes groups. After antigen challenge, the rats of group A, AI, ADI exhibited airway inflammation characterized by significantly elevated eosinophils and neutrophils, group AD only exhibited mild airway inflammation. The serum insulin levels were higher in groups ADI, AI and A (27 mIU/L +/- 8 mIU/L, 83 mIU/L +/- 12 mIU/L, 71 mIU/L +/- 12 mIU/L respectively) compared with their respective control group (group DI, I, C, 15 mIU/L +/- 4 mIU/L, 64 mIU/L +/- 9 mIU/L; 49 mIU/L +/- 14 mIU/L respectively). Immunohistochemistry staining for insulin receptor revealed a diffused distribution pattern of the receptor in the lung tissue. Positive cells infiltrating in the alveolar spaces, submucosa of bronchus, blood vessels, and bronchial mucosa were increased significantly in groups A, AI and ADI. In groups with induced diabetes the expression of insulin receptor mRNA was elevated compared with that in the non-diabetes groups (0.2588 +/- 0.0809 vs 0.0896 +/- 0.0308, P = 0.00). CONCLUSION: Administration of low dose insulin aggravated airway inflammation to antigen provocation in rats. Insulin secretion is increased in the presence of inflammation. In the lung of antigen-challenged rats, insulin receptors on the surface of the infiltrating inflammatory cells and bronchial secretory cells are increased.

[Retrospective analysis of the studies on sleep apnea-hypopnea syndrome in the past twenty years in our country].

OBJECTIVE: To summarize and evaluate the studies on sleep apnea-hypopnea syndrome (SAHA) in our country. METHOD: Articles on the study of SAHS published in major journals of our country from January, 1982 to June, 2002 were evaluated retrospectively. RESULTS: 262 articles were recruited. More papers covering more aspects of this disorder were getting published in the past 20 years. However, basic studies, multidisciplinary studies, more effective therapies and large size, multicenter, and prospective trials were lacking. The study of SAHS in different provinces did not reach the same level. CONCLUSION: Large sampled, multicenter and multidisciplinary prospective trials are needed to study more effective and acceptable therapies as well as the basic mechanism of SAHS.

Chronic intermittent hypoxia aggravates cardiomyocyte apoptosis in rat ovariectomized model.

BACKGROUND: The prevalence of obstructive sleep apnea (OSA) increases after menopause in women, but remains under diagnosed because of social or lifestyle factors. It is important to evaluate the hazards of OSA on cardiovascular disease in menopausal women. We tested the hypothesis that chronic intermittent hypoxia (CIH) may aggravate cardiomyocyte apoptosis in ovariectomized (OVX) Sprague Dawley (SD) rats; the changes of anti-oxidation ability in cardiac muscles may be one of the reasons for cardiomyocyte apoptosis. METHODS: Forty-eight 60-day old female SD rats were randomly divided into a CIH group, OVX group, OVX+CIH (OC) group, and handled control (HC) group, and the rats were exposed either to CIH (nadir O2 6%) or handled normoxic controls. The changes of body weight and whole heart weight were measured. Super oxide dismutase (SOD) and malonaldehyde (MDA) were used to evaluate the level of oxidative stress. TdT-mediated dUTP nick end labeling (TUNEL) was used to measure apoptosis in each rat. Western blotting was used to measure apoptosis associated proteins in cardiac muscle samples from each rat. RESULTS: When compared with the HC and CIH groups, the levels of oxidative stress in the OC and OVX groups were significantly higher. The levels of SOD in the HC, CIH, OC, and OVX groups were (47.99 ± 4.89), (53.60 ± 4.47), (20.99 ± 2.72), and (30.64 ± 3.79) mmol/mg protein; significantly increased in the CIH group (P < 0.05) and significantly decreased in the OC (P < 0.01) and OVX (P < 0.05) groups. The levels of MDA in the HC, CIH, OVX, and OC groups were (1.63 ± 0.20), (1.93 ± 0.77), (3.30 ± 0.39), and (1.95 ± 0.20) mmol/mg protein; it significantly increased in the CIH (P < 0.05), OC (P < 0.01), and OVX (P < 0.05) groups compared with the HC group. Bax protein expression was significantly increased and bcl-2 protein expression was significantly reduced after CIH compared with HC rats (P < 0.05). The protein expression of bax and bcl-2 in the OC group was not significantly different from the CIH group, but the ratio of bax/bcl-2 was significantly increased in the OC group (P < 0.05); this was associated with severe cardiomycyte apoptosis in the OC group. TUNEL confirmed this observation. CONCLUSIONS: This study found that CIH may induce oxidative stress in OVX rats but not in CIH rats, and cause more severe cardiomyocyte apoptosis in OVX rats compared with CIH rats. This means that OVX rats exposed to CIH suffered more severe cardiac injury compared with CIH rats due to reduced antioxidation. These findings may partly explain the reason why OSA has a worse cardiovascular impact on menopausal women, and emphasize the importance of detection and early treatment of OSA in menopausal patients.