早期应用无创通气治疗急性加重期COPD的研究

目的探讨无创正压通气（NIPPV）早期应用治疗急性加重期慢性阻塞性肺疾病（COPD）的指征和价值.方法采用前瞻性随机对照研究将90例COPD患者随机分为标准治疗对照组和标准治疗＋双水平正气道压力通气（BiPAP）观察组,分别于入选后2、24、72h、7d观察生命体征、测定肺功能、监测血气分析和氧饱和度,进行呼吸困难分级和辅助呼吸肌评分,从而比较两组患者的气体交换情况、住院时间、病死率及气管插管率等指标的差异.结果入组后2、24、72h、7d观察组较对照组PaCO2明显降低.观察组总的气管插管率明显降低（P＜0.05）,住院时间明显缩短（P＜0.01）.其中,当PaCO2≥65mmHg时两组患者插管率无明显差异（P＞0.05）,而PaCO2＜65mmHg时观察组较对照组插管率明显下降（P=0.04）.结论 COPD急性加重期早期应用BiPAP可明显增加患者的气体交换,改善患者的预后,提高患者的生活质量.     

Double-blind study of OM-85 in patients with chronic bronchitis or mild chronic obstructive pulmonary disease

BACKGROUND: Interventions against acute exacerbations (AEs) of chronic obstructive pulmonary disease (COPD) are increasingly called for to reduce morbidity, mortality and costs. OM-85, a detoxified immunoactive bacterial extract, has been shown to prevent recurrent exacerbations of bronchitis and COPD. OBJECTIVES: It was the aim of this study to demonstrate the protective effect of OM-85 against recurrent bronchitic exacerbations in patients with chronic bronchitis or mild COPD. The primary end point was the mean rate of AEs occurring within the study period. METHODS: This double-blind multi-centre study enrolled adult outpatients>40 years old of both sexes with a history of chronic bronchitis or mild COPD at the time of an AE. The treatment consisted of one capsule of OM-85 or placebo per day for 30 days, followed by three 10-day courses for months 3, 4 and 5, with a 6-month study duration and monthly control visits. RESULTS: One hundred and forty-two patients were treated with OM-85 and 131 received placebo. By the end of the treatment period, the mean number of AEs in the OM-85 group was 0.61 per patient versus 0.86 per patient in the placebo group (-29%; p=0.03). The difference between treatments was most notable in patients with a history of current or past smoking (-40%; p<0.01). No serious adverse events were attributed to the medication and no significant laboratory changes were reported. CONCLUSIONS: OM-85 significantly reduced the frequency of AEs in patients with a history of chronic bronchitis and mild COPD and was well tolerated. This study confirms the findings of previous trials conducted in elderly patients with chronic bronchitis or COPD.     

Open-label, randomized comparison trial of long-term outcomes of levofloxacin versus standard antibiotic therapy in acute exacerbations of chronic obstructive pulmonary disease

BACKGROUND AND OBJECTIVE: This study investigated whether treating acute exacerbations of COPD (AE-COPD) with levofloxacin modifies the long-term outcome of COPD patients in comparison with standard antibiotic regimens. METHODS: A 6-month open-label clinical trial of AE-COPD patients compared the outcomes of treating with levofloxacin versus standard therapy (clarithromycin, cefuroxime, or amoxicillin/clavulanate) at recommended doses for 10 days. Several variables were analysed: pulse oximetry, FEV1, health-related quality of life, infection-free interval, number of exacerbations, hospitalizations due to an exacerbation and mortality. RESULTS: Of the 116 patients initially enrolled, completion or withdrawal information was available for 50 patients in the levofloxacin arm and 52 in the standard therapy arm. At the end of the study, there were no differences in mortality (17.8% vs. 22.9%, P = 0.53), number of exacerbations (33 vs. 41, P = 0.40), pulse oximetry (median 91.71% vs. 92.46%, P = 0.18), FEV1 (median 51.31% vs. 47.14%, P = 0.30), health-related quality of life (median 8.63 vs. 10.75, P = 0.94) and infection-free interval (median 112 vs. 101 days, P = 0.72), for the levofloxacin and standard therapy, respectively. However, 12 out of 33 (33.6%) exacerbations treated with levofloxacin required in-hospital management versus 27 out of 41 (65.8%) treated with standard therapy (P = 0.02). CONCLUSION: This preliminary study suggests that 10-day treatment of AE-COPD with levofloxacin is associated with a reduction in hospitalizations compared with standard antibiotics despite there being no significant benefit in other outcome variables.     

Impact of salmeterol/fluticasone propionate versus salmeterol on exacerbations in severe chronic obstructive pulmonary disease

RATIONALE: Exacerbations of chronic obstructive pulmonary disease (COPD) greatly contribute to declining health status and the progression of the disease, thereby incurring significant direct and indirect health care costs. The prevention of exacerbations, therefore, is an important treatment goal. OBJECTIVES: To assess the impact of combination therapy with salmeterol/fluticasone propionate compared with salmeterol alone on moderate and severe exacerbations in patients with severe COPD and a history of repeated exacerbations. METHODS: Randomized, double-blind, parallel-group study. After a 4-wk run-in period, 994 clinically stable patients were randomized to one of two treatment groups: 507 patients received the salmeterol/fluticasone combination 50/500 micro g twice daily and 487 received salmeterol 50 micro g twice daily for 44 wk. MAIN RESULTS: The total number of exacerbations was 334 in the combination therapy and 464 in the salmeterol group (p < 0.0001). The annualized rate of moderate and severe exacerbations per patient was 0.92 in the combination therapy and 1.4 in the salmeterol group, corresponding to a 35% decrease. In addition, the mean time to first exacerbation in the combination therapy group was significantly longer compared with that of the salmeterol group (128 vs. 93 d, p < 0.0001). Other endpoints, including health-related quality of life, peak expiratory flow, and use of rescue medication, were significantly improved in the combination therapy group. Both treatments were well tolerated. CONCLUSIONS: This study demonstrates that combination therapy with salmeterol/fluticasone compared with salmeterol monotherapy significantly reduces the frequency of moderate/severe exacerbations in patients with severe COPD.     

The effectiveness of a bronchial drainage technique (ELTGOL) in COPD exacerbations

Background and objective:   Exacerbations of COPD are often characterized by increased mucus production that is difficult to treat and worsens patients' outcome. This study evaluated the efficacy of a chest physiotherapy technique (expiration with the glottis open in the lateral posture, ELTGOL) during acute exacerbations of COPD using as outcome measures sputum volume, length of hospitalization, reduction in dyspnoea (Borg score), improvement in quality of life (assessed by the St George Respiratory Questionnaire) and incidence of COPD exacerbations during follow up.
Methods:   The study recruited 59 patients hospitalized for the treatment of acute exacerbation of COPD, who were randomly assigned to a control group and an intervention group. The control group was treated with standard medical therapy while the intervention group was treated with ELTGOL plus medical therapy. A subgroup of patients was followed for 6 months to verify the effects on COPD exacerbations and need for hospitalizations.
Results:   At the time of hospital discharge there was no significant difference between the two groups in the outcome measures, with the exception of the Borg score, which was significantly improved in the ELTGOL group (4.3 ± 1.5 in the control group vs 3.0 ± 1.8 in the ELTGOL group, P  = 0.004). After 6 months there was no significant difference in the other measured parameters between a subset of the groups available for follow up. During follow up, the ELTGOL group had numerically fewer exacerbations and less need for hospitalization though differences were not statistically significant.
Conclusions:   Chest physiotherapy using the ELTGOL technique has a limited role in patients with mild exacerbation of moderate to severe COPD with a tendency towards fewer exacerbations and hospitalizations.     

High-Dose N-Acetylcysteine in the Prevention of COPD Exacerbations: Rationale and Design of the PANTHEON Study

Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation; from a pathophysiological point of view it involves many components, including mucus hypersecretion, oxidative stress and inflammation.

N-acetylcysteine (NAC) is a mucolytic agent with antioxidant and anti-inflammatory properties. Long-term efficacy of NAC 600mg/d in COPD is controversial; a dose-effect relationship has been demonstrated, but at present it is not known whether a higher dose provides clinical benefits. The PANTHEON Study is a prospective, ICS stratified, randomized, double-blind, placebo-controlled, parallel-group, multi-center trial designed to assess the efficacy and safety of high-dose (1200 mg/daily) NAC treatment for one year in moderate-to-severe COPD patients. The primary endpoint is the annual exacerbation rate. Secondary endpoints include recurrent exacerbations hazard ratio, time to first exacerbation, as well as quality of life and pulmonary function. The hypothesis, design and methodology are described and baseline characteristics of recruited patients are presented. 1006 COPD patients (444 treated with maintenance ICS, 562 ICS naive, aged 66.27±8.76 yrs, average post-bronchodilator FEV₁ 48.95±11.80 of predicted) have been randomized at 34 hospitals in China. Final results of this study will provide objective data on the effects of high-dose (1200 mg/daily) long-term NAC treatment in the prevention of COPD exacerbations and other outcome variables.     

Oral Fabrol (oral N-acetyl-cysteine) in chronic bronchitis

Five hundred and twenty-six patients suffering from chronic bronchitis were randomized to receive either N-acetylcysteine (NAC) or placebo during a 6-month period. The aim was to compare the number of acute exacerbations in the two groups. General practitioners were asked to enter patients with a diagnosis of chronic bronchitis, based on the MRC criteria. We failed to find any statistically significant difference in the number of exacerbations between the two treatment groups although there was a slight trend towards improvement in the NAC group during the first 3 months of the trial. The tolerability was similar for both treatments. Patients taking NAC showed a reduction in number of days on which they were incapacitated and this result was statistically significant.     

Long-term oral n-acetylcysteine reduces exhaled hydrogen peroxide in stable COPD

Oxidative stress caused by airway inflammation is increased in chronic obstructive pulmonary disease (COPD) and may account for the progressive deterioration of structure and function of the respiratory tract observed in this disease. Antioxidant defences of the respiratory tract may be overwhelmed by the oxidant burden in COPD and possibly restored with antioxidant therapy. The level of hydrogen peroxide (H(2)O(2)) concentration in exhaled air condensate (EAC) is a valuable tool for assessing and monitoring oxidative stress. This study aimed to verify the effect of 2-month oral N-acetylcysteine (NAC) treatment compared to placebo on the H(2)O(2) content in EAC of 55 clinically stable COPD patients (48 males), mean age 65.93+/-9.3 years. After clinical examination, pulmonary function tests, and collection of EAC for the basal (T0) assay of H(2)O(2), patients were randomly allocated to group A (usual therapy plus oral NAC 600 mg b.i.d. for 2 months) or group B (usual therapy plus placebo b.i.d. for 2 months). H(2)O(2) assay in EAC was repeated at 15 (T15), 30 (T30), and 60 (T60) days after the start of therapy in each group. All patients were non-smokers or ex smokers for at least 5 years and the two groups were comparable in terms of demographic, respiratory function, and EAC data at baseline. The H(2)O(2) level in EAC of group A was significantly decreased at T15 (1.00+/-0.38 SD microM; p=0.003), T30 (0.91+/-0.44 microM; p=0.007), and T60 (0.83+/-0.41 microM; p=0.000) compared to T0 (1.28+/-0.61 microM). No significant decrease in H(2)O(2) of group B was found at any time point. We conclude that oral NAC 600 mg b.i.d. for 2 months rapidly reduces the oxidant burden in airways of stable COPD patients.     

Intravenous diuretic and vasodilator therapy reduce plasma brain natriuretic peptide levels in acute exacerbation of chronic obstructive pulmonary disease

Background and objective: Plasma concentrations of brain natriuretic peptide (BNP) are elevated in patients with chronic obstructive pulmonary disease (COPD), and high plasma BNP levels are associated with a poor prognosis. We aimed to evaluate the effects of a diuretic and a vasodilator on plasma BNP levels and health‐related quality of life (HRQOL) in patients with acute exacerbations of COPD (AECOPD). Methods: Forty patients with an AECOPD and high plasma BNP levels, but without any clinical evidence of cor pulmonale, were selected. The patients were randomly divided into two groups of 20 patients. In addition to standard treatment for AECOPD, the patients in group I were treated with a mild diuretic, and those in group II were treated with the diuretic and a vasodilator. Twenty patients with stable COPD were selected as a control group. Plasma BNP concentrations were measured on admission and on the third and sixth days. The patients' HRQOL was evaluated using the short‐form 36‐item (SF‐36) questionnaire before and after treatment. Results: Plasma BNP concentrations in patients with AECOPD were significantly decreased after treatment, and this decrease was more striking in group II than in group I. There were no significant differences in SF‐36 domain scores between patients with stable COPD and those with acute exacerbations who were treated with a diuretic and a vasodilator. Conclusions: Plasma BNP levels decreased rapidly in patients with an AECOPD after therapy with a diuretic and a vasodilator, and the treatment did not impair their health status.     

N-乙酰半胱氨酸对COPD患者血中血管内皮素、一氧化氮的影响

目的探讨N-乙酰半胱氨酸对慢性阻塞性肺疾病（COPD）患者血清中血管内皮素及一氧化氮水平的影响。方法AECOPD患者60例，随机分为对照组及NAC组，测定两治疗组治疗前、后血浆内皮素-1（ET—1）和一氧化氮（NO）含量的变化。结果两组治疗后ET—1含量均低于治疗前，而NO高于治疗前（P（0．05）；但所有这些变化均以N-乙酰半胱氨酸组的变化程度更明显（P（0．01）。结论N-乙酰半胱氨酸有助于COPD患者维持体内舒血管因子及缩血管因子平衡，可能对肺动脉高压的形成有一定的预防作用。     

Efficacy of inhaled steroids in undiagnosed subjects at high risk for COPD: results of the detection, intervention, and monitoring of COPD and asthma program

BACKGROUND AND AIM: COPD leads to a progressive decline of pulmonary function. Family physicians treat a substantial number of patients with COPD and are encouraged to start treatment at as early a stage as is possible. This study analyzed the effectiveness of early inhaled corticosteroid treatment on the decline of pulmonary function in COPD patients. PATIENTS AND SETTING: Subjects with a rapid decline in lung function (ie, FEV(1) decline, > 80 mL/yr) who had never before received a diagnosis of asthma or COPD. METHODS: Two-year, randomized, controlled, double-blind clinical trial of fluticasone propionate (250 microg bid; 24 patients) or placebo (25 patients), followed by a 7-month open-label study in which all subjects received fluticasone propionate. The primary outcome was the post-bronchodilator therapy FEV(1,) and secondary outcomes were respiratory symptoms, exacerbations, health state, quality of life, and health-care utilization. RESULTS: After 31 months, there were no statistical differences in post-bronchodilator therapy FEV(1) between the intervention group and the control group. No statistical differences were observed for symptoms, exacerbations, or quality of life, although tendencies were consistently in favor of treatment. There was no significant impact on the direct or indirect costs. CONCLUSIONS: There are no indications that early treatment with inhaled corticosteroids modifies a rapid decline in lung function or respiratory symptoms and quality of life.     

A step-wise application of methylprednisolone versus dexamethasone in the treatment of acute exacerbations of COPD

OBJECTIVE: The aim of the study was to explore the clinical value of a step-wise application of methylprednisolone (MP) compared to dexamethasone (DXM) in acute exacerbations of COPD. METHODOLOGY: One hundred and forty-two patients with an acute exacerbation of COPD were divided randomly into two groups: 71 patients were treated with MP and the other 71 patients were treated with DXM. Otherwise each group was given the same basic treatments: antibiotics, bronchodilators, oxygen therapy as well as standard hospital care. The patients in the MP group were given a tapering dose of MP for 7-14 days, and the patients in the DXM group were given a corresponding tapering dose of DXM for 7-14 days. Then both groups were given a gradually reducing dose of oral prednisone for 2-3 weeks. Two weeks before the prednisone was tapered off, inhaled corticosteroid was introduced. The patients' symptom scores, physical signs, per cent predicted FEV1%, and arterial blood gases were monitored before treatment and after the seventh day of treatment. RESULTS: There was an obvious improvement in symptoms after 1-3 days in all 71 patients in the MP group, with their wheezing being distinctly reduced or disappearing entirely. The maximum benefit that occurred in the MP group (90.14%) was considerably higher than that of the DXM group (25.35%), P < 0.05. The predicted FEV1% in the MP group increased from 46.7 +/- 10.6 to 67.5 +/- 12.4, compared with an increase in the DXM group from 50.1 +/- 7.6 to 58.9 +/- 10.8. The difference between the two groups was significant (P < 0.05). CONCLUSIONS: An adequate and tapering dose of MP used in acute exacerbations of COPD can relieve the inflammatory reaction in airways and reduce airway spasm more promptly than DXM.     

Cost-effectiveness of fluticasone propionate in the treatment of chronic obstructive pulmonary disease: a double-blind randomized,placebo-controlled trial

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a debilitating disease and places a large financial burden on health-care systems and society.We prospectively evaluated the cost-effectiveness offluticasone propionate (FP) treatment in patients with moderate-to-severe COPD, who were symptomatic on regular bronchodilator therapy. METHODS: An economic analysis was performed in a 6-month, randomized, double-blind clinical trial comparing FP 1,000 microg/day with placebo in 281 patients aged 45-79 years with symptomatic moderate-to-severe COPD. Data on clinical efficacy, health-care resource use and productivity loss associated with the management of COPD were prospectively collected. The main outcome measures were the incremental cost-effectiveness of achieving a > or = 10% improvement in FEV1 and of remaining exacerbation-free throughout the study.The economic evaluation was costed from the perspective of the NHS (direct costs) and of society (direct and indirect costs). RESULTS: FP was significantly more effective than placebo in terms of the proportions of patients demonstrating a > or = 10% improvement in FEV1 (32 vs. 19%; P = 0.02) and remaining free of moderate/severe exacerbations (75 vs. 63%; P = 0.02).The difference between the groups in total costs was not significantly different. Incremental cost-effectiveness analyses showed that the additional clinical benefits of FP relativeto placebo, in terms of a > or = 10% improvement in FEV1 or an increased number of patients free of moderate/severe exacerbations, were achieved at minimal additional costs from an NHS perspective (additional 0.25 pounds per day for bath) or at a net saving from a societal perspective. Sensitivity analysis showed that these results were robust to changes in the underlying assumptions. CONCLUSIONS: Treatment with FP was associated with statistically significant clinical benefits in patients with moderate-to-severe COPD currently symptomatic on regular bronchodilator therapy. As the differences in direct and total costs compared with placebo were small and non-significant, this treatment can be considered cost-effective in this patient population.     

Prulifloxacin versus levofloxacin in the treatment of severe COPD patients with acute exacerbations of chronic bronchitis

RationaleAntimicrobial therapy of chronic bronchitis exacerbations in patients with severe chronic obstructive pulmonary disease (COPD) is based on empiric antibiotic treatment.ObjectivesTo evaluate the efficacy of prulifloxacin versus levofloxacin therapy in severe COPD patients with exacerbations of chronic bronchitis.MethodsThis study involved a multicenter, parallel, double-blind, randomized clinical trial. Patients aged 40 years or older, smokers, or ex-smokers (>10 pack-years) with spirometrically confirmed severe COPD (FEV₁ ≤ 50% predicted and FEV₁/FVC ratio < 0.7) and diagnosed with an acute exacerbation of chronic bronchitis were enrolled in the study. Patients were randomized to receive prulifloxacin 600 mg once a day or levofloxacin 500 mg once a day for 7 days.Measurements and main resultsThe primary outcome measure was clinical assessment at the TOC visit (7–10 days after the end of treatment) of signs and symptoms of exacerbation, namely sputum purulence, sputum volume, dyspnoea, cough and body temperature assessed through semi-quantitative scales. The ITT population included 346 (174 prulifloxacin, 172 levofloxacin) out of 351 treated subjects. A total of 161 patients with prulifloxacin (92.5%) and 166 with levofloxacin (96.5%) were considered cured at TOC (the difference in the percentage of cured patients was ?3.98 with 95%CI of ?8.76; 0.79). At the 6-month follow-up, the rates of patients with no relapse of AECB were higher than 95% in both the prulifloxacin and levofloxacin groups.ConclusionsBoth prulifloxacin and levofloxacin showed efficacy rates higher than 90% in the treatment of severe COPD patients with exacerbations of chronic bronchitis, with no statistically significant differences between the two antibiotics. The long-term follow-up confirmed a very low incidence of relapse, endorsing the appropriateness of this therapeutic approach.EUDRACT no. 2006-004167-56.     

Erythromycin and common cold in COPD

STUDY OBJECTIVES: To investigate whether erythromycin therapy lowers the frequency of the common cold and subsequent exacerbation in patients with COPD. DESIGN: Prospective, randomized, controlled, but not blinded, trial. PATIENTS: One hundred nine patients with COPD were enrolled into the study. Patients were randomly assigned to erythromycin therapy or to no active treatment in September 1997. Patients then were observed for 12 months, starting in October, during which time the risk and frequency of catching common colds and COPD exacerbations were investigated. Fifty-five patients received erythromycin at study entry (erythromycin group). The remaining 54 patients received no active treatment (control group). MEASUREMENTS AND RESULTS: The mean (+/- SE) number of common colds for 12 months was significantly lower in the erythromycin group than in the control group (1.24 +/- 0.07 vs 4.54 +/- 0.02, respectively, per person; p = 0.0002). Forty-one patients (76%) in the control group experienced common colds more than once, compared to 7 patients (13%) in the erythromycin group. The relative risk of developing two or more common colds in the control group compared with that in the erythromycin group was 9.26 (95% confidence interval [CI], 3.92 to 31.74; p = 0.0001). Thirty patients (56%) in the control group and 6 patients (11%) in the erythromycin group had one or more exacerbations. The relative risk of experiencing an exacerbation in the control group compared with that in the erythromycin group was 4.71 (95% CI, 1.53 to 14.5; p = 0.007). Significantly more patients were hospitalized due to exacerbations in the control group than in the erythromycin group (p = 0.0007). CONCLUSION: Erythromycin therapy has beneficial effects on the prevention of exacerbations in COPD patients.     

Low-dose budesonide with the addition of an increased dose during exacerbations is effective in long-term asthma control. On behalf of the Italian Study Group

OBJECTIVES: This study was designed to compare the effects of a 6-month treatment with budesonide 100 microg bid (low dose) and 400 microg bid (standard reference dose) in controlling symptoms and lung function in a group of asthmatics with moderate asthma (baseline FEV(1) > or = 50% and < or = 90% of predicted values) previously treated with inhaled beclomethasone dipropionate (500 to 1,000 microg/d). Moreover, we investigated whether or not asthma exacerbations could be treated by a short-term increase in the daily dose of budesonide. METHODS: After a 2-week run-in period and 1-month treatment with a high dose of budesonide (800 microg bid), 213 patients with moderate asthma were assigned to randomized treatments. Daily treatment included budesonide (bid) plus an additional treatment in case of exacerbation (qid for 7 days). Treatments were as follows: budesonide 400 microg plus placebo (group 1); budesonide 100 microg plus budesonide 200 microg (group 2); and budesonide 100 microg plus placebo (group 3). Symptoms and a peak expiratory flow (PEF) diary were recorded and lung function was measured each month. An exacerbation was defined as a decrease in PEF > 30% below baseline values on 2 consecutive days. RESULTS: We found that that 1-month treatment with a high budesonide dose remarkably reduced all asthma symptoms. Moreover, symptoms were under control in all treatment groups throughout the study period. Similarly, lung function improved and remained stable, and no relevant differences between groups were observed. In each treatment group, the majority of patients had no exacerbations. In patients treated with the standard budesonide dose (group 1), the number of exacerbations and days with exacerbations were significantly lower than in group 3 (intention-to-treat analysis). Additionally, patients treated with low budesonide dose plus budesonide (group 2) experienced a significantly lower number of exacerbations and days with exacerbations compared to group 3 (per-protocol analysis). CONCLUSIONS: This study demonstrates that when patients with moderate asthma had reached a stable clinical condition with a high dose of budesonide, a low dose of budesonide (200 microg/d) is as effective as the standard dose (800 microg/d) in the control of symptoms and lung function over a period of several months. Furthermore, results showed that the addition of inhaled budesonide (800 microg/d) at onset of an asthmatic exacerbation has a beneficial clinical effect.     

Effect of High/Low Dose N-Acetylcysteine on Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis

Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and morbidity worldwide, charcterised by persistent airflow limitation, mucus hypersecretion, oxidative stress and airway inflammation. N-acetylcysteine (NAC) have anti-oxidant and anti-inflammatory properties, which have been shown an uncertain benefit in COPD patients. Method: Systematic searches were conducted in Cochrane, Medline and Embase electronic databases. A meta-analysis was performed to evaluate the different effect between high and low-dose NAC treatment on COPD exacerbation. Results: This review yielded 11 studies. The methodological quality of included studies were scored using the Jadad score, with a scale of 1 to 5 (score of 5 being the highest). Data showed high-dose NAC can reduce both the total number of exacerbations (RR = 0.59, 0.47 to 0.74, 95%CI, p < 0.001) and the proportion of patients with at least one exacerbation (RR = 0.76, 0.59 to 0.98, 95%CI, p = 0.03). In the low-dose group, subgroup with jadad ≤ 3 showed a significant decrease (RR = 0.69, 0.61 to 0.77, 95%CI, p < 0.001) in the proportion of patients with exacerbation, the other subgroup with Jadad score > 3 showed no significant decrease (RR = 0.98, 0.90 to 1.06, 95%CI, p = 0.59). And low-dose NAC showed no benifit in the total number of exacerbations (RR = 0.97, 0.68 to 1.37, 95%CI, p = 0.85). Neither high nor low-dose NAC treatment showed benifit in forced expiratory volume in one second(FEV₁)(WMD = 1.08, ?9.97 to 12.13, 95%CI, p = 0.85). Conclusion: Long-term high-dose NAC treatment may lead to a lower rate of exacerbations. But the effect of low-dose NAC treatment remains uncertain. Further researches are needed to confirm this outcome and to clarify its mechanisms.     

Cough-reflex sensitivity to inhaled capsaicin in COPD associated with increased exacerbation frequency

Background and objective:   The causes of exacerbations in COPD patients are poorly understood. This study examined the association between cough-reflex sensitivity in patients with stable COPD and the frequency of subsequent exacerbations.
Methods:   The sampling frame for cases and controls for this study was patients attending a hospital outpatient clinic. cough-reflex sensitivity was evaluated using the log concentration of capsaicin causing five or more coughs (log C₅). Subsequent COPD exacerbations were identified prospectively via symptom-based diaries over a 12-month period.
Results:   The study group comprised 45 COPD subjects and 10 controls. Mean log C₅ was lower in the COPD group than in the control group (0.97 (95% confidence interval (CI): 0.76–1.18) versus 1.26 (95% CI: 0.81–1.71), P  = 0.095). In the COPD group, log C₅ was negatively correlated with serum CRP level ( r  = −0.36, P  = 0.02) and significantly associated with the exacerbation frequency ( r  = −0.38, P  = 0.01). Stepwise multiple regression analysis showed that cough-reflex sensitivity was significantly associated with exacerbation frequency ( r ² = 0.15, P  = 0.01).
Conclusions:   Hypersensitivity of the cough reflex to inhaled capsaicin might reflect airway inflammation in stable COPD patients, which predisposes to frequent exacerbations.     

A Randomized, Single-Blind Study of Lansoprazole for the Prevention of Exacerbations of Chronic Obstructive Pulmonary Disease in Older Patients

OBJECTIVES: To investigate whether proton pump inhibitor (PPI) therapy reduces the frequency of common colds and exacerbations in patients with chronic obstructive pulmonary disease (COPD).
DESIGN: Twelve-month, randomized, observer-blind, controlled trial.
SETTING: A university hospital and three city hospitals in Miyagi prefecture in Japan.
PARTICIPANTS: One hundred patients with COPD (mean age ± SD 74.9 ± 8.2) participated. They were all ex-smokers and had received conventional therapies for COPD, including smoking cessation and bronchodilators. Patients with gastroesophageal reflux disease or gastroduodenal ulcer were excluded.
INTERVENTION: Patients were randomly assigned to conventional therapies (control group) or conventional therapies plus PPI (lansoprazole 15 mg/d; PPI group) and observed for 12 months.
MEASUREMENTS: Frequency of common colds and COPD exacerbations.
RESULTS: The number of exacerbations per person in a year in the PPI group was significantly lower than that in the control group (0.34 ± 0.72 vs 1.18 ± 1.40; P <.001). The adjusted odds ratio with logistic regression for having exacerbation (≥once/year) in the PPI group compared with the control group was 0.23 ( P =.004). In contrast, there was no significant difference in the numbers of common colds per person per year between the PPI group and the control group (1.22 ± 2.09 vs 2.04 ± 3.07; P =.12). PPI therapy significantly reduced the risk of catching frequent common colds (≥3 times/year), the adjusted odds ratio of which was 0.28 ( P =.048).
CONCLUSION: In this single-blind, nonplacebo-controlled trial, lansoprazole was associated with a significant decrease in COPD exacerbations. More definitive clinical trials are warranted.