持续非特异性咳嗽儿童和成人中胃-食管反流病的治疗
2011/03/28
摘要
背景：胃-食管反流病(GORD)是导致41%患者慢性咳嗽的原因。GORD治疗包括保守治疗（饮食控制）、药物治疗（胃肠动力药、H2拮抗剂和质子泵抑制剂[PPI]）和胃底折叠术。
目的：在患GORD和持续咳嗽的儿童和成人患者中，评价GORD治疗在治疗慢性咳嗽中的疗效。这些患者的持续咳嗽与潜在的呼吸道疾病无关（非特异性咳嗽）。
检索策略：我们检索Cochrane气道专家注册组、Cochrane对照试验注册组(CENTRAL) 、MEDLINE、EMBASE、综述和相关文章的参考文献。最后一次检索为2010年4月8日。
入选标准：所有在无原发性肺部疾病的儿童和成人中进行的，有关针对咳嗽的GORD治疗的随机对照试验(RCTs)入选本研究。
数据收集和分析：2名分析人员对试验的质量和提取的数据进行分析。为获得进一步相关信息，我们与作者取得了联系。
主要结果：共计入选19项研究（6项为儿童研究，13项为成人研究）。儿童研究未进行荟萃分析。对婴儿进行的单中心RCT显示，PPI（与安慰剂相比）不能改善咳嗽预后（OR 1.61; 95% CI 0.57～4.55），而且PPI治疗者不良反应显著增加(OR 5.56; 95% CI 1.18～26.25)（4周内需要治疗的不良反应为11[95% CI 3～232]）。在成人患者中，针对GORD的H2拮抗剂、胃肠动力药和保守治疗也无效（缺乏数据）。无胃底折叠术相关的对照研究。在荟萃分析中，我们分析了9项比较PPI（2～3个月）与安慰剂疗效的试验。采用意向治疗法，研究的汇总数据显示，在总体哮喘缓解上，两者无显著差异(OR 0.46; 95% CI 0.19～1.15)。汇总数据还表明，总体咳嗽预后无显著改善（试验结束或咳嗽评分变化）。我们仅发现敏感性上存在显著差异。此外，采用通用方差倒数对交叉试验进行分析显示，在接受PPI治疗的患者中，治疗结束（2～3个月）时，咳嗽评分变化显著改善（标准化平均差异：-0.41; 95% CI -0.75～-0.07）。2项研究报道在治疗5天至2周后，咳嗽得到改善。
结论：对于婴儿，针对GORD治疗的PPI不能改善咳嗽，不能用于咳嗽治疗。对于年长儿童，目前尚未有足够的证据显示，PPI治疗GORD有助于改善GORD相关的咳嗽。对于将咳嗽作为转归指标的研究，临床医生应该了解研究的时间（随着时间自然缓解）和安慰剂疗效。有必要对儿童和成人患者进行双盲、随机对照、平行组试验，期间治疗至少持续2个月，采用有效的主观和客观咳嗽转归指标，同时需包括确定出现反应的时间和对酸性和/或非酸性反流的评估。
（林江涛 审校）
Cochrane Database Syst Rev. 2011 Jan 19;1:CD004823.
Gastro-oesophageal reflux treatment for prolonged non-specific cough in children and adults.
Chang AB, Lasserson TJ, Gaffney J, Connor FL, Garske LA.
Royal Children’s Hospital, Brisbane and Menzies School of Health Research, CDU, Darwin, Queensland Children’s Respiratory Centre and Queensland Children’s Medical Research Institute, Herston Road, Herston, Brisbane, Queensland, Australia, 4029.
Update of:
· Cochrane Database Syst Rev. 2006;(4):CD004823.
Abstract
BACKGROUND: Gastroesophageal reflux disease (GORD) is said to be the causative factor in up to 41% of adults with chronic cough. Treatment for GORD includes conservative measures (diet manipulation), pharmaceutical therapy (motility or prokinetic agents, H(2)-antagonist and proton pump inhibitors (PPI)) and fundoplication.
OBJECTIVES: To evaluate the efficacy of GORD treatment on chronic cough in children and adults with GORD and prolonged cough that is not related to an underlying respiratory disease, i.e. non-specific chronic cough.
SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register, the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, review articles and reference lists of relevant articles. The date of last search was 8 April 2010.
SELECTION CRITERIA: All randomised controlled trials (RCTs) on GORD treatment for cough in children and adults without primary lung disease.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. We contacted study authors for further information.
MAIN RESULTS: We included 19 studies (six paediatric, 13 adults). None of the paediatric studies could be combined for meta-analysis. A single RCT in infants found that PPI (compared to placebo) was not efficacious for cough outcomes (favouring placebo OR 1.61; 95% CI 0.57 to 4.55) but those on PPI had significantly increased adverse events (OR 5.56; 95% CI 1.18 to 26.25) (number needed to treat for harm in four weeks was 11 (95% CI 3 to 232)). In adults, analysis of H(2) antagonist, motility agents and conservative treatment for GORD was not possible (lack of data) and there were no controlled studies of fundoplication. We analysed nine adult studies comparing PPI (two to three months) to placebo for various outcomes in the meta-analysis. Using intention-to-treat, pooled data from studies resulted in no significant difference between treatment and placebo in total resolution of cough (OR 0.46; 95% CI 0.19 to 1.15). Pooled data revealed no overall significant improvement in cough outcomes (end of trial or change in cough scores). We only found significant differences in sensitivity analyses. We found a significant improvement in change of cough scores at end of intervention (two to three months) in those receiving PPI (standardised mean difference -0.41; 95% CI -0.75 to -0.07) using generic inverse variance analysis on cross-over trials. Two studies reported improvement in cough after five days to two weeks of treatment.
AUTHORS’ CONCLUSIONS: PPI is not efficacious for cough associated with GORD symptoms in very young children (including infants) and should not be used for cough outcomes. There is insufficient data in older children to draw any valid conclusions. In adults, there is insufficient evidence to conclude definitely that GORD treatment with PPI is universally beneficial for cough associated with GORD. Clinicians should be cognisant of the period (natural resolution with time) and placebo effect in studies that utilise cough as an outcome measure. Future paediatric and adult studies should be double-blind, randomised controlled and parallel-design, using treatments for at least two months, with validated subjective and objective cough outcomes and include ascertainment of time to respond as well as assessment of acid and/or non-acid reflux.
Cochrane Database Syst Rev. 2011 Jan 19;1:CD004823.
背景：胃-食管反流病(GORD)是导致41%患者慢性咳嗽的原因。GORD治疗包括保守治疗（饮食控制）、药物治疗（胃肠动力药、H2拮抗剂和质子泵抑制剂[PPI]）和胃底折叠术。
目的：在患GORD和持续咳嗽的儿童和成人患者中，评价GORD治疗在治疗慢性咳嗽中的疗效。这些患者的持续咳嗽与潜在的呼吸道疾病无关（非特异性咳嗽）。
检索策略：我们检索Cochrane气道专家注册组、Cochrane对照试验注册组(CENTRAL) 、MEDLINE、EMBASE、综述和相关文章的参考文献。最后一次检索为2010年4月8日。
入选标准：所有在无原发性肺部疾病的儿童和成人中进行的，有关针对咳嗽的GORD治疗的随机对照试验(RCTs)入选本研究。
数据收集和分析：2名分析人员对试验的质量和提取的数据进行分析。为获得进一步相关信息，我们与作者取得了联系。
主要结果：共计入选19项研究（6项为儿童研究，13项为成人研究）。儿童研究未进行荟萃分析。对婴儿进行的单中心RCT显示，PPI（与安慰剂相比）不能改善咳嗽预后（OR 1.61; 95% CI 0.57～4.55），而且PPI治疗者不良反应显著增加(OR 5.56; 95% CI 1.18～26.25)（4周内需要治疗的不良反应为11[95% CI 3～232]）。在成人患者中，针对GORD的H2拮抗剂、胃肠动力药和保守治疗也无效（缺乏数据）。无胃底折叠术相关的对照研究。在荟萃分析中，我们分析了9项比较PPI（2～3个月）与安慰剂疗效的试验。采用意向治疗法，研究的汇总数据显示，在总体哮喘缓解上，两者无显著差异(OR 0.46; 95% CI 0.19～1.15)。汇总数据还表明，总体咳嗽预后无显著改善（试验结束或咳嗽评分变化）。我们仅发现敏感性上存在显著差异。此外，采用通用方差倒数对交叉试验进行分析显示，在接受PPI治疗的患者中，治疗结束（2～3个月）时，咳嗽评分变化显著改善（标准化平均差异：-0.41; 95% CI -0.75～-0.07）。2项研究报道在治疗5天至2周后，咳嗽得到改善。
结论：对于婴儿，针对GORD治疗的PPI不能改善咳嗽，不能用于咳嗽治疗。对于年长儿童，目前尚未有足够的证据显示，PPI治疗GORD有助于改善GORD相关的咳嗽。对于将咳嗽作为转归指标的研究，临床医生应该了解研究的时间（随着时间自然缓解）和安慰剂疗效。有必要对儿童和成人患者进行双盲、随机对照、平行组试验，期间治疗至少持续2个月，采用有效的主观和客观咳嗽转归指标，同时需包括确定出现反应的时间和对酸性和/或非酸性反流的评估。
（林江涛 审校）
Cochrane Database Syst Rev. 2011 Jan 19;1:CD004823.
Gastro-oesophageal reflux treatment for prolonged non-specific cough in children and adults.
Chang AB, Lasserson TJ, Gaffney J, Connor FL, Garske LA.
Royal Children’s Hospital, Brisbane and Menzies School of Health Research, CDU, Darwin, Queensland Children’s Respiratory Centre and Queensland Children’s Medical Research Institute, Herston Road, Herston, Brisbane, Queensland, Australia, 4029.
Update of:
· Cochrane Database Syst Rev. 2006;(4):CD004823.
Abstract
BACKGROUND: Gastroesophageal reflux disease (GORD) is said to be the causative factor in up to 41% of adults with chronic cough. Treatment for GORD includes conservative measures (diet manipulation), pharmaceutical therapy (motility or prokinetic agents, H(2)-antagonist and proton pump inhibitors (PPI)) and fundoplication.
OBJECTIVES: To evaluate the efficacy of GORD treatment on chronic cough in children and adults with GORD and prolonged cough that is not related to an underlying respiratory disease, i.e. non-specific chronic cough.
SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register, the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, review articles and reference lists of relevant articles. The date of last search was 8 April 2010.
SELECTION CRITERIA: All randomised controlled trials (RCTs) on GORD treatment for cough in children and adults without primary lung disease.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. We contacted study authors for further information.
MAIN RESULTS: We included 19 studies (six paediatric, 13 adults). None of the paediatric studies could be combined for meta-analysis. A single RCT in infants found that PPI (compared to placebo) was not efficacious for cough outcomes (favouring placebo OR 1.61; 95% CI 0.57 to 4.55) but those on PPI had significantly increased adverse events (OR 5.56; 95% CI 1.18 to 26.25) (number needed to treat for harm in four weeks was 11 (95% CI 3 to 232)). In adults, analysis of H(2) antagonist, motility agents and conservative treatment for GORD was not possible (lack of data) and there were no controlled studies of fundoplication. We analysed nine adult studies comparing PPI (two to three months) to placebo for various outcomes in the meta-analysis. Using intention-to-treat, pooled data from studies resulted in no significant difference between treatment and placebo in total resolution of cough (OR 0.46; 95% CI 0.19 to 1.15). Pooled data revealed no overall significant improvement in cough outcomes (end of trial or change in cough scores). We only found significant differences in sensitivity analyses. We found a significant improvement in change of cough scores at end of intervention (two to three months) in those receiving PPI (standardised mean difference -0.41; 95% CI -0.75 to -0.07) using generic inverse variance analysis on cross-over trials. Two studies reported improvement in cough after five days to two weeks of treatment.
AUTHORS’ CONCLUSIONS: PPI is not efficacious for cough associated with GORD symptoms in very young children (including infants) and should not be used for cough outcomes. There is insufficient data in older children to draw any valid conclusions. In adults, there is insufficient evidence to conclude definitely that GORD treatment with PPI is universally beneficial for cough associated with GORD. Clinicians should be cognisant of the period (natural resolution with time) and placebo effect in studies that utilise cough as an outcome measure. Future paediatric and adult studies should be double-blind, randomised controlled and parallel-design, using treatments for at least two months, with validated subjective and objective cough outcomes and include ascertainment of time to respond as well as assessment of acid and/or non-acid reflux.
Cochrane Database Syst Rev. 2011 Jan 19;1:CD004823.
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