Article Text

Original research
Associations between gastro-oesophageal reflux disease and a range of diseases: an umbrella review of systematic reviews and meta-analyses
  1. JinJing Tan1,2,
  2. Liqun Li3,
  3. Xiaoyan Huang3,
  4. Chengning Yang3,
  5. Xue Liang3,
  6. Yina Zhao3,
  7. Jieru Xie4,
  8. Ran Chen3,
  9. Daogang Wang3,
  10. Sheng Xie2
  1. 1Graduate School, Jiang Xi University of Traditional Chinese Medicine, Nanchang, Jiangxi, China
  2. 2Department of Administration, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, Guangxi, China
  3. 3Department of Gastroenterology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, Guangxi, China
  4. 4Department of Center of Preventive Disease Treatment, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, Guangxi, China
  1. Correspondence to Dr Sheng Xie; xiesheng2018tougao{at}


Objective Numerous meta-analyses have revealed the association between gastro-oesophageal reflux disease (GORD) and a range of diseases; however, the certainty of the evidence remains unclear. This study aimed to summarise and assess the certainty of evidence derived from meta-analyses.

Methods Embase, PubMed, Web of Science, Cochrane Databases of Systematic Reviews, CNKI and Wangfang databases from their inception to 22 February 2020 were queried for systematic reviews and meta-analyses on the association between GORD and various diseases. The methodological quality of the included studies was assessed using A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2), and evidence certainty was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. Statistical analysis was conducted using Stata V.15.

Results Ten publications with associations between GORD and different types of diseases were included. There was high heterogeneity (I2 >75%) among seven independent meta-analyses. Evidence for publication bias in two independent meta-analyses was also observed. According to the AMSTAR 2 approach, the methodological quality was high for 20% of meta-analyses, moderate for 10%, low for 40% and critically low for 30%. Based on GRADE approach, the certainty of evidence was high for the association between GORD and higher risk of chronic obstructive pulmonary disease (COPD) exacerbation (OR 5.37; 95% CI 2.71 to 10.64) and higher prevalence of oesophageal adenocarcinoma (OR 4.57; 95% CI 3.89 to 5.36), and it was moderate for the association between GORD and higher chronic rhinosinusitis prevalence (OR 2.16; 95% CI 1.37 to 3.48).

Conclusion The association between GORD and a range of diseases was extensively studied, and our findings revealed a high certainty of evidence of the association between GORD and an increased risk of COPD exacerbation as well as increased prevalence of oesophageal adenocarcinoma. Further investigations using systematic reviews and meta-analyses of high methodological quality that include prospective large cohort studies and adjusted confounders are warranted.

PROSPERO registration number CRD42019122264.

  • oesophageal disease
  • public health
  • epidemiology

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  • JT, LL, XH and CY contributed equally.

  • Contributors JT wrote the protocol and registered it in PROSPERO. LL and JT screened the articles according to the eligibility and exclusion criteria. YZ and XL independently searched the databases and imported the yielded articles to EndNote software. LL and CY extracted the data. DW and CY conducted the AMSTAR 2 eveluating. LL and JT conducted the evidence classifications. XH checked the data and results. JX and RC conduct statistical analyses. LL, JT and CY wrote the draft of the paper, and XH revised the paper. SX was contributed in concept design, guidance and arbitrating all discrepancies and was also responsible for the final content.

  • Funding This work was funded by National Natural Science Foundation of China (no. 81573914, no.81460723 and no.82004299); the special foundation for science and technology of guangxi administration of traditional Chinese medicine (no. GZZX15-02); the project of improving the evidence-based ability of specialised diseases (gastro-oesophageal reflux disease) in the field of traditional Chinese medicine (TCM) digestion (no. 2019XZZX-XH003).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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