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Therapeutic effect of nebulized hypertonic saline for muco-obstructive lung diseases: a systematic review and meta-analysis with trial sequential analysis
  1. Yin Zhang1,
  2. Anchao Song2,
  3. Jingyue Liu1,
  4. Jihong Dai1,
  5. Jilei Lin1
  1. 1 Department of Respiratory Disease, Chongqing Medical University Affiliated Children's Hospital, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China
  2. 2 School of Public Health and Management, Chongqing Medical University, Chongqing, China
  1. Correspondence to Dr Jilei Lin, Department of Respiratory Disease, Chongqing Medical University Affiliated Children's Hospital, Chongqing 400000, China; jilei_lin{at}


Overproduction of mucus and impaired clearance play important roles in the pathogenesis of muco-obstructive lung diseases (MOLDs). This study aims to evaluate the therapeutic effect and safety of nebulized hypertonic saline (HS) on MOLDs. Five electronic databases including PubMed, Excerpt Medica Database (EMBASE), Cochrane Central Register of Controlled Trials, and International Standard Randomized Controlled Trial Number Register were searched until June 2019. Randomized controlled trials or randomized controlled crossover trials which investigated the therapeutic effect of HS versus non-HS for MOLDs were included. Twenty-one studies met the eligibility criteria. For cystic fibrosis (CF), although the forced expiratory volume in the first second and forced vital capacity did not improve significantly (mean difference (MD) −0.48, 95% CI −3.72 to 2.76), (MD 1.85, 95% CI −4.31 to 8.01), respectively), the clearance capability of lung and quality of life (QOL) improved significantly in the HS group ((standard mean difference 0.44, 95% CI 0.02 to 0.87), (MD −0.64, 95% CI −)1.14, to 0.13), respectively). However, the results of trial sequential analysis showed the evidence needed more researches to support. The effect of nebulized HS on non-CF bronchiectasis, chronic obstructive pulmonary disease, and primary ciliary dyskinesia also need more evidence to conclude, since current studies are limited and results are inconsistent. Most adverse events of nebulized HS were mild and transient. In summary, the current available evidence suggests that nebulized HS may increase the QOL in CF, but there was no significant improvement in lung function. However, it is not possible to draw firm conclusions for other MOLDs due to limited data.

  • airway obstruction
  • lung diseases
  • mucins
  • pulmonary disease
  • chronic obstructive

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  • Contributors YZ: conception, data search, inclusion and exclusion of studies, data extraction, assessment of methodological quality, data analysis and writing the manuscript. JD: inclusion and exclusion of studies, data extraction and data analysis. JL and AS: data search, inclusion and exclusion of studies, assessment of methodological quality and checking the data of the outcomes. JL: conception, supervision, interpretation of results and checking the first and the final versions of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • 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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