Therapeutic effect of nebulized hypertonic saline for muco-obstructive lung diseases: a systematic review and meta-analysis with trial sequential analysis

J Investig Med. 2021 Mar;69(3):742-748. doi: 10.1136/jim-2020-001479. Epub 2020 Dec 3.


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.

Keywords: airway obstruction; chronic obstructive; lung diseases; mucins; pulmonary disease.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Cystic Fibrosis* / drug therapy
  • Forced Expiratory Volume
  • Humans
  • Lung Diseases, Obstructive* / drug therapy
  • Quality of Life
  • Saline Solution, Hypertonic / therapeutic use*


  • Saline Solution, Hypertonic