The effectiveness of hyaluronic acid in reducing adverse effects associated with inhaled hypertonic saline therapy in patients with cystic fibrosis: A systematic review and meta-analysis

Abstract

# Background Inhaled hypertonic saline (HS) is an effective mucolytic agent in patients with cystic fibrosis (CF). However, adverse events can impair the clinical utility of hypertonic saline (HS) in this patient population. In this study, we aimed to investigate the effectiveness of hyaluronic acid (HA) in reducing these adverse events. # Methods A literature search was conducted across three electronic databases (Medline, Cochrane Central, and EMBASE) from inception through February 2023. Randomized controlled trials (RCTs) assessing the impact of hyaluronic acid (HA) in reducing adverse events in patients taking hypertonic saline (HS) for CF were included in the analysis. Outcomes of interest included cough, throat irritation, unpleasant taste, and FEV1. Evaluations were reported as risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CI). The Cochrane Risk of Bias Tool (CRBT) was employed to assess the quality of RCTs. The New Castle Ottawa Scale was used to assess the quality of observational studies. # Results From the 1960 articles retrieved from the initial search, five relevant studies (n=236 patients) were included in the final analysis. Compared with patients only on HS, patients with HS and HA were significantly less likely to experience cough (RR: 0.45; 95% CI, 0.28--0.72, *p*=0.001), throat irritation (RR: 0.43; 95% CI, 0.22--0.81, *p*= 0.009), and unpleasant smell (RR: 0.43; 95% CI, 0.23 -- 0.80, *p*=0.09). In addition, patients with HS with HA had significantly less forced expiratory volume (FEV1) (MD: -2.97; 95% CI, -3.79---2.15, *p*=0.52) compared to patients only on HS. # Discussion The addition of HA to HS was linked to a better tolerability profile. When HS was coupled with HA, there was a reduction in all side effects. This may permit tolerance of the medication in otherwise difficult patients, improve adherence to patients receiving frequent inhalations, and improve therapeutic outcomes. # Conclusion The addition of HA is advantageous in CF patients who require continuous HS therapy and have previously shown poor tolerance to therapy.