Efficacy of hypertonic saline versus isotonic saline among children with cystic fibrosis: A systematic review and meta-analysis

Abstract

Background Inhaled hypertonic saline (HS) reduces pulmonary exacerbations in patients with cystic fibrosis (CF) aged 6 or more years. However, the effectiveness of HS in improving clinical outcomes in younger children aged 6 or less years is not established. This study examines the efficacy of HS in younger CF patients. Methods Searches were conducted across three databases (Medline, Cochrane Central and EMBASE) from inception through July 2022. Randomized controlled trials assessing the impact of HS in younger CF patients were included. Trials involving only patients greater than 6 years or control group other than isotonic saline (IS) were excluded. Outcomes measured included lung clearance index (LCI), cystic fibrosis questionnaire (CFQ-R) score, spirometry measures, oxygen saturation, respiratory rate, height and weight. Outcomes were reported as mean differences (MDs) with 95% confidence intervals. Results Seven studies ( n = 390 patients) were included in this review. HS significantly reduced the LCI (MD: -0.67; 95%CI, -1.05 to 0.29, P = 0.0006) compared to IS. In addition, HS was associated with significant improvements in height (MD: 2.23; 95%CI, -0.00 to 4.46, P = 0.05) and CFQ-R (MD: 4.30; 95%CI, 0.65–7.95, P = 0.02), but not in oxygen saturation (MD: -0.15; 95%CI, -0.54 to 0.25, P = 0.47), respiratory rate (MD: -0.21; 95%CI, -2.19 to 1.77, P = 0.83) or weight (MD: 0.70; 95%CI, -0.47 to 1.87, P = 0.24). Furthermore, HS did not significantly improve spirometry measures, including FEV 1 (MD: -0.11; 95%CI, -0.21 to 0.43, P = 0.51) and forced vital capacity (MD: 0.27; 95%CI, -0.49 to 1.04, P = 0.48), but significantly improved FEF 25-75 (MD: 0.12; 95% CI, 0.05–0.20; P = 0.002). Discussion Treatment with HS in younger children with CF improves lung clearance, symptoms and quality of life. FEF 25-75 may prove a more sensitive measure for assessing intervention related improvements in pediatric CF trials. Conclusion The findings support HS as a therapeutic method in CF-affected children.

Comment on “Efficacy of hypertonic saline versus isotonic saline among children with cystic fibrosis: A systematic review and meta-analysis”

“…We have read with interest the study by Ullah et al [ 1 ], which found that inhaled hypertonic saline (HS) treatment significantly improves the lung clearance index (LCI), symptoms, lung function and quality of life in children affected by cystic fibrosis (CF) compared with isotonic saline (SI), which would support the use of this intervention in this population. These conclusions were reached by conducting a systematic review (SR), including seven clinical trials with 390 participants.…”

“…Disagreements were resolved by consensus. We used the data from the intervention effect estimation and the risk of bias (RoB) assessment from the studies reported by Ullah et al [ 1 ].…”

“…This approach was not considered for the other outcomes because we did not identify studies that reported MCID thresholds. Regarding the (RoB) assessment of the primary studies included, the SR of Ullah et al [ 1 ] performs this step using a widely used tool such as the one proposed by Cochrane [ 10 ], which already presents a second version [ 11 ]. Ullah et al [ 1 ] rated the “blinding of outcome assessment” domain for the studies by Amin et al [ 5 ] and Subbarao et al [ 6 ] as a high RoB, high RoB for the “incomplete outcome data” domain in the study by Stahl et al [ 7 ], and high RoB for the “other bias” domain in the study by Rosenfeld et al [ 8 ].…”

“…Therefore, considering the certainty of the evidence, our confidence in the estimated effect of HS versus IS in children with CF is at least limited, so the true effect of HS may be substantially different from the estimate of the effect by the review of Ullah et al [ 1 ]. Consequently, it is preferable to give research recommendations in cases of low or very low certainty of the evidence and to increase the number of primary studies of improved quality to assess the possibility of recommending this intervention for most children with CF.…”