The timing of inhalation of hypertonic saline in people with cystic fibrosis

Review question

We reviewed the evidence about whether the timing (in relation to airway clearance techniques or in relation to time of day) of hypertonic saline (a strong, sterile, salt water solution) through a nebuliser improves the physical properties of sputum, stimulates cough, improves clinical outcomes (such as lung function), and improves the perceived effect of airway clearance techniques in cystic fibrosis. This is an update of a previously published Cochrane Review.

Background

Regular inhalation of hypertonic saline improves the clinical outcomes of people with cystic fibrosis. It is not certain whether it is better to inhale hypertonic saline before, during or after clearing the airways with physical techniques, nor whether it is better to inhale it in the morning or in the evening. We looked for trials that compared these different timing regimens.

Search date

The evidence is current to: 28 February 2019.

Study characteristics

The review included three studies with 77 people with cystic fibrosis aged between 18 and 64 years of age. The studies looked at the impact of the timing of hypertonic saline inhalation in relation to airway clearance techniques. The studies reported immediate outcomes after inhalation of hypertonic saline before, during or after physical airway clearance techniques. All studies were short, involving only one to three treatments of each timing regimen.

Key results

While outcomes such as lung function did not show any difference between the regimens, people with cystic fibrosis perceived that inhaling hypertonic saline before or during airway clearance techniques may be more effective and satisfying than inhaling hypertonic saline after airway clearance. No studies comparing morning and evening inhalation were found. The long-term efficacy of hypertonic saline has only been established for twice-daily inhalations; however, if only one dose per day is tolerated, the time of day at which it is inhaled could be based on convenience or tolerability until further evidence is available.

Quality of the evidence

Overall, the quality of the evidence was low. The only issues perhaps affecting the quality related to the fact that it was not possible for participants to be blinded to the treatment they received. However, because the studies were short-term and most of the significant results were based on perceived efficacy, timing of administration of hypertonic saline needs further study.

Authors' conclusions: 

Timing of hypertonic saline inhalation makes little or no difference to lung function (low-certainty evidence). However, inhaling hypertonic saline before or during airway clearance techniques may maximise perceived efficacy and satisfaction. The long-term efficacy of hypertonic saline has only been established for twice-daily inhalations; however, if only one dose per day is tolerated, the time of day at which it is inhaled could be based on convenience or tolerability until evidence comparing these regimens is available.

The identified trials were all of very short intervention periods, so longer-term research could be conducted to establish the effects arising from regular use, which would incorporate the influence of changes in adherence with long-term use, as well as generating data on any adverse effects that occur with long-term use.

Read the full abstract...
Background: 

Inhalation of hypertonic saline improves sputum rheology, accelerates mucociliary clearance and improves clinical outcomes of people with cystic fibrosis. This is an update of a previously published Cochrane Review.

Objectives: 

To determine whether the timing of hypertonic saline inhalation (in relation to airway clearance techniques or in relation to time of day) has an impact on its clinical efficacy in people with cystic fibrosis.

Search strategy: 

We identified relevant randomised and quasi-randomised controlled trials from the Cochrane Cystic Fibrosis Trials Register, the Physiotherapy Evidence Database (PEDro), and international cystic fibrosis conference proceedings.

Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register: 28 February 2019.

Selection criteria: 

Any trial of hypertonic saline in people with cystic fibrosis where timing of inhalation was the randomised element in the study protocol with either: inhalation up to six hours before airway clearance techniques compared to inhalation during airway clearance techniques compared to inhalation up to six hours after airway clearance techniques; or morning compared to evening inhalation with any definition provided by the author.

Data collection and analysis: 

Both authors independently assessed the trials identified by the search for potential inclusion in the review. The certainty of the evidence was assessed using GRADE.

Main results: 

The searches identified 104 trial reports which represented 51 trials, of which three cross-over trials (providing data on 77 participants) met our inclusion criteria. We present three comparisons: inhalation before versus during airway clearance techniques; inhalation before versus after airway clearance techniques; and inhalation during versus after airway clearance techniques. One trial (50 participants), given its three-arm design, was eligible for all three comparisons. No trials compared morning versus evening inhalation of hypertonic saline.

The evidence from the three trials was judged to be of low quality downgraded for limitations (high risk of bias due to blinding) and indirectness (all participants are adults, and therefore not applicable to children). Intervention periods ranged from one treatment to three treatments in one day. There were no clinically important differences between the timing regimens of inhaling hypertonic saline before, during or after airway clearance techniques in the mean amount of improvement in lung function or symptom scores (77 participants), with the between-group comparisons being non-significant (low-certainty evidence). While there may be little or no difference in the rating of satisfaction when hypertonic saline was inhaled before versus during the airway clearance techniques (64 participants) (with the 95% confidence interval including the possibility of both a higher and lower rating of satisfaction), satisfaction may be lower on a 100-mm scale when inhaled after the airway clearance techniques compared to before: mean difference (MD) 20.38 mm (95% confidence interval (CI) 12.10 to 28.66) and when compared to during the techniques, MD 14.80 mm (95% CI 5.70 to 23.90). Perceived effectiveness showed similar results: little or no difference for inhalation before versus during airway clearance techniques (64 participants); may be lower when inhaled after the airway clearance techniques compared to before, MD 10.62 (95% CI 2.54 to 18.70); and also when compared to during the techniques, MD 15.60 (95% CI 7.55 to 23.65). There were no quality of life or adverse events reported in any of the trials.

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