DISCUSSION
Despite having many mucolytic agents to aid ACT in bronchiectasis, research data to guide their use in children are very limited.24 Hypertonic saline as an airway hydrating treatment has not been sufficiently studied even in adults withnon-CF bronchiectasis and to the best of our knowledge we have not found any randomized trials in children with non-CF bronchiectasis that could warrant use of HS in routine management.
Results of this study on use of 3% HS as a mucolytic agent prior to chest physiotherapy in children with non-CF bronchiectasis were promising.
Luis Maize Carro et al (2019) in their review on HS in non-CF bronchiectasis did not find any trials done on paediatric age group and the 3 randomized clinical trials reviewed by them were of patients more than 18 years of age.25 Number of patients in those studies that were done by Kellett et al (2005)21, Kellett et al (2011)22 and Nicolson et al (2012)26 had been 24, 28 and 40 respectively with a dropout rate ranging between10-15%.
Although there was a slightly higher dropout rate (17%) in our study, 52 completed, and some of the reasons were logistic, than individual reasons such as poor compliance.
There were no dropouts due to the adverse effects of 3% saline nebulization in this study similar to two randomized crossover trials on the use of HS (7%) in non-CF bronchiectasis in adults.21,22 In contrary a trial done in Australia with 43 children with CF related bronchiectasis had 50% of its dropouts due to irritating cough and worsening of haemoptysis following HS nebulisations.27
Mean age of the study group (9.51± 2.67) was similar to a study done in India on non-CF bronchiectetic patients (9.6 years).28
The baseline mean FEV1 and FVC of both arms of the trial were between 60-70% reflecting moderate impairments, which could partly be due to the relatively late diagnosis of bronchiectasis (mean ages of diagnosis are 5.6 years in HS group and 6.3 years in the conventional group).Yet this trial demonstrated a significantly higher mean improvement in predicted FEV1 in the HS arm during both phases of the study.
A crossover trial conducted in United Kingdom which studied the effectiveness of 7% hypertonic saline nebulisations in improving lung functions of patients with bronchiectasis showed similar results to this study. The two groups of patients received a random order active HS or Isotonic saline (IS) daily for 3 months and a 4 week wash-out phase was included between phases. Mean predicted FEV1 in the trial had been 66.42±6.1, which was very close to our study results. The improvements in FEV1 and FVC were statistically significant in favour of HS (FEV1=15.1±1.8, p < 0.01; FVC=11.2 ± 0.7, p < 0.01).22The same study showed a significant improvement in frequency of exacerbations in favour of HS (2.14 exacerbations /year in HS group vs. 4.85/year in IS group) keeping with the frequency of exacerbations reported in our study during the first phase (2.5 exacerbations/yearn HS vs. 7.8 exacerbations /year in controls) of the trial.
In contrary, another study which had a higher baseline mean predicted FEV1( 84.8±20.5 in HS group and 80.4±21.1 in control group) did not demonstrate any significant improvement between the two arms after intervention.26 Therefore authors concluded that a significant improvements difficult to observe when there is a higher baseline dynamic lung function test.
Mean improvement in FEV1 and FVC between the two groups were less during phase II compared to phase I and the number of exacerbations between the two groups was also not significantly different. This may be due to the better compliance with the ACT protocol in both groups towards the end of the study period in the majority. Also it could be that after a certain improvement, the base line lung functions have improved and thereafter the rate of improvement would be less.
Murray et al in their randomized cross over trial of chest physiotherapy in non-CF bronchiectasis describes a significant improvement in all domains of lung functions in patients who underwent regular chest physiotherapy compared to the group who received no physiotherapy.29
The results of 3 trials evaluated in a systematic review done in 2017 on various mucoactive agents for chronic, non-CF lung disease have favoured HS over other agents and techniques after 3 months of administration. However, the effects had not been significant at 12 months.30All children of the current study were continued on ACT with HS after completion of the study and the consistency of the effectiveness could be measured in future.
Most of the studies available in the published literature, which used HS, were to compare the effectiveness of Hypertonic saline as a mucocilliary agent with other mucoactive agents. Objective of our study was to compare the effectiveness of HS incorporated ACT to conventional ACT. Therefore even 0.9% saline was not used in the control arm which could improve mucocilliary activity and show clinical improvement. Being an open label study and an unblinded evaluation with short term follow up are some of the limitations than could be seen in this study.