METHODS
Study design and population: This was a randomised, cross-over study conducted at the University Paediatric Unit of the Lady Ridgeway Hospital for Children, Colombo, Sri Lanka from February 2018 to February 2020.
Children aged five to 15 years with clinically diagnosed and radiologically (High Resolution Computer Tomographic scan) confirmed bronchiectasis, without CF, excluded by two negative sweat tests, were included in the study.
Children who were unable to comply with regular follow up, already on regular HS nebulization, diagnosed with chronic colonization ofPseudomonas spp., with a history of hypersensitivity for the medications (salbutamol, HS) or having typical extra pulmonary features of CF, were excluded.
Sample size: Due to lack of data in paediatric population with non-CF bronchiectasis on improvement of FEV1 following ACT, an interim analysis was done once the first 25 patients enrolled to conventional group and completed phase one of the protocol. Mean improvement of FEV1 of them was 5.22(SD=5.75). To detect a 10% improvement with HS with a 95% confidence interval and an 80% power, the calculated sample size was 52(26 in each group)
Study procedure: Parents of eligible patients were explained about the study and parent information sheet was given in their preferred language. After explaining and addressing concerns informed written consent was obtained from parents and the assent from children above 12 years. Afterwards they were registered and a serial number was given. A baseline spirometry was performed and values were recorded.Spirometry was performed using portable MIRspirolab 4 spirometry system according to the ATS guidelines23.Calibration of the spirometer was done regularly and nose clip was applied when forced expiratory manoeuvres are performed. The best three technically acceptable blows were recorded and the best value was recorded.
Computer generated variable blocked randomization was done to allocate patient either to test arm or control arm as shown in Figure 1. Allocation concealment was done with sequentially numbered sealed opaque envelops which were opened to decide the arm of enrolled patients.
The test arm received 200 µg of inhaled salbutamol followed by 3 ml of 3% saline nebulisations prior to chest physiotherapy twice daily for 60 days during the phase I while the control arm receiving 200 µg of inhaled salbutamol followed by chest physiotherapy which is the conventional airway clearance technique.
Parents were adequately trained on the usage of inhaled salbutamol with a metered dose inhaler and a spacer device, home nebulizations and technique of chest physiotherapy. Physiotherapy was given according to a uniform protocol in all children i.e. active cycle of breathing, percussion and vibration along with postural drainage and all parents were trained by a qualified physiotherapist.
Spirometric parameters and number of exacerbations after 60 days of therapy in each arm were documented and a wash out period of 30 days was applied for the two groups from 60 days to 90 days. During the wash out period children were managed with conventional ACT. Thereafter children in the two group’s treatment arms were swapped (test arm to control arm and control arm to test arm) and followed up for the next 60 days and the outcome parameters were measured at the end of second 60 days.