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Introduction
There is increasing evidence that cystic fibrosis (CF) lung disease which is responsible for a shortened life span in most patients begins shortly after birth and progresses even in the absence of clinical signs and symptoms. 1-6 As a result, there is an increasing emphasis on early intervention strategies to prevent lung damage. 7 Forced expiratory volume in 1 s (FEV1 ) has traditionally been the main outcome measure in therapeutic intervention studies. However, its use in young patients with mild CF lung disease is limited by its insensitivity to peripheral airways disease and the need for active cooperation to perform the manoeuvre. 8 Therefore, more sensitive and easier measures of lung function are needed for clinical studies in younger patients with CF with mild disease.
The lung clearance index (LCI) is a measure of ventilation inhomogeneity determined during multiple-breath washout (MBW). Cross-sectional studies done to date in patients with CF suggest that the LCI is more sensitive at detecting lung disease than spirometry. 9-15 The LCI is determined during tidal breathing and the normal range is consistent across the paediatric range beyond infancy. 9-15 The LCI is a potentially useful end point for clinical trials in patients with CF with mild lung disease, but data from interventional and longitudinal studies with the currently used equipment are lacking.
Hypertonic saline (HS; 7%), a therapeutic intervention for patients with CF, is believed to target a direct consequence of cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction, airway surface dehydration, and has previously been shown to increase mucociliary clearance, improve FEV1 and decrease the number of pulmonary exacerbations. 16 17 Due to its mechanism of action, HS is an attractive early intervention strategy, but has never been studied in patients with CF with normal lung function due to the difficulty in assessing its efficacy. Therefore, we designed a study to test the effect of inhalation of HS in paediatric patients with CF with normal spirometry (FEV1 ) using the LCI as the primary outcome measure. Our research hypothesis was that amongst paediatric patients with CF with mild lung disease (ie, FEV1 % predicted >=80%), 4 weeks of HS (7%) inhalation as compared with 4 weeks of isotonic saline (IS; 0.9%) inhalation will...