Among the greatest challenges facing the cystic fibrosis community at present is the apparently simple task of determining whether a treatment is beneficial or not. Most of the traditional outcome measures may no longer be useful—the outlook for cystic fibrosis has improved so dramatically that using survival is impractical; clinical scoring systems such as the Shwachman-Kulczycki score are too subjective and insensitive,¹ and many children have no respiratory symptoms with pulmonary function within the normal range. The vast majority of patients with cystic fibrosis succumb to terminal respiratory failure, and pulmonary function is strongly predictive of survival.² Consequently attention has concentrated on respiratory outcomes, most notably pulmonary function and pulmonary exacerbations. There is however considerable inherent variability in measurements of pulmonary function in cystic fibrosis. The standard measure of pulmonary function is the forced expiratory volume in one second (FEV1), but a change of 10% can be within normal variation.³ There remains no standard definition of a pulmonary exacerbation, although a number of models have been proposed^4–6

The popularity of hypertonic saline in cystic fibrosis increased on the basis of small uncontrolled trials,^7–9 and then waned following a large controlled study that reported little effect on pulmonary function.¹⁰ However a recent large-scale study has catapulted it back into the limelight,¹¹ with extensive coverage in the lay press. It is in this context that we must try to interpret the evidence for or against the use of hypertonic saline in cystic fibrosis.

MODE OF ACTION AND EVIDENCE FOR USE

Cystic fibrosis is a multi-system disorder, caused by mutations in the cystic fibrosis gene. The cystic fibrosis gene encodes for a c-AMP mediated chloride channel known as cystic fibrosis transmembrane conductance regulator (CFTR). In the airway, the defective CFTR …