DNase in cystic fibrosis: the challenge of assessing response and maximising benefit

Since nebulised recombinant human DNase was licensed for use in cystic fibrosis patients in March 1994, controversy has continued over how this relatively expensive drug should be used to maximum benefit. By cleaving DNA released from dead inflammatory cells it is dramatically effective in reducing sputum viscoelasticity in vitro.1 In vivo, phase 2 trials showed encouraging improvements in spirometric2 3 and other inflammatory indices,4 and the major phase 3 trial used to support licensing5 showed that once daily treatment gave a relatively modest (5.8%) improvement in forced expiratory volume in one second (FEV₁) at 24 weeks, with a significant (after age adjustment of the groups) reduction in exacerbations requiring parenteral antibiotics. This large randomised trial (968 patients) was notable, not only for the significance of the mean results, but also for the wide variability of individual responses to treatment. For example, 30% of actively treated patients showed an increase in FEV₁ of over 10%, but 6% had a fall of more than 10% (so, by inference, 64% had a change in FEV₁ of less than …