Long-term effects of aerosolised rhDNase on pulmonary disease progression in patients with cystic fibrosis.

BACKGROUND: After multiple studies, including clinical trials, suggested some mild clinical benefits from the use of rhDNase by patients with cystic fibrosis, a widespread acceptance of the drug has followed. However, long-term effects, specifically on lung disease progression, have not been demonstrated. Experience with the use of this drug in a single cystic fibrosis centre is presented and compared with the trends seen in the patient population of the centre before the introduction of the drug.
METHODS: Patients with cystic fibrosis routinely followed at the University of Minnesota Cystic Fibrosis Center and prescribed rhDNase for at least two years were included in this retrospective study. Data on spirometric parameters (FEV1 and FEV1/FVC), allometric index, and admissions to hospital were retrieved from the centre's database for the two years preceding the prescription of rhDNase and the two years that followed. Trends in pulmonary function and allometric index were analysed by mixed linear modelling, and hospital admission rates for both periods were calculated and compared.
RESULTS: One hundred and ninety patients met the inclusion criteria for the study. In the two years preceding the prescription of rhDNase the trends noted were those of a mild decline in FEV1, a stable FEV1/FVC, and a mild improvement in allometric index. In the two years that followed the prescription of rhDNase a mild decline in all these parameters occurred which was a significant change from the previous period (all p < 0.009). There was no difference between females and males in the trends experienced after the start of rhDNase. By logistic regression analysis only the presence of malnutrition at the time of prescription was associated with a positive trend after the introduction of rhDNase. No significant change in the hospital admission rates occurred, with rates of 0.52 (0.16) and 0.56 (0.21) admissions/patient/year for the periods before and after the prescription of rhDNase, respectively.
CONCLUSIONS: The introduction of rhDNase to the regimen of patients with cystic fibrosis cared for at this centre has not been followed by a positive trend in lung function and nutritional parameters. There are some differences between this patient population and those who participated in previous studies which may help to explain the contrasting findings of this study. However, it is also possible that factors other than mucus clearance need to be improved to achieve a favourable response in disease progression. Patients on this treatment should be followed closely and the benefit judged on an individual basis. More studies are needed to define better the specific indications and use of this form of treatment.