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Predicting response to rhDNase and hypertonic saline in children with cystic fibrosis
Author(s) -
Suri Ranjan,
Metcalfe Christopher,
Wallis Colin,
Bush Andrew
Publication year - 2004
Publication title -
pediatric pulmonology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.866
H-Index - 106
eISSN - 1099-0496
pISSN - 8755-6863
DOI - 10.1002/ppul.10442
Subject(s) - medicine , hypertonic saline , cystic fibrosis , vital capacity , lung function , pulmonary function testing , crossover study , randomized controlled trial , lung , diffusing capacity , placebo , pathology , alternative medicine
Daily recombinant human deoxyribonuclease (rhDNase) is an established but expensive treatment in cystic fibrosis (CF). Alternate‐day rhDNase and hypertonic saline (HS) represent potential cheaper alternative therapies. However, not all patients improve on treatment. To assess response, many CF centers have developed formal n‐of‐1 trials of treatment to find out who benefits. Response to daily rhDNase at 3 months has been shown to be a good predictor of response at 1 year. There are no data correlating individual response at a shorter time period with 3‐month response. We assessed whether individual responses to daily rhDNase, alternate‐day rhDNase, and HS could be predicted from lung function response at 6 weeks, thus shortening the n‐of‐1 trial, or from baseline patient characteristics, therefore avoiding the need for an n‐of‐1 trial. In a randomized crossover trial, 48 CF children were allocated consecutively to 12 weeks of once‐daily 2.5‐mg rhDNase, alternate‐day 2.5‐mg rhDNase, and twice‐daily 5 ml of 7% HS. Forced expiratory volume in 1 sec (FEV 1 ) and forced vital capacity (FVC) were measured at baseline and then at 6 and 12 weeks into each treatment period. Lung function response to the drugs at 6 weeks was highly predictive of response at 3 months. There was some evidence that response to HS was worse in patients with lower baseline lung function. However, there was no association between response to alternate‐day or daily rhDNase and baseline characteristics. In conclusion, response to rhDNase and HS at 6 weeks was highly predictive of response at 3 months. For daily and alternate‐day rhDNase, at least, the drug needs to be administered for at most 6 weeks initially to assess long‐term response to treatment. Response to treatment could not be reliably predicted from baseline characteristics. Pediatr Pulmonol. 2004; 37:305–310. © 2004 Wiely‐Liss, Inc.