J. Derelle et al., RESPIRATORY OUTCOME IN CYSTIC-FIBROSIS PA TIENTS GIVEN SUCCESSIVELY MUCOLYTIC AGENTS FOR 1 YEAR AND DORNASE-ALPHA FOR 1 YEAR, Archives de pediatrie, 5(4), 1998, pp. 371-377
Aim. - Modifications of bronchial secretions in cystic fibrosis patien
ts account for the long-lasting use of mucolytic agents, despite the l
ack of adequately controlled clinical studies supporting this approach
. Hyperviscosity of bronchial secretions mainly depend on their high D
NA content, as a result of degradation of polymorphonuculear neutrophi
ls mobilized by infection and inflammation. This phenomenon has led to
the treatment of respiratory complications with human recombinant deo
xyribonuclease (dornase alfa). In the present study, we compared the c
linical and respiratory outcome in patients receiving mucolytic agents
followed by dornase alfa, each for 1 year. Population and methods. -
Fifty-four patients, aged 5 years or more, have been prospectively fol
lowed for 2 years. They received first a 12-month association of mesna
(two nebulisations per day) and oral ambroxol (60 mg per day, divided
in tow doses), followed by a 12-month treatment with one daily aeroso
l of dornase alfa only (2.5 mg per day). The primary end-points were t
he results of pulmonary function tests. Secondary end-points were subj
ective symptoms, bacterial colonization, consumption of antibiotics, a
nd clinical tolerance. Results. - At the end of the 12-month mucolytic
therapy, a significant decrease of forced expiratory volume/second (F
EV1, -10.5% as compared to baseline values) and forced vital capacity
(FVC,-12.8%) was observed. At the end of 12-month dornase alfa, FEV1 a
nd FVC had increased by 7.7 and 5.3%, respectively. This change was st
atistically significant only for FEV1 in most severely disabled patien
ts. However, forced expiratory flow 25-75% (FEF 25-75) decreased durin
g the 2 year period of observation, by 5.6% the first year and 4.9% th
e second year. The mean number of days with parenteral antibiotics did
not statistically differ between both treatments, except for patients
more than 15 years of age. In this subgroup, the mean number decrease
d from 40 days in the first year to 27 in the second year (P < 0.05).
Acceptability of treatment by the patients themselves was better with
dornase alfa than with mucolytic therapy. However, several episodes of
hemoptysis, frequent in only one case, were associated with the treat
ment by dornase alfa. Conclusion. - Dornase alfa was associated with a
stabilisation, and even a trend to improvement in pulmonary function
tests. This stabilisation is by itself a very encouraging result. Long
-term comparative studies are needed to evaluate the benefits of dorna
se alfa in the treatment of respiratory complications of cystic fibros
is and specify the optimal modalities of its use. Synergistic combinat
ions with mucolytic therapy and/or anti-inflammatory drugs could be vi
ewed as a future prospect. (C) 1998, Elsevier, Paris.