[Respiratory evolution of patient with mucoviscidosis treated with mucolytic agents plus dornase alfa].
OBJECTIVE
Modifications of bronchial secretions in cystic fibrosis patients account for the long-lasting use of mucolytic agents, despite the lack of adequately controlled clinical studies supporting this approach. Hyperviscosity of bronchial secretions mainly depend on their high DNA content, as a result of degradation of polymorphonuclear neutrophils mobilized by infection and inflammation. This phenomenon has led to the treatment of respiratory complications with human recombinant deoxyribonuclease (dornase alfa). In the present study, we compared the clinical and respiratory outcome in patients receiving mucolytic agents followed by dornase alfa, each for 1 year.


METHODS
Fifty-four patients, aged 5 years or more, have been prospectively followed 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 two doses), followed by a 12-month treatment with one daily aerosol of dornase alfa only (2.5 mg per day). The primary end-points were the results of pulmonary function tests. Secondary end-points were subjective symptoms, bacterial colonization, consumption of antibiotics, and clinical tolerance.


RESULTS
At the end of the 12-month mucolytic therapy, a significant decrease of forced expiratory volume/second (FEV1, -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 and FVC had increased by 7.7 and 5.3%, respectively. This change was statistically significant only for FEV1 in most severely disabled patients. However, forced expiratory flow 25-75% (FEF 25-75) decreased during the 2 year period of observation, by 5.6% the first year and 4.9% the 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 decreased 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 treatment by dornase alfa.


CONCLUSIONS
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 dornase alfa in the treatment of respiratory complications of cystic fibrosis and specify the optimal modalities of its use. Synergistic combinations with mucolytic therapy and/or anti-inflammatory drugs could be viewed as a future prospect.
Service de pédiatrie 1, Hôpital d'Enfants, Vandoeuvre-lès-Nancy, France.
J
J
Derelle
E
E
Bertolo-Houriez
F
F
Marchal
M
M
Weber
J M
JM
Virion
M
M
Vidailhet
D000293:Adolescent; D000328:Adult; D000551:Ambroxol / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D003850:Deoxyribonuclease I / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005100:Expectorants / Q000627:therapeutic use*; D005541:Forced Expiratory Volume; D006801:Humans; D015080:Mesna / Q000627:therapeutic use*; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D014797:Vital Capacity
D000900:Anti-Bacterial Agents; D005100:Expectorants; D011994:Recombinant Proteins; D000551:Ambroxol; C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I; D015080:Mesna
Evolution respiratoire de patients atteints de mucoviscidose traités par mucofluidifiants puis par dornase alfa.