RESUMO
OBJECTIVES: To determine the effect of repeated doses of aerosolized recombinant human deoxyribonuclease (rhDNase) on the development of anti-rhDNase antibodies, acute allergic reactions, and pulmonary function in patients with cystic fibrosis. DESIGN: A multicenter, open-label study in which 184 patients received 10 mg aerosolized rhDNase twice a day for 14 days followed by a 14-day washout period for a total of 6 treatment cycles. Serial determinations of anti-rhDNase antibodies and pulmonary functions were performed. RESULTS: Detectable anti-rhDNase antibodies developed in 16 (8.7%) patients. These patients had no changes in their symptoms from the time they entered the trial. Antibodies detected were all of the IgG isotype. Increases in both forced expired volume in 1 second and forced vital capacity were noted from the beginning to the end of each cycle of treatment returning to baseline during the off-treatment period of each cycle. Seropositivity to rhDNase was not associated with allergic reactions and had no relationship on improvement in pulmonary function. CONCLUSIONS: Development of anti-rhDNase antibodies occurred in a small number of patients and was not associated with side effects. Intermittent administration of rhDNase for 24 weeks to patients with cystic fibrosis was well tolerated and was not associated with anaphylaxis in any patient. Pulmonary function improved significantly during the 14-day cycles while rhDNase was administered and returned to baseline when rhDNase was discontinued.
Assuntos
Fibrose Cística/tratamento farmacológico , Desoxirribonucleases/uso terapêutico , Adolescente , Adulto , Aerossóis , Idoso , Formação de Anticorpos , Hiper-Reatividade Brônquica/induzido quimicamente , Criança , Fibrose Cística/imunologia , Fibrose Cística/fisiopatologia , Desoxirribonucleases/administração & dosagem , Desoxirribonucleases/imunologia , Esquema de Medicação , Hipersensibilidade a Drogas/etiologia , Dispneia/tratamento farmacológico , Feminino , Seguimentos , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Imunoglobulina G/biossíntese , Isotipos de Imunoglobulinas/biossíntese , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Proteínas Recombinantes , Segurança , Capacidade Vital/efeitos dos fármacosRESUMO
Dietary supplementation with fish oils high in the omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, may have an antiinflammatory effect. We determined whether patients with cystic fibrosis (CF) could incorporate omega-3 fatty acids into their plasma and cell membrane phospholipids without adverse effects. In this double-blind study, 12 patients with pancreatic insufficiency who have CF (mean age, 12.2 +/- 5.4 (SD) years) and 13 subjects without CF (mean age, 13.4 +/- 6.3 (SD) years) were randomly assigned to ingest 8 gm daily of either encapsulated fish oil (3.2 gm of eicosapentaenoic acid and 2.2 gm of docosahexaenoic acid daily) or olive oil ethyl esters for 6 weeks. Two of seven and two of five patients with CF who received fish and olive oils, respectively, and one of eight and none of five subjects without CF discontinued taking the capsules before 6 weeks because of eructation or diarrhea. Significant incorporation of omega-3 fatty acids into plasma and erythrocyte membrane phospholipids was observed in subjects with and those without CF randomly assigned to the fish oil treatment. For example, in subjects randomly assigned to receive fish oil, the eicosapentaenoic acid/arachidonic acid ratio in plasma increased 9.8-fold, from 0.04 +/- 0.02 (mean +/- SEM) to 0.39 +/- 0.11 (p = 0.02), in the patients with CF (n = 7) and 23.0-fold, from 0.04 +/- 0.01 to 0.92 +/- 0.17 (p = 0.001), in the subjects without CF (n = 8) who received fish oil (p = 0.02, patients with CF vs subjects without CF at 6 weeks). No clinically or statistically significant changes from baseline were observed in platelet aggregation or levels of vitamin E or A in subjects who received fish oil. Future studies are indicated to determine whether omega-3 fatty acid enrichment provides a clinically beneficial antiinflammatory effect in patients with CF.
Assuntos
Fibrose Cística/metabolismo , Insuficiência Pancreática Exócrina/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Óleos de Plantas/metabolismo , Adolescente , Estudos de Casos e Controles , Criança , Fibrose Cística/complicações , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/sangue , Método Duplo-Cego , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/sangue , Eritrócitos/química , Insuficiência Pancreática Exócrina/etiologia , Ácidos Graxos Essenciais/sangue , Ácidos Graxos Ômega-3/administração & dosagem , Humanos , Absorção Intestinal , Óleos de Plantas/administração & dosagemRESUMO
The CFF Consensus Conference concluded with a summary of those outcome measures that would be most useful in studies of patients 6 years of age and older and those measures that would be most useful in studies of the younger population (< 6 years of age) (Table). These measures were further divided into biologic markers most appropriate for initial (phase I and phase II) clinical trials and those especially useful in large, multicenter (phase III) pivotal trials. There is an ongoing need to improve the accuracy and validity of currently available measures of biologic activity and clinical efficacy in CF, especially in the younger population. The conference participants recommended that the following eight issues be addressed as soon as possible: (1) definition of pulmonary exacerbation, (2) broadly applicable methods of testing pulmonary function in small children (ideally a single test for all ages), (3) a comprehensive severity-of-disease score for young children, (4) reliable methods of quantifying chest x-ray and CT scan changes in young patients, (5) simple, inexpensive measures of lung inflammation, (6) a centralized, uniform approach to the establishment of data monitoring committees, (7) a quality of well-being scale for small children, and (8) reliable, reproducible aerosol delivery systems with defined characteristics. In addition, participants recommended that better methods be developed for assessing patients' adherence to research protocols.