RESUMO
OBJECTIVE: Our objective was to determine whether long-term treatment of young patients with cystic fibrosis (CF) with dornase alfa maintains lung function and reduces respiratory tract exacerbations. STUDY DESIGN: This was a 96-week, randomized, double-blind, placebo-controlled trial involving 49 CF centers. Inclusion criteria were age 6 to 10 years and forced vital capacity > or = 85% predicted. Patients were excluded for hospitalization for complications of CF within 2 months and use of dornase alfa within 6 months. Patients were treated with dornase alfa 2.5 mg or placebo once daily with a jet nebulizer and a compressor. RESULTS: Patients were randomized, 239 to dornase alfa and 235 to placebo. At baseline the mean age was 8.4 years, the mean forced expiratory volume in 1 second 95% predicted, the mean forced expiratory flow, midexpiratory phase 85% predicted, and the mean forced vital capacity 102% predicted. At 96 weeks the treatment benefit for dornase alfa compared with placebo in percent predicted (mean +/- SE) was 3.2 +/- 1.2 for forced expiratory volume in 1 second (P =.006), 7.9 +/- 2.3 for forced expiratory flow between 25% and 75% of vital capacity (P =.0008), and 0.7 +/- 1.0 for forced vital capacity (P =.51). The risk of respiratory tract exacerbation was reduced by 34% in patients who received dornase alfa (relative risk 0.66, P =.048). There was no statistically significant difference between the groups in changes in weight-for-age percentile. Adverse event profiles for the treatment groups were similar. CONCLUSIONS: Treatment of young patients with CF with dornase alfa maintains lung function and reduces the risk of exacerbations over a 96-week period.
Assuntos
Fibrose Cística/tratamento farmacológico , Desoxirribonuclease I/uso terapêutico , Expectorantes/uso terapêutico , Pneumopatias/congênito , Pneumopatias/tratamento farmacológico , Pulmão/anormalidades , Proteínas Recombinantes/uso terapêutico , Fatores Etários , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Criança , Fibrose Cística/complicações , Fibrose Cística/fisiopatologia , Desoxirribonuclease I/administração & dosagem , Método Duplo-Cego , Expectorantes/administração & dosagem , Feminino , Humanos , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Pneumopatias/etiologia , Masculino , Proteínas Recombinantes/administração & dosagem , Testes de Função Respiratória , Sistema Respiratório/efeitos dos fármacos , Sistema Respiratório/fisiopatologia , Fatores de Tempo , Resultado do TratamentoRESUMO
We evaluated the functional activities of antibodies, serum bactericidal activity (SBA), and immunoglobulin G (IgG) antibody avidity indices, using sodium thiocyanate (NaSCN) elution, elicited after vaccination with fractional doses of the Haemophilus influenzae type b conjugate (polyribosylribitol phosphate [PRP] conjugated to tetanus toxoid [PRP-T]) vaccine. A cohort of 600 infants from the Dominican Republic were randomized to receive one of three regimens of the PRP-T vaccine at ages 2, 4, and 6 months: full doses (10 microg of PRP antigen), one-half doses (5.0 microg), and one-third doses (3.3 microg) (J. Fernandez et al., Am. J. Trop. Med. Hyg. 62:485-490, 2000). Sixty serum samples, collected at age 7 months, with > or =2.0 microg of anti-PRP IgG per ml were randomly selected for avidity determinations. Geometric mean IgG concentrations were 13, 14, and 17 microg/ml for infants who received the full-dose (n = 19), one-half-dose (n = 19), and one-third-dose (n = 22) regimens, respectively. SBA geometric mean titers (1/dilution) were 85.0, 82.0, and 76.1 in sera from infants receiving the full-, one-half-, and one-third-dose regimens, respectively. Avidity indices (mean +/- standard error weighted average of NaSCN molar concentration x serum dilution factor) were 71.9 +/- 9.4, 123.6 +/- 26.8, and 150.9 +/- 24.9 for the full-, one-half-, and one-third-dose regimens, respectively. Upon comparison, the only significant difference (P = 0.024) found was a greater avidity index for sera from infants receiving the one-third-dose regimen than for sera from infants receiving the the full-dose regimen. We conclude that fractional doses elicit similar functional antibody activities in infants with > or = 2 microg of anti-PRP IgG per ml, corresponding to 89, 90, and 97% of infants receiving three doses of either the full concentration or one-half or one-third of the labeled concentration, respectively. This approach offers an alternative strategy for the prevention of H. influenzae type b disease in countries with limited resources.
Assuntos
Anticorpos Antibacterianos/sangue , Toxoide Diftérico/administração & dosagem , Toxoide Diftérico/imunologia , Infecções por Haemophilus/prevenção & controle , Vacinas Anti-Haemophilus/administração & dosagem , Vacinas Anti-Haemophilus/imunologia , Haemophilus influenzae/imunologia , Estudos de Coortes , Países em Desenvolvimento , Toxoide Diftérico/economia , República Dominicana , Infecções por Haemophilus/imunologia , Vacinas Anti-Haemophilus/economia , Custos de Cuidados de Saúde , Humanos , Imunoglobulina G/sangue , LactenteRESUMO
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
To determine the effects of the pulmonary hypoplasia present at birth in infants with congenital diaphragmatic hernia upon subsequent development of the lung, 19 patients who had undergone surgical repair before the age of one year were studied at ages 6 to 18 years. Total lung capacity and vital capacity averaged 99% of predicted value. Diffusing capacity for carbon monoxide was normal. Forced expiratory volume in one second averaged 89% of predicted value and 80% of vital capacity. Total respiratory system conductance and maximum expiratory flow volume curves obtained during air and helium-oxygen breathing were normal. Xenon 133 radiospirometry performed in nine patients revealed equal distribution of lung volumes on the two sides. Ventilation to the hernia side was reduced in only two patients. Blood flow to the hernia side was reduced in all nine patients. Chest radiographs supported the physiologic observations. These findings are consistent with the persistence of a reduction in the number of branches or generations of pulmonary arteries and bronchi on the side of the hernia. Since a substantial part of the vascular resistance resides in peripheral vessels, this developmental abnormality influences the distribution of pulmonary blood flow, although it has little effect on tests reflecting airway resistance or the distribution of ventilation.