RESUMEN
Despite its apparent benefits, high-dose ibuprofen has been infrequently applied to children with cystic fibrosis. We have noted a decrease in the use of high-dose ibuprofen at our pediatric cystic fibrosis center during the past decade. In this retrospective study, we examined our clinical experience with high-dose ibuprofen and other anti-inflammatory drugs in cystic fibrosis patients. The medical records of all patients, ages 5 to 18 years, followed at the cystic fibrosis center from 1995 to 2002, were reviewed and children were classified into two cohorts: ibuprofen-treated and untreated groups. Patterns of ibuprofen use and pharmacokinetics in treated patients, and for patients who discontinued ibuprofen, the reasons for stopping the medication, including adverse effects, were assessed. Pulmonary function decline and hospitalization rates for each group were compared, examining both intent to treat and patients who continued therapy for at least 4 years. Nearly half of the patients in our pediatric cystic fibrosis center who were prescribed with high-dose ibuprofen discontinued therapy due to adverse events, not because of poor adherence or patient choice. Neither use of high-dose ibuprofen nor its cessation resulted in a significant change in the rate of decline in pulmonary function or influenced hospitalization rates.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Fibrosis Quística/tratamiento farmacológico , Ibuprofeno/uso terapéutico , Enfermedades Pulmonares/tratamiento farmacológico , Adolescente , Antiinflamatorios no Esteroideos/farmacocinética , Niño , Preescolar , Fibrosis Quística/complicaciones , Fibrosis Quística/patología , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Hospitalización , Humanos , Ibuprofeno/farmacocinética , Tiempo de Internación , Enfermedades Pulmonares/etiología , Masculino , Cooperación del Paciente , Pruebas de Función Respiratoria , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
RATIONALE: The underlying defect in the cystic fibrosis (CF) airway leads to defective mucociliary clearance and impaired bacterial killing, resulting in endobronchial infection and inflammation that contributes to progressive lung disease. Little is known about the respiratory microbiota in the early CF airway and its relationship to inflammation. OBJECTIVES: To examine the bacterial microbiota and inflammatory profiles in bronchoalveolar lavage fluid and oropharyngeal secretions in infants with CF. METHODS: Infants with CF from U.S. and Australian centers were enrolled in a prospective, observational study examining the bacterial microbiota and inflammatory profiles of the respiratory tract. Bacterial diversity and density (load) were measured. Lavage samples were analyzed for inflammatory markers (interleukin 8, unbound neutrophil elastase, and absolute neutrophil count) in the epithelial lining fluid. RESULTS: Thirty-two infants (mean age, 4.7 months) underwent bronchoalveolar lavage and oropharyngeal sampling. Shannon diversity strongly correlated between upper and lower airway samples from a given subject, although community compositions differed. Microbial diversity was lower in younger subjects and in those receiving daily antistaphylococcal antibiotic prophylaxis. In lavage samples, reduced diversity correlated with lower interleukin 8 concentration and absolute neutrophil count. CONCLUSIONS: In infants with CF, reduced bacterial diversity in the upper and lower airways was strongly associated with the use of prophylactic antibiotics and younger age at the time of sampling; less diversity in the lower airway correlated with lower inflammation on bronchoalveolar lavage. Our findings suggest modification of the respiratory microbiome in infants with CF may influence airway inflammation.