RESUMO
OBJECTIVE: To evaluate lung transplantation for treatment of surfactant protein B (SP-B) deficiency. STUDY DESIGN: We compared surfactant composition and function from pretransplantation and posttransplantation samples of bronchoalveolar lavage fluid, somatic and lung growth, neurodevelopmental progress, pulmonary function, and pulmonary immunohistology in 3 infants with SP-B deficiency who underwent bilateral lung transplantation at 2 months of age and 3 infants who underwent lung transplantation for other reasons. RESULTS: Two years after transplantation, the 2 surviving infants with SP-B deficiency exhibited comparable somatic growth and cognitive development to the comparison infants. All infants had delays in gross motor development that improved with time. Both groups have exhibited normal gas exchange, lung growth, and pulmonary function. The SP-B-deficient infants have also exhibited normal SP-B expression and pulmonary surfactant function after lung transplantation. In two SP-B-deficient infants antibody to SP-B developed. No pathologic consequences of this antibody were identified. CONCLUSIONS: Apart from the development of anti-SP-B antibody, the outcomes for SP-B-deficient infants after lung transplantation are similar to those of infants who undergo lung transplantation for other reasons. Lung transplantation offers a successful interim therapy until gene replacement for this disease is available.
Assuntos
Transplante de Pulmão , Proteolipídeos , Surfactantes Pulmonares/deficiência , Síndrome do Desconforto Respiratório do Recém-Nascido/cirurgia , Anticorpos/sangue , Líquido da Lavagem Broncoalveolar/química , Feminino , Humanos , Terapia de Imunossupressão/métodos , Lactente , Recém-Nascido , Pulmão/patologia , Pulmão/fisiopatologia , Transplante de Pulmão/imunologia , Transplante de Pulmão/patologia , Transplante de Pulmão/fisiologia , Complicações Pós-Operatórias/epidemiologia , Proteolipídeos/análise , Proteolipídeos/imunologia , Surfactantes Pulmonares/análise , Surfactantes Pulmonares/imunologia , Síndrome do Desconforto Respiratório do Recém-Nascido/imunologia , Síndrome do Desconforto Respiratório do Recém-Nascido/patologia , Sobreviventes , Resultado do TratamentoRESUMO
An infant with a family history of congenital alveolar proteinosis associated with surfactant protein B (SP-B) deficiency was identified when SP-B was not detected in amniotic fluid obtained at 37, 38, and 40 weeks of gestation. Surfactant replacement with commercially available preparations that contained SP-B was begun soon after delivery. Progressive respiratory failure developed despite continued surfactant replacement, corticosteroid therapy, and extracorporeal membrane oxygenation. The infant died at 54 days of age while awaiting lung transplantation. Surfactant extracted from amniotic fluid, bronchoalveolar lavage fluid, and lung tissue had no phosphatidylglycerol; surface tension was 24 dynes/cm (normal, < 10 dynes/cm) and did not decrease with in vitro addition of exogenous SP-B. Pulmonary vascular permeability measured with positron emission tomography was twice normal. At autopsy the alveolar proteinosis pattern was less prominent than that seen in affected siblings. Immunoreactivity of SP-B was absent in type II cells, but numerous foreign body granulomas with central immunoreactivity for SP-B and surfactant protein C were present. We conclude that exogenous surfactant replacement did not normalize surfactant composition, activity, or pulmonary vascular permeability. These findings suggest that endogenous SP-B synthesis is necessary for mature surfactant metabolism and function.