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.
Assuntos
Doenças Fetais/diagnóstico , Diagnóstico Pré-Natal , Proteolipídeos/uso terapêutico , Proteinose Alveolar Pulmonar/diagnóstico , Proteinose Alveolar Pulmonar/tratamento farmacológico , Surfactantes Pulmonares/deficiência , Surfactantes Pulmonares/uso terapêutico , Líquido Amniótico/química , Líquido da Lavagem Broncoalveolar/química , Permeabilidade Capilar , Dexametasona/uso terapêutico , Evolução Fatal , Granuloma de Corpo Estranho/patologia , Humanos , Doença da Membrana Hialina/tratamento farmacológico , Doença da Membrana Hialina/patologia , Recém-Nascido , Pulmão/irrigação sanguínea , Pulmão/patologia , Masculino , Planejamento de Assistência ao Paciente , Proteolipídeos/análise , Proteinose Alveolar Pulmonar/patologia , Surfactantes Pulmonares/análise , Surfactantes Pulmonares/química , Tomografia Computadorizada de EmissãoRESUMO
Seventy children with cystic fibrosis were studied over a 5-year period to assess the relationship between serum immunoglobulin G levels and progression of cystic fibrosis lung disease. Patients were grouped according to their serum IgG values (low, normal, or high) and evaluated with serial pulmonary function testing, radiographic and immunologic studies, and clinical observation. The children with persistent hypogammaglobulinemia G showed significantly better lung function, better weight for age, fewer hospitalizations for pulmonary exacerbations, less colonization with Pseudomonas aeruginosa, and slower decline in pulmonary functions than did age-matched patients with normal or high IgG levels. Death occurred in five of eight (63%) patients with hypergammaglobulinemia, three of 30 (10%) with normogammaglobulinemia, and one of 32 (3%) with hypogammaglobulinemia. No deaths occurred in the 15 patients with persistent hypogammaglobulinemia. These data indicate that children with cystic fibrosis and hypogammaglobulinemia G have milder lung disease and slower deterioration in pulmonary function than do age-matched patients with normal or elevated immunoglobulin G values. The mechanisms accounting for this finding are unclear.
Assuntos
Fibrose Cística/imunologia , Imunoglobulina G/análise , Pneumopatias/imunologia , Agamaglobulinemia/etiologia , Criança , Humanos , Hipergamaglobulinemia/mortalidade , Estudos Longitudinais , Pneumopatias/diagnóstico , Prognóstico , Estudos Prospectivos , Infecções por Pseudomonas/complicações , Testes de Função RespiratóriaRESUMO
Palpable purpura was noted to occur late in the course of some patients with cystic fibrosis. Skin biopsy specimens showed necrotizing venulitis characterized by a perivenular infiltrate composed of neutrophilic leukocytes, fibrin, hypogranulated mast cells, and endothelial cell necrosis. Circulating immune complexes were detected. Recurrent pulmonary infections and the chronic administration of therapeutic agents provide sources of potential antigens.