RESUMO
STUDY OBJECTIVES: Chronic allograft rejection is the leading cause of morbidity and mortality for long-term survivors of lung transplantation. Previous studies have implicated only isolated genes in the development of chronic rejection and have not examined multiple pathways in an individual concurrently. Using microarray technology, we identified and compared gene expression profiling in lung transplant recipients with and without chronic rejection, and follow sequential expression of genes differentially expressed between the two groups. DESIGN: Prospective, cohort study. SETTING: Single lung transplant center. PATIENTS OR PARTICIPANTS: Eleven transplant recipients with chronic rejection were matched with 9 control transplant recipients. INTERVENTIONS: All recipients underwent surveillance bronchoscopies at predetermined times to rule out infection and/or acute rejection. Gene expression profiling was obtained from hybridizing BAL fluid cell RNA to a 96-gene microarray. MEASUREMENTS AND RESULTS: Fifteen genes were found to be significantly differentially expressed between the two patient groups, and they are involved in inflammatory, fibrotic, and apoptotic pathways. Temporal expression of the significant genes demonstrated a change in their levels at the onset of chronic rejection, with normalization to prerejection levels as rejection continued. CONCLUSIONS: We conclude that microarray technology is valuable in studying the mechanism of chronic lung rejection, and the expression of genes in multiple pathways is elevated in patients with chronic lung rejection.
Assuntos
Sequência de Bases/genética , Perfilação da Expressão Gênica , Rejeição de Enxerto/genética , Transplante de Pulmão/patologia , Transplante/patologia , Adulto , Apoptose/genética , Apoptose/fisiologia , Bronquiolite Obliterante/etiologia , Bronquiolite Obliterante/patologia , Bronquiolite Obliterante/fisiopatologia , Estudos de Coortes , Feminino , Regulação da Expressão Gênica/fisiologia , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Humanos , Inflamação/genética , Inflamação/patologia , Inflamação/fisiopatologia , Pulmão/patologia , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Família Multigênica/genética , Análise de Sequência com Séries de Oligonucleotídeos , Estudos Prospectivos , Fibrose Pulmonar/genética , Fibrose Pulmonar/patologia , Fibrose Pulmonar/fisiopatologia , RNA/genéticaRESUMO
Since international recommendations for lung transplant recipients were made in 1998, newer tools for predicting mortality in patients who have end-stage lung disease have been investigated. This article reviews studies for predicting mortality in obstructive, restrictive, pulmonary vascular, and suppurative/bronchiectatic lung disease. Newer considerations for alternative treatments, postoperative risks, and contraindications are also examined. The article aims to provide more accurate data for selecting patients who will benefit from lung transplantation.
