Epigenetics and the developmental origins of lung disease

The developmental origins of disease hypothesis have recently been expanded to include the early origins of lung disease, particularly early events that alter lung development. Intrauterine growth restriction (IUGR), preterm birth with the need for prolonged mechanical ventilation, and maternal tobacco smoke (MTS) or nicotine exposure produce neonatal and adult lung disease. These perinatal insults are characterized by alterations in alveolar formation and changes in the expression of genes that regulate alveolarization, including IGF1 and PPAR gamma. A potential mechanism for such changes in gene expression is epigenetics. IGF1 and PPAR gamma have altered epigenetic states in response to these perinatal insults. Identification of the specific epigenetic mechanisms involved in the developmental origin of lung disease may facilitate identification of molecular biomarkers with the potential to personalize respiratory disease risk assessment and treatment. The purpose of this review is to summarize what is known about the developmental origins of lung disease, the epigenetic contributions to lung disease, and areas that need further investigation. (C) 2011 Elsevier Inc. All rights reserved.