Associate editor: S.D. BrainEnvironmental factors and developmental outcomes in the lung
Introduction
Lung development commences in the fetus and continues postnatally; this process is associated with distinct tightly regulated events that span 5 developmental stages: embryonic, pseudoglandular, canalicular, saccular, and alveolar. During the embryonic stage the future lung appears as an outgrowth of the ventral wall of the primitive foregut to form endodermal buds that invade the adjacent mesenchyme. The subsequent processes involved in the transformation from this small aggregation of cells to the highly complex structures of the respiratory system that include the trachea, extrapulmonary bronchi, intrapulmonary bronchi, bronchioles, the alveolar gas exchange area, and the accompanying pulmonary circulation and neural networks have been comprehensibly reviewed elsewhere (Burri, 1984, Jeffrey, 1998, Kotecha, 2000, Fasouliotis et al., 2002, Sparrow et al., 2004, Hislop, 2005) and briefly summarized in Fig. 1.
The complex architecture of the branching tracheobronchial airway tree and septated alveolar gas exchange area relies heavily on focal cellular proliferation and differentiation of epithelial and mesenchymal populations and on the reorganization of matrix and fibrous connective tissue structures to meet specific functional roles. Since the process of lung development is a continuum beginning early in embryonic life and progressing through to adolescence, factors that interfere with the developmental program during any of the phases of development may result in altered lung function and/or increased risk of disease in later life. Extensive evidence supports a causal relationship between environmental air pollutants and respiratory morbidity and mortality in different age groups, including the developing fetus (Maisonet et al., 2004), children (Schwartz et al., 1994, Heinrich et al., 2002, Schwartz, 2004), adolescents (Frye et al., 2003, Gauderman et al., 2004), adults (Schwartz and Marcus, 1990, Dockery et al., 1993), and the elderly (Saldiva et al., 1995, Boezen et al., 2005). In recent years there has been an increasing awareness of the unique anatomical, physiological and behavioral characteristics inherent to fetuses, infants, and children that raise their specific vulnerability to environmental toxicants. In addition, the interaction between genetic and environmental factors is becoming increasingly recognized as an important factor in the etiology of complex lung diseases. This review summarizes the current knowledge on the enhanced vulnerability of the developing lung to toxicants in the environment.
Section snippets
Age and physiological maturity
The immature lung anatomy and physiology of the fetus and young children is an important contributing factor to their increased susceptibility to injury by lung toxicants (see von Mutius, 2001, Mathieu-Nolf, 2002, Makri et al., 2004, Pinkerton and Joad, 2006). The phases of lung organogenesis during early embryonic development represent critical periods of cellular differentiation and branching morphogenesis, whereas late fetal life and early postnatal life represent periods when the lung
Environmental pollutants that influence lung development
As a principal interface between the environment and the organism, the respiratory tract is extremely vulnerable to the adverse effects of environmental pollutants. The association between exposure (acute and chronic) to environmental pollutants and adverse respiratory symptoms, decreased lung function, and increased exacerbations of cardiopulmonary diseases in infants, children and adults is well documented (Bates, 1995, American Thoracic Society, 1996a, American Thoracic Society, 1996b, Kim,
Summary
There is a growing recognition that several chronic respiratory diseases observed in adults have their etiology in infants, commonly attributed to an increased vulnerability of infants and children to the toxic effects of environmental pollutants. Knowledge about the developmental processes of lung growth and maturation will aid in determining the critical time frames during pre- and postnatal lung development when fetuses, infants, and children are most susceptible to perturbation by
Acknowledgments
RK is supported by grants from the National Institute of Environmental Sciences (NIEHS; PO1 ES00628-29S1) and NIEHS Center for Environmental Health Sciences (ES05707). Dr. A. Graziano's assistance with preparing Fig. 1 and the assembly of all figure images is gratefully acknowledged.
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