Pediatric pulmonary diseases account for almost 50% of deaths in children younger than 1 year and about 20% of all hospitalizations of children younger than 15 years. Approximately 7% of children have a chronic disorder of the lower respiratory system. Understanding the pathophysiology of many pediatric pulmonary diseases requires an appreciation of the normal growth and development of the lung.
The lung has its origins from an outpouching of the foregut during the fourth week of gestation. The development of the lung is divided into five overlapping stages.
Embryonic stage (3–7 weeks’ gestation): The primitive lung bud undergoes asymmetrical branching and then subsequent dichotomous branching, leading to the development of the conducting airways. It also involves the development of the large pulmonary arteries. Abnormalities during this stage result in congenital abnormalities such as lung aplasia, tracheoesophageal fistula, and congenital pulmonary cysts.
Pseudoglandular stage (5–17 weeks’ gestation): The conducting airways (bronchi and bronchioles) form over these 12 weeks. The respiratory epithelium of these airways begins to differentiate, and the presence of cartilage, smooth muscle cells, and mucus glands are first seen. In addition, the pleuroperitoneal cavity divides into two distinct compartments. Abnormalities during this stage lead to pulmonary sequestration, cystic adenomatoid malformation, and congenital diaphragmatic hernia.
Canalicular stage (16–26 weeks’ gestation): This stage witnesses the delineation of the pulmonary acinus. Type I alveolar cells appear; the pulmonary capillary network develops. Abnormalities of development during this stage include neonatal respiratory distress syndrome and lung hypoplasia.
Saccular stage (26–36 weeks’ gestation): Further branching of the terminal saccules takes place, as well as a thinning of the interstitium and fusion of the type I cells and capillary basement membrane in preparation for the lungs’ function as a gas-exchange organ. The beginning of an exponential increase in the epithelial surface area of gas exchange happens during the saccular stage.
Alveolar stage (36 weeks’ gestation to 3–8 years of age): Secondary alveolar septae form to increase the surface area for gas exchange, the capillary network has a rapid phase of growth, and true alveoli develop. New data suggest that postnatal alveolarization may continue for more than 7 years after birth.
At birth, the lung assumes the gas-exchanging function served by the placenta in utero, placing immediate stress on all components of the respiratory system. Any abnormality in the lung, respiratory muscles, chest wall, airway, central respiratory control, or pulmonary circulation may lead to problems at birth. There is mounting evidence that disruption or abnormalities occurring during fetal and neonatal growth and development of the lung may have long-standing effects into adulthood, such as reduced gas exchange, exercise intolerance, asthma, pulmonary hypertension, and an increased risk of chronic obstructive pulmonary disease.
CM: Disrupted lung development and bronchopulmonary dysplasia: opportunities for lung repair and regeneration. Curr Opin Pediatr 2014;26(3):306–314