Lung Disease in Premature Infants
Thais Mauad, M.D., Ph.D.
Jennifer M. Boland, M.D.
Background
One out of every nine live births in the United States and Europe occurs at <37 weeks of gestation, and rates of preterm births are increasing. In countries like the United States, 90% of preterm infants survive, resulting in a high rate of lung disease related to prematurity.
Pulmonary complications of preterm births are seen most frequently in extremely preterm infants (<28 weeks of gestation) and very preterm infants (28 to 31 weeks of gestation). In general, infants born during the canalicular or early saccular stage of lung development have the greatest risk of developing early pulmonary disease and later pulmonary morbidity.
Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease observed as a complication of prematurity. Further, preterm birth predisposes the development of adult respiratory disease, such as asthma and chronic obstructive pulmonary disease.1
Stages of Lung Development and Prematurity
The embryonic lung buds appear as early as 3 to 4 weeks of embryonic life. This bud is an outgrowth of the ventral wall of the primitive foregut, the laryngotracheal groove. The stages of lung development are outlined in Chapter 12.
In the canalicular stage (16 to 28 weeks gestation), respiratory bronchioles, alveolar ducts, and primitive alveoli are formed. There is differentiation of type I and type II pneumocytes and the formation of the alveolar capillary barrier. At 24 weeks of intrauterine life, surfactant protein is detected, an important milestone in lung growth and maturation. The canalicular stage is characterized by enlargement of the peripheral airways and the formation of saccules (dilatation of the acinar tubules) and thinning of the alveolar walls. There is also incremental increase in surfactant production.2,3
The majority of the gas exchange surface is formed during the saccular-alveolar stage, occurring at 27 to 28 weeks of gestation and later. The formation of double capillary walled secondary septa and multiplication of alveoli continue rapidly up to 2 to 3 years after birth.4 A series of hormones, growth factors, and transcriptional factors are involved in each stage of maturation, and deciphering the molecular biology of the developing lung is very important to advance the process of lung regeneration.5
It is estimated that there are 20 to 50 million of alveoli at birth, increasing to 300 to 800 million in adulthood. Alveolar size and surface area increase until after adolescence. Postnatal microvascular maturation occurs up to 2 to 3 years of age, involving fusion of double-walled capillaries into mature single layer alveolar walls, allowing for optimal gas exchange. From age 2 years to young adulthood, lung compartments grow in proportion to lung volume and also linearly with body weight.6
Respiratory Distress Syndrome
Definition
Respiratory distress syndrome (RDS) is immature lung disease in a preterm infant resulting from insufficient surfactant.
Incidence and Risk Factors
The overall incidence of RDS is increasing, in part related to the steep rise in the number of multiple births over the past decades. Advances in medical technology and management (antenatal corticosteroids, artificial surfactant, and protective or noninvasive ventilator strategies) have led to increase in the survival of extremely preterm babies born during the late canalicular stage of lung development, when the thinning of the epithelium in terminal bronchioles permits gas exchange and sustains life, but before the terminal airspaces have formed. Survival before this stage of maturation is only possible when extracorporeal oxygenation is provided (margin of viability).7
The incidence of RDS decreases with gestational age at birth and is about 70% in infants <32 weeks’ gestation.7
Males tend to have higher incidence and severity of RDS because of increased circulating androgens, which delays lung maturation. Black infants develop RDS less frequently, and with less severity, compared to other races. Maternal diabetes, caesarean section, and perinatal asphyxia are associated with increased rates of RDS, whereas prolonged rupture of membranes and chronic fetal stress tend to decrease the incidence of RDS. Antenatal administration of corticosteroids decreases the incidence of RDS, but it is believed also to impair microvascular maturation and cause lung growth arrest.8
Surfactant Physiology and RDS Pathogenesis
Similar to a soap bubble, the alveolus is characterized by high surface tension generated by molecular forces at an air-liquid interface. The physical integrity of the alveolus is maintained by surfactant, composed mostly of phospholipid, especially phosphatidylcholine, which has surface tension-lowering properties. The surfactant proteins
A, B, and C constitute 10% of the pulmonary surfactant and facilitate the formation of phospholipid films at the air-liquid interface. They also function as host defense proteins.8
A, B, and C constitute 10% of the pulmonary surfactant and facilitate the formation of phospholipid films at the air-liquid interface. They also function as host defense proteins.8
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