Lung Hypoplasia and Pediatric Thoracic Insufficiency

GENESIS

Lung hypoplasia implies an abnormal reduction in the weight and/or volume of the lung without the absence of any of its lobes; this condition is different from agenesis or aplasia of the lungs. Lung hypoplasia can result from various phenomena. During the fourth week of gestation, the laryngotracheal groove forms in the esophageal portion of the endotracheal tube, and shortly thereafter lung development begins with the evagination of two buds from the ventral surface of this groove. Between 6 and 16 weeks of gestation, these buds invade the thoracic mesenchyme by dichotomous branching so that the conducting airway system is complete by the end of the 16th week. Formation of the acini begins proximally and proceeds distally in the lung, and alveoli appear as early as 32 weeks and continue to develop throughout childhood.

Decreased lung weight and volume can result from a decreased number of bronchial branches, reduced numbers of alveoli, decreased alveolar size, or any combination of these phenomena. Pulmonary hypoplasia can be associated with various types of problems: oligohydramnios, thoracic wall abnormalities, diaphragmatic hernia, central nervous system abnormalities, or a group of miscellaneous conditions, including fetal hydrops, extralobar sequestration, or cloacal dysgenesis. Restriction of thoracic cage expansion by a small uterine cavity can also rarely be associated with lung hypoplasia. Certain lethal skeletal dysplasias that result in rib shortening and a small thorax (e.g., thanatophoric dysplasia or asphyxiating thoracic dysplasia [ Figs. 18.1 and 18.2 ]) can have the same impact. Thoracic insufficiency syndrome is the inability of the thorax to support normal respiration or lung growth, and this condition includes a wide group of constrictive thoracospinal conditions (congenital scoliosis, skeletal, neuromuscular, and other structural thoracic disorders) ( Figs. 18.3 and 18.4 ). Intervention is primarily via growth-sparing surgery, for which several device options exist, to preserve vertical growth prior to a definitive spinal fusion at skeletal maturity ( Fig. 18.5 ; Table 18.1 ). In a cohort of 42 individuals with thoracic insufficiency syndromes from a pediatric orthopedic clinic that underwent exome sequencing, the identified genes encoded components of the primary cilium, bone, and extracellular matrix. Exome sequencing identified a molecular etiology in 24/42 (57%) of the participants, with short-rib thoracic dysplasia syndromes manifesting the highest molecular diagnostic rate (81%) and DYNC2H1 being the most common gene (7/16; 44%).

Congenital diaphragmatic hernia occurs in approximately 2.3–2.8 per 10,000 live births and it can result in high neonatal morbidity and mortality, largely associated with the severity of pulmonary hypoplasia and pulmonary arterial hypertension. Fetal akinesia that results in diaphragmatic paralysis and failure to swallow amniotic fluid is associated with polyhydramnios, and it leads to a lack of lung expansion and pulmonary hypoplasia. Prolonged oligohydramnios resulting from either renal agenesis or prolonged rupture of membranes can lead to pulmonary hypoplasia. Thus distension of the lung with lung liquid and fetal lung movements are both needed for normal lung growth.

Restrained thoracic growth was initially hypothesized to cause the lungs to remain small and underdeveloped in oligohydramnios sequence, but it is the inhibition of breathing movements (essential for lung growth) and/or abnormal fluid dynamics within the lung that result in decreased intraluminal fluid pressures and cause poor lung growth. The gestational age at the time of premature rupture of membranes relates to the histologic development of the lungs, which can be divided into three stages. During the pseudoglandular stage (5–17 weeks of gestation), all major lung elements are formed except those related to gas exchange. During the canalicular stage (16–25 weeks), terminal bronchioles give rise to respiratory bronchioles and then to thin-walled terminal sacs. During the terminal sac stage (24 weeks to birth), the number of terminal sacs rapidly increases, which increases the total gas exchange area. If oligohydramnios is limited to the terminal sac stage, it does not affect lung growth, but when oligohydramnios is induced during the canalicular stage, it results in a cumulative reduction in lung size. Thus the risk for pulmonary hypoplasia diminishes when oligohydramnios occurs after 24 weeks of gestation. The duration of severe oligohydramnios and the gestational age at which oligohydramnios had its onset are independent risk factors, and severe oligohydramnios lasting more than 14 days with rupture of membranes before 25 weeks results in a mortality rate greater than 90%.