Complications of Development And Congenital Disease
Problems associated with premature birth
Neonatal respiratory distress syndrome (NRDS), otherwise known as hyaline membrane disease, occurs in approximately 2% of all births and is characterized by rapid, laboured breathing and often sternal retraction due to partial collapse of the lungs after each breath. Lung compliance is low. NRDS is most commonly caused by lack of sufficient quantities of surfactant and consequent high surface tension in the alveoli and small airways. Incidence therefore increases sharply with the degree of prematurity (Fig. 17a), although other factors may also reduce production of surfactant. When a premature birth is anticipated, the expectant mother can be treated with corticosteroids (betamethasone) to speed fetal lung development and surfactant production. Treatment with exogenous surfactant in the first 30 minutes after birth, either of natural origin or artificial has also proved to be beneficial Survival of neonates with NRDS often requires high positive-pressure mechanical ventilation and high levels of oxygen.
The large majority of NRDS cases are related to prematurity, with some due to other causes including damage to type II pneumocytes. A very few cases are due to a congenital absence of pulmonary surfactant protein B. These patients do not respond to any form of therapy and tend to die in the f rst few months of life.
Bronchopulmonary dysplasia (chronic lung disease of the new born) is a long term consequence of NRDS, primarily as a result of treatment with high positive-pressure ventilation combined with high levels of oxygen (hyperoxia). The condition is characterized by alterations in the structure and function of airways and pulmonary blood vessels, including increases in airway and vascular smooth muscle and obliteration of some microstructures. This leads to poorly reversible airway obstruction and sometimes pulmonary hypertension (high pulmonary blood pressure). Survivors may retain symptoms for many years, if not for life. There are several similarities to chronic obstructive pulmonary disease (COPD, Chapter 26) and chronic severe asthma in adults.
Several techniques have recently been designed to minimize the incidence of bronchopulmonary dysplasia in infants with NRDS. These include extracorporeal membrane oxygenation (ECMO), where blood is circulated via external apparatus for gas exchange; mechanical ventilation and hyperoxia are therefore not required and some success has been reported. Conversely, ECMO has not been found useful in adults with acute respiratory distress syndrome (ARDS, Chapter 41). Partial ﬂuid ventilation, where the lungs are ventilated with fluid containing oxygen-carrying perfluorocarbons has also been reported to be beneficial Fluid ventilation circumvents problems associated with high surface tension by removing the air-liquid interface and allows small airways to open and contribute to gas exchange.
Congenital diaphragmatic hernia is the most common cause of lung hypoplasia (inadequate development of the lung), with an incidence
of about one in 2000 births. Failure of the diaphragm to fuse with the membranes on the thoracic and peritoneal wall leads to a posterolateral defect, most commonly occurring on the left side ( 85%), through which the abdominal viscera pass (herniate) into the thorax (Fig. 17b). This often includes the stomach, spleen and much of the intestines. The presence of the resultant mass severely restricts lung development and later inflation leading to a significantly reduced lung volume and life-threatening breathing difficulties. The latter are the prime cause of death in congenital diaphragmatic hernia, and most infants will die because the lungs are insufficiently developed to support life outside the uterus. Although surgical correction of the defect is possible both before and after birth, the mortality rate is very high. A related but very much less common condition is eventration of the diaphragm, where half the diaphragm lacks adequate muscle and bulges (eventrates) into the thoracic cavity. The viscera are forced into the pocket so formed, again restricting lung development.
Tracheo-oesophageal ﬁstula (an opening between oesophagus and trachea) is the most common abnormality of the lower respiratory tract itself, with an incidence of about one in 4000 births. Its origins are located in the fourth week of development, when the embryonic respiratory tract starts to develop and divide from the embryonic oesophagus (Chapter 16). Eighty-five percent of cases are associated with the descending part of the oesophagus having a blind ending (oesophageal atresia) (Fig. 17c); the lower part of the oesophagus joins instead to the base of the trachea. As a result, normal feeding is impossible and the gut becomes distended with air. There are also consequences in utero, as normally amniotic flui is ingested by the fetus. Thus, oesophageal atresia is commonly associated with excess amniotic fluid (polyhydramnios), which can lead to severe defects in the central nervous system. Some 5% of cases of tracheo-oesophageal fistul show no atresia but only a fistula and the remainder less common variations. Rare defects involving blockage or narrowing of the trachea itself (tracheal atresia/stenosis) are nearly always accompanied by various types of tracheo-oesophageal fistula
There are many inherited disorders of haemoglobin synthesis. In some (e.g. thalassaemia) there is inadequate production of the normal globin chains, and in others (e.g. HbS in sickle cell disease) there is production of globin chains with an abnormal amino acid sequence. They produce a variety of clinical problems mostly related to anaemia and/or alteration in the solubility (HbS) or oxygen affinity of the abnormal haemoglobin (Chapter 8).
Congenital inﬂuences on respiratory disease: several important respiratory diseases that are discussed in detail in other chapters have definit or implied genetic components, including asthma (Chapter 24), chronic obstructive pulmonary disease (Chapter 26), emphysema (Chapter 26), cystic fibrosi (Chapter 34) and pulmonary arterial hypertension (Chapter 27). Other genetically linked diseases that cause pathological problems primarily in the lung are listed in Fig. 17d.