Hyaline Membrane Disease Imaging 

Respiratory distress syndrome (RDS) of the newborn is an acute lung disease caused by surfactant deficiency. It is seen primarily in neonates younger than 36-38 weeks' gestational age and weighing less than 2500 g. In comparison, hyaline membrane disease (HMD) tends to occur in neonates younger than 32 weeks' gestational age and weighing less than 1200 g. The radiographic features of respiratory distress syndrome are seen in the images below.

The incidence and severity of RDS is inversely related to gestational age. RDS is the most common cause of respiratory failure during the first days after birth. In addition to prematurity, other factors contributing to the development of RDS are maternal diabetes, cesarean delivery without preceding labor,^[1] fetal asphyxia, and being the second born of twins.^{[2, 3]}

The outcome of patients with RDS has improved with the increased use of antenatal steroids to improve pulmonary maturity, early postnatal surfactant therapy to replace surfactant deficiency, and gentle techniques of ventilation to reduce barotrauma to the immature lungs.

Randomized, controlled trials have shown surfactant therapy to be efficacious in treating infants with, or at risk for, respiratory distress syndrome. A study by Soll et al demonstrated that multiple doses of animal-derived surfactant extract provided greater improvement than single-dose therapy did with regard to oxygenation and ventilatory requirements, reduced risk of pneumothorax, and improved survival.^[4]

Lahra et al found that maternal and fetal intrauterine inflammatory responses (chorioamnionitis and umbilical vasculitis) are protective for RDS. In this study, chorioamnionitis with umbilical vasculitis was found to provide a markedly greater reduction of RDS than the presence of chorioamnionitis alone.^[5]

Preferred examination

Respiratory distress syndrome is usually diagnosed with a combination of clinical signs and/or symptoms, chest radiographic findings, and arterial blood gas results.

In RDS, the classic chest radiographic findings consist of pronounced hypoaeration, bilateral diffuse reticulogranular opacities in the pulmonary parenchyma, and peripherally extending air bronchograms.

The reticulogranularity is due to superimposition of multiple acinar nodules caused by atelectatic alveoli. The development of air bronchograms depends on the coalescence of areas of acinar atelectasis around aerated bronchi and bronchioles. In nonintubated infants, cephalic doming of the diaphragms and hypoexpansion are observed. The radiographic features of classic RDS are seen in the image below.

Radiologic spectrum

The radiologic spectrum of RDS ranges from mild to severe (as seen in the images below) and is generally correlated with the severity of the clinical findings. In the early stages of the disease, notable air bronchograms are lacking, because the major bronchi lie in the more anterior portions of the lungs and because alveolar atelectasis tends to involve the dependent areas of the lungs, which are posterior in recumbent infants. However, a bubble appearance, which represents overdistended bronchioles and alveolar ducts, can be observed.

As RDS progresses, the reticulogranular pattern becomes prominent due to coalescence of the small atelectatic areas. This coalescence leads to larger areas of increased lung opacity. As the anterior portions of the lung become involved with microatelectasis, the granularity becomes uniformly distributed, and air bronchograms can be seen.

With increasing severity of disease, progressive opacification of the anterior portions of the lungs cause obscuration of cardiac silhouette and the formation of prominent air bronchograms. With severe disease, the lungs appear opaque and display prominent air bronchograms, with total obscuration of cardiomediastinal silhouette.

In infants with mild to moderate RDS, hypoaeration and reticulogranular opacities persist for 3-5 days. Clearing from the peripheral to the central areas and from the upper lobe to the lower lobe begins at the end of the first week. Infants with severe RDS have progressive hypoaeration and diffuse bilateral opacities. Superimposed parenchymal hemorrhage may be noted. This type of severe and progressive RDS often leads to death, usually within 72 hours.

The radiographic findings of RDS depend on the timing of the administration of surfactant. Early on, despite prevention with surfactant, the lungs are hypoaerated and have a reticulogranular pattern due to interstitial fluid and atelectatic alveoli. The administration of surfactant usually produces some clearing, which may be symmetrical or asymmetrical; the asymmetry usually disappears in 2-5 days.

Because the surfactant is not evenly distributed throughout the lungs, areas of improving lung alternating with areas of unchanged RDS is common. This uneven distribution leads to a radiographic appearance similar to that of other entities, such as neonatal pneumonia and meconium aspiration syndrome. The clearing is sometimes irregular, creating a cystic appearance. Relapse may occur after initial improvement.

Infants who are being ventilated with intermittent positive pressure with positive end-expiratory pressure may have well-aerated lungs without air bronchograms. Infants with severe disease may be unable to expand their lungs; they have total opaque radiographs. Late in the course of the disease, pulmonary edema, air leaks, or pulmonary hemorrhage can affect the radiographic appearance.

With positive-pressure ventilation, the lungs opacity decreases, and they appear radiographically improved. However, the positive pressure required to aerate the lungs can disrupt the epithelium, producing interstitial and alveolar edema. It can also cause the dissection of air into the interlobar septae and their lymphatics, producing pulmonary interstitial emphysema (PIE), which has the appearance of tortuous, 1- to 4-mm linear lucencies that are relatively uniform in size. These radiate outward from the hilar regions. The lucencies do not empty on expiration and extend to the periphery of the lungs. (PIE is shown in the image below.)

PIE can be symmetrical, asymmetrical, or localized to 1 portion of a lung. Peripheral PIE can produce subpleural blebs and ultimately rupture into pleural space to produce pneumothorax (usually tension pneumothorax, shown in the image below), or they can extend centrally to produce pneumomediastinum or pneumopericardium. Because infants are supine and because air rises to the highest point of the thorax, the pneumothorax is located paramediastinally, resulting in the sharp mediastinum sign, whereby the mediastinum/heart is sharply outlined by adjacent free air rather than aerated lung tissue.

A continuous diaphragm sign, which is caused by air in the mediastinum beneath the heart, may be seen with pneumomediastinum. When alveoli rupture, air may become localized and may coalesce in the parenchyma to produce pulmonary pseudocyst. In addition to parenchymal pseudocysts and PIE, alveolar rupture may allow air to enter the pulmonary venous system, leading to systemic air embolism with intravascular air.

After days of ventilatory support, interstitial fibrosis results from the cumulative effect of therapeutic insult to the pulmonary parenchyma. This fibrosis is often accompanied by exudative necrosis and a honeycomb appearance of the lungs on chest radiography. This condition is referred to as bronchopulmonary dysplasia (BPD). The honeycomb appearance represents focally distended alveolar groups in a scarred, and immature lungs.

Because infants with RDS are usually hypoxic, the ductus arteriosus may remain patent. Early in the disease, shunting is from right to left. By the end of first week, shunting becomes left to right as pulmonary artery pressure decreases because of the increased compliance of the healing lungs. Interstitial pulmonary edema may develop. Therefore, when the granular pattern of hyaline membrane disease changes to a homogeneously opaque appearance, pulmonary edema due to patent ductus arteriosus (PDA) or early chronic pulmonary changes should be suspected.

Radiographic findings in conditions mimicking RDS

Meconium aspiration syndrome (shown below) usually occurs in postterm infants, especially in those with meconium staining. Clinical symptoms usually appear 12-24 hours after birth. (In contrast, clinical symptoms of RDS always appear within the first few hours of life.)

The most common radiographic features are hyperaeration and bilateral, diffuse, and grossly patchy areas of increased radiopacity. Pneumothorax in fetal aspiration syndrome is usually not tension pneumothorax; therefore, it often requires no specific therapy. In RDS, the lungs are hypoaerated, and the abnormal lung radiopacities due to alveolar resorption atelectasis are finely granular. In addition, pneumothorax related to RDS is often under tension, and surgical intubation is required.

Transient tachypnea of the newborn (TTN), seen in the image below, usually occurs in term infants, usually after cesarean delivery. Clinical symptoms usually manifest within 6 hours of birth. Radiographic findings include increased or normal lung volume, with interstitial edema and pleural effusions. In RDS, bilateral reticular or granular parenchymal opacities are present for at least 3-4 days, whereas in transient tachypnea, these opacities are fleeting. Hypoaeration is typical of RDS, in contrast to the hyperaeration of transient tachypnea.

Neonatal pneumonia is usually associated with premature rupture of membranes. Clinical symptoms appear less than 6 hours after birth. Radiographic findings include perihilar streaking. Neonatal pneumonia often produces hyperaeration of the lungs, but in general, the areas of pneumonia are focal rather than diffuse. Pleural effusions may be the only distinguishing feature; they are not a feature of uncomplicated RDS but are present in as many as two thirds of patients with pneumonia. Group B beta-hemolytic streptococcal pneumonia often occurs with RDS, or it can mimic the appearance of RDS. Hence, many neonatal units give antibiotics to all neonates with this condition until blood cultures are negative.

Differentiating RDS from diffuse pulmonary hemorrhage may be difficult. One feature that aids in the differential diagnosis is the identification of a pleural effusion. Pleural effusions are rare in RDS but are common in pulmonary hemorrhage.

Degree of confidence

If chest images in a premature infant show reticulogranular opacities, RDS can be diagnosed with 90% confidence.

False positives/negatives

Other entities that may produce opacities similar to those of RDS include immature lung, wet lung disease, neonatal pneumonia, idiopathic hypoglycemia, congestive heart failure, maternal diabetes, and early pulmonary hemorrhage.

Homogeneous opacification of the lungs due to consolidation of the lower lobes may been seen on upper abdominal ultrasonography. In addition, ultrasonography can be useful to diagnose or exclude a simultaneous or complicating pleural effusion.