The pediatric lungs are smaller than the adult lungs, but there are no significant differences in their gross structural anatomy (Fig. 1.1). The right lung has three lobes (upper, middle, and lower), and the left lung has two lobes (upper and lower). The lobes are separated by two pleura-lined fissures on the right (the major and minor fissures) and one fissure on the left (the major fissure) (Figs. 1.1 and 1.2). The lobes are divided into 10 segments on the right and 8 segments on the left (Fig. 1.1). The right upper lobe is composed of apical, anterior, and posterior segments. The right middle lobe is composed of lateral and medial segments. The right lower lobe is composed of superior, medial basal, anterior basal, lateral basal, and posterior basal segments. The left upper lobe is composed of apicoposterior, anterior, superior lingular, and inferior lingular segments. The left lower lobe is composed of superior, anteromedial basal, posterior basal, and lateral basal segments.

Air is conducted to the lungs by a complex network of branching airways that transmit air to the respiratory bronchioles and alveoli. The large airways, including the trachea and bronchi, are discussed in detail in Section 2 (Large Airways) of this book. Bronchial branches contain cartilage within their walls to the level of the 11th generation, where they have a diameter of ˜1 mm (Fig. 1.3). The airways further branch into bronchioles, which are conducting airways that lack cartilage and extend to the level of the 16th generation (Fig. 1.3). The most distal purely conducting airway is the terminal bronchiole, which gives rise to the respiratory bronchioles (Fig. 1.4). Respiratory bronchioles are capable of gas exchange and also conduct air to the alveoli, which represent the primary site of gas exchange in the lungs.

Although the gross structural anatomy of the pediatric lung is identical to that of the adult lung, alveolar development is not complete at birth, and the number of alveoli continues to increase into early childhood. Most of the alveoli have formed by the age of 2 years, and alveolar development is complete by the age of 8 years. Alveoli range in size from

200 to 300 µm and therefore are not visible on routine radiologic imaging (Fig. 1.5). The pulmonary acinus and secondary pulmonary lobule are the smallest components of the lungs visible on radiologic imaging, and it is therefore essential that radiologists be familiar with their appearance in health and disease. The pulmonary acinus is defined as the portion of the lung that is distal to the terminal bronchiole and is composed of a respiratory bronchiole (or bronchioles) and the associated alveolar ducts and sacs. The pulmonary acinus is, therefore, the largest lung unit in which all the airways perform gas exchange.¹ Each acinus contains ˜50 to 400 alveoli. The pulmonary acinus ranges in size from 6 to 10 mm in adolescence and adulthood and can be visualized on high-resolution CT (HRCT).²,³ The acinus is smaller in younger children, ranging in size from 1 to 2 mm in children under 1 year of age and therefore may not be visible.

The secondary pulmonary lobule is the smallest unit of the lung that is separated by connective tissue septations, which are called interlobular septa (Fig. 1.6). Secondary pulmonary lobules are polyhedral in shape, have a mean diameter of 3 mm at birth, and reach a diameter of 13 to 20 mm in adulthood.² Each secondary pulmonary lobule is composed of 3 to 24 acini, with their accompanying terminal bronchioles.⁴,⁵ Each of these terminal bronchioles arises from a central preterminal “lobular bronchiole,” which is located in the center of the secondary pulmonary lobule. Pulmonary arterial branches travel with the bronchioles in the center of the secondary pulmonary lobule. Pulmonary veins and lymphatics are located within the interlobular septa. Thickened interlobular septa may be visualized on CT outlining the polyhedral secondary pulmonary lobule or may be seen on chest radiographs as Kerley B lines (Fig. 1.7).

Collateral pathways of ventilation are structures that allow air, fluid, or other materials to pass between alveoli. Collateral pathways are interrupted by the pleura-lined fissures (unless a fissure is incomplete). Because pulmonary segments are not separated by fissures, collateral pathways connect the segments within a lobe. There are three types of collateral pathways: (1) pores of Kohn, (2) canals of Lambert, and (3) direct small airway anastomoses (Fig. 1.8). Pores of Kohn are apertures in the alveolar septa, which allow direct communication between alveoli.⁶ Canals of Lambert are epithelium-lined channels that connect distal bronchioles and adjacent alveoli. The collateral pathways are not fully formed in the infant and young child and do not mature until later childhood.

The lung receives deoxygenated blood from the pulmonary arteries (Fig. 1.9). The pulmonary arteries travel with the bronchi and bronchioles, branching ˜28 times before reaching the capillary bed. Distal pulmonary arteries called lobular arteries can be visualized in the center of the secondary pulmonary lobule on HRCT, accompanying lobular bronchioles (Fig. 1.7A). Lobular arteries measure ˜1 mm in diameter by adulthood.⁴ Lobular arteries further branch into intralobular and acinar arteries within the secondary pulmonary lobule, accompanying preterminal and terminal bronchioles. Intralobular and acinar arteries range in size from 0.5 to 1 mm in diameter. Intralobular and, occasionally, acinar arteries can be visualized a few millimeters from the pleural surface.

Pulmonary arteries continue to branch into smaller arterioles that are not visible on imaging studies, forming an extensive alveolar capillary network that participates in gas exchange and blood oxygenation. The very large number of alveolar capillaries form a high capacity, low resistance circuit, with a blood pressure six times lower than the systemic pressure. In this system, a large fraction of the alveolar capillaries are minimally perfused at rest. During times of demand, there is increased perfusion of these capillaries, allowing for increased blood oxygenation with minimal change in pulmonary arterial pressure. Pulmonary blood flow is mainly determined by cardiac output but is also affected by systemic pressure, pulmonary gas pressure, and gravity. Pulmonary arterial resistance is modulated by a process called hypoxic pulmonary vasoconstriction, in which smooth muscle within the pulmonary vessels constricts in direct response to hypoxia.⁷,⁸ This process shunts blood away from areas of under-ventilated lung (i.e., atelectasis) to more ventilated lung in order to help match ventilation and perfusion. In cases of global hypoxia in which a large number of pulmonary arterioles vasoconstrict, this process can contribute to pulmonary hypertension.

Gas exchange occurs at the level of the alveolar capillaries and alveoli. The alveolus is only two cell layers thick, composed of type I respiratory epithelial cells and endothelial cells that are fused at their basal laminae. After leaving the alveolar capillaries, oxygenated blood flows into the pulmonary venules, which are located within the interlobular septa. Therefore, the veins travel separately from the bronchial arteries and bronchioles (which are located in the center of the secondary pulmonary lobule) until the level of the large pulmonary veins, which meet the main pulmonary arterial branches and bronchi at the lung hila.

The lungs receive a small amount of systemic oxygenated blood via two to four bronchial arteries, which primarily supply capillary networks within the lamina propria and submucosa of the trachea, mainstem bronchi, and pulmonary arteries⁹ (Fig. 1.10). Venous blood from the large airways primarily drains to systemic bronchial veins, which drain into the right side of the heart via the hemiazygos and azygos veins. Deeper in the lung, deoxygenated bronchial arteriolar blood is drained via the pulmonary venules, which empty into the left heart. The bronchial circulation normally only accounts for ˜0.5% to 1.5% of total cardiac output, and this right-to-left shunting is trivial in the healthy state.⁹ However, the bronchial circulation has potential to grow and expand throughout life, unlike the pulmonary arterial circulation, which does not grow after childhood. Many disease states that promote angiogenesis, including malignancy, inflammatory conditions, and congenital heart disease, cause bronchial artery proliferation that may lead to clinically significant shunting of deoxygenated blood to the left heart.

Many disease states affect the pulmonary lymphatics; therefore, an understanding of their location is essential (Fig. 1.11). The pulmonary lymphatic system is divided into two components: a deep plexus and a superficial plexus.⁹ The deep plexus travels with the pulmonary arteries and bronchi within the bronchovascular bundle and is therefore found in the center of the secondary pulmonary lobule. The superficial plexus is located within the interstitium of the interlobular septa where it travels with the pulmonary veins, as well as within the visceral pleura.⁴,⁹

Lung development has traditionally been divided into five main developmental phases, beginning in the 4th week of gestation and continuing after birth into early childhood. These phases include the: (1) embryonic, (2) pseudoglandular, (3) canalicular, (4) saccular, and (5) alveolar phases (Table 1.1 and Fig. 1.12).

The pulmonary vasculature develops in tandem with the lung parenchyma, beginning during the embryonic phase. The truncus arteriosus divides into the pulmonary trunk and aorta at 8 weeks of gestation.¹⁶ Pulmonary arch arteries, which are derived from the 6th branchial arch arteries, connect to the pulmonary trunk. Vascular precursors within the epithelium of the lung bud undergo a process of vasculogenesis and form an extensive plexus around the respiratory epithelium.¹¹ Preacinar vascular branching is established by 20 weeks of gestation, and intraacinar arteries continue to develop through the alveolar phase. Pulmonary veins arise within the mesenchyme separately from the arteries, eventually residing within the interlobular septa and connecting to the left atrium.¹⁷

The fetal lung is unique among organs because it does not begin functioning until birth. The lung does not participate in oxygenation during fetal life and does not receive the full cardiac output that it requires after birth. The majority of fetal cardiac output does not reach the lungs during fetal life. Blood bypasses the lungs via two right-to-left shunts: the foramen ovale and ductus arteriosus (DA). At birth, flow of oxygenated blood from the placenta stops when the umbilical cord is clamped, and the circulation pattern must rapidly transform to facilitate alveolar oxygenation. A rapid fall in pulmonary vascular resistance (PVR) at birth, caused by lung inflation and increased alveolar oxygen tension, is the key to this transition. This drop in PVR causes an 8- to 10-fold increase in pulmonary blood flow, resulting in increased left atrial pressures that functionally close the one-way valve of the foramen ovale.¹⁵ As a direct response to increased oxygen tension and the withdrawal of maternal prostaglandins, smooth muscle within the DA contracts in order to close it within the first 1 to 2 days of life.¹⁸

Because the principal trigger for this dramatic transition in blood flow is the drop in PVR that occurs at birth, conditions that result in elevated PVR can lead to persistent pulmonary hypertension of the newborn (PPHN), which causes right-toleft shunting and severe hypoxemia. PPHN is most frequently caused by underlying respiratory diseases, such as surfactant deficiency disorder (SDD), infection, meconium aspiration, or perinatal stressors including hypoglycemia and asphyxia. Less frequently, it is caused by an underlying disorder of the pulmonary vasculature, as in congenital diaphragmatic hernia or idiopathic PPHN, in which there is normal lung parenchyma with remodeled pulmonary vasculature.

The fetal lung and airways are filled with fluid until birth. Fetal lung fluid is made by respiratory epithelial cells, with production reaching ˜5 mL/kg/h near the end of gestation.¹⁹ The composition of fetal lung fluid differs from the composition of amniotic fluid, although a small amount of intermixing of fetal lung and amniotic fluid allows for assessment of lung maturation by amniotic fluid sampling.²⁰ Clearance of fetal lung fluid after birth is essential for normal gas exchange in the newborn. Fetal lung liquid production begins to decrease in the days before delivery, and it is normally cleared by the pulmonary lymphatics and vasculature during and immediately after labor.²¹ In cases of cesarean section and precipitous labor, the fluid may not fully be cleared by the time of birth, and retained fetal lung fluid may cause transient respiratory distress.

Surfactant is a substance composed of phospholipids, proteins, neutral lipids, and cholesterol that is present in all mammalian lungs and is essential to lung function.²¹ Surfactant is produced by type II pneumocytes, which secrete it into the alveoli. The principal function of surfactant is to reduce surface tension within the alveoli in order to facilitate uniform alveolar expansion.²²,²³

Surfactant can first be detected within the lamellar bodies of the type II pneumocytes between 20 and 24 weeks of gestation.²³ Lung maturity can be assessed by testing for surfactant components within the amniotic fluid. Before
35 weeks, the lung produces surfactant in smaller amounts than at term, and this surfactant is more susceptible to inactivation.²⁴ By 35 weeks, the amount of surfactant is increased and the chemical composition is mature, containing more saturated phosphatidylcholine, phosphatidylglycerol, and surface proteins, and less phosphatidylinositol.²¹ The process of surfactant maturation can be slowed by insulin and can be accelerated by glucocorticoids and thyroid hormone. This hormone-mediated acceleration of surfactant maturation can be manipulated clinically, and mothers are routinely given glucocorticoids (e.g., betamethasone) 24 to 48 hours prior to preterm delivery. This reduces the incidence of the most significant complication of surfactant deficiency in preterm infants, SDD. When a preterm child is born with SDD, exogenous surfactant can be administered via an endotracheal tube to supplement the small amount of endogenous premature surfactant that is being produced. Although premature birth is the most common clinical scenario in which surfactant deficiency is seen, rare genetic mutations can also be causal. These include mutations in surfactant proteins (SPs) SP-B and SP-C as well as the intracellular transporter ABCA3.²¹

Surfactant production must be balanced with continuous clearance; otherwise, accumulation of excessive surfactant can interfere with oxygenation. Surfactant is constantly being recycled through endocytosis and resecretion by type II pneumocytes, and through phagocytosis and catabolism by macrophages.²¹ In certain disease states, disruption of this process can result in pulmonary alveolar proteinosis (PAP), a condition in which large amounts of surfactant collect within the lung and interfere with normal oxygenation. This rare condition may be caused by a mutation in granulocyte-macrophage colony-stimulating factor (GM-CSF) or its receptor, or by autoantibodies that inactivate GM-CSF.²³

SDD, also known as hyaline membrane disease or respiratory distress syndrome, is primarily a disorder of premature newborns and is the main cause of morbidity and mortality in this patient group. In 2011, 2.1 per 1,000 live births occurred before 27 weeks of gestation, 7.5 per 1,000 occurred at 27 through 31 weeks, and 17.3 per 1,000 occurred at 32 through 34 weeks.⁸⁵ With the increased use of antenatal corticosteroids, exogenous surfactant, and improved mechanical ventilation techniques, survival rates have improved, although survival rates for extremely preterm neonates remains poor. In 2011, 0.7% born before 24 weeks, 31.2% born at 24 weeks,
59.1% born at 25 weeks, 75.3% born at 26 weeks, 93.6% born between 27 and 31 weeks, and 98.9% born between 32 and 34 weeks survived to discharge.⁸⁵ SDD is twice as common in males and white patients.⁸⁶

SDD occurs as a result of deficient surfactant production by immature type II pneumocytes in the preterm neonate. Surfactant reduces surface tension within alveoli, facilitating expansion during respiration. When surfactant is deficient, excessive alveolar collapse results in poor oxygenation. The surfactant-deficient lung produces eosinophilic hyaline membranes that line the respiratory bronchioles and acini and interfere with oxygenation. Hyaline membranes contain necrotic alveolar cells, fibrin, and plasma transudate and develop between 3 and 24 hours after birth. Hypoxia and respiratory acidosis trigger pulmonary arteriolar constriction, resulting in persistent pulmonary hypertension and right-to-left shunting across the patent DA, further exacerbating hypoxemia.⁸⁷ At 36 to 48 hours of life, alveolar macrophages begin to clear the hyaline membranes and type II alveolar cells begin producing mature surfactant.

Treatment strategies for SDD consist of antenatal corticosteroids, exogenous surfactant administration, and supportive ventilation. Corticosteroids are administered to mothers prior to preterm delivery in order to accelerate fetal production of surfactant. At birth, exogenous surfactant is administered via an endotracheal tube as a liquid bolus and the child is turned from side to side in an attempt to distribute it uniformly throughout the lungs. Up to three or four additional doses may be administered in the first 48 hours of life.⁸⁶ Infants and neonates are supported with mechanical ventilation using strategies aimed to reduce barotrauma, which has historically been a major cause of morbidity. For example, modern ventilators are triggered by the child’s spontaneous inhalations and exhalations. Alternatively, high-frequency oscillatory ventilation (HFOV), in which small tidal volumes are delivered at very high rates, is sometimes used. In patients on HFOV, projection of the diaphragm between the 8th and 10th posterior ribs on radiography indicates appropriate lung volumes.

The classic radiographic appearance of untreated SDD is diffuse granular pulmonary opacity or consolidation with air bronchograms and low lung volumes, due to acinar collapse and fluid in the alveoli from capillary leak (Fig. 1.16). Findings are typically present at birth but may not peak in severity until 12 to 24 hours of life.⁸⁶ The classic radiographic appearance is rarely seen in modern practice due to the widespread use of exogenous surfactant. Surfactant is frequently administered immediately after birth, often before the first chest radiograph is obtained. Dinger et al., analyzed the chest radiographs of preterm neonates who were given surfactant and found that 38% demonstrated uniform improvement (Fig. 1.17), 35% had asymmetric improvement, 10% had no change, and 17% developed interstitial emphysema.⁸⁸ Asymmetric improvement is thought to result from uneven distribution of administered exogenous surfactant within the lungs (Fig. 1.18). The asymmetric distribution may produce a radiographic appearance similar to neonatal pneumonia or meconium aspiration.⁸⁶ When surfactant reaches the distal alveoli, it can cause rapid expansion of the acini, which produces small round lucencies on chest radiographs that may mimic interstitial emphysema.⁸⁶ If this pattern is seen, it is essential to consider the patient’s clinical condition: patients typically decompensate in cases of pulmonary interstitial emphysema (PIE) but improve in cases of distal surfactant distribution.⁸⁶

Sudden increase in opacification of the lungs in patients with SDD may be due to atelectasis, pulmonary edema, or pulmonary hemorrhage. Atelectasis frequently results from changes in ventilator settings.⁸⁶ Pulmonary edema may result from improved oxygenation after surfactant administration, which leads to decreased PVR and left-to-right shunting across the patent DA.⁸⁶ Although the mechanism of pulmonary hemorrhage is unclear, it has been suggested that left-to-right shunting across the DA may lead to hemorrhagic pulmonary edema⁸⁹ (Fig. 1.19). Neurogenic pulmonary edema may also occur in cases of large germinal matrix hemorrhage.

With the increased survival of very low-birth-weight (<1,500 g) and extremely low-birth-weight (<1,000 g) infants, a distinct radiographic pattern of lung disease has emerged. This pattern differs from the classic pattern of SDD seen in less severely premature infants. In profoundly premature infants, the chest radiograph may be normal or nearly normal in the first 2 days of life, with findings including minimal radiating perihilar opacity, diffuse fine granularity, normal lung volumes, and absent air bronchograms⁸⁶,⁸⁷,⁹⁰ (Fig. 1.20). The biochemical profile of surfactant phospholipids in these patients is often normal, which may be related to accelerated surfactant maturation, a protective effect of intrauterine stress.⁹⁰ The radiating perihilar opacities are thought to be produced by the immature thickened interstitium, and the
fine granularity is thought to correspond to excessive lung fluid. Patients with this pattern of disease do not fulfill clinical criteria for respiratory distress syndrome, and this condition has been termed “immature lung.”⁹⁰ Despite the lack of chest radiographic findings, affected patients frequently have significant left-to-right shunts across the patent DA, sepsis, bradycardia, and apnea that frequently necessitates mechanical ventilation.⁸⁷ At days 2 and 3 of life, the chest radiograph typically worsens, and there is development of coarse, irregularly distributed lung disease that frequently persists and evolves into a pattern of chronic lung disease.⁸⁶,⁸⁷

Air leak phenomena can occur in SDD due to the negative effects of mechanical ventilation on the immature lung. Manifestations include air dissecting into the pulmonary interstitium (PIE), pneumothorax, pneumomediastinum, and pneumoperitoneum. PIE is discussed in detail in a subsequent section.

Before positive pressure ventilation and oxygen therapy were in widespread use for the treatment of SDD, premature infants who survived beyond 4 days of life typically recovered completely and chest radiographs normalized by 7 to 10 days of life.⁹¹ Infants who did not survive generally died by 3 days of life.⁹¹ This clinical course was dramatically altered when positive pressure ventilation and supplemental oxygen came into common practice. Survival rates improved, but a subset of patients developed a chronic pulmonary syndrome, which was first described by Northway in 1967.⁹² While “bronchopulmonary dysplasia (BPD)” was the original name of this disorder, the current preferred term is “chronic lung disease of infancy.”⁹²

Northway described four stages of BPD. The first stage occurs from days 2 to 3 and is characterized by acute disease with diffuse granularity on chest radiographs, identical to SDD. The second stage occurs from days 4 to 10 and is characterized by near-complete opacification of the lungs. During stage II, there is repair and necrosis of the alveolar epithelium, bronchiolar necrosis with exudates in the bronchiolar lumens, and bronchiolar mucosal squamous metaplasia. By the end of stage II, respiratory compromise begins to slowly improve, and stage III is characterized by a transition to chronic disease. Stage III occurs from days 10 to 20, with chest radiographs typically demonstrating development of small cyst-like lucencies throughout hyperexpanded lungs, which correspond to admixed groups of hyperexpanded and collapsed alveoli (Fig. 1.21). Pathologically, stage III is characterized by mucous secretion, interstitial edema, and pulmonary fibrosis. Stage IV occurs after 1 month of age, with persistent cyst-like lucencies and hyperexpansion that represent more severe manifestations of the findings typically seen in stage III (Fig. 1.22). Pathology at stage IV is characterized by emphysema, atelectasis, peribronchiolar smooth muscle hypertrophy, epithelial metaplasia, and pulmonary fibrosis. Infants often develop cor pulmonale and congestive heart failure as a result of lung disease, and vascular hallmarks of pulmonary hypertension may be seen on pathology. Pulmonary oxygen toxicity from oxygen supplementation and barotrauma from mechanical ventilation were identified as the causes of BPD.

Since 1967, when chronic lung disease of infancy was originally described, there have been dramatic changes in the treatment of SDD. Widespread use of antenatal glucocorticoid therapy, exogenous surfactant, lower oxygen concentrations, and less harmful ventilation techniques have improved survival and resulted in changes in the typical clinical and radiographic features of SDD. In the original series published by Northway, the average gestational age was 34 weeks and the average birth weight was 2,235 g.⁹² With improvements in
therapy, it is now uncommon for SDD to develop in infants born at more than 30 weeks of gestation or with birth weight of >1,200 g.⁹³ With improvements in treatment, a larger number of extremely low-birth-weight infants (<1,000 g) are surviving and eventually developing chronic lung disease. However, these infants often have different clinical and radiographic characteristics than the infants described by Northway. These infants frequently do not demonstrate the typical radiographic findings of RDS, but rather develop a pattern termed “immature lung,” which was described in the previous section (Fig. 1.20). Moreover, lung disease that occurs in this patient group may not be the result of high supplemental oxygen concentrations or positive pressure ventilation⁸⁷ but may be
due to arrested acinar and vascular maturation instead.⁹⁴ This entity has been called the “new BPD” in order to distinguish it from the classic BPD described by Northway.⁹²,⁹⁴

The diagnosis of chronic lung disease of infancy or BPD was traditionally limited to infants who fulfilled several clinical and radiographic criteria, including (1) mechanical ventilation and supplemental oxygen for ≥3 days during the first 2 weeks of life, (2) respiratory distress after 28 days of life, (3) need for supplemental oxygen in order to achieve PaO₂ >50 mm Hg, (4) and characteristic progression through the four radiographic stages of BPD described by Northway.⁹² With increased survival of very low-birth-weight infants who often had different radiographic and clinical features, this definition for BPD became less reliable. In response, a June 2000 National Institute of Child Health and Human Development/National Heart, Lung, and Blood Institute Workshop established new diagnostic criteria for BPD.⁹³ Mild BPD was defined by a need for >21% administered O₂ at 28 days but not at 36 weeks postmenstrual age (PMA). Moderate BPD was defined by a need for >21% administered O₂ at 28 days and a need for <30% administered O₂ at 36 weeks PMA. Severe BPD was defined by a need for >21% O₂ at 28 days and a need for ≥30% O₂ at 36 weeks PMA. Radiographic features were excluded from this categorization, as there were none that increased diagnostic sensitivity or specificity.⁹⁵ As the radiographic features have changed from the original findings described by Northway, many have advocated for use of the term chronic lung disease of infancy to describe this entity; however, the 2000 National Institute of Child Health and Human Development/National Heart, Lung, and Blood Institute Workshop suggested keeping the term BPD because “[this entity] is clearly distinct from the multiple chronic lung diseases later in life.” Many now use the terms interchangeably.

As the clinical, epidemiological, and pathologic features of BPD have changed, the radiographic features have also changed. In 1995, Swischuk et al., described the radiographic findings in 75 premature infants who received surfactant to treat SDD.⁹⁶ Infants of more advanced gestational age (mean gestational age 32 weeks) were more likely to completely clear their lungs following surfactant therapy, with subsequent normal chest radiographs. However, a different pattern emerged in more premature infants. Many went on to develop “hazy-opaque lungs” at 7 to 14 days, in a pattern that has been called “leaky lung syndrome” (LLS).⁹⁶ LLS is thought to result from capillary damage, which leads to transudation of fluid into the pulmonary interstitium and pulmonary edema. Hypoxia and/or oxygen toxicity are potential causes. LLS may occur in infants who do not respond to exogenous surfactant and never clear the initial granular opacities of SDD but also may occur in infants who respond to surfactant and initially clear the granular opacities. Most patients who do not respond to surfactant therapy and develop LLS go on to develop the “bubbly lungs” described in Northway’s stage III and IV BPD. Among patients with LLS who initially responded to surfactant, 35% cleared their lungs by 21 to 28 days and did not develop the “bubbly lungs” of BPD, and the remaining 65% went on to develop “bubbly lungs.” In summary, LLS may occur at 7 to 14 days and may or may not progress to the classic radiographic appearance of BPD.

Treatment of chronic lung disease of infancy or BPD is largely supportive. The major risk factors of mechanical ventilation and high concentration oxygen supplementation are minimized to the lowest levels possible.⁹⁷ Infants with chronic lung disease of infancy are more prone to developing pulmonary edema. Fluid restriction and diuretics may be utilized to manage acute respiratory distress, but they do not lower the incidence or decrease the severity of disease.⁹⁸ Infants with chronic lung disease of infancy frequently have hyperactive airways with smooth muscle hypertrophy and can experience short-term improvements in respiratory status with inhaled bronchodilators including beta agonists and methylxanthines (aminophylline and caffeine).⁹⁷ Although these inhaled agents often provide short-term improvements in respiratory status, there is no evidence that these therapies improve long-term outcomes.⁹⁷,⁹⁹

Systemic corticosteroids have been shown to improve pulmonary function and reduce the incidence of chronic lung disease of infancy.⁹⁷ However, numerous clinically significant side effects occur in this patient population, the most serious being neurologic impairment and increased incidence of cerebral palsy.¹⁰⁰,¹⁰¹,¹⁰² Given these risks, the American Academy of Pediatrics recommends that postnatal systemic steroids only be used in severely ill patients after a discussion of the benefits and risks with the family.¹⁰²,¹⁰³ Inhaled steroids have been utilized, but their effect on long-term outcomes is unclear.⁹⁹ Pulmonary vasodilators including calcium channel blockers and inhaled nitric oxide have been utilized in patients with cor pulmonale and pulmonary hypertension with some short-term clinical improvement, although long-term effects and benefits have not been established.⁹⁷ Optimized nutrition is a critical aspect of care, as malnutrition can stunt alveolar development and decrease respiratory muscle strength, prolonging dependence on mechanical ventilation.⁹⁷

Transient tachypnea of the newborn (TTN) is also known as retained fetal lung fluid, wet lung disease, and transient respiratory distress. TTN is a condition that occurs when there is delayed clearance of fetal lung fluid, which causes respiratory distress within the first 6 hours of life, peaks at 24 hours, and typically improves by 48 to 72 hours. In utero, the lungs are filled with fetal lung fluid, which is essential for normal lung growth. During and immediately after delivery, the fluid is normally cleared via the airway (30%), lymphatics (30%), and capillaries (40%).⁸⁶ This process seems to be aided by the normal vaginal delivery process, and retained fetal lung fluid is more commonly seen in infants born by cesarean section or precipitous vaginal delivery.⁸⁶ The rate of TTN in infants born by cesarean section is 35.5 per 1,000 infants in cases in which labor has not occurred and 12.2 per 1,000 in cases in which labor has occurred, compared to 5.3 per 1,000 in infants born by vaginal delivery.¹⁰⁴,¹⁰⁵ “Thoracic squeeze” that occurs during normal vaginal delivery is often cited as the driving force
behind fetal lung fluid resorption, but this actually appears to play a very small role.¹⁰⁶ The majority of lung fluid is cleared as a result of epithelial sodium channel activity, which is inactive in the fetal lung until adrenergic stimulation occurs at birth.¹⁰⁷,¹⁰⁸,¹⁰⁹,¹¹⁰

The radiographic findings in TTN are similar to the findings in pulmonary edema, as fluid is retained within the pulmonary interstitium. Common findings include increased perihilar lung markings, indistinct pulmonary vasculature, pleural effusion, occasional cardiomegaly, and normal or increased lung volumes (Fig. 1.23). In some cases, the radiographic appearance can be difficult to differentiate from other neonatal lung diseases, and the addition of clinical information such as type of delivery, gestational age, and severity of symptoms is often helpful to the primary interpretation.⁸⁶ Serial radiographs demonstrate rapid clearing of the lungs in the first 2 to 3 days of life, which parallels clinical improvement.

Meconium aspiration syndrome (MAS) is the leading cause of morbidity and mortality in term infants and is the result of fetal meconium aspiration at or around the time of birth.¹¹¹ Meconium staining of the amniotic fluid occurs in ˜10% to 15% of live births, but only ˜5% of affected neonates develop MAS, which is defined as meconium within the airway below the vocal cords.⁸⁶,¹¹¹,¹¹² Aspirated meconium incites chemical pneumonitis within the lungs, inactivates surfactant, and causes small and medium size airway obstruction. Impaired oxygenation may lead to hypoxia-induced PPHN. Pneumonitis in MAS also predisposes to gram-negative bacterial infection. Meconium aspiration is more common in cases of advanced gestation (birth beyond 40 weeks).¹¹² Clinical symptoms can range from mild respiratory distress to severe hypoxia requiring extracorporeal membrane oxygenation (ECMO).

Radiographic findings in MAS include elevated lung volumes, asymmetric “ropey” or “coarse” opacities radiating from the hila, and admixed areas of hyperinflation and atelectasis (Fig. 1.24). Pneumothorax is a frequent complication, seen in 10% to 40% of cases.⁸⁶,¹¹²,¹¹³ Pleural effusion is present in 10% to 20% of cases.⁸⁶,¹¹³ The radiographic findings in MAS are often similar to findings in neonatal pneumonia. Because pneumonia is often difficult to exclude, and there is an increased risk of superimposed pneumonia in MAS, affected patients are often treated with antibiotics.⁸⁶ In a minority of cases, chest radiographs are normal or show only pneumothorax (Fig. 1.25).⁸⁶

Treatment of MAS is focused on maintaining arterial oxygen levels. Mechanical ventilation is optimized to minimize mean airway pressures and help reduce the risk of air leak phenomena, and high-frequency oscillatory or jet ventilation may be employed. Exogenous surfactant is often administered in an effort to replace endogenous surfactant that has been inactivated by meconium.¹¹²,¹¹⁴ Inhaled nitric oxide is frequently used to treat associated PPHN.¹¹⁵ ECMO may be required when severe respiratory compromise persists despite therapy but is reserved for severe cases due to associated poor neurologic outcomes.

Neonatal pneumonia can occur in utero, during labor, or shortly after delivery. The most common causal organism is group B streptococcus (GBS), although a large number of other organisms may be the cause. The most common mechanism of infection is ascending vaginal infection in the setting of prolonged rupture of membranes, although infections can also occur due to hematogenous spread via the placenta or during uneventful vaginal delivery. Signs and symptoms vary and may range from severe respiratory distress to unstable
temperature and hypothermia.¹¹⁶ As symptoms are nonspecific, it is often difficult to distinguish neonatal pneumonia from other causes of respiratory distress based on clinical findings.

The radiographic findings of neonatal pneumonia vary, and a wide spectrum of abnormalities may be seen. Haney et al., described the radiographic features in a series of 30 cases of autopsy-proven neonatal pneumonia, and the most common pattern was bilateral alveolar densities, which was seen in 77% of cases¹¹⁶ (Figs. 1.26 and 1.27). Findings were indistinguishable from SDD in 13% and identical to TTN in 17%, and chest radiographs were normal in 10%.¹¹⁴ Given the broad range of possible radiographic appearances and the crossover with findings in other causes of neonatal lung disease, definitive diagnosis is often not possible based on radiographs alone.

Group B streptococcal infection, in particular, commonly presents with low lung volumes and bilateral granular opacities, and radiographs can have an appearance identical to SDD. One potential differentiating feature is pleural effusion, which is rarely seen in SDD but not infrequent in pneumonia (Fig. 1.28). Other pathogens may cause patchy perihilar opacities with hyperinflation, an appearance that
is radiographically indistinguishable from meconium aspiration. There have been numerous reports of group B streptococcal neonatal pneumonia and sepsis associated with late-onset right-sided congenital diaphragmatic hernia.¹¹⁷ The appearance of the diaphragmatic defect at surgery is identical to that in cases without associated pneumonia. The mechanism for the association is currently unclear.

Chlamydia trachomatis can be transmitted from the mother to the newborn during vaginal delivery. The most common neonatal chlamydia infection is conjunctivitis, and a smaller proportion of patients develop chlamydia pneumonia. The clinical and radiographic features of chlamydia pneumonia differ from those in other causes of neonatal pneumonia. Pneumonia typically presents later, usually between 2 weeks and 3 months of age.⁸⁶ Signs and symptoms may include “staccato cough” and tachypnea with minimal fever and leukocytosis.¹¹⁸ Peripheral eosinophilia is seen in up to 50% of cases.⁸⁶ Although chest radiographic findings are not specific, most radiographs demonstrate bilateral lung hyperinflation and bilateral opacities with a variety of possible patterns including interstitial opacities, atelectasis, reticulonodular opacities, and focal alveolar opacification⁸⁶,¹¹⁹ (Fig. 1.29). Neither pleural effusion nor lobar consolidation are seen in Chlamydia pneumoniae.¹¹⁹ Findings are often indistinguishable from viral pneumonitis due to cytomegalovirus (CMV), respiratory syncytial virus (RSV), or adenovirus.¹¹⁹ Frequently, the radiographic findings in chlamydia pneumonia are more severe than might be suggested by the relatively mild symptoms.⁸⁶,¹¹⁹

Because it can be difficult to differentiate neonatal pneumonia from other causes of neonatal respiratory distress based on both clinical and radiographic parameters, patients with suspected neonatal pneumonia are often presumptively treated with antibiotics. Diagnosis can be established in cases with positive blood or sputum culture, although cultures are often negative.¹²⁰

Mechanical ventilation is frequently required to maintain oxygenation in neonatal lung disease. High airway pressures (barotrauma) and airway overdistension (volutrauma) may lead to rupture of the small airways at the bronchoalveolar junctions, allowing air to dissect into the interstitial spaces of the lung, resulting in a condition called pulmonary interstitial emphysema (PIE).⁸⁷ Air can further dissect through the soft tissues, leading to pneumothorax, pneumomediastinum, pneumopericardium, and/or pneumoperitoneum. Rarely, air can extend into the vasculature and cause air embolism, which is nearly always fatal.¹²¹ The most common risk factors for PIE are prematurity and SDD, although PIE can also be seen in other conditions, including MAS and neonatal pneumonia.

Radiographic features of PIE include bubbly or linear lucencies within the lung that do not conform to the shape of air bronchograms¹²²,¹²³ (Fig. 1.30A). Nonbranching lucencies typically extend from the hila into the periphery of the lung.¹²² PIE may be focal or diffuse and unilateral or bilateral.¹²³ When unilateral, the involved lung can become enlarged and exert mass effect on the mediastinum and adjacent structures. Complications, including pneumothorax, pneumomediastinum, pneumopericardium, and pneumoperitoneum, can be detected on radiographs (Fig. 1.30B).

The bubbly lucencies of PIE can be difficult to differentiate from the bubbly lucencies that occur in chronic lung disease of infancy or BPD. Time course and patient age can be helpful in differentiating these two entities. PIE tends to occur acutely within the 1st week of life, whereas the bubbly lucencies of chronic lung disease of infancy gradually develop around the 3rd week of life and persist.⁹⁶ As previously described, acinar overdistension following surfactant therapy for SDD can produce a radiographic appearance that mimics PIE. When this pattern is seen, consideration of the patient’s clinical condition is often helpful, because PIE-affected patients tend to decompensate, while SDD patients tend to improve when surfactant is successfully delivered to the acini.⁸⁶

When PIE lasts for longer than 1 week, it is called persistent pulmonary interstitial emphysema (PPIE). Like PIE, PPIE can also be localized to a single lobe, or involve multiple lobes within one or both lungs¹²⁴ (Fig. 1.31). The involved portion of the lung may become hyperexpanded and exert mass effect on adjacent structures. The appearance may mimic other lucent lung lesions, including congenital pulmonary airway malformation (CPAM) and congenital lobar emphysema (CLE), but in most cases, previous radiographs demonstrating PIE in the same region help to differentiate among these entities.⁸⁷ In unclear cases, CT can demonstrate air-filled cystic spaces within the interstitium surrounding linear or dot-like structures that represent the bronchovascular bundles.¹²³,¹²⁴,¹²⁵ This appearance is referred to as a “line-and-dot” pattern.¹²⁴

When acute PIE is detected, the neonatal intensive care unit (NICU) staff should be notified immediately, because
it can be a harbinger of other air leak complications including pneumothorax. Acknowledgment of this finding often prompts a change to HFOV.¹²³ The majority of cases of PIE resolve spontaneously, with fewer going on to develop PPIE. First-line management of PPIE is nonoperative, although surgical resection may be required in cases of hyperexpansion with significant mass effect and/or respiratory compromise.¹²³ When surgery is considered, CT is often useful to define the lobar distribution.¹²³,¹²⁴,¹²⁵

Congenital bronchial atresia is a nonvascular congenital lung lesion caused by congenital atresia of a bronchus. Bronchial atresia may occur via one of two proposed mechanisms. According to the first theory, the developing bronchial bud is disrupted during development, and the distal bronchial bud develops normally. The second theory proposes that an ischemic event during lung development leads to stenosis and obliteration of the airway. Regardless of the underlying cause, the result is an atretic bronchus with distal lung parenchyma that does not communicate with the central bronchial tree. Atresia may be proximal, involving a mainstem or lobar bronchus, or distal, involving a segmental or subsegmental bronchus. Distal atresia is more commonly seen in clinical practice, as proximal atresia is usually lethal in the prenatal period.¹³⁶

Bronchial atresia occurs most commonly in the apical or apicoposterior segments of the upper lobes.⁶¹ Normal pulmonary secretions are transported to the central airway by the movement of respiratory cilia, but secretions are unable to clear the atretic segment, leading to formation of a bronchocele. The lung distal to the atretic segment becomes hyperinflated, which is thought to be due to air drift via collateral pathways, including the pores of Kohn and canals of Lambert, or a check-valve phenomenon.¹³⁶ Vascularity of the hyperinflated lung decreases as a result of hypoxia-induced vasoconstriction and stretching of vessels.

Bronchial atresia can be detected on prenatal imaging. In the fetus, amniotic fluid rather than air is trapped within the lung distal to the atretic segment. Therefore, prenatal US may demonstrate a relatively hyperechoic, hyperexpanded portion of the lung, and T2-weighted prenatal MRI may demonstrate a hyperintense, hyperexpanded region of lung due to trapped fluid.¹³⁶ In the rare cases of proximal atresia, the atretic segment is more commonly found on the right. The entire lung or lobe distal to the atretic segment becomes very large, and a centrally located, fluid-filled bronchocele is typically seen.¹³⁶ In proximal atresia, marked enlargement of the involved lung results in inferior vena cava (IVC) compression, hydrops, and hypoplasia of adjacent normal lung, and the condition is usually lethal in the prenatal or early postnatal period.¹³⁷ In distal atresia, the involved segment is also hyperechoic on US and hyperintense on T2-weighed MRI sequences, but the involved segment is smaller, there is usually little associated mass effect, and the associated bronchocele is typically absent or too small to be visualized.¹³⁶ Therefore, prenatal imaging findings in distal bronchial atresia are similar to those in bronchopulmonary sequestration and microcystic CPAM, often rendering distinction among these entities difficult.¹³⁶

Chest radiography is the first-line test for postnatal evaluation of distal bronchial atresia. Early postnatal chest radiographs may demonstrate atelectasis within the lung distal to the atretic segment rather than the classic hyperexpansion and hyperlucency seen later in life. Bronchoceles are often air-filled immediately after birth and may not be seen on chest radiographs until after secretions have collected within the bronchocele, by several months of age.¹³⁶ Once sufficient secretions have collected, a fluid-filled bronchocele, or mucocele, is typically seen as a perihilar round or oval opacity proximal to a lucent overinflated segment of the lung (Fig. 1.32A). The overinflated segment usually remains stable in size, and affected pediatric patients are typically asymptomatic unless superimposed infection occurs. This is an important difference between bronchial atresia and CLE, which is characterized by progressive hyperexpansion soon after birth, which typically causes symptoms such as respiratory distress.¹³⁶

When bronchial atresia is detected on prenatal imaging or chest radiographs, cross-sectional imaging is often indicated for further evaluation and characterization of the underlying lesion. CT is the preferred modality, given its excellent contrast and spatial resolution in air-filled lung. CT typically shows the mucocele as a tubular central opacity, which may have an air-fluid level. The lung distal to the atretic segment is more lucent than adjacent normally aerated lung due to hyperinflation and decreased vascularity (Fig. 1.32B). Use of MRI has been described in the evaluation of bronchial atresia and typically demonstrates the tubular mucocele as hyperintense on T1- and T2-weighted MR images.¹³⁸,¹³⁹ MRI does not demonstrate hyperinflation and decreased vascularity within the lung beyond the atretic bronchus as well as CT, given the relatively signal-poor environment of the lung parenchyma.⁶⁵

Surgical lobectomy or segmentectomy is the current standard treatment in symptomatic patients. CT is typically performed for surgical planning. Management of small, asymptomatic foci of bronchial atresia is more controversial. Some advocate resection of asymptomatic, radiographically diagnosed bronchial atresia given risk of future infection and frequent discovery of CPAM elements on pathology.¹⁴⁰,¹⁴¹ However, large scale studies are currently needed to establish evidence-based guidelines for treatment of these patients.¹³⁶

CLE is a nonvascular lesion that is caused by obstruction of a lobar bronchus. Other names for CLE include congenital lobar hyperinflation and infantile lobar emphysema. CLE occurs when there is hyperexpansion of a lobe of the lung due to narrowing of a lobar bronchus from extrinsic compression, intrinsic narrowing, and/or bronchial cartilage deficiency. CLE has a lobar predilection: left upper lobe > right middle lobe > right upper lobe > right or left lower lobe.¹⁴² There are two main forms of CLE: the classic form and polyalveolar form. The classic form of CLE is characterized by a normal or decreased number of alveoli within the hyperinflated segment. In the polyalveolar form, the number of alveoli within the hyperinflated segment is increased.¹⁴³

The majority of newborns with CLE have symptoms of respiratory distress within the first 6 hours of life. CLE may first be detected on prenatal imaging. Prenatal US may demonstrate a hyperexpanded lobe, which is hyperechoic due to increased trapped fetal fluid, and MRI may show a hyperintense, hyperexpanded lobe on T2-weighted MR imaging.¹⁴⁴,¹⁴⁵ Differentiating CLE from bronchial atresia on fetal imaging is often difficult because the imaging findings are similar.¹⁴⁴ After birth, on the first radiographs, the affected lobe of the lung is typically radiopaque due to entrapped fetal lung fluid. As this fluid is absorbed by the pulmonary lymphatic system, the fluid is replaced with air, and the affected lung becomes hyperlucent. Subsequent radiographs show progressive hyperinflation, which often exerts significant mass effect on the adjacent lung, mediastinum, and diaphragm (Fig. 1.33).

Mass effect frequently results in symptoms, and lobectomy is the current treatment of choice. CT is often performed prior to surgery and is useful for defining the lobar anatomy and depicting the degree of mass effect on adjacent lung and mediastinal structures⁶¹ (Fig. 1.34).

A variety of congenital cysts can arise from the primitive foregut early in fetal development, including bronchogenic cysts, esophageal duplication cysts, and neurenteric cysts. Foregut duplication cysts are uncommon, accounting for <5% of mediastinal masses in the pediatric population.¹⁴⁶ Small foregut duplication cysts are frequently asymptomatic and identified incidentally. Symptoms can occur when cysts are large and exert mass effect on adjacent structures or in the context of superinfection.

Developmentally, bronchogenic cysts occur due to abnormal budding of the ventral lung bud or abnormal branching of the tracheobronchial tree. Bronchogenic cysts are initially closely related to the tracheobronchial tree, but with growth, this continuity may be lost.¹⁴⁶ The majority of bronchogenic cysts are located within the mediastinum, typically adjacent to the trachea or bronchi, although ˜15% are located within the lung parenchyma.¹⁴⁷ Esophageal duplication cysts may be derived from a diverticulum of the dorsal bud of the primitive foregut or caused by aberrant recanalization of the gut. They are usually closely apposed to the esophagus, but like bronchogenic cysts, they can migrate away from their organ of origin during development.¹⁴⁶ Neurenteric cysts occur when there is incomplete separation of the endoderm and notochord, resulting in development of a diverticulum that may form into a posterior mediastinal cyst.¹⁴⁶ Distinction between bronchogenic, esophageal, and neurenteric cysts is artificial, as these congenital cysts often contain elements of more than one foregut structure. For example, cysts attached to the esophagus may contain respiratory epithelium, and cysts attached to the trachea or bronchus may contain squamous epithelium.

Foregut duplication cysts may be detected during prenatal imaging. In cases of bronchogenic cyst, prenatal US most commonly demonstrates a unilocular, centrally located anechoic cyst (Fig. 1.35A) and T2-weighted fetal MRI typically shows a hyperintense cyst with a thin hypointense wall (Fig. 1.35B).¹⁴⁵,¹⁴⁸,¹⁴⁹ Postnatally, foregut duplication cysts typically appear on chest radiographs as middle or posterior mediastinal masses. Bronchogenic cysts, in particular, are
typically located within the middle mediastinum and, less commonly, within the lung parenchyma (Fig. 1.36A). On CT, foregut duplication cysts are typically circumscribed, round, or ovoid nonenhancing lesions with homogeneous fluid attenuation between 0 and 20 Hounsfield units and a thin wall, although density can be higher if there are proteinaceous contents⁶¹ (Fig. 1.36B). On MRI, foregut duplication cysts are typically high in signal on T2-weighted MR images, variable in intensity on T1-weighted MR images depending on the nature of the cyst contents, and lacking enhancing solid components¹⁴² (Fig. 1.36C and D). While mediastinal bronchogenic cysts rarely communicate with the airway, intrapulmonary bronchogenic cysts often do communicate with the airway, increasing the risk of superimposed infection.¹⁵⁰ In cases of superinfection, air-fluid levels may develop and the wall may become thickened, with associated hyperenhancement and adjacent inflammatory changes¹³⁵ (Fig. 1.37).

Symptomatic foregut duplication cysts are treated with surgical resection. Asymptomatic foregut duplication cysts detected in children are also generally surgically resected.¹³⁵ Management of asymptomatic foregut duplication cysts detected in adults is more controversial. An analysis by Kirmani et al., suggests that asymptomatic bronchogenic cysts detected in adults may be managed conservatively according to patient preference, but patients should be advised that ˜45% of patients with asymptomatic lesions eventually go on to develop symptoms. Symptoms may be severe and make later surgery necessary, and there is an estimated 0.7% chance of malignancy.¹⁵¹

Congenital pulmonary airway malformations (CPAMs), formerly known as congenital cystic adenomatoid malformations (CCAMs), are a group of congenitally malformed cystic and solid lung lesions, which are associated with bronchiolar overgrowth and communication with an abnormal bronchial tree that lacks cartilage.¹³⁵,¹⁵⁰ Most CPAMs have conventional pulmonary vascular anatomy, with arterial supply from the pulmonary artery and venous drainage via pulmonary veins.⁶¹ However, pathologic features of CPAM are present in 29% to 33% of lesions with a systemic arterial supply.¹³¹,¹³² With pathological analysis, features of CPAM are frequently seen in other congenital lung lesions.¹³⁰,¹³⁴,¹⁵² For example, Riedlinger et al., found features of CPAM in 91% of extralobar sequestrations, 91% of intralobar sequestrations, and 50% of CLE lesions.¹³⁰

There is a fair amount of controversy surrounding the classification of CPAMs, especially as more studies have shown significant overlap between these and other congenital lung lesions.¹²⁸,¹³⁰,¹³¹,¹³⁵,¹⁵⁰ In 1977, Stocker et al., proposed a classification system that is still used by many.¹⁵³ The original Stocker classification described three types of CCAM: (1) type 1 lesions, characterized by one or more cyst(s) of presumed bronchial or bronchiolar origin measuring larger than 2 cm; (2) type 2 lesions, composed of one or more cysts of presumed bronchiolar origin measuring smaller than 2 cm; and (3) type 3 lesions, which appear macroscopically solid but contain microcysts (<0.5 cm) of presumed bronchiolar origin.

In 2001, Stocker proposed an expansion of this system to include type 0 lesions, which were previously called acinar dysplasia (a condition that is incompatible with life), and type 4 lesions, which are composed of large peripheral lung cysts of presumed distal acinar origin that are often associated with pneumothorax.¹⁵⁴ Although this classification system is widely used, it is not universally accepted.¹²⁸ The term CPAM is now widely preferred to CCAM because macroscopic cysts are only present in types 1, 2, and 4, and adenomatoid proliferation is only present in type 3. CPAM can be radiographically and clinically indistinguishable from cystic type I pleuropulmonary blastoma (PPB),¹⁵⁵,¹⁵⁶,¹⁵⁷,¹⁵⁸ and there is increasing evidence that type 4 CPAM and type I PPB may represent the same or overlapping conditions.¹²⁸,¹⁵²,¹⁵⁷,¹⁵⁹,¹⁶⁰ Many cite the classification system proposed by Langston as an alternative to the Stocker system, in which Stocker type 1 CPAMs are called the “large cyst type,” Stocker type 2 CPAMs are called the “small cyst type,” and Stocker type 3 lesions are considered a type of pulmonary hyperplasia rather than a type of CPAM.¹²⁸

Type 1 CPAMs account for 60% to 65% of all CPAMs. Large type 1 CPAMs may cause mass effect on the adjacent lung and mediastinum and can be symptomatic
soon after birth.¹³³,¹⁴⁴,¹⁵⁵ Smaller type 1 CPAMs may only become symptomatic later in life if superimposed infection occurs or in rare cases of associated malignancy.¹⁵⁵ Type 2 CPAMs account for ˜20% of all CPAMs, and ˜50% of type 2 CPAMs are accompanied by additional congenital anomalies, including cardiovascular malformations, extralobar pulmonary sequestration, tracheoesophageal fistula, renal agenesis, intestinal atresia, and congenital diaphragmatic hernia, leading to poorer prognosis than type 1 CPAMs.¹⁵⁵,¹⁶¹ Type 3 CPAMs account for ˜5% to 10% of all CPAMs and typically present as a solid mass involving an entire lobe. Type 3 CPAMs may be associated with polyhydramnios, fetal hydrops, and significant respiratory symptoms soon after birth.¹⁶² The entity described as type 4 CPAM, which has significant overlap with type I PPB, accounts for ˜10% of CPAMs and may be symptomatic in the newborn period or may present with pneumothorax in older children, a feature which is unusual for other CPAMs.¹⁵⁵

CPAMs are often first detected on screening prenatal US and appear as heterogeneous hyperechoic lesions within the lung, often containing cysts of varying number and size.¹⁴⁴ On T2-weighted fetal MRI, CPAMs are hyperintense to the adjacent lung due to retained fluid within the abnormal lung tissue, and cysts may also be visualized.¹⁴⁴ On fetal imaging, CPAMs are typically categorized as macrocystic cysts (≥5 mm) or microcystic cysts (<5 mm),¹³³ with macrocystic lesions corresponding to Stocker type 1 lesions and microcystic lesions
corresponding to Stocker type 2 lesions.¹³⁵,¹⁴⁴ In lesions without visible cysts, as in some Stocker type 2 lesions and all Stocker type 3 lesions, the hyperechoic, hyperintense lung lesion may be indistinguishable from other congenital lung lesions such as bronchopulmonary sequestration and CLE.¹⁴⁴ CPAMs may be large and can exert mass effect on the adjacent lung and mediastinum.¹⁴⁴ CPAMs most commonly affect a single lobe, although multilobar and bilateral lesions rarely occur.¹⁵⁵ Prenatally diagnosed CPAMs are usually first detected in the 2nd trimester, typically increase in size between 20 and 25 weeks of gestation, and stabilize in size by the end of the 2nd trimester.¹⁴⁴ Twenty to fifty percent decrease in size during the 3rd trimester, but complete involution is rare.¹⁴⁴,¹⁶³,¹⁶⁴

The postnatal imaging appearance of CPAM depends on the type and whether there is superimposed infection or associated mass effect. Given the controversial classification of these lesions, it is best for imaging reports to provide a detailed description of the anatomy, including size, location, number of cysts, size of the largest cyst, relationship with the pulmonary hilum, communication with the bronchial tree, and degree of aeration.⁶¹,¹³³,¹³⁵ The large cyst type 1 lesions contain at least one cyst that is >2 cm in diameter and may have additional smaller cysts (Fig. 1.38). At birth, cysts are initially filled with lung fluid that is replaced with air supplied via the bronchial tree.¹³³ On CT, type 1 lesions appear as one or more large cyst(s), which are typically air-filled, although occasionally contain air-fluid levels⁶¹ (Fig. 1.38B). Septations and nonaerated lung typically separate the cysts of multicystic lesions.¹³⁵ Type 2 lesions typically appear as multicystic, partially air-filled masses or areas of consolidation with cysts smaller than 2 cm⁶¹,¹³⁵ (Fig. 1.39). Stocker type 3 CPAMs, referred to as pulmonary hyperplasia by Langston, are composed of microscopic cysts and, therefore, appear as solid, enhancing masses on CT and MRI (Fig. 1.40). Radiographically, type 3 CPAMs are seen as opacities that are often large and associated with mass effect.⁶¹,¹³⁵ So-called Stocker type 4 CPAMs are composed of large, peripherally located cysts and are radiographically indistinguishable from Stocker type 1 lesions and type I PPB. Type 4 lesions can present with pneumothorax.¹⁵⁵,¹⁵⁷

CPAMs may present later in life with superinfection, and a small number develop malignancy. When infected, CPAMs typically demonstrate consolidation with associated air-fluid levels on chest radiography and a thick, enhancing rim with adjacent parenchymal airspace disease on CT or MRI.⁶¹,¹³⁵,¹⁵⁰ In addition to the association between Stocker type 4 CPAM and type I PPB described earlier, a small number of Stocker type 1 CPAMs reportedly develop bronchoalveolar carcinoma.¹⁵⁹ Rare cases of blastomas, malignant mesenchymomas, and rhabdomyosarcomas arising from CPAMs have also
been reported¹⁶⁵,¹⁶⁶,¹⁶⁷,¹⁶⁸; however, it has been proposed that these cases represent low-grade PPBs rather than CPAMs with malignant degeneration.¹²⁸

Surgical resection is indicated in symptomatic CPAMs, but surgical resection of asymptomatic lesions is more controversial.¹⁶⁹ Many support surgical resection of asymptomatic lesions due to the risks of superimposed infection and malignancy.¹³⁵,¹⁵⁰,¹⁵⁶,¹⁶⁰ However, others do not advocate surgical resection on account of the low incidence of these complications.¹⁷⁰ Presence of the DICER1 gene mutation, which is present in 66% of cases of PPB, also helps guide decisions about surgical resection versus nonoperative management.¹⁷¹

The classic definition of pulmonary sequestration, as first laid forth by Pryce in 1946, is a “disconnected bronchopulmonary mass or cyst with an anomalous arterial supply.”¹⁷² Pulmonary sequestration was later subdivided into two main types: intralobar and extralobar pulmonary sequestration.

Intralobar pulmonary sequestration accounts for 75% of pulmonary sequestrations and is classically defined as a portion of nonfunctioning lung that does not communicate with the tracheobronchial tree, has a systemic arterial supply (typically from the descending thoracic aorta or upper abdominal aorta or one of its branches), contains veins that drain to the pulmonary veins, and shares a visceral pleural covering with the adjacent lung.⁶¹,¹³⁵,¹⁵⁰ The lung tissue in classic intralobar pulmonary sequestration resembles a CPAM lesion, containing cystic spaces that have been linked to the “bronchial atresia sequence.”¹³⁰ Intralobar pulmonary sequestration was traditionally thought to be an acquired lesion that occurred after a chronic inflammatory process recruited systemic blood vessels from the aorta or its branches, but with improved prenatal imaging, a large number of prenatally diagnosed cases of intralobar pulmonary sequestration have challenged this view.¹³³ Intralobar pulmonary sequestration is most commonly isolated, without associated congenital anomalies.¹⁵⁰

Extralobar pulmonary sequestration accounts for the other 25% of pulmonary sequestrations and is defined as nonfunctioning lung tissue that does not communicate with the tracheobronchial tree and has a systemic arterial supply (typically from the descending aorta or one of its branches); however, unlike intralobar pulmonary sequestration, extralobar sequestration has systemic venous drainage (typically to the azygos, hemiazygos, portal, internal mammary, or subclavian veins, or the IVC) and has its own pleural covering separate from that of the adjacent lung.⁶¹,¹³⁵,¹⁵⁰ Extralobar pulmonary sequestrations are most commonly located within the lower lung, more commonly on the left. Less often, they can occur in the mediastinum or pericardium or below the diaphragm. Features of type 2 CPAM are seen in up to 50% of extralobar pulmonary sequestrations. These combination lesions are termed “hybrid lesions.”¹⁷³ Unlike intralobar pulmonary sequestrations, extralobar pulmonary lesions are frequently associated with additional congenital abnormalities including congenital heart disease and diaphragmatic hernia.¹⁵⁰

The classification and description of pulmonary sequestration has had shortcomings from the time the entity was first described. Four of the original seven cases first described by Pryce did not fit his strict definition, and he proposed three variants, including abnormal artery supplying lung with abnormal tracheobronchial connection, abnormal artery supplying lung with normal and abnormal tracheobronchial connection, and abnormal artery supplying lung with a normal tracheobronchial connection.¹⁷⁴ Others have broadened the definition to include normal lung with systemic arterial supply and abnormal lung tissue that maintains a normal bronchial connection but has a systemic arterial supply.¹⁷⁵ Given the shortcomings of the Pryce
categorization, alternative classification systems have been proposed. For example, Clements and Warner created a comprehensive system, using the term “pulmonary malinosculation” to describe “a congenitally abnormal connection or opening of one or more components of the bronchopulmonary vascular complex.”¹²⁶ Another approach described by Langston points out that many different lung malformations may have a systemic arterial supply; on the basis of this fact, the author considers that abnormal systemic arterial supply is an attribute rather than a defining characteristic and encourages use of a descriptive approach.¹²⁸,¹³¹ Despite the existence of valid and widely cited competing classification systems, the terms “intralobar” and “extralobar” pulmonary sequestration seem to be deeply entrenched, and familiarity with the classic definitions and their limitations is essential. As with all congenital lung lesions, the radiologist is advised to focus on imaging features, including location, vascular supply, and appearance of the lesion, and avoid descriptors that may be unclear.

With the wide availability of fetal imaging, pulmonary sequestration is now often first detected prenatally. On prenatal US with Doppler overlay, pulmonary sequestration typically appears as a homogeneous, hyperechoic pulmonary mass with an abnormal systemic arterial supply¹³³ (Fig. 1.41A). On T2-weighted prenatal MRI, sequestration is commonly seen as a homogeneous lesion that is hyperintense compared to the adjacent lung.¹⁷⁶ Abnormal arterial supply can sometimes be visualized on MRI as a flow void extending from the aorta or one of its branches. If the abnormal arterial supply is not visualized, the imaging findings are identical to other congenital lung lesions, including bronchial atresia, CPAM, and CLE.¹³³,¹⁴⁴,¹⁷⁶ Similar to CPAMs, pulmonary sequestrations generally increase in size from the 20th to the 28th week and then decrease in size during the 3rd trimester.¹³⁵ In the 3rd trimester, lesions become much more difficult to detect due to decreased size and a normal increase in the echogenicity and signal intensity of the adjacent lung.¹³⁵
Although many lesions seem to disappear during the 3rd trimester, complete regression is very unusual and followup postnatal cross-sectional imaging is recommended in all cases because radiographs may not detect small lesions.¹⁴⁴,¹⁷⁷

The most common postnatal imaging appearance of pulmonary sequestration is a lung mass within one of the lower lobes (seen in 98% of cases).⁶¹ Although extralobar pulmonary sequestration can occur anywhere from the neck to below the diaphragm, the most common finding on chest radiography is a solid mass within the left lower lobe. Intralobar pulmonary sequestration also tends to occur in the lower lobes, and depending on its internal composition and the presence or absence of superinfection, it can appear as a solid mass, cystic lesion, or consolidation on chest radiographs.¹³⁵

CT or MR angiography with 2D and 3D reformations is recommended in cases of suspected pulmonary sequestration to ensure that associated anomalous vessels are accurately detected⁶¹,⁶⁵ (Fig. 1.41B and C). A study that compared the preoperative diagnostic accuracy of axial, multiplanar (2D), and 3D MDCT images in the evaluation of congenital lung malformations in pediatric patients showed that supplemental multiplanar and 3D images add diagnostic value for lesions associated with anomalous veins¹⁷⁸ (Fig. 1.42). Extralobar pulmonary sequestrations classically appear as solid, enhancing masses with systemic arterial supply and systemic venous drainage. Intralobar pulmonary sequestrations typically become air-filled after fetal lung fluid has cleared.¹³³ The mechanism of aeration is presumably collateral air drift because lesions have an abnormal tracheobronchial connection.¹³⁵ As many as 50% to 90% of pulmonary sequestrations contain elements of CPAM on pathology. Therefore, it is not surprising that cystic elements are frequently identified on cross-sectional imaging.¹³⁰,¹⁷³ In cases with superimposed
infection, findings may include consolidation, air-fluid levels, and increased cyst formation in chronically infected lesions.⁶¹

The standard treatment for symptomatic pulmonary sequestration is surgical resection. Management for asymptomatic lesions continues to be somewhat controversial. Many recommend elective resection of intralobar pulmonary sequestration due to risks of future superimposed infection, pneumothorax, bleeding, and malignant transformation.¹⁷⁹,¹⁸⁰ Extralobar pulmonary sequestrations have a lower rate of complications than intralobar pulmonary sequestrations, and thus, management is more debatable. Extrathoracic extralobar pulmonary sequestration is often managed conservatively without treatment, but intrathoracic lesions are often surgically resected.¹³⁵ Arterial embolization has been reported as a potential alternative to surgery in both intralobar and extralobar pulmonary sequestration in selected cases.¹⁸¹,¹⁸²

Elements of bronchial atresia, CPAM, and CLE often coexist within the same lesion, and hybrid or overlap lesions are often seen¹²⁶,¹²⁸,¹³⁰,¹³¹,¹³⁴,¹⁴⁴ (Figs. 1.43 and 1.44). Langston has proposed that all congenital lung malformations are the consequence of in utero airway obstruction and represent a spectrum of lesions rather than distinct pathological entities with different underlying pathogenetic processes.¹²⁸ Based on this theory, it is not surprising that hybrid lesions are often seen. To determine the frequency of overlap lesions, Riedlinger et al., used a dissection microscope to examine pathologic specimens from 47 congenital lung lesions and found atresia of a bronchus in 100% of extralobar pulmonary sequestrations, 82% of intralobar sequestrations, 70% of CPAMs, and 50% of CLE lesions and found parenchymal changes of CPAM in 91% of extralobar pulmonary sequestrations, 91% of intralobar pulmonary sequestrations, and 50% of CLE lesions.¹³⁰ The high incidence of overlapping histopathologic features emphasizes that the radiologist can be most helpful by providing a description of the congenital lung malformation, focusing on location, airway or GI tract communication, vascular supply, and internal characteristics, rather than attempting to provide a specific diagnosis.

Viral lower respiratory tract infections, which include bronchiolitis and pneumonia, occur via spread of airborne droplets.¹⁹⁶ Viruses primarily infect the respiratory mucosa of the lower respiratory tract. As a result, infected cells become inflamed and necrotic, leading to bronchial wall edema and thickening. Mucus is also produced in response to inflammation. Because children’s airways are relatively smaller than adults’, and children tend to produce more mucus in response to viral infection, they are relatively more susceptible to air trapping and atelectasis due to airway narrowing and mucous plugging. This leads to the typical radiographic findings of pediatric viral respiratory infection, which include symmetric perihilar and peribronchial opacities, bronchial wall thickening, hyperinflation, and atelectasis.¹⁸⁸ It is important to recognize that atelectasis caused by viral infection is frequently misinterpreted as focal consolidation due to bacterial pneumonia.¹⁹³,¹⁹⁷

A variety of viral pathogens may cause respiratory infection in children—pathogens that are most often encountered in clinical practice are discussed in the following section.

Adenoviruses are nonenveloped double-stranded DNA viruses that are most commonly associated with respiratory tract infection
and gastroenteritis but may also cause keratoconjunctivitis, cardiac infection, genitourinary infection, and lymphatic infection. Adenovirus can cause a variety of respiratory tract infections, including otitis media, pharyngitis, tonsillitis, croup, bronchiolitis, bronchitis, pneumonia, and pleural effusion. Up to 20% of pneumonias occurring in children <5 years of age are due to adenovirus.²⁴⁶ Types 3, 7, and 21 have been associated with the most severe disease, and fatalities have been reported with these types and several others.²⁴⁷

Radiographic findings in adenovirus pneumonia may include patchy or diffuse confluent pulmonary opacities, bronchial wall thickening, peribronchial linear opacities, and occasional pleural effusion²⁴⁶,²⁴⁸ (Figs. 1.57 and 1.58). Long-term sequelae develop in a subset of affected pediatric patients and may include bronchiectasis and BO.²⁴⁷,²⁴⁸,²⁴⁹,²⁵⁰

Cytomegalovirus (CMV) is a double-stranded DNA virus from the β-herpesvirus group. CMV is the most common congenital infection in the United States and is a cause of opportunistic infection in pediatric patients with decreased T-cell function, including organ transplant recipients and pediatric patients with AIDS. Infections in the fetus and immunosuppressed children may involve the CNS, liver, and lungs and can lead to petechial hemorrhage, purpura, and hemolytic anemia. Infection in children and adults without immunodeficiency is most commonly asymptomatic, although can cause pharyngitis, tonsillitis, a mononucleosis syndrome characterized by fever, headache, and malaise, or occasionally, pneumonia.²⁵¹ CMV pneumonia in immunocompetent hosts is usually benign and self-limited, but it is a very serious illness with a high mortality rate in immunosuppressed patients.²⁵¹ Infection can occur in the perinatal period and is usually asymptomatic in full-term neonates, although can cause lymphadenopathy, hepatosplenomegaly, hepatitis, or pneumonitis in up to one-third of cases.²⁵² Perinatal CMV pneumonia may occur in premature neonates and can cause protracted severe pneumonitis and subsequent chronic lung disease of infancy.²⁵²,²⁵³

Radiographic findings in CMV pneumonia are often similar to those seen in other viral infections, including hyperinflation with diffuse interstitial or peribronchial opacification (Fig. 1.59).²⁵⁴ Findings on CT may include centrilobular nodules, ground-glass opacities, and consolidation.²⁵⁵,²⁵⁶,²⁵⁷ CMV pneumonia can be complicated with superinfection by gramnegative enteric bacteria and fungi in transplant patients and P jiroveci infection in AIDS patients.²⁵¹

Varicella-zoster virus (VZV) is an alpha herpesvirus that causes varicella (chickenpox) and zoster (shingles). Varicella occurs during primary infection, most often in childhood, and is characterized by fever and pruritic rash. Zoster occurs when latent VZV reactivates within the dorsal root ganglia and causes unilateral skin infection in a dermatomal distribution or other manifestations. Zoster is primarily a disease of adults but can occur in children, particularly in the setting of immunodeficiency. Although rare in children, VZV can cause serious pneumonia in adults.²⁵⁸,²⁵⁹

Chest radiographs in VZV pneumonia typically demonstrate multiple 5- to 10-mm poorly defined nodules²⁶⁰ (Fig. 1.60). On CT, nodules may be coalescent and demonstrate a groundglass halo, or patchy ground-glass opacities may be seen. In the majority of cases, pulmonary nodules and opacities resolve within a week of disappearance of rash but may persist longer in cases of severe disease.²⁶⁰ Nodules may calcify and appear as numerous 2 to 3 mm calcifications that persist after infection has resolved²⁶⁰ (Fig. 1.61).

Epstein-Barr virus (EBV) is a very common double-stranded DNA virus from the herpesvirus family. It is commonly associated with infectious mononucleosis but also plays a central role in the development of numerous lymphoproliferative disorders and malignancies. Rare cases of infectious mononucleosis can have pulmonary involvement, which may be characterized by alveolar opacifications or consolidation that may be diffuse and confluent in severe cases²⁶¹ (Fig. 1.62). Lymphadenopathy and pleural effusions can also be seen.²⁶¹,²⁶²,²⁶³ EBV may also lead to pulmonary manifestations in cases of EBV-associated hemophagocytic lymphohistiocytosis, chronic active EBV infection, LIP in HIV infection, posttransplant lymphoproliferative disorder (PTLD), and pulmonary lymphoma.²⁶⁴

Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) are double-stranded DNA viruses in the human herpesvirus family, which also includes CMV, EBV, VZV, and human herpesviruses (HHV) types 6A, 6B, 7, and 8. HSV is ubiquitous, and clinical manifestations range from no symptoms or mild “fever blisters” to life-threatening disseminated infection in neonates.²⁶⁵ HSV pneumonia is uncommon but has been described in neonates²⁶⁶,²⁶⁷ and may occur in immunocompromised patients.²⁶⁰,²⁶⁵ HSV pneumonia may occur due to extension of oropharyngeal infection into the lower respiratory tract or from hematogenous spread.²⁶⁰ HSV pneumonia is characterized by alveolar necrosis and ulceration on pathology.²⁶⁰

Radiographic findings in reported neonatal cases include diffuse interstitial and alveolar opacifications as well as
bilateral pleural effusions²⁶⁶,²⁶⁷ (Fig. 1.63). Imaging findings in immunocompromised older patients with HSV pneumonia include patchy segmental and subsegmental consolidation, ground-glass opacities, atelectasis, centrilobular nodules, and pleural effusion.²⁶⁸,²⁶⁹,²⁷⁰ HSV-1 pneumonias are frequently associated with coexisting bacterial pneumonia.²⁶⁰

Bacterial pneumonias have three main radiographic appearances: (1) focal consolidation, (2) bronchopneumonia, and (3) atypical pneumonia. It is important to recognize that these patterns are often not seen in young children and are virtually always absent in neonates.¹⁸⁸

The typical imaging appearance of pulmonary consolidation occurs due to filling of alveoli with exudate, inflammatory cells, and fibrin.¹⁹⁶ Consolidation may be lobar, or can take on a spherical shape in children, causing “round pneumonia”²⁷¹,²⁷² (Figs. 1.64 and 1.65). Children are predisposed to developing round pneumonia due to underdeveloped pores of Kohn and
canals of Lambert, and resultant centrifugal spread of infection within the lung leads to spherical consolidation with sharp margins. The mean age for round pneumonia is 5 years, with 75% occurring before 8 years of age and 90% occurring before 12 years of age.²⁷¹

Bronchopneumonia is a term used to describe a different form of bacterial pneumonia that is characterized by peribronchial inflammation, which involves the airways in multiple segments or lobes and then spreads to the adjacent parenchyma, resulting in patchy consolidation.¹⁹⁶

Atypical pneumonia describes an infection in which nonpulmonary symptoms, including headache, sore throat, and pharyngeal exudates, are the major clinical features. Chest radiographs typically demonstrate reticular or band-like opacities in a patchy distribution without a focal region of consolidation.¹⁸⁵

Although certain patterns of bacterial pneumonia are seen more commonly with particular pathogens, there is considerable overlap in the radiographic findings in different bacterial pneumonias. Pertinent clinical and imaging features of the most commonly encountered bacterial pneumonias in the pediatric population are discussed below.