Practice Essentials
Bronchopulmonary dysplasia (BPD) is a chronic pulmonary disorder that results from the use of high positive-pressure mechanical ventilation and high concentration oxygen in neonates with respiratory distress syndrome (RDS) (see the image below). This condition is defined as oxygen dependence at 28 days and is pathologically characterized by inflammation, mucosal necrosis, fibrosis, and smooth muscle hypertrophy of the airways. [1, 2] Radiography is the mainstay imaging test for the diagnosis of BPD, but high-resolution computed tomography (HRCT) may be useful in the further evaluation of BPD. [3, 4, 5, 6, 7, 8]
Because of new strategies over the past 20 years, more very low birth weight infants have survived, resulting in a change in the characteristics of BPD. The so-called “new BPD” displays much less airway damage and alveolar septal fibrosis as compared to previous cases of BPD. [9] BPD remains the most common complication in premature infants, affecting approximately 20,000 to 30,000 infants a year in the United States. [10, 11, 12, 13, 14, 15]
The incidence of BPD varies between 5 and 40%, and is common in preterm infants—10% of infants weighing less than 1500 g and 20% of those weighing less than 1000 g develop this condition. With advances in therapy, BPD is currently uncommon after 30 weeks' gestation or in infants weighing more than 1200 g. [16, 17, 18, 19]
Chest radiograph of an infant with bronchopulmonary dysplasia.
Imaging modalities
Radiography is the mainstay imaging test for the diagnosis of bronchopulmonary dysplasia. [4, 5, 20] Four stages of radiographic changes of BPD have been described: stage I, which is RDS seen in the first week; stage II, which includes generalized haziness and plethora in the second week; stage III, which involves cystic changes and stranding in the third week; and stage IV, which is characterized by hyperinflation, [21] extensive stranding, and an enlarged heart in the fourth week.
High-resolution CT (HRCT) scans are rarely needed in the further evaluation of bronchopulmonary dysplasia. When used, however, HRCT scans show different findings depending on the stage of disease. In stage 1, HRCT scans show changes of respiratory distress syndrome, pneumothorax, and pulmonary interstitial emphysema. In stage 2, interlobular septal thickening is the most common finding. Stage 3 is characterized by linear atelectasis and fibrotic changes. [22, 23, 24, 25]
Although the radiation burden of conventional thoracic CT is greater than that of chest radiography, technological advances such as rotational tube current modulation and adaptive array, as well as dose-optimization programs, have resulted in a significant reduction in CT radiation. In addition, spiral/volumetric acquisitions can produce continuous volumetric data sets with isotropic voxels (three-dimensional pixels) that allow multiplanar reconstruction. Major improvements in scanning children include faster tube rotation speeds, greater numbers of detectors and dual source systems, and immobilization devices to reduce the effects of body movements in newborns. Even at high heart rates typical in neonates, high-pitch CT has been able to demonstrate, in acceptable detail, small, fast-moving structures, such as the pulmonary veins. [26, 27, 28, 29]
Although nuclear medicine studies are nonspecific investigations and not useful in diagnosing BPD, perfusion scintigraphic findings are well correlated with the clinical severity of the disease. Marked ventilation-perfusion mismatch due to the destruction of the lung is observed. Another finding is the loss of gravity-dependent flow distribution.
Lung ultrasound scores have been shown to allow the monitoring of lung aeration and function in extremely preterm infants, [30] Semple et al note, however, that lung ultrasonography does not constitute a potential replacement for plain radiography, because central pathology and important complications arising from misplaced support apparatus or air leaks can be completely missed on ultrasound. [26]
In a study by Alonso-Ojembarrena et al of 59 preterm very low birth weight infants, a lung ultrasound (LUS) score of 5 or above had a sensitivity of 71% and a specificity of 80% for predicting BPD 1 week after birth. At 2 weeks, the sensitivity increased to 74% and the specificity to 100%. An LUS score of 4 or above 4 weeks after birth predicted moderate to severe BPD with a sensitivity of 100% and a specificity of 80%. [31] A study by Oulego-Erroz et al of 42 preterm infants on the 7th day of life found that an LUS score of 8 or more predicted moderate to severe BPD with a sensitivity of 93% and a specificity of 91%. [32]
Hochino et al found that LUS with whole chest scanning helped predict respiratory outcome in patients with BPD. LUS at 28 days of life predicted moderate to severe BPD with an area under the curve of 0.95 (95% confidence interval: 0.91-0.99) and home oxygen therapy with an area under the curve of 0.95 (95% confidence interval: 0.81-1.0). [33]
Stages of BPD
BPD is believed to be a disease of scarring and repair. Although the exact pathophysiology is still unclear, 4 stages in the development of BPD are identified, as follows:
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In stage 1 (1-3 days), the pathologic appearances of BPD are identical to those of hyaline membrane disease and involve the presence of hyaline membranes, atelectasis, vascular hyperemia, and lymphatic dilatation.
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In stage 2 (4-10 days), lung destruction due to stretching of the terminal bronchioles results in ischemic necrosis of airways, inducing immediate reparative changes in the lungs. Bronchiolar obstruction is seen in this stage, and bronchial necrosis, peribronchial fibrosis, and squamous metaplasia produce obliterative bronchiolitis. Hyaline membranes can persist into this stage. Emphysematous coalescence of alveoli is seen.
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Stage 3 (11-20 days) involves progressive repair of the lung, with a decreased number of alveoli, compensatory hypertrophy of the remaining alveoli, and hypertrophy of bronchial wall muscle and glands. Regenerating clear cells and exudation of alveolar macrophages and histiocytes into airways are seen. Airtrapping, pulmonary hyperinflation, tracheomegaly, tracheomalacia, interstitial edema, and ciliary dysfunction may be present.
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In stage 4 (>1 mo), emphysematous alveoli are seen. Pulmonary hypertension eventually results from chronic lung damage, and cor pulmonale ensues. Fibrosis, atelectasis, a cobblestone appearance due to uneven lung aeration, and pleural pseudofissures are often seen. Pulmonary hypertension is caused by thickening of the intima of pulmonary arterioles. Marked hypertrophy of peribronchiolar smooth muscle is present.
Long-term changes
Pathologic changes in long-term survival are interstitial fibrosis, hyperinflation, reduced number of alveoli, reduction in alveolar surface area, arrested acinar development, pseudofissures, airway hyperplasia, and atelectasis. Sequelae of chronic lung disease include pulmonary arterial hypertension and right-sided cardiac failure. [18] Tracheobronchomegaly, tracheomalacia, and ciliary dysfunction are associated findings.
Differential diagnosis and other problems to be considered
BPD should be differentiated from chronic lung disease, which is oxygen dependence at 28 days or 36 weeks' gestation and which is also seen in patients ventilated because of apnea or meconium aspiration. Persistent pulmonary hypertension of the newborn (PPHN) is another consideration.
Infants with Wilson-Mikity syndrome, a chronic lung disease that occurs in 2% of infants who are born preterm with a low birth weight (ie, those without a history of high-pressure ventilation or exposure to high oxygen concentrations), do not develop respiratory distress syndrome. [18, 19] This syndrome is commonly seen between 1 and 2 months of age, and most cases slowly resolve. Chest radiographic findings are normal in the first week, but after that time, they are similar to those of BPD, with hyperinflation, stranding, streaky infiltrates, and cystic changes. Radiographic changes persist for a few months to years after clinical findings resolve.
The differential diagnosis should also include the following:
Radiography
Radiography is the mainstay imaging test for the diagnosis of bronchopulmonary dysplasia (BPD) (see the following image). [20, 4, 5] Four stages of radiographic changes of BPD have been described: stage I, which is respiratory distress syndrome seen in the first week; stage II, which includes generalized haziness and plethora in the second week; stage III, which involves cystic changes and stranding in the third week; and stage IV, which is characterized by hyperinflation, [21] extensive stranding, and an enlarged heart in the fourth week.
Chest radiograph of an infant with bronchopulmonary dysplasia.
Findings can also be described according to the original 4 stages of BPD that Northway et al established [34] :
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In stage 1 (< 3 days), characteristic features of RDS are seen, as well as complications of RDS (eg, pneumothorax and pulmonary interstitial emphysema [PIE]).
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In stage 2 (4-10 days), persistent radiographic findings should alert the clinician to the development of BPD. Fine or course interstitial opacities are frequently seen. This stage has a diffuse distribution and no specific lobar predilection. In severe cases, changes are widespread and coarse.
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Stage 3 (10-20 days) is characterized by a classic bubbly appearance and irregular dense areas, opaque areas.
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In stage 4 (>1 month), images show hyperexpansion of the lung, expanding bubbles, and strands. When present, air trapping is more common in the lower lobes than in the upper lobes. Pulmonary hyperinflation is seen in the most severe cases. Clearly defined Northway stages are hardly seen in current practice, in which RDS is not a prerequisite for BPD.
By day 3, radiographic changes can be seen as pulmonary edema. By 1 week, images may show interstitial edema, septal lines, and loss of the clear outlines of pulmonary vessels. Strandlike opacities may be due to lymphatic engorgement or atelectasis. Cardiomegaly may be seen if patent ductus arteriosus or fluid overload is present. The changes are early and severe if they are caused by infections. Infection and fluid overload are difficult to distinguish on radiographs alone. By the third week, fibrosis and/or atelectasis may be observed in upper lobes.
Hyperinflation can produce right ventricular enlargement, prominent hila due to pulmonary arteries, and pruning of the peripheral pulmonary arteries. In rare cases, the trachea is enlarged and softened.
Long-term changes
The incidence of long-term changes is due to increasing survival of low-birth-weight infants. Radiographic changes gradually clear with age, and in some individuals, complete clearing is observed. Two thirds of patients have some remnant change, such as linear shadows and strands due to fibrosis or pleural pseudofissures, which persists into middle childhood
The anteroposterior (AP) diameter of the chest can be narrow. Air trapping increases the AP diameter of the chest. Hyperexpansion due to scarring and/or hyperplasia of mature alveoli, alveolar-wall distention, or diminished bronchial diameter is seen. Focal hyperlucent areas can be present because of expiratory air trapping.
Development of viral and other bacterial pneumonias can interrupt clearing of the radiographic findings. These pneumonias produce consolidation and atelectatic changes.
The changes can be classified as type I or II and may resolve over months to years; the lungs can become normal. Type I is hazy shadowing without air bronchograms or focal hyperinflation. Type II is less common than type I and is characterized by large-volume lungs and coarse, linear shadows due to scarring and cyst formation.
Modern treatment produces only 2 types of CLD: classic or severe, which can be new or mild. The appearance depends on a balance between inflammation, injury, healing, growth and maturation, prematurity, low birth weight, neonatal respiratory illness, and treatment.
Degree of confidence
Radiographic findings are reliable indicators of future respiratory insufficiency in BPD. In a study by Palta et al, radiographic evidence was more predictive of long-term respiratory outcome than other commonly used criteria, although all criteria were significantly associated with all the outcomes. The investigators assessed the (1) use of supplemental oxygen on day 30 of life, (2) application of comprehensive BPD-severity score at 25-35 days of life developed by a clinician panel, (3) use of supplemental oxygen on day 30 of life with radiographic evidence consistent with BPD at 25-35 days of life, (4) radiographic evidence consistent with BPD alone, and (5) use of supplemental oxygen at 36 weeks' postconceptional age. The criteria were assessed for the outcomes of bronchodilator or steroid use during the first 2 years of life, diagnosis of asthma, and hospitalizations for respiratory causes up to age 5 years. [35]
The radiographic appearance of BPD in middle childhood is described by Griscom et al. [36] However, in a study by Moya et al, using chest radiographs for the prediction of BPD did not have interobserver reliability, except at the 2 extremes of the disease. [6]
The presence of radiographic abnormalities 2 weeks after the onset of respiratory distress syndrome is usually due to BPD. Conditions that mimic the radiologic appearances of BPD are cardiac failure, pulmonary edema, infections, and pulmonary interstitial emphysema.
Computed Tomography
HRCT scans are rarely needed in the further evaluation of bronchopulmonary dysplasia. When used, however, HRCT scans show different findings depending on the stage of disease. [22, 23]
Stages of BPD on HRCT scans
In stage 1, HRCT scans show changes of respiratory distress syndrome, pneumothorax, and pulmonary interstitial emphysema.
In stage 2, interlobular septal thickening is the most common finding. On expiratory scans, air trapping is well depicted as abnormal lucencies. Hyperinflation, areas of atelectasis, consolidation, prominent pulmonary arteries, and an enlarged heart are other features. In severe disease, scans show marked distortion of the lung parenchyma, large cysts, coarse fibrosis, and pulmonary hypertension.
Stage 3 is characterized by linear atelectasis and fibrotic changes, as well as gradual clearing of areas of attenuation.
In the chronic stages in long-term survivors, HRCT can be completely normal, but signs such as the following are often present [37, 38] :
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Air trapping, which can be bilateral, multifocal, or asymmetrical and which are best seen in expiratory scans
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Fibrotic changes, which are seen as linear, reticular, or reticulonodular opacities or as subpleural bands or pleural thickening
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Triangular opacities caused by deep pleural fissuring
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Distortion of the pulmonary architecture
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Decreased diameter of the bronchi and decreased ratio of the diameters of the bronchial artery to the pulmonary artery
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Thickening of the bronchial wall
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Tracheomegaly
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Tracheomalacia
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Enlarged pulmonary arteries
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Right ventricular enlargement
Advances in CT in neonates
Although the radiation burden of conventional thoracic CT is greater than that of chest radiography, technological advances such as rotational tube current modulation and adaptive array, as well as dose-optimization programs, have resulted in a significant reduction in CT radiation. In addition, spiral/volumetric acquisitions can produce continuous volumetric data sets with isotropic voxels (three-dimensional pixels) that allow multiplanar reconstruction. Major improvements in scanning children include faster tube rotation speeds, greater numbers of detectors and dual source systems, and immobilization devices to reduce the effects of body movements in newborns. Even at high heart rates typical in neonates, high-pitch CT has been able to demonstrate, in acceptable detail, small, fast-moving structures, such as the pulmonary veins. [26, 27, 28, 29]
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Chest radiograph of an infant with bronchopulmonary dysplasia.
