Imaging in Bronchopulmonary Dysplasia

Overview

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. High-resolution computed tomography CT (HRCT) scans may be useful in the further evaluation of BPD.^{[3, 4, 5, 6, 7]}

View Image

Chest radiograph of an infant with bronchopulmonary dysplasia.

With advances in medical management, BPD has become the most common cause of chronic lung disease (CLD) in children.^{[2, 8, 9, 10, 11, 12]}The incidence of BPD varies between 5% and 40%, and it is 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 of gestation or in infants weighing more than 1200 g.

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. However, in current clinical practice, these 4 stages are not clearly discerned in a particular patient. (See Radiograph.)

In stage 1 (1-3 d), 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.

In stage 2 (4-10 d), 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.

Stage 3 (11-20 d) 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.

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 CLD include pulmonary arterial hypertension and right-sided cardiac failure.^[13]Tracheobronchomegaly, tracheomalacia, and ciliary dysfunction are associated findings.

Differential diagnosis and other problems to be considered

BPD should be differentiated from CLD, which is oxygen dependence at 28 days or 36 weeks of 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 CLD that occurs in 2% of infants who were 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 RDS.^{[13, 14]}This syndrome is commonly seen between age 1 and 2 months, and most cases slowly resolve. Chest radiographic findings are normal in the first week, but later 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:

Aspiration Pneumonia
Bronchiectasis
Bronchogenic Cyst
Congenital Lobar Emphysema
Cystic Fibrosis, Thoracic
Emphysema
Esophageal Atresia/Tracheoesophageal Fistula
Hyaline Membrane Disease
Idiopathic Pulmonary Fibrosis
Patent Ductus Arteriosus
Pneumonia, Neonatal
Pneumonia, Viral

References

Radiography

Radiography is the mainstay imaging test for the diagnosis of bronchopulmonary dysplasia (BPD) (see the following image).^{[15, 4, 5]}

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Chest radiograph of an infant with bronchopulmonary dysplasia.

Stages of radiographic changes

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,^[16]extensive stranding, and an enlarged heart in the fourth week.

Findings can also be described according to the original 4 stages of BPD that Northway et al established^[17]:

In stage 1 (<3 days), characteristic features of RDS are seen, as can complications of RDS (eg, pneumothorax and pulmonary interstitial emphysema [PIE]).
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.
Stage 3 (10-20 days) is characterized by a classic bubbly appearance and irregular dense areas, opaque areas.
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 PDA 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, the cause of which is still unknown. 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 follows 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 among 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.^[18]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.^[18]

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.^[18](For the radiographic appearance of BPD in middle childhood, see Griscom et al.^[19]) 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]

False positives/negatives

The presence of radiographic abnormalities 2 weeks after the onset of RDS is usually due to BPD. Conditions that mimic the radiologic appearances of BPD are cardiac failure, pulmonary edema, infections, and PIE.

References

Computed Tomography

HRCT scans are rarely needed in the further evaluation of bronchopulmonary dysplasia (BPD). When used, however, HRCT scans show different findings depending on the stage of disease.^{[20, 21]}

Stages of BPD on HRCT scans

In stage 1, HRCT scans show changes of RDS, pneumothorax, and PIE.

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, scan can be completely normal, but signs such as the following are often present^{[22, 23]}:

Air trapping, which can be bilateral, multifocal, or asymmetrical and which are best seen in expiratory scans
Fibrotic changes, which are seen as linear, reticular, or reticulonodular opacities or as subpleural bands or pleural thickening
Triangular opacities caused by deep pleural fissuring
Distortion of the pulmonary architecture
Decreased diameter of the bronchi and decreased ratio of the diameters of the bronchial artery to the pulmonary artery
Bronchiectasis
Thickening of the bronchial wall
Tracheomegaly
Tracheomalacia
Enlarged pulmonary arteries
Right ventricular enlargement
Pulmonary edema

References

Nuclear Imaging

Marked ventilation-perfusion mismatch due to the destruction of the lung is observed. Another finding is the loss of gravity-dependent flow distribution. However, 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.

References

Author

Prabhakar Rajiah, MD, MBBS, FRCR, Associate Professor, Department of Radiology, Division of Cardiothoracic Imaging, Associate Director of Computer Tomography (CT) and Magnetic Resonance Imaging (MRI), UT Southwestern Medical Center