AUTHOR AND EDITOR INFORMATION

Section 1 of 8  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Nuclear Medicine
• Intervention
• References

INTRODUCTION

Section 2 of 8  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Nuclear Medicine
• Intervention
• References

Background

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). It is defined as oxygen dependence at 28 days. BPD is pathologically characterized by inflammation, mucosal necrosis, fibrosis, and smooth muscle hypertrophy of the airways. With advances in medical management, BPD has become the most common cause of chronic lung disease (CLD) in children.

Pathophysiology

BPD was a term that Northway et al first used in 1967, when they discovered this condition in babies who had been ventilated with high pressures and high oxygen concentrations. It was subsequently found that BPD can occur in low-birth-weight infants receiving ventilation even without high pressures or high oxygen concentrations.

Definitions of BPD

The definition of BPD has evolved with time. They are based on the requirement of oxygen and ventilatory support in the neonatal period.

In 1967, Northway et al defined BPD as CLD caused in preterm infants with respiratory distress who were treated with oxygen and mechanical ventilation, with certain clinical, radiologic, and histologic findings.

In 1988, Shennan et al defined BPD as a requirement for supplemental oxygen therapy to maintain the reference-range arterial partial pressure of oxygen (PaO₂) at 36 weeks' corrected age in infants weighing less than 1500 g. BPD is caused by high oxygen concentration, which produces toxic free radicals that damage the developing lung. This damage gradually heals by scarring, resulting in fibrosis and emphysema. Epithelial regeneration by metaplasia produces intimal thickening and pulmonary hypertension.

In 2003, Bancalari et al defined BPD as a sustained need for supplemental oxygen therapy to maintain (PaO₂) of greater than 50 mm at 28 days after birth, with associated radiologic changes.

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.

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.

In current clinical practice, these 4 stages are not clearly discerned in a particular patient. The onset of BPD is usually insidious, with no sequential progression in the stages. The disease is usually mild.

Etiologic factors

The following factors play a role in the development of BPD:

• Preterm delivery (immature lungs): The disease is common in children delivered before 32 weeks' gestation and in those weighing less than 1000 g.
• High oxygen concentration (free radical–induced lung damage worsened by deficient antioxidants): A high oxygen concentration is an etiologic factor in patients with immature lungs, and any concentration greater than 60% is associated with a high incidence of the disease.
• Mechanical ventilation (large tidal volume and reduced lung compliance)
• RDS that requires mechanical ventilation: Sustained positive-pressure ventilation in preterm infants with RDS results in dilatation of the terminal bronchioles, which causes ischemic necrosis of the distal airways. Resultant pulmonary interstitial emphysema (PIE) and pneumothorax produce chronic lung damage. Although mechanical ventilation in RDS may be the original cause, it also occurs in patients with diaphragmatic hernia, persistent pulmonary hypertension of the newborn, meconium aspiration, and other diseases that require prolonged mechanical ventilation. RDS is not an absolute requirement for the development of BPD because the disease can occur in those receiving mechanical ventilation to manage other diseases.
• Familial factors (atopy, allergy, and/or asthma)
• Infectious agents (eg, Ureaplasma urealyticum): U urealyticum is the most common infectious agent responsible for BPD, producing early and severe changes of BPD within 3 weeks. Other bacterial and fungal agents are also implicated.
• Air leaks (eg, those due to pulmonary interstitial pneumonia)
• Patent ductus arteriosus (PDA): Pulmonary edema reduces lung compliance and increases airway resistance.
• Nutritional and/or vitamin A or E deficiency
• Bacterial pneumonias
• Fluid overload
• Miscellaneous factors - Low indigenous steroid levels, imbalance between elastase and proteinase inhibitors, defective antioxidant system

A combination of the factors listed above, such as mechanical ventilation, high concentration of inspired oxygen, deficient antioxidant system, nutritional deficiencies, infection, elastase-proteinase inhibitor imbalance, PDA, and excessive fluid intake, result in acute lung injury, causing airway and vascular damage. The airways react with metaplasia and smooth muscle hypertrophy, resulting in emphysema and atelectasis, while the vascular tree responds with increased capillary permeability, producing edema and hypertrophy of the smooth muscle. This process eventually terminates with the fibrosis of CLD.

Long-term survival

Increasing numbers of patients are surviving long term because of efficient and effective management in the neonatal period.

Pathologic changes in this stage of 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.

Tracheobronchomegaly, tracheomalacia, and ciliary dysfunction are associated findings.

Frequency

United States

BPD is the most common chronic pulmonary disorder in infancy. The incidence varies between 5% and 40%. About 10% of infants weighing less than 1500 g and 20% of those weighing less than 1000 g develop BPD.

International

The incidence of CLD is increasing despite the reduction in mortality rate as a result of surfactant and steroid use. This change is because of improved survival of neonatal patients.

Mortality/Morbidity

The mortality rate is approximately 25-30%.

• Patients with severe BPD can develop progressive respiratory failure. Cor pulmonale develops because of right ventricular failure secondary to pulmonary hypertension. Babies in this condition have signs of cardiac failure with hepatomegaly, anasarca, and weight gain.
• Survivors can have frequent respiratory infections. Growth retardation and major developmental defects are seen in one third of all survivors.
• Risk factors for CLD are related to gestational age, weight, and duration of ventilatory support. CLD is associated with gastroesophageal reflux, tracheobronchomalacia, airway collapse, pulmonary hypertensions, systemic hypertension, airway complications, and adverse neurodevelopmental outcomes.

Race

No racial predilection is known.

Sex

No predilection is observed.

Age

BPD is common in preterm infants. With advances in therapy, it is currently uncommon after 30 weeks of gestation or in infants weighing more than 1200 g.

The incidence increases among low-birth-weight babies in each gestational age group: 35% in patients weighing 510-750 g and 26% in those weighing 751-1000 g.

Clinical Details

The classic clinical history is that of a preterm child who has RDS and who is receiving mechanical ventilation. Clinical improvement may be followed by sudden deterioration because of the development of BPD.

Management is ventilation and oxygenation at pressures above 7 kPa. Weaning from the ventilator is helped by reducing the patient's fluid intake, by giving diuretics, and by closing the ductus arteriosus. Infections are treated with antibiotics. Theophylline and steroids are helpful in managing this disease. Infections with respiratory syncytial virus (RSV) are treated with ribavirin.

Once established, maintenance of oxygenation is vital to prevent pulmonary hypertension. Permissive hypercapnia reduces pressures. Steroids reduce the requirement for home oxygenation, allow for early weaning, and reduce CLD, but they can cause perforation of hollow viscera, cerebral palsy, or retarded brain growth.

Other problems to be considered include aspiration pneumonias, chronic pneumonia, heart failure due to PDA, and Wilson-Mikity syndrome. Wilson-Mikity syndrome is 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. The exact etiology is not known, but proposed factors include airtrapping, fluid overload secondary to chronic PDA, recurrent aspiration, infection, rickets, and surfactant deficiency.

Clinical history taking is essential for differential diagnosis. Infants with Wilson-Mikity syndrome do not develop RDS. Clinical features include respiratory dyspnea, tachypnea, cyanosis, apnea, and in-drawing of the respiratory muscles. 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.

BPD should be differentiated from CLD, which is oxygen dependance at 28 days or 36 weeks of gestation and which is also seen in patients ventilated because of apnea or meconium aspiration.

Preferred Examination

Radiography is the mainstay imaging test for the diagnosis of BPD.

High-resolution CT (HRCT) scans may be useful in the further evaluation of BPD.

DIFFERENTIALS

Section 3 of 8  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Nuclear Medicine
• Intervention
• References

Other Problems to be Considered

Wilson-Mikity syndrome
Respiratory distress syndrome
Persistent pulmonary hypertension of the newborn

RADIOGRAPH

Section 4 of 8  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Nuclear Medicine
• Intervention
• References

Findings

Radiography is the mainstay imaging test for the diagnosis of BPD.

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, 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 (1967) established. In stage 1 ( <3 d), characteristic features of RDS are seen, as can complications of RDS (eg, pneumothorax and PIE). In stage 2 (4-10 d), 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 d) is characterized by a classic bubbly appearance and irregular dense areas, opaque areas. In stage 4 (>1 mo), images show hyperexpansion of the lung, expanding bubbles, and strands. When present, airtrapping 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, where 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. Airtrapping increases the AP diameter of the chest. Hyperexpansion due to scarring and/or hyperplasia of mature alveoli, alveolar-wall distension, or diminished bronchial diameter is seen. Focal hyperlucent areas can be present because of expiratory airtrapping.

Development of viral and other bacterial pneumonias can interrupt clearing of the radiographic findings. These pneumonias produce consolidation and atelectatic changes.

Changes can be classified as follows: Type I is hazy shadowing without air bronchograms or focal hyperinflation. Type II is less common than type I. Type II is characterized by large-volume lungs and coarse, linear shadows due to scarring and cyst formation.

These findings may resolve over months to years, and the lungs can become normal.

Causes of CLD include aspiration, recurrent infections, PDA, and cardiac lesions. 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.

Palta et al (1998) assessed the following criteria (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.

These 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. Although all criteria were significantly associated with all the outcomes, radiographic evidence was most predictive.

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.

CT SCAN

Section 5 of 8  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Nuclear Medicine
• Intervention
• References

Findings

HRCT scans are rarely needed in the further evaluation of BPD.

HRCT scans show different findings depending on the stage of disease.

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

In stage 2, interlobular septal thickening is the most common finding. On expiratory scans, airtrapping 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:

• 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

NUCLEAR MEDICINE

Section 6 of 8  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Nuclear Medicine
• Intervention
• References

Findings

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

Degree of Confidence

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.

INTERVENTION

Section 7 of 8  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Nuclear Medicine
• Intervention
• References

Patients with mild BPD require only few weeks of oxygenation with high concentrations. The disease resolves slowly, and the clinical features progressively improve. Some patients may need prolonged oxygen therapy.

REFERENCES

Section 8 of 8

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Nuclear Medicine
• Intervention
• References

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Article Last Updated: Jun 9, 2006