What is chronic lung disease (CLD) in premature newborns?

Chronic Lung Disease (CLD) in Premature Newborns

Chronic lung disease of infancy (CLDI) is a heterogeneous group of respiratory disorders that most commonly develops in premature infants—especially those born at less than 1,000 g—following acute neonatal lung injury, typically from respiratory distress syndrome requiring mechanical ventilation and supplemental oxygen. 1

Definition and Core Pathophysiology

The term bronchopulmonary dysplasia (BPD) specifically describes chronic lung disease that develops after oxygen and/or ventilator therapy for respiratory distress syndrome in preterm newborns, representing the most common form of CLDI. 1

The modern form of this disease differs substantially from historical descriptions:

• Current CLDI primarily results from intrauterine inflammation and premature extrauterine lung development, characterized by alveolar simplification rather than the fibrosis and barotrauma-induced injury seen in earlier eras. 1, 2
• The pathophysiology involves multiple mechanisms: surfactant deficiency leading to alveolar collapse, high alveolar capillary permeability allowing protein leak that further inhibits surfactant function, and inflammatory cascades triggered by both the underlying disease and necessary interventions. 2
• Structural abnormalities include airway wall thickening from increased smooth muscle mass, alveolar hypoplasia, and pulmonary vascular remodeling, which account for the clinical manifestations of hypoxemia, hypercapnia, tachypnea, and recurrent wheezing. 3

Epidemiology and Risk Factors

The highest-risk population is clearly defined:

• Infants with birth weights less than 1,000 g have the greatest incidence, with 90-92% requiring surfactant therapy even after antenatal steroid exposure. 2
• At 27 weeks gestation or earlier, the incidence of RDS—the primary precursor to BPD—remains extremely high despite antenatal corticosteroids. 2
• Multiple gestation pregnancies and absence of antenatal corticosteroid administration increase risk. 2

Evolution and Clinical Phases

The disease progresses through distinct pathological stages:

• The early inflammatory phase (clinically indistinguishable from RDS) features persistent hyaline membranes, epithelial necrosis, and inflammatory cell influx. 4
• The subacute fibroproliferative phase (weeks to months) shows type II pneumocyte hyperplasia, bronchial smooth muscle hypertrophy, and interstitial fibrosis, with persistent respiratory distress and oxygen dependence. 4
• The chronic phase (up to 1 year) involves airway remodeling, with many patients experiencing cyanotic spells, pulmonary hypertension, right heart failure, and severe feeding problems with poor somatic growth. 4

Diagnostic Criteria

The diagnosis of "new BPD" is based on oxygen requirement at 36 weeks postmenstrual age, though this definition has limitations since supplemental oxygen is sometimes used unnecessarily. 5 This modern definition reflects the evolution from severe BPD with coarse infiltrates and microcystic changes to a milder phenotype following widespread surfactant and prenatal corticosteroid use in the 1990s. 5

Long-Term Respiratory Outcomes and Prognosis

CLDI predisposes to abnormal lung function in childhood independently from premature birth alone, with persistent airway obstruction and hyperreactivity extending into adulthood. 2

Specific functional abnormalities include:

• Average FEV₁ remains approximately 80% of control subjects at 6-15 years of age. 2
• Airway resistance and responsiveness remain elevated, with increased residual volume and RV/total lung capacity ratios indicating persistent air trapping. 4
• Of all obstructive lung diseases in humans, BPD has the earliest onset and probably lasts the longest, with the most severely affected patients remaining symptomatic into adulthood. 6
• Environmental variables like smoking can contribute to persistent airflow obstruction, raising serious concerns about respiratory function evolution in middle and old age. 3, 6

Multisystem Complications

CLDI is truly a multisystem disorder with far-reaching consequences beyond the respiratory system. 1 The American Thoracic Society emphasizes that precipitating and complicating conditions affect multiple organ systems, requiring an interdisciplinary approach to care. 1

Critical Clinical Pitfall

Never administer surfactant to infants with congenital diaphragmatic hernia presenting with respiratory distress, as this increases mortality, ECMO requirements, and chronic lung disease. 7 This represents a surgical cause of neonatal respiratory distress that mimics but is fundamentally different from RDS-related CLDI.