The term ‘bronchopulmonary dysplasia’ (BPD) was first used by Northway et al. in 1967 to describe a chronic form of injury to the lungs caused by barotrauma and oxygen injury in preterm infants requiring mechanical ventilation. Despite significant advances in preterm infant care in the past few decades, including the development of surfactant as well as newer and gentler modes of ventilation, the prevalence of BPD continues to remain high. These new strategies have allowed the survival of very low birth weight infants and resulted in a change in the characteristics of BPD. Jobe coined the term “new BPD” in 1999 to describe the chronic lung disease in preterm infants at that time. This “new BPD” demonstrated much less airway damage and alveolar septal fibrosis when compared to “old BPD” which was characterized by dysmorphic microvasculature and alveolar simplification.
Bronchopulmonary dysplasia is a multifactorial pathology that is influenced by a variety of prenatal and postnatal factors affecting the mother and infant. The various prenatal risk factors that influence the development of BPD include:
Similarly, various postnatal factors predispose premature infants to develop BPD including:
The incidence of BPD varies significantly between different centers because of variation in perinatal practices, differences in management styles and lack of consistent definition of BPD. The highest observed rate of BPD is in infants born at a lower gestational age (GA) and lower birth weight. The data from the neonatal research network reports the incidence of BPD in very low birth weight infants (birth weight less than 1500 grams) to be 40 to 68% depending on the definition of BPD used. This incidence was found to be inversely proportional to the GA of the infant The other demographic risk factors associated with BPD include male sex, low birth weight, white race, impaired growth for GA and family history of asthma.
Injury from mechanical ventilation and reactive oxygen species to premature lungs in the presence of antenatal factors predisposing the lungs to BPD form the basis of pathogenesis of BPD in preterm neonates. This myriad of events leads to an exaggerated inflammatory response with an increase in proinflammatory cytokines like interleukin(IL)-6, IL 8, tumor necrosis factor alpha etc along with growth factors (transforming growth factor ) and angiogenic factors (vascular endothelial growth factor, angiopoietin 2) which ultimately results in aberrant tissue repair and arrest in lung development. Dysregulated vascular and arrested alveolar development form the basis of the pathology seen in “new BPD.”
Bronchopulmonary dysplasia occurs when lung development arrests in the late canalicular to saccular stages of lung development. The pathology in BPD characteristically demonstrates decreased septation and alveolar hypoplasia resulting in simplified large alveoli and reduced area available for gaseous exchange. There is also dysregulated vasculature with smooth muscle hyperplasia in pulmonary vessels and abnormal alveolar capillaries. Additionally, there is also the presence of increased interstitial fibroproliferation and alveolar septation.
The clinical phenotype of infants with BPD is very variable. Depending on the severity of their disease they may or may not need respiratory support. Some may be tachypneic and depending on the degree of pulmonary edema may have signs of respiratory distress like retractions, rales and increased work of breathing.
Evaluation of BPD involves assessment of blood gas, chest x-ray and evaluating the nutritional status of the patient. An arterial blood gas may reveal hypoxia, hypercarbia or acidosis. These patients remain on continuous pulse oximetry to help target adequate oxygen saturation. Many centers also utilize transcutaneous carbon dioxide monitoring to evaluate the ventilation of the infant.
Chest radiographs may show decreased lung volumes, hyperinflation, areas of atelectasis, pulmonary edema, and pulmonary interstitial emphysema. High-resolution CT may demonstrate abnormalities not readily seen with routine chest radiography. Infants with moderate or severe BPD must be screened for pulmonary hypertension(PH) at 36 PMA using an echocardiogram. Some centers chose to screen all patients with BPD since the morbidity and mortality associated with the diagnosis of PH in BPD are quite high.
The diagnosis of BPD is made clinically based on the GA, postmenstrual age (PMA), oxygen exposure and oxygen requirement at 36 weeks PMA. In 2001, the National Institute of Child Health and Human Development (NICHD) workshop proposed the current definition where infants born at less than or equal to 32 weeks GA with 28 days of oxygen exposure get diagnosed with mild, moderate or severe BPD at 36 weeks PMA based on their respiratory support at that time. Table 1 illustrates the definition used for diagnosing and classifying the severity of the disease.
This definition still has many deficiencies and does not adequately predict respiratory outcomes; hence in 2016, the NICHD workshop on BPD proposed a revision of this definition. The suggested refinement suggests utilizing radiographic confirmation and accounts for the newer modes of non-invasive ventilation. Although this new definition classifies BPD further, it does not address the primary limitation of utilizing the treatment modality as the primary factor defining the disease and its severity.
The global aim in the management of infants with BPD is to support them while lung growth occurs, limit further injury to the lungs, optimize lung function and detect complications associated with BPD. The various measures employed in the care of these infants are-
BPD is a chronic illness that persists beyond discharge from the hospital and into adulthood. Infants with BPD have a 50% chance of readmission to the hospital during their first year of life. They have an increased risk of developing reactive airway disease, asthma, emphysema, and RSV bronchiolitis. BPD also affects their growth and neurodevelopmental outcome. VLBW infants with BPD are more likely to have delays in fine and gross motor skills, and language.
Infants with BPD are at high risk for cardiopulmonary sequelae like pulmonary hypertension (PH), cor pulmonale, and systemic hypertension. A recent meta-analysis reported an accumulative estimated prevalence of PH in BPD to be 20% and can be as high as 40% in severe BPD. A newer, prospective study showed that BPD-associated pulmonary hypertension (BPD-PH) affects at least 8 to 25% of extremely low birth weight (birth weight less than 1000g) infants. Retrospective studies demonstrate a 2-year morbidity rate of 26 to 47% in patients with BPD-PH.
BPD is one of the most prevalent morbidities associated with prematurity and carries associations with the following complications-
Bronchopulmonary dysplasia (BPD) is a severe disease that affects babies who are born early and need to be in the NICU. It causes breathing problems in babies and occurs because their lungs are not well developed and ready to do the work of breathing. These babies often need to have a breathing tube and are connected to a breathing machine to help them breathe. They may need several medications during their hospital stay to help with this lung disease. Some babies may also require home oxygen and may need to return to the hospital if they develop respiratory infections. Babies with BPD also need more energy and may require extra nutrition.
Babies who have BPD may develop other problems such as:
While in the NICU the doctors must be vigilant for these problems. Even after discharge, the baby may require followup for with doctors and developmental specialists.
Optimizing care of infants with BPD requires a multidisciplinary team approach that includes a neonatologist, nurses, pediatric pulmonologist, respiratory therapist, nutritionist, physical and occupational therapists, social worker and child life specialist. Training of the parent prior to discharge is critical. At the time of transition from hospital to home, adequate discharge planning is essential with setting up follow appointments and making sure parents have all the supplies necessary for taking care of their child.
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