Regular articlePulmonary hypertension in bronchopulmonary dysplasia
Section snippets
Background
Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease of infancy in the United States and complicates the course of more than 30% of extremely preterm infants, resulting in 10,000 new cases annually in the United States. While prenatal steroids and surfactants have reduced the rates of acute respiratory failure and improved survival, very limited progress has been made in reducing the rates of BPD. Multiple therapies, such as non-invasive ventilation, vitamin A, caffeine,
Pathophysiology
In contrast to the classic features of fibroproliferative BPD as originally described by Northway and others, lung disease in today's post-surfactant era is characterized by impaired alveolarization and compromised vasculogenesis which occurs when the preterm lung attempts to adapt to air breathing.13 Findings observed in both pre- and post-surfactant BPD include vascular remodeling (Fig. 1), increased vascular tone and altered vasoreactivity.14, 15 These features, along with the decreased
Screening and diagnosis
The development of standardized, clinically useful algorithms for the identification of infants with BPD-associated PH remains an important topic of investigation. Symptoms of PH often overlap those of BPD itself, including hypoxia, pulmonary instability, poor feeding and failure to thrive. Furthermore, the emergence of symptoms may indicate that the disease has already progressed to a late, less reversible phase, thereby supporting arguments for screening all infants at risk. Significant
Management
While the presence of PH does not always correlate with severity of BPD, the approach to prevention and management of PH should include optimization of respiratory function and nutritional support to limit lung injury and facilitate lung growth. While support of respiratory function may include use of diuretics, inhaled steroids and/or bronchodilators, none of these have been shown to reduce the severity of BPD-associated PH. Infants should also be evaluated for structural airway abnormalities,
Pulmonary vasodilators
The general management strategies described previously may prove insufficient for infants with severe or progressive vascular disease, prompting consideration of the use of pulmonary vasodilators. While experience with these medications in the BPD population is steadily growing, knowledge regarding their long-term safety and efficacy remains limited.
Stem cell therapies
Recent animal and human studies suggest that damage or depletion of epithelial and/or vascular stem cells in the developing lung likely contributes to the pathogenesis of BPD.75 For instance, hyperoxia-induced BPD in neonatal rats is associated with decreased circulating and resident mesenchymal stem cells (MSC).76 Administration of bone marrow-derived mesenchymal stem cells or multipotent stromal cells prevents the compromised alveolar and vascular development observed in the murine
Conclusion
While numerous questions remain unanswered with respect to optimal screening protocols and clinical management of infants with BPD-associated PH, it is clear that the condition is relatively common in ELBW or growth-restricted premature infants in the modern post-surfactant era, and that the diagnosis carries a tremendous burden of morbidity and mortality. Great efforts are being made to better characterize the prevalence, clinical course and response to acute and chronic therapy. Experience
References (78)
- et al.
Long-term outcomes of bronchopulmonary dysplasia
Semin Fetal Neonatal Med
(2009) - et al.
Neurodevelopmental outcome of bronchopulmonary dysplasia
Semin Perinatol
(2006) - et al.
General and respiratory health outcomes in adult survivors of bronchopulmonary dysplasia: a systematic review
Chest
(2012) - et al.
Pulmonary hypertension in chronic neonatal lung disease
Paediatr Respir Rev
(2010) - et al.
Pulmonary hypertension in bronchopulmonary dysplasia
Progr Pediatr Cardiol
(2009) - et al.
Risk of cardiac catheterization under anaesthesia in children with pulmonary hypertension
Br J Anaesth
(2007) - et al.
Plasma brain natriuretic peptide levels increase in proportion to the extent of right ventricular dysfunction in pulmonary hypertension
J Am Coll Cardiol
(1998) - et al.
Usefulness of serial N-terminal pro-B-type natriuretic peptide measurements for determining prognosis in patients with pulmonary arterial hypertension
Am J Cardiol
(2011) - et al.
Acute hemodynamic effects and home therapy using a novel pulsed nasal nitric oxide delivery system in children and young adults with pulmonary hypertension
Am J Cardiol
(2003) - et al.
Long-term treatment with sildenafil citrate in pulmonary arterial hypertension: SUPER-2
Chest
(2011)