Advances in emerging treatment options to prevent bronchopulmonary dysplasia

ABSTRACT

Introduction: Bronchopulmonary dysplasia (BPD) is common sequaelae of premature birth. It can be complicated by the development of pulmonary hypertension (PH), which significantly increases mortality.

Areas covered: The aim of this review is to evaluate emerging drug therapies for prevention and treatment of BPD and associated PH. These include superoxide dismutase, macrolides, Clara secretary cell protein, α-1 protease inhibitors, pentoxifylline, melatonin, inositol, N-acetyl cysteine, allopurinol, cimetidine, pulmonary vasodilators and mesenchymal stem cells (MSC). We have also included discussion on longer standing therapies such as corticosteroids, caffeine and vitamin A.

Expert opinion: Corticosteroid administration systemically, but not by inhalation, caffeine and vitamin A reduce BPD. Enhancing endogenous anti-oxidant mechanisms through supplementation with superoxide dismutase or Clara cell secretory protein has yielded encouraging results. Azithromycin, a macrolide used to treat Ureaplasma infection, also has anti-inflammatory properties and has been shown to reduce BPD. Sildenafil reduces the echocardiographic markers of pulmonary hypertension associated with BPD, but has not been shown to prevent BPD. In animal models and a small Phase I study MSC administration has resulted in promising results. Appropriately powered studies with long term outcomes are required to assess the efficacy of all these treatments.

KEYWORDS:

• Bronchopulmonary dysplasia
• antioxidant
• prematurity
• nitric oxide

Article highlights

• Azithromycin reduces BPD when used prophylactically and in infants colonized with Ureaplasma

• In animal models of BPD recombinant Clara cell secretory protein reduced lung inflammation.

• An RCT of recombinant superoxide dismutase demonstrated improved long term respiratory outcomes, such as reduction in asthma medications and hospitalization with respiratory illness

• Meta-analysis highlighted vitamin A reduced BPD, but not long term outcomes and there was considerable heterogeneity of included trials.

• Sildenafil improved echocardiographic markers of pulmonary hypertension associated with BPD, but did not prevent BPD.

• Administration of mesenchymal stem cells have improved short term outcomes in animal models and in a small phase one study.

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Declaration of interest

A Greenough has held grants from various ventilator manufacturers and has received honoraria for giving lectures. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.