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Jury still out on best therapies for bronchopulmonary dysplasia

Wright CJ. Pediatrics. 2011;doi:10.1542/peds.2010-3875.

Ongoing research is focusing on potential therapies to limit inflammation in the preterm lung, but data on the best therapies for preventing bronchopulmonary dysplasia are lacking, according to a review published online.

Clyde J. Wright, MD, of the neonatology division at The Children’s Hospital of Philadelphia, and Haresh Kirpalani, BM, of the clinical epidemiology division at McMaster University, Hamilton, Ontario, Canada, discussed currently used therapies and promising developments in the field of bronchopulmonary dysplasia (BPD).

They said although BPD is associated with severe morbidity and mortality in premature infants, clinicians have few therapeutic options.

Research is divided over the benefits of steroids to prevent BPD, but steroids are recommended for those premature infants with ventilator dependency or infants at risk of developing BPD. “Thus, determining an infant’s risk of developing BPD becomes even more clinically important,” Wright and Kirpalani wrote. “Simple lung mechanics are unlikely to be helpful. Although exhaled [nitric oxide] has been proposed as a marker of inflammation, whether it is a better predictor of BPD over simple clinical predictors (eg, birth weight) remains unclear. However, end-tidal carbon monoxide on day-of-life 14 does predict BPD well (OR=15.17; 95% CI, 2.02-113.8).”

The review urged further research into predictive tools for infants at risk for BPD. The researchers said dexamethasone has been advocated, but concerns about early dexamethasone use and possible complications have prompted evaluation of other methods, such as hydrocortisone, for preventing BPD. However, a review of randomized controlled trials showed no effect from hydrocortisone use. The reviewers said, however, these trials used relatively low doses and were somewhat underpowered.

The report indicated that data on the anti-inflammatory properties of nitric oxide and antioxidants, as well as azithromycin, to decrease BPD have all been relatively underpowered to definitively answer whether these therapies are helpful.

“It remains eminently arguable that given the limited treatment options for the prevention of BPD, and its serious consequences, the use of glucocorticoids is appropriate for specific patients at high risk of developing BPD,” the researchers wrote.

Disclosure: The study was funded by the NIH. The researchers report no relevant financial disclosures.

In their state-of-the-art review article, Wright and Kirpalani (Pediatrics, 2011) discuss the existing evidence for therapies that target inflammation in order to prevent or ameliorate bronchopulmonary dysplasia (BPD), a condition that affects about 45% of preterm infants of birth weight <1250 g or <28 weeks' gestation. BPD is associated with poor neurodevelopmental outcomes and long term pulmonary dysfunction in these infants. Unfortunately, the authors conclude that neonatologists currently have few novel therapeutic options. Studies are in progress that will evaluate such therapies as azithromycin for Ureaplasma sp. colonization, and hydrocortisone for facilitation of extubation. In the meantime, neonatologists will need to adhere to a "less is best" strategy of less endotracheal intubation, less oxygen and less sepsis, while utilizing more nasal continuous positive airway pressure (CPAP) and permissive hypercapnea.

Pablo J. Sanchez, MD
Infectious Diseases in Children Editorial Board member

Disclosure: Dr. Sanchez reports no relevant financial disclosures.

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