A New Approach to Severe BPD Therapy

Columbus, OH — June 2018

The standard ventilatory approach for babies with bronchopulmonary dysplasia (BPD) is called “gentle ventilation” or fast-rate low tidal volume ventilation. But new data from clinician-scientists at the Comprehensive Center for Bronchopulmonary Dysplasia at Nationwide Children’s Hospital suggest that a different ventilatory approach may be more appropriate for more than 90 percent of infants with severe BPD.

The team’s study, which prospectively collected data on more than 110 infants with severe BPD, resulted in the description of three separate BPD phenotypes: obstructive, mixed obstructive and restrictive, and pure restrictive. Only 9 percent of patients had pure restrictive BPD. The remaining children had mixed or obstructive phenotypes, displaying lung function similar to people with asthma during infant pulmonary function tests. According to Edward Shepherd, MD, section chief of Neonatology at Nationwide Children’s and lead author on the paper, the study’s clinical implications are dramatic.

“‘Gentle ventilation’ is great for preventing BPD. But our data show that once children have severe BPD, their pulmonary function is different, so gentle ventilation won’t work effectively for about 90 percent of these patients,” says Dr. Shepherd. The phenotype descriptions and pulmonary function data were published in May in Pediatrics. “The strategy neonatologists have long assumed would be optimal really isn’t. Now we know the vast majority of these kids need a different ventilatory approach, specific to their obstructive phenotype.”

The preferred ventilatory approach for obstructive cases uses slow, deep breaths a few times each minute rather than the shallow, frequent breaths associated with gentle ventilation.

“We have already implemented treatment changes based on the phenotype and pulmonary function test data, and our patients have benefitted enormously,” says Dr. Shepherd. “Our hope is that other centers will improve as much as we have.”

The researchers conducted infant pulmonary function testing on infants with severe BPD who were not improving as expected. Fifty-six patients (51 percent) had obstructive, 44 (40 percent) had mixed and 10 (9 percent) had restrictive phenotypes. Although these phenotypes had previously been suspected due to symptoms in BPD survivors, they had never been confirmed in such young babies. Median postmenstrual age of participants was 52 weeks and median weight was 4.4 kg.

The team hopes to develop bedside tests or biomarkers to diagnose phenotypes without pulmonary function tests in the future, but Dr. Shepherd believes the findings reveal a fairly clear strategy for proceeding with clinical care even without a formal test. Due to the overwhelming proportion of patients with obstructive phenotypes, he says, the default ventilatory approach for severe BPD cases should become the slow-rate, asthma-oriented approach. In cases where infants do not respond, clinicians can assume they are one of the few pure restrictive BPD patients and switch back to “gentle” therapy.

“It’s rare to have a disease state where the diagnosis or appropriate treatment is predictable at least 90 percent of the time,” says Dr. Shepherd. “Knowing that this is the case with severe BPD, people should have confidence in using this new information as a roadmap for ventilatory care.”

Shepherd EG, Clouse BJ, Hasenstab KA, et al. Infant pulmonary function testing and phenotypes in severe bronchopulmonary dysplasia. Pediatrics. 2018 May; 141(5).