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Rates Of Bronchopulmonary Dysplasia Decreased After Implementation Of Prevention Bundle

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Development and implementation of a novel bronchopulmonary dysplasia prevention system of care was associated with a sustained decrease in rates of bronchopulmonary dysplasia in infants, according to data published in JAMA Network Open.

"Bronchopulmonary dysplasia, or chronic lung disease, is a common, serious complication of prematurity. The incidence of [bronchopulmonary dysplasia] remains high and has been mostly unchanged during the last decade, ranging from 20% in California to 28% across the U.S. And 42% among infants less than 28 weeks' gestation," Maria Fe B. Villosis, MD, neonatal pediatrician in the department of pediatrics at Kaiser Permanente Panorama City, California, and colleagues wrote in JAMA Network Open. "Various interventions for the prevention of [bronchopulmonary dysplasia] have been studied, although their individual effects on bronchopulmonary dysplasia have either been modest or have influenced only short-term benefits. Significant variation in risk-adjusted rates of [bronchopulmonary dysplasia] holds out the hope that there are existing care practice interventions that, if identified and propagated, could significantly decrease [bronchopulmonary dysplasia] rates."

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Researchers conducted a quality improvement study of 484 infants (mean gestational age, 28.6 weeks; 52.1% female) with birth weights of 501 g to 1,500 g who were admitted to a level 3 neonatal ICU in the Kaiser Permanente Southern California health care system from 2009 to 2019. The researchers focused on three study periods: baseline (2009) when there was an increased rate of bronchopulmonary dysplasia; initial changes based on ongoing cycles of Plan-Do-Study-Act (2010-2014); and full implementation of successive Plan-Do-Study-Act results (2015-2019).

A multidisciplinary team, including neonatologists, respiratory therapists and NICU nurses were involved in the quality improvement team. The quality improvement team developed key drivers for bronchopulmonary dysplasia prevention. The drivers included: a shared mental model focused on prevention of bronchopulmonary dysplasia; prevention to support postnatal lung growth and minimize inflammatory cascade and oxygen toxicity; consistent management to minimize variations in care; and management based on developmental stages of the lung, according to the study. In response to these key drivers, the team's care practices evolved.

The primary outcome, bronchopulmonary dysplasia in infants with less than 33 weeks' gestational age, decreased from 31% to 1.6% during the study period (P < .001).

In addition, the researchers reported that the standardized morbidity ratio for adjusted bronchopulmonary dysplasia in infants with less than 33 weeks' gestational age was decreased from 1.2 in 2009 to 0.4 in 2019, according to the results.

There was also a decrease in rates of combined bronchopulmonary dysplasia severity grades 1, 2 and 3 (24.1% to 9.3%; P for trend < .008); grade 2 bronchopulmonary dysplasia rates decreased from 10.3% to 2.7% (P for trend = .02), according to the results.

Oxygen at home discharge decreased from 13.8% to 2.2% (P = .03),. One infant required tracheostomy tube placement in the 2015-2019 period, according to the results.

Researchers also observed a decrease in adjusted median postmenstrual age at home discharge from 38.2 weeks in 2009 to 36.8 weeks in 2017 to 2019, according to the results.

There was no changed in adjusted mortality during the study.

"We observed a substantial, sustained decrease in bronchopulmonary dysplasia rates in association with the development and implementation of a detailed bronchopulmonary dysplasia prevention bundle. Our success may be associated with a shared mental model of care that bronchopulmonary dysplasia is preventable, the details of the system of care, and the consistency of its execution," the researchers wrote. "We believe the bundle of care described in this report is sufficiently detailed to enable researchers to assess whether these outcomes can be replicated at other centers."

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Severe Bronchopulmonary Dysplasia Includes 3 Distinct Phenotypes

April 05, 2018

2 min read

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Preterm infants hospitalized in the neonatal ICU diagnosed with severe bronchopulmonary dysplasia had three distinct phenotypes, as determined by infant pulmonary function testing, according to study results published in Pediatrics.

"Bronchopulmonary dysplasia (BPD) is the most common morbidity in extremely preterm infants," Edward G. Shepherd, MD, of the Comprehensive Center for Bronchopulmonary Dysplasia and the Neonatal Aerodigestive Program, and the department of pediatrics, The Ohio State University, Columbus, and colleagues wrote. "Despite advances in neonatal care that have led to improved survival of extremely preterm infants, there has been no decrease in the incidence of BPD among survivors."

"There is significant practice variation in the approach to [severe BPD (sBPD)] both within an institution and among institutions," the researchers continued "This lack of standardization in care for patients with sPBD arises from the lack of good definition for BPD and the widely variable patient presentation and clinical course."

Shepherd and colleagues prospectively collected data on infants who were hospitalized in the neonatal ICU with SBPD between May 1, 2003, and June 30, 2016.

Through infant pulmonary function testing (iPFT), the infants were classified into three separate phenotypes, including obstructive (forced expiratory volume at 0.5 seconds [FEV0.5] <80% predicted and total lung capacity [TLC] ≥90% predicted), restrictive (TLC < 90% predicted and FEV0.5 and/or forced vital capacity [FVC] ≥90% predicted) or mixed (TLC <90% predicted and FEV0.5 and/or FVC<90% predicted).

Preterm infants with severe bronchopulmonary dysplasia demonstrated three distinct phenotypes. Patients with the purely restrictive phenotype were more likely to be weaned relatively quickly from positive pressure and were discharged from the hospital without mechanical ventilation.

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There were 110 infants included in the study who had a median gestational age at birth of 25 weeks (interquartile range [IQR], 24-27 weeks) and a median birth weight of 707 g (IRQ, 581-925 g). When IPFT was conducted, the patients had a median postmenstrual age of 52 weeks (IRG, 45-63 weeks) and median weight of 4.4 kg (IRG, 3.7-7.0 kg).

Slightly more than half of the infants (51%) had the obstructive phenotype, whereas 40% had mixed and 9% had the restrictive phenotype.

Most of the infants in the obstructive cohort (86%) and mixed cohort (78%) had moderate or severe obstruction. Among the infants classified as restrictive, 70% experienced moderate restriction, with the rest experiencing mild restriction.

The obstructive cohort had the highest bronchodilator response (74%), followed by mixed (63%) and restrictive (25%).

"Patients with sBPD demonstrated three distinct iPFT phenotypes: obstructive, restrictive and mixed," the researchers concluded. "The obstructive phenotype was the most prevalent and was associated with greater birth weight. Although seen in only 9% of patients with sBPD, the purely restrictive phenotype and its diagnosis may be important from a therapeutic prospective because these patients can likely be weaned relatively quickly from positive pressure, and none of the purely restrictive patients were discharged from the hospital win mechanical ventilation."  – by Bruce Thiel

 

Disclosures: The authors report no relevant financial disclosures.

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Premature Babies With Bronchopulmonary Dysplasia Have More Stem Cells At Birth

In the first large-scale clinical study to characterize stem cells from the umbilical cord blood and tissues of premature infants with bronchopulmonary dysplasia – a severe, chronic lung disease – researchers found that these babies had more stem cells at birth. They also found that a growth factor (G-CSF), which is responsible for stem cell migration and differentiation, is decreased in these infants. Based on these results, researchers speculate that the increase in cord stem cells might play an early role in the development of bronchopulmonary dysplasia, which is usually diagnosed when the infant is 2-3 months old. Their findings, published in the Frontiers in Pediatrics, also add to the identification of disease risk factors, as well as contribute to the research into cell-based therapies for prevention and management of bronchopulmonary dysplasia.

We want to be able to use stem cell therapies to regenerate the damaged and underdeveloped lungs of premature infants with bronchopulmonary dysplasia. Our characterization of cord stem cells in these infants is a big step toward development of stem cell therapies to manage and possibly prevent this challenging disease."

Karen Mestan, MD, MSCI, senior author and neonatologist at Ann & Robert H. Lurie Children's Hospital of Chicago and Associate Professor of Pediatrics at Northwestern University Feinberg School of Medicine

About 10,000 babies a year develop bronchopulmonary dysplasia. Premature infants, and especially those born more than 10 weeks preterm and weigh less than two pounds, are at highest risk. However, there are no clear predictors of this disease.

To study the stem cell differences between premature infants who develop bronchopulmonary dysplasia and those who do not, Dr. Mestan and colleagues collected cord blood and tissue from 200 preemies of different gestational ages. They measured the percentage of hematopoietic stem cells (those circulating in blood) and mesenchymal stem cells (those derived from umbilical cord tissue). They also evaluated biochemical factors in cord blood plasma.

"We need more research to understand why premature infants who later are diagnosed with bronchopulmonary dysplasia are born with more hematopoietic and mesenchymal stem cells," says Dr. Mestan. "Their stem cells might not be functioning properly, or maybe they are not mobilized effectively to differentiate into healthy blood or tissue cells."

Clinically, the increase in cord stem cells, if validated by more studies, might be one of the risk factors for bronchopulmonary dysplasia.

"As we get better at predicting this disease and have more tools to intervene, we'll be able to individualize management of preemies and deliver the right treatment at the right time to improve outcomes," says Dr. Mestan.

Source:

Journal reference:

Chaudhury, S., et al. (2019) Variations in Umbilical Cord Hematopoietic and Mesenchymal Stem Cells with Bronchopulmonary Dysplasia. Frontiers in Pediatrics. Doi.Org/10.3389/fped.2019.00475.

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