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Infant Pulmonary Function Testing and Phenotypes in Severe Bronchopulmonary Dysplasia
Edward G Shepherd1,2, Brian J Clouse1,3, Kathryn A Hasenstab3
1Comprehensive Center for Bronchopulmonary Dysplasia and the Neonatal Aerodigestive Program, and.
Insights
Infant pulmonary function testing identified distinct obstructive, restrictive, and mixed phenotypes in severe bronchopulmonary dysplasia (sBPD) patients. This suggests sBPD management could be personalized based on these identified pulmonary function phenotypes.
Area of Science:
- Neonatal Medicine
- Pediatric Pulmonology
- Respiratory Physiology
Background:
- Severe bronchopulmonary dysplasia (sBPD) management is empirical and varies widely.
- Current sBPD definition relies on respiratory support needs.
- Distinct patient phenotypes within sBPD are suspected but not well-defined.
Purpose of the Study:
- To test the hypothesis that infant pulmonary function testing (iPFT) reveals distinct phenotypes in infants with sBPD.
- To characterize these phenotypes during the initial NICU stay.
Main Methods:
- Prospective cohort study of infants with sBPD (May 2003-June 2016).
- Infant pulmonary function testing (iPFT) used for classification.
- Patients categorized into obstructive, restrictive, or mixed phenotypes based on iPFT data.
Main Results:
- 51% obstructive, 40% mixed, and 9% restrictive phenotypes identified.
- 86% of obstructive and 78% of mixed groups showed moderate/severe obstruction.
- 70% of restrictive patients had moderate restriction; 74% of obstructive and 63% of mixed groups responded to bronchodilators.
Conclusions:
- Severe BPD encompasses distinct pulmonary function phenotypes.
- Future diagnostic approaches should focus on bedside phenotyping.
- Therapeutic trials should consider pulmonary function phenotyping for patient selection.
Background:
The definition of severe bronchopulmonary dysplasia (sBPD) is based on respiratory support needs. The management of a patient with sBPD remains empirical and is highly variable among providers. Our objective in this study was to test the hypothesis that infant pulmonary function testing (iPFT) would reveal distinct phenotypes in patients with established sBPD during the initial NICU stay.
Methods:
A prospective cohort study with data prospectively collected on infants with sBPD from May 1, 2003, to June 30, 2016. iPFT data were used to classify the patients as obstructive, restrictive, or mixed.
Results:
The median gestational age at birth was 25 weeks (interquartile range [IQR], 24-27 weeks) and the median birth weight was 707 g (IQR, 581-925 g). At the time of iPFT, the median postmenstrual age was 52 weeks (IQR, 45-63 weeks), and the median weight was 4.4 kg (IQR, 3.7-6.0 kg). There were 56 (51%) patients with obstructive, 44 (40%) with mixed, and 10 (9%) with restrictive phenotypes. Moderate or severe obstruction was seen in 86% of the obstructive group and 78% of the mixed group. Of the restrictive patients, 70% had moderate and 30% had mild restriction. Bronchodilator response was seen in 74% of obstructive, 63% of mixed, and 25% of restrictive patients.
Conclusions:
Our findings reveal that sBPD as it is currently defined includes distinct phenotypes. Future researchers of diagnostic approaches to this population should consider the development of bedside tests to define phenotypes, and researchers in future therapeutic trials should consider the use of pulmonary function phenotyping in patient recruitment.
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