1 of 47

BPD Definitions

2 of 47

Outline

The early papers
The NIH definition
The physiologic definition
The NIH 2018 update
The 2017 Canadian Neonatal Network definition
The 2019 Neonatal Research Network definition
Comparisons

3 of 47

Content prepared by

�Dr. Benjamin Courchia MD

&

Dr. Daphna Yasova Barbeau MD

4 of 47

The early papers…

5 of 47

Northway, W. H., Rosan, R. C. & Porter, D. Y. Pulmonary Disease Following Respirator Therapy of Hyaline-Membrane Disease — Bronchopulmonary Dysplasia. New Engl J Medicine 276, 357–368 (1967).

6 of 47

Northway, W. H., Rosan, R. C. & Porter, D. Y. Pulmonary Disease Following Respirator Therapy of Hyaline-Membrane Disease — Bronchopulmonary Dysplasia. New Engl J Medicine 276, 357–368 (1967).

7 of 47

Northway, W. H., Rosan, R. C. & Porter, D. Y. Pulmonary Disease Following Respirator Therapy of Hyaline-Membrane Disease — Bronchopulmonary Dysplasia. New Engl J Medicine 276, 357–368 (1967).

8 of 47

In 1978, the National Heart, Lung, and Blood Institute (NHLBI) sponsored a workshop to establish better definitions for what BPD was at the time.
BPD was summarized as: The disease which is associated with intensive therapy for respiratory difficulty in the newborn infant and which leads to chronic lung disease characterized by hypoxia, hypercarbia, and oxygen dependence with an associated chest radiograph showing hyperexpansion and focal hyperlucency alternating with strands of opacification.
It advised that “The clinical, physiologic, radiologic, and histologic criteria for diagnosing the disease, however, need to be more precisely defined.”
At that time, the consensus was that BPD can be defined as 28 days of oxygen exposure with characteristic radiographic changes

Ibrahim, J. & Bhandari, V. The definition of bronchopulmonary dysplasia: an evolving dilemma. Pediatr Res 84, 586–588 (2018).

9 of 47

Shennan, A. T., Dunn, M. S., Ohlsson, A., Lennox, K. & Hoskins, E. M. Abnormal Pulmonary Outcomes in Premature Infants: Prediction From Oxygen Requirement in the Neonatal Period. Pediatrics 82, 527–532 (1988).

10 of 47

Shennan, A. T., Dunn, M. S., Ohlsson, A., Lennox, K. & Hoskins, E. M. Abnormal Pulmonary Outcomes in Premature Infants: Prediction From Oxygen Requirement in the Neonatal Period. Pediatrics 82, 527–532 (1988).

11 of 47

Shennan, A. T., Dunn, M. S., Ohlsson, A., Lennox, K. & Hoskins, E. M. Abnormal Pulmonary Outcomes in Premature Infants: Prediction From Oxygen Requirement in the Neonatal Period. Pediatrics 82, 527–532 (1988).

12 of 47

Husain, A. N., Siddiqui, N. H. & Stocker, J. T. Pathology of arrested acinar development in postsurfactant bronchopulmonary dysplasia. Hum Pathol 29, 710–717 (1998).

Finally, as the use of surfactant became widespread the pathology of BPD changed, yet again.

In that study of 22 BPD patients, the author separated the infants who had received surfactant and those who had not.

They selected babies who had passed away and on whom autopsy was performed.

They compared the lung biopsy and looked at radial alveolar count, mean linear intercept and the extent of fibrosis.

They concluded that

the amount of alveolar septal fibrosis is substantially less and tends to be more diffuse in S-BPD than in NS-BPD;
during the period after birth, there is a partial to complete arrest in acinar development (alveolar saccular and alveolar) of similar severity for S-BPD and NS-BPD; and
even though on histological examination there are minimal changes, RAC, MLA, and their ratio may be used to support the diagnosis of BPD and help in assessing the amount of lung damage that occurs in S-BPD

13 of 47

The NIH definition

14 of 47

Jobe, A. H. The New BPD. Neoreviews 7, e531–e545 (2006).

The “new” BPD

15 of 47

Jobe, A. H. & Bancalari, E. NICHD / NHLBI / ORD Workshop Summary. Am J Resp Crit Care 163, 1723--1729 (2001).

In June of 2000, a workshop was organized by the National Institute of Child Health and Human Development (NICHD) and the National heart, lung and blood institute (NHLBI), together with the Office of Rare Diseases (ORD), held in Bethesda Maryland, with the following goals:

Review the definition of BPD and lung injury in very preterm infants
Identify gaps in knowledge about lung development
Describe the best indicators of outcome for infants with BPD
Determine priorities for future research

16 of 47

Jobe, A. H. & Bancalari, E. NICHD / NHLBI / ORD Workshop Summary. Am J Resp Crit Care 163, 1723--1729 (2001).

17 of 47

Jobe, A. H. & Bancalari, E. NICHD / NHLBI / ORD Workshop Summary. Am J Resp Crit Care 163, 1723--1729 (2001).

18 of 47

The physiologic definitions

19 of 47

Walsh, M. C., Wilson-Costello, D., Zadell, A., Newman, N. & Fanaroff, A. Safety, Reliability, and validity of a physiologic definition of bronchopulmonary dysplasia. J Perinatol 23, 451--456 (2003).

20 of 47

Walsh, M. C., Wilson-Costello, D., Zadell, A., Newman, N. & Fanaroff, A. Safety, Reliability, and validity of a physiologic definition of bronchopulmonary dysplasia. J Perinatol 23, 451--456 (2003).

21 of 47

The NIH 2018 update

22 of 47

Higgins, R. D. et al. Bronchopulmonary Dysplasia: Executive Summary of a Workshop. J Pediatrics 197, 300--308 (2018).

23 of 47

Higgins, R. D. et al. Bronchopulmonary Dysplasia: Executive Summary of a Workshop. J Pediatrics 197, 300--308 (2018).

24 of 47

The Canadian Neonatal Network Definition

25 of 47

Isayama, T. et al. Revisiting the Definition of Bronchopulmonary Dysplasia: Effect of Changing Panoply of Respiratory Support for Preterm Neonates. Jama Pediatr 171, 271 (2017).

26 of 47

Isayama, T. et al. Revisiting the Definition of Bronchopulmonary Dysplasia: Effect of Changing Panoply of Respiratory Support for Preterm Neonates. Jama Pediatr 171, 271 (2017).

oxygen at 28 days of age
oxygen and/or respiratory positive-pressure support (oxygen/RS) at 28 days
oxygen at 36 weeks’ PMA
oxygen/RS at 36 weeks’ PMA
oxygen at 28 days and oxygen/RS at 36 weeks’ PMA
oxygen/RS at 28 days of age and at 36 weeks’ PMA\

BPD Definitions that were tested:

27 of 47

Isayama, T. et al. Revisiting the Definition of Bronchopulmonary Dysplasia: Effect of Changing Panoply of Respiratory Support for Preterm Neonates. Jama Pediatr 171, 271 (2017).

28 of 47

Isayama, T. et al. Revisiting the Definition of Bronchopulmonary Dysplasia: Effect of Changing Panoply of Respiratory Support for Preterm Neonates. Jama Pediatr 171, 271 (2017).

29 of 47

Isayama, T. et al. Revisiting the Definition of Bronchopulmonary Dysplasia: Effect of Changing Panoply of Respiratory Support for Preterm Neonates. Jama Pediatr 171, 271 (2017).

30 of 47

Isayama, T. et al. Revisiting the Definition of Bronchopulmonary Dysplasia: Effect of Changing Panoply of Respiratory Support for Preterm Neonates. Jama Pediatr 171, 271 (2017).

31 of 47

Isayama, T. et al. Revisiting the Definition of Bronchopulmonary Dysplasia: Effect of Changing Panoply of Respiratory Support for Preterm Neonates. Jama Pediatr 171, 271 (2017).

oxygen/RS at 36 weeks’ PMA was the best among all contemporary definitions of BPD to predict serious severe respiratory morbidity at 18 to 21 months corrected age with the highest AUC.

Also, oxygen/RS at 40 weeks’ PMA was most strongly associated with serious respiratory outcome among those at each of 34 to 44 weeks’ PMA.

32 of 47

The Neonatal Research Network Definition

33 of 47

Jensen, E. A. et al. The Diagnosis of Bronchopulmonary Dysplasia in Very Preterm Infants. An Evidence-based Approach. Am J Resp Crit Care 200, 751–759 (2019).

This paper published in 2019 outlines in its introduction where the current framework at the time fell short of what was needed when it comes to BPD definition. "These initial criteria provided a much-needed diagnostic framework, but they were not designed to predict later outcomes”

"Unfortunately, these widely used criteria are no longer valid. They do not reflect contemporary neonatal respiratory care, including the widespread use of high-flow nasal cannula, and may not adequately predict childhood outcomes in contemporary very preterm infants.”

The aim of the study was to determine which of several revised, severity- graded diagnostic criteria best predict clinically meaningful respiratory and neurodevelopmental outcomes measured at 18–26 months’ corrected age in very preterm infants.

34 of 47

Jensen, E. A. et al. The Diagnosis of Bronchopulmonary Dysplasia in Very Preterm Infants. An Evidence-based Approach. Am J Resp Crit Care 200, 751–759 (2019).

The primary outcome:

how each of these 18 definitions predicted the composite outcome of death between 36wks and 18-26mo or serious respiratory morbidity �

The secondary outcome:

composite outcome of of late death or moderate to severe neurodevelopmental impairment at 18 – 26 months ’ corrected age.

35 of 47

Jensen, E. A. et al. The Diagnosis of Bronchopulmonary Dysplasia in Very Preterm Infants. An Evidence-based Approach. Am J Resp Crit Care 200, 751–759 (2019).

36 of 47

Jensen, E. A. et al. The Diagnosis of Bronchopulmonary Dysplasia in Very Preterm Infants. An Evidence-based Approach. Am J Resp Crit Care 200, 751–759 (2019).

37 of 47

Jensen, E. A. et al. The Diagnosis of Bronchopulmonary Dysplasia in Very Preterm Infants. An Evidence-based Approach. Am J Resp Crit Care 200, 751–759 (2019).

No BPD	Grade I	Grade II	Grade III
No respiratory support (room air)	≤ 2 LPM Nasal Cannula (NC) (any FiO2)	> 2 LPM NC, nCPAP, NIMV (any Fio2)	Invasive ventilation (any FiO2)

38 of 47

Comparing Definitions

39 of 47