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An Overview of

Bronchopulmonary Dysplasia

Roy Maynard, M.D.

May 31, 2011

The Good, The Bad and The Ugly

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Abby - day 3

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Abby - 4 months

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Abby - 1½ years

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Overview

• Epidemiology • Pathophysiology • “Old” vs. “New” BPD • Clinical and laboratory • Management • Outcome • Conclusions

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Historical Perspectives of BPD

• Non-existent disease until advent of mechanical

ventilation for ill newborns in the 60’s.

• First description by Northway in 1967.

• Initial report mostly in larger, more mature

premature newborns treated with mechanical

ventilation.

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Definition of BPD

• Bancalari defined BPD as need for ventilation,

oxygen requirement at 28 days and abnormal CXR.

• Shennan proposed need for supplemental oxygen at

36 weeks corrected gestational age.

• Walsh (et al.) developed physiologic definition:

35–37 weeks, treated with mechanical ventilation,

CPAP or supplemental oxygen needing 30% oxygen

to keep sats 90%–96%.

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Definition

• ATS proposed correct term is bronchopulmonary

dysplasia (BPD) so as to differentiate BPD from

other causes of chronic respiratory disorders in

infants.

• Chronic lung disease of prematurity is another term

commonly used.

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Epidemiology

• Less than 30 weeks gestation (usually 28 weeks or less).

• Birth weight <1250 grams. • Males > females. • The lower the gestational age, the greater the risk. • Due to increased survival in VLBW babies,

prevalence of BPD is increased. • Severity of the new BPD is less than the old BPD.

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Adjusted CLD at 36 Weeks: 2002

Vermont Oxford Children’s-Minneapolis

69

64

44

32

22

18

11

8

3028

0

10

20

30

40

50

60

70

80

501-750g 751-1000g 1001-1250g 1251-1500g 501-1500g

% O

cc

urr

en

ce

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5 Stages of Lung Development

http://www.cincinnatichildrens.org/research/div/pulmonary-biology/morphogenesis.htm.

Accessed on June 7, 2010.

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Pathophysiology

• Old BPD pre-surfactant era

• New BPD post-surfactant era

•Genetic predisposition (polygenic ?)

•Oxygen toxicity

•Pulmonary inflammation/chemical mediators

•Barotrauma vs volutrauma

•Infection/chorioamnionitis/preeclampsia

•Stage of lung growth

•Alveolar simplification

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Pathophysiology

http://www.nature.com/jp/journal/v26/n1s/thumbs/7211476f1th.jpg. Accessed on June 7, 2010.

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Stages of “Old” BPD

4 stages:

•Acute lung injury •Oxidative bronchiolitis •Proliferative bronchiolitis •Obliterative fibroproliferative bronchiolitis

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Histopathology of “Old” BPD

• Altered inflation pattern of atelectasis and

overinflation

• Severe airway epithelial lesions (hyperplasia,

squamous metaplasia)

• Airway smooth muscle hyperplasia

• Prominent vascular hypertensive lesions

• Decreased internal surface area and alveoli

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Pathophysiology

http://www.cheo.on.ca/en/bpdtellme. Accessed on June 7, 2010.

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Pattern of Alternating Atelectasis and Overinflation Old BPD

T. Allen Merritt, MD., William H. Northway, Jr., MD., Bruce R. Boynton, MD. Contemporary Issues in Fetal and

Neonatal Medicine. 4 Bronchopulmonary Dysplasia. Boston: Blackwell Scientific Publications; 1988:165.

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Histopathology of “New” BPD

• Decreased, large and simplified alveoli (alveolar hypoplasia, decreased acinar complexity)

• Decreased, dysmorphic capillaries • Variable interstitial fibroproliferation • Less severe arterial/arteriolar vascular lesions • Negligible airway epithelial lesions • Variable airway smooth muscle hyperplasia

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Comparison of Normal Lungs and New BPD

Jobe, A. NeoReviews Vol.7 No.10 2006 e531 2006.

A. 5-month-old infant born at term. B. Infant who has BPD, born at 28 weeks’ gestation, lung biopsy at 8 months.

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Clinical

• Physical exam • Tachypnea • Tachycardia • Increased work of breathing • Retractions • Nasal flaring • Grunting • Crackles

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Laboratory Findings in Infants with BPD

• ABG

• Chronic respiratory acidosis with compensatory

metabolic alkalosis, hypoxia

• CXR

• Normal-to-increased lung volumes

• Bilateral interstitial changes of a variable nature

• Pulmonary function

• Decreased lung/respiratory compliance

• Increased airway resistance/obstruction

• Airway hyper responsiveness/asthma

• Ventilation/perfusion abnormalities

• Cardiac

• Pulmonary hypertension

• Silent ASD

• Aorta-pulmonary collaterals

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Progression of BPD- Patient 1116

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Progression of BPD- Patient 1116

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Progression of BPD- Patient 1116

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Lung Repair and Remodeling

• Severe BPD may be associated with abnormal

vascular remodeling

• Decreased angiogenesis

• Vascular reactivity

• Narrowing of blood vessel diameter

• Pulmonary hypertension

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Biochemistry

• Alterations in growth factors predispose

developmental arrest of lung in the new BPD

•TGF-beta1 decreased

•VEGF decreased

•TGF-alpha decreased

•PDGF decreased

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Management

• Diet

•Increased energy requirements

•Vitamin A

•120 kcal/kg/day

•NG or GT supplementation

•Swallowing dysfunction (vocal cord paralysis

following PDA ligation)

• Immunizations

•RSV (synagis, H1N1, influenza)

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Management

• Medications

-- Diuretics

• Bronchodilators

• Albuterol/Levoalbuterol

-- Methlyxanthines

• Corticosteroids

• Dexmethasone

• Prednisolone • Budesonide

• Oxygen

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Respiratory Pump Function

• The ability of the pump to bring about normal gas

exchange is dependent on the balance between the

mechanical load placed on the pump and the

intrinsic function of the respiratory muscles.

• Respiratory muscle fatigue is a state that develops

when respiratory muscles are unable to maintain the

targeted force output on repeated contractions and

is reversible with rest.

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Optimum Medical Criteria for Home Management of Chronic Respiratory Failure in Infants with Bronchopulmonary Dysplasia

• Clinical

•Positive trend on growth curve (weight)

•Stamina for periods of play

•Extended period of stability

• Physiologic

•30% or less oxygen

•pCO2 less than 50 torr

•IMV of 30 or less

•Stable airway, mature fistula

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Goals of Home Mechanical Ventilation

• Increase chest wall mobility and lung growth (wean steroids)

• Prevention of respiratory failure (neuromuscular disorders)

• Prevent atelectasis/prevent overinflation

• Provide respiratory muscle rest

• Minimize iatrogenic lung injury

• Prevent respiratory muscle atrophy

• Liberation from mechanical ventilation

• Safe environment

• Family bonding and nurturing

• Promote normal growth and development

• Reduce costs

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Physiologic Changes Promoting Liberation from Mechanical Ventilation

• Change in muscle fiber cell type composition of the

diaphragm (type II cells to type I cells )

• Lung growth

• Increased compliance

• Decreased airway resistance

• Increased alveoli—increased surface area for

gas exchange; improve V/Q mismatch, decrease

oxygen needs and decrease pCO2

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Physiologic Changes Promoting Liberation from Mechanical Ventilation

• Chest wall

• Increase ossification—more rigid, less

compliant, stabilize lung volumes

• Dynamic FRC—changes to static FRC

• Increased stability of small and large airways

• Increase respiratory muscle pump function

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Weaning

• No single ventilator mode or strategy has been

shown to be more effective than another in weaning

children from mechanical ventilation.

• The most common strategy used is called sprinting

or diaphragm training. The diaphragm is the most

important respiratory muscle.

• Dependent on underlying diagnosis.

• Complicating factors may stall weaning.

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Weaning

• SIMV and pressure support

•Wean down pressure support first 15-10-8

• SIMV

•Wean rate to background (20) then CPAP trials during

the day or periods of decreased IMV, allow muscles to

rest at night

• Nocturnal ventilation

•Increase nose filter trials or trach collar time during the

day with gradual reduction in nocturnal IMV to CPAP

• Trach collar and nose filter combination 24 hrs/day for 3

months, then airway evaluation by ENT for decannulation

• Oxygen requirement is not a limiting factor

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Monitoring During the Weaning Process

• Weight gain and feeding habits • Stamina for play time • Oxygen needs • End-tidal CO2 • Developmental progress • Work of breathing • Pulmonary hypertension

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4 8 12 16 20 24

Time (months)

Inc

rea

sin

g A

cu

ity

Positive Outcome for BPD with Respiratory Failure

Trach Home

Off vent

Decannulation

•

•

•

•

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BPD

The Good

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Jackson- Day 1

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Progression of BPD- Patient 1115

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Progression of BPD- Patient 1115

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Jackson- 4 months

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Progression of BPD- Patient 1115

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Jackson- 4 months

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Jackson- 18 months

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Progression of BPD- Patient 1115

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Progression of BPD

The Bad

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Cystic Bronchopulmonary Dysplasia

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Cystic Bronchopulmonary Dysplasia

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Cystic Bronchopulmonary Dysplasia

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Cystic Bronchopulmonary Dysplasia

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Causes of Death

• Progression of disease • Unexplained arrest • Disconnection • Hemorrhage • Inappropriate weaning • Unrelated illness • Abdominal catastrophe/sepsis • Sudden airway compromise

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Negative Outcome for BPD with Respiratory Failure

4 8 12 16 20 24

Time (months)

Inc

rea

sin

g A

cu

ity

Trach Lung Transplant

•

•

Death

•

Trach •

Trach

Death

• Trach

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Severe BPD

The Ugly

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Severe BPD Pre-Lung Transplant

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Chest X-Ray Post-Lung Transplant

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Chest X-Ray Post-Lung Transplant

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Long-Term Outcome

• Severe BPD associated with poorer neurodevelopmental outcome--males worse than females

• Increased risk for abnormal PFT but many not

symptomatic (obstructive lung disease) • Increased risk for asthma • Increased incidence of abnormal chest CT

abnormalities • Increased risk for COPD as adults?

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24-Week Female -BPD/Clinical Asthma- Age 8

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27-Week Male Twin- S/P Trach, Vent- Age 9

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22 ½ Week Female- S/P Trach, Vent- Age 7

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Conclusions

• The “new” BPD represents an arrest in lung development.

• Long-term pulmonary function is generally low-normal or mildly

abnormal for majority of the “new BPD.”

• Post chronic respiratory failure patients are more likely to have

obstructive pulmonary disease.

• At risk for long-term respiratory morbidity, hospitalization, asthma

and COPD; recent study suggests 2.4-fold increase risk for asthma.

• Neurodevelopmental outcome correlates with severity of lung

disease, clearly an increase in ADHD (increase 60%) and autism.

• Uncommon disease among infants with birth weights >1500 grams.

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Q & A

Thank you for

attending!