A glance at:

Bronchopulmonary Dysplasia

Mohammad Rezaei

Pediatric Pulmonologist

The 2010 NICHD Neonatal Research Network estimated that as many as 68% of VLBW infants can be diagnosed with BPD.

BPD First described by Northway & colleagues in 1967

Prematures with RDS:

Died in first week

or

Survived without Respiratory morbidity

improved survival

But

new chronic lung disease in a group of premature infants who had RDS and had received prolonged ventilation with high FiO2

resulted in dramatic changes in the clinical course and outcomes of premature newborns with RDS.

the overall incidence of BPD has not declined over the past decade

But

its severity has been clearly modulated by changes in clinical practice.

Before

1960

1960Introduction

of mechanical ventilation

prenatal steroid usesurfactant therapy

management of PDA new ventilator strategy

improved nutritionAnd …..

DEFINITION

In 1979, Bancalari and colleague offered the first alterationto Northway’s original definition:

• supplemental oxygen requirement at 28 days

• chronic changes on chest radiograph

• tachypnea with crackles or retractions.

in 1988: a criterion for BPD was then defined as oxygensupplementation at 36 weeks’ postmenstrual age (PMA).

At June 2000: New definition by NIH consensus conference

DEFINITION by NIH consensus conference

*A physiologic test confirming theneed of supplemental oxygen beperformed.

A day of treatment with oxygen21% means that the infant receivedoxygen 21% for more than 12 h onthat day.

Treatment with oxygen 21% and/orpositive pressure at 36 wk PMA, orat 56 d postnatal age or discharge,should not reflect an “acute” event,but should rather reflect the infant’susual daily therapy for several dayspreceding and following 36 wk PMA,56 d postnatal age, or discharge.

EPIDEMIOLOGY

Pulmonary immaturity is the primary risk factor for BPD

Risk of BPD is inversely related to both birthweight and gestational age at birth.

• (85% in neonates between 500-699 g)

• (5% in infants with birth weights >1500 g)

Currently, most infants who develop BPD are born with extreme prematurity, and 75% of cases have birth weights <1000 g

Factors that modify BPD risk :

gestational immaturity

lower birth weight

male sex

white or nonblack race

family history of asthma

SGA

absence of maternal glucocorticoid treatment

lower Apgar scores

perinatal asphyxia

respiratory distress syndrome.

Smoking

pre-eclampsia

Chorioamnionitis

intrauterine growth restriction

Early respiratory support

greater severity of initial pulmonary disease ( pneumothorax, pulmonary interstitial emphysema, and severe atelectasis)

patent ductus arteriosus

pulmonary edema

higher weight-adjusted fluid intake

earlier use of parenteral lipid

light-exposed parenteral nutrition

duration of oxygen therapy.

duration and approach to mechanical ventilation (High FiO2/ High PIP/ High RR/ Low PEEP)

Colonization or infection with Ureaplasmaurealyticum

postnatal sepsis

PATHOLOGY

“Old” BPD VS “New” BPD

PATHOLOGY

“New” BPD: disruption of distal Lung growth

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

PATHOGENESIS

Oxygen Toxicity

Lungs of premature infants are relatively

deficient in antioxidant

enzyme system

High O2:Increases theproduction of

ROS

BPD

Ventilator-Induced Lung Injury (VILI)

•Mechanical ventilation

• volutrauma

• phasic stretch or overdistention of the lung

“volutrauma

• lung inflammation

• Permeability edema

• structural changes

•BPD

Inflammation

plays a central role in the pathobiology of BPD

Oxygen toxicity, volutrauma, and infection can induce early and sustained inflammatory responses that promote the recruitment and activation of neutrophils, which persists in infants who develop BPD.

Genetic Susceptibility

risk for developing BPD is markedly influenced by complex interactions between genetic and environmental risk factors.

as strong a role for genetic factors in BPD as observed in such complex diseases in adults as:

systemic hypertension (30%)

cancer (42%)

psychiatric disorders (> 60%)

PATHOGENESIS

Infection

PDA

PATHOPHYSIOLOGY

PATHOPHYSIOLOGY

Respiratory Function

Pulmonary Circulation

Endothelial cells are particularly susceptible to oxidant injury due to hyperoxiaor inflammation.

smooth muscle cell proliferation, precocious maturation of immature pericytes into mature smooth muscle cells, and incorporation of fibroblasts into the vessel wall and surrounding adventitia

Structural changes in the lung vasculature contribute to high pulmonary vascular resistance (PVR) due to narrowing

Decreased angiogenesis may limit vascular surface area, causing further elevations of PVR

a marked vasoconstrictor response to acute hypoxia

Early injury to the lung circulation leads to the rapid development of PH

In severe BPD, decreased vascular growth occurs in conjunction with marked reductions in alveolar formation impairs gas exchange causes marked hypoxemia

Cardiovascular Abnormalities

In addition to pulmonary vascular disease and right ventricular hypertrophy, other cardiovascular abnormalities associated with BPD include:

left ventricular hypertrophy (LVH)

systemic hypertension

development of prominent systemic-to-pulmonary collateral vessels.

PATHOPHYSIOLOGY

Respiratory Function

Pulmonary Circulation

Cardiovascular Abnormalities

LONG-TERM OUTCOME

Approximately 50% of infants with BPD will require hospital re-admission during early childhood

rate of hospitalization generally declines during the second and third year of life

but lung function studies often show limited reserve even in patients with minimal overt respiratory signs

LONG-TERM OUTCOME

Infants with severe BPD often develop COPD.

In the majority of BPD infants, lung growth and remodeling during infancy results in progressive improvement of gas exchange, lung function, and level of oxygen therapy.

few BPD patients remain oxygen dependent beyond 2 years of age.

Lung function is usually in the low-normal range by 2 to 3 years of age, but air flow abnormalities may remain.

LONG-TERM OUTCOME

Although pulmonary function in most survivors with BPD improves over time and permits normal activity, abnormalities detected by PFT often persist through adolescence, including increased airway resistance and reactivity.

LONG-TERM OUTCOME

Chest x-ray findings during follow-up are generally nonspecific (typically including hyperinflation with peribronchial

cuffing and scattered interstitial infiltrates consistent with fibrosis,

edema, or atelectasis.)

These findings tend to clear with age and are very insensitive markers of changes in lung function.

CT scans ??

PREVENTION

there is no single therapy or prevention strategy except for the prevention of premature birth.

PREVENTION

Antenatal Steroids

NIV

Strategy of mechanical vetilation

Fluid restreiction ??

Treatment of PDA ?

Nutritional support

Vit A ?

Corticosteroids ?

Caffeine (reduce the risk of BPD by 50%)

iNO ?

TREATMENT

Supplemental oxygen

Diuretics

Bronchodilators

Steroids

Antiviral Immunization

Pulmonary Hypertension

TREATMENT

Supplemental oxygen

remains a mainstay of therapy for infants with BPD

(most appropriate target for oxygen saturation levels ??)

TREATMENT

Diuretics

improve pulmonary compliance and airway resistance by reducing lung edema

furosemide

thiazides and spironolactone

TREATMENT

Bronchodilators

Infants with BPD have airway smooth muscle hypertrophy and often have signs of bronchial hyperreactivity that acutely improve with bronchodilator therapy; but response rates are variable.

β-agonists and anticholinergics

Methylxanthines ,aminophylline and caffeine

TREATMENT

Steroids

Overall, glucocorticoid treatment improves lung mechanics and gas exchange, facilitating earlier extubation.

one study showed that inhaled steroids can improve the rate of successful extubation and reduce the need for systemic steroids.

TREATMENT

Antiviral Immunization

Infants with BPD are at increased risk of recurrent respiratory tract infections, especially those due to RSV

The American Academy of Pediatrics recommendations include the use of Palivizumab or RSV-IVIG prophylaxis for infants and children <2 years of age with BPD who required oxygen therapy for their lung disease prior to RSV season. Older infants with more severe BPD may benefit from prophylaxis for two RSV seasons.

TREATMENT

Pulmonary Hypertension

initial clinical strategy for the management of PH in infants with BPD begins with treating the underlying lung disease.

(extensive evaluation for chronic reflux and aspiration, structural airway abnormalities (e.g., tonsillar and adenoidal hypertrophy, vocal cord paralysis, subglottic stenosis, and tracheomalacia), assessments of bronchial reactivity, improving lung edema and airway function, and other pulmonary considerations.)

Periods of acute hypoxia, whether intermittent or prolonged, can often contribute to late PH in BPD ----> sleep study

strongly encourage cardiac catheterization prior to the initiation of chronic therapy

Current therapies : NO, sildenafil, endothelin-receptor antagonists (ETRAs), and calcium channel blockers

sildenafil or bosentan

When you stop learning, You stop growing