Bronchopulmonar y Dysplasia (BPD) is a chronic lung disease of prematurity. It was historically described in the 1960s and has two forms - classical BPD involving extensive fibrosis and new BPD characterized by arrested lung development. The incidence increases with lower gestational age. Risk factors include genetics, inflammation, infection, oxidative stress, mechanical ventilation, poor nutrition and surfactant dysfunction. Prevention focuses on antenatal steroids, gentle resuscitation with low oxygen, early CPAP/NIPPV, synchronized ventilation, adequate nutrition and fluid restriction to avoid pulmonary edema.

1. Bronchopulmonar
y Dysplasia
-An UpdateClinics in Perinatolgy-December 2015

2. Historical overview:
• MC chronic lung disease of childhood.
• First described Northway et al in 1967.
• Classical BPD and New BPD.
• New BPD-Tiny PT who has had minimal initial
RD,with arrested lung development affecting
both alveolgenesis and pulmonary vascular bed.

4. • Defintion: Need for O2 ,CPAP at 36wks PMA

5. Epidemology:
• Relatively rare in infants born beyond 32-34wks of gestation,
increasing in immature infants less than 26 wks of GA
• Incidence :Acc to NICHD database(2003) incidence is about
< 1000 grams---23.2%
1000-1249 g---8.4%
1250-1499 g---5.4%
• No Indian database . Study from PGI -2002
< 1000 grams---50%
1000-1249 g---8.1%
1250-1499 g---2.3%
• Increasing severity associated with decreasing GA, Male and White
race.
• Level of respiratory support after initial recovery from RDS ,may be
best predictor of risk of subsequent RDS

6. Pathogenesis:

9. Pathological findings:
• Classical BPD: Extensive alveolar fibrosis,
airway abnormalities, vascular remodeling.
• New BPD: Uniformly inflated lungs, minimal
airway injury with less prominent fibrosis.
Decrease in alveolar number(alveolar
hypoplasia) and dysregulated microvascular
growth.

10. Etiological factors:
1)Host Susceptibility and Genetic factors:
• 50-80% variance in BPD is due to genetic factors
• Family h/o asthma,HRAD may increase risk of
BPD.
• SNP for genes involved in encoding
inflammation,immunity,IL,surfactant,proteases
etc are associated with increased risk.
• Factors affecting alveolgenesis and vascular
remodeling-VEGF,NO,TGF-b and factors affecting
oxidative response.

11. Etiological factors:
2)Inflammation: plays major role in development of
BPD.
• Inflammatory response may be due to increased
cytokines in amniotic fluid, Infection,Oxidant
damage,Volutrauma.
• Increased neutrophil in tracheal aspirate by 2nd
day.
• Macrophages release oxygen free radical and
Fibronectin,TGF-b(stimultes mesenchymal
,inhibits epithelial)

12. Inflammatory markers in tracheal
aspirate in BPD
TNF-a
IL-1,6,8 and 10
TGF-b
Elastase
MMPs
Neutrophils
Endothelin,ICAM-1

13. Etiological factors:
3)Neonatal Infection:
• Airway microbial colonization including
Ureaplasma urealyticum is associated with
lung inflammation and BPD.
• Recovery of Mycoplasma and Ureplasma from
cord blood has been associate with increased
incidence of BPD.
• Early antibiotic theraphy doesn’t alter
incidence of BPD.

15. Etiological factors:
4)Oxygen Toxicity and Oxidative Stress:

18. Etiological factors:
5)Mechanical Ventilation (VALI):Alistir described BPD
as”oxygen plus pressure plus time”.
• Barotrauma,Volutrauma,Atelectrauma
• Excessive volume than pressure most imp factor.
• High pressure without high volume doesn’t cause lung
injury.
• Excessive tissue stretch leads to biotrauma and initiates
cascade of lung injury.
• PRVC is preferred method for minimizing VALI

20. Etiological factors:
5)Pulmonary edema and PDA:
• Abnormal lung fluid balance contribute to BPD
• PDA,higher fluid intake and lesser weight loss in
first 10 days are independent risk factors
associated with BPD.
• BPD and PDA are strongly associated with each
other,no current definitive evidence to determine
whether treatment of PDA reduces incidence of
BPD.
• B/O Bhagyashree 21 days baby remains to be O2
dependent ,has PDA,has not lost weight since
birth

21. Etiological factors:
6)Poor Nutrition:
• All risk factors are intensified by inadequate
nutritional status.
• Inadequate nutrition reduces alveolar
number,that can be reversed by normalizing
nutrition.
• Vitamin A deficiency has been associated with
disruption of epithelial cell integrity.
• Deficency of Vit E potentiates oxygen free radical
injury.

22. Etiological factors:
7)Surfactant Dysfunction: is common in ELBW
babies after a week of intubation.
• Infection or respiratory deterioration
associated with worsening surfactant function.
• SP-B is down regulated by TGF-B.
• Large multicenter trial under progress to study
use of SP-B and NO in preventing BPD.

23. Etiological factors:
8)Adrenal Insufficiency:
• Premature infants have less mature HPA axis
leading to inadequate response to
inflammatory lung injury.
• Low cortisol at D3-D7 contributed minimally
to increasing risk of BPD.
• PROPHET study-no relation btw low cortisol
and BPD.

24. • Majority are ELBW who require prolong
respiratory support.
• Initially require low FiO2.
• Usually develop infection and/or pneumonia is
1st week resulting in respiratory deterioration.
• High level O2 and ventilator support
administered during these stages sets up cycle
of ongoing ventilator support and lung injury.
Clinical features:New BPD

25. 4 DISTINCT STAGES DESCRIBED BY NORTHWAY
• Stage 1- Hyaline membrane,Alveolar and
interstitial oedema,Necrosis of bronchial mucosa.
• Stage 2 -Areas of Emphysema, Atelectasis ,Areas
of necrosis and repair of bronchial mucosa.
• Stage3- Cystic areas with hyperinflation,
Bronchial metaplasia and hyperplasia, Interstitial
oedema.
• Stage 4- Hyperinflation, Interstitial streak
densities, Flatter chest

28. • Infants with new BPD show only haziness
reflecting diffuse loss of lung volume or
increased lung fluid.
• Occasionally they have dense areas of
segmental or lobar atelectasis or pneumonic
infiltrates, but they do not show severe over
inflation.

29. Prevention of BPD:
1)Non Pharmocological theraphy:
CPAP
NIPPV
Lung protective ventilation
Nutrition with Vitamin supplements
2)Pharmacogical Theraphy:
Antenatal Steroids
Caffeine
iNO
Diuretics
Post natal Steroids
Bronchodilator theraphy

30. BEFORE BIRTH
• Prenatal antibiotics and infection prevention
Prompt treatment of chorioamnionitis with
antibiotics.
• ANTENATAL STEROIDS
Use of antenatal steroids in mothers at risk for
delivering a premature infant reduces the
incidence of neonatal deaths and RDS but does
not reduce the incidence of CLD.

31. In delivery room
• The goal in babies being resuscitated at birth,whether born
at term or preterm, should be an oxygen saturation value in
the interquartile range of preductal saturations
• These targets may be achieved by initiating resuscitation
with air or a blended oxygen and titrating the oxygen
concentration to achieve an SpO2 in the target range using
pulse oximetry
• If blended oxygen is not available, resuscitation should be
initiated with air .
• If the baby is bradycardic (HR 60 per minute) after 90
seconds of resuscitation------ increase to 100 % o2.
• Use lower target inflation pressure range between 20- 25
cm h2o.

32. VENTILATORY STRATEGIES
Continuous positive airway pressure (CPAP):
• Early initiation of nasal CPAP has been shown to reduce
the need for intubation and mechanical ventilation.
NIPPV
• Nasal intermittent positive pressure ventilation (NIPPV)
is a method of augmenting NCPAP by delivering
ventilator breaths via nasal prongs
• NIPPV reduces the incidence of symptoms of extubation
failure and need for reintubation within 48 hours to
one week more effectively than NCPAP; however, it has
no effect on chronic lung disease or mortality.

33. SYNCHRONIZED MECHANICAL VENTILATION &HIGH
FREQUENCY POSITIVE PRESSURE VENTILATION (HFPPV)
• During asynchronized mechanical ventilation,
positive airway pressure and spontaneous
inspiration coincide. If synchronous ventilation is
provided, adequate gas exchange should be
achieved at lower peak airway pressures,
potentially reducing baro/volutrauma, air leak
and bronchopulmonary dysplasia.
• Compared to conventional ventilation, benefit is
demonstrated for both HFPPV and triggered
ventilation with regard to a reduction in air leak
and a shorter duration of ventilation but no
difference in incidence of BPD .

34. Nutrition:
• Metabolic rate and energy expenditure are
elevated in BPD
• Infants developing BPD require 20 to 40% more
calories than their age-matched healthy controls.
• Caloric requirement varies from 120 to 150
Kcal/kg/day
• Protein intake of 3.5 – 4 g/kg/day is needed
• Enteral feeding is often delayed in these infants
due to gastrointestinal immaturity, parenteral
nutrition with proteins and lipids should be
initiated as soon as possible after birth and
fortified human milk when possible.

35. Fluid restriction:
• Restricted fluid intake avoid pulmonary edema
and improve pulmonary function – reducing risk
of mortality and BPD
Restricted versus liberal water intake for preventing morbidity and mortality
in preterm infants. Cochrane Database Syst Rev 2008
• Adequate nutrition must be provided
modest – 140- 150 ml/kg/day
Severe – 110 – 120 ml/kg/day- milk should be
supplemented to ~ 30 cal/oz, iron and vitamins-
supplemented

36. Hypoxic episodes in BPD

39. THANK YOU