1. Bronchopulmonary
Dysplasia (BPD)
Dr Varsha Atul Shah

2. Back ground
 Develops in neonates treated with O2 & PPV .
 Originally described by Northway in 1967 using
clinical , radiographic & histologic criteria .
 Bancalari refined definition using ventilation
criteria , O2 requirement @ 28days to keep
PaO2>50mmhg & abnormalities in chest x –ray .

3. Back ground
 Shennan proposed in 1988 criteria of O2
requirement @ 36 weeks corrected GA .
 Antenatal steroids , early surfactant Rx &
gentle modes of ventilation minimize
severity of lung injury .

4. Pathophysiology
 Multifactorial
 Major organ systems - lungs & heart
 Alveolar stage of lung development - 36wks GA
to 18 months post conception
 Mechanical ventilation & O2 interferes with
alveolar & pulmonary vascular development in
preterm mammals .
 Severe BPD Pulmonary HT & abnormal
pulmonary vascular development .

5. Stages of BPD
 Defined by Northway in 1967
 Stage 1 - similar to uncomplicated RDS
 Stage 2 - pulmonary parenchymal opacities
with bubbly appearance of lungs
 Stage 3 & 4 – areas of atelectasis ,
hyperinflation & fibrous sheaths
 Recently CT & MRI of chest – reveals more
details of lung injury

6. Frequency of BPD
 Dependent on definition used in NICU .
 Using criteria of O2 requirement @ 28 days
frequency range from 17% - 57% .
 Survival of VLBW infants improved with
surfactant Actual prevalence of BPD has
increased .

7. Mortality/Morbidity of BPD
 Infants with severe BPD Increased risk of
pulmonary morbidity & mortality within the
first 2 years of life .

8. Pulmonary Complications of
BPD
 Increased resistance & airway reactivity
evident in early stages of BPD along with
increased FRC .
 Severe BPD Significant airway
obstruction with expiratory flow limitations
& further increased FRC secondary to air
trapping & hyperinflation

9. Volume trauma &
Barotrauma
 Rx of RDS – surfactant replacement , O2 ,
CPAP & mechanical ventilation .
 Increased PPV required to recruit all alveoli
to Px atelectasis in immature lungsLung
injuryInflammatory cascade .
 Trauma secondary to PPV-Barotrauma
 VolumetraumaLung injury secondary to
excess TV from increased PPV .

10. Volume trauma &
Barotrauma
 Severity of lung immaturity & effects of
surfactant deficiency determines PPV .
 Severe lung immaturityAlveolar number
is reducedincreased PP transmitted to
distal bronchioles .
 Surfactant deficiencysome alveoli
collapse while others hyper inflate .

11. Volume trauma &
Barotrauma
 Increased PPV to recruit all
alveoliCompliant alveoli & terminal
bronchioles ruptureleaks air in to
interstiumPIEIncrease risk of BPD
 Using SIMV compared to IMV in infants
<1000g showed less BPD .

12. O2 & Antioxidants
 O2 accept electrons in it’s outer ringForm
O2 free radicalsCell membrane
destruction
 Antioxidants(AO)Antagonise O2 free
radicals
 Neonates-Relatively AO deficient
 Major antioxidants – super oxide
dismutase , glutathione peroxidase &
catalase

13. O2 & Antioxidants
 Antioxidant enzyme level increase during
last trimester .
 Preterm birthIncreased risk of exposure
to O2 free radicals

14. Inflammation
 Activation of inflammatory mediatorsIn acute
lung injury
 Activation of leukocytes by O2 free radicals ,
barotrauma & infectionDestruction & abnormal
lung repairAcute lung injuryBPD
 Leukocytes & lipid byproducts of cell membrane
destructionActivate inflammatory cascade

15. Inflammation
 Lipoxigenase & cyclooxigenase pathways are
involved in the inflammatory cascade
 Inflammatory mediators are recovered in tracheal
aspirate of newly ventilated preterm who later
develops BPD
 Metabolites of
mediatorsvasodilatationincreased capillary
permeabilityalbumin leakage & inhibition of
surfactant functionrisk of barotrauma

16. Inflammation
 Neutrophils – release collegenase &
elastasedestroy lung tissue
 Hydroxyproline & elastin recovered in
urine of preterms who develops BPD
 Di2ethylhexylphthalate(DEHP) degradation
product of used ET tubeslung injury
 A study in 1996 found that increased
interleukin 6 in umbilical cord plasma

17. Infection
 Maternal cervical colonization/ preterm
neonatal tracheal colonization of
U.urealyticum associated with high risk of
BPD

18. Nutrition
 Inadequate nutrition supplementation of
preterm compound the damage by
barotrauma , inflammatory cascade
activation & deficient AO stores
 Acute stage of CLDincreased energy
expenditure
 New born ratsnutritionally
depriveddecreased lung weight

19. Nutrition
 Cu , Zn , Mn deficiencypredispose to
lung injury
 Vit A & E prevent lipid peroxidation &
maintain cell integrity
 Extreme prematurity – large amounts of
H2O needed to compensate loss from thin
skin

20. Nutrition
 Increased fluid administration increased
risk of development of PDA & pulmonary
edema(PE)
 High vent settings & high O2 needed to Rx
PDA & PE
 Early PDA Rx – improve pulmonary
function but no effect on incidence of BPD

21. Genetics
 Strong family history of asthma & atopy
increase risk of development & severity of
BPD

22. CVS Changes
 Endothelial cell proliferation
 Smooth muscle cell hypertrophy
 Vascular obliteration
 Serial EKG – right ventricular hypertrophy
 Echocardiogram – abnormal right
ventricular systolic function & left
ventricular hypertrophy

23. CVS Changes
 Persistent right ventricular hypertrophy/
fixed pulmonary hypertension unresponsive
to supplemental O2 leads to poor prognosis

24. Airway
 Trachea & main stem bronchi -
abnormalities depend on duration &
frequency of intubation & ventilation
 Diffuse or focal mucosal edema ,
necrosis/ulceration occur
 Earliest changes from light
microscopyloss of cilia in columnar
epithelium , dysplasia/necrosis of the cells

25. Airway
 Neutrophils , lymphocyte infiltrate & goblet
cell hyperplasiaincreased mucus
production
 Granulation tissue & upper airway scarring
from deep suctioning & repeated ET
intubation results in
laryngotracheomalacia , subglottic stenosis
& vocal cord paralysis

26. Airway
 Necrotizing bronchiolitis – results from
edema , inflammatory exudate & necrosis
of epithelial cells .
 Inflammatory cells , exudates & cellular
debris obstruct terminal airways
 Activation & proliferation of
fibroblastsperibronchial fibrosis &
obliterative fibroproliferative bronchiolitis

28. Radiologic Findings
 Decreased lung volumes
 Areas of atelectasis
 Hyperinflation
 Lung haziness
 PIE

30. Histologic Findings
 In 1996 Cherukupalli & colleagues
described 4 pathologic stages
 Acute lung injury
 Exudative bronchiolitis
 Proliferative bronchiolitis
 Obliterative fibroproliferative bronchiolitis

33. Medical care in BPD
 Prevention
 Mechanical ventilation
 O2 therapy
 Nutritional support
 Medications

34. Mechanical Ventilation
 O2 & PPV life saving
 Aggressive weaning to NCPAP eliminate need of
PPV
 Intubation primarily for surfactant therapy &
quickly extubation to NCPAP decrease need for
prolong PPV
 If infant needs O2 & PPV gentle modes of
ventilation employed to maintain pH 7.28 – 7.40 ,
pCo2 45 – 65 , pO2 50- 70

35. Mechanical Ventilation
 Pulse oximetry & transcutaneous Co2
mesurements – provide information of
oxygenation & ventilation with minimal
patient discomfort
 SIMV – provide information on TV &
minute volumes which minimize O2
toxicity & barotrauma/volumetrauma
 SIMV – allow infant to set own IT & rate

36. Mechanical Ventilation
 When weaning from vent & O2 difficult – when
adequate TV & low FiO2 achievedtrial of
extubation & NCPAP
 Commonly extubation failuresecondary to
atrophy & fatigue of respiratory muscles
 Optimization of nutrition & diuretics – contribute
to successful weaning from vent
 Meticulous nursing care – essential to ensure
airway patency & facilitate extubation

37. O2 Therapy
 Chronic hypoxia & airway
remodelingpulmonary HT & cor
pulmanale
 O2stimulate production of NOsmooth
muscle relaxationvasodilatation

38. O2 Therapy
 Repeated desats secondary to hypoxia
results from- decreased respiratory drive
- altered pulmonary mechanics
- excessive stimulation
- bronchospasm
 Hyperoxiaworsen BPD as preterms have
a relative deficiency of AO

39. O2 Therapy
 O2 requirement increase during stressful
procedures & feedingstherefore wean O2
slowly
 Keep sats 88% - 92%
 High altitudesmay require O2 many
months
 PRBC transfusionincrease O2 carrying
capacity in anemic(hct<30%) preterms

40. O2 Therapy
 Study in 1988 found increased O2 content
& systemic O2 transport , decreased O2
consumption & requirement after blood Tx
 Need for multiple Tx & donor exposures
decreased byerythropoetin , iron
supplements & decreased phlebotomy
requirements

41. Nutritional Support
 Infant with BPD- increased energy
requirements
 Early TPN – compensate for catabolic state
of preterm
 Avoid excessive non N calories increase
CO2 & complicate weaning
 Early insertion of central linesmaximize
calories in TPN

42. Nutritional Support
 Rapid & early administration of increased
lipidsworsen hyperbillirubinemia & BPD
through billirubin displacement from
albumin & pulmonary vascular lipid
deposition respectively .
 Excessive glucose loadincrease O2
consumption , respiratory drive &
glucoseuria.

43. Nutritional Support
 Cu , Mn , & Zn essential cofactors in AO
defenses
 Early initiation of small enteral feeds with
EBM , slow & steady increase in
volumefacilitate tolerance of feeds
 Needs 120 – 150 Kcal/kg/day to gain
weight

44. Medical Therapy
 Diuretics
 Systemic bronchodilators

45. Diuretics
 Furesemide (Lasix) Rx of choice
 Decrease PIE & pulmonary vascular
resistance
 Facilitate weaning from PPV , O2 /both
 Adverse effects – hyponatremia ,
hypokalemia , hypercalciuria , cholelithiasis
, nephrocalcinosis & ototoxicity

46. Diuretics
 Careful parenteral & enteral supplements
compensate adverse effects
 Thiazide & spiranolactone for long term Rx

47. Systemic Bronchodilators
 Methylxanthines – increase respiratory
drive , decrease apnea , improve
diaphragmatic contractility
 Smooth muscle relaxation – decrease
pulmonary vascular resistance & increase
lung compliance
 Exhibit diuretic effects

48. Systemic Bronchodilators
 Theophyline – metabolized primarily to
caffeine in liver
 Adverse effects – increase heart rate ,
GER , agitation & seizures

49. Prognosis
 Pulmonary function slowly improves
secondary to continued lung & airway
growth & healing
 Northway- Airway hyperactivity , abnormal
pulmonary functions , hyperinflation in
chest x ray persists in to adult hood
 A study in 1990 found gradual decrease in
symptom frequency in children 6 – 9 yrs