Bronchopulmonary dysplasia (BPD) develops in preterm neonates treated with oxygen and positive pressure ventilation. It is characterized by impaired lung development and long term pulmonary complications. Risk factors include prematurity, mechanical ventilation, oxygen therapy, infection and poor nutrition. BPD causes abnormalities in lung structure and function such as decreased lung volumes, air trapping and pulmonary hypertension. Treatment focuses on prevention through gentle ventilation, optimized nutrition and diuretics to facilitate weaning from oxygen and ventilation support.

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