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An Overview of
Bronchopulmonary Dysplasia
The Good, The Bad and The Ugly

       Roy Maynard, M.D.
         May 31, 2011



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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




                            5 of 63
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%.




                                                      7 of 63
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
               80

               70
                     69

               60         64
% Occurrence




               50
                                44
               40

               30                    32
                                                                       30
                                                                            28
               20                            22
                                                  18
               10                                         11
                                                               8

                0
                    501-750g   751-1000g   1001-1250g   1251-1500g   501-1500g




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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.




                                                                                                      17 of 63
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




A. 5-month-old infant born at term.               B. Infant who has BPD, born at
                                                  28 weeks’ gestation, lung
                                                  biopsy at 8 months.
Jobe, A. NeoReviews Vol.7 No.10 2006 e531 2006.




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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




                                                 25 of 63
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




                                    28 of 63
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




                                                           32 of 63
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



                                                                  35 of 63
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




                                            36 of 63
Positive Outcome for BPD
                         with Respiratory Failure

                    Trach   Home
Increasing Acuity




                        •       •

                                                  Off vent
                                              •



                                                             •
                    4       8       12         16            20             24
                                    Time (months)                Decannulation




                                                                             37 of 63
BPD




The Good



           38 of 63
Jackson- Day 1




                 39 of 63
Progression of BPD- Patient 1115




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Progression of BPD- Patient 1115




                             41 of 63
Jackson- 4 months




                    42 of 63
Progression of BPD- Patient 1115




                             43 of 63
Jackson- 4 months




                    44 of 63
Jackson- 18 months




                     45 of 63
Progression of BPD- Patient 1115




                             46 of 63
Progression of BPD




   The Bad



                     47 of 63
Cystic Bronchopulmonary Dysplasia




                             48 of 63
Cystic Bronchopulmonary Dysplasia




                             49 of 63
Cystic Bronchopulmonary Dysplasia




                             50 of 63
Cystic Bronchopulmonary Dysplasia




                             51 of 63
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

                                                           • Death
Increasing Acuity




                    Trach
                                      •
                                   Lung Transplant
                      •



                      4        8           12         16        20   24
                                           Time (months)




                                                                      53 of 63
Severe BPD




The Ugly



             54 of 63
Severe BPD Pre-Lung Transplant




                           55 of 63
Chest X-Ray Post-Lung Transplant




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Chest X-Ray Post-Lung Transplant




                            57 of 63
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?




                                                 58 of 63
24-Week Female -BPD/Clinical Asthma- Age 8




                                     59 of 63
27-Week Male Twin- S/P Trach, Vent- Age 9




                                    60 of 63
22 ½ Week Female- S/P Trach, Vent- Age 7




                                    61 of 63
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.




                                                                      62 of 63
Q&A




Thank you for
  attending!




                63 of 63

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An Overview of Bronchopumonary Displasia (BPD)

  • 1. An Overview of Bronchopulmonary Dysplasia The Good, The Bad and The Ugly Roy Maynard, M.D. May 31, 2011 1 of 63
  • 2. Abby - day 3 2 of 63
  • 3. Abby - 4 months 3 of 63
  • 4. Abby - 1½ years 4 of 63
  • 5. Overview • Epidemiology • Pathophysiology • “Old” vs. “New” BPD • Clinical and laboratory • Management • Outcome • Conclusions 5 of 63
  • 6. 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. 6 of 63
  • 7. 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%. 7 of 63
  • 8. 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. 8 of 63
  • 9. 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. 9 of 63
  • 10. Adjusted CLD at 36 Weeks: 2002 Vermont Oxford Children’s-Minneapolis 80 70 69 60 64 % Occurrence 50 44 40 30 32 30 28 20 22 18 10 11 8 0 501-750g 751-1000g 1001-1250g 1251-1500g 501-1500g 10 of 63
  • 11. 5 Stages of Lung Development http://www.cincinnatichildrens.org/research/div/pulmonary-biology/morphogenesis.htm. Accessed on June 7, 2010. 11 of 63
  • 12. 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 12 of 63
  • 14. Stages of “Old” BPD 4 stages: •Acute lung injury •Oxidative bronchiolitis •Proliferative bronchiolitis •Obliterative fibroproliferative bronchiolitis 14 of 63
  • 15. 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 15 of 63
  • 17. 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. 17 of 63
  • 18. 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 18 of 63
  • 19. Comparison of Normal Lungs and New BPD A. 5-month-old infant born at term. B. Infant who has BPD, born at 28 weeks’ gestation, lung biopsy at 8 months. Jobe, A. NeoReviews Vol.7 No.10 2006 e531 2006. 19 of 63
  • 20. Clinical • Physical exam • Tachypnea • Tachycardia • Increased work of breathing • Retractions • Nasal flaring • Grunting • Crackles 20 of 63
  • 21. 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 21 of 63
  • 22. Progression of BPD- Patient 1116 22 of 63
  • 23. Progression of BPD- Patient 1116 23 of 63
  • 24. Progression of BPD- Patient 1116 24 of 63
  • 25. Lung Repair and Remodeling • Severe BPD may be associated with abnormal vascular remodeling • Decreased angiogenesis • Vascular reactivity • Narrowing of blood vessel diameter • Pulmonary hypertension 25 of 63
  • 26. Biochemistry • Alterations in growth factors predispose developmental arrest of lung in the new BPD •TGF-beta1 decreased •VEGF decreased •TGF-alpha decreased •PDGF decreased 26 of 63
  • 27. 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) 27 of 63
  • 28. Management • Medications -- Diuretics • Bronchodilators • Albuterol/Levoalbuterol -- Methlyxanthines • Corticosteroids • Dexmethasone • Prednisolone • Budesonide • Oxygen 28 of 63
  • 29. 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. 29 of 63
  • 30. 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 30 of 63
  • 31. 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 31 of 63
  • 32. 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 32 of 63
  • 33. 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 33 of 63
  • 34. 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. 34 of 63
  • 35. 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 35 of 63
  • 36. 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 36 of 63
  • 37. Positive Outcome for BPD with Respiratory Failure Trach Home Increasing Acuity • • Off vent • • 4 8 12 16 20 24 Time (months) Decannulation 37 of 63
  • 38. BPD The Good 38 of 63
  • 39. Jackson- Day 1 39 of 63
  • 40. Progression of BPD- Patient 1115 40 of 63
  • 41. Progression of BPD- Patient 1115 41 of 63
  • 42. Jackson- 4 months 42 of 63
  • 43. Progression of BPD- Patient 1115 43 of 63
  • 44. Jackson- 4 months 44 of 63
  • 45. Jackson- 18 months 45 of 63
  • 46. Progression of BPD- Patient 1115 46 of 63
  • 47. Progression of BPD The Bad 47 of 63
  • 52. Causes of Death • Progression of disease • Unexplained arrest • Disconnection • Hemorrhage • Inappropriate weaning • Unrelated illness • Abdominal catastrophe/sepsis • Sudden airway compromise 52 of 63
  • 53. Negative Outcome for BPD with Respiratory Failure • Death Increasing Acuity Trach • Lung Transplant • 4 8 12 16 20 24 Time (months) 53 of 63
  • 55. Severe BPD Pre-Lung Transplant 55 of 63
  • 56. Chest X-Ray Post-Lung Transplant 56 of 63
  • 57. Chest X-Ray Post-Lung Transplant 57 of 63
  • 58. 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? 58 of 63
  • 59. 24-Week Female -BPD/Clinical Asthma- Age 8 59 of 63
  • 60. 27-Week Male Twin- S/P Trach, Vent- Age 9 60 of 63
  • 61. 22 ½ Week Female- S/P Trach, Vent- Age 7 61 of 63
  • 62. 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. 62 of 63
  • 63. Q&A Thank you for attending! 63 of 63