1. SpR Training Day, 5/10/06 Dr Russell Peek
Chronic Lung Disease
SpR Training Day, 5/10/06
Dr Russell Peek

2. Objectives By the end of this session, you will:
have evaluated the use of systemic corticosteroids in the ventilated preterm infant;
be able to discuss the role of other treatments in prevention and management of chronic lung disease;
appreciate important issues in discharge planning for the infant with chronic lung disease;
understand long term outcomes for infants with chronic lung disease.

3. Systemic Corticosteroids
Chronic lung disease is an inflammatory process
Corticosteroids are potent anti-inflammatory agents
Why not try corticosteroids to prevent or treat chronic lung disease?

4. Scenario
Peter, born after spontaneous preterm labour at 26 weeks, is now 15 days old. He has been ventilated since birth. A patent arterial duct was successfully treated with a single course of ibuprofen.
SIMV 28/6 FiO Not tolerant of weaning.
Chest xray: evolving CLD.
Should he receive steroids?

5. Task
In 3 groups discuss the Cochrane reviews of early, moderately early and late use of corticosteroids.

6. Task
Prepare a brief presentation to give to the rest of the group considering the following issues:
effectiveness in preventing chronic lung disease
short term side effects
long term outcomes
clinical ‘bottom line’

7. Cochrane Conclusions
Methodological quality of long term studies limited
Assessment before school age in most
Insufficient power to detect adverse long term outcomes.
Benefits may not outweigh potential adverse effects
Use as rescue therapy
Minimise dose and duration.

8. Recent evidence: The DART study
Low dose dexamethasone
facilitates extubation, (OR 11.2)
shortens duration of intubation, (14 vs. 21 days)
reduces oxygen requirements
no significant effect on
blood glucose or BP
mortality or oxygen requirement at 36 weeks
Low-dose dexamethasone facilitates extubation among chronically ventilator dependent infants: a multicenter, international, randomised controlled trial. Doyle et al. Pediatrics (2006): 117; 75-83

9. Kaplan-Meier Plot

10. Counselling parents
Having discussed the Cochrane reviews and the DART study, how would you counsel parents if you were considering corticosteroids for their child?

11. Other Treatment Strategies
Other prophylaxis or treatment strategies:
anti-inflammatory
bronchodilation
specific nutritients
antibiotic
etc

12. Inhaled Corticosteroids
No difference in effectiveness or side-effect profiles for inhaled versus systemic steroids
No long term outcome data
Not recommended based on current evidence

13. Sodium Cromoglycate
A mast cell stabiliser that inhibits neutrophil activation and neutrophil chemotaxis.
No evidence from RCTs of a role in prevention of CLD.

14. Inhaled Bronchodilators
Insufficient data to reliably assess use of salbutamol for prevention of CLD.
Further clinical trials are necessary to assess bronchodilators for prophylaxis or treatment.

15. Vitamin A
Vitamin A is necessary for normal lung growth and integrity of respiratory tract epithelial cells
Studies involved repeat im. doses
Modest reduction in death or oxygen dependence at 1 month (RR 0.93, NNT 20)
Modest reduction in oxygen dependence at 36 weeks postnatal age (RR 0.87, NNT 14)

16. Vitamin E An antioxidant Deficiency worsens oxygen toxicity
No evidence that routine supplementation prevents CLD

17. Inositol component of phospholipids
critical role in surfactant synthesis
supplementation reduced risk of CLD or death in 1 small study
further evidence required

18. Selenium a part of glutathione peroxidase
acts synergistically with vitamin E
supplementation produced no reduction in CLD or days of oxygen therapy

19. Glutamine essential for rapidly dividing cells
not present in routine TPN
supplementation produced no reduction in BPD in one study

20. Superoxide Dismutase
Free oxygen radicals implicated in the pathogenesis of chronic lung disease in preterm infants
Currently insufficient evidence about efficacy in preventing chronic lung disease

21. Diuretics - systemic
Lung disease in preterm infants is often complicated with lung oedema
Administration of diuretics improves pulmonary mechanics in CLD
Little evidence to support any benefit on need for ventilatory support, length of hospital stay or long-term outcome
In preterm infants > 3 weeks of age with CLD

22. Diuretics - inhaled
A single dose of aerosolized furosemide improves pulmonary mechanics
Lack of data concerning effects on important clinical outcomes
Not currently recommended

23. Antibiotics
Ureaplasma urealyticum postulated as a cause of CLD (not proven)
Erythromycin has been investigated in 2 small studies
No statistically significant effect on CLD, death or combined outcome of CLD or death

24. Alpha 1 Proteinase inhibitor
Aim to counteract enzymatic damage to lung tissues with prophylactic proteinase inhibitor
No reduction in risk of CLD at 36 weeks
No reduction in adverse neuro-developmental outcomes
No significant difference in other respiratory parameters.

25. Nutrition Babies with CLD feed less well than other preterm infants
have lower fluid intakes
have increased energy expenditure
often have abnormal growth patterns
are at risk of ongoing faltering growth

26. The Energy Balance Equation

27. Nutrition No evidence base for nutrition in CLD
ideal energy intake
optimum mix of protein/CHO/fat
rates of growth
In general, supplemented feeds are used

28. Nutrition Monitor weight, height and OFC
Height ‘catch up’ can continue to age 10
Weight gain is often more problematic

29. Discharge Planning
Peter is now 1 week past term and has stable saturations in 50cc low flow oxygen. He is fully bottle fed.
What issues should be considered before discharge and at the discharge planning meeting?

30. Discharge Planning Home oxygen therapy Resuscitation training
oximeter? apnoea alarm?
Resuscitation training
Vaccination
Risks of smoking and infection
Nutrition and growth
Medication
Follow up

31. Oxygen therapy
In adults, pulmonary hypertension occurs <90% saturation
Normal babies have saturations >95%
Growth is poorer with saturations <92%
Aim for >94% at home; minimise time <90%

32. O2 Saturation Study

33. Long term outlook Pulmonary function Improvement occurs to age 8
Reduced lung volumes (VC, FEV1)
Decreased lung compliance
Decreased airway conductance
Improvement occurs to age 8
Generally fail to achieve normal values

34. Long term outlook Functional outcome - illness
More respiratory morbidity in early life
Cough and wheeze with respiratory viruses
Functional outcome - exercise
Similar endurance in mid childhood
Similar maximal oxygen consumption
More desaturation
Faster, shallower breathing

35. Objectives By the end of this session, you will:
have evaluated the use of systemic corticosteroids in the ventilated preterm infant;
be able to discuss the role of other treatments in prevention and management of chronic lung disease;
appreciate important issues in discharge planning for the infant with chronic lung disease;
understand long term outcomes for infants with chronic lung disease.

36. Any Questions?

37. Summary
Chronic lung disease is associated with morbidity into childhood and adolescence
Few pharmacological approaches to treatment or prevention have proven useful
Attention should be given to optimising oxygen saturations and nutrition
Discharge planning is essential