Long-term follow-up of lung transplant
recipients
Specificities of the paediatric lung
transplant recipient
Paul Aurora
Respiratory and Cardiothoracic Transplant Units
Great Ormond Street Hospital for Children
Portex Respiratory Unit, Institute of Child Health
London, UK
Key points
• What are the main issues regarding post-transplant
monitoring in children?
• How should this care be delivered?
• What should the local paediatrician monitor routinely?
• How do you deal with a sick child?
Post transplant monitoring
Introduction
• Early survival post transplant is much improved, but
long term care is still a challenge
• Goal is for long term survival (10 years?) with normal
growth, development, and quality of life
Pulmonary complications
• Complications with graft are the main impediment to
good long-term outcome, i.e.
– Rejection
– Infection
– Bronchiolitis Obliterans Syndrome (BOS)
• BOS has multifactorial origin, but repeated rejection
and infection are probable causes
• Early detection and treatment are essential
Graft monitoring, 1: Symptoms
• Rejection and lower respiratory infection can present
with mild, non-specific symptoms
– Dyspnoea
– Reduced exercise tolerance
– Cough
– Low grade fever
– Malaise
• The child and family must be educated as to the
importance of these symptoms
Graft monitoring, 2: Lung function
• Most children over 4 years age can perform
spirometry, following training
• Outcome measures (and quality control criteria) may
need to be modified, e.g. report FEV0.75 rather than
FEV1
• Monitor in clinic, but also at home
• Drop of greater than 10% should cause concern
WHICH ANIMATION …?
…FLYING
...CANDLES? …BALLOON?
TOASTER?
Only for initial Too complex for Ideal for
training or PEF the very young preschoolers
Graft monitoring, 2: Lung function
• Children aged 6 years and older can perform eNO
manoeuvres using similar techniques to adults
• In younger children modified techniques are probably
necessary
Graft monitoring, 2: Lung function
• Data from Estenne and colleagues suggest that gas
mixing studies allow earlier detection of graft
dysfunction than spirometry
• Although the single breath washout test is not
possible in young children, a modified version of
multiple-breath washout can be performed instead
Graft monitoring, 2: Lung function
• Lung function testing in infants is usually performed
during (sedated) sleep
• Variety of techniques available, which mirror tests
performed in adults
Forced expiratory maneuvers adapted for use in
infants
Graft monitoring, 3: Transbronchial biopsy
• As for adults, is essential for distinguishing between
rejection and infection
• Difficult to perform successfully with small
bronchoscopes, but newer generation scopes may be
better
• Use of X-ray screening is essential, and general
anaesthesia via laryngeal mask airway is helpful
Graft monitoring, 3: Transbronchial biopsy
• Biopsies should be performed in sick children, where
diagnosis is uncertain
• Use of routine biopsy in well children is controversial
• Most paediatric centres perform biopsies regularly in
first year
Graft monitoring, 4: Radiology
• Plain radiographs performed regularly post-
transplant, but don’t distinguish between rejection
and infection
• Either process may be present with normal
radiograph
Graft monitoring, 4: Radiology
• New generation of multislice scanners allow rapid
acquisition of HRCT data
• Speed of scanner means that sedation is not
necessary even in very young children
• Protocols MUST be adjusted to minimise radiation
exposure
• What is the role?
Post transplant OB, inspiratory film
Post transplant OB, expiratory film
Post-transplant infections
• Primary viral infections more common in paediatric
recipients as many will not have previous exposure
• Measles and varicella can be fatal post transplant
• Essential to immunise pre-transplant, and to advise
family regarding precautions
Post-transplant infections
• Post transplant lymphoproliferative disease is much
more common in children
• Presents clinically with lymphadenopathy, anaemia,
low grade pyrexia, malaise…
• Possible to monitor quantitative EBV count by PCR,
but is this of any help?
Post-transplant infections
• Also be aware of
– CMV infection
– respiratory viruses
– PCP
– fungi
– Low grade bacterial infection
– As for adults
Non allogeneic causes of BOS
• Recent interest in role of gastrooesophageal reflux,
bacterial infections
• Approach should be same as for adult subjects
Side-effects of immunosuppression
• Maintenance therapy usually triple:
– ciclosporin or tacrolimus
– azathioprine or MMF
– corticosteroids
• As well as immunosuppression itself, all agents have
specific side effects
• Common to adult patients, but still v important
Side-effects of immunosuppression
• Ciclosporin and tacrolimus are nephrotoxic, this is
partly dose related and reversible, but there is also
irreversible progressive component
• Marrow suppression with aza/MMF
• Diabetes mellitus, particularly in children with CF on
tacrolimus
Other CF complications
• Bone density is abnormal in many children,
particularly those with CF
• Also need to be aware of non-respiratory
complications of CF
Growth failure
• Many children referred for transplant already have
growth failure
• This is worsened by corticosteroids
• Reduce dose as much as possible
• Growth hormone is controversial
Do the lungs grow?
• Yes, provided the child remains healthy
– Forced expiratory flows increase as expected,
suggesting that airways grow
– Do alveoli multiply, or do they distend?
Psychosocial issues
• Many children are socially and physically immature
prior to transplant
• Behavioural difficulties post transplant are common
• Greatest concern is non-adherence to therapy,
particularly amongst adolescents
How is this delivered?
Surgical staff
Pharmacist Medical staff Nursing staff Psychologist
Local Other medical
paediatrician Child and surgical
teams
Community
team Invasive Non invasive
Monitoring Monitoring
i.e. catheter studies i.e. cardiac and
Local respiratory
and bronchoscopy
pharmacist physiology
Anaesthesia
Pharmacist Medical staff Nursing staff Psychologist
Child
Local
paediatrician
GP Community nurses
School Wider family and friends
What should the local
paediatrician do?
Shared care
• Lung transplantation in children is uncommon
• Large centres produce better outcomes
• Only a small number of transplant centres are
needed, and many patients will live a long way from
the transplant centre
• Shared care with the local paediatrician or paediatric
pulmonologist is essential
Shared care
• The local team will see the child regularly in clinic
• On each occasion
– Spirometry
– Full Blood Count
– Renal function / blood biochemistry
– Immunosuppressant blood levels
must be performed
Shared care
• Any concerns?
Phone the transplant centre
Shared care
• If a child presents unwell, with respiratory symptoms
– Remember that it is very difficult to distinguish
rejection from infection
– Prompt treatment is essential
– Biopsy may be necessary
Shared care
• So, if a child presents unwell, with respiratory
symptoms
Phone the transplant centre
(Unless, you have been running shared care for some time, you
know the child well, and it is clear that the child does not have
rejection)
Shared care
• If a child presents with gastroenteritis
– Check tacrolimus level and renal function
– Ensure well hydrated
– Then,
Phone the transplant centre
Shared care
• If a child presents with unusual symptoms, eg.
Anaemia, malaise, lymphadenopathy, and the cause
is not obvious..
Phone the transplant centre
Summary
• Outcomes following lung transplantation are
improving
• Good outcomes depend on close monitoring and
rapid investigation and treatment of any
complications
• Close liaison between transplant centre and local
team is essential
• If in doubt, pick up the telephone!