Lung transplant Flashcards
What are age criteria for lung transplant?
Unilateral
Bilateral
Heart & lung
Unilateral: <65 yo
Bilateral: <60
Heart & lung: <55
However there is strong arguments for functional age rather than chronological aging
What are general indications for lung transplantation? (not disease specific) - 4
Age <65
Severe disease refractory to medical therapy where risk of death within 2 years >50%
Absence of non-pulmonary comorbidities that would limit life-expectancy to <5 years post-transplant
Satisfactory psychosocial profile & support system
What are absolute contraindications to lung transplantation?
- Active or recent malignancy (<2 years)
- Active/uncontrolled Infection - HIV, Hep B/C, infection with difficult source control
- Active substance use: smoking, alcohol, drugs
- Significant organ dysfunction
- Severe psychiatric comorbidities or record of repeated poor adherence
- Lack of consistent & reliable social support system
What are relative contraindications for lung transplantation? (4)
Diabetes
Osteoporosis
Obesity or malnutrition
Atypical mycobacterial colonisation of lungs
What is the problem with pleurodesis when a transplantation is considered?
Higher risk of intraoperative bleeding, especially when cardiopulmonary bypass is used. But it is not a contraindication.
What are the complications of lung transplant? (primarily to do with transplant itself, rather than meds)
Complications of the transplant itself
Immediate/Early (within 1st year)
- Primary graft dysfunction (from ischaemic reperfusion injury) → noncardiogenic APO
- Ischaemic injury to airway (bronchial arteries) → airway dysfunction, bronchial stenosis more chronically.
- Infection: pseudomonas, s. aureus, CMV (very common even with prophylaxis - 1/3 develops)
- Rejection: acute cellular rejection (50% within 1year)
Chronic / Delayed
- Rejection as above
- BOS (Bronchiolitis Obliterans Syndrome) - most common cause of chronic allograft dysfunction
Complications of immunosuppression/medications (DR HODS PRAM)
What is the main risk factor for CMV disease? (1)
Sero-discordant pair: i.e. donor +ve, recipient -ve
What is the correlation between CMV viral titre with the tissue specific disease?
Not great.
Hence to be absolutely sure patient need Bx or BAL to exclude inclusion bodies.
Duration of CMV prophylaxis post lung transplant?
6 months for donor +ve / recipient -ve patient
3-6 month for recipient +ve patient
Consider 12 months prophylaxis (shown to be superior to 6 months in recent RCT)
What are 3 most common microorganisms causing bronchial pneumonia during early period after transplant?
Pseudomonas
Staph aureus
CMV
How does primary graft dysfunction present? Why does it occur? What is management?
Presents with non-cardiogenic APO within 72 hours of transplant, in absence of any identifiable cause.
Occurs due to ischaemic reperfusion injury
Treatment is supportive
Why does airway dysfunction during perioperative period following lung transplant? What are 2 potential longer-term complications?
During lung transplant, no attempt is made to establish systemic blood flow to the bronchial arteries - so donor bronchus has to derive blood supply from the venous system → always at risk of ischaemic injury.
Can result in severe airway dehisence.
Longer term complications are
- Devitalised area can be nidus for fungal super infection
- Bronchial stenosis
Treatment for Aspergillus?
Voriconazole.
Second lines - Amphotericin, Echinocandins
60% mortality post lung-transplant
Bronchiolitis obliterans following lung transplant.
Why does it occur?
When does it occur?
How common is it?
How would you pick it up?
Treatment?
This occurs due to the fibro-proliferative process that obliterates the airway. Initially small airways but eventually larger airways. It is a manifestation of chronic rejection.
Usually presents after 2 years from transplant
FEV1 is used as surrogate marker - defined by unexplained decline in FEV1 by 20%
50% develop in 5 years, 75% in 10 years
Aggressive increase in immunosuppression may stabilise it but cannot be reversed.
Poor prognosis.
What are 3 risk factors for Bronchiolitis Obliterans?
Number / severity of acute rejection
HLA mismatch
Early infections
What are pharmacological management for bronchiolitis obliterans / chronic graft rejection?
This requires advice from expert transplant team and MDT discussion
Mortality rate is up to 55%
- Addition of long term Azithromycin (250mg OD 5d then 250mg 3 times/wk)
- Optimise immunosuppression - consider making following switches
CsA → tacrolimus
AZA → Mycophenolate
Consider Everolimus/Sirolimus
- Consider re-transplantation
Lung transplant - history?
P: when, how many lungs (or re-transplanted) +/- heart, original lung disease +/- PHTN? How successful was it from your point of view?
R: who was the donor? degree of HLA mismatch, CMV serodiscordant pair? Prophylaxis? Prolonged ischaemic time?
I: pre-transplantation work-up (Angio, TTE, CT, PFT) - less important if was already transplanted. Any recent CT or bronchoscopy/BAL (suspect BOS / infection)
Complications: primary graft failure/airway dysfunction (_acute SOB/APO - how long hospitalised, any inpatient complication_s/ICU admissions), bronchial stenosis (any stenting/dilatation), difficult infections (organisms).
Complications from ImmSx: DR HODS PrAM**
M: current regime, past regime (ask specifically for Tac/CsA/AZA/MMF/Siro/Everolimus). Why were they changed/ceased? Any plan for re-transplantation. Do you have a transplant nurse or anyone you can contact if any problems?
C: Compliance & Current status - what is baseline ET and now, symptoms, hospital admissions last 12 months, how is the patient coping with complications/medications (adherence!). How often followed up.
P: insight
Lung transplant examination - things to comment on?
Scar, ecchymosis, cushingoid
SOB at rest
ET - get patient to walk backwards and forwards
End-inspiratory pops & squeaks (advanced BOS is associated with bronchiectasis)
Signs of infection
What is your approach to investigating this patient with previous lung transplant presenting with progressively worsening SOB/cough? Start with DDx (5).
Most concerning DDx = infection (esp. CMV, Pseud, Staph A, Aspergillus - that has high mortality), acute cellular rejection (if within 1 year) and BOS (chronic rejection). Other DDx includes bronchial stenosis, disease recurrence, then others (PE, anaemia, CCF, arrythmia, renal failure, acidosis…etc).
T: Spirometry / PFT (? FEV1 decline >10%), CXR (new infiltrate) are the key, HRCT (new lesions, evidence of air trapping, bronchiectasis), sputum culture, septic work-up, CMV viral load, aspergillus IgG, IgE, total serum IgE, precipitins.
Consider bronchoscopy/BAL, especially if infection suspected and CXR shows new infiltrate. (MCS/cytology/cell counts differential/viral PCR) +/- biopsy (no biopsy if advanced airflow obstruction). Look for raised neutrophils (25-50%), fibrous scarring, inclusion bodies (CMV). Biopsy /BAL is used to exclude other causes of dyspnoea.
E: consider CTPA, ECG (arrythmia/ischaemia), TTE (HF), FBC (anaemia), EUC (renal failure in context of CNIs)
S: ABG + inflammatory markers
How would you investigate for a patient with a recent lung transplant presenting with fever, SOB and cough? (few months ago) - and what do you look for?
Main concern is acute rejection (cell vs. ab mediated).
Key investigations are:
- Spirometry: a decline in FEV1 and FVC or both
- HRCT: severity, distribution of disease, guide bronchoscopy.
**3. Bronchoscopy:
- BAL: lymphocytic alveolitis, decreased CD4/CD8 ratio. This is in contrast with neutrophilic alveolitis, which is a common finding in the 1st few months of transplant. However, neutrophilia after 3 month may indicate BOS.
Transbronchial biopsies (6-10 biopsies). Do IHC for C4d (Ab-med rejection)
Can do other usual investigations - but above are specific for acute cellular rejection.
Implication of using antifungal agents for transplant patients?
Drug interaction. Voriconazole and posaconazole both increases CsA, Tac and Sirolimus level substantially - dose reduction required
- Tac to 1/3
- CsA to 1/2
- Sirolumus to 1/10
Azole class drugs are generally Cyp2C9 inhibitor and P-glycoprotein substrates.
How would you investigate suspected chronic lung allograft dysfunction (CLAD)? - 3
Spirometry/PFT looking for FEV1 decline 10%, and decline in FVC/TLC.
HRCT: air trapping, infiltrates, bronchiectasis
Bronchoscopy + Histopathology - obliterative bronchiolitis (obstructive) or parenchymal fibrosis (restrictive)
GORD spiel in lung transplant
Important as it may cause direct damage to lung parenchyma + it upregulates innate immune system (increased risk of rejection)
Patient maybe asymptomatic.
Need to hit them hard.
- Non-pharm: no late dinner/meals, elevate head of the bed
- PPI
- H1 Antagonist: Nizatidine
- Sucralfate
- Consider Surgery (nissan fundoplication) - if pH and manometry study is positive.
