Lung transplant

Question 1

What are age criteria for lung transplant?

Unilateral

Bilateral

Heart & lung

Answer 1

Unilateral: <65 yo

Bilateral: <60

Heart & lung: <55

However there is strong arguments for functional age rather than chronological aging

Question 2

What are general indications for lung transplantation? (not disease specific) - 4

Answer 2

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

Question 3

What are absolute contraindications to lung transplantation?

Answer 3

1. Active or recent malignancy (<2 years)
2. Active/uncontrolled Infection - HIV, Hep B/C, infection with difficult source control
3. Active substance use: smoking, alcohol, drugs
4. Significant organ dysfunction
5. Severe psychiatric comorbidities or record of repeated poor adherence
6. Lack of consistent & reliable social support system

Question 4

What are relative contraindications for lung transplantation? (4)

Answer 4

Diabetes

Osteoporosis

Obesity or malnutrition

Atypical mycobacterial colonisation of lungs

Question 5

What is the problem with pleurodesis when a transplantation is considered?

Answer 5

Higher risk of intraoperative bleeding, especially when cardiopulmonary bypass is used. But it is not a contraindication.

Question 6

What are the complications of lung transplant? (primarily to do with transplant itself, rather than meds)

Answer 6

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)

Question 7

What is the main risk factor for CMV disease? (1)

Answer 7

Sero-discordant pair: i.e. donor +ve, recipient -ve

Question 8

What is the correlation between CMV viral titre with the tissue specific disease?

Answer 8

Not great.

Hence to be absolutely sure patient need Bx or BAL to exclude inclusion bodies.

Question 9

Duration of CMV prophylaxis post lung transplant?

Answer 9

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)

Question 10

What are 3 most common microorganisms causing bronchial pneumonia during early period after transplant?

Answer 10

Pseudomonas

Staph aureus

CMV

Question 11

How does primary graft dysfunction present? Why does it occur? What is management?

Answer 11

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

Question 12

Why does airway dysfunction during perioperative period following lung transplant? What are 2 potential longer-term complications?

Answer 12

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

1. Devitalised area can be nidus for fungal super infection
2. Bronchial stenosis

Question 13

Treatment for Aspergillus?

Answer 13

Voriconazole.

Second lines - Amphotericin, Echinocandins

60% mortality post lung-transplant

Question 14

Bronchiolitis obliterans following lung transplant.

Why does it occur?

When does it occur?

How common is it?

How would you pick it up?

Treatment?

Answer 14

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.

Question 15

What are 3 risk factors for Bronchiolitis Obliterans?

Answer 15

Number / severity of acute rejection

HLA mismatch

Early infections

Question 16

What are pharmacological management for bronchiolitis obliterans / chronic graft rejection?

Answer 16

This requires advice from expert transplant team and MDT discussion

Mortality rate is up to 55%

1. Addition of long term Azithromycin (250mg OD 5d then 250mg 3 times/wk)
2. Optimise immunosuppression - consider making following switches

CsA → tacrolimus

AZA → Mycophenolate

Consider Everolimus/Sirolimus

3. Consider re-transplantation

Question 17

Lung transplant - history?

Answer 17

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

Question 18

Lung transplant examination - things to comment on?

Answer 18

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

Question 19

What is your approach to investigating this patient with previous lung transplant presenting with progressively worsening SOB/cough? Start with DDx (5).

Answer 19

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

Question 20

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?

Answer 20

Main concern is acute rejection (cell vs. ab mediated).

Key investigations are:

1. Spirometry: a decline in FEV1 and FVC or both
2. 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.

Question 21

Implication of using antifungal agents for transplant patients?

Answer 21

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.

Question 22

How would you investigate suspected chronic lung allograft dysfunction (CLAD)? - 3

Answer 22

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)

Question 23

GORD spiel in lung transplant

Answer 23

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.

1. Non-pharm: no late dinner/meals, elevate head of the bed
2. PPI
3. H1 Antagonist: Nizatidine
4. Sucralfate
5. Consider Surgery (nissan fundoplication) - if pH and manometry study is positive.