Lung Transplantation: Recognise suitable recipients, know when to refer to transplant centre, basic understanding of morbidity and mortality following lung transplant

Question 1

Definition of lung transplantation

Answer 1

Life-saving treatment for patients with end-stage respiratory failure not responding to other medical or surgical interventions

Question 2

Indication by condition for lung transplant over time

Answer 2

Always a large cohort due to copd, shrinking percentage of cystic fibrosis, IPF increasing

Question 3

Cystic fibrosis patients who meet criteria for lung transplant - criteria?

Answer 3

Chronic resp failure (type 1 or 2)
NIV dependence
Frequent hospitalisations - infections, haemoptysis
Pulmonary HTN
Rapid decline

Question 4

Why fewer Cystic Fibrosis patients needing lung transplant?

Answer 4

Gene modulator therapy from 2020 - CTFR modulator therapy e.g. Trikafta

Question 5

COPD patient who meet criteria for lung transplant - criteria?

Answer 5

Bode index > or = 7 (measurment of degree of exertional dyspnoea)
Very severe airflow obstruction FEV1 < 20%
Frequent exacerbations
Hypercapnoeic respiratory failure

NB: transplant for copd is more about improving QOL rather than improving survival and often times people can life WITH copd longer than they do after lung transplant - its just that their QOL may be better after lung transplant. The survival benefit is highest for those with greater exertional dyspnoea - but they must not be so frail that they are unable to take part in rehab post transplant. COPD frailty asst:

Compliant participation in pulmonary rehab
Meet targets for muscle strength (quads, grip)
BMI in healthy range
6MWT < 300m

Question 6

Interstitial lung disease patients who meet criteria for lung transplant - criteria?

Answer 6

This group of patients is quite heterogeneous due to multiple different aetiologies for their ILD. Often referred too late.
Criteria:
10% decline in FVC over 6months
15% decline in DLCO over 6months
O2 sats < 88% on 6MWT
Distance < 250m or decline in distance by 50m over 6months
Pulm HTN
Worsening of CT findings

Question 7

Sub-types of patients (in terms of prognosis) with Idiopathic Pulmonary Fibrosis

Answer 7

3 groups

1. Rapidly progress and die within 2 years of dx
2. Stable, only exacerbations take away further lung function, but it is not recovered
3. Slow progressive type, also lose lung function to exacerbations

Question 8

Pulmonary HTN patients who meet criteria for lung transplant - criteria?

Answer 8

Idiopathic pulm HTN
Pulmonary veno-occlusive disease
Pulmonary haemangiomatomata
Congenital heart disease with Eisenmenger syndrome
NB: patients with HTN 2 to valvular heart disease or LV failure typically do not undergo lung transplantation

Question 9

Risk stratification groups in patients with pulm HTN

Answer 9

4 risk groups

1. Low
2. Intermediate low
3. Intermediate high
4. High

Risk assessment tools e.g. French Method, COMPERA method, REVEAL score - involving parameters such as NYHA, 6MWD, RAP, Cardiac index) - allows us to stratify into above groups

NB: High risk patients more likely to get CLAD (chronic lung allograft dysfunction) - as per French method (and is suggested by the other methods)

Question 10

Disease specific evaluation for ILD - what are some factors to pay special attention to?

Answer 10

Presence of GORD post lung transplant (as can occur in scleroderma patients) is associated with higher risk of graft dysfunction

Telomere-associated ILD (can have bone marrow i.e. haematological, liver, renal involvement - may be less tolerant of cell cycle inhibitors or trt with valganciclovir for CMV prophylaxis - so v important not to have CMV mismatch for these patients!)

Connective tissue

Age

Frailty

Question 11

Why is it important to identify ‘high risk’ patients?

Answer 11

• More likely to die on the transplant wait list
• Higher risk of complications post transplant

Question 12

Absolute contraindications to lung transplant?

Answer 12

• Recent history of malignancy (cancer free survival > 5 yrs acceptable, low Gleason score prostate ca an be dealt with post transplant)
• Certain infections e.g. Burkholderia cepacia (CF patients)
• Untreatable significant dysfunction of another organ i.e. heart (IHD), liver, kidney (unless combined transplant being considered)
• Uncorrectable bleeding diathesis
• Significant chest wall or spinal deformity)

Question 13

Difficult contraindications to lung transplant

Answer 13

• Mental health
• Psychosocial factors
• Substance abuse/dependence (ex-smoker 6 months minimum)
• Lack of support

Need to be able to cope with the lifestyle required post lung tx (regimented medication adherence, being invested in your health)

Question 14

Relative contraindications to lung transplant

Answer 14

• BMI > 30
• Infection with TB, NTM - need to complete trt first!
• Lack of rehab efforts
• Age > 65
• Acute medical deterioration
• Previous thoracic surgery

Question 15

Types of lung transplantation

Answer 15

• Single lung (advantage for difficult to find donors, restrictive lung disease, disadvantage native lung still source of infection/malignancy so overall mortality is higher for single lung transplants)
• Bilateral sequential Single Lung (‘double lung transplant’ - indicates the site of anastomosis is at main bronchus c.f. for single lung tx where site of anastomosis is trachea - the main bronchus is associated with better perfusion and less complications c.f. anastomosis at site of trachea)
• Heart lung transplants (now almost exclusively performed in patients with congenital heart disease and Eisenmenger Syndrome, though in the past was also used for those with pulm HTN but we now know that if the lung is replaced in someone with pulm HTN the R heart eventually recovers on its own)
• Heart, lung, liver - Cystic fibrosis, alpha 1 antitrypsin def

Question 16

Donor organ allocation for lung transplant?

Answer 16

Based on
- Location - exclusively offered in Melboure, locals prioritised
- Blood group
- Size
- Presence of preformed HLA antibodies (e.g. from previous blood transfusions, pregnancy)

NB: Australia does not have national Lung Allocation Score so individual states have priority lists
Urgent national list requires Australia wide approval

Question 17

What are the complications post lung transplant?

Answer 17

Hyperacute:
Donor-recipient mismatch - hardly occurs anymore

Early:
Bleeding
Primary graft dysfunction (hypoxia, Xray changes and ventilator-dependence -more likely if recipient had pulm HTN with RV failure, if long ischaemic time of donor organ - often need ECMO for several days before organ recovers)
Pleural and other surgical complications
AKI

Intermediate:
Acute cellular rejection (T cell med)
Acute antibody mediated rejection
Airway complications (dehiscence of anastomosis, stenosis of anastamosis e.g. if on ECMO, blood flow away from pulm vessels ischaemic injury leads to stenosis )
Vascular - pulmonary vein stenosis
PE
Infections
Metabolic

Late:
Chronic lung allograft dysfunction e.g. Bronchiolitis obliterans, restrictive allograft syndrome
Post-transplant lymphoproliferative disease PTLD - if donor has EBV and recipient is EBV naive
Primary disease recurrence (rare)
HTN
Renal impairment (calcineurin inhibitor toxicity e.g. cyclosporin, tacrolimus
Post transplantation diabetes common

Question 18

What is bronchiolitis obliterans syndrome? “popcorn lung”

Answer 18

Irreversible loss of lung function following lung transplantation - occurs in ~50% of patients by 5 yrs following lung tx

Question 19

What is the 5 year survival post lung tx?

Answer 19

Currently sits ~70% worldwide