Lung Transplantation Flashcards
(8 cards)
What is the long-term survival in lung transplantation?
Double lung – 7-8 years
Single lung – 5 years
What are the indications (general and disease specific) for lung transplantation?
Overall
* Progressive and advanced
* Deteriorating despite maximal therapy
* Poor QOL and/or 2 year mortality >50%
* No significant untreatable cardiac/hepatic/renal disease
* Completed pulmonary rehab
COPD and other Obstructive disease – any of:-
* FEV1 <20% and
- TLCO <20% or
- Homogenous emphysema distribution
* Hospitalisation for exacerbation with acute hypercapnia (>6.5) and worsening hypoxia
* PHT or cor pulmonale
* HODE score >7
IPF – any of:-
* TLCO <40% with clinical deterioration
* Fall in TLCO ≥15% over 6 months
* Fall in FVC ≥10% over 6 months
* Desaturation <88% on 6MWT
* Acute, rapid deterioration preceding diagnosis
CF and Bronchiectasis – any of:-
* FEV1 ≤30% or FEV1 >30% with rapid progressive deterioration (rapid fall in FEV1, increasing exacerbation frequency)
* History of ICU/HDU admission for exacerbation
* Oxygen dependent respiratory failure, hypercapnia or pulmonary hypertension
* Severe haemoptysis despite embolization
* Pneumothorax with advanced disease
* Young (<20) men with rapid deterioration
PAH – any of:-
* WHO functional class III or IV despite 3 months parenteral therapy
* Worsening right heart failure with increasing fluid retention despite medial therapy
* Declining 6MWT to <350m despite medical therapy
* Need for continuous IV inotropic support
* mRAP >15 and CI <2 on RH catheter despite optimal therapy
What are the contraindications for lung transplantation?
Absolute
* Severe and untreatable extrapulmonary organ dysfunction
* Solid organ or haematological malignancy within 5 years of listing (excluding SCC or BCC)
* Unstable critical condition (sepsis, shock)
* Uncontrolled extrapulmonary manifestation of systemic disease
* Severe untreatable psychiatric illness
* BMI >35
* Active or recent (6 months) substance addiction (cigarette smokers, alcohol abuse illicit drugs)
* Significant chest wall or spinal deformity
* Non-adherence with treatment or OP follow-up
* Lack of social support sufficient to compromise post-transplant outcomes
Relative
* Age >60
* Poorly controlled chronic medical condition associated with end-organ damage (HTN, DM, CAD, CKD with eGFR <50
* Severe or symptomatic osteoporosis
* BMI >30
* BMI <17
* Poor rehab potential (sarcopenia, frailty)
* Mechanical ventilation (excluding NIV)
* Chronic high dose oral prednisolone (>15mg/day)
* Extensive pleural thickening
* Colonization (highly resistant pathogens or Burkholderia cenocepacia)
* Previous (cleared) infection with M. Abscessus
* Aspergilloma with extensive cavitation
* Chronic extrapulmonary infection (HIV, HBV, HCV)
What are the essential pre-operative investigations for lung transplantation?
- Thoracic Imaging
- HRCT
- Cardiac
- ECG
- ECHO
- Microbiology
- Sputum microbiology
- Blood
- Blood group
- LFTs
- Serology
- HIV
- CMV
- HBV
- HCV
- Physiological
- 6MWT
- Other
- 24hr Cr clearance
What immunosuppression is used post-lung transplant?
Tripple immunosuppression with:-
* Steroids (prednisolone)
* Cell cycle inhibitor (MMF or Azathioprine
* Calcineurin Inhibitor (ciclosporin or tacrolimus)
- Mechanism: blocks T-cell proliferation
- Side-effects: renal failure, PRES
What are the important post-operative investigations post-transplant?
- Bronchoscopy with BAL and biopsy (pre-discharge)
- Spirometry
- Usually stable from 3 months post-transplant
- Sustained falls ≥10-15% are concerning
What are the early post-lung transplant complications?
Primary Graft Dysfunction
* Timing: within 72hrs of transplant
* Cause: preservation and ischaemia-reperfusion injury
* Features: pulmonary infiltrates, hypoxaemia, diffuse alveolar damage, organising pneumonia on biopsy
* Diagnosis: exclude other causes (overload, pneumonia, hyperacute rejection, aspiration, anastomotic occlusion)
* Management: supportive
* Prognosis: poor, high mortality (40-60%
Acute Cellular Rejection
* Timing: within 3 months of transplant
* Cause: T-cells reacting to donor HLA and other antigens
* Features:-
- Common (60%)
- Symptoms: often asymptomatic, malaise, fever, dyspnoea, cough, hypoxia. Similar presentation to pneumonia or COP
- Radiology: CXR – normal, non-specific infiltrates
- Spirometry: fall >10%
- Recurrent rejection -> risk factor for BOS
* Diagnosis: ideally TBB for histology (perivascular lymphocytic infiltrates)
* Management
- IV methylprednisolone pulsing for 3/12
- Then high-dose prednisolone
- Plasmapheresis if no response
Airway Complications
* Anastomotic stenosis
- Timing: Weeks-months post-transplant
- Features: wheeze, recurrent pneumonia, suboptimal lung function
- Management: balloon dilatation or endobronchial stent
* Dehiscence of bronchial anastomosis
- Complete – rare, requires immediate surgery/re-transplantation
- Partial – managed conservatively, drain pneumothorax, reduce steroid dose
Infection
* Bacterial
- Timing: early (first month) or late (associated with BOS)
- Microbiology: typically gram-negative organisms, especially P. Aeruginosa
- Continue immunosuppression
* CMV
- High risk: seronegative recipients from seropositive donors
Risk of pneumonitis -> valganciclovir
- Risk factor for BOS and bacterial/fungal superinfection
* Aspergillus
- Frequent coloniser post-transplant, clinical infection is rare
- Timing of infection: 2 months post-transplant
- Treatment: itraconazole or voriconazole or amphotericin B
Drug-Related Complications
* Typical drugs – ciclosporin, tacrolimus, azathioprine, MMF, prednisolone
* Problems – interactions, and side-effects, nephrotoxicity, osteoporosis
Non-Pulmonary Complications
* VTE
* Arrhythmias
* Hyperammonaemia (rare, serious early complication)
* HTN
* Renal failure
* Hyperlipidaemia
* DM
* Stroke
* IHD
What are the late lung transplant complications?
Chronic Lung Allograft Dysfunction (CLAD) – 2 main types:-
* Bronchiolitis Obliterans Syndrome (BOS)
- Timing: increasing prevalence over time, rare in first 6 months
- Cause: unclear, likely immune mediated injury following trigger
- Risk factors: previous episodes of recurrent rejection, infection (CMV, aspergillus, pseudomonas), anti-HLA antibodies pre-transplant, GORD, non-compliance)
- Features:-
Persistent and progressive FEV1 decline in absence of other causes
Insidious onset dyspnoea and cough
CXR – nil
HRCT – expiratory air trapping and peripheral bronchiectasis
- Diagnosis
Histology – small airway fibroproliferation, associated pulmonary vascular atherosclerosis – TBBs low sensitivity
Clinical if absence of histology - unexplained + sustained (>3 weeks) fall in FEV 80% peak value post-transplant
- Management – challenging, aim is to stabilise or reduce rate of progression
Modify immunosuppression
Investigate for infection – treat aggressively
Azithromycin helps
- Prognosis: poor
* Restrictive Allograft Syndrome (RAS)
- Features:-
Restrictive spirometry
Allograft upper lob fibrosis
- Prognosis: very poor
Malignancy
* Increased risk of certain malignancies
- Lymphoma
- Other EBV-PTLDs (post-transplant related diseases – carcinomas (lip, skin, vulval), Kaposi’s Sarcoma
* Timing
- Most lymphomas within 1st year – site lung allograft most common
- Later presentations – usually disseminated
* Management:-
- At transplant centre (not local haematologists)
- Involves:-
Reducing immunosuppression
Antivirals and/or rituximab
Recurrence of Primary Disease
