Lung transplantation for interstitial lung disease

Siddhartha G. Kapnadak; Ganesh Raghu

doi:10.1183/16000617.0017-2021

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FIGURE 1
Suggested approach for management of progressive interstitial lung disease (ILD) a) before and b) after lung transplantation (LTx). HRCT: high-resolution computed tomography; CTD: connective tissue disease; GOR: gastro-oesophageal reflux; DLTx: double lung transplantation; SLTx: single lung transplantation; CLAD: chronic lung allograft dysfunction; MDS: myelodysplastic syndrome; EBV: Epstein–Barr virus. ^#: ILD care should preferably be undertaken by experts in ILD in an experienced centre.
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FIGURE 2
Examples of post-transplant complications in the native fibrotic lung after single lung transplantation (SLTx). a) Images from a 57-year-old male 12 years after left SLTx for familial idiopathic pulmonary fibrosis; i) demonstrates a mycetoma in the native right upper lobe on axial computed tomography images. Bronchoalveolar lavage cultures from the (native) right upper lobe as well as from the (allograft) left upper lobe grew Aspergillus fumigatus. He was treated with prolonged voriconazole, but surveillance imaging showed increasing size of the mycetoma at ii) 13 and iii) 14 years post-transplant, with iv) sagittal imaging also demonstrating several new, smaller mycetomas. b) Images from a 62-year-old male 21 months after left SLTx for rheumatoid arthritis-associated interstitial lung disease. On axial computed tomography, i) demonstrates a small nodule versus focus of scarring superimposed upon underlying fibrosis in the native lung (arrow). ii, iii) Surveillance imaging demonstrated evolution into a clear nodule which increased in size over 5 months (arrows). iv) Positron emission tomography (sagittal image) confirmed a hypermetabolic right upper lobe nodule, along with multiple hypermetabolic lesions in the liver consistent with metastases. Percutaneous biopsy of the lung nodule confirmed adenocarcinoma. The patient died at 29 months post-transplant due to complications from brain metastases.

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TABLE 1

Criteria for referral and listing for lung transplantation in patients with interstitial lung disease (ILD)

Timing of referral^#	Timing of listing
Histopathological UIP	Hospitalisation for respiratory decline, pneumothorax or acute exacerbation
Radiographic probable or definite UIP pattern	Desaturation to <88% on 6MWT or >50 m decline in 6MWD over 6 months
FVC <80% or D_LCO <40% pred	Pulmonary hypertension on right heart catheterisation or echocardiography
Relative decline in pulmonary function over the past 2 years: FVC ≥10% or D_LCO ≥15% or FVC ≥5% with symptomatic or radiographic progression	Absolute decline in pulmonary function over the past 6 months despite appropriate treatment: FVC >10% or D_LCO >10% or FVC >5% with radiographic progression
Any resting or exertional oxygen requirement
For inflammatory ILDs, disease progression despite treatment

Referral or listing should be considered if meeting any one criterion. UIP: usual interstitial pneumonia; FVC: forced vital capacity; D_LCO: diffusing capacity of the lung for carbon monoxide; 6MWT: 6-min walk test; 6MWD: 6-min walk distance. ^#: earlier referral is recommended for patients with connective tissue disease or familial idiopathic pulmonary fibrosis to address potential extrapulmonary manifestations. Reproduced and modified from [13] with permission.

TABLE 2

Risk factors for adverse post-transplant outcomes in candidates for lung transplantation

General	High or substantially increased risk	Absolute contraindications
Age 65–70 years GFR 40–60 mL·min⁻¹·1.73 m⁻² CAD including prior CABG LV ejection fraction 40–50% Peripheral vascular disease Connective tissue disease Severe GOR Oesophageal dysmotility Bone marrow dysfunction Osteoporosis BMI 30–34.9 kg·m⁻² BMI 16–17 kg·m⁻² Frailty Hypoalbuminaemia Poorly controlled diabetes Edible marijuana Scedosporium apiospermum infection HIV with undetectable viral load Previous thoracic surgery including pleurodesis Mechanical ventilation Re-transplantation	Age >70 years Severe CAD requiring CABG at transplant LV ejection fraction <40% Significant cerebrovascular disease Severe oesophageal dysmotility Untreatable haematological disorders (bleeding diathesis, thrombophilia, severe bone marrow dysfunction) BMI ≥35 kg·m⁻² BMI <16 kg·m⁻² Limited functional status with poor rehabilitation potential Psychiatric, psychological or cognitive conditions with potential to interfere with medical adherence Unreliable support system Lack of understanding of disease and/or transplant despite teaching Mycobacterium abscessus infection Lomentospora prolificans infection Burkholderia cenocepacia or gladioli infection Hepatitis B or C infection with detectable viral load and liver fibrosis Chest wall or spinal deformity expected to cause restriction after transplant Extracorporeal life support Re-transplantation for restrictive CLAD, antibody-mediated rejection or within 1 year following initial lung transplant	Lack of patient willingness or acceptance of transplant Malignancy with high risk of death or recurrence GFR <40 mL·min⁻¹·1.73 m⁻² unless being considered for multi-organ transplant Acute coronary syndrome within 30 days (excluding demand ischaemia) Stroke within 30 days Liver cirrhosis with portal hypertension or synthetic dysfunction unless being considered for multi-organ transplant Acute liver failure Acute renal failure with rising creatinine or on dialysis and low likelihood of recovery Active extrapulmonary infection including septic shock Active tuberculosis infection HIV infection with detectable viral load Severely limited functional status with poor rehabilitation potential Progressive cognitive impairment Repeated episodes of nonadherence without evidence of improvement Active substance use or dependence including current tobacco use, vaping, marijuana smoking or intravenous drug use Other severe uncontrolled medical condition expected to limit survival after transplant

GFR: glomerular filtration rate; CAD: coronary artery disease; CABG: coronary artery bypass grafting; LV: left ventricular; GOR: gastro-oesophageal reflux; BMI: body mass index; CLAD: chronic lung allograft dysfunction. Reproduced and modified from [13] with permission.

TABLE 3

Common risk factors for adverse post-lung transplant outcomes in candidates with interstitial lung disease

Advanced age

Overweight status

Telomere biology disorders

Prior thoracic surgery

Limited functional status, deconditioning, frailty

Gastro-oesophageal reflux

High-risk atherosclerotic disease

Connective tissue disease manifestations

Corticosteroids, other immunosuppressants

Acute exacerbations

Active mechanical ventilation

TABLE 4

Morbidity rates in survivors at 5 years after lung transplantation for interstitial lung disease

	Idiopathic interstitial pneumonia % of survivors with listed diagnosis	Other interstitial lung diseases % of survivors with listed diagnosis
Hypertension	79.5	80.0
Creatinine >2.5 mg·dL⁻¹	35.8	34.4
Chronic dialysis or renal transplant	2.7	2.7
Hyperlipidaemia	63.4	57.1
Diabetes	37.7	33.2