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      Drugs & Diseases > Clinical Procedures

      Lung Transplantation Guidelines

      Updated: Apr 08, 2022
      • Author: Bryan A Whitson, MD, PhD; Chief Editor: Mary C Mancini, MD, PhD, MMM  more...
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      Guidelines

      Guidelines Summary

      Selection of Lung Transplantation Candidates

      In 2014, the International Society for Heart and Lung Transplantation (ISHLT) released an updated consensus opinion regarding the appropriate timing of referral and listing of candidates for lung transplantation. The statement concluded that lung transplantation should be considered for adults with chronic, end-stage lung disease who meet all the following general criteria [16] :

      • High (>50%) risk of death from lung disease within 2 years if lung transplantation is not performed.

      • High (>80%) likelihood of surviving at least 90 days after lung transplantation.

      • High (>80%) likelihood of 5-year post-transplant survival from a general medical perspective provided that there is adequate graft function.

      Absolute contraindication include [16] :

      • Malignancy in the last 2 years, with the exception of non-melanoma localized skin cancer that has been treated appropriately (a 5-y disease-free interval is prudent)

      • Untreatable advanced dysfunction of another major organ system unless combined organ transplantation can be performed

      • Atherosclerotic disease with suspected or confirmed end-organ ischemia or dysfunction and/or coronary artery disease not amenable to revascularization.

      • Acute medical instability such as acute sepsis, myocardial infarction, and liver failure.

      • Uncorrectable bleeding diathesis.

      • Chronic infection with highly virulent and/or resistant microbes that are poorly controlled pre-transplant.

      • Active Mycobacterium tuberculosis infection.

      • Significant chest wall or spinal deformity expected to cause severe restriction after transplantation.

      • Obesity (body mass index ≥35.0 kg/m2).

      • History of repeated or prolonged episodes of non-adherence to medical therapy that are perceived to increase the risk of non-adherence after transplantation.

      • Psychiatric conditions associated with the inability to cooperate with the medical/allied health care team and/or adhere with complex medical therapy.

      • Absence of an adequate or reliable social support system.

      • Severely limited functional status with poor rehabilitation potential.

      • Substance abuse or dependence. Meaningful and/or long-term participation in therapy should be required before offering lung transplantation. Serial blood and urine testing can be used to verify abstinence from substances that are of concern.

      Relative contraindications include:

      • Adults >75 years old are unlikely to be candidates for lung transplantation in most cases. Although age by itself should not be considered a contraindication to transplant, increasing age generally is associated with comorbid conditions that are either absolute or relative contraindications.

      • Obesity (BMI 30.0–34.9 kg/m2)

      • Progressive or severe malnutrition.

      • Severe, symptomatic osteoporosis.

      • Prior chest surgery with lung resection.

      • Mechanical ventilation and/or extracorporeal life support (ECLS). 

      • Infection with highly resistant or virulent bacteria, fungi, and certain strains of mycobacteria (e.g., chronic extrapulmonary infection expected to worsen after transplantation).

      • Patients with atherosclerotic disease at risk for end-organ disease after lung transplantation; with regard to coronary artery disease, some patients will be candidates for percutaneous coronary intervention or coronary artery bypass graft (CABG) preoperatively or, in some instances, combined lung transplant and CABG. 

      • Lung transplantation can be considered in patients infected with hepatitis B and/or C who are stable on appropriate therapy without significant clinical, radiologic, or biochemical signs of cirrhosis or portal hypertension. Lung transplantation in candidates with hepatitis B and/or C should be performed in centers with experienced hepatology units.

      • Lung transplantation can be considered in HIV-positive patients with undetectable HIV-RNA, and compliant on combined anti-retroviral therapy. The most suitable candidates should have no current acquired immunodeficiency syndrome–defining illness. Lung transplantation in HIV-positive candidates should be performed in centers with expertise in the care of HIV-positive patients.

      • Lung transplantation can be considered in patients infected with Burkholderia cenocepacia, Burkholderia gladioli, and multi-drug–resistant Mycobacterium abscessus if the infection is sufficiently treated preoperatively and there is a reasonable expectation for adequate control postoperatively. To be considered suitable transplant candidates, these patients should be evaluated by centers with significant experience managing these infections in the transplant setting, and patients should be made aware of the increased risk of transplant because of these infections.

      • Other medical conditions that have not resulted in end-stage organ damage, such as diabetes mellitus, systemic hypertension, epilepsy, central venous obstruction, peptic ulcer disease, or gastroesophageal reflux, should be optimally treated before transplantation.

      Next:

      Disease-specific Candidate Selection

      The International Society for Heart and Lung Transplantation consensus opinion includes recommendations for the timing of referral and of listing for lung transplantation by specific diseases as summarized below. [16]

      COPD

      Timing of referral:

      • Disease is progressive, despite treatment including medication, pulmonary rehabilitation, and oxygen therapy.

      • Patient is not a candidate for endoscopic or surgical LVRS. Simultaneous referral of patients with COPD for both lung transplant and LVRS evaluation is appropriate.

      • BODE index >5

      • Paco2 >50 mm Hg and/or Pao2 < 60 mm Hg 

      • FEV1 < 25% predicted.

      Timing of listing (presence of one criterion is sufficient):

      • BODE index ≥7.

      • FEV1 < 15% to 20% predicted.

      • Three or more severe exacerbations during the preceding year.

      • One severe exacerbation with acute hypercapnic respiratory failure.

      • Moderate to severe pulmonary hypertension.

      Interstitial lung disease

      Timing of referral:

      • Evidence of usual interstitial pneumonitis (UIP) or fibrosing non-specific interstitial pneumonitis (NSIP), regardless of lung function.

      • FVC < 80% predicted or DLCO < 40% predicted.

      • Any dyspnea or functional limitation attributable to lung disease.

      • Any oxygen requirement, even if only during exertion.

      • For inflammatory interstitial lung disease (ILD), failure to improve dyspnea, oxygen requirement, and/or lung function after a clinically indicated trial of medical therapy.

      Timing of listing:

      • Decline in FVC ≥10% during 6 months of follow-up 

      • Decline in DLCO ≥15% during 6 months of follow-up.

      • Desaturation to < 88% or distance < 250 m on 6-minute-walk test or >50 m decline in 6-minute-walk distance over a 6-month period.

      • Pulmonary hypertension on right heart catheterization or 2-dimensional echocardiography.

      • Hospitalization because of respiratory decline, pneumothorax, or acute exacerbation.

      Cystic fibrosis

      Timing of referral:

      • FEV1 that has fallen to 30% or a patient with advanced disease with a rapidly falling FEV1 

      • A 6-minute walk distance < 400 m.

      • Development of pulmonary hypertension in the absence of a hypoxic exacerbation (as defined by PAP >35 mm Hg on echocardiography or mean PAP >25 mm Hg measured by right heart catheterization).

      • Clinical decline characterized by increasing frequency of exacerbations associated with any of the following:

        • An episode of acute respiratory failure requiring non-invasive ventilation.

        • Increasing antibiotic resistance and poor clinical recovery from exacerbations.

        • Worsening nutritional status despite supplementation.

        • Pneumothorax.

        • Life-threatening hemoptysis despite bronchial embolization.

      Timing of listing:

      • Chronic respiratory failure.

        • With hypoxia alone (PaO2< 60 mm Hg).

        • With hypercapnia (PaCO2  >50 mm Hg).

      • Long-term non-invasive ventilation therapy

      • Pulmonary hypertension

      • Frequent hospitalization

      • Rapid lung function decline

      • World Health Organization Functional Class IV

      Pulmonary vascular diseases

      Timing of referral:

      • NYHA Functional Class III or IV symptoms during escalating therapy

      • Rapidly progressive disease (assuming weight and rehabilitation concerns not present)

      • Use of parenteral targeted pulmonary arterial hypertension (PAH) therapy regardless of symptoms or NYHA Functional Class

      • Known or suspected pulmonary veno-occlusive disease (PVOD) or pulmonary capillary hemangiomatosis

      Timing of transplant listing:

      • NYHA Functional Class III or IV despite a trial of at least 3 months of combination therapy including prostanoids

      • Cardiac index < 2 liters/min/m2

      • Mean right atrial pressure >15 mm Hg

      • 6-minute walk test < 350 m

      • Development of significant hemoptysis, pericardial effusion, or signs of progressive right heart failure 

       

      Previous
      Next:

      Antibody-mediated Rejection of the Lung

      In 2016, the International Society for Heart and Lung Transplantation (ISHLT) published a consensus opinion of the definition and diagnostic criteria for pulmonary antibody-mediated rejection (AMR). AMR as categorized as either clinical or subclinical with the following definitions [56] :

      Clinical AMR : 

      "The presence of allograft dysfunction (defined as alterations in pulmonary physiology, gas exchange properties, radiologic features or deteriorating functional performance) associated with AMR. Clinical AMR may be asymptomatic, such as a small but significant change in pulmonary physiology."

      Sub-clinical AMR: 

      "Histologic criteria of AMR detected on surveillance transbronchial biopsies (with or without C4d and with or without the presence of DSA) in the absence of allograft dysfunction."

      Clinical AMR is further categorized by ISHLT as definite, probable and possible based on the degree of certainty of the presence or absence of a number of pathologic, serologic, clinical and immunologic criteria that include [56] :

      • Presence of donor-specific anti–human leukocyte antigen antibodies (DSA)
      • Characteristic lung histology
      • Evidence of complement 4d (C4d) within the graft.

      Exclusion of other causes of allograft dysfunction increases confidence in the diagnosis but is not essential. 

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