Lung Transplant

History

  • First Lung Transplant: first performed in 1963

Indications


Contraindications

  • xxx

Ex Vivo Lung Perfusion (EVLP) for High-Risk Donor Lungs

  • Background: >80% of lungs are potentially injured (and considered not suitable for transplantation)
  • Technique: normothermic lung perfusion of high-risk lungs in ex vivo circuit -> allows assessment of function prior to transplantation
  • Clinical Efficacy: transplantation of high-risk donor lungs which were physiologically stable during 4 hrs of ex vivo perfusion led to similar results to those obtained with conventionally-selected lungs [MEDLINE]
    • Rate of primary graft dysfunction at 72 hrs after transplantation was not increased

Complications

Airway Anastomotic Complications

Vascular Anastomotic Complications

  • Pulmonary Artery Kinking
  • Pulmonary Artery Stenosis
  • Pulmonary Vein Thrombosis

Phrenic Nerve Injury/Diaphragmatic Dysfunction

Pleural Complications

Creation of “Buffalo Chest” (Pleuro-Pleural Communication) (see Buffalo Chest, [[Buffalo Chest]])

  • Epidemiology: the term “buffalo chest” originates from the American bison (buffalo), one of the few mammals which normally has bilaterally-interconnected pleural spaces
    • This anatomic feature of the buffalo made it easier for Great Plains American Indians to kill the buffalo with a single arrow shot to the thorax (which resulted in bilateral pneumothorax and rapid death of the animal)
  • Etiology: occurs following lung transplant, major invasive thoracic procedures (mediastinal surgery), etc
  • Physiology: pleuro-pleural communication
  • Clinical: increases the risk of bilateral pneumothorax (see Pneumothorax, [[Pneumothorax]])

Infection

  • General Comments
    • xxx
  • Pseudomonas Aeruginosa (see Pseudomonas Aeruginosa, [[Pseudomonas Aeruginosa]])
    • xxx
  • Other Bacteria
  • Cytomegalovirus (CMV) (see Cytomegalovirus, [[Cytomegalovirus]])
    • CMV has historically been the most common viral pathogen in lung transplant recipients: incidence has considerably decreased with the use of CMV prophylaxis
  • Aspergillus (see Aspergillus, [[Aspergillus]]):
    • Tracheobronchial Aspergillosis
    • Invasive Aspergillosis

Malignancy

Lung Cancer (see Lung Cancer, [[Lung Cancer]])

  • xxx

Post-Transplant Lymphoproliferative Disorder (PTLD)

  • xxx

Native Lung Hyperinflation

  • xxxx

Venous Thromboembolism

Lung Transplant Rejection/Dysfunction (Lung Transplant Rejection, [[Lung Transplant Rejection]])

Primary Lung Graft Dysfunction (Ischemia-Reperfusion Lung Injury, Early Graft Dysfunction, Pulmonary Reimplantation Response, Pulmonary Reimplantation Pulmonary Edema) (see Primary Lung Graft Dysfunction, [[Primary Lung Graft Dysfunction]])

  • Onset: within 72 hrs
  • Physiology
    • Pre-Transplant Factors
    • Retrieval/Cold Storage of the Graft
    • Ischemic-Reperfusion Lung Injury
    • Post-Transplant Factors
  • Clinical
    • Clinical Grading System (Most Commonly Applied to Bilateral Lung Transplants): calculated on arrival to ICU after transplant and at 24/48/72 hrs
      • Grade 0: pO2/FiO2 >300 + normal chest x-ray
      • Grade 1: pO2/FiO2 >300 + diffuse allograft infiltrates on chest x-ray
      • Grade 2: pO2/FiO2 200-300
      • Grade 3: paO2/FiO2 <200
    • Crucial to Exclude Hyperacute Lung Transplant Rejection (see Hyperacute Lung Transplant Rejection, [[Hyperacute Lung Transplant Rejection]])
      • Pre-transplant panel reactive antibody (PRA) testing should be reviewed: risk of antibody mediated rejection increases with increasing PRA levels (especially with PRA levels >10%)
      • Direct cross match between the donor and recipient should also be performed with flow cytometry
    • Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome, [[Acute Respiratory Distress Syndrome]])
      • Decreased Pulmonary Compliance
      • Hypoxemia (see Hypoxemia, [[Hypoxemia]]): due to Intrapulmonary shunt
      • Increased Pulmonary Vascular Resistance (PVR)

Antibody-Mediated (Humoral) Lung Transplant Rejection

  • Hyperacute Lung Transplant Rejection (see Hyperacute Lung Transplant Rejection, [[Hyperacute Lung Transplant Rejection]])
    • Epidemiology: has become a rare type of rejection (due to more sensitive and specific pre-transplant screening for HLA antibodies
    • Onset: min-hours (usually within 24 hrs post-transplant)
    • Physiology: reaction of preformed recipient donor-specific antibodies, usually directed against foreign donor human leukocyte antigens (HLA)
      • Less commonly, antibodies may be directed against donor ABO blood group or endothelial antigens
    • Clinical Manifestations
      • Copious Pink Frothy Pulmonary Edema Fluid
      • Rapid Onset of Severe Hypoxemia/Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome, [[Acute Respiratory Distress Syndrome]])
      • Hypotension (see Hypotension, [[Hypotension]])
    • Prognosis: high mortality rate
  • Acute Antibody-Mediated Lung Transplant Rejection (see Acute Antibody-Mediated Lung Transplant Rejection, [[Acute Antibody-Mediated Lung Transplant Rejection]])
    • Epidemiology: occurs in approximately 4% of lung transplants (although exact diagnostic criteria have not been firmly established)
    • Onset: weeks-months
      • Median: 258 days post-transplant
      • Range: 1 week to >1 year (the majority of cases are diagnosed between 1-12 mo, although some cases have been reported years after transplant)
    • Physiology: reaction of recipient preformed donor-specific antibodies against foreign donor human leukocyte antigens (HLA)
      • Believed to be due to antibodies that were present at a low titer prior to transplantation or developed after transplantation -> clinical disease develops in the transplanted lung weeks-months after transplant
    • Clinical: acute onset of respiratory symptoms (usually severe enough to require hospitalization)
      • Cough (see Cough, [[Cough]])
      • Dyspnea (see Dyspnea, [[Dyspnea]]): 100% of cases
      • Fever (see Fever, [[Fever]])
      • Hemoptysis (see Hemoptysis, [[Hemoptysis]]): 25% of cases
      • Hypoxemia (see Hypoxemia, [[Hypoxemia]])
      • Respiratory Failure (see Respiratory Failure, [[Respiratory Failure]]): 18% of cases
    • Prognosis: may be fulminant (sometimes fatal)
      • Median Survival After Diagnosis: 593 days
      • Survivors have increased risk of developing chronic lung allograft dysfunction

Acute Lung Transplant Rejection (Acute Cellular Lung Transplant Rejection) (see Acute Lung Transplant Rejection, [[Acute Lung Transplant Rejection]])

  • Epidemiology: acute cellular lung transplant rejection is the predominant type of acute lung transplant rejection
  • Onset: days-months
  • Physiology: T-lymphocyte recognition of foreign donor HLA antigens
  • Diagnosis
    • CXR: alveolar or intrstitial infiltrates, pleural effusion
    • Chest CT: ground-glass infiltrates, alveolar infiltrates, interlobular septal thickening
    • Pulmonary Function Tests (PFT’s): proportional decrease in FEV1 and FVC
    • Trans-Bronchial Biopsy (TBB): high yield
    • Lung Biopsy: peri-vascular lymphocytic infiltrates
  • Clinical Manifestations
  • Treatment
  • Prognosis: favorable response to treatment

Chronic Lung Transplant Rejection (Bronchiolitis Obliterans Syndrome) (see Chronic Lung Transplant Rejection, [[Chronic Lung Transplant Rejection]])

  • Onset: beyond first year
  • Mechanistic Risk Factors
    • Prior Acute Rejection
    • Lymphocytic Bronchiolitis
    • Respiratory Viruses
    • Primary Graft Dysfunction
    • Silent Aspiration
  • Diagnosis
    • CXR: normal (or may demonstrate hyperinflation)
    • Chest CT: “tree-in-bud” opacities, bronchiectasis, air trapping
    • Pulmonary Function Tests (PFT’s): disproportionate decrease in FEV1 with worsening osbtruction
    • Trans-Bronchial Biopsy (TBB): low yield
    • Lung Biopsy: bronchiolar submucosal inflammation and fibrosis, luminal obliteration
  • Clinical Manifestations
    • Chronic Cough (see Cough, [[Cough]])
    • Dyspnea (see Dyspnea, [[Dyspnea]])
    • Recurrent Bouts of Purulent Bronchitis (see Acute Bronchitis, [[Acute Bronchitis]])
  • Treatment: uncertain
    • Azithromycin (Zithromax) (see Azithromycin, [[Azithromycin]])
  • Prognosis: poor response to treatment -> results in progressive allograft dysfunction

Restrictive Allograft Syndrome

  • Epidemiology: not universally-accepted in the transplant community as a distinct entity
  • Clinical
    • Restrictive Pulmonary Function Tests (PFT’s) (see Pulmonary Function Tests, [[Pulmonary Function Tests]])
    • Upper Lobe- Predominant Fibrotic Changes

Recurrence of Primary Disease in Lung Allograft


References

  • Images in Clinical Medicine: “Buffalo Chest”. N Engl J Med 2003; 349:1829; November 6, 2003; DOI: 10.1056/NEJMicm010281
  • Case of the month: Buffalo chest: a case of bilateral pneumothoraces due to pleuropleural communication. Emerg Med J. 2006 Jun; 23(6): 483–486 [MEDLINE]
  • Normothermic ex vivo lung perfusion in clinical lung transplantation. N Engl J Med 2011;364:1431-1440 [MEDLINE]