Lung Transplant – MD Nexus

History

First Lung Transplant: first performed in 1963

Indications

Chronic Obstructive Pulmonary Disease (COPD) (see Chronic Obstructive Pulmonary Disease, [[Chronic Obstructive Pulmonary Disease]])
- Alpha-1 Antitrypsin Deficiency (A1AT Deficiency) (see Alpha-1 Antitrypsin Deficiency, [[Alpha-1 Antitrypsin Deficiency]])
Cystic Fibrosis (CF) (see Cystic Fibrosis, [[Cystic Fibrosis]])
Idiopathic Pulmonary Arterial Hypertension (IPAH) (see Idiopathic Pulmonary Arterial Hypertension, [[Idiopathic Pulmonary Arterial Hypertension]])
Idiopathic Pulmonary Fibrosis (IPF) (see Idiopathic Pulmonary Fibrosis, [[Idiopathic Pulmonary Fibrosis]])
Lymphangioleiomyomatosis (LAM) (see Lymphangioleiomyomatosis, [[Lymphangioleiomyomatosis]])
Pulmonary Veno-Occlusive Disease (see Pulmonary Veno-Occlusive Disease, [[Pulmonary Veno-Occlusive Disease]])
Tuberous Sclerosis (see Tuberous Sclerosis, [[Tuberous Sclerosis]])

Contraindications

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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

Bronchial Anastomotic Stenosis (see Bronchial Stenosis, [[Bronchial Stenosis]])
Tracheobronchomalacia (see Tracheomalacia, [[Tracheomalacia]] and Bronchomalacia, [[Bronchomalacia]])

Vascular Anastomotic Complications

Pulmonary Artery Kinking
Pulmonary Artery Stenosis
Pulmonary Vein Thrombosis

Phrenic Nerve Injury/Diaphragmatic Dysfunction

Unilateral Diaphragmatic Paralysis (see Unilateral Diaphragmatic Paralysis, [[Unilateral Diaphragmatic Paralysis]])

Pleural Complications

Bronchopleural Fistula (see Bronchopleural Fistula, [[Bronchopleural Fistula]])
Chylothorax (see Pleural Effusion-Chylothorax, [[Pleural Effusion-Chylothorax]])
Hemothorax (see Pleural Effusion-Hemothorax, [[Pleural Effusion-Hemothorax]])
Pleural Effusion (see Pleural Effusion-Exudate, [[Pleural Effusion-Exudate]]): pleural effusion is common in the first 2 weeks after lung transplant
- Sampling is not required unless effusion is large or infection is suspected
Pneumothorax (see Pneumothorax, [[Pneumothorax]])

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]])

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Post-Transplant Lymphoproliferative Disorder (PTLD)

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Native Lung Hyperinflation

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Venous Thromboembolism

Acute Pulmonary Embolism (PE) (see Acute Pulmonary Embolism, [[Acute Pulmonary Embolism]])
Deep Venous Thrombosis (DVT) (see Deep Venous Thrombosis, [[Deep Venous Thrombosis]])

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
- Cough (see Cough, [[Cough]])
- Dyspnea (see Dyspnea, [[Dyspnea]])
- Hypoxemia (see Hypoxemia, [[Hypoxemia]])
- Leukocytosis (see Leukocytosis, [[Leukocytosis]])
- Low-Grade Fever (see Fever, [[Fever]])
- Pleural Effusion (see Pleural Effusion-Exudate, [[Pleural Effusion-Exudate]])
- Pulmonary Infiltrates/Pneumonia (see Pneumonia, [[Pneumonia]])
Treatment
- High-Dose Corticosteroids (see Corticosteroids, [[Corticosteroids]])
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

Alpha-1 Antitrypsin Deficiency (see Alpha-1 Antitrypsin Deficiency, [[Alpha-1 Antitrypsin Deficiency]])
Bronchioloalveolar Carcinoma (see Lung Cancer, [[Lung Cancer]])
Desquamative Interstitial Pneumonia (DIP) (see Desquamative Interstitial Pneumonia, [[Desquamative Interstitial Pneumonia]])
Diffuse Panbronchiolitis (see Diffuse Panbronchiolitis, [[Diffuse Panbronchiolitis]])
Hard Metal Pneumoconiosis (see Hard Metal Pneumoconiosis, [[Hard Metal Pneumoconiosis]])
Idiopathic Pulmonary Hemosiderosis (see Idiopathic Pulmonary Hemosiderosis, [[Idiopathic Pulmonary Hemosiderosis]])
Langerhans Cell Histiocytosis (see Langerhans Cell Histiocytosis, [[Langerhans Cell Histiocytosis]])
Lymphangioleiomyomatosis (LAM) (see Lymphangioleiomyomatosis, [[Lymphangioleiomyomatosis]])
Polymyositis-Associated Interstitial Lung Disease (see Polydermatomyositis, [[Polydermatomyositis]])
Pulmonary Alveolar Proteinosis (PAP) (see Pulmonary Alveolar Proteinosis, [[Pulmonary Alveolar Proteinosis]])
Pulmonary Veno-Occlusive Disease (VOD) (see Pulmonary Veno-Occlusive Disease, [[Pulmonary Veno-Occlusive Disease]])
Sarcoidosis (see Sarcoidosis, [[Sarcoidosis]]): high pathologic recurrence rate has been reported
- Usually discovered incidentally when noncaseating granulomas are found on lung biopsy specimens: these pathologic recurrences do not adversely affect outcome

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]