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A. Introductionnavigator

  1. Less than 1000 lung-only transplants are performed in USA annually
  2. Less than 20% of cadavaric lungs are suitable for transplantation
  3. Over 2500 candidates for lung transplants in USA
  4. May be life-saving proceedure for many with endstage lung and heart/lung disease
  5. Different types of operations have been devised for specific indications (see below)
  6. Routine prospective HLA crossmatching is not performed
  7. Donors and recipients are matched on major blood groups and size (sometimes CMV status)
  8. Transplantation of lungs from non-heart-beating donor has been accomplished [3]
  9. Living-lobar lung transplantation has been performed in children awaiting full transplant [2]
  10. Lung is more immunogenic than heart and other organs, increasing rejection risks

B. Indicationsnavigator

  1. Endstage Lung disease of many causes where no alternatives are available
  2. For patients with a high risk of death within 2-3 years
  3. Chronic Obstructive Pulmonary Disease (COPD)
    1. FEV1<25% of predicted after bronchodilator
    2. Clinically significant hypoxemia or hypercapnia
    3. Clinically significant pulmonary hypertension (P-HTN)
    4. Rapid decline in lung function
    5. Frequent, severe exacerbations
    6. Bilateral transplant leads to longer survival than single transplant, particular in age <60 [13]
  4. Cystic Fibrosis
    1. FEV1<30% of predicted value OR
    2. Rapidly declining lung functions OR
    3. Frequent severe exacerbations OR
    4. Progressive weight loss
    5. Female sex and age of <18 years with FEV1 >30%
    6. Life expectancy <2 years, poor quality of life, and no contraindications [4]
    7. Transplant is beneficial only in CF patients with life expectancy <30% at 5 years based on new prediction measure [5]
    8. However, it is not clear that lung transplant improves survival in CF [6]
    9. Second most common indication for transplantation
  5. Primary Pulmonary Hypertension
    1. NHYA functional Class III or IV
    2. Mean pulmonary-artery pressure >55 mm Hg
    3. Mean right atrial pressure >15 mm Hg
    4. Cardiac index <2 liters/min/m2
    5. Failure of medical therapy (especially IV epoprostenol)
  6. Eisenmenger's Syndrome (NYHA Class III or IV)
  7. Toxic Fume Inhalation with severe lung destruction
  8. Pneumoconiosis
  9. Chemotherapy induced pulmonary failure

C. Absolute Contraindications [1]navigator

  1. Severe extrapulmonary organ dysfunction
    1. Renal insufficiency with creatinine clearance <50mL/min
    2. Hepatic dysfunction with coagulopathy or portal hypertension
    3. Left ventricular dysfunction or severe coronary artery disease
    4. Consider heart-lung transplantation if severe cardiac disease present
  2. Acute, critical illness
  3. Active cancer or recent history of cancer with substantial likelihood of recurrence
  4. Active extrapulmonary infection (chronic hepatitis B or C virus)
  5. Severe psychiatric illness
  6. Non-compliance with therapy
  7. Drug or alcohol dependence or abuse
  8. Active or recent (within 6 months) cigarette smoking
  9. Severe malnutrition (<70% ideal body weight)
  10. Marked obesity (>130% of ideal body weight)
  11. Inability to walk with poor rehabilitation potential

D. Relative Contraindications [1]navigator

  1. Chronic medical conditions poorly controlled or with target organ damage
  2. Daily requirements for >20mg prednisone or equivalent
  3. Mechanical invasive ventilation
  4. Extensive pleural thickening from prior thoracic surgery or infection
  5. Active rheumatologic disease
  6. Preoperative colonization of airways with pan-resistant bacteria (in CF patients)
  7. Presence of Burkholderia cepacia - high risk of perioperative severe infection and death
  8. Presence of aspirgillus is not a risk factor foor poor outcome

E. Transplant Operationsnavigator

  1. Single Lung Transplantation
    1. Most commonly used operation
    2. Not used in cystic fibrosis and bronchiectasis
    3. Is effective in patients with primary P-HTN
    4. Acceptable for emphysema (marginal overdistention of remaining diseased lung)
    5. Permits increase in number of recipients
  2. Bilateral Sequential Transplantation
    1. Bilateral transplantations in single step are not typically performed
    2. Instead, sequential transplants alleviate need for heart-lung bypass
    3. Used for cystic fibrosis and other bronchiectasis
    4. May also be used for primary P-HTN
  3. Heart-Lung Transplantation
    1. Mainly for cases where cardiac function is severely impaired
    2. Also for severe coronary artery disease with lung dysfunction]
    3. Not essential in cases with cor pulmonale, since right ventricular function can return
  4. Lobe Transplantation from Living Donor
    1. Bilateral implantation of lower lobes from living donors
    2. Donors should be larger than recipient
    3. Similar intermediate outcomes to cadavaric lung transplants
    4. Donation of a lobe decreased lung volumes by ~15% without apparent clinical impact

F. Immunosuppression [7] navigator

  1. All patients receive induction immunosuppression with:
    1. Cyclosporine A (CsA) 4mg/kg if creatinine <1.2mg/dL
    2. Azathioprine intravenously or mycophenolate mofetil oral
  2. Lymphocyte ablation is used in some centers
    1. OKT3 mouse anti-human CD3 monoclonal antibody is most commonly used
    2. Anti-thymocyte globulin (ATG) is less commonly used at present
  3. Postoperative
    1. Methylprednisolone 125mg iv every 8 hours x 3 doses
    2. CsA - titrate doses given every 12 hours to trough level 250-300ng/mL
    3. Tacrolimus (FK506) may be substituted for cyclosporine
    4. OKT3 - 2.5-5mg iv each day for first two weeks in some centers
    5. Prednisone - begin after OKT3; 1mg/kg daily for 2 weeks (then maintenance doses)
  4. Maintenance
    1. CsA oral - titrate to trough level 100-125ng/mL after 6-8 weeks or tacrolimus
    2. CsA inhaled (300mg inhaled 3X per week) added to standard maintenance reduced chronic (but not acute) rejection and improved survival [10]
    3. Prednisone - 0.3mg/kg daily for 26 weeks, then 0.2mg/kg daily
    4. Azathioprine - 1-2.5mg/kg daily; decrease for leukocyte count <4K/µL
    5. Mycophenolate (CellCept®) is often used in place of azathioprine
  5. Predicting rejection may be possible by measuring hepatocyte growth factor (HGF) levels [8]

G. Outcomesnavigator

  1. Overall Lung Graft Survival [11]
    1. One Year: 77%
    2. Five Year: 44%
    3. Ten year: 19%
  2. Cystic Fibrosis [4]
    1. One year survival 74%
    2. Five year survival ~33%
    3. Five year survival without transplant ~16%
    4. Overall, lung transplantation reduced risk of death for the entire cohort ~70%
  3. Improvement in quality of life following transplantation in most patients
  4. Acute rejection and infectious complications are major problems
  5. Infections [12]
    1. Likely organism depends primarily on time from transplant
    2. First month: donor infection, pretransplant existing infection, surgical infection
    3. Months 1-6: Epstein-Barr virus (EBV), cytomegovirus (CMV; ~50% of fevers in this period), human herpesvirus 6 (HHV-6), Pneumocystis carinii, Listeria monocytogenes, various fungi
    4. After 6 months: chronic viral infection, opportunistic infections
  6. Xenotransplantation is being investigated due to severe organ shortage

H. Complications navigator

  1. Early Graft Dysfunction
    1. Usually due to operative technical and cardiac complications
    2. Usually occur in first month after transplant
    3. Reperfusion injury may play some role
  2. Infection
    1. Difficult to distinguish from acute rejection episode
    2. Bacterial infections, usually in the lung, are common
    3. Cytomegalovirus (CMV) are a major problem
    4. Epstein-Barr Virus associated lymphoproliferative disorders occur
    5. Aspirgillus may also occur
  3. Acute Rejection
    1. T cell mediated event usually after 1 month and within 3 months of transplant
    2. Symptoms vary, but usually include low grade fever, dyspnea, cough, DOE
    3. Bronchoalveolar lavage (BAL) and lung biopsy are usual diagnostic methods
    4. CD8+ T lymphocytes are most commonly found in acute rejection
    5. Histopathology shows bronchiolitis obliterans (acute and chronic rejection)
    6. Treatment includes pulse methylprednisolone (10mg/kg/day x 3 days)
    7. Maintenance prednisone doses may be increased following acute rejection
    8. OKT3, FK506 (Tacrolimus) and/or methotrexate may also be used
  4. Bronchiolitis Obliterans
    1. Occurs in ~65% of patients surviving more than 5 years
    2. Acute rejection is likely the initiating event
    3. Suspicion in patients with progressive airflow obstruction
    4. Fall in mid-expiratory rates (FEV1-25/75) often precedes fall in FEV1
    5. Highly variable rate of progressive decline
  5. Bronchioloalveolar carcinoma may recur in tranplanted lung [9]

Resources navigator

calcAa Gradient

References navigator

  1. Arcasoy SM and Kotloff RM. 1999. NEJM. 340(14):1081 abstract
  2. Webber SA, McCurry K, Zeevi A. 2006. Lancet. 368(9529):53 abstract
  3. Steen S, Sjoberg T, Pierre L, et al. 2001. Lancet. 357(9259):825 abstract
  4. Aurora P, Whitehead B, Wade A, et al. 1999. Lancet. 354(9190):1591 abstract
  5. Liou TG, Adler FR, Cahill BC, et al. 2001. JAMA. 286(21):2683 abstract
  6. Liou TG, Adler FR, Cox DR, Cahill BC. 2007. NEJM. 357(21):2143 abstract
  7. Halloran PF. 2004. NEJM. 351(26):2715 abstract
  8. Aharinejad S, Taghavi S, Klepetko W, Abraham D. 2004. Lancet. 363(9420):1503 abstract
  9. Garver RI Jr, Zorn GL, Wu X, et al. 1999. NEJM. 340(14):1071 abstract
  10. Iacono AT, Johnson BA, Grgurich WF, et al. 2006. NEJM. 354(2):141 abstract
  11. Sayegh MH and Carpenter CB. 2004. NEJM. 351(26):2761 abstract
  12. Rubin RH, Gilman MD, Kradin RL. 2006. NEJM. 354(2):180 (Case Record) abstract
  13. Thabut G, Christie JD, Ravaud P, et al. 2008. Lancet. 371(9614):744 abstract