LUNG TRANSPLANTATION

ISKANDER AL-GITHMI, M.D., FRCSC, FRCSC (Ts & CDs), FCCP.

Assistant Professor of Surgery

Division of Cardiothoracic Surgery

King Abdulaziz University

History:

First human lung transplantation was performed by Dr. James Hardy in June 1963 at the University of Mississippi.

Between 1963 & 1978, 38 lung transplant were done around the world. Two recipients live longer than one month.

Lung and heart-lung transplantation were introduced into clinical practice in 1981 CSA era.

History (con’t.)

First successful transplantation in the world was done in 1983 at the University of Toronto. J. Cooper

Over 15,000 lung transplantation have now been performed worldwide. (ISHLT) statistics.

What Are Lung Transplantation For?

Indications:Obstructive air way disease (29%)

- COPD- Alpha 1 antitrypsin deficiency

Idiopathic pulmonary fibrosis (19%)Septic pulmonary disease (16%)

- Bronchiectasis- cystic fibrosis

Primary pulmonary hypertension (11%)

Other Varieties (11%)

e.g. - sarcoidosis

- lymphangioliomyomatosis (LAM)

- eosinophilic granuloma

Who are not transplantable?

Contra-indications:

Age > 65 years

Active smoking

Poor compliance with the treatment

Severe active infections (HIV, Hepatitis B & C)

Con’t.

Active malignancy within the past two years.

Drugs or alcohol abuse.

Dysfunction of major other organs

- renal dysfunction

- untreatable CAD or LV dysfunction

- liver dysfunction

Recipient Selective Criteria:

End-stage pulmonary disease with life expectancy < 2 yrs.

Absence of severe extra pulmonary diseases.

Strong motivation towards the idea of lung transplantation.

Severe functional limitation, but potential for rehabilitation.

Excellent psychosocial support.

Donor Selective Criteria:

Age < 65 years

No significant lung diseases

Acceptable CXR

PaO2 > 300mm Hg on F102 1.0 and PEEP 5 cm for 5 min.

Bronchoscopy - clear

Con’t.

Viral studies are negative (HIV and Hepatitis B & C)

Donor – recipient size matching

Medical Conditions – Impact on eligibility for treatment

Symptomatic osteoporosis

Corticosteroid

Nutritional issues

Psychosocial issues

Colonization of air ways with fungi or atypical mycobacteria

Guidelines for Timing Referral

Chronic obstructive pulmonary disease and a1-antitrypsin deficiency amphysema

Postbronchodilator FEV1 < 25% predicted

Resting hypoxia: PaO2 < 55 to 60 mm HgHypercapniaSecondary pulmonary hypertension

Clinical course rapid rate of decline of FEV1 or life-threatening exacerbationsCystic fibrosis

Postbronchodilator FEV1 < 30% predicted

Resting hypoxia: PaO2 < 55 mm HgHypercapniaClinical course: increasing frequency and severity of exacerbations

Idiopathic pulmonary fibrosisVC, TLC < 60-65% predictedResting hypoxiaSecondary pulmonary hypertensionClinical, radiographic, or physiologic progression on medical therapy

Primary pulmonary hypertensionNew York Heart Association functional class III or IVMean right atrial pressure > 10 mm HgMean pulmonary arterial pressure > 50 mm HgCardiac index < 2.5 L/min/m2

•Which transplantation procedure?

Living Donor Lobar Lung Transplantation (LDLT)

- The first living donor lung transplant was reported in 1990. Throughout the world there have been approximately 100 such procedure done to date.

- The outcomes for recipients are similar to those who have received lungs from Cadaveric donors.

- All living donor lung transplantation have been done utilizing a single lower lobe from each donor which account for about 25% of TLC for each.

Recipients Selection for LDLT

- Similar as for cadaveric donors.- All candidates are first assessed and

listed for cadaveric lung transplantation.- Potential recipient must be large

enough to receive the lower lobe of an adult donor – at least the size of an average six year old (90 cm in height).

Selection of Potential Donors

- Age 18 – 60 years- Blood group compatible with recipient- Of sufficient size- Have normal lungs by clinical, radiographic

and physiological assessment.

Con’t.

- No other significant medical illnesses- No history of hepatitis or HIV- Be willing to undergo complete psychological

and psychiatric assessment.- Be willing to undergo complete physical

assessment.

What Are the Benefits of LDLT?

- To reduce the number of patient dying while awaiting cadaveric transplantation.

- Ability to schedule surgery on a non-urgent basis.

- Ability to time transplantation before the recipient becomes too ill.

Con’t.

- Shorter ischemic times.- Avoidance of hemodynamic instability

associated with maintenance of cadaveric donor.

Operative goals:

The operation should provide the highest degree of operative safety and the greatest cardio pulmonary rehabilitation.

Is the lung transplantation safe?

Complications:

Early graft dysfunction – is an acute lung injury that is related to preservation and ischemia reperfusion.

- referred to a clinical scenario as pulmonary infiltrate and poor oxygenation.

- main consideration are rejection and infection.

Con’t.

Airway complications:

- Dehiscence

- Stenosis

- Bronchomalacia

Con’t.

Rejection- is the single most important limitation to long-term survival.- Acute rejection

* incidence – high* infrequently fatal* the principal risk factor for

chronic rejection

Why might the lung be prone to rejection?

Con’t.

- The lung has an extensive vasculature and circulating immune system.

- The lung is constantly exposed to extrinsic infectious agents.

Con’t.

Infection

- is the leading cause of early and late morbidity and mortality.

- wide spectrum of pathogens.

- bacterial pneumonia and CMV pneumonitis have been the most problematic.

Why is the lung allograft so prone to infection?

Con’t.

- The lung allograft is denervated – cough reflex is depressed.

- Mucociliary clearance is depressed.- Lymphatic drainage is disrupted.- Immunisystems are suppressed by anti

rejection medications.

Con’t.

Lymphoproliferative Disease (PTLD)- the prevalence is 6%- most cases developed in the first year- the risk has been marked by increased in recipient who have had EBV-sero negative before transplantation and have acquired a primary EBV infection afterwards.

Con’t.

Outcomes

- gauged by survival

- quality of life

- cost-effectiveness

Con’t.

Quality of life

- the usual way of measuring the quality of life for lung transplantation is the improvement of pulmonary function test.

Con’t.Cost and Cost-effectivenessAnalysis conducted at the University of Washington Medical Center- mean charge was $164,989- the average charges to post-transplantation care were $16, 628 per month during first 6 months and $5,440 per month during the 2nd month.- Lifetime cost was projected to be $424,853

Con’t.

Conclusion:

- lung transplantation has expanded rapidly in the last decade.

- chronic allograft rejection is a major impediment to long term survival.

- progress in immunobiology will likely determine the state of the art.