Lung TransplantationDr. Rikin Hasnani

• Indication in specific Disease conditions• Contraindications• Recipient selection• Donor Selection • Surgical considerations • Complications

Indication in Specific Disease conditions

COPD • Guidelines for referral• BODE index exceeding 5• Guidelines for transplantation• Patients with a BODE index of 7–10 with at least one of the following:• History of hospitalization for exacerbation associated with acute

hypercapnia (PCO2 exceeding 50 mm Hg)• Pulmonary hypertension or cor pulmonale, or both, despite oxygen therapy• FEV1 of less than 20% and either DlCO of less than 20% or homogeneous

distribution of emphysema

• The most common indication for lung transplantation is obstructive lung disease, with COPD accounting for more than one-third of all lung transplants and emphysema due to α1-antitrypsin deficiency accounting for 8% of all lung transplants. • Patients with COPD tend to remain relatively stable for long periods,

albeit with a reduced quality of life. • It is now apparent that lung transplantation not only provides marked

symptomatic and functional palliation for these patients but improved survival as well.

Idiopathic Pulmonary Fibrosis/NonspecificInterstitial Pneumonia (NSIP)• Timing of referral:• Histopathologic or radiographic evidence of usual interstitial

pneumonitis(UIP)or fibrosing non-specific interstitial pneumonitis(NSIP),regardless of lung function.• Abnormal 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 6monthsof follow-up.• Desaturation to < 88% or distance < 250m on 6-minute- walk test or

50m 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.

• Interstitial lung diseases are the indication for lung transplantation in 24% of patients who undergo lung transplantation. • The most common cause is idiopathic pulmonary fibrosis (IPF),

whereas sarcoidosis, collagen vascular disease–associated interstitial lung disease, and drug induced lung disease account for the remainder.

Cystic Fibrosis/Bronchiectasis• Guidelines for referral• FEV1 below 30% predicted or a rapid decline in FEV1—in particular in young female

patients• Exacerbation of pulmonary disease requiring ICU stay• Increasing frequency of exacerbations requiring antibiotic therapy• Refractory and/or recurrent pneumothorax• Recurrent hemoptysis not controlled by embolization• Guidelines for transplantation• Oxygen-dependent respiratory failure• Hypercapnia• Pulmonary hypertension

• Septic lung disease, including cystic fibrosis and other types of bronchiectasis, accounts for approximately 20% of patients undergoing lung transplantation. • Candidates with focal or unilateral disease can sometimes be

managed with medical treatment or surgical resection of the affected area. • However when the disease is bilateral, and the natural history is one

of recurrent infection and progressive respiratory failure lung transplantation is indicated.

PAH• Guidelines for referral• NYHA functional class III or IV, irrespective of ongoing therapy• Rapidly progressive disease• Guidelines for transplantation• Persistent NYHA class III or IV on maximal medical therapy• Low (<350 m) or declining 6-MWT• Falling therapy with intravenous epoprostenol, or equivalent• Cardiac index of less than 2 L/min/m2• Right atrial pressure exceeding 15 mm Hg

Sarcoidosis • Guidelines for referral• NYHA functional class III or IV• Guidelines for transplantation• Impairment of exercise tolerance (NYHA functional class III or IV) and

any of the following:• Hypoxemia at rest• Pulmonary hypertension• Elevated right atrial pressure exceeding 15 mm Hg

Lymphangioleiomyomatosis (LAM)/PulmonaryLangerhans Cell Histiocytosis• Guidelines for referral• NYHA functional class III or IV• Guidelines for transplantation• Severe impairment in lung function and exercise capacity (e.g.,

V˙O2max <50% predicted)• Hypoxemia at rest

Contraindications

Absolute Contraindications for Lung Transplantation• Malignancy in the last 2 y, with the exception of cutaneous squamous and basal

cell tumors. In general, a 5-y disease-free interval is prudent. • The role of lung transplantation in localized lepidic Adenocarcinoma,

adenocarcinoma in situ .• • Untreatable advanced dysfunction of another major organ system (e.g., heart,

liver, or kidney). Coronary artery disease not amenable to percutaneous intervention or bypass grafting, or associated with significant impairment of left ventricular function, is an absolute contraindication to lung transplantation, but heart–lung transplantation could be considered in highly selected cases • • Noncurable chronic extrapulmonary infection including chronic active viral

hepatitis B, hepatitis C, and human immunodeficiency Virus

• • Significant chest wall/spinal deformity• • Documented nonadherence or inability to follow through with

medical therapy or office follow-up, or both• • Untreatable psychiatric or psychologic condition associated with the

inability to cooperate or comply with medical therapy• • Absence of a consistent or reliable social support system• • Substance addiction (e.g., alcohol, tobacco, or narcotics) that is

either active or within the last 6 m

Relative Contraindications • Age older than 65 y. Older patients have less optimal survival, likely

due to comorbidities, and therefore, recipient age should be a factor in candidate selection. • The presence of several relative contraindications can combine to

increase the risks of transplantation above a safe Threshold• • Critical or unstable clinical condition (e.g., shock, mechanical

ventilation or extracorporeal membrane oxygenation)• • Severely limited functional status with poor rehabilitation potential• • Colonization with highly resistant or highly virulent bacteria, fungi,

or mycobacteria

• Severe obesity defined as a body mass index (BMI) exceeding 30 kg/m2• • Severe or symptomatic osteoporosis• • Mechanical ventilation. Carefully selected candidates on mechanical ventilation

without other acute or chronic organ dysfunction, who are able to actively participate in a meaningful rehabilitation program, may be successfully transplanted• • Other medical conditions that have not resulted in end-stage organ damage, such

as diabetes mellitus, systemic hypertension, peptic ulcer disease, or gastroesophageal reflux should be optimally treated before transplantation. • Patients with coronary artery disease may undergo percutaneous intervention

before transplantation or coronary artery bypass grafting concurrent with the procedure

Recipient Selection • the evaluation of a potential candidate for lung transplantation include a

complete assessment of cardiopulmonary function and the patient’s general health in addition to a thorough evaluation of psychosocial status. • A battery of screening tests is required, and patient is evaluated by

members of the transplant team, including pulmonologists, cardiologists, thoracic surgeons, psychiatrists, and social workers is done.• The so-called “best candidates” are those who are deemed to have a

superior chance of obtaining both an immediate survival benefit and an enduring quality-of-life benefit.

Lung Allocation Score• The lung allocation score (LAS) is used to prioritize waiting list candidates

based on a combination of waitlist urgency and post-transplant survival. • Waitlist urgency is defined as what is expected to happen to a candidate,

given his or her characteristics, in the next year if he or she doesn’t receive a transplant. • Post-transplant survival is defined as what is expected to happen to a

candidate, given his or her characteristics, in the first year after a transplant if he or she does receive the transplant.• LAS has a range from 0 to 100. Higher lung allocation scores indicate the

patient is more likely to benefit from a lung transplant.

Other consideration • Blood compatibility• Age of Donor

• Distance from Donor Hospital

• Hematology -Complete blood count , platelet count, PT, PTT, ESR• BioChemistry – electrolytes. LFT, Lipid profile• Renal function - Urinalysis, 24 h for calcium and creatinine• Endocrine- TSH, LH, FSH, vitamin D, testosterone (males), estradiol (females)• Infectious disease - Sputum (Gram stain, C + S, fungal smear and culture, AFB

smear and culture), CMV (IgG and IgM), hepatitis B (antigen/antibody), hepatitis C, herpes, Varicella, EBV, HIV, toxoplasma PPD• Immunology - ABO blood type and cross match, MHC typing, HLA antibody

screen), vasculitic screen for interstitial lung disease, pulmonary hypertension• Radiology - Chest radiograph, high-resolution chest CT scan, quantitative V/Q

scan, quantitative bone density, abdominal ultrasonography, sinus CT• Cardiology- ECG, echocardiogram with pulse Doppler imaging, right heart

catheterization, left heart catheterization• Pulmonary- Pulmonary function tests (spirometry, lung volumes, Dlco),

arterial blood gases, cardiopulmonary exercise test

Characteristics of a Lung Donor• Age <60 y• Cigarette smoking <20-30 pack-years• No significant prior thoracic surgery on the side of the donor lung• Normal chest radiograph of the donor lung• Adequate gas exchange of the donor lung• PaO2 > 300 mm Hg on FiO2 1.0, PEEP ≥5 cm• PvO2 > 450 mm Hg on FiO2 1.0, PEEP ≥5 cm• Bronchoscopic evaluation demonstrating absence of mucosal inflammation or

aspiration• No significant pulmonary trauma or anatomic abnormalities

Transplant procedure selectionSingle-lung transplantation• Obstructive lung disease• Restrictive lung diseaseBilateral-lung transplantation• Obstructive lung disease (patient <60 y old)• Septic lung disease• Idiopathic pulmonary arterial hypertension• Eisenmenger syndrome with a correctable shunt defectCombined heart–lung transplantation• Significant intrinsic left ventricular dysfunction (LVEF <45%)• Significant coronary artery disease, not amenable to nonsurgical interventions• Eisenmenger syndrome with an irreparable shunt defect

Lung preservation • Satisfactory graft function can be obtained after ischemic intervals as

long as 6 to 8 hours.• Two techniques are currently being used for lung preservation,• 1. Extracorporeal core cooling (ECC)• 2. Hypothermic flush perfusion

Surgical considerations

Single Lung Transplant• The approach to single-lung transplantation requires an initial decision regarding the

side of implantation.• Most commonly, the native lung with the least pulmonary function based on

preoperative V/Q scans is excised. • In some patients, however, specific technical factors, such as a prior pleurodesis,

may override this factor. • When the function of the two lungs is equal or when the need for CPB is anticipated,

the right side is preferred because of the greater ease of surgical exposure and the institution of CPB via the ascending aorta and right atrium.

• A right-sided approach also facilitates exposure for closure of intracardiac defects in patients with Eisenmenger syndrome.

• Despite the potential differences in size of the right and left hemithorax, there is no long-term difference in outcome following right or left single- lung transplantation.

• Exposure through rt 5th or 4th ICS• Groin is included in surgical field• The donor lung is prepared for implantation and then wrapped in

sponges soaked with cold crystalloid solution and placed into the hemithorax. • The bronchial anastomosis is performed first followed by veins and

arteries.

Bilateral Lung Transplant• Although most commonly referred to as bilateral lung transplantation,

the most frequently performed bilateral procedure is more accurately described as bilateral sequential single-lung transplantation. • This procedure has a significantly lower incidence of anastomotic

complications than the en bloc double-lung procedure , and is technically less difficult to perform than en bloc double lung with simultaneous bronchial artery revascularization.• Exposure by bilateral anterior thoracotomies, clamshell incision, or

median sternotomy

Postoperative management• Ventilator management• Fluid management• Antimicrobials- bacterial, fungal, viral, pneumocystis• Immunosuppression –• use a three-drug regimen for immunosuppression comprising a

Calcineurin Inhibitor , a cell-cycle inhibitor and a corticosteroid, with the hope of obtaining additive effects in terms of immune suppression while limiting drug toxicities• Tacrolimus + Azathioprine+ Methylprednisolone is most common

regimen used.

Complications

Surgical Complication• Hemorrhage • Pulmonary artery obstruction can occur as a result of anastomotic stenosis,

kinking, or extrinsic compression.• Pulmonary venous or left atrial anastomotic obstruction can also occur

because of faulty anastomotic technique, kinking upon closure of the chest, or thrombus.• About 20% of patients have Primary graft dysfunction , characterized by severe

early abnormalities of lung function, with rapidly progressive pulmonary edema, persistent pulmonary hypertension, and markedly diminished pulmonary compliance that occurs rapidly after graft implantation.• PGD is the most common cause of early mortality after lung transplantation

and is associated with long-term sequelae including BOS and increased mortality

• Pneumothorax• Pleural effusion• Bronchial ischemia, localized bbronchomalacia, bronchial stenosis,

bronchial dehiscence are airway complications• Atrial fibrillation, pancreatitis, gastroparesis, pseudo obstruction.

• Infections – bacterial, viral• Rejection – • Acute rejection -AR is characterized by perivascular and subendothelial mononuclear

cellular infiltrates . • Airway inflammation, particularly lymphocytic bronchiolitis, may also be seen as a

component of AR.• Clinically, patients may manifest dyspnea, low-grade fever, hypoxemia, and pulmonary

infiltrates on chest radiograph. • More commonly, however, the patient is asymptomatic.• Flexible bronchoscopy with BAL and transbronchial biopsy is the most useful method of

differentiating AR from infection. • BAL is most useful in excluding infection and is not generally helpful in confirming

rejection.

Chronic Rejection • CR in the lung may affect either the pulmonary vasculature or the

airway.• Typically, CR in the lung is manifested histologically by obliterative

bronchiolitis and consists of dense eosinophilic scarring of the membranous and respiratory bronchioles . • This is accompanied physiologically by evidence of airflow obstruction

as assessed by simple spirometry. • Clinically, progressive dyspnea occurs, although a gradual decline in

FEV1 or in expiratory flow rates often precedes symptoms.

• The lung has a great deal of physiologic reserve so that by the time the patient is symptomatic the process is usually far advanced. • Further progression of this process leads to worsening dyspnea and

bronchiectasis with secondary infection. • Although this form of CR is uncommon in the first 3 months after lung

transplantation, up to 50% of patients develop it within 5 years and the mortality at 3 years after diagnosis is 40% or higher.• Occasionally, accelerated sclerosis of the pulmonary arteries and

veins may be encountered in lung allografts.

Bronchiolitis Obliterans Syndrome• The term BOS has been introduced as a noninvasive means to identify

patients thought to have CR of the lung involving the airways.

Neoplastic Complications• Immunosuppression increases the risk of development of neoplasms after

lung transplantation.• The malignancy for which risk is increased are squamous cell cancers of the

lip and skin, Kaposi sarcoma, soft tissue sarcomas, carcinomas of the vulva and perineum, and hepatobiliary tumors. • Colon cancer appears to be more common in cystic fibrosis patients after

transplant.• The most common malignancy seen after lung transplantation is a type of B-

cell lymphoid proliferation known as post transplant lymphoproliferative disorder(PTLD). PTLD represents a morphologically diverse group of polyclonal lymphoid proliferations. • The pathogenesis of PTLD appears to be related to EBV infection of B

lymphocytes that are free to proliferate as a result of the recipient’s immunosuppression.

Survival • Early mortality following lung transplantation has decreased significantly over the

past decade• Longer-term survival data indicate a cumulative survival rate above 80% at 1 year. • Survival curves vary significantly at 1 year, depending on the disease for which

transplantation was performed.• Patients with emphysema and those with cystic fibrosis appear to have a survival

advantage over patients with pulmonary fibrosis at this time point. • Beyond the first year, BOS begins to have a significant impact on survival, leading

to an overall survival rate of only approximately 65% at 5 years. • Causes of death in this period include infection and BOS, which can be identified

in up to half of the patients who survive to 5 years. • Malignancy, usually PTLD, is the third most common cause of late mortality

following lung transplantation.

Thank You