This document discusses lung transplantation, including indications, contraindications, recipient selection, donor selection, and surgical considerations. The most common indications for lung transplantation are COPD, idiopathic pulmonary fibrosis, cystic fibrosis/bronchiectasis, and PAH. Absolute contraindications include recent malignancy or uncontrolled infection/disease. Recipient selection involves evaluating cardiopulmonary function and psychosocial status. Donor lungs should be from donors under age 60 with less than 20-30 pack-years smoking history and adequate gas exchange.

1. Lung Transplantation
Dr. Rikin Hasnani

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

3. Indication in Specific Disease
conditions

4. 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

6. • 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.

7. Idiopathic Pulmonary Fibrosis/Nonspecific
Interstitial 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.

8. • 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.

9. • 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.

10. 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

11. • 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.

12. 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

13. 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

14. Lymphangioleiomyomatosis (LAM)/Pulmonary
Langerhans 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

15. Contraindications

16. 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

18. • • 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

19. 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

20. • 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

21. 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.

22. 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.

23. Other consideration
• Blood compatibility
• Age of Donor
• Distance from Donor Hospital

24. • 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

25. 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

26. Transplant procedure selection
Single-lung transplantation
• Obstructive lung disease
• Restrictive lung disease
Bilateral-lung transplantation
• Obstructive lung disease (patient <60 y old)
• Septic lung disease
• Idiopathic pulmonary arterial hypertension
• Eisenmenger syndrome with a correctable shunt defect
Combined 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

27. 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

28. Surgical considerations

29. 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.

30. • 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.

32. 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

34. 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.

35. Complications

36. 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

37. • Pneumothorax
• Pleural effusion
• Bronchial ischemia, localized bbronchomalacia, bronchial stenosis,
bronchial dehiscence are airway complications
• Atrial fibrillation, pancreatitis, gastroparesis, pseudo obstruction.

38. • 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.

39. 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.

40. • 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.

41. 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.

42. 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.

43. 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.

44. Thank You