Lung transplantation

LUNG TRANSPLANTATION
Thomas Kurian
1

Introduction
• Lung transplantation involves removal of one
or both diseased lungs from a patient and the
replacement of the lungs with healthy organs
from a donor
• May refer to single, double, or even heart-lung
transplantation
• Accepted modality of treatment for end stage
lung disease that is unresponsive to medical
therapy
2

Purpose
• To replace a lung that no longer functions with
a healthy lung.
• To perform a lung transplantation, there
should be potential for rehabilitated breathing
function.
• Other medical treatments should be
attempted before transplantation.
3

History of procedure
• First human lung transplantation was done in
1963. Recipient of the lung transplant
survived only 18 days.
1983- Dr. Joel Cooper- first successful single
lung transplant
1985- Cooper / Patterson- double lung
transplant
4

• Dr. Denton Cooley and associates were the
first to attempt heart-lung transplantation in
1968.
• First heart-lung transplant in India- 3 May
1999 at Madras Medical Mission.
5

AGE DISTRIBUTION OF LUNG TRANSPLANT
RECIPIENTS
6
0
5
10
15
20
25
18-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-65 66+
Recipient Age
%oftransplants
J Heart Lung Transplant 2008;27: 937-983

Indications for lung transplantation
• Obstructive lung disease:
A. Chronic obstructive pulmonary disease
• Restrictive lung diseases:
A. Idiopathic pulmonary fibrosis (IPF)
B. Interstitial lung disease
7

Indications for lung transplantation
• Septic lung disease:
A. Cystic fibrosis (CF)
B. Bilateral bronchiectasis
• Pulmonary vascular disease:
A. Primary pulmonary hypertension (PPH)
B. Eisenmenger’s syndrome
8

ADULT LUNG TRANSPLANTATION: Indications for Single Lung Transplants (Transplants:
January 1995 - June 2007)
50%
28%
2%
1%2%
7%
10%
Alpha-1 COPD CF IPF PPH Re-TX Other*
*Other includes:
Sarcoidosis: 2.1%
Bronchiectasis: 0.4%
Congenital Heart Disease: 0.2%
LAM: 0.7%
OB (non-ReTx): 0.5%
Miscellaneous: 5.8%

ADULT LUNG TRANSPLANTATION: Indications for Bilateral/Double Lung Transplants (Transplants:
24%
14%
18%
8%
28%
6% 2%
Alpha-1 COPD CF IPF PPH Re-Tx Other*
*Other includes:
Sarcoidosis: 3.0%
LAM: 1.2%
OB (non-ReTx): 1.1%
Miscellaneous: 6.6%

Disease specific selection criteria
COPD
Patient with BODE index 7 to 10 and at least 1 of
the following:
1. FEV1 < 25% predicted ( without reversibility)
2. PaCO2 >55 mm of Hg
3. Elevated pulmonary artery pressure (PAP)
4. Cor pulmonale
11

Other indices shown to correlate mortality-
1)subjective breathlessness
2)weight loss
3)exercise tolerance
4)hospitalization
5) lung morphology
12

The BODE Index For COPD
Can Fam Physician 2008;54:706-11

Idiopathic Pulmonary Fibrosis
• Highest attrition rate with waiting list
mortality 30%
• Initially, “refer all patients”
• Patients with exercise induced desaturation
are ideal candidates
14

 Current consensus-
1) Symptomatic progressive disease despite 3
months of medical therapy
2) Rest or exercise induced desaturation
3) Symptomatic with-
VC< 60-70% predicted
DLCO < 50-60% predicted
15

Cystic fibrosis
• FEV1 <30% of predicted normal value
• PaCO2 >50 mm Hg
• Pao2 <50 mm Hg
• PAH
16

 Prognostic criteria-
1)age
2)sex
3)FEV1
4)weight for age
5)Pancreatic insufficiency
6)D.M.
7)S.aureus
8)B.cepacia
9)No. of acute exacerberations
17

Symptomatic progressive disease
despite optimal medical treatment for
3 months
Cardiac index < 2 lit/min/m2
Right atrial pessure>15 mm Hg
PAP mean > 55 mm Hg
18
Primary Pulmonary Hypertension

Eisenmengers syndrome
• Better prognosis than patients with PPH
with similar PAP levels
• Epoprostenol therapy improved survival &
reduced need for transplantation
• Heart -lung transplantation is preferred
19

Sarcoidosis
• Most patients benign course
• In 10-20% permanent sequel
• Which stage ?
• FVC < 50% & FEV1 < 40%
20

Contra-indication (Absolute)
• Malignancy in the last 2 years
• Non-curable chronic extra pulmonary
infection including chronic active
hepatitis B , C , and HIV
• Untreatable advanced dysfunction of
another major organ system
• Current cigarette smoking
21

• Poor nutritional status
• Poor rehabilitation potential
• Significant psychosocial problems
• Substance abuse
• History of medical noncompliance
• Active Tuberculosis
22

Relative Contraindications :
• Age : advanced age is associated with
higher mortality rates
• Age cut-off
55 years for -Heart-lung transplantation,
60 years for- Bilateral lung transplantation,
65 years for -Single-lung transplantation.
23

• Ventilator dependence
• A prolonged wait while the patient is on a
mechanical ventilator may lead to various
complications such as infections, cardiovascular de-
conditioning.
• Psychosocial issues
24

• Decreased Body weight
• Obesity (BMI >30)
• Extra pulmonary organ dysfunction
25

Laboratory studies :
• Arterial blood gases (ABG )
• Pulmonary function tests (PFTs)
• Computerized tomography (CT)
• Ventilation perfusion scan (lung scan, V/Q
scan)
• Electrocardiogram (ECG)
26

• Echocardiogram (ECHO)
• Blood test : Complete blood count , Coagulation
profile.
• HIV, hepatitis B, hepatitis C
27

Donor-related issues:
• Younger than 65 years for lung transplantation
and younger than 45 years for heart-lung
transplantation
• Absence of severe chest trauma or infection
• Absence of prolonged cardiac arrest
• Minimal pulmonary secretions
• Negative screens for HIV, hepatitis C, and
hepatitis B
28

• Blood type (ABO) compatibility
• Close match of lung size between donor and
recipient
• PaO2 > 300 mm Hg on 100% fraction of
inspired oxygen
• Clear chest radiograph
• No history of malignant neoplasms
29

Surgical techniques
• Heart–lung transplantation
• Single lung transplantation
• Double lung transplantation

Heart–lung transplantation
• Reserved for patients with combined parenchymal and
cardiac disease
• Is it useful for cor pulmonale?
• After excision of the heart and lungs of the donor en bloc,
the trachea is anastomosed in the recipient just above the
carina
• The integrity of the anastomosis is maintained as a result of
extensive collateral arterial blood supply to the lower
trachea from the coronary arteries.

Advantages
immediate restoration of normal cardiac
output (an important factor in patients with
severe pulmonary hypertension)

Disadvantage
• Requires cardiopulmonary bypass
• Significantly higher risk of perioperative bleeding
• Heart can also be involved in chronic rejection
• The use of both lungs and heart limits the number of potential
recipients who can beneﬁt from the donation
• The results are poorer

Single lung transplant (SLT)
• Most common indication (~ 60%)  COPD
• Other indications :
– Pulmonary fibrosis and
– Primary or secondary pulmonary hypertension.

Single lung transplant (SLT)
• For SLT, the native lung with the poorest pulmonary function
according to the preoperative quantitative perfusion scan is
excised.
• Exclude bronchiectasis
• The lung is exposed via a posterolateral thoracotomy through the
fifth intercostal space.

Single lung transplantation(SLT)
• Advantages
– potentially two lung recipients and one cardiac recipient can be
treated with organs from one donor.
– No cardiopulmonary bypass is needed and so patients up to the
age of 65 years are being considered for this form of
transplantation.
– Perioperative bleeding is limited.

Double lung transplantation(DLT)
• Performed as two sequential lung transplants, one side followed by
the other.
• Operation of choice for cystic fibrosis and bronchiectasis, and is
also now advocated for patients with primary pulmonary
hypertension .
• No need for cardiopulmonary bypass and the risk of bleeding is
less than in HLT.

Intraoperative details
Bilateral sequential SLT is associated with a lower
incidence of bronchial complications than the en-
bloc DLT procedure and is technically less difficult to
perform than en-bloc DLT.
The exposure for bilateral sequential lung
transplantation is via bilateral anterolateral
thoracotomies through the fourth or fifth intercostal
space, connected by a transverse sternotomy, i.e.,
the "clam-shell" incision.

Living lobar transplant
• Involves bilateral implantation of the lower lobes from 2 blood
group–compatible living donors.
• Donation of a lobe decreases the donor's lung volume by an
average of approximately 15% and is not associated with long-
term functional limitation
• The need for close matching between the donor and recipient is not
necessary

Lung preservation
 Reduce the risks of fluid overload and to check for
pneumonia prior to death.
 The donor operation involves cannulation of the
pulmonary artery and infusion of either prostacyclin or
prostaglandin E2

Lung preservation
 Preserved inflated at 4°C
 total ischaemic time below 4 h.
 Pretreatment by steroids decreases ischemic lung graft Injury.
 Explanted organ is inflated, with 100% oxygen

Pre operative care
 Medical & psychosocial evaluation.
 Assessment of patient‘s physical health
 In preoperative phase the patient is assessed for
cardiac output & renal functions .
 Psychosocial evaluation
45

Post operative care
 The patient is observed for excessive
bleeding.
 Monitor vital signs ,ECG ,ABG values ,urine
output, O2 level analysis & chest tube
drainage.
 The patient may be started on mechanical
ventilation for 24 to 48 hours.
46

Post operative care
 Serum electrolytes ,complete blood count,
chest radiographs are obtained daily.
 Fluids are restricted.
 Lung sounds are auscultated.
 Severity of peripheral edema is monitored.
 Pain control is important to allow deep
breathing & coughing with chest
physiotherapy. 47

Post operative care
 The patient with lung transplantation is at high risk to
develop infection
 Isolation
 Monitor the patient for clinical manifestation of infection
48

Complications
49
Causes of respiratory failure
Early
 ischemia reperfusion
injury
 infection
 technical problems
 acute rejection
>3months
 Infections
 BOS
Curr.opin.Crit.care 2006 Feb;12, 19-24

Ischemia reperfusion injury
50
 Most frequent cause of early mortality
 presents as ALI / ARDS
 noncardiogenic pulmonary edema related to effect of free oxygen radicals and
cytokines

Post lung transplantation chest radiograph
Chest radiograph performed 24 hours following right unilateral lung transplantation - within normal limits.

Ischemia reperfusion injury
Seventy-two hours following lung transplantation

Ischaemia reperfusion injury
53
 Treatment-
A) diuretics
B) maximal ventilatory support
 Newer modalities
A) inhaled nitric oxide
B) inhaled prostacyclin
 Course-
resolves in 48-72 hrs

Complications
54
Early
 ischemia reperfusion injury
 infection
 acute rejection
>3months
 Infections
 BOS

Infections
55
 Bacterial
A) pseudomonas
B) nocardia
C) legionella , mycobacteria (rare)
 Routine antibiotic prophylaxis reduced the incidence
 Sputum cultures & antibiotic sensitivity done every 3
months

Viral infections
56
CMV predominates
 within 30-100 days after transplant
 occurs as reactivation or primary infection
(donor)
 routine prophylaxis replaced by close
monitoring
 Treatment-gancyclovir 5mg/kg for 2-3
weeks

57
 HSV&VZV can cause pnuemonia
 Acyclovir prophylaxis effective in patients not on
gancyclovir
 EBV related post-transplant lymphoproliferative
disease
 Recently Rituximab ( anti CD20 Ab) found effective

Fungal infections
58
 Aspergillus most common
1) ulcerative tracheitis
2) bronchitis
3) pneumonitis
4) disseminated disease
5) ABPA
 I.V. or aerolised amphotericin-B used for
prophylaxis

Other rarer organisms
59
 Histoplasma
 Sedosporium
 Pnuemocystis jirovecii

Complications
60
Early
injury
 infection
 acute rejection
>3months
 Infections
 BOS

Rejection
61
 Acute rejection-
 < 7 days onset
 low grade fever, dyspnoea
 CXR- 1) Clear
2) illdefined infiltrates
3) pleural effusion
 reduced FEV1

Acute rejection
62
 TBLB - gold standard in diagnosis
 Treatment- bolus I.V. steroids + increase in
maintenance immunosuppression
 role of surveillance bronchoscopy to detect
rejection early is controversial

Acute lung rejection
 Characterized by perivascular mononuclear cell infiltrates with extension into the
adjacent alveolar septa

Acute and resolving lung rejection
(A) Chest radiograph illustrates
bilateral infiltrates characteristic of
acute pulmonary rejection.
(B) Follow-up radiograph after
pulsed methylprednisolone
treatment of acute rejection
demonstrating resolution of
infiltrates

Complications
65
Early
injury
 infection
 acute rejection
>3months
 Infections
 BOS

Chronic rejection
66
 Bronchiolitis Oblitrans Syndrome (BOA) :
 Predominantly a small airway disease
 occurs in 50% patients surviving for 5 years
 onset > 6months
 major cause of mortality
 CXR- can be normal, late cases- bronchiectesis
 HRCT- mottled appearance with peripheral
lucency

67
 TBLB- gold standard
 Role of induced sputum & BAL-
1) Induced sputum – RANTES levels
and eosinophils correlate with BOS
development
2) BAL- IL8 & neutrophil levels have
negative correlation

Chronic airway rejection
 Bronchiolitis obliterans: characterized by luminal narrowing or
replacement by dense eosinophilic collagenous scar tissue.
Inflammatory cells may be seen in this case

70
 Treatment- variable course even
without treatment
 various immunosuppressive regimens
tried
 macrolides under evaluation

71
 Factors associated-
1) CMV pnuemonitis
2) HLA mismatch
3) GERD

Immunosuppressive therapy
Majority receive a triple-drug maintenance regimen
calcineurin inhibitor (either cyclosporine or
tacrolimus),
cell-cycle inhibitor (either mycophenolate
mofetil or azathioprine)
 steroids.

Immunosuppression
The first-line treatment of an episode of acute
rejection is high-dose intravenous steroid pulses.
For recurrent acute rejection, the strategy is to
switch from cyclosporine to tacrolimus.
73

Post-op. Management
Antimicrobial therapy
• Bacterial prophylaxis
• HSV prophylaxis → Acyclovir
• PCP → Cotrimoxazole
• Candida → Nystatin
• CMV -- Ganciclovir

Prognosis
• Mortality rate is higher for patients with primary pulmonary
hypertension, idiopathic pulmonary fibrosis, or sarcoidosis and
lower for those with COPD or α1-antitrypsin deficiency.
• Mortality risk factors include cytomegalovirus mismatching,
human leukocyte antigen mismatching, diabetes, and prior need for
mechanical ventilation or inotropic support.

76
• Exercise capacity has been the most
interesting functional outcome observes in
lung transplant recipient .
• Typically transplant recipient can walk 100
to 120m/min within 6 months of
transplantation.

LUNG TRANSPLANT IN INDIA
Ist lung transplantation : 3 may 1999 (HLT) in Madras Medical
Mission ,by Dr K M Cherian
Pt expired after 36 days
1st SLT : 11 July 2012 @ Hinduja hospital , Mumbai for IPF by Dr
Jnanesh Thacker .

LUNG TRANSPLANT IN INDIA
List of approved hospital in India for lung
transplantation
Frontier Life Line, R-30-C Amabattur Industrial
Estate, Chennai .
Chettinad Hospital and Research Institute,
Kelambakkam, Kancheepuram District
,Tamilnadu
Apollo Hospitals Enterprises Ltd., Chennai
PSG Super Specialty Hospital, Peelamedu,
Coimbatore
Global Hospitals and Health City, No/439 Cheran
Nagar, Perumbakkam, Chennai 600 100

79
Cost of Lung Transplantation in
India
• Surgery alone cost Rs 10 lakh.
• The ICU and medications will work
up to an equal amount

Question
Ist successful single lung transplant was done by
1. James hardy
2. Cooper
3. Demikhov
4. Peterson

Question
Most common indication of bilateral lung transplant
a. COPD
b. Pulmonary fibrosis
c. Cystic fibrosis
d. Pulmonary hypertention

ADULT LUNG TRANSPLANTATION: Indications for Bilateral/Double Lung Transplants (Transplants:
26%
16%
17%
7%
27%
5% 2%
Alpha-1 COPD CF IPF IPAH Re-Tx Other*
*Other includes:
Pulmonary Fibrosis, Other: 2.9%
Sarcoidosis: 3.0%
LAM: 1.1%
Connective Tissue Disease: 1.3%
OB (non-ReTx): 1.3%
Miscellaneous: 1.7%
ISHLT 2011ISHLT
J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132

Question
Earliest test to detect early graft failure
1. CxR
2. Spirometry
3. ABG
4. CT-thorax

Lung transplantation

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