Thoracic Organ Transplantation

1
Thoracic Organ Transplantation

• A. Rüçhan Akar
• Ankara University School of Medicine
• Department of Cardiovascular Surgery
• January-2004
• Contributions to Rakar_at_medicine.ankara.edu.tr

2
to donate ones organs after death is an
act of charity that involves no risk at all
yet can provide another human being with
the gift of life
Sir Roy Calne, 1970 A Gift of Life
3
Heart Transplantation
4
Alexis Carrel Triangulating vessels for an
end-to-end anastomosis 1901 Alexis Carrel and
Charles Guthrie First heterotopic heart
transplantation in dog 1905 Nobel Prize, 1912
5
Frank MannMayo Clinic

• Allograft rejection
• biological incompatibility between donor and
  recepient manifested by impressive leukocyte
  infiltration

6
Prof. Vladimir P. Demikhov 1946 First
intrathoracic heterotopic heart allograft his
two-headed dog two days after the
operation First heart-lung block
transplantation was not reported in the Western
World until 1962
7
John H. Gibbon Father of the cardiopulmonary
bypass pump May-1953
8
Tom Starzl, 1963 father of liver
transplantation
9
Historical Milestones

• experimental orthotopic cardiac transplantation
• Goldberg et al. (Maryland Un.) 1958
• description of anastomoses of atrial cuffs
• Cass and Brock (Guys Hosp.) 1959
• operative techniques, graft preservation
• Norman Shumway and Richard Lower (Stanford Un.)
  1960

10
James HardyUniversity of Mississippi

• 1964- The first human cardiac transplant with
  xenograft (chimpanzee)
• Early mortality (the primate heart was unable to
  maintain the recepients circulatory load)

11
Barnard, De Bakey, Kantrowitz
12
Jesus, its going to work
Christiaan Barnard Groote Schuur Hospital,
South Africa 552 a.m. Sunday 3rd Dec. 1967
13

• First Successful Clinical
• Orthotopic Heart Transplantation
• Christiaan Barnard
• Groote Schuur Hospital, South Africa
• 3rd Dec. 1967
• donor 24 year old brain death woman injured by
  a car
• recipient 54 year old male with end-stage IHD
• survival 18 days
• cause of death Pseudomonas aeruginosa pneumonia

14
Louis Washkansky on his hospital bed after heart
transplantation
15
(No Transcript)
16
Norman E Shumway operative techniques, graft
preservation 4th human heart transplantation 6th
Jan 1968
17

• 1968
• 102 heart transplantations performed in many
  centers all over the world
• 1970
• poor outcome stopped activities in most centers,
• Stanford team continued efforts to develop
  techniques and treatments

18
Tolypocladium inflatum the primitive fungus from
which Cyclosporine is extracted
1980s, (beginning of modern era for
transplantation Cyclosporine A used in clinical
heart transplantation FDA approval-1983
19
Adult Heart Transplantation Indications

• Cardiomyopathy 46
• Coronary artery disease 45
• Valvular 3.5
• Congenital 1.8
• Re-transplantation 2
• Misc.. 1.6

15th official report-1998 The registry of the
International Society for Heart and Lung
Transplantation
20
Paediatric Heart Transplantation Indications

• Congenital heart disease 46
• Cardiomyopathy 44
• Misc.. 6.4
• Re-transplantation 3.6

15th official report-1998 The registry of the
International Society for Heart and Lung
Transplantation
21
Recipient Exclusion Criteria for Cardiac
Transplantation
(I)

• Age gt 70 (controversial)
• Fixed pulmonary hypertension
• PVR gt 6 Wood Units
• Transpulmonary gradient gt 15 mmHg
• coexistent systemic illness with poor prognosis
• coexisting neoplasm other than skin cancer
• HIV/AIDS ( CD4 count lt 200 cells/mm3)
• SLE or sarcoid that has multisystem involvement
• irreversible renal dysfunction
• irreversible hepatic dysfunction

22

Recipient Exclusion Criteria for Cardiac
Transplantation
(II)

• irreversible pulmonary parenchymal disease
• Severe PVD or cerebrovascular disease
• peptic ulcer disease
• IDDM with end-organ damage
• past malignancy
• active infection
• acute pulmonary embolism
• current or recent diverticulitis
• myocardial infiltrative disease
• severe obesity, cachexia
• severe osteoporosis
• psychosocial instability or substance abuse
  (alcohol, drug)

23
Evaluation of Potential Cardiac Recipient

• Comprehensive history
• Physical examination
• CXR
• 12-lead ECG
• Hematologic and biochemical profile
• Infectious disease serologies
• Exercise test with VO2max
• Right heart catheterization
• Coronary angiography
• Endomyocardial biopsy (for non-ischemic HF)

24
Evaluation of Potential Cardiac Recipient

• Thyroid function studies
• Fasting and postprandial blood sugar
• Creatinine clearance
• Lipoprotein electrophoresis
• Viral titers
• Fungal serologies
• Holter monitor
• Echocardiogram
• Pulmonary function tests
• Panel reactive antibody screen
• HLA typing

25
Indications for Cardiac Transplantation

• Prognosis for 1-year survival without
  transplantation should be less than 50

26
Indications for Cardiac Transplantation

• Low EF lt 20
• Reduced VO2max (lt 10ml/kg/min)
• Reduced serum Na lt 135mEq/dL
• High PCWP gt 25 mmHg
• Elevated plasma norepinephrine gt 600pg/mL
• Increased cardiothoracic ratio

27
Management of Potential Cardiac Recipient

• Pharmalogical
• ACE inhibitors
• beta blockers
• diuretics (especially spironolactone)
• Pharmalogical bridge to TX
• Milrinone
• Dobutamine
• Dopamine

28
Management of Potential Cardiac Recipient

• Mechanical bridge to TX
• IABP
• Ventricular assist device (VAD)
• Total artificial heart (TAH)
• AICD (for life threatening ventricular
  arrhythmias)

29
The CARDIAC Donor
30

• goals of donor organ assessment
• prevent disease transmission
• ensure optimal graft function

31
Criteria for Brain Death

• absent cortical cerebral function
• unreceptivity, unresponsiveness
• apnea
• absent brain stem reflexes
• oculovestibular, oculo-cephalic reflexes,
• corneal, pupillary, cough, gag reflexes
• cause of coma is known
• irreversibility over a 12-24 hours

32
Standard UNOS Requirements

• certification of brain death
• consent for organ donation
• donor family and coroner
• donor information
• age, height, weight, ABO blood group, gender
• negative hepatitis, HIV, syphilis

33
Cardiac Donor Criteria

• age newborn to 55
• ABO match / weight match
• no history of cardiac disease or severe thoracic
  trauma
• no prolonged CPR, hypotension, or hypoxemia
• no evidence of systemic infection
• free of hepatitis antigen and HIV antibodies
• normal ECG and echocardiogram
• inotropic support dopamine lt 10 mg/kg/min
• CVP 8-12 mmHg

34
Donor Heart Exclusion Criteria

• age gt 60 years
• malignancy with extra-cranial metastatic
  potential
• systemic sepsis or endocarditis
• significant coronary artery disease
• poor ventricular function
• anatomic heart disease likely to lead to
  shortening of the recipient's expected life span
• major chest injury
• prolonged cardiac arrest, repeated cardioversions

35
Organ Recovery Rates

• kidney 95
• liver 77
• heart 50
• lung 16
• 1994 UNOS annual report
• (4845 cadaveric donors)

36
Thoracic Organ Recovery Co-ordination

• thoracic organ recovery team
• two surgeons
• transplant coordinator
• scrub nurse
• perfusionist

37
Review of the Donor Chart

• the brain death notes
• consent
• release from the coroner
• blood type
• clinical records
• ECG, CXR, Echocardiogram

38

• 10-20 of brain dead patients with suitable
  hearts actually become heart donors !
• 32 of potential heart transplant recipients die
  waiting for an organ !

Alexander JW, Vaughn WK. Transplantation 1991
51 135-141.
39
Donor Heart Management

• before brain death aiming to minimize cerebral
  edema
• fluid restriction, diuretics, mannitol (volume
  depleted)
• after brain death
• hypovolemic, hypotensive, high-dose inotropic
  support ( diabetes insipidus in 50 of donors)
• first step for donor resuscitation
• fluid resuscitation restore normovolemia
• colloids- 50 less fluid administration
• avoid fluid overload

40
Donor Heart Management

• monitoring
• CVP
• Arterial line
• Swan-Ganz catheter,
• if haemodynamically unstable

41
Donor Heart Management

• CVP monitoring is essential
• right ventricular distension !
• Mean arterial pressure 80-90 mmHg
• CVP 5-12 mmHg
• PCWP lt 12 mmHg
• colloid to replace previous hours urine loss
• blood ( Hb gt 10 g/dl)

42
Donor Heart Management

• Inotropic support
• dopamine 2-10 mcg/kg/min
• Noradrenaline or phenylephrine (SVR 1000-1200
  dynes.sec5.)
• no inodilator (Dobutamine, Milrinone)
• Vasopressin for DI (0.8-1.0 U/hr or sc, im)

43
Donor Heart Management

• medication
• broad spectrum antibiotics (cephalosporin)
• T3 (4mcg bolus, followed by 3mcg/hr)
• methylprednisolone (500 mg bolus)
• insulin (blood glucose 4-6 mmol/L)
• Thermoregulation 34-36oC

44
Steps in Heart Graft Procurement

• incise right SPV and IVC
• apply topical saline (4 0C)
• cardiectomy ( dividing cavae, aorta, pulmonary
  veins, pulmonary artery)
• bag in saline, excluding air
• transport in ice

• assess donor
• examine heart for trauma, atherosclerosis,
  valvular disease, congenital defects.
• heparin 30,000 IU
• ligate SVC, clamp IVC
• clamp aorta
• start cardioplegia (500mL through 14-gauge needle)

45
Pitfalls in Heart Graft Procurement

• failure to monitor heart closely during
  multiorgan dissection
• failure to heparinize
• allowance of right or left distension
• inadequate attention to cooling and storage for
  transport

46
Cardiac Preservation

• ischaemic times of 4-6 hrs are considered the
  upper limit for cardiac grafts
• the exception
• in infant donor population, ischaemic times may
  range up to 8 hrs with normal post-operative
  function

47
Post-operative Myocardial Dysfunction

• Suboptimal donor management
• Hypothermia
• Ischemia-reperfusion injury
• Depletion of energy stores

48
Crystalloid Cardioplegia

• Extracellular
• (low to mod K, high Na )
• Stanford
• Hopkins
• St. Thomas Hospital

• Intracellular
• (high K, low Na )
• University of Wisconsin
• Euro-Collins
• Bretschneider (HTK)

Substrate enhancement mannitol, lactobionate,
raffinose, histidine, Adenosine, L-pyruvate,
L-glutamate, allopurinol, glutathione,
superoxide dismutase, catalase Leukocyte
depletion
49
Orthotopic Heart Transplantation

• Gold standard

50
Heterotopic Heart Transplantation

• Irreversible pulmonary hypertension
• Significant donor-recipient mismatch

51
Denervated Heart

• Delayed catecholamine response
• Distinct P wave from the innervated atrial
  remnant
• Orthostotic hypotension
• Carotid sinus massage, Valsalva maneuver, and
  atropine have no effect on SA node firing or AV
  conduction

52
Early Allograft Failure

• Accounts for up to 25 of perioperative deaths
  (especially right heart failure)
• Multifactorial
• pulmonary hypertension
• ischemic injury during preservation
• acute rejection

53

• Post-transplant Concerns

rejection
infection
immunosuppression
54
Rejection

• hyperacute preformed antibodies (humoral)
• acute both cellular and humoral
• MHC I II antigens
• Antigen presenting cells (APC)
• activated T-lymphocytes
• chronic persistent cell-mediated
• allograft vasculopathy (AV)
• obliterative bronchiolitis (OB)

55
Hyperacute Rejection

• preformed antibodies that immediately bind to and
  activate the endothelium
• Initiation of complement and coagulation cascade
• Edema, hemorrhage, trombosis
• Anti-class 1 Abs are more destructive

56
Hyperacute Rejection

• Prevention identify pre-existing Abs to HLA
  antigens
• Panel crossmatching exposing recepients serum
  to panels of donor cells
• If the patient is determined to react gt10 of the
  panel, prospective crossmatching is recommended
  between the lymphocytes from the proposed donor
  and the recepients serum

57
Acute Rejection

• Both cellular and humoral immunity
• Macrophages, cytokines, T lymphocytes (more
  cellular)
• Most common within weeks to months
• 80 of the episodes occur in the first 3 months
  postop
• A decrease in the blood level of
  immunosupressants or upregulation of
  alloreactivity owing to viral infection

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Risk Factors for Acute Rejection

• Female gender
• HLA mismatches
• Allografts from younger or female donor

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Diagnosis of Acute Rejection

• Low grade fever
• Malaise
• Leukocytosis
• Pericardial friction rub
• Supraventricular arrhytmias
• Low cardiac output
• Reduced exercise tolerance
• Signs of congestive heart failure

RV endomyocardial biopsy- Gold standard
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ISHLT Standard Cardiac Biopsy Grading System

• 0 No rejection No lymphocytic infiltration
• 1A Focal, mild No necrosis, focal infiltrate
• 1B Diffuse, mild No necrosis, Diffuse
  infiltrate
• 2 Focal, moderate one focus of infiltration
  or focal myocyte damage
• 3A Multifocal, moderate rejection myocyte
  damage, multifocal aggressive infiltration
• 3B Diffuse, borderline severe rejection myocyte
  necrosis, diffuse infiltration
• 4 Severe rejection diffuse aggressive WBC
  infiltration with myocyte necrosis edema,
  hemorrhage, vasculitis

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Treatment of Acute RejectionGrade 3B or 4

• 3 days of IV methylprednisolone 1000 mg/day
• Repeat endomyocardial biopsy in one week
• No improvement- second pulse-steroid

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Chronic Rejection

• Persistent cell-mediated rejection
• Progressive myocardial fibrosis and dysfunction
• Allograft vasculopathy (AV)
• prevalence 60 within 5 years of heart
  transplantation
• Near complete-occlusion of the coronary arteries
• Leading cause of death after first year following
  heart Tx

63
Allograft vasculopathy Graft Vascular
DiseaseTransplant-accelerated Arterial Disease

• diffuse concentric intimal thickening
• widespread endothelial damage
• progressive reduction of lumen size
• angiography slow run-off
• Perform coronary angiogram annually
• Intracoronary ultrasound (IVUS) more sensitive

64
Risk Factors for Allograft vasculopathy

• Donor age gt 35
• HLA mismatching (HLA A and DR)
• Hypertriglyceridemia
• Frequent acute rejections
• Documented recipient CMV infection

65
Allograft vasculopathy Graft Vascular
DiseaseTransplant-accelerated Arterial Disease

• Near-luminal occlusion by neointimal
  proliferation progressive smooth muscle
  proliferation in the intima
• Uniform pattern
• Accumulations of extracellular lipid
• Infiltrates of T cells that circle the entire
  vessel (characteristic)

66
Allograft vasculopathy
M.J. Davies Atlas of Coronary Artery Disease
1998 Lippincott-Raven Publishers
67
Allograft vasculopathy concentric wall
thickening
M.J. Davies Atlas of Coronary Artery Disease
1998 Lippincott-Raven Publishers
68
Immunosuppression

• Corticosteroids
• Cytokine Synthesis Inhibitors
• Cyclosporin A (CsA)
• Tacrolimus (FK506)
• DNA Synthesis Inhibitors
• Azathioprine (AZA)
• Mycophenolate mofetil (MMF)
• Brequinar sodium (BQR)
• IL-2 Signal Transduction Inhibitors
• Rapamycin (sirolimus RPM)
• Receptor Antogonists and Monoclonal Antibodies
  (ATG, OKT3)

69
Corticosteroids

• Mediated through intracellular receptors that
  alter gene transcription
• Anti-inflammatory (blockade of NFKB-induced
  transcription of inflammatory cytokines and
  adhesion molecules)
• metabolic side effects such as muscle wasting and
  diabetes derive from positive transcriptional
  effects
• Induce apoptosis in malignant T cells (good
  choise in the setting of post-transplant
  lymphoproliferative disorder)

70
Corticosteroid Complications

• Water and salt retention (weight gain,
  hypertension)
• Glucose intolerance
• Peptic and esophageal ulceration, GI bleeding
• Osteoporosis
• Gout
• Cushingoid appereance
• Cataracts
• Hyperlipidemia
• Poor wound healing

71
Corticosteroid regimen

• Methylprednisolone
• 500 mg IV (induction after protamine)
• 125 mg IV TDS (early postop)
• Prednisone
• 1 mg/kg PO QDS
• Tapered to 0.4 mg/kg by 2 weeks
• 0.2 mg/kg PO QDS (maintanance)

72
Cytokine Synthesis Inhibitors
73
Tolypocladium inflatum the primitive fungus from
which Cyclosporine is extracted
1980s, Cyclosporine A used in clinical heart
transplantation FDA approval-1983
74
Cyclosporine A (CsA) Neoral (microemulsion
formula)

• Inhibits the gene activation necessary for IL-2
  production by Helper T-lymphocytes
• Inhibits the function of a
• Ca activated Calcineurin phospatase
• More selective immunosupression

75
Cyclosporine Complications

• Nephrotoxicity- (30 of heart TX recipients
  develop)
• Hypertension (in up to 90 heart TX recipients)
• Cholelithiasis
• Neurotoxicity (seizures, tremor)
• Hirsutism
• Gingival hyperplasia
• Hyperkalemia
• Hyperuricemia
• Pericardial effusion

76
Cyclosporine regimen

• Preoperative 4-10 mg/kg PO
• Immediate postop 0.5 mg/kg/day IV
• Maintenance 5-10 mg/kg/day PO
• Dose adjusted to maintain serum levels between
  200-300 ng/mL

77
FK506 (Tacrolimus)

• Introduced to patients in Pittsburgh in 1988
• Combines with similar but different cytosolic
  protein (compared with CsA) and complexes with
  the same Ca activated Calcineurin to prevent
  activation of NFAT
• Particularly successful in patients with
  refractory acute rejection following a switch
  from CsA based regimen (RESCUE AGENT)

78
DNA Synthesis Inhibitors
79
Azathioprine (AZA)

• Inhibits the synthesis of nucleotides necessary
  for DNAs in rapidly dividing cells
• Inhibits purine synthesis (both DNA and RNA)
• Dose adjustments to maintain leukocyte count
  4000-5000/mm3.

80
Azathioprine Complications

• Bone marrow suppression (usually dose related)
• Pancreatitis
• Drug induced hepatitis
• Cholestatic jaundice
• Nausea, vomiting, abdominal pain
• Alopecia

81
Mycophenolate mofetil (MMF) CellCept

• More selective for T and B cells than AZA
• Lymphocyte spesific Inhibition of purine
  synthesis
• Reduction in acute rejection events and Ab
  production compared to AZA
• Has largely replaced AZA
• Dose 1 gr PO or IV BD

82
IL-2 Signal Transduction Inhibitors
83
Rapamycin (Sirolimus RPM)

• Structurally similar to FK506 (tacrolimus)
• Binds to FK binding protein (FKBP)
• RPM/FKBP binds to a lipid kinase and prevents the
  signalling between IL-2 receptor activation and
  cell-cycle initiation
• Induces cell cycle arrest in B cells and smooth
  muscle cells
• Final result antiproliferative effect

84
Receptor Antogonists and Monoclonal Antibodies
85

Receptor Antogonists and Monoclonal Antibodies

• ATG
• rabbit antihuman thymocyte globulin
• Polyclonal anti-T-cell preparation
• Fc-rec-mediated cell lysis or complement-dependent
  cell lysis
• Abs can decrease the level of T cells to less
  than 10 of normal
• OKT3
• Murine anti-human CD3 monoclonal Ab
• (on cytotoxic T-lymphocytes)
• Greatest benefit on rescue therapy
• Developed in 1980s

86
Nonpharmacologic Immunsupressive Strategies

• Total lymphoid irradiation
• Photopheresis
• Apheresis

87
Infection
early death 15 late death 40

• bacterial (most common)
• viral
• CMV ganciclovir
• Herpes simplex, Herpes Zoster acyclovir
• Ebstein-Barr interferon
• fungal
• Candidiasis nystatin, itracanosole
• Aspergillosis amphotericin B or Itracanasole
• protozoal
• Pneumocystis carinii TMP-SMX or pentamidine

88
Donor Transmitted Infection

• CMV
• Toxoplasma Gondii
• HBV
• HCV
• HIV

89
Results of Heart Transplantation

• operative mortality 5-10
• 1-year survival 80
• 3-5 year survival 70
• 12 year survival 37
• 50 survival 8.7 years
• mortality rate 4 per year (year 1-14)

90
Recipient Factors for 1-year Mortality

• odds ratio
• re-transplant 2.61
• IABP/ VAD 1.87
• ventilator support 1.87
• age lt 5 years 3.75
• gt 60 years 1.42
• Female gender (donor or recipient)

91
Donor Factors for 1-year Mortality

• odds ratio
• age (gt 40 years) 1.34
• ischaemic time ( gt 3.5 hrs) 1.27
• female donor 1.24
• 15th official report-1998
• The registry of the International Society for
  heart and lung transplantation

92
Morbid Conditions After Heart Transplantation(fi
rst 3 years)

• drug-treated hypertension
• renal dysfunction
• drug-treated hyperlipidemia
• drug-treated diabetes
• malignancy

15th official report-1998 The registry of the
International Society for heart and lung
transplantation
93
Lung Transplantation
94
Historical Milestones

• Prof. Vladimir P. Demikhov
• 1940s first succesful method of
• en bloc heart-lung transplantation in 67 dogs,
• longest survivor 6 days

95
Lung Transplantation

• First human lung transplant- 1963
• Dr. James Hardy, University of Mississippi,
• 58-year-old man with lung cancer
• survival 18 days
• First heart-lung transplant- 1981
• Reitz, Stanford University
• First lung transplant with prolonged
  survival-1983
• Toronto Lung Transplant Group
• survival 6 years
• En-bloc double lung replacement
• Patterson-1988

96
Lung Transplantation Indications

• Obstructive lung disease
• COPD
• Alpha-1 antitripsin deficiency emphysema
• Cystic fibrosis (CF)
• Restrictive lung disease
• Idiopathic pulmonary fibrosis (IPF)
• Pulmonary hypertension
• Primary pulmonary hypertension (PPH)
• Eisenmengers syndrome

97
Lung Transplantation other indications

• sarcoidosis
• lymphangiomyomatosis
• pulmonary fibrosis from prior chemo- or
  radiotherapy
• idiopathic bronchiectasis
• repeat lung transplantation

98
Indications for Lung Transplantation

• ill enough to need a transplant
• not so ill as to be unable to stand the surgery
• Candidates should have a life expectancy of less
  than 18-24 months

99
Heart-lung Transplantation Indications

• reserved for
• irreversible cardiac dysfunction or complex
  cardiac defects
• end-stage pulmonary vascular or parenchymal
  disease
• Congenital (Eisenmengers syndrome) 32
• Primary pulmonary hypertension 25
• Cystic Fibrosis and other septic lung disease 16

100
Recipient Selection for Lung Transplantation

• clinically and physiologically severe lung
  disease
• limited life expectancy (12-24 months)
• age lt 50 yrs. (Heart-Lung Tx) lt 55 yrs.
  (Bilateral Lung Tx) lt 60 yrs.
  (Single Lung Tx)
• satisfactory nutritional status
• appropriate mental state (well motivated,
  compliant, satisfactory psychosocial profile)

101
Contraindications to Lung Transplantation

• Acutely ill/ unstable (eg. Mechanical
  ventilation)
• Significant disease of other organ systems
  (renal dysfunction, biopsy proven liver
  disease)
• Uncontrolled sepsis, panresistant respiratory
  flora
• Infection with HIV, HBV, HCV
• Uncontrolled neoplasm
• Still smoking
• Drug/alcohol abuse
• Non-compliant with treatment

102
Lung, Heart-Lung Transplant Evaluation
normal cardiac function and anatomy
yes
no
CF or bronchiectasis
reversible or surgically correctable
yes
yes
no
no
double lung
single lung
heart-lung
103
Donor Lung EvaluationConcerns/questions

• history of smoking, aspiration, date of
  intubation
• evidence of chest trauma
• colour, consistency, and amount of tracheal
  aspirates
• quality of breath sounds
• CXR report (within 4 hrs)
• sputum gram stain and fungal stain
• arterial blood gases

104
Heart lung and Lung Donor Selection Criteria

• Age lt 40 (heart-lung), lt 50 (lung)
• no history of pulmonary disease or long-term
  heavy smoking (less than 20 packs-years)
• PO2 gt 140 mmHg (21 kPa) on FiO2 of 40 at 5 PEEP
• PO2 gt 300 mmHg (49 kPa) on FiO2 of 100 at 5
  PEEP
• clear lung parenchyma on CXR
• no evidence of pulmonary infection by Gram stain
  and KOH preparation (fungus and yeast)

105
Heart lung and Lung Donor Selection Criteria

• acceptable lung compliance
• (peak inspiratory pressure lt 30mmHg at tidal
  volume lt 15ml/kg)
• appropriate size match
• absence of thoracic trauma
• HIV negative

106
Alpha-1 Antitripsin Deficiency

• congenital, 1/1500 to 1/5000
• lack of protection against neutrophil elastase in
  the distal airways
• severe bullous emphysema (basilar pattern) fourth
  or fifth decades of life
• obstructive physiology

107
Cystic Fibrosis (I)

• inherited, autosomal reccessive
• 1/2500 births
• 1/25 of the population is a carrier
• defect on the long arm of chromosome 7
• codes cystic fibrosis trans-membrane conductance
  regulator (CFTR)
• CFTR functions as a chloride channel in the
  membrane of epithelial cells

108
Cystic Fibrosis (II)

• affects all exocrine glands
• most common cause of end-stage COPD in the first
  three decades of life
• poor ciliary clearance, mucous plugging
  excessive, thick viscid secretions
• chronic pulmonary sepsis

109
Cystic Fibrosis (III)

• Upper airway
• sinusitis, nasal polyps
• Lungs
• infection
• airways obstruction
• bronchiectasis
• respiratory failure
• pneumothorax
• haemoptysis
• allergic aspergillosis
• Salty sweat
• Clubbing
• Arthropathy
• Male infertility

Pancreas malabsorption, malnutrition diabetes In
testines meconium ileus distal intestinal
obstruction rectal prolapse Liver biliary
cirrhosis hepatosplenomegaly portal
hypertension gallstones Psycosocial problems
110
Idiopathic Pulmonary Fibrosis (IPF)

• most common restrictive lung disease requiring
  lung transplant
• interstitial collagen deposition
• loss of pulmonary compliance
• diminished lung volumes
• reduction in the diffusing capacity
• secondary pulmonary hypertension
• median survival lt 5 years

111
Primary Pulmonary Hypertension (PPH)

• idiopathic
• affecting small pulmonary arteries
• (luminal obliteration)
• elevated PVR and RV afterload
• more often females
• median survival 2.8 years
• normal pulmonary mechanics

112
Referral Guidelines for Lung Tx COPD, alpha-1
antitrypsin deficiency, CF

• postbronchodilator FEV1 lt 30 predicted
• resting hypoxia PO2 lt 7.5 kPa (55-60 mmHg)
• hypercapnia PCO2 gt 6.5 kPa (50 mmHg)
• severe secondary pulmonary hypertension
• clinical course
• increasing exacerbations
• decline of FEV1
• weight loss

113
Referral Guidelines for Lung TxPrimary Pulmonary
Hypertension

• NYHA III or IV
• mean RA pressure gt 10 mmHg
• mean PA pressure gt 50 mmHg
• CI lt 2.5 L/min/m2

114
number of lung transplant procedures by year
115
Lung transplantation

• 1-year survival 70
• 5 -year survival 43
• Slight survival advantage for BLT

116
Lung transplantation Causes of deaths after 90
days (n407)

• Infection 29
• BO/Rejection 28
• Malignancy 6
• Respiratory failure 6
• CMV 4
• Haemorrhage 2
• Heart failure 2
• Other 21

117
Bronchiolitis Obliterans Syndrome (BOS or OB)

• First described in 1984
• obstruction and destruction of bronchioles, dense
  fibrosis, mucus plugging
• average latent period 15 months
• prevalence 60-70 within 5 years after lung TX
• serial decline in FEV1 reliable and
  reproducible pulmonary function test
• most sensitive test for detection of OB is a fall
  in forced expiratory flow between 25 and 75 of
  FVC (FEF 25-75)
• FEF50/FVC lt 0.7 for 6 weeks most sensitive
  predictor of OB
• progression over several months

118
Bronchiolitis Obliterans Syndrome (BOS or OB)

• Transbronchial biopsy- Gold standard
• Histologic diagnosis
• dense eosinophilic submucosal scar tissue that
  partially or totally obliterates the lumen of
  small (2mm) airways (terminal and respiratory
  bronchioles)
• Decline of gt 20 in FEV1 (in the absence of
  infection or other process)- diagnostic

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Risk Factors for Bronchiolitis Obliterans
Syndrome

• CMV pneumonitis
• Other pulmonary infections
• HLA mismatching
• Graft ischemic times gt 6-8 hours
• Donor age gt 55

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Treatment Bronchiolitis Obliterans Syndrome

• Prednisone increased to 0.6-1.0 mg/kg/day
• slowly tapered to 0.2 mg/kg/day
• optimize CyA and AZA
• Restart Ganciclovir (risk of reactivation of CMV)
• Relapse rates gt 50
• Retransplantation is the only option for terminal
  respiratory failure secondary to OB