Brian Locke

Lung Transplant

Indications

Contraindicatoins

###Immunosuppresion

3 cell model = targets for immunosuppression

  1. Class 1 = vs nucleated cells
  2. Class 2 = vs all cells
  3. APCs -> T-lymphs

Stages:

  • Induction = as it happens (in surgery). Goal = reduce t-cell proliferation. Commonly now done with Basilixumab (IL-2 / CD25) 0,4d and methylpred 500mg
  • Maintenance = rest of life. NF-Kb agents and prednisone

Primarily targetted toward T-cells

  1. Calcineurin Inhibs: tacrolimus (cyclosporine not used) Cause nephrotoxicity by increasing afferent tone and magnesium wasting (as well as potassium elevation), metallic taste, and DM

  2. Cell cycle / Anti-metabolites: azathioprine, mycophenolate. Leukopenia and hepatotoxicity. GI tolerance with mycophenolate (particularly with Cellcept formulation)

  3. mTor inhibitors = sirolimus (causes leg edema and pulm tox), everolimus (gets in the way of wound healing so not used as induction). Often a replacement if patients develope CNI AE

Serologies (IgG Viremia donoor and recipient); most adults EBV+, CMV+. Dz shows up as malaise. -CMV for viremia -EBV for PTLD. viremia -Toxo

###Surgery:

Bronch is done on the donor to identify abnormalities (big bronchus, abnormalities in lobar anatomy)

[ ] what to look for on these.

Bronch on Day 0 and 7 (and 21) Extubate ASAP

Surgery: 3 sets of anastamoses

  1. Bronch
  2. PA
  3. PV

Some ischemia in the lung after, due to NO bronchial artery anastomses (tried for a while at Mayo, no benefit).

Prone to pleural effusions after - leave chest tube in for a while, until output drops. .

Complications

Immediate complications:

  • Infections 1st month usually related to donor or nosocomial infection. (Impaired cellular immunity, particularly)
  • Secretions, mucus plugging / mucociliary elevator is disrupted.
  • Also, prolonged post-transplant operative courses and trouble with debility (pre-transplant comorbidities).
  • Primary graft dysfunction aka ischemia reperfusion injury - ARDS-like response. Non-cardiogenic pulm edema from donor (e.g. at brain death). Starts 2-3h after transplant.
  • Ischemic airway complications (related due to the low pressure perfusion from the Pulm vessels - not Bronchial) - e.g. dehiscence. Stenosis/vanishing airway and bronchomalacia later.

(Why did they name all the immunosuppression -limus)

1-6 month = latent (e.g. CMV) or opportunistic (e.g. aspergillus, which the ischemic tissue in the airway predisposes them to)

Rejection

Transplant HLA match doesn't need to be complete?

  • Hyperacute rejection: preformed antibodies against donor antigens e.g. ABO mismatch, HLA haplotype matching (100 antigens tested to avoid pre-sensitized match) - 'virtual crossmatch' . Tested with PRA (panel rejection antibodies)
  • Acute cellular rejection. T-cell mediated by antigen presentation. FEV1 drop (10% from best baseline), dx with TBBx. BAL should be mostly macrophages. Lymphocytes in perivascular spaces. If neutrophilic = needs workup For infections etc.
  • Chronic rejection - bronchiolitis obliterates syndrome now part of an umbrella of CLAD - chronic lung allograft dysfunction. Also includes restrictive allograft syndrome (RAS - often upper lobe pleural changes - much faster progression) . Dx by PFTs, CT can support. FEF 25-75 particularly useful ('mid flow')

B-cell component? (Antibody humoral mediated/ AMR). Need antibody/antigen complexes in the graft. Controversial how much this occurs. DSA would also indicate (if ab present at transplant, it would be PRA. If developed after transplant, DSA).

GERD can predispose to non-alloimmune (e.g. not HLA mediated) rejection.

Malignancies generally (esp invasive SCC), and specifically PTLD (esp if EBV+ donor, EBV-):

  • B-cell lymphoma driven by EBV (usually) and immunosuppression
  • presents with 'intussusception' (gut), effusion?, nodules in the lung.
  • EBV PCR, highest risk EBV+(donor)/EBV-(recipe) based on IgG serologies at time of transplantation.
  • tx w reduced immune suppression and std. cancer treatment (e.g. ritux)