Observership in UPMC（University of Pittsburgh Medical Center）4/18~4/22
1013568m #80 Nonaka Hideaki
・The outline of lung transplant
Lung transplantation is an important mode of therapy for patients with a variety ofend-stage lung diseases. The most common diseases that lead to lung transplant are
chronic obstructive pulmonary disease, interstitial lung disease, cystic fibrosis, alpha-1
antitrypsin deficiency, and idiopathic pulmonary hypertension.
The qualification for recipient includes consideration of the severity of the underlying
lung disease, likelihood of benefit from lung transplantation, presence of comorbid
diseases, age of the candidate, ability to participate in an exercise program, nutritional
status, psychosocial support and so on. On the other hand, the donor ideally shouldhave good lung function (P/F ratio > about 300, no pulmonary edema on chest
radiograph, and PEEP = about 5 cm H2O).
If these conditions are matched, transplant surgery is scheduled and carried out.
Four types of transplant procedures are generally available.〔1〕Single lungtransplantation (SLT)〔2〕Bilateral lung transplantation (BLT)〔3〕Transplantation of lobes from living related donors〔4〕Heart-lungtransplantation (HLT) . Before perfusion of the transplanted lung, immunosuppression
is begun with loading doses of cyclosporine or azathioprine and methylprednisolone.
Postoperatively, the three-drug maintenance regimen is begun, using cyclosporine or
tacrolimus, azathioprine or mycophenolate mofetil, and prednisone.
Just after the surgery, ischemia-reperfusion injury(IR injury) is the main cause of
primary graft dysfunction. Inhaled nitric oxide (iNO) and extracorporeal membrane
oxygenation (ECMO) may be useful in the management of severe cases of ischemiareperfusion injury.
Lung function improves over the first three to six months after transplant and is thenstable. Transbronchial lung biopsy is a safe and effective method for identifying acuterejection and infection. Routine surveillance transbronchial biopsy is carried out about
once a month for the first three months after transplantation.
After the first year, bronchiolitis obliterans syndrome(BOS) and restrictive allograftsyndrome (RAS) is the main cause of the chronic lung dysfunction. BOS is especiallythe serious complication because the incidence of BOS approaches 50% within 5 yearsof transplant, and survival 5 years after the onset of BOS is only 30%~40%.
・The characteristic problems of lung transplantation
The number of lung transplantation is lower than other organ transplantation
because of its low procurement rates from deceased donors. In fact, Lungs areharvested from only 15 percent of all deceased donors, while kidneys and livers areharvested from 88 percent and hearts from 30 percent of deceased donors. This
disparity is likely due to the lung's vulnerability to potential complications that often
arise before and after donor brain death such as thoracic trauma, aspiration, ventilator
associated lung injury, pneumonia, and lung edema.
Moreover, the survival after lung transplantation is too short compared with otherorgan transplantation. The median survival for all adult recipients is 5.7 years,
whereas the median survival for adult and pediatric heart transplants performed
between 1982 and June 2013 was 11 years. This is because the lung graft is vulnerabile
to the complications such as ARDS, RAS, and BOS.
・ex vivoIn order to improve the quality of thegraft and prevent the complications
such as lung edema and IR injury, exvivo lung perfusion is being explored.
Ex vivo is the devise which create theliving body like environment outside ofthe living body. Actually studies
suggest that ex vivo lung perfusion andreconditioning may ameliorate lung injury in some cases and allow transplantationfrom donors previously deemed unsuitable.
In UPMC, ex vivo is also used for the research of the complications, especially BOS.
BOS is chronic lung allograft dysfunction and is one of the main cause of mortalityafter lung transplant. The researchers try various surgery ways with ex vivo andinjured grafts and check out how the lung cells get injured. If we can find out the way
to cure or prevent this complication, the survival after lung transplant will improveextremely.