The Main Obstacles To Success

There are many challenges to the further development of clinical lung transplantation: donor shortage, high mortality in waiting, reperfusion injury, acute rejection, infection, and BOS.

1. Donor shortages and waiting death rates

At most lung transplant centers in the United States, the time to register for a lung transplant is 18-24 months. Recent data show that 16% of patients awaiting lung transplantation die while waiting for donor procedures compared with 12% and 7% for liver and kidney transplants, respectively. The maximum lung preservation time is still unknown. The Toronto Lung Transplant Group reported that when the donor's lung mass is good, the time of pulmonary cold ischemia has reached 12 hours. Many large lung transplant centers in the world are remotely located. Other transplant groups receive Both body and marginal lung donors have been used and there is no difference in 1-year and 5-year survival rates between long-term acquisition and other groups. Borderline lung donors are generally not used for single lung transplant recipients, and marginal lungs, especially emphysematous patients, can be used without hesitation in dual lung transplantation.

2. ischemia-reperfusion injury

Approximately 15% of lung transplant recipients experience clinically severe ischemia-reperfusion injury (I / R I). I / R I non-cardiopulmonary edema as a typical manifestation occurred in 12 hours after lung transplantation. It is the most common cause of early death and long-term ICU. Patients with I / R I use protective ventilator support, active diuresis and inhaled NO. Available in emergency situations ECMO. ECMO was used in 12 patients at B-J Hospital in Washington, DC, and 7 patients survived. ECMO was started within 24 hours after transplantation in all 7 patients before irreversible lung injury occurred.

3. acute rejection

Although the dose and drug concentration levels of immunosuppression in lung transplantation outnumber those of other essential organ transplants, a biopsy confirmed the rate of acute rejection of one year after lung transplantation as high as 80%. The gold standard for the diagnosis of acute rejection is the histological examination of the lung parenchyma obtained from multiple bronchial biopsies. The pathological feature of acute rejection is perivascular lymphocyte infiltration. Fiber-optic biopsy has proven to be effective and safe. Two weeks after transplantation, a routine broncho-fibrous copy can be performed and rechecked at 1, 2, 3, 6 and 12 months after surgery. Fiberoptic bronchoscopy was performed 2 weeks after the acute rejection treatment to evaluate the therapeutic effect.The treatment of acute rejection is based on the severity of the disease, relapse, and the patient's condition. The typical treatment is an intravenous administration of methylprednisolone (20 mg/kg) three days prior to the maintenance dose. Lymphocyte monoclonal antibodies (eg, ATGAM, OKT3) are used for relapse and refractory rejection.

4. infection

Early bacterial infection after transplantation is the most common and is the leading cause of death during this period. The most commonly involved organs are those that are transplanted. In adult lung transplants, infection accounts for 25% of all deaths, while living lobular infections account for 53.4% of deaths.Cytomegalovirus (CMV) disease is the most common postoperative infectious complication, with a reported infection rate of 13-15% in transplant patients. The risk of CMV-negative lung transplant recipients is highest for recipients with CMV negative, Transplants that are negative in both recipients and donors are generally not seen. Prophylactic treatment is given to high-risk, life-threatening patients routinely given ganciclovir (5 mg/kg) intravenously daily for 12 weeks, usually starting 7-14 days after transplantation.
Fungal infections can occur early and late after transplantation. Candida albicans is often found alone after transplantation and usually manifests as localized and systemic infections. Aspergillosis is present in the autologous lung of patients with a single lung transplant. Candida infections can be treated with systemic and inhaled amphotericin and fluconazole. For all fungal infections require long-term continuous treatment.

5. chronic graft loss and bronchial obstruction syndrome (BOS)

Chronic graft failure is a histopathologically clinical pathological syndrome characterized by bronchioles. Clinical manifestations of 3 months after transplantation or longer to rule out the causes of bronchial lung infection progressive severe dyspnea. The incidence of acute rejection in the clinic is positively correlated with CMV pneumonia and positively correlated with the development of BOS. Increased donor age and ischemic time were positively correlated with the development of BOS.
One, three, and five years of lung transplantation without BOS were 85%, 65%, 47%. BOS is the leading cause of death in adult lung transplants. Over 80% of deaths are lung causes after more than 1 year of survival, 30% of which are due to bronchial obstruction, many of whom can not recover from lung infection due to severe obstruction of the airways or to the treatment of BOS As a result of immunosuppression, the limitations of BOS treatment are changing the choice of immunosuppressive drugs. BOS is an accumulation of immune-mediated processes that are caused by chronic rejection. The presence of HLA-I antibodies has been shown to predict the progression of BOS. Further studies have found that the presence of this antibody is earlier than the progress of BOS, so purposeful early intervention to improve immune tolerance is the most promising way to reduce chronic rejection.

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