The first human lung transplantation was performed by Dr. James Hardy at the University of Mississippi in 1963, followed by more than 40 unsuccessful cases over the next 20 years. 1983 saw the beginning of modern lung transplantation when Dr. Cooper at the University of Toronto successfully performed a single-lung transplant on a patient with pulmonary fibrosis who survived for more than 6.5 years, and now more than 20,000 clinical lung transplants have been performed worldwide. Many patients have survived long term and have a good quality of life after lung transplantation.
Lung transplantation related knowledge
1. What is lung transplantation? Lung transplantation is also commonly known as lung replacement.
The lung is the organ that provides oxygen to the whole body. There is no part of our body that can survive without oxygen. The function of the lung includes ventilation and gas exchange: ventilation means to inhale oxygen from the air into the alveoli and exhale carbon dioxide from the alveoli; gas exchange means to absorb oxygen from the alveoli into the blood for distribution throughout the body and to exchange carbon dioxide from the blood into the alveoli. Impairment of either ventilation or ventilatory function can lead to a decline in lung function.
When a person’s lung function progressively decreases to a certain level, it will seriously affect his mobility, even requiring oxygen to sustain life, and at any time, the condition can suddenly deteriorate and become life-threatening due to factors such as infection. In this case, only lung transplantation can save his life.
2. Which patients need lung transplantation?
Patients with benign end-stage lung diseases:
① emphysema, chronic asthma, bronchiectasis
② diffuse bronchiectasis
Pulmonary fibrosis, interstitial lung disease (including infections and drugs) from various causes
interstitial lung lesions, lymphangioleiomyomatosis, protein deposition, etc.)
①Various occupational lung diseases (silicosis, etc.)
②Pulmonary arterial hypertension, primary or secondary
③Nodular disease
④ systemic autoimmune diseases (scleroderma, etc.) causing lung damage
Most patients with bronchoalveolar cell carcinoma die from respiratory failure caused by reduced gas exchange area in the distal airway obstruction lung, which is also one of the indications for lung transplantation if medication is ineffective.
3. Which patients can be lung transplant?
(1) Patients with various symptoms, irreversible, progressive exacerbation, other treatments
(1) Patients with various end-stage lung diseases that are irreversible, progressive, and ineffective with other treatments.
(2) Life-threatening complications, such as pneumothorax and hemoptysis.
(3) No malignant neoplasm, no important organ disease such as heart, liver or kidney within 5 years; (except for fine bronchoalveolar cell carcinoma and cutaneous basal cell carcinoma, except for lung, kidney and lung-liver transplantation in the same period)
(4) Significant limitation of normal life, or oxygen dependence, but can walk.
(5) Normal mental status, able to cooperate with treatment.
(6) Nutritional status can tolerate surgery and has potential for recovery;
(7) Generally, age <65 years for single-lung transplantation and <60 years for double-lung transplantation.
4. Which patients cannot receive lung transplantation?
(1) Acute extra-pulmonary infections.
(2) Those with prohibited immunosuppressive agents.
(3) Poor liver and kidney function: creatinine clearance < 50 mg/ml/min, HIV (+), HBV-Ag (+), HVC-Ag (+), and liver biopsy confirmed liver fibrosis.
(4) Very poor general condition.
(5) Other organ failure
5. Single or double lung transplantation?
Patients who need lung transplantation have poor function of both lungs. Single lung transplantation means that one of the lungs is removed and replaced with a new lung, usually the lung with relatively poor function is chosen. However, in infectious end-stage lung disease, systemic immunosuppression after single-lung transplantation will lead to the spread of infection in the other autologous lung, which is often fatal, and therefore must receive a double-lung transplant, in which both infected lungs are removed and replaced with new lungs.
Even in non-infectious disease, there are cases where a double lung transplant is safer, with relatively simple post-operative management and better results. Although the technique of double lung transplantation is more complex, with the development of technology, there is currently no significant difference in the success rate and cost of the procedure compared to single lung transplantation, while the improvement in long-term lung function and long-term survival rates are better than those of single lung transplantation. Therefore, double lung transplantation has almost replaced single lung transplantation in experienced lung transplantation centers abroad.
Indications for double lung transplantation.
(1) Suitable for all patients with single-lung transplantation who are less than 60 years old (age limit can be relaxed appropriately according to the patient’s actual condition). Patients who are relatively young have better results with double lung transplantation.
(2) End-stage infectious lung disease (e.g., cystic fibrosis, diffuse bronchiectasis, etc.).
(3) Severe obstructive lung disease with significant increased pulmonary artery pressure and right heart insufficiency.
(4) Double lung transplantation to help safely get through the procedure when donor quality is poor.
(5) Patients with non-infectious end-stage lung disease with a history of recurrent secondary infections, such as colonization with drug-resistant bacteria (e.g. Burkholderia cepacia, Pseudomonas aeruginosa, etc.) in the lungs, should undergo double lung transplantation.
(6) Patients with primary pulmonary hypertension who receive single lung transplantation have difficult perioperative management, high mortality and only limited improvement in postoperative quality of life, therefore, double lung transplantation is a better choice.
6. What are the results of lung transplantation?
So far, more than 20,000 lung transplants have been performed worldwide, so it is a very mature treatment. It not only prolongs the life of the patient, but also greatly improves the quality of life. Overall, the success rate of the surgery can reach over 90%, the 3- and 5-year survival rates can reach over 70% and 60%, and most patients can return to normal work after surgery. With the update of anti-rejection drugs, long-term survival after lung transplantation is increasing. Thus, lung transplantation has become a safe and effective treatment for benign end-stage lung disease. Post-transplant complications including infection and rejection have been well prevented and treated with effective drugs. However, strict postoperative follow-up and close patient cooperation are very important to reduce these complications and improve outcomes
Clinical lung transplantation
1. Donor selection.
Age <55 years; no history of lung disease; normal chest radiograph; normal alveolar gas exchange (pao2>=300mmHg when fio2=1, 0 and peep=5cmh20); normal bronchoscopy; negative hepatitis B index and HIV negative; ABO blood type consistent with the recipient; donor lung size compatible with the recipient. Due to the shortage of donors, the current criteria for foreign donors have been relaxed, and marginal donors, living lung lobe donors, splitting the whole lung into upper and lower lobe donors and cardiac arrest lung donors have all been used clinically.
2, Recipient selection.
A: COPD
3, waiting for donor lung
BODE INDEX>5 can be included in the waiting list for donor lung.
4.Transplantation pointer
BODE INDEX 7-10 with at least one of the following on the transplant list: CO2 over 50 mmhg during hospitalization; pulmonary hypertension or pulmonary heart disease; FEV1<20%,dlco<20%< span="">with diffuse emphysema.
B: Cystic fibrosis and bronchiectasis
Waiting for donor lung
1: FEV1 <30%, or rapid decline in fev1, especially in young women. < span="">
2: Deterioration with shortness of breath requiring ICU treatment.
3: Deterioration and shortness of breath requiring antibiotic therapy.
4: Difficult to control as well as recurrent pneumothorax.
5: Recurrent coughing of blood that remains uncontrolled after embolization therapy.
Pointers for transplantation.
1: Respiratory failure after deoxygenation
2: Hypercapnia
3: pulmonary hypertension
C: idiopathic pulmonary fibrosis and non-specific interstitial pneumonia
Awaiting donor lung.
Histologically or biopsy confirmed idiopathic pulmonary fibrosis and non-specific interstitial pneumonia
Guidelines for idiopathic pulmonary fibrosis transplantation.
1: DLC0 <39%< span="">
2: FVC decline of more than 10% within 6 months
3: SO2 after 6-minute walk test: 88%
4: Pulmonary honeycomb-like changes on HRCT
Pointers for non-specific interstitial pneumonia transplantation.
1: DLCO <35%< span="">
2: 10% decrease in FVC or 15% decrease in DLCO within the last 6 months
D:Primary pulmonary hypertension
Awaiting donor lung
1: New York cardiac function class 3-4.
2: Rapid disease progression.
Pointers for transplantation
1: Sustained New York cardiac function grade 3-4 under optimal therapy
2: 6 minute walk test << span="">350m
3: Failure of intravenous drug administration
4: Cardiac index << span="">2
5: Right atrial pressure exceeding 15mmhg.
3. Surgical approach
The anterolateral incision is usually chosen for single-lung transplantation, and bilateral anterolateral incisions with or without sternal transection can be chosen for double-lung transplantation.
The surgery is divided into double lung transplantation, single lung transplantation and lobar transplantation.
The application of CBP and ECMO: CPB is generally not required for adult single-lung transplantation, CPB is used for overall double-lung transplantation, and CPB is used for sequential double-lung transplantation depending on the specific situation. pediatric lung transplantation and lobar transplantation are done under CPB. indications for CPB are: ① hypercapnia and acidosis cannot be corrected with drugs; ② PaO2 <6 or 7 kpa ( 50 mmhg; ③ circulatory instability or surgical malpractice, etc. cpb can be performed via the femoral artery, or via aortic and right atrial cannulation in the case of right lung transplantation. It should be considered in patients with early graft loss, severe respiratory failure and cardiac insufficiency after lung transplantation.
4. Immunosuppression
Immunosuppression in lung transplantation is by and large the standard triplet regimen of cyclosporine A (CsA), azathioprine and corticosteroids. When tacrolimus (FK506) and mycophenolate mofetil (MMF) have been used in lung transplantation, the standard regimen has toxicity, ineffectiveness, rejection, relapse, or the presence of fine bronchial obstruction syndrome when using these drugs as second or third line drugs. Sirolimus, ravamycin, everolimus and leflunomide are also in clinical use but no reliable reports are available.
5.Lung transplantation cost
Generally speaking, the total cost of lung transplantation during hospitalization is 200,000-300,000 RMB, and the postoperative period requires long-term anti-rejection medication, which varies according to the variety of drugs. However, with the localization of the drugs and the gradual downward adjustment of the doses taken, the cost will gradually decrease. Patients with real financial difficulties should contact us as soon as possible, and we will provide humanitarian help through various channels as we can.
6. Factors affecting the success or failure of lung transplantation
A: Donor shortage Currently, the waiting time for a donor in the United States is about 18-24 months, and about 16% of patients die of exacerbation while waiting for a donor.
B: Ischemia-reperfusion injury Severe ischemia-reperfusion injury occurs in approximately 15% of lung transplant recipients clinically, typified by noncardiogenic pulmonary edema, occurring within 12 hours of lung transplantation. It is the most common cause of early death and prolonged ICU. Once it occurs protective ventilatory support, aggressive diuresis and inhaled NO can be used, and ECMO is used in emergency situations.
C:Acute rejection The gold standard for the diagnosis of acute rejection is histological examination of lung parenchyma obtained from multiple bronchial biopsies. The pathology of acute rejection is characterized by perivascular lymphocytic infiltration. Fibronectomy biopsy has been shown to be effective and safe. Fibrinoscopy can be routinely performed 2 weeks after transplantation and repeated at 1, 2, 3, 6, and 12 months postoperatively, and 2 weeks after treatment for acute rejection to assess treatment efficacy. The treatment of acute rejection depends mainly on the severity of the disease, whether it is recurrent or not and the condition of the patient. The classical treatment is high-dose hormone shock therapy, usually for 3 days, and then gradually reduced according to the situation.
D: Infection Bacterial infections in the early post-transplant period are the most common and the main cause of death during this period. The organs most commonly involved are those of the transplant donor. Infections account for 25% of deaths in adult lung transplants and 53.4% of deaths in living lung lobar transplants. Cytomegalovirus (CMV) disease is the most common postoperative infectious complication, with a reported infection rate of 13-15% in transplant patients, and the risk of infection is highest in recipient CMV-negative and donor CMV-positive lung transplants, while it is usually not seen in transplants that are negative for both recipient and donor. Prophylactic therapy is used in high-risk patients with severe life-threatening conditions, with ganciclovir (5 mg/kg) routinely given intravenously daily for 12 weeks as prophylaxis, usually starting 7-14 days after transplantation. Fungal infections can occur in the early and late post-transplant period. Candida albicans is often seen alone after transplantation and usually presents as a local and systemic infection. In patients with single-lung transplants who have autologous lungs with Aspergillus, Candida infections can be treated with a combination of systemic and inhaled amphotericin and Daflucan. Long-term continuous treatment is required for all fungal infections.
E:Bronchial obstruction syndrome (BOS) BOS is the leading cause of death in adult lung transplantation. After survival beyond 1 year, more than 80% of deaths are of pulmonary origin, 30% of which are due to bronchial obstruction. many patients fail to recover from pulmonary infections due to severe airway obstruction or as a result of immunosuppression associated with the treatment of BOS, and restrictions on the treatment of BOS are changing the choice of immunosuppressive drugs. bOS is an accumulation of immune-mediated processes that are caused by chronic rejection of BOS. 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 predates the progression of BOS, so purposeful early intervention to improve immune tolerance is the most promising approach to mitigate chronic rejection.
The whole process of lung transplantation
(1) You should consult about lung transplantation as early as possible when your respiratory function has significantly decreased and has significantly affected your quality of life.
(2) If your condition meets the indication for lung transplantation, you will be scheduled for necessary tests, which include: pulmonary function measurements, blood gas analysis, cardiac ultrasound, X-ray, and blood tests, which can be completed and results obtained within 1-2 days. Those with severe disease will be accompanied by a dedicated lung transplant team to complete them. There are two possible outcomes of the evaluation: early lung transplantation or no lung transplantation for the time being. If the latter is the case, we will develop an appropriate treatment plan to improve quality of life and delay lung transplantation as much as possible.
(3) If the patient requires a lung transplant at the earliest possible date, the patient will be placed on a waiting list for a donor lung. Prior to this, the patient and family should meet with the head of the lung transplant team, Professor Gao Chengxin, and you have the right to be informed of all the circumstances and to complete all signatures regarding surgery and other tests prior to treatment on a completely voluntary basis. Provide contact details to ensure that you can be contacted at any time.
(4) After entering the waiting list, i.e. before the surgery. This includes the necessary tests, medication during the waiting process, nutritional support, an exercise program designed to improve post-operative recovery potential, and counseling on pre- and post-operative lung transplantation. An individualized program will be developed based on the condition, with regular follow-up visits and timely adjustments. Patients who have been waiting longer than 6 months must receive an updated evaluation.
(5) With a suitable donor lung, we will decide on the recipient patient based on blood type, severity of disease, waiting time, and donor size, and notify the recipient patient as soon as possible. Patients have a green channel to be admitted in the shortest possible time and complete the hospitalization procedures. After completing the preoperative preparation, depending on the arrival time of the donor, the patient is admitted to the operating room 2-3 hours earlier, and after the operation, he/she is admitted to the intensive care unit, and after the condition is stabilized, he/she is admitted to the ward care unit and then transferred to the general ward. If no serious complications or other conditions occur, the patient is usually discharged from the hospital 2-3 weeks after surgery.