What Factors Affect Lung Transplant Survival?

Chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), pulmonary cystic fibrosis, -1 antitrypsin deficiency, and idiopathic pulmonary hypertension, these diseases account for 85% of the entire lung transplant disease spectrum. The remaining 15% consist of relatively small amounts of diseases such as sarcoidosis and pulmonary lymphangioleiomyomatosis. Over the past 15 years, with the gradual maturation of lung transplantation technology, donor preservation, and perioperative management, the one-year survival rate of lung transplantation has increased from 70% to 85% in the past.

Pan Xufeng	(Attending physician)	Department of Thoracic Surgery, Shanghai Chest Hospital
Shi Jianxin	(Deputy Chief Physician)	Department of Thoracic Surgery, Shanghai Chest Hospital
Zhao Yan	(Chief physician)	Department of Thoracic Surgery, Shanghai Chest Hospital

Chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), pulmonary cystic fibrosis, -1 antitrypsin deficiency, and idiopathic pulmonary hypertension. These diseases account for 85% of the entire lung transplantation disease spectrum. The remaining 15% consist of relatively small amounts of diseases such as sarcoidosis and pulmonary lymphangioleiomyomatosis. Over the past 15 years, with the gradual maturation of lung transplantation technology, donor preservation, and perioperative management, the one-year survival rate of lung transplantation has increased from 70% to 85% in the past.

Types of lung transplant diseases

Mainly: chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), pulmonary cystic fibrosis, -1 antitrypsin deficiency, idiopathic pulmonary hypertension, these diseases account for the entire lung transplantation disease spectrum 85%. The remaining 15% consist of relatively small amounts of diseases such as sarcoidosis and pulmonary lymphangioleiomyomatosis. The International Heart and Lung Transplant Association registered more than 23,000 patients in more than 100 transplant centers around the world. According to the 2009 registration report, the median survival time for lung transplant patients was about 5.4 years, of which the median for double lung transplantation was Survival time was better than single lung transplantation (6.6 years vs 4.6 years).

Indications for lung transplant surgery

The general indications for lung transplant recipients are: severely impaired function in end-stage benign lung disease, ineffective medical medicine and general surgical treatment, severely restricted daily activities, life expectancy of only 1-2 years, and no other important organ functions Exhaustion. The recipient selection criteria jointly developed by the American Thoracic Surgery Association and the International Heart and Lung Transplantation Association are: suitable age (see below): 55-year-old heart-lung transplantation, 65-year single-lung transplantation, 60-year double-lung transplantation; serious clinical and physiological functions; Drug treatment is ineffective or lacking; life expectancy is limited; ideal nutritional status; socio-psychological status and emotional control are satisfactory ^[1] .

Indications for inclusion in the lung transplant list

Indications for inclusion in the lung transplant list
Disease name	Lung function	Arterial blood gas	other
Emphysema	FEV1 <25% of expected value	PCO2> 55 mm Hg and PO2 <60 mm Hg	pulmonary hypertension
Pulmonary cystic fibrosis	FEV1 <25% of expected value	PCO2> 55 mm Hg and PO2 <60 mm Hg	Frequent hospitalization
Idiopathic pulmonary fibrosis	FVC <60% of expected value; DLCO <60% of expected value; FVC or DLCO decreased by more than 10% during the follow-up in the past 6 months	Hypoxia after activity	Ineffective medical treatment
pulmonary hypertension			Pulmonary hypertension remains grade - after drug control

Contraindications to lung transplantation

Uncontrolled lung or extrapulmonary infections; a history of malignancy in the past two years; severe dysfunction of other important organs; severe coronary artery disease or heart failure; severe chest or spinal deformity; no smoking cessation; medication or Alcohol dependence; unresolved mental illness or inability to cooperate with treatment; HIV infection; active hepatitis B or C.

Lung transplant surgery

There are four types of surgical methods for lung transplantation: single lung transplantation, double lung transplantation, heart and lung transplantation, and living lung transplantation. The choice of surgical method is affected by many factors, including the recipient's disease, age, severity of the condition, the experience of the transplant center, and the scarcity of the donor. Patients with idiopathic pulmonary hypertension have relatively difficult perioperative management after single lung transplantation. Therefore, many people have advocated double lung transplantation or combined heart-lung transplantation. For infectious diseases such as pulmonary cystic fibrosis and bronchiectasis, double lung transplantation is currently advocated, because the autologous lung on the other side is a very serious source of infection, which can cause damage to the donor lung and the quality of life after transplant Serious impact. In recent years, the proportion of double lung transplantation has gradually increased. The increasing perioperative experience and the good prognosis and quality of life of patients have made single lung transplantation the most popular method of lung transplantation.

Lung transplant skin incision selection

For bilateral lung transplantation, bilateral anterolateral incisions and chamshell incisions (that is, bilateral anterolateral thoracotomy and transection of the sternum) are common. Common lung incisions include anterolateral or posterolateral incisions.

Lung Transplant Immunization Program

Rejection between the graft and the host is one of the main problems facing lung transplantation. In order to reduce the graft-to-host immune response, all lung transplant patients need to take immunosuppressants for life. The immunosuppression schemes we currently use mainly include immune induction and immune maintenance. Standard immune induction protocols include rabbit or horse anti-thymocyte immunoglobulin (ATG) and mouse monoclonal anti-CD-3 cell antibody (OKT3). Recently, the application of antibodies to the interleukin-2 receptor (daclizumab and basiliximab) has drawn more and more interest. It mainly acts on the chain of the interleukin-2 receptor. Immune maintenance options often include multiple drugs: calmodulin inhibitors (cyclosporine A or FK506), cell cycle inhibitors (azathioprine or know), and hormones.

Common complications of lung transplantation

Lung transplant infection

Infection is the most important complication in the early post-transplant period and the most common cause of perioperative death. Bacterial infection is the most important cause of perioperative disease. Candida, mold, herpes simplex virus and cytomegalovirus are common. Broad-spectrum antibiotics are routinely used during the perioperative period. The choice of antibiotics usually requires coverage of possible pathogens in the donor and recipient. Antibiotics are usually used empirically before the susceptibility results are available, and adjustments should be made accordingly after the susceptibility results are available. If mold or Candida albicans are isolated from early secretion specimens, even if there is no evidence of invasion or spread, preventative medication should be considered. Fluconazole 100-200mg is administered orally or intravenously once a day to prevent Candida infection. Itraconazole 200mg orally twice daily or aerosolized 10-15mg amphotericin to prevent Aspergillus infection. CMV virus infection is most likely to occur when the donor CMV antibody is positive and the recipient CMV antibody is negative. For RCMV- / DCMV + patients, valganciclovir is routinely applied for 6 months to prevent viral infection, and for RCMV +, valganciclovir is used for 3-6 months.

Lung transplantation ischemia-reperfusion injury

Ischemic reperfusion injury is a type of acute lung injury, accompanied by alveolar destruction and increased vascular permeability. The early incidence rate after transplantation is 10-15%. Moderate to severe ischemia-reperfusion injury is usually accompanied by impaired oxygenation, decreased pulmonary compliance, increased pulmonary arterial pressure, and chest radiograph. Ischemia-reperfusion injury is the main cause of primary graft failure. The International Heart and Lung Transplant Association's recommendations for grading primary graft dysfunction are as follows:

Grade 0- PaO2 / FiO2> 300 and normal imaging

Grade 1- PaO2 / FiO2> 300 and there are scattered infiltration shadows on the chest radiograph

Grade 2- PaO2 / FiO2 between 200-300

Grade 3- PaO2 / FiO2 <200

Compared with low graft dysfunction, Grade 3 graft dysfunction has been reported to be associated with an increased mortality within 90 days after surgery (17% vs 9%). The risk factors for Grade 3 graft dysfunction include overage of the donor, smoking history of the donor over 200 years old, recipient pulmonary hypertension, and primary transplantation disease.

Airway complications of lung transplantation

Complications of the bronchial anastomosis include stenosis, rupture, and softening of the trachea. Anastomotic stenosis is the most common complication. Airway complications are one of the main complications and the leading cause of death after lung transplantation. Poor blood supply to the donor bronchus is one of the important causes of airway complications, but in terms of current transplantation techniques, it is possible to avoid donor bronchial ischemia without having to perform bronchial artery reconstruction. The donor bronchial blood supply depends on the pulmonary artery blood supply within a few days after operation. Shortening the length of the donor bronchus can reduce the possibility of postoperative bronchial ischemia. Generally, we require the donor bronchus to be broken at two levels at the upper lobe opening The proximal main bronchus of the cartilage ring can effectively reduce the ischemic part of the donor bronchus and greatly reduce the probability of airway complications. Airway complications can be diagnosed through a series of methods. Monitoring of the anastomosis after routine application of bronchoscopy can detect airway complications early. Occasionally, CT examination can also find airway stenosis and rupture for some other reasons. And other complications, actually in clinical work we found that CT is very useful for diagnosing and evaluating airway complications. Airway stenosis is usually accompanied by dyspnea, wheezing, and a decrease in FEV1, and bronchoscopy can make a clear diagnosis. In the normal bronchial anastomosis, complete anastomotic sutures and intact epithelium can be seen. Occasionally, superficial necrosis of the epithelium is seen, which generally does not cause any problems. Membrane defects generally heal under conservative treatment, while cartilage defects usually cause late airway stenosis. Severe bronchial rupture (greater than 50% circumference) generally requires some intervention to ensure the integrity and patency of the airway. Occasionally, severe rupture causes the bronchial cavity to communicate with the pleural cavity, resulting in pneumothorax and severe air leaks. If the lungs are fully expanded and the chest cavity is fully drained, the fistula will eventually heal and generally there will be no stenosis. There is also a severe mediastinal emphysema caused by bronchial rupture that directly communicates with the mediastinum. If the lungs are fully dilated, a mediastinal drainage tube can be placed at the anastomotic opening through a mediastinoscopy, which usually also results in satisfactory healing of the muzzle without leaving a narrow. It has been reported in the literature that the incidence of anastomotic dehiscence in patients receiving early transplantation with rapamycin is high. Therefore, early application of rapamycin after transplantation requires caution. After lung transplantation, the anastomotic stoma is prone to fungal infection due to ischemia and other reasons. Candida albicans and Aspergillus are potential pathogens that can cause fatal infections at the anastomosis. Nunley et al. Counted 61 patients with bronchial anastomotic fungal infection and found that most of the infection was caused by Aspergillus. After anastomotic fungal infection, the probability of airway stenosis was 46.7%, which was significantly higher than that of the fungal-free group. Specific anastomotic complications following a fungal infection include bronchoconstriction, bronchomegaly, and major bleeding. Endotracheal stent, balloon dilatation, electrocautery, laser, etc. play a role in the management of airway complications. If there is a false membrane in the anastomosis of the bronchoscopy, a biopsy should be performed immediately to eliminate the fungal infection. Once the diagnosis is made, systemic and local nebulized antifungal drugs are usually used. Nebulized antifungal drugs can directly reach the lesion.

Acute rejection of lung transplantation

Acute rejection is a very important problem in the development of lung transplantation. It was a very difficult and often fatal problem in the 1960s and 1970s. It was not until the emergence of cyclosporine that the incidence of acute rejection after transplantation was greatly reduced, and this also directly made the success of human lung transplantation in the 1980s possible. However, despite the continuous development of immunosuppressive drugs, acute rejection occurs from time to time in clinical work.

Acute rejection usually has the highest probability in the first few months after lung transplantation, and the probability gradually decreases over time. Acute rejection is an inflammation of the blood vessels and airways surrounding lymphocytes. At present, acute rejection (especially recurrent acute rejection) is a risk factor for chronic obstructive bronchiolitis. The role of humoral immunity in acute rejection is still controversial, and some evidence shows that capillary inflammation is a humoral immune mediator. Therefore, anti-HLA antibodies may play a very important role in the middle. Antibody-mediated rejection is not effective for hormone therapy, and often requires some other treatments: plasma exchange, intravenous gamma globulin, and rituximab.

The clinical manifestations of acute rejection are not specific. The main symptoms include low fever, shortness of breath, cough, hypoxia, leukocytosis, and decreased lung function. Imaging findings: Infiltrates around the hilum, pulmonary interstitial edema, and thoracic exudation are early manifestations of acute rejection, but they are not specific. It is very difficult to distinguish acute rejection from pulmonary infections based on clinical manifestations, but it is also important to make timely and accurate judgments because the treatment methods of the two are completely different. Acute rejection that occurs late in transplantation has no specific manifestations in imaging. Many transplant centers recommend that patients use a family pulmonary function monitor to monitor graft function after discharge. Once the graft function is stable, the daily measurement data will vary by 5% However, a decrease of FEV1 and FVC by more than 10% over two days indicates the possibility of infection or rejection. The diagnosis of graft rejection after lung transplantation also needs to be combined with bronchoscopy biopsy. We recommend that patients undergo routine transbronchoscopic lung biopsy in January, March, June, December, 18, and 24 months after surgery. When patients with infection or rejection symptoms appear after transplantation, many clinical lung transplantation centers use bronchoscopy for alveolar lavage or bronchoscopic lung biopsy to further distinguish and confirm that the specificity of this invasive examination is about 69% about. Biopsy generally requires 3-5 good tissue blocks. Generally, for patients with double lung transplantation and cardiopulmonary transplantation, only the transplanted lung on the biopsy side is required, but the location of the biopsy usually chooses different lung lobes and lung segments .

For the treatment of acute rejection, a large dose of hormonal shock is usually used, 500 mg-1000 mg / day of methylprednisolone, for three consecutive days. Clinical symptoms usually resolve after 24-48 hours of administration, and lung function returns to baseline levels within a few weeks. Prednisone was then changed to 0.5 mg-1 mg / kg / day, and after a few weeks it was changed to oral administration. There is still no standard treatment plan for persistent or repetitive acute rejection, but there are also some related reports such as: once again high-dose hormone shock, cyclosporine changed to tacrolimus, azathioprine changed to know, Cyclosporine nebulization, methotrexate treatment, anti-lymphocyte globulin (OKT3, ATGAM, etc.).

Chronic rejection of lung transplantation

Chronic rejection is the most important factor affecting the long-term survival of patients after lung transplantation. Chronic rejection is mainly divided into chronic vascular rejection and chronic airway rejection. Chronic vascular rejection is a relatively small manifestation of chronic rejection, which is manifested as pulmonary sclerosis. Chronic airway rejection is a relatively common condition that manifests histologically as obstructive bronchiolitis (OB). Obstructive bronchiolitis is very common after lung transplantation. Early pathological manifestations include submucosal lymphocyte inflammation and rupture of small airway epithelium, followed by fibrous mucoid granulation tissue hyperplasia and obstruction of the airway lumen.

There is still controversy about the etiology of OB. At present, there are several possible causes: acute rejection, chronic rejection, cytomegalovirus infection, primary graft failure, gastroesophageal reflux, and type of lung transplantation.

Clinical manifestations: OB-related clinical symptoms are non-specific, irritating dry cough often occurs early in the disease, dyspnea after activity, imaging findings are normal, pulmonary function tests show obstructive changes, especially the decrease in medium-term flow rate, and sputum test results ( -), No abnormal signs in the lungs. In the late stage of the disease, cough and sputum often occur, and imaging shows excessive inflation or dilatation. Pulmonary function shows severe obstructive ventilation disorder. Pseudomonas aeruginosa can be seen on sputum examination, and abnormal signs in the lung can be heard ^[2] .

The BOS classification is as follows

Classification of occlusive bronchiolitis syndrome (2002)
BOS 0	FEV1> 90% baseline value and FEF 25% -75%> 75% baseline value
BOS 0P	FEV1 is between 81-90% of baseline and FEF 25% -75% 75% of baseline
BOS 1	FEV1 is between 66-80% of baseline
BOS 2	FEV1 is between 51-65% of the baseline
BOS 3	FEV1 50% of baseline value

There are several methods for the treatment of OB: such as changing immunosuppressive agents, external light therapy, whole body lymphoid tissue irradiation, plasma exchange, inhalation of cyclosporine, etc., but so far there is no very effective method to treat and reverse OB . At present, the best advice for OB after lung transplantation is prevention-oriented, especially to strengthen immunosuppression early to reduce the degree of acute rejection.

Prognosis of lung transplantation

Over the past 15 years, with the gradual maturation of lung transplantation technology, donor preservation, and perioperative management, the one-year survival rate of lung transplantation has increased from 70% to 85% in the past. However, the long-term survival rate has not improved significantly, which also indicates that the main problem facing lung transplantation is the biological incompatibility between the recipient and the donor. In the first year after transplantation, infection is the leading cause of death, and recipients are at high risk of infection from bacteria, fungi, viruses, and protozoa. Acute infection is relatively rare after one year of transplantation. The main cause of death after one year of transplantation is coexisting chronic rejection, infection and other complications.

Survival time after lung transplantation
disease	1 year survival (%)	3 years survival (%)
Primary pulmonary hypertension	74.2	59.9
Pulmonary cystic fibrosis	82.0	64.7
Idiopathic pulmonary fibrosis	71.2	55.9
-1 antitrypsin deficiency	73.5	60.3
Emphysema (COPD)	83.7	65.2

Precautions after lung transplantation

Closely monitor the concentration of FK506 and inform the doctor in the transplant group.

Closely monitor liver and kidney function, blood routine, and pay attention to the side effects of immunosuppressants.

Follow up the chest radiograph, chest CT, lung function, bronchoscopy, 6-minute walking experiment, blood gas, cardiac ultrasound, bone density, etc. strictly according to the doctor's requirements.

Pay attention to prevent infection and pay attention to details of life:

Lung transplant environment

1. Keep your living environment clean and tidy.

2. Don't work or visit any building or decoration site and facilities. Dust is very harmful. Wear a mask if you have to be in such a place.

Lung transplant exercise and activity

1. Avoid raising flowers and grass in the garden in the first year after transplantation. After one year, gloves and masks can be used to plant flowers. When mowing in the courtyard, stay indoors.

2. Pay attention to exercise. Walking helps to expand the lungs and increase physical fitness. Please inform your doctor and get their permission before attempting any heavy exercise.

3. Avoid close contact with pets. Don't add new pets at home, especially birds. Ask family and friends to help clean up and avoid dust.

4. Do not go to work or school without your doctor's permission.

Lung transplant diet

1. Healthy diet structure to ensure the intake of various nutrients. Adequate nutrition can help the body prevent various infections.

2. Drink plenty of water. Water, fruit juice and various sports drinks are all good.

Lung transplant daily hygiene

1. Wash your hands frequently with soap and warm water, especially before eating, after washing and contact with contaminated items.

2. Take a bath every day to maintain personal hygiene.

Lung Transplant Oral Hygiene

1. Check your mouth and gums daily. Tell your doctor if you find your gums swollen for more than two days. (Gum swelling may be a side effect of infection or immunosuppressive drugs, especially cyclosporine).

2. Always clean your teeth and gums after three meals. Use small, soft-bristled toothbrushes and fluoride toothpaste.

3. Use dental floss daily to remove foreign objects from the teeth.

4. Keep your teeth clean and comfortable.

Lung transplant visitor

1. Restrict visitors.

2. If the visitor has symptoms of cold or flu, please come back after healed.

Lung transplant wound management

Keep the skin clean and intact. Do not scratch or scratch it to prevent infection. If you accidentally cut your skin, clean it with water, soap, and hydrogen peroxide. Dry the damaged wound and cover it with sterile gauze or a band-aid.

Remaining considerations for lung transplantation

1. Take your temperature daily. Tell your doctor if it exceeds 37.8 ° C, it may be an early manifestation of the infection.

2. Check the neck, armpits, and groin area for lumps. Tell your doctor if you find something abnormal.

3. Pneumonia vaccine can be injected, and influenza vaccine can be given every year.

4. Female patients undergo breast examinations monthly. Female patients must undergo pelvic examinations on a regular basis.

5. Male patients undergo prostate examinations and prostate-specific antigen (PSA) examinations annually.