Lung transplant

from Wikipedia, the free encyclopedia

The lung transplantation (LTX, Lutx or LTPL) is a form of treatment for advanced lung diseases and is the transplantation of a lung (single lung transplantation), both lungs (bilateral lung transplantation) or only of one or more lung lobes from one organ donor to a receiver. Heart-lung transplantation, i.e. the transplantation of both lungs together with the heart, is only rarely performed today, especially in patients with heart defects  . For several years, is also primarily for tubercular children the possibility of a so-called live-lung transplantation ( English living-related lung transplant ), that is the transplantation of a respective lobe of two living donors to a mostly very young recipients.

history

Since the 1980s, lung transplantation has developed from an experimental technique to an established treatment option for serious diseases of the lungs and pulmonary circulation. This progress was made possible above all by the improved surgical technique and organ preservation, the more precise selection criteria as well as more sophisticated diagnostics, prophylaxis and treatment of rejection reactions and infections. However, the goal of all efforts is still to reduce the incidence and mortality of the so-called bronchiolitis obliterans syndrome (BOS), which still affects the long-term results of lung transplantation the most.

In the 1940s, Russian surgeon Vladimir Demichow performed over 100 experimental heart-lung transplants in dogs without a heart-lung machine or immunosuppression . He was able to show that these transplanted organs could keep the test animals alive for at least a short time. These results were confirmed by Dominique Métras in France in 1950 and Hardin in the USA in 1954. As a result - thanks in particular to the introduction of the heart-lung machine by Webb - James D. Hardy succeeded in 1963 with the first unilateral lung transplant in humans. However, the patient only survived for 18 days. By 1980 a total of 3 heart-lung and 38 single cell transplants had been performed in humans. With the exception of one patient, who survived 10 months, all died within three months. With the introduction of ciclosporin in 1981, a new era in transplant surgery including LTPL began. In March 1981 Bruce Reitz performed the first long-term successful heart-lung transplant in Stanford. The further technical developments in isolated lung transplantation were mainly shaped by the work of Joel Cooper and colleagues in Toronto and later in St. Louis. This group performed the first single lung transplant in 1983, the first en bloc double lung transplant in 1986, and the first sequential bilateral lung transplant in 1989.

In 1993, Stanford Medical Center's Vaughn Starnes became the first surgeon to perform a lung transplant on living relatives. He took one lung each from the father and mother and transplanted them to the 12-year-old daughter.

By mid-2005, more than 18,000 lung transplants had been performed worldwide, around half of which were individual transplants. The mean one- and five-year survival rates worldwide are 70% and 50% respectively. However, individual centers now achieve a five-year survival of around 80%. There are several cases of second, third and even fourth lung transplants in Germany, with patients depending on a new lung donor every five years on average.

Lung transplant centers

Only a few hospitals in Germany can transplant lungs. Most lung transplants are performed at the Hannover Medical School ; in second place is the hospital of the University of Munich .

In Austria, the Vienna General Hospital is a lung transplant center with more than 100 transplants per year. From 1989 to the beginning of 2018, Walter Klepetko was head of the lung transplant program.

There are two centers in Switzerland: the one for German-speaking Switzerland at the University Hospital Zurich (USZ) and the Center Romandie as a cooperation between the two university hospitals in Lausanne ( CHUV ) and Geneva ( HUG ).

The largest childhood and adolescent lung transplant program is located in the United States at St. Louis Children's Hospital in St. Louis, Missouri .

Indications

The indication for LTPL takes place in an advanced stage of a disease of the lungs or the pulmonary circulation , after all conservative treatment options have been exhausted maximum. In this phase, patients suffer even at the slightest exertion, sometimes even at rest with shortness of breath ( dyspnea () NYHA class III-IV). The expected life expectancy without a transplant is then often only about 6 to 18 months. It is of course very difficult to assess this in individual cases and depends above all on the underlying disease. These are mainly the following:

It is known from studies that in COPD, the life expectancy after indication for long-term oxygen therapy, i.e. with an oxygen partial pressure <55 mmHg (<7.3 kPa), and a lung function with an FEV1 of 30 to 40%, the two-year survival rate is still around 80 % is. The situation is completely different with cystic fibrosis , because an LTPL must be considered in these patients with the same values ​​mentioned above. The indication for pulmonary hypertension is also difficult, where, for example, the measured pressure values ​​in the pulmonary circulation do not play a decisive role in determining the indication for LTPL.

A simple but important test to assess general physical limitations is the 6 or 12-minute walk test, in which transplant candidates can usually walk significantly less than 400 or 600 meters.

The upper age limit for a lung transplant is currently around 65 years. More important than the chronological age, however, is the biological age, i.e. the general and nutritional status, the absence of disorders of other organ systems and a stable psychosocial situation. The ideal time for the transplant is therefore often difficult to determine and depends above all on the individual course of the disease. In particular, it is important to capture the moment at which the patient's condition begins to deteriorate rapidly. Important indications for this are a rapid decline in lung function values, increasing use of oxygen, repeated right heart decompensations, frequent exacerbations and hospitalizations, threatened bed rest and, in particular, beginning weight loss despite optimal nutrition.

The term “transplant window” coined by the Stanford Group illustrates very well the importance of these considerations with regard to the fact that the patient is not considered too early, but also not too late, for a possible lung transplant. For many patients , the most important factor in the decision to have a transplant is the severely restricted quality of life , which makes life no longer worth living for them.

Contraindications

Absolute contraindications for LTPL have become rare with medical advances in recent years. These are primarily severe systemic diseases such as sepsis , untreatable blood coagulation disorders , severe general arteriosclerosis or tumors that have not been successfully treated for more than 5 years. Functional disorders of other organs such as chronic kidney failure , liver failure or heart failure are now relative contraindications, since in such patients a combined transplant, for example of the lungs and kidneys, is also possible in selected cases. On the other hand, a transplant is extremely problematic in the case of severe diseases of the nervous system, serious psychiatric illnesses, as well as abuse of drugs, alcohol or nicotine. Unlike in the past, most centers now also perform LTPL in cases in which operations on the thorax have previously been carried out or who have severe adhesions in the chest cavity.

Technology of the LTPL

The type of transplant depends on the underlying disease. Lung diseases associated with chronic infections, such as cystic fibrosis or bronchiectasis, require bilateral LTPL. For all other lung diseases, a single LTPL is theoretically possible, provided that there is no relevant circulatory disorder of the pulmonary vessels with an increase in pulmonary arterial blood pressure ( pulmonary hypertension ). Until recently, it was the method of choice for pulmonary fibrosis or pulmonary emphysema. In recent years, however, it has been shown that transplantation of only one lung often causes problems with the remaining other diseased lungs, such as severe infections. That is why a bilateral LTPL is often carried out in these cases today. This also has the advantage that lung function is significantly better after the transplant. The disadvantage, however, is that an organ donor can only transplant one patient instead of two. A heart-lung transplant is now only necessary for uncorrectable heart defects with Eisenmenger's reaction . This is based on the knowledge gained in recent years that even with severe failure of the right heart due to pulmonary hypertension, it recovers completely within a few days to weeks. The technology of the LTPL is largely standardized today. The opening of the chest cavity is nowadays mostly done through a lateral incision between the 8th and 9th rib. After the diseased lungs have been removed, first the bronchi, then the pulmonary veins with a piece of the auricle, and finally the pulmonary arteries of the donor lung with the corresponding structures at the recipient are connected by a suture. With bilateral LTPL, immediately after transplanting one lung, the other is transplanted using the same technique. It is often even possible to operate without a heart-lung machine, since during the transplantation of the first lung the patient can be adequately supplied with oxygen by ventilating the remaining other diseased lungs, and then ventilating the "new one" while the second lung is being replaced “Donor lung can be done. Usually, however, circulatory support systems such as ECMO ( extracorporeal membrane oxygenation ) are used or kept ready during the operation . If there are no complications, the patients are usually weaned from the ventilator within a few hours and transferred from the intensive care unit to the normal ward after two to three days. As part of intensive medical care, the ECMO and dialysis machines are used as required. This is followed by rapid mobilization under intensive physiotherapeutic care. The total clinical treatment takes about 3 weeks. The course is somewhat delayed, especially in patients with pulmonary hypertension, and complications occur in 10–20% that require a significantly longer stay in the intensive care unit and a longer stay in hospital.

Procedure-specific postoperative complications

In the first few weeks after LTPL, surgical problems such as bleeding, paralysis of the diaphragm, gaping or narrowing of the seams on the bronchi and pulmonary vessels, acute lung or heart failure and infections are the most common complications. The most common complications are from the first to the sixth month acute rejection reactions and infections with bacteria, viruses and fungi. In the long-term, i.e. after the sixth month after LTPL, bronchiolitis obliterans , which is probably primarily based on a chronic rejection reaction , or bronchiolitis obliterans syndrome (BOS), is the most serious complication. The acute rejection reaction after LTPL has become rarer today thanks to improved immunosuppression. It is seen in about a third of patients, and some have two or more such episodes. The acute rejection reaction is based on a defense mechanism of the body against the foreign organ. Under the microscope, an accumulation of inflammatory cells around the small pulmonary vessels is found in the tissue. While in the first 3–4 weeks the patients often have fever, shortness of breath or changes in the lung x-ray, the acute rejection reaction usually proceeds without symptoms and can only be achieved on the basis of a daily check of the lung function and regular transbronchial lung biopsies , i.e. one Tissue sampling using bronchoscopy can be recorded. The acute rejection reaction can always be treated well with the administration of high-dose cortisone , but it is one of the most important risk factors for the later development of BOS.

Infections after LTPL manifest themselves mostly as pneumonia. But sepsis, infections of the gastrointestinal tract, kidneys and urinary tract or the nervous system also occur. The most common causes are various bacteria, viruses (especially the cytomegalovirus ) and fungi ( Aspergillus fumigatus , Pneumocystis jirovecii ). With good prophylaxis, these infections can usually be prevented or their severity can be reduced.

Bronchiolitis obliterans syndrome (BOS)

Without a doubt, the BOS is the most important and most serious complication after LTPL. Over the years, it occurs in up to 50 percent of patients and is a clinical picture that is characterized by a deterioration in lung function that usually begins slowly, but unfortunately in many cases unstoppable. Histologically, BOS manifests itself through scarring and ultimately destruction of the bronchioles and plugs of tissue in the small airways and alveoli. However, since transbronchial lung biopsy is often ineffective, the diagnosis is based on lung function. In BOS there is a deterioration in FEV1 compared to the average of the two best values ​​measured postoperatively. A distinction is made between the following stages of the BOS:

  • Stage 0 FEV1> 90% of baseline
  • Stage 0-p FEV1 81–90% of baseline
  • Stage 1 FEV1 66–80% of baseline
  • Stage 2 FEV1 51-65% of baseline
  • Stage 3 FEV1 <50% of baseline

The cause of the BOS is not entirely clear. Most authors are of the opinion that this is a form of chronic rejection reaction, which is possibly the result of missed or untreated acute rejection reactions. Today it is believed that many other factors such as repeated infections or undetected nocturnal aspiration of gastric juice ( gastroesophageal reflux ) play an important role. A connection with the cytomegalovirus is discussed again and again, but has not yet been clearly proven. BOS occurs most frequently 1–2 years after LTPL. If it starts later, the most common cause is poor patient compliance , i.e. unreliable medication intake.

The prophylaxis of BOS consists primarily in the early diagnosis and treatment of acute rejection reactions, in the consequent prevention and treatment of infections, in measures against gastroesophageal reflux, and in the intensive care and motivation of the patient to improve drug compliance. Treating an existing BOS is difficult. In about 1/3 of the cases, an improvement can be achieved with increased immunosuppression. A third of the patients show an inpatient course. In another third, however, there is a persistent deterioration in lung function that cannot be influenced, so that ultimately only a new transplant is possible.

Movie

  • A new lung for Manja . 60 min. Documentary, Germany 2006, first broadcast. Director: Till Lehmann (story of a 31-year-old mother and her husband, baker - at times her carer, from Mecklenburg-Western Pomerania).

Web links

Studies:

  • Transplant results. In a collective study (Collaborative Transplant Study), the results from 400 transplant centers in 45 countries on kidney, heart, lung, liver and pancreas transplants are summarized and continuously updated.

Individual evidence

  1. ↑ derStandard.at: Head of the day: Niki Laudas Transplanteur . Article dated August 10, 2018, accessed August 11, 2018.
  2. ↑ Lauda: Why the Vienna General Hospital is considered a global center for lung transplants . Article dated August 3, 2018, accessed August 11, 2018.
  3. ↑ Lung Transplant Program | St. Louis Childrens Hospital. Retrieved February 20, 2019 .