Life Expectancy After Lung Transplant Cystic Fibrosis – The success of lung transplantation has improved over time, as reflected in long-term survival and functional outcomes. Even if the procedure is successful, many problems and complications occur throughout the life of the lung transplant recipient. With proper monitoring and treatment, the frequency and severity of these problems can be reduced. However, lung transplant outcomes will only improve significantly if there are better ways to prevent and effectively treat chronic rejection.
Lung transplantation is an accepted treatment option for end-stage patients with many types of lung disease. Although early LT experiences in the 1960s and 1970s had very poor results, the practice has become more promising since the 1980s. This is due to the first successful lung (heart-lung) transplant at Stanford University in 1981, when the immunosuppressant drug cyclosporin A appeared. Shortly after the success of heart-lung transplantation, both single lung transplantation (HLT), single lung transplantation (SLT), and sequential double lung transplantation (DLT) became treatment options for selected candidates in the mid- to late 1980s. Since then, around 1,500 lung transplants are performed worldwide each year, a number limited only by the lack of donor organs. Despite the overall success of these procedures, significant challenges remain that limit quality of life (QoL) and long-term survival. Some of these problems occur in all organ transplant recipients. However, some of them are unique to LT.
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Compared to liver and kidney transplants, the long-term outcome of transplants is worse (statistics for small bowel transplants are actually worse than for kidney transplants: 1-year mortality 76.9%
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59.3% 3-year RT mortality) 1. Several factors contribute to this problem, but the most limiting are bronchiolitis obliterans (OB; histological correlates of chronic rejection) and infection. Both chronic rejection and infection occur more frequently and earlier in lung transplants than in other solid organ transplants. The reasons for the high rejection rate of lung transplants are not well understood. However, it should be noted that, unlike other solid organ transplants (except for the small intestine), lung allografts are in direct contact with the external environment, so they can be directly damaged by inhaled foreign substances and infections. Such non-immune damage initiates a cascade of events that triggers an immune response and ultimately leads to allograft rejection. In addition, in addition to disruption of mucosal clearance mechanisms as a result of the transplantation procedure, pulmonary allografts are impaired in neural and lymphatic drainage, leading to removal of foreign substances, microorganisms, and secretions. 2. Lungs are at constant risk from direct alloimmune rejection, similar to other solid organ transplants, in addition to environmental exposures.
An important factor affecting survival outcomes is the disease state of the various types of RT. Each of these diseases is accompanied by multiple factors that directly affect short- and long-term survival outcomes. Patients with chronic obstructive pulmonary disease (COPD) have the best short- and long-term survival, while patients with idiopathic pulmonary fibrosis (IPF) and pulmonary hypertension have worse outcomes. Therefore, when evaluating survival statistics, it is important to do so in relation to the underlying lung disease. Differences in survival for various underlying diseases while patients are waiting for a transplant are also important. Relatedly, patients with IPF are more likely to die while waiting, while patients with COPD are the most likely to survive longer on the waiting list. Therefore, it is important to consider post-transplant outcomes in the context of the natural history of the disease. A thorough understanding of these issues not only helps patients determine the right time for transplantation, but also influences the allocation of donor organs to patients with various diseases.
Another observation that may affect survival is the type of transplant. A recent analysis from the International Society of Heart and Lung Transplantation (ISHLT) registry showed a small survival advantage for patients who received DLT compared with SLT procedures (Fig. 1⇓) 3. Further data analysis from the International Meyer Registry
. 4 showed that the survival advantage of the DLT procedure extended to 60 years of age in patients with COPD. Similar results in patients with COPD were reported by a group at Washington University in St. Louis, Missouri, USA, in a 13-year retrospective study of their experience 5. There are many hypotheses as to why DLT may last longer. – advantage of the existence of time. , but one study showed a reduction in bronchiolitis obliterans syndrome (BOS) in patients who received DLT 6. However, as Hadjiliadis points out, there are problems with interpreting this result.
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. 6, there is evidence that the formation of OV in a transplanted single lung leads to a significant decrease in forced expiratory volume (FEV) in one second.
; pulmonary functional reserve is low) and hyperinflation of the alveoli impairs allograft function. In any case, the potential benefit of DLT may be overshadowed by the potential benefit of treating twice as many patients with SLT. This question is still discussed, especially in relation to certain diseases. Controversy remains as to whether bilateral lung transplantation (BLT) or HLT is best for primary pulmonary hypertension in addition to pulmonary septic disease. Similarly, in Eisenmenger syndrome secondary to a simple septal defect, there is controversy as to whether HLT or BLT/SLT with repair of the defect is optimal. Data from the ISHLT3 registry showed no difference in outcomes between SLT and BLT for primary pulmonary hypertension, and no head-to-head comparisons of LT.
HLT in this chapter. Interestingly, for patients with Eisenmenger syndrome associated with ventricular septal defect, data from the ISHLT/United Network of Organ Sharing (UNOS) 7 registry show improved survival with HLT compared with BLT with defect closure. However, there is a growing body of evidence supporting the role of BLT and defect closure to increase the use of available donor organs 8–10 .
Although the success of LT can be assessed by several different outcome measures, survival has long been the most important criterion for evaluating transplant procedures. Survival outcomes for LT and HLT are monitored by the ISHLT/UNOS registry database. Collected from a very large cohort of patients over a decade, these data provide doctors with the information they need to assess a potential recipient’s “possibility” after a transplant. LT survival curves derived from pooled data from 1990 to 2000 are shown in figure 2⇓ 3 . The curve is characterized by a steep decline in the first year followed by a slower but steady decline in subsequent years. Interestingly, recent experience has improved overall survival (Fig. 3⇓). However, this improvement was only the result of a reduction in perioperative mortality and a small change in the slope of the long-term survival curve. Experience in surgical technique, preoperative care, antimicrobial prophylaxis, and recipient selection influenced early outcomes. Over time, not only treatment regimens have changed and improved, but also the characteristics of selected donors and recipients. As the difficulty of obtaining donor organs has increased, the range of potential donors has expanded. In particular, the increasing age of donors may have a significant impact on survival after transplantation.
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Despite the improvement in postoperative survival, the slope of the long-term survival curve continues to erode, reflecting the problem of chronic rejection in the absence of effective treatment. This observation is disappointing given the ever-expanding range of immunosuppressive drugs and the understanding of pharmacokinetic and pharmacodynamic principles associated with their use.
There are several serious complications that commonly occur after RT and, unfortunately, often result in significant morbidity and mortality (table 1 ⇓ ). In addition to these, many other problems have a significant impact on outcomes such as cardiovascular, gastrointestinal complications, and cancer.
Data from the ISHLT registry show that infection is the leading cause of death in the first year after transplantation. Infection is usually the result of serious surgical complications (excessive bleeding, complications of vascular and respiratory anastomosis,
) and primary graft dysfunction/severe ischemia-reperfusion injury. Patients with certain medical conditions are at greater risk for postoperative complications than others. For example, patients with cystic fibrosis are at increased risk of perioperative infection due to chronic sinus infections prior to transplantation. Patients with congenital heart defects who have undergone multiple previous corrective surgeries are at increased risk of bleeding during the transplant procedure 8, 11. Patients with severe pulmonary hypertension treated with SLT are at increased risk of severe ischemia-reperfusion injury and require a longer postoperative period. . mechanical ventilation 10. Similarly, older donor lung recipients (>50 years)
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