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Long-term outcomes and management of lung transplant recipients

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Lung transplantation is an established treatment for patients with end-stage lung disease. Improvements in immunosuppression and therapeutic management of infections have resulted in improved long-term survival and a decline in allograft rejection. Allograft rejection continues to be a serious complication following lung transplantation, thereby leading to acute graft failure and, subsequently, chronic lung allograft dysfunction (CLAD). Bronchiolitis obliterans syndrome (BOS), the most common phenotype of CLAD, is the leading cause of late mortality and morbidity in lung recipients, with 50% having developed BOS within 5 years of lung transplantation. Infections in lung transplant recipients are also a significant complication and represent the most common cause of death within the first year. The success of lung transplantation depends on careful management of immunosuppressive regimens to reduce the rate of rejection, while monitoring recipients for infections and complications to help identify problems early. The long-term outcomes and management of lung transplant recipients are critically based on modulating natural immune response of the recipient to prevent acute and chronic rejection. Understanding the immune mechanisms and temporal correlation of acute and chronic rejection is thus critical in the long-term management of lung recipients.

Section snippets

Acute cellular rejection (T-Lymphocyte rejection)

Acute cellular rejection (ACR) is the predominant type of rejection in lung transplant that affects the vasculature and small airways, thus potentially resulting in acute graft dysfunction and failure over time. The key distinction between acute and chronic rejection is the presence of irreversible airway fibrosis. ACR is an important risk factor for the development of bronchiolitis obliterans syndrome (BOS), and its severity, particularly the pathologic evidence of lymphocytic bronchiolitis,

Antibody-mediated rejection (humoral rejection)

Hyperacute rejection is a form of rejection that occurs rapidly after transplantation and is caused by preformed anti-HLA antibodies, and it is associated with an extremely high mortality. Fortunately, given the advances in HLA screening, the incidence of hyperacute rejection after lung transplantation is now extremely rare. The other form of humoral rejection, antibody-mediated rejection (AMR), is associated with four specific factors: (1) donor-specific anti-HLA antibodies (DSAs), (2)

Chronic rejection

Lung transplantation remains the only viable treatment option for patients with end-stage lung disease; however, long-term survival of these patients remains limited because of chronic lung allograft dysfunction, with BOS as the leading cause of late mortality and morbidity. Bronchiolitis obliterans is a small airway disease, mofetil triggered by an insult to small airway epithelial and subepithelial cells with the subsequent formation of excessive fibrosis and airway constriction. Ultimately,

Viral infections

Infectious complications remain a significant cause of morbidity and mortality in lung transplant recipients. Lung transplant recipients are at increased risk of infection for multiple reasons, including continuous exposure of the allograft to environmental microorganisms, denervation of the lung resulting in impaired cough reflex, dysfunctional mucociliary clearance, impaired lymphatic drainage, and immunosuppression.

Several viral infections have been associated with poor long-term outcomes in

Postlung transplantation medical complications

Patients with end-stage lung disease waiting for a transplant have varying significant comorbidities, which are typically chronic in nature. These comorbidities require ongoing management and may be exacerbated posttransplant, potentially resulting in poor quality of life and shortened posttransplant survival.

Immunosuppressive medications contribute to cardiovascular comorbidities such as hyperlipidemia, diabetes, hypertension, and renal disease. Coronary artery disease is accelerated in

Long-term outcomes of lung transplantation

Advancements in surgical techniques and immunosuppression have resulted in improved survival outcomes in lung recipients. The survival of lung recipients is lower than that of other solid organ transplant recipients; the median survival after lung transplantation is 5.8 years, compared to a 70% 5-year survival after heart transplantation [Fig. 1] [66].

Survival, functional status, and quality of life are the leading measures of posttransplant outcomes. High-volume transplant centers on average

Conclusion

Our understanding of ACR remains a work in progress and requires an ongoing collaborative effort between lung transplant centers across the world, to gain a better understanding of ACR pathogenesis and diagnostics. ACR remains an important cause of early graft failure, and it is an important risk factor for CLAD, ultimately affecting long-term outcomes.

Despite advances in immunotherapy, chronic rejection continues to limit long-term survival in lung transplant recipients and exacerbate existing

Conflict of interest statement

None.

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