This chapter presents a commentary on the lung-specific complications following transplantation and this should be used to drive the investigation plan and management. Shared care protocols with effective communication should be organized in patients who live at a distance from the transplant center to ensure that local follow-up includes monitoring of the lung function and imaging. Acute rejection can be identified on lung biopsies obtained via transbronchial biopsy (TBBx) at fiberoptic bronchoscopy. Many transplant centers perform regular bronchoscopy and TBBx in addition to spirometry in the first year to enable early diagnosis and treatment of asymptomatic rejection, with the aim of preserving graft function and protecting against bronchiolitis obliterans syndrome (BOS). Recently the importance of detecting early, subclinical BOS before irreversible fibroproliferative disease has become established has been recognized, and a new stage of BOS 0-p has been added.

This chapter outlines the events involved in the adaptive and innate immune responses to a transplant and the subsequent mechanisms of rejection, concluding with current clinical and experimental strategies to protect transplants from immune-mediated damage. The recognition of foreign antigens by naive host (recipient) T cells is a principal step in the rejection process. Allorecognition in the presence of costimulation results in the activation and expansion of T-cells that recognize the mismatched donor alloantigens. Immunosuppressive therapy can be credited with the vast improvements in transplant survival. The chapter explores the underlying mechanisms of action in relation to the immunobiology. Newer monoclonal antibodies include alemtuzumab, rituximab, basiliximab, and daclizumab, which target specific T-cell surface proteins. The advances in immunosuppression have improved short- and medium-term graft survival rates and reduced the rates of acute rejection, but this has not been followed by a comparable reduction in long-term graft dysfunction rates.

This chapter focuses on current practice, as informed by past experiences and as a basis for understanding newer therapeutics on the horizon. Long-term survival of allograft in humans first occurred with the introduction of azathioprine (AZA). Early use of cyclosporine (CyA) in animals and humans as monotherapy seemed effective in preventing acute rejection crises. Mycophenolate mofetil (MMF) was a new modified preparation of an older agent that enhanced its absorption and stability. Maintenance immunosuppression is the long-term therapy required to ensure allograft survival, administered with the dual intentions of avoiding both immunological injury and drug-related toxicity. Discovery of new agents is informed by our evolving understanding of how immunological processes injure allograft, with substantial attention now being devoted to antibody-mediated injury and lymphoid tissue of B-cell lineage. It is now common to use biologics, such as polyclonal or monoclonal antibodies, for a short time as induction of acute rejection.