Chest
Volume 140, Issue 2, August 2011, Pages 502-508
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Translating Basic Research into Clinical Practice
Bronchiolitis Obliterans Syndrome: The Final Frontier for Lung Transplantation

https://doi.org/10.1378/chest.10-2838Get rights and content

Bronchiolitis obliterans syndrome (BOS) is a form of chronic lung allograft dysfunction that affects a majority of lung transplant recipients and is the principal factor limiting long-term transplant survival. BOS is characterized by progressive airflow obstruction unexplained by acute rejection, infection, or other coexistent condition. Although BOS is a proven useful clinical syndrome that identifies patients at increased risk for death, its clinical course and underlying causative factors are now recognized to be increasingly heterogeneous. Regardless of the clinical history, the primary pathologic correlate of BOS is bronchiolitis obliterans, a condition of intraluminal airway fibrosis. This article highlights the body of developing research illustrating the mechanisms by which BOS is mediated, including alloimmune reactivity, the emerging roles of humoral and autoimmunity, activation of innate immune cells, and response to nonimmune-related allograft insults, such as infection and aspiration. In addition, we underscore emerging clinical implications and promising future translational research directions that have the potential to advance our knowledge and improve patient outcomes.

Section snippets

Alloimmune T-Cell Reactivity

The rarity of BO in patients without transplantation emphasizes the fundamental role of alloimmune T-cell reactivity in the development of this condition. Acute cellular rejection is the most consistently described risk factor for BOS. Specifically, both acute vascular (A-grade) rejection, especially if histologically severe,7 and lymphocytic bronchiolitis (B-grade) rejection are associated with a significantly increased risk of BOS.8 Animal tracheal transplantation models demonstrate

Conclusions

BOS is the principal factor limiting long-term survival and quality of life after lung transplantation. Alloimmune reactivity plays a fundamental role in the development of BOS, and although T cells have been the traditional target of posttransplant immunosuppression, more potent T-cell-suppressing agents and innovative means of immunosuppressive drug delivery may further minimize the impact of the alloimmune response. Importantly, several exciting novel mechanisms, including antibody-mediated

Acknowledgments

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

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