An update on current treatment strategies for managing bronchiolitis obliterans syndrome after lung transplantation

ABSTRACT

Introduction

Bronchiolitis obliterans syndrome (BOS), a subtype of chronic lung allograft dysfunction, is quite common, with up to half of all lung recipients developing BOS within 5 years of transplantation. Preventive efforts are aimed at alleviating known risk factors of BOS development, while the primary goal of treatment is to delay the irreversible, fibrotic airway changes, and progressive loss of lung function.

Areas covered

This narrative review will briefly discuss the updated definition, clinical presentation, pathogenesis, risk factors, and survival after BOS while paying particular attention to the salient evidence for optimal preventive strategies and treatments based on investigations in the modern era.

Expert opinion

Future translational research focused on further characterizing the complex interplay between immune and nonimmune mechanisms mediating chronic lung rejection is the first step toward mitigating risk of allograft injury, improving early disease detection with noninvasive biomarkers, and ultimately, developing an effective, targeted therapy that can extend the life of the lung allograft.

KEYWORDS:

• Bronchiolitis obliterans syndrome
• risk factors
• treatment
• lung transplantation
• chronic lung allograft dysfunction

Article highlights

• Bronchiolitis obliterans syndrome (BOS) is a subtype of chronic lung allograft dysfunction (CLAD) that affects a majority of lung transplant recipients and significantly impairs the long-term survivability of the procedure.

• BOS is mediated by several risk factors that elicit a mixed anti-donor response between de novo-developed donor-specific antibodies, autoantibodies, and non-immune-related allograft insults which promote exosome release.

• Prompt preventive strategies to address the above risk factors focus on treating any viral, bacterial, or fungal infections, acute rejection episodes, and GERD symptoms, among others.

• Investigations conducted in lieu of the updated CLAD classification system have established the value of pharmacologic therapy (i.e., azithromycin and montelukast) and other notable interventions in preventing or treating BOS phenotype CLAD.

• Non-invasive, immune biomarkers have improved the early detection of allograft dysfunction and impending rejection.

• Targeted therapeutics against known pathophysiologic mechanisms of allograft injury and rejection may demonstrate great promise in improving freedom from CLAD and overall survival after transplant.

Acknowledgments

The authors would like to thank Kristine Nally and Billie Glasscock for their assistance in editing and submitting this manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Each individual listed as an author on this manuscript contributed substantially and in accordance with the guidelines of the International Committee of Medical Journal Editors.

Additional information

Funding

This paper was not funded. The author T.Mohanakumar is supported by NIH R01 HL056643.