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Review

Emerging biomarkers in chronic lung allograft dysfunction

ORCID Icon &
Pages 467-475
Received 22 Jan 2020
Accepted 03 Mar 2020
Accepted author version posted online: 05 Mar 2020
Published online: 12 Mar 2020
 

ABSTRACT

Introduction: Lung transplantation remains an important treatment for patients with end stage lung disease. Chronic lung allograft dysfunction (CLAD) remains the greatest limiting factor for long term survival. As the diagnosis of CLAD is based on pulmonary function tests, significant lung injury is required before a diagnosis is feasible, likely when irreversible damage has already occurred. Therefore, research is ongoing for early CLAD recognition, with biomarkers making up a substantial amount of this research.

Areas covered: The purpose of this review is to describe available biomarkers, focusing on those which aid in predicting CLAD and distinguishing between different CLAD phenotypes. We describe biomarkers presenting in bronchial alveolar lavage (BAL) as well as circulating in peripheral blood, both of which offer an appealing alternative to lung biopsy.

Expert opinion: Development of CLAD involves complex, multiple immune and nonimmune mechanisms. Therefore, evaluation of potential CLAD biomarkers serves a dual purpose: clinically, the goal remains early detection and identification of patients at increased risk. Simultaneously, biomarkers offer insight into the different mechanisms involved in the pathophysiology of CLAD, leading to the development of possible interventions. The ultimate goal is the development of both preventive and early intervention strategies for CLAD to improve the overall survival of our lung transplant recipients.

Article highlights

  • CLAD remains the primary limitation to long-term survival for lung transplant recipients (LTR). Its development involves complex, multiple immune and non-immune mechanisms. Therefore, identifying CLAD biomarkers serves both as a tool for early detection as well as offers insight into these complex mechanisms.

  • This review focuses on CLAD biomarkers that are found in BAL or peripheral blood and have been shown to aid in predicting CLAD as well as to help distinguish between different CLAD phenotypes.

  • Of these biomarkers, significant promise lays in donor derived cell free DNA (ddcfDNA) and gene expression analysis. These tools provide a broader insight into various forms of lung injury, may be useful in differentiating patterns of injury and have the potential for pre-clinical identification of allograft dysfunction.

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.

Reviewers disclosure

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

Additional information

Funding

This paper was not funded.

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