Reviews and feature article
Using biomarkers in the assessment of airways disease

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A biomarker provides a window on underlying disease activity. This is helpful when the pathology, treatment response, or both are heterogeneous or when trying to interpret nonspecific respiratory symptoms in patients with comorbidities. The successful application of a biomarker result is critically dependent on the specific question being addressed and the performance characteristics of the biomarker in relation to that question in the context of pretest probabilities. Negative prediction might be the best way to use a biomarker, such as a D-dimer, pro–brain natriuretic peptide, and exhaled nitric oxide. In this review the role of biomarkers in airways disease (notably induced sputum eosinophils and exhaled nitric oxide) is considered in relation to risk stratification, identification of treatment responders, identification of a clinical phenotype, monitoring of disease, and new drug development.

Section snippets

Using a biomarker: What are the clinical objectives?

The measurement of a biomarker can have several objectives. It is important to understand those that can and, just as importantly, those that cannot be served by making the measurement. There are several domains (Table II), and the proven utility of a biomarker in one domain may not be the case for another.

Diagnosis

The success with which a biomarker operates in diagnostic decision making depends on its performance characteristics. The terminology is familiar: sensitivity, specificity, PPV and negative predictive value (NPV), and likelihood ratios (LRs, both positive and negative). Unfortunately, familiarity with the terms does not guarantee that we understand them, and this often leads to inappropriate expectations and mistaken applications of a diagnostic test.

A sensitive test identifies most subjects

Anti-inflammatory therapy in patients with airways disease

The most clinically important role for a biomarker in airways disease management is to predict the response to anti-inflammatory treatment. Current guidelines for asthma recommend a universal step-up regimen rather than a selective approach,52 but in fact, the response to ICS therapy is heterogeneous, and nonresponders are common.53, 54 In the Gaining Optimal Asthma Control study approximately 30% of patients did not achieve asthma control despite progressive increases in their inhaled

Summary

The use of biomarkers in respiratory medicine is in its infancy. Successive studies proclaim the relevance of yet another biomarker for the clinical evaluation of airways disease, but the pathway from identification to clinical application is long and complex. Yet there is an urgent need to develop biomarkers that enable clinicians to distinguish one clinical phenotype from another. Even more importantly, biomarkers should be aimed at identifying treatment responders. Targeted therapy is the

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    Series editors: Joshua A. Boyce, MD, Fred Finkelman, MD, William T. Shearer, MD, PhD, and Donata Vercelli, MD

    Disclosure of potential conflict of interest: D. R. Taylor has received lecture fees from Aerocrine AB.

    Terms in boldface and italics are defined in the glossary on page 928.

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