Clinical utility of asthma biomarkers: from bench to bedside

Abstract

Asthma is a chronic disease characterized by airway inflammation, bronchial hyperresponsiveness, and recurrent episodes of reversible airway obstruction. The disease is very heterogeneous in onset, course, and response to treatment, and seems to encompass a broad collection of heterogeneous disease subtypes with different underlying pathophysiological mechanisms. There is a strong need for easily interpreted clinical biomarkers to assess the nature and severity of the disease. Currently available biomarkers for clinical practice – for example markers in bronchial lavage, bronchial biopsies, sputum, or fraction of exhaled nitric oxide (FeNO) – are limited due to invasiveness or lack of specificity. The assessment of markers in peripheral blood might be a good alternative to study airway inflammation more specifically, compared to FeNO, and in a less invasive manner, compared to bronchoalveolar lavage, biopsies, or sputum induction. In addition, promising novel biomarkers are discovered in the field of breath metabolomics (eg, volatile organic compounds) and (pharmaco)genomics. Biomarker research in asthma is increasingly shifting from the assessment of the value of single biomarkers to multidimensional approaches in which the clinical value of a combination of various markers is studied. This could eventually lead to the development of a clinically applicable algorithm composed of various markers and clinical features to phenotype asthma and improve diagnosis and asthma management.

Keywords:

• asthma
• airway inflammation
• biological markers
• pharmacogenomics
• metabolomics

Disclosure

Susanne JH Vijverberg has been paid by an unrestricted grant from GlaxoSmithKline (GSK). Bart Hilvering has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. Jan AM Raaijmakers is a part-time professor at the Utrecht University, Vice-President External Scientifc Collaborations for GSK in Europe, and holds stock in GSK. Anke-Hilse Maitland-van der Zee received an unrestricted grant from GSK. Furthermore, the department of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, which employs authors Susanne JH Vijverberg, Jan AM Raaijmakers, and Anke-Hilse Maitland-van der Zee, has received unrestricted research funding from the Netherlands Organisation for Health Research and Development, the Dutch Health Care Insurance Board, the Royal Dutch Pharmacists Association, the private public-funded Top Institute Pharma, including co-funding from universities, government, the EU Innovative Medicines Initiative, EU 7th Framework Program, the Dutch Medicines Evaluation Board, the Dutch Ministry of Health, and industry (including GSK, Pfizer, and others). Jan-Willem Lammers and Leo Koenderman are full professors in the Department of Respiratory Medicine at the University Medical Centre Utrecht. Both collaborated in a TI-Pharma–funded project. TI-Pharma is a public private partnership between the Universities of Utrecht, Groningen, Maastricht, the Dutch government, GSK, Nycomed, and Danone.