Clinical utility of asthma biomarkers: from bench to bedside

Susanne Jh Vijverberg, Bart Hilvering, Jan Am Raaijmakers, Jan-Willem J Lammers, Anke-Hilse Maitland-van der Zee, Leo Koenderman, Susanne Jh Vijverberg, Bart Hilvering, Jan Am Raaijmakers, Jan-Willem J Lammers, Anke-Hilse Maitland-van der Zee, Leo Koenderman

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: airway inflammation; asthma; biological markers; metabolomics; pharmacogenomics.

Figures

Figure 1
Figure 1
Asthma biomarkers. Abbreviations: BAL, bronchoalveolar lavage; ECP, eosinophil cationic protein; FeNO, fraction of exhaled nitric oxide; IgE, immunoglobulin E; uLTE4, urinary leukotriene E4.
Figure 2
Figure 2
Inflammatory phenotypes of adult asthma patients obtained by sputum induction. (A) Eosinophilic type; marked by the presence of eosinophils ≥3% (red arrow). The hollow arrow indicates an alveolar macrophage. (B) Neutrophilic type; marked by the presence of neutrophils (blue arrow) ≥61%. The hollow arrow indicates an alveolar macrophage. (C) Mixed type; marked by the presence of both eosinophils (red arrow) ≥3% and neutrophils (blue arrow) ≥61%. (D) Paucigranulocytic type; marked by a lack of eosinophils (<3%) and neutrophils (<61%). The arrow shows a ciliated pseudostratified columnar airway epithelial cell (black arrow), a neutrophil with phagocytosed bacteria inside (blue arrow) and an alveolar macrophage (hollow arrow). May-Grünwald/Giemsa staining, photograph at 100× magnification, courtesy of Dr JAM van der Linden (UMC Utrecht, The Netherlands).

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