Review
Biomarkers in asthma and allergic rhinitis

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Abstract

A biological marker (biomarker) is a physical sign or laboratory measurement that can serve as an indicator of biological or pathophysiological processes or as a response to a therapeutic intervention. An applicable biomarker possesses the characteristics of clinical relevance (sensitivity and specificity for the disease) and is responsive to treatment effects, in combination with simplicity, reliability and repeatability of the sampling technique. Presently, there are several biomarkers for asthma and allergic rhinitis that can be obtained by non-invasive or semi-invasive airway sampling methods meeting at least some of these criteria.

In clinical practice, such biomarkers can provide complementary information to conventional disease markers, including clinical signs, spirometry and PC20methacholine or histamine. Consequently, biomarkers can aid to establish the diagnosis, in staging and monitoring of the disease activity/progression or in predicting or monitoring of a treatment response. Especially in (young) children, reliable, non-invasive biomarkers would be valuable.

Apart from diagnostic purposes, biomarkers can also be used as (surrogate) markers to predict a (novel) drug’s efficacy in target populations. Therefore, biomarkers are increasingly applied in early drug development.

When implementing biomarkers in clinical practice or trials of asthma and allergic rhinitis, it is important to consider the heterogeneous nature of the inflammatory response which should direct the selection of adequate biomarkers. Some biomarker sampling techniques await further development and/or validation, and should therefore be applied as a “back up” of established biomarkers or methods. In addition, some biomarkers or sampling techniques are less suitable for (very young) children. Hence, on a case by case basis, a decision needs to be made what biomarker is adequate for the target population or purpose pursued.

Future development of more sophisticated sampling methods and quantification techniques, such as – omics and biomedical imaging, will enable detection of adequate biomarkers for both clinical and research applications.

Section snippets

Pathophysiology of allergic airways disease

The pathogenesis of asthma and allergic rhinitis is complex. The expression of either or both disorders in an individual largely depends on interactions between several susceptibility genes and environmental factors [1], [2], [3]. Atopy is the key factor predisposing for the development of allergic airways disease [4]. Despite modern technologies enabling to unravel several inflammatory mechanisms of allergic airway disease, presently, still many etiological and pathophysiological questions

Biomarkers in asthma and allergic rhinitis: definitions and criteria

A biological marker (biomarker) is a physical sign or laboratory measurement that can serve as an indicator of biological or pathophysiological processes or a response to a pharmacological intervention [22]. There is an ongoing exploration of new biomarkers and initially, all biological compounds of the inflammatory cascade could be eligible candidates. Ideally, a biomarker should have the following characteristics [22]:

  • Clinical relevance: indicating a clear relationship between the biomarker

Sampling techniques of the lower airways

Overall, there are three types of sampling methodologies of the lower airways: invasive sampling requiring flexible bronchoscopy, semi-invasive sampling by induced sputum and non-invasive sampling of the volatile inflammatory components in exhaled air.

Biomarkers in allergic rhinitis

The signs and symptoms of allergic rhinitis are the result of an IgE-mediated allergic reaction involving different cells, mediators, cytokines, chemokines, neuropeptides, chemokines and other components in a complex immunological network [1]. In clinical practice or trials of allergic rhinitis, most evaluation methods of clinical symptoms (by composite symptom scores) and measurements techniques of nasal patency (by rhinomanometry and acoustic rhinometry) are hampered by the lack of

Biomarkers in childhood asthma

Like in adults, asthma in children is characterised by chronic airway inflammation, based on evidence from bronchial biopsies [215], BAL [216] and sputum [217]. Even during asymptomatic disease episodes, airway inflammation can be demonstrated [218]. A Dutch bronchial biopsy study demonstrated chronic airway inflammation in asymptomatic adolescents, who were thought to have outgrown their early childhood asthma, possibly indicating a risk of disease relapse later in life [219]. Therefore,

Overall conclusion

Non-invasive and semi-invasive sampling methods of the upper and lower airways offer a large variety of potential biomarkers of asthma and allergic rhinitis. In view of the complex inflammatory airway response in both asthma and allergic rhinitis, multiple biomarkers should be sampled, whenever possible. Biomarkers can be useful tools in both clinical practice (diagnosis, disease monitoring) and clinical research including drug development. Further development and validation of sophisticated

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