Biomarkers of eosinophilic inflammation in asthma

Abstract

Eosinophils are mediators of allergic inflammation and are implicated in the pathogenesis of numerous conditions including asthma, parasitic infections, neoplasms, hyper-eosinophilic syndromes, vasculitic disorders, and organ-specific conditions. Assessing eosinophilic inflammation is therefore important in establishing a diagnosis, in monitoring and assessing response to treatment, and in testing novel therapeutics. Clinical markers of atopy and eosinophilic inflammation include indirect tests such as lung function, exhaled breath condensate analysis, fractional exhaled nitric oxide, serum immunoglobulin E levels and serum periostin. Direct measures, which quantify but do not anatomically localise inflammation include blood eosinophil counts, serum or plasma eosinophil cationic protein and sputum eosinophil levels. Cytology from bronchoalveolar lavage and histology from endobronchial and transbronchial biopsies are better at localising inflammation but are more invasive. Novel approaches using radiolabelled eosinophils with single-photon emission computed tomography, offer the prospect of non-invasive methods to localise eosinophilic inflammation.

Keywords::

• allergy
• biomarkers
• biopsy
• eosinophils
• inflammation
• nitric oxide
• radioligands
• SPECT-CT
• sputum

Financial & competing interests disclosure

The work from the Chilvers laboratory is supported by Asthma UK (08/11); the Medical Research Council (grant number MR/J00345X/1); the Wellcome Trust (grant number 098351/Z/12/Z); Biotechnology and Biological Sciences Research Council (grant number BB/H531100/1); and Cambridge National Institute for Health Research Biomedical Research Centre. The authors have no other 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.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Eosinophils are key mediators of allergic inflammation and play a pathogenic role in numerous conditions including parasitic infections, neoplasms, hyper-eosinophilic syndromes, vasculitic disorders and organ-specific conditions affecting the lung, nose, skin and gastrointestinal tract.

• Assessing eosinophilic inflammation is essential for the diagnosis and monitoring of diseases, and for testing the efficacy of novel therapeutics.

• Indirect markers of atopic status, eosinophilic inflammation and asthma include, serum IgE levels, lung function tests, blood and sputum eosinophilia, exhaled breath condensates and exhaled nitric oxide.

• Bronchoalveolar lavage samples the airway directly but may not accurately reflect tissue eosinophilia.

• Endobronchial and transbronchial biopsy reflects tissue eosinophilia, but this test is invasive and associated with complications.

• Novel eosinophil biomarkers include assaying eosinophil granule proteins and searching for clinically relevant polymorphisms of regulatory pathways.

• Radiolabeled eosinophils coupled with single-photon emission computed tomography offers the prospect of a non-invasive test that localizes focal eosinophilic inflammation in vivo.

Notes