Lung function decline and variable airway inflammation – potential asthma biomarker?

Published Online: June 10, 2014

Asthma is associated with eosinophilic airway inflammation, which can be measured using induced sputum. Induced sputum is an important treatment stratification tool in severe asthma and has been utilized to stratify response to a variety of therapies—including inhaled/oral corticosteroids and biological targeted therapies directed at cytokines driving airway eosinophilia e.g. IL-5—that are emerging as new treatments in the clinic. Sputum eosinophilia has been shown to be associated with severe asthma attacks and airflow obstruction cross-sectionally, but few studies have evaluated airway eosinophilia over time and its impact upon asthma risk.

In a manuscript recently published in The Journal of Allergy and Clinical Immunology (JACI), Newby, Brook, Brightling, Siddiqui and colleagues used statistical modeling techniques to evaluate whether airway eosinophilia measured in sputum was associated with lung function and its decline among a cohort of severe asthmatics. Perhaps more importantly they also examined whether there were different ‘phenotypes’ or subgroups of patients with lung function decline based upon both the amplitude and variation of eosinophilic airway inflammation over time. The authors used the forced expiratory volume in 1 second (FEV1), a common lung function test, to study decline of lung health.

The authors found that FEV1 trajectories in severe asthma were highly variable and patient specific. The overall population decline was relatively small (25.7 mls/year) after adjusting for common confounders such as asthma attacks. The authors found that both the mean (amplitude) and standard deviation (variability) of eosinophilic airway inflammation over time were significantly associated with FEV1 and subsequently utilized statistical modeling to identify whether there were subgroups of patients with different patterns of declines. Three different longitudinal eosinophilic patient subgroups were identified: (1) non-eosinophilic with low variation (mean decline of 14.0 mls/annum), (2) eosinophilic with high variation (mean decline of 40.9 mls/annum) and (3) eosinophilic with low variation (mean decline (19.2 mls/annum).

The observations in this report suggest that the variability in eosinophilic airway inflammation over time, rather than amplitude, may be an important factor in determining asthma risk. However current practice in pharmacotherapy trials targeting eosinophilic airway inflammation is to modulate the amplitude of eosinophilic airway inflammation only. It is possible that amplitude and variability have discrete and independent biological mechanisms and further studies are required to evaluate this concept in asthma and may yield new asthma biomarkers for clinical trials targeting eosinophils.

This research was funded by the European Union, Airways Disease Predicting Outcomes Using Patient Specific Models ‘AirPROM’ project. Future research within this program will develop mathematical models of background eosinophilia, and effects of therapeutic intervention, to investigate amplitude and variability over time, and apply them to clinical trial datasets.

The Journal of Allergy and Clinical Immunology (JACI) is the official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

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