Biomarker-based asthma phenotypes of corticosteroid response

Abstract

Background Asthma is a heterogeneous disease with different phenotypes. Inhaled corticosteroid (ICS) therapy is a mainstay of treatment for asthma but the clinical response to ICS is variable. Objective We hypothesized that a panel of inflammatory biomarkers i.e. FENO, sputum eosinophils and urinary BromoTyrosine (BrTyr) might predict steroid responsiveness. Methods The original study, from which this analysis originates, comprised 2 phases: a steroid naïve phase 1 and a 28-day trial of ICS (phase 2) during which times, FENO, sputum eosinophils, and urinary BrTyr were measured. Response to ICS was based on clinical improvements including: ≥12% increase in FEV1; ≥0.5 point decrease in Asthma Control Questionnaire; and ≥2 doubling dose increase in provocation concentration of adenosine 5′-monophosphate causing a 20% fall in FEV1 (PC20 AMP). Healthy controls were also evaluated in this study for comparison of biomarkers to asthmatics. Results Asthmatics had higher than normal FENO, sputum eosinophils and urinary BrTyr at steroid naïve phase and after ICS. After 28-day trial of ICS, FENO decreased in 82% of asthmatics, sputum eosinophils decreased in 60% and urinary BrTyr decreased in 58%. Each of the biomarkers at steroid naïve phase had utility for predicting steroid- responsiveness, but the combination of high FENO and high urinary BrTyr had the best power (13.3 fold; p<0.01) to predict a favorable response to ICS. However, the magnitude of decrease of biomarkers was unrelated to the magnitude of clinical response to ICS. Conclusion A noninvasive panel of biomarkers in steroid naïve asthmatics predicts clinical responsiveness to ICS.

Biomarkers to identify sputum eosinophilia in different adult asthma phenotypes

“…Discordance between different biomarkers for airway eosinophilia has been reported previously [17,29]. More interestingly, discordance between various biomarkers of the effects of anti-inflammatory therapy or ability to predict asthma attacks have also been noted [7,29,30]. These data suggest that discordance between biomarkers in different asthma phenotypes may point towards different underlying mechanisms.…”

“…In our study, total IgE was relatively more accurate in predicting sputum eosinophilia in nonobese patients compared to obese patients, but had lower diagnostic accuracy than the other two biomarkers. Discordance between different biomarkers for airway eosinophilia has been reported previously [17,29]. More interestingly, discordance between various biomarkers of the effects of anti-inflammatory therapy or ability to predict asthma attacks have also been noted [7,29,30].…”

Inhaled corticosteroid dose response in asthma

“…264 This is problematic, not least due to the cumbersome nature of inflammatory and 265 challenge measurements that are difficult to perform in a community setting; 266 albeit measuring blood eosinophils might be part of the solution 16 . Cowan et al 267 have suggested using a panel of inflammatory biomarkers to better enable 268 prediction of ICS responsiveness in asthma 46 , but delivery of such a test remains 269 the most difficult hurdle. Even simply using the asthma control questionnaire 24 270 itself seems to be a good predictor of future risk 8 .…”

Phenotyping Asthma and COPD

“…Serum periostin was identified as a secreted product of IL-13-stimulated bronchial epithelial cells 54 , and has been closely correlated with airway eosinophilia in some 55 , but not all 56,57 , studies. Some 58,59 , but not all 57 , studies suggest a combination of biomarkers gives better prediction of clinical outcomes. Since blood eosinophils are easily accessible, show the best association with airway eosinophilia, and are predictive of treatment response, this biomarker shows great promise for the identification of the eosinophilic endotype in clinical practice.…”