Biomarkers to identify sputum eosinophilia in different adult asthma phenotypes

Abstract

Several biomarkers have been used to assess sputum eosinophilia in asthma. It has been suggested that the diagnostic accuracy of these biomarkers might differ between asthma phenotypes. We investigated the accuracy of biomarkers in detecting sputum eosinophilia (⩾3%) in different adult asthma phenotypes.Levels of eosinophils in blood and sputum, exhaled nitric oxide fraction (FeNO) and total immunoglobulin (Ig)E from 336 adult patients, enrolled in three prospective observational clinical trials and recruited at five pulmonology outpatient departments, were analysed. Areas under the receiver operating characteristics curves (AUC) for detecting sputum eosinophilia were calculated and compared between severe and mild, obese and nonobese, atopic and nonatopic and (ex-)smoking and never-smoking asthma patients.Sputum eosinophilia was present in 116 patients (35%). In the total group the AUC was 0.83 (95% CI 0.78-0.87) for blood eosinophils, 0.82 (0.77-0.87) for FeNO and 0.69 (0.63-0.75) for total IgE. AUCs were similar for blood eosinophils and FeNO between different phenotypes. Total IgE was less accurate in detecting sputum eosinophilia in atopic and obese patients than in nonatopic and nonobese patients.Blood eosinophils and FeNO had comparable diagnostic accuracy (superior to total IgE) in identifying sputum eosinophilia in adult asthma patients, irrespective of asthma phenotype such as severe, nonatopic, obese and smoking-related asthma. @ERSpublications FeNO and blood eosinophils can be used to detect sputum eosinophilia in adult asthma patients regardless of phenotype

Improving the diagnosis of eosinophilic asthma

“…Unfortunately, the results of these studies are not fully conclusive. One study did not find an improvement in accuracy when combining blood eosinophils, FeNO, and periostin as compared to one of the single biomarkers [46], whereas another study did find a small enhancement in accuracy when combining FeNO and blood eosinophils [50]. Adding IgE to these models did not lead to any improvement of the results.…”

“…From these results, the authors concluded that using a cutoff of 0.45 × 10 9 /L or higher for blood eosinophilia could safely predict airway eosinophilia. Also other studies reported that a blood eosinophil threshold ≥0.4 × 10 9 /L could predict sputum eosinophilia with high probability [8,50]. Westerhof et al not only found a specificity of 95% for blood eosinophils ≥0.41 × 10 9 /L to rule in, but also a sensitivity of 96% for ≤0.09 × 10 9 /L eosinophils to rule out sputum eosinophilia [50].…”

“…When comparing blood eosinophils with IgE, the results were not conclusive. Remarkably, Westerhof and colleagues, when comparing atopic and non-atopic patients with asthma, found poorer accuracy of total IgE for detecting sputum eosinophilia in atopic patients, suggesting that in these patients IgE has no value in distinguishing between those with or without sputum eosinophilia [50]. Thus, of all currently available biomarkers to detect eosinophilic asthma, IgE seems to be the least useful.…”

“…Only few studies have specifically looked at the accuracy of a combination of two or more biomarkers to detect eosinophilic airway inflammation [26,46,50]. Unfortunately, the results of these studies are not fully conclusive.…”

“…Threshold values with high sensitivity or high specificity to detect elevated sputum eosinophils have also been reported for FeNO [8,34,42,50,[66][67][68]. However, these thresholds vary widely depending on the technique that is being used, and the population under study.…”