Treatment Resistance in Severe Asthma Patients With a Combination of High Fraction of Exhaled Nitric Oxide and Low Blood Eosinophil Counts
Background: Combining a fraction of exhaled nitric oxide (FeNO) and blood eosinophil count (B-EOS) may be a useful strategy for administration of biologics such as anti-IgE or anti-IL-5 to patients with type 2 inflammatory-predominant severe asthma and is important to be elucidated considering the i...
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.836635/full |
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| author | Yuki Hoshino Yuki Hoshino Tomoyuki Soma Tomoyuki Soma Yoshitaka Uchida Yoshitaka Uchida Yuki Shiko Kazuyuki Nakagome Kazuyuki Nakagome Makoto Nagata Makoto Nagata |
| author_facet | Yuki Hoshino Yuki Hoshino Tomoyuki Soma Tomoyuki Soma Yoshitaka Uchida Yoshitaka Uchida Yuki Shiko Kazuyuki Nakagome Kazuyuki Nakagome Makoto Nagata Makoto Nagata |
| author_sort | Yuki Hoshino |
| collection | DOAJ |
| description | Background: Combining a fraction of exhaled nitric oxide (FeNO) and blood eosinophil count (B-EOS) may be a useful strategy for administration of biologics such as anti-IgE or anti-IL-5 to patients with type 2 inflammatory-predominant severe asthma and is important to be elucidated considering the increasing use of biologics.Methods: This cross-sectional study analyzed the clinical data from 114 adult patients with severe asthma, who were treated at Saitama Medical University Hospital. The eligible patients were stratified into four subgroups defined by thresholds of FeNO and blood eosinophil (B-EOS) counts to detect sputum eosinophilia, using the receiver operating characteristic curve analysis. A total of 75 patients with optimal samples were stratified into four subtypes defined by thresholds of sputum eosinophilia and neutrophilia. Clinical characteristics, pattern of biologics, and distribution of sputum subtypes were analyzed in the stratified subclasses according to the FeNO and B-EOS thresholds. The asthma exacerbation (AE)-free time of the FeNO/B-EOS subgroups and any biologics treatment including anti-IgE or anti-IL-5 use were examined using the Kaplan–Meier method. The hazard ratios (HRs) for AE-free time were examined using the Cox proportional hazard model.Results: The optimal cutoff values for prediction of sputum eosinophilia were defined as ≥2.7% wherein for FeNO as ≥27 ppb and B-EOS as ≥265/µL were considered. The high-FeNO subgroups showed significant high total IgE, compared with the low FeNO. The high-FeNO/high-B-EOS and the high-FeNO/low-B-EOS subgroups showed the largest prevalence of mepolizumab and benralizumab use among the other FeNO/B-EOS, respectively. The high-FeNO/low-B-EOS showed the largest frequency of AEs, high HR, and the shortest AE-free time, among the other FeNO/B-EOS. The sputum eosinophil-predominant subtype was the great majority in the high FeNO/high B-EOS. A diverse distribution of sputum leukocyte-predominant subtype was observed in the other FeNO/B-EOS. The subsequent AE-free time and its HR were comparable among the biologics use groups.Conclusion: The strategy of classifying severe asthma based on the combination of FeNO and B-EOS proposes particular refractory type 2 severe asthma and underlying airway inflammation as a feasible trait for optimal biologics use. |
| first_indexed | 2024-12-10T11:37:05Z |
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| id | doaj.art-f8a9ec86961543e2a20794d172c69084 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-10T11:37:05Z |
| publishDate | 2022-04-01 |
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| spelling | doaj.art-f8a9ec86961543e2a20794d172c690842022-12-22T01:50:23ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-04-011310.3389/fphar.2022.836635836635Treatment Resistance in Severe Asthma Patients With a Combination of High Fraction of Exhaled Nitric Oxide and Low Blood Eosinophil CountsYuki Hoshino0Yuki Hoshino1Tomoyuki Soma2Tomoyuki Soma3Yoshitaka Uchida4Yoshitaka Uchida5Yuki Shiko6Kazuyuki Nakagome7Kazuyuki Nakagome8Makoto Nagata9Makoto Nagata10Department of Respiratory Medicine, Saitama Medical University, Saitama, JapanAllergy Center, Saitama Medical University, Saitama, JapanDepartment of Respiratory Medicine, Saitama Medical University, Saitama, JapanAllergy Center, Saitama Medical University, Saitama, JapanDepartment of Respiratory Medicine, Saitama Medical University, Saitama, JapanAllergy Center, Saitama Medical University, Saitama, JapanResearch Administration Center, Saitama Medical University, Saitama, JapanDepartment of Respiratory Medicine, Saitama Medical University, Saitama, JapanAllergy Center, Saitama Medical University, Saitama, JapanDepartment of Respiratory Medicine, Saitama Medical University, Saitama, JapanAllergy Center, Saitama Medical University, Saitama, JapanBackground: Combining a fraction of exhaled nitric oxide (FeNO) and blood eosinophil count (B-EOS) may be a useful strategy for administration of biologics such as anti-IgE or anti-IL-5 to patients with type 2 inflammatory-predominant severe asthma and is important to be elucidated considering the increasing use of biologics.Methods: This cross-sectional study analyzed the clinical data from 114 adult patients with severe asthma, who were treated at Saitama Medical University Hospital. The eligible patients were stratified into four subgroups defined by thresholds of FeNO and blood eosinophil (B-EOS) counts to detect sputum eosinophilia, using the receiver operating characteristic curve analysis. A total of 75 patients with optimal samples were stratified into four subtypes defined by thresholds of sputum eosinophilia and neutrophilia. Clinical characteristics, pattern of biologics, and distribution of sputum subtypes were analyzed in the stratified subclasses according to the FeNO and B-EOS thresholds. The asthma exacerbation (AE)-free time of the FeNO/B-EOS subgroups and any biologics treatment including anti-IgE or anti-IL-5 use were examined using the Kaplan–Meier method. The hazard ratios (HRs) for AE-free time were examined using the Cox proportional hazard model.Results: The optimal cutoff values for prediction of sputum eosinophilia were defined as ≥2.7% wherein for FeNO as ≥27 ppb and B-EOS as ≥265/µL were considered. The high-FeNO subgroups showed significant high total IgE, compared with the low FeNO. The high-FeNO/high-B-EOS and the high-FeNO/low-B-EOS subgroups showed the largest prevalence of mepolizumab and benralizumab use among the other FeNO/B-EOS, respectively. The high-FeNO/low-B-EOS showed the largest frequency of AEs, high HR, and the shortest AE-free time, among the other FeNO/B-EOS. The sputum eosinophil-predominant subtype was the great majority in the high FeNO/high B-EOS. A diverse distribution of sputum leukocyte-predominant subtype was observed in the other FeNO/B-EOS. The subsequent AE-free time and its HR were comparable among the biologics use groups.Conclusion: The strategy of classifying severe asthma based on the combination of FeNO and B-EOS proposes particular refractory type 2 severe asthma and underlying airway inflammation as a feasible trait for optimal biologics use.https://www.frontiersin.org/articles/10.3389/fphar.2022.836635/fullblood eosinophil countfraction of exhaled nitric oxide (feno)sputum eosinophiliasputum neutrophil-predominantasthma exacerbation (AE)anti-IL-5 biologics |
| spellingShingle | Yuki Hoshino Yuki Hoshino Tomoyuki Soma Tomoyuki Soma Yoshitaka Uchida Yoshitaka Uchida Yuki Shiko Kazuyuki Nakagome Kazuyuki Nakagome Makoto Nagata Makoto Nagata Treatment Resistance in Severe Asthma Patients With a Combination of High Fraction of Exhaled Nitric Oxide and Low Blood Eosinophil Counts Frontiers in Pharmacology blood eosinophil count fraction of exhaled nitric oxide (feno) sputum eosinophilia sputum neutrophil-predominant asthma exacerbation (AE) anti-IL-5 biologics |
| title | Treatment Resistance in Severe Asthma Patients With a Combination of High Fraction of Exhaled Nitric Oxide and Low Blood Eosinophil Counts |
| title_full | Treatment Resistance in Severe Asthma Patients With a Combination of High Fraction of Exhaled Nitric Oxide and Low Blood Eosinophil Counts |
| title_fullStr | Treatment Resistance in Severe Asthma Patients With a Combination of High Fraction of Exhaled Nitric Oxide and Low Blood Eosinophil Counts |
| title_full_unstemmed | Treatment Resistance in Severe Asthma Patients With a Combination of High Fraction of Exhaled Nitric Oxide and Low Blood Eosinophil Counts |
| title_short | Treatment Resistance in Severe Asthma Patients With a Combination of High Fraction of Exhaled Nitric Oxide and Low Blood Eosinophil Counts |
| title_sort | treatment resistance in severe asthma patients with a combination of high fraction of exhaled nitric oxide and low blood eosinophil counts |
| topic | blood eosinophil count fraction of exhaled nitric oxide (feno) sputum eosinophilia sputum neutrophil-predominant asthma exacerbation (AE) anti-IL-5 biologics |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.836635/full |
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