Determination of the cutoff values of Th2 markers for the prediction of future exacerbation in severe asthma: An analysis from the Hokkaido Severe Asthma Cohort Study

Kimura, Hirokazu; Makita, Hironi; Taniguchi, Natsuko; Takei, Nozomu; Matsumoto, M.; Kimura, Hironobu; Goudarzi, Houman; Shimizu, Kaoruko; Suzuki, Masaru; Nishimura, Masaharu; Konno, Satoshi

doi:10.1016/j.alit.2020.09.001

Cited by 8 publications

(11 citation statements)

References 27 publications

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“…In the study by Denton et al, 6 a large cohort of severe asthma patients from the International Severe Asthma Registry (ISAR) study had a similar incidence of asthma exacerbations between T2-high and T2-low patients. Conversely, the incidence of asthma exacerbations in T2-high severe asthma patients was higher than in T2-low patients in the Kimura et al 9 and Haughney et al 21 studies. These differences may derive from the differences in biomarkers, the criteria used to categorize severe asthma patients as T2-high or T2-low, and general patient characteristics in each study (eg, Haughney et al used a cutoff point of 400 cells/μL to categorize patients as being in the high eosinophil or low eosinophil groups, and had a younger patient population).…”

Section: Discussionmentioning

confidence: 77%

“…In this study, the proportions of patients with asthma exacerbation were similar between the T2-high population (30.6%, 95% CI: 26.9–34.4) and T2-low population (34.6%, 95% CI: 26.6–43.3). However, the results of the studies by Kimura et al 9 and Denton et al 6 were inconsistent in terms of asthma exacerbations in T2-high and T2-low severe asthma patients. In the study by Denton et al, 6 a large cohort of severe asthma patients from the International Severe Asthma Registry (ISAR) study had a similar incidence of asthma exacerbations between T2-high and T2-low patients.…”

Section: Discussionmentioning

confidence: 96%

“… 8 The exacerbation risk was found to be higher in severe asthma patients with T2-high features than in those with severe asthma and without any T2-high features. 9 Conversely, other studies did not show a higher exacerbation rate in severe asthma patients with T2-high features. 6 , 10 The discrepancy in the results was attributed to the small samples of T2-low severe asthma patients and the inclusion of severe asthma patients treated with biologics which affected the T2 biomarkers value.…”

Section: Introductionmentioning

confidence: 87%

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A Retrospective Claims Database Study to Clarify Disease Burden of Severe Asthma Patients with Type 2 High or Low Inflammation

Harada

Makita

Fukui

et al. 2023

JAA

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Purpose The disease burden of severe asthma patients stratified by type 2 (T2) biomarkers is not well studied in large patient samples, especially for T2-low severe asthma patients. Using a Japanese medical record database, we investigated disease and economic burdens in T2-high and T2-low severe asthma patients. Patients and Methods Data of severe asthma patients (receiving high-dose inhaled corticosteroids and additional asthma-related controller medications or oral corticosteroids [OCS] prescription [≥183 days] during the 1-year baseline period) were analyzed in the Real World Data database, comprising electronic medical records from Japanese medical institutions. Severe asthma patients were stratified into a T2-high population with higher eosinophils (≥150 cells/μL) and/or higher total immunoglobulin E (IgE, ≥75 IU/mL) or a T2-low population with lower eosinophils (<150 cells/μL) and lower total IgE (<75 IU/mL). The incidence of asthma exacerbation events and drug costs were analyzed for each population. Different T2 thresholds were explored, including eosinophil count 300 cells/μL and/or IgE 150 IU/mL. Results Of the 732 severe asthma patients, 599 (81.8%) patients had T2-high type, and 133 (18.2%) had T2-low type. Proportions of the T2-high patients (30.6%) with asthma exacerbations, defined as a composite outcome, including OCS burst, injectable steroid use, and hospitalization, were similar to those of T2-low type (34.6%). The annual drug cost was similar between T2-high (175,487 JPY) and T2-low (165,322 JPY) populations. Conclusion In this large-scale study, both T2-high and T2-low severe asthma patients in Japan were shown to have a high disease burden and high economic burden, suggesting an unmet treatment need.

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Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 87%

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A Retrospective Claims Database Study to Clarify Disease Burden of Severe Asthma Patients with Type 2 High or Low Inflammation

Harada

Makita

Fukui

et al. 2023

JAA

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“…the reduction in exacerbations was 42–52% in SPIRIT, compared with 23% in the LUSTER studies. Previous studies have indicated that increased blood eosinophil count may be associated with more frequent asthma exacerbations [ 20 , 21 ]. In the present study the reduction in exacerbations was observed for both the overall population and the high eosinophil subpopulation.…”

Section: Discussionmentioning

confidence: 99%

Long-term safety and exploratory efficacy of fevipiprant in patients with inadequately controlled asthma: the SPIRIT randomised clinical trial

Máspero¹,

Agache

Kamei

et al. 2021

Respir Res

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Background The prostaglandin D2 (PGD2) receptor 2 (DP2 receptor) pathway is an important regulator of the inflammatory cascade in asthma, which can be stimulated by allergic or non-allergic triggers. Fevipiprant is an oral, non-steroidal, highly selective, reversible antagonist of the DP2 receptor that inhibits the binding of PGD2 and its metabolites. Methods SPIRIT, a 2-treatment period (52-week, double-blind and optional 104-week single-blind), randomised, placebo-controlled, multicentre, parallel-group study, assessed the long-term safety of fevipiprant (150 mg and 450 mg o.d.) added to standard of care in patients ≥ 12 years with uncontrolled asthma. Stratified block randomisation was used. Patients were randomised in an approximate ratio of 3:3:1 (fevipiprant 150 mg, fevipiprant 450 mg or placebo). Patients were either newly enrolled or had participated in a previous fevipiprant Phase 3 trial. Primary endpoints were: time-to-first treatment emergent adverse event (AE); serious AE; and AE leading to discontinuation from study treatment. Data from both treatment periods were combined for analyses. Data were collected during study site visits. Results In total, 1093 patients were randomised to receive fevipiprant 150 mg, 1085 to fevipiprant 450 mg, and 360 to placebo. Overall, 1184 patients had ≥ 52 weeks’ treatment, while 163 received ≥ 104 weeks’ treatment. Both doses were well tolerated, with a safety profile similar to placebo both in new patients and in those enrolled from previous studies. In exploratory analyses, reduced rates of moderate-to-severe asthma exacerbations, increased time-to-first moderate-to-severe asthma exacerbation and improved FEV1 were observed for both doses of fevipiprant versus placebo; these were without multiplicity adjustment and should be interpreted with caution. SPIRIT was terminated early, on 16 December 2019, by the Sponsor. Conclusions In patients with uncontrolled asthma, the addition of fevipiprant had a favourable long-term safety profile. Trial registration Clinicaltrials.gov, NCT03052517, prospectively registered 23 January 2017, https://clinicaltrials.gov/ct2/show/NCT03052517.

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“…These data suggested that increased CXCL14 in induced sputum might be involved in eosinophilic and allergic inflammation. FeNO, EOS#, and serum IgE are considered biomarkers of Th2 inflammation, according to the cutoff value of FeNO (30 ppb), EOS# (0.3 × 10 9 cells/mL), and IgE (100 IU/mL) [34][35][36][37], asthma patients with any two of the more significant than the cutoff value can be defined as Th2 phenotype. Based on these criteria, we found both the mRNA and protein levels of CXCL14 were sig- nificantly upregulated in the higher levels of FeNO (>30 ppb) than in the lower levels of FeNO (<30 ppb) (p < 0.05) (Fig.…”

Section: The Expression Of Cxcl14 Was Significantly Associated With E...mentioning

confidence: 99%

Elevated CXCL14 in Induced Sputum Was Associated with Eosinophilic Inflammation and Airway Obstruction in Patients with Asthma

Shi

et al. 2022

Int Arch Allergy Immunol

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Introduction: CXCL14 involved in inflammatory processes was upregulated in the asthma expression profile datasets in our pilot study. However, the expression of CXCL14 in induced sputum and its potential clinical role in asthma were poorly reported. Objective: We sought to detect CXCL14 expression in airway epithelium and induced sputum cells of asthma and explore its potential clinical implications. Methods: The expression of CXCL14 in asthma was analyzed using R software based on multiple microarray datasets, including GSE43696, GSE63142, GSE67940, and GSE76262. Subsequent verification of the CXCL14 expression pattern in induced sputum and bronchial epithelium cells was performed by qRT-PCR and ELISA. Besides, the correlations between CXCL14 and eosinophilic inflammation indicators (FeNO, EOS#, and IgE), Th2 signature genes (SERPINB2, POSTN, and CLCA1), inflammatory cytokines (IL-4, IL-5, IL-10, IL-13, IL-25, IL-33, TSLP, IL-8, IL-17A, IFN-γ, and IL-2), and airway obstruction indicators (pulmonary function and mucin secretion) were further explored. Results: The expression of CXCL14 in epithelium and sputum cells was upregulated in asthma and positively correlated with clinical eosinophilic indicators. The protein levels of CXCL14 were positively associated with Th2 signature genes (SERPINB2, POSTN, and CLCA1) and Th2 cytokines (IL-4, IL-5, IL-10, IL-13, IL-25, IL-33, and TSLP). Increased expression of CXCL14 was also observed in BEAS-2B cells stimulated by the cytokine IL-4. Furthermore, the expression of CXCL14 was positively correlated with MUC5AC secretion and negatively associated with pulmonary function. Conclusions: Upregulated CXCL14 in asthma was positively correlated with inflammatory indicators and negatively correlated with pulmonary function, which indicated that upregulated CXCL14 might act as a pathogenic gene through involvement in Th2 inflammation in asthma.

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Determination of the cutoff values of Th2 markers for the prediction of future exacerbation in severe asthma: An analysis from the Hokkaido Severe Asthma Cohort Study

Cited by 8 publications

References 27 publications

A Retrospective Claims Database Study to Clarify Disease Burden of Severe Asthma Patients with Type 2 High or Low Inflammation

A Retrospective Claims Database Study to Clarify Disease Burden of Severe Asthma Patients with Type 2 High or Low Inflammation

Long-term safety and exploratory efficacy of fevipiprant in patients with inadequately controlled asthma: the SPIRIT randomised clinical trial

Elevated CXCL14 in Induced Sputum Was Associated with Eosinophilic Inflammation and Airway Obstruction in Patients with Asthma

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