Prospective predictors of exacerbation status in severe asthma over a 3‐year follow‐up

Kimura, Hiroyuki; Konno, Satoshi; Makita, Hironi; Taniguchi, Natsuko; Shimizu, Kaoruko; Suzuki, Masanobu; Goudarzi, Houman; Nakamaru, Yuji; Ono, Junya; Ohta, Shoichiro; Izuhara, Kenji; Ito, Yoichi M.; Wenzel, Sally E.; Nishimura, Masaharu; investigators, Hi-CARAT

doi:10.1111/cea.13170

Cited by 55 publications

(41 citation statements)

References 28 publications

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“…The study is based on data from the Hokkaido Severe Asthma Cohort Study (Hi-CARAT), which has previously been described in detail 10,11 . Patients with severe asthma were enrolled from Hokkaido University Hospital (Sapporo, Japan) and 29 a liated hospitals and clinics between February 2010 and September 2012.…”

Section: Study Protocol and Participantsmentioning

confidence: 99%

“…This study was registered in the University Hospital Medical Information Network Center Clinical Trials Registry system (https://upload.umin.ac.jp/cgi-openbin/ctr/ctr_view.cgi?recptno=R000003917). The diagnosis of severe asthma is based on the American Thoracic Society (ATS) criteria for refractory asthma published in 2000 12 , with slight modi cations 2,10,11 . Participants stayed at Hokkaido University Hospital for 2 days for initial screening and were followed up every 1 year on an outpatient basis for 3 years.…”

Section: Study Protocol and Participantsmentioning

confidence: 99%

“…FeNO levels were measured four times: at the initial screening at visit entry (VE), 1 year later (V1), 2 years later (V2), and 3 years after VE (V3). Detailed measurements of other biomarkers have been described in detail in previous reports 2, 10,11 .…”

Section: Feno Measurementmentioning

confidence: 99%

“…High FeNO levels have also been reported to be associated with good short-term response to ICS 8,9 . We previously reported that in patients with severe asthma, FeNO at baseline had a signi cant potential to predict future exacerbations 10 . However, the signi cance of longitudinal assessment of FeNO, including its variability, in the clinical course of severe asthma, especially the development of exacerbations, remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Annual fractional exhaled nitric oxide measurements and exacerbations in severe asthma: a multicenter observational cohort study

Abe

Suzuki

Kimura

et al. 2020

Preprint

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Background: Fractional exhaled nitric oxide (FeNO) reflects eosinophilic inflammation of the airways. However, the significance of longitudinal assessment of FeNO, including its variability, in the clinical course of severe asthma remains unclear. The aim of this study is to examine the association between long-term changes in FeNO and the development of exacerbations in severe asthma.Methods: Among the severe asthma patients enrolled in the Hokkaido Severe Asthma Cohort Study, 100 patients with severe asthma who completed a 3-year follow-up in which FeNO was measured annually were included. According to the FeNO level at baseline, 1 year, and 2 years, the patients were classified into three groups: the sustained high group (≥50 ppb at all three visits), the sustained low group (<25 ppb at all three visits), and the intermediate group (other). Subjects in the intermediate group were further classified into two groups based on the median value of the coefficient of variation (CV) of FeNO during the 3 years (high CV and low CV intermediate groups). Results: The sustained high group experienced shorter exacerbation-free survival and more frequent exacerbations than the sustained low group (median number of exacerbation events, 3 vs. 0, p = 0.01). In the intermediate group, the high CV group experienced shorter exacerbation-free survival than the low CV group, and the CV of FeNO was an independent contributing factor to the development of exacerbations.Conclusion: Persistence of FeNO above 50 ppb over the years as well as the presence of large variations in FeNO levels were associated with the development of exacerbations in patients with severe asthma.

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Section: Study Protocol and Participantsmentioning

confidence: 99%

Section: Study Protocol and Participantsmentioning

confidence: 99%

Section: Feno Measurementmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Annual fractional exhaled nitric oxide measurements and exacerbations in severe asthma: a multicenter observational cohort study

Abe

Suzuki

Kimura

et al. 2020

Preprint

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“…In this issue of the Journal, Kimura et al have looked for clinical and biomarker features associated with asthma exacerbations in adults with severe asthma. They followed 105 participants annually for 3 years.…”

mentioning

confidence: 99%

The benefits of allergy patient support groups

Roberts

2018

Clin Experimental Allergy

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Large‐scale plasma proteomics can reveal distinct endotypes in chronic obstructive pulmonary disease and severe asthma

Suzuki

Cole

Konno

et al. 2021

Clinical & Translational All

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Background Chronic airway diseases including chronic obstructive pulmonary disease (COPD) and asthma are heterogenous in nature and endotypes within are underpinned by complex biology. This study aimed to investigate the utility of proteomic profiling of plasma combined with bioinformatic mining, and to define molecular endotypes and expand our knowledge of the underlying biology in chronic respiratory diseases. Methods The plasma proteome was evaluated using an aptamer‐based affinity proteomics platform (SOMAscan®), representing 1238 proteins in 34 subjects with stable COPD and 51 subjects with stable but severe asthma. For each disease, we evaluated a range of clinical/demographic characteristics including bronchodilator reversibility, blood eosinophilia levels, and smoking history. We applied modified bioinformatic approaches used in the evaluation of RNA transcriptomics. Results Subjects with COPD and severe asthma were distinguished from each other by 365 different protein abundancies, with differential pathway networks and upstream modulators. Furthermore, molecular endotypes within each disease could be defined. The protein groups that defined these endotypes had both known and novel biology including groups significantly enriched in exosomal markers derived from immune/inflammatory cells. Finally, we observed associations to clinical characteristics that previously have been under‐explored. Conclusion This investigational study evaluating the plasma proteome in clinically‐phenotyped subjects with chronic airway diseases provides support that such a method can be used to define molecular endotypes and pathobiological mechanisms that underpins these endotypes. It provided new concepts about the complexity of molecular pathways that define these diseases. In the longer term, such information will help to refine treatment options for defined groups.

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Prospective predictors of exacerbation status in severe asthma over a 3‐year follow‐up

Abstract: Measurement of FeNO has a significant potential to predict future asthma exacerbation, which is independent of the "past exacerbation history."

Cited by 55 publications

References 28 publications

Annual fractional exhaled nitric oxide measurements and exacerbations in severe asthma: a multicenter observational cohort study

Annual fractional exhaled nitric oxide measurements and exacerbations in severe asthma: a multicenter observational cohort study

The benefits of allergy patient support groups

Large‐scale plasma proteomics can reveal distinct endotypes in chronic obstructive pulmonary disease and severe asthma

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