Utility of serum YKL-40 levels for identification of patients with asthma and COPD

Gon, Yasuhiro; Maruoka, Shuichiro; Ito, Reiko; Mizumura, Kenji; Kozu, Yutaka; Hiranuma, Hisato; Hattori, Tomohiro; Takahashi, Masakazu; Hikichi, Mari; Hashimoto, Shigeo

doi:10.1016/j.alit.2017.02.010

Cited by 19 publications

(21 citation statements)

References 9 publications

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“…In fact, more pronounced upregulation of YKL-40 in COPD patients than in asthma patients was reported in Jame’s recent studies [ 24 ]. This is consistent with our present study and it suggest that YKL-40 is associated with COPD-related pathophysiology in addition to Th2-type inflammation; thus, it may be a potential biomarker to clinically identify ACO [ 30 ] and more investigations are needed in the future to elaborate the role of YKL-40 in the pathogenesis of chronic airway diseases.…”

Section: Discussionsupporting

confidence: 92%

Plasma YKL-40 and NGAL are useful in distinguishing ACO from asthma and COPD

Wang

Luo

et al. 2018

Respir Res

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BackgroundAsthma-chronic obstructive pulmonary disorder (COPD) overlap (ACO) is characterized by the coexistence of features of both asthma and COPD and is associated with rapid progress and a poor prognosis. Thus, the early recognition of ACO is crucial.ObjectivesWe sought to explore the plasma levels of biomarkers associated with asthma (periostin, TSLP and YKL-40), COPD (NGAL) and their possible correlation with lung function, the bronchodilator response and radiographic imaging in patients with asthma, COPD and with features of ACO.MethodsWe enrolled 423 subjects from 6 clinical centers. All participants underwent blood collection, lung function measurements, bronchodilator response tests and high-resolution CT. Correlations of the plasma biomarkers with lung function, the bronchodilator response and percentemphysema were calculated by Spearman’s rank correlation and multivariate stepwise regressionanalysis.Results1) Patients with features of ACO had lower plasma YKL-40 than COPD patients and a moderate elevated plasma level of NGAL compared with asthma patients. 2) Patients with features of ACO had an intermediate degree of airflow obstruction, the bronchodilator response and emphysema between patients with COPD and asthma. 3) Plasma YKL-40 was negatively correlated with lung function and with the bronchodilator response, and plasma NGAL was positively correlated with the extent of emphysema.ConclusionsPlasma YKL-40 is a promising candidate for distinguishing between patients with features of ACO and COPD patients, while plasma NGAL may be a valuable biomarker for differentiating between patients with features of ACO and asthma patients.Clinical trial registrationChiCTR-OOC-16009221.

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Section: Discussionsupporting

confidence: 92%

Plasma YKL-40 and NGAL are useful in distinguishing ACO from asthma and COPD

Wang

Luo

et al. 2018

Respir Res

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“…However, Type2 biomarkers may be useful in diagnosing ACO derived from COPD because adding an ICS to the treatment regimen is critical for such patients. Previous studies assessed the usefulness of several biomarkers in distinguishing ACO from asthma and COPD [ 167 , 168 , 169 ]. Wang et al found that plasma YKL-40 and neutrophil gelatinase-associated lipocalin (NGAL), but not the periostin, levels, were higher in COPD patients than in patients with asthma or ACO [ 167 ].…”

Section: Emerging Type2 Biomarkers In Copdmentioning

confidence: 99%

“…There was also no difference in serum periostin among the three patient groups. Gon et al reported that the serum YKL-40 levels were significantly higher in patients with ACO and COPD than in those with asthma, suggesting neutrophilic inflammation in ACO patients [ 169 ]. Together, these reports clarified the usefulness of some biomarkers in differentiating between asthma, COPD, and ACO.…”

Section: Emerging Type2 Biomarkers In Copdmentioning

confidence: 99%

Role of Type2 Inflammatory Biomarkers in Chronic Obstructive Pulmonary Disease

Oishi

Matsunaga

Shirai

et al. 2020

JCM

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Airway inflammation in chronic obstructive pulmonary disease (COPD) is typically thought to be driven by Type1 immune responses, while Type2 inflammation appears to be present in definite proportions in the stable state and during exacerbations. In fact, some COPD patients showed gene expression of Type2 inflammation in the airway, and this subset was associated with the inhaled corticosteroid (ICS) response. Interestingly enough, the relationship between COPD and diseases associated with Type2 inflammation from the perspective of impaired lung development is increasingly highlighted by recent epidemiologic studies on the origin of COPD. Therefore, many researchers have shown an interest in the prevalence and the role of existent Type2 biomarkers such as sputum and blood eosinophils, exhaled nitric oxide fraction, and atopy, not only in asthma but also in COPD. Although the evidence about Type2 biomarkers in COPD is inconsistent and less robust, Type2 biomarkers have shown some potential when analyzing various clinical outcomes or therapeutic response to ICS. In this article, we review the existent and emerging Type2 biomarkers with clinically higher applicability in the management of COPD.

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“…The higher levels of blood neutrophils in patients with NA compared with EA, along with the correlation between YKL-40 and blood neutrophils (absolute numbers and percentage) in our study, strengthen the association of serum YKL-40 with NA. In addition, recent studies [47–49] found that YKL-40 levels in chronic obstructive pulmonary disease (COPD) and asthma–COPD overlap (ACO) were higher than asthma, which is consistent with increased neutrophilic inflammation in these diseases. However, similar to the recent findings by James et al [22], our study did not observe relationship between serum YKL-40 and sputum neutrophils, which may be explained by different specimens although it indicated a moderate correlation between sputum and serum YKL-40 values [46].…”

Section: Discussionmentioning

confidence: 62%

Chitinase-like protein YKL-40 correlates with inflammatory phenotypes, anti-asthma responsiveness and future exacerbations

et al. 2019

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Background Asthma is a heterogeneous chronic airway disease, which may be classified into different phenotypes. YKL-40 is a chitin-binding glycoprotein with unclear functions, but its expression is associated with inflammation and tissue remodeling. However, few studies have explored whether YKL-40 is associated with inflammatory phenotypes of asthma. Methods The study had two parts. Study I ( n = 115) was a one-year prospective cohort designed to explore the relationship of serum YKL-40 levels with inflammatory phenotypes of asthma at baseline, and during exacerbations. Study II ( n = 62) was a four-week prospective cohort designed to define whether serum YKL-40 levels could predict responses to a fixed anti-asthma regimen. YKL-40, IL-6 and CCL22 levels were detected using ELISA, and a sputum inflammatory panel (including IL-1β, IL-5, IL-8 and TNF-α) was assessed using Luminex-based MILLIPLEX assay. Results Study I: Serum YKL-40 levels in non-eosinophilic asthma (NEA) i.e. neutrophilic (47.77 [29.59, 74.97] ng/mL, n = 40) and paucigranulocytic (47.36 [28.81, 61.68] ng/mL, n = 31) were significantly elevated compared with eosinophilic asthma (31.05 [22.41, 51.10] ng/mL, n = 44) ( P = 0.015). Serum YKL-40levels positively correlated with blood neutrophils, sputum IL-1β and plasma IL-6 but negatively correlated with serum IgE and blood eosinophils (all P ≤ 0.05). Baseline YKL-40 levels predicted moderate to severe exacerbations within a one-year period (aOR = 4.13, 95% CI = [1.08, 15.83]). Study II: Serum YKL-40 was an independent biomarker of negative responses to anti-asthma regimens (adjusted Odds Ratio [aOR] = 0.82, 95% CI = [0.71, 0.96]. Conclusions These studies show that YKL-40 is a non-type 2 inflammatory signature for NEA, which could predict responsiveness or insensitivity to anti-asthma medications and more exacerbations. Further studies are needed to assess whether monitoring YKL-40 levels could provide potential implications for clinical relevance. Electronic supplementary material The online version of this article (10.1186/s12931-019-1051-9) contains supplementary material, which is available to authorized users.

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Utility of serum YKL-40 levels for identification of patients with asthma and COPD

Cited by 19 publications

References 9 publications

Plasma YKL-40 and NGAL are useful in distinguishing ACO from asthma and COPD

Plasma YKL-40 and NGAL are useful in distinguishing ACO from asthma and COPD

Role of Type2 Inflammatory Biomarkers in Chronic Obstructive Pulmonary Disease

Chitinase-like protein YKL-40 correlates with inflammatory phenotypes, anti-asthma responsiveness and future exacerbations

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