Abstract
BackgroundAsthma 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.MethodsThe 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.ResultsStudy 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].ConclusionsThese 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.
Highlights
Asthma is a heterogeneous chronic airway disease, which may be classified into different phenotypes
Characteristics of subjects grouped by airway inflammatory phenotypes As there were only two participants with a mixed granulocytic inflammatory phenotype in study I, they were not included in the analysis
Airway and systemic inflammation Compared with the eosinophilic asthma (EA) subjects, the Neutrophilic asthma (NA) group had higher levels of blood neutrophils (56.50 ± 7.67 vs. 61.96 ± 8.76, P = 0.003 for percentage), plasma CCL22 (600.7 [398.8, 968.2] vs. 920.6 [604.6, 1108.5] pg/mL, P = 0.029), sputum neutrophils (0.88 [0.36, 3.32] vs. 5.93 [2.57, 11.70] × 106/L, P < 0.001 for absolute numbers, and 42.50 [15.50, 57.75] vs. 87.25 [70.25, 96.00] %, P = 0.029 for percentage), sputum IL-1β (11.90 [5.77, 28.71] vs. 67.09 [8.64, 476.99] pg/mL, P < 0.001), IL-8 (1272.00 [638.28, 2047.75] vs. 2218.00 [1014.00, 3702.00] pg/mL, P = 0.009) and tumor necrosis factor (TNF)-α (10.10 [4.66, 20.19] vs. 34.02 [8.64, 63.80] pg/mL, P = 0.001), but lower eosinophils in blood and sputum (Table 2)
Summary
Asthma is a heterogeneous chronic airway disease, which may be classified into different phenotypes. Asthma is an inflammatory disease characterized by airway hyper-responsiveness and remodeling [1], and may be classified into different phenotypes [2, 3]. A group of proteins recently discovered to be potential biomarkers of asthma are the chitinases and chitinase-like proteins Two members of this family, the enzymatically active chitotriosidase and the enzymatically inactive chitinase-like protein YKL-40, may play important roles in driving asthma disease pathogenesis. A few studies have found negative correlations between YKL-40 and these biomarkers [1, 20, 22] It remains unclear if YKL-40 is differentially expressed in eosinophilic and non-eosinophilic asthma (EA and NEA). We hypothesized YKL-40 would be a specific biomarker for NEA
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
