Predictive significance of Charcot-Leyden Crystal mRNA levels in nasal brushing for nasal polyp recurrence

Qi, Sihan; Yan, Bing; Liu, C; Wang, C; Zhang, Luo

doi:10.4193/rhin19.296

Cited by 29 publications

(33 citation statements)

References 48 publications

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“…Recurrence was de ned as the presence of nasal polyps observed under nasal endoscopy, together with at least one symptom (nasal obstruction, rhinorrhea, headache/facial pain, reduction or loss of smell, sleep disturbance/fatigue) lasting at least 1 week, despite appropriate intranasal corticosteroid treatment. The postoperative follow-up period was 18 months for assessment of recurrence/non-recurrence of nasal polyps [1,21]. All patients were followedup after weeks 1, 2, 4, and 12, and then once every three months for up to 18 months by the same surgeon, who was blinded to all laboratory data [21].…”

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confidence: 99%

“…The postoperative follow-up period was 18 months for assessment of recurrence/non-recurrence of nasal polyps [1,21]. All patients were followedup after weeks 1, 2, 4, and 12, and then once every three months for up to 18 months by the same surgeon, who was blinded to all laboratory data [21]. Nasal tissue samples were collected from the inferior turbinate of control subjects and the nasal polyps of CRSwNP patients during surgery.…”

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confidence: 99%

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Distinct Type 2-high Inflammation Associated Molecular Signatures of Chronic Rhinosinusitis with Nasal Polyps with Comorbid Asthma

Wang

Luan

et al. 2020

Preprint

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Abstract Background: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and comorbid asthma have more severe disease and are difficult to treat. However, the molecular endotypes associated with CRSwNP with comorbid asthma (CRSwNP+AS) are not clear. This study aimed to investigate the characteristics of type 2 inflammation and the molecular signatures associated with CRSwNP+AS. Methods: A total of 195 subjects; including 65 CRSwNP+AS patients, 99 patients with CRSwNP-alone, and 31 healthy control subjects; were enrolled in the study. Nasal tissues from patients with CRSwNP+AS, CRSwNP-alone and control subjects were assessed for infiltration of inflammatory cells and concentrations of total IgE. Whole-transcriptome sequencing was performed and differentially expressed (DE) mRNAs and long non-coding RNAs (lncRNAs) and their associated pathways were analyzed. The correlations between type 2 cytokines and local eosinophils, tissue IgE, and transcriptome signatures were evaluated. Results: Significantly higher local eosinophil infiltration and higher levels of total IgE were found in nasal tissues from CRSwNP+AS patients than in nasal tissues from CRSwNP-alone patients. Furthermore, atopy and recurrence were significantly more frequent in patients with CRSwNP+AS than in patients with CRSwNP-alone (62.5% vs 28.6% and 66.7% vs 26.9%, respectively). RNA sequencing analysis identified 1988 common DE-mRNAs, and 176 common DE-lncRNAs shared by CRSwNP+AS versus control and CRSwNP-alone versus control. Weighted gene coexpression network analysis (WGCNA) identified LINC01146 as hub lncRNA dysregulated in both subtypes of CRSwNP. Overall, 968 DE-mRNAs and 312 DE-lncRNAs were identified between CRSwNP+AS and CRSwNP-alone. Both pathway enrichment analysis and WGCNA indicated that the phenotypic traits of CRSwNP+AS were mainly associated with higher activities of arachidonic acid metabolism, type 2 cytokines related pathway and fibrinolysis pathway, and lower activity of IL-17 signalling pathway. Furthermore, the expression of type 2 cytokines; IL5 and IL13, was positively correlated with local eosinophil infiltration, tissue IgE level, and the expression of DE-mRNAs that related to arachidonic acid metabolism. Moreover, WGCNA identified HK3-006 as hub lncRNA in yellow module that most positively correlated with phenotypic traits of CRSwNP+AS. Conclusions: Patients with CRSwNP+AS have distinct type 2-high inflammation-associated molecular signatures in nasal tissues compared to patients with CRSwNP-alone.

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confidence: 99%

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Distinct Type 2-high Inflammation Associated Molecular Signatures of Chronic Rhinosinusitis with Nasal Polyps with Comorbid Asthma

Wang

Luan

et al. 2020

Preprint

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“…Persson et al [32] have reported that crystallized CLCs are key features of severe eosinophilic inflammatory airway diseases, including asthma and CRSwNP. In our recently published study, we have confirmed a promising predictive significance of mRNA level of CLC in polyp tissue for eosinophilic CRSwNP and in nasal brushing for polyp recurrence [33, 34]. In addition, our previous study reported CLC protein concentrations in nasal secretions were significantly elevated in patients with better response to oral glucocorticoids (GCs) and higher percentage of tissue eosinophilia [35].…”

Section: Introductionmentioning

confidence: 62%

Predictive Significance of Charcot-Leyden Crystal Protein in Nasal Secretions in Recurrent Chronic Rhinosinusitis with Nasal Polyps

Yan

Wang

et al. 2020

Int Arch Allergy Immunol

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Introduction: The recurrence occurs frequently among patients with chronic rhinosinusitis with nasal polyps (CRSwNP), and predictors that could be conveniently detected during practice in outpatient service are needed. Objective: We aimed to illustrate that the concentration of Charcot-Leyden crystal (CLC) in nasal secretions can effectively and noninvasively predict polyp recurrence. Methods: 108 patients with CRSwNP were divided into recurrence (n = 68) and recurrence-free (n = 40) groups. Preoperative CLC concentrations in nasal secretions were collected and detected by ELISA. Polyp tissues were harvested during biopsy or endoscopic sinus surgery and were evaluated for inflammatory cells by histopathological staining. Demographic information and the clinical characteristics of each patient were reviewed for associations with recurrence. Binary logistic regression analysis was performed to determine predictive factors for polyp recurrence. Receiver operating characteristic (ROC) curves and the Youden index were performed to determine their predictive values. Survival analysis was performed to compare recurrence risk of patients with different CLC concentrations. Results: Sixty-eight (62.96%) patients developed recurrence during a 12- to 33-month postoperative follow-up. CLC concentrations in nasal secretions were positively correlated with eosinophil percent in polyp tissue and peripheral blood and were significantly higher in patients of the recurrence group than in the patients of the recurrence-free group (p < 0.001). Binary logistic regression and ROC curve demonstrated that CLC protein in nasal secretions is predictive of polyp recurrence. According to the Youden index, a CLC concentration of 34.24 ng/mL can predict postoperative polyp recurrence with 92.6% sensitivity and 87.5% specificity. Patients with CLC concentrations higher than the cutoff value yielded a higher risk of recurrence (p < 0.001, HR = 11.31, 95% CI: 6.41–19.98). Conclusions: CLC protein in nasal secretions may serve as a promising noninvasive biomarker to predict CRSwNP recurrence.

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“…Clinically, increased levels of CLC protein have been reported to be present in nasal secretions in AR [13, 14], sputum in asthma [12], and nasal lavage fluid in patients with the aspirin-sensitive respiratory disease [39]. More recently, we have demonstrated that CLC mRNA and protein might serve as a marker in the identification of eosinophilic CRSwNP [40] as well as a reliable and alternative method for the prediction of glucocorticoid response in CRSwNP patients [15] and nasal polyp recurrence [41].…”

Section: Discussionmentioning

confidence: 99%

Charcot-Leyden Crystal Protein in Nasal Secretions of Patients with Nonallergic Rhinitis with Eosinophilia Syndrome

Zhang¹,

Yan²,

Wang³

et al. 2020

Int Arch Allergy Immunol

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Introduction: Charcot-Leyden crystal (CLC) protein has been regarded as a hallmark of eosinophilic inflammation. Objective: The purpose of this study was to investigate the role and levels of CLC protein in patients with nonallergic rhinitis with eosinophilia syndrome (NARES). Methods: Overall, 39 NARES patients and 19 controls were recruited. The severity of nasal symptoms was measured by visual analogue scale and serum and local specific immunoglobulin E were determined in all patients. Nasal eosinophilia was assessed by semiquantitative analysis of eosinophils in nasal scrapings. Nasal secretion CLC protein concentrations were evaluated by ELISA. Results: CLC protein concentrations were significantly higher in NARES patients than in controls (p < 0.0001). Nasal secretion CLC protein levels were significantly correlated with the degree of eosinophilia in nasal scrapings (rs = 0.331; p = 0.04) in NARES patients. Patients with high CLC protein concentrations displayed more severe nasal symptoms than patients with low CLC protein concentrations (p = 0.0080), particularly, nasal itching (p = 0.0029). Pilot study in 8 NARES patients demonstrated that treatment for 1 month with intranasal fluticasone propionate significantly decreased the nasal secretion CLC protein concentrations from baseline levels (p = 0.0335) and markedly attenuated the degree of swelling of inferior turbinate. Conclusions: CLC protein levels are significantly higher in nasal secretions of NARES patients and associated with the degree of nasal eosinophilia and the severity of nasal symptoms. Significantly, nasal secretion CLC protein levels obviously decreased after treatment with intranasal corticosteroids, suggesting its possible role in evaluating the medical treatment.

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Predictive significance of Charcot-Leyden Crystal mRNA levels in nasal brushing for nasal polyp recurrence

Cited by 29 publications

References 48 publications

Distinct Type 2-high Inflammation Associated Molecular Signatures of Chronic Rhinosinusitis with Nasal Polyps with Comorbid Asthma

Distinct Type 2-high Inflammation Associated Molecular Signatures of Chronic Rhinosinusitis with Nasal Polyps with Comorbid Asthma

Predictive Significance of Charcot-Leyden Crystal Protein in Nasal Secretions in Recurrent Chronic Rhinosinusitis with Nasal Polyps

Charcot-Leyden Crystal Protein in Nasal Secretions of Patients with Nonallergic Rhinitis with Eosinophilia Syndrome

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