Hyperuricemia Increases the Risk of Postoperative Recurrence in Chinese Patients with Chronic Rhinosinusitis.

Background: Elevated serum uric acid is crucial in the pathophysiology of chronic inflammatory diseases. However, its impact on chronic rhinosinusitis (CRS) recurrence risk is unknown. This study investigates the association between elevated serum uric acid and the risk of CRS recurrence. Methods: A retrospective cohort study was conducted on 1004 CRS patients (including 638 males and 366 females) who received functional endoscopic sinus surgery. All patients were followed up for more than 2 years, and categorized into subgroups based on phenotype, gender, and postoperative recurrence. Cox regression analysis was performed to evaluate the associations between serum uric acid and the risk of CRS recurrence. Results: After categorization, 104 males had hyperuricemia, and 54 females presented hyperuricemia. The rate of recurrent CRS in the hyperuricemia group was significantly higher compared to the non-hyperuricemia group in both males and females (P<0.05). In both male and female patients, the rate of hyperuricemia and uric acid levels were elevated in the recurrent CRS group in comparison with the non-recurrent CRS group (P<0.05). Unadjusted and adjusted Cox regression analysis demonstrated that serum uric acid was an independent risk factor for CRS recurrence (P<0.05). The receiver operator characteristic curve showed that serum uric acid was a potential biomarker for predicting the recurrence of CRS and its phenotypes in both genders (P<0.05). Conclusion: There is a close relationship between elevated serum uric acid and the recurrence risk of CRS and its phenotypes, suggesting that serum uric acid may be a novel biomarker for predicting recurrent CRS.

PPARγ attenuates cellular senescence of alveolar macrophages in asthma-COPD overlap.

BACKGROUND: Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) represents a complex condition characterized by shared clinical and pathophysiological features of asthma and COPD in older individuals. However, the pathophysiology of ACO remains unexplored. We aimed to identify the major inflammatory cells in ACO, examine senescence within these cells, and elucidate the genes responsible for regulating senescence. METHODS: Bioinformatic analyses were performed to investigate major cell types and cellular senescence signatures in a public single-cell RNA sequencing (scRNA-Seq) dataset derived from the lung tissues of patients with ACO. Similar analyses were carried out in an independent cohort study Immune Mechanisms Severe Asthma (IMSA), which included bulk RNA-Seq and CyTOF data from bronchoalveolar lavage fluid (BALF) samples. RESULTS: The analysis of the scRNA-Seq data revealed that monocytes/ macrophages were the predominant cell type in the lung tissues of ACO patients, constituting more than 50% of the cells analyzed. Lung monocytes/macrophages from patients with ACO exhibited a lower prevalence of senescence as defined by lower enrichment scores of SenMayo and expression levels of cellular senescence markers. Intriguingly, analysis of the IMSA dataset showed similar results in patients with severe asthma. They also exhibited a lower prevalence of senescence, particularly in airway CD206 + macrophages, along with increased cytokine expression (e.g., IL-4, IL-13, and IL-22). Further exploration identified alveolar macrophages as a major subtype of monocytes/macrophages driving cellular senescence in ACO. Differentially expressed genes related to oxidation-reduction, cytokines, and growth factors were implicated in regulating senescence in alveolar macrophages. PPARγ (Peroxisome Proliferator-Activated Receptor Gamma) emerged as one of the predominant regulators modulating the senescent signature of alveolar macrophages in ACO. CONCLUSION: The findings suggest that senescence in macrophages, particularly alveolar macrophages, plays a crucial role in the pathophysiology of ACO. Furthermore, PPARγ may represent a potential therapeutic target for interventions aimed at modulating senescence-associated processes in ACO.Key words ACO, Asthma, COPD, Macrophages, Senescence, PPARγ.

PPARγ Attenuates Cellular Senescence of Alveolar Macrophages in Asthma- COPD Overlap.

Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) represents a complex condition characterized by shared clinical and pathophysiological features of asthma and COPD in older individuals. However, the pathophysiology of ACO remains unexplored. We aimed to identify the major inflammatory cells in ACO, examine senescence within these cells, and elucidate the genes responsible for regulating senescence. Bioinformatic analyses were performed to investigate major cell types and cellular senescence signatures in a public single-cell RNA sequencing (scRNA-Seq) dataset derived from the lung tissues of patients with ACO. Similar analyses were carried out in an independent cohort study Immune Mechanisms Severe Asthma (IMSA), which included bulk RNA-Seq and CyTOF data from bronchoalveolar lavage fluid (BALF) samples. The analysis of the scRNA-Seq data revealed that monocytes/ macrophages were the predominant cell type in the lung tissues of ACO patients, constituting more than 50% of the cells analyzed. Lung monocytes/macrophages from patients with ACO exhibited a lower prevalence of senescence as defined by lower enrichment scores of SenMayo and expression levels of cellular senescence markers. Intriguingly, analysis of the IMSA dataset showed similar results in patients with severe asthma. They also exhibited a lower prevalence of senescence, particularly in airway CD206 + macrophages, along with increased cytokine expression (e.g., IL-4, IL-13, and IL-22). Further exploration identified alveolar macrophages as a major subtype of monocytes/macrophages driving cellular senescence in ACO. Differentially expressed genes related to oxidation-reduction, cytokines, and growth factors were implicated in regulating senescence in alveolar macrophages. PPARγ (Peroxisome Proliferator-Activated Receptor Gamma) emerged as one of the predominant regulators modulating the senescent signature of alveolar macrophages in ACO. Collectively, the findings suggest that senescence in macrophages, particularly alveolar macrophages, plays a crucial role in the pathophysiology of ACO. Furthermore, PPARγ may represent a potential therapeutic target for interventions aimed at modulating senescence-associated processes in ACO.

Does skin prick test response intensity predict symptom severity and efficacy of subcutaneous immunotherapy in allergic rhinitis?

OBJECTIVES: To investigate the effect of response intensity of allergen skin prick test (SPT) on symptom severity and long-term efficacy of dust mite subcutaneous immunotherapy (SCIT) in allergic rhinitis (AR). METHODS: AR Patients diagnosed with dust mite allergy and completed 3 years of SCIT were collected and classified into three groups: grade 2 (SPT of + +), grade 3 (SPT of + + +) and grade 4 (SPT of + + + +). Comparisons between groups were performed to examine the associations of SPT categories and symptom severity and the long-term efficacy of SCIT in AR. RESULTS: 181 AR patients were included. There was no significant difference in the baseline TNSS, SMS, RQLQ and VAS, and particularly to symptom severity grading among three SPT grade groups (P > 0.05). The moderate-severe AR was more likely to be smoking and accompany with asthma and had higher prevalence of sensitization to cockroach, mixed grass and tree pollen than mild AR (P < 0.05). Prevalence of sensitization to cockroach, mixed grass, ragweed and animal dander was increased in AR patients with asthma and allergic conjunctivitis (P < 0.05). Furthermore, after 3 years of SCIT, no statistical differences in TNSS, SMS, RQLQ, VAS and long-term efficacy were observed among the three SPT grade groups (P > 0.05). Similarly, long-term outcomes of patients with different SPT grades did not differ among different clinical characteristics and different efficacy determination criteria (P > 0.05). CONCLUSIONS: The SPT response intensity cannot be used as an objective evaluation index for symptom severity and the long-term efficacy of SCIT in AR patients.

Long-Term Efficacy and Safety of Subcutaneous Immunotherapy in Monosensitized and Polysensitized Children With Allergic Rhinitis.

OBJECTIVE: To evaluate the efficacy and safety of dust mite subcutaneous immunotherapy (SCIT) in monosensitized and polysensitized children with allergic rhinitis (AR). STUDY DESIGN: Prospective cohort study. SETTING: Tertiary referral center. METHODS: One hundred thirty children were enrolled and categorized into 2 groups: monosensitized to only dust mites and polysensitized to at least 1 additional allergen beyond dust mites. All patients received SCIT targeting dust mites for 3 years, followed by a 5-year monitoring period. The Total Nasal Symptom Score (TNSS), Symptom and Medication Score (SMS), Visual Analogue Scale (VAS), and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) were assessed before SCIT (T0); at 1 (T1) and 2 (T2) years of SCIT; immediately after SCIT (T3); and 2 years post-SCIT (T5). Safety was assessed based on adverse events (AEs). RESULTS: Fifty-one monosensitized and 50 polysensitized children completed the study. At T3, 47 monosensitized and 46 polysensitized children were effectively treated, with no significant between-group difference in efficacy (P > .05). The TNSS, SMS, VAS scores, and RQLQ score were significantly lower at T1, T2, T3, and T5 than at T0 in both groups (P < .05). The differences in the TNSS, SMS, VAS score, and RQLQ score between the 2 groups were nonsignificant at T0, T1, T2, and T3 (P > .05), but significant at T5 (P < .05). No serious AEs were reported. CONCLUSION: Monosensitized and polysensitized children exhibited similar beneficial efficacy and safety after 3 years of dust mite SCIT. Monosensitized children derived more benefits 2 years after discontinuation.

Evaluation of Intralymphatic Immunotherapy in Allergic Rhinitis Patients: A Systematic Review and Meta-analysis.

Background: Intralymphatic immunotherapy (ILIT) is short-course administration of allergen-specific immunotherapy (AIT). This study is aimed at assessing the clinical efficacy and safety of ILIT in patients with allergic rhinitis (AR). Methods: MEDLINE, PUBMED, and Cochrane Library were used to conduct electronic searches for clinical trials comparing ILIT and placebo in patients with AR. The final search took place on August 24, 2022. Cochrane Handbook for Systematic Reviews of Interventions was used to assess the risk of bias in the included studies. The outcomes included combined symptom and medication scores (CSMS), visual analog scale (VAS), allergic rhinoconjunctivitis quality of life (RQLQ), Skin-prick test (SPT), and adverse events (AEs). Data were synthesized as mean difference (MD)/standard mean difference (SMD) or risk difference (RD) and 95% confidence interval (CI). Results: Thirteen studies (454 participants) were included in this study. The ILIT group had better clinical improvement on the CSMS (random effects model, SMD-0.85, 95% CI [-1.58, -0.11], P = 0.02) and RQLQ (fixed-effects model, MD-0.42, 95% CI [0.69, 0.15], P = 0.003) than the placebo group. The booster injection was beneficial for CSMS (P < 0.0001), and the 4-week injection interval was superior to the 2-week injection period for improving VAS (P < 0.0001). Local swelling or erythema was the main AE following injection (random effects model, RD 0.16, 95% CI [0.05, 0.27], P = 0.005). Discussion. For individuals with AR, ILIT is safe and effective. ILIT alleviates clinical symptoms and reduces pharmaceutical consumption without causing severe AEs. However, the validity of this study is compromised by the substantial heterogeneity and risk of bias in the included researches. RegistrationCRD42022355329.

Significance of leukocyte-specific transcript 1 levels in nasal mucosal tissue to predict recurrence of nasal polyps

Abstract Objective: Chronic Rhinosinusitis with Polyps (CRSwNP) is characterized by high heterogeneity and postoperative recurrence rate. This study aims to explore the clinical significance of tissue Leukocyte-Specific Transcript 1 (LST1) in predicting CRSwNP recurrence. Methods: We enrolled 62 CRSwNP patients including 30 primary CRSwNP and 32 recurrent CRSwNP patients, and 40 Healthy Controls (HC). Tissue samples were collected. Tissue LST1 expression was assessed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR), Western Blotting (WB) and Immunofluorescence (IF) staining. The predictive values of LST1 expression for CRSwNP postoperative recurrence were assessed through the Receiver Operating Characteristic (ROC) curves. Results: The tissue levels of LST1 were significantly increased in the CRSwNP group than the HC group, especially in the recurrent group, and the elevated LST1 mRNA levels were positively correlated with the peripheral eosinophil percentages, tissue eosinophil counts and percentages. IF staining results showed that the LST1 protein levels were higher in CRSwNP patients, especially in the recurrent patients than in the HC group. ROC curves highlighted that tissue LST1 levels were associated with recurrent CRSwNP and exhibited a higher predictive ability for postoperative CRSwNP recurrence. Conclusion: This was the first report suggesting that LST1 expression was upregulated and associated with mucosal eosinophil infiltration and CRSwNP recurrence. Tissue LST1 could be a promising biomarker for predicting postoperative recurrence in CRwNP patients.

Elevated body mass index increased the risk of recurrence in Chinese patients with chronic rhinosinusitis.

BACKGROUND: Elevated body mass index (BMI) has been associated with an increased prevalence of chronic rhinosinusitis (CRS). However, the impact of BMI on the risk of recurrence of CRS is unknown. This study aimed to investigate the association between BMI and the risk of CRS recurrence. MATERIAL AND METHODS: A retrospective cohort study was conducted and recruited 1057 CRS patients who underwent functional endoscopic sinus surgery (FESS). All subjects were classified into four groups: "underweight", "normal weight", "overweight", and "obese". Multivariate regression analysis was performed to examine the associations between BMI categories and other factors and the risk of CRS recurrence. RESULTS: The rate of recurrent CRS was significantly higher in the overweight group and obese group than in the normal weight group (P < 0.05). Unadjusted and adjusted logistic regression analyses demonstrated that overweight and obesity exhibited an increased risk of CRS recurrence as compared to patients with normal weight (P < 0.05). Furthermore, all patients were divided into primary CRS group and recurrent CRS group, and the BMI, duration of disease and rate of allergic rhinitis were vastly increased in the recurrent group than in the primary group (P < 0.05). Univariate and multivariate regression analysis showed that BMI and duration of disease were the dominant risk factors of CRS recurrence (P < 0.05). CONCLUSION: Overweight and obesity presented significant impacts on the CRS recurrence, and elevated BMI were associated with an increased risk of CRS recurrence independently from traditional risk factors. A longer duration of disease was correlated with a higher risk of CRS recurrence.

Significance of leukocyte-specific transcript 1 levels in nasal mucosal tissue to predict recurrence of nasal polyps.

OBJECTIVE: Chronic Rhinosinusitis with Polyps (CRSwNP) is characterized by high heterogeneity and postoperative recurrence rate. This study aims to explore the clinical significance of tissue Leukocyte-Specific Transcript 1 (LST1) in predicting CRSwNP recurrence. METHODS: We enrolled 62 CRSwNP patients including 30 primary CRSwNP and 32 recurrent CRSwNP patients, and 40 Healthy Controls (HC). Tissue samples were collected. Tissue LST1 expression was assessed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR), Western Blotting (WB) and Immunofluorescence (IF) staining. The predictive values of LST1 expression for CRSwNP postoperative recurrence were assessed through the Receiver Operating Characteristic (ROC) curves. RESULTS: The tissue levels of LST1 were significantly increased in the CRSwNP group than the HC group, especially in the recurrent group, and the elevated LST1 mRNA levels were positively correlated with the peripheral eosinophil percentages, tissue eosinophil counts and percentages. IF staining results showed that the LST1 protein levels were higher in CRSwNP patients, especially in the recurrent patients than in the HC group. ROC curves highlighted that tissue LST1 levels were associated with recurrent CRSwNP and exhibited a higher predictive ability for postoperative CRSwNP recurrence. CONCLUSION: This was the first report suggesting that LST1 expression was upregulated and associated with mucosal eosinophil infiltration and CRSwNP recurrence. Tissue LST1 could be a promising biomarker for predicting postoperative recurrence in CRwNP patients. LEVEL OF EVIDENCE: Level 5.

Relationship of hearing impairment, social participation and depressive symptoms to the incidence of frailty in a community cohort.

BACKGROUND: The mediating effect of social participation and depressive symptoms on the relationship between hearing impairment and frailty remains unclear. METHODS: A total of 3981 participants from three waves of the China Health and Retirement Longitudinal Study (CHARLS) were included. The outcome was incidental frailty. Hearing impairment, social participation, and depressive symptoms were the main variables. Cox regression models and structural equation models were adopted to examine the relationship between hearing impairment, social participation, depressive symptoms, and the incidence of frailty, with adjustments for demographic characteristics and lifestyle variables at baseline. RESULTS: Hearing impairment (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.12, 1.74), social participation (HR 0.72, 95% CI 0.55, 0.94), and depressive symptoms (HR 1.78, 95% CI 1.37, 2.30) were associated with the incidence of frailty. Hearing impairment was associated with frailty not only through social participation (ß = 0.015, 95% CI 0.003, 0.037) and depressive symptoms (ß = 0.070, 95% CI 0.037, 0.116) separately but also through social participation and depressive symptoms sequentially (ß = 0.002, 95% CI 0.001, 0.004). Furthermore, the effect of social participation on frailty occurred in participants with hearing impairment, while the effect of depressive symptoms on frailty occurred in participants with normal hearing status. CONCLUSIONS: Hearing impairment is associated with frailty, in which social participation and depressive symptoms partly mediate the association. The effect of social participation and depressive symptoms on frailty varies across hearing statuses. Integrated and comprehensive intervention measures, including hearing screenings, promoting social participation, and improving depressive symptoms, are suggested to prevent frailty.

The Role of Noncoding RNA in Airway Allergic Diseases through Regulation of T Cell Subsets.

Allergic rhinitis and asthma are common airway allergic diseases, the incidence of which has increased annually in recent years. The human body is frequently exposed to allergens and environmental irritants that trigger immune and inflammatory responses, resulting in altered gene expression. Mounting evidence suggested that epigenetic alterations were strongly associated with the progression and severity of allergic diseases. Noncoding RNAs (ncRNAs) are a class of transcribed RNA molecules that cannot be translated into polypeptides and consist of three major categories, microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). Previous studies showed that ncRNAs were involved in the physiopathological mechanisms of airway allergic diseases and contributed to their occurrence and development. This article reviews the current state of understanding of the role of noncoding RNAs in airway allergic diseases, highlights the limitations of recent studies, and outlines the prospects for further research to facilitate the clinical translation of noncoding RNAs as therapeutic targets and biomarkers.

Exosomes Derived hsa-miR-4669 as a Novel Biomarker for Early Predicting the Response of Subcutaneous Immunotherapy in Pediatric Allergic Rhinitis.

Purpose: Subcutaneous immunotherapy (SCIT) is an effective treatment for pediatric allergic rhinitis (AR), but its efficacy fluctuates among individuals. This study aims to identify the profile of serum exosomes derived microRNAs (miRNAs) and evaluate their capacities to early predict SCIT efficacy in pediatric AR. Patients and Methods: High-throughput sequencing was applied to identify the miRNA of serum exosomes in AR children. GO enrichment and KEGG pathway analysis were performed to enrich the biological annotations of target mRNAs of miRNAs. Then we validated differentially expressed miRNAs in two independent cohorts by RT-qPCR. Logistic regression and receiver operating characteristic curve (ROC) were applied to evaluate the abilities of identified miRNAs in predicting the efficacy of SCIT in AR children. Results: A total of 812 miRNAs were detected in the serum exosomes, including 16 upregulated and 14 downregulated. Differentially expressed genes are enriched in the biological process of developmental process and regulation of cellular process, and gathered in pathways such as the signaling pathways regulating pluripotency of stem cells and the Wnt signaling pathway. In the first validation cohort, hsa-miR-4669 (P=0.009) and hsa-miR-4686 (P=0.032) were significantly downregulated in the effective group than the ineffective group, while hsa-miR-3196 (P=0.015) was upregulated. In the second cohort, hsa-miR-4669 level (P<0.0001) was downregulated in the effective group than the ineffective group. In addition, logistic regression revealed that hsa-miR-4669 level was correlated with the visual analogue scale (r=0.323, P=0.001) and total nasal symptoms score (r=0.269, P =0.007). ROC curve highlighted that hsa-miR-4669 level exhibited a reliable accuracy in predicting SCIT efficacy in pediatric AR (AUC=0.785). Conclusion: Serum exosomes derived miRNA were associated with the efficacy of SCIT. Serum exosomes derived hsa-miR-4669 might serve as a novel biomarker for early predicting the response of SCIT in AR children.

Predictive Value of Nasal Nitric Oxide and Serum NOS2 Levels in the Efficacy of Subcutaneous Immunotherapy in Pediatric Patients with Allergic Rhinitis.

Background: Subcutaneous immunotherapy (SCIT) is an effective therapy for allergic rhinitis (AR), but some AR patients still do not benefit from it. Nasal nitric oxide (nNO) and inducible nitric oxide synthase (iNOS/NOS2) act important roles in AR. This study aims to explore the abilities of serum NOS2 and nNO in predicting the clinical efficacy of SCIT in AR patients. Methods: We recruited 40 healthy controls (HCs) and 120 AR patients in this study. Serum NOS2 and nNO levels were compared between the two groups. In the AR group, patients underwent and finished 1-year of SCIT, and divided into the effective and ineffective groups, and the relationships between serum NOS2 and nNO levels and efficacy of SCIT were evaluated. Results: The serum NOS2 and nNO levels were higher in AR patients than HCs. In the effective group, the serum NOS2 and nNO levels were increased than the ineffective group. ROC curves presented that a combination of serum NOS2 and nNO exhibited promising predictive ability in predicting the clinical efficacy of SCIT. Conclusions: Serum NOS2 and nNO levels were enhanced in AR patients and might affect the efficacy of SCIT. The combined use of serum NOS2 and nNO levels could be a reliable and useful method for predicting the clinical efficacy of SCIT.

Circulating C-X-C Motif Ligand 13 as a Biomarker for Early Predicting Efficacy of Subcutaneous Immunotherapy in Children With Chronic Allergic Rhinitis.

Background: C-X-C motif ligand 13 (CXCL13) and B cell-activating factor (BAFF) are proven to be involved in inflammatory diseases, but their role in allergic rhinitis (AR) remains unclear. The aim of this study was to investigate the role of serum CXCL13 and BAFF in AR and their clinical values as objective biomarkers to predict the efficacy of subcutaneous immunotherapy (SCIT). Methods: We prospectively recruited 90 children with AR treated with SCIT and collected their serum specimens before SCIT. One-year follow-up was conducted for all patients, and they were categorized into effective and ineffective groups based on efficacy. The serum concentrations of CXCL13 and BAFF were detected and compared between the two groups. A validation cohort of 52 responders and 26 non-responders were further assessed for both cytokines and serum CXCL13 and BAFF levels were assayed by enzyme-linked immunosorbent assay (ELISA). Results: Eighty children completed the follow-up schedule, and 56 children were categorized into the effective group and 24 children into the ineffective group. The serum levels of CXCL13 in the effective group were clearly higher than those in the ineffective group (P < 0.05). Receiver operating characteristic (ROC) curves revealed the potential values of CXCL13 as a biomarker in predicting the response of SCIT. Further, in the validation cohort, ELISA results demonstrated that serum CXCL13 levels were increased in responders than non-responders (P < 0.05). ROC curves showed good accuracy of serum CXCL13 in predicting the efficacy of SCIT. Conclusion: Our discovery-validation study demonstrated that circulating CXCL13 might serve as a novel biomarker to predict the outcome of SCIT in childhood AR. The findings indicated that CXCL13 was involved in the pathological mechanisms of AR and made help to the fundamental therapeutic mechanism of SCIT.

Elevated ALCAM Expression Associated with Endotypes and Postoperative Recurrence in Chronic Rhinosinusitis with Nasal Polyps.

BACKGROUND: Chronic rhinosinusitis with polyps (CRSwNP) is characterized by high heterogeneity and postoperative recurrence rate. This study aimed to explore the clinical significance of activated leukocyte cell adhesion molecule (ALCAM) in endotyping CRSwNP and predicting its recurrence. METHODS: We recruited 120 CRSwNP patients including 70 non-eosinophilic CRSwNP (neCRSwNP) and 50 eosinophilic CRSwNP (eCRSwNP) patients, and 40 healthy controls (HCs). Serum and tissue samples were collected. Serum ALCAM levels were detected by enzyme-linked immunosorbent assay (ELISA), and tissue ALCAM expression was assessed by reverse transcription-polymerase chain reaction (RT-PCR), Western blotting (WB) and immunohistochemistry (IHC). The predictive values of ALCAM expression for CRSwNP endotypes and postoperative recurrence were assessed. RESULTS: The serum levels of ALCAM were significantly increased in CRSwNP patients in comparison with HCs and were correlated with the peripheral eosinophil count, tissue eosinophil counts, and percentage. Multivariate analysis and receiver operating characteristic (ROC) curve highlighted that serum ALCAM levels were associated with CRSwNP endotypes. Tissue ALCAM expression was significantly enhanced in CRSwNP patients, especially in eCRSwNP patients. At the end of the study, 110 patients completed the follow-up schedule, 78 patients were categorized into the non-recurrent group, and the other 32 patients were included in the recurrent group. The serum ALCAM levels were elevated in the recurrent group compared with the non-recurrent group, and ALCAM expression in the tissue was significantly elevated. The ROC curve exhibited a high predictive ability of serum ALCAM in predicting postoperative recurrence. Logistic regression and Kaplan-Meier curves demonstrated that serum ALCAM was an independent risk factor for postoperative recurrence. CONCLUSION: This is the first report suggesting that ALCAM expression was upregulated and associated with mucosal eosinophil infiltration and CRSwNP recurrence. Serum ALCAM could be a promising biomarker for distinguishing endotypes and predicting postoperative recurrence in CRwNP patients.

Serum YKL-40 Levels Predict Endotypes and Associate with Postoperative Recurrence in Patients with Chronic Rhinosinusitis with Nasal Polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a global health concern with high heterogeneity and rate of postoperative recidivation. YKL-40 is a pivotal pro-inflammatory mediator to promote Th2 immune response which is involved in many inflammatory diseases. This study aimed to investigate the predictive value of serum YKL-40 in CRSwNP endotypes and postoperative recurrence. METHODS: We recruited 80 primary CRSwNP, 40 recurrent CRSwNP patients and 40 healthy controls (HCs) in this study, and the serum and tissue specimens were collected. The middle turbinate mucosa tissue collected from patients undergoing septoplasty was used as control. Serum YKL-40 concentrations were detected by enzyme-linked immunosorbent assay (ELISA), and tissue YKL-40 mRNA and protein levels were examined using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). The difference of YKL-40 expression was compared among different group. Multivariate analysis and receiver operating characteristic (ROC) curve were performed to evaluate the value of serum YKL-40 in discriminating eosinophilic CRSwNP (eCRSwNP) and predicting postoperative recurrence. RESULTS: The serum YKL-40 levels in CRSwNP patients were higher than HCs, especially in eCRSwNP patients (p < 0.05). The elevated YKL-40 levels positively correlated with blood eosinophil percentage, tissue eosinophil counts and percentages (p < 0.05). The serum YKL-40 levels in recurrent CRSwNP patients were markedly enhanced than primary CRSwNP patients (p < 0.05). The YKL-40 mRNA and protein levels were significantly elevated in CRSwNP patients compared to HCs, especially in eCRSwNP and recurrent CRSwNP group. Multivariate analysis and ROC curve exhibited that serum YKL-40 might be a promising indicator in distinguishing CRSwNP endotypes and predicting postoperative recurrence. CONCLUSION: Our data suggested that YKL-40 might be unregulated in CRSwNP and associated with mucosal eosinophilia and recurrence. Serum YKL-40 appeared to a novel biomarker for predicting CRSwNP endotypes and postoperative recurrence of CRSwNP.

[The role of serum B cell activation factor in the diagnosis and phenotypes of chronic rhinosinusitis with nasal polyps].

Objective:To investigate the changes of serum B cell activating factor（BAFF） levels in chronic rhinosinusitis with nasal polyps（CRSwNP） patients and its predictive value in phenotypes. Methods:Forty healthy volunteers（control group） and 77 patients with CRSwNP were recruited in the present study, all CRSwNP patients were divided into eosinophilic（neCRSwNP group, n=40） and non-eosinophilic（eCRSwNP group, n=37） according to the degree of eosinophil infiltration in postoperative histological sections. Serum samples were collected from all subjects, and serum BAFF levels were detected by ELISA, and the relationships between BAFF levels and clinical variables were evaluated. The predictive value of serum BAFF in distinguishing eCRSwNP was evaluated by receiver operating curve（ROC） and Logistic regression. Results:BAFF concentrations in the serum of CRSwNP patients were（1.2±0.4） ng/mL, which were higher than control group（[0.8±0.3]ng/mL）. In addition, serum BAFF levels in eCRSwNP group were （1.3±0.5） ng/mL, which were higher than neCRSwNP group（[1.1±0.2]ng/mL）, and both groups were higher than control groupt（P<0.05）. The elevated serum BAFF levels in CRSwNP patients were positively correlated with the tissue eosinophil percentage（r=0.629, P<0.001） and counts（r=0.563, P<0.001）, peripheral blood eosinophil percentage（r=0.411, P=0.002） and counts（r=0.501, P<0.001）, and serum total IgE（r=0.178, P=0.021）. Multivariate Logistic regression showed that serum BAFF level was an independent factor associated with CRSwNP phenotypes（OR=3.652, P=0.001）. ROC analysis suggested that serum BAFF exhibited a good predictive value for eCRSwNP（AUC=0.885）. Conclusion:Serum BAFF levels were increased in CRSwNP patients and associated with the degree of systemic and polyp eosinophilic inflammation. Preoperative evaluation of serum BAFF level maybe clinically meaningful for distinguishing CRSwNP phenotypes.

The role of serum macrophage migration inhibitory factor in preoperative prediction of chronic rhinosinusitis with nasal polyps endotypes.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly heterogeneous disease and can be categorized into eosinophilic CRSwNP (eCRSwNP) and non-eosinophilic CRSwNP (neCRSwNP). Exploring effective biomarkers to distinguish endotypes is important for personalized therapies. The present study aims to evaluate the predictive value of serum MIF in CRSwNP endotypes. METHODS: One hundred and twenty CRSwNP patients, including 51 eCRSwNP and 69 neCRSwNP, 40 chronic rhinosinusitis without nasal polyps (CRSsNP) patients and 40 healthy controls (HC) were enrolled. Serum MIF levels were determined by enzyme-linked immunosorbent assay (ELISA). The patients' clinical variables were analyzed for correlations with serum MIF. Receiver operating characteristic (ROC) curve and multivariate analysis were utilized to assess the predictive value of serum MIF in CRSwNP endotypes. RESULTS: The serum MIF levels were significantly higher in CRSwNP group than CRSsNP group and HC group (P < 0.001), and the serum MIF levels were increased in eCRSwNP compared to neCRSwNP group (P = 0.006). Elevated serum MIF levels were significantly correlated with blood eosinophil (B-EOS) count (r = 0.411, P < 0.001), B-EOS percentage (r = 0.377, P < 0.001), visual analog scale score (r = 0.204, P = 0.025), tissue eosinophil (T-EOS) count (r = 0.705, P < 0.001) and T-EOS percentage (r = 0.671, P < 0.001) in CRSwNP patients. ROC curve demonstrated that serum MIF exhibited good preoperative prediction in CRSwNP endotypes (area under the curve = 0.925, P < 0.001). Multivariate regression analysis showed that serum MIF was an independent factor associated with CRSwNP endotypes. CONCLUSIONS: This was the first study identifying serum MIF as a possible specific biomarker for preoperatively distinguishing CRSwNP endotypes. Furthermore, the serum MIF levels were found to be closely associated with the degree of mucosal eosinophil infiltration.

Circulating MIF Associated With Disease Severity and Clinical Response of Sublingual Immunotherapy in House Dust Mite-Induced Allergic Rhinitis.

Background: Macrophage migration inhibitory factor (MIF) is described as a pro-inflammatory cytokine involved in many inflammatory and allergic disorders, but the role of MIF in allergic rhinitis (AR) remains poorly clarified. The aim of this study was to investigate the association between circulating MIF levels and house dust mite (HDM)-induced AR, and evaluate MIF as a potential biomarker in reflecting disease severity and predicting the clinical response of sublingual immunotherapy (SLIT) in HDM-induced AR patients. Methods: In this study, we enrolled 160 persistent HDM-induced AR patients (AR group), including 48 mild AR patients (MAR group) and 112 moderate-severe AR patients (MSAR group), and 77 healthy controls (HC group). Circulating levels of MIF were measured by ELISA, and the relationship between MIF concentrations and disease severity was assessed. In the MSAR group, 106 patients were assigned to receive SLIT for 3 years. At the end of the study, patients were categorized into good response group and poor response group, and associations between clinical variables or biomarkers and clinical response were analyzed by the multivariate regression analysis. Results: The concentrations of serum MIF were significantly higher in AR patients than in HCs, especially in those with MSAR. Moreover, circulating MIF levels were positively correlated with TNSS, VAS, serum HDM-specific IgE, total IgE, blood eosinophil count, and blood eosinophil percentage (all p < 0.05). Eighty MSAR patients finally completed SLIT, 45 patients obtained good response, and 35 patients resulted in poor response. The serum levels of MIF were significantly lower in the good-response group than in the poor-response group (p < 0.001). The receiver operating characteristic analysis for MIF showed good accuracy for predicting clinical response of SLIT (area under the curve = 0.877, p < 0.001). The multivariate regression analysis demonstrated that serum MIF was an independent factor for SLIT responsiveness. Conclusion: Serum MIF appeared to be an important biological indicator in reflecting disease severity and an independent predictor for clinical responsiveness of SLIT in HDM-induced AR patients.

[Clinical characteristics of neuroendocrine carcinoma of nose and skull base and analysis of curative effect of endoscopic surgery].

Objective:To investigate the clinical features of neuroendocrine carcinoma of nose and skull base and the efficacy and prognosis of endoscopic resection. Methods:The clinical data of 7 patients with neuroendocrine carcinoma of nose and skull base treated by endoscopic surgery were retrospectively analyzed. According to the international TNM staging, there were 1 case of stage Ⅰ, 1 case of stage Ⅱ, 1 case of stage Ⅲ, 1 case of stage ⅣA and 3 cases of stage ⅣB. All patients were treated by endoscopic surgery, including 1 case of postoperative radiotherapy, 1 case of chemotherapy and 3 cases of radiotherapy and chemotherapy. Results:During the follow-up of 9-58 months, 2 cases died after recurrence, 1 case had ipsilateral cervical lymph node metastasis（tumor-free survival after neck dissection）, and 4 cases had tumor-free survival at the last follow-up. Conclusion:At present, there is no standard treatment for neuroendocrine carcinoma of the nose and skull base. The comprehensive treatment based on complete resection of the tumor by endoscopic surgery is an effective and feasible treatment.