Risk factors for asthma in patients with allergic rhinitis in eastern China.

BACKGROUND: Asthma is one of the most common chronic diseases among children and adults and can lead to a high health and socioeconomic burden. Allergic rhinitis (AR) often precedes the development of asthma. This study aims to clarify the risk factors for cocurrent asthma in patients with AR in eastern China. METHODS: A cross-sectional study of 3739 patients with AR was performed in eastern China. Patients meeting the criteria for AR were evaluated using a skin-prick test (SPT) of 16 common aeroallergens. A logistic regression analysis was used to assess the risk factors of asthma in patients with AR. RESULTS: The prevalence of asthma in patients with AR was 14.23%. The patients sensitive to dust mites (D. farinae and D. pteronyssinus) had the highest prevalence (76.84% and 73.68%). A significant difference was found in sensitization to four types of allergens (D. farinae, D. pteronyssinus, dog dander, Alternaria alternata) in patients with AR with and without asthma. The strongest risk factor for asthma in patients with AR was an allergy to Aspergillus fumigatus (adjusted OR, 2.42; 95% CI, 1.50-3.90), followed by allergy to D. pteronyssinus (adjusted OR, 2.06; 1.30-3.27), and allergy to dog dander (adjusted OR, 1.92; 1.24-2.97). Various risk factors that are independently associated with asthma in patients with AR were found in different age groups. CONCLUSIONS: We observed a difference in risk factors in patients with AR with and without asthma. Clarifying the risk factors for asthma in patients with AR is important and may be beneficial to the optimal interventions of asthma.

Abnormal Expression of YAP Is Associated With Proliferation, Differentiation, Neutrophil Infiltration, and Adverse Outcome in Patients With Nasal Inverted Papilloma.

BACKGROUND: Nasal inverted papilloma (NIP) is a common benign tumor. Yes-associated protein (YAP) is the core effector molecule of the Hippo pathway, which regulates the proliferation and differentiation of airway epithelium. While its role in proliferation may be connected to NIP formation, no definitive association has been made between them. METHODS: We compared the difference of YAP expression and proliferation level between the control inferior turbinate, NP (nasal polyps), and NIP groups. In addition, we further used PCR, immunofluorescence, and immunohistochemistry to investigate YAP's role in the proliferation and differentiation of the nasal epithelium and inflammatory cell infiltration, correlating them with different grades of epithelial remodeling. We further used an IL-13 remodeling condition to investigate YAP's role in differentiation in an in vitro air-liquid interface (ALI) human nasal epithelial cell (hNECs) model. Finally, we also explored the correlation between YAP expression and clinical indicators of NIP. RESULTS: The expression of YAP/active YAP in the NIP group was significantly higher than that in the NP group and control group. Moreover, within the NIP group, the higher grade of epithelial remodeling was associated with higher YAP induced proliferation, leading to reduced ciliated cells and goblet cells. The finding was further verified using an IL-13 remodeling condition in differentiating ALI hNECs. Furthermore, YAP expression was positively correlated with proliferation and neutrophil infiltration in NIP. YAP expression was also significantly increased in NIP patients with adverse outcomes. CONCLUSION: Abnormal expression of YAP/active YAP is associated with proliferation, differentiation, neutrophil infiltration, and adverse outcome in NIP and may present a novel target for diagnosis and intervention in NIP.

Severity of Rhinosinusitis: Comparison Between Visual Analog Scale Given by Patients and Otorhinolaryngologists.

BACKGROUND: Visual Analog Scale (VAS) as determined by the patient is recommended by the European Position Paper on Rhinosinusitis and Nasal Polyps 2012 in evaluation of the total severity of the chronic rhinosinusitis (CRS) patients' symptoms. OBJECTIVE: To evaluate the correlation between evaluations performed by otorhinolaryngologists and CRS patients with commonly used systems. METHODS: Scores of VAS and Sino-Nasal Outcome Test-20 (SNOT-20) Chinese version were obtained from 110 CRS patients with nasal polyps (CRSwNPs, n = 61) and without nasal polyps (CRSsNPs, n = 49) before surgery, which were compared with scores of Lund-Kennedy endoscopic staging system, the Lund-Mackay computed tomography (CT) staging system, and VAS from 3 attending otorhinolaryngologists. RESULTS: The median VAS scores given by CRS patients (6.0; 4.25-7.5) do not correlate significantly with the VAS scores by the 3 otorhinolaryngologists (5.5; 4.83-6.5) with a correlation coefficient of .218 (-0.146 to 0.466). For CRS patients, there was only a moderate correlation between scores of VAS and the SNOT-20 (r = .37), and no significant difference of VAS scores between CRSwNP and CRSsNP, and between unilateral and bilateral nasal polys. For otorhinolaryngologists, a higher median VAS score was found in CRSwNP (6.0; 5.17-7.0), especially in bilateral (6.0; 5.0-7.08) and revision surgery (6.08; 5.33-7.63). The VAS scores of otorhinolaryngologists correlated significantly with the Lund-Mackay CT score (r = .7536) and Lund-Kennedy endoscopic staging (r = .5947). CONCLUSIONS: VAS scores between patients and physicians are not correlated significantly in this study, but they fall within the same therapeutic range and do not change the clinical management of the patients.

An Integrated Analysis of Radial Spoke Head and Outer Dynein Arm Protein Defects and Ciliogenesis Abnormality in Nasal Polyps.

Background: Nasal polyp (NP) is a chronic upper airway inflammatory disease that is frequently triggered by defective host-defense. However, the mechanisms underlying the impaired barrier function such as cilia-mediated mucociliary clearance remain poorly understood. Objective: To assess ciliary ultrastructural and ciliogenesis marker expression and the phenotypes of ciliated cells in NP. Methods: NP biopsy samples were obtained from 97 NP patients and inferior turbinate from 32 healthy controls. Immunofluorescence staining, quantitative polymerase chain reaction, and single-cell cytospin staining were performed. We classified the patterns of radial spoke head protein (RSPH) 1, 4A (RSPH4A), 9 (RSPH9), and dynein axonemal heavy chain 5 (DNAH5) localization. A semi-quantitative scoring system was developed to assess their expression patterns and associations with ciliogenesis markers [centrosomal protein 110 (CP110) and forkhead box j1 (FOXJ1)]. Results: Median scores of RSPH1, RSPH4A, RSPH9, and DNAH5 were significantly higher in NP than in healthy controls, particularly in eosinophilic NPs. Expression pattern scores of RSPH1, RSPH4A, RSPH9, and DNAH5 correlated positively with each other in both groups. In primary-cell specimens, abnormal expression patterns were significantly more common in NP. The total fluorescence intensity of CP110 and FOXJ1 was significantly higher in NPs and correlated positively with expression pattern scores of RSPH1, RSPH4A, RSPH9, and DNAH5. A trend towards lengthened cilia was observed in NP. Conclusion: In the chronic airway inflammatory milieu, the up-regulated ciliogenesis correlates with the abnormal expression of ciliary ultrastructural markers (i.e., DNAH5) in NP (particularly eosinophilic NP).

Whole-transcriptome sequencing reveals heightened inflammation and defective host defence responses in chronic rhinosinusitis with nasal polyps.

INTRODUCTION: The pathways underlying chronic rhinosinusitis with nasal polyps (CRSwNP) are unclear. We conducted genome-wide gene expression analysis to determine pathways and candidate gene sets associated with CRSwNP. METHODS: We performed whole-transcriptome RNA sequencing on 42 polyp (CRSwNP-NP) and 33 paired nonpolyp inferior turbinate (CRSwNP-IT) tissues from patients with CRSwNP and 28 inferior turbinate samples from non-CRS controls (CS-IT). We analysed the differentially expressed genes (DEGs) and the gene sets that were enriched in functional pathways. RESULTS: Principal component-informed analysis revealed cilium function and immune regulation as the two main Gene Ontology (GO) categories differentiating CRSwNP patients from controls. We detected 6182 and 1592 DEGs between CRSwNP-NP versus CS-IT and between CRSwNP-NP versus CRSwNP-IT tissues, respectively. Atopy status did not have a major impact on gene expression in various tissues. GO analysis on these DEGs implicated extracellular matrix (ECM) disassembly, O-glycan processing, angiogenesis and host viral response in CRSwNP pathogenesis. Ingenuity Pathway Analysis identified significant enrichment of type 1 interferon signalling and axonal guidance canonical pathways, angiogenesis, and collagen and fibrotic changes in CRSwNP (CRSwNP-NP and CRSwNP-IT) tissues compared with CS-IT. Finally, gene set enrichment analysis implicated sets of genes co-regulated in processes associated with inflammatory response and aberrant cell differentiation in polyp formation. CONCLUSIONS: Gene signatures involved in defective host defences (including cilia dysfunction and immune dysregulation), inflammation and abnormal metabolism of ECM are implicated in CRSwNP. Functional validation of these gene expression patterns will open opportunities for CRSwNP therapeutic interventions such as biologics and immunomodulators.

Olfactory Change Pattern after Endoscopic Sinus Surgery in Chronic Rhinosinusitis with Olfactory Dysfunction.

OBJECTIVE: To determine the change pattern of olfactory function in chronic rhinosinusitis (CRS) with olfactory dysfunction after endoscopic sinus surgery (ESS), and its association with inspection scores. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Second Hospital of Shandong University, China, from December 2014 to January 2016. METHODOLOGY: Thirty-four CRS with nasal polyps (CRSwNP) patients and 14 CRS without nasal polyps (CRSsNP) patients were evaluated preoperatively by T&T olfactory test, olfactory VAS test, SNOT-20score and Lund-Mackay CT score. Outcomes were re-evaluated at 1 month, 3 months and 6 months postoperatively. RESULTS: Both olfactory and SNOT-20 scores showed significant improvement within 6 months in both CRSwNP and CRSsNP groups. Patients with anosmia in T&T test showed the largest degree of improvement. No significant recovery of olfactory dysfunction was observed at 1 month and 3 months in CRSsNP groups postoperative. In CRSwNP, the olfactory scores were correlated with the CT scores significantly (r=0.649, p<0.001; r=0.625, p<0.001). However, no correlation was found between the SNOT-20 score and olfactory score preoperatively. CONCLUSION: Our study has confirmed that the therapeutic effects of ESS on olfactory function last for up to 6 months, particularly in patients with CRSwNP. Although the therapeutic effects plateaued at 3 months postoperatively, the olfactory function continues to recover between 3 and 6 months.

Motile Ciliary Disorders in Chronic Airway Inflammatory Diseases: Critical Target for Interventions.

PURPOSE OF REVIEW: Impaired mucociliary clearance has been implicated in chronic upper and lower airway inflammatory diseases (i.e., allergic and non-allergic rhinitis, chronic rhinosinusitis with or without nasal polyps and asthma). How motile ciliary disorders (impaired ciliogenesis, ciliary beating and ultrastructural defects) are implicated in chronic airway inflammatory diseases is not fully understood. Elaboration of the role of motile ciliary disorders may serve as therapeutic targets for improving mucociliary clearance, thereby complementing contemporary disease management. RECENT FINDINGS: We have summarized the manifestations of motile ciliary disorders and addressed the underlying associations with chronic airway inflammatory diseases. A panel of established and novel diagnostic tests and therapeutic interventions are outlined. Physicians should be vigilant in screening for motile ciliary disorders, particularly in patients with co-existing upper and lower airway inflammatory diseases. Proper assessment and treatment of motile ciliary disorders may have added value to the management and prevention of chronic airway inflammatory diseases.