Wentong Xia

The antimicrobial protein short palate, lung, and nasal epithelium clone 1 (SPLUNC1) is differentially modulated in eosinophilic and noneosinophilic chronic rhinosinusitis with nasal polyps

BACKGROUND Chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly heterogeneous disease with aberrant host defense responses. However, whether innate immunity is similarly impaired in patients with eosinophilic and those with noneosinophilic CRSwNP remains unclear. OBJECTIVES We sought to evaluate the expression and possible modulation of short palate, lung, and nasal epithelium clone 1 (SPLUNC1), an innate immune molecule, in the 2 CRSwNP subsets. METHODS Polyp tissue and uncinate processes were collected from 40 patients with CRSwNP, 27 patients with chronic rhinosinusitis without nasal polyps (CRSsNP), and 22 control subjects. Expression of SPLUNC1; Toll-like receptor (TLR) 2, TLR3, and TLR4; and the proinflammatory cytokines IL-1α, IL-4, IL-13, IL-17A, and IFN-γ was examined in nasal tissues. Additionally, SPLUNC1 expression in response to specific inflammatory stimulation was measured in cultured polyp epithelial cells and A549 cells. RESULTS Polyp tissues exhibited significantly decreased expression of SPLUNC1 and other innate immune molecules compared with uncinate process tissues from patients with CRSwNP (P < .05), patients with CRSsNP, and healthy control subjects. Moreover, the eosinophilic CRSwNP subset exhibited significantly decreased SPLUNC1 expression and numbers of submucosal glands, as well as significantly increased IL-4 and IL-13 mRNA levels, compared with the noneosinophilic subset (P < .05). Accordingly, SPLUNC1 expression in polyp epithelial cells was significantly inhibited by IL-4 and IL-13 stimulation in vitro but was significantly upregulated after stimulation with TLR agonists and glucocorticoids (P < .05). CONCLUSION Differential SPLUNC1 suppression between the eosinophilic and noneosinophilic CRSwNP subsets suggests that they possess distinct pathogenic mechanisms. This finding might benefit the design of appropriate therapeutic interventions targeted to each subset.

Elevated serum osteopontin level is associated with blood eosinophilia and asthma comorbidity in patients with allergic rhinitis.

From the Division of Immunology, Children’s Hospital, Boston, Mass; the Department of Pediatrics, Harvard Medical School, Boston, Mass; the Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon; the Unit e de G en etique M edicale, Universit e Saint Joseph, Beirut, Lebanon; the CNRS-Institut de G en etique Humaine et Universit e Montpellier 2, Montpellier, France; the Division of Pediatric Hematology and Oncology, Children’s Center for Cancer and Blood Diseases, Rafik Hariri University Hospital, Beirut, Lebanon; and the Department of Pediatrics, ‘‘Angelo Nocivelli’’ Institute for Molecular Medicine, University of Brescia, Brescia, Italy. E-mail: raif.geha@childrens.harvard.edu. *These authors contributed equally to this work. This study was supported by USPHS grants 1P01AI076210-01A1 (to R.S.G. and L.D.N.) and T32AI007512 (to R.S.G. and J.C.), a grant from the Dubai Harvard Foundation for Medical Research (R.S.G.), and a grant provided by the Jeffrey Modell Foundation (to L.D.N.). Disclosure of potential conflict of interest: J. Chou received research support from the National Institutes of Health (NIH). L. D. Notarangelo received research support from the NIAID-NIH and the Jeffrey Modell Foundation. R. Geha received research support from the NIH and the Jeffrey Modell Foundation. The rest of the authors declare that they have no relevant conflicts of interest.

Aspirin-exacerbated respiratory disease in China: a cohort investigation and literature review.

Background Although the prevalence of aspirin-exacerbated respiratory disease (AERD) in western populations is high, AERD is rather rare in China, and few related studies have been published to date. Methods We performed a prospective cohort investigation on the incidence of AERD in patients with chronic rhinosinusitis (CRS) in southern China. A literature search of the China Academic Journal Network Publishing Database was conducted to obtain an overview of the incidence of AERD in the Chinese population, and previous studies on the incidence of AERD were reviewed. Results We found 2 patients with aspirin hypersensitivity among 351 consecutive CRS (309 with nasal polyps [NPs]) patients, suggesting a rate of 0.57% in the CRS population. Forty-five articles about AERD were obtained by Chinese-language literature searches. In total, 346 cases of AERD were reported during the past 30 years. Conclusion Given the large population of NPs in China, the prevalence of AERD is very low, and this may be related to the reduced levels of nasal tissue eosinophilia and subsequent low asthma comorbidity.

Interleukin-17A Promotes MUC5AC Expression and Goblet Cell Hyperplasia in Nasal Polyps via the Act1-Mediated Pathway

Background Recent studies demonstrated that nasal polyps (NP) patients in China and other Asian regions possessed distinct Th17-dominant inflammation and enhanced tissue remodeling. However, the mechanism underlying these observations is not fully understood. This study sought to evaluate the association of interleukin (IL)-17A with MUC5AC expression and goblet cell hyperplasia in Chinese NP patients and to characterize the signaling pathway underlying IL-17A-induced MUC5AC expression in vitro. Method We enrolled 25 NP patients and 22 normal controls and examined the expression of IL-17A, MUC5AC and act1 in polyp tissues by immunohistochemical (IHC) staining, quantitative polymerase chain reaction (qPCR) and western blot. Moreover, by using an in vitro culture system of polyp epithelial cells (PECs), IL-17A-induced gene expression was screened in cultured PECs by DNA microarray. The expression of IL-17RA, IL-17RC, act1 and MUC5AC and the activation of the MAPK pathway (ERK, p38 and JNK), were further examined in cultured PECs and NCI-H292 cells by qPCR and western blotting, respectively. Results We found that increased IL-17A production was significantly correlated with MUC5AC and act1 expression and goblet cell hyperplasia in polyp tissues (p<0.05). IL-17A significantly stimulated the expression of IL-17RA, IL-17RC, act1 and MUC5AC, and the activation of the MAPK pathway in cultured PECs and NCI-H292 cells (p<0.05). In addition, IL-17RA, IL-17RC and act1 siRNA significantly blocked IL-17A-induced MUC5AC production in vitro (p<0.05). Conclusion Our results suggest that IL-17A plays a crucial role in stimulating the production of MUC5AC and goblet cell hyperplasia through the act1-mediated signaling pathway and may suggest a promising strategy for the management of Th17-dominant NP patients.

Sensitivity of MUC5AC to topical corticosteroid is negatively associated with interleukin-17A in patients with allergic rhinitis.

Background Although Interleukin (IL)-17A has been suggested to play a role in corticosteroid hyporesponsiveness, whether IL-17A is able to affect the sensitivity of MUC5AC to intranasal corticosteroid treatment in patients with allergic rhinitis (AR) is unclear. Methods Twenty patients with moderate to severe AR were enrolled in this study and the expression of MUC5AC, IL-17A, and glucocorticoid receptor beta (GR beta) was detected using immunochemical staining and quantitative reverse transcription polymerase chain reaction (RT-PCR) before and after treatment with fluticasone propionate (FP) nasal spray for 4 weeks, respectively. In addition, the effects of FP on IL-13– and IL-17A–induced MUC5AC and GR beta were also evaluated in the primarily cultured human nasal epithelial cells (HNECs) in vitro. Results The increased MUC5AC expression was associated with IL-17A levels in AR, and IL-17A was found to affect the inhibition of MUC5AC by corticosteroid treatment. Both IL-13 and IL-17A significantly promoted MUC5AC mRNA expression in HNECs, and FP treatment was able to significantly inhibit MUC5AC mRNA expression in HNECs induced by IL-13 but not for that induced by IL-17A. Also, IL-17A but not IL-13 promoted GR beta mRNA expression in HNECs, which was not affected by administration of corticosteroid. Conclusion Our results suggest that the sensitivity of MUC5AC to topical corticosteroid is negatively associated with IL-17A in AR patients. This might help us to gain more insight into the pathophysiology and the pharmacotherapeutic mechanisms on AR treatment.

Suppression of connexin 26 is related to protease-activated receptor 2-mediated pathway in patients with allergic rhinitis.

Background Connexin (Cx) 26 plays a key role in maintaining the integrity of tight junctions. However, the expression and modulation of Cx26 in allergic rhinitis (AR) has not been well understood. Methods We detected the expression of Cx26 in house-dust mite (HDM)–sensitized AR patients and investigated the Cx26 production and modulation in primary human nasal epithelial cells (HNECs) and BEAS-2B cells after treatment with the allergen Der p 1 from Dermatophagoides pteronyssinus. Results We found that the mRNA and protein levels of Cx26 were significantly down-regulated in AR patients compared with the control. Der p 1 was found to induce protease-activated receptor 2 (PAR2) expression and suppress Cx26 production significantly in vitro. PAR2 siRNA was shown to prevent the suppression of Cx26 induced by Der p 1 in BEAS-2B cells. Conclusion The suppression of Cx26 in HDM-sensitized AR patients is related to a PAR2-mediated pathway and might serve during the initiation and maintenance of AR. Targeting the PAR2-mediated Cx26 suppression may be a potential means of preventing allergic sensitization.

High and low doses of clarithromycin treatment are associated with different clinical efficacies and immunomodulatory properties in chronic rhinosinusitis

BACKGROUND Low-dose clarithromycin has been recommended for the treatment of chronic rhinosinusitis without nasal polyps. However, it is uncertain whether a high dose of clarithromycin is more effective than a low dose. METHODS Forty-three chronic rhinosinusitis patients were randomised to low-dose or high-dose clarithromycin groups, and clinical efficacy was evaluated. Pre- and post-treatment measures included: nasal symptom assessment, endoscopic inspection (Lund-Kennedy system), a quality of life questionnaire (the Sino-Nasal Outcome Test 20) and examination of cytokine levels (interleukin-5 and -8) in nasal secretions. RESULTS The high dose of clarithromycin was significantly better in terms of clinical efficacy than the low dose for the treatment of chronic rhinosinusitis (p < 0.025). Significant differences in nasal cytokine levels (interleukin-5 and -8) were also observed between the low-dose and high-dose groups after short-term clarithromycin treatment (p < 0.025). CONCLUSION Short-term, high-dose clarithromycin appears to be more effective for the treatment of chronic rhinosinusitis than low-dose clarithromycin.

Increased IL-22 level in allergic rhinitis significantly correlates with clinical severity.

Backgroud IL-22 regulates various processes and has been linked to diverse effects. However, the importance of IL-22 in the pathogenesis of allergic rhinitis (AR) remains poorly understood. This study sought to evaluate the levels of IL-22 and IL-17A in AR patients and their association with clinical severity of AR. Methods Thirty-six AR patients and 22 normal controls were enrolled in this study. The frequencies of IL-22+, IL-17A+, and IL-9+ T helper (Th) cells in peripheral blood of AR patients and normal controls were examined by flow cytometry. Serum levels of IL-22 and IL-17A in AR patients and normal controls were determined by ELISA. The clinical relevance of the percentages of IL-22+ and IL-17A+ Th cells as well as serum IL-22 and IL-17A levels were evaluated. Results The frequencies of IL-22+ and IL-17A+ Th cells, but not IL-9+ Th cells, were significantly increased compared with those in normal controls (p < 0.05). Frequencies of IL-22+ and IL-17A+ Th cells in peripheral blood of AR patients significantly correlated with visual analog scale scores of nasal symptoms (nasal congestion and rhinorrhea; p < 0.05). Moreover, the serum levels of IL-22 and IL-1 were significantly increased compared with those in normal controls (p < 0.05) and significantly correlated with the levels of Dermatophagoides pteronyssinus and Dermatophagoides farinae specific IgE in AR patients. Conclusion Our findings suggested that IL-22 as well as IL-17A may play an important role in the regulation of Th2-skewed inflammation in AR patients.

Suppression of TIM-1 predicates clinical efficacy of sublingual immunotherapy for allergic rhinitis in children

OBJECTIVE To evaluate the clinical efficacy of sublingual immunotherapy (SLIT) with house-dust mite (HDM) extract and to examine the change of biomarkers (TIM-1, IL-5 and IL-10) after 6-month SLIT in children with allergic rhinitis (AR). METHODS One hundred and sixteen HDM-sensitized children with persistent AR were enrolled to assess the clinical efficacy of SLIT by determining the individual nasal symptom score (INSS) and total nasal symptom scores (TNSS) after 6-month SLIT. Moreover, the mRNA expression of TIM-1, IL-5 and IL-10 in peripheral blood mononuclear cells (PBMCs) was examined in 16 well-controlled and 12 uncontrolled AR patients using quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS After 6-month SLIT, both TNSS and INSS scores were significantly decreased compared with the baseline value (p < 0.01). The rates for well-controlled, partly controlled and uncontrolled children were 43.1%, 32.8% and 24.1%, respectively. Accordingly, the mRNA levels of TIM-1 and IL-5 decreased significantly and IL-10 mRNA level increased significantly compared with the baseline value in well-controlled children (p < 0.05). CONCLUSION Our findings suggest SLIT with HDM extract is effective and safe for AR children and TIM-1 may be considered as an indicator for evaluating the clinical efficacy of SLIT.

A hospital-based survey on the prevalence of bronchial asthma in patients with allergic rhinitis in southern China.

Background The prevalence of bronchial asthma (BA) and the underlying risk factors in patients with allergic rhinitis (AR) in China are largely unknown. Thus, this study is designed to assess the BA comorbidity in AR patients in two cities (Guangzhou and Zhuhai) of southern China and to determine the risk factors of BA in these AR patients. Methods We performed a cross-sectional, hospital-based survey in two modernized cities in southern China. The BA prevalence was evaluated in 1931 AR patients. Participants were asked to complete a questionnaire containing specific items for AR and BA. A logistic regression analysis was used to assess the risk factors of BA comorbidity in AR patients. Results The prevalence of concomitant BA in AR patients is 5.33% (103/1931). Most of the participants (98.4%) were sensitized to more than one allergen, and the most common sensitization was to house-dust mites. The strongest risk factor of BA determined by a multiple logistic regression analysis was a duration of AR of >5 years (adjusted odds ratio [OR], 8.67; 95% confidence interval [CI], 3.74–20.06), followed by smoking (adjusted OR, 7.21; 95% CI, 1.86–8.23) and self-medication with antibiotics (adjusted OR, 6.35; 95% CI, 3.43–11.78). Conclusion Our findings suggested the risk factors of concomitant BA in AR patients may be helpful to establish preventive strategies.