Chinese Society of Allergy and Chinese Society of Otorhinolaryngology-Head and Neck Surgery Guideline for Chronic Rhinosinusitis

The current document is based on a consensus reached by a panel of experts from the Chinese Society of Allergy and the Chinese Society of Otorhinolaryngology-Head and Neck Surgery, Rhinology Group. Chronic rhinosinusitis (CRS) affects approximately 8% of Chinese adults. The inflammatory and remodeling mechanisms of CRS in the Chinese population differ from those observed in the populations of European descent. Recently, precision medicine has been used to treat inflammation by targeting key biomarkers that are involved in the process. However, there are no CRS guidelines or a consensus available from China that can be shared with the international academia. The guidelines presented in this paper cover the epidemiology, economic burden, genetics and epigenetics, mechanisms, phenotypes and endotypes, diagnosis and differential diagnosis, management, and the current status of CRS in China. These guidelines—with a focus on China—will improve the abilities of clinical and medical staff during the treatment of CRS. Additionally, they will help international agencies in improving the verification of CRS endotypes, mapping of eosinophilic shifts, the identification of suitable biomarkers for endotyping, and predicting responses to therapies. In conclusion, these guidelines will help select therapies, such as pharmacotherapy, surgical approaches and innovative biotherapeutics, which are tailored to each of the individual CRS endotypes.

Particulate Matter 2.5 Causes Deficiency in Barrier Integrity in Human Nasal Epithelial Cells

PURPOSE: The effect of air pollution-related particulate matter (PM) on epithelial barrier function and tight junction (TJ) expression in human nasal mucosa has not been studied to date. This study therefore aimed to assess the direct impact of PM with an aerodynamic diameter less than 2.5 μm (PM2.5) on the barrier function and TJ molecular expression of human nasal epithelial cells. METHODS: Air-liquid interface cultures were established with epithelial cells derived from noninflammatory nasal mucosal tissue collected from patients undergoing paranasal sinus surgery. Confluent cultures were exposed to 50 or 100 µg/mL PM2.5 for up to 72 hours, and assessed for 1) epithelial barrier integrity as measured by transepithelial resistance (TER) and permeability of fluorescein isothiocyanate (FITC) 4 kDa; 2) expression of TJs using real-time quantitative polymerase chain reaction and immunofluorescence staining, and 3) proinflammatory cytokines by luminometric bead array or enzyme-linked immunosorbent assay. RESULTS: Compared to control medium, 50 and/or 100 µg/mL PM2.5-treatment 1) significantly decreased TER and increased FITC permeability, which could not be restored by budesonide pretreatment; 2) significantly decreased the expression of claudin-1 messenger RNA, claudin-1, occludin and ZO-1 protein; and 3) significantly increased production of the cytokines interleukin-8, TIMP metallopeptidase inhibitor 1 and thymic stromal lymphopoietin. CONCLUSIONS: Exposure to PM2.5 may lead to loss of barrier function in human nasal epithelium through decreased expression of TJ proteins and increased release of proinflammatory cytokines. These results suggest an important mechanism of susceptibility to rhinitis and rhinosinusitis in highly PM2.5-polluted areas.

Comparison of Long-term Efficacy of Subcutaneous Immunotherapy in Pediatric and Adult Patients With Allergic Rhinitis

PURPOSE: Data comparing the long-term efficacy and safety of subcutaneous immunotherapy (SCIT) using house dust mite (HDM) in children and adults with allergic rhinitis (AR) are limited. This study aimed to compare the long-term effects of HDM-SCIT in a cohort of Chinese pediatric and adult patients with AR. METHODS: A total of 124 pediatric and adult AR patients received HDM-SCIT for 3 years, with 118 patients being followed-up for 2 years. Prior to treatment (baseline), at the end of the 3-year treatment periods (third year) and 2 years after the discontinuation of treatment (fifth year), all patients were evaluated for total nasal symptom scores (TNSS), daily medication score (DMS), total combined score (TCS; symptoms [nasal + ocular] + DMS) and quality of life (QoL). Safety was assessed according to adverse events reported. RESULTS: After 3-year treatment, HDM-SCIT significantly improved symptoms and QoL scores at the end of the third and fifth years in both groups. Better improvements were observed in the third and fifth years based on baseline, in children compared to adults (TNSSΔ3: 6.66 vs. 5.41, P = 0.011; TCSΔ3: 4.30 vs. 3.83, P = 0.027 and TNSSΔ5: 6.16 vs. 4.86, P = 0.037; TCSΔ5: 4.11 vs. 3.62, P = 0.044).Shorter duration of AR history before SCIT (<10 vs. ≥10 years) resulted in better improvements at the end of the third and fifth years (TCSΔ3: 4.12 vs. 3.13, P = 0.036; TCSΔ5: 3.90 vs. 3.09, P = 0.033). HDM-SCIT was safe and comparable in both children and adults with AR. CONCLUSIONS: Children with AR may achieve better long-term efficacy of HDM-SCIT than adults with AR.

Short-term Haze Exposure Predisposes Healthy Volunteers to Nasal Inflammation

PURPOSE: This study aimed to investigate the impact of short-term haze exposure on nasal inflammation in healthy volunteers. METHODS: Thirty-three healthy university students were assessed for nasal symptoms, nasal patency, upper and lower respiratory tract nitric oxide (NO) as well as inflammatory mediators and neuropeptides in nasal secretions before and after a 5-day haze episode. Peripheral blood mononuclear cells (PBMCs) were stimulated with particulate matter with an aerodynamic diameter of less than 2.5 μm (PM(2.5)), and cytokines in the supernatants were examined. RESULTS: Mild nasal symptoms were reported by some participants during the haze episode. Objective measures of nasal patency demonstrated that nasal airway resistance was significantly increased from baseline levels, while nasal cavity volume and minimum cross-sectional area were significantly decreased. Similarly, the levels of nasal and exhaled NO, eotaxin, interleukin (IL)-5, chemokine (C-C motif) ligand 17, IL-8, substance P, nerve growth factor and vasoactive intestinal peptides in nasal secretions were significantly increased from baseline values following the haze episode. In contrast, the levels of interferon-γ, IL-10, transforming growth factor-β and neuropeptide Y were significantly decreased. Incubation with 0.1-10 μg/mL PM(2.5) significantly increased release of IL-1β, IL-4, IL-5, IL-8 and IL-10 from PBMCs. CONCLUSIONS: Short-term haze exposure may lead to nasal inflammation and hypersensitivity in healthy subjects predominantly by Th2 cytokine-mediated immune responses.

Comparison of Corticosteroids by 3 Approaches to the Treatment of Chronic Rhinosinusitis With Nasal Polyps

PURPOSE: Corticosteroids are regarded as the mainstay of medical treatment of eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP). To date, a head-to-head comparison of the efficacy and safety of glucocorticoid preparations administered via different routes for the treatment of chronic rhinosinusitis with nasal polyps has not been reported. To compare the efficacy and safety of steroids administered via the oral, intranasal spray and transnasal nebulization routes in the management of ECRSwNP over a short course. METHODS: Overall, 91 patients with ECRSwNP were recruited prospectively and randomized to receive either oral methylprednisolone, budesonide inhalation suspension (BIS) via transnasal nebulization, or budesonide nasal spray (BNS) for 2 weeks. Nasal symptoms and polyp sizes were assessed before and after the treatment. Similarly, nasal polyp samples were evaluated for immunological and tissue remodeling markers. Serum cortisol levels were assessed as a safety outcome. RESULTS: Oral methylprednisolone and BIS decreased symptoms and polyp sizes to a significantly greater extent from baseline (P < 0.05) than BNS. Similarly, BIS and oral methylprednisolone significantly reduced eosinophils, T helper 2 cells, eosinophil cationic protein, interleukin (IL)-5, and expression of matrix metalloproteinases 2 and 9, and significantly increased type 1 regulatory T cells, IL-10, transforming growth factor-β, and tissue inhibitor of metalloproteinases 1 and 2 in nasal polyps to a greater extent than BNS. Post-treatment serum cortisol levels were significantly decreased by oral methylprednisolone compared to BIS or BNS, which did not significantly alter the cortisol levels. CONCLUSIONS: A short course of BIS transnasal nebulization is more efficacious compared to BNS in the management of ECRSwNP and is safer than oral methylprednisolone with respect to hypothalamic-pituitary-adrenal axis function.

Chinese Society of Allergy Guidelines for Diagnosis and Treatment of Allergic Rhinitis

Allergic rhinitis (AR) is a global health problem that causes major illnesses and disabilities worldwide. Epidemiologic studies have demonstrated that the prevalence of AR has increased progressively over the last few decades in more developed countries and currently affects up to 40% of the population worldwide. Likewise, a rising trend of AR has also been observed over the last 2–3 decades in developing countries including China, with the prevalence of AR varying widely in these countries. A survey of self-reported AR over a 6-year period in the general Chinese adult population reported that the standardized prevalence of adult AR increased from 11.1% in 2005 to 17.6% in 2011. An increasing number of original articles and imporclinical trials on the epidemiology, pathophysiologic mechanisms, diagnosis, management and comorbidities of AR in Chinese subjects have been published in international peer-reviewed journals over the past 2 decades, and substantially added to our understanding of this disease as a global problem. Although guidelines for the diagnosis and treatment of AR in Chinese subjects have also been published, they have not been translated into English and therefore not generally accessible for reference to non-Chinese speaking international medical communities. Moreover, methods for the diagnosis and treatment of AR in China have not been standardized entirely and some patients are still treated according to regional preferences. Thus, the present guidelines have been developed by the Chinese Society of Allergy to be accessible to both national and international medical communities involved in the management of AR patients. These guidelines have been prepared in line with existing international guidelines to provide evidence-based recommendations for the diagnosis and management of AR in China.

Mechanisms underlying glucocorticoid resistance in chronic rhinosinusitis with nasal polyps / 中华耳鼻咽喉头颈外科杂志

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease that occurs in the nasal and sinus mucosa, which is a common disease in otorhinolaryngology. At present, CRSwNP can be effectively treated by glucocorticoids (GC). GC binds to GC receptors in the nasal mucosa, affects the expression of inflammatory genes, inhibits the activation and action of eosinophils, T cell-associated inflammatory responses in nasal polyps, as well as tissue remodeling. However, there are some patients fall reponse to GC, so called GC resistance. The study suggests that the possible mechanism of CRSwNP GC resistance is mainly related to GC receptor abnormal, the role of cytokines and transcription factors, such as Th cells and IL-8. In addition, MAPK-related kinases and histone deacetylase in the GC signaling pathway also play important roles in the GC resistance process. This paper reviews the mechanism of GC treatment of CRSwNP, the mechanism of GC resistance and alternative treatment of GC.

Evaluation of preoperative and postoperative structure, function, symptom between two different operations in patients with inferior turbinate hypertrophy / 中国耳鼻咽喉头颈外科

OBJECTIVE To evaluate the clinical outcome of submucosal inferior turbinectomy and outfracture surgery of inferior turbinates. METHODS All patients receiving two different operations were measured by acoustic rhinometry and questionnaire of QOL at preoperative 1 week and postoperative 12 months, seperately. RESULTS Forty-seven patients with inferior turbinate hypertrophy were enrolled in this study. Evaluation of SNOT-20 discovered both surgeries could improve patients' QOL with similar outcome. Preoperative '5 important items' in patients with inferior turbinate hypertrophy were 'lack of a good night's sleep', 'need to blow nose', 'thick nasal discharge', 'fatigue' and 'dizziness'. Postperative '5 important items' were 'postnasal discharge', 'runny nose', 'sneezing', 'reduced concentration' and 'reduced productivity'. Both surgeries could make acoustic rhinometry parameters change obviously, such as minimal cross-sectional area, 0-5 cm nasal volume(NV) and 2-5 cm NV. Furthermore, submucosal inferior turbinectomy produced more volume in nasal cavity than outfacture surgery, (7.28±2.01)cm3 vs (6.01±1.22)cm3, (5.99±1.87)cm3 vs (4.23±1.08)cm3(P<0.05), seperately. There was no correlation between the data of SNOT-20 and acoustic rhinometry. CONCLUSION We recommend outfracture surgery of inferior turbinate as the preferred surgical choice for patients with mild inferior turbinate hypertrophy.

The value of sinonasal CT scan in diagnosing of eosinophilic chronic rhinosinusitis with nasal polyps / 中华耳鼻咽喉头颈外科杂志

Objective@#To compare the value of sinonasal CT scan with other clinical parameters in the pre-diagnosis of eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP).@*Methods@#From January to May of 2016, One hundred and fifty consecutive CRSwNP patients (90 eCRSwNP and 60 non-eosinophilic CRSwNP) undergoing endoscopic functional sinus surgery in Beijing Tongren Hospital were recruited in this study. Preoperative CT scan, skin prick test (SPT) and oral fractional exhaled nitric oxide (FeNO) measurements were performed in each patient and full blood count with differential analysis was performed within 1 week before surgery. t test and X2 test were used to compare the age, gender, history of surgery, onset of asthma, history of allergy, CT scores' ratio for the ethmoid sinus and maxillary sinus (E/M ratio) and presence of osteoneogenesis of two groups. Mann-Whitney analysis was used to compare the total Lund-Mackay scores, FeNO and blood eosinophil counts of two groups. Logistic regression analysis and receiver operating characteristic (ROC) curve were used to assess the predictive value of clinical parameters.@*Results@#E/M ratio, FeNO, blood eosinophil percentage of eCRSwNP group was significantly higher than those of non-eosinophilic CRSwNP group [3.56±0.37 vs 1.80±0.10, (34.4±18.1) μg/L vs (22.1±11.7) μg/L, 8.19%±1.50% vs 4.55%±5.60%; χ2 value was 0.900; t value was 0.994 and 0.900, respectively; all P<0.05]. E/M ratio had the highest predictive value, with area under curve (AUC) value of 0.938. The cut-off point of 2.59 for E/M ratio demonstrated a sensitivity of 94.3% and a specificity of 89.6% for eCRSwNP.@*Conclusion@#The E/M ratio is a more useful predictor in the diagnosis of eCRSwNP compared to other clinical parameters.

The efficacy and safety of budesonide inhalation suspension via transnasal nebulization compared with oral corticosteroids in chronic rhinosinusitis with nasal polyps / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To evaluate the efficacy and safety of a short course of nebulized budesonide via transnasal inhalation in chronic rhinosinusitis with nasal polyps.@*METHOD@#Fifty patients with severe eosinophilic nasal polyps were randomized devided into study group (n = 25) and control group (n = 25). The study group received budesonide inhalation suspension (1 mg twice daily) via transnasal nebulization for one week and the control group received oral prednisone (24 mg QD). Visual analogue scales (VAS) of nasal symptoms, endoscopic polyp scores (kennedy scores) and morning serum cortisol concentrations were assessed in both groups pre- and post-treatment. Operation time and surgical field bleeding were evaluated.@*RESULT@#Four subjects dropped out in control group. Budesonide transnasal nebulization caused a significant improvement in all nasal symptoms especially nasal obstruction (baseline: 8.25 ± 0.53; after treatment: 4.97 ± 0.97, P 0.05], but all values were still located in normal range (normal range: 5-25 μg/dl). Conversely, the morning serum cortisol concentration in oral prednisone group was lower than normal limit [baseline (18.19 ± 2.81) μg/dl, after treatment (2.26 ± 0.70) μg/dl, P < 0.01].@*CONCLUSION@#Twice daily budesonide transnasal nebulization is an effective and safe treatment as evidenced by significant improvements in nasal symptoms and reduction in polyp size, coupled with an absence of hypothalamic-pituitary-adrenal axis suppression, which is safer than the systemic corticosteroids. Budesonide transnasal nebulization offers a viable treatment option for CRSwNP before operation.

Imbalance between Th1 and Th2 cells in cord blood is influenced by maternal allergic rhinitis and associated with atopic dermatitis during the first two years of life / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the influence of maternal atopy on cord blood effector T cells and to identify these biologic markers as predictors of atopic dermatitis (AD).</p><p><b>METHODS</b>Seventy mother-infant pairs were recruited in this prospective birth cohort study. Suspected factors for allergy, including maternal allergic history, total serum IgE, and maternal age at birth, were collected. Mother peripheral blood samples and cord blood were obtained and assayed for the percentage of interferon-γ (IFN-γ) and interleukin 4 (IL-4) producing T cells(Th1 and Th2 respectively) using flow cytometry. Their offspring at the age of 2 years old were evaluated by their dermatologist whether they had AD. Statistical analysis was performed using multiple logistic regression models and receiver-operating characteristic curve was employed to predict atopic dermatitis.</p><p><b>RESULTS</b>Twenty-one allergic and 49 nonallergic mothers were recruited in this study. During the first two years of life, 15.7% children (n = 11) developed a physician-diagnosed AD (all children were the only child in the family). In group with maternal allergic rhinitis, a significantly increased percentage of Th2 was observed in peripheral blood of mother (7.10[1.18;16.1]% vs. 0.37[0.25;0.72]%, U = 10.0, P < 0.05) and cord blood of newborns (1.02[0.57;1.34]% vs. 0.21[0.15;0.42]%, U = 127.5, P < 0.05), respectively. Maternal atopic history did not affect the percentage of Th1 cells in cord blood (0.69[0.40;1.12]% vs.0.50[0.31;0.66]%, U = 361.0, P > 0.05). Children with reduced Th1/Th2 ratio in cord blood had a higher risk to develop AD (OR = 1.72, P = 0.001) . The model including Th1/Th2, maternal allergy, maternal age at birth and maternal total IgE showed high ability to discriminate children with and without AD. AUC was 0.907 (95% CI: 0.804-1.011, P < 0.001).</p><p><b>CONCLUSIONS</b>Elevated IL-4⁺CD4⁺ T cells in cord blood were of relevance with maternal allergic history. Imbalance between Th1 cell and Th2 cell at birth are associated with maternal allergy and promoted subsequent AD development.</p>

The efficacy and safety of a short course of budesonide inhalation suspension via transnasal nebulization in chronic rhinosinusitis with nasal polyps / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To evaluate the efficacy and safety of a short course of nebulized budesonide via transnasal inhalation in chronic rhinosinusitis with nasal polyps.@*METHOD@#Thirty patients with severe eosinophilic nasal polyps were randomized into experimental group (n=15) and control group (n=15). The experimental group received nebulised budesonide suspension (1 mg twice daily) via transnasal inhalation for one week and control group-received budesonide nasal spray (256 microg twice daily). Visual analogue scales (VAS)of nasal symptoms (including nasal obstruction, nasal discharge, loss of smell, and headache/facial pain) and endoscopic polyp scores (Kennedy scores) and morning serum cortisol concentration were performed to both groups before and after the treatment.@*RESULT@#Nebulized budesonide inhalation caused a significant improvement in all nasal symptoms especially nasal obstruction (baseline: 8.4 +/- 0.7; after treatment: 4.0 +/- 0.8, P<0.01) and reduced polyp size compared with before treatment. Additionally, the patients treated with nebulized budesonide showed more obvious improvement in nasal symptoms and polyp size than control group. The morning serum cortisol concentration was mild decreased after one week treatment in nebulized steroid group [baseline: (17.6 +/- 2.4) microg/dl, after treatment: (14.8 +/- 2.6) microg/dl, P<0.01], but all values still were located in normal range (normal range: 5-25 microg/dl).@*CONCLUSION@#A short course of nebulized budesonide transnasal inhalation can rapidly improve nasal symptoms, reduce polyp size, and does not cause obvious HPA axis suppression. Based on these, it is recommend that transnasal inhalation with nebulized budesonide suspension should be performed as a pre-operative routine in patients with nasal polyp.