1.The efficacy and safety of budesonide inhalation suspension via transnasal nebulization compared with oral corticosteroids in chronic rhinosinusitis with nasal polyps.
Hongfei LOU ; Chengshuo WANG ; Luo ZHANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2015;29(9):792-796
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 < 0.01) and reduced polyp size significantly (baseline: 4.64 ± 0.63; after treatment: 3.40 ± 0.76, P < 0.01) compared to pre-treatment. The patients treated with oral prednisone, however, showed more obvious improvement in nasal symptoms and polyp size, shorter operation time and better surgical field than budesonide group. Additionally, the morning serum cortisol concentration was mildly decreased after one week treatment in budesonide group [baseline (17.18 ± 2.83) μg/dl, after treatment (16.24 ± 2.93) μg/dl, 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.
Administration, Inhalation
;
Budesonide
;
administration & dosage
;
therapeutic use
;
Chronic Disease
;
Humans
;
Hydrocortisone
;
blood
;
Hypothalamo-Hypophyseal System
;
Nasal Obstruction
;
Nasal Polyps
;
complications
;
drug therapy
;
Pituitary-Adrenal System
;
Prednisone
;
therapeutic use
;
Rhinitis
;
complications
;
drug therapy
;
Sinusitis
;
complications
;
drug therapy
;
Suspensions
2.Evaluation of preoperative and postoperative structure, function, symptom between two different operations in patients with inferior turbinate hypertrophy
Ming ZHENG ; Xiangdong WANG ; Hui QING ; Chengshuo WANG ; Xiaohong SONG ; Hongfei LOU ; Kuiji WANG ; Luo ZHANG
Chinese Archives of Otolaryngology-Head and Neck Surgery 2017;24(7):359-364
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.
3.The efficacy and safety of a short course of budesonide inhalation suspension via transnasal nebulization in chronic rhinosinusitis with nasal polyps.
Chengshuo WANG ; Hongfei LOU ; Wei LOU ; Luo ZHANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2012;26(8):347-350
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.
Administration, Inhalation
;
Adult
;
Budesonide
;
administration & dosage
;
adverse effects
;
therapeutic use
;
Female
;
Humans
;
Male
;
Middle Aged
;
Nasal Polyps
;
complications
;
drug therapy
;
Nebulizers and Vaporizers
;
Sinusitis
;
complications
;
drug therapy
;
Suspensions
;
Treatment Outcome
;
Young Adult
4.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.
Hongfei LOU ; Yujing FU ; Chengshuo WANG ; Yang WANG ; Luo ZHANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2014;49(5):390-394
OBJECTIVETo investigate the influence of maternal atopy on cord blood effector T cells and to identify these biologic markers as predictors of atopic dermatitis (AD).
METHODSSeventy 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.
RESULTSTwenty-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).
CONCLUSIONSElevated 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.
Adult ; Child, Preschool ; Dermatitis, Atopic ; immunology ; Female ; Fetal Blood ; cytology ; Flow Cytometry ; Humans ; Immunoglobulin E ; blood ; Infant ; Infant, Newborn ; Mothers ; Prospective Studies ; Rhinitis, Allergic ; blood ; immunology ; Th1 Cells ; cytology ; Th1-Th2 Balance ; Th2 Cells ; cytology
5.Comparison of Long-term Efficacy of Subcutaneous Immunotherapy in Pediatric and Adult Patients With Allergic Rhinitis.
Yanran HUANG ; Chengshuo WANG ; Feifei CAO ; Yan ZHAO ; Hongfei LOU ; Luo ZHANG
Allergy, Asthma & Immunology Research 2019;11(1):68-78
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.
Adult*
;
Asian Continental Ancestry Group
;
Child
;
Cohort Studies
;
Humans
;
Immunotherapy*
;
Pyroglyphidae
;
Quality of Life
;
Rhinitis, Allergic*
;
Treatment Outcome
6.Comparison of Corticosteroids by 3 Approaches to the Treatment of Chronic Rhinosinusitis With Nasal Polyps
Yunyun ZHANG ; Hongfei LOU ; Yang WANG ; Ying LI ; Luo ZHANG ; Chengshuo WANG
Allergy, Asthma & Immunology Research 2019;11(4):482-497
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.
Adrenal Cortex Hormones
;
Budesonide
;
Eosinophil Cationic Protein
;
Eosinophils
;
Glucocorticoids
;
Humans
;
Hydrocortisone
;
Inhalation
;
Interleukin-10
;
Interleukins
;
Matrix Metalloproteinases
;
Methylprednisolone
;
Nasal Polyps
;
Polyps
;
Prospective Studies
;
Steroids
;
T-Lymphocytes, Regulatory
;
Tissue Inhibitor of Metalloproteinases
7.Short-term Haze Exposure Predisposes Healthy Volunteers to Nasal Inflammation
Mu XIAN ; Kuiji WANG ; Hongfei LOU ; Yang WANG ; Luo ZHANG ; Chengshuo WANG
Allergy, Asthma & Immunology Research 2019;11(5):632-643
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.
Air Pollution
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Airway Resistance
;
Cytokines
;
Healthy Volunteers
;
Humans
;
Hypersensitivity
;
Inflammation
;
Interleukin-10
;
Interleukin-4
;
Interleukin-5
;
Interleukin-8
;
Interleukins
;
Nasal Cavity
;
Nerve Growth Factor
;
Neuropeptide Y
;
Neuropeptides
;
Nitric Oxide
;
Particulate Matter
;
Peptides
;
Respiratory System
;
Substance P
8.Particulate Matter 2.5 Causes Deficiency in Barrier Integrity in Human Nasal Epithelial Cells
Mu XIAN ; Siyuan MA ; Kuiji WANG ; Hongfei LOU ; Yang WANG ; Luo ZHANG ; Chengshuo WANG ; Cezmi A AKDIS
Allergy, Asthma & Immunology Research 2020;12(1):56-71
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.
Asthma
;
Budesonide
;
Claudin-1
;
Cytokines
;
Enzyme-Linked Immunosorbent Assay
;
Epithelial Cells
;
Fluorescein
;
Fluorescein-5-isothiocyanate
;
Fluorescent Antibody Technique
;
Humans
;
Interleukin-8
;
Mucous Membrane
;
Nasal Mucosa
;
Occludin
;
Particulate Matter
;
Permeability
;
Polymerase Chain Reaction
;
Rhinitis
;
RNA, Messenger
;
Tight Junctions
9.Chinese Society of Allergy Guidelines for Diagnosis and Treatment of Allergic Rhinitis.
Lei CHENG ; Jianjun CHEN ; Qingling FU ; Shaoheng HE ; Huabin LI ; Zheng LIU ; Guolin TAN ; Zezhang TAO ; Dehui WANG ; Weiping WEN ; Rui XU ; Yu XU ; Qintai YANG ; Chonghua ZHANG ; Gehua ZHANG ; Ruxin ZHANG ; Yuan ZHANG ; Bing ZHOU ; Dongdong ZHU ; Luquan CHEN ; Xinyan CUI ; Yuqin DENG ; Zhiqiang GUO ; Zhenxiao HUANG ; Zizhen HUANG ; Houyong LI ; Jingyun LI ; Wenting LI ; Yanqing LI ; Lin XI ; Hongfei LOU ; Meiping LU ; Yuhui OUYANG ; Wendan SHI ; Xiaoyao TAO ; Huiqin TIAN ; Chengshuo WANG ; Min WANG ; Nan WANG ; Xiangdong WANG ; Hui XIE ; Shaoqing YU ; Renwu ZHAO ; Ming ZHENG ; Han ZHOU ; Luping ZHU ; Luo ZHANG
Allergy, Asthma & Immunology Research 2018;10(4):300-353
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.
Adult
;
Asian Continental Ancestry Group*
;
China
;
Comorbidity
;
Developed Countries
;
Developing Countries
;
Diagnosis*
;
Epidemiologic Studies
;
Epidemiology
;
Global Health
;
Humans
;
Hypersensitivity*
;
Prevalence
;
Rhinitis, Allergic*
10.Chinese Society of Allergy and Chinese Society of Otorhinolaryngology-Head and Neck Surgery Guideline for Chronic Rhinosinusitis
Zheng LIU ; Jianjun CHEN ; Lei CHENG ; Huabin LI ; Shixi LIU ; Hongfei LOU ; Jianbo SHI ; Ying SUN ; Dehui WANG ; Chengshuo WANG ; Xiangdong WANG ; Yongxiang WEI ; Weiping WEN ; Pingchang YANG ; Qintai YANG ; Gehua ZHANG ; Yuan ZHANG ; Changqing ZHAO ; Dongdong ZHU ; Li ZHU ; Fenghong CHEN ; Yi DONG ; Qingling FU ; Jingyun LI ; Yanqing LI ; Chengyao LIU ; Feng LIU ; Meiping LU ; Yifan MENG ; Jichao SHA ; Wenyu SHE ; Lili SHI ; Kuiji WANG ; Jinmei XUE ; Luoying YANG ; Min YIN ; Lichuan ZHANG ; Ming ZHENG ; Bing ZHOU ; Luo ZHANG
Allergy, Asthma & Immunology Research 2020;12(2):176-237
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.
Adult
;
Asian Continental Ancestry Group
;
Biomarkers
;
China
;
Consensus
;
Diagnosis
;
Diagnosis, Differential
;
Drug Therapy
;
Eosinophils
;
Epidemiology
;
Epigenomics
;
Genetics
;
Humans
;
Hypersensitivity
;
Inflammation
;
International Agencies
;
Medical Staff
;
Neck
;
Phenotype
;
Precision Medicine