Study On The Relationship Between Adenoid Hypertrophy And Allergic Rhinitis In Children

Background:Adenoid Hypertrophy（AH）is a common disease in pediatric otolaryngology.Adenoids are part of the pharyngeal lymphatic ring,which promotes the development of the immune system early in life and resists inhaled microorganisms.The volume of adenoids gradually increases with age in childhood,reaches a maximum at about 5-6 years of age,and progressively shrinks at 8-9 years of age.Under physiological conditions,hypertrophic adenoids can partially cover the posterior nostrils and protect the airway by adhering,filtering,and buffering the airflow in the nasal cavity.The pathologically enlarged adenoids can partially or entirely block the posterior nostrils,causing nasal ventilation obstacles,causing microorganisms to accumulate in the nasal cavity,and causing inflammation in the nasal cavity.Suppose the nasal cavity inflammation is not effectively treated.In that case,the continuous inflammatory response will further damage the upper respiratory tract mucosa.It may stimulate β receptors through the nerve endings of exposed epithelial cells,causing the excitability of β receptors to be down-regulated,leading to high airways.The reaction further leads to the occurrence of asthma.Allergic rhinitis（Allergic Rhinitis,AR）is one of the common diseases of children.About 61%of children in the United States are diagnosed with AR before the age of 6.Atopic individuals produce AR after exposure to allergens.It is non-infectious and chronic in the nasal mucosa that involves releasing inflammatory factors mediated by IgE and a variety of immunocompetent cells（mast cells,T,B lymphocytes,etc.）.Inflammatory diseases.Symptoms such as runny nose,nasal itching,sneezing,and nasal congestion will appear after the onset of the child.In severe cases,it may affect the everyday life and growth of the child.Both AH and AR can occur at the same time.The incidence of AH in children with AR is about 21.2%.Hypertrophic adenoid tissue can partially or entirely block the posterior nostrils,resulting in nasal congestion,mouth breathing,etc.,similar to AR.Symptoms,which may cause or further aggravate AR symptoms in children.There is a particular pathophysiological relationship between AH and AR.The accumulation and activation of eosinophils often accompany AR.In the adenoid and tonsil tissues of sensitized children,the number of eosinophils is also significantly higher than that of non-sensitized children.The mechanism may be the children.After sensitization by inhalation of allergens,the immune microenvironment of the adenoid tissue changes,resulting in more eosinophils,CD1+Langerhans cells,and so on.In addition,AH and AR are both related to the accumulation of leukotrienes.Cysteinyl leukotrienes act as inflammatory mediators,including LTB4,LTC4,LTD4,LTD5,LTE4,etc.By binding to leukotriene type Ⅰ receptors,a series of airway reactions occur,causing tissue edema and vascular permeability to Increase,further aggravate eosinophil infiltration.Most views believe that AH is positively correlated with AR in terms of morbidity and severity of clinical symptoms.However,in some studies,some scholars have reached different conclusions.Ameli et al.found that AH may have nothing to do with AR,and in subsequent studies proposed that the size of adenoids is negatively related to the degree of nasal congestion,and the larger the turbinate,the smaller the adenoids.However,Eren et al.believed that AH was negatively correlated with AR.However,the reports of the scholars as mentioned above have not further studied the potential mechanism of action.This study explores the differences in cytokines and inflammatory cells in peripheral blood and adenoid tissues of AH patients with and without AR and provides a theoretical basis for studying the correlation between AH and AR.Methods:One hundred two children with adenoid hypertrophy who underwent adenoidectomy were included in this study.1.All patients received serum-specific IgE tests.According to the test results,102 children were divided into the AH group（n=54）and the AH+AR group（n=48）.2.According to pure-tone hearing threshold measurement,acoustic impedance,and fiber otoscope examination results,compare the two groups’ prevalence of secretory otitis media.3.Measure the number and percentage of eosinophils,neutrophils,and basophils in the peripheral blood of children.4.Stain the adenoid tissue with hematoxylin-eosin（HE）,calculate the number of eosinophils in the adenoid tissue under a 400X microscope,and analyze the eosinophil infiltration of the adenoid tissue between the two groups.5.Extract the total RNA of adenoid tissues and perform real-time quantitative PCR（RT-qPCR）to detect the expression of cytokines closely related to AR.The cytokines we tested include Th-1 related cytokines,mainly including IL-2,IL-8,IL-12,TNF-α,and IFN-γ;Th-2 related cytokines,mainly including IL-4,IL-5,IL-10,IL-13,IL-18,IL-33,and IL-25.Allergy-related receptors include H1R,H2R,H3R,H4R,LTR1,LTR2,and GCR.Results:1.Forty-eight（47%）hospitalized children were diagnosed with AR,which is significantly higher than the incidence of allergic rhinitis in Chinese children.2.There was no significant difference in the prevalence of secretory otitis media between the two groups,but there was a rising trend in the AH+AR group（p=0.428）.3.The number and percentage of eosinophils in peripheral blood and adenoid tissues in the AH+AR group were higher than those in the AH group.The difference was statistically significant（p<0.0001,p=0.0014）.There was no statistically significant difference in the number and percentage of neutrophils and basophils（P>0.05）.4.The difference was statistically significant,the expression of multiple cytokines in the AH+AR and the AH group.Compared with the AH group,the expressions of IL-8,IL-12,and IFN-γ in the AH+AR group were reduced,with p values of 0.032,0.022,0.042;The expression of IL-4,IL-18,IL-33,H2R,LTR1 LTR2,and GCR increased,and the p values were 0.013,0.008,0.023,0.048,0.004,0.012,0.010,respectively.Conclusion:Allergic rhinitis may be an important cause of adenoid hypertrophy in children.In children with allergic rhinitis,the pathological mechanism of adenoid hypertrophy may be related to tissue eosinophilia and type 2（or Th2）inflammation.AH with and without AR are different in some inflammatory indicators and should be treated differently in clinical practice.Background:Tonsils and adenoid hypertrophy（Adenotonsillar hypertrophy,ATH）are the most common cause of upper respiratory tract obstruction in children.Adenoids and tonsil tissues are located at the entrance of the respiratory tract,and they are the first point of contact for inhaled allergens.Although the cause of ATH has not been clarified,there have been reports showing that allergies are closely related to ATH.Studies have shown that in children with allergic rhinitis（AR）,the prevalence of adenoid and tonsil diseases is significantly higher,but there are also reports that the prevalence of AR in ATH is comparable to that of an age-matched control group.Resemblance.Due to the decisive role of tonsil and adenoid tissue in the immune response,chronic and repetitive inflammation in and around the tonsil and adenoid tissue may be an important cause of ATH.Allergy is one of the most common inflammations of the upper respiratory tract.Allergic rhinitis is a clinically defined disease with four typical symptoms:runny nose,nasal congestion,nasal itching,and sneezing.It is an immunoglobulin E（Immunoglobulin E,IgE）mediated type I hypersensitivity reaction,and eosinophil infiltration occurs in the nasal mucosa exposed to allergens.Allergic diseases can cause inflammation of adenoids and tonsil tissues,leading to the formation of allergic inflammation,resulting in a large number of IgE-positive plasma cells/mast cells,allergen-specific IgE（Specific Immunoglobulin E,sIgE）,and eosinophils.Infiltration in the tissue.In the absence of a systemic allergic reaction,local allergic reactions can also occur in adenoids and tonsil tissues,producing sIgE.Studies have shown that the total IgE and house dust mite sIgE antibodies produced in adenoid tissue homogenates of allergic children are significantly higher than in non-allergic children.These antibodies may cause the infiltration of eosinophils in the adenoid tissues of allergic children,And further stimulate the hyperplasia of tonsils and adenoids,so it is imperative to determine whether children with ATH are in an allergic state.Serum-specific IgE tests and skin prick tests are widely used to diagnose allergic rhinitis,but both of these tests have certain limitations.In our previous research,we found that increased eosinophils in peripheral blood and tissues may support the diagnosis of AR.This study aims to evaluate whether inflammatory cells and total IgE in the blood of children with ATH can be used to predict ATH allergic status.Methods:1.A retrospective analysis of the clinical data of 234 children undergoing adenoidectomy and＆or tonsillectomy.2.Record the blood routine parameters of the child before surgery,including neutrophil count,eosinophil count,basophil count,lymphocyte count,and MPV（mean platelet volume）,and calculate neutrophils The ratio of cells to lymphocytes,eosinophils to lymphocytes,and basophils to lymphocytes.3.Test total IgE and specific IgE of common allergens before surgery.4.Compare the above parameters between the allergic and non-allergic groups to evaluate the value of inflammatory blood cells and total IgE in predicting the allergic state of children.Results:1.35.47%of children with ATH are atopic,and dust mites（d2）,house dust mites（d1）,and molds（mx2）are the most common allergens.2.In children with allergic ATH,the peripheral blood eosinophil count,eosinophil/lymphocyte value,and serum total IgE were significantly increased in the inhaled allergen allergy group and the food allergen allergy group（respectively:p<0.001 and p<0.001,p<0.001 and p=0.003,p<0.001 and p<0.001）.The peripheral blood basophil count of children with ATH in the food allergen allergy group was significantly higher than in the non-allergic group（p=0.001）.3.The results of receiver operating characteristic curve（ROC）analysis show that total systemic IgE has a significant advantage in diagnosing allergy in children with ATH,and its cut-off value is 46.55 and above {area under the curve（AUC）=0.837[95%CI:0.788 to 0.886];p<0.001;sensitivity:0.88;specificity:0.669｝.4.Peripheral blood eosinophil count and eosinophil to lymphocyte ratio can also predict the positive result of the ATH child allergy test,the cut-off value is 0.295[AUC=0.721（95%CI:0.652 to 0.789）;p<0.001;Sensitivity:0.467;Specificity:0.907]and 0.082[AUC=0.685（95%CI:0.614 to 0.756）;p<0.001;Sensitivity:0.489;Specificity:0.815].Conclusion:By observing the total peripheral blood IgE,eosinophil count,and eosinophil to lymphocyte ratio in ATH,the presence of allergies can be predicted,which will guide us to treat ATH accurately and significantly reduce medical costs.Background:Adenoids are a group of peripheral lymphoid tissues located in the nasopharynx.Adenoid Hypertrophy（AH）,also known as proliferative hypertrophy,is a common and frequently occurring disease in childhood.About 1/3 of children younger than seven years old have adenoid hypertrophy;among 7-10-year-old children,about 1/5 have adenoid hypertrophy;10-15-year-old children have adenoid hypertrophy.The ratio is about 10%.In children with allergic rhinitis（Allergic Rhinitis,AR）,the incidence of adenoid hypertrophy is about 46.4%.Common symptoms of adenoid hypertrophy include nasal congestion,sleep apnea,snoring,recurrent otitis media,eustachian tube dysfunction,recurrent sinusitis,etc.These symptoms or complications are similar to those of allergic rhinitis and are accompanied by allergic rhinitis.Rhinitis is more common in children.AH,and AR is more related than other allergic diseases.This is because the anatomical positions of the nasopharynx and the nasal cavity are the closest,and the lymphatic drainage in these areas is the same,which increases the contact between adenoids and respiratory allergens,causing AH to happen.The existence of AR is a risk factor for AH.Immunoglobulin E（IgE）-mediated inflammation in the nasal mucosa plays an important role in the occurrence and development of these two diseases.When AH does not cause any clinical symptoms,no intervention is required.Surgical resection is currently the main clinical treatment measure when it causes corresponding clinical symptoms such as snoring,mouth breathing,and sleep apnea.Adenoidectomy is currently the most important treatment for adenoid hypertrophy in children.Adenoid and tonsillectomy can improve the symptoms related to obstruction,such as snoring and open mouth breathing,and improve allergies in children.The symptoms of rhinitis,but not all children can relieve the symptoms of upper airway obstruction after surgery.More than one-third of the children still have different degrees of airway obstruction after adenoidectomy.Children with adenoid hypertrophy with AR have more severe preoperative snoring,nasal congestion,rhinorrhea,and other symptoms.Children with simple adenoid hypertrophy after adenoidectomy are more likely than those with AR with adenoid hypertrophy.The improvement of symptoms is more obvious.Respiratory allergens are often found in children with AH,and respiratory allergens play a certain role in the occurrence and development of AH.Through the determination of cysteinyl leukotriene LTC4 and LTD5 in children with AH,it is found that LTC4 and LTD5 are involved in the proliferation and hypertrophy of adenoids and their expression level is positively correlated with the degree of AH proliferation.Serum LTB4 is another important inflammatory factor involved in AH,and its level in serum is related to the severity of AR and AH.Adenoidectomy is a trauma to children after all.Our previous study found that children with adenoid hypertrophy with allergic rhinitis had significantly increased eosinophils in their peripheral blood and adenoid tissues,and leukotrienes,histamine,and leukotrienes in adenoid tissues.The expression of allergy-related receptors such as glucocorticoids is also significantly increased.Studies have shown that montelukast sodium,as a leukotriene receptor antagonist,effectively treats adenoid hypertrophy.Montelukast sodium combined with intranasal hormones（such as mometasone furoate）can obtain a better clinical effect than simply using intranasal hormones to treat adenoid hypertrophy in children.Montelukast sodium,loratadine combined with mometasone furoate for children with AR and AH can reduce the probability of disease recurrence and improve the therapeutic effect.In the "Guidelines for the Diagnosis and Treatment of Obstructive Sleep Apnea in Chinese Children"（2020）,for children with mild and moderate OSA,clinically evaluated as adenoid and＆or tonsil hypertrophy,especially adenoid hypertrophy Children,except for other oral,maxillofacial and upper airway obstruction problems,nasal glucocorticoid and montelukast sodium are recommended as therapeutic drugs;especially for children with rhinitis symptoms such as nasal congestion,runny nose,sneezing,and obstructive nasal sounds,Nasal glucocorticoids can be used as recommended.Among them,for children with moderate to severe OSA and clear adenoids and＆or tonsillar hypertrophy,adenoid and＆or tonsillectomy is still the first choice.The guidelines do not distinguish whether children are combined with AR,and there is no more individualized treatment guidance plan for the specific conditions of the children.The guidelines suggest that the age of conservative treatment of drugs is more than two years old,the duration of nasal glucocorticoids is usually six weeks,and the course of leukotriene receptor antagonists is recommended to be three months.Through this study,we included 3-12 years old children with AH to explore and analyze the specific therapeutic effects of 3-month conservative drug treatment on children with AH with or without AR,which is an individualized treatment for clinical adenoid hypertrophy.Provide a reference plan.Methods:1.Select 236 children with adenoid hypertrophy treated at the Otorhinolaryngology-Head and Neck Surgery Clinic of Rizhao People’s Hospital from October 2019 to April 2021.Whether they were combined with AR,they were divided into 123 cases in the AH group and 113 cases in the AH+AR group.2.All children received regular medical treatment for three months,nasal spray hormone（mometasone furoate nasal spray）,antihistamine（loratadine granules）,leukotriene receptor antagonist（Montelukast Sodium Chewable Tablets）.3.To compare the degree of nostril blockage by adenoids under fiberopharyngoscopy before and after drug treatment between the two groups.4.The visual analog scale（VAS）was used to evaluate the obstruction symptoms（snoring,mouth breathing,nasal congestion）and allergic symptoms（runny nose,nasal itching,sneezing）before and after drug treatment in children.Results:1.General information.A total of 123 patients in the AH group were 6.0（4.0,8.0）years old,of which 78 were male children（63.4%）.A total of 113 patients in the AH+AR group were 6.0（4.0,7.5）years old,of which 76 were male children（67.3%）.There was no statistical difference in age between the two groups of children（P=0.683）;the proportion of patients in both groups was higher,and there was no statistical difference between the two groups（P=0.538）.2.Pre-treatment nasal endoscopic measurement,the percentage of nostril degree after adenoid obstruction in the AH group was 78.0（64.0,87.0）,and the percentage in the AH+AR group was 79.0（64.0,88.0）.There was no difference between the two groups（P>0.05）.In the AH group,the degree of nostril obstruction after adenoids decreased to 76.0（61.0,85.0）at one month after treatment,76.0（57.0,81.0）at two months after treatment,and 75.0（55.0,80.0）at three months after treatment.In the AH+AR group,the degree of nostril obstruction after adenoids decreased to 78.0（61.0,83.5）at one month after treatment,72.0（57.0,78.0）at two months after treatment,and 68.0（53.0,74.0）at three months after treatment.The degree of improvement in nostril obstruction in children in the AH+AR group was significantly greater than that in the AH group（P<0.001）.3.Comparing the clinical symptoms VAS scores with those before treatment,the decrease in the VAS scores of nasal congestion and snoring symptoms in children in the AH+AR group was more significant than that in children in the AH group at two months and three months after treatment（P<0.001）.The VAS scores of children with mouth-opening respiratory symptoms decreased significantly in the AH+AR group after two and three months of treatment（P<0.01）.One month after treatment,two months,and three months after treatment,the scores of nasal itching,sneezing,and runny nose symptoms in children in the AH+AR group decreased significantly more than those in the AH group（P<0.001）.Conclusion:Whether adenoid hypertrophy is combined with AR,the effect of drug treatment is different.AR is an important factor of adenoid hypertrophy in children.Active treatment of AR can effectively reduce the adenoid volume and improve the clinical symptoms of children.Drug treatment is adhered to for children with adenoid hypertrophy and AR,and most children can be treated conservatively with drugs to avoid surgery.In children with adenoid hypertrophy without AR,although the adenoid volume is significantly reduced after drug treatment compared with before treatment,the reduction is significantly smaller than that of patients with AR,and the clinical symptoms are not improved well.For patients with simple AH who meet the indications for surgery,Surgical treatment should be timely.