Recurrent Otitis Media With Effusion Research Articles

Effects of trypsin and pepsin detection on chronic otitis media with effusion

Chronic otitis media with effusion (COME) is a common cause of hearing loss in children and adults. Laryngopharyngeal reflux (LPR) is often overlooked in the clinical management of COME complicated by LPR. This study aimed to investigate the presence and concentration of trypsin and pepsin in the middle ear effusion (MEE), as well as the recurrence rate of otitis media with effusion (OME) in COME patients with trypsin-/pepsin-positive MEE after acid-suppressive treatment (AST). In this study, trypsin and pepsin were found in the MEE of COME patients. Follow-up results showed that the recurrence rate of OME within 1 year was significantly lower in the AST group than in the non-AST group. Taken together, patients with COME can be offered pepsin detection of MEE, and if the pepsin test is positive, acid-suppressing drugs such as proton pump inhibitors could be recommended to prevent the recurrence of OME.

Natural history of otitis media with effusion without hearing loss in children under 12 years: a systematic review

ObjectiveThis study aimed to evaluate the natural history of otitis media with effusion (OME) without hearing loss in children under 12 years.MethodsWe performed a systematic search in Embase, CINAHL, MEDLINE,...

Modifiable risk factors for developing otitis media with effusion in children under 12 years in high-income countries: a systematic review

ObjectiveTo systematically assess the modifiable risk factors for developing otitis media with effusion (OME) in children under 12 years.MethodsWe searched Embase, MEDLINE, INAHTA database, CENTRAL, CDSR and Epistemonikos for cohort...

Otitis media with effusion in patients with COVID-19: A single-center study in China

BackgroundThe swift global spread of coronavirus disease 2019 (COVID-19), a respiratory ailment primarily marked by pulmonary symptoms, has been linked to the involvement of various organs, including the intestines, kidneys, throat, and ears. Otitis media with effusion (OME), often succeeding an upper respiratory tract infection, mirrors its incidence. As a respiratory infectious disease, it prompts the query of whether the COVID-19 pandemic has spurred an uptick in OME and whether the COVID-19 virus persists in middle ear effusion (MEE) for an extended period. MethodsTo gauge the incidence of OME in the population during the COVID-19 pandemic, a tailored questionnaire was disseminated and subsequently analyzed. Assessing the rise in OME incidence during the pandemic, we compared the proportion of OME cases in the otology outpatient department between pandemic and non-pandemic periods. Statistical analysis involved a t-test. Simultaneously, MEE was collected from patients with COVID-19-associated OME during the pandemic to ascertain the presence of SARS-CoV-2 in MEE via polymerase chain reaction. ResultsBased on the questionnaire data, the estimated OME incidence in the population is approximately 31.4 %. In contrast to the non-pandemic period, the percentage variation in the OME outpatient proportion was 71.4 % (P < 0.05). Among the 61 MEE samples, 13 polymerase chain reaction results were positive, constituting 21.31 %. Nasopharyngeal swabs yielded negative results. Notably, only one patient experienced OME recurrence after 1 month of auripuncture. ConclusionsCOVID-19 can trigger an escalation in OME cases. Even when nasopharyngeal swabs show negative results, SARS-CoV-2 can endure in MEE for an extended duration, suggesting the potential for asymptomatic COVID-19 transmission and recurrence within the population.

Determination of Tympanostomy Tube Types for Otitis Media with Effusion in Patients with Cleft Palate: Comparison between Paparella Type 1 and Type 2 Tubes.

This study examined the effects of different types of tympanostomy tubes in pediatric patients undergoing cleft palate (CP) surgery in order to provide guidance for the proper insertion of tympanostomy tubes in the management of otitis media with effusion (OME). A total of 101 ears with middle ear effusion in 51 patients with CP were included in this study. Patients underwent palatoplasty and tympanostomy tube surgery at the same time. The type of tube inserted (Paparella type 1 or 2), the severity of CP, and types of palatoplasty surgeries were investigated. All patients were followed up for at least 6 months, and recurrence rates, complications, and reinsertion surgery were evaluated. The rate of OME recurrence after spontaneous tube extrusion was significantly higher in the type 1 group than in the type 2 group (44.3% vs. 19.4%, respectively, p = 0.016). Persistent eardrum perforation was more common in the type 2 group than in the type 1 group (41.9% vs. 12.9%, respectively, p = 0.001). The tube reinsertion rate was higher in the type 1 group than in the type 2 group (22.9% vs. 3.2%, respectively, p = 0.015). The tube reinsertion rate decreased to 8.6% in cases of palatoplasty with Sommerlad's technique, even with type 1 tube insertion, which was not significantly different from the reinsertion rate in the type 2 group (3.7%, p = 0.439). The Paparella type 1 tube would be a better choice in cases of palatoplasty performed using Sommerlad's technique, particularly considering the higher rate of persistent eardrum perforation after extrusion associated with the Paparella type 2 tube. Alternatively, a larger size type 2 tube may be considered in other surgeries to decrease the frequency of recurrence and tube reinsertion.

Causal Relationship Between Body Mass Index and Risk of Otitis Media with Effusion in Children: A Mendelian Randomization Study

BackgroundBody mass index(BMI) in children appears to be associated with Otitis media with effusion(OME) in observational studies, but the causal relationship is not clear.MethodsA two-sample Mendelian randomization (MR) study was used to explore the causal relationship between childhood BMI and OME in people of European ancestry. Genome-wide association studies (GWAS) of childhood BMI were used as exposures (n = 61,111), while GWAS of OME were used as outcomes (n = 429,290). The weighted inverse variance method (IVW) was used as a baseline method to test for causality. In addition, MR-Egger, simple mode analysis, weighted median, and weighted mode were used as complementary methods.MR-PRESSO analysis, MR-Egger intercept analysis, and Cochran’s Q statistical analysis were also used to detect possible directional heterogeneity and polymorphism. To assess this association, we used ratios (OR) with 95% confidence intervals (ci). All statistical analyses were performed in R.ResultsWe selected 22 genome-wide significant single nucleotide polymorphisms (SNPs) from GWAS as instrumental variables (IVW). the IVW approach showed evidence supporting a causal relationship between BMI and OME in children (β = 0.265, SE = 0.113, P = 0.018). MR-Egger regression showed that targeted polymorphisms were unlikely to bias the results bias (intercept=-0.022; P = 0.488), but there was no causal relationship between BMI and OME (β = 0.584, SE = 0.465, P = 0.224). Although the results of the IVW and MR Egger analyses were not consistent, the IVW analysis maintained higher precision, and the Cochran Q test, heterogeneity and polymorphism tests showed no heterogeneity, no directionality and no polymorphism.ConclusionsMR studies suggest that genetically predicted body mass index in childhood is associated with an increased risk of OME. Notably, given the limitations of this study, the mechanism of association between body mass index and OME in childhood needs further investigation. These results support the importance of effective management of obesity, which may reduce OME occurrence and decrease OME recurrence.

Long Term Study of Otitis Media with Effusion after Palatoplasty and Myringotomy with Ventilation Tube Insertion

Objective: To identify the incidence of recurrent otitis media in cleft palate patients after palatoplasty and myringotomy \14 ";"&gt;with ventilation tube (VT) insertion in addition to identifying risk factors of recurrent otitis media with effusion (OME). Material and Methods: This retrospective cohort study was conducted from; January 2002 – December 2014. A total of 120 non- syndromic cleft palate patients were included and analyzed for risk factors contributing to recurrent otitis \14 ";"&gt;media with effusion. Results: \14 ";"&gt;In total, 77.5% of the VT slipped off at 10 months after their initial operation. The incidence of recurrent OME was 54.2% at 7 months after VT slipped off. Significant risk factors that were associated to recurrent OME included: complete cleft palate, two-stage palatoplasty and VT slip-off (p-value&lt;0.05). Conclusion: \14 ";"&gt;The incidence of recurrence OME was 54.2%, and risk factors for recurrence OME are VT slipped off, complete cleft palate and two-stage palatoplasty.

How long do tympanostomy ventilation tubes last in pediatric patients with otitis media with effusion or adhesion? A study using Kaplan-Meier survival analysis

ObjectiveThe purpose of this study was to evaluate the functional duration and survival rate of tympanostomy ventilation tubes and the complications associated with their use in pediatric patients who underwent tube insertion for otitis media with effusion (OME). Complications were analyzed including recurrence and tympanic membrane perforation after the tube removal or extrusion. MethodsAltogether, 447 ears from 234 pediatric patients younger than 15 years of age were studied retrospectively. All patients had undergone long-term tympanostomy ventilation tube: the Goode T-tube insertion for OME at the Osaka Women's and Children's Hospital, which is the pediatrics specialty hospital between April 2014 and March 2016. They were typically followed up every 3–4 months or more frequently if necessary due to otorrhea or tube infection. Subsequently, the tube duration, survival rates of the tube especially at 22 months after insertion defined as “full-term placement”, and the rates of recurrence and perforation were calculated and statistically evaluated. ResultsOf 447 ears, 335 ears from 184 patients underwent their first tube insertion, and 112 ears from 64 patients underwent their second or subsequent tube insertion within the targeted period. Two hundred ears from 106 patients were associated with a cleft palate. The survival rate at full-term placement was 51.7%. The recurrence rate was 56.3%, and the rate of the tympanic perforation was 8.5%. ConclusionsApproximately half of the tubes survived for 22 months. The perforation rate was relatively low; however, recurrence of OME was seen in more than half the ears.

Clinical characteristics of atelectatic eardrums and adhesive otitis media in children

ObjectivesAtelectatic eardrum and adhesive otitis media in children are related to persistent otitis media with effusion (OME) and eustachian tube dysfunction in infancy. However, the pathogenesis of these diseases is not fully understood, and some cases even progress to pars tensa cholesteatoma. This study analyzed the clinical characteristics of children with atelectatic eardrum and adhesive otitis media to clarify associated causes of and risk factors for progression of these middle ear pathologies in children. Patients and methodsThis retroactive study included 38 ears of 31 children with atelectatic eardrums (atelectasis group), and 19 ears of 17 children with adhesive otitis media (adhesive OM group). Thirty-two contralateral non-cholesteatoma ears of 32 children with congenital cholesteatoma were also examined as a control group. Participants were aged 15 or younger. Life history (obtained via questionnaire), associated diseases, hearing acuity, aeration and development of the temporal bone were investigated. ResultsAll children in the atelectasis and adhesive OM groups had a history of recurrent acute otitis media (rAOM) and/or OME. The prevalence of perennial allergic rhinitis was 18 cases (58%) in the atelectasis group and 16 cases (94%) in the adhesive OM group. The prevalence of perennial allergic rhinitis was significantly higher in the adhesive OM group compared to the control group (P < 0.01). The development of mastoid air cells, categorized by MC classification, showed MC0 + MC1 (poor pneumatization) in 19 ears (50.0%) with atelectatic eardrums and 12 ears (63.2%) with adhesive OM. Poor pneumatized mastoid was more frequently observed in the ears of the atelectasis and adhesive OM groups compared to the control group (P < 0.01). No significant difference was found in regards to aeration of the middle ear between the two groups; however, aeration was significantly poorer in both groups compared to the control group (P < 0.01). Three characteristics were analyzed using multivariate logistic regression: perennial allergic rhinitis (odds ratio [OR] 4.319, P = 0.013), poor mastoid pneumatization (OR 8.457, P = 0.012), and pars flaccida retraction pocket (OR 20.897, P = 0.006). These characteristics were shown to be significant risk factors for atelectatic eardrums and adhesive OM. In addition, the predisposition to perennial allergic rhinitis was shown to be the most important factor in the progression from atelectatic eardrum to adhesive otitis media (OR 16.615, P = 0.012). ConclusionChildren with perennial allergic rhinitis, poor development of mastoid air cells, poor aeration of the temporal bone, and with pars flaccida retraction pocket were at an increased risk of developing an atelectatic eardrum and adhesive OM. In particular, perennial allergic rhinitis was shown to be a significant risk factor in the progression from atelectatic eardrum to adhesive otitis media. Allergic inflammation may affect not only the nasal passages but also the eustachian tube, resulting in persistent middle ear dysfunction. Therefore, children with rAOM/OME who have these risk factors should be carefully monitored and treat over time in effort to prevent progression of pathology.

Outcome of the ‘waiting until spontaneous extrusion’ strategy for long-term tympanostomy tube placement in children with cleft palate

Background Otitis media with effusion (OME) in children with cleft palate (CP) is known to be refractory to treatment and most of these patients undergo surgery for ventilation tube (VT) placement. Objectives To identify the outcomes of children with CP using long-term VT with a ‘waiting until spontaneous extrusion’ strategy. Material and methods We retrospectively reviewed the medical records of all children with CP who visited our department from December 2016 to November 2017 and who received long-term VT placement in our department. Risk factors related to residual perforation and recurrence of OME were analyzed. Results A total of 106 children were included in this study. Our statistical analysis of 94 ears followed for more than three months after VT loss revealed that longer VT placement was associated with residual perforation, and shorter VT placement was associated with OME recurrence. Although a longer duration of VT placement was associated with an increased rate, extremely long-term VT placement was not associated with residual perforation, as expected. Half of the VTs were spontaneously extruded at 40 months after insertion. Conclusions and Significance Long-term VT insertion using a waiting until spontaneous extrusion strategy is a potential option for children with CP.

Prognosis of otitis media with effusion in pediatric patients with cleft palate during language-acquisition period treated by simultaneous tympanostomy tube placement with palatoplasty

ObjectiveCleft palate (CP) in children is frequently complicated by otitis media with effusion (OME) due to Eustachian tube dysfunction. Although tympanostomy tube (TT) placement can be beneficial in the treatment of OME to prevent short-term hearing loss, there is no consensus regarding the indications for and timing of TT insertion. The present study was performed to define the safety and effectiveness of simultaneous TT placement with palatoplasty during the language-acquisition period. MethodsWe retrospectively reviewed the medical charts of pediatric patients who underwent palatoplasty for CP in a tertiary medical center, Kyoto University Hospital, from June 2010 to October 2018. The TT retention time was estimated using the Kaplan-Meier method. The incidence of OME recurrence was compared among four Veau classification groups based on the patients' sex, type of CP, median TT retention time, and type of fluid. ResultsSeventy-six subjects (150 ears) were enrolled in the study. The median follow-up duration was 48.7 months (range, 18.2–108.0 months) after the first TT placement. A first TT retention time of <20.1 months was a significant risk factor for OME recurrence. Subjects with maxillofacial anomaly complex and subjects with cleft lip and palate and an alveolar cleft showed a significantly higher OME recurrence rate than subjects with clefts only in the hard and/or soft palate. There was no significant difference in the occurrence of sequelae between subjects with only a single TT placement and subjects with more than one TT placement. ConclusionsBased on the findings of the present study, it is reasonable to perform TT insertion at the same time as palatoplasty on patients who meet the indications. This technique may reduce the number of times the patient requires general anesthesia and maintain good middle ear condition during the period of language acquisition between 1 and 3 years of age.

Auditory temporal processinzg in children with history of recurrent otitis media with effusion

Objective Several studies report that a history of recurrent otitis media with effusion (OME) can affect the development of the central auditory system and its processing. The aim of the present study was to determine the effects of recurrent OME on the auditory temporal processing using the Gap-In-Noise (GIN) test in children with a positive history in their first five years. Materials and methods In this study, 12 children between 8 and 10 years old were selected. The control group was matched according to the age of study cohort. The GIN test was conducted to assess temporal processing and the approximate threshold and percentage of correct responses were calculated for all participants. Nonparametric test was used to analyze the data. Result Results of the GIN test showed significant differences between the OME and control group (p < .001). Children with recurrent OME performed worse than the control group in this test. No significant difference was observed between the right and left ear performance in both groups (p > .05). Conclusion The study results indicate that, children with recurrent OME suffer from auditory temporal processing to some degree.

When Should a Retained Tympanostomy Tube be Removed?

When Should a Retained Tympanostomy Tube be Removed?

Prevalence and associated risk factors of recurrent otitis media with effusion in children in Upper Egypt.

ObjectiveWe conducted this study to determine the associations of possible risk factors and prevalence of recurrent otitis media with effusion (OME) in a cohort of children in Upper Egypt.MethodsThis was a cross-sectional study undertaken in two tertiary referral centers in Upper Egypt. Associations of possible risk factors with prevalence of recurrent OME were studied. Multi-factor logistic regression analysis was done to recognize the statistically significant risk factors associated with recurrent OME.ResultsWe collected the data of 2003 pediatric patients, of which 1016 were males (50.7%). A total number of 310 children have OME, including 159 males (51.3%). The prevalence rate of OME in our cohort was 15.5%. Multi-factor logistic regression analysis of the risk factors related to recurrent OME showed it was strongly associated with adenoid hypertrophy (P < 0.0001), tonsil hypertrophy (P < 0.0001), sinusitis (P < 0.0001), posterior nostril polyps (P = 0.009), allergic rhinitis (P < 0.0001), recurrent URTIs (P = 0.029) and gastroesophageal reflux (P = 0.031).ConclusionsOur study showed that recurrent OME in children in Upper Egypt is a common multifactorial problem, especially in young age. In our locality, allergic rhinitis, recurrent upper respiratory tract infections, gastroesophageal reflux, adenoid and tonsil hypertrophy were the most important associated factors related to the etiopathogenesis of OME.

Antibiotics for otitis media with effusion in children.

Otitis media with effusion (OME), one of the most common diseases in early childhood, is a self-limited illness1 with an estimated recurrence rate of 50% within 24 months2 . OME is characterized by an accumulation of fluid in the middle ear without symptoms or signs of acute infection.3 In most cases OME causes mild hearing impairment for a short period. OME in the pediatric population can lead to diminished hearing which in theory could hinder early learning. Some studies have shown an association with adult hearing loss as well.4 In one study, for instance, OME and recurrent otitis media before the age of 3 were weakly associated with worse classroom concentration, mathematical skills, oral performance and reading skills5 .

Predictors of Otitis Media with Effusion Recurrence Following Myringotomy.

Otitis media with effusion (OME) is the most common cause of acquired pediatric hearing loss. The treatment of persistent OME includes myringotomy with or without tube insertion, with a reported recurrence rate of 19.9-40%. This study aims to investigate the recurrence rate of OME and its predictors following myringotomy. A retrospective study that included 345 ears that underwent myringotomy for persistent OME in 179 pediatric patients during 2016-2018. Patients were followed for 36-48months post myringotomy procedure to detect the recurrence rate. The study sample was divided into two groups based on recurrence status, and the groups were compared using chi-square test and independent T-test. Significant variables (p-value ≤ 0.05) were included in the logistic regression model to determine the predictors of OME recurrence after myringotomy. OME recurrence was detected in 85 ears (24.64%). The OME recurrence rate is higher in patients who underwent myringotomy alone compared to myringotomy with tube insertion (44.1% vs. 22.8%). The insertion of a tympanostomy tube decreases the recurrence rate of OME by 59.9% (OR 0.401; 95% CI 0.162-0.933). The other socio-demographic and clinical characteristics such as age, siblings, daycare attendance, passive smoking, previous acute otitis media, atopy, and adenoidectomy did not significantly influence OME recurrence (p-value > 0.05). The recurrence rate of OME following myringotomy is high. Myringotomy with tube insertion significantly decreases the recurrence rate and the need for further surgeries compared to myringotomy alone. Adenoidectomy and the patient's age have no impact on the recurrence rate of OME.

Clinical Factors Associated With the Outcomes of Long-Term Middle Ear Ventilation Tube Insertion in Pediatric Patients.

Ventilation tube (VT) insertion is the most common treatment for otitis media with effusion (OME). However, OME recurrence and persistent tympanic membrane (TM) perforation after VT removal are encountered in a certain percentage of such children. This study was performed to determine the outcomes of children who underwent long-term VT insertion. A total of 326 ears from 192 patients were analyzed. The associations among the patient age, sex, history of OME, history of repeated acute otitis media, placement duration, whether the VT had been removed intentionally or spontaneously, and the outcome (persistent TM perforation or OME recurrence) were analyzed. The outcomes of multiple VT tube insertions were also reviewed. We also analyzed whether or not local or general anesthesia was associated with the early spontaneous extrusion of the VT. The OME recurrence and TM perforation rates were 29% (96/326 sides) and 17% (57/326 sides), respectively, for first insertions. In addition, 96 (29%) sides underwent ≥2 insertions. The shorter the duration for which the VT was retained in the middle ear, the more significant the rate of increase in OME recurrence. The OME recurrence was observed more often when VT was spontaneously removed than when intentionally removed. The rate of persistent TM perforation was significantly associated with male sex. Persistent TM perforation was not observed in patients who underwent 4 or 5 insertions. The anesthesia method did not significantly influence the timing of spontaneous extrusion of VT. The retention period of VT should be at least 2 years, and VT removal at the age of 7 might be a viable strategy. Multiple VT insertions are recommended for patients with recurrent OME. Ventilation tube under local anesthesia is an effective option for tolerable children.

The short-term and long-term efficacy of balloon dilatation Eustachian tuboplasty and tympanostomy tubes in children patients with recurrent otitis media with effusion

Objective:To evaluate the short-term and long-term efficacy of balloon dilatation Eustachian tuboplasty（BET） and insertion of tympanostomy tubes in the treatment of recurrent otitis media with effusion（OME） in children, and to provide new ideas for the treatment of OME. Method:We made a retrospective analysis of 29 OME patients who had accepted BET and insertion of tympanostomy tubes in Beijing Children's Hospital. Their case history, the past history of insertion of tympanostomy tubes or adenoidectomy, and the audiometry and Eustachian tube function before surgery and 1 month, 6 months, 9 months, 12 months, 18 months, 24 months and 36 months after surgery were recorded. Statistical software was used to evaluate the recovery of Eustachian tube function and the prognosis of OME. Result:The average pure tone audiometry（PTA） of 29 patients was 17.5, 22.5, 18.5, 22.5, 18.5, 22.5, 22.5 dB at 1 month, 6 months, 9 months, 12 months, 18 months, 24 months and 36 months postoperatively. All the 29 patients'PTA was normal. ETS before surgery was 2.404±2.168. ETS of 1 month, 6 months, 9 months and 12 months after surgery was 4.064±3.003, 5.230±2.790, 5.787±2.170, 6.490±2.292 respectively. There was significant difference between preoperative and postoperative（P<0.01）. Conclusion:BET was a safe and reliable surgery for the treatment of OME in children. Its obvious effect was manifested at least 9 months after surgery. Therefore, tympanostomy tubes and BET were recommended doing at the same time for the treatment of OME with eustachian tube dysfunction. At the same time, in order to decrease the risk of recurrent OME, we recommended to take the tubes out until 12 months after surgery.

Effect of vascular endothelial growth factor and its receptors in adult otitis media with effusion.

Some studies have demonstrated that vascular endothelial growth factor (VEGF) plays a critical role in the pathogenesis of otitis media with effusion (OME) in animal models. However, the levels of VEGF and its receptors in adult OME have not been clarified. Our study was designed to detect the levels of VEGF and its receptors in adult OME and explore their relationship with effusion types, duration and prognosis of OME. 61 patients with secretory otitis media were enrolled including 21 males and 40 females, with an average age of 54.7 ± 17.5years. The middle-ear effusions were collected by tympanocentesis or myringotomy. The protein concentrations were determined by enzyme-linked immunosorbent assay and messenger RNA by real-time quantitative PCR. VEGF level was higher in AOME group, but not correlated with the recurrence of OME. VEGFR1 and VEGFR2 levels were lower in recurrent group compared with non-recurrent group. VEGFR2 level was higher in serous effusions than mucoid effusions. VEGF messenger RNA was positively correlated both with HIF-1α and MUC5B. VEGF and its receptors function to induce the production of middle-ear effusions (MEEs) at acute stage of OME rather than chronic or recurrent stage, which is mainly mediated by HIF-1α pathway. The formation of mucoid effusions is associated with MUC5B and VEGFR2, but not with duration and recurrence of OME.

Advances in the role of adenoid hypertrophy in the pathogenesis of otitis media with effusion in children

Adenoid hypertrophy(AH) and otitis media with effusion (OME) are both common diseases in pediatric otorhinolaryngology and are often associated with each other. Children are often diagnosed with otitis media with effusion and adenoid hypertrophy(OME/AH). Adenoids are immune lymphoid tissues of children's upper respiratory tract, and are important barriers against upper respiratory tract infections.During an upper respiratory tract infection,bacteria or viruses repeatedly stimulate immune lymphoid tissue to cause hyperplasia,and pathological hypertrophy is often accompanied by OME and other related symptoms.In recurrent or chronic OME, hyperproliferative adenoids are usually excised indicating that the two diseases may have a certain correlation. Recently,more and more studies have shown that AH plays an important role in the pathogenesis of OME in children. This article elucidates the role of AH in the pathogenesis of childhood OME from adenoid mechanical obstruction,adenoid bacterial and bacterial biofilm, adenoid local immune regulation, and IgE-mediated allergic reaction.