Associations between pollen and allergic rhinitis in children and adolescents

Allergic rhinitis (AR) is a type of rhinitis accompanied by sensitization to allergens. One of the most clinically important allergens is pollen. Recently, due to climate change and CO 2 air pollution, the flowering period starts earlier and persists longer. In addition, antigenicity due to environmental pollution is also being strengthened. As a result, the sensitization rate to pollen antigens is on the rise. It is known that the prevalence of AR especially caused by pollen is rapidly escalating. Although the causal relationship between pollen exposure and the severity of rhinitis is not precisely established, an association of rhinitis symptoms with the time of pollen scattering exists. In addition, the mixed effect of environmental pollution and pollen may play a role in the development of rhinitis symptoms. Therefore, in order to avoid pollen, it is necessary to constantly improve pollen forecast and minimize the contact with pollen indoors and outdoors. Treatment of AR should be performed according to guidelines. Also, continuous efforts to solve the environmental problems affecting the ecology of pollen are needed.

Effects of outdoor air pollution on children with allergic rhinitis

The global worsening of air pollution has decreased the quality of life. Air pollutants can induce oxidative stress, epigenetic changes, and alterations to microRNA expression in the airway and skin, leading to immune dysregulation. Previous epidemiological studies suggest a strong association between outdoor environmental pollution and childhood allergic disease, especially allergic rhinitis (AR). Moreover, traffic-related air pollution has increased the severity and incidence of AR, and heavy traffic has been associated with an increased prevalence of AR. Thus, this review aimed to define outdoor environmental pollution and clarify the mechanisms by which air pollutants aggravate AR. In addition, we performed a systematic review and meta-analysis to summarize the findings of several domestic and international epidemiological and clinical studies about the effects of air pollution on AR in children.

Risk factors and protective factors in pediatric patients with allergic rhinitis

Among allergic diseases of the Korean pediatric population, allergic rhinitis shows the most rapidly increasing prevalence. Its economic burden is substantial in many Asian countries including South Korea. This investigation of its risk factors aims to reduce the socioeconomic burden by blocking exposure of susceptible individuals to identified causes. However, the risk factors of allergic rhinitis varied considerably depending on the seasons, geographical locations, and populations involved. This review article primarily deals with studies on the risk factors for allergic rhinitis in Korean children that were published during the last 10 years and additionally investigates associated large scale international studies. Our investigation identified several single-nucleotide polymorphisms, inhalant allergens, pollution, tobacco smoke, chemicals, and family affluence as risk factors for allergic rhinitis. In contrast, breastfeeding, older sibling, and microbial diversity were protective factors against allergic rhinitis. This suggests that various genetic and environmental factors might affect the manifestation and presentation of allergic rhinitis complexly. These findings are beneficial as they can provide insights into modifiable risk factors that may hinder the development of allergic rhinitis.

Main epidemiological characteristics and natural history of pediatric allergic rhinitis

Allergic rhinitis (AR) is one of the most common allergic diseases characterized by stuffy nose, rhinorrhea, sneezing, and itching. Researchers have indicated an increase in the prevalence of AR and younger-age onset during the last few decades. The increasing burden of AR has caused many researchers to investigate time trends of the prevalence of AR and to identify its risk factors. The most commonly used epidemiological studies are cross-sectional ones such as the International Study of Asthma and Allergies in Childhood study and big data from National Health Insurance Service or National Health and Nutrition Examination Survey. However, these studies have many limitations including recall bias, selection bias, and deficit of objective evaluation. Furthermore, crosssectional studies cannot reflect new risk factors associated with the development of AR. New epidemiological studies will be needed to cover genetic factors, environmental changes, microbiomes, and lifestyles that are known to be risk factors for AR. Further studies will be needed to determine the prevalence, natural history, and risk factors of AR in order to advance our understanding of the pathophysiology, prevention, and management of comorbidities of AR.

Analysis of PC20-FEF25%-75% and △FVC in the methacholine bronchial provocation test

Purpose@#Forced expiratory flow between 25% and 75% (FEF 25%-75%) is known to sensitively reflect bronchial obstruction. Methacholine challenge test (MCT) has shown varying reduction levels of forced vital capacity (FVC) with the reduction in forced expiratory volume in 1 second (FEV1) in asthma. The aim of this study was to evaluate the clinical implication of provocative concentration causing a 20% fall in FEF 25%-75%(PC 20-FEF 25%-75%) and the percentage fall in FVC at the PC 20 dose of methacholine (△FVC). @*Methods@#A total of 194 children who visited the hospital due to respiratory symptoms and underwent MCT were analyzed retrospectively. The patients were divided into 3 groups. Group I had both PC 20-FEV1 and PC 20-FEF 25%-75% above 16 mg/mL; group II had a PC 20-FEF 25%-75% that fell below 16 mg/mL but PC 20-FEV1 was 16 mg/mL or above; group III had a PC 20-FEV1and a PC 20-FEF 25%-75% that both fell below 16 mg/mL. @*Results@#In group II, PC 20-FEV1 was lower (P = 0.026) and the rate of change in FEV1 and FEF 25%-75% from baseline to 16 mg/mL of methacholine concentration was greater than in group I (both P< 0.001). Levels of PC 20-FEF 25%-75% were higher in group II compared to group III (P < 0.001). △FVC showed a correlation with PC 20-FEV1 (P < 0.001) only in the whole group. @*Conclusion@#In asthmatic children, PC 20-FEF 25%-75% may be associated with bronchial hyperresponsiveness. △FVC was not associated with other parameters in either group. For subjects with a positive finding of PC 20-FEF 25%-75% and a negative finding of MCT, the progression to asthma can be suspected.

Correlations of induced sputum eosinophils with blood allergic markers in pediatric asthma and eosinophilic bronchitis

Purpose@#Induced sputum eosinophil count is useful for the evaluation and diagnosis of asthma and eosinophilic bronchitis (EB).The aim of this study was to evaluate the correlation of induced sputum eosinophil count with various allergic indicators, including the peripheral blood eosinophil count, in pediatric asthma and EB. @*Methods@#From May 2014 to July 2018, 126 children visited Kyungpook National University Children’s Hospital, and underwent methacholine bronchial challenge test and sputum induction. Peripheral blood eosinophil counts, serum eosinophil cationic protein (ECP), serum total IgE, immunoCAP for inhalant allergens, and skin prick test were performed in the study subjects. @*Results@#In the asthma group, the eosinophil count of induced sputum correlated with peripheral blood eosinophils (r=0.279, P=0.043).The concordance rates of sputum and peripheral blood eosinophil count in the asthma and EB groups were 64.1% and 25.7%, respectively. The number of eosinophils in the sputum also correlated with serum total IgE, ECP, and specific IgE to Dermatophagoides farinae, Dermatophagoides pteronyssinus, and Aspergillus in the asthma group. @*Conclusion@#The number of eosinophils in the induced sputum correlated with peripheral blood in the asthma group. However, a third of subjects were discordant. Therefore, we need to keep in mind the possibility of discordance when predicting the degree of airway eosinophilic inflammation using the peripheral blood eosinophils. In EB, the number of induced sputum eosinophils did not correlate with the number of peripheral blood eosinophils, which may be attributed to the difference in mechanism. Further studies are warranted.

Is determining nasal eosinophil count and nasal eosinophil peroxidase concentration clinically useful in children with rhinits? / 소아과

No abstract available.

The association between asthma and Kawasaki disease

Kawasaki disease (KD) is a systemic vasculitis and the most common cause of acquired heart disease among preschool-aged children. Asthma is one of the most common chronic illness of childhood. There is increasing interest in the potential link between inflammatory diseases and allergic diseases, and there is increasing epidemiologic evidence for an association of KD and allergic disease. In regards to asthma, 9 studies have been reported about its association with KD; 5 of them showed positive associations between these 2 diseases, while 4 of them showed no association. There are some possible underlying mechanisms for this association. The serum IgE levels are found to be increased and there is a Th2-predominant immune response in KD. These are common findings of asthma. Human leukocyte antigen-G/regT cells and SMAD3/transforming growth factor-beta might also be involved in the pathogenesis of both diseases. Asthma may increase susceptibility to KD and tends to lead to immune dysregulation. Clinician's recognition of the increased risks of KD and other asthma-related comorbidities among patients with asthma may enable early identification and intervention. The early identification and management of comorbidities may ultimately reduce the economic and social burden of these chronic conditions.

Life-threatening Hemorrhage Caused by Mandibular Arteriovenous Malformation: A Case Report

Arteriovenous malformation (AVM) of the mandible is a rare vascular condition that can manifest as a wide range of symptoms and, on rare occasions, cause fatal hemorrhage. The symptoms of mandibular AVM can range from soft tissue swelling and tooth mobility to severe hemorrhage. The recognition of early symptoms is crucial for the prevention of a fatal hemorrhage and for the proper diagnosis and treatment of mandibular AVM. For emergency hemostasis of a ruptured mandibular AVM, manual compression with gauze, topical thrombin, absorbable hemostat, suturing the lesion, and replanting the extracted tooth is recommended. Multiple treatment options for mandibular AVM are available, such as arterial embolization, venous embolization, direct surgical closure, and bone resection. A combination of treatment options should be considered in complicated cases. We report a case of a 10-year-old girl with a previous history of telangiectasia on the right cheek presented with cardiac arrest resulting from massive bleeding immediately after a tooth extraction.

Renal involvement in children and adolescents with inflammatory bowel disease / 소아과

PURPOSE: The incidence of inflammatory bowel disease (IBD) is rapidly increasing, and several reports have described the renal complications of IBD. We sought to evaluate the clinical manifestations of renal complications in children with IBD in order to enable early detection and prompt treatment of the complications. METHODS: We retrospectively reviewed the medical records of 456 children and adolescents aged < 20 years who had been diagnosed with IBD since 2000. We analyzed patient age, sex, medication use, IBD disease activity, and clinical manifestations of renal symptoms. RESULTS: Our study comprising 456 children with IBD included 299 boys (65.6%) and 157 girls (34.4%). The study included 346 children with Crohn disease and 110 children with ulcerative colitis. The incidence of kidney-related symptoms was 14.7%, which was significantly higher than that in normal children. We observed 26 children (38.8%) with isolated hematuria, 30 children (44.8%) with isolated proteinuria, and 11 children (16.4%) with hematuria and concomitant proteinuria. A renal biopsy was performed in 7 children. Histopathological examination revealed immunoglobulin A nephropathy in 5 children (71.4%). All children presented with mild disease and well-controlled disease activity of IBD. CONCLUSION: Children with IBD are more likely to show kidney-related symptoms than healthy children and adolescents are. Therefore, regular screening of urine and evaluation of renal function in such children are necessary for early detection of renal complications.

Clinical characteristics of total IgE in pediatric allergic disease

PURPOSE: Serum total and specific IgE levels have been widely used to diagnose allergic disease. However, it has recently been suggested that serum total IgE does not properly reflect specific IgE. Therefore, we evaluated the clinical significance of serum total IgE in pediatric allergic disease. METHODS: This study included 633 patients who visited Kyungpook National University Children's Hospital between March 2013 and April 2015. We used immunoCAP, an inhalant multiple allergen simultaneous test (MAST), and food MAST to measure specific IgE. We used a skin prick test in some patients and measured serum total IgE, eosinophil count, and serum eosinophil cationic protein in all patients. RESULTS: There was a positive correlation between serum total IgE and antigen level in the inhalant immunoCAP test. Specifically, the sum of immunoCAP levels was highly correlated with serum total IgE (r=0.631, P<0.001). Moreover, there was a positive correlation between serum total IgE and the sum of food immunoCAP levels (r=0.323, P<0.001). Among the food immunoCAP antigens, milk was highly correlated with serum total IgE (r=0.558, P<0.001). There was a positive correlation between serum total IgE and the sum of class levels of inhalant/food MAST tests (r=0.709, P<0.001 and r=0.686, P<0.001, respectively). There was also a positive correlation between serum total IgE and the number of positive skin prick tests (r=0.445, P<0.001). CONCLUSION: Serum total IgE may reflect the sum of serum specific IgE levels in pediatric allergic disease.

Comorbidities and Phenotypes of Rhinitis in Korean Children and Adolescents: A Cross-sectional, Multicenter Study

PURPOSE: Rhinitis is a nasal inflammatory disease in children and adolescents. However, little is known about the phenotypes and characteristics of allergic rhinitis (AR) in Korean children and adolescents. The objective of this study was to analyze the symptoms and comorbidities of rhinitis, to compare AR to non-allergic rhinitis (NAR), and to reveal the phenotypes and features of AR in a Korean pediatric population. METHODS: Patients under 18 years of age with rhinitis symptoms were recruited from January 2013 to January 2015 by pediatric allergists. We analyzed symptoms, phenotypes, comorbidities, and allergen sensitization in this cross-sectional, multicenter study. RESULTS: Medical records were collected from 11 hospitals. The AR group has 641 (68.3%) patients, with 63.2% of boys and 7.5 (±3.4) years of mean age. The NAR group has 136 (14.5%) patients, with 55.1% of boys and 5.5 (±2.9) years of mean age. Moderate-severe persistent AR affected 41.2% of AR patients. Nasal obstruction was more common in NAR patients (P<0.050), whereas AR patients sneezed more (P<0.050) and more commonly had conjunctivitis, asthma, and otitis media (P<0.050). Sinusitis was the most common comorbidity in both groups. Allergen sensitization was caused by house dust mites (HDMs) (90.2%), pollen (38.7%), and animal dander (24.8%) in AR patients. Pollen and animal dander sensitization significantly increased age-dependently (P<0.050), but 91.9% of AR patients were already sensitized to HDMs before 5 years old. CONCLUSIONS: Our study revealed that AR was more prevalent than NAR and that 41.2% of AR presented with moderate-severe disease in Korean pediatric populations. Sinusitis was the most common comorbidity, and sleep disturbance was associated with the severity of rhinitis. The majority of AR patients were sensitized to HDMs in preschool ages. Further studies, including nationwide and longitudinal data, will help understand the relationship between these diseases.

Systemic steroid treatment of acute bronchiolitis: A retrospective study

PURPOSE: Previous studies have reported that clinical efficacy of steroid therapy for acute bronchiolitis is controversial. However, since it is still frequently used in clinical practice, we sought to re-evaluate its effectiveness. METHODS: This study included 277 children with acute bronchiolitis who were admitted to Kyungpook National University Children's Hospital from March 2013 to July 2016. Erythrocyte sedimentation rates, C-reactive protein (CRP) levels, and viral polymerase chain reaction testing results were obtained, and respiratory rate (RR) was measured periodically. Forty-eight patients were treated with an intravenous (IV) steroid (17.3%, IV group) and 19 patients were treated with a per oral (PO) steroid medication (6.9%, PO group). The remaining 210 patients were steroid-free patients (74.2%, nonsteroid group). RESULTS: RR and CRP levels were higher in the IV group, along with a longer hospitalization period and duration of wheezing. The rate of change from the fastest initial RR to the mean RR on the first treatment day was greatest in the IV group; this finding was statistically significant after controlling for initial RR (16.06% in the IV group, 3.94% in the PO group, 4.90% in the nonsteroid group; P < 0.01). CONCLUSION: There was a trend of IV steroid treatment toward more severe bronchiolitis. A significant reduction in RR on the first day of steroid treatment was observed in IV steroid-treated patients. IV steroid therapy may play a positive role in initial RR stabilization for severe bronchiolitis.

Two patients with Mycoplasma pneumoniae pneumonia progressing to acute respiratory distress syndrome

Mycoplasma pneumoniae pneumonia is one of the most prevalent community-acquired pneumonias in pediatric patients. It commonly presents with mild respiratory symptoms and is well controlled by macrolide antibiotics. Rarely, it can progress to acute respiratory distress syndrome (ARDS) despite appropriate antibiotic therapy, and systemic corticosteroids and quinolone antibiotics are required. We recently treated 2 patients who presented with M. pneumoniae pneumonia with ARDS. Case 1: A 17-year-old girl was admitted with pneumonia that showed no response to antibiotics and progressed to ARDS, which required initiation of mechanical ventilation therapy. The patient was negative for M. pneumoniae IgM; but positive for, M. pneumoniae. After treatment with methylprednisolone and levofloxacin, rapid improvement was observed in both clinical manifestations and chest radiographic findings. Two days after discontinuing a 5-day methylprednisolone treatment regimen, she developed fever, and investigations revealed an elevated C-reactive protein level; this necessitated additional methylprednisolone treatment. Subsequently, she showed complete recovery with no sequelae. Case 2: A 14-year-old girl was admitted with M. pneumoniae pneumonia with ARDS that required mechanical ventilation therapy. She showed a IgM titers against M. pneumoniae of 1:320. After treatment with antibiotics and methylprednisolone, she recovered and was discharged at 48 admission days; however, mild dyspnea persisted. The chest computed tomography showed multiple bronchiectasis areas. After 15 days, because of aggravated dyspnea, she was readmitted and adminis-tered methylprednisolone pulse therapy. Despite 3 courses of methylprednisolone pulse therapy, she still showed mild dyspnea.

Clinical Evaluation of Techniques for Measuring Nasal-Specific Immunoglobulin E in Pediatric Patients

Currently used methods for collecting nasal-specific immunoglobulin E (IgE) require administration of a large amount of saline into the nostrils, which is difficult in children. We designed two methods that are easy to use in children. We measured nasal-specific IgE and evaluated clinical characteristics of nasal-specific IgE in pediatric rhinitis. This study included 82 patients who visited Kyungpook National University Children's Hospital from December 2014 to July 2016 with rhinitis symptoms. Thirty patients used the spray method, and 52 patients used the swab method. We examined nasal-specific IgE to Dermatophagoides farinae, Dermatophagoides pteronyssinus, Alternaria, birch, and weed mix. Thirty patients had nasal-specific IgE concentrations of ≥ 0.35 kIU/L. There was a positive correlation between nasal-specific IgE and serum-specific IgE to D. farinae and D. pteronyssinus (r = 0.548, P < 0.001; r = 0.656, P < 0.001). If we regard positivity of skin prick test as standard, cutoff point of nasal-specific IgE to D. farinae was 0.11 kIU/L and to D. pteronyssinus was 0.12 kIU/L. Based on these cutoff points, five patients would be considered to have local allergic rhinitis. The methods showed relatively high positivity for nasal-specific IgE, which reflected the serum-specific IgE as well. These methods can be considered to diagnose local allergic rhinitis in children.

Basophil Markers for Identification and Activation in the Indirect Basophil Activation Test by Flow Cytometry for Diagnosis of Autoimmune Urticaria

BACKGROUND: The indirect basophil activation test using flow cytometry is a promising tool for autoimmune urticaria diagnosis. We aimed to identify better donor basophils (from atopic vs. non-atopic donors and interleukin-3 primed vs. unprimed basophils) and improve basophil identification and activation markers (eotaxin CC chemokine receptor-3 [CCR3] vs. CD123 and CD63 vs. CD203c). METHODS: Donor basophils were obtained from non-atopic and atopic group O donors. Positive control sera were artificially prepared to simulate autoimmune urticaria patients' sera. Patient sera were obtained from nine children with chronic urticaria. Assay sensitivity was compared among each variation by using positive control sera (n=21), applying cutoff values defined from negative control sera (n=20). RESULTS: For basophil identification, a combination of CCR3 and CD123 markers revealed a higher correlation with automated complete blood count (r=0.530) compared with that observed using CD123 (r=0.498) or CCR3 alone (r=0.195). Three activation markers on the atopic donor basophils attained 100% assay sensitivity: CD203c on unprimed basophils, CD63+CD203+ or CD63 alone on primed basophils; however, these markers on the non-atopic donor basophils attained lower assay sensitivity. CONCLUSIONS: For basophil identification markers, a combination of CD123 and CCR3 is recommended, while CD123 alone may be used as an alternative. Donor basophils should be obtained from an atopic donor. For basophil activation markers, either CD203c alone on unprimed basophils or CD203c and CD63 on primed basophils are recommended, while CD63 alone on primed basophils may be used as an alternative.

Deficiency of antidiuretic hormone: a rare cause of massive polyuria after kidney transplantation / 소아과

A 15-year-old boy, who was diagnosed with Alport syndrome and end-stage renal disease, received a renal transplant from a living-related donor. On postoperative day 1, his daily urine output was 10,000 mL despite normal graft function. His laboratory findings including urine, serum osmolality, and antidiuretic hormone levels showed signs similar to central diabetes insipidus, so he was administered desmopressin acetate nasal spray. After administering the desmopressin, urine specific gravity and osmolality increased abruptly, and daily urine output declined to the normal range. The desmopressin acetate was tapered gradually and discontinued 3 months later. Graft function was good, and urine output was maintained within the normal range without desmopressin 20 months after the transplantation. We present a case of a massive polyuria due to transient deficiency of antidiuretic hormone with the necessity of desmopressin therapy immediately after kidney transplantation in a pediatric patient.

Differences in Features and Course of Mucosal Type Eosinophilic Gastroenteritis between Korean Infants and Children

Eosinophilic gastroenteritis (EGE) is a disorder characterized by eosinophilic infiltration of the bowel wall and various gastrointestinal (GI) manifestations. This study aimed to evaluate the characteristics of EGE in infants and children. A total of 22 patients were diagnosed with histologic EGE (hEGE) or possible EGE (pEGE). Serum specific IgE levels, peripheral eosinophil counts, and endoscopic biopsies were carried out. In the hEGE group (n = 13), initial symptoms included hematemesis, abdominal pain, and vomiting. Three of the subjects had normal endoscopic findings. Eight patients were categorized into the infant group and 5 into the child group. All patients in the infant group showed clinical improvement after switching from cow's milk feeding to special formula or breast feeding. The infant group showed a higher eosinophil count in the gastric mucosal biopsy than the child group. In the pEGE group (n = 9) initial symptoms included hematemesis, abdominal pain, and vomiting. Seven patients in this group showed a good response to treatment with restriction of the suspected foods and/or the administration of ketotifen. Both hEGE and pEGE groups showed clinical improvement after restriction of suspected foods in the majority of cases and also showed a similar clinical course. EGE should be considered in the differential diagnosis of patients with chronic abdominal pain, vomiting, and hematemesis of unknown cause. The infant group may have a better prognosis than the child group if treated properly.

Vitamin D serum levels in children with allergic and vasomotor rhinitis / 소아과

PURPOSE: In addition to regulating calcium and phosphorus homeostasis and bone metabolism, vitamin D is known as an immune modulator. Recently, there has been increased worldwide interest in the association between low levels of vitamin D and allergic diseases. The purpose of this study was to assess the relationship between serum vitamin D levels and allergic/vasomotor rhinitis (AR/VR) in children. METHODS: This study included 164 patients. The sample included 59 patients with AR, 42 patients with VR, and 63 controls. Their ages ranged from 0 to 16 years. We examined the levels of 25-hydroxyvitamin D, Immunoglobulin E, specific IgE, and eosinophil cationic protein; peripheral blood eosinophil count; and the results of a skin prick test. RESULTS: Serum 25-hydroxyvitamin D levels were 19.0+/-8.5 ng/mL in the AR group, 25.5+/-10.9 ng/mL in the VR group, and 26.9+/-10.7 ng/mL in the control group. After adjustment for body mass index and season at the time of blood sampling, vitamin D levels in the AR group were lower than those of the VR group (P=0.003) and control group (P<0.001). Vitamin D levels were inversely correlated with Immunoglobulin E levels (r=-0.317, P<0.001). AR patients with food allergy or atopic dermatitis did not have lower levels of 25-hydroxyvitamin D than AR patients without these diseases. CONCLUSION: This study demonstrates a possible relationship between vitamin D levels and allergic rhinitis in Korean children.

Symptomatic differences between allergic and nonallergic rhinitis in children

PURPOSE: Children and adolescent have high prevalences of allergic rhinitis (AR) and nonallergic rhinitis (NAR) as well as adult. The purpose of this study was to assess the symptomatic differences between AR and NAR in children. METHODS: This study included 138 patients with 2 or more of rhinitis symptoms, including rhinorrhea, nasal obstruction, nasal itching, and sneezing for over 1 hour on most days who visited Kyungpook National University Children's Hospital between March 2013 and June 2014. The levels of total IgE, specific IgE, eosinophil cationic protein, peripheral blood eosinophil count, and the skin prick test were carried out. All the patients or parents were asked to fill out a rhinitis symptom questionnaire and contents were rechecked by physician during the consultation. The symptoms of rhinorrhea, sneezing, nasal itching, nasal obstruction and eye itching were checked. Family history and comorbidity were also evaluated. RESULTS: Ninety-one patients were diagnosed with AR, 47 patients with NAR. Their age ranged from 1 to 16 years. AR patients had more sneezing, nasal pruritus and eye symptoms than NAR patients (P=0.003, P=0.036, and P=0.003, respectively). CONCLUSION: This study shows that the several symptomatic differences may help to diagnose the AR. It will be helpful in establishing diagnostic and treatment plans for rhinitis patients before allergic tests.