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Relationship between skin-prick tests, the multiple allergosorbent test and symptoms of allergic disease.

In 47 atopic subjects, skin-prick testing to 10 common allergens was performed, and specific IgE to the same allergens was assessed by the multi-allergosorbent chemiluminescent assay (MAST-CLA). Overall agreement between the tests was 66.4% for conventionally positive skin tests (weal diameter greater than or equal to 3 mm), rising to 78.5% when a positive skin test was defined as having a weal diameter greater than or equal to 5 mm. Agreement between the tests was statistically significant for all allergens except Alternaria. A history was obtained from each subject of the presence or absence of allergic symptoms on exposure to cats, and whether there was a history of grass pollen allergy. MAST-CLA testing for specific IgE to cat dander predicted a history of cat allergy with an efficiency of 74.5%, while a positive MAST-CLA test for Cocksfoot grass predicted a history of grass pollen allergy with an efficiency of 85.1%. Similar results were obtained on skin testing for these allergens. We conclude that MAST-CLA gave results comparable to those obtained by skin-prick testing, and correlated equally well with the history of allergic symptoms.

Adult↗

Effects of maternal diet during late pregnancy and lactation on the development of atopic diseases in infants up to 18 months of age--in-vivo results.

One hundred and sixty-two women with respiratory allergy to animal danders and/or pollens were randomly allocated to a diet consisting of either a very low ingestion of hens' egg and cows' milk or a daily ingestion of one hens' egg and about 11 of cows' milk during the last 3 months of pregnancy. One hundred and sixty-three infants were followed prospectively up to 18 months of age when the cumulated incidence of atopic disease in each child was evaluated blindly. No significant differences in the distribution of atopic disease were found among the infants in relation to the maternal diet during late pregnancy. The numbers of skin-prick tests positive to ovalbumin, ovomucoid, beta-lactoglobulin and cows' milk were likewise not influenced by differences in the maternal diet during late pregnancy. Genetic factors rather than maternal diet during the perinatal period probably have a greater effect on the incidence of atopic diseases during early infancy.

Adult↗

Birth season variation in asthma and allergic rhinitis.

The prevalence of asthma and allergic rhinitis was analysed in relation to birth month in two cohorts of 18-year-old males born in 1953 (n = 55,393) and 1963 (n = 57,150), in schoolchildren (n = 19,814) and in children with defined specific allergies (n = 1080). Among the 18-year-olds, a marked variation with respect to birth season was only found in those born in 1963, with the highest prevalence of asthma in those born August-January and of allergic rhinitis in those born November-May. In the schoolchildren with allergic rhinitis the birth season pattern was found to be similar to that in the conscripts born in 1963. The influence of month of birth on the onset of allergic rhinitis was maximum about 6 years of age and was not seen before 2, and after 10 years of age. Obvious similarities in birth season patterns were found between the unselected populations and the children with defined pollen and animal dander allergies. The differences in birth season pattern between the two cohorts of 18-year-olds were interpreted as an effect of unidentified adjuvant factors that might have developed over a 10-year period.

Adolescent↗

Mite allergy and exposure to storage mites and house dust mites in farmers.

Sensitization to house dust mites, storage mites and other common inhalation allergens was studied in 144 farmers using SPT and RAST. The study population was selected from a random sample of 808 farmers and consisted of 47 persons who had declared themselves to suffer from asthma, 63 persons who had reported respiratory symptoms, and 34 healthy persons without respiratory symptoms. The most prevalent RAST was towards storage mites and was found in 17% of farmers who suffered from asthma and was estimated to occur in 5% of the random sample of farmers. A positive RAST to house dust mites was found in 17% of farmers who reported to suffer from asthma. Sensitization to pollens, animal dander and grain species was rare. A positive RAST to moulds was not found. There was a strong association between a positive RAST to house dust mites and a positive RAST to storage mites (odds ratio 21.0). A positive RAST to storage mites was significantly associated with living in a dwelling in the past which was recalled as damp (odds ratio 4.9). A high number of house dust mites was found in nearly all dwellings (median count 148 mites/0.1 g dust) and a high number of storage mites was found in some dwellings. This study suggests that in humid and temperate regions of Europe, allergy to storage mites in farmers is not caused exclusively by occupational exposure but damp housing conditions and indoor exposure to storage mites may also be important.

Agriculture↗

Relationship between IgG1 and IgG4 antibodies to foods and the development of IgE antibodies to inhalant allergens. II. Increased levels of IgG antibodies to foods in children who subsequently develop IgE antibodies to inhalant allergens.

In the present investigation we have tested the hypothesis that children with a high IgG antibody response to foods have an increased risk of developing IgE antibodies to inhalant allergens. Sera from 106 children with an increased risk of developing IgE-mediated allergy were analysed. During the follow-up, in 54 of these children IgE antibodies to inhalant allergens appeared. A positive/negative IgG1 and IgG4 anti-food score was determined as described previously: sera from age-clustered unselected children were tested for the levels of IgG1 and IgG4 antibodies to common foods. For each IgG RAST and each age group, the 75-percentile was chosen as cut-off value. Each antibody level was thus converted into a positive (higher than the 75-percentile of the age group) or negative value. The number of positive tests was used as the score. High-risk children with a high IgG1 anti-food score more often developed inhalant-specific IgE antibodies than high-risk children with low IgG1 titres: 50% of the children with a high IgG1 anti-food score developed IgE antibodies to grass pollen. Fifty per cent of the children with a high and 14% of the children with a low IgG1 anti-food score developed IgE antibodies to cat dander. For the prediction of the development of IgE anti-mite (house dust mite), the IgG4 anti-food scores appeared less useful than the IgG1 anti-food scores; 46% of the IgG4 high responders versus 22% of the IgG4 low responders acquired IgE anti-mite, whereas for IgG1 these percentages were 73 and 19, respectively.

Allergens↗

Sensitivity to common allergens: relation to respiratory symptoms and bronchial hyper-responsiveness in children from three different climatic areas of Australia.

In order to examine further the relation between atopy, as defined by skin-prick tests, and respiratory illness, we studied three populations of schoolchildren aged 8-11 years and living in different climatic areas of New South Wales, Australia. Skin-prick tests were performed using 13 commercial allergen extracts. Respiratory and allergic symptoms were assessed using a self-administered questionnaire to parents and bronchial hyper-responsiveness (BHR) was measured by histamine inhalation test. We defined current asthma as BHR together with symptoms of wheeze in the 12 months prior to study. Children with one or more positive skin weals of greater than or equal to 3 mm had significantly more recent wheeze, hayfever, eczema and BHR than children with smaller weals (P less than 0.001). In each area, 95-97% of all atopic children were sensitized to one of the following seven allergens: house dust, Dermatophagoides farinae, D. pteronyssinus, cat dander, plantain, rye grass, and Alternaria tenuis. Thus, these seven selected allergen extracts and a skin weal of 3 mm could be used to detect clinically relevant atopy in these populations of children. Sensitivity to house dust mite had the strongest independent association with current asthma in all three areas. The associations of other allergen sensitivities with BHR or current asthma were area dependent, indicating the influence of local allergen levels on respiratory illness in children. The potency of house dust mite sensitivity in increasing the risk of children having BHR and current asthma is confirmed.

Allergens↗

Comparison between MAGIC LITE- and CAP-system: two automated specific IgE antibody assays.

The MAGIC LITE system, a newly developed immunochemiluminometric assay for specific and total IgE antibody using paramagnetic particles coupled with standardized allergens as solid phase, was compared to the CAP system, a recently introduced immunoassay based on a cellulose polymer encased in a capsule. A total of 357 serum samples of patients with suspected inhalant allergies and a positive skin prick test (SPT) to common allergens (birch, timothy-grass, mugwort, cat dander, Dermatophagoides pteronyssinus, Alternaria) were investigated. Fifty SPT negative subjects served as controls (total number of tests in each assay = 1600). Both assays were highly precise (overall intra-assay and inter-assay coefficients of variation were 2.9% and 4.5% in MAGIC LITE, 4.7% and 5.5% in CAP) and showed excellent linearity (mean r2 of eightfold log2 serum dilutions were 99.7% and 99.3% in MAGIC LITE and CAP). Good correlations were found between the absolute specific IgE antibody values detected by both methods (correlation coefficient r: birth 0.86, grass 0.93, mugwort 0.96, cat 0.91, D. pteronyssinus 0.73, Alternaria 0.90). Excellent specificity (greater than or equal to 98%) occurred in both assays and with all allergens, and sensitivity was related to the allergen (MAGIC LITE/CAP): birch 91%/89%, grass 83%/90%, mugwort 50%/69%, cat 83%/83%, D. pteronyssinus 72%/78%, Alternaria 75%/81%. Our results indicate that both in vitro tests are useful tools for the detection of specific IgE antibody.

Allergens↗

Atopy in childhood. I. Gender and allergen related risks for development of hay fever and asthma.

Reasons for the gender differences in prevalence rates for asthma remain unclear. We have examined the relationships between allergen skin-test reactions and diagnoses of hay fever and asthma in New Zealand boys and girls examined at the age of 13 years. Information on current and past wheezing, diagnosed asthma, and hay fever was obtained for 662 subjects (341 boys) of a birth cohort followed longitudinally to the age of 13 years, using a physician-administered questionnaire. Atopic status was determined by skin-prick tests to 11 common allergens. The proportion of 13-year-old boys with current asthma was 1.6 times higher and of ever-diagnosed asthma 1.4 times higher than in girls, but the prevalence of recurrent wheeze (> or = three episodes per year) not diagnosed as asthma, or of hay fever, was not significantly different between the sexes. The prevalence of diagnosed asthma increased with increasing numbers of positive skin tests, but hay fever without asthma was little affected above one positive skin-test. Boys had a greater prevalence of any positive skin-test (50.1% vs 37.1%), two or more positive tests (29.3% vs 21.8%), and responses to house dust mite (34.0% vs 23.1%) and cat (14.7% vs 11.2%). Gender differences for asthma became insignificant when adjusted for skin-test responsiveness to house dust mite and/or cat. The proportion of children with diagnosed asthma increased with increasing size of weals to house dust mite and cat dander. Gender differences in allergen sensitivities partly explain the gender differences in diagnosed asthma in children. In both sexes, risk of asthma was primarily associated with sensitization to indoor allergens (house dust mite and cat), and was related to the magnitude of the skin-test response, while the risk of hay fever was primarily associated with grass pollen sensitivity.

Adolescent↗

Bronchial provocation with cat allergen: correlation between the individual IgE-CRIE pattern and the occurrence of a late allergic reaction.

Twenty-one mild asthmatic patients allergic to cat dander underwent a bronchial provocation test (BPT) with a cat extract. An early allergic response (EAR) was observed in all 21 patients and a late allergic response (LAR) in 8/21 patients. In the EAR, the patients with subsequent LAR had a greater fall in FEV1. Their baseline FEV1, and total dose of inhaled allergen were not significantly different from patients who did not develop a LAR, but their serum specific IgE level was higher. Crossed immunoelectrophoresis (CIE) of the same cat extract showed that it contained eight different proteins. An IgE-CRIE was obtained from all 21 patients, using radiolabelled anti-IgE and autoradiography. Radiolabelled standards allowed a semiquantitative scoring of the radiostaining. The CRIE pattern of the eight patients with LAR showed a higher score of radiostaining and a greater number of proteins bound to IgE. The two major allergen cat albumin and Fel dI bound equally to IgE of patients with and without LAR whereas another protein (antigen No. 7) bound to IgE of 100% of patients with LAR but of only 38% of patients without LAR. These data suggest that the pattern of the IgE response to specific proteins of a cat extract may be related to the occurrence of LAR after BPT with this allergen.

Adolescent↗

Total and specific serum IgE levels in adults: relationship to sex, age and environmental factors.

We studied total and specific serum IgE levels cross-sectionally, potential predictors of obstructive lung disease, in a stratified random sample of 18-73-year-old adults (n = 1512). The attendance rate was 84%. The total IgE level and prevalences of specific IgE antibodies against house dust mite and cat were higher for men than for women. Specific IgE levels decreased by increasing age, while total IgE decreased in women only. Smokers had a higher IgE level than non-smokers, while non-smokers had more often specific IgE antibodies against timothy and birch than smokers. Subjects with occupational dust or gas exposure had a higher total IgE level than unexposed. The general population prevalences were for specific IgE antibodies against timothy 4.5%, house dust mite 3.2%, birch 2.6%, cat dander 1.6% mould 0.2% and against any of these 7.6%. In a multivariate analysis age, occupational dust or gas exposure as well as the interaction terms between sex and age and between smoking and pack-years were independent predictors for total IgE levels. Male sex, young age, never having smoked and the season of the year were independent predictors for having one or more of the five specific IgE antibodies. Subjects with total serum IgE in the highest quintile (> or = 66 kU/l) had an adjusted odds ratio of 37 (95% confidence interval: 11-120) for having one or more of the specific IgE antibodies examined, compared with those in the lowest quintile (< 5 kU/l). Demographic and environmental factors were thus predictors of total and specific IgE levels in this adult community.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Cow milk allergy within the spectrum of atopic disorders.

In order to examine the relationship between cow milk allergy (CMA) and atopic disorders in childhood, a consecutive group of 42 infants with IgE mediated CMA was followed for at least 2 years. The incidence of sensitization to common food and inhalant antigens and the development of eczema, asthma, and food allergies was examined for the cohort and compared between patients whose CMA remitted and those with persistent disease. In this cohort the prevalence of eczema was 57%, asthma 69%, egg allergy 67%, peanut allergy 55%, and 83% of infants demonstrated positive skin-prick tests to three or more allergens. At the end of the study CMA had remitted in 13 patients (median age 44 months) whereas in 29 patients it persisted (median age 44 months). Although there was no significant difference in the incidence of eczema or asthma during the study between these two patient groups, the incidence of allergy to egg and peanut butter was significantly greater for children with persistent CMA. Consistent with our hypothesis that children with persistent CMA have a more severe dysregulation of IgE synthesis than those whose disease remits, patients with persistent CMA had a significantly higher incidence of and level of skin sensitivity to inhalant and other dietary allergens. Sensitization to the inhalant allergens Dermatophagoides pteronyssinus, cat dander and rye grass was frequently seen in early infancy and increased during the study period. Thus, children with IgE mediated CMA frequently generate IgE responses to multiple dietary and inhalant allergens in infancy and early childhood and develop immediate hypersensitivity to other foods as well as clinical eczema, and asthma.

Allergens↗

Lack of association between HLA-DQ and -DR genotypes and asthma in southern Chinese patients.

Asthma is an inflammatory disease with a strong genetic predisposition. We have studied a group of unrelated asthmatic patients of southern Chinese origin on their HLA-DR and -DQ regions using molecular techniques and compared them with 104 healthy controls of the same ethnic origin. Restriction fragment length polymorphism (RFLP) was used to genotype the MHC class II DR beta, DQ alpha and DQ beta loci of the subjects. Polymerase chain reaction (PCR) using sequence specific primer (SSP) for DQ beta genes was also performed. No significant difference was found in the HLA-DQ and -DR loci between the patients and the controls. All patients had their serum IgE antibody levels measured, bronchial reactivity assessed by histamine broncho-provocation and cutaneous reactivity to common allergens determined by skin-prick tests to Dermatophagoides pteronyssinus, Dermatophagoides farinae, mixed grass pollens, Aspergillus fumigatus, cat fur and dog dander and they were classified respectively. The HLA-DR and -DQ genotypes of these subgroups of patients were compared. There was no significant difference among these subgroups of patients according to their serum IgE levels, the degree of bronchial reactivity and whether they were positive for the skin tests for the various allergens respectively. The results suggest that HLA-DQ and -DR genotypes are not associated with asthma in southern Chinese people.

Adolescent↗

Are maternal psychosocial factors associated with cord immunoglobulin E in addition to family atopic history and mother immunoglobulin E?

BACKGROUND: Atopy in maternal and family histories is known to be a risk factor for elevated umbilical cord immunoglobulin E (cIgE). However, the association between cIgE and psychosocial factors remains under investigation. OBJECTIVE: To explore whether psychosocial factors in addition to atopy contribute to elevated cIgE. METHODS: Four private maternity hospitals fitting the quantile levels of SO(2) in 2000 cooperated with us by recruiting participants for this study: pairs of mothers and neonates living within 3-km catchment areas of air-monitoring stations. We used a questionnaire to collect exposure data, and the Pharmacia UniCap IgE assay test system to determine the levels of IgE in gravidas and cord blood. RESULTS: Between July 2001 and March 2003, 334 mother and neonate pairs participated in this study. The frequencies of sensitization, serum IgE (sIgE)>100 IU/mL, or cIgE> or =0.35 IU/mL were not different between the four different hospitals. By multi-variate logistic regression analysis adjusted for environmental factors, genetic factors, and psychosocial factors, the risk factors for elevated cIgE were being a male neonate (odds ratio (OR)=3.5, 95% confidence interval (CI)=[1.5, 8.5]), carpets at home (OR=3.0, 95% CI=[1.02, 8.4]), maternal allergy to dog dander (OR=9.7, 95% CI=[1.2, 98.8], maternal total serum IgE>100 IU/mL (OR=5.1, 95% CI=[2.2, 12.8]), maternal regularly/mostly/often self-reported nervousness (OR=4.0, 95% CI=[1.3, 12.8]), family income 11,574-17 361 US dollars/year (OR=3.7, 95% CI=[1.3, 11.5]), incense burning (OR=4.0, 95% CI=[1.4, 13.3]), and atopy in maternal grandparents (OR=4.8, 95% CI=[1.7, 14.0]). By principle component analysis and logistic regression, psychosocial stress (beta +/- standard error=0.26+/-0.13, P=0.04) was associated with increased cIgE. CONCLUSION: Psychosocial factors are potentially important risk factors for elevated cIgE.

Adult↗

Relationship between aeroallergen and food allergen sensitization in childhood.

BACKGROUND: Previous studies measuring the prevalence of allergen sensitization have been relatively small and used small numbers of allergens. To effectively evaluate children with atopic disease, we need an accurate knowledge of which allergens are important. OBJECTIVE: To measure the prevalence of sensitization within a large unselected birth cohort, to examine the associations between sensitization to different allergens and determine whether atopy can be defined by a small panel of allergens. METHODS: The Avon Longitudinal Study of Parents and Children is a population-based birth cohort of 13,638 singletons surviving to 4 weeks of age. The cohort was skin tested at 7 years of age to house dust mite (Dermatophagoides pteronyssinus), grass pollens, cat, peanuts, mixed tree nuts and egg and one of three other panels: animal danders, foods or aeroallergens. Sensitization was defined as a weal diameter of > or =3 mm. The strength of associations between sensitization to different allergens was tested by calculating the odds ratio adjusted for sensitization to D. pteronyssinus and grass pollen and gender. RESULTS: Valid data were obtained from 6412 singletons. Sensitization was most common to aeroallergens: grass pollens (8.5%), D. pteronyssinus (7.8%), cat (4.9%), D. farinae (3.6%), dog (2.7%), horse (1.4%), rabbit (1.4%). Of the foods tested, the most common sensitization was to peanut (1.4%) and mixed tree nuts (1.0%). More than 95% of subjects with sensitization to any of the 29 allergens tested were sensitized to one of grass, D. pteronyssinus or cat allergen. There were strong associations of multiple sensitizations both within and between different allergen classes (pollens, animals, foods, peanut and tree nuts). CONCLUSIONS: Seven-year-old children in the UK are primarily sensitized to aeroallergens, but also to peanuts and tree nuts. There are strong associations between sensitization within allergen groups as well as between allergen groups. Further studies are required to observe whether similar associations are seen with clinical allergy to these allergens.

Air Pollution↗

Targeting adenosine receptors in the treatment of allergic rhinitis: a randomized, double-blind, placebo-controlled study.

BACKGROUND: There is evidence that adenosine plays a role in the pathogenesis of asthma and rhinitis; however, it is currently unclear whether adenosine receptors are useful therapeutic targets in the treatment of allergic airway diseases. OBJECTIVE: The study evaluated the efficacy of intranasal treatment with an adenosine A(2A) receptor agonist/adenosine A(3) receptor antagonist (50 micro g), administered twice daily for 7 days, to reduce nasal symptoms and release of inflammatory mediators following intranasal allergen challenge in patients with allergic rhinitis (AR). The compound was compared with twice-daily treatment with intranasal fluticasone proprionate nasal spray (FPANS) for 7 days. METHODS: A randomized, double-blind, double-dummy, placebo-controlled, three-way balanced, incomplete block, crossover study was conducted on 48 males with verified AR. Following intranasal challenge with either an extract from the house dust mite (HDM), Dermatophagoides pteronyssinus, rye grass or cat dander, nasal responses and the concentrations of albumin, tryptase, myeloperoxidase, eosinophilic cationic protein, epithelial neutrophil-activating protein-78 (ENA-78), IL-5 and IL-8 in nasal secretions were measured and treatment groups were compared. RESULTS: Drug improved nasal blockage but had no significant effect on rhinorrhoea, number of sneezes or peak nasal inspiratory flow measurements when compared with placebo. Drug reduced tryptase release after EAR but did not significantly reduce the levels of other mediators. CONCLUSION: A novel agonist/antagonist of adenosine A(2A) and A(3) receptors appears to have limited clinical benefit in both the early-phase and the late-phase response to intranasal allergen challenge. However, reduction of some pro-inflammatory mediators suggests that comparable, more selective compounds may have additional benefits meriting further investigation.

Adenosine A2 Receptor Antagonists↗

Atopy patch testing with aeroallergens in patients with atopic dermatitis and controls in Singapore.

The role of allergy in atopic dermatitis is controversial. The atopy patch test (APT) has been used to investigate the association between atopic dermatitis and aeroallergen allergy. To determine the proportion of patients with atopic dermatitis with positive patch tests to common local aeroallergens and to compare this to controls with and without respiratory atopy, we performed APT, skin-prick tests (SPT) and IgE radioallergosorbent tests (RAST) on 73 patients with atopic dermatitis and on 38 nonatopic controls (13 with and 25 without respiratory atopy). The allergens used were house dust mite, cat dander, Bermuda grass and German cockroach. Only the APT for house dust mite showed a significant difference between the two groups. APT for house dust mite correlated with the RAST test, while APT for cat fur correlated with the SPT. The APT may be useful to evaluate aeroallergens in atopic dermatitis, but further work is needed to make it more reliable.

Adolescent↗

Hydrocortisone enhances total IgE levels--but not the synthesis of allergen-specific IgE--in a monocyte-dependent manner.

Recently, hydrocortisone (HC), when combined with human IL-4, has been reported to increase IgE levels in supernatants (SN) of in vitro cultured leucocytes. In this study we investigated the influence of HC on allergen-specific IgE synthesis. Moreover, we examined the relevance of different cell types in this respect. Peripheral blood mononuclear cells (PBMC), T-cell depleted PBMC, CD14-depleted PBMC and highly purified B cells from 10 allergic (birch pollen and/or grass pollen) patients and five non-allergic individuals were investigated. The cells were incubated with HC and/or recombinant human IL-4 (rIL-4) for 8 days. A considerable increase of total IgE was observed in HC/rIL-4-stimulated cultures compared with rIL-4 alone, HC alone or non-stimulated cultures. We demonstrate that this effect depends on the presence of monocytes in in vitro cultures. These results were seen in every experiment, irrespective of healthy or atopic state of the blood donor. The increase of IgE could not be attributed to a rise of birch pollen-and/or grass pollen-specific IgE in patients allergic to these allergens, as shown by IgE-immunoblot. Radio-allergosorbent test (RAST) investigations of HC/rIL-4-stimulated cells cultures from allergic and non-allergic patients confirmed that HC/rIL-4-induced elevated IgE production was also not due to increased production of IgE, specific for important aero-allergens (pollens, house dust mite or animal dander). Therefore we conclude that newly synthesized IgE is not specific for allergens, but that sequential isotype switching in human B cells leads to increased polyclonal IgE production.

Allergens↗

The role of atopy in Maltese patients with chronic rhinitis.

The global prevalence of allergic rhinitis has been on the increase and recent clinical experience in Malta has shown a similar trend. The aim of this study was to investigate the role of atopy in 415 patients presenting with rhinitis of at least 3 months duration, and to identify the common allergens responsible. Presenting clinical features, past and family history of seasonal allergic symptoms, exposure to cigarette smoking, pet ownership and occupation were analysed. All patients were skin tested for common allergens. Fifty-five per cent of patients were atopic, the main allergens responsible being house dust mite, cat dander and grass pollen. Rhinorrhoea and sneezing were significantly more common in atopic patients, who were more likely to have a past history and family history of seasonal asthma, eczema or rhinoconjunctivitis. Skin test-negative patients with idiopathic rhinitis were mostly females and tended to present a decade later. Differentiation between atopic and idiopathic chronic rhinitis may be helpful in the clinical setting in order to help predict response to treatment.

Adolescent↗