Efficacy and safety of sublingual immunotherapy using house dust mite tablet for 1-4 years old children with perennial allergic rhinitis.

BACKGROUND: Sublingual immunotherapy (SLIT) for perennial allergic rhinitis (AR) has not been extensively studied in preschoolers. We investigated the efficacy and safety of house dust mite (HDM) SLIT-tablet for children aged 1-4 years. METHODS: Children aged 1-4 years with AR were divided into SLIT (n = 22) and control (n = 12) groups based on their guardians' preferences. The SLIT group received a daily dose of 10,000 JAU of HDM SLIT-tablet for 12 months, whereas the control group received symptomatic treatment only. RESULTS: The baseline median age was 41 and 34 months in the SLIT and control groups, respectively, and the median AR symptom score was 4 for both groups. Compared with baseline, the AR symptom score had decreased significantly in the SLIT group after 12 months (score: 3, p = .002), whereas it tended to increase in the control group (score: 6, p = .08). Adverse reactions to SLIT were mild and occurred in eight patients (36%). In the SLIT group, Dermatophagoides (D.) farinae-specific IgE (sIgE) levels increased during the first 6 months and decreased to baseline levels at 12 months. In the control group, D. farinae-sIgE levels had increased significantly at 12 months compared to baseline (p = .01). D. farinae-specific IgG4 and HDM IgE-blocking factor levels were significantly increased at 12 months compared to baseline in the SLIT group only (p < .001). A lower wheezing frequency was seen in the SLIT group (0.3%) compared to the control group (0.7%). CONCLUSION: This pilot study demonstrated the efficacy, safety, and immunomodulatory effects of HDM SLIT-tablet in preschoolers with AR.

A modified schedule of multiple aeroallergen ultra-rush immunotherapy in perennial allergic rhinitis: safety, efficacy, and T lymphocyte cell population studies.

BACKGROUND: This study assessed whether a modified immunotherapy schedule for allergic rhinitis could be safe and efficient. Ultra-rush immunotherapy (URIT) rapidly desensitizes patients to aeroallergens. OBJECTIVE: We aimed to develop a modified URIT protocol in 3 days to achieve the target dose while observing whether it could improve this situation and decrease the time to achieve the maintenance dose. METHODS: The URIT was exercised in 21 patients with perennial allergic rhinitis. Premeditations were given to the patients 3 days prior to the immunotherapy and during the 3 days injections immunotherapy: pred nisolone, ranitidine, and Airokast/montelukast. Finally, the T cell population frequencies of patients prior to and after immunotherapy, including T helper 1, T helper 2, cytotoxic T lymphocytes, and regulatory T cells, were studied using flow cytometry. During the URIT protocol, 21 patients received 291 injections. RESULT: Six patients (28.6%) showed systemic reactions in our study. All systemic reactions occurred on the third day by the 1:1 dilution of the maintenance dose. These systemic reactions occurred in three patients after 13 injections, and the three remaining patients showed systemic reactions following the last injection. No systemic reaction was observed on the first and second day of the therapy, and the risk of systemic reaction with every injection was about 2%. Among the T cell populations, CD3+ and CD8+ cells decreased significantly. CONCLUSION: The findings emphasized that URIT, alongside premedication with a high dose of antihistamine, helped to achieve the maintenance dose and control clinical manifestations.

Short-term and long-term efficacy of sublingual immunotherapy in different courses for house dust mite-induced allergic rhinitis.

PURPOSE: Sublingual immunotherapy (SLIT) has been proven to be an effective and safe treatment for patients with house dust mite (HDM)-induced allergic rhinitis (AR) to achieve short-term and long-term efficacy. This study aimed to investigate the relationship between SLIT duration and long-term efficacy. MATERIALS AND METHODS: This study involved 134 patients who underwent SLIT between 2019 and 2021 (in the 2-year group), between 2018 and 2021(in the 3-year group), or between 2017 and 2021 (in the 4-year group). The total nasal symptoms score (TNSS), total medication score (TMS), visual analogue scale (VAS), the Mini Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ) and adverse events (AEs) were assessed at baseline, after treatment (2021) and one year after the treatment completion (2022). The correlation between MiniRQLQ and other indicators was also analyzed. RESULTS: After SLIT, patients in all three groups showed significant improvements in TNSS, TMS, VAS and MiniRQLQ scores (all p < 0.001). These improvements were sustained even one year after SLIT. Patients who received 3-4 years of SLIT showed significant improvement compared with those who received 2 years of SLIT in all clinical outcomes (all p < 0.01). The analysis showed positive correlations between the MiniRQLQ and TNSS, TMS, and VAS (all p < 0.001). No significant difference was observed in the AE rate in all three groups (p > 0.05). CONCLUSION: Different duration of HDM SLIT could generate various short-term and long-term clinical efficacy. The MiniRQLQ could be applied to evaluate SLIT efficacy in clinical practice.

[LONGITUDINAL EVALUATION OF EFFICACY OF SUBLINGUAL IMMUNOTHERAPY IN PEDIATRIC PERENNIAL ALLERGIC RHINITIS USING LABORATORY EXAMINATIONS AND IN VIVO BIOMARKERS].

OBJECTIVE: The purpose of this study was to evaluate the efficacy of sublingual immunotherapy (SLIT) with house dust mite (HDM) on pediatric perennial allergic rhinitis (AR) based on longitudinal assessment of nasal symptoms, laboratory examination, and in vivo biomarkers. METHOD: The subjects included 40 children with perennial AR who had SLIT with HDM for 2 years. Nasal symptoms, medications, skin prick tests, nasal provocation tests, and peripheral blood tests were evaluated before, 6 months, one year and two years after the onset of SLIT. RESULTS: Total nasal symptom scores, prick test wheal diameter, and peripheral blood eosinophil count decreased in 6 months. Total nasal symptom scores continued to decrease from 6 months to 2 years. Symptom-medication scores and nasal provocation test responses decreased in 1 year. Symptom-medication scores continued to decline from 1 to 2 years. Medication scores and nasal eosinophilia decreased in 2 years. Serum specific IgE to HDM slightly increased transiently and decreased in 2 years. The severity of symptoms and specific IgE to HDM at the baseline, and changes of symptoms and specific IgE to HDM during the first six months and first one year of SLIT were correlated with improvement in symptom scores over two years of SLUT. TNSS at baseline was correlated with that at second year. CONCLUSION: Longitudinal assessment of symptoms, allergen specific IgE, and in vivo biomarkers showed the effectiveness of SLIT. Symptom scores and allergen specific IgE may also be early predictive factors of SLIT efficacy in children with AR.

Does allergen immunotherapy for allergic rhinitis prevent asthma?

Asthma and allergic rhinitis (AR) have overlapping clinical and pathologic features, sustained by an underlying T helper 2 bias, resulting in airway inflammation that extends from the nose to the lung. Children who are monosensitized often develop polysensitization over time, and they are at high risk of developing asthma. The effect of allergen immunotherapy (AIT) is allergen specific, resulting in symptom improvement and reduction in medication requirement. It is the only known treatment that alters the natural history of allergic disease and induces long-term remission. A bystander or allergen-nonspecific effect of AIT has also been proposed-that AIT to 1 allergen might reduce the risk of development of sensitization to other allergens. Furthermore, several observational studies and clinical trials, in seasonal (pollen) and perennial (house dust mite) AR, have investigated a protective effect of AIT to prevent asthma. The overall evidence favors an asthma preventive effect of AIT in AR to grass and birch tree pollen. Fewer studies have investigated the use of AIT in children with perennial AR due to house dust mite allergy to prevent asthma, and the results are less convincing. The use of AIT to reduce the risk of progression to asthma, in children with AR, potentially has high impact, and it will make AIT more attractive and cost-effective. However, most studies have been of small sample size or of poor design, using different allergens and AIT methodology, making it challenging to draw firm conclusions. There is a need to do adequately powered studies with optimal design and assess cost-effectiveness of this strategy.

The IgE Blocking Activity Induced by Dermatophagoides pteronyssinus Subcutaneous Immunotherapy Does Not Correlate with Specific IgA but with IgG4 in both Serum and Saliva.

BACKGROUND: The role of salivary-specific IgG4 and IgA in subcutaneous immunotherapy (SCIT) is not well defined. We aimed to investigate the change of IgG4 and IgA in both serum and saliva and their correlations with IgE-blocking-factor (IgE-BF) during SCIT. METHOD: 307 Dermatophagoides pteronyssinus (DP) allergic rhinitis and/or asthma patients were recruited for this study. 286 patients received DP-SCIT for 1 year. Twenty-one patients received only symptomatic treatment. DP-, Der p 1-, and Der p 2-specific IgE in serum, specific-IgG4 and Der p 2-specific IgA1 and IgA2 in both serum and saliva were measured at timepoints 0, 4, and 12 months during DP-SCIT. Correlation between salivary and serological IgG4, IgA, and their correlation with DP-specific IgE-BF measured in serum was evaluated. RESULTS: During DP-SCIT, the allergen-specific IgG4 in both saliva and serum increased and correlated significantly, the correlation becomes stronger over the treatment time. DP-specific IgE-BF significantly correlated with DP-specific IgG4 in serum (p < 0.0001) at different timepoints and in saliva at 12 months of SCIT (p < 0.01). No change in Der p 2-specific IgA during DP-SCIT was observed, and the IgA in serum did not correlate with IgA in saliva. There was no correlation between DP IgE-BF and Der p 2-specific IgA in serum or saliva. The control group did not exhibit significant changes in any antibody level measured. CONCLUSION: The IgE blocking activity induced by DP-SCIT treatment correlated with specific IgG4 and not IgA. The IgG4 in saliva correlates with serum IgG4 and can be an alternative immunological marker beyond 1 year of SCIT treatment.

The evolution of allergy immunotherapy.

OBJECTIVE: The objective of this review is to trace the evolution of the art and science of allergy immunotherapy (AIT). DATA SOURCES: Original reports relating to the evolution of the concept of respiratory allergy and its specific treatment were identified by following references in journal articles, review articles, and allergy textbooks from the mid-20th century to the present. STUDY SELECTIONS: Studies highlighting substantial milestones in the evolution of the practice of allergy immunotherapy were included. RESULTS: The story of AIT begins with the recognition of hay fever as a distinct entity and subsequent studies that established grass pollen as one of the causes. This knowledge led several investigators, most notable Leonard Noon and John Freeman who worked at St. Mary's Hospital in London, to attempt to induce tolerance giving grass pollen extract by injection to their patients. After the publication of the work of Noon and Freeman in 1911, the practice of AIT spread rapidly and was applied to many other pollen allergens besides grass and for perennial rhinitis and asthma. The early studies were largely anecdotal, but over the past 60 to 70 years, studies of AIT have been conducted with increasingly sophisticated scientific methods. Nowadays, not only is the practice of AIT based on carefully conducted studies, but the underlying immunologic basis of allergy and the response to AIT have also been and still are being firmly established. CONCLUSION: Both the art and the science behind the practice of AIT have been established by a solid base of clinical and immunologic studies.

Aqueous intradermal low-dose house dust mite immunotherapy in tropical settings: a valid cost-effective approach for developing nations?

INTRODUCTION: Aqueous allergen injections, an effective and century-old technique, is considered a second-line approach in daily clinical practice. Inconveniences still surround conventional subcutaneous immunotherapy (SCIT) administration, such as a need for frequent injections, prolonged up-dosing schedules, elevated costs, and the unlikely possibility of a systemic reaction. The intradermal immunotherapy route (IDR) might favorably impact many of the aforementioned issues (Table 1). House dust mite (HDM) allergens are the main perennial sensitizers in the tropics, and as such, are solely employed in immunotherapy treatments. METHODS: We carried out a year-long real-life study in 25 perennial allergic rhinitis children, symptomatic on exposure to house dust, employing an intradermal low-dose allergen mix consisting of 50 ng of Dermatophagoides pteronyssinus/Dermatophagoides farinae and 120 ng of Blomia tropicalis, under a unique cost-wise protocol. Basal symptoms/signs and face Visual Analog Scale (fVAS) scores were recorded for 2 weeks and later compared with those registered throughout the 1-year treatment. Serum-specific IgG4 and IL-10 levels were employed in the assessment of the immune responses. RESULTS: Symptoms/signs and fVAS scores were significantly reduced from days 42 and 49, respectively, and remained so until treatment completion. Increases in specific IgG4's and IL-10 levels reflected significant immune responses. Injections were well tolerated and families reported improved health status (quality of life, QoL). CONCLUSIONS: A unique cost-effective immunotherapy alternative for deprived allergic communities in tropical settings is depicted; further research is needed.

Clinical efficacy and safety of cervical intralymphatic immunotherapy for house dust mite allergic rhinitis: A pilot study.

BACKGROUND: Previous studies have demonstrated that intralymphatic immunotherapy (ILIT), a less time-consuming alternative to conventional subcutaneous immunotherapy (SCIT), is safe and effective. However, because of the private location of inguinal lymph nodes, inguinal ILIT is relatively inconvenient. We proposed a novel form of ILIT that involves 3 injections of allergen into cervical lymph nodes. The aim of this study is to determine the clinical efficacy and safety of cervical ILIT on house dust mite induced allergic rhinitis (AR) in adults. METHODS: In this study, we performed a prospective cohort study to determine the clinical efficacy and safety of cervical ILIT on house dust mite induced AR in adults, by comparing the symptom scores, quality-of-life scores (QOLS) and drug scores (use of rescue medication) before and after treatment. Meanwhile, side events were also recorded. RESULTS: Cervical ILIT elicited no moderate-severe adverse events. Patients receiving cervical ILIT experienced a significant improvement in nasal symptoms, eye symptoms and quality of life, as compared to baseline (P all <0.001). A reduction in the use of rescue medication was also demonstrated (P < 0.001). CONCLUSIONS: In this first-in-human clinical study, cervical ILIT was demonstrated safe and induced allergen tolerance after 3 injections.

Assessment of taste functions in allergic rhinitis patients undergoing allergen-specific immunotherapy.

BACKGROUND: We evaluated taste functions of patients with perennial allergic rhinitis (AR) before and after allergen-specific immunotherapy (AIT). METHODS: The study was designed as a prospective clinical study in our tertiary care hospital. Patients (n = 21) who were diagnosed with perennial AR on the basis of physical examination, skin prick test of at least 3* for HDM allergen and treated with AIT were enrolled in this study. A control group (n = 21) was selected from patients who were given intranasal steroids (INS) for perennial AR. Both groups had self-reported hyposmia and subjective loss of the sense of taste before treatment. Taste strips (Burghart, Wedel, Germany) were used for the taste identification scores before and after 6 months treatment. RESULTS: A total of 42 subjects were included, with a mean age of 24.1 ± 7.9 years (range 15-43 years). Overall, the AIT group showed more of an improvement of taste function, observed in the total average test scores, compared to the INS group (p < 0.05), but no change was detected between the groups before treatment. No difference was found for the bitter taste scores between the study groups (p = 0.053). CONCLUSION: Subcutaneous allergen immunotherapy resulted in more of an improvement in taste function than intranasal steroids. Further studies are needed.

2020 ARIA CARE PATHWAYS FOR ALLERGIC RHINITIS - GEORGIA.

Allergic rhinitis is the most common chronic disease worldwide. Treatment guidelines have improved the knowledge on rhinitis and have had a significant impact on AR management. In 20 years, ARIA has considerably evolved from the first multi-morbidity guideline in respiratory diseases to the digital transformation of health and care. Allergic rhinitis in Georgia, Next-generation ARIA-GRADE guidelines and ARIA, 2020 care pathways for Allergen Immunotherapy have been discussed in this review.

House dust mite sublingual-swallow immunotherapy in perennial rhinitis: a double-blind, placebo-controlled Iranian study.

Sensitivity to house dust mite allergens in the development of allergic rhinitis has a key role. In this study, the clinical and immunological effects of high dose Dermatophagoides farinae sublingual immunotherapy (SLIT) versus placebo were compared. Forty poly-sensitized patients, ages 6-33 years, with allergic rhinitis and positive allergic reaction to the mites were enrolled in the study. Twenty-one patients were placed in the SLIT group and 19 in the placebo group. Expression levels of IL-10, TGF-ß, FOXP3 and IL-17 were measured by using real-time PCR before and after the administration of sublingual immunotherapy. Clinical efficacy was estimated by the reduction rate of symptom/medication scores in the SLIT group compared with placebo treatment. After 6 months of SLIT, TGF-ß expression levels were increased compared to pre-treatment (P less than 0.05). SLIT with D. Farinae extract is an effective treatment for poly-sensitized patients with allergic rhinitis. TGF-ß mediated T-cell suppression may be an important mechanism in the first 6 months of SLIT.

Amsterdam positional OSA classification: the AASM 2012 recommended hypopnoea criteria increases the number of positional therapy candidates.

PURPOSE: This study examined the effect of hypopnoea criteria on the prevalence of positional obstructive sleep apnoea (pOSA) identified under the Amsterdam Positional OSA Classification (APOC) system. METHODS: Three hundred three consecutive patients undertaking polysomnography (PSG) for the suspicion of OSA were included in this retrospective investigation. PSGs were scored using both the 2007 American Academy of Sleep Medicine (AASM) recommended hypopnoea criteria (AASM2007Rec) and the 2012 AASM recommended hypopnoea criteria (AASM2012Rec). For each hypopnoea criteria, OSA patients were grouped according to the APOC categories (I, II or II) or else deemed non-APOC if they did not meet the APOC criteria. Outcome measures, such as Functional Outcomes of Sleep Questionnaire (FOSQ), MOS 36-item short-form health survey (SF-36) and psychomotor vigilance task (PVT), were also compared between the groups. RESULTS: The AASM2012Rec increased the prevalence of OSA compared to AASM2007Rec. The AASM2012Rec trebled the number of APOC I patients compared to AASM2007Rec (297% increase) as well as increased the proportion of females in the APOC I group. AASM2012Rec did not change the number of APOC II and APOC III patients. In fact, the same patients were present in these categories irrespective of hypopnoea criteria. The proportion of non-APOC patients proportionally decreased with the AASM2012Rec criteria. There were no differences in outcome measures between the AASM2012Rec and AASM2007Rec groups. CONCLUSIONS: This study demonstrates that, compared to AASM2007Rec, AASM2012Rec increases the prevalence of who could be successfully treated with positional therapy. The proportion of females with pOSA also increases as a consequence of AASM2012Rec.

Treatment effect of sublingual immunotherapy tablets and pharmacotherapies for seasonal and perennial allergic rhinitis: Pooled analyses.

BACKGROUND: Data comparing the treatment effect of allergy immunotherapy and pharmacotherapy are lacking. OBJECTIVE: We sought to indirectly compare the treatment effect of sublingual immunotherapy (SLIT)-tablets with pharmacotherapy for seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR). METHODS: Pooled data from randomized, double-blind, placebo-controlled trials for the clinical development programs of selected allergic rhinitis treatments were evaluated. Total nasal symptom scores (TNSSs) relative to placebo were compared. Subjects scored symptoms daily during entire pollen seasons in 6 timothy grass SLIT-tablet trials (n = 3094) and 2 ragweed SLIT-tablet trials (n = 658) and during the last 8 weeks of treatment in 2 house dust mite (HDM) SLIT-tablet trials (n = 1768). Subjects scored symptoms daily in 7 montelukast (10 mg, n = 6799), 9 desloratadine (5 mg, n = 4455), and 8 mometasone furoate nasal spray (MFNS; 200 µg daily, n = 2140) SAR or PAR trials. SLIT-tablet trials allowed rescue medication use, whereas most pharmacotherapy trials did not. A fixed-effect meta-analysis method estimated differences in on-treatment average TNSSs. RESULTS: In grass and ragweed SLIT-tablet trials, overall improvement in TNSSs relative to placebo was 16.3% and 17.1%, respectively. In HDM SLIT-tablet trials, TNSS overall improvement relative to placebo was 16.1%. In the montelukast, desloratadine, and MFNS trials, TNSS overall improvement relative to placebo was 5.4%, 8.5%, and 22.2%, respectively, for SAR trials, and 3.7%, 4.8%, and 11.2%, respectively, for PAR trials. CONCLUSIONS: Although comparisons were limited by study design heterogeneity and use of rescue medications in SLIT-tablet trials, effects on nasal symptoms with timothy grass and ragweed SLIT-tablets were nearly as great as with MFNS and numerically greater than with montelukast and desloratadine for SAR. HDM SLIT-tablet effects were numerically greater than all pharmacotherapies for PAR. SLIT-tablets offer the additional benefit of long-term efficacy.

[Possibilities of azelastine in the treatment of chronic rhinitis]. / Vozmozhnosti azelastina v terapii khronicheskogo rinita.

There is considered modern classification of rhinitis and the accents in diagnostic and therapeutic approaches to patients with this disease are indicated, as well as the possibilities of using topical intranasal antihistamines in the treatment of allergic, vasomotor and medicamentous rhinitis.

Health care resource use and associated costs among patients with seasonal versus perennial allergic rhinitis.

BACKGROUND: Health care resource use (HRU) and costs among patients with seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR) have not been widely studied. OBJECTIVE: To develop an algorithm to classify patients with SAR and patients with PAR, and to evaluate treatment patterns, HRU, and costs among these patients. METHODS: Patients with allergic rhinitis (AR) were identified retrospectively by using electronic medical records and administrative claims data, with an index date as the earlier of the date of AR diagnosis or allergy medication use. Patients with AR were followed-up from 12 months before the index date through 12 months after the index date (follow-up) and were classified as SAR or PAR based on medication patterns during follow-up. AR-related HRU, allergy immunotherapy administration, and costs per patient per year during follow-up were compared between patients with SAR and those with PAR, with analyses stratified by asthma diagnosis before the index date and by physician specialty (primary care physician versus specialist). RESULTS: Approximately 23% of patients with AR were classified as having PAR and 77% as having SAR. During follow-up, the patients with PAR had more allergy medication prescriptions versus the patients with SAR (8.0 versus 2.4 prescriptions), higher prescription medication costs ($1551 versus $313), higher allergy immunotherapy cost ($180 versus. $118), and higher total AR-related costs ($1944 versus $643); all with p < 0.001. Patients with asthma had higher costs than those without asthma. Patients seen by a specialist has higher costs than those treated by a primary care physician. CONCLUSION: Patients with PAR experienced more AR-related prescription drug use and higher health care costs than patients with SAR, with prescription drug costs being the main cost driver. Treatments that reduce the need for ongoing prescription medication use have the potential to be cost saving.

Persons with allergy symptoms use alternative medicine more often.

INTRODUCTION: The aim of the study is to indicate the relation between the use of alternative medicine and the occurrence of allergic diseases in the Polish population of adults in the age of 20-44 years. Moreover the additional aim of the study is to define the relation between the sex, age and place of living and the use of alternative medicine. MATERIAL AND METHODS: The data from the project Epidemiology of Allergic Diseases in Poland (ECAP) has been used for analysis. This project was a continuation of the European Community Respiratory Health Survey II. The questions on alternative medicine were asked to the group of 4671 respondents in the age of 20-44 years. Additionally outpatient tests were performed in order to confirm the diagnosis of allergic diseases. RESULTS: The total of 22.2% of respondents that participated in the study have ever used alternative medicine (n = 4621). A statistically significant relation between the use of alternative medicine and declaration of allergic diseases and asthma symptoms has been demonstrated (p < 0.001). No statistically significant relation between the use of alternative medicine by persons diagnosed by a doctor with any form of asthma or seasonal allergic rhinitis (p > 0.05) has been demonstrated. CONCLUSIONS: The occurrence of allergic diseases and asthma influences the frequency of alternative medicine use. However the frequency of alternative medicine use does not depend on allergic disease or asthma being confirmed by a doctor.

Sequential engagement of FcεRI on Mast Cells and Basophil Histamine H(4) Receptor and FcεRI in Allergic Rhinitis.

Histamine H(4) receptor (H(4)R)-deficient mice (H(4)R(-/-)), H(4)R antagonist-treated wild-type (WT) mice, and WT mice depleted of basophils failed to develop early (EPR) or late phase (LPR) nasal responses following allergen sensitization and challenge. Basophil transfer from WT but not H(4)R(-/-) mice restored the EPR and LPR in H(4)R(-/-) mice. Following passive sensitization with OVA-specific IgE, FcεRI(-/-) recipients of WT basophils plus OVA and histamine developed an EPR and LPR. OVA-IgE passively sensitized FcεRI(-/-) recipients of H(4)R(-/-) basophils and OVA and histamine challenge failed to develop an EPR or LPR, and basophils were not detected in nasal tissue. In contrast, recipients of basophils from IL-13(-/-) and IL-4(-/-)/IL-13(-/-) mice developed an EPR but not an LPR. These results demonstrate the development of allergic rhinitis proceeded in two distinct stages: histamine release from FcεRI-activated mast cells, followed by histamine-mediated recruitment of H(4)R-expressing basophils to the nasal cavity and activation through FcεRI.