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.

Factors contributing to the diagnosis and onset prediction of perennial allergic rhinitis in high-risk children: A sub-analysis of the CHIBA study.

BACKGROUND: This study aimed to clarify the diagnostic and predictive factors for perennial allergic rhinitis (PAR) onset in children by analyzing the results of the Chiba High-risk Birth Cohort for Allergy study, which examined newborns with a family history of allergies. METHODS: Overall, 306 pregnant women were recruited. Their newborns were examined by otolaryngologists and pediatric allergists at 1, 2, and 5 years of age. Participants with clinical and laboratory data available at all consultation points were considered eligible. RESULTS: Among 187 eligible participants, the prevalence rates of PAR were 2.1%, 4.3%, and 24.1% at 1, 2, and 5 years of age, respectively. AR-specific nasal local findings and eosinophils in nasal smear were observed in a substantial number of patients with PAR at 1 and 2 years of age. Factors present up to 2 years of age that were associated with PAR onset at 5 years of age, in descending order, were as follows: sensitization to house dust mites (HDM), nasal eosinophilia, and sensitization to cat dander. In 44 cases with HDM sensitization, nasal eosinophilia up to 2 years of age achieved a sensitivity of 76.0% and a specificity of 73.7% for predicting PAR onset at 5 years. CONCLUSIONS: Rhinitis findings and nasal eosinophilia are useful auxiliary diagnostic items for pediatric PAR. Sensitization to HDM and nasal eosinophilia were the most influential factors associated with future PAR onset. A combination of these factors may facilitate the prediction of PAR onset.

Effect of the Use of Intranasal Spray of Essential Oils in Patients with Perennial Allergic Rhinitis: A Prospective Study.

INTRODUCTION: Among allergic rhinitis (AR) symptoms, nasal obstruction particularly affects the quality of life. Antihistamines and intranasal corticosteroids are the most frequently prescribed symptomatic drugs, but their efficacy is often incomplete. Essential oils (EO) have shown an anti-inflammatory effect and potential in treating patients with AR. The aim of this study was to evaluate the effectiveness of a hypertonic EO-based nasal spray on perennial AR (PAR) symptoms. METHODS: This prospective, open-label, non-randomized, multicentric trial included 43 patients with PAR sensitized to mites, not controlled for more than a year. All were treated with Puressentiel® Respiratory-Decongestant Nasal Spray for 30 days. Their usual treatment remained unchanged during the study period. Before and after treatment, each participant filled out a rhinitis questionnaire, the Allergic Rhinitis Control Test (ARCT). A nasal inspiratory peak flow (NIPF) was performed. RESULTS: The mean ARCT was 16.4 and 20.5 at D0 and D30, respectively (p < 0.001); the mean increase between D0 and D30 was 4.1 (p < 0.001). The proportion of patients with controlled rhinitis after 30 days of treatment was 69.8 versus 14% before treatment (p < 0.001). The mean NIPF was 86.5 L/min and 105.1 L/min at D0 and D30, respectively (p < 0.001); the mean increase between D0 and D30 was 18.5 L/min. CONCLUSION: A hypertonic EO-based nasal spray could be a new and natural option in the management of PAR. It could also be used as an add-on therapy when nasal symptoms are not fully controlled.

IgE and IgG4 Repertoire in Asymptomatic HDM-Sensitized and HDM-Induced Allergic Rhinitis Patients.

INTRODUCTION: Asymptomatic sensitization is defined as the presence of positive skin prick test (SPT) and/or positive serum allergen-specific IgE in the absence of clinical allergic symptoms. Currently, there is no convincing explanation why some people with positive allergen tests do not show symptoms. We aimed to investigate the house dust mite (HDM)-specific IgE and IgG4 repertoire in asymptomatic HDM-sensitized subjects and HDM-induced allergic rhinitis (AR) patients. METHODS: A total of 48 subjects sensitized to HDM were included in this study: 27 had AR with/without asthma (symptomatic group), and 21 had no allergic symptoms (asymptomatic group). Six healthy individuals served as control group. Peripheral blood samples were collected for serum IgE and IgG4 assay and basophil activation tests (BATs). IgE and IgG4 assay included antibodies to Dermatophagoides (Der) p1, 2, 7, 10, 21, 23, and Der f1, 2. RESULTS: AR patients had a larger wheal diameter of SPT (7.0 vs. 3.0 mm, p < 0.0001) and a higher specific IgE to Der p (15.50 vs. 0.70 KU/L, p < 0.0001) than asymptomatic subjects. They also showed more frequent sensitization to Der p1 and Der p2 (both p < 0.05). However, the total IgE and specific IgG4 did not differ significantly between the 2 groups. The basophil activation response after being stimulated with HDM was observed to be higher in AR patients (all p < 0.05). CONCLUSIONS: There are differences in SPT, serum-specific IgE to Der p, component allergen Der p1 and Der p2 level and BAT between AR patients and asymptomatic subjects sensitized to HDM. IgG4 alone cannot differentiate asymptomatic individuals from AR patients.

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.

Characterization of severe asthma in the pediatric population.

INTRODUCTION AND OBJECTIVES: Relationship between the causal mechanisms of pediatric severe asthma and severity of symptoms would be helpful for developing personalized strategies for treatment and prevention. MATERIALS AND METHODS: For this study, 698 medical histories of asthmatics between 6 and 18 years of age were reviewed in a period of 2 years. Variables analyzed were: age, sex, ethnicity, perinatological history, allergy history, asthma predictive index (API), exposure to tobacco, heavy traffic or epithelium, lung function, age of onset of symptoms, hospitalization admissions/PICU, systemic corticosteroids, daily symptoms control, device prescribe for daily control, and adherence. RESULTS: A total of 86 children with severe asthma were included (12.3%). Mean age 13.3 +/- 1.86 years, sex ratio1:1, mean age of symptom onset 2.765 +/- 3.06 years, mean IgE 1076.18KU / L +/- 1136, mean eosinophils 604c / mcl +/- 511.9, mean of FEV1 93.15% +/- 16.3. Evidently, 70 children (81.4%) had positive API, 68 (79.1%) rhinitis, 34 (39.5%) atopic dermatitis. 73 (83.9%) sensitized to inhalants and 56 (65.1%) to dermatophagoides, 39 (45.3%) passive smokers, 19 (22.1%) exposure to heavy traffic; 55 (64%) showed symptoms with exercise, 35 (40.7%) had audible wheezing. The mean systemic corticosteroid cycles/year was 3.63 +/- 3.23, mean PICU admissions 0.36 +/- 0.83, mean hospital admissions 4.31 +/- 5.3, average emergency room visits/year 19.44 +/- 16.28. 38 (56.7%) had good adherence, 44 (51%) used an MDI device and 39 (45.3%) used dry powder. CONCLUSIONS: Children with severe asthma meet the following criteria: premature, positive API, rhinitis, atopic dermatitis, high IgE, eosinophilia, passive smokers, exposure to heavy traffic, decreased lung function, and low adherence to controller medication.

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.

An endothelial microRNA-1-regulated network controls eosinophil trafficking in asthma and chronic rhinosinusitis.

BACKGROUND: Airway eosinophilia is a prominent feature of asthma and chronic rhinosinusitis (CRS), and the endothelium plays a key role in eosinophil trafficking. To date, microRNA-1 (miR-1) is the only microRNA known to be regulated in the lung endothelium in asthma models. OBJECTIVE: We sought to determine the role of endothelial miR-1 in allergic airway inflammation. METHODS: We measured microRNA and mRNA expression using quantitative RT-PCR. We used ovalbumin and house dust mite models of asthma. Endothelium-specific overexpression of miR-1 was achieved through lentiviral vector delivery or induction of a transgene. Tissue eosinophilia was quantified by using Congo red and anti-eosinophil peroxidase staining. We measured eosinophil binding with a Sykes-Moore adhesion chamber. Target recruitment to RNA-induced silencing complex was assessed by using anti-Argonaute2 RNA immunoprecipitation. Surface P-selectin levels were measured by using flow cytometry. RESULTS: Serum miR-1 levels had inverse correlations with sputum eosinophilia, airway obstruction, and number of hospitalizations in asthmatic patients and sinonasal tissue eosinophilia in patients with CRS. IL-13 stimulation decreased miR-1 levels in human lung endothelium. Endothelium-specific overexpression of miR-1 reduced airway eosinophilia and asthma phenotypes in murine models and inhibited IL-13-induced eosinophil binding to endothelial cells. miR-1 recruited P-selectin, thymic stromal lymphopoietin, eotaxin-3, and thrombopoietin receptor to the RNA-induced silencing complex; downregulated these genes in the lung endothelium; and reduced surface P-selectin levels in IL-13-stimulated endothelial cells. In our asthma and CRS cohorts, miR-1 levels correlated inversely with its target genes. CONCLUSION: Endothelial miR-1 regulates eosinophil trafficking in the setting of allergic airway inflammation. miR-1 has therapeutic potential in asthmatic patients and patients with CRS.

Comparison of sensitization and prevalence of Japanese cedar pollen and mite-induced perennial allergic rhinitis between 2006 and 2016 in hospital workers in Japan.

BACKGROUND: The prevalence of allergic rhinitis (AR) is increasing worldwide, mainly due to an increase in antigen exposure. We conducted an epidemiological study involving the staff of the University of Fukui Hospital and its associated hospital in 2006. There were 1540 participants aged ≥20 years, and the rates of Japanese cedar (JC) pollinosis and mite-induced perennial allergic rhinitis (PAR) were 36.8% and 15.8%, respectively. In 2016, we conducted a second survey. METHODS: The rate of sensitization to JC pollen and mites and the prevalence of JC pollinosis and mite-induced PAR were analyzed based on data from questionnaires and antigen-specific immunoglobulin E (IgE) levels. RESULTS: In the present study, we analyzed data of 1472 participants aged between 20 and 59 years. Total sensitization to JC pollen and total prevalence of JC pollinosis were 57.8% (851/1472) and 40.8% (601/1472), respectively. Total sensitization to mites and total prevalence of mite-induced PAR were 41.4% (610/1472) and 18.8% (276/1472), respectively. Total prevalence of JC pollinosis and mite-induced PAR increased significantly over a decade. Among the 334 people who participated in the 2006 and 2016 cross-sectional studies, 13% of JC pollinosis and 36% of mite-induced PAR experienced remission. However, since the number of new onset cases was higher that the number of remission cases, a slight increase in prevalence was observed over a decade. CONCLUSIONS: The prevalence of JC pollinosis and mite-induced PAR continues to show increasing trends, accompanied by an increase in antigen exposure. The remission rate of JC pollinosis was particularly low.

Sensitization to Furry Animals and Clinical Relevance of House Dust Mite-Induced Allergic Rhinitis in Guangzhou, China.

INTRODUCTION: The impact of furry animal allergens on house dust mite (HDM)-induced allergic rhinitis (AR) is unclear. OBJECTIVE: We aimed to investigate the co-sensitization and cross-sensitization of furry animal allergens and assess their clinical relevance with HDM-induced AR. METHODS: We enrolled 268 patients with HDM-induced AR who were diagnosed with skin prick tests positive for dogs and/or cats. Specific immunoglobulin E (sIgE) for dogs (e1) and cats (e2), their components (Can f 1-5 and Fel d 1-2), and other uncommon furry animal extracts were measured. Symptoms and quality of life were assessed with a visual analog scale (VAS). RESULTS: The VAS scores for the AR and asthma (AS; n = 166), moderate-to-severe persistent-AR (n = 132), and e1P (positive)-e2P (n = 89) groups were higher than those for single AR (n = 102), other AR classifications, and other AR sensitization profiles, respectively. The IgE positivity rates for components such as Can f 1-3 and Fel d 2 and those for rats, sheep, mice, cows, and horses were highest in e1P-e2P patients. Can f 1-4, Fel d 1, Fel d 2, or the combined allergens were positively correlated with VAS scores. AR combined with AS and sensitization to Can f 4, Fel d 1, or mice were risk factors for HDM-induced AR with VAS scores ≥5. CONCLUSIONS: Extensive cross-sensitization or co-sensitization was found between Can f 1-3, Fel d 2, or rat, sheep, mouse, cow, and horse extracts. Higher sIgE levels for Can f 1-4 and Fel d 1-2 or a higher number of furry animal allergens lead to more severe symptoms and a reduced quality of life. Combined with AS, sensitization to Can f 4, Fel d 1, or mice were risk factors for moderate-to-severe HDM-induced AR.

Effects of Perennial Allergen Immunotherapy in Allergic Rhinitis in Patients with/without Asthma: A-Randomized Controlled Real-Life Study.

BACKGROUND: There have been very few studiesin real-life settingscomparing the treatment effects of allergen immunotherapy (AIT) and pharmacotherapy for perennial allergic rhinitis (AR). OBJECTIVE: This study was performed to compare AIT and pharmacotherapy in terms of their effects on the symptom control and quality of life (QOL) of AR patients with/without asthma. METHODS: A total of 250 patients diagnosed with AR with/without asthma were included and assigned to the immunotherapy (AIT plus pharmacological treatment) or control (pharmacological treatment only) group. Clinical and medication scores, QOL scores, and lung function (forced expiratory volume in one second as a percentage; FEV1%) were measured at baseline and 3 years after the start of treatment. RESULTS: This study showed that there was clinical improvement in AR symptoms in the AIT group, whereas standard pharmacotherapy alone had no significant effect on nasal symptoms. The QOL and satisfaction scores, as evaluated with a visual analogue scale (VAS), were further improved compared to the pharmacotherapy group. There was a significant improvement in medication scores in both AIT groups. According to our results, while total asthma scores and asthma control test scores were significantly improved in the HDM AIT group, they did not change in the Parietaria pollen AIT group. In our study FEV1% was increased compared to the baseline value in the AIT group, but it was not statistically significant. On the other hand, FEV1% remained without any improvement in patients on standard pharmacotherapy. CONCLUSION: Perennial AIT was found to be superior to pharmacotherapy in decreasing symptoms as well as in improving QOL scores in AR patients with/without asthma. HDM AIT was more effective for asthma symptoms than Parietaria pollen AIT.

Assessing the health impact of interventions for baker's allergy and asthma in supermarket bakeries: a group randomised trial.

PURPOSE: To assess the impact of an intervention for baker's allergy and asthma in supermarket bakeries. METHODS: A group randomised trial conducted in 31 bakeries (n = 337 bakers) that were randomly assigned to one of two intervention groups (n = 244 bakers) and a control group (n = 93 bakers). Health data collected prior to and 1-year after the intervention included information obtained from an ECRHS questionnaire; tests for atopy and serum-specific IgE to cereal flours; fractional exhaled nitric oxide (FeNO). Data from the two intervention groups were combined to form one intervention group for purposes of the statistical analysis. RESULTS: At 1 year of follow-up, the incidence and level of decline of work-related ocular-nasal and chest symptoms, sensitisation status and elevated FeNO (FeNO > 25 ppb) was similar in both intervention and control groups. The mean FeNO difference was also similar across both groups (2.2 ppb vs 1.7 ppb, p = 0.86). In those with FeNO > 25 ppb at baseline, the decline was greater in the intervention compared to control group (16.9 ppb vs 7.7 ppb, p = 0.24). Multivariate logistic regression models (adjusting for smoking, baseline sensitisation to cereal flour, baseline FeNO > 25 ppb) did not demonstrate an appreciable FeNO decline (≥ 10%) in the intervention compared to control group. However, stratification by the presence of work-related ocular-nasal symptoms in bakers at baseline demonstrated a significant FeNO decline (≥ 10%) in the intervention compared to the control group (OR 3.73, CI 1.22-11.42). CONCLUSION: This study demonstrates some evidence of an intervention effect on FeNO 1 year after an intervention, particularly in bakers with work-related ocular-nasal symptoms.

Could FeNO Predict Asthma in Patients with House Dust Mites Allergic Rhinitis?

Background and Objectives: The evolution of allergic rhinitis to asthma is a part of "atopic march". The aim of this study was to analyze possible predictive markers for asthma occurrence in patients with allergic rhinitis to house dust mites (HDM). Materials and Methods: Fifty-eight patients with persistent allergic rhinitis (PAR) were included. The clinical, biological evaluation and fractionated exhaled nitric oxide (FeNO) measurement were performed at enrolment. The patients were clinically evaluated after one year to determine asthma occurrence. Results: The severity of rhinitis symptoms, levels of total immunoglobulin E (IgE), ICAM-1, VCAM-1, E-selectin and IL-6, but not IL-8 and TNF-α were higher in patients with allergic rhinitis who developed asthma compared to non-asthmatics, but the differences were not significant to considered them as predictive factors for asthma occurrence. The risk of asthma was independently influenced by patients aged over 30 years ((OR-3.74; CI95% 0.86-16.31; p = 0.07), a duration of allergic rhinitis over 12 months ((OR-4.20; CI95% 0.88-20; p = 0.07) and a basal FeNO over 28 parts per billion (pbb) ((OR-18.68; CI95% 3.79-92.05; p < 0.001). Conclusion: Clinical and biological parameters may predict asthma occurrence in patients with persistent allergic rhinitis to HDM. Adult patients with a longer duration of rhinitis symptoms and a high level of FeNO have a greater risk to develop asthma.

Triamcinolone Acetonide versus Fluticasone Propionate in the Treatment of Perennial Allergic Rhinitis: A Randomized, Parallel-Group Trial.

BACKGROUND: Intranasal sprays are recommended as targeted therapy for allergic rhinitis (AR). Triamcinolone acetonide is a nasal corticosteroid preparation indicated for the treatment of seasonal and perennial AR (PAR) in different countries worldwide. OBJECTIVES: In order to determine the efficacy of triamcinolone acetonide in the treatment of PAR, the non-inferiority of triamcinolone acetonide to fluticasone propionate was assessed in Russian adults. METHODS: In this randomized, double-blind, parallel-group, multicenter, prospective, non-inferiority, phase III clinical trial, a total of 260 patients with persistent PAR were randomized to receive either triamcinolone acetonide or fluticasone propionate nasal sprays for 4 weeks. The efficacy in symptom control was evaluated using the reflective total nasal symptom score (rTNSS) from baseline (day 0) to day 28. Safety was assessed through the reporting of adverse events. RESULTS: The rTNSS mean values decreased from baseline to the end of study treatment (day 28) in both groups: -8.2 ± 3.0 in the triamcinolone acetonide arm versus -8.0 ± 2.8 in the fluticasone propionate arm. The mean difference between the groups (triamcinolone acetonide - fluticasone propionate) for rTNSS change from baseline was -0.2 (95% confidence interval -0.89 to 0.54), with an upper confidence limit of 0.54, which is lower than the non-inferiority margin of 0.8. Triamcinolone acetonide was well tolerated, with no difference in adverse event occurrence compared with fluticasone propionate. CONCLUSIONS: Triamcinolone acetonide proved to be non-inferior to fluticasone propionate in adult patients with PAR; both treatments decreased rTNSS values and showed a good safety profile.

MP29-02 reduces nasal hyperreactivity and nasal mediators in patients with house dust mite-allergic rhinitis.

BACKGROUND: Nasal hyperreactivity (NHR) is an important clinical feature of allergic rhinitis (AR). The efficacy of MP29-02 (azelastine hydrochloride (AZE) and fluticasone propionate [FP]) nasal spray on local inflammatory mediators and NHR in AR is unknown. We tested if MP29-02 decreases inflammatory mediators and NHR in AR and if this effect is due to restoration of nasal epithelial barrier function. METHODS: A 4-week double-blinded placebo-controlled trial with MP29-02 treatment was conducted in 28 patients with house dust mite (HDM) AR. The presence of NHR was evaluated by measuring reduction in nasal flow upon cold dry air exposure. The effects of AZE ± FP on barrier integrity and airway inflammation were studied in a murine model of HDM-induced NHR and on reduced activation of murine sensory neurons and human mast cells. RESULTS: MP29-02 but not placebo reduced NHR (P < .0001 vs P = .21), levels of substance P (P = .026 vs P = .941), and ß-hexosaminidase (P = .036 vs P = .632) in human nasal secretions. In wild-type C57BL6 mice, the reduction in ß-hexosaminidase levels (P < .0001) by AZE + FP treatment upon HDM challenge was found in parallel with a decreased transmucosal passage (P = .0012) and completely reversed eosinophilic inflammation (P = .0013). In vitro, repeated applications of AZE + FP desensitized sensory neurons expressing the transient receptor potential channels TRPA1 and TRPV1. AZE + FP reduced MC degranulation to the same extent as AZE alone. CONCLUSION: MP29-02 treatment reduces inflammatory mediators and NHR in AR. The effects of AZE + FP on MC degranulation, nasal epithelial barrier integrity, and TRP channels provide novel insights into the pathophysiology of allergic rhinitis.

Study toward resolving the controversy over the definition of allergic fungal rhinosinusitis.

Dysbiosis of the microbiome on the airway mucosa leads to the development of chronic inflammatory and allergic disorders. The aim of this study was to consider the potential diagnostic criteria for allergic fungal rhinosinusitis (AFRS) and nonallergic fungal rhinosinusitis (FRS), and the role of fungal presence in an environment for the development of AFRS. In this study, 136 patients were divided into two groups: patients with positive specific immunoglobulin E (sIgE) and fungal finding (AFRS group), and patients with negative sIgE and positive fungal finding (FRS group). The study design included: anamnesis data, sIgE, eosinophil count and skin-prick test, rhinology and computerized tomography (CT) observation and mycological finding. Our results showed: (i) the prevalence in Serbia is: AFRS 1.3%, FRS 2.8%; (ii) 30.4% patients with sIgE+ had more often severe and recurrent chronic rhinosinusitis (CRS) (P = .005) and the presence of polyps (P = .025); (iii) 46.4% patients with sIgE+ had positive fungi on the sinonasal mucosa and were considered as AFRS; (iv) patients with AFRS had more frequent asthma (P = .024) and chronicity of CRS >10 years (P = .000). The persistent fungal presence and prolonged duration of CRS could be a silent threat for the progression of inflammation and development of FRS. Lavage with hypertonic-NaCl should be included in the everyday hygiene routine in an effort to decrease fungal load and antigenic exposure. The presence of allergological parameters and better response to corticosteroid therapy in AFRS patients should be considered as crucial diagnostic criteria for AFRS.

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.

Dog allergy: can a prevalent or exclusive sensitization to Can f 5 be considered a lucky or negative event in real life?

Summary: Recent studies have shown the increasing relevance of allergic sensitization to Can f 5 (a prostatic kallikrein), which is an androgen-regulated protein expressed in the prostate and detectable only in male dogs. Can f 5 can be a prevalent or exclusive sensitizing agent in a considerable percentage of dog-allergic patients. Its specific allergenic characteristics are able to induce possible negative as well as positive clinical effects in individuals sensitized to dogs. In the present article we pointed out the possible pros or cons of sensitization to this allergen in real life. Further studies should be carried out to correctly assess some peculiar characteristics of Can f 5, in order to support the most of positive aspects and remedy at best the negative effects.

Symptomatic treatment of pollen-related allergic rhinoconjunctivitis in children: randomized controlled trial.

BACKGROUND: About 12% of children are affected by allergic rhinoconjunctivitis (AR). Although the main symptomatic treatments are intranasal corticosteroids (INCS) (daily or on demand) and oral antihistamines, it remains unclear which treatment provides the best relief of symptoms. Therefore, this study examines whether daily use of INCS is superior to on-demand use or to oral antihistamines on demand. METHODS: A single-blinded randomized controlled trial in children (aged 6-18 years) with pollen-related AR. Patients received either INCS daily (fluticasone propionate), INCS on demand (fluticasone propionate) or oral antihistamine on demand (levocetirizine) for 3 months during the grass pollen season. A daily online symptom diary on both nose and eye symptoms was completed. The primary outcome was the percentage of symptom-free days. RESULTS: A total of 150 children were randomized. The percentage symptom-free days was in favour of INCS on demand (30%) compared with INCS daily (22%), that is 8% difference (95% CI -5 to +21%; not significant). The antihistamine on-demand group had 15% symptom-free days, that is 7% difference compared to INCS daily (95% CI -6 to +19%;, not significant). Patients in the INCS on-demand group used on average 61% less fluticasone than patients in the INCS daily group during the study period (P < 0.0001). CONCLUSIONS: This trial with three parallel treatment groups shows that INCS daily was not superior to INCS on demand or to antihistamine on demand regarding the number of symptom-free days. An on-demand INCS strategy has the advantage of a lower overall corticosteroid exposure and less costs.