Allergen Provocation Research Articles

The role of local allergy in the nasal inflammation.

Local allergic inflammation (LAI) is recognized recently. 'entopy' was used to define LAI, which was positively correlated with allergen provocation testing, local sIgE up-regulation, inflammatory mediator secretion, and a lack of systemic allergy. The study of LAI is in its infancy and focuses mainly on the respiratory system. It is closely related to nasal inflammation and plays important roles in patients with nonallergic rhinitis (NAR), nonallergic chronic sinusitis with nasal polyps (CRSwNP), and nonallergic fungal rhinosinusitis (NAFRS). Based on studies using nasal allergen provocation testing, 40-57% of patients with NAR exhibited positive results and could be diagnosed as local allergic rhinitis. Total IgE and common airborne allergen-sIgE were up-regulated in eosinophilic CRSwNP patients compared to noneosinophilic CRSwNP patients and healthy controls, possibly due to local allergic inflammation. Some researchers also found that the level of local sIgE was increased in patients with NAFRS; they suggested that local allergic inflammation occurs in NAFRS. Studies of LAI will increase our understanding of nasal inflammation and help to establish novel treatments. However, the diagnosis of local allergic inflammation is complex due to the lack of convenient detection methods. The relationship between local allergic inflammation and systemic allergic inflammation is unclear, and an appropriate treatment for local allergic inflammation is required.

Mucosal Type 2 Innate Lymphoid Cells Are a Key Component of the Allergic Response to Aeroallergens.

Newly characterized type 2 innate lymphoid cells (ILC2s) display potent type 2 effector functionality; however, their contribution to allergic airways inflammation and asthma is poorly understood. Mucosal biopsy used to characterize the airway mucosa is invasive, poorly tolerated, and does not allow for sequential sampling. To assess the role of ILC2s during nasal allergen challenge in subjects with allergic rhinitis using novel noninvasive methodology. We used a human experimental allergen challenge model, with flow cytometric analysis of nasal curettage samples, to assess the recruitment of ILC2s and granulocytes to the upper airways of subjects with atopy and healthy subjects after allergen provocation. Soluble mediators in the nasal lining fluid were measured using nasosorption. After an allergen challenge, subjects with atopy displayed rapid induction of upper airway symptoms, an enrichment of ILC2s, eosinophils, and neutrophils, along with increased production of IL-5, prostaglandin D2, and eosinophil and T-helper type 2 cell chemokines compared with healthy subjects. The most pronounced ILC2 recruitment was observed in subjects with elevated serum IgE and airway eosinophilia. The rapid recruitment of ILC2s to the upper airways of allergic patients with rhinitis, and their association with key type 2 mediators, highlights their likely important role in the early allergic response to aeroallergens in the airways. The novel methodology described herein enables the analysis of rare cell populations from noninvasive serial tissue sampling.

Development of eosinophilic inflammation is independent of B-T cell interaction in a chronic house dust mite-driven asthma model.

Chronic exposure to environmental triggers, such as house dust mite (HDM), drives T helper 2 (Th2) cell-mediated asthma. Recent evidence has shown that B-T cell interaction, and in particular germinal centre reactions and follicular T helper (Tfh) cells are required for the development of eosinophilic airway inflammation in HDM-driven models containing a sensitization and challenge phase. Whether B-T cell interactions are essential for pulmonary eosinophilic inflammation following chronic allergen provocation remains unknown. In this study, we investigated the importance of B-T cell interaction in the development of eosinophilic airway inflammation and pulmonary remodelling in a chronic HDM-driven asthma model. We exposed C57BL/6, Cd40l-/- , and Mb1-/- mice to HDM three times a week for five consecutive weeks. Chronic HDM exposure induced a pronounced eosinophilic allergic airway inflammation in broncho-alveolar lavage fluid (BALf) and lung tissue, associated with the formation of immunologically active inducible bronchus-associated lymphoid tissue (iBALT) in the lungs. The absence of B cells or lack of CD40L signalling did not hamper eosinophilic inflammation in the airways, although the number of Tfh and Th2 cells was substantially reduced in the lungs. Importantly, type 2 innate lymphoid cell (ILC2) numbers in BALf and lung were not affected by the absence of B cells or B-T cell interaction. Furthermore, eosinophilic airway inflammation is not sufficient to induce pulmonary remodelling and airway hyperresponsiveness. From these findings, we conclude that B-T cell interaction is required for robust Tfh and Th2 cell induction, but not essential for eosinophilic airway inflammation during a chronic HDM-driven asthma model.

Synthesis, Pharmacological Profile and Docking Studies of New Sulfonamides Designed as Phosphodiesterase-4 Inhibitors.

Prior investigations showed that increased levels of cyclic AMP down-regulate lung inflammatory changes, stimulating the interest in phosphodiesterase (PDE)4 as therapeutic target. Here, we described the synthesis, pharmacological profile and docking properties of a novel sulfonamide series (5 and 6a-k) designed as PDE4 inhibitors. Compounds were screened for their selectivity against the four isoforms of human PDE4 using an IMAP fluorescence polarized protocol. The effect on allergen- or LPS-induced lung inflammation and airway hyper-reactivity (AHR) was studied in A/J mice, while the xylazine/ketamine-induced anesthesia test was employed as a behavioral correlate of emesis in rodents. As compared to rolipram, the most promising screened compound, 6a (LASSBio-448) presented a better inhibitory index concerning PDE4D/PDE4A or PDE4D/PDE4B. Accordingly, docking analyses of the putative interactions of LASSBio-448 revealed similar poses in the active site of PDE4A and PDE4C, but slight unlike orientations in PDE4B and PDE4D. LASSBio-448 (100 mg/kg, oral), 1 h before provocation, inhibited allergen-induced eosinophil accumulation in BAL fluid and lung tissue samples. Under an interventional approach, LASSBio-448 reversed ongoing lung eosinophilic infiltration, mucus exacerbation, peribronchiolar fibrosis and AHR by allergen provocation, in a mechanism clearly associated with blockade of pro-inflammatory mediators such as IL-4, IL-5, IL-13 and eotaxin-2. LASSBio-448 (2.5 and 10 mg/kg) also prevented inflammation and AHR induced by LPS. Finally, the sulfonamide derivative was shown to be less pro-emetic than rolipram and cilomilast in the assay employed. These findings suggest that LASSBio-448 is a new PDE4 inhibitor with marked potential to prevent and reverse pivotal pathological features of diseases characterized by lung inflammation, such as asthma.

Local allergic rhinitis in children: Novel diagnostic features and potential biomarkers.

Local allergic rhinitis (LAR) is a phenotype of rhinitis that has been poorly studied in children. It is characterized by the same symptoms of allergic rhinitis but with the absence of markers of systemic atopy. To identify children affected by LAR and to analyze the pathogenesis of this disease. We chose to focus our attention on interleukin (IL) and thymic stromal lymphopoietin (TSLP). We enrolled 20 children affected by nonallergic rhinitis (negative skin-prick test results and serum specific immunoglobulin E [sIgE] values). Each patient underwent a nasal allergen provocation test (NAPT) with dust mite and grass pollen. Before and after NAPT, nasal lavage was performed to detect sIgE, IL-5, and TSLP; anterior active rhinomanometry was used to evaluate changes in nasal obstruction. Two patients were positive to a nonspecific NAPT and, thus, were excluded from the study. Of the remaining 18 children, 12 (66.7%) had positive results to at least one NAPT. Among these 12 patients, nasal sIgE levels for Dermatophagoides pteronyssinus, Dermatophagoides farinae, and Lolium perenne increased significantly after NAPT (D. pteronyssinus, p < 0.005; D. farinae, p < 0.05; L. perenne, p < 0.05). Nasal IL-5 levels showed a significant increase after NAPT (p ≤ 0.006), and this increase was significantly higher in children who had positive NAPT results than in those patients with negative NAPT results (p ≤ 0.03). Among the 12 children who had a positive NAPT result, nasal TSLP was detected in 4 patients (33.3%) and its levels showed a relevant increase after NAPT, even though the difference did not reach statistical significance (p ≤ 0.061). Observed results raise the importance of better refining the diagnostic protocol for LAR in children. Nasal TSLP and IL-5 levels offer new insights concerning localized allergic inflammation, although the role of nasal sIgE has still to be clarified.

Conjunctival allergen provocation test : guidelines for daily practice.

Conjunctival allergen provocation test (CAPT) reproduces the events occurring by instilling an allergen on the ocular surface. This paper is the compilation of a task force focussed on practical aspects of this technique based on the analysis of 131 papers. Main mechanisms involved are reviewed. Indications are diagnosing the allergen(s)-triggering symptoms in IgE-mediated ocular allergy in seasonal, acute or perennial forms of allergic conjunctivitis, especially when the relevance of the allergen is not obvious or in polysensitized patients. Contraindications are limited to ongoing systemic severe pathology, asthma and eye diseases. CAPT should be delayed if receiving systemic steroids or antihistamines. Local treatment should be interrupted according to the half-life of each drug. Prerequisites are as follows: obtaining informed consent; evidencing of an allergen by skin prick tests and/or serum-specific IgE dosages; being able to deal with an unlikely event such as acute asthma exacerbation, urticaria or anaphylaxis, or an exacerbation of allergic conjunctivitis. Allergen extracts should be diluted locally prior to administration. Positive criteria are based on itching or quoted according to a composite score. An alternative scoring is based on itching. CAPT remains underused in daily practice, although it is a safe and simple procedure which can provide valuable clinical information.

The proportion of local allergic rhinitis to Dermatophagoides pteronyssinus in children.

Local allergic rhinitis (LAR) is diagnosed by the positive response to nasal allergen provocation test (NAPT) to aeroallergen and/or local synthesis of specific IgE (sIgE). This entity is found in half of the adults with non-allergic rhinitis (NAR). In children, very few data of the prevalence and characteristics of LAR were reported. Children 8-18years with NAR were recruited. A NAPT with Dermatophagoides pteronyssinus extract (NAPT-Dp) at 200, 600, and 2000AU/ml, respectively, at 15-min interval was performed. The immediate response was assessed using the clinical symptom score, peak nasal inspiratory flow (PNIF), and acoustic rhinometry (ARM). The nasal tryptase and sIgE-Dp were measured at baseline and 15min and 1h after a positive NAPT-Dp. Two allergic rhinitis (AR) patients were used as positive controls. Fifty-four NAR children (61.1% boys) with the mean±SD age of 11.1±2.1years were enrolled. The median duration of disease was 6.3years. The most frequent comorbidity was asthma (38.9%). Eighty-seven percent of patients had mild persistent severity. NAPT-Dp was positive in 2/54 (3.7%) of NAR children who had increased symptom score and decreased minimal cross-sectional area (MCA) on ARM as well as PNIF. However, there was no change in the nasal tryptase and sIgE-Dp. The control AR patients had positive NAPT-Dp and increased nasal tryptase at 15min without the change of sIgE-Dp. LAR is an uncommon condition in children. Further investigation in a large population of children with NAR is needed.

Local allergic rhinitis: A critical reappraisal from a paediatric perspective.

The so-called local allergic rhinitis (LAR) has been proposed as a phenotype of rhinitis with Th2-driven prominent local allergic inflammation, nasal synthesis of specific IgE and a positive response to a nasal allergen provocation test, in the absence of 'systemic' atopy (negative skin prick test and serum allergen-specific IgE antibodies). To date, available data on LAR are mostly focused on adults. The purpose of this 'Rostrum' was to critically discuss data and implications of the 'LAR concept' in paediatrics. In the natural history of rhinitis due to IgE-mediated reactions triggered by exposure to allergens, a 'LAR' can be either the initial, transient stage of classical allergic rhinitis or a stable phenotype never evolving to 'systemic' IgE sensitization. Given the present difficulties in performing routinely nasal allergen provocation test in children, the development of sensitive and specific tests to detect IgE in the child's nasal secretions is a research priority. We suggest also the hypothetical role of allergen immunoprophylaxis or immunotherapy in LAR. Last, the term 'local allergic rhinitis' may be inappropriate, as rhinitis is always 'local', while IgE sensitization can be either 'local' or 'systemic'.

Regulation of melanocortin 1 receptor in allergic rhinitis in vitro and in vivo.

α-melanocyte-stimulating hormone (α-MSH) was shown to inhibit allergic airway inflammation and exert suppressive effects on human basophils. This study aims to extend our current knowledge on the melanocortin 1 receptor (MC1R) expression in nasal tissue of patients with allergic rhinitis (AR) and functional effects of α-MSH in human basophils especially from patients with allergic rhinitis. MC1R expression before and after nasal allergen provocation was studied in nasal mucosal tissue of AR patients and in a mouse model of allergic airway inflammation using immunofluorescence. In vitro regulation of the MC1R and CD203c surface expression on whole-blood basophils of patients with AR and controls was assessed with flow cytometry. Functional effects of α-MSH on isolated basophils were analysed regarding apoptosis with flow cytometry and chemotaxis using a Boyden chamber assay. We detected an accumulation of MC1R-positive basophils in nasal mucosa tissue of patients with AR 24 h after nasal allergen provocation. Such accumulation was not present in mucosa sections from healthy controls. In mice with allergic airway inflammation, we found a clear accumulation of MC1R-positive basophils in the nasal tissue compared to control mice. MC1R expression was inducible in AR patients and controls by stimulation with anti-IgE. α-MSH inhibited anti-IgE and grass pollen induced upregulation of CD203c, but had no effect on chemotaxis or apoptosis of basophils in vitro. MC1R-positive basophils accumulate in the nasal mucosa of patients with AR after nasal allergen provocation. Since α-MSH suppresses proinflammatory effector functions in human basophils via the MC1R, it constitutes an interesting novel target for modulating the allergic inflammatory response.

Intralymphatic immunotherapy induces allergen specific plasmablasts and increases tolerance to skin prick testing in a pilot study.

BackgroundAllergen Immunotherapy is a promising treatment of allergy. Seven patients with rhinoconjunctivitis to grass allergen were treated with intralymphatic immunotherapy (ILIT) to explore whether this treatment could be performed. Effect of treatment was assessed as change in symptom medication score, response in skin prick test and nasal allergen provocation. ILIT deposits allergen in an inguinal lymph node to elicit a strong immune stimulus. This allowed us to monitor appearance of allergen specific plasmablasts 7 days after allergen injection.FindingsIn an open trial of seven patients with a history of symptomatic allergic rhinoconjunctivitis due to grass pollen, three injections of allergen into inguinal lymph nodes were performed with monthly intervals. Allergen injections induced grass allergen specific plasmablasts expressing other isotypes than IgE after 7 days, induced a trend toward improvement in symptom and medication score and rhinoconjunctivitis-related quality of life during the grass pollen season 2013 and significantly raised the threshold in nasal allergen challenge and titrated skin prick testing. Mild side-effects were recorded after 3 of the 21 of injections (14 %).ConclusionsThis pilot study shows that ILIT may induce allergen specific plasmablasts, and confirms an effect on provocation of mast cells in skin and nasal mucosa during the ensuing winter.

Bortezomib treatment diminishes hazelnut-induced intestinal anaphylaxis in mice.

Food allergy is a common health problem and can cause anaphylaxis. Avoidance of the offending food allergen is still the mainstay therapeutic approach. In this study, we investigated the role of plasma cell reduction by proteasome inhibition in a murine model of food allergy and examined the impact of this treatment on the systemic and local immune response. For this purpose, intestinal anaphylaxis was induced in BALB/c mice with the food allergen hazelnut, in conjunction with different adjuvants (alum and Staphylococcal enterotoxin B SEB) and different administration routes (oral and intraperitoneal). In both models, allergy symptoms were observed, but the clinical severity was more pronounced in the hazelnut-alum model than in the hazelnut-SEB model. Accordingly, allergen-specific immunoglobulin E (IgE) against hazelnut was detectable, and mast cell protease-1 in serum was increased after allergen provocation. Treatment with the proteasome inhibitor bortezomib reduced plasma cells and resulted in an abolishment of hazelnut allergen-specific IgE, which was associated with amelioration of clinical symptoms as well as a significant decrease in both CD19(+) and follicular B lymphocytes. Our data demonstrate the importance of allergen-specific IgE in food allergy and point to B cells as potential therapeutic targets for its treatment.

English

Local allergic rhinitis (LAR) is a phenotype of allergic rhinitis characterized by the presence of a localized immune response in the nasal mucosa of patients with negative skin prick test (SPT) results and undetectable serum specific IgE (sIgE). It unknown whether LAR is limited to areas with low or moderate aeroallergen exposure. To explore the presence of LAR and the clinical and immunological characteristics of this entity in geographic areas with high grass pollen loads. A cross-sectional observational study was carried out in 2 hospitals in central Spain (Madrid and Ciudad Real). Sixty-one patients with seasonal rhinitis and negative SPT results and undetectable serum sIgE were evaluated using a clinical questionnaire, determination of serum total IgE, and a nasal allergen provocation test (NAPT) with Phleum species. The response to NAPT was monitored using assessment of nasal symptoms, acoustic rhinometry, and determination of sIgE, tryptase, and eosinophil cationic protein in the nasal cavity. Seasonal LAR was detected in 37 patients (61%) using the techniques described above. Eleven percent of patients with LAR were adolescents or children, and 14% reported onset of rhinitis in childhood. Most patients reported persistent-moderate seasonal nasal symptoms, and 41% reported worsening of the disease during the last 2 years. Conjunctivitis was the most common comorbidity, affecting 95% of cases. LAR to grass pollen is relevant in patients with seasonal symptoms indicative of allergic rhinitis but with a negative skin test result who live in areas with high allergenic pollen loads. This entity should be included the differential diagnosis of rhinitis.

The response to nasal allergen provocation with grass pollen is reduced inpatients with chronic rhinosinusitis with nasal polyposis and grass sensitization.

The majority of grass pollen-sensitized rhinitis patients develops allergic symptoms when exposed to the causal allergen and shows a positive nasal allergen provocation test (NAPT). Chronic rhinosinusitis with nasal polyposis (CRSwNP) patients, also characterized by eosinophilic inflammation and local IgE production, can suffer from comorbid inhalant allergy, but may show a different response to allergens. We aimed to explore the allergic response to grass pollen allergens by NAPT in grass pollen-sensitized CRSwNP patients. Twelve grass pollen-sensitized CRSwNP patients underwent NAPT with grass pollen and were compared with 12 grass pollen allergic rhinitis patients, 12 control patients and 12 CRSwNP patients without grass pollen sensitization. A positive NAPT was based on change in nasal airflow and symptoms. Further, VAS scores of different symptoms were noted before and after NAPT. Biomarkers such as total IgE, grass pollen-specific IgE and tryptase were measured in serum and nasal secretions. NAPT was positive in 6 of 12 of the grass pollen-sensitized CRSwNP patients, and another four patients developed allergic symptoms not fulfilling the criteria of positivity. In contrast, all patients with allergic rhinitis developed a positive provocation test, whereas in the control group one of the patients and in the non-sensitized CRSwNP group two of the patients developed a positive provocation test. These results show that allergen exposure induces an attenuated clinical response in patients with CRSwNP and sensitization to grass pollen as compared with grass pollen allergic rhinitis patients.

Immunologic alterations and efficacy of subcutaneous immunotherapy with Dermatophagoides pteronyssinus in monosensitized and polysensitized patients

BackgroundThere is a continuing debate about whether monoallergen subcutaneous immunotherapy (SCIT) is able to modulate immune and clinical responses toward main causal allergen in polysensitized patients. ObjectiveTo investigate short-term immunologic changes and clinical effectiveness of SCIT with Dermatophagoides pteronyssinus in monosensitized and polysensitized patients who have rhinitis with or without asthma. MethodsNineteen monosensitized and 24 polysensitized patients participated in this prospective, self-placebo-controlled, interventional study. Cluster immunotherapy with D pteronyssinus was administered after 2 months of placebo in both groups. Immunologic parameters, including CD203c expression on basophils after allergen stimulation, total IgE, specific IgE, and specific IgG4, were evaluated at baseline, after placebo, and after immunotherapy. Clinical effectiveness was assessed using monthly symptom-medication scores, visual analog scale, quality-of-life questionnaire, and nasal allergen provocation test. ResultsAt baseline, polysensitized patients had higher CD203c expression on basophils than monosensitized patients (P = .007). Activated basophils expressing CD203c, total IgE, and specific IgG4 were significantly increased after immunotherapy compared with baseline and placebo in the polysensitized group (P < .025). After immunotherapy, specific IgE and D pteronyssinus–induced CD203c expression were significantly higher in polysensitized than monosensitized patients (P < .05). The total symptom scores and the Mini Rhinoconjunctivitis Quality of Life Questionnaire scores in polysensitized patients and the visual analog scale scores in both groups were lower after immunotherapy compared with baseline and placebo (P < .025). Titrated nasal allergen provocation test with D pteronyssinus increased after immunotherapy in the monosensitized group (P < .05). ConclusionThis study indicates that monosensitized and polysensitized patients have distinct humoral response and basophil behavior to SCIT. However, a single-allergen immunotherapy corresponding to the most clinically troublesome allergy in polysensitized patients can lead to early clinical efficacy comparable to that seen in monosensitized patients. Trial Registrationclinicaltrials.gov Identifier: NCT01795846.

The importance of mold sensitivity in nonallergic rhinitis patients.

In recent studies, local specific immunoglobulin E (sIgE) production against allergens in nasal mucosa and a positive response to a nasal allergen provocation test (NAPT) have been demonstrated in some patients initially diagnosed as nonallergic rhinitis (NAR) or idiopathic rhinitis (IR). The aim of this study was to evaluate the presence of local allergic rhinitis (LAR) in patients who experience rhinitis symptoms in indoor and outdoor moldy conditions and to investigate the role of the NAPT in diagnosis. A total of 40 NAR patients with a history of persistent rhinitis and who had negative skin-prick tests (SPTs) and serum sIgE levels to common aeroallergens, as well as 20 healthy subjects were included in the study. NAPTs were performed with Aspergillus fumigatus (group 1) or a mixture of Alternaria alternata and Cladosporium herbarum extracts (group 2). In patient nasal lavage fluids, tryptase and mold sIgE levels were not significantly different from the control group. NAPT with Aspergillus fumigatus was positive in 8 of 12 NAR patients (66.6%) in group 1 and NAPT with the mixture of extracts was positive in 9 of 13 NAR patients (69.2%) in group 2. This study suggests that LAR may exist in a significant number of the persistent rhinitis patients who were previously considered as NAR based on negative SPTs or serum sIgE tests. To the best of our knowledge, this is the first study evaluating a nasal local allergic response to both indoor and outdoor molds.

Intralymphatic immunotherapy of pollen-induced rhinoconjunctivitis: a double-blind placebo-controlled trial.

BackgroundAllergen-specific immunotherapy represents the only disease-modifying treatment for allergic diseases. We and others have previously demonstrated that intralymphatic immunotherapy (ILIT), a less time-consuming alternative to conventional subcutaneous immunotherapy (SCIT), is safe and effective. However, this has recently been disputed. The aim of this study was therefore to expand our previous trial, further assessing the safety and efficacy of ILIT.MethodsThirty-six patients with pollen-induced rhinoconjunctivitis were randomised to receive three intralymphatic inguinal injections of active allergen (1000 SQ-U birch- or grass-pollen) or placebo. Clinical effects, safety and circulating immunological markers were assessed before, 4 weeks after treatment and at the end of the consecutive pollen season.ResultsNo moderate or severe reactions were recorded following ILIT. Patients receiving active ILIT experienced a significant improvement in self-recorded seasonal allergic symptoms, as compared to placebo (p = 0.05). In a subgroup of these patients (“improved”), a reduction in nasal symptoms following nasal allergen provocation was also demonstrated. No changes in total IgE or IgG4 were found. However, the affinity of allergen specific IgG4 following active treatment was significantly increased, as compared to non-improved patients (p = 0.04). This could be correlated with clinical improvement, on an individual level.ConclusionsThis double-blinded placebo-controlled study confirms that ILIT is a safe and effective treatment for pollen-induced rhinoconjunctivitis, markedly reducing seasonal allergic symptoms.Trial registrationEudraCT: 2009-016815-39Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-016-0324-9) contains supplementary material, which is available to authorized users.

The impact of food allergens on airway responsiveness in schoolchildren with asthma: A DBPCFC study.

Despite the growing evidence of a possible link between asthma and food allergy (FA), so far, the involvement of food in inducing respiratory symptoms has not been fully evaluated. The objective of this study was to evaluate the impact of food allergens on respiratory symptoms and bronchial reactivity (BHR) in schoolchildren with asthma. The initial study group consisted of 362 children with asthma. In the end, 22 children with concomitant FA, and 18 without FA, were selected to participate in the study. Spirometry and Methacholine Inhalation Challenge (MIC) were conducted prior to and after the completion of a double blind placebo control food challenge (DBPCFC). The food-induced asthmatic reactions were observed in nine (2.5%) out of all 362 children with asthma. Mean FEV1 prior to and after allergen or placebo challenge did not differ between the groups studied. Increase of BHR after DBPCFC was seen in 17 (4.7%) children with asthma. The mean PC20 value in children with FA was 1.41 ± 1.12 mg/ml prior to the allergen challenge and 0.86 ± 0.71 mg/ml (P = 0.002) after the test, whereas these values were 1.93 ± 1.68 mg/ml and 2.02 ± 1.75 mg/ml, respectively, in children without FA (P > 0.05). Significant differences were noted after the allergen provocation in children with FA as compared to children without FA (P = 0.007). Although food allergens are a rare trigger of food-induced asthmatic reactions in schoolchildren with asthma, they could enhance BHR, despite a lack of evident clinical respiratory signs and decreased in FEV1 values after food challenge. Pediatr Pulmonol. 2016;51:787-795. © 2016 Wiley Periodicals, Inc.

Dynamic Changes in Heart Rate Variability and Nasal Airflow Resistance during Nasal Allergen Provocation Test.

Allergic rhinitis is a major chronic respiratory disease and an immunoneuronal disorder. We aimed at providing further knowledge on the function of the neural system in nasal allergic reaction. Here, a method to assess simultaneously the nasal airflow resistance and the underlying function of autonomic nervous system (ANS) is presented and used during the nasal provocation of allergic and nonallergic subjects. Continuous nasal airflow resistance and spectral heart rate variability parameters show in detail the timing and intensity differences in subjects' reactions. After the provocation, the nasal airflow resistance of allergic subjects showed a positive trend, whereas LF/HF (Low Frequency/High Frequency) ratio and LF power showed a negative trend. This could imply a gradual sympathetic withdrawal in allergic subjects after the allergen provocation. The groups differed significantly by these physiological descriptors. The proposed method opens entirely new opportunities to research accurately concomitant changes in nasal breathing function and ANS.

Induction of Bronchial Tolerance After 1 Cycle of Monophosphoryl-A-Adjuvanted Specific Immunotherapy in Children With Grass Pollen Allergies.

PurposeSubcutaneous allergen-specific immunotherapy (SCIT) is a well-established and clinically effective method to treat allergic diseases, such as rhinitis and asthma. It remains unclear how soon after initiation of an ultra-short course of grass pollen immunotherapy adjuvanted with monophosphoryl lipid A (MPL)-specific bronchial tolerance can be induced.MethodsIn a prospective study of 69 children double-sensitized to birch and grass pollens (51 males, average age 11.1 years), development of bronchial tolerance after 1 cycle of SCIT for grass was evaluated. In all the patients, the bronchial allergen provocation test (BAP) was performed before and after treatment. According to the results of the first BAP, the patients were divided into 2 groups: those showing a negative BAP with a decrease in FEV1 of <20% (seasonal allergic rhinitis [SAR] group, n=47); and those showing a positive BAP with a decrease in FEV1 of ≥20% (SAR with allergic asthma [SAR and Asthma] group, n=22). All the patients received MPL-adjuvanted, ultra-short course immunotherapy for birch, but only those with a positive BAP to grass received MPL-SCIT for grass.ResultsAfter the pollen season, the BAP in the SAR group remained unchanged, while it was improved in the SAR and Asthma group (decrease in FEV1 of 28.8% vs 12.5%, P<0.01). The IgG4 levels increased after SCIT (median before SCIT 0.34 to 11.4 after SCIT), whereas the total and specific IgE levels remained unchanged.ConclusionsAfter 1 cycle of MPL-SCIT, specific bronchial tolerance may be significantly induced, whereas in patients without SCIT, bronchial hyperactivity may remain unchanged.

Seasonal proteome changes of nasal mucus reflect perennial inflammatory response and reduced defence mechanisms and plasticity in allergic rhinitis

IntroductionNasal mucus and its proteins are a defence against allergens. We sought to investigate dynamic proteome changes in allergic rhinitis upon environmental allergen provocation. MethodsNasal mucus was collected in and out of pollen season from allergic rhinitis patients (N=10) and healthy controls (N=12). Liquid chromatography–tandem mass spectrometry was performed. Proteins were identified by SwissProt database search and quantified from normalized areas under curve of precursor ion chromatograms. Gene enrichment analysis was performed with Cytoscape/BINGO software. ResultsIn total 430 different proteins were detected in both groups, 203 (47.2%) were newly identified. In allergics CLU and IGKC were significantly more abundant in season (2.2 and 2.1-fold respectively). GSTP1 (0.5-fold), ELANE (0.4-fold), HIST1H2BK (0.3-fold), S100A8 (0.2-fold), S100A12 (0.2-fold) and ARHGDIB (0.1-fold) were significantly less abundant in season. In healthy controls UBC, TUBA1B, HBB and FABP5 were only present in season. Ig kappa chain V-I region DEE (5.3-fold), CLU (5.0-fold), TXN (4.3-fold), MSMB (3.2-fold) and Ig heavy chain V-III region BRO (2.7-fold) were significantly more abundant in season. MUC5B (0.5-fold), SLPI (0.2-fold) and S100P (0.2-fold) were significantly less abundant in season. ConclusionContrary to their symptoms allergic rhinitis patients show perennial inflammatory response lacking adequate reaction to allergens in season. Biological significanceMany studies dealing with allergic rhinitis are focused on the nasal epithelium. This is the first study to analyse the nasal mucus as primary defence barrier on a proteomic level in and out of pollen season and contrary to the leading opinion shows that allergic patients show a perennial inflammatory response with reduced reaction to allergens whereas healthy controls react on proteome basis towards enhanced defence in season despite lacking allergic sensitization.