Pollen Inhalation Research Articles

IgE-Mediated Allergy and Asymptomatic Sensitization to Cannabis Allergens-Review of Current Knowledge and Presentation of Six Cases.

Cannabis allergy is a relatively new phenomenon described in the 1970s. Its increased frequency has been observed over the last years due to the increasing therapeutic and recreational use of cannabis-based products. Sensitization possibly leading to allergy symptoms can occur not only through the smoking of cannabis, but also through ingestion, the inhalation of pollen, or direct contact. The severity of symptoms varies from benign pruritus to anaphylaxis. There is scant information available to support clinicians throughout the entire therapeutic process, starting from diagnosis and ending in treatment. In this review, we present six cases of patients in whom molecular in vitro testing revealed sensitization to cannabis extract and/or cannabis-derived nsLTP molecules (Can s 3). Based on these cases, we raise important questions regarding this topic. The article discusses current proposals and highlights the importance of further research not only on cannabis allergy but also on asymptomatic sensitization to cannabis allergens, which may be ascertained in some percentage of the population.

Numerical and experimental analysis of pollen inhalation exposure in nasal airways following various middle turbinectomy

BackgroundMiddle turbinectomy (MT) has always been controversial. MT significantly alters the anatomy and redistributes the inhaled air. The current study is designed to quantify the effect of MT with varying resection volumes on airflow and associated pollen inhalation exposure characteristics in the nasal airways. MethodsSix realistic models following bilateral comprehensive Functional Endoscopic Sinus Surgery (FESS) deriving from CT images were constructed and their corresponding post-MT models with four types of MT procedures were virtually conducted. Inhalation exposure to pollen particles was simulated by the Computational Fluid-Particle Dynamics (CFPD) approach and validated through in vitro experiments. ResultsFollowing the excision of the middle turbinate, a significant escalation in airflow was observed within the upper-middle region of the nasal cavities. Pollen deposition was observed to be more prominent in the nasal septum, laryngopharynx, and maxillary sinus, varying with the types of MT procedures. Notably, particles with diameters smaller than 50 μm exhibited two distinct “high peaks” and three “small peaks” within the nasal airways. ConclusionMT resulted in increased airflow volume within the upper-middle region of the nasal cavities. Following MT, notable shifts in pollen particle deposition hot spots were observed, transitioning from the nasal vestibule, nasal septum, and middle meatus to the nasal septum and laryngopharynx. These findings are anticipated to contribute valuable perspectives on pollen inhalation exposure risk assessments following diverse MT surgical interventions.

The calcium-antagonist activity of the material released by olive pollen (PMR), tested on Ca2+-cytosolic of PE/CA-PJ15 cells

Inhalation of olive pollen (Olea europaea L.) is one of the main causes of allergy in Mediterranean countries and some areas of North America. The response to allergens consists in the production of inflammatory cytokines which is mediated by the deregulation of Ca2+ signals. In this study, the biological activity of the material released in olive pollen hydration (PMR) was tested on Ca2+ cytosolic of PE/CA-PJ15 cells (PJ-15). Ca2+ cytosolic was determined by fluorometric assay with the cell line PE/CA-PJ15 (PJ-15) labeled with the fluorescent probe FURA 2 AM. The material released in olive pollen hydration (PMR) was analyzed by HPLC for the determination of phenolic acids. PMR was subjected to fractionation by gel filtration, and the fractions with Ca2+-chelating activity were tested with SDS-PAGE and the single bands characterized by proteomic analysis. PMR showed high Ca2+-chelating activity and is able of blocking the increase Ca2+-cytosolic produced by thapsigargin (TG). PMR then restored Ca2+ homeostasis in PJ-15 cells deregulated by the endoplasmic reticulum Ca2+-ATPases inhibitor. It is therefore possible that PMR can antagonize the effects of allergens on Ca2+ cytosolic. The analytical characterization of the material released by the pollen highlighted in the pollen allergen Ole e 3 and in the p-coumaric acid the possible culprits of the Ca2+-antagonist activity of PMR. Furthermore, the sequence of Ole e 3 could provide information for the possible construction of a synthetic peptide to be used in an allergy-targeted Ca2+-antagonist therapy.

Combined synoptic and regional weather patterns affecting atmospheric Poaceae pollen concentrations in Sydney, Australia

Inhalation of grass pollen can result in acute exacerbation of asthma, prompting questions about how grass pollen reaches metropolitan areas. We establish typical atmospheric Poaceae (grass) pollen concentrations recorded at two pollen samplers within the Sydney basin in eastern Australia and analyse their correlation with each other and meteorological variables. We determine the effect of synoptic and regional airflow on Poaceae pollen transport during a period of extreme (≥ 100 grains m−3 air) concentration and characterise the meteorology. Finally, we tested the hypothesis that most Poaceae pollen captured by the pollen samplers originated from local sources. Fifteen months of daily pollen data, three days of hourly atmospheric Poaceae pollen concentrations and fifteen months of hourly meteorology from two locations within the Sydney basin were used. Weather Research Forecasting (WRF), Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) modelling and conditional bivariate probability functions (CBPF) were used to assess Poaceae pollen transport. Most Poaceae pollen collected was estimated to be from local sources under low wind speeds. Extreme daily Poaceae pollen concentrations were rare, and there was no strong evidence to support long-distance Poaceae pollen transport into the Sydney basin or across the greater Sydney metropolitan area. Daily average pollen concentrations mask sudden increases in atmospheric Poaceae pollen, which may put a significant and sudden strain on the healthcare system. Mapping of Poaceae pollen sources within Sydney and accurate prediction of pollen concentrations are the first steps to an advanced warning system necessary to pre-empt the healthcare resources needed during pollen season.

Airborne Pollen Reached Severe Levels During the Spring Season in an Underserved Community with High Asthma rates in Jacksonville Florida

Duval County, Florida is divided into 6 Health Zones. The most urban is Health Zone 1 (HZN1) of which 75% of its 109,314 residents are African Americans. It has the highest rate of asthma related hospitalization of the 6 health zones. During Spring 2013, we showed significant elevation of serum IgE from 200 random residents of the community of which 14% had levels greater than 10,000 ng/ml. Pollen inhalation is a risk factor for allergic conditions. Therefore, we hypothesized that pollen is a contributing factor for the elevated levels of IgE and the high rate of asthma in HZN1.

The comparison between the effect of Glycyrrhizae uralensis (Gan-Cao) and Montelukast on the expression of T-bet and GATA-3 genes in children with allergic asthma.

Pediatric allergic asthma is a chronic disease that affects the lungs and airways. If a child is exposed to certain stimulants such as pollen inhalation, colds, or respiratory infections, the lungs become inflamed and if left untreated can lead to dangerous asthma attacks. One of the most important treatments for this disease is the use of leukotriene modulators, such as montelukast. But recently, due to easier access, cheaper prices and fewer side effects, attention has shifted to non-chemical treatments. Gan-Cao (Glycyrrhizae uralensis), as traditional Chinese medicine, has been proved to have a good therapeutic effect on experimental allergic asthma. But its anti-asthma mechanism is currently unclear. Therefore, the study aimed the comparison between the effect of Gan-Cao and montelukast on the expression of T-bet and GATA-3 genes in children with allergic asthma. For this purpose, fifty children with allergic asthma were divided into two groups. The first group was treated with montelukast for one month. The second group was treated with Gan-Cao root extract. Then the peripheral blood mononuclear cells were isolated, their RNA was extracted, and the relative expression of T-bet and GATA3 transcription factors was evaluated by Real-time PCR. The relationship between them and risk factors for asthma was assessed by relevant statistical tests. The result showed the expression of the GATA3 gene (P = 0.102), T-bet gene (P = 0.888), and the expression ratio of T-bet/GATA-3 genes (P = 0.061) was not significantly different between the two groups. It showed that Gan-Cao can affect the expression of these genes just as much as montelukast. Therefore, this Chinese herb can be used as an alternative or supplement medicine to treat allergic asthma in children.

Pollen antigens and atmospheric circulation driven seasonal respiratory viral outbreak and its implication to the Covid-19 pandemic

The patterns of respiratory virus illness are expressed differently between temperate and tropical climates. Tropical outbreaks often peak in wet seasons. Temperate outbreaks typically peak during the winter. The prevailing causal hypotheses focus on sunlight, temperature and humidity variations. Yet no consistent factors have been identified to sufficiently explain seasonal virus emergence and decline at any latitude. Here we demonstrate close connections among global-scale atmospheric circulations, IgE antibody enhancement through seasonal pollen inhalation, and respiratory virus patterns at any populated latitude, with a focus on the US. Pollens emerge each Spring, and the renewed IgE titers in the population are argued to terminate each winter peak of respiratory illness. Globally circulated airborne viruses are postulated to subsequently deposit across the Southern US during lower zonal geostrophic winds each late Summer. This seasonally refreshed viral load is postulated to trigger a new influenza outbreak, once the existing IgE antibodies diminish to a critical value each Fall. Our study offers a new and consistent explanation for the seasonal diminishment of respiratory viral illnesses in temperate climates, the subdued seasonal signature in the tropics, the annually circulated virus phenotypes, and the northerly migration of influenza across the US every year. Our integrated geospatial and IgE hypothesis provides a new perspective for prediction, mitigation and prevention of the outbreak and spread of seasonal respiratory viruses including Covid-19 pandemic.

Allelic variation of gliadin-encoding genes in a collection of tetraploid wheat genotypes

Wheat is one of the main crops bred worldwide. Durum wheat, specifically, is a key element of the Mediterranean diet, representing an élite crop grown in Italy. Durum wheat nutritional and technological values are largely due to the grain protein content (GPC), a complex genetic trait strongly affected by environmental factors and management practices. In the last decades, several breeding programs have been focused on improving GPC by both traditional and innovative approaches. Among seed storage proteins, prolamins, including both gliadins and glutenins, represent the major component. These two classes of proteins are indeed responsible of gluten formation and confer the extensibility and elasticity to the dough. Besides being of crucial importance for both technological properties and rheological characteristics, prolamins, and especially gliadins, have been found to be major triggers for human health, as involved in a number of wheat consumption-related conditions, such as the celiac disease, non-celiac gluten sensitivity, defined as the onset of a variety of manifestations related to wheat, rye and barley ingestion, and wheat allergies, both due to wheat ingestion or inhalation (of flour or pollen). The identification of loci responsible for the gliadin expression, and particularly of polymorphism in the aforementioned genes, which could result in a lower immunogenic/toxic potential, could be of great importance in breeding programs. For this purpose, we screened a collection of tetraploid wheat genotypes for allelic variants of annotated gliadin genes in the durum wheat genome, in order to identify genetic resources available to breeders to improve wheat nutritional and technological properties. Phylogenetic analysis among different species of Triticum genus and an in silico expression data analysis may also be useful in the exploitation of the complex scenario of gliadin–glutenin interaction and gluten role in the adverse reactions due to wheat consumption.

Cari p 1, a Novel Polygalacturonase Allergen From Papaya Acting as Respiratory and Food Sensitizer.

Papaya has been reported to elicit IgE-mediated hypersensitivity via pollen inhalation and fruit consumption. Certain papaya sensitive patients with food allergy were found to experience recurrent respiratory distresses even after quitting the consumption of fruits. This observation prompted us to investigate the allergens commonly present in fruits and pollen grains of papaya. A discovery approach consisting of immunoproteomic detection followed by molecular characterization led to the identification of a novel papaya allergen designated as Cari p 1. This allergen was detected as a 56 kDa IgE-reactive protein from pollen as well as fruit proteome through serological analysis. The protein was identified as an endopolygalacturonase by tandem mass spectrometry. Full length Cari p 1 cDNA was isolated from papaya pollen, cloned in expression vector, and purified as recombinant allergen. The recombinant protein was monomeric and displayed pectinolytic activity. Recombinant Cari p 1 reacted with IgE-antibodies of all the papaya sensitized patient sera. In addition to IgE-reactivity, rCari p 1 displayed allergenic activity by stimulating histamine release from IgE-sensitized granulocytes. CD-spectroscopy of rCari p 1 revealed the presence of predominantly β-sheet characters. The melting curve of the allergen showed partial refolding from a fully denatured state indicating the possible presence of conformational IgE-epitopes characteristic of inhalant allergens in addition to the linear IgE-epitopes of food allergens. The expression of this allergen in papaya fruits was detected by immunoblot with anti-Cari p 1 rabbit IgG and reconfirmed by PCR. In an in vivo mouse model, rCari p 1 exhibited a comparable level of inflammatory responses in the lung and duodenum tissues explaining the dual role of Cari p 1 allergen in respiratory sensitization via pollen inhalation and sensitization of gut mucosa via fruit consumption. Purified rCari p 1 can be used a marker allergen for component-resolved molecular diagnosis. Further immunological studies on Cari p 1 are warranted to design immunotherapeutic vaccine for the clinical management of papaya allergy.

Problems related to mask use in hay fever sufferers by repeated surveys

PurposeMany Japanese hay fever (HF) sufferers wear a hygienic face mask to prevent pollen inhalation, but most find it very uncomfortable. The purpose of this paper is to identify the problems associated with mask wearing through repeated surveys. This information can be used in the improved design of a hygienic face mask that can be worn without discomfort by HF sufferers.Design/methodology/approachIn 2009 (n=1,519), 2012 (n=2,994), and 2015 (n=3,213), repeated surveys of university students were conducted. HF sufferers were queried regarding symptoms, countermeasures, and problems associated with wearing a hygienic face mask. Holistic perspectives for each year were obtained by a co-occurrence analysis of the aggregated data. The triplet co-occurrence of specific problems was compared among the surveys using the χ2 test. Temporary and contemporary co-occurrence relationships were also determined.FindingsMost Japanese university students with HF wore a hygienic face mask. In each survey, the most common problems associated with mask use were related to its thermal, hygroscopic, and air-flow properties. Contemporary problems with co-occurrence relationships were “humidity,” “breathing difficulty,” and “mist over eyeglasses” for males and, “humidity,” “breathing difficulty,” and “make-up coming off” for females.Originality/valueThe results of this study will contribute to improving hygienic face mask design. The co-occurrence of contemporary problems related to mask use was identified by comparing the results obtained in each year. The thermal, hygroscopic, and air flow properties of the mask cause these problems, and the air gap between the mask and the wearer’s face influences the inherent physical properties of the mask. To measure the air gap, a suitable hydrostatic pressure-balanced experimental method was applied, and the data were demonstrated experimentally.

Cry1Ab protein from Bacillus thuringiensis and MON810 cry1Ab-transgenic maize exerts no adjuvant effect after airway exposure.

The genetically modified (GM) maize event MON810 has been inserted with a processed version of the transgene, cry1Ab, derived from the soil bacterium Bacillus thuringiensis (Bt) to express proteins with insecticidal properties. Such proteins may introduce new allergens and also act as adjuvants that promote allergic responses. While focus has been on safe consumption and hence the oral exposure to GM food and feed, little is known regarding inhalation of pollen and desiccated airborne plant material from GM crops. The aim of this study was to investigate whether plant material from the Cry1Ab-expressing maize variety MON810, or trypsin-activated Cry1Ab (trypCry1Ab) protein produced in recombinant bacteria, may act as adjuvants against the allergen ovalbumin (OVA) in a mouse model of airway allergy. A clear proallergic adjuvant effect of the mucosal adjuvant cholera toxin (CT) was demonstrated, determined as increased specific IgE, eosinophils and Th2 cytokines in MLN cell supernates, while no elevation in OVA-specific antibodies or cytokine release from MLN cells after stimulation with OVA were observed in mice receiving Cry1Ab-containing plant materials or the trypCry1Ab protein. Our data suggest that Cry1Ab proteins had no detectable systemic adjuvant effect in mice after airway exposure. Further experiments with purified plant proteins, as well as long-term exposures needs be conducted to further evaluate exposures experienced in real-life situations.

Humoral and cellular immune responses in mice after airway administration of Bacillus thuringiensis Cry1Ab and MON810 cry1Ab-transgenic maize

Genetically modified (GM) crops may bring new proteins with immunogenic and allergenic properties into the food and feed chains. The most commonly grown GM maize, MON810, expresses a modified version of the insecticidal Cry1Ab protein originating in the soil bacterium Bacillus thuringiensis (Bt). Immune reactions following inhalation of pollen and debris from such plants have been scarcely studied. We exposed BALB/c mice to purified Cry1Ab proteins and Cry1Ab-containing MON810 plant materials by intranasal installation. No anti-Cry1Ab antibodies were detected following exposure to the plant materials. Exposure to purified Cry1Ab resulted in specific anti-Cry1Ab IgG1 and IgE production, indicating inherent immunogenicity and allergenicity. Mice exposed to leaf extracts from both MON810 and unmodified maize demonstrated influx of lymphocytes and eosinophils in the broncho-alveolar lavage, and increased cytokine release in mediastinal lymph node cells. The results indicate that the airway exposure to Cry1Ab proteins may be a route of practical relevance.

From pollinosis to digestive allergy

Pollinosis is defined as the appearance of respiratory symptoms (rhinoconjunctivitis and/or asthma) as a result of the inhalation of pollen to which the individual is sensitized. Pollen allergy becomes all the more relevant on taking into account that it may be responsible for the development of plant food allergy, or may even constitute the direct cause of esophageal, gastric and/or intestinal inflammation in the context of a digestive allergic process. Pollen can act as a source of allergens that induce primary sensitization in the host as a result of inhalation, with secondary allergy to plant foods containing shared allergens via a cross-reactivity mechanism. The observed pattern of plant food allergy depends on the dietary habits of the population in a given geographical setting, and on the pollination found in that setting. Pollinosis may account for the greater or lesser prevalence of allergy to certain plant foods, and for the severity of the associated reactions. Beyond the digestive tract inflammation that may result from allergy to a given food, pollinosis is also intrinsically able to generate a clinically relevant or irrelevant Th2-mediated inflammatory response at digestive level, and may even give rise to eosinophilic esophagitis. Inter-relation with the airway may also extend to the digestive tract as a consequence of the systemic response that characterizes allergic disease.

Identification of allergenic pollen grains in 36 olive (Olea europaea) cultivars grown in Jordan

Inhalation of olive pollen is a major cause of allergic respiratory diseases in Mediterranean region. Using bags attached to the branches, pollens were collected from 36 olive cultivars grown in Jordan just before bloom. Proteins were extracted from pollens and analysed by SDS-PAGE and immunoblotting using antisera collected from patients with history of olive pollen-allergy. Immunoblot results showed that 25 cultivars contained one or two allergenic proteins in the range of 15–72 kDa with majority of the proteins corresponding to 15–20 kDa, while remainders did not exhibit any allergenic protein. Seven cultivars exhibited three allergenic proteins and only two cultivars exhibited four allergenic proteins and thus, were considered potentially hyperallergenic cultivars. This study highlights the great variability in the antigenic and allergenic composition of Olea europaea pollen extracts which may serve as guidance for selecting the olive tree cultivars that could be planted in urban areas.

Oral exposure to Mal d 1 affects the immune response in patients with birch pollen allergy

Antibodies and T cells specific for the major birch pollen allergen Bet v 1 cross-react with structurally related food allergens, such as Mal d 1 in apple. We sought to evaluate the effects of oral uptake of Mal d 1 on the allergen-specific immune response in patients with birch pollen allergy. Patients received 50 μg of rBet v 1 sublingually on 2 consecutive days outside of the birch pollen season. One year later, equal amounts of rMal d 1 were administered. Blood samples were collected before and after oral exposure, as well as before and after the intermediate birch pollen season. Allergen-specific IgE levels were determined by using ImmunoCAP. Proliferation of allergen-stimulated PBMCs was assessed, as well as the expression of IL-5, IL-13, IL-10, IFN-γ, and forkhead box protein 3 (Foxp3) in isolated T cells (real-time PCR). Allergen-specific T-cell lines were analyzed for epitope recognition. Orally administered Bet v 1 transiently reduced Bet v 1-specific serum IgE levels, as well as Bet v 1- and Mal d 1-induced T-cell proliferation, and enhanced the expression of IL-5, IL-10, and Foxp3. Orally applied Mal d 1 significantly decreased Bet v 1- and Mal d 1-specific IgE levels and induced IL-5 and IL-10 but no Foxp3 expression. In contrast to Bet v 1, Mal d 1 triggered IFN-γ production and T cells with a different epitope repertoire. Inhalation of birch pollen significantly enhanced allergen-specific IgE levels, T-cell proliferation, and IL-5, IL-10, IL-13, and Foxp3 expression. Two sublingual administrations of 50 μg of Mal d 1 were well tolerated and induced transient immune responses seen during peripheral tolerance development. Thus recombinant Mal d 1 might be suitable and relevant for sublingual treatment of birch pollen-related apple allergy.

A Case of Occupational Rhinitis Induced by Maize Pollen Exposure in a Farmer: Detection of IgE-Binding Components

Corn is a major staple food, along with rice and wheat, in many parts of the world. There are several reports of hypersensitivity to maize pollen. However, cases of occupational allergic rhinitis induced by inhalation of maize pollen are very rare. We herein report the case of a 67-year-old male with occupational rhinitis caused by occupational exposure to maize pollen in a cornfield. He showed positive responses to maize pollen, as well as grass pollens, in skin prick tests. A high level of serum immunoglobulin E (IgE) specific to maize pollen extracts was detected by an enzyme-linked immunosorbent assay (ELISA). Laboratory tests showed a high serum level of total IgE (724 kU/L) and a high level of IgE specific to maize pollen (8.32 kU/L) using the Immuno-CAP system. Occupational rhinitis was confirmed by a nasal provocation test with maize pollen extracts. IgE ELISA inhibition tests showed antibody cross-reactivity between maize pollen and grass pollen extracts. IgE immunoblotting using maize pollen extracts demonstrated a 27 kDa IgE-binding component. These findings suggest that maize pollen can induce IgE-mediated occupational rhinitis in exposed workers.

Omega-3 polyunsaturated fatty acids and bronchial inflammation in grass pollen allergy after allergen challenge

RATIO: Asthma is a major public health problem, with bronchial inflammation as the therapeutic target. The role of dietary fish oil derived polyunsaturated fatty acids (PUFAs) in allergic inflammation is controversial. Most asthmatics suffer from mild disease and non-pharmacologic interventions are attractive. This study investigates the anti-inflammatory potential of nutritional PUFAs in an experimentally induced bronchial inflammation. We examined 38 grass pollen allergic asthmatics and 19 controls. History of dietary PUFA intake was compared with levels of PUFAs in erythrocyte membranes, and stratified according to low (25th quartile; Q25) and high (75th quartile; Q75) ratios of omega-3 (n-3) to omega-6 (n-6) PUFAs as a surrogate for anti-inflammatory (Q75) or proinflammatory (Q25) effects. Bronchial inflammation was simulated with one-step inhalation of grass pollen. Bronchial response (exhaled nitric monoxide, eNO as surrogate for inflammation, decrease of FEV(1)) was correlated with levels of PUFAs in erythrocyte membranes. Ratios of n-3/n-6 PUFA were significantly lower in asthmatics than in healthy controls. Levels of eNO were significantly higher in Q25 asthmatics than in Q75 asthmatics (p=0.040). There was a trend of higher bronchial hyperreactivity in Q25 asthmatics (median PD(20) 0.27 vs. 0.14; n.s.), induced by specific bronchial challenge with grass pollen (FEV(1) decrease 16.7 vs. 23.1%; n.s.). When stratifying for erythrocyte membrane PUFA content as a surrogate for alimentary intake, we found mild effects on bronchial allergic inflammation. Future intervention studies with pharmacological PUFA doses appear suitable to clarify dietary PUFA role as an adjunctive intervention to the established treatment of asthma. ClinicalTrials.gov No. NCT00519740.

Involvement of kinins and tachykinins in the development of nasal hyperresponsiveness in a guinea pig pollinosis model

Although it has been suggested that kinins and tachykinins may be involved in the pathogenesis of allergic rhinitis, inhibitors of these mediators have not yet to be developed for use as therapeutic drugs. Therefore, this study examined whether kinins and tachykinins are involved in the induction of nasal symptoms in a guinea pig pollinosis model.Sensitized guinea pigs were challenged by forced inhalation of pollen once a week. Sneezing and nasal blockage were observed after pollen challenges. Nasal hyperresponsiveness to an intranasal application of leukotriene (LT) D4 was assessed 2 days after an antigen challenge.Neither bradykinin receptor (B1 and B2) antagonists nor tachykinin receptor (NK1 and NK2) antagonists inhibited sneezing and nasal blockage. In contrast, these antagonists significantly suppressed the development of nasal hyperresponsiveness. An especially strong inhibition was noted for the B2 receptor and the NK2 receptor antagonists. Furthermore, exogenous intranasal instillation of kinins (bradykinin and des-Arg10-kallidin) and tachykinins (neurokinin A and substance P) produced nasal hyperresponsiveness that was similar to the antigen-antibody reaction. On the other hand, immediately after a pollen challenge, an increase was noted in the amount of bradykinin in the nasal cavity lavage fluid, followed by elevation of tachykinin levels.These results indicate that kinins and tachykinins mediate the development of nasal hyperresponsiveness by preferentially activating B2 and NK2 receptors. Therefore, these receptor antagonists may prove effective in the treatment of allergic rhinitis.

Experimental and seasonal exposure to birch pollen in allergic rhinitis and allergic asthma with regard to the inflammatory response

Seasonal allergy is an interesting model to study the pathophysiological mechanisms involved in allergic inflammation. However, experimental allergen exposure is easier to perform and standardise. The primary aim of this study was to compare the inflammatory responses to high-dose bronchial challenge and natural exposure during birch pollen season. The second aim was to compare the responses of patients with allergic rhinitis and allergic asthma, respectively to both types of allergen exposure. Fifteen birch pollen-allergic patients (seven with asthma and eight with rhinitis) and five healthy individuals were studied during pollen season and after challenge with birch allergen. Symptoms, medication and peak expiratory flow rate (PEFR) were recorded, and blood samples, spirometry and induced sputum were analysed during season and after challenge. Patients with allergic asthma demonstrated a greater bronchial responsiveness to bronchial provocation with birch allergen than patients with rhinitis (P = 0.04) whereas no difference was found regarding nasal challenge. No significant association was found between the level of responsiveness and the inflammatory response after seasonal exposure. Seasonal exposure was related to a more marked systemic inflammatory blood-eosinophil increase than bronchial challenge [(median) (0.25 vs 0.11 x 109/L, P = 0.03)] and after nasal challenge, respectively [(median) (0.25 vs 0.04 x 109/L, P = 0.003)]. A significant correlation in eosinophil cationic protein in induced sputum was found between the experimental and seasonal exposure (rho = 0.62, P = 0.02). Bronchial allergen challenge with inhalation of birch pollen gives a similar inflammatory response in the airway but less systemic inflammation than seasonal exposure in birch pollen allergic patients with asthma and rhinitis.

Important roles of tachykinins in the development of allergic nasal hyperresponsiveness in guinea‐pigs

Although it has been suggested that the use of tachykinin receptor antagonists might prove to be an effective treatment for allergic rhinitis (AR), they are not used clinically. Therefore, we decided to examine the effects of tachykinin receptor antagonists on AR symptoms in an appropriate experimental model. To evaluate newly developed tachykinin receptor antagonists in a Japanese cedar pollen-induced AR model and to determine their effect on allergen-induced sneezing, nasal blockage, and nasal hyperresponsiveness (NHR). Sensitized guinea-pigs were challenged by forced inhalation of pollen once every week. Sneezing and nasal blockage were observed after pollen challenges. NHR (nasal blockage) to an intranasal application of leukotriene D(4) was assessed 2 days after an antigen challenge. We also evaluated whether intranasal dosing with a tachykinin causes NHR. NK(1) and NK(2) receptor antagonists were administered before an intranasal treatment with antigen or tachykinin. Amounts of tachykinins present in nasal cavity lavage fluid were measured by an enzyme immunoassay. Although an NK(1) and NK(2) receptor dual antagonist showed no effect on pollen-induced sneezing and biphasic nasal blockage, it did completely suppress the development of NHR. Experiments using specific NK(1) or NK(2) receptor antagonists revealed that NK(2) receptor activation was preferentially involved in the development of hyperresponsiveness. Increases in the levels of substance P (SP) and neurokinin A (NKA) in the nasal tissue were noted 20 min-1 h after the challenge. Intranasal instillation of either SP or NKA-induced NHR, which was almost completely inhibited by NK(2) receptor antagonists and partially inhibited by NK(1) receptor antagonists. SP and NKA, which are released early after the challenge, mediate the development of NHR by preferentially activating NK(2) receptors. Therefore, NK(2) receptor antagonists might prove to be effective treatment of AR.