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Allergen Exposure (allergen + exposure)
Selected AbstractsIgE-Mediated Asthma and Rhinitis I: A Role of Allergen Exposure?BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 5 2002Gunnar D. Nielsen The IgE antibodies and associated cellular responses are responsible for the allergic airway diseases, allergic rhinitis and allergic asthma, which are increasing in societies with Western life style. Aeroallergens may have different potential to sensitize exposed subjects. Thus, there are only a limited number of important groups of aeroallergens, which are those from house dust mites, cockroaches, pets, pollens, and moulds. Allergy follows to a certain extent the pharmacological/toxicological paradigm of dose-response relationship. Unlike effects of pharmacologically and toxicologically active substances, allergens elicit their adverse effects in a two-stage process. In the first stage the immunologically naļve individual is sensitized to the allergen. In the second stage renewed exposure to the allergen elicits the disease response. Also, high concentrations of aeroallergens may induce immunological tolerance. The scientific literature suggests that many environmental factors contribute to the increase in sensitization and development of airway allergies. Nevertheless, the dose-response relationships apply (within certain limits) both to the sensitization itself and to the exacerbation of the diseases. This suggest that exposure reduction may be one of the methods for reduction of risk, in relation to control of the allergic airway diseases. [source] Environment and prednisone interactions in the treatment of recurrent airway obstruction (heaves)EQUINE VETERINARY JOURNAL, Issue 5 2000C. A. Jackson Summary Recurrent airway obstruction (RAO) or heaves is a manifestation of a hypersensitivity to dust, moulds, and spores in the environment of a susceptible horse. Although in the majority of RAO-affected horses, clinical remission can be achieved by keeping horses at pasture to reduce their allergen exposure, this often is not practicable. For this reason, we investigated if changing the environment of a single stall in a 4 stall stable was sufficient to improve lung function and reduce inflammation in RAO-affected horses. In addition, we determined if addition of oral prednisone provided additional benefit. Twelve RAO-susceptible horses were stabled, fed hay, and bedded on straw until they developed airway obstruction. At this point, bedding was changed to wood shavings and they were fed a pelleted diet for 2 weeks. Lung function was measured and bronchoalveolar lavage was performed before and 3, 7, and 14 days after environmental modification. In a crossover design, horses were treated for the 14 days with prednisone tablets (2.2 mg/kg bwt, q. 24 h). Horses then returned to pasture for 30 days. Airway obstruction was greatest before environmental modification. Significant improvement in lung function occurred within 3 days of the change in environment and continued to Day 7. Airway function was best after 30 days at pasture. The clinical response achieved by environmental modification was not significantly improved by addition of oral prednisone. The total number of cells, total neutrophils, and percent neutrophils was greatest before environmental modification. In the absence of prednisone, total and percent neutrophils did not decrease until Day 14 and total cell number until 30 days at pasture. In the presence of prednisone, total cells and total and percent neutrophils decreased by Day 3 and again at pasture. The fact that lung function can be improved within 3 days by environmental management alone emphasises the need for allergen reduction as the cornerstone of treatment of RAO. Although prednisone induced a more rapid reduction in airway inflammation, this was not associated with a more rapid improvement in airway function. [source] A novel model of sensitization and oral tolerance to peanut proteinIMMUNOLOGY, Issue 3 2004Jessica Strid Summary The prevalence of food allergic diseases is rising and poses an increasing clinical problem. Peanut allergy affects around 1% of the population and is a common food allergy associated with severe clinical manifestations. The exact route of primary sensitization is unknown although the gastrointestinal immune system is likely to play an important role. Exposure of the gastrointestinal tract to soluble antigens normally leads to a state of antigen-specific systemic hyporesponsiveness (oral tolerance). A deviation from this process is thought to be responsible for food-allergic diseases. In this study, we have developed a murine model to investigate immunoregulatory processes after ingestion of peanut protein and compared this to a model of oral tolerance to chicken egg ovalbumin (OVA). We demonstrate that oral tolerance induction is highly dose dependent and differs for the allergenic proteins peanut and OVA. Tolerance to peanut requires a significantly higher oral dose than tolerance to OVA. Low doses of peanut are more likely to induce oral sensitization and increased production of interleukin-4 and specific immunoglobulin E upon challenge. When tolerance is induced both T helper 1 and 2 responses are suppressed. These results show that oral tolerance to peanut can be induced experimentally but that peanut proteins have a potent sensitizing effect. This model can now be used to define regulatory mechanisms following oral exposure to allergenic proteins on local, mucosal and systemic immunity and to investigate the immunomodulating effects of non-oral routes of allergen exposure on the development of allergic sensitization to peanut and other food allergens. [source] Treatment principles of atopic dermatitisJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 1 2002K. Thestrup-Pedersen Abstract Atopic dermatitis (AD) is today the most common, chronic inflammatory skin disease among children in developed countries. Its cumulative prevalence varies from 20% in northern Europe and the USA to approximately 5% in Mediterranean countries. As a chronic disease it puts a special demand on treatment. There is no curative therapy, but competent guidance on treatment principles can control the disease in most, if not all children. This article summarizes the evidence-based knowledge that relates to the treatment of atopic eczema. It also gives advice and opinions on prophylactic measures as these are the focus of interest from most parents. Learning objective This article should enable you to give advice and guidance to parents of children with AD, including what is necessary for diagnosis, what is of value and importance considering allergies and allergological investigations, allergen exposure, prophylactic measures, diets and indoor environment. Finally, you should be able to explain the diversity of treatment principles for parents. [source] The allergen Bet v 1 in fractions of ambient air deviates from birch pollen countsALLERGY, Issue 7 2010J. T. M. Buters To cite this article: Buters JTM, Weichenmeier I, Ochs S, Pusch G, Kreyling W, Boere AJF, Schober W, Behrendt H. The allergen Bet v 1 in fractions of ambient air deviates from birch pollen counts. Allergy 2010; 65: 850,858. Abstract Background:, Proof is lacking that pollen count is representative for allergen exposure, also because allergens were found in nonpollen-bearing fractions of ambient air. Objective:, We monitored simultaneously birch pollen and the major birch pollen allergen Bet v 1 in different size fractions of ambient air from 2004 till 2007 in Munich, Germany. Methods:, Air was sampled with a ChemVol® high-volume cascade impactor equipped with stages for particulate matter (PM)>10 ,m, 10 ,m>PM>2.5 ,m, and 2.5 ,m>PM>0.12 ,m. Allergen was determined with a Bet v 1-specific ELISA. Pollen count was assessed with a Burkard pollen trap. We also measured the development of allergen in pollen during ripening. Results:, About 93 ± 3% of Bet v 1 was found in the PM,>,10 ,m fraction, the fraction containing birch pollen. We did not measure any Bet v 1 in 2.5 ,m,>,PM,>,0.12 ,m. Either in Munich no allergen was in this fraction or the allergen was absorbed to diesel soot particles that also deposit in this fraction. Pollen released 115% more Bet v 1 in 2007 than in 2004. Also within 1 year, the release of allergen from the same amount of pollen varied more than 10-fold between different days. This difference was explained by a rapidly increasing expression of Bet v 1 in pollen in the week just before pollination. Depending on the day the pollen is released during ripening, its potency varies. Conclusion:, In general, pollen count and allergen in ambient air follow the same temporal trends. However, because a 10-fold difference can exist in allergen potency of birch pollen, symptoms might be difficult to correlate with pollen counts, but perhaps better with allergen exposure. [source] Time-series nasal epithelial transcriptomics during natural pollen exposure in healthy subjects and allergic patientsALLERGY, Issue 2 2010P. Mattila To cite this article: Mattila P, Renkonen J, Toppila-Salmi S, Parviainen V, Joenväärä S, Alff-Tuomala S, Nicorici D, Renkonen R. Time-series nasal epithelial transcriptomics during natural pollen exposure in healthy subjects and allergic patients. Allergy 2010; 65: 175,183. Abstract Background:, The role of epithelium has recently awakened interest in the studies of type I hypersensitivity. Objective:, We analysed the nasal transcriptomics epithelial response to natural birch pollen exposure in a time series manner. Methods:, Human nasal epithelial cell swabs were collected from birch pollen allergic patients and healthy controls in winter season. In addition, four specimens at weekly intervals were collected from the same subjects during natural birch pollen exposure in spring and transcriptomic analyses were performed. Results:, The nasal epithelium of healthy subjects responded vigorously to allergen exposure. The immune response was a dominating category of this response. Notably, the healthy subjects did not display any clinical symptoms regardless of this response detected by transcriptomic analysis. Concomitantly, the epithelium of allergic subjects responded also, but with a different set of responders. In allergic patients the regulation of dyneins, the molecular motors of intracellular transport dominated. This further supports our previous hypothesis that the birch pollen exposure results in an active uptake of allergen into the epithelium only in allergic subjects but not in healthy controls. Conclusion:, We showed that birch pollen allergen causes a defence response in healthy subjects, but not in allergic subjects. Instead, allergic patients actively transport pollen allergen through the epithelium to tissue mast cells. Our study showed that new hypotheses can arise from the application of discovery driven methodologies. To understand complex multifactorial diseases, such as type I hypersensitivity, this kind of hypotheses might be worth further analyses. [source] Efficacy of desloratadine in intermittent allergic rhinitis: a GA2LEN studyALLERGY, Issue 10 2009J. Bousquet Background:, The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines proposed a classification for allergic rhinitis based on the duration of symptoms (intermittent, persistent) rather than on the time of allergen exposure (seasonal, perennial). There is no placebo-controlled, randomized clinical trial on intermittent allergic rhinitis (IAR) to date. Desloratadine (DL) is recommended for the first-line treatment of seasonal and perennial allergic rhinitis. Objectives:, To assess the efficacy and safety of DL in subjects with IAR based on the ARIA classification. Methods:, Patients over 12 years of age with IAR were assessed over 15 days of treatment with DL 5 mg once daily (n = 276) or placebo (n = 271). The primary endpoint was the AM/PM reflective total 5 symptom score (T5SS). Secondary endpoints included AM/PM instantaneous T5SS and individual symptoms, therapeutic response, symptom severity by visual analogue scale, and quality-of-life. Results:, The mean reduction of AM/PM reflective T5SS was significantly greater with DL than with placebo over 15 days (,3.01 vs,2.13, P < 0.001) and on each individual day (P < 0.05). Mean AM instantaneous T5SS was reduced significantly with DL compared to placebo as early as day 2 (,1.84 vs,0.89; P < 0.001). The therapeutic response and improvement in quality-of-life were significantly greater with DL than with placebo (P < 0.001 for each). The frequency of treatment-related adverse events was low and similar between DL (7.2%) and placebo (7.0%). Conclusions:, This is the first large trial to show that treatment can be effective in IAR. Desloratadine was effective and safe. [source] Early production of thymic stromal lymphopoietin precedes infiltration of dendritic cells expressing its receptor in allergen-induced late phase cutaneous responses in atopic subjectsALLERGY, Issue 7 2009C. J. Corrigan Background:, Thymic stromal lymphopoietin (TSLP) is an interleukin (IL)-7-like cytokine that triggers dendritic cell-mediated T helper (Th)2 inflammatory responses through a receptor consisting of a heterodimer of the IL-7 receptor alpha (IL-7R,) chain and the TSLP receptor (TSLPR), which resembles the cytokine receptor common gamma chain. Dendritic cells activated by TSLP prime development of CD4+ T cells into Th2 cells contributing to the pathogenesis of allergic inflammation. We hypothesized that allergen exposure induces expression of TSLP and results in recruitment of TSLPR bearing cells in the cutaneous allergen-induced late-phase reaction (LPR) in atopic subjects. Methods:, Skin biopsies were obtained from atopic subjects (n = 9) at various times after cutaneous allergen challenge. In situ hybridization and immunohistochemistry were used to determine TSLP mRNA expression and to measure infiltration of TSLPR+ DC in skin LPR. RT-PCR and flow cytometry were employed to analyse TSLPR expression on isolated blood DC. Results:, Allergen-induced skin TSLP expression occurred as early as 1 h after allergen challenge, whereas TSLPR+ and CD11c+ cells infiltrated relatively late (24,48 h). The majority of TSLPR+ cells were DC co-expressing blood DC antigen-1 (BDCA-1) or BDCA-2. Freshly isolated blood DC expressed both TSLPR and IL-7R, chains. Maturation and stimulation with TSLP or polyriboinosinic,polyribocytidylic acid in vitro upregulated the expression of both TSLPR and IL-7R, chains in DC but not in chemoattractant receptor-homologous molecule expressed on Th2 cells+ CD4+ T cells. Conclusion:, The data suggest that TSLP plays a role in augmenting, through DC recruitment and activation, the development of Th2-type T cells in allergic inflammation. [source] Prolonged antigen-exposure with carbohydrate particle based vaccination prevents allergic immune responses in sensitized miceALLERGY, Issue 6 2009S. Thunberg Background:, Defined particles carrying tightly bound allergens at high density have been suggested as alternatives in allergy vaccination. Carbohydrate based particles (CBP), sized 2 ,m, provide a platform for covalent coupling of allergens. Objective:, To investigate the mechanisms of antigen presentation by CBP, as well as cellular and humoral responses after vaccination with the major cat allergen Fel d 1, covalently coupled to CBP. Methods:, Mice (n = 10/group) were subcutaneously vaccinated with CBP-rFel d 1, CBP or phosphate buffer saline (PBS) before sensitization with rFel d 1 and challenged with cat dander extract. Fluorescent and 75Se-radiolabeled tracking of allergens and particles were performed with flow cytometry and whole-body autoradiography. Humoral, cellular and regulatory immune responses were analyzed by ELISA and flow cytometry. Cytokines were measured in bronchoalveolar lavage fluid and splenocyte cultures. Results:, CBP-rFel d 1 prevented induction of airway inflammation and induced allergen-specific T-cell anergy. CBP-rFel d 1 also induced rapid IgM and IgG1-responses compared with soluble rFel d 1. Particles were phagocytosed by antigen-presenting cells and transported to draining lymph nodes and spleen. Moreover, antigen coupled to CBP remained longer at the injection site compared with alum. Conclusions:, Covalent coupling of rFel d 1 to CBP induces rapid antibody production, prevents induction of allergic immune responses and systemic allergen spreading. Thus, CBP comprise several attractive adjuvant features for use in allergy vaccination. Clinical Implications:, Prolonged allergen exposure through covalent coupling to particles suitable for phagocytosis, provides an adjuvant for safer and efficient allergy vaccination. [source] TRPV1-mediated itch in seasonal allergic rhinitisALLERGY, Issue 5 2009L. Alenmyr Background:, Patients with allergic rhinitis may be abnormally sensitive to stimulation of the ion channel transient receptor potential vanilloid-1 (TRPV1). Aim of the study:, To examine effects of various TRP ion channel activators on sensory symptoms in allergic rhinitis prior to and during seasonal allergen exposure. Methods:, Nasal challenges were carried out with the TRPV1-activators capsaicin, anandamide and olvanil. Moreover, challenges were performed with mustard oil (allylisothiocyanate) and cinnamaldehyde as well as menthol, activators of TRPA1 and TRPM8, respectively. Nasal symptoms were monitored after each challenge and compared with symptoms reported following corresponding sham challenges. Symptoms recorded after challenge prior to pollen season were also compared with challenge-induced symptoms during pollen season. Results:, The TRPV1, TRPA1 and TRPM8-activators produced sensory symptoms dominated by pain and smart. During seasonal allergen exposure, but not prior to season, TRPV1-activators also induced itch. Furthermore, the seasonal challenge to the TRPV1-activator olvanil was associated with rhinorrhoea. Conclusion:, Patients with allergic rhinitis feature an increased itch response to TRPV1 stimulation at seasonal allergen exposure. We suggest that this reflects part of the hyperresponsiveness that characterizes on-going allergic rhinitis. Intervention with the TRPV1-signalling pathway may offer potential treatments of this condition. [source] Immunomodulatory properties of Lactobacillus plantarum and its use as a recombinant vaccine against mite allergyALLERGY, Issue 3 2009P. Rigaux Background:, Selected lactic acid bacteria were reported to prevent atopic dermatitis and experimental asthma but the mechanisms of their immunomodulatory effects are not fully elucidated. In this study, the signaling pathways triggered by Lactobacillus plantarum NCIMB8826 were investigated and the potential use of this strain producing a variant of the mite allergen Der p 1 as live vaccine vehicle was evaluated. Methods:, Mouse bone marrow-derived dendritic cells were stimulated with wild-type or a L. plantarum teichoic acid mutant to evaluate the secretion of cytokines. A recombinant L. plantarum expressing Der p 1 was engineered, its in vitro immunomodulatory properties were characterized and its prophylactic potential was evaluated in a Der p 1-sensitization murine model. Results:, Mouse dendritic cells stimulated by L. plantarum triggered the release of interleukin-10 (IL-10), IL-12 p40, IL-12 p70 and tumor necrosis factor-alpha (TNF-,). IL-12 p40 secretion was dependent on nuclear factor-,B (NF-,B), mitogen-activated protein (MAP) kinases, Toll-like receptor 2 (TLR2), TLR9 and on the bacterial teichoic acid composition. Recombinant L. plantarum producing Der p 1 exhibited similar immunostimulatory properties as wild-type. Prophylactic intranasal pretreatment of mice with this recombinant strain prevented the development of the typical Th2-biased allergic response by a drastic reduction of specific IgE and the induction of protective allergen-specific IgG2a antibodies. Moreover, both wild-type or recombinant L. plantarum reduced airway eosinophilia following aerosolized allergen exposure and IL-5 secretion upon allergen restimulation. Conclusion:, By combining both Th1-type immunostimulatory properties and an efficient allergen delivery capacity, recombinant L. plantarum producing Der p 1 represents a promising vaccine against house dust mite allergy. [source] Nerve growth factor localization in the nasal mucosa of patients with persistent allergic rhinitisALLERGY, Issue 1 2009M. Bresciani Background and objectives:, Nerve growth factor (NGF) and NGF receptors have been shown to be expressed by structural and infiltrating inflammatory cells in the human allergic bronchial mucosa and conjunctiva. In the nose, a positive immunostaining for NGF was recently reported in biopsies of subjects undergoing surgery for refractory nasal obstruction. This study was aimed at studying by immunohistochemistry NGF expression and localization in the nasal mucosa from subjects with moderate/severe persistent allergic rhinitis and natural allergen exposure. Methods:, Immunostaining for NGF, tryptase and eosinophil cationic protein was performed in human nasal turbinate sections of 25 patients affected by persistent allergic rhinitis and sensitization to Dermatophagoides pteronyssinus. Results:, NGF was consistently expressed in the epithelium and in the submucosa of allergic rhinitic subjects, preferentially localized in eosinophils and mast cells. A strong NGF immunostaining was found in mucous cells of the epithelial lining and in the submucosal glands. Conclusions:, As previously shown for allergic asthma and allergic conjunctivitis, NGF is also detectable in the nasal mucosa of patients with persistent allergic rhinitis. The preferential NGF localization in mucous cells of the epithelial lining and in the submucosal glands suggests a possible role for NGF in modulating secretion in allergic rhinitis and possibly other allergic diseases. [source] Dietary intake in sensitized children with recurrent wheeze and healthy controls: a nested case,control studyALLERGY, Issue 4 2006C. S. Murray Background:, The rising prevalence of asthma and allergic disease remains unexplained. Several risk factors have been implicated including diet, in particular poly-unsaturated fats and antioxidant intake. Methods:, A nested case,control study comparing the dietary intake of sensitized children with recurrent wheeze (age 3,5 years) and nonsensitized children who had never wheezed was carried out within an unselected population-based cohort. Cases and controls were matched for age, sex, parental atopy, indoor allergen exposure and pet ownership. Dietary intake was assessed using a validated semi-quantitative food frequency questionnaire and nutrient analysis program. Results:, Thirty-seven case,control pairs (23 male, mean age 4.4 years) participated. Daily total polyunsaturated fat intake was significantly higher in sensitized wheezers (g/day, geometric mean, 95% confidence intervals: 7.1, 6.4,7.9) compared with nonsensitized nonwheezy children (5.6, 5.0,6.3, P = 0.003). Daily omega-3 and omega-6 fat intakes were not significantly different between the two groups. No significant differences were found in intake of any antioxidant or antioxidant cofactors between the groups. Conclusions:, Young sensitized wheezy children had a significantly higher total polyunsaturated fat intake compared with nonsensitized nonwheezy children. However, we were unable to distinguish a significant difference in specific poly-unsaturated fat intakes. Otherwise the children in both groups had a very similar nutritional intake. [source] Allergic rhinitis in the child and associated comorbiditiesPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 1-Part-II 2010Tania Sih Sih T, Mion O. Allergic rhinitis in the child and associated comorbidities. Pediatr Allergy Immunol 2010: 21: e107,e113. © 2009 John Wiley & Sons A/S Allergic rhinitis (AR) typically presents after the second year of life, but the exact prevalence in early life is unknown. AR affects 10,30% of the population, with the greatest frequency found in children and adolescents. It appears that the prevalence has increased in the pediatric population. As the childs' immune system develops between the 1st and 4th yr of life, those with an atopic predisposition begin to express allergic disease with a clear Th2 response to allergen exposure, resulting in symptoms. In pediatric AR, two or more seasons of pollen exposure are generally needed for sensitization, so allergy testing to seasonal allergens (trees, grasses, and weeds) should be conducted after the age of 2 or 3 years. Sensitization to perennial allergens (animals, dust mites, and cockroaches) may manifest several months after exposure. Classification of AR includes measurement of frequency and duration of symptoms. Intermittent AR is defined as symptoms for <4 days/wk or <4 consecutive weeks. Persistent AR is defined as occurring for more than 4 days/wk and more than 4 consecutive weeks. AR is associated with impairments in quality of life, sleep disorders, emotional problems, and impairment in activities such as work and school productivity and social functioning. AR can also be graded in severity , either mild or moderate/severe. There are comorbidities associated with AR. The chronic effects of the inflammatory process affect lungs, ears, growth, and others. AR can induce medical complications, learning problems and sleep-related complaints, such as obstructive sleep apnea syndrome and chronic and acute sinusitis, acute otitis media, serous otitis media, and aggravation of adenoidal hypertrophy and asthma. [source] Messages from the German Multicentre Allergy StudyPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 2002Renate Nickel Several birth cohort studies have been initiated during the past two decades to study environmental and genetic risk factors for atopic dermatitis, asthma and allergic rhinitis. This article summarizes results from the German Multicentre Allergy Study (MAS), which has followed children (initially 1314) from birth (in 1990) to the present time. The effects of immunizations, allergen exposure, early sensitization patterns as well as upper airway infections on the subsequent development of asthma and atopy at school age are described. Furthermore, candidate gene studies of atopic dermatitis and increased total serum IgE levels on chromosomes 5q, 12q and 17q in MAS-children and their parents are outlined. [source] ,Difficult Asthma': Can Symptoms be Controlled in a Structured Environment?PEDIATRIC PULMONOLOGY, Issue 8 2009K. De Boeck MD Abstract Objective Difficult asthma implies persistent asthma symptoms despite therapy with high doses of inhaled corticosteroids. The objective was to evaluate children with difficult asthma in a setting that excludes aggravating factors such as poor treatment adherence and adverse environmental influences. Patients and Methods Sixty children (,6 years) had been referred because of difficult asthma to the rehabilitation centre over a period of 10 years. The diagnosis of poor asthma symptom control was confirmed if exacerbations continued during stay in the centre or if symptoms interfered with daily activities at least 3 times a week. Results The median stay at the centre was 5 months. In four patients a diagnosis other than asthma was made. In five patients symptom control remained difficult. In the remaining 51 children, asthma symptoms became well controlled. Many factors contributed to poor asthma control in the home setting: poor treatment adherence (n,=,32), parental smoking (n,=,22), allergen exposure (n,=,10). Psychosocial problems occurred in 36 children. Contributing factors often co-existed. During stay at the centre, lung function improved in the group with well controlled asthma symptoms (P,<,0.001) but not in the group with continued poor symptom control. In the majority of children who obtained good symptom control, this persisted in the years following discharge. Conclusion Of 60 children referred with a diagnosis of difficult asthma, optimal medical management in a structured environment resulted in good symptom control in 51 patients; symptom control remained poor in 5 patients, a diagnosis other than asthma was made in 4 patients. Pediatr Pulmonol. 2009; 44:743,748. © 2009 Wiley-Liss, Inc. [source] A randomized, double-blind, placebo-controlled exploratory study to evaluate the potential of pycnogenol® for improving allergic rhinitis symptomsPHYTOTHERAPY RESEARCH, Issue 8 2010Dale Wilson Abstract The potential of Pycnogenol® for relieving allergic rhinitis (birch pollen) symptoms was explored in a double-blind, placebo-controlled trial. In 2008 19 subjects started treatment 3 weeks prior to the onset of birch pollen season in Ontario, Canada. While there was an improvement of eye and nasal symptoms with Pycnogenol, there was no significance versus placebo. It was postulated that Pycnogenol may require a lag-time between the start of therapy and the onset of action. Therefore 39 subjects were treated 5,8 weeks prior to the 2009 birch allergy season. The evaluation of subjects in 2009 showed much lower scores for eye (,35%) and nasal (,20.5%) symptoms with Pycnogenol compared with placebo. In succession of the allergy season birch specific IgE increased by 31.9% in the placebo group compared with only 19.4% in the Pycnogenol group. Detailed analysis suggested that symptom-relief was better the longer subjects were on Pycnogenol prior to the allergen exposure. The best results were found with subjects who took Pycnogenol 7,8 weeks ahead of the allergy season. With the limited number of 39 patients statistical predications were unattainable. In conclusion, Pycnogenol improved allergic rhinitis symptoms when supplementation was started at least 5 weeks before the onset of the allergy season. Copyright © 2010 John Wiley & Sons, Ltd. [source] Prolonged Allergen Challenge in Murine Nasal Allergic Rhinitis: Nasal Airway Remodeling and Adaptation of Nasal Airway ResponsivenessTHE LARYNGOSCOPE, Issue 5 2007Muneo Nakaya MD Abstract Background: Nasal airway remodeling exists in allergic rhinitis, but it appears to be far less extensive than in asthma. However, there has been little study about nasal airway remodeling and no study using mice models. It has been reported that airway hyperresponsiveness decreased after prolonged allergen challenge in a chronic murine asthma model together with the progression of remodeling. However, there has been no study of the relation of remodeling and airway responsiveness in nasal allergy. Therefore, we have undertaken this investigation to characterize nasal airway structural changes after prolonged allergen challenge and to examine the relationship between nasal airway hyperresponsivity and remodeling. Methods: We prepared murine allergic rhinitis for ovalbumin. Mice were subsequently challenged three times a week with ovalbumin from day 19 to days 53, 88, and 130. We examined allergen-induced nasal symptoms and objective nasal hyperresponsiveness using the enhanced pause system. Moreover, the pathologic changes were investigated after allergen challenge. Results: The extended allergen challenge protocol caused significant nasal airway remodeling. Specifically, remodeling was characterized by goblet cell hyperplasia and deposition of collagen in the submucosal area. Allergen-induced nasal hyperresponsiveness was first increased but gradually decreased in nasal symptoms and Penh after prolonged allergen challenge. Conclusions: We have demonstrated that a remodeling of nasal mucosa in a murine allergic rhinitis model prolonged allergen exposure. Moreover, prolonged allergen exposure induced a reduction of nasal hyperresponsiveness together with a progression of nasal remodeling. [source] Double-blind placebo-controlled house dust mite control measures in adult patients with atopic dermatitisBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2001C. Gutgesell Background Avoidance of allergens has been shown to be of benefit in patients with atopic asthma sensitized to indoor allergens. In atopic dermatitis, there is so far little information about the effect of house dust mite elimination strategies. Objectives We therefore performed a randomized controlled study of house dust mite control in patients with this disease. Methods Twenty adult patients with moderate to severe atopic dermatitis were included. Inclusion criteria were a positive RAST to house dust mite antigen (CAP class >,3) and a concentration of >,2 µg g,1 of the house dust mite antigen Der p1 in the patient's mattress dust. Patients were randomized to either the active treatment group (allergen-impermeable mattress encasing, acaricide spray containing tannic acid and benzylbenzoate) or a control group (allergen-permeable encasing, spray containing water and traces of ethanol). Severity of disease was estimated every 2 months by an established score (SCORAD), and eosinophil cationic protein (ECP) in the serum was determined by enzyme-linked immunosorbent assay. Furthermore, the use of topical steroids was quantified. Patients assessed daytime pruritus and pruritus-induced sleeplessness weekly on a visual analogue scale. The study lasted 1 year. Results At the end of the study, the active treatment group showed a statistically significant reduction in Der p1 exposure as compared with the control group. However, when comparing the change from the start to the end of the study, there was no statistically significant difference between active treatment and control groups as measured by the SCORAD score and by ECP levels in the serum. Some patients in the active treatment group reported less pruritus-induced sleeplessness, but there was no statistically significant difference between the two treatment groups. Conclusions For adult patients with atopic dermatitis it was shown that 1 year of house dust mite avoidance reduced the allergen exposure, but an improvement of overall disease activity was not demonstrated. [source] Surfactant protein D inhibits mite-induced alveolar macrophage and dendritic cell activations through TLR signalling and DC-SIGN expressionCLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2010C-F Liu Summary Background Surfactant protein D (SP-D), a secreted pattern recognition molecule associated with pulmonary innate immunity, has been shown to mediate the clearance of pathogens in multiple ways. However, how SP-D interacts with alveolar macrophages (AMs) and dendritic cells (DCs) during allergen exposure remains unclear. Objective This study was performed to characterize the immunomodulatory effects of SP-D on mite allergen (Dermatophagoides pteronyssinus, Der p)-induced inflammatory signalling in AMs and DCs. Methods Murine AM, alveolar macrophage cell line derived from BALB/c mice (MH-S cells), and human monocyte-derived dendritic cells (MDDC) were used as model systems. The production of nitric oxide (NO) and TNF-,, expression of surface Toll-like receptors (TLRs), and expression of the C-type lectin receptor known as dendritic cell (DC)-specific ICAM-grabbing non-integrin (DC-SIGN) were measured as a function of pretreatment with SP-D and subsequent exposure to Der p. Der p-dependent cellular activations that were modified by SP-D in these model systems were then identified. Results Pretreatment of MH-S cells with SP-D reduced Der p-dependent production of NO, TNF-,, and the downstream activations of IL-1 receptor-associated kinase, mitogen activated protein kinase (MAPK) kinase, and nuclear factor-,B. SP-D interacted with CD14 such that CD14 binding to Der p was inhibited and Der p-induced signalling via TLRs was blocked. DC-SIGN expression was suppressed by Der p in MH-S and MDDC; this down-regulation of DC-SIGN expression was prevented by pretreatment with SP-D. Conclusions These results indicated that the inhibition of Der p-induced activation of MH-S and MDDC by SP-D is mediated through suppression of the CD14/TLR signalling pathway and maintenance of DC-SIGN expression, which may protect allergen-induced airway inflammation. Cite this as: C-F Liu, M. Rivere, H-J Huang, G. Puzo and J-Y Wang, Clinical & Experimental Allergy, 2010 (40) 111,122. [source] Gene expression studies in cultured dendritic cells: new indicators for the discrimination of skin sensitizers and irritants in vitroCLINICAL & EXPERIMENTAL ALLERGY, Issue 6 2009S. Szameit Summary Background The replacement of animal tests for the detection of the sensitizing potential of chemicals is of great importance due to current legislation. One promising approach for the development of an in vitro assay is the exposure of immature dendritic cells (iDCs) to contact sensitizers and irritants, followed by an analysis of the maturation status of the cells. Objective The aim of this study was to further investigate the performance of our previously developed targeted microarray, the immune toxicity chip. In addition, we aimed to identify new marker genes for the discrimination of allergens and irritants using whole-genome microarrays. Methods Monocyte-derived iDCs were exposed to contact sensitizers and irritants in concentrations resulting in 10,20% cytotoxicity, as determined by dose,response curves. Changes in gene expression were analysed using the immune toxicity chip and a commercially available whole-genome microarray. Results Using the immune toxicity chip, we could identify a panel of marker genes suitable to discriminate strong allergens and irritants. Analysis with the whole-genome array revealed additional genes that are differentially expressed after allergen exposure, but not after irritant exposure. Hierarchical clustering of these genes showed distinct groups representing the different chemicals. Conclusion Here we show that our test system based on an immune-specific microarray is suitable for the discrimination of strong allergens and irritants. Genes detected as differentially expressed with the whole-genome array and previously not connected to the maturation process of DCs might be suitable candidate genes for the identification of weaker sensitizers. [source] Role of STAT6 and SMAD2 in a model of chronic allergen exposure: a mouse strain comparison studyCLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2009J. A. Hirota Summary Background Asthma is a disease characterized by variable and reversible airway obstruction and is associated with airway inflammation, airway remodelling (including goblet cell hyperplasia, increased collagen deposition and increased smooth muscle mass) and increased airway responsiveness. It is believed that airway inflammation plays a critical role in the development of airway remodelling, with IL-13 and TGF-,1 pathways being strongly associated with the disease progression. Mouse models of asthma are capable of recapitulating some components of asthma and have been used to look at both IL-13 and TGF-,1 pathways, which use STAT6 and SMAD2 signalling molecules, respectively. Objectives Using brief and chronic models of allergen exposure, we utilized BALB/c and C57Bl/6 to explore the hypothesis that observed differences in responses to allergen between these mouse strains will involve fundamental differences in IL-13 and TGF-,1 responses. Methods The following outcome measurements were performed: airway physiology, bronchoalveolar lavage cell counts/cytokine analysis, histology, immunoblots and gene expression assays. Results We demonstrate in BALB/c mice an IL-13-dependent phosphorylation of STAT6, nuclear localized in inflammatory cells, which is associated with indices of airway remodelling and development of airway dysfunction. In BALB/c mice, phosphorylation of SMAD2 is delayed relative to STAT6 activation and also involves an IL-13-dependent mechanism. In contrast, despite an allergen-induced increase in IL-4, IL-13 and eosinophils, C57Bl/6 demonstrates a reduced and distinct pattern of phosphorylated STAT6, no SMAD2 phosphorylation changes and fail to develop indices of remodelling or changes in airway function. Conclusion The activation of signalling pathways and nuclear translocation of signalling molecules downstream of IL-13 and TGF-,1 further support the central role of these molecules in the pathology and dysfunction in animal models of asthma. Activation of signalling pathways downstream from IL-13 and TGF-,1 may be more relevant in disease progression than elevations in airway inflammation alone. [source] Cysteinyl leukotrienes: multi-functional mediators in allergic rhinitisCLINICAL & EXPERIMENTAL ALLERGY, Issue 6 2006M. Peters-Golden Summary Cysteinyl leukotrienes (CysLTs) are a family of inflammatory lipid mediators synthesized from arachidonic acid by a variety of cells, including mast cells, eosinophils, basophils, and macrophages. This article reviews the data for the role of CysLTs as multi-functional mediators in allergic rhinitis (AR). We review the evidence that: (1) CysLTs are released from inflammatory cells that participate in AR, (2) receptors for CysLTs are located in nasal tissue, (3) CysLTs are increased in patients with AR and are released following allergen exposure, (4) administration of CysLTs reproduces the symptoms of AR, (5) CysLTs play roles in the maturation, as well as tissue recruitment, of inflammatory cells, and (6) a complex inter-regulation between CysLTs and a variety of other inflammatory mediators exists. [source] The ,microflora hypothesis' of allergic diseasesCLINICAL & EXPERIMENTAL ALLERGY, Issue 12 2005M. C. Noverr Summary Increasingly, epidemiologic and clinical data support the hypothesis that perturbations in the gastrointestinal (GI) microbiota because of antibiotic use and dietary differences in ,industrialized' countries have disrupted the normal microbiota-mediated mechanisms of immunological tolerance in the mucosa, leading to an increase in the incidence of allergic airway disease. The data supporting this ,microflora hypothesis' includes correlations between allergic airway disease and (1) antibiotic use early in life, (2) altered fecal microbiota and (3) dietary changes over the past two decades. Our laboratory has recently demonstrated that mice can develop allergic airway responses to allergens if their endogenous microbiota is altered at the time of first allergen exposure. These experimental and clinical observations are consistent with other studies demonstrating that the endogenous microbiota plays a significant role in shaping the development of the immune system. Data are beginning to accumulate that a ,balanced' microbiota plays a positive role in maintaining mucosal immunologic tolerance long after post-natal development. Other studies have demonstrated that even small volumes delivered to the nasopharynx largely end up in the GI tract, suggesting that airway tolerance and oral tolerance may operate simultaneously. The mechanism of microbiota modulation of host immunity is not known; however, host and microbial oxylipins are one potential set of immunomodulatory molecules that may control mucosal tolerance. The cumulative data are beginning to support the notion that probiotic and prebiotic strategies be considered for patients coming off of antibiotic therapy. [source] Transgenic mice expressing the T cell antigen receptor specific for an immunodominant epitope of a major allergen of house dust mite develop an asthmatic phenotype on exposure of the airways to allergenCLINICAL & EXPERIMENTAL ALLERGY, Issue 7 2005E. R. Jarman Summary Background Current studies on mechanisms underlying allergen-induced pulmonary inflammation and asthma are hampered by the lack of appropriate physiological in vivo models that reflect the natural route of allergen exposure and sensitization. Objective To generate and phenotype a transgenic mouse strain expressing the T cell receptor (TCR) specific for an immunodominant domain of the major inhalant allergen Dermatophagoides pteronyssinus species of house dust mite (Der p 1), for the development of an in vivo model of allergic asthma. Methods Der p 1 transgenic mice were generated using TCR-,, derived from a CD4+ T cell hybridoma reactive with Der p 1 residues p 110,131. The frequency and functional activity of peripheral T cells were determined and parameters of airway inflammation assessed following allergen challenge of the airways with Der p 1. Results CD4+ T cells are functionally active, exhibiting dose-dependent proliferation and IL-4 production on primary stimulation with Der p 1 or Der p 1, p 110,131 in vitro, independent of in vivo antigen priming. On sensitization of the airways with allergen, in the absence of systemic priming or the application of adjuvants, the TCR transgenic mice develop airway inflammation characterized by a marked lymphocytic and eosinophilic infiltrate with goblet cell hyperplasia and enhanced mucin production. Conclusion The Der p 1 TCR transgenic mice provide a model for investigating the pathophysiological mechanisms of pulmonary inflammation following sensitization by exposure of the airways to allergen and for investigating the mode of action and efficacy of novel immunotherapeutics. [source] Fecal microbiota in sensitized wheezy and non-sensitized non-wheezy children: a nested case,control studyCLINICAL & EXPERIMENTAL ALLERGY, Issue 6 2005C. S. Murray Summary Background It has been suggested that intestinal microbiota of allergic and non-allergic children differs in composition, and that microbiota,immune system interactions may predispose children to develop sensitization. Previous studies have examined fecal microbiota of allergic children with atopic dermatitis, but little is known about that of atopic wheezy children. Objective To investigate the composition of the fecal microbiota of young sensitized wheezy and non-sensitized non-wheezy children, using molecular methods. Methods Within the context of a prospective birth cohort, we carried out a nested case,control study of sensitized wheezy children (cases) and non-sensitized non-wheezy controls. Cases and controls were matched for age, sex, parental atopy, allergen exposure, and pet ownership. We evaluated the composition of fecal microbiota by nucleic acid-based methods (PCR combined with denaturing gradient gel electrophoresis and quantification of bifidobacteria by fluorescent in situ hybridization). Results Thirty-three case,control pairs (mean age 4.4 years) provided stool samples. Comparison of total bacterial community profiles showed that each child had a unique fecal microbiota (mean Dice's similarity coefficient 22%, range 3.3,60.8%). There was no difference between the groups in prevalence of Lactic Acid bacteria (12/33 vs. 11/33, P=0.8) or bifidobacteria (30/33 vs. 31/33, P=1.00, cases vs. controls). The bifidobacterial species detected were similar in both groups. The percentage of bifidobacteria in total fecal microflora was no different between cases (median 1.7%, range 0,20.8%) and controls (1.9%, 0,18.2%, P=0.7). However, cases with eczema had significantly fewer bifidobacteria (median 1.6%, range 0,4.8%) than their controls (4.0%, 1.9,18.2%, P=0.05). Conclusion We found no differences in fecal microbiota composition between sensitized wheezy and non-sensitized, non-wheezy children aged 3,5 years using nucleic acid-based methods. Differences appear to be isolated to those allergic children with eczema. [source] Surfactant protein D deficiency influences allergic immune responsesCLINICAL & EXPERIMENTAL ALLERGY, Issue 12 2004B. Schaub Summary Background The collectin surfactant protein D (SP-D) confers protection against pulmonary infection and inflammation. Recent data suggest a role for SP-D in the modulation of allergic inflammation. Objective The aim of this study is to characterize the immune responses of SP-D-deficient (SP-D,/,) mice in a kinetic model of allergic inflammation. We determined whether allergic parameters were enhanced in SP-D,/, mice in vivo. Further, we examined whether functional immune responses in vitro such as lymphocyte proliferation (LP) and cytokine production were modulated in the absence of SP-D. Methods In vivo, wild-type (WT) and SP-D,/, mice were sensitized and challenged with the allergen ovalbumin (OVA) and assessed for allergic parameters (bronchoalveolar lavage (BAL) eosinophils, IL-13 production, pulmonary IFN-,, IL-10 expression) at early time points (1 and 3 days of challenge) in comparison with late time points (7 days of challenge). In vitro, spleen cells from WT and SP-D,/, mice were stimulated with the mitogen concanavalin A (ConA) and lipid A (LpA) and analysed for LP, IL-13 and IFN-, production. Toll-like receptor 4 (TLR4), ligand for LpA, was assessed by mRNA expression and immunohistochemistry in vivo. Results Following allergen exposure in vivo, SP-D,/, mice expressed higher BAL eosinophils and IL-13 concentrations and lower IFN-, expression at early time points compared with WT mice. IL-10 expression was increased at early time points in SP-D,/, compared with WT mice. Allergen-induced TLR4 expression was increased in WT, but not in SP-D,/, mice. After stimulation with LpA and ConA in vitro LP was increased and IFN-, concentration was decreased in SP-D,/, mice. Conclusion SP-D may be critical for the modulation of early stages of allergic inflammation in vivo. [source] Desloratadine partially inhibits the augmented bacterial responses in the sinuses of allergic and infected miceCLINICAL & EXPERIMENTAL ALLERGY, Issue 10 2004V. Kirtsreesakul Summary Background Allergic rhinitis (AR) is considered a major predisposing factor for the development of acute bacterial rhinosinusitis. How AR augments a bacterial infection is unknown. Objective Our purpose in this study was to test whether an H1 receptor antagonist, desloratadine, could reduce the augmented effect of an ongoing allergic reaction on acute bacterial rhinosinusitis. Methods Three groups of infected and ovalbumin (OVA)-sensitized mice were studied: (1) infected and allergic mice treated with desloratadine, (2) infected and allergic mice treated with placebo, and (3) infected mice. A fourth group of uninfected, non-sensitized mice served as a control for the cellular changes. BALB/c mice were sensitized by two intraperitoneal injections of OVA given 8 days apart. One day after the second injection, the mice were nasally exposed daily to 6% OVA (the groups treated with desloratadine or placebo) or phosphate-buffered saline (PBS) (the infection-only group) for 5 days. After the second OVA exposure, the mice were intranasally inoculated with Streptococcus pneumoniae. Desloratadine or placebo was given daily throughout the OVA exposure period. Nasal allergic symptoms were observed by counting of nasal rubbing and sneezing for 10 min after OVA or PBS nasal challenge. On day 5 post-infection, nasal lavage culture was done, and the inflammatory cells in the sinuses were evaluated by flow cytometry. Results Mice that were made allergic, infected, and treated with placebo showed more organisms and phagocytes than did only infect mice. They also manifested allergic nasal symptoms and eosinophil influx into the sinuses. Desloratadine treatment during allergen exposure reduced allergic symptoms and reduced sinonasal infection (P<0.05). There tended to be less myeloid cell and neutrophil influx (P=0.09 both), but not eosinophil influx (P=0.85) compared with that in the placebo-treated group. Conclusion Desloratadine treatment during nasal challenge inhibited allergic symptoms and reduced sinonasal infection, suggesting that histamine via an H1 receptor plays a role in the augmented infection in mice with an ongoing allergic reaction. [source] The placenta: a portal of fetal allergen exposureCLINICAL & EXPERIMENTAL ALLERGY, Issue 11 2002Catherine A. Thornton No abstract is available for this article. [source] A rapid test for detection of mite allergens in homesCLINICAL & EXPERIMENTAL ALLERGY, Issue 11 2002A. Tsay Summary Background International guidelines recommend allergen avoidance for asthma management, but do not include making assessments of allergen exposure. Mite allergen exposure cannot be assumed, especially in geographical regions where climatic conditions vary. Objective To develop a rapid test that would enable consumers to detect mite allergen in the home. Methods A lateral flow test using gold labelled antibody for mite group 2 allergen was developed as part of a detection kit incorporating the MITEST dust sampling device. Dust samples were assayed by ELISA for group 1 and group 2 allergens and by using the rapid test. The tests were compared as indices of mite allergen exposure. Results There was a good correlation between group 1 and group 2 levels by ELISA (n = 349, r = 0.60, P < 0.001). In a multi-centre study of 65 homes (263 dust samples) in five countries, there was a strong correlation between ELISA and the rapid test. Most samples with high scores in the test (43/48, 90%) contained > 1 µg/m2 group 2 allergen, whereas most low samples contained < 1 µg/m2 (50/64, 78%). Differences between mean group 2 levels of samples that scored low (0.28 µg/m2), medium (1.68 µg/m2) or high (3.18 µg/m2) on the test were highly significant (P 0.007 to < 0.001). Conclusions A simple rapid test has been developed that detects mite allergen in the home within 10 min. The mite screening test should educate consumers about allergen exposure and encourage compliance with allergen-avoidance procedures. This technology has applications for the detection of other common environmental allergens. [source] | ||||||||||||||||||||||||||||