Showing papers in "Clinical & Experimental Allergy in 2002"

H1‐antihistamines: inverse agonism, anti‐inflammatory actions and cardiac effects

Abstract: This review addresses novel concepts of histamine H1-receptor function and attempts to relate them to the anti-inflammatory effects of H1-antihistamines. Furthermore, the molecular mechanisms underlying the cardiotoxic effects of H1-antihistamines are discussed. H1-receptors are G-protein-coupled-receptors (GPCRs), the inactive and active conformations of which coexist in equilibrium. The degree receptor activation in the absence of histamine is its 'constitutive activity'. In this two-state model, histamine acts as an agonist by combining with and stabilizing the activated conformation of the H1-receptor to shift the equilibrium towards the activated state. Drugs classified previously as antagonists act as either inverse agonists or neutral antagonists. Inverse agonists combine with and stabilize the inactive conformation of the receptor to shift the equilibrium towards the inactive state. Thus, they may down-regulate constitutive receptor activity, even in the absence of histamine. Neutral antagonists combine equally with both conformations of the receptor, do not affect basal receptor activity but do interfere with agonist binding. All H1-antihistamines examined to date are inverse agonists. As the term 'H1-receptor antagonists' is obviously erroneous, we suggest that it be replaced by 'H1-antihistamines'. The observations that H1-receptors modulate NF-kappaB activation and that there are complex interactions between GPCRs, has allowed us to postulate receptor dependent-mechanisms for some anti-inflammatory effects of H1-antihistamines, e.g. inhibition of ICAM-1 expression and the effects of bradykinin. Finally, the finding that blockade of HERG1 K+ channels is the mechanism by which some H1-antihistamines may cause cardiac arrhythmias has allowed the development of preclinical tests to predict such activity.

Antenatal determinants of neonatal immune responses to allergens.

Abstract: Background The environmental factors responsible for recent increases in the prevalence of asthma and atopic disease have been assumed to act after birth. Their possible effects on fetal immune development in utero have not been investigated systematically, although sensitization to allergens may occur before birth. Objective This prospective study determined whether the risk factors for asthma and atopic disease, namely family history of atopic disease, maternal smoking, birth order, or maternal dietary intake of antioxidant vitamins, exert antenatal effects on the fetal immune system that may predispose to childhood atopy. Methods The T helper (Th) cell proliferative responses of cord blood mononuclear cells (CBMC) from a sample of 223 neonates, representative of children born to a cohort of 2000 pregnant women, were measured and related to family, maternal and environmental factors associated with the pregnancy. Results The magnitude of CBMC-proliferative responses to allergens increased significantly in association with a family history of atopic disease or maternal smoking, and decreased significantly with increasing birth order and high maternal dietary intake of vitamin E. The epidemiological association between birth order and atopy may therefore be a consequence of antenatal influences rather than of protective effects of childhood infections. The association between maternal intake of vitamin E and CBMC responsiveness suggests that diet during pregnancy may influence the fetal immune system in such a way as to modulate the risk of childhood atopy. Conclusion These results provide a new insight into the aetiology of atopic disease by demonstrating that the maternal environmental risk factors for atopy, diet, birth order and smoking, influence the development of the fetal immune system. This raises the prospect of preventative public health interventions during pregnancy.

Flow cytometric basophil activation test by detection of CD63 expression in patients with immediate-type reactions to betalactam antibiotics.

Abstract: Background In this study, we used flow cytometry to determine the percentage of activated basophils that expressed the CD63 marker after in vitro stimulation by different betalactam antibiotics. The diagnostic reliability of the technique was assessed, as well as its correlation with specific IgE. Methods Fifty-eight patients with clinical allergy to betalactam antibiotics and presenting positive skin tests to at least one of the allergens (minor determinant mixture (MDM), benzylpenicilloyl-polylysine (PPL), penicillin, ampicillin, amoxicillin, cephalosporins) were tested. Thirty subjects non-allergic to betalactams were also studied as controls. The flow assay stimulation test (FAST) uses flow cytometry to determine the percentage of basophils that express CD63 as an activation marker after in vitro stimulation with allergen. Double labelling with monoclonal antibodies anti-CD63-PE and anti-IgE FITC was used. Results The allergic patients show a statistically greater number of activated basophils than the control subjects, after the incubation of cells with all the betalactams at various concentrations. The sensitivity of the technique is 50%, the specificity 93.3%, the likelihood ratio for a positive value 7.46 and the likelihood ratio for a negative value 0.54. In spite of having a greater sensitivity (37.9%) and specificity (86.7%) than CAP, differences between sensitivity and specificities of both techniques (CAP and FAST) do not reach statistical significance. Conclusion The basophil activation test is a particularly useful technique in the diagnosis of patients with IgE-mediated allergy to betalactams and allows the identification of 50% of patients. Used in conjunction with CAP, it allows the identification of 65.5% of such patients.

Breastfeeding duration is a risk factor for atopic eczema

Abstract: Background The results of numerous studies on the influence of breastfeeding in the prevention of atopic disorders are often contradictory. One of the most important problems is confounding by other lifestyle factors. Objective The aim of the present study was to analyse the effect of any breastfeeding duration on the prevalence of atopic eczema in the first seven years of life taking into account other risk factors. Methods In an observational birth cohort study 1314 infants born in 1990 were followed-up for seven years. At 3, 6, 12, 18, 24 months and every year thereafter, parents were interviewed and filled in questionnaires, children were examined and blood was taken for in vitro allergy tests. Generalized Estimation Equations (GEE)-models were used to model risk factors for the prevalence of atopic eczema and for confounder adjustment Results Breastfeeding was carried out for longer if at least one parent had eczema, the mother was older, did not smoke in pregnancy, and the family had a high social status. The prevalence of atopic eczema in the first seven years increased with each year of age (OR 1.05; 95% CI 1.01-1.09 for each year), with each additional month of breastfeeding (1.03; 1.00-1.06 for each additional month), with a history of parental atopic eczema (2.06; 1.38-3.08), and if other atopic signs and symptoms appeared, especially specific sensitization (1.53; 1.25-1.88), and asthma (1.41; 1.07-1.85). Although breastfeeding should be recommended for all infants, it does not prevent eczema in children with a genetic risk. Conclusion Parental eczema is the major risk factor for eczema. But in this study, each month of breastfeeding also increased the risk.

Montelukast for treating seasonal allergic rhinitis: a randomized, double-blind, placebo-controlled trial performed in the spring

Abstract: Summary Background Cysteinyl leukotrienes are important proinflammatory mediators believed to have a role in allergic rhinitis. Objective This multicentre, randomized, double-blind, placebo- and active-controlled trial evaluated the effectiveness and tolerability of montelukast, a cysteinyl leukotriene receptor antagonist, for treating patients with seasonal allergic rhinitis. Methods After a 3- to 5-day, single-blind placebo run-in period, 1302 male and female patients (aged 15–81 years) with active allergic rhinitis symptoms were randomly assigned to receive montelukast 10 mg (n = 348), loratadine 10 mg (n = 602), or placebo (n = 352) administered once daily at bedtime for 2 weeks during the spring allergy season. Results Mean patient characteristics and symptom scores at baseline were similar for the three treatment groups. The primary end-point, daytime nasal symptoms score (mean of nasal congestion, rhinorrhea, nasal pruritus, and sneezing scores; 0–3 scale), improved from baseline during treatment by (least squares mean, 95% confidence interval) − 0.37 (− 0.43, − 0.31), − 0.47 (− 0.52, − 0.43), and − 0.24 (− 0.29, − 0.18) in the montelukast, loratadine, and placebo groups, respectively (P ≤ 0.001 comparing each active treatment with placebo). Mean changes from baseline in all other diary-based scores, including night-time and eye symptom scores, were significantly greater for each active treatment than for placebo. The rhinoconjunctivitis quality of life overall score improved significantly with montelukast and with loratadine as compared with placebo. Montelukast and loratadine showed a safety profile comparable to that of placebo. Conclusion Montelukast is well tolerated and provides improvements in daytime and night-time symptoms, as well as quality of life parameters, for patients with seasonal allergic rhinitis.

Human mast cells stimulate fibroblast proliferation, collagen synthesis and lattice contraction: a direct role for mast cells in skin fibrosis.

Abstract: Background Mast cells, the key cells of immediate hypersensitivity type reactions, have also been postulated to have a central role in influencing tissue remodelling and fibrosis occurring in the skin. Objective Our aim was to investigate the direct role of human mast cells (HMC) in skin fibrotic processes, by assessing the effects of the addition of the human mast cell line HMC-1 to human skin fibroblasts, and to identify the responsible mediators. Methods HMC-1 sonicates were added to human skin fibroblasts and the following parameters were evaluated: proliferation ([3H]-thymidine), collagen synthesis ([3H] proline), activity of matrix metalloproteinases (MMPs) (zymography) and tissue inhibitors of metalloproteinases (TIMPs) (reverse zymography), and collagen gel contraction. Results HMC-1 sonicate increased significantly both proliferation and collagen production in the human skin fibroblasts and these properties were not affected by heating of the sonicate (56 degrees C, 30 min, or 100 degrees C, 3 min). Two main mast cell mediators, histamine and tryptase, were found to be responsible for the increase in fibroblast proliferation and collagen production. HMC-1 sonicate did not display any pre-formed gelatinase activity, and its addition to the fibroblasts did not change their pro-MMP-2 and MMP-2 activity. On the other hand, HMC-1 were found to possess TIMP-1 and TIMP-2. Addition of HMC-1 had no effect on fibroblasts TIMP-1 but induced a dose-dependent increase of TIMP-2 activity. In addition, HMC-1 sonicate seeded together with the fibroblasts in tri-dimensional collagen gel significantly enhanced their contraction. Conclusion We have shown that human mast cells, by granule-stored and therefore quickly releasable mediators, increase human skin fibroblast proliferation, collagen synthesis, TIMP-2 and collagen gel contraction. Therefore, mast cells have a direct and potentiating role in skin remodelling and fibrosis.

Lactobacillus casei strain Shirota suppresses serum immunoglobulin E and immunoglobulin G1 responses and systemic anaphylaxis in a food allergy model.

Abstract: Summary Background Our previous study using allergen-sensitized murine splenocyte cultures has shown that Lactobacillus casei strain Shirota (LcS), a lactic acid bacterium widely used as a starter for fermented milk products, suppresses IgE production through promoting a dominant Th1-type response mediated by IL-12 induction. Objective We tried to evaluate the ability of LcS to suppress both IgE response and allergic reactions in vivo using a food allergy model with ovalbumin-specific T cell receptor transgenic (OVA-TCR-Tg) mice. Methods The ability of heat-killed LcS to induce IL-12 in serum was tested. OVA-TCR-Tg mice were fed a diet containing OVA for 4 weeks and injected with LcS intraperitoneally three times in the first week of this period. Cytokine and antibody secretion by splenocytes, and serum IgE and IgG1 responses were examined. The inhibitory effect of LcS on systemic anaphylaxis induced by intravenous challenge of OVA-fed OVA-TCR-Tg mice with OVA was also tested. Results Intraperitoneal injection of LcS induced an IL-12 response in the serum of OVA-TCR-Tg mice. In the food allergy model, LcS administration skewed the pattern of cytokine production by splenocytes toward Th1 dominance, and suppressed IgE and IgG1 secretion by splenocytes. The ability of LcS to modulate cytokine production was blocked by anti-IL-12 antibody treatment. LcS also inhibited serum OVA-specific IgE and IgG1 responses and diminished systemic anaphylaxis. Conclusion LcS administration suppresses IgE and IgG1 responses and systemic allergic reactions in a food allergy model, suggesting a possible use of this lactic acid bacterium in preventing food allergy.

Coincidence of immune-mediated diseases driven by Th1 and Th2 subsets suggests a common aetiology. A population-based study using computerized general practice data.

Abstract: Background The recent rise in the prevalence of immune-mediated diseases has been attributed to environmental factors such as a lack of microbial challenge, or dietary change, that deviate the overall balance between mutually antagonistic subsets of T helper (Th) cells. Objective An alternative proposal is that recent environmental changes have resulted in an immune system that is more likely to produce both Th1 and Th 2 responses against benign antigens. The prediction of this hypothesis, that Th1 and Th 2-mediated diseases are not mutually exclusive, and may be positively associated, is tested here in a whole population. Methods Data from General Practices participating in the Scottish Continuous Morbidity Recording (CMR) project were used to determine the coincidence of the major Th 2-mediated atopic diseases; asthma, eczema and allergic rhinitis, with the Th1-mediated autoimmune conditions; type I diabetes, rheumatoid arthritis and psoriasis. We also identified the prescription rates of inhaled therapy for asthma in patients with Th1-mediated disease. Results There was a significant increase in the risk of presenting with a Th1-mediated autoimmune condition in patients with a history of allergic disease (standardized prevalence ratio (95% confidence interval) 1.28 (1.18–1.37)). Likewise, the standardized prevalence ratios of presenting with either eczema (1.67 (1.48–1.87)) or allergic rhinitis (1.22 (1.02–1.44)) were significantly increased in subjects with a history of Th1-mediated disease. There was a particularly strong association between current psoriasis and current eczema (standardized prevalence ratio of psoriasis in subjects with eczema 2.88, 95% confidence interval (CI) 2.38–3.45). There was also a significant increase in prescriptions for inhaled asthma therapy in patients with Th1 disease. Conclusion It is concluded that Th1- and Th 2-mediated diseases are significantly associated in a large General Practice population. This finding supports the proposal that autoimmune and atopic diseases share risk factors that increase the propensity of the immune system to generate both Th1- and Th 2-mediated inappropriate responses to non-pathological antigens.

Grass pollen sublingual immunotherapy for seasonal rhinoconjunctivitis: a randomized controlled trial.

Abstract: Summary Background Previous studies suggest that sublingual immunotherapy (SLIT) represents a safer alternative to injection immunotherapy but equivalent efficacy is yet to be confirmed. Objective To evaluate the efficacy and safety of SLIT in grass pollen-induced seasonal rhinoconjunctivitis. Methods A randomized, placebo-controlled trial in 56 adults over 18 months. Outcome measures included diary scores of seasonal symptoms and medication use, overall assessments, conjunctival and intradermal provocation tests and serum antibody measurements. To investigate possible mechanisms, sublingual biopsies were taken for measurement of local T cells, antigen-presenting cells and IL-12 mRNA expression. Results There were no significant differences between the immunotherapy (IT) and placebo groups for diary symptom scores (P = 0.48) or rescue medication (P = 0.19). The patients' overall assessment of hayfever severity compared with previous years showed a highly significant improvement in favour of the IT group (P < 0.02). After treatment the late skin response was smaller (P = 0.003) and the ratio of serum allergen-specific IgG4/IgE was higher (P = 0.05) in the IT group. Both of these variables correlated with the clinical response to SLIT. There were no differences between groups in either the sublingual epithelium or lamina propria for numbers of CD3+ cells (epithelium: P = 0.9, lamina propria: P = 0.2), CD1a+ cells (P = 0.3, P = 0.25), CD68+ cells (P = 0.9, P = 1.0) or IL-12 mRNA+ cells (P = 0.6, P = 0.4). Local side-effects were minor and there were no serious treatment-related adverse events. Conclusion Grass pollen sublingual immunotherapy was well tolerated. Although there was no significant change in diary scores, the improvement in overall assessments, which correlated with inhibition of the late skin response and increases in serum IgG4 : IgE ratio, indicates the need for larger, dose-ranging studies.

Role of interleukin-13 in eosinophil accumulation and airway remodelling in a mouse model of chronic asthma.

Abstract: Summary Background Interleukin-13 is believed to be important in asthmatic inflammation and airway hyper-reactivity. Objective To investigate the role of IL-13 in chronic asthma, using an improved experimental model of asthma that reproduces most of the morphological features of the human disease. Methods BALB/c mice or gene-targeted mice deficient in their ability to produce IL-13 or the IL-4 receptor α-chain (IL-4Rα) were sensitized to ovalbumin and exposed to aerosolized antigen for 30 min/day on 3 days/week for 6 weeks. Intraepithelial eosinophils, accumulation of chronic inflammatory cells in the airway wall, subepithelial fibrosis, epithelial hypertrophy and numbers of mucous cells were quantified histomorphometrically. Airway hyper-reactivity (AHR) to a cholinergic agonist was assessed by barometric plethysmography. Results Compared with wild-type animals, IL-13 -/- mice exhibited diminished accumulation of eosinophils and chronic inflammatory cells, as well as reduced subepithelial fibrosis, epithelial hypertrophy and mucous cell hyperplasia (P < 0.01 for all comparisons). In contrast, AHR was still demonstrable in IL -13 -/- mice. In IL-4Rα -/- mice the inflammatory response, subepithelial fibrosis and AHR were similar to wild-type mice, although the receptor-deficient mice had significantly less epithelial hypertrophy and mucous cell hyperplasia. Conclusion These results imply a critical role for IL-13 in accumulation of intraepithelial eosinophils in chronic asthma, as well as in epithelial and subepithelial remodelling. In addition, they suggest that in chronic asthma, IL-13 may be capable of signalling via a pathway that does not involve IL-4Rα.

Expression and activation of 15‐lipoxygenase pathway in severe asthma: relationship to eosinophilic phenotype and collagen deposition

Abstract: Summary Background Although 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), a product of 15-lipoxygenase (15-LO), may be involved in mild to moderate asthma, little is known about its potential roles in severe asthma. Objectives This study was performed to evaluate 15(S)-HETE levels in bronchoalveolar lavage fluid (BALF) from severe asthmatics with and without airway eosinophils and from the control groups. In addition, 15-LO protein expression was examined in endobronchial biopsy, while its expression and activation were evaluated in BAL cells. Results While 15(S)-HETE levels in BALF were significantly higher in all severe asthmatics than normal subjects, severe asthmatics with airway eosinophils had the highest levels compared with mild, moderate asthmatics and normal subjects. 15(S)-HETE levels were associated with tissue eosinophil numbers, sub-basement membrane thickness and BALF tissue inhibitor of metalloproteinase-1 levels, and were accompanied by increased 15-LO expression in bronchial epithelium. In addition, activation of 15-LO was suggested by the increased proportion of 15-LO in the cytoplasmic membrane of alveolar macrophages from severe asthmatics. Conclusion The data suggest that severe asthmatics with persistent airway eosinophils manifest high levels of 15(S)-HETE in BALF, which may be associated with airway fibrosis. It is likely that 15-LO expression and activation by airway cells explain the increased 15(S)-HETE levels.

Increased Th1 and Th2 allergen-induced cytokine responses in children with atopic disease.

Abstract: Summary Background Polyclonal cytokine responses following stimulation of T cells with mitogens or superantigens provides information on cytokine production from a wide range of T cells. Alternatively allergen-induced T cell responses can provide information on cytokine production by allergen-reactive T cells. While there is evidence of increased Th2 and reduced Th1 cytokine production following T cell stimulation with non-specific mitogens and superantigens, the evidence that Th1 cytokine production to allergens is decreased in line with a postulated imbalance in Th1/Th2 responses is unclear, with studies finding decreased, no difference or increased IFN-γ responses to allergens in atopic subjects. Objective To examine childhood polyclonal and allergen-induced cytokine responses in parallel to evaluate cytokine imbalances in childhood atopic disease. Methods PBMC cytokine responses were examined in response to a polyclonal stimulus, staphylococcal superantigen (SEB), in parallel with two inhalant allergens, house dust mite (HDM) and rye grass pollen (RYE), and an ingested allergen, ovalbumin (OVA), in (a) 35 healthy children (non-atopic) and (b) 36 children with atopic disease (asthma, eczema and/or rhinitis) (atopic). Results Atopic children had significantly reduced IFN-γ and increased IL-4 and IL-5 but not IL13 production to SEB superantigen stimulation when compared with non-atopic children. HDM and RYE allergens stimulated significantly increased IFN-γ, IL-5 and IL-13, while OVA stimulated significantly increased IFN-γ production in atopic children. Conclusion We show that a polyclonal stimulus induces a reduced Th1 (IFN-γ) and increased Th2 (IL-4 and IL-5) cytokine pattern. In contrast, the allergen-induced cytokine responses in atopic children were associated with both increased Th1 (INF-γ) and Th2 (IL-5 and IL-13) cytokine production. The increased Th1 response to allergen is likely to reflect prior sensitization and indicates that increases in both Th1 and Th2 cytokine production to allergens exists concomitantly with a decreased Th1 response to a polyclonal stimulus in atopic children.

Expression and function of the ST2 gene in a murine model of allergic airway inflammation.

Abstract: Summary Background We have recently reported that soluble ST2 protein levels are elevated in the sera of patients with asthma, and correlate well with the severity of asthma exacerbation. However, the role, function, and kinetics of soluble ST2 expression in asthma remain unclear. Objective The objective of the present study was to clarify the function and kinetics of soluble murine (m) ST2 expression in a murine asthma model. Methods We analyzed the kinetics of gene and protein expression of mST2 in sera or lung tissue after allergen (ovalbumin; OVA) challenge in a murine model of allergic airway inflammation, the effects of mST2 protein on OVA-induced Th2 cytokine production in vitro from splenocytes of sensitized mice, and the effects of soluble mST2 on Th2-dependent allergic airway inflammation by in vivo gene transfer of mST2. Results Serum mST2 protein levels increased to the maximal level 3 h after the allergen challenge, before serum IL-5 levels peaked. The mRNA expression of mST2 in lung tissue was induced after the allergen challenge, while that in the spleen was constitutively detected. Furthermore, pre-treatment with mST2 protein significantly inhibited the production of IL-4 and IL-5, but not IFN-γ, from OVA-stimulated splenocytes in vitro, and intravenous mST2 gene transfer resulted in a drastic reduction in the number of eosinophils and in the levels of IL-4 and IL-5 in bronchoalveolar lavage fluid, compared with those in response to transfer of non-coding plasmid vector or of lipid alone. Conclusion These results suggest that increases in endogenous mST2 protein after allergen exposure may modulate Th2-mediated airway inflammation, and that in vivo gene transfer of mST2 can be applicable to use in a novel immunotherapy for allergic diseases.

Low prevalence of atopy in young Danish farmers and farming students born and raised on a farm.

Abstract: Background Recent studies have shown that in several countries atopic sensitization to common allergens (common atopy) and atopic symptoms are markedly less prevalent in children living on a farm, compared with non-farm children living in the same rural areas. Living conditions on farms may, however, vary largely between different countries. It is also not yet known whether the ‘protective’ effect of a farm environment can also be found in adults. Materials and methods Common atopy and respiratory health were assessed by skin prick tests (SPT), questionnaire and measurement of bronchial hyper-responsiveness (BHR) in the Sund Stald (SUS) study, a cohort study on respiratory health in Danish farming students and conscripts from the same rural areas as controls. Results of SPT were confirmed by IgE serology in all SPT+ subjects and a subset of SPT– subjects. Prevalences of common atopy, respiratory symptoms and bronchial hyper- responsiveness were compared for farmers and controls, and for those who had or had not lived on a farm in early childhood. Results In multiple logistic regression analyses adjusting for ever smoking and a familial history of allergy, both being a farmer (ORs 0.62–0.75) and having had a farm childhood (ORs 0.55–0.75) appeared to contribute independently to a lower risk of sensitization to common allergens as assessed by SPT and IgE serology. A farm childhood was also inversely associated with high total IgE (OR 0.68), presence of respiratory symptoms (ORs 0.69–0.79) and BHR (OR 0.61) in these analyses. Direction and strength of the association between being a farmer and respiratory symptoms or BHR varied widely (ORs 0.69–1.28). Conclusion The ‘anti-atopy’ protective effect of a farm childhood could be confirmed in Danish farming students: prevalences of positive SPT, specific and total IgE, allergic symptoms and BHR were lower in those being born or raised on a farm. Past exposure to the farm environment in early childhood may therefore also contribute to a lower risk of atopic sensitization and disease at a later age.

The Proteolytic Activity of the Major Dust Mite Allergen Der P 1 Conditions Dendritic Cells to Produce Less interleukin-12: Allergen-Induced Th2 Bias Determined at the Dendritic Cell Level

Abstract: Summary Background The proteolytic activity of the house dust mite allergen Der p 1 has recently been shown to bias Th cell subset development in favour of Th2. Apart from its direct effect on T cells, it is conceivable that the proteolytic activity of Der p 1 may induce the generation of dendritic cells (DCs) that favour a Th2 response. Objective To study the effect of the proteolytic activity of Der p 1 on DC functions; namely cell surface phenotype, IL-12 production and ability to favour a Th2 response. Methods We have generated immature DCs from peripheral blood monocytes, matured them with LPS in the presence of either proteolytically active or inactive Der p 1 and compared their functions using flow cytometric analysis. Results Here we demonstrate for the first time that DCs that have been matured in the presence of proteolytically active Der p 1 produce significantly less IL-12, compared to DCs that have been matured in the presence of proteolytically inactive Der p 1. The suppression of IL-12 production was due to the cleavage of CD40 by the proteolytic activity of Der p 1, hence rendering the DCs less responsive to stimulation through the CD40L-CD40 pathway. Furthermore, we demonstrate that DCs that have been matured in the presence of proteolytically active Der p 1 induce the production of significantly less IFN-γ and more IL-4 by CD4 T cells, compared to DCs that have been matured in the presence of proteolytically inactive Der p 1. Conclusions Collectively, our data provide compelling evidence for the role of the proteolytic activity of Der p 1 in directing DCs to induce Th2 subset development.

Stressful life events promote the manifestation of asthma and atopic diseases

Abstract: Background Psychosocial stress is known to aggravate asthma. Less is known about the impact of stressful life events on the expression of asthma and atopic disorders. Objective To determine whether the onset of asthma, allergic rhinitis or conjunctivitis, and atopic dermatitis, are associated with stressful life events. Methods A postal survey on risk factors for asthma and atopic diseases was carried out among 10 667 Finnish first-year university students aged 18-25 years. Stressful life events, (i) severe disease or death of a family member, and (ii) parental or personal conflicts, were retrospectively recorded during the preceding year, 1-5 years, 6-10 years, and more than 10 years prior to the survey response. In a case-control setting, conditional multiple logistic regression analysis was used to assess the temporal association between major stressful life events occurring during a period either preceding, concomitant or subsequent with subject's diagnoses. Results Concomitant parental and personal conflicts increased the risk of asthma (OR 1.72, 95% CI 1.10-2.69) when adjusted by parental asthma, education and passive smoking at early age. Concomitant severe disease or death of mother, father or spouse (OR 1.52, 95% CI 1.09-2.16) and precedent parental and personal conflicts (OR 1.75, 95% CI 1.15-2.77) increased the risk of manifestation of allergic rhinoconjunctivitis when adjusted for parental atopic disease, education and passive smoking. Subjects' asthma and atopic dermatitis, but not allergic rhinoconjunctivitis, were related to excess of subsequent stressful life events. Conclusion An association between stressful life events and subjects' asthma, allergic rhinoconjunctivitis and atopic dermatitis is suggested.

Early, current and past pet ownership: associations with sensitization, bronchial responsiveness and allergic symptoms in school children

Abstract: Background Studies have suggested that early contact with pets may prevent the development of allergy and asthma. Objective To study the association between early, current and past pet ownership and sensitization, bronchial responsiveness and allergic symptoms in school children. Methods A population of almost 3000 primary school children was investigated using protocols of the International Study on Asthma and Allergies in Childhood (ISAAC). Allergic symptoms were measured using the parent-completed ISAAC questionnaire. Sensitization to common allergens was measured using skin prick tests (SPT)s and/or serum immunoglobulin (Ig)E determinations. Bronchial responsiveness was tested using a hypertonic saline challenge. Pet ownership was investigated by questionnaire. Current, past and early exposure to pets was documented separately for cats, dogs, rodents and birds. The data on current, past and early pet exposure were then related to allergic symptoms, sensitization and bronchial responsiveness. Results Among children currently exposed to pets, there was significantly less sensitization to cat (odds ratio (OR) = 0.69) and dog (OR = 0.63) allergens, indoor allergens in general (OR = 0.64), and outdoor allergens (OR = 0.60) compared to children who never had pets in the home. There was also less hayfever (OR = 0.66) and rhinitis (OR = 0.76). In contrast, wheeze, asthma and bronchial responsiveness were not associated with current pet ownership. Odds ratios associated with past pet ownership were generally above unity, and significant for asthma in the adjusted analysis (OR = 1.85), suggesting selective avoidance in families with sensitized and/or symptomatic children. Pet ownership in the first two years of life only showed an inverse association with sensitization to pollen: OR = 0.71 for having had furry or feathery pets in general in the first two years of life, and OR = 0.73 for having had cats and/or dogs in the first two years of life, compared to not having had pets in the first two years of life. Conclusion These results suggest that the inverse association between current pet ownership and sensitization and hayfever symptoms was partly due to the removal of pets in families with sensitized and/or symptomatic children. Pet ownership in the first two years of life only seemed to offer some protection against sensitization to pollen.

Association of body mass index with respiratory symptoms and atopy: results from the European Community Respiratory Health Survey.

Abstract: Summary Background There are several reports showing that obese adults report more respiratory symptoms suggestive of asthma than those who are not obese. Objective To determine the association of body mass index with respiratory symptoms and atopy in young adults Method Information collected from 15 454 participants in the European Community Respiratory Health Survey, a multicentre cross-sectional survey of young adults, was analysed to determine the association of body mass index with respiratory symptoms and atopy. Results Men and women with a body mass index of greater than 30 were at an increased risk of wheeze with shortness of breath compared with those with a body mass of 20–24.99 (OR in men 1.85, 95% confidence interval 1.41–2.42; OR in women 2.03, 95% confidence interval 1.59–2.58). Similar associations were observed for other symptoms suggestive of asthma. Body mass index was not associated with ‘hayfever or nasal allergies’, specific IgE to house dust mite, grass or cat or with total IgE in men or women. Conclusion Reported associations of body mass index with symptoms suggestive of asthma are unlikely to be explained by a higher risk of atopy in the obese. Alternative explanations must be sought.

Paradoxical low nasal nitric oxide in nasal polyposis

Abstract: Summary Background Nitric oxide (NO) is synthesized in the respiratory tract. Three isoforms of NO synthase have been described in man, with the inducible form related to inflammatory disease. In the paranasal sinuses constitutive production of nitric oxide has been demonstrated, with levels of 20–25 p.p.m. being found in sinus puncture. Nasal polyposis is a chronic inflammatory condition in which inducible nitric oxide synthase (iNOS) expression is elevated in nasal polyp epithelium. Objectives 1. Measurement of upper airway nitric oxide in nasal polyposis patients compared with those with allergic rhinitis, and with normal controls. 2. To assess the effect of polyp treatment on nasal NO levels. Methods NO levels (parts per billion) were measured in nasal and pulmonary exhaled air using a LR 2000 Logan Sinclair nitric oxide gas analyser. This utilizes the chemiluminescence principle. Eighty-two patients were studied: 44 with rhinitis, but without polyps, and 38 with nasal polyps. NO levels were compared with those of 20 normal controls. In 23 further polyp patients, levels were measured pre- and post-treatment and the changes were compared with alterations in polyp size, as assessed by rigid nasendoscopy. Results Nasal NO levels were significantly lower (Kruskal–Wallis, P = 0.000, χ2 = 27.5, d.f. = 3) in patients with polyps than those found in uncomplicated allergic rhinitis. NO levels were correlated directly with extent of polyposis as graded by the Lund-McKay index. Successful treatment, with reduction in polyp volume, was associated with a rise in NO levels (P = 0.042). Conclusion NO levels are low in nasal polyposis, despite high levels of iNOS, possibly related to blockage of the ostiomeatal complex and failure of NO generated constitutively in the sinuses to reach the nasal airway. A rise in the NO levels is seen with successful polyp treatment, and is proportional to the reduction in endoscopically assessed polyp size, suggesting that with both medical and surgical therapy, the ostiomeatal complex obstruction is decreasing. We propose the following scenario. Nasal NO levels are the result of two processes: inducible NO production by inflamed nasal mucosa plus constitutive sinus mucosal production, detectable in normals. In uncomplicated allergic rhinitis with patent sinus ostia NO levels tend to be elevated, but when inflammation is sufficient to obstruct sinus ostia (as in nasal polyps), NO levels fall because sinus NO makes the major contribution.

Atypical nasal challenges in patients with idiopathic rhinitis: more evidence for the existence of allergy in the absence of atopy?

Abstract: Summary Background The pathophysiology of idiopathic rhinitis is unknown although evidence is accumulating to suggest that many patients may have a localized form of allergic rhinitis in the absence of other atopic symptoms and markers. This study compares detailed nasal challenge results obtained from patients with idiopathic rhinitis to those of atopic and normal controls. Methods Patients with idiopathic rhinitis (n = 23), perennial allergic rhinitis (n = 8) and normal controls (n = 8) underwent a normal saline challenge to exclude hyper-reactivity and then bilateral nasal allergen challenges. Nasal patency was assessed by anterior active rhinomanometry. Results All of the patients with atopic rhinitis demonstrated positive bilateral allergen challenges. All normal control subjects had bilateral negative challenges. Two patients in the idiopathic group tested positively to saline and were excluded from further study with 62% of the remainder testing positive to allergens. Of the idiopathic patients testing positive, 85% were sensitive to house dust mite. Conclusion A significant proportion of patients with idiopathic rhinitis have positive nasal challenges, the vast majority to house dust mite allergen. These findings add to the weight of evidence that suggests ‘localized allergy’ may exist in the absence of systemic atopic markers.

An oral introduction of intestinal bacteria prevents the development of a long-term Th2-skewed immunological memory induced by neonatal antibiotic treatment in mice.

Abstract: Summary Background Recent epidemiological studies indicate that antibiotic use in infancy may be associated with an increased risk of developing atopy. Our previous work on animals demonstrated that kanamycin use during infancy promotes a shift in the Th1/Th2 balance towards a Th2-dominant immunity. Objective The first purpose of this study is to clarify whether or not the supplementation of intestinal bacteria can reverse such a Th2-skewed response induced by neonatal antibiotic use. The second objective is to elucidate the contribution of genetic factors to antibiotic-induced immune-deviation. Methods BALB/c or C57BL/6 mice at 3 weeks of age were orally administered 600 µg/day of kanamycin sulphate for seven consecutive days. Thereafter, the mice were inoculated with one type of intestinal bacterial species: Enterococcus faecalis, Lactobacillus acidophilus or Bacteroides vulgatus. Blood samples were collected 10 weeks after the cessation of kanamycin treatment, and the effect of the kanamycin treatment on Th1/Th2 balance was evaluated based on in vivo antibody levels. Results A kanamycin-induced elevation of the serum IgE levels was reversed by the supplementation with Enterococcus faecalis, and to a lesser extent by that with Lactobacillus acidophilus. The IgE/IgG2a ratio in the mice supplemented with Enterococcus faecalis significantly decreased in comparison with that in the kanamycin-treated mice without any bacterial supplementation, while such a ratio was enhanced in the mice inoculated with Bacteroides vulgatus. No antibiotic-induced Th2-skewed response was seen in C57BL/6 mice that are genetically biased towards Th1-dominant immunity. Conclusion These results suggest that adequate probiotic intervention after antibiotic treatment may improve the intestinal ecosystem, and thereby prevent the Th2-shifted immunity induced by neonatal antibiotic use. In addition, the difference of genetic backgrounds also contributes to such an antibiotic-induced Th2-skewed response.

High prevalence of current asthma and active smoking effect among the elderly

Abstract: Summary Background Although asthma is a common cause of morbidity in adults, relatively few objectively measured population studies of asthma prevalence in adult populations have been conducted. Objective To evaluate the prevalence of asthma, based on both a questionnaire and methacholine bronchial provocation test, and to determine the risk factors of asthma prevalence in an adult population. Methods A total of 2467 adults, who were randomly selected from metropolitan urban, non-metropolitan urban and rural areas, responded to the modified ISAAC questionnaire, and underwent methacholine bronchial provocation tests and skin prick tests to locally common aeroallergens. Results The prevalence of current asthma based on the questionnaire and the methacholine challenge was 2.0% in adults younger than 40, 3.8% in 40- to 54-year-olds, 7.7% in 55- to 64-year-olds and 12.7% in those aged 65 or higher. For subjects of 55–64 years, active smoking was found to be significantly related with the prevalence of current asthma and bronchial hyper-responsiveness, although smoking was positively associated with percentage predictive value of forced expiratory volume of 1 s (FEV1). Conclusion The prevalence of current asthma is common among the elderly, and active smoking may play an important role in the development of asthma and bronchial hyper-responsiveness among the elderly.

Type I allergy to natural rubber latex and type IV allergy to rubber chemicals in health care workers with glove‐related skin symptoms

Abstract: Background It has been established that there are type I and type IV allergens in latex gloves. Objective The purpose of the study was to establish the prevalence of rubber glove-induced skin symptoms among health care workers in one Italian hospital. Methods Health care workers (n = 1584) were evaluated using a written questionnaire and 295 respondents with glove-induced skin symptoms were tested. We performed: skin prick test with latex glove extract and commercial latex, and environmental and food allergens; glove use test; patch tests with a rubber additive series; and RASTs. Results Hospital employees who used or had used latex gloves at work were 1294. Three hundred and sixteen (24.4%) reported glove-induced symptoms, namely, cutaneous symptoms in all the cases and non-cutaneous symptoms in 105 subjects (8.1%). Twenty-seven of the 295 symptomatic employees tested (9.1%) were latex sensitive. Thirty-one patients (10.5%) exhibited positive patch test to rubber-related allergens. The most positive readings were obtained from the Thiuram mix and the Carba mix, with 12 and 9 positivities, respectively. The risk factors for latex skin sensitization were: a previous history of atopy and asthma; history of surgery; pre-existing hand dermatitis; work-related symptoms; and positive skin tests to common inhalant and certain foods (P < 0.05). Subjects who exhibited positive patch test were significantly more likely to have a prior hand dermatitis (P < 0.001). Of the 295 cases, 275 (93.2%) were contact dermatitis (CD), 13 (4.4%) contact urticaria (CU) (including protein CD) and 7 (2.4%) CD associated with CU. Conclusions Our results show a high prevalence of rubber glove-induced dermatoses among the employees in one Italian hospital. The majority of skin complaints of latex gloves are related to skin irritation rather than to allergy. The immediate allergy to latex and the delayed allergy to rubber chemicals suggest that all the health care workers with glove-related dermatitis should undergo both skin prick test and glove use test to detect type I hypersensitivity to latex, and patch test to detect type IV hypersensitivity to rubber chemicals.

The impact of climate and traffic-related NO2 on the prevalence of asthma and allergic rhinitis in Italy

Abstract: BACKGROUND Environmental factors are likely to be involved in explaining the wide geographical variation in asthma and atopic diseases that has been documented in many recent epidemiological studies. AIM To evaluate to what extent climate and outdoor NO2 pollution can explain the geographical variation in the prevalence of asthma and allergic rhinitis, and to estimate the relative risk for exposure to different levels of these two factors. METHODS The impact of climate and long-term exposure to nitrogen dioxide (NO2) pollution on asthma and allergic rhinitis was assessed in a cross-sectional study, carried out during 1998 to 2000 on young adults aged 20 to 44 years (n = 18 873), living in 13 areas from two different Italian climatic regions (subcontinental and Mediterranean). RESULTS Mediterranean areas had a significantly higher prevalence of asthma-like symptoms (P < 0.001), higher annual mean temperature (16.2 degrees C vs. 12.9 degrees C), lower temperature range (16.0 C degrees vs. 22.1 degrees C) and lower NO2 levels (31.46 microg/m3 vs. 57.99 microg/m3) than subcontinental ones. Mediterranean climate was associated with an increased risk of wheeze (OR = 1.23; 95% CI 1.13 to 1.35), tightness in the chest (OR = 1.21; 95% CI 1.11 to 1.33), shortness of breath (OR = 1.21; 95% CI 1.08 to 1.36) and asthma attacks (OR = 1.19; 95% CI 1.07 to 1.31). After adjusting for climate, an increase of 18.3 microg/m3 in NO2 levels moderately increased the risk of asthma attacks (OR = 1.13; 95% CI 0.98 to 1.32), tightness in the chest (OR = 1.11; 95% CI 0.98 to 1.26) and wheeze (OR = 1.11; 95% CI 0.96 to 1.28). When the levels of outdoor NO2 exposure rose, the prevalence of allergic rhinitis increased significantly in the Mediterranean region (OR = 1.38; 95% CI 1.12 to 1.69), but not in the subcontinental one (OR = 1.03; 95% CI 0.83 to 1.28). CONCLUSION Our results show that the prevalence of asthma increases when annual mean temperature increases and temperature range decreases. Furthermore, climate interacts with NO2 outdoor exposure, increasing the risk for allergic rhinitis in people exposed to high stable temperatures. A long-term role for the effect of traffic pollution on asthma is also suggested.

Accuracy of eosinophils and eosinophil cationic protein to predict steroid improvement in asthma

Abstract: Background There is a large variability in clinical response to corticosteroid treatment in patients with asthma. Several markers of inflammation like eosinophils and eosinophil cationic protein (ECP), as well as exhaled nitric oxide (NO), are good candidates to predict clinical response. Aim We wanted to determine whether we could actually predict a favourable response to inhaled corticosteroids in individual patients. Methods One hundred and twenty patients with unstable asthma were treated with either prednisolone 30 mg/day, fluticasone propionate 1000 mug/day b.i.d. or fluticasone propionate 250 mug/day b.i.d., both via Diskhaler. They were treated during 2 weeks, in a double-blind, parallel group, double dummy design. We measured eosinophils and ECP in blood and sputum, and exhaled nitric oxide as inflammatory parameters before and after 2 weeks in order to predict the changes in forced expiratory volume in 1 s (FEV1), provocative concentration of methacholine causing a 20% fall in FEV1 (PC20 Mch), and asthma quality of life (QOL). Secondly, to test whether these results were applicable in clinical practice we determined the individual prediction of corticosteroid response. Results We fond that changes in FEV1, PC20 Mch and QOL with corticosteroids were predominantly predicted by their respective baseline value and to a smaller extent by eosinophils in blood or sputum. ECP, measured in blood or sputum, was certainly not better than eosinophils in predicting clinical response to corticosteroids. Smoking status was an additional predictor for change in FEV1, but not for change in PC20 Mch or QOL. Prediction of a good clinical response was poor. For instance, high sputum eosinophils (greater than or equal to 3%) correctly predicted an improvement in PC20 Mch in only 65% of the patients. Conclusion Our findings show that baseline values of the clinical parameters used as outcome parameters are the major predictors of clinical response to corticosteroids. Eosinophil percentage in blood or sputum adds to this, whereas ECP provides no additional information. Correct prediction of clinical response in an individual patient, however, remains poor with our currently used clinical and inflammatory parameters.

Relationship between allergic rhinitis, disturbed cognitive functions and psychological well‐being

Abstract: Background Symptomatic allergic rhinitis reduces quality of life as a result of the symptoms experienced and possibly as a result of impaired psychological well-being and cognitive functioning. Few investigations have measured cognitive functions objectively and it remains uncertain whether allergic rhinitis leads to an objective reduction in cognitive functions. Objective To evaluate the relationship between symptomatic allergic rhinitis, cognitive functions and psychological well-being. Differences between subjective and objective cognitive impairments were evaluated. Methods The cognitive functions (working memory, memory retrieval, speed of information processing and flexibility of information processing) and psychological well-being of 26 patients with symptomatic allergic rhinitis and 36 healthy controls matched for intelligence, education, age and sex were compared. The influence of education, intelligence, sex and age was considered. Results Overall, psychological well-being was significantly impaired in the patient group, as shown by higher scores in feelings of insufficiency, complaints of somatization, sleep disturbances and depressive feelings, whereas cognitive function was not. Conclusions Allergic rhinitis was related to significantly impaired psychological well-being and to perceived impaired cognitive functioning. However, no significant objective impairment of cognitive functioning was found. Allergic patients may temporarily put more effort into sustaining performance, resulting in earlier exhaustion, which is not noticed during assessment but which impairs psychological well-being.

Increase of allergen-specific immunoglobulin E antibodies from 1973 to 1994 in a Finnish population and a possible relationship to Helicobacter pylori infections.

Abstract: Background The prevalence of atopic diseases – hayfever, asthma and eczema – has increased over the past decades. The increase may be associated with decreased rates of infections such as measles, hepatitis A, tuberculosis, toxoplasmosis, and, as recently suggested, Helicobacter pylori gastritis. Objective Since the increase of atopy has been mainly based on clinical studies, we wanted to study the prevalence of allergen-specific Immunoglobulin (Ig)E antibodies in two cross-sectional, adult population-based serum samples two decades apart. Since the sera had been tested for H. pylori antibodies, we also had a chance to look for a possible relationship between these two findings. Methods We determined the prevalence rate of allergen-specific serum IgE antibodies against birch and timothy pollen, and cat and dog epithelium allergens by the radioallergosorbent test in a 15–54-years-old Finnish population using 326 sera collected in 1973 and 319 sera collected in 1994 from randomly selected subjects. Results From 1973 to 1994 allergen-specific IgE prevalence rates and IgE antibody levels rose. In 1994, the prevalence rate of positive findings in 15–24-year-old population had increased from 11 to 38% (3.5-fold increase, P = 0.0001, OR 5.12, CI 95% 2.32–11.3). In older 10-year age groups similar trends did not reach significance, but the overall change was significant with all three cut-off levels of allergen-specific IgE analysed. The percentage of IgE-positive persons rose mainly in the subgroup with no H. pylori antibodies. In 1994 21% of the H. pylori-negative subjects had IgE antibodies compared with 5% of the H. pylori-positive subjects (in 1973 11% in both subgroups). Conclusions IgE-based evidence for an increase in IgE-mediated allergy was uncovered. The increase occurred mainly in the subgroup with no antibodies to H. pylori, which support the hypothesis that H. pylori could be one of the microbes counteracting atopy.

Intranasal application of chitin microparticles down-regulates symptoms of allergic hypersensitivity to Dermatophagoides pteronyssinus and Aspergillus fumigatus in murine models of allergy.

Abstract: Summary Background Previous studies have demonstrated that chitin in the form of microparticles that can be phagocytosed is a potent macrophage stimulator and promotes a Th1 cytokine response and it has been shown that oral administration of chitin microparticles is effective in down-regulating serum IgE and lung eosinophilia in a mouse model of ragweed allergy. To date there have been no studies on the effectivness of directly applying chitin microparticles to the respiratory tract as a treatment for allergic symptoms. Objective To test the effectivness of chitin microparticles when given intranasally as a treatment for the symptoms of respiratory allergy and allergic asthma and to compare its effectivness in two different mouse models of allergy, namely to Dermatophagoides pteronyssinus and Aspergillus fumigatus. Results The intranasal application of microgram doses of chitin microparticles is an effective treatment for reducing serum IgE and peripheral blood eosinophilia, airway hyper-responsiveness and lung inflammation in both allergy models results in elevation in Th1 cytokines IL-12, IFN-γ and TNF-α and reduction in IL-4 production during allergen challenge. Conclusion Chitin microparticle suspensions have Th1 immunostimulatory properties and are effective when administered intranasally in mice. The stimulation of the nasal associated lymphoid tissue with chitin microparticles could offer a novel and natural approach to treating allergic disease in humans.

The range of minimum provoking doses in hazelnut‐allergic patients as determined by double‐blind, placebo‐controlled food challenges

Abstract: Background: The risk for allergic reactions depends on the sensitivity of individuals and the quantities of offending food ingested. The sensitivity varies among allergic individuals, as does the threshold dose of a food allergen capable of inducing an allergic reaction. Objective: This study aimed at determining the distribution of minimum provoking doses of hazelnut in a hazelnut-allergic population. Methods: Thirty-one patients with a history of hazelnut-related allergic symptoms, a positive skin prick test to hazelnut and/or an elevated specific IgE level, were included. Double-blind, placebo-controlled food challenges (DBPCFC) were performed with seven increasing doses of dried hazelnut (1 mg to 1 g hazelnut protein) randomly interspersed with seven placebo doses. Results: Twenty-nine patients had a positive challenge. Itching of the oral cavity and/or lips was the first symptom in all cases. Additional gastrointestinal symptoms were reported in five patients and difficulty in swallowing in one patient. Lip swelling was observed in two patients, followed by generalized urticaria in one of these. Threshold doses for eliciting subjective reactions varied from a dose of 1 mg up to 100 mg hazelnut protein (equivalent to 6.4-640 mg hazelnut meal). Extrapolation of the dose-response curve showed that 50% of our hazelnut-allergic population will suffer from an allergic reaction after ingestion of 6 mg (95% CI, 2-11 mg) of hazelnut protein. Objective symptoms were observed in two patients after 1 and 1000 mg, respectively. Conclusion: DBPCFCs demonstrated threshold doses in half of the hazelnut-allergic patients similar to doses previously described to be hidden in consumer products. This stresses the need for careful labelling and strategies to prevent and detect contamination of food products with hazelnut residues. Chemicals/CAS: Allergens

Rapid response of circulating myeloid dendritic cells to inhaled allergen in asthmatic subjects.

Abstract: Summary Background Dendritic cells (DC) are thought to play a key role in the initiation and maintenance of T cell immunity to inhaled antigens. While the density of DC within the bronchial mucosa is increased in stable asthma, there is little information currently available concerning the effects of allergen inhalation on DC in subjects with asthma. Objectives To enumerate changes in the numbers of circulating CD33 + myeloid DC in asthmatics, before and after allergen challenge. Methods Blood DC numbers were enumerated by flow cytometry before and at 3, 6 and 24 h after inhaled allergen and diluent in 10 mild, allergic asthmatic subjects. Results Blood DC numbers rapidly fell from 3.42 ± 0.30 × 10 7 /L at baseline, to 2.10 ± 0.17 × 10 7 /L by 3 h post-challenge (P < 0.01), and remained significantly below baseline values at both 6 and 24 h following allergen challenge. No such changes in DC numbers were noted after diluent challenge. A similar, early fall in circulating lymphocytes was also noted post-allergen challenge, whereas changes in circulating eosinophil and neutrophil numbers occurred more slowly. Conclusions A significant proportion of myeloid DC rapidly ‘disappear’ from the circulation following allergen inhalation, suggesting that margination of circulating myeloid DC, and their recruitment into the airway mucosa, is an important feature of the immune response to inhaled allergen.