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Eosinophilic Inflammation (eosinophilic + inflammation)

Distribution by Scientific Domains

Medical Sciences	100%

Distribution within Medical Sciences

Allergy & Clinical Immunology	66%
General & Internal Medicine	10%
5 Other Subdomains	24%

Selected Abstracts

Clinical and inflammatory features of occupational asthma caused by persulphate salts in comparison with asthma associated with occupational rhinitis

ALLERGY, Issue 6 2010
G. Moscato
To cite this article: Moscato G, Pala G, Perfetti L, Frascaroli M, Pignatti P. Clinical and inflammatory features of occupational asthma caused by persulphate salts in comparison with asthma associated with occupational rhinitis. Allergy 2010; 65: 784,790. Abstract Background:, The relationships between asthma and rhinitis are still a crucial point in respiratory allergy and have scarcely been analysed in occupational setting. We aimed to compare the clinical and inflammatory features of subjects with occupational asthma only (OA) to subjects with OA associated to occupational rhinitis (OAR) caused by persulphate salts. Methods:, The clinical charts of 26 subjects diagnosed in our Unit as respiratory allergy caused by ammonium persulphate (AP), confirmed by specific inhalation challenge (SIC), were reviewed. Twenty-two out of twenty-six patients underwent pre-SIC-induced sputum challenge test (IS) and 24/26 underwent nasal secretion collection and processing. Results:, Twelve out of twenty-six patients received a diagnosis of OA-only and 14/26 of OAR. Duration of exposure before diagnosis, latency period between the beginning of exposure and asthma symptom onset, basal FEV1, airway reactivity to methacholine and asthma severity did not differ in the two groups. Eosinophilic inflammation of upper and lower airways characterized both groups. Eosinophil percentage in IS tended to be higher in OAR [11.9 (5.575,13.925)%] than in OA-only [2.95 (0.225,12.5)%] (P = 0.31). Eosinophilia in nasal secretions was present both in subjects with OAR [55 (46,71)%] and in subjects with OA-only [38 (15,73.5)%], without any significant difference. Discussion:, Our results indicate that OA because of ammonium persulphate coexists with occupational rhinitis in half of the patients. Unexpectedly, rhinitis did not seem to have an impact on the natural history of asthma. The finding of nasal inflammation in subjects with OA-only without clinical manifestations of rhinitis supports the united airway disease concept in occupational respiratory allergy as a result of persulphates. [source]

Long-term frontal sinus patency after endoscopic frontal sinusotomy,

THE LARYNGOSCOPE, Issue 6 2009
Yvonne Chan MD
Abstract Background: The frontal recess is the drainage pathway that connects the frontal sinus to the anterior ethmoid sinus. Mechanical obstruction is the primary cause of chronic frontal sinusitis with or without a secondary inflammatory process. Eosinophilic inflammation is one of the underlying causes for chronic rhinosinusitis. Objectives/Hyphothesis: To evaluate long-term frontal sinus patency after endoscopic frontal sinusotomy in chronic rhinosinusitis patients and to assess the effect of eosinophilic inflammation on frontal sinus patency. Study Design: Retrospective chart review. Symptom assessment and archived endoscopic photographs were prospectively collected on patients who underwent frontal sinusotomy between 7-1-1999 and 12-31-2000. Subjective symptom improvements were evaluated using the SNOT-20 = 20-item Sino-Nasal Outcome Test. Objective findings of endoscopic frontal sinus patency were documented by archived digital photography. Results: A total of 161 patients with 294 frontal sinuses who underwent endoscopic frontal sinus surgery in the 18 months had an average follow-up of 45.9 months. The patient population was divided into two groups: 58 patients had eosinophilic CRS (ECRS), and 103 patients had CRS without eosinophils (non-ECRS). The mean follow-up for patients with ECRS is 61.6 months and 37.0 months for non-ECRS patients. The non-ECRS patients had a documented endoscopic frontal sinus patency of 90%, and the ECRS patients had an endoscopic frontal sinus patency of 85%. The overall frontal ostium patency rate for all patients was 88.0%. Conclusions: Long-term endoscopic confirmation of frontal ostium patency demonstrates that endoscopic frontal sinusotomy can yield high quality, durable results. There was no significant difference in patency results between ECRS and non-ECRS patients. Laryngoscope, 2009 [source]

Markers of eosinophilic inflammation and risk prediction in patients with coronary artery disease

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2006
C. Falcone
Abstract Background, The eotaxin family comprises three distinct peptides (eotaxin, eotaxin-2 and eotaxin-3) which have been implicated in eosinophilic inflammation. In vitro and clinical studies suggest that eotaxins could play a role in vascular inflammation, but no data are available on their prognostic significance in patients with angiographically documented coronary artery disease (CAD). Materials and methods, Baseline plasma samples were obtained from 1014 patients with documented CAD. We tested the predictive effect of markers of eosinophilic inflammation and C-reactive protein (CRP) on death from cardiovascular causes and nonfatal myocardial infarction over a 2·7,4·1-year follow-up period. Results, Unexpectedly, lower eotaxin-3 concentrations were observed in patients with adverse cardiovascular events, whereas both eotaxin and eotaxin-2 showed no association with risk. After adjustment for most potential confounders, patients in the upper-quartile of eotaxin-3 levels had a 0·42 hazard-ratio (95% CI, 0·29,0·61, P < 0·001) for adverse events compared with subjects in the lower-quartile. The highest risk of future cardiovascular events was observed in subjects with combined elevation of CRP and reduction of eotaxin-3; 4·4 hazard-ratio (95% CI, 2·1,9·5, P < 0·001). Importantly, receiver-operating-characteristic curves analysis suggested a superior prognostic value of eotaxin-3 compared with CRP for predicting cardiac events in patients with CAD. Conclusions, Low levels of eotaxin-3 are an independent predictor of future adverse cardiovascular events in patients with CAD and may be useful for risk stratification. [source]

Airway inflammation in subjects with gastro-oesophageal reflux and gastro-oesophageal reflux-related asthma

JOURNAL OF INTERNAL MEDICINE, Issue 3 2006
G. E. CARPAGNANO
Abstract. Study objectives., Asthma and gastro-oesophageal reflux (GER) are both characterized by airway inflammation. Design., The purposes of this work were (i) to study airway inflammation in patients troubled by gastro-oesophageal reflux (GER) and GER associated with asthma, (ii) to ascertain whether GER can aggravate asthma by exacerbating the pre-existing airway inflammation and oxidative stress and (iii) to establish the validity of analysing breath condensate and induced sputum when studying the airways of subjects affected by GER. Patient s and methods., We enrolled 14 patients affected by mild asthma associated with GER (40 ±12 years), nine with mild but persistent asthma (39 ± 13 years), eight with GER (35 ± 11 years) and 17 healthy subjects (37 ± 9 years). Sputum cell counts and concentrations of interleukin-4 (IL-4), IL-6 and 8-isoprostane were measured in breath condensate and supernatant. Measurements and results., GER-related asthma is characterized by an eosinophilic inflammation, as determined by elevated concentrations of IL-4 in breath condensate and sputum supernatant, and by sputum cell analysis. GER alone presents a neutrophilic pattern of inflammation when determined by elevated concentrations of IL-6 in sputum cell analysis. A concomitant increase has been found in 8-isoprostane in GER associated (or not associated) with asthma. Conclusions., We conclude that GER is characterized by a neutrophilic airway inflammation and by increased oxidative stress. GER does not however aggravate pre-existing airway inflammation in asthma patients. Determinations of inflammatory and oxidant markers in the breath condensate of subjects with GER reflect these measured in the induced sputum. [source]

Anti-inflammatory, analgesic and anti-oedematous effects of Lafoensia pacari extract and ellagic acid

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2006
Alexandre P. Rogerio
Lafoensia pacari St. Hil. (Lythraceae) is used in traditional medicine to treat inflammation. Previously, we demonstrated the anti-inflammatory effect that the ethanolic extract of L. pacari has in Toxocara canis infection (a model of systemic eosinophilia). In this study, we tested the antiinflammatory activity of the same L. pacari extract in mice injected intraperitoneally with ,-glucan present in fraction 1 (F1) of the Histoplasma capsulatum cell wall (a model of acute eosinophilic inflammation). We also determined the anti-oedematous, analgesic and anti-pyretic effects of L. pacari extract in carrageenan-induced paw oedema, acetic acid writhing and LPS-induced fever, respectively. L. pacari extract significantly inhibited leucocyte recruitment into the peritoneal cavity induced by ,-glucan. In addition, the L. pacari extract presented significant analgesic, anti-oedematous and anti-pyretic effects. Bioassay-guided fractionation of the L. pacari extract in the F1 model led us to identify ellagic acid. As did the extract, ellagic acid presented anti-inflammatory, anti-oedematous and analgesic effects. However, ellagic acid had no anti-pyretic effect, suggesting that other compounds present in the plant stem are responsible for this effect. Nevertheless, our results demonstrate potential therapeutic effects of L. pacari extract and ellagic acid, providing new prospects for the development of drugs to treat pain, oedema and inflammation. [source]

Inflammatory profiles in nasal mucosa of patients with persistent vs intermittent allergic rhinitis

ALLERGY, Issue 9 2010
F. Liu
To cite this article: Liu F, Zhang J, Liu Y, Zhang N, Holtappels G, Lin P, Liu S, Bachert C. Inflammatory profiles in nasal mucosa of patients with persistent vs intermittent allergic rhinitis. Allergy 2010; 65: 1149,1157. Abstract Background:, To date there is little information on the inflammatory profiles of patients suffering from persistent (PER) and intermittent allergic rhinitis (IAR). Also, it is not clear whether differences exist in eosinophilic inflammation and/or T-helper cell sub-populations and their markers. The aim of this study was to primarily evaluate the inflammatory profiles of patients with moderate/severe PER and IAR. Methods:, Inferior nasal turbinate tissue was obtained from 12 PER, 12 IAR and 12 nonallergic nonrhinitic (control) patients, and symptoms (visual analogue scales, VAS) and impairment of life was monitored. All tissues were assessed for eosinophil and mast cell numbers by immunohistochemistry; IL-5, ECP and IgE concentrations by immunoassay; mRNA for transcription factors GATA-3, T-bet, FOXP3 and RORc by quantitative real-time polymerase chain reaction; and IgE-induced release of LTC4/D4/E4 and PGD2in vitro. Results:, Eosinophils and mast cells were significantly increased in patients with PER and patients with IAR compared to control subjects; by patients with PER demonstrating even significantly greater increase of both cell types than patients with IAR. Similarly, ECP IL-5, GATA-3 mRNA expression and IgE-induced release of LTC4/D4/E4 and PGD2 from mast cells were significantly increased in patients with PER compared to patients with IAR. In contrast, the expression of T-bet, FOXP3 or RORc mRNA was not significantly different in the PER, IAR or control patients. Conclusion:, The findings from the present study suggest that PER is characterized by a significantly greater eosinophilic and predominantly Th2 cell-mediated nasal inflammatory profile compared to IAR. [source]

Conjunctival effects of a selective nasal pollen provocation

ALLERGY, Issue 9 2010
I. Callebaut
To cite this article: Callebaut I, Spielberg L, Hox V, Bobic S, Jorissen M, Stalmans I, Scadding G, Ceuppens JL, Hellings PW. Conjunctival effects of a selective nasal pollen provocation. Allergy 2010; 65: 1173,1181. Abstract Background:, Several clinical and experimental observations suggest that allergen deposition in the nose may partially be responsible for the induction of conjunctival symptoms in allergic rhinitis. The aims of this study were to evaluate the induction of conjunctival symptoms by selective nasal allergen provocation and to assess the feasibility of the different tools for evaluation of conjunctival allergic inflammation. Methods:, Grass pollen allergic subjects with rhinoconjunctivitis symptoms during the pollen season (n = 12) underwent a nasal sham and grass pollen provocation extra-seasonally. Nasal and conjunctival symptoms were scored using the Visual Analogue Scale (VAS) system at baseline, 15 min, 1 h and 24 h after provocation. In addition to Peak Nasal Inspiratory flow (PNIF) measurements, conjunctival inflammation and vascular congestion were evaluated and histamine and substance P levels in tear fluid were measured. Results:, Selective nasal grass pollen provocation induced ocular pruritus, lacrimation and conjunctival vascular congestion. PNIF values correlated inversely with lacrimation (r = ,0.71, P < 0.001) and ocular pruritus (r = ,0.41, P < 0.05). Four out of 11 patients showed a conjunctival eosinophilic inflammation and levels of histamine (r = 0.73, P < 0.05) and substance P (r = 0.67, P = 0.05) in tear fluid correlated with conjunctival symptoms. Conclusion:, Selective nasal grass pollen provocation induced conjunctival inflammation, ocular pruritus and lacrimation, which correlated with histamine and substance P levels in tear fluid and inversely with the PNIF values. These data show a naso-ocular interaction in allergic rhinitis and offer objective tools for evaluation of conjunctival inflammation in allergic rhinoconjunctivitis. [source]

IL-5 expression and release from human CD34 cells in vitro; ex vivo evidence from cases of asthma and Churg,Strauss syndrome

ALLERGY, Issue 7 2010
A. Bossios
To cite this article: Bossios A, Sjöstrand M, Dahlborn A-K, Samitas K, Malmhäll C, Gaga M, Lötvall J. IL-5 expression and release from human CD34 cells in vitro; ex vivo evidence from cases of asthma and Churg,Strauss syndrome. Allergy 2010; 65: 831,839. Abstract Background:, Eosinophils develop from hematopoietic CD34+ progenitor cells in the bone marrow (BM) under the influence of Interleukin-5 (IL-5). The primary source of IL-5 is T-lymphocytes, although other sources may exist. The aims of this study were to determine whether CD34+ cells from human peripheral blood (PB) and BM have the capacity to produce IL-5 when stimulated in vitro, and secondly, whether an elevated number of IL-5-producing CD34+ cells can be found in situ in ongoing eosinophilic disease. Methods:, CD34+ cells from PB and BM were stimulated in vitro, and IL-5 production and release was assessed by ELISA, ELISPOT, flow cytometry and immunocytochemistry. Blood and BM from a patient with Churg,Strauss syndrome were analyzed by flow cytometry for CD34+/IL-5+ cells, and immunohistochemical staining of CD34+/IL-5+ cells in bronchial biopsies from an asthmatic patient was performed. Results:, Both PB and BM CD34+ cells can produce and release IL-5 when stimulated in vitro. In the Churg,Strauss patient, IL-5-producing CD34+ cells were found in PB and BM. Oral glucocorticoid treatment markedly decreased the number of IL-5-positive CD34 cells in the BM. CD34+/IL-5+ cells were present in a patient with asthma. Conclusion:, CD34+ cells in blood and BM are capable of producing IL-5 both in vitro and in vivo in humans, arguing that these cells may have the capacity to contribute to eosinophilic inflammation. Consequently, targeting CD34+ progenitor cells that produce and release IL-5 may be effective in reducing the mobilization of eosinophil lineage-committed cells in eosinophilic-driven diseases. [source]

Objective assessments of allergic and nonallergic rhinitis in young children

ALLERGY, Issue 10 2009
B. L. K. Chawes
Background:, Allergic and nonallergic rhinitis are common childhood disorders. Objective:, To study nasal eosinophilia and nasal airway patency in young children with allergic and nonallergic rhinitis to assess the pathology behind such diagnoses. Methods:, We investigated 255 children at six years of age from the Copenhagen Prospective Study on Asthma in Childhood birth cohort assessing rhinitis history, specific immunoglobulin E relevant to rhinitis symptoms, nasal eosinophilia and nasal airway patency by acoustic rhinometry before and after decongestion. Associations were studied in a multivariate graphical model corrected for gender, height and nasal steroid usage. Results:, Allergic rhinitis was significantly and directly associated with irreversible nasal airway obstruction (reduced decongested nasal airway patency) (P = 0.004), whereas nonallergic rhinitis was not. Both allergic rhinitis (P = 0.000) and nonallergic rhinitis (P = 0.014) were directly and significantly associated with nasal eosinophilia, but this association was stronger for allergic rhinitis. Conclusion:, Allergic rhinitis and nonallergic rhinitis are of different pathologies as suggested from their different associations not only to allergy but importantly also to irreversible nasal airway obstruction and eosinophilic inflammation. Allergic rhinitis was significantly associated with nasal eosinophilia and irreversible nasal airway obstruction suggesting chronic inflammation and structural remodeling of the nasal mucosa in children at the age of 6 years. Nonallergic rhinitis exhibited no change in the nasal airway patency, but some nasal mucosal eosinophilia albeit less than children with allergic rhinitis. [source]

Relation between inflammation and symptoms in asthma

ALLERGY, Issue 3 2009
I. Tillie-Leblond
Asthma symptoms are the main reason for healthcare utilization and are a fundamental parameter for the evaluation of asthma control. Currently, asthma is defined as a chronic inflammatory disease. A French expert group studied the association between inflammation and asthma symptoms by carrying out a critical review of the international literature. Uncontrolled asthmatics have an increased number of polynuclear eosinophils in the induced sputum and an increased production of exhaled NO. Control by anti-inflammatory treatment is accompanied by a reduction in bronchial eosinophilia and exhaled NO. Asthma symptoms are the result of complex mechanisms and many factors modify their perception. Experimental data suggest that there is a relationship between the perception of symptoms and eosinophilic inflammation and that inhaled corticoid therapy improves this perception. Although they are still not applicable in routine practice, follow-up strategies based on the evaluation of inflammation are thought to be more effective in reducing exacerbations than those usually recommended based on symptoms and sequential analysis of respiratory function. Inhaled corticosteroid therapy is the reference disease-modifying therapy for persistent asthma. Recent studies demonstrated that adjustment of anti-inflammatory treatment based on symptoms is an effective strategy to prevent exacerbations and reduce the total number of doses of inhaled corticosteroids. [source]

Eosinophils in bronchial mucosa of asthmatics after allergen challenge: effect of anti-IgE treatment

ALLERGY, Issue 1 2009
E. L. J. Van Rensen
Background:, Anti-IgE, omalizumab, inhibits the allergen response in patients with asthma. This has not been directly related to changes in inflammatory conditions. We hypothesized that anti-IgE exerts its effects by reducing airway inflammation. To that end, the effect of anti-IgE on allergen-induced inflammation in bronchial biopsies in 25 patients with asthma was investigated in a randomized, double-blind, placebo-controlled study. Methods:, Allergen challenge followed by a bronchoscopy at 24 h was performed at baseline and after 12 weeks of treatment with anti-IgE or placebo. Provocative concentration that causes a 20% fall in forced expiratory volume in 1 s (PC20) methacholine and induced sputum was performed at baseline, 8 and 12 weeks of treatment. Changes in the early and late responses to allergen, PC20, inflammatory cells in biopsies and sputum were assessed. Results:, Both the early and late asthmatic responses were suppressed to 15.3% and 4.7% following anti-IgE treatment as compared with placebo (P < 0.002). This was paralleled by a decrease in eosinophil counts in sputum (4,0.5%) and postallergen biopsies (15,2 cells/0.1 mm2) (P < 0.03). Furthermore, biopsy IgE+ cells were significantly reduced between both the groups, whereas high-affinity IgE receptor and CD4+ cells were decreased within the anti-IgE group. There were no significant differences for PC20 methacholine. Conclusion:, The response to inhaled allergen in asthma is diminished by anti-IgE, which in bronchial mucosa is paralleled by a reduction in eosinophils and a decline in IgE-bearing cells postallergen without changing PC20 methacholine. This suggests that the benefits of anti-IgE in asthma may be explained by a decrease in eosinophilic inflammation and IgE-bearing cells. [source]

Indices of lower airway inflammation in children monosensitized to house dust mite after nasal allergen challenge

ALLERGY, Issue 10 2008
A. Inal
Background:, There are few available data assessing the united airway disease and its systemic aspects in children. With this study, we aimed to investigate the inflammation markers of upper and lower airways before and after nasal allergen challenge in mite sensitive children with different clinical expression of the allergic disease. Methods:, Four study groups were formed: rhinitis only, without bronchial hyper-responsiveness (R, n = 10), rhinitis with asthma (R + A, n = 22), atopic asymptomatics (AA, n = 8) and nonallergic healthy controls (C, n = 10). Blood eosinophils, nasal and sputum eosinophils, sputum eosinophil cationic protein (ECP) and cys-LTs, and serum ECP levels were measured before and 24 h after nasal allergen challenge. Results:, The groups were comparable in terms of age and gender. Cumulative symptom scores recorded during and 1 h after nasal challenge were not significantly different between patients with R, R + A and AA groups. At T24, the children belonging to R, R + A and AA showed significant increases in nasal eosinophils (P < 0.01, P < 0.001, and P = 0.01, respectively), sputum eosinophils (P = 0.01, P < 0.001, and P < 0.05, respectively) and blood eosinophils (P < 0.01, P < 0.001, and P < 0.05, respectively). Similarly, increases in sputum ECP (P < 0.01, P < 0.001, and P = 0.07, respectively) and sputum cys-LT levels (P = 0.07, P < 0.001, and P < 0.05, respectively) were detected in children belonging to these three groups at T24. Sputum eosinophils significantly correlated with blood eosinophils (r = 0.54, P < 0.001) and sputum ECP (r = 0.58, P < 0.001) at T24. Conclusions:, This study showed that nasal allergen challenge increased markers of eosinophilic inflammation in both upper and lower airways of children monosensitized to mites, even before the onset of clinical symptoms. [source]

Chronic inflammation in asthma: a contest of persistence vs resolution

ALLERGY, Issue 9 2008
C. L. Van Hove
Recent investigations have highlighted that endogenous anti-inflammatory mediators and immune regulating mechanisms are important for the resolution of inflammatory processes. A disruption of these mechanisms can be causally related not only to the initiation of unnecessary inflammation, but also to the persistence of several chronic inflammatory diseases. In asthma, chronic Th-2 driven eosinophilic inflammation of the airways is one of the central abnormalities. To date, elucidating the role of the different pro-inflammatory mediators involved in orchestrating the inflammatory processes in asthma has been the subject of intense research in both humans and animal models. However, the counter-regulatory mechanisms that co-determine the outcome in the contest of resolution vs persistence of the eosinophilic airway inflammation remain poorly understood. These are currently being investigated in animal models of chronic asthma. Elucidating these mechanisms is of relevance, since it can give rise to a new therapeutic approach in the treatment of chronic airway inflammation in asthmatics. This novel concept of treatment involves the stimulation of endogenous anti-inflammatory pathways, rather than solely antagonising the various pro-inflammatory mediators. Here, we review and discuss the current knowledge about these endogenous anti-inflammatory mediators in clinical and experimental asthma. [source]

Comparison of atopic and nonatopic children with chronic cough: Bronchoalveolar lavage cell profile,

PEDIATRIC PULMONOLOGY, Issue 10 2007
Flavia de A Ferreira MD
Abstract Chronic cough is a common complaint in children and its relationship with asthma is controversial. The aim of the present study was to determine the pattern of airway inflammation in atopic and nonatopic children with chronic cough, and to investigate whether atopy is a predictive factor for eosinophilic inflammation in cough. Bronchoalveolar lavage (BAL; three aliquots of 1 ml/kg saline) was performed in the right middle lobe of 24 (11 atopic and 13 nonatopic) children with persistent cough (8 females, 16 males), mean age 4.7 years (range: 1,11). Atopy was defined as an elevated total serum IgE or a positive RAST test. Both atopic and nonatopic children with persistent cough had an increase in total cells/ml in BAL (atopic: median 39,×,104, range: 20,123; nonatopic: median 22,×,104, range: 17,132) compared to nonatopic controls (median 11,×,104, range 9,30). The increases were mainly in neutrophils (atopic: median 17%, range 2.5,88.5%; nonatopic: median 6%, range 1.0,55.0%) compared to controls (median 1.55%, range 0.5,7.0%; atopics vs. controls, P,<,0.005). There were no significant increases in eosinophils, lymphocytes, epithelial cells, or mast cells. Eosinophils were elevated in only 5/11 atopic and none of the nonatopic children. The increased percentage of neutrophils in the BAL fluid of atopic and nonatopic children with persistent cough could be due to an underlying inflammatory process driving the cough, or even conceivably, due to the effect of coughing itself. In this highly selected series, the absence of eosinophilic inflammation in the majority suggests that most would be predicted not to respond to inhaled corticosteroid therapy. This study underscores the need to be cautious about treating coughing children with inhaled corticosteroids, even in the context of a tertiary referral practice. Pediatr Pulmonol. 2007;42:857,863. © 2007 Wiley-Liss, Inc. [source]

Long-term frontal sinus patency after endoscopic frontal sinusotomy,

Role of Local Immunoglobulin E Specific for Alternaria alternata in the Pathogenesis of Nasal Polyposis,

THE LARYNGOSCOPE, Issue 1 2008
Albert Sabirov MD
Abstract Objective/Hypothesis: The role of fungal pathogens in the etiology of nasal polyposis remains unclear. The aim of this study was to determine whether there was a correlation between the presence of Alternaria -specific immunoglobulin (Ig)E antibodies, eosinophilic inflammation, and the development of nasal polyps. Study Design: Prospective study. Methods: Serum and nasal tissue homogenates from 21 patients with manifestations of chronic sinusitis with nasal polyps were compared with specimens from 13 chronic sinusitis patients without polyps and 8 healthy controls. The Phadia ImmunoCAP and enzyme-linked immunosorbent assay were used to quantify levels of total IgE and Alternaria -specific (IgE, IgG, and IgA) antibodies. Eosinophil cationic protein (ECP) and tryptase levels were measured in tissue homogenates, whereas the inflammatory response was evaluated using tissue eosinophil counts in tissue samples. Results: Serum analysis revealed no difference in the levels of total IgE and Alternaria -specific IgE, IgG, and IgA antibodies between the study groups. In contrast, the levels of Alternaria -specific IgE in tissue with polyps were significantly higher than in nonpolyp tissue. Increases in total tissue IgE paralleled increased levels of Alternaria -specific IgG and IgA antibodies in chronic sinusitis with nasal polyps as compared with control groups. A positive correlation was found between Alternaria -specific IgE and ECP in tissue. Increased mean levels of ECP corresponded to increased eosinophil counts in the group of patients with polyps. Conclusions:Alternaria -specific IgE and eosinophilic inflammation in nasal tissue correlates with the incidence of nasal polyps irrespective of specific IgE antibodies in serum. Together, the correlation between the local immune responses and the eosinophilic inflammation in nasal polyps suggests a possible role of Alternaria in the pathogenesis of nasal polyposis. [source]

Cellular characteristics of non-allergic eosinophilic conjunctivitis

ACTA OPHTHALMOLOGICA, Issue 2 2010
Osmo Kari
Abstract. Purpose:, This study examines the histology of conjunctival biopsy samples from patients with persistent allergic eosinophilic conjunctivitis (AEC) or non-allergic eosinophilic conjunctivitis (NAEC). Methods:, Fourteen patients with conjunctivitis and eosinophilia in cytology samples were included in the study. Seven had positive skin-prick tests (the AEC group) and seven had negative skin-prick tests (the NAEC group). Eight asymptomatic subjects with negative skin-prick tests served as a control group. In conjunctival biopsies eosinophils were identified with monoclonal antibodies. Mast cells were identified by specific immunostaining and tryptase-positive granules were counted around them. The percentage of degranulated mast cells was used as a measure of cell activation. Eosinophil and goblet cell numbers were counted, epithelial thickness was measured, and the symptoms were characterized and graded. Results:, The numbers of eosinophils in biopsies were higher in patients with AEC than in healthy controls (p = 0.010). The proportion of activated mast cells tended to be higher in AEC patients (65%) than in NAEC patients (48%) or control subjects (40%). Patients with AEC had more goblet cells than control subjects (p = 0.049) and their epithelial layer was thicker (p = 0.054). Patients with AEC had more severe symptoms than control subjects (p = 0.0005), whereas the symptoms of NAEC patients did not differ statistically from those of controls (p = 0.065). Conclusions:, Patients with NAEC were characterized by mild eosinophilic inflammation and only minor structural conjunctival changes. The condition seems to run a relatively mild but persistent clinical course. [source]

Early-life co-administration of cockroach allergen and endotoxin augments pulmonary and systemic responses

CLINICAL & EXPERIMENTAL ALLERGY, Issue 7 2009
K. Kulhankova
Summary Background Environmental exposures to cockroach allergen and endotoxin are recognized epidemiological risk factors for the early development of allergies and asthma in children. Because of this, it is important to examine the role of early-life concurrent inhalation exposures to cockroach allergen and endotoxin in the pathogenesis of allergic airways disease. Objective We examined the effects of repeated concomitant endotoxin and cockroach allergen inhalation on the pulmonary and systemic immune responses of newborn and juvenile mice. Methods C3H/HeBFeJ mice were exposed to inhaled endotoxin and cockroach allergen via intranasal instillation from day 2 to 21 after birth, and systemic and pulmonary responses were examined in serum, bronchoalveolar lavage fluid, and lung tissue. Results Cockroach allergen exposures induced pulmonary eosinophilic inflammation, total and allergen-specific IgE, IgG1, and IgG2a production, and alveolar remodelling. Co-exposures with endotoxin and cockroach allergen significantly increased serum IgE and IgG1, lung inflammation, and alveolar wall thickness, and decreased airspace volume density. Importantly, compared with exposures with individual substances, the responses to co-exposures were more than additive. Conclusions Repeated inhalation exposures of neonatal and juvenile mice to endotoxin and cockroach allergen increased the pulmonary inflammatory and systemic immune responses in a synergistic manner and enhanced alveolar remodelling in the developing lung. These data underscore the importance of evaluating the effect of multiple, concurrent environmental exposures, and of using an experimental model that incorporates clinically relevant timing and route of exposures. [source]

A mechanism of benefit of soy genistein in asthma: inhibition of eosinophil p38-dependent leukotriene synthesis

CLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2008
R. Kalhan
Summary Background Dietary intake of the soy isoflavone genistein is associated with reduced severity of asthma, but the mechanisms responsible for this effect are unknown. Objective To determine whether genistein blocks eosinophil leukotriene C4 (LTC4) synthesis and to evaluate the mechanism of this effect, and to assess the impact of a 4-week period of soy isoflavone dietary supplementation on indices of eosinophilic inflammation in asthma patients. Methods Human peripheral blood eosinophils were stimulated in the absence and presence of genistein, and LTC4 synthesis was measured. 5-lipoxygenase (5-LO) nuclear membrane translocation was assessed by confocal immunofluorescence microscopy. Mitogen-activated protein (MAP) kinase activation was determined by immunoblot. Human subjects with mild-to-moderate persistent asthma and minimal or no soy intake were given a soy isoflavone supplement (100 mg/day) for 4 weeks. The fraction of exhaled nitric oxide (FENO) and ex vivo eosinophil LTC4 production were assessed before and after the soy isoflavone treatment period. Results Genistein inhibited eosinophil LTC4 synthesis (IC50 80 nm), blocked phosphorylation of p38 MAP kinase and its downstream target MAPKAP-2, and reduced translocation of 5-LO to the nuclear membrane. In patients with asthma, following 4 weeks of dietary soy isoflavone supplementation, ex vivo eosinophil LTC4 synthesis decreased by 33% (N=11, P=0.02) and FENO decreased by 18% (N=13, P=0.03). Conclusion At physiologically relevant concentrations, genistein inhibits eosinophil LTC4 synthesis in vitro, probably by blocking p38- and MAPKAP-2-dependent activation of 5-LO. In asthma patients, dietary soy isoflavone supplementation reduces eosinophil LTC4 synthesis and eosinophilic airway inflammation. These results support a potential role for soy isoflavones in the treatment of asthma. [source]

Aggravation of bronchial eosinophilia in mice by nasal and bronchial exposure to Staphylococcus aureus enterotoxin B

CLINICAL & EXPERIMENTAL ALLERGY, Issue 8 2006
P. W. Hellings
Summary Background The role of bacterial enterotoxins like Staphylococcus aureus enterotoxin B (SEB) in allergic asthma remains unknown. We used a mouse model of airway allergy to study the effects of nasal or bronchial contact with SEB on bronchial allergic inflammation. Methods The features of allergic asthma were induced in ovalbumin (OVA)-sensitized mice (days 1,13) by repeated exposures to nebulized OVA (days 33,37). Nasal or bronchial application of SEB was performed on three occasions (days 33,35,37), and the effects on bronchial inflammation, IgE titres and expression levels of mRNA for T helper type 2 cytokines and other inflammatory mediators were evaluated. Results Both nasal and bronchial SEB enhanced the allergen-induced bronchial inflammation, as reflected by more eosinophilic inflammation in the airway lumen and in bronchial tissue. Aggravation of experimental asthma correlated with higher expression of mRNA for IL-5, IL-4, IFN-,, IL-12 p40, eotaxin-1 and TGF-, in bronchi. In addition, nasal SEB elevated concentrations of IL-4, IL-5 and IFN-, in serum and bronchial SEB increased titres of OVA-specific and total IgE in serum. Conclusion Our data illustrate the potential of both nasal as well as bronchial SEB to aggravate several features of allergic asthma in a mouse model. [source]

Interleukin-4 increases murine airway response to kinins, via up-regulation of bradykinin B1 -receptors and altered signalling along mitogen-activated protein kinase pathways

CLINICAL & EXPERIMENTAL ALLERGY, Issue 8 2004
M. Bryborn
Summary Background IL-4 is believed to play a role in asthma and chronic obstructive pulmonary disease through promotion of eosinophilic inflammation and mucus hypersecretion. Whether IL-4 can induce a direct effect on airway smooth muscle remains unknown. Objective To investigate the effect of IL-4 on airway smooth muscle, focusing on the contractile response to des-Arg9 -bradykinin and bradykinin. Methods Tracheal segments from murine airways were cultured for 1,8 days in the absence and presence of IL-4. The smooth muscle response induced by des-Arg9 -bradykinin and bradykinin was investigated in myographs. Expression levels for the IL-4-, bradykinin B1 - and B2 -receptors were characterized using RT-PCR. Specific inhibitors were used to study signal changes along the IL-4 receptor- (IL-4R-) coupled mitogen-activated protein (MAP) kinase (MAPK) pathways. Results IL-4 treatment increased the contractile response to des-Arg9 -bradykinin and bradykinin in a concentration- and time-dependent manner. Dexamethasone and the transcriptional inhibitor actinomycin D blocked this effect. c-Jun N-terminal kinase inhibitor SP600125 also blocked the effect of both des-Arg9 -bradykinin and bradykinin, whereas p38 inhibitor SB203580 blocked only the former and the MAPKK inhibitor PD098059, only the latter agonist responses. IL-4 treatment increased the mRNA levels representing bradykinin B1 - but not B2 -receptors. Levels of IL-4R were not altered during culture. Conclusion Long-term exposure to IL-4 increases the contractile response induced by des-Arg9 -bradykinin and bradykinin in cultured murine airways. This effect appears to be mediated via an up-regulation of B1 -receptors and altered signalling along the MAPK pathways. [source]

Rosmarinic acid in perilla extract inhibits allergic inflammation induced by mite allergen, in a mouse model

CLINICAL & EXPERIMENTAL ALLERGY, Issue 6 2004
C. Sanbongi
Summary Background Perilla and its constituent rosmarinic acid have been suggested to have anti-allergic activity. However, few studies have examined the effects on allergic asthma. Objective The purpose of this study was to evaluate the effect of oral administration of perilla leaf extract, which contains high amount of rosmarinic acid, on a murine model of allergic asthma induced by house dust mite allergen. Methods C3H/He mice were sensitized by intratracheal administration of Dermatophagoides farinae (Der f). Mice were orally treated with rosmarinic acid in perilla extract (PE) (1.5 mg/mouse/day). Results Der f challenge of sensitized mice elicited pulmonary eosinophilic inflammation, accompanied by an increase in lung expression of IL-4 and IL-5, and eotaxin. Daily treatment with rosmarinic acid in PE significantly prevented the increases in the numbers of eosinophils in bronchoalveolar lavage fluids and also in those around murine airways. Rosmarinic acid in PE treatment also inhibited the enhanced protein expression of IL-4 and IL-5, and eotaxin in the lungs of sensitized mice. Der f challenge also enhanced allergen-specific IgG1, which were also inhibited by rosmarinic acid in PE. Conclusion These results suggest that oral administration of perilla-derived rosmarinic acid is an effective intervention for allergic asthma, possibly through the amelioration of increases in cytokines, chemokines, and allergen-specific antibody. [source]

Induction of eotaxin production by interleukin-4, interleukin-13 and lipopolysaccharide by nasal fibroblasts

CLINICAL & EXPERIMENTAL ALLERGY, Issue 5 2004
M. Nonaka
Summary Background There is growing evidence that eotaxin is a key mediator in the development of tissue eosinophilia. Fibroblasts are a major source of eotaxin. The severity of diseases with eosinophilic inflammation like nasal polyposis, atopic dermatitis and asthma, where Th2-type cytokines (IL-4 and IL-13) and TGF-, are expressed locally, was shown to correlate with bacterial factors such as lipopolysaccharide (LPS) rather than allergen. Objective We examined eotaxin production by nasal fibroblasts stimulated with IL-4 or IL-13 alone or in combination with LPS, and the effect of TGF-,1 on it. Moreover, we compared the magnitude of eotaxin produced by nasal fibroblasts with that produced by lung or skin fibroblasts. Methods Fibroblast lines were established from human biopsy tissue. The expression of eotaxin mRNA was evaluated by RT-PCR. The amount of eotaxin in the supernatants was measured by ELISA. Results IL-4, but not IL-13, synergized with LPS to produce eotaxin in a dose- and time-dependent manner. Sequential treatment of nasal fibroblasts with IL-4 and LPS did not have any effect. But when IL-4 and LPS were added together, synergy for eotaxin production was observed. Moreover, this synergy was observed in nasal and skin fibroblasts, but not in lung fibroblasts. The production of eotaxin by IL-4 and LPS was modulated by TGF-,1. Conclusion These results suggest that a co-stimulus like LPS is necessary for IL-4 to make a strong induction of eotaxin in eosinophilic inflammations such as nasal polyposis. Modulation by TGF-,1 may have important implications for the development of eosinophilic inflammation. [source]

Transient contribution of mast cells to pulmonary eosinophilia but not to hyper-responsiveness

CLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2002
K. Ogawa
Background We have recently demonstrated that the transfer of interleukin (IL)-5-producing CD4+ T cell clones into unprimed mice is sufficient for the development of eosinophilic inflammation in the bronchial mucosa upon antigen inhalation. Objective The aim of this study was to elucidate the possible contribution of mast cells in eosinophilic inflammation and bronchial hyper-responsiveness (BHR), and to discriminate between the roles of CD4+ T cells and mast cells. Methods Mast cell-deficient mice (WBB6F1-W/Wv) and their congenic normal littermates (WBB6F1,+/+) were immunized with ovalbumin and challenged by inhalation with the relevant antigen. Results Airway eosinophilia was induced with equivalent intensity in +/+ and W/Wv mice 6, 24, 96 and 216 h after antigen inhalation. In contrast, 48 h after antigen challenge, eosinophilic infiltration into the bronchial mucosa was significantly less pronounced in W/Wv mice than in +/+ mice. Anti-CD4 monoclonal antibody (mAb), anti-IL-5 mAb, and cyclosporin A were administered next, demonstrating that the airway eosinophilia of W/Wv mice induced 48 h after antigen challenge was almost completely inhibited by each of these three treatments, but that of +/+ mice was significantly less susceptible. Bronchial responsiveness to acetylcholine was increased 48 h after antigen challenge and was not significantly different between +/+ and W/Wv mice. Administration of anti-IL-5 mAb completely inhibited the development of BHR in both +/+ and W/Wv mice. Conclusion These results indicate that, in mice, mast cells do have a supplemental role in the development of pulmonary eosinophilia but not BHR. CD4+ T cells totally regulate these responses by producing IL-5. [source]

Allergen-induced airway inflammation and bronchial responsiveness in interleukin-5 receptor , chain-deficient mice

CLINICAL & EXPERIMENTAL ALLERGY, Issue 6 2000
Tanaka
Objective The role of IL-5 receptor , chain (IL-5R,) in the onset of bronchial hyperresponsiveness (BHR) to acetylcholine was investigated by testing IL-5R, knockout (IL-5R, KO) mice. Methods Mice were immunized with antigen at intervals of 12 days. Starting 10 days after the secondary immunization, mice were exposed to antigen three times every fourth day. Twenty-four hours after the last antigen challenge, bronchial responsiveness to acetylcholine was measured and bronchoalveolar lavage was carried out. Results Twenty-four hours after the last antigen inhalation, total and differential cells counts of bronchoalveolar lavage revealed a significant increase in eosinophils and lymphocytes in ovalbumin-exposed wild-type mice. In IL-5R, KO mice, there was little increase of eosinophils in bronchoalveolar lavage fluid (BALF). The production of IL-5 in BALF increased in both mice after repeated antigen challenge, and there was no significant difference between wild-type and IL-5R, KO mice. Similar to the BAL study, histological sections of lung tissue from ovalbumin-exposed wild-type mice exhibited airway eosinophilic inflammation, which was attenuated by the deficiency of IL-5R, chain. There was no significant difference in serum antigen-specific IgE levels between wild-type and IL-5R, KO mice after immunization nor antigen inhalation. Repeated antigen provocation caused BHR to acetylcholine in wild-type mice. In contrast, no BHR was observed in IL-5R, KO mice after repeated inhalation of antigen. Conclusion These findings indicate that IL-5R, plays an important role in the development of antigen-induced airway eosinophilia and BHR in mice. [source]

Interleukin-13 and tumour necrosis factor-, synergistically induce eotaxin production in human nasal fibroblasts

CLINICAL & EXPERIMENTAL ALLERGY, Issue 3 2000
Terada
Background There is increasing evidence that eotaxin is a key mediator in the development of tissue eosinophilia. However, the mechanism involved in the production of eotaxin has yet to be clarified. Most recently, it has been shown that interleukin (IL) -4 induces eotaxin in dermal fibroblasts. A novel cytokine termed IL-13, which binds to the ,-chain of the IL-4 receptor, shares many biological activities with IL-4. It is known that fibroblasts express the IL-4 receptor and produce collagen type I upon stimulation with IL-4. Objective We investigated whether IL-13, as well as IL-4, are able to induce eotaxin production in human nasal mucosal fibroblasts (HNMFs). Furthermore, we investigated the effect of costimulation of IL-13 and TNF, on eotaxin production. Methods HNMFs, isolated from inferior nasal mucosa samples, were stimulated by various kind of cytokines for 1,36 h at 37 °C in 5% CO2. The change in the expression of eotaxin mRNA was then evaluated by reverse transcriptase-polymerase chain reaction and the Southern blot analysis. The amount of eotaxin in the culture media was measured by ELISA. Results IL-13 as well as IL-4 dose-dependently induced eotaxin expression in HNMFs. Furthermore, IL-13 and TNF, synergistically induced eotaxin expression in HNMFs, while they hardly induced eotaxin expression in endothelial cells, epithelial cells or eosinophils. The synergy was observed when pre-incubation of HNMFs with IL-13 was followed by a stimulation with TNF,, or HNMFs were simultaneously stimulated with IL-13 and TNF,. Conclusion These results strongly indicate that IL-13, as well as IL-4, may be important in eotaxin-mediated eosinophilic inflammation in nasal mucosa. In addition, in nasal mucosa, fibroblasts are the major cell source for eotaxin. [source]

CCR3-active chemokines influence eosinophil adhesion to endothelial cells under static and flow conditions

CLINICAL & EXPERIMENTAL ALLERGY REVIEWS, Issue 1 2007
H. Tachimoto
Summary We recently demonstrated that CCR3-active chemokines promote rapid detachment of eosinophils bound to vascular cell adhesion molecule-1 (VCAM-1) in vitro. Eosinophils adhered well to immobilized human recombinant VCAM-1 primarily via ,4,1 integrin. Eotaxin-2, a CCR3-specific chemokine, induced eosinophil de-adhesion from VCAM-1. In contrast, very few eosinophils spontaneously adhered to bovine serum albumin (BSA), and eosinophil adhesion to BSA was enhanced by eotaxin-2 over a similar nm range of concentrations. This enhancement of BSA adhesion was dependent on ,2 integrins. Eosinophil ,4,1 integrins can mediate rolling on VCAM-1 under physiological flow conditions. Although we observed a reduction of eosinophil accumulation on immobilized VCAM-1 in response to eotaxin-2 under physiological flow conditions, this reduction of adhesion was not observed when VCAM-1 and intercellular adhesion molecule-1 (ICAM-1) were co-immobilized. Based on antibody-blocking studies, this appears to be caused by a chemokine-induced shift in integrin usage away from ,1 integrin-dominated interactions with VCAM-1 towards ,2 integrin-dominated interactions with ICAM-1. Our results confirm the important role of integrins and chemokines in selective eosinophil migration processes. CCR3-active chemokines may be necessary to facilitate de-adhesion from luminal VCAM-1 and to facilitate the process of diapedesis by shifting integrin usage in eosinophils away from ,1 integrin-dominated interactions with VCAM-1 towards ,2 integrin-dominated interactions with ICAM-1. The critical importance of integrins and chemokines in eosinophilic inflammation lends support for targeting these molecules with novel therapeutic agents. [source]

Natural killer T cells are dispensable in the development of allergen-induced airway hyperresponsiveness, inflammation and remodelling in a mouse model of chronic asthma

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2010
Y.-I. Koh
Summary Natural killer T (NK T) cells have been shown to play an essential role in the development of allergen-induced airway hyperresponsiveness (AHR) and/or airway inflammation in mouse models of acute asthma. Recently, NK T cells have been reported to be required for the development of AHR in a virus induced chronic asthma model. We investigated whether NK T cells were required for the development of allergen-induced AHR, airway inflammation and airway remodelling in a mouse model of chronic asthma. CD1d,/, mice that lack NK T cells were used for the experiments. In the chronic model, AHR, eosinophilic inflammation, remodelling characteristics including mucus metaplasia, subepithelial fibrosis and increased mass of the airway smooth muscle, T helper type 2 (Th2) immune response and immunoglobulin (Ig)E production were equally increased in both CD1d,/, mice and wild-type mice. However, in the acute model, AHR, eosinophilic inflammation, Th2 immune response and IgE production were significantly decreased in the CD1d,/, mice compared to wild-type. CD1d-dependent NK T cells may not be required for the development of allergen-induced AHR, eosinophilic airway inflammation and airway remodelling in chronic asthma model, although they play a role in the development of AHR and eosinophilic inflammation in acute asthma model. [source]