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Bronchial Asthma (bronchial + asthma)
Selected AbstractsThe Oldest Patient with Bronchial AsthmaAUSTRALASIAN JOURNAL ON AGEING, Issue 2 2001Koichi Kurishima This case report purports to describe the oldest asthma patient ever reported, a 96-year old male with a 46-year asthma history. We emphasize not only his age, but also the fact that he continues to have significant reversibility, at least he did at age more than 90-year old. [source] IL-5-induced airway eosinophilia , the key to asthma?IMMUNOLOGICAL REVIEWS, Issue 1 2001Eckard Hamelmann Summary: Bronchial asthma is a chronic inflammatory airway disease defined by reversible airway obstruction and non-specific airway hyper-responsiveness (AHR). Although profound insights have been made into the pathophysiology of asthma, the exact mechanisms inducing and regulating the disease are still not fully understood. Yet, it is generally accepted that the pathological changes in asthma are induced by a chronic inflammatory process which is characterized by infiltration of the bronchial mucosa with lymphocytes and eosinophils, increased mucus production and submucosal edema. There is increasing evidence that an imbalance in the T-helper (Th) cell response of genetically predisposed individuals to common environmental antigens plays a pivotal role in the pathogenesis of allergic bronchial asthma and other atopic disorders. Following allergic sensitization, T cells from atopic patients tend to produce elevated levels of Th2-type cytokines, especially interleukin (IL)-4, IL-13, IL-5 and IL-6, which induce and regulate IgE production and eosinophil airway infiltration. In this review, the role of Th2-type cytokines, IgE and airway eosinophils in the induction of airway inflammation and AHR is discussed, and animal studies of asthma and AHR, mainly in rodents will be considered. A better understanding of the underlying mechanisms leading to asthma pathology may yield more specific immunological strategies for the treatment of this disease which is increasing worldwide. I thank the many colleagues in the laboratory of Dr. E. W. Gelfand, National Jewish Research Center, Denver CO, USA, for continuous support and encouragement. E.H. is a fellow of the Deutsche Forschungsgemeinschaft (DFG Ha 2162/1-1 and 2-1). [source] Omega-3 fatty acids, vitamin C and Zn supplementation in asthmatic children: a randomized self-controlled studyACTA PAEDIATRICA, Issue 4 2009Mohammed Al Biltagi Abstract Objectives: Bronchial asthma is a chronic inflammatory airways disease. Nutritional intervention is an important tool to decrease the severity of many chronic inflammatory diseases including asthma. The aim of this study is to evaluate the role of omega-3 fatty acids, vitamin C and Zn in children with moderately persistent asthma. Patients and Methods: Randomly assigned, placebo-self-controlled 60 children with moderate persistent asthma completed the study, were subjected to alternating phases of supplementation with omega-3 fatty acids, vitamin C and Zn either singly or in combination separated with washout phases. Childhood asthma control test (C-ACT), pulmonary function tests and sputum inflammatory markers were evaluated at the beginning of the study and at the end of each therapeutic phase. Results: There was a significant improvement of C-ACT, pulmonary function tests and sputum inflammatory markers with diet supplementation with omega-3 fatty acids, vitamin C and Zn (p < 0.001*). There was also significant improvement with the combined use of the three supplementations than single use of any one of them (p < 0.001*). Conclusion: Diet supplementation with omega-3 fatty acids, Zn and vitamin C significantly improved asthma control test, pulmonary function tests and pulmonary inflammatory markers in children with moderately persistent bronchial asthma either singly or in combination. [source] Mannose binding lectin gene polymorphisms and asthmaCLINICAL & EXPERIMENTAL ALLERGY, Issue 9 2007X. Wang Summary Background Bronchial asthma is a chronic inflammatory disorder of the airways. Recently, it has been suggested that complement plays significant roles in asthma. Mannose-binding lectin (MBL) is one of the key molecules in complement activation pathways that are associated with several infectious and immune disorders. Subjects and method To investigate whether MBL plays roles in asthma, we analysed MBL2 polymorphisms (allele B, H/L and Y/X) and plasma MBL levels in a Japanese adult population including 232 healthy controls and 579 asthmatics. Results Although there was linkage disequilibrium among the three polymorphisms, each polymorphism significantly affects serum MBL levels independently. However, there were no significant differences between asthmatics and controls in MBL2 genotype distribution and in MBL concentrations [1.47±0.07(SE) mg/L for asthmatics and 1.66±0.14 mg/L for controls, P=0.2]. MBL levels and genotype have no significant relationship with serum IgE, pulmonary functions, and the severity of asthma. Conclusion Although plasma MBL levels depend on the MBL2 polymorphisms, these polymorphisms and plasma MBL levels are not associated with the asthma phenotype. [source] P03 Type-I and -IV hypersensitivity to platinum saltsCONTACT DERMATITIS, Issue 3 2004Willeke Kamphof A 28-year-old female analytical chemist visited our patch test clinic with initially complaints of severe hand dermatitis. Later on she developed rhinitis, bronchial asthma and tightness of the chest. The complaints seemed work related: her condition improved during holidays and on sick leaves. She worked in a laboratory with several platinum salts and used different kinds of gloves (latex, nitril, etc.). Methods:, Patch tests were performed with the European Standard series and prick tests with common inhalant allergens. Patch-, prick- and open patch tests were carried out with various aqueous dilutions of platinum chloride (PtCl2). Results:, Patch tests with 0.01,2% PtCl2 were positive on day 2, 3 and 6, and at 0.001% a follicular reaction was found. The prick-test was already positive at the lowest concentration tested (0.001%). The open patch test, carried out retro-auricular, showed a positive reaction at 1 and 2% PtCl2 after 20 min. Controls in healthy volunteers (n = 5) were all negative. Discussion:, It is well known that platinum salts can cause type-I hypersensitivity reactions like allergic rhinitis, conjunctivitis, bronchial asthma and urticaria, also referred to as platinosis. Contact dermatitis to platinum salts, however, is very rare. In our patch test clinic, 78 patients were tested between 1987 and 2001 with PtCl2 2%. Only 2 women showed a positive patch test for PtCl2. The patient presented here, stopped working with platinum salts and recovered from all complaints. We interpret our case as occupational type-I and type-IV hypersensitivity to platinum salts with mucosal and dermal manifestations. [source] Neuropharmacology and therapeutic potential of cannabinoidsADDICTION BIOLOGY, Issue 1 2000Roger G. Pertwee Mammalian tissues contain at least two types of cannabinoid receptor, CB 1, found mainly on neurones and CB 2, found mainly in immune cells. Endogenous ligands for these receptors have also been identified. These endocannabinoids and their receptors constitute the endogenous cannabinoid system. Two cannabinoid receptor agonists, ,9 -tetrahydrocannabinol and nabilone, are used clinically as anti-emetics or to boost appetite. Additional therapeutic uses of cannabinoids may include the suppression of some multiple sclerosis and spinal injury symptoms, the management of pain, bronchial asthma and glaucoma, and the prevention of neurotoxicity. There are also potential clinical applications for CB 1 receptor antagonists, in the management of acute schizophrenia and cognitive/memory dysfunctions and as appetite suppressants. Future research is likely to be directed at characterizing the endogenous cannabinoid system more completely, at obtaining more conclusive clinical data about cannabinoids with regard to both beneficial and adverse effects, at developing improved cannabinoid formulations and modes of administration for use in the clinic and at devising clinical strategies for separating out the sought-after effects of CB 1 receptor agonists from their psychotropic and other unwanted effects. [source] Ovalbumin-induced sensitization affects non-quantal acetylcholine release from motor nerve terminals and alters contractility of skeletal muscles in miceEXPERIMENTAL PHYSIOLOGY, Issue 2 2009Alexander Y. Teplov Skeletal muscles play key roles in the development of various pathologies, including bronchial asthma and several types of auto-immune disorders, e.g. polymyositis. Since most of these maladies have an immunological/allergic element, this paper is devoted to assessing the impact of immunobiological reorganization on the functional properties of isolated skeletal muscles in mice. A combination of two methods (myography and electrophysiology) was used to evaluate extensor digitorum longus (EDL) and diaphragmatic muscle (DM) in this regard. Conventional myographic technique showed that ovalbumin-induced sensitization (OS) produced different changes in the contractile properties of EDL and DM. The amplitudes of carbachol (CCh)-induced contractions increased in DM but decreased in EDL. Those changes were inversely related to OS-mediated changes of non-quantal acetylcholine (ACh) release intensity within the muscle endplate, as shown by the electrophysiologically measured H-effect. These results clearly show that OS-mediated changes of non-quantal ACh release alter the functional properties of postjunctional ACh receptors and therefore contribute to the disturbance of CCh-induced contractility of skeletal muscles. Other mechanisms of OS-mediated changes of skeletal muscle contractility are also proposed and discussed. [source] Cost Convergence between Public and For-Profit Hospitals under Prospective Payment and High Competition in TaiwanHEALTH SERVICES RESEARCH, Issue 6p2 2004Sudha Xirasagar Objective. To test the hypotheses that: (1) average adjusted costs per discharge are higher in high-competition relative to low-competition markets, and (2) increased competition is associated with cost convergence between public and for-profit (FP) hospitals for case payment diagnoses, but not for cost-plus reimbursed diagnoses. Data Sources. Taiwan's National Health Insurance database; 325,851 inpatient claims for cesarean section, vaginal delivery, prostatectomy, and thyroidectomy (all case payment), and bronchial asthma and cholelithiasis (both cost-based payment). Study Design. Retrospective population-based, cross-sectional study. Data Analysis. Diagnosis-wise regression analyses were done to explore associations between cost per discharge and hospital ownership under high and low competition, adjusted for clinical severity and institutional characteristics. Principal Findings. Adjusted costs per discharge are higher for all diagnoses in high-competition markets. For case payment diagnoses, the magnitudes of adjusted cost differences between public and FP hospitals are lower under high competition relative to low competition. This is not so for the cost-based diagnoses. Conclusions. We find that the empirical evidence supports both our hypotheses. [source] IL-5-induced airway eosinophilia , the key to asthma?IMMUNOLOGICAL REVIEWS, Issue 1 2001Eckard Hamelmann Summary: Bronchial asthma is a chronic inflammatory airway disease defined by reversible airway obstruction and non-specific airway hyper-responsiveness (AHR). Although profound insights have been made into the pathophysiology of asthma, the exact mechanisms inducing and regulating the disease are still not fully understood. Yet, it is generally accepted that the pathological changes in asthma are induced by a chronic inflammatory process which is characterized by infiltration of the bronchial mucosa with lymphocytes and eosinophils, increased mucus production and submucosal edema. There is increasing evidence that an imbalance in the T-helper (Th) cell response of genetically predisposed individuals to common environmental antigens plays a pivotal role in the pathogenesis of allergic bronchial asthma and other atopic disorders. Following allergic sensitization, T cells from atopic patients tend to produce elevated levels of Th2-type cytokines, especially interleukin (IL)-4, IL-13, IL-5 and IL-6, which induce and regulate IgE production and eosinophil airway infiltration. In this review, the role of Th2-type cytokines, IgE and airway eosinophils in the induction of airway inflammation and AHR is discussed, and animal studies of asthma and AHR, mainly in rodents will be considered. A better understanding of the underlying mechanisms leading to asthma pathology may yield more specific immunological strategies for the treatment of this disease which is increasing worldwide. I thank the many colleagues in the laboratory of Dr. E. W. Gelfand, National Jewish Research Center, Denver CO, USA, for continuous support and encouragement. E.H. is a fellow of the Deutsche Forschungsgemeinschaft (DFG Ha 2162/1-1 and 2-1). [source] Genetic polymorphisms of chitotriosidase in Caucasian children with bronchial asthmaINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 3 2006S. Bierbaum Summary In humans, two types of chitinases have been identified: chitotriosidase I (CHIT1) and acid mammalian chitinase (AMCase). They are enzymes that cleave chitin, a polysaccharide contained in many different human parasites. So far, only little is known about their function in human and especially in human diseases. Recently we have described association of polymorphisms of AMCase with bronchial asthma in a pediatric population. In this study we were interested in whether CHIT1 is also involved in the genetics of asthma. The amino acid variants Gly102Ser and Ala442Gly, as well as a 24 bp duplication within CHIT1, were typed by means of restriction fragment length polymorphisms on 322 children with asthma and 270 randomly chosen adult controls. Statistical analyses made use of the Armitage's trend test; haplotypes were calculated by famhap and fastehplus. The amino acid variants showed no association with bronchial asthma. The 24 bp duplication, previously shown to completely demolish CHIT1 activity, was also evenly distributed between asthmatics and controls. Finally, the haplotype showed no association with the disease. We conclude from our results that CHIT1 does not play a major role in the development of bronchial asthma in Caucasian children. The results might also imply that the two human chitinases that have been identified so far have quite distinct functions in human diseases even though they have the same substrate. [source] Common polymorphisms and alternative splicing in the ILT3 gene are not associated with atopyINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 3 2000A. Heinzmann Recently, a linkage of the chromosomal region 19q13.4 with bronchial asthma has been demonstrated. This region harbours the so-called leucocyte receptor cluster with the gene for immunoglobulin-like-transcript 3 (ILT3) as a member. ILT3 represents an inhibitory receptor bearing three immunoreceptor tyrosine inhibitory motifs (ITIM). The protein mediates downregulation of cell activation through recruitment of different SH2-containing protein tyrosine phosphatases. With regard to the negative immunoregulatory function particularly on B-cells, ILT3 represents a candidate gene for atopy and asthma. The aim of this study was to screen for common polymorphisms in the gene coding for ILT3 and to test for association with the atopic phenotype. Using single-stranded conformal polymorphism-analysis and direct genomic sequencing seven polymorphisms, three mutations, a common deletion of 7 bp in the third intron and evidence for further alternative splicing of the ILT3 gene were found. Although no association was found with atopy phenotypes, it might prove useful to test for association with bronchial asthma. [source] Predicting Recurrence of Vasovagal Syncope: A Simple Risk Score for the Clinical RoutineJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 4 2009MUHAMMET A. AYDIN M.D. Background: Predictors for recurrence of syncope are lacking in patients with vasovagal syncope. The aim of this study was to identify risk factors for recurrence of syncope and develop a simple prognostic risk score of clinical value. Methods: Two hundred seventy-six patients with a history of vasovagal syncope were prospectively followed for 2 years. Diagnosis of vasovagal syncope was based on clinical history and negative standard work-up. Inclusion in the study was independent from the result of the head-up tilt test, which was performed in all cases. Risk factors for syncope recurrence were evaluated by the Cox proportional hazards regression model and implemented in a risk score, which was validated with the log-rank test and an internal cross-validation. Results: The Cox-regression analysis identified the number of previous syncopal events, history of bronchial asthma, and female gender as predictors for syncope recurrence (all P < 0.05). In contrast, head-up tilt test response had no predictive value (P = 0.881). Developing a risk score, study patients were identified as having high (recurrence rate during 2 years of follow-up: 37.2%), intermediate (24.8%), and low (6.5%) risk for syncope recurrence (receiver operating characteristic [ROC] of score 0.83, P < 0.01; Log-rank test for event-free survival, P < 0.005). Conclusions: In patients with vasovagal syncope, risk of recurrence can be stratified and is predictable based on a simple risk score. [source] TAP1 gene AccI polymorphism is associated with atopic bronchial asthmaJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 2 2003Liang-Wen Hang Abstract Asthma is a hyperresponsive airway disease that may involve inflammation responses. A transporter associated with the antigen processing 1 gene (TAP1) is involved in antigen processing, and is therefore considered to play a role in the pathogenesis of bronchial asthma. The aim of this study was to test whether the polymorphisms of the TAP1 gene are a genetic marker for susceptibility to bronchial asthma. A normal control group comprised of 43 healthy people, and 116 patients with allergic asthma were examined in this study. The polymorphism was detected by polymerase chain reaction (PCR)-based restriction analysis. Associations between atopic bronchial asthma and TAP1 polymorphisms were evaluated. The results revealed no significant differences between normal individuals and asthmatics in regard to the TAP1 gene DpnII polymorphism (P=0.752). However, there was a significant difference between the control and asthma groups as regards the TAP1 gene AccI polymorphism (P=0.020). The odds ratio (OR) of GG homozygotes of the TAP1 AccI polymorphism was 229.8 compared with the AA homozygote group. The results show that the AccI polymorphism may be an indicator for atopic bronchial asthma. J. Clin. Lab. Anal. 17:57,60, 2003. © 2003 Wiley-Liss, Inc. [source] Anti-allergic properties of Mangifera indica L. extract (Vimang) and contribution of its glucosylxanthone mangiferinJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2006Dagmar García Rivera Vimang is the brand name of formulations containing an extract of Mangifera indica L., ethnopharmacologically used in Cuba for the treatment of some immunopathological disorders, including bronchial asthma, atopic dermatitis and other allergic diseases. However, the effects of Vimang on allergic response have not been reported until now. In this study, the effects of Vimang and mangiferin, a C-glucosylxanthone isolated from the extract, on different parameters of allergic response are reported. Vimang and mangiferin showed a significant dose-dependent inhibition of IgE production in mice and anaphylaxis reaction in rats, histamine-induced vascular permeability and the histamine release induced by compound 48/80 from rat mast cells, and of lymphocyte proliferative response as evidence of the reduction of the amount of B and T lymphocytes able to contribute to allergic response. In these experiments, ketotifen, promethazine and disodium cromoglicate were used as reference drugs. Furthermore, we demonstrated that Vimang had an effect on an in-vivo model of inflammatory allergy mediated by mast cells. These results constitute the first report of the anti-allergic properties of Vimang on allergic models, as well as suggesting that this natural extract could be successfully used in the treatment of allergic disorders. Mangiferin, the major compound of Vimang, contributes to the anti-allergic effects of the extract. [source] Determination of montelukast sodium by capillary electrophoresisJOURNAL OF SEPARATION SCIENCE, JSS, Issue 6-7 2008Yuliya Shakalisava Abstract This work verifies the potential of CE in the analysis of significant impurities of montelukast sodium , an active ingredient for the treatment of bronchial asthma. Using 20 mM borate buffer pH 9.2 with 10 mM SDS and 10 mM (2-hydroxypropyl)-,-CD (2HP-,-CD) it was possible to separate montelukast and several impurities, including its cis -isomer, after exposure to light and oxygen. The obtained method surpasses a chromatographic method for montelukast sodium in terms of time of analysis (9 min of CE analysis vs. 35 min HPLC) and efficiency (CE offered over 900 000 theoretical plates for montelukast). Good repeatability of the method was supported by the low % RSD for the migration time of montelukast (0.53%). For the first time, the capillary electrophoretic method was employed for temporal study of the degradation of montelukast. The results showed that degradation of montelukast and the formation of the cis -isomer mainly occurred during the first 2 days of exposure, and occurred to a higher degree when there was no contact with the air (oxygen) in the exposed sample. [source] Angiogenesis and lymphangiogenesis in bronchial asthmaALLERGY, Issue 8 2010A. Detoraki To cite this article: Detoraki A, Granata F, Staibano S, Rossi FW, Marone G, Genovese A. Angiogenesis and lymphangiogenesis in bronchial asthma. Allergy 2010; 65: 946,958. Abstract Neovascularization plays a prominent role in inflammation and tissue remodeling in several chronic inflammatory disorders. Vessel number and size, vascular surface area and vascular leakage are all increased in biopsies from patients with asthma. High levels of VEGF and other angiogenic factors have been detected in tissues and biological samples of patients with asthma and correlate with disease activity and inversely with airway hyper-responsiveness. Inflammation in the lung stimulates the growth of new blood vessels and these contribute to the airway obstruction or airway hyper-responsiveness, or both. Effector cells of inflammation (human lung mast cells, basophils, eosinophils, macrophages, etc.) are major sources of a vast array of angiogenic and lymphangiogenic factors. Inhaled corticosteroids reduce vascularity and growth factor expression and might modulate bronchial vascular remodeling in asthma. Specific antagonists to VEGF and other angiogenic factors and their receptors might help to control chronic airway inflammation and vascular remodeling and offer a novel approach for the treatment of chronic inflammatory lung disorders. [source] Instability of the structure and allergenic protein content in Arizona cypress pollenALLERGY, Issue 12 2009Y. Shahali Background:, The allergenic characteristics of pollen and their levels of expression may vary depending on the plant species, the degree of maturation and the influence of environmental factors such as climate and atmospheric pollution. The objective of this survey was the comparison of the structure and allergenic protein content in Arizona cypress (Cupressus arizonica, CA) pollen collected just after microsporangia dehiscence and 2 weeks later in urban areas. Methods:, The morphology and structure of pollen were examined by scanning electron microscopy. Pollen protein content was quantitatively and qualitatively investigated by Bradford protein assay, SDS-PAGE and densitometric analysis respectively. Fifteen allergic subjects, according to their clinical history of seasonal rhino-conjunctivitis and bronchial asthma have been selected for skin prick testing and ImmunoCap using CA standard allergen and for immunoblotting using extracts of CA mature pollen collected from Tehran. Results:, After 2 weeks, numerous cracks and collapses appeared in pollen surfaces. Western blotting performed by using extracts of pollen collected from Tehran, revealed that sera-specific immunoglobulin E of all allergic subjects reacted to a 35 kDa protein. The presence of this new major allergen and the decrease of Cup a 1 provide reliable explications about the low efficiency of standard commercial allergens in the diagnosis of the CA pollen allergy in Tehran. Conclusion:, The instability of the pollen structure and protein content affects CA pollen allergenic properties. This study also suggests that to optimize CA standard allergen preparations, the eventual variability of pollen allergenic components have to be considered for each region. [source] Natural killer T cells expressing IFN-, and IL-4 in lesional skin of atopic eczemaALLERGY, Issue 11 2009D. Simon Background:, The inflammation of atopic eczema (AE) is orchestrated not only by T cells predominantly but also B cells, eosinophils and dendritic cells. Recently, a role of invariant natural killer T (NKT) cells has been reported in bronchial asthma and allergy. Natural killer T cells express a restricted repertoire of T-cell receptor ,/, and produce interferon (IFN)-, and/or interleukin (IL)-4 upon activation. Aim of the study:, To determine the presence of NKT cells in lesional AE skin in comparison with other eczematous disorders and to analyse their cytokine expression. Methods:, Immunofluorescence stainings were carried out using antibodies recognizing NKT cells, CD3+ and CD4+ cells, IFN-, and IL-4. Results:, Natural killer T cells have been detected in small numbers in the majority of AE specimens as well as in atopy patch test (APT) reactions, allergic contact dermatitis (ACD) and irritant contact dermatitis (ICD). In AE, the proportion of NKT cells among CD3+ cells was approximately 5%. NKT cells expressed both IFN-, and IL-4 in AE, APT and ACD but predominantly IFN-, in ICD. Conclusion:, Natural killer T cells are part of the inflammatory infiltrate of AE as well as APT, ACD and ICD, suggesting a pathogenic role of NKT cells in eczematous skin disorders. The pattern of IFN-, and IL-4 cytokine expression by NKT cells varied depending on the type of eczematous disease. [source] Regulatory T cells in bronchial asthmaALLERGY, Issue 3 2009K. Ryanna The main focus of this review was the role of a specific subset of T cells with immunomodulatory or immunosuppressive activities, termed regulatory T cells (Tregs), in the pathogenesis and treatment of bronchial asthma. Evidence that these cells are important in maintaining immune homeostasis in health and exhibit impaired activity in active disease will be discussed. Their therapeutic potential is perhaps best highlighted by evidence that therapies with demonstrated efficacy in allergic and asthmatic disease are associated with the induction or restoration of regulatory T-cell function, e.g. glucocorticoids, allergen immunotherapy. Strategies to improve the safety and efficacy of these treatments and that induce or boost Tregs in bronchial asthma are discussed. [source] Mast cell activation after adenosine inhalation challenge in patients with bronchial asthmaALLERGY, Issue 1 2008G. Bochenek No abstract is available for this article. [source] Alternative splicing of cyclooxygenase-1 gene: altered expression in leucocytes from patients with bronchial asthma and association with aspirin-induced 15-HETE releaseALLERGY, Issue 6 2007M. L. Kowalski Background:, Cyclooxygenase-1 (COX-1) is a key enzyme involved in generation of prostanoids, important mediators and modulators of asthmatic inflammation. In a subpopulation of aspirin-sensitive asthmatics (ASA) inhibition of COX-1 by nonsteroidal anti-inflammatory drugs results in activation of inflammatory cells and development of symptoms. Alternatively spliced variants of COX-1 lacking 111 bp from exon 9 were described previously but have never been identified in human leucocytes peripheral blood leucocytes (PBL) or upper airway epithelial cells. We aimed to assess the expression of spliced variants of COX-1 mRNA in PBLs from patients with asthma and in healthy subjects (HS) referring the expression to patients characteristics (including ASA-sensitivity) and to aspirin-triggered 15-hydroxyeicosatetraenoic acid (15-HETE) generation. Methods:, The study included 30 patients with ASA, 30 patients with aspirin-tolerant asthma (ATA) and 30 HS serving as controls. Nasal polyps for epithelial cell cultures were obtained from 10 patients with chronic rhinosinusitis. Expression of full length and spliced variants of COX-1 enzyme was detected by RT-PCR and presented as the ratio of full-length COX-1 to alternatively spliced COX-1 mRNA [COX-1 alternative splicing index (COX-1 AS index)]. Release of eicosanoids (PGE2 and 15-HETE) by PBLs was measured with enzyme immunoassay. Results:, In both PBLs and airway epithelial cells the expression of full-length product prevailed over spliced variants of COX-1 enzyme. Cyclooxygenase-1 AS index was significantly lower in asthmatics as compared to HS (1.96 ± 0.71 vs 2.41 ± 0.99, P < 0.05) indicating the relatively higher expression of the alternative transcript in asthmatic patients. Cyclooxygenase-1 AS index was not different between ASA and ATA groups (mean 1.90 ± 0.66 vs 2.02 ± 0.76, respectively, P = 0.39). There was no significant association between COX-1 AS index and mean daily dose of inhaled glucocorticosteroids or pulmonary function tests (FEV1, FVC) but in ASA group a weak correlation with daily dose of oral glucocorticosteroids was found (r = 0.39; P = 0.03). In ASA patients there was a significant positive correlation between the COX-1 AS index and the percentage of aspirin-triggered increase in 15-HETE generation (r = 0.51; P < 0.03). Conclusions:, Alternatively spliced variants of COX-1 mRNA are differently expressed in patients with bronchial asthma and may be associated with aspirin-triggered 15-HETE generation. [source] German cockroach proteases regulate matrix metalloproteinase-9 in human bronchial epithelial cellsALLERGY, Issue 8 2006K. Page Background:, Matrix metalloproteinases (MMPs) digest extracellular matrix proteins and may play a role in the pathogenesis of bronchial asthma. MMP-9 levels are increased in the bronchoalveolar lavage fluid and sputum of asthmatics compared with that of controls. As exposure to cockroaches is an environmental risk factor for asthma, we sought to investigate the role of German cockroach fecal remnants (frass) on MMP-9 expression. Methods:, Human bronchial epithelial cells (16HBE14o-) and primary normal human bronchial epithelial cells were treated with cockroach frass in the absence or presence of tumor necrosis factor (TNF),. MMP-9 mRNA, protein levels and pro-MMP-9 activity were determined using real-time polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA) and zymogram assays. Pretreatment of frass with aprotinin abolished protease activity. PD98059, a chemical inhibitor of extracellular signal regulated kinase (ERK), and SLIGKV, an activator of protease-activated receptor (PAR)-2 were also used. AP-1DNA binding was determined by electrophoretic mobility shift assay (EMSA) and ERK phosphorylation by Western blot analysis. Results:, Cockroach frass augmented TNF, -mediated MMP-9 mRNA and protein expression by a mechanism dependent on active serine proteases within frass and not on endogenous endotoxin. Frass increased ERK phosphorylation, and chemical inhibition of ERK attenuated cockroaches' effects on MMP-9. Serine proteases are known to activate the PAR-2 receptor. We found that selective activation of PAR-2 using the peptide SLIGKV augmented TNF, -induced MMP-9 protein levels and increased ERK phosphorylation. Frass and SLIGKV each increased AP-1 translocation and DNA binding. Conclusions:, These data suggest that German cockroach frass contains active serine proteases which augment TNF, -induced MMP-9 expression by a mechanism involving PAR-2, ERK and AP-1. [source] Neurogenic mechanisms in bronchial inflammatory diseasesALLERGY, Issue 11 2004D. A. Groneberg Neurogenic inflammation encompasses the release of neuropeptides from airway nerves leading to inflammatory effects. This neurogenic inflammatory response of the airways can be initiated by exogenous irritants such as cigarette smoke or gases and is characterized by a bi-directional linkage between airway nerves and airway inflammation. The event of neurogenic inflammation may participate in the development and progression of chronic inflammatory airway diseases such as allergic asthma or chronic obstructive pulmonary disease (COPD). The molecular mechanisms underlying neurogenic inflammation are orchestrated by a large number of neuropeptides including tachykinins such as substance P and neurokinin A, or calcitonin gene-related peptide. Also, other biologically active peptides such as neuropeptide tyrosine, vasoactive intestinal polypeptide or endogenous opioids may modulate the inflammatory response and recently, novel tachykinins such as virokinin and hemokinins were identified. Whereas the different aspects of neurogenic inflammation have been studied in detail in laboratory animal models, only little is known about the role of airway neurogenic inflammation in human diseases. However, different functional properties of airway nerves may be used as targets for future therapeutic strategies and recent clinical data indicates that novel dual receptor antagonists may be relevant new drugs for bronchial asthma or COPD. [source] Airborne viable fungi in Riyadh and allergenic response of their extractsMYCOSES, Issue 9-10 2001A. S. Al-Suwaini Luftbürtige Pilze; Allergenität; Antigenität; Prick-Test; Saudi-Arabien. Summary. The allergenicity and antigenicity of various airborne fungi isolated from the atmosphere of Riyadh were studied. Protein nitrogen contents were estimated and found to range from 0.9 mg ml,1 for Cladosporium to 2.1 mg ml,1 for Aspergillus extracts. Sodium dodecyl sulphate,polyacrylamide gel electrophoresis analysis for those extracts exhibited a number of protein bands of higher molecular weight between 13 and 80 kDa for Alternaria, Ulocladium, Penicillium, Aspergillus and Cladosporium. Extracts in both aqueous and lyophilized forms were sterilized and tested for diagnostic skin prick test in 100 consecutive patients having bronchial asthma and allergic rhinitis. Overall, 13% of patients reacted positively to fungal extracts, revealing allergic sensitization to these fungi. These findings necessitate further investigation as regards the purification and characterization of these local extracts for better diagnostic use in patients in Saudi Arabia. Zusammenfassung. Es wurde die Allergenität und Antigenität mehrerer luftbürtiger Pilze untersucht, die aus der Luft von Riad isoliert worden waren. Hierzu wurden Pilzextrakte hergestellt, deren Proteinstickstoffgehalt zwischen 0.9 mg ml,1 bei Cladosporium und 2.1 mg ml,1 bei Aspergillus lag. Die SDS,PAGE-Analyse zeigte eine Anzahl von Proteinbanden höheren Molekulargewichts zwischen 13 und 80 kDa für Alternaria, Ulocladium, Penicillium, Aspergillus und Cladosporium. Die sowohl wässrigen wie lyophilisierten Extrakte wurden sterilisiert und an 100 unausgewählten Patienten mit Bronchialasthma und allergischer Rhinitis im Pricktest getestet. Ingesamt 13% der Patienten reagierten auf die Extrakte positiv, was für eine allergische Sensibilisierung gegen diese Pilze spricht. [source] Clinicopathological studies of peripheral neuropathy in Churg,Strauss syndromeNEUROPATHOLOGY, Issue 4 2002Toshiko Nagashima Clinicopathological studies were performed on the visceral organs and the sural nerve of a male patient with Churg,Strauss syndrome (CSS) in order to understand the mechanisms of peripheral nervous system damage. A 67-year-old man, with a 2-year history of bronchial asthma, developed acutely painful paraplegia and dyspnea. Laboratory data showed a leukocytosis, an elevated serum creatinine kinase (CK) and marked eosionophilia. Autoantibodies including p- and c-ANCA were negative. Electrophysiological studies revealed a severe sensory-motor neuropathy of multiple mononeuritis type. Steroid pulse therapy performed a day after biopsy of skin, muscle and sural nerve was effective in resolving his respiratory and neurological dysfunction but a perforation of an intestinal ulcer occurred which required surgical intervention. In the biopsied sural nerve and the surgically resected intestine and mesentery there was vasculitis with fibrinoid necrosis accompanied by numerous eosinophils and macrophages containing eosinophil cationic protein (ECP). These findings suggest that in addition to ischemic changes due to vasculitis some neurotoxic substances generated by the eosinophils may be involved in the development of neuropathy in CSS. [source] Obesity and the prevalence of allergic diseases in schoolchildrenPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 6 2008Takashi Kusunoki Although the association between obesity and bronchial asthma (BA) has been gaining more attention, few studies have been conducted concerning the relationship between obesity and other allergic diseases. The objective of this study was to determine whether and how childhood obesity is associated with allergic diseases other than BA, such as atopic dermatitis (AD), allergic rhinitis (AR), allergic conjunctivitis (AC), and either AR or AC (AR/AC). A questionnaire was administered to the parents of 50,086 Japanese schoolchildren. Associations between childhood obesity and the various allergic diseases were evaluated by univariate and multivariate logistic models. Significant associations were found between higher body mass index (BMI) and AD (p = 0.03), and lower BMI and AC (p < 0.0001), and AR/AC (p < 0.0001). There was a significantly higher prevalence of BA in girls with obesity (p = 0.009) than in those without obesity. Significantly lower prevalence of AC (p = 0.01) and AR/AC (p = 0.002) among children with obesity, and AR (p = 0.04) and AR/AC (p = 0.0004) among boys with obesity were observed than those without obesity. Those who were obese and had AD were significantly more likely to have severe symptoms (p = 0.01). Overall, childhood obesity has positive associations with BA prevalence and AD severity, whereas it has negative associations with AR and AC prevalence, especially among boys. Changes in the immunologic balance accompanied by obesity might have different effects on each type of allergic disease. Exploring the mechanisms by which childhood obesity affects allergic status should lead to new management options for childhood allergy. [source] Is affluence a risk factor for bronchial asthma and type 1 diabetes?PEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 7 2006Alberto Tedeschi In the last decades, an increase in bronchial asthma and type 1 diabetes occurrence has been observed in affluent countries, and a positive association between the two disorders has been demonstrated at the population level. This association could be explained by common risk factors predisposing to both disorders. Altered environmental and lifestyle conditions, possibly related to socio-economic status, might account for the rising trend of the two disorders. To test this hypothesis, we calculated the correlation between the occurrence of type 1 diabetes and asthma, the gross national product (GNP) and the infant mortality rate, in several European and extra-European countries. GNP was positively correlated with the incidence of type 1 diabetes and with symptoms of asthma in European (rsp: 0.53 and 0.69; p = 0.001 and p < 0.0001, respectively) and extra-European countries (rsp: 0.44 and 0.46; p = 0.04 for both diseases). Infant mortality rate was inversely correlated with GNP and with the occurrences of the two diseases in Europe (rsp: ,0.66, p < 0.0001 for type 1 diabetes; rsp:, 0.51, p = 0.01 for asthma). In extra-European countries, a significant relationship was found between infant mortality and asthma (rsp: ,0.46; p = 0.03); a trend towards a negative correlation between infant mortality and type 1 diabetes was also found, although no statistical significance was reached (rsp: ,0.21; p = 0.31). This analysis indicates that type 1 diabetes and asthma are positively associated with the GNP at the population level. Similarly, countries with low infant mortality rates tend to have a higher incidence of these immune-mediated diseases. Although GNP reflects many societal and lifestyle differences, it is notable that a high socio-economic status implies a reduced or delayed exposure to infectious agents. The reduced pressure of infectious agents on the immune system throughout life might contribute to increase the susceptibility to bronchial asthma and type 1 diabetes. [source] Circulating adhesion molecules in sera of asthmatic childrenPEDIATRIC PULMONOLOGY, Issue 4 2002Ren-Bin Tang MD Abstract Infiltration of cells into the lung in asthma is regulated by several expressions of cell adhesion molecules (CAMs) on cells present in the airways, and may play a role in the pathogenesis of bronchial asthma. We sought to evaluate the role of serum concentrations of the soluble forms of intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and E-selectin (sE-selectin) in the control of disease activity in acute asthma. Circulating levels of sICAM-1, sVCAM-1, and sE-selectin in sera from 15 normal control subjects and from 20 allergic asthmatic children with acute exacerbations who had returned to stable condition were determined by using commercially available enzyme-linked immunosorbent assay kits. The mean concentration of serum sICAM-1 levels was significantly higher during an acute exacerbation of asthmatic children than in those with stable asthma (19.41,±,10.65 ng/mL vs. 13.46,±,5.44 ng/mL; P,<,0.001) or in control subjects (9.83,±,2.02 ng/mL; P,<,0.001). For sVCAM-1 and sE-selectin, the mean serum concentration of sVCAM-1 was slightly higher in children during an acute exacerbation asthma than when stable. However, the differences did not reach statistical significance. The mean serum concentrations of sVCAM-1 and sE-selectin in acute asthma or stable asthma were significiantly higher than in control subjects. This study provides further evidence that serum concentrations of sICAM-1, sVCAM-1, and sE-selectin are increased in acute asthma. These findings further confirm that leukocyte endothelial adhesion plays a role in inflammmatory airway disease. Pediatr Pulmonol. 2002; 33:249,254. © 2002 Wiley-Liss, Inc. [source] Eosinophil cationic protein in infants with respiratory syncytial virus bronchiolitis: Predictive value for subsequent development of persistent wheezingPEDIATRIC PULMONOLOGY, Issue 6 2001Massimo Pifferi MD Abstract Infants with acute bronchiolitis during the first months of life are at increased risk of developing persistent wheezing and bronchial asthma later in life. The study of eosinophil cationic protein (ECP) suggests that eosinophil-related inflammatory mechanisms may play a role in respiratory syncytial virus (RSV) bronchiolitis. The aim of our study was to verify whether serum ECP (s-ECP) measurements are useful in predicting the development of persistent wheezing in children affected by RSV bronchiolitis during a 5 years follow-up period. Forty-eight infants were enrolled prospectively (mean age: 153.5 days). All had a clinical and radiological diagnosis of acute bronchiolitis and confirmed RSV infection. Peripheral eosinophil counts, levels of s-ECP, and serum IgE concentrations were measured during bronchiolitis. Five years later the children were re-evaluated in regard to their respiratory symptoms (standardized questionnaires) and atopic status (specific IgE levels). We observed significantly higher s-ECP levels (P <,0.001) at enrollment in subjects who developed persistent wheezing compared to subjects who did not show late wheezing. Initial s-ECP values allowed significant and correct prediction of persistent wheezing (P <,0.001). The risk to develop respiratory symptoms was 9.73 higher for infants with s-ECP levels ,,8,,g/L than for those with s-ECP levels <8,,g/L (P <,0.0001). In conclusion, our study suggests that s-ECP levels in infants with bronchiolitis are useful in predicting the risk to develop wheezing in the subsequent 5 years. Pediatr Pulmonol. 2001; 31:419,424. © 2001 Wiley-Liss, Inc. [source] Evaluation of allergic sensitization and gastroesophageal reflux disease in children with recurrent croupPEDIATRICS INTERNATIONAL, Issue 5 2009Zafer Arslan Abstract Background:, Croup, which is seen commonly in childhood, is a disorder that can be recurrent and progress to bronchial asthma. In the present study the prevalence of gastroesophageal reflux (GER) and atopy and the response to therapy were investigated in children with recurrent croup. Methods:, Between October 2003 and June 2004, 57 patients with acute stridor were admitted to the emergency room. The patients who had at least three croup episodes and patients with first croup episode were compared. Results:, Thirty-two children had recurrent croup history, GER was found in of 62.5%, and atopy in 17.2%. Atopy was not found in any children with first croup episode. The difference was significant. In addition it was found that atopic dermatitis, previous history of wheezing and established atopy increased the risk of croup recurrence. Alone or combined inhaled corticosteroids and GER therapy were administered, and 77.7% of the patients responded very well. Conclusion:, GER and atopy should be investigated in patients with recurrent spasmodic croup. Recurrent croup is a non-specific manifestation of atopy. Patients with atopy should be followed closely for developing bronchial asthma. [source] | ||||||||||||||||||||||||||||||||||