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Hyperresponsiveness
Kinds of Hyperresponsiveness Selected AbstractsHypersensitivity to titanium osteosynthesis with impaired fracture healing, eczema, and T-cell hyperresponsiveness in vitro: case report and review of the literatureCONTACT DERMATITIS, Issue 4 2006Peter Thomas There are very few reports on hypersensitivity reactions in association with titanium-based materials so that the existence of allergy to titanium is still put in question. We report on a patient in whom impaired fracture healing and eczema localized to the perioperative area developed upon titanium-based osteosynthesis. Patch testing gave no reactions to titanium nor to nickel, chromium, or cobalt. However, in the lymphocyte transformation test, the patient's lymphocytes showed markedly enhanced proliferation in vitro to titanium. After removal of the titanium material, fracture healing was achieved and the eczema cleared. Parallel to this, in vitro hyperreactivity to titanium disappeared. Although contact allergic reactions to titanium have been very rarely reported, these findings support a diagnosis of titanium allergy in our patient. [source] Discrepancy between acute and chronic toxicity induced by imidacloprid and its metabolites in Apis melliferaENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 11 2001Séverine Suchail Abstract Imidaclopridi a systemic nitroguanidine insecticide that belongs to theneonicotinoid family. As an agonist of the acetylcholine receptor, it attacks the insect nervous system and is extremely effective against various sucking and mining pests. Oral acute and chronic toxicity of imidacloprid and its main metabolites (5-hydroxyimidacloprid, 4,5-dihydroxyimidacloprid, desnitroimidacloprid, 6-chloronicotinic acid, olefin, and urea derivative) were investigated in Apis mellifera. Acute intoxication by imidacloprid or its metabolites resulted in the rapid appearance of neurotoxicity symptoms, such as hyperresponsiveness, hyperactivity, and trembling and led to hyporesponsiveness and hypoactivity. For acute toxicity tests, bees were treated with doses of toxic compounds ranging from 1 to 1,000 ng/bee (10,10,000 ,g/kg). Acute toxicity (LD50) values of imidacloprid were about 60 ng/bee (600 ,g/kg) at 48 h and about 40 ng/bee (400 ,g/kg) at 72 and 96 h. Out of the six imidacloprid metabolites tested, only two (5-hydroxyimidacloprid and olefin) exhibited a toxicity close to that of imidacloprid. Olefin LD50 values were lower than those of imidacloprid. The 5-hydroxyimidacloprid showed a lower toxicity than imidacloprid with a LD50 four to six times higher than that of imidacloprid. Urea also appeared as a compound of nonnegligible toxicity by eliciting close to 40% mortality at 1,000 ng/bee (10,000 ,g/kg). However, no significant toxicity was observed with 4,5-dihydroxyimidacloprid, 6-chloronicotinic acid, and desnitroimidacloprid in the range of doses tested. To test chronic toxicity, worker bees were fed sucrose solutions containing 0.1, 1, and 10 ,g/L of imidacloprid and its metabolites for 10 d. Fifty percent mortality was reached at approximately 8 d. Hence, considering that sucrose syrup was consumed at the mean rate of 12 ,l/d and per bee, after an 8-d period the cumulated doses were approximately 0.01, 0.1, and 1 ng/bee (0.1, 1, and 10 ,g/kg). Thus, all tested compounds were toxic at doses 30 to 3,000 (olefin), 60 to 6,000 (imidacloprid), 200 to 20,000 (5-OH-imidacloprid), and >1,000 to 100,000 (remaining metabolites) times lower than those required to produce the same effect in acute intoxication studies. For all products tested, bee mortality was induced only 72 h after the onset of intoxication. [source] Mast cells play a key role in the developmentof late airway hyperresponsiveness through TNF-,in a murine model of asthmaEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2007Young-Suk Kim Abstract We have investigated the role of TNF-, in mast cell-mediated late airway hyperresponsiveness (AHR) using mast cell-deficient WBB6F1- W/Wv (W/Wv) mice in a murine model of asthma, which exhibits a biphasic increase in AHR. TNF-, levels in the airway and magnitude of late AHR in response to airway allergen challenge were severely impaired in W/Wv mice compared to their littermates. In addition to TNF-,, cytosolic phospholipase A2 (cPLA2) phosphorylation and enzymatic activity in the lungs were also impaired in W/Wv mice. Either anti-TNF-, antibody or an inhibitor of cPLA2 abolished late AHR in congeneic +/+ mice. Intratracheal administration of TNF-, resulted in increases in late AHR, cPLA2 phosphorylation, cPLA2 activity, and phosphorylation of mitogen-activated protein kinases. Mast cell replacement restored airway TNF-, level, cPLA2 phosphorylation and enzymatic activity in the lungs as well as late AHR in W/Wv mice. These data indicate that mast cells play a key role in the development of late AHR through liberation of TNF-,. [source] The natural history of asthma from childhood to adulthoodINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 8 2007M. S. Koh Summary Medical Practitioners are often questioned regarding the prognosis of a child with asthma. We have performed a literature review of the natural history of childhood asthmatics. Factors which affect the natural history and prognosis of childhood asthma are discussed. Current evidence suggests that evolution of asthma severity is fairly predictable. Features of childhood asthma such as severity, duration, atopy, bronchial hyperresponsiveness and exposure to smoking can predict the course of asthma into adulthood. Most children with mild intermittent asthma will outgrow their asthma, or have mild episodic asthma. Early commencement of anti-inflammatory therapy, such as inhaled corticosteroids may prevent the progression of the disease. Most patients with mild asthma have good functional outcome and low healthcare utilisation. [source] Piperine inhibits eosinophil infiltration and airway hyperresponsiveness by suppressing T cell activity and Th2 cytokine production in the ovalbumin-induced asthma modelJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2009Seung-Hyung Kim Abstract Objectives This study aimed to investigate the effect of piperine on airway hyper-responsiveness, pulmonary eosinophilic infiltration, various immune cell phenotypes, Th2 cytokine production, immunoglobulin E and histamine production in a murine model of asthma. Methods Asthma was induced in Balb/c mice by ovalbumin sensitization and inhalation. Piperine (4.5 and 2.25 mg/kg) was orally administered 5 times a week for 8 weeks. At 1 day after the last ovalbumin exposure, airway hyperresponsiveness was determined and samples of bronchoalveolar lavage fluid, lung cells and serum were collected for further analysis. Key findings Piperine-treated groups had suppressed eosinophil infiltration, allergic airway inflammation and airway hyperresponsiveness, and these occurred by suppression of the production of interleukin-4, interleukin-5, immunoglobulin E and histamine. Moreover, polymerase chain reaction products for thymus and activation regulated chemokine from lung cell RNA preparations were decreased in the piperine-treated group compared with control groups, although transforming growth factor-, products were increased in the piperine-treated group. Conclusions The results suggest that the therapeutic mechanism by which piperine effectively treats asthma is based on a reduction of Th2 cytokines (interleukin-4, interleukin-5), eosinophil infiltration, and by marked reduction of thymus and activation regulated chemokine, eotaxin-2 and interleukin-13 mRNA expression (especially transcription of nuclear factor-, dependent genes) in lung tissue, as well as reduced interleukin-4, interleukin-5 and eotaxin levels in bronchoalveolar lavage fluid, and histamine and ovalbumin-specific immunoglobulin E production in serum. [source] Risk factors of new-onset asthma in adults: a population-based international cohort studyALLERGY, Issue 8 2010J. M. Antó To cite this article: Antó JM, Sunyer J, Basagańa X, Garcia-Esteban R, Cerveri I, de Marco R, Heinrich J, Janson C, Jarvis D, Kogevinas M, Kuenzli N, Leynaert B, Svanes C, Wjst M, Gislason T, Burney P. Risk factors of new-onset asthma in adults: a population-based international cohort study. Allergy 2010; 65: 1021,1030 Abstract Background:, The occurrence of new-onset asthma during adulthood is common, but there is insufficient understanding of its determinants including the role of atopy. Objective:, To assess the risk factors for the development of new-onset asthma in middle-aged adults and to compare them according to atopy. Methods:, A longitudinal analysis of 9175 young adults who participated in two surveys of the European Community Respiratory Health Survey (ECRHS) conducted 9 years apart. Findings:, We observed 179 cases of new-onset asthma among 4588 participants who were free of asthma and reported at the beginning of the follow-up that they had never had asthma (4.5 per 1000 person-years). In a logistic regression, the following risk factors were found to increase the risk of new-onset asthma: female gender (OR: 1.97; 95% confidence interval (CI): 1.38,2.81), bronchial hyperresponsiveness (3.25; 2.19,4.83), atopy (1.55;1.08,2.21), FEV1 < 100 % predicted (1.87;1.34,2.62), nasal allergy (1.98;1.39,2.84) and maternal asthma (1.91;1.13;3.21). Obesity, respiratory infections in early life and high-risk occupations increased the risk of new-onset asthma although we had limited power to confirm their role. Among the atopics, total IgE and sensitization to cat were independently related to the risk of new-onset asthma. The proportion of new-onset asthma attributable to atopy varied from 12% to 21%. Conclusion:, Adults reporting that they had never had asthma were at a substantial risk of new-onset asthma as a result of multiple independent risk factors including lung function. Atopy explains a small proportion of new-onset adult asthma. [source] Eccrine sweat response in children with asthmaALLERGY, Issue 5 2010A. Oflu To cite this article: Oflu A, Soyer OU, Tuncer A, Sackesen C, Kalayci O. Eccrine sweat response in children with asthma. Allergy 2010; 65: 645,648. Abstract Background:, Even though there is a general conviction among parents of asthmatic children and pediatricians that asthmatic children sweat more than healthy ones, this has not been formally tested. Aim:, To determine sweating response and factors affecting this response in children with asthma and compare these findings with healthy children. Method:, Eighty-two children with asthma and 51 healthy controls aged 6,18 years were enrolled in the study. Transepidermal water loss (TEWL) was measured on palmar, volar, forehead, and back surfaces before and after exercise and was expressed as the difference between the measurements recorded before and after exercise. Results:, Transepidermal water loss measurements (after exercise , resting) on the palmar surface were higher in children with asthma [22.8 g/m2 h (15,34.3)] compared with healthy children [15.2 g/m2 h (6,22.2)] (P < 0.001). However, a gender stratified analysis showed that the TEWL measurements were higher on all surfaces only in boys but not in girls. Within the group of asthmatic children, TEWL measurements on the volar surface and back were lower in patients using anti-inflammatory therapy compared with those who were on as needed bronchodilator therapy only. Conclusion:, Our results show that asthma is associated with a higher rate of sweating response to exercise in boys, and anti-inflammatory treatment decreases the amount of sweating. The relationship of eccrine sweating with muscarinic receptor response and methacholine hyperresponsiveness remains to be determined. [source] Inhaled vs subcutaneous effects of a dual IL-4/IL-13 antagonist in a monkey model of asthmaALLERGY, Issue 1 2010A. Tomkinson Abstract Background:, Pitrakinra is a recombinant protein derived from human interleukin-4 (IL-4) that binds to IL-4R, and acts as a competitive antagonist of IL-4 and IL-13. The studies reported here compare the dose-ranging effects of pitrakinra on allergen-induced airway hyperresponsiveness (AHR) and airway eosinophilia when administered subcutaneously (s.c.) or by inhalation to the Ascaris suum -sensitive cynomolgus monkey for the purpose of elucidating the primary site of pitrakinra's anti-asthmatic action. Methods:, Airway responsiveness to inhaled methacholine and bronchoalveolar lavage cell composition was determined before and after three allergen exposures with a 1-week course of twice-daily (b.i.d.) s.c. or inhaled pitrakinra or placebo treatment. Results:, Treatment with s.c. pitrakinra significantly reduced allergen-induced AHR, with a maximum effect of a 2.8- to 3.8-fold increase in methacholine PC100 relative to control (P < 0.05) observed at b.i.d. s.c. doses of 0.05,0.5 mg/kg. Inhaled pitrakinra also significantly reduced AHR with a similar maximum effect of a 2.8- to 3.2-fold increase in methacholine PC100 relative to control (P < 0.05) at nominal b.i.d. doses of 3,100 mg. The maximal effect on AHR following inhalation was observed at a plasma concentration which exhibited no efficacy via the subcutaneous route. The effect of pitrakinra on lung eosinophilia was not statistically significant following either route of administration, although lung eosinophil count was reduced in all studies relative to control. Conclusion:, Local administration of pitrakinra to the lung is sufficient to inhibit AHR, one of the cardinal features of asthma, indicating the therapeutic potential of inhaled pitrakinra in the treatment of atopic asthma. [source] Targeting the allergen to oral dendritic cells with mucoadhesive chitosan particles enhances tolerance inductionALLERGY, Issue 7 2009N. Saint-Lu Background:, Sublingual immunotherapy (SLIT) efficacy could be improved by formulations facilitating allergen contact with the oral mucosa and uptake by antigen-presenting cells (APCs). Methods:, Two types of chitosan microparticles, differing in size and surface charge, were tested in vitro for their capacity to improve antigen uptake and presentation by murine bone marrow-derived dendritic cells (BMDCs) or purified oral APCs. T-cell priming in cervical lymph nodes (LNs) was assessed by intravenous transfer of carboxyfluorescein diacetate succinimidyl ester-labelled ovalbumin (OVA)-specific CD4+ T cells and flow cytometry analysis. Ovalbumin-sensitized BALB/c mice were treated sublingually with soluble or chitosan-formulated OVA twice a week for 2 months. Airway hyperresponsiveness (AHR), lung inflammation and T-cell responses in cervical and mediastinal LNs were assessed by whole-body plethysmography, lung histology and Cytometric Bead Array technology, respectively. Results:, Only a mucoadhesive (i.e. highly positively charged) and microparticulate form of chitosan enhances OVA uptake, processing and presentation by murine BMDCs and oral APCs. Targeting OVA to dendritic cells with this formulation increases specific T-cell proliferation and IFN-,/IL-10 secretion in vitro, as well as T-cell priming in cervical LNs in vivo. Sublingual administration of such chitosan-formulated OVA particles enhances tolerance induction in mice with established asthma, with a dramatic reduction of both AHR, lung inflammation, eosinophil numbers in bronchoalveolar lavages, as well as antigen-specific Th2 responses in mediastinal LNs. Conclusions:, Mucoadhesive chitosan microparticles represent a valid formulation for sublingual allergy vaccines. [source] Smoke exposure interacts with ADAM33 polymorphisms in the development of lung function and hyperresponsivenessALLERGY, Issue 6 2009N. E. Reijmerink Introduction:,ADAM33 is the first identified asthma gene by positional cloning, especially asthma combined with bronchial hyperresponsiveness (BHR). Moreover, ADAM33 is associated with early-life lung function and decline of forced expiratory volume in 1 s (FEV1) in the general population. In utero and postnatal cigarette smoke exposure (CSE) are associated with reduced lung function, and development of BHR and asthma. We hypothesized that this may occur via interaction with ADAM33. Aim:, To replicate the role of ADAM33 in childhood lung function and development of BHR and asthma. Furthermore, we investigated gene,environment interaction of ADAM33 with in utero and postnatal CSE in the Dutch PIAMA cohort. Methods:, Six ADAM33 single-nucleotide polymorphisms (SNPs) were genotyped. Rint was measured at age 4 and 8 years, FEV1 and BHR at age 8 years; asthma was based on questionnaire data at age 8. Results:, In the total cohort, the rs511898 A, rs528557 C, and rs2280090 A alleles increased the risk to develop asthma (+BHR). There existed interaction between in utero but not postnatal CSE and the rs528557 and rs3918396 SNPs with respect to development of BHR, the rs3918396 SNP with Rint at age 8 and the rs528557 SNP with FEV1% predicted. Conclusions:, We confirm associations between ADAM33 and the development of asthma (+BHR). This is the first study suggesting that interaction of in utero CSE with ADAM33 results in reduced lung function and the development of BHR, which needs further confirmation. [source] Airway wall geometry in asthma and nonasthmatic eosinophilic bronchitisALLERGY, Issue 6 2009S. Siddiqui Background:, Variable airflow obstruction and airway hyperresponsiveness (AHR) are features of asthma, which are absent in nonasthmatic eosinophilic bronchitis (EB). Airway remodelling is characteristic of both conditions suggesting that remodelling and airway dysfunction are disassociated, but whether the airway geometry differs between asthma and nonasthmatic EB is uncertain. Methods:, We assessed airway geometry by computed tomography (CT) imaging in asthma vs EB. A total of 12 subjects with mild,moderate asthma, 14 subjects with refractory asthma, 10 subjects with EB and 11 healthy volunteers were recruited. Subjects had a narrow collimation (0.75 mm) CT scan from the aortic arch to the carina to capture the right upper lobe apical segmental bronchus (RB1). In subjects with asthma and EB, CT scans were performed before and after a 2-week course of oral prednisolone (0.5 mg/kg). Results:, Mild,moderate and refractory asthma were associated with RB1 wall thickening in contrast to subjects with nonasthmatic EB who had maintained RB1 patency without wall thickening [mean (SD) % wall area and luminal area mild-t0-moderate asthma 67.7 (7.3)% and 6.6 (2.8) mm2/m2, refractory asthma 67.3 (5.6)% and 6.7 (3.4) mm2/m2, healthy control group 59.7 (6.3)% and 8.7 (3.8) mm2/m2, EB 61.4 (7.8)% and 11.1 (4.6) mm2/m2 respectively; P < 0.05]. Airway wall thickening of non-RB1 airways generation three to six was a feature of asthma only. There was no change in airway geometry of RB1 after prednisolone. Proximal airway wall thickening was associated with AHR in asthma (r = ,0.56; P = 0.02). Conclusions:, Maintained airway patency in EB may protect against the development of AHR, whereas airway wall thickening may promote AHR in asthma. [source] Sputum eosinophilia: an early marker of bronchial response to occupational agentsALLERGY, Issue 5 2009O. Vandenplas Background:, False-negative responses to specific inhalation challenge (SIC) with occupational agents may occur. We explored whether assessing changes in sputum cell counts would help improve the identification of bronchial reactivity to occupational agents during SICs. Methods:, The predictive value of the changes in sputum cell counts after a negative FEV1 response to a first challenge exposure to an occupational agent was determined using the changes in airway calibre observed during repeated challenges as the ,gold standard'. The study included 68 subjects investigated for work-related asthma in a tertiary centre. After a control day, the subjects were challenged with the suspected occupational agent(s) for up to 2 h. All subjects who did not show an asthmatic reaction were re-challenged on the following day. Additional challenges were proposed to those who demonstrated a , 2% increase in sputum eosinophils or an increase in nonspecific bronchial hyperresponsiveness to histamine after the second challenge day. Results:, Six of the 35 subjects without changes in FEV1 on the first challenge developed an asthmatic reaction on subsequent challenges. ROC analysis revealed that a >3% increase in sputum eosinophils at the end of the first challenge day was the most accurate parameter for predicting the development of an asthmatic response on subsequent challenges with a sensitivity of 67% and a specificity of 97%. Conclusions:, An increase in sputum eosinophils is an early marker of specific bronchial reactivity to occupational agents, which may help to identify subjects who will develop an asthmatic reaction only after repeated exposure. [source] TRPV1-mediated itch in seasonal allergic rhinitisALLERGY, Issue 5 2009L. Alenmyr Background:, Patients with allergic rhinitis may be abnormally sensitive to stimulation of the ion channel transient receptor potential vanilloid-1 (TRPV1). Aim of the study:, To examine effects of various TRP ion channel activators on sensory symptoms in allergic rhinitis prior to and during seasonal allergen exposure. Methods:, Nasal challenges were carried out with the TRPV1-activators capsaicin, anandamide and olvanil. Moreover, challenges were performed with mustard oil (allylisothiocyanate) and cinnamaldehyde as well as menthol, activators of TRPA1 and TRPM8, respectively. Nasal symptoms were monitored after each challenge and compared with symptoms reported following corresponding sham challenges. Symptoms recorded after challenge prior to pollen season were also compared with challenge-induced symptoms during pollen season. Results:, The TRPV1, TRPA1 and TRPM8-activators produced sensory symptoms dominated by pain and smart. During seasonal allergen exposure, but not prior to season, TRPV1-activators also induced itch. Furthermore, the seasonal challenge to the TRPV1-activator olvanil was associated with rhinorrhoea. Conclusion:, Patients with allergic rhinitis feature an increased itch response to TRPV1 stimulation at seasonal allergen exposure. We suggest that this reflects part of the hyperresponsiveness that characterizes on-going allergic rhinitis. Intervention with the TRPV1-signalling pathway may offer potential treatments of this condition. [source] Predictors of bronchial hyperresponsiveness in chronic rhinosinusitis with nasal polypALLERGY, Issue 1 2009D. H. Han Background:, Chronic rhinosinusitis with nasal polyposis (CRSNP) and asthma are inflammatory lesions of the respiratory epithelium. This study was conducted to evaluate predictive factors of bronchial hyperresponsiveness (BHR) in patients with CRSNP. Methods:, BHR was evaluated using a methacholine bronchoprovocation test (MBPT) in 122 consecutive patients newly diagnosed with CRSNP at Seoul National University Hospital from January 2004 to June 2006. The following parameters were analyzed and compared between the BHR and non-BHR groups: symptoms, atopic status, current smoking, disease severity of CRSNP based on the Lund,Mackay scoring system of sinus CT, and counts of eosinophils in the serum and nasal tissues. Results:, Thirty-five percent of the patients were found to have BHR, and BHR was found to occur more frequently in patients that were currently suffering from sneezing (P = 0.007). In addition, the mean eosinophil counts of the serum and nasal tissues were higher in the BHR group than in the non-BHR group (P = 0.001 for the serum, P = 0.045 for the nasal tissues), and the eosinophil counts of the serum correlated to those of the nasal tissues (r = 0.334, P = 0.013). The disease severity, as determined by the Lund,Mackay scoring system, was not different between the two groups (P > 0.05). The best cutoff serum eosinophil count for predicting BHR in CRSNP patients was determined to be 300 cells/,l (sensitivity 70%, specificity 70%). Conclusion:, Taken together, these results indicate that moderate to severe sneezing and a serum eosinophil count , 300 cells/,l may be predictive factors for BHR in patients with CRSNP. [source] Distinct association of genetic variations of vascular endothelial growth factor, transforming growth factor-,, and fibroblast growth factor receptors with atopy and airway hyperresponsivenessALLERGY, Issue 4 2008H.-K. Park Background:, Recent studies showed that high levels of transforming growth factor (TGF)-,1 in the airways reduced airway responsiveness, which was reversed in conditions of basic fibroblast growth factor (FGF2) deficiency, whereas high levels of vascular endothelial growth factor (VEGF) enhanced airway sensitization to allergens and airway hyperresponsiveness (AHR). Objective:, We investigated the effect of single-nucleotide polymorphisms (SNPs) in the VEGF, TGF-,1, and FGF2 receptors on the expression of atopy and AHR in the general population. Methods:, Atopy and AHR were evaluated in a cohort of 2055 children and adolescents. Direct sequencing was used to identify informative SNPs (minor allele frequency >5%) in the receptors of candidate genes. Tagging SNPs were scored using the high-throughput single-base pair extension method, and the statistical significance of these scores was assessed via haplotype analysis. Results:, Informative SNPs were identified for VEGF receptors 1 (Flt-1); TGF-, receptor 3 (TGFBR3); and FGR receptors 1, 2, and 4 (FGFR1, FGFR2, and FGFR4), and 13 tagging SNPs were scored in the cohort. Atopy was significantly associated with haplotypes of TGFBR3, FGFR1, and FGFR2. Meanwhile, AHR was significantly associated with haplotypes of Flt-1, FGFR1, and FGFR4. However, atopy was not associated with genetic variations of Flt-1 and FGFR4, whereas AHR not associated with TGFBR3 and FGFR2. Conclusion:, The expression of atopy and AHR is distinctly associated with genetic variations in VEGF, TGF-,1, and FGFR in the Korean population. [source] Increased prostaglandin E2 levels in the airway of patients with eosinophilic bronchitisALLERGY, Issue 1 2008B. Sastre Background:, Eosinophilic bronchitis is a common cause of chronic cough, which like asthma is characterized by sputum eosinophilia, but unlike asthma there is no variable airflow obstruction or airway hyperresponsiveness. We tested the hypothesis that the different airway function in patients with eosinophilic bronchitis and asthma could be caused by an imbalance in the production of bronchoconstrictor (LTC4) and bronchoprotective (prostaglandin E2; PGE2) lipid mediators. Methods:, We measured cytokines levels, proinflammatory mediators and eicosanoids concentration in sputum from 13 subjects with nonasthmatic eosinophilic bronchitis, 13 subjects with asthma, and 11 healthy control subjects. Cytokines mRNA levels were measured by real time PCR, proinflammatory mediators, PGE2, and LTC4 were measured by enzyme immunoassays. Results:, The median sputum eosinophil count was not statistically different in patients with asthma (7.95%) and eosinophilic bronchitis (15.29%). The levels of mRNA specific to interleukin-5 (IL-5), IL-4, IL-10, IL-13, interferon , (IFN-,), IL-2, vascular endothelial growth factor and transforming growth factor , were similar in both conditions. In addition, no differences were found between asthma and eosinophilic bronchitis in proinflammatory cytokines, such as IL-8, IFN-, and tumor necrosis factor , (TNF-,) levels. Sputum cysteinyl-leukotrienes concentration was raised both in eosinophilic bronchitis and asthma patients. We found that induced sputum PGE2 concentrations were significantly increased in subjects with eosinophilic bronchitis (838.3 ± 612 pg/ml) when compared with asthmatic (7.54 ± 2.14 pg/ml) and healthy subjects (4 ± 1.3 pg/ml). Conclusion:, This data suggest that the difference in airway function observed in subjects with eosinophilic bronchitis and asthma could be due to differences in PGE2 production in the airways. [source] Mechanisms of virus-induced asthma exacerbations: state-of-the-art.ALLERGY, Issue 5 2007A GA2LEN, InterAirways document Viral infections of the respiratory tract are the most common precipitants of acute asthma exacerbations. Exacerbations are only poorly responsive to current asthma therapies and new approaches to therapy are needed. Viruses, most frequently human rhinoviruses (RV), infect the airway epithelium, generate local and systemic immune responses, as well as neural responses, inducing inflammation and airway hyperresponsiveness. Using in vitro and in vivo experimental models the role of various proinflammatory or anti-inflammatory mediators, antiviral responses and molecular pathways that lead from infection to symptoms has been partly unravelled. In particular, mechanisms of susceptibility to viral infection have been identified and the bronchial epithelium appeared to be a key player. Nevertheless, additional understanding of the integration between the diverse elements of the antiviral response, especially in the context of allergic airway inflammation, as well as the interactions between viral infections and other stimuli that affect airway inflammation and responsiveness may lead to novel strategies in treating and/or preventing asthma exacerbations. This review presents the current knowledge and highlights areas in need of further research. [source] Omalizumab decreases nonspecific airway hyperresponsiveness in vitroALLERGY, Issue 2 2007P. Berger Background:, In asthmatic patients, both symptoms and hyperresponsiveness are related to immunoglobulin E (IgE) concentration in serum. The anti-IgE monoclonal antibody omalizumab improved the control of asthma, but its effect on airway hyperresponsiveness is controversial. Passive sensitization reproduced in vitro a bronchial hyperresponsiveness, an increase in IgE bearing cells, and a mast cell degranulation. This study was designed to examine the effect of omalizumab on passive sensitization-induced hyperresponsiveness, alterations in IgE positive inflammatory cells and mast cell degranulation within the bronchial wall. Methods:, Proximal (3,5 mm diameter) and distal (0.5,1.5 mm diameter) human bronchi dissected out from 10 lung specimens were incubated in normal or asthmatic serum containing various concentrations of omalizumab. Contractile responses to histamine or Dermatophagoides pteronyssinus (D. pter) were recorded using an organ bath system and expressed as percentage of maximal contractile response to acetylcholine (ACh). Immunohistochemistry was performed using monoclonal antibodies directed against IgE or tryptase. Mast cells were classified as fully granulated (type I), partly (type II) or largely degranulated (type III). Results:, The specific bronchial hyperresponsiveness to D. pter and the nonspecific bronchial hyperresponsiveness to histamine following passive sensitization were significantly inhibited by omalizumab in both distal and proximal airways. Passive sensitization-induced increase in IgE positive cells was also abolished by omalizumab in a concentration dependent manner. Mast cell degranulation which was inhibited by omalizumab was positively correlated with the contractile response to D. pter. Conclusions:, Omalizumab blocks specific and nonspecific bronchial hyperresponsiveness. Anti-IgE also decreases IgE bearing cell number and mast cell degranulation. [source] Relationship between adipokines and manifestations of childhood asthmaPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 6 2008Kyung W. Kim Although the prevalences of asthma and obesity are increasing substantially in recent decades, very little is known about the possible association between them. We evaluated the roles of leptin, adiponectin, and resistin, which are adipokines produced by adipose tissue, on childhood asthma, and their association with pulmonary function and bronchial hyperresponsiveness. We studied 149 atopic asthmatic children, 37 non-atopic asthmatic children, and 54 healthy children. Body mass index was calculated using height and weight, which were measured on the same day that pulmonary function tests and methacholine challenge tests were performed. Skin prick tests were performed, and total eosinophil count, total serum immunoglobulin E (IgE), serum eosinophil cationic protein, leptin, adiponectin, and resistin were measured in all subjects. Atopic asthmatics had lower resistin levels compared with non-atopic asthma and control groups, but leptin and adiponectin did not show any difference among these three groups. Resistin demonstrated positive correlation with methacholine PC20 and negative correlations with eosinophil count and serum total IgE. Leptin and adiponectin showed associations with forced expiratory volume in 1 s or forced expiratory flow between 25,75%. Multiple regression analysis revealed that resistin was a significant predictive factor for asthma. There was no direct association between asthma and leptin or adiponectin. Our findings suggest that resistin may play a negative predictive role in asthma. Adiponectin and leptin showed close associations with pulmonary function and may have disease-modifying effects in children with asthma. [source] Increase in the prevalence of rhinitis among Danish children from 1986 to 2001PEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 2 2007Kĺre Hĺkansson In recent decades, there has been a worldwide increase in the prevalence of atopic diseases. The aim of this study was to investigate whether there has been a change in the prevalence of rhinitis among children in Denmark from 1986 to 2001. We compared data from two random population-based samples of Danish children, aged 7,17 yr, who were examined in 1986 (n = 527) and 2001 (n = 480) using similar designs. Symptoms of rhinitis, skin test reactivity, and bronchial responsiveness to inhaled histamine were assessed. The prevalence of rhinitis increased from 11.8% in 1986 to 23.3% in 2001 (p < 0.001). The increase was most pronounced among subjects who suffered from non-allergic rhinitis (p < 0.001), and among subjects with severe symptoms (p < 0.001). The prevalence of asymptomatic positive skin prick test (SPT) decreased substantially (p < 0.001). A history of asthma and parental atopic disease were strong predictors of non-allergic rhinitis, whereas a history of asthma, parental atopic disease, bronchial hyperresponsiveness, eczema, and age at examination were statistically significant predictors of allergic rhinitis. The prevalence of non-allergic rhinitis among Danish children has increased substantially from 1986 to 2001. Furthermore, in general more severe symptoms of rhinitis were observed in 2001 compared with 1986. These results underline the importance of using objective measurements such as skin test reactivity when estimating time trends in the prevalence of allergic airways disease, as clinical interviews alone can be misleading. [source] Steroid-sensitive indices of airway inflammation in children with seasonal allergic rhinitisPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 1 2003Peter Meyer Previous studies involving adults have demonstrated that airway glucocorticosteroids inhibit plasma exudation and eosinophil activity in allergic rhinitis. This study explores the possibility that plasma exudation, exudative responsiveness, and the occurrence of eosinophil activity-related proteins are glucocorticosteroid-sensitive nasal mucosal indices in allergic children. Using a placebo-controlled, parallel-group design effects of nasal budesonide (64 µg per nasal cavity b.i.d) were determined in children with seasonal allergic rhinitis. Nasal lavage fluid levels of eotaxin, eosinophil cationic protein (ECP), and ,2 -macroglobulin, indicating plasma exudation, were determined, the latter with and without challenge with topical histamine. Nasal lavage fluid levels of ,2 -macroglobulin and ECP increased significantly during the pollen season, and the acute plasma exudation response to histamine was significantly greater during than outside the season. There was a trend towards a seasonal increase in nasal lavage fluid levels of eotaxin. Budesonide significantly inhibited the seasonal increase in ,2 -macroglobulin as well as the exudative hyperresponsiveness to histamine. Any tendency of increases in mucosal output of eotaxin and ECP was abolished by the glucocorticosteroid treatment. We conclude that mucosal exudation of plasma, as a global sign of active inflammatory processes, is a glucocorticosteroid-sensitive facet of allergic rhinitis in children. Exudative hyperresponsiveness, potentially caused by several weeks of mucosal inflammation, emerges as a significant feature of allergic rhinitis in children, and its development is prevented by local treatment with a glucocorticosteroid drug. The seasonal increase in ECP and the trend for an increase in eotaxin were absent in the glucocorticosteroid-treated subjects. [source] Airway hyperresponsiveness and acute chest syndrome in children with sickle cell anemiaPEDIATRIC PULMONOLOGY, Issue 3 2007Karl P. Sylvester PhD Abstract To determine the occurrence and magnitude of airway hyperresponsiveness (AHR) in children with sickle cell anemia (SCA) who had or had not had acute chest syndrome (ACS) episodes. A subsidiary aim was to determine whether cold air and exercise challenge testing gave similar results in children with SCA. AHR would be greater in SCA children who had had an ACS episode compared to those who had not. Prospective observational study. Forty-two SCA children (median age of 11.5 [range 6.1,16.8] years); 12 children had been previously hospitalized for an ACS episode. AHR was assessed by the change in forced expiratory volume in 1 sec (FEV1) to a cold air challenge and in a subset of the children to an exercise challenge. A positive result to either challenge was deemed to have occurred if the FEV1 fell by at least 10% from the pre-challenge baseline. The magnitude of change in FEV1 following the cold air challenge was similar in children who had or had not had an ACS episode. Six children had a positive response to the cold air challenge (AHR); none had had an ACS hospitalization. Similar proportions of children responded to the cold air and exercise challenge and the magnitude of response to the two tests was similar. Some children, however, responded only to a cold air challenge and others only to an exercise challenge. SCA children who had had an ACS hospitalization episode compared to those who had not were not more likely to respond to a cold air challenge. Importantly, if AHR is to be correctly diagnosed, some SCA children will require to undergo both cold air and exercise challenge testing. Pediatr Pulmonol. 2007; 42:272,276. © 2007 Wiley-Liss, Inc. [source] Bronchial hyperresponsiveness, atopy, and bronchoalveolar lavage eosinophils in persistent middle lobe syndromePEDIATRIC PULMONOLOGY, Issue 9 2006Kostas N. Priftis MD Abstract Most cases of middle lobe syndrome (MLS) in children are considered to be due to asthma and may recover spontaneously; however, in persistent MLS, repeated episodes of infection often institute a vicious cycle that may lead to persistent symptoms and bronchial hyperresponsiveness (BHR). The present study was undertaken to investigate whether asthma, as an underlying diagnosis, is predictive of a favorable outcome of children with persistent MLS. We evaluated 53 children with MLS who underwent an aggressive management protocol that included fiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL). These patients were compared to two other groups: one consisting of children with current asthma but no evidence of MLS (N,=,40) and another of non-asthmatic controls (N,=,42), matched for age and sex. Prevalence of sensitization (,1 aeroallergen) did not differ between patients with MLS and "non-asthmatics" but was significantly lower than that of "current asthmatics." A positive response to methacholine bronchial challenge was observed with increased frequency among children with MLS when compared to "current asthmatic" and non-asthmatic children. Multivariate logistic regression analysis revealed a positive correlation between an increased number of eosinophils in the BAL fluid (BALF) and a favorable outcome, whereas no correlation was detected between sensitization or BHR and BAL cellular components. In conclusion, children with MLS have an increased prevalence of BHR, even when compared to asthmatics, but exhibit prevalence of atopy similar to that of non-asthmatics. An increased eosinophilic BALF count is predictive of symptomatic but not radiographic improvement of MLS patients after aggressive anti-asthma management. Pediatr Pulmonol. © 2006 Wiley-Liss, Inc. [source] Airway function measurements and the long-term follow-up of survivors of preterm birth with and without chronic lung diseasePEDIATRIC PULMONOLOGY, Issue 6 2006Indra Narang MRCPCH Abstract This seventh paper in a review series on different aspects of chronic lung disease following preterm birth focuses on the current knowledge of respiratory symptoms, airway function, airway hyperresponsiveness, and exercise capacity from childhood to adulthood. This paper further considers the long-term implications of these studies for both future research and clinical practice. Pediatr Pulmonol. © 2006 Wiley-Liss, Inc. [source] Risk factors of bronchial hyperresponsiveness in children with wheezing-associated respiratory infectionPEDIATRIC PULMONOLOGY, Issue 1 2005Sitthivuddhi Futrakul MD Abstract The objectives of this study were to identify possible risk factors of bronchial hyperesponsiveness (BHR) in children up to 5 years of age with wheezing-associated respiratory infection (WARI), and to study the prevalence of BHR. Children up to 5 years of age with WARI were enrolled in the study. The parents or caregivers of children were asked about their demographic data and clinical histories. Physical examination and clinical score assessment were performed. Pulmonary function tests, i.e., tidal breathing flow volume (TBFV), were performed to measure tidal breathing parameters before and after salbutamol nebulization. If volume at peak tidal expiratory flow/expiratory tidal volume and time to peak expiratory flow/total expiratory time increased ,20%, or tidal expiratory flow at 25% of tidal volume/peak tidal expiratory flow increased ,20% after nebulization therapy, BHR was diagnosed. The number in the positive BHR group was used to calculate the prevalence of BHR, and clinical features were compared with those of the negative BHR group. Categorical data were analyzed for statistical significance (P,<,0.05) by chi-square test or Fisher's exact test, or Student's t -test, as appropriate. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for those with statistical significance. One hundred and six wheezing children underwent pulmonary function tests before and after salbutamol nebulization. With the aforementioned criteria, 41 cases (38.7%) were diagnosed with BHR. History of reactive airway disease, (OR, 6.31; 95% CI, 1.68,25), maternal history of asthma (OR, 3.45; 95% CI, 1.34,9), breastfeeding less than 3 months (OR, 3.18; 95% CI, 1.26,8.12), and passive smoking (OR, 3; 95% CI, 1.15,7.62) were significant risk factors of BHR. The eosinophil count was significantly higher in the BHR (+) group particularly, in children 1,5 years of age (P,,,0.01). Patchy infiltrates were more commonly found in patients with negative BHR but not statistically significant. In conclusion, a history of reactive airway disease, maternal history, breastfeeding less than 3 months, and passive smoking were significant risk factors for BHR. Pediatr Pulmonol. © 2005 Wiley-Liss, Inc. [source] Outcome in adulthood of asymptomatic airway hyperresponsiveness in childhood: A longitudinal population studyPEDIATRIC PULMONOLOGY, Issue 3 2002Finn Rasmussen MD Abstract The clinical outcome of asymptomatic airway hyperresponsiveness (AHR) first detected in childhood is sparsely reported, with conflicting results. We used a birth cohort of 1,037 children followed to age 26 years to assess the clinical outcome of asymptomatic AHR to methacholine first documented in study members at age 9 years. Of 547 study members who denied wheezing symptoms ever at age 9 years, 41 (7.5%) showed AHR. Forty showed methacholine responsiveness, with a provocation concentration of methacholine that elicted a 20% drop in forced expired volume in 1 sec (PC20),,,8 mg/mL, and one had baseline airway obstruction with a bronchodilator response exceeding 10%. Of these 41 study members, 18 (44%), 11 (27%), and 4 (10%) maintained AHR in 1, 2, and 3 later assessments, respectively, while 23 (56%) manifested AHR only at age 9. Compared with asymptomatic study members without AHR, those with asymptomatic AHR at age 9 years were more likely to report asthma and wheeze at any subsequent assessment, were more likely to have high IgE levels and eosinophils at ages 11 and 21, and more often demonstrated positive responses to skin allergen testing at ages 13 and 21 years. Persistent AHR at later assessments increased these likelihoods further. In conclusion, asymptomatic children with AHR are more likely to develop asthma and atopy later in life compared with asymptomatic children without AHR. Persistent AHR, even though initially asymptomatic, was associated with an even greater increased risk of development of asthma. We suggest that rather than considering AHR as a marker of asthma, it should be regarded as a parallel pathological process that may lead to subsequent symptoms and clinical evidence of asthma. Pediatr Pulmonol. 2002; 34:164,171. © 2002 Wiley-Liss, Inc. [source] Extrathoracic airway responsiveness in children with asthma-like symptoms, including chronic persistent coughPEDIATRIC PULMONOLOGY, Issue 3 2002Ipek Turktas MD Abstract Asthma-like symptoms, including chronic persistent cough, are not always specific for classical asthma. In order to investigate whether assessment of extrathoracic airway hyperresponsiveness (EAHR) during methacholine bronchial challenge helped in the evaluation of pediatric patients with asthma-like symptoms such as chronic cough, we examined 133 consecutive, unselected patients (mean age, 10.06,±,2.16 years) who had neither established asthma nor bronchial obstruction previously. We recorded the forced mid-inspiratory flow (FIF50) as an index of extrathoracic airway narrowing. In addition, a 25% decrease in FIF50 (PD25FIF50) below the cutoff concentration of ,,8 mg/mL methacholine was assumed to indicate EAHR. According to the methacholine response, 81 patients had EAHR, and 41 of them had combined EAHR and bronchial hyperresponsiveness (BHR); 39 patients had only BHR. Airway hyperresponsiveness was not demonstrated in 13 patients and not in any of the control children. When patients with cough as the sole presenting symptom (60.9%) were compared with those with cough and wheeze (20.3%), those with cough alone had a significantly greater probability of having EAHR (OR, 4.16; 95% CI, 1.32,13.13) and a lower probability of having BHR (OR, 0.70; CI, 0.25,1.95) than those with cough and wheeze. Patients with cough, wheeze, and dyspnea (18.8%) had a significantly greater chance of having BHR than those with cough alone (OR, 5.08; CI, 1.55,16.64). Patients with cough and wheeze as compared with those with cough, wheeze, and dyspnea had significantly greater probability of having both EAHR and BHR (OR, 4.71; CI, 1.94,11.47). In order to ascertain the clinical relevance of EAHR, we assessed in the second part of the study whether the effects of treatment of the underlying disease would result in relief of airway hyperresponsiveness. Rhinosinusitis and perennial allergic rhinitis accounted for EAHR in 71 patients, and 34 of them also demonstrated BHR. They received specific therapy for their upper airway diseases for 4 weeks. Compared with values before treatment, FIF50 and forced expiratory volume in 1 sec (FEV1) did not change significantly. The dose of methacholine causing a 20% fall in FEV1 (PD20FEV1) and PD25FIF50 values were significantly increased from 2.40,±,1.39 to 4.22,±,1.13 mg /mL (P,<,0.001) and from 1.03,±,1.75 to 8.71,±,1.21 mg /mL (P,<,0.0001), respectively. We conclude that measurements of EAHR and BHR are the most important ways to evaluate children with asthma-like symptoms, including chronic persistent cough when chest X-rays and pulmonary function tests remain within normal limits. Therefore, empirical treatment is not necessary when these investigations are available. Our results suggest that specific treatment of inflammation in the upper airways reversed persistant cough, and may play an important role in modulating lower airways responsiveness in patients with concomitant BHR. Pediatr Pulmonol. 2002; 34:172,180. © 2002 Wiley-Liss, Inc. [source] Mechanisms of cholinergic dysfunction in rabbits following recurrent aspiration of cow's milk,PEDIATRIC PULMONOLOGY, Issue 6 2001Gary L. Larsen MD Abstract Recurrent aspiration of cow's milk has been shown to alter neural control of airways in young rabbits (Gelfand et al., 1997). The purpose of this study was to define the mechanisms responsible for in vitro cholinergic hyperresponsiveness in this model. Beginning at 1 week of age, rabbits received either 0.5 mL/kg whole cow's milk or sterile saline intranasally while under light anesthesia. This was repeated each weekday for 2 weeks. At 8 weeks of age, rabbits were sacrificed. Portions of lungs underwent lavage with sterile saline. Tracheal smooth muscle (TSM) segments were also removed. Segments were assessed for acetylcholine (ACh) release by high-performance liquid chromatography ( HPLC) with electrochemical detection or acetylcholinesterase (AChE) kinetic activity by spectrophotometry. Substance P (SP), a neuropeptide that can increase ACh release from nerves, was also assessed using an enzyme immunoassay to define the content in lavage and TSM segments. Immunohistochemistry for SP within airways was also assessed. We found that recurrent aspiration of milk led to statistically significant alterations in many parameters. Acetylcholine release was significantly greater in segments of airways from rabbits that had aspirated cow's milk (27.5,±,1.7 vs. 20.1,±,1.6 pmol/min/g tissue) than saline. At the same time, AChE activity was less in the group that aspirated milk (8.7,±,0.4 vs. 10.2,±,0.5 nmol/min/mg protein) compared to saline. The amount of SP within both lavage as well as tissue homogenates was greater in the group that had aspirated the foreign protein (159.1,±,28.9 vs. 41.9,±,5.2 pmol/mg protein in lavage; 158.7,±,31.9 vs. 80.5,±,7.8 pmol/mg protein in tissues) than saline controls. While total cholinergic nerve density as assessed by choline acetyltransferase was not significantly different between groups, SP-positive immunoreactive nerves were easily identified in the group that aspirated cow's milk. This study suggests that cholinergic hyperresponsiveness caused by repeated aspiration of milk is due to several abnormalities, including prejunctional (increase in ACh release) as well as junctional (decrease in AChE) mechanisms within the airways. In addition, an upregulation of SP within airways is part of this process. Pediatr Pulmonol. 2001; 32:409,417. © 2001 Wiley-Liss, Inc. [source] Association of tobacco smoke exposure and respiratory syncitial virus infection with airways reactivity in early childhoodPEDIATRIC PULMONOLOGY, Issue 6 2001Alan Adler MD Abstract Exposure to infectious agents and environmental tobacco smoke are thought to induce bronchial hyperresponsiveness (BHR). This study was undertaken to determine the effects of passive exposure to tobacco smoke and respiratory syncitial virus (RSV) lower respiratory infection (LRI) during infancy on the occurrence of BHR in the first 2 years of life. Eighty-six cases of documented RSV (mean age, 188 days) and 78 controls (mean age, 162 days) were enrolled from the clinic and in-patient service of a single hospital. None had a history of prior LRI. Subjects were studied at 6-month intervals up to 19 months of age with a standardized respiratory illness and parental smoking questionnaire, partial expiratory flow-volume curves by the "hug" (rapid thoracic compression) technique, and methacholine challenge. Exposure to maternal and paternal cigarette smoking, maternal history of asthma, and mold exposure were associated with decreased levels of length-corrected maximal flow at functional residual capacity (V,maxFRC). RSV-LRI was not related to V,maxFRC. After adjustment of V,maxFRC for these factors, V,maxFRC was a significantly and positively correlated with a methacholine concentration provoking a 40% fall in V,maxFRC (PC40) and negatively correlated with dose-response slope. After adjustment for V,maxFRC, there were no independent effects of tobacco smoke exposure or RSV-LRI on methacholine responses. These data do not support a role for RSV as a risk factor for airways reactivity in childhood and indicate that exposure to tobacco smoke affects airways reactivity through its effects on airways. Pediatr Pulmonol. 2001; 32:418,427. © 2001 Wiley-Liss, Inc. [source] Inflammation and remodeling in the adult and child with asthmaPEDIATRIC PULMONOLOGY, Issue S21 2001Peter Jeffery MSc Abstract Inflammation and remodeling are characteristic features of the conducting airways in asthma, but the relationships between inflammation, inappropriate remodeling, bronchial hyperresponsiveness, and reduced pulmonary function are still unclear. In both adults and children with asthma, there are structural changes of the conducting airways that include injury and loss of the surface epithelium, thickening of the reticular basement membrane, increases of underlying collagen, blood vessels, and airway smooth muscle, and plugging of the airways by exudate. Bronchial biopsies obtained from persons with mild stable asthma already demonstrate the presence of inflammation. Many of the inflammatory and structural changes begin early in childhood. Whereas corticosteroids markedly reduce many aspects of inflammation, it is not known whether and how they affect the changes associated with airway wall remodeling. Leukotriene receptor antagonists appear to be antiinflammatory and able to reduce the proliferation of bronchial smooth muscle. Pediatr Pulmonol. 2001; Supplement 21:3,16. © 2001 Wiley-Liss, Inc. [source] | |||||||||||||||||||||||||||||||