Bronchial hyperresponsiveness (or other combinations with airway or hyperreactivity) is a state characterised by easily triggered bronchospasm (contraction of the bronchioles or small airways). Bronchial hyperresponsiveness can be assessed with a bronchial challenge test. This most often uses products like methacholine or histamine. These chemicals trigger bronchospasm in normal individuals as well, but people with bronchial hyperresponsiveness have a lower threshold. Bronchial hyperresponsiveness is a hallmark of asthma but also occurs frequently in people suffering from chronic obstructive pulmonary disease (COPD). In the Lung Health Study, bronchial hyperresponsiveness was present in approximately two-thirds of patients with non-severe COPD, and this predicted lung function decline independently of other factors. In asthma it tends to be reversible with bronchodilator therapy, while this is not the case in COPD. Bronchial hyperresponsiveness has been associated with gas cooking among subjects ...
Bronchial hyperresponsiveness (or other combinations with airway or hyperreactivity) is a state characterised by easily triggered bronchospasm (contraction of the bronchioles or small airways).. Bronchial hyperresponsiveness can be assessed with a bronchial challenge test. This most often uses products like methacholine or histamine. These chemicals trigger bronchospasm in normal individuals as well, but people with bronchial hyperresponsiveness have a lower threshold.. Bronchial hyperresponsiveness is a hallmark of asthma but also occurs frequently in people suffering from chronic obstructive pulmonary disease (COPD). In the Lung Heart Study, bronchial hyperresponsiveness was present in approximately two-thirds of patients with non-severe COPD, and this predicted lung function decline independently of other factors. In asthma it tends to be reversible with bronchodilator therapy, while this is not the case in COPD. ...
TY - JOUR. T1 - Requirement for neuropeptide Y in the development of type 2 responses and allergen-induced airway hyperresponsiveness and inflammation. AU - Oda, Naohiro. AU - Miyahara, X. Nobuaki. AU - Taniguchi, Akihiko. AU - Morichika, Daisuke. AU - Senoo, Satoru. AU - Fujii, Utako. AU - Itano, Junko. AU - Gion, Yuka. AU - Kiura, Katsuyuki. AU - Kanehiro, Arihiko. AU - Maeda, Yoshinobu. PY - 2019/3. Y1 - 2019/3. N2 - Neuro-peptide Y (NPY) is a neurotransmitter that is widely expressed in the brain and peripheral nervous system. Various immune cells express the NPY Y 1 receptor. NPY modulates these cells via its Y 1 receptor; however, involvement of NPY in the pathophysiology of bronchial asthma, particularly airway hyperresponsiveness (AHR), has not been defined. NPY-deficient and wild-type mice were intranasally sensitized and challenged to house dust mite (HDM) extract, and airway responses were monitored. After sensitization and challenge, NPY-deficient mice showed significantly lower AHR ...
The results of this study indicate that four weeks of treatment with inhaled steroids leads to improvements in airway hyperresponsiveness, sputum eosinophil numbers, and levels of exhaled NO in patients with mild atopic asthma. In addition, it appears that the improvements in these markers are lost two weeks after cessation of treatment. This suggests that each of these markers may be useful for monitoring patients with asthma, even though there might be small differences between the markers in their earliest response to anti-inflammatory treatment.. To our knowledge this is the first study to compare the treatment induced changes in airway hyperresponsiveness to histamine, eosinophil counts in induced sputum, and exhaled NO levels in a group of asthmatic patients. Our study confirms and extends the results of others who have shown the beneficial effect of glucocorticosteroids on each of these markers separately. Like Kraan et al, we found an improvement of two doubling doses in airway ...
This is a Phase 3 study to determine the sensitivity and specificity of the Aridol bronchial challenge test to detect bronchial hyperresponsiveness in patients with suspected asthma. Patients with suspected asthma of either gender, aged between 6 and 50 years, with only mildly impaired lung function (FEV1 ,70%) are to be tested with three different bronchial hyperresponsiveness challenges (Aridol, exercise and methacholine), and the results compared. A clinical diagnosis will also be made at the end of the study ...
The aim of this study was to assess the effectiveness of an asthma prevalence video questionnaire, a standard written questionnaire based on the IUATLD Bronchial Symptoms Questionnaire and a new written questionnaire designed for an international study of asthma and allergies in childhood ISAAC in predicting bronchial hyper-responsiveness BHR...
Wilson, AM, Gray, RD, Hall, IP and Lipworth, BJ (2006) The effect of beta2-adrenoceptor haplotypes on bronchial hyper-responsiveness in patients with asthma. Allergy, 61 (2). pp. 254-259. ISSN 1398-9995 Full text not available from this repository. (Request a copy ...
TY - JOUR. T1 - Histamine forming capacity (HFC) and its modulation by H3 receptor ligands in a model of bronchial hyper-responsiveness. AU - Allen, Marcus. AU - Graham, P.. AU - Morris, G.. PY - 1996/3/1. Y1 - 1996/3/1. M3 - Article. VL - 45. SP - 118. EP - 122. JO - Inflammation Research. JF - Inflammation Research. SN - 1023-3830. IS - 3. ER - ...
To study the role of CD8+ T cells in allergic sensitization, we examined the effects of in vivo depletion of CD8+ T cells prior to sensitization on IgE production, immediate type cutaneous hypersensitivity and development of altered airway responsiveness. BALB/c mice were thymectomized and treated with anti-CD8 antibody resulting in depletion of CD8+ T cells (,1%) in spleen and lymphoid tissues. In these mice, sensitization to ovalbumin (OVA) via the airways still resulted in IgE anti-OVA responses and immediate cutaneous reactions to OVA, but the animals were unable to develop airway hyperresponsiveness, eosinophil infiltration of the lung parenchyma, or IL-5 production in the local lymph nodes of the airway. Transfer of CD8+ T cells from naive animals during sensitization (on day 8 of the 10-d protocol) fully restored the ability to develop airway hyperresponsiveness and this was accompanied by IL-5 production and eosinophil accumulation in the lung. These data indicate a critical role for ...
In mice, CD4+ T cells are alone sufficient to mediate many of the pathognomonic changes that occur in human asthma by a mechanism dependent upon IL-4, but independent of IL-5, IgE, or both. Clarification of the role played by CD4+ T cells is likely to stimulate important therapeutic advances in trea …
Lin, J.T., Hiroshi, I., Suzuki, T., et al. (1994) Eosinophilic Airway Inflammation and Airway Hyperresponsiveness. Chinese Journal of Tuberculosis and Respiratory Diseases, 17, 213-215.
TY - JOUR. T1 - Corticosteroids enhance CD8+ T cell-mediated airway hyperresponsiveness and allergic inflammation by upregulating leukotriene B4 receptor 1. AU - Ohnishi, Hiroshi. AU - Miyahara, Nobuaki. AU - Dakhama, Azzeddine. AU - Takeda, Katsuyuki. AU - Mathis, Steven. AU - Haribabu, Bodduluri. AU - Gelfand, Erwin W.. PY - 2008/4. Y1 - 2008/4. N2 - Background: Leukotriene B4 (LTB4) is a potent inflammatory lipid mediator that binds to LTB4 receptor 1 (BLT1). Ligation of BLT1 by LTB4 plays an important role in the recruitment of effector memory CD8+ T cells into the airways of sensitized and challenged mice. Objectives: The effects of the corticosteroid dexamethasone (DEX) on BLT1-expressing effector memory CD8+ T cells and effector memory CD8+ T cell-mediated airway hyperresponsiveness (AHR) and allergic inflammation were determined. Methods: Effector memory CD8+ T cells were generated from ovalbumin257-264-primed mononuclear cells from OT-1 mice in the presence of IL-2. In some cultures DEX ...
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Critical role for IL-13 in the development of allergen-induced airway hyperreactivity.: Airway hyperresponsiveness to a variety of specific and nonspecific stim
Sigma-Aldrich offers abstracts and full-text articles by [Ching-Feng Huang, Ho-Jen Peng, Chia-Chao Wu, Wen-Tsung Lo, Yu-Lueng Shih, Tzee-Chung Wu].
TY - JOUR. T1 - Airway hyperresponsiveness. T2 - From molecules to bedside. AU - Sieck, Gary C. PY - 2003/7/1. Y1 - 2003/7/1. UR - http://www.scopus.com/inward/record.url?scp=0038309533&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0038309533&partnerID=8YFLogxK. M3 - Article. C2 - 12794089. AN - SCOPUS:0038309533. VL - 95. SP - 1. EP - 2. JO - Journal of Applied Physiology. JF - Journal of Applied Physiology. SN - 8750-7587. IS - 1. ER - ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
These studies of Ormdl3Δ2-3/Δ2-3/CC10 mice demonstrate that selectively inhibiting ORMDL3 in airway epithelial cells plays a significant role in induction of allergen-induced increases in AHR in vivo through a pathway independent of inflammation and associated with a pathway of increased S1P generation, which can induce increased smooth muscle contraction. These results further suggest that utilizing an inhalation therapeutic approach in asthma targeting a selective significant reduction in ORMDL3 expression in airway epithelium may paradoxically result in increased AHR as a consequence of increased epithelial-derived S1P increasing airway smooth muscle contractility. Whether an inhalation therapy targeting a less than complete inhibition of ORMDL3 expression by airway epithelium would also result in increased AHR is at present unknown. However, a therapy inducing only partial inhibition of ORMDL3 expression in the airway may also not be an effective therapy in asthma.. In this study, we ...
Fig. 5. Concentration-response curves for the inhibition of the EFS-evoked contractions of the guinea pig-isolated trachea incubated for 4 days with TNF-α (100 ng/ml) by Δ9-THC (A) and CP55940 (B) in the presence of ethanol (vehicle), AM251 (3 × 10−9 M), or JTE907 (3 × 10−8 M). EFS parameters: 5-second trains every 100 seconds at 5-Hz frequency, 0.5-millisecond pulse width, and a voltage 10% greater than the voltage required to evoke maximal contractions. Each curve was fitted by nonlinear regression analysis. Each symbol represents the mean value of inhibition of the contractions expressed as a percentage reduction of the amplitude of the contractions measured immediately before the addition of any drug to the organ bath. Vertical lines indicate S.E.M., n = 6 for each curve. AM251 or ethanol was added 20 minutes before the first addition of the agonist. ...
Asthma is a chronic disease of the airways characterized by airway hyperresponsiveness, airway inflammation, and airway remodeling. Eosinophils migrate to the airways and play a significant role in the pathogenesis of ...
TY - JOUR. T1 - Novel immunomodulatory oligonucleotides prevent development of allergic airway inflammation and airway hyperresponsiveness in asthma. AU - Agrawal, Devendra K.. AU - Edwan, Jehad. AU - Kandimalla, Ekambar R.. AU - Yu, Dong. AU - Bhagat, Lakshmi. AU - Wang, Daqing. AU - Agrawal, Sudhir. PY - 2004/1. Y1 - 2004/1. N2 - Oligodeoxynucleotides containing unmethylated CpG motifs (CpG oligos) have been shown to prevent development of allergic airway inflammation and airway hyperresponsiveness (AHR) in mouse models of asthma. Recently, we reported immunomodulatory oligonucleotides (IMOs) containing novel structures (immunomers) and synthetic immunostimulatory CpR (R=2′-deoxy-7- deazguanosine) motifs show potent stimulatory activity with distinct cytokine secretion profiles. Since type 2 T cells predominate in asthma and increase in type 1 cells can prevent the differentiation of naïve T lymphocytes to a type 2 phenotype, we hypothesized that IMOs can prevent the development of allergic ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
article{733304be-b795-4682-8916-cd1774ecdcab, abstract = {Cigarette smoke exposure is strongly associated with airway hyperreactivity (AHR) which is the main characteristic seen in asthma. The intracellular MAPK signaling pathways are suggested to be associated with the airway damage to the AHR. In the present study, we hypothesize that secondhand cigarette smoke (SHS) exposure upregulates the bronchial contractile receptors via activation of the Raf/ERK/MAPK pathway.}, articleno = {e44170}, author = {Cao, Lei and Zhang, Yaping and Cao, Yong-Xiao and Edvinsson, Lars and Xu, Cang-Bao}, issn = {1932-6203}, language = {eng}, number = {8}, publisher = {Public Library of Science}, series = {PLoS ONE}, title = {Secondhand Smoke Exposure Causes Bronchial Hyperreactivity via Transcriptionally Upregulated Endothelin and 5-hydroxytryptamine 2A Receptors.}, url = {http://dx.doi.org/10.1371/journal.pone.0044170}, volume = {7}, year = {2012 ...
Nonspecific bronchial hyperreactivity (BHR) has been reported to occur in patients with bronchiectasis. To evaluate this further, we studied 77 patients with stable bronchiectasis (noncystic fibrosis) with special reference to the prevalence of BHR to methacholine (MCh), and its relation to lung function, sputum characteristics, concommitant asthma, and atopy. The concentration of MCh required to produce a fall of 20% in forced expiratory volume in 1 s (FEV 1), PC 20, was determined by Wrights nebulization tidal breathing method. BHR defined by a PC 20 ≤ 8 mg/ml was found in 21 of 47 (45%) subjects who underwent bronchial challenge. Presence of BHR was positively associated with low baseline spirometric values, diagnosis of asthma, long duration of disease, and elevated total IgE on univariant analysis, and was significantly related to FEV 1/forced vital capacity (FVC) ratio and asthma on multiple regression analysis. Ten of the 21 hyperreactive subjects did not have clinical asthma, whereas ...
BACKGROUND: Although there is convincing evidence that the prevalence of asthma among children has increased over the last three decades, it remains uncertain whether such an upward trend has occurred in adults. The aim of this study was to assess whether the prevalence of asthma has changed in young Belgian adults in recent years. METHODS: A retrospective analysis was conducted of available statistics from the Belgian Armed Forces for the period 1978-91 because conscripts who reported a history of past or current asthma at call-up examination underwent standardised assessment of non-specific airway responsiveness by military chest physicians. Exemption from military service due to asthma was strictly based on the objective evidence of airway hyperresponsiveness. RESULTS: A mean of 48,331 conscripts aged 17-31 years were examined annually from 1978 to 1991. The prevalence of reported asthma rose from 2.4% in 1978 to 7.2% in 1991, while the proportion of asthmatics with airway hyperresponsiveness ...
Wheezing during infancy has been linked to early loss of pulmonary function. We prospectively investigated the relation between bronchial hyperresponsiveness (BHR) and progressive impairment of pulmonary function in a cohort of asthmatic infants followed until age 9 years. We studied 129 infants who had had at least three episodes of wheezing. Physical examinations, baseline lung function tests and methacholine challenge tests were scheduled at ages 16 months and 5, 7 and 9 years. Eighty-three children completed follow-up. Twenty-four (29%) infants had wheezing that persisted at 9 years of age. Clinical outcome at age 9 years was significantly predicted by symptoms at 5 years of age and by parental atopy. Specific airway resistance (sRaw) was altered in persistent wheezers as early as 5 years of age, and did not change thereafter. Ninety-five per cent of the children still responded to methacholine at the end of follow-up. The degree of BHR at 9 years was significantly related to current clinical status
TY - JOUR. T1 - Endothelin receptor alterations in equine airway hyperreactivity. AU - Venugopal, Changaram S.. AU - Polikepahad, Sumanth. AU - Holmes, Earnestine P.. AU - Vanden Heuvel, John Patrick. AU - Leas, Tara L.. AU - Moore, Rustin M.. PY - 2006/1/1. Y1 - 2006/1/1. N2 - The purpose of this study was to evaluate the role of endothelin-1 (ET-1) and its receptors in the airway hyperreactivity of horses with obstructive pulmonary disease associated with summer pasture (SPAOPD). The right diaphragmatic lobe of the lung of 8 clinically healthy (unaffected) and 8 SPAOPD-affected horses was collected immediately after euthanasia. Bronchial rings (4 mm wide) were prepared and mounted in organ baths and attached to force transducers interfaced with a polygraph. Four rings were used to study each ET-1 receptor; 1 ring served as the control, and the other 3 were incubated with 10-9, 10-7, or 10-5 M of either BQ-123, an ETA-receptor antagonist, or IRL-1038, an ETB-receptor antagonist. Cumulative ...
0117] 1. Gavett, S. H., X. Chen, F. Finkelman, and M. Wills-Karp. 1994. Depletion of murine CD4+ T lymphocytes prevents antigen-induced airway hyperreactivity and pulmonary eosinophilia. Am J Respir Cell Mol Biol 10:587-593. [0118] 2. Umetsu, D. T., J. J. McIntire, O. Akbari, C. Macaubas, and R. H. DeKruyff. 2002. Asthma: an epidemic of dysregulated immunity. Nat Immunol 3:715-720. [0119] 3. Hogan, S. P., K. I. Matthaei, J. M. Young, A. Koskinen, I. G. Young, and P. S. Foster. 1998. A novel T cell-regulated mechanism modulating allergen-induced airways hyperreactivity in BALB/c mice independently of IL-4 and IL-5. J Immunol 161:1501-1509. [0120] 4. Wills-Karp, M., J. Luyimbazi, X. Xu, B. Schofield, T. Y. Neben, C. L. Karp, and D. D. Donaldson. 1998. Interleukin-13: central mediator of allergic asthma. Science 282:2258-2261. [0121] 5. Robinson, D. S., Q. Hamid, S. Ying, A. Tsicopoulos, J. Barkans, A. M. Bentley, C. Corrigan, S. R. Durham, and A. B. Kay. 1992. Predominant TH2-like bronchoalveolar ...
To the Editors: We read with interest the recent paper by van den Nieuwenhof et al. 1 who reported no statistically significant association of airway hyperresponsiveness (AHR) with asthma incidence over 14 yrs in 123 asymptomatic adolescents aged 10-22 yrs at baseline. They concluded that AHR is not a risk factor for the development of asthma in adulthood and that screening for AHR in adolescents to detect subjects at risk for asthma cannot be recommended. We similarly assessed the association between AHR at baseline and asthma incidence over 11.4 yrs among 172 asymptomatic children (44.2% with AHR (provocative dose causing a 20% fall in forced expiratory volume in one second ,4 mg methacholine) at baseline) and 517 adults (31.7% with AHR at baseline) from the Epidemiological Study on the Genetics and Environment of Asthma (EGEA) 2, 3. Asymptomatic adults were defined as those with a null symptomatic score according to Pekkanen et al. 4 over the previous 12 months. The score is based on ...
Interleukin (IL)-1 causes airway inflammation, enhances airway smooth muscle responsiveness, and alters neurotransmitter expression in sensory, sympathetic, and myenteric neurons. This study examines the role of intrinsic airway neurons in airway hyperresponsiveness (AHR) induced by IL-1. Ferrets were instilled intratracheally with IL-1 (0.3 g/0.3 ml) or saline (0.3 ml) once daily for 5 days. Tra
The NF-κB/Rel family of transcription factors regulates the expression of multiple genes that have been implicated in immune and inflammatory responses, including asthma (8, 16). Analyzing the effects of germline deletions or mutations of specific NF-κB/Rel subunits will elucidate their roles in various inflammatory diseases, including asthma. The present study demonstrates that absence of c-Rel is associated not only with significant attenuation of allergen-induced pulmonary and BAL eosinophilia but also with inhibition of total IgE and the physiological correlate of allergic airway inflammation, AHR. p50−/− mice do not develop eosinophilic airway inflammation in response to allergen sensitization and challenge, concomitant with a lack of IL-5 and eotaxin production; total serum IgE and AHR were not examined (27). The phenotype and immune system defects of c-Rel−/− mice are distinct from those of p50−/− mice (23, 24).. One explanation for the blunted response of c-Rel−/− mice ...
Discussion BHR occurred in 21%, and 6% presented BHRms. The latter is in line with the reported prevalence of physician-diagnosed asthma (7%) in Helsinki (6). We found no discrepancy with results of the European Community Respiratory Health Survey in which the prevalence of BHR ranged from 3% to 28% among 16 countries, with a median prevalence of 13% (34).. We assessed BHR by two cut-off levels of PD15FEV1 indicating different severity levels of BHR, thus showing variations and differences in importance of the determinants assessed. For most of the determinants, ORs were higher, parallel with BHR severity. Our results, however, revealed that some risk factors for BHR and asthma, like severe respiratory infection in childhood, were associated with the higher PD15FEV1 cut-off level only.. The strongest determinant of BHR was decreased FEV1 (,80% of predicted) when combined with airway obstruction (defined as FEV1/FVC , 88% of predicted). But, studies on the association of BHR with allergic ...
DESCRIPTION (provided by applicant): Inflammatory cell recruitment into the lungs and airway hyperresponsiveness are key components of asthma. The allergen-induced inflammatory response in the lungs results from the interaction of key airway resident cells and inflammatory cells that release local mediators. Airway smooth muscle (ASM) participates in the inflammatory response of the lungs by phenotypic changes that include synthesizing inflammatory mediators as well as an increase in contractility. Although anti-inflammatory agents and beta-adrenergic bronchodilators remain the primary treatment for chronic and acute episodes of bronchoconstriction, there is a great need for newer therapeutic targets that can modify the development and treatment of asthma. For that reason, molecular targets that might be predicted to suppress allergic inflammatory responses as well as bronchoconstriction are highly desirable. Actin dynamics is well established as the primary mechanism for motility and migration ...
In the course of the follow-up of 206 previously obstructive bronchitis children, the effect of parental smoking upon the occurrence of respiratory diseases, the yearly frequency of wheezing episodes and the age until the obstructive episodes used to return have been investigated. Familial and mater …
BACKGROUND:. Asthma is a respiratory disease characterized by variable airways obstruction, airways inflammation and bronchial hyperresponsiveness (BHR). There are recent increases in asthma mortality and prevalence in the US, especially in African-Americans. Multiple studies suggest that both genetic and environmental factors are important in asthma susceptibility.. The study was recommended by the Pulmonary Diseases Advisory Committee at its February 1991 meeting and given concept approval by the May 1991 National Heart, Lung, and Blood Advisory Council. The Request for Applications was released in October 1992.. DESIGN NARRATIVE:. The CSGA was composed of five centers (Johns Hopkins University, University of Chicago, University of Maryland, University of Minnesota, and a data coordinating center at Wake Forest). At each center, families were ascertained through two siblings with asthma. All family members were characterized with spirometry, bronchial responsiveness to methacholine or ...
Rationale: In asthma, airway inflammation, obstruction and reactivity may lead to ventilation heterogeneity; our understanding of this process is limited in asthmatic chi..
Tale M. Torjussen, Karin C. Lødrup Carlsen, Monica C. Munthe-Kaas, Petter Mowinckel, Kai-Håkon Carlsen, Peter J. Helms, Jorrit Gerritsen, Moira K. Whyte, Warren Lenney, Dag E. Undlien, Kevin V. Shianna, Guohua Zhu and Sreekumar G. Pillai Alpha-nicotinic acetylcholine receptor and tobacco smoke exposure: Effects on bronchial hyperresponsiveness in children Pediatric Allergy and Immunology 23. Version of Record online: 21 OCT 2011 , DOI: 10.1111/j.1399-3038.2011.01222.x. Complete the form below and we will send an e-mail message containing a link to the selected article on your behalf. Required = Required Field. ...
Asthma is a heterogeneous disease or an inflammatory disorder of the airway related to the airflow impediment and bronchial hyper-responsiveness which ranges in severity across the continuum of the diseases. Here, adequate control cannot be achieved in a considerable ratio thought the application of possible treatments
Asthma, Rhinitis, Risk, Population, Adults, Allergy, Association, Bronchi, Mite, Nose, Risk Factor, Risks, Classification, Electrodiagnosis, Syndrome, Adult, Bronchial Hyperreactivity, Children, Methacholine, Odds Ratio
Airway inflammation is a state of irritation in the airways caused by the immune system responding to a perceived threat. If the...
p,Asthma is a chronic respiratory disease which is characterized by reversible bronchoconstriction, airway hyperresponsiveness, and airway inflammation. Allergen inhalation by sensitized atopic asthmatics enhances airway hyperresponsiveness and inflammation, providing a model to study mild asthma exacerbation. Airway inflammation can be measured non-invasively from airway secretions by sputum induction. Prior to starting this thesis, information on allergen-induced inflammation measured from sputum was limited. Furthermore, the pro- or anti-inflammatory effects of asthma therapies had not been investigated using this model of allergen-induced airway inflammation. The aim of this thesis was to first characterize the allergen-induced changes in sputum inflammatory cells and determine the repeatability of measurements of sputum inflammatory cells following allergen inhalation challenge. In addition, this thesis was aimed to investigate the pro- or anti-inflammatory effects of asthma therapies on ...
TY - JOUR. T1 - Ovalbumin-sensitized mice are good models for airway hyperresponsiveness but not acute physiological responses to allergen inhalation. AU - Zosky, G. R.. AU - Larcombe, A. N.. AU - White, O. J.. AU - Burchell, J. T.. AU - Janosi, T. Z.. AU - Hantos, Z.. AU - Holt, P. G.. AU - Sly, P. D.. AU - Turner, D. J.. PY - 2008/5. Y1 - 2008/5. N2 - Background: Asthma is a chronic inflammatory disease that is characterized clinically by airway hyperresponsiveness (AHR) to bronchoconstricting agents. The physiological response of the asthmatic lung to inhaled allergen is often characterized by two distinct phases: an early-phase response (EPR) within the first hour following exposure that subsides and a late-phase response (LPR) that is more prolonged and may occur several hours later. Mouse models of asthma have become increasingly popular and should be designed to exhibit an EPR, LPR and AHR. Objective: To determine whether a common model of asthma is capable of demonstrating an EPR, LPR ...
Asthma is one of the most common clinical symptoms in Churg-Strauss syndrome (CSS). However, it is not known how lung function and bronchial hyperresponsiveness (BHR) prior to the development of CSS differs from asthmatics do not develop CSS. This retrospective cohort study was conducted to predict the onset of CSS and facilitate diagnosis in the early phase of the disease. We examined 24 pre-CSS asthmatic patients and 294 non-CSS asthmatic patients for clinical features, percent forced expiratory volume at 1 second (%FEV1), BHR to acetylcholine, and evaluated eosinophils (%) in the peripheral blood at their first hospital visit for asthma treatment. All of the 24 pre-CSS patients had adult-onset asthma. The asthma of 87.5% of pre-CSS patients at the first hospital visit before the onset of CSS was severe and was complicated by sinusitis. The eosinophils (%) in the peripheral blood was significantly higher than in non-CSS asthmatic patients. The %FEV1 in both the patients with severe asthma and ...
Asthma is a common chronic inflammatory airway disease with reported increasing incidence over the world. Definition of asthma includes variable obstruction of the airways and increase in bronchial responsiveness to various stimuli. Drug treatment for asthma traditionally consists of bronchodilatory beta-receptor-agonists, often in combination with anti-inflammatory remedies such as corticosteroids.. Salbutamol, a beta-receptor-agonist, has two stereo-isomers, R-salbutamol and Ssalbutamol, and is mostly given as a racemate. The ability for bronchodilation rests in the R-isomer, whereas the S-isomer has been suspected to increase bronchial hyperresponsiveness. Salbutamol m1dergoes stereo-selective metabolism favouring the Renantiomer. This leaves the S-enantiomer to rest for longer time in the body, and gives SiR-ratios in plasma exceeding one.. Pharmacokinetic stndies were performed in twenty-two healthy volunteers. Stereoselective metabolism was more pronounced after oral delivery than after ...
Exposure to ozone, which is a major component of air pollution, induces a form of asthma that occurs in the absence of adaptive immunity. Although ozone-induced asthma is characterized by airway neutrophilia, and not eosinophilia, it is nevertheless associated with airway hyperreactivity (AHR), which is a cardinal feature of asthma. Because AHR induced by allergens requires the presence of natural killer T (NKT) cells, we asked whether ozone-induced AHR had similar requirements. We found that repeated exposure of wild-type (WT) mice to ozone induced severe AHR associated with an increase in airway NKT cells, neutrophils, and macrophages. Surprisingly, NKT cell-deficient (CD1d-/- and Jα18-/-) mice failed to develop ozone-induced AHR. Further, treatment of WT mice with an anti-CD1d mAb blocked NKT cell activation and prevented ozone-induced AHR. Moreover, ozone-induced, but not allergen-induced, AHR was associated with NKT cells producing interleukin (IL)-17, and failed to occur in IL-17-/- mice nor in
STUDY OBJECTIVE: This study examined the impact on childrens respiratory health of a government air quality intervention that restricted the sulphur content of fuels to 0.5% from July 1990 onwards. DESIGN/SETTING/PARTICIPANTS: This study examined the changes, one and two years after the introduction of the intervention, in airway hyperreactivity of non-asthmatic and non-wheezing, primary 4, 5, and 6, school children aged 9-12 years living in a polluted district compared with those in a less polluted district. Bronchial hyperreactivity (BHR)(a 20% decrease in FEV1 provoked by a cumulative dose of histamine less than 7.8 mumol) and bronchial reactivity slope (BR slope) (percentage change in logarithmic scale in FEV1 per unit dose of histamine) were used to estimate responses to a histamine challenge. The between districts differences after the intervention were studied to assess the effectiveness of the intervention. MAIN RESULTS: In cohorts, comparing measurements made before the intervention ...
Interleukin (IL)-4-producing-CD8 (cytotoxic T cells, Tc) contribute to lung eosinophilia and airway hyper-responsiveness (AHR) to an antigen. CD4+CD25+ regulatory T cells (Tregs) attenuate airway inflammation and AHR. This study investigated whether Tregs decrease Tc2frequencies in ovalbumin (OVA)-induced asthma model of mice. Female C57BL/6 mice were sensitized with OVA intraperitoneally and challenged with OVA intranasally to induce allergic asthma model. Tregs were sorted by fluorescence activated cell sorting (FACS) and magnetic activated cell sorting (MACS) microbeads. OVA-sensitized mice were injected with Tregs or phosphate buffer saline (PBS) by tail vein ahead of the first challenge. Airway inflammation and airway hyper-responsiveness (AHR)were evaluated by histological analysis and invasive method, respectively. OVA-specific IgE and cytokine levels were detected by ELISA. Flow cytometry was used to detect the percentages of Tc1 and Tc2. Gata3 and T-bet mRNA was determined by ...
TY - JOUR. T1 - Induction of epithelial immune-response genes in a mouse model of viral bronchitis and hyperreactivity. AU - Walter, M. J.. AU - Kajiwara, N.. AU - Sampath, D.. AU - Rucker, J.. AU - Holtzman, M. J.. PY - 1998/12/1. Y1 - 1998/12/1. N2 - Our work indicates that viral replication or Interferon (IFN)-y treatment upregulates expression of a subset of immune-response genes (ICAM-1, RANTES, and Stall) in isolated airway epithelial cells, and that this pathway is also activated during asthmatic airway inflammation and hyperreactivity. To define the determinants for induction of gene expression during viral infection in vivo, we developed a mouse model of viral bronchitis and hyperreactivity using Sendai virus and C57BL/6 mice in which we were able to titer the dose of virus to cause a reversible bronchitis/bronchiolitis with viral antigen and immune cell (predominantly mononuclear cell) infiltrate restricted to these airway sites. The site of viral replication and immune cell influx ...
Our study highlights the expression of the CaSR in ASM and identifies a fundamental pathophysiological role for this receptor in the context of asthma. The fact that inflammatory cationic proteins known to correlate with asthma severity can activate the CaSR expressed by ASM cells at physiologically relevant concentrations to elevate [Ca2+]i and increase the contractility of the ASM nonspecifically provides both a rational explanation for the genesis of nonspecific AHR in asthma and a basis for the direct mechanistic link between this phenomenon and airway inflammation. These findings raise the possibility that the CaSR directly influences mechanisms involved in inflammatory cell recruitment and activation. In turn, production of asthma-relevant cytokines can further increase CaSR expression, thereby generating a positive feedback loop. Thus, locally delivered calcilytics would have the advantage of breaking this cycle by reducing inflammation and by blunting ASM hyperresponsiveness. Indeed, in ...
Asthma affects 8-9% of the US population. Asthma related costs are estimated to exceed $56 billion annually with half of this due to a small subpopulation (,10%) of asthmatics whose disease is inadequately controlled by current therapy. This, together with evidence that long acting bronchodilator use can increase asthma severity has precipitated a critical need for novel asthma therapeutics. My laboratory identified key phenotypic elements of moderate to severe human asthma in horses with pasture asthma, including airway hyper-responsiveness to methacholine challenge at doses ,/=1 mg/ml, chronic neutrophilic airway inflammation, and comprehensive airway structural changes collectively termed airway remodeling. Airway hyper-responsiveness persists for life. The condition is chronic and progressive and corticosteroids have diminishing efficacy unless horses are removed from the offending environment. These collective attributes address complexities of severe human asthma that are not otherwise ...