Airway hyperresponsiveness

Airway hyperresponsiveness is an exaggerated propensity for airways to narrow too easily in response to a wide variety of stimuli. Airway hyperresponsiveness... 

The activation of mast cells by allergen initiates the asthma symptoms within minutes after allergen contact, the early allergic response (EAR), within horns the late allergic response (LAR), and within years and after rqDeated asthma episodes, chronic airway inflammation, airway remodeling, and airway hyperresponsiveness. 

Airway hyperresponsiveness is an exaggerated airway narrowing in response to a variety of unspecific stimuli. It can be measured by bronchial provocation with histamine, methacholine or adenosine. The reason for hyperresponsiveness may be stimulation of sensory nerves that are located within the epithelium. They become easily accessible after denudation of the... 

ROS, reactive oxygen species AHR, airway hyperresponsiveness MMP, matrix metalloprotease. Correlates with cough and chronic bronchitis. bNumber increases with disease severity. 

AS, Chung KF, Sturton G, Wong SIT, McKenzie AN Blocking IL-25 prevents airway hyperresponsiveness in allergic asthma. J Allergy Clin Immunol 2007 120 1324-1331. 

Miyahara N, Balhorn A, Dakhama A, Gelfand EW 126 IL-lO-treated dendritic cells decrease airway hyperresponsiveness and airway inflammation in mice. J Allergy Clin Immunol 2007 119 1241-1250. 

Dusser, D.J., Jacoby, D.B., Djokic, T.D., Borson, D.B. and Nadel J.A. (1989). Virus induces airway hyperresponsiveness to taehykinins by decreasing neutral endopeptidase. Am. Rev. Resp. Dis. 139, A352. 

Gordon, T., Sheppard, D., McDonald, D., Distefano, S. and Scypinski, L. (1985). Airway hyperresponsiveness and inOam-mation induced by toluene diisocyanate in guinea-pigs. Am. Rev. Resp. Dis. 132, 1106-1112. 

Yeadon, M., Eve, D. and Payne, A.N. (1993c). Induction of airway hyperresponsiveness increases the potency of BW B70C, a 5-lipoxygenase inhibitor, to prevent allergic bron-choconstriction in sensitised guinea-pigs. Br. J. Pharmacol. 108, 186P. 

Other therapeutic uses of cannabinoid agonists have been reported. The potential of cannabinoids as a treatment for asthma is supported experimentally. A CBi agonist, (i )-methanandamide (21), inhibited nerve growth factor (NGF)-induced airway hyperresponsiveness in vivo [251]. The antipruritic effect of cannabinoids has been reported, the action being mediated by both CBi and CB2 pathways [252]. Treatment with cannabis extract improved urinary tract symptoms of multiple sclerosis patients significantly in an open-label pilot study [253]. 

Asthma is characterized by inflammation, airway hyperresponsiveness (AHR), and airway obstruction. Inhaled antigens... 

In the late phase response, activated airway cells release inflammatory cytokines and chemokines, recruiting inflammatory cells into the lungs. The late phase response occurs 4 to 6 hours after the initial allergen challenge and results in a less intense bronchoconstriction as well as increased airway hyperresponsiveness and airway inflammation.6... 

Airway hyperresponsiveness is defined as the exaggerated ability of the airways to narrow in response to a variety of stimuli. Although AHR exists in patients without asthma, it is a characteristic feature of asthma and appears to be directly related to airway inflammation and the severity of asthma.1,3 Treatment of airway inflammation with inhaled corticosteroids attenuates AHR in asthma but does not eliminate it.1 Clinically, AHR manifests as increased variability of airway function. Although not commonly used to diagnose asthma, AHR can be evaluated clinically using a methacholine or histamine bronchoprovocation test. 

Schuh JM, Power CA, Proudfoot AE, Kunkel SL, Lukacs NW, Hogaboam CM. Airway hyperresponsiveness, but not airway remodeling, is attenuated during chronic pulmonary allergic responses to Aspergillus in CCR4 / mice. FASEB J 2002 16(10) 1313—1315. 

Ying S, Robinson DS, Meng Q, et al. Enhanced expression of eotaxin and CCR3 mRNA and protein in atopic asthma. Association with airway hyperresponsive-... 

Gonzalo JA, Lloyd CM, Wen D, et al. The coordinated action of CC chemokines in the lung orchestrates allergic inflammation and airway hyperresponsiveness. J... 

MacLean JA, De Sanctis GT, Ackerman KG, et al. CC chemokine receptor-2 is not essential for the development of antigen-induced pulmonary eosinophilia and airway hyperresponsiveness. J Immunol 2000 165(ll) 6568-6575. 

The desired outcome in the pharmacological treatment of asthma is to prevent or relieve the reversible airway obstruction and airway hyperresponsiveness caused by the inflammatory process. Therefore, categories of medications include bronchodilators and anti-inflammatory drugs. 

Park, J.W., et al., Complement activation is critical to airway hyperresponsiveness after acute ozone exposure, Am. J. Respir. Crit. Care Med. 169, 6, 726, 2004. 

In sensitized asthmatic individuals, antigen challenge generally causes a Type I (IgE-mediated) immediate hypersensitivity response by release of preformed mediators, including histamine, and prostaglandins, which are responsible for bronchoconstric-tion and increased vascular permeability. Between 2 and 8 hours after the immediate response, asthmatics experience a more severe and prolonged (late phase) reaction that is characterized by mucus hyper-secretion, bronchoconstriction, airway hyperresponsiveness to a variety of nonspecific stimuli (e.g., histamine, methacholine), and airway inflammation characterized by eosinophils. This later response is driven by leukotrienes, chemokines and cytokines synthesized by activated mast cells and Th2 cells. Both proteins and haptens have been associated with these types of reactions. 

Strickland DH, Stumbles PA, Zosky GR, Subrata LS, Thomas JA, Turner DJ, Sly PD, Holt PG Reversal of airway hyperresponsiveness by induction of airway mucosal CD4+CD25+ regulatory T cells. J Exp Med 2006 203 2649-2660. 

Wills-Karp M Immunologic basis of antigen-induced airway hyperresponsiveness. Annu Rev Immunol 1999 17 ... 

Taube C, Wei X, Swasey CH, et al Mast cells, FceRI, and IL-13 are required for development of airway hyperresponsiveness after aerosolized allergen exposure in the absence of adjuvant. J Immunol 2004 172 6398-6406. 

Kim YS.KoHM, Kang Nl.etal Mast cells play a key role in the development of late airway hyperresponsiveness through TNF-oi in a murine model of asthma. Eur J Immunol 2007 37 1107-1115. 

Inhaled and intravenous histamine causes bronchoconstriction as one of the first recognized properties of histamine, which is inhibited by Hi antihistamines. As a manifestation of airway hyperresponsiveness, asthmatic individuals are more sensitive to the bronchoconstrictor effect of histamine than normal individuals. In addition, in vitro studies have shown increased histamine release in basophils and mast cells obtained from asthmatic subjects compared with... 

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