Airway hyperresponsiveness response

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... 

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. 

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. 

Leckie MJ, ten Brinke A, Khan J, Diamant Z, O Connor BJ, Walls CM, Mathur AK, Cowley HC, Chung KF, Djukanovic R, Hansel TT, Holgate ST, Sterk PJ, Barnes PJ Effects of an inter-leukin-5 blocking monoclonal antibody on eosinophils, airway hyperresponsiveness, and the late asthmatic response. Lancet 2000 356 2144-2148. 

Edwan JH, Perry G, Talmadge JE, Agrawal DK Flt-3 Ligand reverses late allergic response and airway hyperresponsiveness in a mouse model of allergic inflammation. J Immunol 2004 172 5016-5023. 

Elwood W, Lotval JO, Barnes PJ, Fan Chung K (1992) Effect of dexamethasone and cyclosporin A on allergen-induced airway hyperresponsiveness and inflammatory cell responses in sensitised Brown Norway rats. Am Rev Resp Dis 145 1289-1294 Elwood W, Barnes PJ, Sakamoto T, Fan Chung K (1993) Allergen-induced airway hyperresponsiveness in Brown Norway rat role of parasympathetic mechanisms. J Appl Physiol 75 279-284... 

Abraham WM, Ahmed A, Sabater JR, et al. Selectin blockade prevents antigen-induced late bronchial responses and airway hyperresponsiveness in allergic sheep. Am. J. Respir. Crit. Care Med. 1999 159 1205-1214. 

Block late reaction to allergen and reduce airway hyperresponsiveness. inhibit production of cytokines responsible for initiation of inflammatory cascade. 

Abraham, W.M., Sielczak, M.W., Ahmed, A., Cortes, A., Lauredo, I. T., Kim, J., Pepinsky, B., Benjamin, C.D., Leone, D.R, Lobb, RR and Weller, P.F. (1994). Anti-a4 intergrin mediates antigen-induced late bronchial responses and prolonged airway hyperresponsiveness in sheep. J. Clin. Invest. 93, 776-787. 

Airway hyperresponsiveness in children is mostly associated with airway inflammation due to IgE sensitisation [63-65]. Chronic asthma is mainly associated with sensitisation to indoor allergens (house dust mites, animal dander, cockroaches etc), which are more important than the outdoor allergens, probably because of the time spent indoors [2, 66, 67]. Several studies have demonstrated a relationship (in a dose-dependent manner) between exposure and presence of IgE antibody [68-71], as well as a clear association between presence of IgE antibody and development of asthma [65, 70-78]. However, no significant direct association between early exposure to indoor allergens and development of asthma up to the age of 7 years was found in a recent study [72]. Importantly, such an association should only be expected as regards allergic asthma. A dose-response relationship between exposure to house dust mites and development and severity of asthma has been demonstrated [74, 75]. Other longitudinal studies have shown that sensitisation to house dust mites and animal dander antedate, and are a risk factor for development of asthma in children [65, 71, 78, 79]. 

KAROL, M.H.,TOLLERUD, D.J., CAMPBELL, T.P., FABBRI, L MAESTRELLI, P, SAETTA, M. MAPP, C.E. (1994) Predictive value of airways hyperresponsiveness and circulating IgE for identifying types of responses to toluene diisocyanate inhalation challenge. American Journal of Respiratory and Critical Care Medicine, 149, 611-615. 

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