Asthma 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. 

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. 

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... 

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. 

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

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. 

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 corticosteroids mediate a variety of immunological actions and are commonly used in the treatment of allergic asthma [28]. However, not all patients respond well to this treatment and some are steroid-resistant. In a recent study, Tantisira et al. [29] described a new genetic non-synonymous variation in TBX21 that encodes for the transcription factor T-bet (T-box expressed in T cells) associated with significant improvement of the airway hyperresponsiveness in children affected by allergic asthma [30]. Noteworthy, the... 

Kim SH, Bae JS, Suh CH, Nahm DH, Holloway JW, Park HS. (2005) Polymorphism of tandem repeat in promoter of 5-lipoxygenase in ASA-intolerant asthma a positive association with airway hyperresponsiveness. Allergy. 60, 760-765. 

The antibodies to IL-4 inhibit allergen-induced airway hyperresponsiveness (AHR), globlet cell metaplasia and pulmonary eosinophilia in animal models. Inhibition of IL-4 by soluble IL-4 receptor (SIL-4R, Nuvance) has proven to be very promising in treating asthma. Clinical trials with recombinant SIL-4R administered by a single weekly dose of 3 mg via nebulization have been effective in controlling the symptoms of moderate persistent asthma. 

Cromones such as cromolyn sodium (Intal, Nasal-crom) and nedocromil sodium (Tilade) can help prevent bronchospasm in people with asthma. These drugs are not bronchodilators and will not reverse bronchoconstriction during an asthmatic attack. Hence, these agents must be taken prior to the onset of bronchoconstriction, and they must typically be administered prophylactically to prevent asthma attacks that are initiated by specific, well-defined activities (e.g., exercise, exposure to a friend s pet, pollen).107 Likewise, the regular use of these drugs several times each day for several months may decrease airway hyperresponsiveness so that the incidence of asthmatic attacks decreases.102,113... 

There is evidence that both occupational and environmental exposures to chemicals (both proteins and haptens) can result in the induction or exacerbation of respiratory allergies (Table 19.6). Of particular concern is the induction of allergic asthma. In sensitized asthmatic individuals the antigen challenge generally causes a type I (IgE-mediated) immediate hypersensitivity response with release of mediators responsible for bronchoconstriction. Between 2 and 8 hours after the immediate response, asthmatics experience a more severe and prolonged (late phase) reaction that is characterized by mucus hypersecretion, bronchoconstriction, airway hyperresponsiveness to a variety of nonspecific stimuli (e.g., histamine, methacholine), and airway inflammation characterized by eosinophils. This later response is not mediated by IgE. 

Ohashi, Y., Motojima, S., Fukuda, T. and Makino, S. (1992). Airway hyperresponsiveness, increased intracellular spaces of bronchial epithelium, and increased infiltration of eosinophils and lymphocytes in bronchial mucosa in asthma. Am. Rev. Respir. Dis. 145, 1469-1476. 

Pare, P.D. (1993). Hyperplasia and hypertrophy of ASM in asthma the cause of airway hyperresponsiveness. Eur. Respir. J. 6, 228s. 

IL-9 is a member of the Th2 cytokine family and has been implicated as an essential factor in determining mucosal immunity and susceptibility to atopic asthma. It has also been found in association with severe asthma and to cause airway hyperresponsiveness. ... 

Meurs H, Maarsingh H, Zaagsma J. Arginase and asthma novel insights into nitric oxide homeostasis and airway hyperresponsiveness. Trends Pharmacol Sci 2003 24 450-5. 

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