Bronchial hyperresponsiveness

A characteristic pathophysiological feature of asthma is bronchial hyperresponsiveness (BHR), the exj erated bronchoconstrictor response of the airways to a wide 

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Asthma is an extremely complex condition characterized by variable and reversible airways obstmction combiaed with nonspecific bronchial hypersensitivity (1 3). The cause of asthma, which is not always readily diagnosed (4), remains unknown. Days, if not weeks, ate needed to document the spontaneous reversal of the airways obstmction ia some patients. Asthmatics experience both an immediate hypersensitivity response and a delayed late-phase reaction, each mediated by a different pathway. Chronic asthma has come to be viewed as an inflammatory disease (5). The late-phase reaction plays a key role ia iaduciag and maintaining the inflammatory state which ia turn is thought to iaduce the bronchial hyperresponsiveness (6). The airways obstmction results from both contraction of airways smooth muscle and excessive bronchial edema. Edema, a characteristic of inflammatory states, is accompanied, ia this case, by the formation of a viscous mucus which can completely block the small airways. 

Theophylline s predominant mode of action appears to be bronchocHlation. However, it has also been shown that prophylactic acHriinistration of theophylline provides some protection from asthma attacks and suppresses the late-phase response (67,68). Some researchers beHeve that at therapeutic semm concentrations theophylline may inhibit the development of airway inflammation (69). There are conflicting reports on the effect of theophylline on allergen-induced bronchial hyperresponsiveness some clinical stucHes report a reduction in hyper-responsiveness, others do not (69,70). Theophylline clearly does not reverse the general bronchial hyperresponsiveness over the course of long-term therapy (71). Because of the relationship between... 

Single dose or short-term treatment with aerosolized steroids inhibits both the late asthmatic response and allergen-induced bronchial hyperresponsiveness (45,92). However it does not affect the early asthmatic response nor does it induce bronchodilation (45,92). Long-term treatment with steroids protects against both the early and late asthmatic responses and also reduces bronchial hyperresponsiveness (44,71,86,93). Over time, the airways relax (dilate) and measures of airway function, such as forced expiratory volume in one second (FEV ), gradually return to almost normal levels. 

Bronchial Asthma. Figure 2 Mechanisms of bronchial hyperresponsiveness. Toxic products from eosinophils [cationic peptides, reactive oxygen species (ROS)] cause epithelial injury. Nerve endings become easily accessible to mediators from mast cells, eosinophils [eosinophil-derived neurotoxin (EDN)], and neutrophils, and to airborne toxicants such as S02. Activation of nerve endings stimulates effector cells like mucosal glands and airway smooth muscle either directly or by cholinergic reflexes. 

Siroux V. Curt F. Oryszczyn MP, Maccario J, Kauff-mann F Role of gender and hormone-related events on IgE. atopy, and eosinophils in the Epidemiological Study on the Genetics and Environment of Asthma, dO bronchial hyperresponsiveness and atopy. J Allergy Clin Immunol 2004 114 491-498. 

Rak S. Lowhagen O, Venge P The effect of immunotherapy on bronchial hyperresponsiveness and eosinophil cationic protein in pollen-allergic patients. J Allergy Chn Immunol 1988 82 470-480. 

The ultimate mode of reduction in function, which, if sufficiently severe, results in death, is blood oxygen desaturation and accumulation of carbon dioxide. However, the inflammatory changes that the insults listed above can evoke and contribute to interference with the perfusion/ventilation relationship are varied and have different expressions in diverse lung disorders bronchial hyperresponsiveness after ozone or nitrous oxide... 

Yeadon, M., Wilkinson, D. and Payne, A.N. (1990). Ozone induces bronchial hyperresponsiveness to inhaled substance P through functional inhibition of enkephalinase. Br. J. Pharmacol. 99, 191P. 

BCF Basophil chemotactic factor B-CFC Basophil colony-forming cell BCG Bacillus Calmette-Guerin BCNU l,3-bis(2-chloroethyl)-l-nitrosourea bFGF Basic fibroblast growth fiictor Bg Birbeck granules BHR Bronchial hyperresponsiveness BHT Butylated hydroxyroluene b.i.d. Bis in die (twice a day)... 

D Amato M, Vitiani LR, Petrelli G et al. Association of persistent bronchial hyperresponsiveness with beta2-adrenocep-tor (ADRB2) haplotypes. A population study. Am J Respir Crit Care Med 1998 158 1968-1973. 

The National Asthma Education and Prevention Program (NAEPP) defines asthma as a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role. In susceptible individuals, inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, and coughing. These episodes are usually associated with airflow obstruction that is often reversible either spontaneously or with treatment. The inflammation also causes an increase in bronchial hyperresponsiveness (BHR) to a variety of stimuli. 

Bryce PJ, Geha R, Oettgen HC Desloratadine inhibits allergen-induced airway inflammation and bronchial hyperresponsiveness and alters T-cell responses in murine models of asthma. J Allergy Clin Immunol 2003 112 149-158. 

Docebenone has shown anti-inflammatory effects in several animal models following local dosing phorbol ester-induced oedema and neutrophil influx in mouse skin [208,209], arachidonate-induced plasma extravasation in rabbit skin [210], the pleural reversed passive Arthus reaction in rats [211], and GPB [212], An oral dose of 80 mg/kg reduced infarct size, LTB4 levels and neutrophil infiltration in a rat myocardial infarction model [213,214], and in a rat brain ischaemia-reperfusion model oedema and LTC4 levels were reduced at 200 mg/kg [107]. Significant, but not dramatic, improvement in nasal symptoms was seen in humans following 150 mg of docebenone twice daily for 8 weeks [215], but there was no effect on bronchial hyperresponsiveness to acetylcholine in asthmatics [216]. 

Yoshida, S., Sakamoto, H., Ishizaki, Y., et al. (2000) Efficacy of leukotriene receptor antagonist in bronchial hyperresponsiveness and hypersensitivity to analgesic in aspirin-intolerant asthma. Clin. Exp. Allergy. 30, 64-70. 

Aizawa, H., Shigyo, M., Nogami, H., Hirose, T., and Kara, N. (1996) BAY u3405, a thromboxane Aj antagonist, reduces bronchial hyperresponsiveness in asthmatics. Chest 109, 338-342. 

Fujimura, M., Nakatsumi, Y., Nishi, K., Kasahara, K., and Matsuda, T. (1995) Involvement of thromboxane A in bronchial hyperresponsiveness of asthma. Kanazawa Asthma Research Group. Pulm. Pharmacol. 8, 251-257. 

Some studies of survivors of massive chlorine exposures have shown either persistent obstructive or restrictive deficits, but pre-exposure data on these patients were not available. Persistent respiratory symptoms, bronchial obstruction, and bronchial hyperresponsiveness were observed in 82%, 23%, and 41 % of chronically exposed pulp mill workers, respectively, 18-24 months after cessation of exposure." In most cases it is not known whether prolonged symptoms after chlorine exposure are due to aggravation of preexisting conditions such as tuberculosis, asthma, chronic obstructive pulmonary disease, or heart disease." "... 

Antagonists at the A3 receptor would prevent periodic exacerbations of asthma and lead over the longer term to a reduction in airways inflammation and bronchial hyperresponsiveness. 

Bai TR, Weir T, Walker B, Salvatore CA, Johnson RG, Jacobson MA (1994) Localization of adenosine-A3 receptors by in-situ hybridization in human lung. FASEB J 8 A800 Barnes PJ (1989) New concepts in the pathogenesis of bronchial hyperresponsiveness and asthma. J Allergy Clin Immunol 83(6) 1013-1026... 

Polosa R, Ciamarra I, Mangano G, Prosperini G, Pistorio MP, Vancheri C, Crimi N (2000) Bronchial hyperresponsiveness and airway inflammation markers in nonasthmatics with allergic rhinitis. Eur Respir J 15(l) 30-35... 

Doupnik CA, Leming LM, O Donnell JR, et al. 1988. Time course of bronchial hyperresponsiveness mediator release and neutrophil infiltration following acrolein exposure in guinea-pig. In Joint Annual Meeting American Lung Association and The American Thoracic Society, Las Vegas, NV, May 8-11, 1988. Am Rev Respir Dis 137 (4 Part 21) 244. 

Certain proteins and low-molecular-weight (<3000) compounds have the potential to cause allergic sensitization. Responses to subsequent inhalation exposure include pulmonary inflammation, increased mucus secretion, specific bronchial hyperreactivity to the offending allergen, and nonspecific bronchial hyperresponsiveness to challenge with an agonist such as methacholine. These symptoms are... 

Asthma is a chronic inflammatory condition characterized by bronchial hyperresponsiveness and reversible airway obstruction. Cytokine release from a variety of cell types such as eosinophils, lymphocytes and other inflammatory cells produces epithelial sloughing, plasma protein extravasation from the tracheobronchial microcirculation and airway remodeling.1,2 Bronchial mucosal inflammation is present in all patients. The primary goal of asthma management is to maintain control of the disease process by reducing symptoms and improving lung function. 

Bradley, B.L., Azzawi, M., Jacobson, M., Assoufi, B., Collins, J.V., Irani, A.A., Schwartz, L.B., Durham, S.R, Jeffery, P.K. and Kay, A.B. (1991). Eosinophils, T-lymphocytes, mast cells, neutrophils and macrophages in bronchial biopsy specimens from atopic subjects with asthma - comparison with biopsy specimens from atopic subjects without asthma and normal control subjects and relationship to bronchial hyperresponsiveness. J. Allergy Chn. Immunol. 88,661-674. 

Casale, T.B., Wood, D., Richerson, H.B., Trapp, S., Metzger, W.J., Zavala, D. and Hunninghake, G.W. (1987). Bron-choalveolar lavage fluid H levels in allergic asthmatics are associated with methachoUne bronchial hyperresponsiveness. J. Clin. Invest. 79, 1197-1203. 

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