The Late Asthmatic Response

In contrast to the acute mediator-induced bronchocon-striction and mucosal oedema characteristic of the EAR, there is now considerable evidence that the LAR is associated with inflammatory cell accumulation and activation. This situation is generally considered to be analogous to that seen in chronic airway inflammation, but some caution is needed in extrapolating the results of 

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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. 

Leckie MJ, ten Brinke A, Khan J, et al. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 2000 356(9248) 2144-2148. 

Lai CK, Twentyman OP, Holgate ST. The effect of an increase in inhaled allergen dose after rimiterol hydrobromide on the occurrence and magnitude of the late asthmatic response and the associated change in nonspecific bronchial responsiveness Am Rev Respir Dis 1989 140(4) 917-23. 

Cartier, A., Thomson, N.C., Frith, P.A., Roberts, R and Har-greave, F.E. (1982). Allergen-induced increase in bronchial responsiveness to H relationship to the late asthmatic response and change in airway calibre. J. Allergy Clin. Immunol. 70, 170-177. 

Inhibits degranulation of mast cells also inhibits release of histamine and SRS-A (a leukotriene) from the mast cell. This inhibits the early asthmatic response by stabilizing the mast cell also inhibits the late asthmatic response. It has no intrinsic bronchodilator, antihistaminic, anticholinergic, vasoconstrictor, or anti-inflammatory activity. 

Thromboxane A2 is produced by alveolar macrophages, fibroblasts, epithelial cells, neutrophils, and platelets within the lung. Indirect evidence from animal models suggests that thromboxane A2 may have several effects, including bronchoconstriction, involvement in the late asthmatic response, and involvement in the development of airway inflammation and BHR. Potent and specific thromboxane synthetase inhibitors will be crucial tools for understanding the role of thromboxanes in asthma. 

The Late Asthmatic Response as a Model for Clinical Asthma... 

COOKSON, W.O.C.M., CRADDOCK, C.F., BENSON, M.K. DURHAM, S.R. (1989) Falls in peripheral eosinophil counts parallel the late asthmatic response. American Review of Respiratory Disease, 139, 458 -62. 

Mast cells release histamines, leukotrienes and other mediators of the inflammatory process. Mast cell stabilizer drugs inhibit the early asthmatic response and the late asthmatic response. They have no bronchodilator effect nor do they have any effect on any inflammatory mediators already released in the body. They are indicated for the prevention of bronchospasms and bronchial asthma attacks. They are administered by aerosol inhalation. The exact action of the drugs have not been determined. However, they are believed to have a modest effect in lowering the required dose of corticosteroids. The most common mast stabilizer dmgs are cromolyn (Intal) and nedocromil (Tilade). 

Dmgs that help control asthma and act as good maintenance therapy generally reduced the allergen-induced responses, including the late asthmatic response, while agents with minimal effect on these last, such as calcium channel blockers and antihistamines, were not found useful for this purpose (111,112). 

Cartier A, Thomson NC, Erith PA, Roberts R, Hargreave FE. Allergen-induced inaease in bronchial responsiveness to histamine relationship to the late asthmatic response and change in airway caliber. J Allergy Clin Immunol 1982 70 170-177. 

Marsh WR, Irvin CG, Murphy KR, Behrens BL, Larsen GL. Inaeases in airway reactivity to histamine and inflammatory cells in bronchoalveolar lavage afta the late asthmatic response in an animal model. Am Rev Respir Dis 1985 131 875-879. 

The role of IgE in the late asthmatic response has been established in human studies in which it has been shown that pretreatment of asthmatic subjects with rhuMAb-E25—a nonanaphylactogenic anti-IgE monoclonal antibody—attenuates the LAR (Fig. 1) (35). This study established a role for IgE in the LAR— a role that had been debated up to that point (60). It also provided suggestive evidence that anti-IgE treatment attenuates allergen-induced airway eosinophilia. 

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