Early asthmatic responses

The bronchospasm that occurs immediately after aeroallergen inhalation in allergic asthmatic subjects is at least partly an IgE-mediated immediate hypersensitivity reaction (1). At least two lines of evidence support this mechanism for the early asthmatic response. Eirst, pretreatment with an anti-IgE monoclonal antibody attenuates the early phase response in asthmatic subjects (Fig. 1) (2,3). Second, analysis of bronchoalveolar lavage fluid collected immediately after air- 

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Many of the preformed and newly synthesized mediators released from activated mast cells cause smooth muscle contraction either directly or indirectly, and acute bronchoconstriction is considered the principal mechanism of airway obstruction during the early asthmatic reaction. For example, histamine, PGD2, PGF2a, thromboxane B2, LTC4, and LTD4 are thought to cause contraction of airway smooth muscle directly (14-17), whereas the contraction caused by tryptase and PAF is indirect (18-21). Although all of these mediators have the poten- 

In summary, current information suggests that the mechanism of airway narrowing during the early asthmatic response is an acute bronchoconstrictor response caused mainly by an IgE-dependent immediate hypersensitivity reaction. Of the preformed and newly synthesized mediators released from mast cells during these reactions, the cysteinyl leukotrienes appear to be the most important in the pathogenesis of the EAR. 

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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. 

Boulet LP, Chapman KR, Cote J, Kalra S, et al. 1997. Inhibitory effects of an anti-IgE antibody E25 on allergen-induced early asthmatic response. Am J Respir Crit Care Med. 155 1835-1840. 

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. 

Inflammatory disease associated with bronchial hyperactivity (BHR), bronchospasm, T mucus secretion, edema, and cellular infiltration. Early asthmatic responses (EAR) lasting from 30 to 60 min are associated with bronchospasm from the actions of released histamine and leukotrienes late asthmatic responses (LAR) involve infiltration of eosinophils and lymphocytes into airways - > bronchoconstriction and inflammation with mucus plugging. 

Inhaled Allergen Challenge as a Model of Asthma 2.3.I Mast Cells and the Early Asthmatic Response... 

Early asthmatic responses (EAR) lasting firom 30 to 60 minutes are associated with bronchospasm from the actions of released histamine and leukotrienes. 

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). 

Figure 1 Allergen-induced isolated early asthmatic response (EAR). FEV, (L) is on the vertical axis and time (hr) post-aUergen inhalation on the horizontal axis. Inhalation of ragweed allergen extract caused a 30% fall in FEV, maximal at 10 minutes and resolved by 2 hours (sohd tine) the response following inhaled diluent is shown in the dotted line.

Cockcroft DW, Murdock KY. Comparative effects of inhaled salbutamol, sodium cromoglycate and beclomethasone dipropionate on aUergen-induced early asthmatic responses, late asthmatic responses and increased bronchial responsiveness to histamine. J Allergy Chn Immunol 1987 79 734-740. 

Swystun VA, Bhagat R, Kaha S, Jennings B, Cockcroft DW. Comparison of 3 different doses of budesonide and placebo on the early asthmatic response (EAR) to inhaled allergen. J Allergy Clin Immunol 1998 102 363-367. 

Cockcroft DW, McFarland CP, O Byrne PM, Manning P, Friend JL, Rutherford BC, Swystun VA. Beclometbasone given after the early asthmatic response inhibits the late response and the increased methacholine responsiveness and cromolyn does not. J Allergy Clin Immunol 1993 91 1163-1168. 

Cieslewicz G, Tomkinson A, Adler A, et al. The late, but not early, asthmatic response is dependent on IL-5 and correlates with eosinophil infiltration. J Clin Invest 1999 104 301-308. 

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