Bronchoconstrictor reaction

Beta-agonists, indirectly via c-AMP, act on mast cell p2-receptors inhibiting the release of bronchoconstrictor mediators such as histamine. Slow-reacting substance of anaphylaxis (SRS-A), now known to be leukotriene D3 and D4 (Fig. 5-5), and eosinophil chemo-tactic factor of anaphylaxis (ECF-A) may also have their release inhibited by c-AMP. Leukotriene D, which is a mediator of hypersensitivity reactions, may still have an important role in causing asthmatic symptoms. In fact, it is 100 times more effective than histamine in producing vascular permeability. 

Aspirin is known to cause serious reactions in certain patients with asthma (Cooke 1919). The patients can also have rhinorrhea and nasal polyps that may precede the bronchoconstrictor type of intolerance to aspirin for months or years. This triad of symptoms is common in middle-aged women. The aspirin-sensitive patients often show intolerance to other analgesics (Smith 1971). Speer (1958) reported that color additives can precipitate asthma. Aspirin-sensitive patients with asthma also cross-react to tartrazine in 8%-15% of the cases (Chafee and Setti-PANE 1967 Samter and Beers 1967 Hosen 1972 Settipane and Pudupakkam 1975 Delaney 1976) and to various benzoates (Juhlin et al. 1972 Rosenhall and Zetterstrom 1973). Hypersensitivity to food colorants, preservatives, and analgesics was studied in 504 patients with asthma and rhinitis by Rosenhall (1977). Hypersensitivity to at least one of the substances was found in 106 patients. In 33 patients sensitive to tartrazine 42% were intolerant to aspirin and 39% to sodium benzoate. Rosenhall also tested his patients with other azo dyes such as Sunset Yellow and New Coccine as well as the non-azo dyes carmine and patent blue. The method of examination and reproducibility of the results were studied in detail. Dietary treatment was found to be effective in some patients in preventing exacerbations of the disease but on the whole had no influence on the course of the disease or the need for medication. 

A family of endogenous metabolites of ->arachi-donic acid via the lipoxygenase pathway, chemically related to the ->prostaglandins and - thromboxanes. Members of the group are potent bronchoconstrictors that play an important role in the immediate hypersensitivity reactions and they have been proposed as mediators of the inflammatory process and some are potent chemotactic agents. 

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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