Asthma late asthmatic response

Chronic exposure to fumes of heated glacial acetic acid in a canning factory has been associated with a late airway response resulting in chronic inflammation and severe bronchial asthma. Inhalation challenge induced a late asthmatic response, confirming sensitization. ... 

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... 

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). 

Diamant, Z., Timmers, M. C., van, d,V., Page, C. P., van der Meet, F. J., and Sterk, P. J. (1996). Effect of inhaled heparin on allergen-induced early and late asthmatic responses in patients with atopic asthma. Am. J. Respir. Crit. Care. Med. 153, 1790-1795. 

Respiratory A 25-year-old woman developed symptoms of rhinoconjunctivitis and asthma, attributed to an allergy to cyanoacrylate in a fingernail adhesive gel, which as a manicurist she had used for 6 months [41 ]. Skin prick tests were positive with dog and cat dander and grass pollens. Patch tests were positive with nickel, cadmium, and silver salts. An inhalation challenge with cyanoacrylate for 30 minutes elicited a late asthmatic response, with a 24% fall in FEVi, with rhinorrhea and asthma that worsened progressively until she received short-acting P2-adrenoceptor agonists. 

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). 

Wenzel SE, Westcott JY, Larsen GL. Bronchoalveolar lavage fluid mediator levels 5 minutes after allergen challenge in atopic subjects with asthma relationship to the development of late asthmatic responses. J Allergy Clin Immunol 1991 87 540-548. 

Iwamura and Ueda [386] described compound (611) as a CB2 selective inverse agonist in a patent application. The potential therapeutic roles of CB2 antagonists are not clearly defined at the moment, although roles in regulation of the immune system and inflammation have been widely proposed. This patent application describes that activity of compound (611) in a mouse model of asthma, in which the compound suppressed immediate and late-phase asthmatic response and airway hyper-responsiveness. 

Studies of omalizumab in asthmatic volunteers showed that its administration over 10 weeks lowered plasma IgE to undetectable levels and significantly reduced the magnitude of both the early and the late bronchospastic responses to antigen challenge. Clinical trials have shown repeated intravenous or subcutaneous injection of anti-IgE MAb to lessen asthma severity and reduce the corticosteroid requirement in patients with moderate to severe disease, especially those with a clear environmental antigen precipitating factor, and to improve nasal and conjunctival symptoms in patients with perennial or seasonal allergic rhinitis. 

Challenge of sensitized subjects with inhaled allergen has been a vital experimental approach in asthma research since the first bronchoprovocation studies were performed by Max Samter in Berlin in 1933. Allergen inhalation results in an early bronchoconstrictor ( asthmatic ) response (EAR) at 5 to 10 minutes lasting up to an hour and, in about half of subjects, a late bronchoconstrictor response (LAR) starting at 2 to 3 hours and lasting for 12 to 24 hours (Pepys, 1973). 

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