Development Of Late Asthmatic Reaction Research Articles

Role of histamine in allergen-induced asthmatic reactions, bronchial hyperreactivity and inflammation in unrestrained guinea pigs

In a new model using conscious, unrestrained and ovalbumin-sensitized guinea pigs, we investigated the effects of the selective histamine H 1 receptor antagonist, mepyramine, on the development of allergen-induced early and late asthmatic reactions, bronchial hyperreactivity and airway inflammation, having each animal as its own control. In guinea pigs responding to a first allergen exposure with an early as well as a late asthmatic reaction (82% of the animals) a second, identical, allergen provocation was performed, in the absence (control) or presence of 1 mg/ml mepyramine aerosol, inhaled for 10 min, 1 h before provocation. The mepyramine treatment significantly reduced both early and late asthamatic reactions and prevented the development of bronchial hyperreactivity to histamine and methacholine after both reactions. Examination of the bronchoalveolar lavage fluid 24 h after the second allergen provocation revealed a general reduction of inflammatory cells after mepyramine treatment. The results indicate that histamine, released during the early asthmatic reaction, contributes to the development of the late asthmatic reaction as well as of early and late bronchial hyperreactivity, possibly via an effect on airway inflammation.

Airway Inflammation during Late Asthmatic Reactions Induced by Toluene Diisocyanate

To determine the importance of airway inflammation for the development of late asthmatic reactions, we examined sensitized subjects during late asthmatic reactions induced by exposure to toluene diisocyanate (TDI) in the laboratory. Late asthmatic reactions are associated with a transient increase of bronchial responsiveness and, at the same time, with an increase of neutrophils followed by eosinophils, and of LTB4 and albumin in bronchoalveolar lavage fluid. Late asthmatic reactions, increased bronchial responsiveness, and increase of neutrophils, eosinophils, LTB4, and albumin concentration in bronchoalveolar lavage induced by exposure to TDI are all prevented by pretreatment with prednisone but not with the nonsteroidal anti-inflammatory agent indomethacin. Aerosolized steroids (beclomethasone and dexamethasone isonicotinate) completely inhibit late asthmatic reactions induced by TDI, whereas theophylline has a partial, and verapamil, ketotifen, and cromolyn have no protective effect. These results suggest that late asthmatic reactions induced by TDI may be caused by airway inflammation, and that anti-inflammatory steroids should be recommended in the prophylaxis of TDI asthma.

Asthma due to inhaled chemical agents‐the macrolide antibiotic Spiramycin

One year after starting work in the pharmaceutical industry a 35-year-old non-atopic maintenance engineer developed attacks of sneezing, coughing and breathlessness. These occurred at home during the evening and early morning, never at work during the day. His employment involved contact with a wide variety of chemical agents including the macrolide antibiotic spiramycin. Inhalation challenge tests carried out in hospital with gradually increasing quantities of spiramycin reproduced his symptoms and led to the development of late asthmatic reactions, during which the FEV1 fell by 25% and the FEV1/FVC ratio by 15%. No change occurred in the single breath CO transfer factor nor were crepitations heard over the lung fields which remained normal on chest X-ray. The patient showed positive immediate skin prick tests to spiramycin and developed blood eosinophilia during the late asthma attacks. Inhalation of sodium cromoglycate either before, or before and hourly after the provocation challenge for 6 hr, failed to prevent the late asthma, although its onset was further delayed. On leaving the pharmaceutical industry the patient's symptoms improved but did not finally clear until his wife, who had worked in a clerical capacity in the same factory also ceased her employment.