No abstract

The effects of 800 micrograms of inhaled SK&F 104353, a peptidoleukotriene receptor antagonist, and of 20 mg disodium cromoglycate (DSCG) on exercise-induced bronchoconstriction were compared in 18 asthmatic patients. The study was conducted according to a double-blind, crossover, randomized, placebo-controlled design. Two baseline exercise tests were carried out, and pulmonary function tests were done before and at 1, 5, 10, 15, 20, and 30 min after completion of the exercise. Patients showing a 20% or greater decrease in FEV1 in both exercise challenges entered the blinded portion of the study. When placebo was administered before exercise, FEV1 fell to the same extent as during the baseline phase. After SK&F 104353 and DSCG, the bronchoconstriction was attenuated. The mean maximal percentage fall in FEV1 after exercise was 29% after placebo and 20% after SK&F 104353 and DSCG. The differences between the two active treatments did not reach the 5% level of statistical significance, though at 20 min SK&F 104353 showed a more pronounced effect than DSCG. The protective effect suggests an important role of leukotrienes in the pathogenesis of exercise-induced bronchoconstriction.

Inhaled frusemide effectively prevents the bronchial obstructive response to allergens and to a number of nonallergic stimuli. In most of the experimental models in which it has been tested, the protective effect of frusemide has been evaluated for only a short time after administration. In aspirin-sensitive patients, acetylsalicylic acid causes an asthmatic reaction which typically lasts for 2 h or more after exposure. We investigated the presence and duration of the protective effect of inhaled frusemide against the bronchial response to aspirin in sensitive patients, using a specific inhalation challenge with lysine acetylsalicylate (LASA). In the first study, eight subjects with aspirin-asthma underwent two bronchial challenges with a single dose of lysine acetylsalicylate administered through a jet nebulizer, after treatment with 40 mg inhaled frusemide or placebo, according to a randomized, double-blind protocol. Forced expiratory volume in one second (FEV1) was monitored for 120 min after challenge. In the second study in eight patients, the protocol was modified by the use of a dosimeter for delivery of lysine acetylsalicylate, by reducing the dose of lysine acetylsalicylate to avoid intense reactions, and by extending the follow-up to 4 h. In the first study, after placebo, FEV1 gradually decreased, reaching a maximum decrement of 39 +/- 3% at 120min. Inhaled frusemide exerted a significant protection at all time-points, although this activity appeared to decrease with time. In the second study, after placebo, inhaled lysine acetylsalicylate caused a gradual decrease in FEV1, which reached a maximum decrement at 180 min.(ABSTRACT TRUNCATED AT 250 WORDS)

SummaryA wide range of experimental evidence shows that bronchial eosinophilic inflammation plays a major role in the pathogenesis of the asthmatic syndromes characterised by reversible airway obstruction and bronchial hyperresponsiveness. A treatment aimed at controlling inflammation is therefore of primary importance in these pathological conditions. To date, corticosteroids have been routinely used for this purpose, but their administration is often accompanied by serious side effects. Cromoglycate and cromoglycate-like compounds have been proposed as alternative anti-inflammatory agents, but because their anti-inflammatory activity is relatively low, they can replace corticosteroids only in mild asthma. In the most severe forms of asthma, gold salts and methotrexate have demonstrated a steroid-sparing effect, but at the cost of a high incidence of toxic effects.Little attention has been devoted to the use of NSAIDs in asthma for 2 principal reasons. In acute studies, NSAIDs such as aspirin (acetylsalicylic acid) and indomethacin have not shown satisfactory bronchodilator or antireactive activity. More importantly, NSAIDs have traditionally been associated with a relatively high frequency of severe obstructive reactions in patients with asthma.However, nimesulide, a recently developed NSAID, has proven to be safe in NSAID-sensitive patients. Moreover, in guinea-pigs, the drug exhibits good antianaphylactic activity and an impressive antihistaminic effect that is not shared by other NSAIDs such as indomethacin. On the basis of these findings, nimesulide can be considered as a potential antireactive-antiasthmatic agent, of which further clinical investigation is justified.

No abstract