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We have investigated the effects of CP-96,345 and SR-48968, new nonpeptide (neurokinin) NK1 and NK2 receptor antagonists, respectively, against bronchoconstriction and airway microvascular leakage induced by inhaled sodium metabisulfite (MBS) in anesthetized guinea pigs. Lung resistance (RL) was measured for 6 min after challenge, followed by measurement of extravasation of Evans blue dye into airway tissues, used as an index of airway microvascular leakage. MBS (80 mM, 30 breaths) caused a significant increase in RL and leakage of dye at all airway levels. CP-96,345 (2 mg/kg, intravenous) but not SR-48968 (1.5 mg/kg, intravenous) significantly inhibited the leakage of dye at all airway levels except for trachea. Each antagonist inhibited significantly the maximal increase in RL. The combination had a significant additive effect against the bronchoconstriction, when compared with SR-48968 alone, and significantly inhibited the leakage of dye at the same airway levels as CP-96,345. We conclude that bronchoconstriction induced by inhaled MBS is, at least partly, mediated by activation of both NK1 and NK2 receptors, and the airway microvascular leakage by NK1 receptor stimulation alone.

Recognition of sulfite sensitivity by the practicing dermatologist has become increasingly important. A wide spectrum of anaphylactoid reactions can occur after ingestion of sulfite additives in foods and medications. We report the case of a 47-year-old man with severe acute intermittent urticaria. A placebo-controlled oral challenge test with 50 mg sodium disulfite resulted in an acute urticaria attack. A biopsy taken 5 h after the appearance of the urticaria demonstrated a leukocytoclastic vasculitis with eosinophilia. Avoiding foods and drugs containing sulfites is often difficult due to its widespread use. Therefore, the patient should be equipped with a medical emergency kit.

Oral challenge tests were carried out with sodium metabisulfite solution doses of 5, 10, 25, 50 and 100 mg, dissolved in 20 ml of citric acid, and administered to 20 children aged 7-14 years with steroid-dependent bronchial asthma. A single-blind challenge protocol was performed initially and the positive responses were confirmed by double-blind challenge. Initially, 6 of 20 presented a positive reaction, confirmed in 4 of 20 by double-blind challenge. Only 1 child was clinically suspected of exhibiting intolerance to this agent. The prevalence of the challenge test using sodium metabisulfite in children with steroid-dependent bronchial asthma was 20%.

Sulfiting agents are antioxidants widely used in both food and pharmaceutical industries. They have been identified as responsible for adverse severe reactions. A case is reported of anaphylactoid shock during epidural anaesthesia for caesarean section. The responsible agent was metabisulfite, additive agent of local anesthetics containing epinephrine.

Metabisulfite intolerance is encountered in 8 p. 100 of cases of extrinsic asthma and in 20 p. 100 of cases of the "aspirin triad" with nasosinusal polyposis, asthma and aspirin sensitivity. The possibility that anaphylactoid shock or acute severe asthma leading to status asthmaticus, might be related to sulfite sensitivity must be well known. Two case reports are set out. The first observation is that of a 35-year-old woman suffering from intrinsic asthma with alcohol intolerance, who developed status asthmaticus a few minutes after intravenous administration of Doxycycline associated with a metabisulfite preservative. The other 33-year-old patient presented with an acute bronchospasm in the course of a fiberoscopy using Lidocaine associated by mishap with epinephrine, as local anesthetic. The authors point to the miscellaneous drugs containing sulfites, that are employed in asthmatics by different routes, i.e. parenteral, oral, inhalational and other local treatments. Heavy metabisulfite intake may also arise from daily alcohol consumption. Sulfite intolerance could contribute to the persistence of chronic inflammatory processes in bronchial asthma and therefore should be systematically investigated.

Sulfites are widely used as preservatives in the food and pharmaceutical industries. In the United States more than 250 cases of sulfite-related adverse reactions, including anaphylactic shock, asthmatic attacks, urticaria and angioedema, nausea, abdominal pain and diarrhea, seizures and death, have been reported, including 6 deaths allegedly associated with restaurant food containing sulfites. In Canada 10 sulfite-related adverse reactions have been documented, and 1 death suspected to be sulfite-related has occurred. The exact mechanism of sulfite-induced reactions is unknown. Practising physicians should be aware of the clinical manifestations of sulfite-related adverse reactions as well as which foods and pharmaceuticals contain sulfites. Cases should be reported to health officials and proper advice given to the victims to prevent further exposure to sulfites. The food industry, including beer and wine manufacturers, and the pharmaceutical industry should consider using alternative preservatives. In the interim, they should list any sulfites in their products.