In the atopic patient with asthma, allergens are an important cause of chronic airway inflammation and symptoms. Natural exposure to seasonal allergens, such as grass pollen, may result in exacerbation of asthma, increased airway responsiveness (i.e., increased susceptibility of the airways to constrict), and an increased frequency of emergency room visits. Removal of patients from exposure to indoor allergens, such as dust mites, results in a marked reduction in symptoms, less airway responsiveness, and a decrease in drug requirements. In the pulmonary function laboratory, inhalation of increasing doses of allergen, in a safe and controlled manner (allergen bronchoprovocation), produces physiological responses similar to those observed after natural exposure. These include an immediate decrease in the forced expiratory volume in 1 second (FEV1) that is rapid in onset but short in duration (early response), a subsequent gradual decline in FEV1 4-8 hours after allergen inhalation that is sustained (late response), an increase in airway responsiveness, and infiltration of the airway mucosa by inflammatory cells. Drugs that are effective as maintenance therapy for chronic asthma generally attenuate the late response to allergen bronchoprovocation, and those with antiinflammatory effects (e.g., inhaled corticosteroids) also attenuate the allergen-induced increase in airway responsiveness and cellular infiltration of the airways. However, the magnitude of drug effect in this clinical model does not correlate well with the drug's relative efficacy in chronic asthma. In contrast, drugs that have no effect in this clinical model, such as calcium channel blockers, ketotifen, and antihistamines, are ineffective as maintenance therapy for chronic asthma. Thus, it appears that allergen bronchoprovocation is most useful as a screening tool for excluding drugs that are unlikely to be effective for chronic asthma and for determining whether a drug has antiinflammatory and/or immunomodulatory actions on the airway mucosa.

Allergens↗

PubMedDate not supplied

Preservatives in nebulizer solutions: risks without benefit.

Edetate disodium (EDTA) and benzalkonium chloride (BAC) are often present as preservative or stabilizing agents in nebulizer solutions used to treat asthma and chronic obstructive pulmonary disease. Benzalkonium chloride is a potent bronchoconstrictor when inhaled in concentrations similar to those in which it is present in these solutions. Inclusion of BAC (together with EDTA) in the ipratropium bromide (Atrovent) nebulizer solution resulted in paradoxic bronchoconstriction in some asthmatic patients and an overall reduction in bronchodilator efficacy. The presence of BAC in albuterol nebulizer solutions does not affect the short-term bronchodilator response to a single dose, although case reports suggest that its repeated use in patients with severe asthma may result in paradoxic bronchoconstriction. When inhaled by asthmatic subjects, EDTA also causes dose-dependent bronchoconstriction, although it is less potent than BAC. The use of preservative-free bronchodilator nebulizer solutions does not result in clinically significant bacterial contamination if they are dispensed in sterile unit-dose vials, in volumes and concentrations that do not require modification by the user. Despite this evidence, in the United States a number of solutions, including some preparations of albuterol, contain either BAC or EDTA. Current regulations do not require that the concentration of preservatives be documented on the product; however, considerably different doses of BAC are delivered with different products. For example, a standard 2.5-mg dose of albuterol nebulizer solution contains 50 microg of BAC when administered from the multidose dropper bottle and 300 microg from the unit-dose screw-cap product. Furthermore, it is legal for pharmacists to substitute or compound solutions containing high concentrations of BAC when the physician has prescribed a preservative-free product. We recommend that the United States follow the practice of most Western countries and withdraw bronchodilator nebulizer solutions that contain preservatives such as BAC. We further recommend that the solutions should be prepared under sterile conditions, formulated preservative free, and made available in unit-dose vials.

Benzalkonium Compounds↗