Objective: Using a example of natural allergen exposure.

Objective: Using a example of natural allergen exposure, we examined the power of regular treatment with salmeterol in succession allergen-induced changes in airway responsiveness and exhaled nitric oxide (ENO).

Design: Double-blind, randomized, parallel-group study

Setting: Specialist allergy unit in a university hospital.

Patients: Asthmatic patients sensitized to pollen allergens were randomly allocated to monotherapy with salmeterol (n = 14) or placebo (n = 13)

Interventions: Salmeterol, 25 [micro]g, and placebo inhalers, brace puffs bid, for 6 weeks.

Measurements: Spirometry, the flush of a provocative concentration of a substance (methacholine) causing a 20% fall in FE[Vsub1] (P[Csub20]) the P[Csub20] plain for adenosine 5'-monophosphate (AMP), and ENO were measured before the pollen season and were repeated at the height of the pollen season after 6 weeks of treatment with salmeterol or placebo.

Results: The decrease in FE[Vsub1] during the pollen season was significantly larger in the placebo assemblage than in the salmeterol assemblage the mean difference in the change between the collections being 0.20 L (95% confidence interval, 003 to 035; p = 0047) Changes in P[Csub20] for methacholine, P[Csub20] for AMP, and ENO horizontals were not significantly different between treatment assemblages However, a mean ([+ or -] SEM) decrease in the P[Csub20] for methacholine of -10 [+ or -] 04 doubling concentrations was observ within the placebo dispose (p = 0.03), whereas no significant changes were observ within the salmeterol cluster A significant decrease in P[Csub20] for AMP (doubling concentrations) was observ within the placebo cluster (-2.1 [+ or -] 06; p = 0003) and the salmeterol assign places to (-1.5 [+ or -] 04; p = 0003) ENO concentrations increased significantly among the placebo and the salmeterol form into groupss during natural pollen exposure.

Conclusion: These observations indicate that natural allergen exposing and the regular use of salmeterol are not associated with a greater increase in ENO and airway responsiveness than allergen in all senses alone.

Key words: adenosine 5'-monophosphate; airway responsiveness; allergens; allergic asthma; methacholine; nitric oxide; salmeterol

Abbreviations: AMP = adenosine 5'-monophosphate; CI = confidence interval; ENO = exhaled nitric oxide; MDI = metered-dose inhaler; NO = nitric oxide; P[Csub20] = provocative concentration of a substance causing a 20% fall in FE[Vsub1]; ppb = parts by billion

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Inhaled [[beta].sub.2]-adrenergic agonists are the most numerous effective of the available bronchodilator mix with drugss used to treat acute asthma symptoms. (1) However, there is a disquiet that treatment with short-acting [[beta].sub.2]-agonists may be causally associated with the increase in asthma morbidity. (2) Partly as a come of these concerns, the International Asthma Guidelines (3) praise that inhaled [[beta].sub.2]-agonists be used "as required" for the relief of symptoms rather than as part of a regularly scheduled regimen.

Salmeterol is a real effective [[beta].sub.2]-agonist, with long-lasting bronchodilator activity up to 12 h It is commended in combination with anti-inflammatory agents (such as inhaled corticosteroids) in patients with chronic asthma, particularly moderate and strait-laced persistent disease. (3) Concern that the adverse issues of regular short-acting inhaled [[beta].sub.2]-agonists in succession asthma morbidity also might come to one's mind with salmeterol has been a major factor in many clinical trials. Salmeterol studies have demonstrated no increase in asthma exacerbations compared with placebo uniform when used without anti-inflammatory mix with drugss (4,5) However, several studies have demonstrated that the regular use of inhaled salmeterol abouts tolerance to their bronchoprotective event against bronchospasm induced by exercise, (6) allergens, (7) and methacholine. (8) The los of [beta]-agonist protection against bronchoconstriction is more pronounced in relation to the validity of inhaled adenosine 5'-monophosphate (AMP), (9) which induces bronchospasm indirectly by means of the activation of mast enclosed spaces (10) than to the purport of inhaled methacholine, which causes bronchoconstriction mainly from the direct stimulation of eholinergic receptors in succession airway smooth muscle.

a certain studies (11) have demonstrated an increased responsiveness to methacholine after the regular use of salmeterol, although others have not. (512) Furthermore, regular treatment with salmeterol enhances allergen-induced early bronchoconstrictor answers (13) Subsequent clinical studies (14) also have glance ated that, compared to placebo, 1 week of regular therapy with salmeterol may lead to an increase in airway inflammation 24 h after allergen challenge. Consequently it was hypothesized that, especially in allergic asthmatic patients, there might be an interactive drift on inflammation between the regular use of [[beta].sub.2]-agonists and the position to allergens, resulting in an increased airway responsiveness. (15) It remains, however, unclear by what mode relevant the observations made subject to conditions of laboratory challenge with large quantities of allergen are to the natural course of asthma.

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