The quality of evidence is downgraded by study limitations (unclear allocation concealment) and by indirectness (it is unclear how directly pulmonary function measures relate to what participants feel).
Short-acting beta2-agonists are recommended as preventive treatment before exercise if the patient has exercise-induced symptoms despite adequate treatment with inhaled corticosteroids. Long-acting beta-agonists can be used if short-acting beta-agonists are not effective.
A Cochrane review [Abstract] 1 included 53 studies with a total of 1 139 subjects with exercise-induced asthma or exercise-induced bronchoconstriction; both conditions are referred to by the acronymous EIA, independently from the presence of an underlying chronic clinical disease. 30 studies allowed and 23 studies did not allow concomitant inhaled corticosteroid (ICS) treatment, 3 studies did not allow ICS on study day or ICS was suspended 12 hours before exercise challenge, and 7 studies did not report on ICS use. Forty-five studies addressed the effect of a single beta2-agonist administration, and 8 focused on long-term treatment. 20 studies were performed in children, 18 in adults and 12 in both children and adults; 3 papers did not provide sufficient information to allocate people according to age. 42 studies examined short-acting beta2-agonists (SABA; short-term administration 40 studies and long-term administration 2 studies) and 27 studies long-acting beta2-agonists (LABA; short-term administration 21 studies and long-term administration 6 studies).
The 45 studies evaluating short-term beta2-agonist administration (single administration) included 77 arms of active treatment (49 SABA and 28 LABA) in comparison with placebo. Meta-analysis of studies showed that both SABA and LABA administered as preventive treatment (within the time-effect period set at 1 hour for SABA and at 12 hours for LABA) prevented exercise-induced asthma, as shown by the primary outcome of the maximum fall in FEV1 which was lower in the intervention group compared with placebo (MD -17.67%, 95% CI -19.51 to -15.84%, statistical heterogeneity I2 =71%). The subgroup analysis of studies performed in adults compared with those performed in children showed high heterogeneity confined to children, despite the comparable mean bronchoprotective effect. Secondary outcomes on other pulmonary function parameters confirmed a more positive and protective effect of beta2-agonists on EIA compared with placebo. Occurrence of side effects was not significantly different between beta2-agonists and placebo.
Long-term administration of beta2-agonist was addressed in only 8 studies (5 cross-over studies with 50 adults and 14 children, and 3 parallel-group studies with 102 adults and 40 children); 2 studies examined SABA, and 6 studies LABA. Treatment periods ranged from 7 to 29 days. Meta-analysis was not performed due to limited number of studies, small population samples and different study designs and drugs tested.Overall evaluation of the included long-term studies suggested a beta2-agonist bronchoprotective effect for the first dose of treatment. However, long-term use of both SABA and LABA induced the onset of tolerance and decreased the duration of drug effect, even after a short treatment period. The few available data on concomitant therapy with inhaled corticosteroids did not allow a firm statement about their potential influence on the response to beta2-agonists.
Taking LABA without background inhaled steroids is considered unsafe and is not currently recommended in most of the clinical guidelines for asthma. More studies are needed to determine whether it is safe to administer inhaled beta2-agonists alone to people who experience asthma symptoms when exercising.
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