Exercise-induced bronchoconstriction and asthma

Abstract

Objectives: The objectives are: (1) To assess diagnostic test characteristics of six alternative index tests compared with the selected reference standard-a standardized exercise challenge test (ECT) in patients with suspected exercise-induced bronchoconstriction or asthma (EIB/EIA); (2) to determine the efficacy of a single prophylactic dose of four pharmacologic and one nonpharmacologic interventions vs. placebo to attenuate EIB/EIA in patients with diagnosed EIB/EIA; and (3) to determine if regular daily treatment with short-acting or long-acting beta-agonists (SABA or LABA) causes patients with EIA to develop tachyphylaxis when additional prophylactic doses are used pre-exercise.

Data sources: A systematic and comprehensive literature search was conducted in 14 electronic databases (Diagnosis) and the Cochrane Airways Register (Therapy).

Review methods: Study selection, quality assessment, and data extraction were conducted independently by two reviewers. The primary outcome was the maximum percent fall in the post-exercise forced expiratory volume in 1 second (percent fall FEV1). The diagnostic threshold for a positive ECT was a percent fall FEV1 of 10% or more. Sensitivity (SN) and specificity (SP) were calculated. For therapy, mean differences (MD) in the percent fall FEV1 and 95% confidence intervals (CI) (random effects model) were calculated. A positive MD indicates the intervention works better than the control.

Results: For the diagnostic reviews, 5,318 citations yielded 28 relevant studies; for the therapy reviews, 1,634 citations yielded 109 relevant RCTs. Diagnostic test results versus ECT: self-reported history (2 studies) SN=36-8 percent; SP=85-86 percent; sport specific challenges (5 studies) SN=0-100 percent, SP=0-100 percent; eucapnic voluntary hyperpnea (7 studies) SN=25-90 percent, SP=0-71 percent; free running asthma screening test (3 studies) SN=60-67 percent, SP=47-67 percent; mannitol (3 studies) SN=58-96 percent, SP=65-78 percent. All SN and SP calculations indicated substantial heterogeneity that could not be explained by sensitivity or subgroup analyses. Therapy results: SABA offered greater protection than mast cell stabilizers (MCS) (12 studies); MD=6.8 (95 percent CI: 4.5, 9.2) but combining them offered no additional benefit; SABA versus MCS plus SABA (5 studies) MD=1.3 (95 percent CI: -6.3, 8.9). Leukotriene receptor antagonists (LTRA), MCS, ipratropium bromide, and interval warmup routines provided statistically significant attenuation of EIA when compared with placebo; inhaled corticosteroids (ICS) and other warmup routines did not. Single-dose intervention versus placebo results are: LTRA (9 studies) MD=8.9 (95 percent CI: 6.9, 11.0); MCS (nedocromil sodium) (17 studies) MD=15.6 (95 percent CI: 13.2, 18.2); interval warmup versus no warmup (4 studies) MD=10.6 (95 percent CI: 6.5, 14.7); ICS (4 studies) MD=5.0 (95 percent CI: 0.0, 9.9); continuous low intensity warmup versus no warmup (3 studies) MD=12.6 (95 percent CI: -1.5, 26.7); continuous high intensity warmup versus no warmup (2 studies) MD=9.8 (95 percent CI: -6.4, 26.0). After daily LABA (salmeterol) use for 3 to 4 weeks (4 studies), the percent fall FEV1 following an ECT at 2 and 4 weeks was greater than at day 1 in the LABA arm indicating that tachyphylaxis to prophylactic LABA use occurred. Daily SABA use for 1 week (1 study) also indicated development of tachyphylaxis. However, both LABA and SABA continued to have an attenuating effect on EIA.

Conclusions: Given the small number of studies comparing EIB/EIA diagnostic tests, the heterogeneity of the study populations, and the varied study methodologies, there is no clear evidence that any of the index tests are a suitable replacement for a standardized ECT to diagnose EIB/EIA in the general population. All bronchodilator agents and most anti-inflammatory agents when used as pretreatment are somewhat effective in attenuating the percent fall FEV1 associated with EIA.