Introduction A proportion of patients with asthma develops a refractory period, during which the bronchoconstrictor response to a second indirect challenge is reduced. A better understanding of factors associated with the development of refractoriness is potentially important as the refractory period may be the vestigial expression of a bronchoprotective pathway that may be pathogenically important and could be manipulated for therapeutic effect. We investigated factors associated with refractoriness in 10 subjects with mild to moderate asthma.
Methods Subjects were recruited from primary care, had mild to moderate (Step 1 or 2 BTS guideline) asthma and were aged 18–50 years. Subjects underwent a standardised laboratory exercise challenge test breathing cold dry air. Those who had a positive test (>15% fall in FEV1) were observed until lung function returned to within 5% of baseline and then underwent a further standardised exercise challenge test. The refractory index was calculated on the % reduction in the maximum percent fall in FEV1 between the first and second challenge. On a separate occasion the subjects undertook a sodium metabisulphite challenge test (a known, indirectly acting bronchoconstrictor) and a PD20 (MBS PD20) was calculated for this from interpolation of the log-dose response curve.
Results 22 individuals were screened to find 10 (1F; 9M) with a positive exercise test; these then went on to have a second challenge test. The mean (SEM) fall in FEV1 was 24.9% (2.4) and 13.7% (2.5) with first and second challenge respectively. The mean (SEM) refractory index was 50.1% (6.5). There was no correlation between the refractory index and age, sex, FEV1 % predicted, FVC, FEV1/FVC ratio, MBS PD20, or % fall in FEV1 on first challenge.
Conclusions Our findings suggest that refractoriness is independent of baseline lung function and the magnitude of the response to the initial challenge. Further studies are required to determine whether other demographic factors are associated with this phenomenon.
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