EFFECTS OF DIURNAL-VARIATION AND PROLONGED REFRACTORINESS ON REPEATEDMEASUREMENTS OF AIRWAYS RESPONSIVENESS TO METHACHOLINE

Background - A number of studies have suggested that diurnal variation in airways responsiveness underlies the circadian rhythm of ventilato ry function in asthma. Measurements of airways responsiveness are ther efore often performed at standardised times in order to avoid this pos sible effect, but this is not practical for epidemiological studies. R efractoriness to methacholine has also been reported and this, too, co uld confound the results of methacholine tests repeated over short int ervals. This investigation was carried out to evaluate the possible ma gnitude of diurnal variation and refractoriness in repeated measures o f airways responsiveness to methacholine. Methods - To investigate diu rnal variation in airways responsiveness, 24 asthmatic subjects aged 1 8-45 underwent five methacholine tests over three days which were not necessarily consecutive: day 1 at 08:00 hours; day 2 at 08:00 hours, 1 4:00 hours, 20:00 hours; day 3 at 20:00 hours. To investigate refracto riness a retrospective analysis was undertaken of all paired methachol ine tests performed in individuals within our unit between 1984 and 19 90 where there had been no intervention likely to affect the results. Results - The first investigation revealed no diurnal change in airway s responsiveness although there was a change in FEV(1). Mean PD20 did, however, increase 1.57 fold from 08:00 hours on day 1 to 08:00 hours on day 2 for subjects studied on consecutive days. The second investig ation confirmed that a test interval of up to 24 hours (but not of 48 or more hours) was associated with a refractory index (PD20 test 2/PID 20 test 1) of >1. Conclusions - No diurnal variation in airways respon siveness was detected for measurements made between 08:00 hours and 20 :00 hours, but an interval between successive tests of up to 24 hours was associated with refractoriness. Diurnal variation is not likely to exert an important confounding effect on methacholine tests carried o ut between 08:00 hours and 20:00 hours, but confounding could result f rom refractoriness if tests are repeated at intervals up to 24 hours.