With placebo, there was a difference between morning and evening PEF of 61.0±45.0 L/min (mean ±SEM; p<0.01; n = 18), or a fall in morning PEF of 17.3 ±2.0 percent (expressed as a percentage of evening PEF). The percentage fall in PEF after 200μg of oxitropium bromide was not significantly different from that after placebo (15.6±3.1 percent), but there was a significant reduction in the percentage of morning fell after 400μg (10.3 ± 3.3 percent; p<0.05) (Fig 1). There was no significant difference in evening PEF between either period of treatment with the drug and placebo. Analysis of bronchodilator response (increase in PEF after 200μg of inhaled albuterol in the morning and evening), bronchodilator usage (number of extra puffs of albuterol used at night), and patient s symptom scores revealed no significant differences between the three periods of treatment. No significant side effects from treatment with oxitropium were recorded.
From closer examination of the data, it became obvious that some patients had responsed to treatment with oxitropium and that this response was dose-dependent. To further analyze this, patients in whom the fell in PEF between evening and morning was reduced by more than 10 percent with treatment with 400μg of oxitropium bromide when compared to placebo were defined as “responders.” Subsequent analysis showed that in nine of the 18 patients who fulfilled this criterion, a dose-dependent response to oxitropium was observed, with both 200μg (11.5±4.4 percent) and 400μg (5.0 ±4.5 percent) significantly reducing the early morning fell in PEF (p<0.01 when compared to placebo (19.1 ±3.2 percent) (Fig 1); however, in the group of nine “nonresponders,” there was no significant difference between placebo (15.6 ±2.6 percent) and 200μg (19.7±4.0 percent) or 400μg of oxitropium bromide (15.6 ±4.4 percent). There were no significant diflFerences between responders and nonresponders in terms of age, atopic status, duration of asthma, severity of asthma, extra use of inhaled albuterol at night, or bronchodilator response to inhaled albuterol. Seven of the nine responders preferred treatment with oxitropium, whereas none of the nonresponders did so.
Figure 1. Effect of oxitropium (OKI) on early morning PEF in asthmatic patients. Fall in early morning PEF is measured as percent of evening PEF. Means (± SE) are shown, with levels of significance (two-way AN OVA) compared to placebo. “Responders” showed more than 10 percent improvement after oxitropium.