Recommendations on interpreting tests of bronchodilator responsiveness (BDR) are conflicting. We investigated the dependence of BDR criteria on sex, age, height, ethnicity and severity of respiratory impairment.
BDR tests were available from clinical patients in the Netherlands, New Zealand and the USA (N=15,278, 51.7% females) and surveys in Canada, Norway and five Latin-American countries (N=16,250, 54.7% females). BDR in FEV1, FVC and FEV1/ FVC was expressed as absolute change, % baseline, % predicted and z-score.
Change (Δ) in FEV1 and FVC in mL was unrelated to the baseline value but biased towards age, height, sex and level of airways obstruction; ΔFEV1 was significantly lower in African Americans. In 1106 subjects with a low FEV1 (200-1621mL) the FEV1 increased 12-44.7% baseline but <200mL. Expressing BDR as percentage of predicted or z-score attenuated the bias and made the 200mL criterion redundant, but reduced positive responses by half. ΔFEV1 % baseline increased with the level of airflow obstruction but decreased with severe obstruction when expressed as z-scores or % predicted; ΔFVC, however expressed, increased with the level of airflow obstruction.
Expressing FEV1 responsiveness as % baseline spuriously suggests that responsiveness increases with the severity of respiratory impairment. Expressing change in FEV1 or FVC as % predicted or in z-scores eliminates this artefact and renders the required 200mL minimum increase redundant. In severe airways obstruction ΔFVC should be critically evaluated as an index of clinically important relief of hyperinflation, with implications for bronchodilator drug trials.