Respiratory epidemiology Table 3 subgroups Variables FEV1-based measures DFEV1 (ml) DFEV1i (%) DFEV1p (%) FVC-based measures DFVC (ml) DFVCi (%) DFVCp (%) Upper 95th percentiles with 95% CI (unweighted values) for bronchodilator responses for whole study population, healthy and COPD Study population All N1¼10 217 314 (306 to 324) 14.6 (14.1 to 15.3) 10.6 (10.3 to 10.9) N2¼9546 395 (381 to 414) 13.3 (12.7 to 13.9) 10.8 (10.4 to 11.4) Men N1¼4826 354 (340 to 368) 14.0 (13.2 to 14.6) 10.2 (9.9 to 10.6) N2¼4560 454 (419 to 486) 12.6 (11.8 to 13.4) 10.4 (9.7 to 10.8) Women N1¼5391 265 (257 to 278) 15.4 (14.5 to 16.0) 10.9 (10.5 to 11.3) N2¼4986 347 (328 to 374) 14.1 (13.2 to 15.1) 11.6 (10.7 to 12.5) Healthy Subgroup Men and women N1¼3922 291 (279 to 309) 12.5 (11.9 to 13.2) 10.1 (9.7 to 10.7) N2¼3593 337 (317 to 358) 11.2 (10.5 to 12.2) 9.6 (9.1 to 10.3) COPD GS2+ Men and women N1¼1009 371 (343 to 402) 30.9 (27.8 to 33.8) 13.1 (12.3 to 14.6) N2¼976 635 (591 to 678) 29.4 (26.6 to 31.6) 18.0 (17.0 to 19.7) COPD GS2+ (without asthma) Men and women N1¼745 341 (323 to 381) 27.7 (21.6 to 30.9) 12.3 (11.6 to 13.5) N2¼723 619 (547 to 668) 26.7 (24.4 to 30.6) 17.3 (15.7 to 18.8) DFEV1 (ml) and DFVC (ml) are absolute change after bronchodilator; DFEV1i and DFVCi are change as a per cent of initial value; DFEV1p and DFVCp are change as per cent of predicted value. N1 is number with non-missing FEV1 values and N2 is number with non-missing FVC values. COPD GS2+ ¼ FEV1/FVC <0.7 and FEV1% predicted<80%; COPD GS2+, without asthma ¼ COPD GS2+ but with no self-reported diagnosis of asthma. In the COPD subgroups, the CIs for individual sites were large due to small sample size (<50). COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 s; FVC, forced vital capacity. with the ﬁndings reported in clinical trials of patients with COPD, using ATS reversibility criteria.4 These ﬁndings support the use of lung volume-based measures of reversibility in addi- tion to FEV1-based measures in patients with more severe COPD.26 In this analysis the thresholds for BDR for healthy people were derived from random samples of adults aged 40 years and over in the general population. According to the ERS guidelines, an ambiguous BDR should exceed spontaneous variability and the response observed in healthy individuals.13 Yet, evidence for the different published criteria had largely been based on data of selected patients with airﬂow limitation.8 9 14e17 28 Existing data on the upper limit of the BDR in the healthy population are few and dated,18 29 although a recent study of unselected urban population in Iceland reported a 95th percentile of 9% for increase in FEV1 from baseline (%DFEV1i).19 Therefore, the results from this study add to reference values from smaller population studies from single countries18e20 and provided global reference values for the interpretation of bronchodilator testing. Two separate approaches have been used to derive reference values for a BDR. The ﬁrst method was to assume that values greater than the 95th percentile in distribution of healthy subjects was abnormal.18 The second method was to measure the short-term spontaneous variation or placebo-induced changes in FEV1 in patients.15e17 The ﬁrst method was used in this study. The joint ATS-ERS guidelines10 recommendation of 12% percentage change from baseline and 200 ml absolute changes in FEV1 and/or FVC in an individual subject to identify a positive/signiﬁcant BDR was derived using the second approach, but recognised the need to obtain references in healthy populations based on the ﬁrst method. Thus, the results Figure 1 Absolute change in forced expiratory volume in 1 s (FEV1) in ml after bronchodilator (DFEV1) expressed as 95th percentile with 95% CI in healthy non-smokers. Those sites whose estimates are most stable get greater weight (right-hand column) in constructing the pooled estimate of 284 ml. We observed signiﬁcant heterogeneity across sites (p¼0.008), with 54% of the overall variability in the data attributable to siteesite variability. Thorax 2012;67:718e726. doi:10.1136/thoraxjnl-2011-201445 721