Small Airway Impairment and Bronchial Hyperresponsiveness in Asthma Onset

Purpose: Our study tried to find a relationship between baseline FEF25-75% and airway hyperresponsiveness (AHR) and whether a greater FEF25-75% impairment may be a marker of a more severe hyperresponsiveness in subjects with normal FEV1 and FEV1/FVC and suggestive asthma symptoms. Besides, we tried to asses a FEF25-75% cut-off value to identify hyper-reactive subjects. Methods: 4,172 subjects (2,042 M; mean age: 38.3 +/- 14.9; mean FEV1% predicted: 100.5 +/- 12.7 and FEV1/FVC: 85.4 +/- 6.8) were examined after performing a methacholine (Mch) test. All subjects reported a symptom onset within 3 years before the test Subjects with PD20<400 or >400 mu g were arbitrarily considered affected by moderate/severe and borderline AHR, respectively. Results: PD20 values were 213 (IQR, 86-557), 340 (IQR, 157-872) and 433 (IQR, 196-1032) mu g in subjects with baseline FEF25-75 <= 50%, FEF25- m between 50 and 70% and FEF25-75>70% respectively (P<0.0001). Only in moderate/severe hyper-reactive subjects (excluded borderlines), PD20 was lower in the FEF25-75 <= 50% subgroup than in the 1 with FEF25-75>70%. The hyperreactive subjects percentage, was higher in those with FEF25-75 <= 50% and lower in those with FEF25-75>70% (P<0.0001). FEF25-75<50% (compared to FEF25-75>70%) was a higher AHR risk factor, especially in subjects with moderate/severe AHR (OR, 2.18; IQR, 1.41-3.37; P<0.0001). Thresholds yielding the highest combined sensitivity/specificity for FEF25-75% were 75.19 (area under curve [AUC], 0.653) and 74.95 (AUC. 0.688) in subjects with PD20<2,400 and <400 mu g respectively. FEV1, FVC, and FEV1/FVC measured in subjects with different FEF25-75 <= 50%, FEF25-75>50 and <= 70% or FEF25-75>70% levels were similar both in normoreactive and hyperreactive subjects. Conclusions: At asthma onset reduced baseline FEF25-75 values with normal FEV1 and FEV1/FVC may predict AHR. Detectable predictive cut-off values do not exist because even normoreactive subjects can show lower FEF25-75 values. Furthermore, a greater FEF25-75 reduction may be associated to a more severe AHR, suggesting a possible FEF25-75 role in the management of asthma when FEV1 and FEV1/FVC are normal.