Small Airway Impairment and Bronchial Hyperresponsiveness in Asthma Onset

PURPOSE: Our study tried to find a relationship between baseline FEF(25-75)% and airway hyperresponsiveness (AHR) and whether a greater FEF(25-75)% 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 FEF(25-75)% 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 µg 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) µg in subjects with baseline FEF(25-75)≤50%, FEF(25-75) between 50 and 70% and FEF(25-75)>70% respectively (P<0.0001). Only in moderate/severe hyper-reactive subjects (excluded borderlines), PD20 was lower in the FEF(25-75)≤50% subgroup than in the 1 with FEF(25-75)>70%. The hyperreactive subjects percentage, was higher in those with FEF(25-75)≤50% and lower in those with FEF(25-75)>70% (P<0.0001). FEF(25-75)<50% (compared to FEF(25-75)>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 FEF(25-75)% were 75.19 (area under curve [AUC]: 0.653) and 74.95 (AUC:0.688) in subjects with PD20<2,400 and <400 µg respectively. FEV1, FVC, and FEV1/FVC measured in subjects with different FEF(25-75)≤50%, FEF(25-75)>50 and ≤70% or FEF(25-75)>70% levels were similar both in normoreactive and hyperreactive subjects. CONCLUSIONS: At asthma onset, reduced baseline FEF(25-75) 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 FEF(25-75) values. Furthermore, a greater FEF(25-75) reduction may be associated to a more severe AHR, suggesting a possible FEF(25-75) role in the management of asthma when FEV1 and FEV1/FVC are normal.