The FEF25-75 and its Decline as a Predictor of Methacholine Responsiveness in Children

Background. Methacholine challenge (MCC) is an important diagnostic tool for asthma, especially in patients in whom routine pulmonary function testing (PFT) is normal or equivocal. The basis for a positive test per American Thoracic Society (ATS) guidelines is a methacholine concentration 16 mg/mL that causes a 20% decrease in forced expiratory volume in 1 second (FEV1) (termed the PC20 for FEV1). There is little information in the medical literature that utilizes other flow rates during MCC, including small airway function parameters such as the forced expiratory flow rate 25-75% (FEF25 -75). We question whether the FEF25 -75 may be a useful parameter to monitor during MCC and whether it may be predictive of a positive MCC. Hypothesis. The baseline FEF25 -75 and its decline during a MCC are useful in the interpretation of a MCC. Methods. We retrospectively analyzed all MCC performed at this institution between December 1998 and December 2006. Parameters reviewed included age, gender, race, weight, height, baseline PFT data including FVC, FEV1, FEF25 -75, and forced expiratory time, methacholine PC20 for FEV1, the relative changes from baseline for FEV1 and FEF25 -75 during the MCC, and clinical symptoms during the MCC. Results. A total of 532 MCC were completed during the 8-year study period in children 4 to 18 years of age. A total of 203 MCC (38%) were positive (defined by a PC20 16 mg/mL) and 329 studies were negative (62%). The baseline % predicted FEF25 -75 in positive MCC was 82.4 21.9 vs. 98.7 21.3 in the negative studies (p 0.001). The FEF25 -75/FVC ratio in positive MCC was 0.82 0.21 vs. 0.97 0.23 in negative studies (p 0.001). In the positive MCC, the decrease in FEF25 -75 was much faster and of much greater degree than in the negative challenges. When a significant reduction in FEF25 -75 was defined as greater than 10% by the second concentration of methacholine (0.25 mg/mL), the sensitivity for a positive MCC was 63%, the specificity was 71%, the positive predictive value was 57%, and the negative predictive value was 76%. A comparison of the baseline FEF25 -75 to the PC20 for the positive MCCs revealed no statistical significance. Conclusions. The FEF25 -75 and its decline during a MCC appear to be useful information and potentially predictive of a positive MCC. We suggest that the forced expiratory flow rate 25-75% (FEF25 -75) be considered as an adjunct to the FEV1 to define a positive study.