Validating the clinical utility of sGaw as a response variable in methacholine challenge testing

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Introduction: Airway hyperresponsiveness (AHR) is a characteristic feature of asthma diagnosed using the methacholine challenge test (MCT) based on a drop in FEV1 > 20 % from baseline at a concentration of < 8 mg/mL (provocative concentration 20 denoted PC20). However, there are other physiological responses to methacholine, of which airway resistance—as measured by specific airway conductance, sGaw—has been suggested as an alternative to diagnosing AHR. A positive sGaw is denoted by a drop greater than 40% from baseline at a concentration of < 8 mg/ml (PC40). We sought to determine the clinical utility of sGaw vs FEV1 in diagnosing AHR and its association with asthma.

Methods: We conducted a retrospective chart review of 300 randomly selected MCTs at University of Vermont Medical Center between 2015 to 2017. Data from 211 charts were used towards the final analysis; charts missing data were excluded. We reviewed demographics, smoking status, clinical symptoms, MCT numerical results, and whether a clinical diagnosis of asthma was documented. Data was sorted into the following categories: positive challenge by PC20; positive by PC40 only; positive by either PC20 or PC40; positive by both PC20 and PC40; or negative by PC20 and PC40 (no AHR). Values were presented as a mean (SD) or median (IQR) depending on its distribution. We used ANOVA, Wilcoxon test, chi-square test and Spearman’s rank correlation for statistical analysis.

Results: Notable demographic data included a mean age group of 53 (11) years, 141 women (67%) and 70 men (33%), a median BMI of 29 (24-34) kg/m2; 80 (38%) current or former smokers with a median pack-year history of 15 (5-33) and time since smoking of 22 (10-35) years; overall normal baseline lung function including FEV1, FEV1/FVC ratio, TLC, DLCO and sGaw values. A total of 177 patients had a clinical diagnosis of asthma. There were many more patients in the PC40-only category (n=119) compared to the PC20 category (n=52). The change in FEV1 or FVC was less in the PC40-only group compared to the PC20 group as expected. The changes in sGaw were similar among all groups; the PC20 group had a 57% fall in sGaw at the time they reached their maximal concentration of methacholine. Considering that 93% of the PC40-only group had a clinical diagnosis of asthma, 111 of the 177 patients with a diagnosis of asthma (63%) would have been missed by PC20 alone.

Conclusion: sGaw is more sensitive than FEV1 for diagnosing AHR from MCT. The majority of patients with AHR defined by PC40 had a clinical diagnosis of asthma, validating PC40 as clinically relevant and useful.

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