Minimal clinically important difference for impulse oscillometry in adults with asthma

Abstract

Background: Impulse oscillometry (IOS) allows an effort-independent evaluation of small airway function in asthma. Unfortunately, well-determined minimal clinically important differences (MCIDs) for IOS measures are lacking. Here, we provide MCIDs for frequently used IOS measures, namely frequency dependence of resistance (FDR) and area of reactance (AX), in patients with asthma.

Methods: We performed IOS at baseline and 1 year later in adult patients with mild-to-severe asthma (n=235). In a two-step approach, we first applied a distribution-based method to statistically determine the MCID. Next, we validated the proposed MCID according to patient-reported outcome measures (PROMs): Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Questionnaire-7 (ACQ-7) and Asthma Control Test (ACT). We used multivariable analyses to investigate the proposed MCIDs as predictors for improvements in PROMs compared with the established MCID of forced expiratory volume in 1 s (FEV1).

Results: The proposed MCID was a decline of ≥0.06 kPa·L-1·s-1 and ≥0.65 kPa·L-1 for FDR and AX, respectively. Patients who had changes beyond the MCIDs for both FDR and AX showed greater improvements in all PROMs than those who had not. The mean improvements in PROMs were beyond the established MCIDs for ACQ-7 and AQLQ, and approximated the MCID for ACT. Multivariable analyses demonstrated the MCIDs for both FDR and AX as independent predictors for the MCIDs of all PROMs. The MCID for FDR was a stronger predictor of all PROMs than the MCID for FEV1.

Conclusions: This study provides MCIDs for IOS-derived measures in adult patients with asthma and emphasises that small airway function is a distinguished end-point beyond the conventional measure of FEV1.

Conflict of interest statement

Conflicts of interest: M. Abdo received travel support from Chiesi and consulting fees from AstraZeneca, all outside the submitted work. E. von Mutius reports personal fees from Pharmaventures, OM Pharma SA, Springer-Verlag GmbH, Elsevier GmbH, Elsevier Ltd, Peptinnovate Ltd, Turun Yliopisto, Tampereen Yliopisto, Helsingin Yliopisto, European Respiratory Society, Deutsche Pharmazeutische Gesellschaft eV, Massachusetts Medical Society, Chinese University of Hongkong, Boehringer Ingelheim, ProtectImmun GmbH, Faculteit Diergeneeskunde, Universität Salzburg, Georg Thieme Verlag, Japanese Society of Pediatric Allergy and Clinical Immunology, and Universiteit Utrecht, all outside the submitted work. K.F. Rabe reports grants from Boehringer Ingelheim and AstraZeneca, as well as personal fees from Boehringer Ingelheim, AstraZeneca, Novartis, Roche, Chiesi Pharmaceuticals, Regeneron, Sanofi and Berlin-Chemie. F. Trinkmann received travel support from Actelion, Berlin-Chemie, Boehringer Ingelheim, Chiesi, Novartis, Mundipharma, TEVA, AstraZeneca, Berlin-Chemie, Bristol-Myers Squibb, Chiesi, GlaxoSmithKline, Novartis, Roche and Sanofi-Aventis, all outside the submitted work. T. Bahmer reports grants from Bundesministerium für Bildung und Forschung (BMBF) (an unrestricted research grant for the German Center for Lung Research (DZL)), during the conduct of the study, and personal fees from AstraZeneca, GlaxoSmithKline, Novartis and Roche, outside the submitted work. The remaining authors report no relevant conflicts of interest.

Copyright ©The authors 2023.

Figures

FIGURE 1

Box plots demonstrating the improvements in patient-reported outcome measures of asthma control and quality of life based on improvements beyond the minimal clinically important differences (MCIDs) for a–c) frequency dependence of resistance (FDR (kPa·L−1·s−1)) and d–e) area of reactance (AX (kPa·L−1)). Patients (n=48) with improvements in FDR beyond the proposed MCID (≥0.06 kPa·L−1·s−1) had mean±sd improvements of −0.71±0.89, 2.70±3.79 and 0.74±0.72 for Asthma Control Questionnaire 7 (ACQ-7), Asthma Control Test (ACT) and Asthma Quality of Life Questionnaire (AQLQ) scores, respectively. Patients (n=43) with improvements in AX beyond the proposed MCID (≥0.65 kPa·L−1) had mean±sd improvements of −0.79±0.93, 2.53±4.0 and 0.72±0.81 for ACQ-7, ACT and AQLQ scores, respectively. Boxes represent median and interquartile range (IQR); whiskers represent minimum and maximum values. If there are outliers, whiskers are then by default 1.5×IQR.