RT Journal Article SR Electronic T1 Methacholine Challenges: comparison of different tidal breathing challenge methods JF ERJ Open Research JO erjor FD European Respiratory Society SP 00282-2021 DO 10.1183/23120541.00282-2021 A1 James Dean A1 Natalie Jackson A1 Brett Keidel-Morgan A1 Daniel Hamer A1 Dave Singh YR 2021 UL http://openres.ersjournals.com/content/early/2021/08/12/23120541.00282-2021.abstract AB Tidal breathing methacholine challenges are now recommended by guidelines, to avoid the bronchoprotective effects of deep inhalation. This study compared different tidal breathing methacholine challenge methods, assessed the agreement between tidal dosimetric and continuous output challenges, and challenge repeatability with different methods. 15 asthma patients performed dosimetric challenges and a continuous output breath actuated challenge, all at least 3 days apart. All subjects had a pre-bronchodilator forced expired volume in 1 s (FEV1) ≥65% predicted, and PD20 <1.2 mg. Of the dosimetric challenges, one method increased methacholine concentration (standard dosimetric challenge), and one adjusted nebuliser output time to increase dose (adjusted dosimetric challenge). The adjusted dosimetric and continuous output challenges were performed twice on separate days to assess for repeatability. All challenges were matched for dose at each dose step. The mean PD20 ratio of the standard dosimetric challenge to the adjusted dosimetric challenge was 0.90 (CI: 0.66–1.23; p=0.49), and intraclass correlation coefficient (ICC)=0.82. Repeated adjusted dosimetric challenges had an ICC=0.62 for PD20. Repeated continuous output challenges had an ICC =0.74 for PD20. The adjusted dosimetric and continuous output challenges correlated (r=0.69, p=0.0043; ICC: 0.65), but PD20 was higher for the adjusted dosimetric challenge (mean PD20 ratio=2.31; CI: 1.57–3.40; p=0.0004). Tidal dosimetric methacholine challenge using adjustment of nebuliser output produces results with good repeatability. The results of this adjusted dosimetric method differed from the continuous output method, underscoring that the results of different methacholine challenge methodologies may not be directly comparable.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.JD; the author declares that they have no competing interests.NJ; the author declares that they have no competing interests.BKM; the author declares that they have no competing interests.DH; the author declares that they have no competing interests.DS has received sponsorship to attend international meetings, honoraria for lecturing or attending advisory boards and research grants from Aerogen, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, CSL Behring, Epiendo, Genentech, GlaxoSmithKline, Glenmark, Gossamerbio, Kinaset, Menarini, Novartis, Pulmatrix, Sanofi, Teva, Theravance and Verona.