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(Chest. 2005;128:1248-1251.)
© 2005 American College of Chest Physicians

Lack of Tachyphylaxis to Methacholine at 24 h*

Donald W. Cockcroft, BSc, MD, FCCP and Beth E. Davis, BSc

Department of Medicine, Division of Respirology, Critical Care, and Sleep Medicine, University of Saskatchewan, Royal University Hospital, Saskatoon, SK, Canada.

Correspondence to: Donald W. Cockcroft, BSc, MD, FCCP, Royal University Hospital, Division of Respirology, Critical Care and Sleep Medicine, 103 Hospital Dr, Ellis Hall, Fifth Floor, Saskatoon, SK, S7N 0W8 Canada; e-mail: cockcroft{at}sask.usask.ca

Objective: To examine for tachyphylaxis to methacholine at 24 h and to use these data to assess the repeatability of the provocative concentration of a substance causing a 20% fall in FEV1 (PC20) for methacholine and to obtain statistical power calculations.

Design: Retrospective review of four double-blind, placebo-controlled studies with two methacholine PC20 values measured at 24-h intervals.

Setting: Tertiary university hospital bronchoprovocation laboratory.

Patients: Thirty-two subjects with mild-to-moderate well-controlled asthma.

Interventions: The placebo arms of the four studies were examined.

Measurements: Methacholine PC20 (using 2-min tidal breathing method) initial determination and repeat testing at 24 h.

Results: The geometric mean PC20 values were 1.57 mg/mL (95% confidence interval [CI], 1.0 to 2.4 mg/mL) and 1.62 mg/mL (95% CI, 1.0 to 2.6 mg/mL NSD; p = 0.64). The mean absolute difference between the two measurements was < 0.4 doubling concentrations, and 31 of 32 measurements had both values within one doubling concentration. These data provide a statistical power of 92% for 10 subjects to show a one-half concentration {Delta}PC20 and a mean power of 99 ± 1% to show a one-concentration {Delta}PC20.

Conclusions: There is no evidence for methacholine tachyphylaxis at 24 h in subjects with asthma. At 24 h, the average repeatability was well within a one-half concentration change, and individually 31 of 32 measurements (97%) were within one doubling concentration.

Key Words: methacholine • power calculation • repeatability • tachyphylaxis • tolerance






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