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(Chest. 2000;118:1371-1377.)
© 2000 American College of Chest Physicians

Different Response to Doubling and Fourfold Dose Increases in Methacholine Provocation Tests in Healthy Subjects*

Britt-Marie Sundblad, BSc; Per Malmberg, MD, PhD and Kjell Larsson, MD, PhD, FCCP

* From the Programme for Respiratory Health and Climate, National Institute for Working Life, Stockholm, Sweden.

Correspondence to: Britt-Marie Sundblad, BSc, Program for Respiratory Health and Climate, National Institute for Working Life, S-112 79 Stockholm, Sweden; e-mail: Britt-Marie.Sundblad{at}niwl.se

Rationale: In a modified methacholine provocation test that was used to study changes in airway responsiveness to occupational irritants or sensitizers in healthy subjects, two protocols were used: a long protocol (doubling methacholine concentrations between dose steps) or a short protocol (fourfold increases in concentration). This modified methacholine provocation allows measurements of the provocative dose causing 20% decrease in FEV1 (PD20) in a high proportion of a normal population.

Methods: The distribution of PD20 was investigated in healthy nonatopic men without history of allergy or asthma symptoms using the long protocol (n = 101) or the short protocol (n = 309). In addition, 30 healthy subjects underwent methacholine provocation tests using both protocols.

Results: PD20 was defined in 79% of subjects with the long protocol and in 48% of subjects with the short protocol. The provocative concentration of methacholine causing a 20% decline in FEV1 (PC20) and PD20 were significantly lower using the long protocol: long-protocol PC20 (median [25th to 75th percentile]), 19.9 mg/mL (3.9 to > 32 mg/mL) compared with short-protocol PC20, > 32 mg/mL (8.7 to >32 mg/mL; p < 0.0001); long-protocol PD20, 4.2 mg (1.6 to 20 mg) compared with short-protocol PD20, > 13.7 (2.6 to > 13.7 mg; p = 0.006). The differences in PD20 using short and long protocols were confirmed in a randomized trial of 30 healthy subjects tested with both protocols.

Conclusion: Using doubling concentrations, PC20 and PD20 could be defined in a higher proportion of healthy subjects than a protocol using fourfold dose increases. Furthermore, the doubling protocol results in a PD20 estimate that is less than half the value obtained when using a protocol with fourfold concentrations between dose steps. The difference remains, whether the methacholine effect is regarded as cumulative or noncumulative. The explanation for the difference between the protocols is unclear.

Key Words: bronchial responsiveness • dose step • methacholine provocation test






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