The methacholine bronchoprovocation test can be used to document hyperresponsiveness of the bronchi to a stimulus. Other compounds such as histamine or adenosine monophosphate can also be used as provocative agents.


Methacholine is a short-acting cholinergic drug. The bronchoconstriction it produces is transient and can be reversed with inhaled bronchodilator medications.


One endpoint for the bronchoprovocation test is the PD20, or provocation dose (PD) that produces a 20% decline from the patient's baseline FEV1.


Another endpoint that is used is the PC20, or the provocation concentration (PC) that produces a 20% decline from the patient's baseline FEV1.


The starting concentration of methacholine is prepared, typically 10 to 25 mg/mL. Sequential 50% dilutions (1 in 2) are then made. The number of different concentrations in the provocation test varies, but often is 7 concentrations. Each concentration is inhaled 5 times.


The data for the PD20 is plotted with the X-axis the methacholine dose and the Y-axis the FEV1. The value for the PD20 often must be extrapolated from the data. Since the doses are serial dilutions the data along the X-axis needs to be converted to logarithms.


The data is usually nonlinear. The simplest way to extrapolate the PD20 is to draw a line from the last dose of methacholine with an FEV1 above 80% of baseline FEV1 to the first dose of methacholine below 80% of baseline FEV1. A second or third order equation can be used to model the data but is more complex.


percent decrease in FEV1 at a given dose =

= ((FEV1 at baseline) - (FEV1 at dose)) / (FEV1 at baseline) * 100%


percent decrease in FEV1 from baseline =

= ((SLOPE) * LOG10(provocative doses)) + (INTERCEPT)



• LOG10, SLOPE and INTERCEPT are MS EXCEL functions.


metacholine dose at PD20 =

= 10^((20% - (INTERCEPT)) / (SLOPE))))



• The PD20 defining hyperresponsiveness varies with different authors.

• The higher the cutoff for the PD20 the more sensitive the test but the less specific. A lower cutoff is more specific but may miss mild hyperresponsiveness.


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