Recommended Changes to Methacholine Challenge Testing May Be Difficult to Apply for Most Labs

Aaron B. Holley, MD


March 15, 2019

The guidelines[1] on using methacholine challenge testing (MCCT) to evaluate for airway hyperresponsiveness (AHR), published in 2000, provided a figure that allowed clinicians to calculate posttest probability of AHR based on pretest probability and the methacholine concentration at which the forced expiratory volume in 1 second (FEV1) drops below 20% of its baseline (provocative concentration, PC20).

I have worked at academic pulmonary centers my entire career, and this figure has served as the basis for all teaching on MCCT and interpretation of results.

But a lot has changed since 2000.

Owing to the proliferation of available nebulizers and dosimeters and to differing protocols, PC20 can no longer be used to establish AHR.[2,3] When the MCCT guidelines came out in 2000, PC20 was considered a reasonable surrogate for PD20, the provocative dose of methacholine at which FEV1 drops below 20% of its baseline. The updated MCCT guidelines,[2] published in the European literature and endorsed by the American Thoracic Society (ATS), recommend using PD20 to ensure accuracy and equivalency between devices, protocols, and labs.

Using PD20 instead of PC20 has physiologic and practical implications that affect the patients, providers, and industry. PC20 is easy to calculate because the concentration of medicine delivered to the patient is known at all points during the test. To calculate PD20, one needs to know the effective dose the patient receives at each concentration. This varies by protocol, speed, and nebulizer specifications. In short, it is difficult to calculate.

Unfortunately, it is also now clear that PC20 is not a reasonable surrogate for PD20. Unless all labs start reporting PD20, there will be no way to accurately quantify AHR. Without knowing AHR, we cannot know if the patient has asthma.

There is a simple fix for this.

The authors of the updated MCCT guidelines recently wrote an editorial calling on the medical industry to report precise nebulizer specifications for their devices.[3] This would include establishing the effective doses received by the patient at each step in their protocol so that PD20 can easily be calculated. That way, the burden would not be on labs across the country but rather on the industry. This information is provided by the manufacturer of the nebulizer we use at our lab, and we have been calculating PD20 since 2009. It is not hard when the manufacturer provides you with the required information.

Change is never easy, though-and this editorial was received with some trepidation.[4]

PC20 has been used for almost 20 years now, and PD20 is hard to establish if the manufacturer does not do it for you. Those lung function labs that use nebulizers made by manufacturers that do not provide the data needed to calculate PD20 are left to figure out device specifications on their own. Outside large medical centers, this is unlikely to happen. These labs can switch to a nebulizer where specifications are provided, but this is not easy either. It is expensive, and most medical devices come with service contracts.

The bottom line is that if you do not use PD20, you cannot quantify AHR.

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