PC₂₀ versus PD₂₀: Why Change a Scientifically Well-Established and Clinically Relevant Test?

To the Editor:

We read with interest the article by Coates and colleagues (1). The authors elaborate on the recently published “ERS Technical Standard on Bronchial Challenge Testing: General Considerations and Performance of Methacholine Challenge Tests” (2) and suggest that PD₂₀ (the provocative dose of methacholine [MCh] that results in a 20% fall in FEV₁) should replace PC₂₀ (the provocative concentration of MCh that results in a 20% fall in FEV₁). We have the following comments:

• 1.MCh dose versus concentration: Based on the suggested new standard for using dose instead of concentration of MCh to evaluate and report airway reactivity, the authors recommended using a mechanical breath simulator to collect MCh on a filter representing the mouth and calculate the deposited dose. Alternatively, they suggest that nebulizer manufacturers should provide those who perform MCh challenge tests with information regarding the aerosol output characteristics of their nebulizer. No mechanism is suggested regarding how to make this happen, and pulmonary function testing (PFT) laboratories are left with considerable confusion as to how to proceed.
• 2.Nebulizer replication studies: The authors cite recent articles comparing the original Wright nebulizers with newer nebulizers (specifically the SOLO Aerogen vibrating mesh device and the Aero Eclipse). These papers showed that PD₂₀, but not PC₂₀, was independent of the delivery system used. However, these nebulizers are infrequently used in most PFT laboratories. We wonder if it is not essential to replicate their findings against other commonly used nebulizers.
• 3.Nebulizer cost and durability: Vibrating mesh nebulizers are expensive and have well-known problems involving mesh clogging and circuit issues. Also, their mass median aerodynamic diameter is considerably larger than that of the Wright small-volume nebulizer.

We wonder how replacing concentration × 2 minutes at each doubling concentration with the hyperprecision “dose” would improve our ability to provide more clinically relevant answers. In particular, we have found no studies that showed this change to be of sufficiently increased benefit to offset the considerable increase in cost and difficulty of obtaining similar data in virtually all current PFT labs.

If the authors’ recommendations are adopted before such evidence is available, a widely used important test for airway hyperreactivity would become a test that is exclusive to a relatively small number of academic PFT labs in large centers, thus inconveniencing patients in smaller communities who must travel, often many miles, to the centers that are able to implement the change!