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

From the Authors:

We thank Drs. Amirav and Newhouse for their letter and interest in our editorial on characterizing nebulizer performance for methacholine challenge tests (1). We respectfully disagree with the premise of their letter. We believe that the science and clinical relevance of the previous 1999 guidelines need to be updated. The main problem is that the English-Wright nebulizer is no longer widely available, and if pulmonary function labs were to use as a substitute currently available nebulizers that have much higher aerosol output than the English-Wright nebulizer, every concentration step would deliver a much higher stimulus dose than intended by the 1999 guidelines.

Regarding the need to calculate a delivered methacholine dose, the authors state that we offered no mechanism for how to compel nebulizer manufacturers to characterize the performance of their nebulizer. This was, in fact, the main purpose of our letter: to call out to the manufacturers to provide this essential service. We acknowledged that this would be beyond the capabilities of most pulmonary function labs, but it should be very much achievable by nebulizer manufacturers and aerosol scientists. Our hope was that this letter would emphasize to manufacturers that the American Thoracic Society and European Respiratory Society are counting on them to help the pulmonary function lab community.

The authors also suggest that the data cited regarding the comparison of the English-Wright nebulizer with other nebulizers should include information about other commonly used nebulizers. We certainly agree, and remain hopeful that such data will be forthcoming. The data we cited, including those obtained with a vibrating mesh nebulizer, were simply meant as examples of how dose, not concentration, should be the common unit of measurement across devices.

Regarding the point made about how the current recommendations might not provide more clinically relevant information, we would like to emphasize that at present there is significant variability in the way methacholine challenge tests are performed, resulting in the potential for imprecision and diagnostic error. No other diagnostic test in modern medicine would allow such a lack of rigorous standards or interlaboratory variation. With better defined and updated methodology, physicians can now have more confidence in the results of testing.