CO2 response testing, still crazy after all these years.

I’ve had several exercise tests come across my desk lately where the patient had an elevated Ve-VCO2 slope. An elevated Ve-VCO2 slope during exercise is usually taken as a sign of pulmonary vascular disease however these patients had a normal DLCO so I have been reviewing the literature to try to get a better understanding of what the Ve-VCO2 slope is trying to tell us in these cases.

Although the majority of the literature on Ve-VCO2 response indicates that it is likely due to some form of pulmonary vascular disease (micro-fracturing of the pulmonary capillaries, increased pulmonary vascular resistance, V-Q mismatching) there are some investigators that feel that in some individuals it is more likely due to an increased ventilatory chemosensitivity to CO2. It has been over 25 years since I last performed a CO2 response test and at that time there was no particular consensus on how the test should be performed. Since chemosensitivity may have a distinct bearing on Ve-VCO2 slope I thought it would be a good idea to also review the literature on CO2 response and see what has happened in the meantime.

After spending some time reading a couple dozen research papers it doesn’t seem as if much has changed. The CO2 Response landscape remains without an overall consensus and if anything has become more confusing, not less. There are two major approaches to measuring CO2 response and each of these approaches has at least two ways of analyzing the test data.

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What does Peak Flow have to do with back-extrapolation?

Well, everything, actually. Surprisingly enough they are intimately related to each other.

One of my current projects is to develop specifications for computer software designed to analyze spirometry results. Determining the “real” start of a spirometry effort using back-extrapolation is a critical part of accurately measuring FEV1 and all other timed values (FEV3, FEV6, TET). The ATS-ERS statement on spirometry includes recommendations for the back-extrapolation process, but this explanation shows its roots in old-school volume-time oriented spirometry:

“For manual measurements, the back extrapolation method traces back from the steepest slope on the volume-time curve. For computerized back extrapolation it is recommended that the largest slope averaged over an 80-ms period is used.” 

ATS back extrapolation

From: ATS/ERS Standardisation of Spirometry, page 324.

I was thinking about how to write software to do this when it occurred to me that the steepest slope of the volume-time curve is by definition the peak flow. This is probably something like re-inventing the wheel because I am sure this has been noticed before (probably by all the programmers that have done this before me) but I’ve never seen it written up this way.

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