The lungs are the gas exchange organ of the body. The mechanical aspects of the lung, which do of course have a bearing on gas exchange, can be assessed by spirometry and lung volume tests but for a complete assessment of an individual’s lung function a diffusing capacity test (DLCO) must be performed as well. The actual gas exchange rate at any moment can be highly variable and depends on a number of factors such as cardiac output, pulmonary capillary blood volume and ventilation-perfusion matching that are difficult to measure. For this reason the diffusing capacity test, more so perhaps than any other pulmonary function test, must be performed in a highly standardized way in order to produce results that can be meaningfully trended over time and meaningfully compared to other individuals.

One of the recognized abnormalities of a flow-volume loop is a sawtooth profile due to flow oscillations that are superimposed on either the maximal expiratory or inspiratory flow curve, or the tidal loop. Sawtooth pattern on a flow-volume loop The sawtooth pattern occurs in only a small fraction of patients but it is quite noticeable when you see it. Estimates of the number of individuals with flow oscillation range from 1.4% to 13.4% with the higher estimates being observed primarily with inspiratory loops. Since many spirometry efforts are concentrated solely on exhalation this means that it may frequently go unrecognized. Recently, I had several reports with distinct sawtooth flow-volume loops come across my desk within a short time period and for this reason thought it might be interesting to re-visit this old subject. I call it old only because most of the research on sawtooth profiles was done in the 1970’s and 1980’s and not much has been published since then.

I had mentioned previously that my PFT Lab has been questioned why the percent predicted Residual Volume (RV) measurements on some research patients were coming out so much lower at my lab than at some other PFT Labs. At that time the researchers had not shared the results they had from these patients so we could only speculate that either our RV’s were actually lower or that the predicted RV values used by the other PFT Labs were different than ours. We finally got a copy of the PFT report for one of these patients and it turns out that both answers were correct.

I’ve noticed for a while that there has often been more variance between DLCO tests than I’d like to see. Some of this is of course attributable to differences in the way the patient performs each test. I am not overly surprised to see tests with different inspired volumes, different breath-holding times, different inspiratory times etc. etc. produce different results (in fact I am surprised that so many tests that have been performed differently frequently end up with almost identical results).

The plethysmographic technique for measuring lung volumes determines FRC first and then uses a slow vital capacity maneuver to calculate TLC and RV. FRC is defined as the volume of the lung at the end of a normal exhalation. The two components of the SVC maneuver that are used to calculate TLC and RV are the Inspiratory Capacity (IC) and the Expiratory Reserve Volume (ERV) and they too are measured relative to FRC. It would therefore seem to be important to have an accurate notion as to where FRC is in relation to TLC and RV when measuring lung volumes.

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.

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:

A physician associated with my PFT lab has become an investigator for a device study intended for patients with severe COPD. One of the major criteria for patients to be able to enroll in this study is a severely elevated Residual Volume (RV). Patients who have met this criteria at other PFT labs in New England have been referred to this study but when they have been re-tested in my lab their Residual Volumes are coming out lower and almost none of these patient have met this criteria. We have been asked why this is the case because they are now having difficulty finding patients that qualify for the study.

We’ve been aware of this particular issue for several years. My PFT lab has had some turnover lately and the newer staff aren’t familiar with this problem so it has re-appeared in some of the reports I have been reviewing. Our lab has a mix of flow-based and volume-based test systems. This problem is peculiar to only the volume-based systems that have a vertically mounted volume-displacement spirometer and is due in part to mechanical issues but also to some underlying assumptions made by the test software.

The FEV1 and FEV1/FVC ratio seems to have become the predominant, if not the sole factor for determining the presence of airway obstruction. It is true that a reduced FEV1/FVC ratio provides a strong and reliable signal for this purpose but its limitations have also been recognized for quite a while. The most obvious one is that the FEV1/FVC ratio will be falsely elevated when the FVC is underestimated. This is the primary factor driving the interest in FEV6 and the FEV1/FEV6 ratio. Less well appreciated is the fact that there are many causes and sites within the airways that can be involved in airway obstruction and that the focus on the FEV1/FVC ratio may cause certain forms of airway obstruction to be overlooked.