When is a change in FVC significant?

Most of the COPD patients that are seen in my lab tend to have little change in their FEV1 from visit to visit but their FVC often changes significantly. A change in FVC is usually related to how long a patient is able to exhale and this in turn is usually related to how well they are feeling at the time. This would seem to imply that a significant change in FVC, particularly for a patient with COPD, is, if not clinically significant, at least clinically important even when the FEV1 hasn’t changed.

The problem with this is that expiratory time can be affected by things other than how the patient is feeling. Dyspnea and fatigue, of course. As importantly some technicians are better at motivating patients than other technicians so it can also be related to which technician is performing their tests. Even when the same technician is involved however, there is no guarantee that the level of motivation or a patient’s response to that motivation will be the same.

So how do you know if a change in FVC clinically significant or not?

Recently a spirometry report from a patient with very severe COPD came across my desk. When comparing the results to those of the last visit I could see that there had been a small (but not significant) increase in FEV1 but at the same time there had been a large (and significant) increase in FVC.

Visit 1: Observed: %Predicted:
FVC (L): 1.28 36%
FEV1(L): 0.53 19%
FEV1/FVC: 41 53%
Visit 2: Observed: %Predicted:
FVC (L): 1.93 55%
FEV1(L): 0.60 22%
FEV1/FVC: 31 40%

Expiratory time is not on our trend report but this got me curious so I pulled up the test data from the patient’s previous visit. From this I could see that the expiratory time had also improved.

  Expiratory Time:
Visit 1: 11.1
Visit 2: 15.0

But it also seemed that the improvement in FVC was greater than the increase in expiratory time could account for. Even with all of the test data in front of me however, there is no easy way to be sure this was the case and for this reason I downloaded the raw spirometry test data for both visits into a spreadsheet. After aligning the volume-time curves (based on their peak flow and FEV1), I truncated the longer FVC so it matched the shorter one, calculated the difference between the two curves and then graphed the results:
delta-fvc-graph

It was immediately evident that there was an improvement in exhaled volume throughout exhalation. It was also evident that there was a steady increase in volume occurring throughout the exhalation. To some extent this can be also seen when the flow-volume loops from the two visits are overlayed.

delta-fvc-fvl-overlay

But I’d have to say it’s a lot more apparent on the volume-time curve than it is on the flow-volume loop.

Comparing the two volume-time curves seems to be a really good way to determine whether a change in FVC is clinically significant because it is easy to see whether the improvement is occurring simply because of an increase in expiratory time or because expiratory flow rates have improved. The problem is that this kind of comparison is not available in our lab software and in fact I don’t know of any lab software where it is possible. Unfortunately, because it takes a while to create the volume-time graphs it’s really not practical to do this on any kind of a routine basis.

However, the point of making the comparison was to see whether or not the change in FVC was only because there was a change in expiratory time. One measurement that provides a volume that is standardized by time and is routinely available in most test systems is the FEV6.

Note: The FEV6 and the FEV1/FEV6 ratio have been put forward as a replacement for the FVC and FEV1/FVC ratio a number of times but this has never seemed to gain any real traction. There are a number of reasons for this, partly because the FEV1/FEV6 ratio isn’t quite as sensitive as the FEV1/FVC ratio in assessing airway obstruction but I think this is more because the FEV6 is at its core an arbitrary value and does not reside in the same conceptual space as the FVC.

The FEV6 is measured long enough after the start of exhalation that even a relatively small change in expiratory flow rates over this interval can accumulate into a significant change in FEV6. When I looked at the FEV6 for the two visits, this was the case:

  FEV6:
Visit 1: 1.08 L
Visit 2: 1.33 L

Changes in FVC, particularly for patients with COPD, are often clinically significant. There are a number of confounding factors for FVC however, and for this reason a significant change in FVC is not necessarily clinically significant. This also means that the absence of a change in FVC does not mean that a significant change in expiratory flow rates hasn’t occurred. Since the FEV6 is not dependent on expiratory time in the same way that the FVC is, a change in FEV6 is going to be a more reliable indicator of changes in expiratory flow than the FVC.

This brings up an interesting question and that is occasionally when doing pre- and post-bronchodilator spirometry only the FVC increases significantly. I’ve discussed this previously and at the time I considered this to be an acceptable sign of a positive bronchodilator response even when it was largely due to an increase in expiratory time. I reviewed the example I had used at that time and found that the FEV6 had increased by 0.23 L (+14%) so it was still likely a positive bronchodilator response but at the moment I’m a lot more doubtful that an increase in expiratory time by itself, particularly if unaccompanied by a change in flow rates, should be considered a positive bronchodilator response.

The FEV1 and FEV1/FVC ratio are the primary indicators of airway obstruction and it is the lack of a significant change in FEV1 following an inhaled bronchodilator that is one of the definitions of COPD. A number of studies have shown however, that individuals with COPD often have a decrease in hyperinflation (increase in IC) and a decrease in dyspnea when using a bronchodilator. I am not aware of any study that has looked at the post-bronchodilator changes in FEV6 by itself (all the literature I’ve found has looked at the FEV1/FEV6 ratio and not the FEV6) and the FEV6 may well not be an indicator in the same way that IC can be. FVC does change over time in patients with COPD however, and the FEV6 is an easy way to determine whether or not these changes reflect a real change in expiratory airflow or are instead due to a confounding factor.

I would also note that there have frequently been attempts to measure the “terminal flows” (flow rates near RV) during a forced exhalation. Terminal flows are usually regarded as a reflection of flow through the smaller airways of the lung. Towards this end measurements such as the FEF75-85 and the FEV10% have been proposed but these values are highly dependent on the measured FVC and for this reason have poor repeatability and sensitivity. I’m not going to suggest that the FEV6 could be used as a measure of terminal flows, but it does seem that changes in the FEV6 would likely correlate with changes in terminal flows (at least in patients with COPD).

For all these reasons I’d recommend adding FEV6 to trend reports as a “truth check” on changes in FVC and as a starting point I don’t see any reason not to use what my lab considers to be a significant change in FEV1 and FVC (+/- 10% and +/- 0.20 L) when assessing changes in FEV6.

The FVC is defined as the maximal amount of air that can be exhaled after a maximal inhalation. The FVC is, of course, a function of an individual’s lung volume but for patients with lung disease, and in particular those with COPD, the FVC is also a function of expiratory time, dyspnea, fatigue and motivation as well as the amount of airway obstruction. For these reasons a change in FVC from one visit to another may or may not be clinically significant. A visual comparison of volume-time curves is able to show changes in flow rates during exhalation and for this reason can be used to determine if a change in FVC is due to a change in expiratory time or a change in expiratory flow rates (or both). Conversely, even when the FVC doesn’t change that doesn’t mean that expiratory flow rates haven’t changed and this is something that a comparison of the volume-time curves can also show. At the present time the option to compare volume-time curves from different patient visits isn’t available in any lab software. FEV6 however, is available and because it is measured at a specific time interval after the start of exhalation, changes in FEV6 will reflect changes in expiratory flow rates over that interval. Comparing the FEV6 from visit to visit can therefore help determine the cause of any change (or lack of change) in FVC.

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1 thought on “When is a change in FVC significant?

  1. Very good information. I see too many people following a strict 6 second guideline for office spirometry. I think you know that too. Poor training.

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