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.

The FEF25-75 (aka MMEF) was originally proposed as way to determine the presence of small airways disease but it has since been shown to be an unreliable indicator. Most of the pulmonary physicians I work with have expressed doubt that there is such a thing as small airways disease but that doesn’t mean that some patients don’t have mild airway obstruction that is not evident when assessed solely by the FEV1/FVC ratio.

One of the ways to think about what happens during an exhalation is a concept called time constants. It is all too easy of to think of the lung as a single unit when of course it actually has five lobes, tens of thousands of acini and millions of alveoli. Airway obstruction does not occur homogeneously across the lung, but in different amounts in different areas. An area of the lung that empties quickly has a short time-constant. One that empties slowly, because of airway narrowing or a loss of elasticity, has a long time-constant.

Even the healthiest lungs will have a few areas with long time constants, but when the lungs as a whole have a short time-constant then they will empty quickly and this will be shown by a normal flow-volume loop and volume time curve. As lung disease progresses the number of lung units with a long time-constant start to predominate and the exhalation time increases. This is shown by a progressively more obstructive pattern on the flow-volume loop and volume-time curve.

It is the terminal expiratory flow rates, those that occur after the FEV1, that are affected earliest when the number of lung units with long time-constants increases. It is for this reason that a number of investigators have proposed using the FEV3/FVC ratio both as a substitute for the FEF25-75 and as an indicator of early and mild airway obstruction.

Normal values for the FEV3 and FEV3/FVC ratio were first proposed several decades ago but more recently Hanson et al re-analyzed the NHANESIII database and developed a set of Adult reference equations for the FEV3/FVC ratio:

Studies have indicated that over 10% of patients with a normal FEV1/FVC ratio have an abnormal FEV3/FVC ratio. Investigators have also shown that these patients tend to show an overall pattern of mild airway obstruction. The FEV1 and FEV1/FVC ratio, although within normal limits, tends to be at the lower limits of normal. The RV and RV/TLC ratio tends to be mildly elevated and the DLCO tends to be at or slightly below the normal cutoff.

My own experience with the FEV3/FVC ratio is somewhat equivocal because during a trial period several years ago I rarely saw a patient with a reduced FEV3/FVC ratio that didn’t also have a reduced FEV1/FVC ratio. In retrospect however, it is evident I was comparing apples to oranges. Specifically, my lab was not using the NHANESIII reference equations at that time and we use an FEV1/FVC ratio that is 95% of predicted as the cutoff for normalacy. The NHANESIII LLN for the FEV1/FVC ratio is roughly 89% of the predicted FEV1/FVC ratio which means that if we used the LLN we would have characterized fewer patients as being obstructed and I would likely have found more patients that met the criteria I was looking for.

During the trial period several years ago I was also unable to create any interest in the use of the FEV3/FVC ratio among the department’s physicians but this is likely due at least in part to the fact that only one significant paper on the use of the FEV3/FVC ratio existed at that time. Since then several more papers have been published, each of which has expanded and concurred with the original premise that a reduced FEV3/FVC ratio is an indicator of airway obstruction.

I think the FEV3/FVC ratio concept shows value but I also need to point out that it suffers from the same limitation that the FEV1/FVC ratio does which is that it depends on the accuracy of the FVC. For this reason I would like to see a study that looked at the FEV3/FEV6 ratio. I suspect that because the FEV6 is also a function of terminal flow rates that any decreases in the FEV3/FEV6 ratio may be too subtle to be of value but it would be useful to know nonetheless.

I would also like to see one or more longitudinal studies as well. This would help make it clearer whether the FEV3/FVC ratio is truly an indicator of early airway obstruction or not.

The FEV3/FVC ratio looks to be a useful adjunct towards assessing airway obstruction. It is hard to find fault with the premise that it is more sensitive to reductions in terminal expiratory flow than the FEV1/FVC ratio and therefore more sensitive to early or mild airway obstruction as well. Whether or not there is such a thing as small airways disease I think the FEV3/FVC ratio is clearly superior to the FEF25-75 and should replace that value both on reports and in the assessment process.

References:

Hansen JE, Sun X-G, Wasserman K. Discriminating measures and normal values for expiratory obstruction. Chest 2006; 129: 369-377.

Lam DCL, Fong DYT, Yu WC, Ko FWS, Lau ACW, Chan JWM, Choo KL, Mok TYW, Tam CY, Ip MSM, Chan-Yeung MM. FEV3, FEV6 and their derivatives for detecting airflow obstruction in adult Chinese. Int J Tuberc Lung Dis 2012; 16(5): 681-686.

Lutfi MF. Acceptable alternatives for forced vital capacity in the spirometric diagnosis of bronchial asthma. Int J Appl Basic Med Res 2011 1(1): 20-23.

Mehrparvar H, Rahimian M, Mirmohammadi SJ, Gheidi A, Mostaghaci M, Lotfi MH, Comparison of FEV3/FEV6, FEV1/FVC3 and FEV1/FEV6 with usual spirometric indices. Respirology 2012; 17: 541-546.

Morris ZQ, Coz A, Starosta D. An isolated reduction of the FEV3/FVC ratio is an indicator of mild lung injury. Chest 2013; 144(4): 1117-1123.

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