What’s normal about the FEV1/FVC ratio?

The FEV1/FVC ratio is used to estimate the presence and degree of airway obstruction. For well over thirty years my lab has used an FEV1/FVC ratio of 95% of predicted as the cutoff for normalcy. This value (carved onto a stone tablet by the way) had been brought to the lab by a founding physician who had come to the department from the NIH in the 1970′s. Since the software and hardware upgrade this summer our PFT Lab has switched to the NHANES III spirometry reference equations but we have so far resisted changing our 95% cutoff to the lower limit of normal (LLN). This is due in part to inertia but also in part to a mistrust in the concept of LLN. We have been steadily re-evaluating all of our testing criteria and have turned again to the FEV1/FVC ratio with the question as to whether our 95% cutoff is over-zealous or whether the LLN is too lax.

Strictly speaking LLN is a statistical concept. In the NHANES III study (and most others) it is computed as the mean predicted value minus 1.645 times the standard estimate of error. Unlike the reference equations for FVC and FEV1 which use both height and age as factors, the NHANES III reference equations for the FEV1/FVC ratio are derived solely from age. It is not clear to me this is completely correct and I have discussed some of the discrepancies between the NHANES III predicted FEV1/FVC ratio and height in a prior posting but it does make analyzing the LLN for the ratio easy.For adult, Caucasian males the reference equations are:

Predicted FEV1/FVC ratio = 88.066 – (0.2066 x age), LLN = 78.388 – (0.2066 x age)

This means the LLN for all ages and heights of adult white males is therefore equal to {78.388/88.066} or 89% of predicted. Calculated similarly, the LLN for the adults of all races and sexes also approximates 89% (range 88.3% to 89.9%).

Since the LLN is the bottom 5 percent of the observed FEV1/FVC ratios there is a high probability that these patients have some form of airway obstruction and a number of studies have shown a good correspondence between a FEV1/FVC ratio below the LLN and the symptoms and diagnosis of COPD. But a diagnosis of COPD does not necessarily rest on a FEV1/FVC ratio below the LLN. GOLD (Global Initiative for Chronic Obstructive Lung Disease) uses an observed (not percent predicted) FEV1/FVC ratio below 0.70 as a primary criteria for classifying COPD. Elderly patients in particular can have an observed FEV1/FVC ratio below 0.70 yet above the LLN and this has been used as a legitimate criticism of the GOLD criteria. At least one study however, has shown that there are elevated hospitalization and mortality rates due to respiratory causes in patients with airway obstruction by GOLD criteria but a FEV1/FVC ratio above the LLN.

I do not doubt that patients with a FEV1/FVC ratio below the LLN likely have significant airway obstruction that meets the criteria for COPD and I also do not doubt that being able to provide a definitive diagnosis of COPD is an important component in patient care. I think the main question however, when comparing the NHANES III LLN and our cutoff of 95% of predicted is whether airway obstruction needs to meet COPD criteria to be able to be classified as airway obstruction and I don’t think it does. Regardless of the level of severity assigned to it, the presence of COPD indicates that airway obstruction is already relatively advanced. What is needed is an evidence-based cutoff for normalcy that is clinically relevant for levels of obstruction below COPD and that, unfortunately, is not available.

The difficulty in creating an evidence-based cutoff is the same as that of creating the predicted values in the first place: what is normal? Population studies attempt to control this by selecting healthy, asymptomatic subjects. This does not mean however, that a subject that has not been hospitalized, is not on medication and appears healthy is actually “normal” and this has to be part of the reason why population studies show bell-shaped curves.

Selecting a cutoff is going to be a subjective judgment that, at least presently, cannot be backed by objective evidence. My personal opinion is that the NHANES III LLN is too conservative. It is based on a statistical concept that is likely valid for a wide range of biological systems but it is far from clear to me that statistical significance is the same as clinical significance. I also think that our 95% cutoff is closer to the truth but at the same time I am well aware that I am biased by the fact that this is what I’ve used for a good part of my professional career and am likely to see the evidence that supports it, not the evidence that argues against.

It should also be remembered that the FEV1/FVC ratio is not the sole factor in diagnosing airway obstruction. A 10% decrease (or even increase) in a patient’s FEV1 from one visit to another would be considered to be a significant change and clinically would likely be taken as an indication of underlying airway obstruction. A patient that had baseline spirometry that was WNL but showed a significant increase in FEV1 following a bronchodilator or a significant decrease in FEV1 during a methacholine challenge would also likely to be considered to have airway obstruction or at least the clinical potential for it. Finally, there is a small fraction of asthmatics that show a symmetrically decreased FVC and FEV1 with a normal FEV1/FVC ratio (and often a normal peak flow!) during exacerbations who in a sense aren’t even on the radar in this discussion.

I think that an important question at this point is why do we need and use cutoffs in the first place? Isn’t it a bit silly knowing full well the myriad problems involved getting an accurate FEV1/FVC ratio in the first place that we would consider a value a tiny fraction below a cutoff to be abnormal and another value a tiny fraction above the cutoff to be normal? The reality is that for an FEV1/FVC ratio between 100% of predicted and say, the LLN, there is a continuum of probabilities that a patient does or does not have airway obstruction. The other reality is that humans do not do well with shades of gray and prefer black and white.

So choose a cutoff that makes clinical sense to you but at the same time remember that whatever you choose is a line in the sand and that the FEV1/FVC ratio, whatever the cutoff, is not the sole evidence for airway obstruction.

 

References:
Brusasco V, Crapo R, Viegi G, et al. ATS/ERS Task Force: Standardisation of lung function testing. Interpretive strategies for lung function tests. Eur Respir J 2005; 26: 948-968.

Celli BR, Halbert RJ, Isonaku S, Schau B. Population impact of different definitions of airway obstruction. Eur Respir J 2003; 22: 268-273.

Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general U.S. Population. Am J Respir Crit Care Med 1999; 159: 179-187.

Mannino DM, Buist SA, Vollmer WM. Chronic obstructive pulmonary disease in the older adult: what defines abnormal lung function. Thorax 2007; 62: 237-241.

Mannino DM, Diaz-Guzman E. Interpreting lung function data using 80% predicted and fixed thresholds identifies patients at increased risk of mortality. Chest 2012; 141: 73-80.

Stanojevic S, Wade A, Stocks J, Hankinson J, Coates AL, Rosenthal M, Corey M, Lebecque P, Cole TJ. Reference ranges for spirometry across all ages: a new approach. Amer J Respir Crit Care Med 2008; 177: 253-260.

Swanney MP, Ruppel G, Enright PL, Pedersen OF, Crapo RO, Miller MR, Jensen RL, Falaschetti E, Schouten JP, Hankinson JL, Stocks J, Quanjer PH. Using the lower limit of normal for the FEV1/FVC ratio reduces misclassification of airway obstruction. Thorax 2008; 63: 1046-1051.

Vaz Fragoso CA, Concato J, McAvay G, Van Ness PH, Rochester CL, Yaggi HK, Gill TM. The ratio of FEV1 to FVC as a basis for establishing Chronic Obstructive Pulmonary Disease. Amer J Respir Crit Care Med 2010; 181: 446-451.

Vollmer WM, B Gislason, Burney P, Enright PL, Gulsivik A, Kocabas A, Buist AS. Comparison of spirometry criteria for the diagnosis of COPD: results from the BOLD study. Eur Respir J 2009; 34: 588-597.

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