FEV₁/FEV₆ May Misdiagnose Patients With COPD

To the Editor:

We read with great interest the paper by Wang et al¹ proposing the use of FEV₁/FEV₆ as a reliable index for diagnosing COPD. Although the utility of FEV₆ has been demonstrated in some clinical scenarios,^2,3 we are concerned that the current study reaches conclusions that may result in the misclassification of patients as having COPD.

Our main cause for concern is the authors' use of the fixed ratio of FEV₁/FVC <0.70 as the standard against which the FEV₁/FEV₆ was compared. The authors recognize the potential problem of using the fixed cutoff to diagnose COPD, but this is of extreme importance in preventing misdiagnosis of COPD in older adults. Although there has been ongoing debate regarding the use of the fixed ratio, numerous studies have identified the problem of misclassification of older adults when the natural history of the decline in FEV₁ and FVC are not taken into account.^4–6 In addition, this paper used an FEV₁ <80% predicted in conjunction with the faulty fixed ratio to define subjects who had COPD. For this purpose, the study used a predicted set derived from whites rather than from the local population. Defining the presence of moderate airway obstruction as an FEV₁ <80% has been shown to misclassify subjects because of age, sex, and ethnicity biases, depending on the reference equations chosen.⁷ Kim et al⁸ showed that applying the third National Health and Nutrition Examination Survey (NHANES III) FEV₁ reference equations to Asians misclassified 30% of never-smokers when compared with an ethnically specific equation.

In the data presented, there was very little difference between the mean values for FEV₆ and FVC in males and females; however, there were no comparisons made for the youngest or oldest subjects. The exhalation times associated with FVC were not reported, although the authors reported that “obtaining 99% of the FVC in 6.64 s is sufficient.” They also report that FEV₆ was obtained in >80% of the tests, suggesting that up to 20% of the tests did not achieve the 6 s criterion. It is therefore not surprising that this study found significant agreement between the FEV₁/FEV₆ and the FEV₁/FVC with likelihood ratios approaching 100% for a fixed cutoff of 0.72.

We compared the FEV₁ and FEV₁/FVC (predicted and lower limits of normal) for males and females at age 80 y, since older patients are at a higher risk of being misdiagnosed with COPD. Table 1 lists these comparisons based on the Knudson 1983 reference equations⁹ along with those from the Global Lungs Initiative¹⁰ published in 2012. (Predicted and lower limits of normal for FEV₆ are not available for Knudson⁹ or the Global Lungs Initiative.¹⁰) Since Shaanxi province lies near the dividing line used for Northeast Asians and Southeast Asians in the Global Lungs Initiative, we included predicted values based on both groups. Except for Northeast Asian males, the lower limits of normal for FEV₁ are all <80% of the predicted, and the lower limits of normal for the FEV₁/FVC are all <0.70. The authors' methodology indicates a high incidence of COPD in female never-smokers. For example, if the 24 current and former female smokers in the authors' study¹ are assumed to have COPD, 53 (11%) never-smokers would be diagnosed with COPD using their methodology. The prevalence of COPD in female never-smokers in China has been shown to be ∼5% when using the lower limit of normal for FEV₁/FVC.¹¹

The American Thoracic Society/European Respiratory Society guidelines recommend using the lower limit of normal for both the FEV₁/FVC and FEV₁ for interpretation of spirometry.¹² Using fixed cutoffs for the ratio, whether FEV₁/FVC or FEV₁/FEV₆, risks misclassifying older adults. In addition, grading severity using 80% of the predicted FEV₁ as the lower limit of normal introduces age, sex, and ethnicity biases as well. Most modern spirometers can report lower limits of normal using up-to-date reference equations. Spirometric determination of airway obstruction is just one tool in assessing whether a patient has COPD. Primary care practitioners who encounter patients with signs and symptoms suggesting COPD should apply statistically valid methods when interpreting spirometry data.

• Copyright © 2016 by Daedalus Enterprises