Is forced expiratory volume in six seconds a valid alternative to forced vital capacity?

To the Editors:

We have read with interest the article by Hansen et al. 1 in a recent issue of the European Respiratory Journal, stating that the use of forced expiratory volume in six seconds (FEV₆) reduces the sensitivity of obstructive lung disease detection. Their study population of 3,515 current smokers, with a 17.5% prevalence of obstruction, found a sensitivity of only 76.8% and a specificity of 98.2% when comparing FEV₁/FEV₆ with FEV₁/forced vital capacity (FVC) below their respective 95% lower limits of normal (LLN). Based on this low sensitivity, Hansen et al. 1 concluded that FEV₁/FEV₆ is less reliable than FEV₁/FVC as a screening parameter for the detection of obstruction.

The lower sensitivity obtained by Hansen et al. 1 with respect to previous studies, in which sensitivity typically ranged between 92–95% 2–5, was attributed to differences in study population. Hansen et al. 1 contended that previous studies comparing the performance of FEV₆ and FVC in detecting obstruction 3–5 had too few mildly obstructive and normal subjects. However, Hansen et al. 1 cite another study, by Akpinar-Elci et al. 2, which showed 92% sensitivity and 98% specificity for the detection of obstruction; this is despite a prevalence of obstruction of only 14.5% in 1,139 nonpatients in a workplace setting. In general, these participants are healthy, and obviously median spirometry values are closer to the LLN than for groups of symptomatic patients referred to a pulmonary function laboratory.

In the study by Hansen et al. 1, the “minimal obstructed” group represents the largest group (59%) of all subjects considered obstructive. Minimal obstruction was defined as FEV₁/FVC and/or FEV₃/FVC below the 95% LLN, combined with FEV₁ between 80–120% predicted. However, the rationale for using this criterion of possible morbidity only holds in populations with respiratory diseases; for healthy subjects, the meaning of a low FEV₁/FVC with a normal FEV₁ is unclear 6. The proportion of subjects with respiratory diseases studied by Hansen et al. 1 is not explicitly mentioned, but is likely to be small. Therefore, a substantial proportion of subjects labelled with “minimal obstruction” could be normal. Figure 3 in the paper by Hansen et al. 1 clearly shows that the number of false negatives in the “minimal obstructed” group represents more than half of all false negatives; this could introduce a serious bias to the results.

In previous studies by us and others 2–5, most of the discordant cases had FEV₁/FVC and FEV₁/FEV₆ values close to their respective LLN, i.e. in a range where diagnosis of obstruction is questionable. Values close to the LLN can be assumed from table 5 in the paper by Hansen et al. 1, because the mean deviation is only 2.64%. Considering the day-to-day variability of spirometry, the minimally obstructive subjects could easily shift between the normal and obstruction categories on different testing occasions. Therefore, one could question the clinical relevance of detecting borderline obstruction.

In addition, we should be careful when comparing two diagnostic tests with each other in the absence of a true gold standard. In reality, FEV₁/FVC is more of a “de facto standard”, and by using it as a gold standard for the detection of obstruction, FEV₆ can never be shown to outperform FVC in the denominator of this ratio to better reflect true airway obstruction. This is particularly true when studying a population with FEV₁/FVC and FEV₁/FEV₆ values close to their respective LLN.

The increasing difference between FEV₆ and FVC volumes with increasing age and severity of obstruction is probably irrelevant in terms of identifying airway obstruction, because the deficit in airflow will be present long before 6 s. Moreover, spirometric detection of airway obstruction is a matter of categorisation and not of quantitative agreement. As long as FEV₁/FVC and FEV₁/FEV₆ values stay on the same side of their respective cut-off points the absolute values of these ratios are of little clinical importance, because once obstruction is established, the severity of this obstruction will be evaluated using FEV₁ 6.

In conclusion, the main advantage of using forced expiratory volume in six seconds values in primary care is to assist with the quality of testing. Forced expiratory volume in six seconds is more reliable than forced vital capacity, and using the 6 s cut-off eliminates the need for prolonged exhalations, eliminates the need to meet reproducible forced vital capacity values, and is an easier test for patients to perform. In practice, the advantages of using forced expiratory volume in six seconds values may well more than compensate for the small differences in classification of patients′ results that are clustered around the lower limits of normal.