Classifying the Severity of COPD: Are We There Yet? Editorial for “Coton, S. et al. Severity of Airflow Obstruction in Chronic Obstructive Pulmonary Disease (COPD): Proposal for a New Classification”

The forced expiratory volume in one second (FEV₁) is the bedrock of objective measures of lung function. Spirometry, which for this discussion I will limit to measurement of FEV₁, Forced Vital Capacity (FVC) and the ratio of FEV₁/FVC, is, or should be, widely used for the objective assessment of wide range of disorders (1) and in clinic it can be used as general assessment of overall health or even screening (2, 3). The indices obtained from the spirogram, especially the FEV₁, have long been shown to be predictive or diagnostic of chronic obstructive pulmonary disease (COPD) (4), asthma, cystic fibrosis, lung cancer, and even heart disease (5). FEV₁ is predictive and prognostic of the decline in lung function in patients with COPD (6), risk of lung cancer in smokers with COPD (7) and even more remarkably, premature death (8–11). Indeed, one could easily come to the not unreasonable conclusion that the FEV₁ is perhaps the most useful measurement made in the clinic.

So why does the FEV₁, and by extension, FVC and FEV₁/FVC perform so well? It may be because the FEV₁ is basically similar to well-performing composite questionnaires like the Asthma Control Test or St. George Respiratory questionnaire. These questionnaires are composed of multiple questions that seek to capture various aspects or domains of the impact of disease on the patient. An ideal questionnaire captures all the varied aspects of the disease process in a way that the person affected can reliably assess and report a response. Spirometry, while developed in the 1800s, was advanced by consideration of the flow-volume relationship in 1958 (12) when Hyatt and Fry were the first to recognize that the shape of the curve held important information, especially when they considered flow-volume loops from patients with COPD. Since then, we have come to a better understanding of the flow and volume relationship, which informs our interpretation about decreases in FEV₁. Like the composite questionnaire, FEV₁ and FVC are effected by an array of factors; if we just consider maximal expiration, it is effected by respiratory muscle strength, the elastance of the chest wall, central airway caliber at high flow rates and smaller airway caliber at lower flow rates, elastic recoil and forced vital capacity. As a result, one cannot make definitive mechanistic conclusions from an isolated measure of FEV₁, FVC, or even FEV₁/FVC; yet the FEV₁ or FVC detects lung dysfunction and disease in a surprisingly robust fashion just because not a single factor but the integration of many factors can determine decreases in FEV, or FVC. This is especially true in the COPD patients.

It is often assumed that little more can be learned or developed in terms of measuring lung function but we can dispel this common wisdom by recent advances in our understanding of the role of spirometry in assessing lung disease by considering the case of COPD and the promulgation of the Global initiative for chronic Obstructive Lung Disease (GOLD) criteria. In the current issue of the journal, Coton and associates (13) representing the Burden of Obstructive Lung Disease investigators have assessed a new scheme for the classification of obstruction in a cohort of 1993 participants from around the world who had confirmed, chronic airflow limitation. The authors subdivided the cohort by post bronchodilator FEV₁/FVC values that were below the lower limits of normal, appreciating the effect of age, Lower Limit of Normal (LLN) intercept, and mean square error for males and females. Cut points for the categories of FEV₁/FVC were set to yield proportionately similar-sized groups to the FEV₁-based GOLD stages. They report that this new FEV₁/FVC classification yielded agreement with the GOLD FEV₁ stages in 47–60% and for the whole group it was 55%; that is, only fair to moderate agreement. However, the two criteria were similar in an ability to predict dyspnea, quality of life, or exacerbations.

So what is the advantage of using FEV₁/FVC ratio instead of the tried and true FEV₁? Several, it turns out. First, it mitigates the need for predicted equations and ethnic background adjustments, because as the authors point out, the virtue of using the FEV₁/FVC is that it results in a decreased dependency on the uncertainties as to what reference equations to use, and in particular, the difficulties of assessing lung function in mixed race populations or populations where reference equations simply do not exist. Hopefully using such classification scheme may shift the discussion away from reference values and toward coming to a better understanding of the pathophysiological process at play.

Second, this study shows that in patients with COPD the FEV₁ is highly dependent on the FVC, which in turn is dependent on the total lung capacity (TLC) and residual volume (RV). This dependency has been pointed out both in asthma (143) and in COPD (10). The correlation of FEV₁ to FVC in the current study was striking as they report a correlation coefficient of 0.9; moreover, as previously reported, FVC is prognostic of survival (10). It is interesting to note that as FEV₁ and FEV₁/FVC are nearly equivalent in terms of identification of obstruction, association to exacerbation and dyspnea and the same is most certainly the case for FVC and by extension FEV₆ (14). Why is this important? It suggests that the real process that should be investigated in COPD may not be airway narrowing but loss of lung volume. Accordingly, the focus should shift to the factors that determine TLC such as respiratory muscle strength, elastance of the chest wall and lung and RV where airway closure is the principle determinant.

The study of Coton et al reminds us that John Hutchinson, who first reported in 1846 the measurement of vital capacity in some 2130 individuals, recognized that decreases in vital capacity were of significance in lung disease. Further, he tried to promote using measurements of Vital Capacity (VC) for actuarial predictions for selling life insurance (15). It appears that he got it right and now 170 years later we need to take spirometry to the next step.

Declaration of interest

C.G. Irvin is a scientific consultant for Acorda, Methapharm and Medical Graphics Corporation. In the last year, he has received speaker fees/honoraria from AstraZeneca and the Mayo Clinic. He is an employee of the University of Vermont and the University of Vermont Medical Center.

Funding

This work was supported by American Lung Association – Airway Clinical Research Center (NIH P30 GM10 3532, R25 GM 116701, P50 DA36114). C.G. Irvin is funded by the American Lung association and NIH (P30 GM103532, T32 HL076122).