COPD (confusion over proper diagnosis) in the zone of maximum uncertainty

In an excellent statement on chronic obstructive lung disease (COPD) that focuses on questions that are relevant for the patient's well-being and quality of life [1, 2], one issue should have received more critical attention. For research into COPD, it is vital that the diagnosis of airway obstruction, which traditionally hinges on a forced expiratory volume in 1s (FEV1)/forced vital capacity (FVC) ratio below a threshold, can be accurately established. Celli et al. [1, 2] state that this threshold is uncertain, leaving the recommendations open ended to some extent. They refer to the discussion whether in ascertaining a diagnosis of COPD the threshold for the FEV1/FVC ratio should be the lower limit of normal (LLN), defined in respiratory medicine as the 5th centile in a representative sample of healthy nonsmokers, or the post-bronchodilator FEV1/FVC of 0.7 first proposed in 2001 by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) group [3]. The latter threshold has not been clinically validated; it was intended to simplify recognition and increase awareness of COPD, particularly in less developed countries where the LLN might not be presented with the test results. The use of the fixed ratio has been extensively criticised. Cross-sectional data show that it leads to underestimating the prevalence of airflow limitation in younger people and to large overestimates in those older than 45years. In 80-year-old healthy subjects, this leads to a 75-80% false positive rate [4]. The Burden of Obstructive Lung Disease (BOLD) group also routinely uses the LLN cut-off for reporting the prevalence of abnormal ventilatory function [5]. Follow-up studies have shed light on the question of whether observations in the zone between the fixed ratio and LLN represent respiratory disease. In asymptomatic subjects and very elderly subjects, an FEV1/FVC above the LLN but below 0.7 was not associated with premature death [6-10], an abnormal decline in FEV1 [11-13], respiratory care use [11], hospitalisation [10] or quality of life [11]. Conversely, an FEV1/FVC ratio below the LLN is associated with increased risk of hospitalisation [10] and mortality [8-10, 12, 13]. Three reports [9, 16, 17] suggested that use of the LLN cut-off would miss individuals at risk, but these findings have been contested [18-21].