© 2003 American Thoracic Society
Gold Stage 0To the Editor:We read with interest the article by Vestbo and Lange (1) who conclude, "GOLD Stage 0 is of little help in identifying subjects at risk for COPD." This statement may deeply influence the future strategies for the early detection and prevention of COPD but it seems to be much too definitive when considering the limitations of the study. First, approximately 3,500 subjects died during follow-up (2). Since the authors have previously shown an association between COPD and mortality (3), it would be useful to know how many of them had GOLD Stage 0 at baseline. Moreover, a response rate of 58% at third examination should refrain from strong conclusion. Second, subjects with self-reported asthma at any of the surveys were excluded. Previously, the authors stated (2) "ex-smokers have a higher incidence of self reported asthma than never-smokers. It is likely that subjects may perceive chronic obstructive pulmonary disease as asthma, hence the relationship between smoking cessation and asthma may be due to misclassification." Moreover, about half of the subjects with new asthma also reported chronic bronchitis. These subjects also had the poorest lung function. Thus, their exclusion from the present analysis is a substantial bias. Third, GOLD Stage 0 was found to be not constant; in fact, about half of the subjects with the Stage 0 at baseline reported no chronic phlegm during follow-up. Previously, the authors found disappearance of mucus hypersecretion to be less associated with FEV1 decline than persistent mucus hypersecretion (4). Thus, it would be interesting to also analyze the subgroup of subjects in which Stage 0 is a stable feature. Most importantly, the finding of the disappearance of chronic mucus hypersecretion associated with young age and smoking cessation goes in the opposite direction of the authors' conclusions, indicating the opportunity of an early detection of these subjects to promote smoking cessation. Fourth, it is important to consider the validity of self-reported symptoms in epidemiology; particularly, chronic cough and phlegm could have different pathogenesis, such as rhinosinusitis or bronchiectasis, and not necessarily go on to develop bronchial obstruction (5, 6). Specific items able to identify subjects with post nasal drip should be included in the screening questionnaires for future epidemiological studies. We think that these are key points to address in epidemiology before definitively abandoning GOLD Stage 0, especially in the absence of alternative markers of susceptibility in the population.
University of Pavia Pavia, Italy REFERENCES
From the Authors:We thank Dr. Cerveri and colleagues for their comments. Whereas we recognize the important global health policy aspects of promoting the concept of an "at risk" population regarding COPD and the appropriateness of stating that chronic respiratory symptoms are markers of an ongoing pathological process in the airways, we remain doubtful about the ability of GOLD Stage 0 to predict later COPD (1). We will try to respond to the four objections put forward by Cerveri and colleagues.In a long-term follow-up study, mortality and subsequent non-attendance always pose problems. After 15 years of follow-up, 24% of subjects without COPD and without chronic symptoms had died, whereas this was the case for 30% of subjects with GOLD Stage 0. In a multivariate Cox model with age, sex, smoking (yes/no), and inhalation (yes/no) as covariates and subjects without Stage 0 as reference category, Stage 0 had a hazard ratio of 1.09 (95% confidence interval 0.95–1.25, p = 0.22). The overall response rate at the third examination was 58%; however, the survey population is a dynamic population and among those who took part in the first survey the subsequent attendance rate was 70.5%. We still believe subjects with asthma should be excluded from a study of GOLD Stage 0. In our point of view, asthma per se is a risk factor for COPD (2, 3). In a previous study where we found smoking cessation to be associated with incident self-reported asthma (4), we suggested that one explanation could be misclassification. However, other explanations were suggested and the incident asthma patients with mucus hypersecretion and low lung function referred to were not Stage 0 patients at baseline. The size of our database unfortunately precludes meaningful stratified analyses of prognosis of Stage 0 depending on self-reported asthma at various time-points. We found that Stage 0 was not a stable feature but we only have information at baseline, after 5, and after 15 years. We believe caution is warranted when findings from the entire population about changes in mucus and lung function decline (5) are used for the specific subjects in Stage 0. Among those with Stage 0 at the second survey, approximately half of them were Stage 0 at baseline and half of them had had no symptoms. After an additional 10 years, 14% with "new" Stage 0 and 18% with "stable" Stage 0 had developed COPD Stage 1+. This small difference does not seem to warrant special follow-up of Stage 0 for establishing whether it is stable or not. However, we strongly believe that efforts should be made to promote smoking cessation, and if studies show that GOLD Stage 0 can enhance these efforts this feature alone may justify the staging. Finally, we are not familiar with large-scale epidemiological surveys attempting to further analyze causes of cough and phlegm in detail.
Hvidovre University Hospital Hvidovre, Denmark REFERENCES
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