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More work is needed on the concept of staging of COPD
As a junior doctor I once worked in a hospital where the leading consultant in medicine refused to accept the diagnosis of asthma in patients older than 40 years. To him, airflow obstruction was “asthma” in the young and “chronic bronchitis” in the elderly. While it soon became apparent that asthma does occur after the age of 40, the likelihood of significant airflow limitation occurring in young adults who have never had asthma has always seemed small to me. In this issue of Thorax De Marco et al describe the prevalence of chronic obstructive pulmonary disease (COPD) in young adults taking part in the European Community Respiratory Health Survey (ECRHS).1 They found COPD to be a considerable issue; in total, 3.6% had COPD stage I+ according to the NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD)2 and 11.8% had chronic respiratory symptoms without airflow limitation—that is, COPD GOLD stage 0.
The study raises several questions relating to methodology, findings, and interpretation. Diagnosis and staging of COPD was done according to the GOLD guidelines2 using an FEV1/FVC ratio of 0.7 and FEV1 cut off points of 80%, 50%, and 30%. In subjects aged 20–44 years a ratio of 0.7 will not overestimate airflow obstruction—more likely it will underestimate it. The major challenge seems to be exclusion of asthma and the approach of De Marco et al can, to some extent, be questioned. In contrast to GOLD recommendations, prebronchodilator FEV1 was used for staging but this seems acceptable in the epidemiological setting where administration of bronchodilators is often not feasible. Patients with self-reported asthma without cough/phlegm were excluded while those with both self-reported asthma and chronic symptoms were considered to have COPD with coexisting asthma. The latter seems intuitively correct in a 44 year old heavy smoker with a smoking history of 30 pack years, but is it true in the 20 year old never smoker with self-reported asthma? Unfortunately, no valid answers exist; GOLD has not attempted to separate stage 0 COPD from symptomatic asthma, and only for subjects with irreversible airflow limitation does GOLD acknowledge the problem: “Poorly reversible airflow limitation associated with bronchiectasis, cystic fibrosis, tuberculosis, or asthma is not included except insofar as these conditions overlap with COPD”.2 In the Copenhagen City Heart Study cohort3 54% of women and 63% of men with self-reported asthma had chronic productive cough; this will presumably remain an issue for debate for some time.
COPD stage 0 denoting subjects “at risk” was introduced by GOLD, but the concept cannot be regarded as evidence based and remains controversial.4,5 It is, nevertheless, intriguing that the prevalence of chronic symptoms in 20–44 year old subjects is more than 10% on average and as high as 24% in Spain. Risk factors did not differ substantially between stages 0 and I+, and a recent Italian study has shown that stages 0 and I differ little in health status.6 Still, we do need prospective studies of stage 0 including various outcomes. We also have to make clear the reason for applying staging to COPD. Undoubtedly, staging facilitates communication and comparison of study results. It is, however, less clear that it reflects biological changes over time. The concept of cancer staging—where, by definition, patients progress through the stages—may not be valid in COPD. While it is unlikely for anyone to have stage III or IV without passing through earlier stages, COPD stage I can undoubtedly develop without the patient ever having been in stage 0.4 Years of looking at the “Fletcher diagram”7 have anchored the impression of rapid decline so firmly in our minds that we may tend to forget that, through impaired growth of lung function in childhood and early adolescence, any superimposed airflow obstruction at a later age could very well start the patient off in COPD stage II.8 For this and other reasons, more work on the concept of staging of COPD is clearly needed.
COPD is a burden in the elderly, but it is not a disease of the elderly alone. The notion of COPD in young adults was confirmed by the “confronting COPD” study,9 but whereas that study used doctor’s diagnosis and presence of symptoms, the ECRHS study has verified the diagnosis with spirometric testing in random population samples, enabling us to quantify the problem. Unfortunately, the study by De Marco et al does not tell us the prevalence of doctor diagnosed COPD in their cohort. COPD is often undiagnosed10 and, based on data from the IBERPOC study, this is even more so in younger patients11 and in women more than in men.11,12 In this respect, the ECRHS study showed COPD to be more prevalent in men than in women. When biological explanations are applied to these findings, caution is probably warranted. Better information is available in this area from longitudinal studies13 and, in addition, detailed information on smoking such as age of starting and inhalation is essential for adjusting properly for sex differences in smoking habits when addressing susceptibility.14
With the study by De Marco et al, however, COPD epidemiologists now have to join asthma epidemiologists in praising the ECRHS. One important question remains: How should these findings change our perception of COPD? They probably should not! The strengths of the paper lie in the finding that COPD is a widespread problem in young adults and the implications of the quantification. To limit case finding and/or screening for COPD to middle aged or elderly subjects would be missing a window of opportunity based on these findings.
More work is needed on the concept of staging of COPD