The frequency of false-positive COPD diagnosis is high. This could expose many patients in whom there is certainly no obstruction to the possible side effects of drugs.
Prof. Paul Enright wrote the book Office Spirometry together with Dr. Robert Hyatt in 1987, which encouraged primary care physicians to diagnose COPD early. The book stated at the time: "All patients over 40 years of age who smoke cigarettes should have spirometry performed, [but] we do not advocate mass screening.”
In 2008, Enright wrote an editorial for the journal Nature that discussed the use and misuse of spirometry in practices.1 The message was that a normal peak expiratory flow (PEF) excludes clinically relevant COPD. And he recommended that smokers with a low PEF should be referred to spirometry (with pre- and post-bronchodilation, BD) and reporting if good quality inhalers are not guaranteed in practice.
A review by the author, also published in Nature a few months ago, summarises studies on the diagnosis of mild COPD that have been published since the 2008 editorial.2
Up to now, there have been many studies on the underdiagnosis of COPD, but significantly less on the overdiagnosis of COPD.
A large multi-center survey from 2019 examined patients in 20 countries in whom other physicians had diagnosed COPD. In 62%, no obstruction was detected in spirometry after BD (Tiffeneau-Pinelli index above lower limit, FEV1/ FVC > LLN).3 Almost half of these patients (46%) were using respiratory therapeutics at the time of the study. The prevalence of false-positive diagnoses showed a wide, location-dependent variation, ranging from 1.9% in low and middle-income countries to 4.9% in high-income countries.
False-positive diagnoses were more common in women and were associated with higher levels of education, current or past smoking, and comorbidities such as asthma or heart disease. "The rates of over-diagnosed patients are unacceptably high, resulting in many patients using inhaled drugs daily that they do not need," writes Enright in the current review.2 The likelihood that such drugs will continue to be prescribed for many years after misdiagnosis is high.
How can this be? An analysis of 28 studies filtered out the following main reasons for over- and misdiagnosis: physicians did not perform spirometry after BD to make a diagnosis, the results were misinterpreted, or comorbidities with similar symptoms and abnormal spirometry (such as asthma or heart failure) were not considered.4
Another study of smokers with respiratory symptoms and a diagnosis of COPD (from primary care) underlines this: 85% had no obstruction post BD.5 Only slightly more than half of those diagnosed had ever received spirometry in their lives (the average time since the last spirometry was 47 months).
Enright already appealed in his 2008 editorial: "Spirometry is used absolutely insufficiently by general practitioners; inhalers are often prescribed indiscriminately. Inhalers for COPD are expensive and carry the risk of serious side effects, so they should not be prescribed to current or former smokers without confirmation of severe airway obstruction "1. All guidelines agree that single spirometry without obstruction rules out COPD in such patients.2
Enright is critical of the GOLD guidelines, which are financially supported by the industry. He believes that they define mild and moderate COPD inadequately. The absolute majority of smokers with low Tiffeneau-Pinelli index but normal FEV1 are classified as mild COPD (formerly GOLD stage I). However, data from the 'COPDGene' study (over 10 thousand smokers, 45-81 years) suggest that these patients have normal pulmonary phenotypes (measured by SGRQ questionnaire, 6-minute walk test, BD reversibility, CT lung with % emphysema, % air-trapping and small airway size).6
False-positive COPD is also associated with the missed opportunity to identify other causes of chronic cough (such as rhinosinusitis, asthma, GERD), bronchiectasis) or dyspnea (heart failure) for which there are very effective therapies. If patients are given the wrong diagnosis, the symptoms may persist - which unfortunately often leads to an escalation of the therapy and thus increased costs and a greater potential for side effects.
Abbreviations:
BD - Bronchodilation
COPD - Chronic obstructive pulmonary disease
FEV1 - Forced expiratory volume in 1 second
FVC - Forced vital capacity
GERD - Gastroesophageal reflux disease
LLN - Lower limit value
PEF - Peak expiratory flow
References:
1. Enright, P. The use and abuse of office spirometry. Primary Care Respiratory Journal 17, 238–242 (2008).
2. Enright, P. & Fragoso, C. V. GPs should not try to detect mild COPD. npj Primary Care Respiratory Medicine 30, 1–3 (2020).
3. Sator, L. et al. Overdiagnosis of COPD in Subjects With Unobstructed Spirometry: A BOLD Analysis. CHEST 156, 277–288 (2019).
4. Thomas, E. T., Glasziou, P. & Dobler, C. C. Use of the terms “overdiagnosis” and “misdiagnosis” in the COPD literature: a rapid review. Breathe 15, e8–e19 (2019).
5. Heffler, E. et al. Misdiagnosis of asthma and COPD and underuse of spirometry in primary care unselected patients. Respiratory Medicine 142, 48–52 (2018).
6. Vaz Fragoso, C. A. et al. Phenotype of Normal Spirometry in an Aging Population. Am J Respir Crit Care Med 192, 817–825 (2015).