Gps should not try to detect mild copd

More than 40 years ago, Robert Hyatt and Paul Enright at The Mayo Clinic in Minnesota wrote an office spirometry book in which primary care practitioners were encouraged to detect COPD

early1, and concluded: “Spirometry should be performed for all patients over the age of 40 years who smoke cigarettes [but] we do not advocate mass screening”. More than 10 years ago,

Enright wrote an editorial for this journal about the use and abuse of office spirometry, concluding that a normal peak expiratory flow (PEF) rules out clinically important COPD, and for

smokers with a low PEF, before prescribing expensive daily inhalers, GPs should refer the patient to a local service for good-quality pre- and post-bronchodilator (BD) spirometry and

interpretation2. Here, we review studies about detecting mild COPD published since that editorial. First, the rates of COPD overdiagnosis are now unacceptably high, causing many patients to

be taking a daily inhaler that they do not need. A 2019 review of 28 studies reporting rates of COPD overdiagnosis and misdiagnosis3 found the following causes: (1) physicians did not use

post-BD spirometry to establish the diagnosis; (2) the results were incorrectly interpreted; (3) co-morbidities with similar symptoms and abnormal spirometry (such as asthma or heart

failure) were not considered; (4) spirometry was normal during a follow-up exam. For example, 31% of over 6000 patients admitted to a community teaching hospital with COPD as the leading

diagnosis had normal spirometry results during their hospital stay4. One-third of 187 patients with dyspnea who had been previously diagnosed with both chronic heart failure and COPD did not

have airway obstruction5. In another study of smokers with respiratory symptoms and a diagnosis of COPD, over 85% did not have post-BD airway obstruction6. All guidelines agree that a

single spirometry test without airflow obstruction (the “O” in COPD) rules out COPD for that patient. Since 2001, the industry-sponsored GOLD guidelines for COPD have inappropriately defined

“mild” and “moderate” COPD7. The vast majority of smokers with a low FEV1/FVC ratio but a normal FEV1, are labeled as having mild COPD (the old GOLD stage 1). But according to the large

COPDGene study (>10,000 smokers, ages 45–81), they have normal pulmonary phenotypes: dyspnea grade, SGRQ, 6-min walking distance, bronchodilator reversibility, and lung CT scans (%

emphysema, % gas trapping, and small airway dimensions)8. In other words, their respiratory symptoms are not due to mild COPD, and a search for other causes of their respiratory symptoms

should be undertaken. Those who are smokers must be encouraged and helped to quit smoking, and inhalers are not indicated unless they have asthma. Josephs et al. identified over 14,000

patients with a COPD diagnosis from a large UK database9 and reviewed all of their prescriptions and spirometry test results. During their median COPD duration of 5 years, about half had

persistent airflow obstruction (AFO), i.e., low FEV1/FVC at all visits, one-third had intermittent AFO, 11% never had AFO (_n_ = 1434), and 13% never had a spirometry test. Despite absent

AFO, more than half of the 1434 patients were taking a LABA, LAMA, ICS, or combination inhaler every day, including those without a history of asthma. The authors concluded that “patients

without AFO require clinical reassessment, as they may be receiving inappropriate, potentially harmful, and costly medications that may not benefit them, while the true cause of their

symptoms may have been missed”. Another UK audit of medical records included 48,105 patients with a diagnosis of COPD10. Only 19% had post-BD spirometry. Of these, 25% (_n_ = 2255) did not

have AFO. Patients with spirometry incompatible with their COPD diagnosis were more likely female, never-smokers, more obese, and have a higher FEV1. In a population-based sample of adults

from 20 countries, more than half of those reporting a physician’s diagnosis of COPD had entirely normal spirometry, and over half of them reported current use of a respiratory medication11.

Second, the opportunity to diagnose other causes of chronic cough, such as rhinosinusitis, asthma, GERD, and bronchiectasis, is missed. Also, dyspnea due to heart failure is missed. All

these diseases have very effective treatments. A Mayo Clinic review of the 2018 GOLD guidelines concluded that COPD “is commonly both overdiagnosed and underdiagnosed because of lack of

spirometry testing among symptomatic patients”. This results in inappropriate therapy for many patients and delayed diagnosis of other treatable conditions12. Some of the final diagnoses can

be ischemic heart disease, congestive heart failure, subglottic stenosis, and pulmonary hypertension, all of which are serious and could lead to patient harm, if unrecognized13. “In

addition to this risk, patients are often on long-term inhaled therapy unnecessarily, leading both to potential side-effects and significant ongoing healthcare costs, as these drugs are

likely to be issued for many years after the misdiagnosis. If the wrong diagnosis is made, patients are also likely to remain symptomatic, and potentially have their treatment stepped up,

adding to both the cost and potential for side-effects. At a societal level, overdiagnosis of asthma may lead to significant opportunity cost, as resources required elsewhere are

inappropriately spent on over-diagnosed asthma”14. Although this author was talking about asthma, the same is true of the misdiagnosis of COPD. Third, “pre-COPD”, “mild” COPD, and “early”

COPD are not diseases, and do not need detection or treatment because no combination of inhaled drugs slows the progression of COPD in a continuing smoker. Clinically important COPD takes

decades to develop in susceptible smokers. During this time, large groups of these susceptible smokers may statistically significantly differ (_p_ < 0.05) in some respect from the larger

group of smokers who will not develop COPD. For example, many types of pulmonary function tests (body plethysmography, diffusing capacity (DLCO), forced oscillation, etc.) and

cardiopulmonary exercise tests will become borderline abnormal in susceptible smokers before AFO is detected by spirometry15,16,17,18,19,20. However, these test results are highly unreliable

for predicting progression to clinically important COPD21,22. Emphysema can be detected using advanced processing of thoracic CT scans in smokers with normal spirometry. The COPDGene study

and others showed that most GOLD stage 1 “mild COPD” smokers had evidence of emphysema (>5%) or airway thickening on quantitative CT-scan analysis23,24. However, the positive predictive

power of these tests for clinically important COPD is poor. Age-specific reference equations for % emphysema and % gas trapping as determined in healthy populations of asymptomatic lifelong

nonsmokers are unavailable25. Thus, emphysema seen on lung CT scans may be “senile emphysema” due to normal aging26. CT-measured emphysema without AFO was associated with all-cause mortality

in a very large study27. However, participants who were characterized as “without airflow obstruction” included those with restriction (a reduced FVC but normal FEV1/FVC), which is often

due to heart failure or sarcopenia28. Borderline airway obstruction has been associated with higher respiratory morbidity during long-term follow-up; however, both asthma and COPD could have

caused the morbidity29,30,31. Many pulmonary physicians (most of whom have industry funding) are optimistic that the early detection of mild COPD will become important20,32. However, a

recent review of mild COPD admitted that: “Future research should address two major issues: first, whether mild airflow limitation represents an early stage of COPD and … whether regular

treatment should be considered for COPD patients with mild airflow limitation…”33. Finally, aging-related concerns further inform the low clinical value of establishing a diagnosis of mild

COPD. Ultimately, it is the rapid aging of populations worldwide (1.5 billion persons will be aged ≥65 years by 2050)34 that highlights the low clinical value of mild COPD. Older persons

have a high burden of respiratory symptoms that are often multifactorial, due to age-related increases in multimorbidity (62% of Americans aged ≥65 years have two or more chronic

conditions), medication-related adverse effects, and high rates of severe deconditioning35. In such a clinical setting, even with age-appropriate spirometric criteria, mild COPD is only

modestly associated with respiratory symptoms, and is otherwise not associated with poor exercise performance36. Mild COPD is defined by the World Health Organization as a patient who has a

chronic cough or dyspnea, but is able to walk long distances and climb stairs. It has a very low disability weight (lower than mild diarrhea)37. Hence, ascribing disability to mild COPD (and

attempting to treat it) is clinically inappropriate, especially in older patients. In summary, we recommend that primary care practitioners (i) do not diagnose or treat COPD until two or

more spirometry tests demonstrate moderate-to-severe airway obstruction; (ii) rule out COPD with a normal peak flow38,39; (iii) refer patients with respiratory symptoms to a facility where

good-quality spirometry is done. Also, it has been said that “everything is “COPD” until the correct diagnosis is made,” so carefully consider causes of a chronic cough or dyspnea other than

COPD, even in elderly smokers with abnormal spirometry. Finally, for dyspneic patients with spirometric restriction (a low FVC), we recommend obtaining a chest X-ray (or lung CT scan), a

DLCO test, and B-naturetic protein test. REFERENCES * Enright, P. L. & Hyatt, R. E. _Office Spirometry, A Practical Guide to the Selection and Use of Spirometers_ (Lea and Febiger,

Philadelphia, 1987). * Enright, P. The use and abuse of office spirometry. _Prim. Care Respir. J._ 17, 238–242 (2008). Article  Google Scholar  * 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). Article  Google Scholar  * Spero, K., Bayasi, G., Beaudry, L.,

Barber, K. R. & Khorfan, F. Overdiagnosis of COPD in hospitalized patients. _Int J. Chron. Obstruct Pulmon Dis._ 12, 2417–2423 (2017). Article  Google Scholar  * Minasian, A. G. et al.

COPD in chronic heart failure: less common than previously thought? _Heart Lung_ 42, 365–371 (2013). Article  Google Scholar  * Heffler, E. et al. Misdiagnosis of asthma and COPD and

underuse of spirometry in primary care unselected patients. _Respir. Med._ 142, 48–52 (2018). Article  Google Scholar  * GOLD. _Global Strategy for the Diagnosis, Management and Prevention

of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD)_. https://goldcopd.org/ (2018). * Vaz Fragoso, C. A. et al. Phenotype of normal spirometry in an aging population. _Am.

J. Respir. Crit. Care Med._ 192, 817–825 (2015). Article  Google Scholar  * Josephs, L., Culliford, D., Johnson, M. & Thomas, M. COPD overdiagnosis in primary care: a UK observational

study of consistency of airflow obstruction. _NPJ Prim. Care Respir. Med._ 29, 33 (2019). Article  Google Scholar  * Fisk, M. et al. Inaccurate diagnosis of COPD: the Welsh National COPD

Audit. _Br. J. Gen. Pr._ 69, e1–e7 (2019). Article  Google Scholar  * Sator, L. et al. Overdiagnosis of COPD in subjects with unobstructed spirometry: a BOLD analysis. _Chest_ 156, 277–288

(2019). Article  Google Scholar  * Mirza, S., Clay, R. D., Koslow, M. A. & Scanlon, P. D. COPD guidelines: a review of the 2018 GOLD report. _Mayo Clin. Proc._ 93, 1488–1502 (2018).

Article  Google Scholar  * Aaron, S. D. et al. Diagnostic instability and reversals of COPD diagnosis in individuals with mild to moderate airflow obstruction. _Am. J. Respir. Crit. Care

Med._ 196, 306–314 (2017). Article  Google Scholar  * Kavanagh, J., Jackson, D. J. & Kent, B. D. Over- and under-diagnosis in asthma. _Breathe_ 15, e20–e27 (2019). Article  Google

Scholar  * Frantz, S. et al. Impulse oscillometry may be of value in detecting early manifestations of COPD. _Respir. Med._ 106, 1116–1123 (2012). Article  CAS  Google Scholar  * Elbehairy,

A. F., Guenette, J. A. & Faisal, A. Mechanisms of exertional dyspnoea in symptomatic smokers without COPD. _Eur. Respir. J._ 48, 694–705 (2016). Article  Google Scholar  * Harvey, B. G.

et al. Risk of COPD with obstruction in active smokers with normal spirometry and reduced diffusion capacity. _Eur. Respir. J._ 46, 1589–1597 (2015). Article  CAS  Google Scholar  *

Guenette, J. A. et al. Mechanisms of exercise intolerance in global initiative for COPD grade 1 COPD. _Eur. Respir. J._ 44, 1177–1187 (2014). Article  Google Scholar  * O’Donnell, D. E.,

Laveneziana, P., Webb, K. & Neder, J. A. COPD: clinical integrative physiology. _Clin. Chest Med._ 35, 51–69 (2014). Article  Google Scholar  * Hoesterey, D. et al. Spirometric indices

of early airflow impairment in individuals at risk of developing COPD: spirometry beyond FEV1/FVC. _Respir. Med._ 156, 58–68 (2019). Article  Google Scholar  * Vaz Fragoso, C. A., Concato,

J., McAvay, G., Van Ness, P. H. & Gill, T. M. Respiratory impairment and COPD hospitalisation in older persons: a competing risk analysis. _Eur. Respir. J._ 40, 37–44 (2012). Article 

Google Scholar  * Vaz Fragoso, C. A. et al. Respiratory impairment in older persons: when less means more. _Am. J. Med._ 126, 49–57 (2013). Article  Google Scholar  * Regan, E. A. et al.

Clinical and radiologic disease in smokers with normal spirometry. _J. Am. Med. Assoc._ 175, 1539–1549 (2015). Google Scholar  * Pirozzi, C. S. et al. Heterogeneous burden of lung disease in

smokers with borderline airflow obstruction. _Respir. Res._ 19, 223 (2018). Article  Google Scholar  * Smith, B. M. & Barr, R. G. Establishing normal reference values in quantitative

computed tomography of emphysema. _J. Thorac. Imaging_ 28, 280–283 (2013). Article  Google Scholar  * Vaz Fragoso, C. A. Epidemiology of COPD in aging populations. _COPD_ 13, 125–129 (2016).

Article  Google Scholar  * Oelsner, E. C. et al. Association between emphysema-like lung on cardiac computed tomography and mortality in persons without airflow obstruction: a cohort study.

_Ann. Intern. Med._ 161, 863–873 (2014). Article  Google Scholar  * Vaz Fragoso, C. A. et al. Spirometry, static lung volumes, and diffusing capacity. _Respir. Care._ 62, 1137–1147 (2017).

Article  Google Scholar  * Park, H. J. et al. Significant predictors of medically diagnosed COPD in patients with preserved ratio impaired spirometry: a 3-year cohort study. _Respir. Res._

19, 185 (2018). Article  Google Scholar  * Bhatt, S. P. et al. Discriminative accuracy of FEV1:FVC thresholds for COPD-related hospitalization and mortality. _J. Am. Med. Assoc._ 321,

2438–2447 (2019). Article  Google Scholar  * Scichilone, N. et al. Choosing wisely: practical considerations on treatment efficacy and safety of asthma in the elderly. _Clin. Mol. Allergy.:

CMA_ 13, 7 (2015). Article  Google Scholar  * Rennard, S. I. & Drummond, M. B. Early chronic obstructive pulmonary disease: definition, assessment, and prevention. _Lancet_ 385,

1778–1788 (2015). Article  Google Scholar  * Rossi, Andrea et al. Chronic obstructive pulmonary disease with mild airflow limitation: current knowledge and proposal for future research - a

consensus document from six scientific societies. _Int. J. COPD_ 12, 2593–2610 (2017). Article  Google Scholar  * World Health Organization. _Global Health and Aging. National Institute on

Aging, National Institutes of Health_, No. 11-7737 (NIH Publication, 2011). * Mangin, D. et al. International group for reducing inappropriate medication use & polypharmacy (IGRIMUP):

position statement and 10 recommendations for action. _Drugs Aging_ 35, 575–587 (2018). Article  Google Scholar  * Vaz Fragoso, C. A. et al. Phenotype of spirometric impairment in an aging

population. _Am. J. Respir. Crit. Care Med._ 193, 727–735 (2016). Article  Google Scholar  * Salomon, J. A. et al. Disability weights for the global burden of disease 2013 study. _Lancet

Glob. Health_ 3, e712–e723 (2015). Article  Google Scholar  * Jithoo, A. et al. Case-finding options for COPD: results from the burden of obstructive lung disease study. _Eur. Respir. J._

41, 548–555 (2013). Article  Google Scholar  * Thorat, Y., Salvi, S. & Kodgule, R. Peak flow meter with a questionnaire and mini-spirometer to help detect asthma and COPD in real-life

clinical practice: a cross-sectional study. _NPJ Prim. Care Respir. Med._ 27, 32 (2017). Article  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department

of Medicine, the University of Arizona, Tucson, AZ, USA Paul Enright * Clinical Epidemiology Research Center, VA Connecticut Healthcare System, Mailcode 151B, West Haven, CT, USA Carlos Vaz

Fragoso Authors * Paul Enright View author publications You can also search for this author inPubMed Google Scholar * Carlos Vaz Fragoso View author publications You can also search for

this author inPubMed Google Scholar CONTRIBUTIONS Both authors contributed to the writing, added references, and edited the final draft before submission. CORRESPONDING AUTHORS

Correspondence to Paul Enright or Carlos Vaz Fragoso. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing interests. ADDITIONAL INFORMATION PUBLISHER’S NOTE Springer

Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. RIGHTS AND PERMISSIONS OPEN ACCESS This article is licensed under a Creative

Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the

original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in

the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended

use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit

http://creativecommons.org/licenses/by/4.0/. Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Enright, P., Fragoso, C.V. GPs should not try to detect mild COPD. _npj Prim. Care

Respir. Med._ 30, 20 (2020). https://doi.org/10.1038/s41533-020-0176-0 Download citation * Received: 10 January 2020 * Accepted: 07 April 2020 * Published: 11 May 2020 * DOI:

https://doi.org/10.1038/s41533-020-0176-0 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not

currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative