Don't Diagnose Mild COPD Without Confirming Airway Obstruction after an Inhaled Bronchodilator

Spirometry results from the excellent PLATINO study of COPD prevalence in Latin American countries, as reported in this issue ([1]), provide 3 important lessons for both clinicians and pulmonary epidemiologists:

1. People with a low pre-test probability for COPD should not be screened for COPD;

2. Values below the 5th percentile of FEV₁/FVC from healthy subjects should be used to detect airway obstruction (not the fixed ratio 0.70 recommended by GOLD); and

3. Post-bronchodilator (post-BD) spirometry must be done for smokers with mild pre-BD airway obstruction, since up to one-third do not have COPD.

The multi-center PLATINO study used a spirometer with excellent quality checks and demonstrated long-term accuracy ([2]). A strict spirometry quality assurance program, with the same standardized protocol used by the Burden of Obstructive Lung Disease (BOLD) Initiative ([3]), successfully produced 95% of pre- and post-BD test sessions exceeding American Thoracic Society 1994 goals. Multiple methods of interpreting airflow limitation and describing BD reversibility were analyzed and compared. In short, the study design, population-based sampling and spirometry methods, results, and analyses were superb.

1. The investigators wisely separated the adults into two groups: low pre-test probability for COPD and high pre-test probability (risk) for COPD. The very low prevalence of airway obstruction (about 6% overall) in those with low pre-test probability for COPD argues strongly that screening spirometry should not be done for people without respiratory symptoms, less than 10 years of smoking, no history of asthma, and low workplace exposures to respiratory hazards. Unfortunately, screening spirometry programs at sporting events in the United States have targeted tens of thousands of such individuals during the past 5 years ([4]). In our opinion, the “selling of sickness” in relatively low risk populations will detract from legitimate COPD case-finding among high risk patients in primary care settings ([5]).

2. The PLATINO investigators also confirmed previous studies demonstrating that the overly simplistic 2001 GOLD definition of airway obstruction ([6]) using a fixed ratio (0.70) causes a very large false positive rate in older people ([7]). Since almost all studies show that in healthy subjects the FEV₁/FVC falls with normal aging ([8]) to well below 0.7, and that all office spirometers have a microprocessor which computes the appropriate lower limit of the normal range (the 5th percentile) for spirometry variables, we are not impressed with rationalizations for continued support of an arbitrary fixed ratio to define airway obstruction. The GOLD group acknowledged this in their 2006 update of recommendations ([9]): “However, because the process of aging does affect lung volumes, the use of this fixed ratio may result in over diagnosis of COPD in the elderly, especially of mild disease. Using the lower limit of normal (LLN) values for FEV1/FVC, that are based on the normal distribution and classify the bottom 5% of the healthy population as abnormal, is one way to minimize the potential misclassification.” Considering the paucity of evidence for a benefit from any intervention for mild COPD other than smoking cessation ([10], [11]), falsely affixing a COPD label is likely to cause more harm than good ([12]).

3. The results of PLATINO spirometry also conclusively demonstrate that post-BD testing (as recommended by most guidelines) is necessary before affixing the COPD label on any subject with respiratory symptoms and mild (pre-BD) airway obstruction. About one-third of those with pre-BD airway obstruction did not have airway obstruction post-BD (firmly ruling out COPD). While spirometry testing is generally under-utilized for patients with respiratory symptoms and for confirming a diagnosis of COPD, those who do provide spirometry in their office almost never take the extra time for post-BD spirometry ([13], [14], [15]). Since asthma is nearly as common as COPD in adults with respiratory symptoms, the lack of post-BD spirometry means that asthma is often misdiagnosed as COPD. Such faulty medical decision-making hurts patients since the treatment and prognosis of asthma differs substantially from that of COPD.

It's easy to confuse the concepts of BD-responsiveness and post-BD airway obstruction when attempting to differentiate asthma from COPD in adults. In patients with an increased pre-test probability of asthma, baseline airway obstruction with a “significant” BD response increases the (post-test) probability of asthma. On the other hand, the lack of BD-responsiveness does not rule out asthma in such patients, and thus provides no clinically important information.

In patients with a high pre-test probability of COPD, moderate to severe post-BD airway obstruction confirms COPD, and normal post-BD spirometry rules out COPD. However, BD responsiveness in adult smokers (with or without baseline airway obstruction) rarely provides clinically useful information. It varies widely from visit-to-visit ([16], [17]), does not increase the probability of COPD, and does not substantially increase the likelihood of response to bronchodilator or corticosteroid therapy ([18]).