In this issue of the journal, Çolak and coworkers (Citation1) report the association of body mass index (BMI from malnutrition to morbid obesity) with airflow obstruction from a large Copenhagen cohort. They found that all indices of body habitus (BMI, waist circumference, waist-hip ratio, and abdominal height) were independently and positively associated with four commonly used spirometric indices of airflow limitation, in both women and men. For example, in current smokers, a higher BMI was associated with a lower FVC and thus a higher FEV1/FVC.
Previous studies have shown that obesity has two primary effects on spirometry results. The first is that the expiratory reserve volume approaches zero (Citation2). In other words, fat people cannot blow out air from their resting respiratory position (the bottom end of their tidal volume). This inability reduces their FVC (and slow vital capacity) by a few hundred milliliters, but does not lower their FEV1. Thus, the ratio of FEV1 to FVC is increased. The second effect, due to the accumulation of fat around the rib cage with more severe obesity, is restriction of the ability to take a deep breath. This chest wall restriction lowers the inspiratory capacity, the vital capacity, and the FEV1, all by about the same amount (thus not affecting the FEV1/FVC ratio). Notice in Figure 2 from the Danish study (Citation1) that the association between BMI and FEV1/FVC becomes insignificant in the severely obese range (BMI 30–50 kg/m2).
Based on their results, the Danish authors worry that COPD is under-diagnosed and under-treated in adults who are increasingly overweight or obese and suggest not to dismiss the diagnosis of COPD when FEV1/FVC is between 0.70 and 0.75. While their study design and analyses are excellent, we disagree with this concern because spirometry (regardless of how the numbers are interpreted) simply cannot reliably detect early COPD and obesity may bias the severity classification.
The false positive and false negative rates for what is called “mild to moderate COPD” when defined using the faulty fixed ratio FEV1/FVC < 0.70 are both too high. A large fraction of smokers given the label of mild or moderate COPD do not subsequently develop clinically-important COPD, even when they continue to smoke (Citation3). Their FEV1 remains the same over many years, or declines with aging at the same slow rate as never-smokers (Citation4). Even when the lower limit of the normal range (LLN) of the FEV1/FVC is used to define airflow obstruction, one in twenty people have test results below the 5th percentile of the bell-shaped frequency-distribution curve of healthy people. It should be kept in mind that it is standard practice to accept a false-positive rate of 5% for most medical tests. In addition, some healthy adults may have low FEV1/FVC from childhood and adolescence, due to “dysanaptic lung growth” (Citation5), without symptoms or evidence of other lung function abnormalities (Citation6).
Our confidence that the spirometry result of an adult smoker is due to COPD (a true-positive) should only become high when the FEV1/FVC ratio is below the LLN and the post-bronchodilator FEV1 is below 60% predicted, which approximates its LLN in elderly people (Citation7) and is near the middle of the overly-broad GOLD stage II. We should consider prescribing a daily COPD drug only for such patients who are highly likely to have clinically-important COPD. The clinical practice guidelines for COPD endorsed by four professional societies state that “Treatment for stable COPD should be reserved for patients who have respiratory symptoms and FEV1 less than 60% predicted, as documented by spirometry.” (Citation8).
Even when a diagnosis of COPD is established with both FEV1/FVC and FEV1 below LLN, an obese patient is more likely to be over-treated than a lean patient. The Danish study shows that the FEV1 is reduced due to obesity (by an average of 7% predicted, see Table 1), so COPD severity will often be rated as more severe for which more intensive COPD therapy is recommended; yet bronchodilators will not help the restriction (and lower FEV1) due to obesity. More than three-quarters of the obese Danish adults reported dyspnea on exertion, which is likely due to poor cardiovascular conditioning, heavy body weight, and increased work of breathing due to chest wall restriction (Citation9). This dyspnea will push them into the new GOLD category (from patient group A to B or C to D) calling for more intense daily treatment with long-acting bronchodilators or addition of inhaled corticosteroids (Citation10), which will be ineffective for relieving the dyspnea caused by obesity-related factors. Furthermore, results from the Copenhagen study demonstrated that among people with COPD those with obesity were at lower risk for respiratory and all-cause mortality than those with normal-weight (Citation11). This “paradox” was more evident in severe than moderate/mild COPD, which raises the question whether it could be the result of an over-grading of COPD severity due to the obesity-related reduction of FEV1.
In conclusion, Çolak and coworkers (Citation1) suggest that obesity may lead to under-diagnosis of COPD if based on FEV1/FVC only. However, because of the obesity-related restriction, the severity of COPD may be over-rated. Because of these limitations of simple spirometry, a more comprehensive diagnostic approach is needed in obese patients before establishing a treatment for COPD.
Declaration of Interest
The authors have no conflicting interests to declare.
Acknowledgement
This editorial is dedicated to the memory of Ben Burrows and Mike Lebowitz, who were superb pulmonary epidemiologists.
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