SAN DIEGO -- The apparent "obesity paradox" in chronic obstructive pulmonary disease (COPD) is a head-scratcher for physicians: Studies suggest that COPD patients who are overweight and obese have an advantage in terms of both mortality and morbidity. Now, however, a new study finds that COPD patients who are extremely overweight -- i.e., those with a body mass index (BMI) above 40 -- do not gain this benefit.
"Our results, combined with the work of others, suggest that BMI is an important factor physicians should consider when evaluating mortality risk in patients with COPD," said Emily Brigham, MD, MHS, of Johns Hopkins University School of Medicine in Baltimore, who presented the findings at the .
Among the previous data showing that being overweight bestows a survival advantage on COPD patients, she noted, is a 2018 study by , which found that the effect "is more evident for subjects with severe bronchial obstruction -- i.e., a lower FEV1 -- while in mild-moderate conditions, the weight-related mortality shows a behavior similar to that observed in the general population."
Brigham explained to ѻý that agreement is lacking on whether the obesity paradox is directly related to excess fat. For example, if that was the case, suggested, "clinicians may be tempted to recommend weight gain to their patients." In fact, those authors said, other factors may be more important than weight itself: "Overweight/obese patients tended to have better preserved lung function, muscle mass, and exercise capacity -- all important predictors of mortality in this disease."
For the by Brigham and colleagues, the team examined data from the SUMMIT trial, a double-blind, randomized controlled study that examined the use of fluticasone furoate and vilanterol in adults with moderate COPD and cardiac risk. A total of 16,485 adults from 43 nations were included, all with histories of smoking at least 10 packs a day.
"As expected, the majority of mortality was attributable to cardiovascular causes," Brigham said. "This held true in all BMI categories."
The study found that underweight patients (i.e., with a BMI < 20) had a higher mortality rate compared with those of normal weight (BMI 20-25) at HR 1.31, 95% CI, 1.04-1.64. Those with with BMI > 40 also had a mortality disadvantage (HR 1.36, 95% CI, 1.00-1.86).
Compared with in the normal weight group, mortality was lower in the overweight group (BMI 25 to 30: HR 0.62, 95% CI, 0.52-0.73) and the two obese groups (BMI 30-35: HR 0.75, 95% CI, 0.62-0.90; and BMI 35-40: HR 0.85, 95% CI, 0.66-1.10).
Why might the obesity paradox fade out at higher BMIs? "Higher BMI is associated with a higher prevalence of a number of diseases that contribute to mortality, including metabolic and cardiovascular diseases," Brigham said. "We also know that at the extremes of obesity, lung function is reduced -- something that is particularly consequential in patients with COPD whose lung function is already compromised. It is reasonable to expect that at some threshold the positive effects of BMI in this population will be overwhelmed by the negative health consequences of obesity, as we see here."
She cautioned, however, that the study does not prove causality: "Confounding of the relationships we see may still exist. For example, a large number of the participants with low BMI were from Asia, and we couldn't completely account for regional differences that may affect the relationship between BMI and outcomes."
Even so, she said, the study has implications for practice. "If I have a patient with moderate COPD in my clinic and known cardiovascular disease or risk factors, I have increased concern about his or her mortality risk when he or she is underweight or has a BMI greater than 40.
"Regardless of the underlying lung disease, discussing nutrition and physical activity is an important part of caring for our patients, and sharing the results of studies such as this can provide motivation for change."
Disclosures
The study was funded by GlaxoSmothKline.
Brigham reported having no relevant disclosures; co-authors reported various disclosures, including relationships with GlaxoSmithKline.
Primary Source
American Thoracic Society
Brigham E, et al "Challenging the obesity paradox: Effect of extreme obesity on COPD mortality in patients with heightened cardiovascular risk" ATS 2018; Abstract A7495.