COPD and the “Obesity Paradox:” Is a Higher BMI Protective?

A high body mass index (BMI) has been linked to elevated mortality in the general population.¹ In individuals with chronic obstructive pulmonary disease (COPD), however, a low BMI (≤21 kg/m²) is associated with increased mortality.² Some findings suggest that obesity may be protective in this patient population; this “obesity paradox,” has also been noted in research focused on cardiovascular disease.³

BMI “has been shown to contribute to the expression of COPD phenotypes, through its influence on pulmonary mechanics, systemic inflammation and its biomarkers, and ultimately on mortality,” wrote the investigators in an article published in 2014 in Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation.² “However, the association between BMI to specific comorbidities and longitudinal outcomes in patients with COPD has been less well characterized.”

To explore these associations, the researchers conducted a multicenter observational study to investigate rates of COPD-related comorbidities and other factors at various BMI levels in 1659 patients with COPD from the BODE (Body Mass Index, Airway Obstruction, Dyspnea, Exercise Capacity) cohort study. They also explored potential links between these comorbidities and increased mortality risk.

Patients were divided into 5 BMI categories: BMI <21 kg/m² (underweight), BMI 21 to24.9 kg/m² (normal weight), BMI 25 to29.9 kg/m² (overweight), BMI 30-34.9 kg/m² (obesity type I), and BMI ≥35 kg/ m² (obesity type II and III). They were followed for a median of 51 months (interquartile range  27-77).

The researchers discovered the following differences across the BMI spectrum:

• BMI ≤21 kg/m² (considered underweight) was associated with an increased prevalence of abdominal aortic aneurism, peripheral artery disease, osteoporosis, and substance abuse, as well as prostate cancer in men.
• BMI ≥30 kg/ m² (considered obese or very obese) was associated with an elevated prevalence of diabetes, systemic hypertension, pulmonary hypertension, hyperlipidemia, chronic renal failure, congestive heart failure, sleep apnea, gout, venous insufficiency, degenerative joint disease, and erectile dysfunction in men.
• Across all BMI categories, there was a similar prevalence of other comorbidities found to increase mortality risk in COPD, including pulmonary fibrosis, atrial fibrillation, and cancers and gastric/ duodenal ulcer.^4,5
• BMI showed an inverse relationship to the ratio of forced expiratory volume in 1 second (FEV₁) to forced vital capacity, the BODE index, and hyperinflation.
• BMI had a U-shaped association with the modified Medical Research Council dyspnea (mMRC) scale and the St. George’s Respiratory Questionnaire (SGRQ).
• BMI showed an inverse U-shaped association with exercise capacity (6-minute walk distance [6MWD])
• From the lowest to highest BMI categories, the crude mortality rates were 60%, 43%, 37%, 36%, and 28%, respectively (P <.0001). 
• Although the lowest BMI group had the fewest comorbidities, there were more respiratory deaths in this group compared with the other groups.

Overall, these findings “provide evidence of an association between BMI, the clinical expression of comorbidity clusters, and outcomes in patients with COPD,” the investigators concluded. Although the reasons for the apparent obesity paradox are still unclear, these results support the “hypothesis of time differential where obese and very obese COPD individuals may experience a slower process with potential clinical intervention (long-term killer, short-term protection) than the rapid effect of cachexia-malnutrition, a short-term killer for which there is little success with known interventions.”

For additional insight into the relationship between body weight and COPD, Pulmonology Advisor interviewed Wayne Tsuang, MD, a pulmonologist at the Cleveland Clinic in Ohio, and Nadia Hansel, MD, MPH, associate dean for research and associate professor of medicine at Johns Hopkins Medicine in Baltimore, Maryland.

Pulmonology Advisor: What is known about the relationship between obesity/overweight and COPD?

Dr Tsuang: More than one-third of patients with COPD are obese.⁶ Obesity is known to be associated with immune system dysfunction, [so] it could be harder for an obese patient to recover from a flare of COPD with a weak immune system.

Obesity/overweight also predisposes patients to many other [conditions] such as diabetes, heart failure, hypertension, and hyperlipidemia, as well as symptoms such as shortness of breath. All of these can can predispose patients to exacerbations of COPD and make recovery more challenging.

Dr Hansel: Lambert, et al, had a nice article in Chest [in] 2017 demonstrating the role of obesity/overweight in COPD.⁶ Increasing obesity class was independently associated with worse respiratory-specific and general quality of life (St George’s Respiratory Questionnaire [SGRQ] and Short Form Health Survey-36 [version 2] score, respectively), reduced 6MWD, increased dyspnea (modified Medical Research Council [mMRC] Dyspnea Scale score ≥2), and greater odds of severe acute exacerbation of COPD. 

Pulmonology Advisor: What are the takeaways/treatment implications for our clinician audience?

Dr Tsuang: [One of] the most important therapies for COPD is regular exercise, which can be hard for patients who are obese/overweight. Therefore, counseling patients on weight loss becomes even more important. Losing weight directly results in less stress to [the] lungs with COPD. I tell [patients with] COPD who are obese to imagine they are walking around carrying a bag of concrete. If they could let go of that bag think how much easier it would be to walk. Being obese is like walking around carrying that concrete bag. If they can lose the weight I promise them they will breathe and feel better.

Dr Hansel: There have been no large-scale weight loss intervention studies in COPD, [al]though there is one ongoing pragmatic weight loss trial (INSIGHT) funded by the National Institutes of Health. Despite the lack of randomized controlled trials confirming the benefit of weight loss in overweight/obese patients with COPD, it seems prudent to encourage weight loss in these individuals. This must be done with caution given that cachexia and sarcopenia are associated with poor outcomes in patients with COPD.

Pulmonology Advisor: What should be next steps in this area, in terms of research or otherwise?

Dr Tsuang: There are several efforts underway to screen for and detect COPD earlier. Earlier diagnosis can lead to earlier treatment, which could improve a patient’s quality of life.

Dr Hansel: There is a need for randomized controlled trials to determine the respective benefit of dietary interventions, physical activity, and weight loss on COPD outcomes.

References

1. Abdelaal M, le Roux CW Docherty NG. Morbidity and mortality associated with obesity. Ann Transl Med. 2017;5(7):161.
2. Divo MJ, Cabrera C, Casanova C, et al. Comorbidity distribution, clinical expression and survival in COPD patients with different body mass index. Chronic Obstr Pulm Dis. 2014;1(2):229-238.  
3. Chang VW, Langa KM, Weir D, Iwashyna TJ. The obesity paradox and incident cardiovascular disease: a population-based study. PLoS One.  2017;12(12):e0188636.
4. Pischon T, Boeing H, Hoffmann K, et al. General and abdominal adiposity and risk of death in Europe. N Engl J Med. 2008;359(20):2105-2120.
5. Divo MJ, Cote C, de Torres JP, et al; BODE Collaborative Group. Comorbidities and risk of mortality in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012;186(2):155-161.
6. Lambert AA, Putcha N, Drummond MB, et al; COPDGene Investigators. Obesity is associated with increased morbidity in moderate to severe COPD. Chest. 2017;151(1):68-77.