Article scientifique

OBESITY AND COPD: IS FATTER REALLY BETTER? Authors:

Roxana G Galesanu1, Sarah Bernard , Karine Marquis1, Yves Laçasse1, Paul Poirier1, Jean

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Bourbeau , and François Maltais

Affiliation :

'Centre de recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, Canada. 2Respiratory, Epidemiology and Clinical Research Unit, Montreal Chest Institute of the Royal Victoria Hospital, McGill University Health Centre, McGill University.

RG Galesanu was recipient of a research training award of the Respiratory Health Network of the Fonds de la Recherche en Santé du Québec (FRSQ). This work was supported by the Respiratory Health Network of the FRSQ and by an unrestricted grant from GlaxoSmithKline, Canada.

Running head: Obesity and COPD

Word count: 2953

Address of correspondence: Dr François Maltais

Institut Universitaire de Cardiologie et de Pneumologie de Québec 2725 Chemin Ste-Foy Québec, Québec Canada G1V4G5 Tel: 418-656-4747 Fax:418-656-4762 E-mail: francois.maltais(2>med.ulaval.ca

Abstract

Objective: Overweight/obesity is associated with longer survival in chronically ill patients, a phenomenon refer to as the obesity paradox. We investigated whether the positive association between increased body weight and survival is due to fat accumulation or to confounding factors.

Methods: 190 patients with stable COPD with a longitudinal follow-up to assess survival status were enrolled. Anthropometric measurements, pulmonary function tests, midthigh muscle cross-sectional area (MTCSACT), arterial blood gas and exercise testing data were

obtained. Patients were categorized into two subgroups according to a body mass index (BMI) < or > 25 kg/m2.

Results: 72 patients (38%) died during the mean follow-up period of 72 ± 34 months. Survival tended to be better in the overweight/obese patients but this difference did not

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reach statistical significance. Patients with a BMI > 25 kg/m had a better lung function and a larger MTCSACT than those with a BMI < 25 kg/m2 (p < 0.001). Overweight/obese

patients also had a significantly higher peak workrate than patients with a BMI < 25 kg/m2

(p < 0.001). PaÛ2 and PaCÛ2 were not significantly different in the two groups. When adjusted for PaC02, peak workrate and MTCSACT, patients with low BMI tended to have a

better survival.

Conclusion: These results suggest important confounders such as disease severity, exercise capacity and muscle mass should be considered when interpreting the association between increased BMI and survival in COPD.

Introduction

Chronic obstructive pulmonary disease (COPD) is becoming a global health epidemic. Even though a "preventable and treatable disease", COPD is expected to rise from the sixth to the third commonest cause of death worldwide in 2020 and to become the fifth most common cause of chronic disability worldwide by the same year . Besides progressive airflow limitation, air trapping and progressive shortness of breath, COPD also

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has significant systemic repercussions , one of them being weight loss and skeletal muscle atrophy. These body composition abnormalities are associated with increased mortality, independent of lung function impairment .

The current global obesity epidemic is changing the nature of the nutritional abnormalities seen in patients with COPD. In fact, a rapidly growing proportion of patients with COPD do not exhibit low body weight but rather overweight and obesity . Based on the existing link between obesity and reduced life expectancy, systemic hypertension, type 2 diabetes, cancer, and cardiovascular diseases , it is tempted to speculate that body weight excess would also be deleterious for patients with COPD.

C O ~T

In patients affected from chronic heart ' or kidney diseases , overweight and obesity paradoxically seems to prolong survival, a phenomenon referred to as the "obesity

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paradox" or "reverse epidemiology" ' . From study to study, this observation appears to be robust and is valid up to a body mass index (BMI) of 40 kg/m2. The obesity paradox may

also exist in COPD, a statement based on the inverse relationship between mortality and BMI in this patient population ' . However, this finding is not universal .

Why would excess body weight protect against premature mortality in chronic diseases such as COPD? In a previous study we submitted that this epidemiological association could be explained by several confounding variables influencing the relationship between body weight and survival and that could not always be taken into

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account by statistical analyses . For example, we and others have reported that overweight or obese patients with COPD tend to get medical attention with better preserved expiratory flows and less hyperinflation compared to their lean counterparts. Obese patients

with COPD also tend to have greater muscle mass compared lean patients . These observations are important because of the high prognostic impact of these variables. If true, they would also suggest that accumulating fat may not be the reason why increased BMI may be associated with better survival in patients with COPD.

This study was undertaken to address the following questions: i) is overweight/obesity associated with better survival in COPD and ii) are there important confounding factors that should be taken into account when evaluating the relationship between survival and BMI in this diseases. We hypothesized that increased BMI would be associated with improved survival and that this relationship can be largely explained by confounders such as severity of lung impairment, muscle mass and exercise capacity that are not typically dealt with in large epidemiological studies looking at the relationship between body weight and survival in COPD. To test these hypotheses, we took advantage of a longitudinal cohort of patients with COPD that were recruited between 1995 and 2005 in our institution. Part of the data pertaining to this cohort has been published in an investigation of the role of muscle wasting and survival in COPD . Since this first publication, the cohort has been expanded and the follow-up has been prolonged.