Exercise Capacity, Airflow Limitation in COPD Is Associated With Fat-Free Mass

Patients with COPD with normal weight and high FFMI had the least airflow limitation and the highest level of physical activity and exercise capacity.

In chronic obstructive pulmonary disease (COPD), a patient’s fat-free mass index (FFMI) affects exercise capacity, health-related quality of life (HRQoL), and the level of systemic inflammation, although the effect of FFMI on these factors differs depending upon the patient’s BMI. These are among study findings published in Chest.

Body composition alterations, including low FFMI, are recognized risk factors for mortality and future exacerbations in patients with COPD and may occur irrespective of the patient’s body weight. Investigators sought to determine whether using FFMI to stratify patients with COPD within the same body mass index (BMI) classification group would help to characterize patients with respect to their capabilities and risks. The researchers also assessed the independent associations between fat-free mass vs fat mass with exercise capacity, HRQoL, and systemic inflammation in each BMI group.

Investigators analyzed baseline data from 2137 patients from the prospective, observational, multicenter COPD and Systemic Consequences-Comorbidities Network (COSYCONET) trial (ClinicalTrials.gov Identifier: NCT01245933), which was conducted at 31 centers in Germany. Patients analyzed were in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1 to 4 of COPD (n = 197, 887, 812, and 241 for stages 1, 2, 3, and 4, respectively); were 61% male; had a median (SD) age of 65 (8) years; and had a median forced expiratory volume in 1 second (FEV1) of 52.5 (18.8) percent predicted.

The investigators divided patients into 4 BMI groups: (1) pre-obese (BMI 25 to <30 kg/m2); (2) obese (BMI 30 to <35 kg/m2); (3) underweight (BMI <21 kg/m2): and (4) normal-weight (BMI 21 to <25 kg/m2). General linear model univariate regression analysis was used to evaluate the differences among patients with low, normal, or high FFMI in each BMI group.

Clinicians and researchers should consider screening patients with COPD for body composition abnormalities through a combination of BMI and FFMI classifications rather than each of the two indexes alone.

The researchers found 12.3% of participants were underweight, 31.3% were normal weight, 39.6% were pre-obese, and 16.8% were obese, and that the FFMI for these groups were 81%, 53%, 42%, and 39%, respectively. Thus, the proportion of patients with low FFMI decreased based on the increases in BMI.

The cohort of patients with normal weight and high FFMI had the lowest degree of airflow limitation (FEV1, 59.5 [20.7] percent predicted), the lowest proportion of patients with modified Medical Research Council scores less than 2 (27%), the highest levels of physical activity (median International Physical Activity Questionnaire score, 3732 [1386-7391]), the best exercise capacity (6-minute walk distance [6MWD], 77 [17] percent predicted), and a median health-related quality of life total score (measured by the Saint George’s Respiratory Questionnaire for COPD) of 37 (22).

Underweight patients who had normal and high FFMI had improved exercise capacity vs underweight patients with low FFMI. Pre-obese patients with normal and high FFMI had better lung function, exercise capacity, and physical activity vs pre-obese patients with low FFMI.

After adjustment for all covariates, fat-free mass was associated with the 6MWD in underweight participants (3.68 meters [95% CI, 1.50-5.85 meters] per kg of FFM). Among participants in the normal weight and pre-obese groups, fat-free mass was not associated with the 6MWD after adjustment for FEV1, lung transfer factor for CO, and pack-years of smoking (P ≥.129).

Study limitations include the use of bioelectrical impedance analysis to assess body composition. In addition, the reference values were derived from individuals aged 45 to 69 years, and about 33% of the patients were older than 70 years. Furthermore, the cross-sectional analysis can only report associations and not causal relationships.

“Using a large data set of a COPD cohort we demonstrated that depending on BMI, body composition is differently associated with exercise capacity, HRQL, and systemic inflammation,” stated the investigators. “Clinicians and researchers should consider screening patients with COPD for body composition abnormalities through a combination of BMI and FFMI classifications rather than each of the two indexes alone.”

Disclosure: This research is supported by unrestricted grants from AstraZeneca GmbH, Bayer Schering Pharma AG, Boehringer Ingelheim Pharma GmbH & Co KG, Chiesi GmbH, GlaxoSmithKline, Grifols Deutschland GmbH, MSD Sharp & Dohme GmbH, Mundipharma GmbH, Novartis Deutschland GmbH, Pfizer Pharma GmbH, Takeda Pharma Vertrieb GmbH & Co KG, and Teva GmbH for patient investigations and laboratory measurements. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Machado FVC, Vogelmeier CF, Jörres RA et al. Differential impact of low fat-free mass in people with COPD based on body mass index classifications: results from COSYCONET. Chest. Published online December 2, 2022. doi:10.1016/j.chest.2022.11.040