Antagonistic implications of sarcopenia and abdominal obesity on physical performance in COPD

Discussion

This is the first study presenting the prevalence of sarcopenia and abdominal obesity, to characterise its functional implications and predictive value for physical functioning in a representative group of Dutch COPD patients eligible for pulmonary rehabilitation.

To date, the prevalence of sarcopenia has only been explored in a non-institutionalised civilian population of South Korea (32.8% of male and 12.2% of female COPD patients) [11]. Clearly, the current proportions overshadow the prevalence in South Korea, but the latter was reported in a relatively healthy population, as individuals admitted to hospital or nursing homes were not included. The higher prevalence of sarcopenia in COPD than in the healthy elderly (based on available literature [10]) reflects the suggested accelerated ageing in COPD, which is further supported by the reported shorter telomere length in COPD patients [18]. Potential catabolic triggers for inducing the sarcopenic process in COPD include physical inactivity, oxidative stress, inflammation, use of glucocorticosteroids and hypoxia [19]. As described in the recently published ERS statement on nutritional assessment and therapy in COPD [6], abnormally low FFMI in normal-to-underweight COPD patients is based on well-established adverse effects of low FFMI on physical performance and survival, and defined as a FFMI below age- and sex-specific 10th-percentile values. Depending on the cut-off value, prevalence rates range from 15 to 35 [3, 20, 21], but are low or absent in overweight and obese subjects. Although we did not use BMI-specific ASMI reference values as recently proposed by Prado et al. [22], a high prevalence of the sarcopenic phenotype persisted across all BMI categories, including 74.5% of overweight and 53.7% of obese patients. The ASMI cutoffs for sarcopenia are therefore particularly useful to diagnose abnormal body composition in overweight and obese patients. This concept has also been observed in patients with non-small cell lung cancer, in which 59% of the overweight patients were sarcopenic [23].

For the diagnosis of sarcopenia, the European Working Group on Sarcopenia in Older People (EWGSOP) recommends using the presence of low physical function (strength or performance) next to low ASMI [9]. One study aimed to verify the association between ASMI and physical functioning in older COPD outpatients [24]. However, they only assessed 6MWD as a measure for physical functioning and concluded that FEV₁ was a stronger predictor of physical functioning in COPD patients than body composition. Another study demonstrated that skeletal muscle weakness in COPD patients was due to loss of ASM, but was not related to airflow obstruction [25]. We explored the relation between low ASMI and a comprehensive set of functional outcome measures in the current population of COPD patients, as the relative influence of muscle mass versus impaired lung function on performance might differ between tests [24, 26, 27]. Indeed, we showed that sarcopenia (in general and expressed per kilogram ASM) is not only accompanied by impaired muscle strength, but also with impaired exercise performance, which was more pronounced for peak workload than for 6MWD. Although actual V′_O2peak was lowest in sarcopenic patients, they showed the highest V′_O2peak expressed as % predicted. This is due to the lower predicted values for this group, which are based on weight-class. Non-sarcopenic patients were generally overweight to obese and overall showed better physical functioning, typically reflecting the “obesity paradox” (stating that obesity is, on one hand, associated with better survival and some functional outcomes but, on the other hand, also associated with increased risk of cardiovascular and metabolic diseases). Referring to the high prevalence of abdominal obesity in COPD patients [12] and, moreover, in sarcopenic patients [11], it was relevant to investigate if and in what direction coexistence of abdominal obesity further affected physical functioning in COPD patients. This group of sarcopenic patients with concomitant abdominal obesity generally displayed a higher physical functioning than sarcopenic patients without abdominal obesity. This finding corresponds to previous literature reporting that exercise capacity is preserved or even increased in obese COPD patients during cycling (non-weight bearing exercise) [28, 29], except when walking is used as testing modality (weight bearing exercise) [30]. A potential explanation for this functional improvement in advanced COPD might be a lowering effect of obesity on resting and dynamic hyperinflation as established determinant of exercise impairment in COPD [29, 31]. Nonetheless, this condition of excessive body weight with a disproportional low muscle mass (i.e. sarcopenic obesity) may exert cumulative risks on metabolic and cardiovascular health, resulting in increased morbidity and mortality [32]. Loss of muscle mass can result in decreased muscle oxidative capacity which is related to metabolic disorders including diabetes and metabolic syndrome in non-obese individuals [33]. Decreased oxidative capacity may even be more pronounced in COPD due to a muscle fibre I to II shift. Indeed, a recent population study demonstrated an association between sarcopenia and metabolic syndrome in male COPD patients [11]. Although conclusive data were not available in the present study, abdominal obesity was accompanied by higher CRP-levels, corresponding with recent data indicating that excessive abdominal FM contributes to the systemic inflammation in COPD, which in turn is an important risk factor for cardiovascular disease [4, 34]. Albeit abdominal obesity seem to be protective in the present study, the effect on cardiovascular co-morbidity should be further evaluated in subsequent study in order to be able to point out the net effect of this phenotype.

In our COPD patients, a three-compartment body composition model (including ASMI, BMC and A/G%FM) had a higher predictive value for physical functioning than a two-compartment model (including FFMI and FMI) or one-compartment model (BMI). Nonetheless, differences were found in the predictive values of the body composition variables when comparing physical functioning outcomes, but also when comparing men with women. ASMI positively contributed to muscle strength, peak workload and CET (CET only in men), whereas A/G%FM positively contributed to muscle strength and 6MWD in men, but negatively to 6MWD in women. The better prediction of ASMI for muscle strength and peak workload as compared with CET and 6MWD can be attributed to the direct interaction between muscle mass and weakness in this population, whereas muscle endurance is suggested to be affected by multiple additional factors related to COPD [35]. Noticeable is the independent contribution of BMC to endurance in the regression model. Lower functional performance has been described in patients with osteoporosis, but a contribution of the bone mass to functional performance has never been shown so far.

Our analyses revealed more sex variations, as all reported physical functioning outcomes significantly differed across body composition phenotypes in men, but in women no differences could be detected in CET and 6MWD across body composition phenotypes. Moreover, the coexistence of abdominal obesity next to sarcopenia resulted in higher muscle strength, peak workload and CET in men, while this only applied for muscle strength in women. Therefore, especially sarcopenic men might be protected for physical functioning by the presence of abdominal obesity. However, the reason for the sex difference in the functional impact of abdominal obesity is unclear. Nonetheless, sex differences in the degree of muscle function impairment have also been found in cancer patients [36, 37]. Its underlying mechanism may differ between men and women, suggesting that the degree of physical impairment is affected by sexual dimorphism [36].

Some shortcomings of the current study need to be considered. Because of the cross-sectional nature of our data, we were not able to identify cause–effect relationships. Another limitation was the lack of data on (unintended) weight loss to assess the relative contribution of cachexia (unintentional weight loss >5% in 6 months and low FFMI) to sarcopenia. Additionally, the current results cannot be generalised to the whole COPD population, because the studied patient sample consisted exclusively of patients referred for pulmonary rehabilitation. However, these patients pertain an interesting population because of their functional impairments.

Future research is necessary to further unravel the causes and effects of sarcopenia and abdominal obesity in COPD. Nonetheless, the current findings indicate that assessment of the three-compartimental body composition (ASMI, A/G%FM and BMC) might be favourable over distinction between FFMI and FMI, indicated by 1) the high persisting prevalence's of sarcopenia and abdominal obesity in all BMI categories; 2) its discrimination for impaired muscle strength and endurance; and 3) the higher predictive value of the three-compartment regression model compared to the one- or two-compartment models.