European Journal of Cardiovascular Medicine

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease. Although preventable, once established it cannot be cured, but effective self-management strategies can decrease the burden of disease and improve the quality of life¹.

COPD is characterized by a range of pathophysiologic changes contributing to a highly variable clinical presentation as well as heterogeneity among the patients. One of the main consequences of the disease is the progressive loss of skeletal muscle mass and the presence of several bioenergetic abnormalities, mainly expressed by weight loss.²

The above systemic effects might enhance the clinical symptoms significantly, and have a negative impact on quality of life^3,4.  Currently, the nutritional status of subjects with COPD is primarily evaluated using body mass index^5.Weight loss and low body mass index (BMI) are negative prognostic factors for survival independent of other prognostic indices based on the degree of pulmonary dysfunction⁶. However, alterations in body composition can occur in COPD in the absence of clinically evident weight loss⁵.

The body mass is comprised of two compartments: fat mass and fat-free mass (FFM). The first is, a metabolic inactive energy store, whereas the latter contains the metabolically active organs, skeletal muscle being the largest of these organs. Recent studies suggest that fat-free mass index (FFMI) provides information in addition to BMI⁷. This might be attributed to the fact that loss of skeletal muscle mass is the main cause of weight loss in COPD, whereas loss of fat mass contributes to a lesser extent, leading to the plausible theory that FFMI reflects the muscle mass better than BMI.

COPD severity is significantly correlated with Low FFMI. Despite the fact that disease severity is assessed only with variables expressing airflow limitation and obstruction, parameters associated to weight loss are also considered important in assessing the disease prognosis and are also an important independent determinants of COPD outcomes^8,9.

COPD is characterized by persistent airflow limitation and decline in exercise tolerance.¹⁰,¹¹Regular assessment of COPD patients by measurement of exercise capacity indicates the ability of the individual to increase ventilation and cardiac output in response to the demands of exercise. It also measures the degree of peripheral muscular conditioning, motivation, and the intensity of exertional symptoms as perceived by the COPD patient. Compared with other alternative exercise tests including cardiopulmonary exercise test and the shuttle walk test, the 6-minute walk test (6MWT) is a relatively simple and economical method for assessing the functional status of cardiopulmonary disease and has been widely used in patient management of COPD.¹²

All diagnosed cases of stable COPD (post-bronchodilator FEV1/FVC < 0.7) visiting the OPD of Pulmonary Medicine Department, IGMC Shimla

Inclusion criteria:

1.All consecutive stable COPD patients aged 40–75 years diagnosed as per GOLD criteria willing to participate after obtaining informed consent.

Exclusion criteria:         

1.Respiratory infections in last four weeks.

2.Active lesion of tuberculosis

3.Diagnosed cases of malignancy.

4.COPD patients with hypertension, diabetes mellitus, chronic kidney disease, hepatic diseases.

5.COPD patients with neuromuscular, musculoskeletal, peripheral vascular, cardiovascular disorders which limit the capacity to perform the 6- min walk test.

6.Subjects who had past abdominal or chest surgeries.

Ethical consideration: The research protocol was reviewed and approved by concerned institutional ethical review committee.

Data collection

All consecutive, clinically stable COPD patients of 40-75 years of age presenting in the Department of Pulmonary Medicine were screened for enrollment in the study after obtaining informed consent. Diagnosis of COPD was done based on symptoms, physical examination, and Pulmonary Function Tests. Severity of COPD was done based on the global initiative for chronic obstructive lung disease (GOLD) criteria.

Anthropometric measurements: Height, Weight, Waist circumference, Hip circumference, BMI were also measured.

Pulmonary Function Test:

The spirometric examination was done using an electronic portable PC based spirometer with printer (MODEL – VITALLOGRAPH- COMPACT BUCKINGHAM, ENGLAND). It fulfilled the accuracy and the precision criteria as per the American Thoracic Society.

Body composition measurement

Body composition was assessed by Multi - frequency bio-electrical impedance analysis   using BODY STAT, Quad scan 4000 according to the recommendations in NIH Technology Assessment Statement.FFMI was measured by multifrequency bioelectrical impedance in kg/m² according to the equation, FFMI = fat- free mass/ height².

Six- minute walk test parameters in COPD patients

Six-minute walk test was performed in all patients of COPD. The mean value of SpO2, heart rate and distance covered were compared between COPD GOLD stage 1&2 and GOLD stage 3&4.

STATISTICAL ANALYSIS

The data was reported as frequency and percentage for categorical variables and mean ± SD for continuous variables with normal distribution. The prevalence of malnutrition in COPD patients was reported as percentage with 95% Confidence interval. Two-sided p value <0.05 was taken as statistically significant. A multiple stepwise linear model was established to identify factors independently associated with Fat Free Mass Index. The data was analysed using IBM SPSS STATISTICS 2.0 software.

Patient’s characteristics are summarized in Table 1. FFMI was significantly lower in patients with COPD GOLD stage (3&4) as compared to COPD GOLD stage (1& 2) with p=0.035. BMI was significantly higher in patients with COPD Gold stage (1& 2) with p = 0.008. FEV1, FEV1/FVC and 6MWD were significantly higher in stage 1&2 (p<0.001, p<0.001, p=0.016 respectively).

Table 1: Baseline Characteristics of the 48 Patients Stratified according to GOLD Staging of COPD

Correlation of data for the whole study group is summarized in Table 2. In the present study on linear regression, we found that the independent predictors for low fat free mass index with statistically significant difference were female gender (beta= -0.216 and p=0.034) and low BMI (beta=-0.678 and p=<0.001).

In present study, COPD patients of GOLD stages 1&2 and 3 & 4 have been compared. The mean BMI of patients of COPD GOLD stage 1&2 was found to be 22.86±4.40 kg/m² and COPD GOLD stage 3&4 was found to be 19.77±3.31 kg/m²,the difference being statistically significant (p=0.008).

The mean value of FFMI of COPD Gold stage 1&2 was 15.73±3.45 kg/m² and COPD Gold stage 3&4 was 13.77±2.77 kg/m², where the difference is statistically significant (p=0.035).In harmony with our study, the studies conducted by Vestbo et al⁸, Ischaki et al¹⁴ also proved gradually declining BMI and FFMI in COPD patients where they were categorised into COPD GOLD stage 1,2,3 and 4.

Our study revealed that values of FFMI& BMI were higher in early stages of COPD. Other studies conducted by Vestbo et al⁸, Ischaki et al¹⁴are also supportingthat fat-free mass index (FFMI) and BMI gradually declines as the severity of COPD increases. This might be attributed to various factors like high resting energy expenditure due to increase work of breathing or inadequate dietry intake, hypoxia, inflammation etc. The fact that loss of skeletal muscle mass is the main cause of weight loss in COPD, resulting in low BMI & FFMI,thus, creating a graveimpact in the severe stages of COPD. Also, there is an evidence that FFMI is a better indicator of muscle mass than BMI ¹⁴, hence the body weight/mass in severe COPD patients is maximally affected by FFMI.

The study result showed that FFMI was highly correlated with BMI and provided information beyond BMI regarding variables expressing disease severity.Progressively increasing dyspnea (as expressed by mMRC scale), more severe airway bstruction (as expressed by percentage of predicted FEV1 ) may represent critical factors leading to the systemic consequences that affect the FMI as disease progresses¹⁴. Various studies have also reported an association between BMI and mortality risk in COPD¹⁵. A study has also shown that FFMI can predict three years COPD mortality in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) cohort study¹⁶. The results of our study also show FFMI as a better independent predictor of systemic disease severity than BMI.

Table 2:  Univariate and Multivariate analysis of risk factors of low FFMI.

Our study revealed that with the increase in severity of COPD, there was a decrease in 6MWD. The 6MWD in GOLD stage 1&2 and GOLD stage 3&4 were 424.32± 95.82 metres and 356.96 ±90.52 metres respectively. The pre-walk(p=0.049)and post-walk Spo2 (p=0.026)were found to be significantly lower in severe COPD compared to mild-moderate COPD. Although, the change in SpO₂ was higher in severe COPD patients, but not statistically significant(p=0.520). Similarly, the pre-walk, post-walk heart rate and the change in heart rate showed insignificant difference between the mild-moderate and severe COPD cases. Identical results showing significantly lesser 6MWD in severe COPD patients were obtained by Ischaki et al¹⁴.

COPD is characterized by persistent airflow limitation, resulting in decline in exercise tolerance due to chronic hypoxic state and hence, reduced 6 Minute Walk Distance. Measurement of exercise capacity assesses the ability of the individual to increase ventilation and cardiac output in response to the demands of exercise, thus records the exercise tolerance. It also measures the degree of peripheral muscular conditioning, motivation, and the intensity of exertional symptoms as perceived by the patient. This inexpensive 6 min walk test reflects the activities of daily living¹², and is used to analyse disease severity and assess patient progress before and after clinical interventions such as Pulmonary Rehabilitation⁸.  The skeletal muscle mass diminishing from the early stages of COPD leads to reduced exercise tolerance and mild exercise inability that can be improved through a rehabilitation program. It can also serve as a powerful tool to assess the disease prognosis and has also been used along with measures of lung function, BMI and dyspnea to calculate the BODE index.⁷

In synchronicity with other studies we conclude that an abnormal body composition is an important non-pulmonary impairment that modulates the risk of functional limitation in COPD. Fat-free mass index (FFMI) accurately determines the nutritional status of the COPD patients and may be closely correlated with COPD severity and exercise capacity.

FFMI values were lower in those stages where severe airflow limitation and obstruction exists. Low FFMI has a significant correlation with impaired pulmonary function and it may serve as useful predictor of COPD severity in addition to BMI. Therefore, these patients require special attention for nutritional intervention to achieve effective pulmonary rehabilitation.Assessment of FFMI should be considered in the routine assessment of COPD and should be incorporated in standard treatment/management of COPD patients, as it is a powerful predictor of COPD severity and its progression. Also, evaluation of FFMI can be considered to establish, wether any relationship exists between initial values of FFMI and the progression of severity of COPD.

We also conclude that six- minute walk test is an important index of exercise tolerance and nutritional level in patients with COPD, where the patients with severe COPD who have poor functional status as measured by 6MWD have a high potential mortality. In addition, the present study highlights the role of Pulmonary Rehabilitaion which can alter the progression of severity in COPD patients. This information directs the  clinical interventions to simultaneously cover the active treatment and symptomatic treatment in the management of COPD patients. In addition, 6Min Walk Test can be used as a tool to assess, monitor and plan the treatment module of COPD patients with low FFMI.

However, there are few limitations in this study. More women should be enrolled as the female subjects were fewer due to the relatively low morbidity of COPD in women. Future studies should be conducted using MRI and dual–x-ray absorptiometry, as bioelectrical impedance may be less precise than these techniques, for the assessment of body composition. BIA may be less precise than other techniques, such as MRI and DXA, for the assessment of FFMI, hence, more precise tecniques can be used further on^16,17Also, the sample size in the present study was small. The results would have been more significant if larger number of cases were enrolled in the study. Hence, we advocate to recruit a greater number of study population with equal enrolment of the female subjects in our future researches.

We also advise the precise differentiation of the basic cause of chronic weight loss due to low FFMI and explore the expected attributable causes like decrease dietary intake, increased energy expenditure and prolonged chronic inflammation, that COPD patients are exposed to.Another mentionable limiting factor of our study is that  it did not measure the correlation between FFMI and exercise capacity such as a six-minute walk distance. Astudy showed a close relationship between 6-MWD and FFMI¹⁴.

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