Pulmonary rehabilitation outcome in chronic obstructive pulmonary disease patients with a different body composition

Context Change in body composition is commonly present in chronic obstructive pulmonary disease (COPD) patients. Aim The aim of this study was to investigate the effects of pulmonary rehabilitation program (PRP) on COPD patients who have a different body composition. Materials and methods In this study, we measure;Deg;BM;Deg;I and fat-free mass index (FFMI) using a single-frequency bioelectrical impedance analysis apparatus to classify patients into three categories: Group 1 nonmuscle depleted;Deg;BM;Deg;I greater than or equal to 21 kg/m2 and FFMI greater than or equal to 16. Group 2 muscle depleted;Deg;BM;Deg;I greater than or equal to 21 kg/m2 and FFMI less than 16 in men or FFMI less than 15 in women. Group 3 muscle depleted with cachexia;Deg;BM;Deg;I less than 21 kg/m2 and FFMI less than 16 in men or FFMI less than 15 in women. PRP outcomes were assessed by the improvement in pulmonary function severity, exercise capacity by 6-min walk test, dyspnea score by modified-British Medical Research Council, and health status by combined assessment test score and arterial blood gas improvements. Results Forty-four patients with FFMI were measured by bioelectrical impedance analysis. The patients were mainly elderly men (N=35; 79%), who have a mean age of 65 years with different global initiative obstructive lung disease stage I–IV. In the nonmuscle depleted group, there were statistically significant improvements in the mean values of FFMI (kg/m2) while in the muscle depleted group there were improvements as regards the mean values of dyspnea score by modified-British Medical Research Council; in the cachectic group there were statistically significant improvements in the mean values of BMI (kg/m2), forced expiratory volume in the first second (FEV1), forced expiratory volume in first second divided by forced vital capacity ratio, combined assessment test score after PRP. Conclusions A comprehensive PRP outcome change in COPD patients with different body compositions.


Introduction
Chronic obstructive pulmonary disease (COPD) is a common, preventable, and treatable disease that is characterized by respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases [1].
Measurement of BMI may not accurately reflect changes in body composition in COPD. Body weight consists of fat mass and fat-free mass (FFM), which includes water and body cell mass (bones, internal organs, muscle). Measurement of body cell mass can be performed by measurement of fat-free mass index (FFMI) [2]. COPD patients have concomitant chronic diseases linked to the same risk factors, that is, aging, smoking, and inactivity, which may have a great impact on health status and survival in those patients. Skeletal muscle dysfunction is characterized by sarcopenia (loss of muscle cells) and abnormal function of the cells [3]. Inflammatory mediators may contribute to skeletal muscle wasting and cachexia. The association between low body cell mass and worsening prognosis is a common observation in COPD patients [4].
Cachexia and muscle depletion are characterized by FFM depletion, which can be estimated using skinfold anthropometric measurement and bioelectrical impedance analysis (BIA) [5]. FFM measurement by BIA is easy to perform and has shown significant correlations to reference measurements methods such as magnetic resonance imaging [6].
Pulmonary rehabilitation is a comprehensive intervention including exercise, nutritional counselling, psychological counselling, and education about the disease nature, progression, prevention of exacerbation, and breathing exercises, which lead to improvement in clinical outcomes such as quality of life, dyspnea score, and exercise capacity [7].
Thus, the aim of this study was to assess pulmonary rehabilitation outcome on COPD patients with different body compositions.

Materials
A retrospective, randomized, controlled study in the period from June 2016 to October 2018 .The study protocol was reviewed by the appropriate Ethics Committee, from Faculty of Medicine, Beni Suef University. All patients gave their informed, written consent before study inclusion.
The study population consists of 44 patients with a clinical diagnosis of COPD and confirmed by doing pulmonary function tests they were chosen from the Outpatient Clinic of Chest Diseases Department, at Faculty of Medicine, Beni-Suef University

Inclusion criteria
Diagnosis of COPD patients was established by full clinical history and examination, history of cigarette or shisha smoking or history of indoor biomass fuel exposure, and spirometric measurements that demonstrated irreversible airflow obstruction. All patients were required to fulfill the criteria of COPD according to latest global initiative obstructive lung disease (GOLD) 2019 classification. Patients must have had at least 3 months of smoking cessation.

Exclusion criteria
Patients with acute exacerbation; patients with acute respiratory failure; and patients with joint, muscle, and neurological disorders unable to do pulmonary rehabilitation exercises; patients with cardiac failure class III or IV NYHA, neoplastic disease, and hyperthyroidism were excluded, as these can be causes of weight loss. Patients who had contraindications for BIA measurement, such as those with defibrillator placement or pacemakers, were excluded from the study.

Study design
Patients were classified by body composition into three different groups based on BMI and FFM depletion: (1) Group 1: nonmuscle depleted BMI greater than or equal to 21 kg/m 2 and FFMI greater than or equal to 16. (2) Group 2: muscle depleted BMI greater than or equal to 21 kg/m 2 and FFMI less than 16 in men or FFMI less than 15 in women. (3) Group 3: muscle depleted with cachexia BMI less than 21 kg/m 2 and FFMI less than 16 in men or FFMI less than 15 in women.

Study outcome
All tests were performed before and after pulmonary rehabilitation program: (1) Assessment of exercise capacity by 6-min walk test (6MWT) [8].
Assessment of functional severity by spirometry [12].
This was performed by MasterScreen PFT.

Pulmonary rehabilitation program
The pulmonary rehabilitation program (PRP) consists of a 1 h session three times a week for a 8-week period. Patients underwent strengthening, endurance exercise, and respiratory muscle exercises. They exercised on a treadmill and on a cycle ergometer. They also performed light floor exercises with and without weights and stretching exercises as per ATS guidelines for pulmonary rehabilitation [2].
BMI measurement is calculated by dividing the weight in kilograms by height in meters squared. FFMI measurement: The bioelectrical impedance technique is a reliable and valid approach for estimation of human body composition. This method is safe, noninvasive, and provides rapid measurements. The procedure involves sending a very small current of 800 μA at an alternating frequency of 50 kHz through the body and measuring its resistance. We used Body Fat Analyzer BT 905 (BIA BT-905) (Skylark Device Co., Taipei, Taiwan). Both instruments required electrode placements at specific sites on the wrist, distal second metacarpal, ankle, and distal second metatarsal. Therefore, 'whole-body' BIA was measured. FFMI is measured by dividing the FFM in kilograms by height in meters squared.

Statistical analysis
The statistical analysis was performed using SPSS 19 (SPSS, Chicago, IL, USA). Results are presented as the mean±SD, and proportional data are presented as percentages. Groups were compared using one-way analysis of variance. Two groups were compared using the independent samples t-test. Relevant indicators of COPD were correlated using Spearman's correlation or Pearson's correlation analysis.
A P value of less than 0.05 was considered statistically significant.

Results
This study was done on 44 COPD patients. The age of the patients ranged from 52 to 78 years with a mean age of 65 years. Of the patients 35 (79%) were men and nine (20%) were women. Clinical characteristics of the studied patients with different stages of COPD according to GOLD classification and 11 patients were nonmuscle depleted with a BMI more than or equal to 21 kg/m 2 and FFMI greater than or equal to 16 and 16 patients with muscle depleted BMI greater than or equal to 21 kg/m 2 and FFMI less than 16 and 17 patients with cachexia BMI less than 21 kg/m 2 and FFMI less than 16. The groups were well balanced in terms of comorbidities and age as in Table 1. Also, the sample size was determined according to the duration of the study.
In the nonmuscle depleted group, there were statistically significant differences as regards the mean values of FFMI (kg/m 2 ) mean±SD (64±22) to be mean±SD (68.10±15.10) after PRP but there were improvements regarding other variables but nonstatistically significant differences as shown in Table 2. In the muscle depleted group, there were statistically significant differences as regards the mean values of dyspnea score by mMRC mean±SD (2.93±1.1) to be mean±SD (2.37±0.78), but there were improvements regarding other variables but nonstatistically significant differences as given in  Table 4.
Comparison between nonmuscle depleted, muscle depleted, and cachectic group before PRP showed statistically significant difference as regards the mean values of BMI (kg/m 2 ), FFMI (kg/m 2 ), SpO 2 , FEV 1 , dyspnea (mMRC), CAT score as in Table 5, while after PRP there were statistically significant differences as regards the mean values of PCO 2 , FEV 1 , dyspnea (mMRC), and CAT score as in Table 6.
Regarding FFMI as the lowest mean values in the cachectic group 28±10 to be 40.39±13.81 after PRP, followed by the muscle depleted group 38±14 to be 47.87±13.60 after PRP and the highest value was in the nonmuscle depleted group 64±22 which was also found to be 68.10±15.10 after PRP, with statistically significant difference between them before PRP but nonsignificant after PRP.
In this study, the lowest mean values of FEV 1 found in the cachectic group 28±10 to be 40.39±13.81 after PRP, followed by the muscle depleted group 38±14     value was in the nonmuscle depleted group 2.18±1 to be 1.54±0.5 after PRP. The lowest mean values of CAT score found in the muscle depleted group were 11.93±6 and 17.12±6.9 after PRP, followed by the cachectic group to be 12.56±5.2 and 18.3±6.6 after PRP and the highest value was in the nonmuscle depleted group 24.45±8.8 and 27.09±5.5 after PRP.

Discussion
PRP improves the health status and exercise capacity in COPD patients with different body compositions, but there was significant improvement in functional severity and health status in COPD patients with muscle depleted with cachexia while dyspnea score improved significantly in patients with muscle depleted without cachexia but FFMI significantly increased in the non-muscle depleted COPD patients. FFMI significantly correlated with dyspnea, exercise capacity, pulmonary function, and respiratory muscle function and may be a predictor of COPD severity due to enhanced protein catabolism in COPD patients with muscle mass depletion [13]. Previous studies have reported that the muscle mass depletion subgroup, defined as BMI less than 21 kg/m 2 and FFMI less than 16 in men or FFMI less than 15 in women, was more prevalent in COPD GOLD stage IV more than patients in GOLD stages II and III [14]. So our results agree with the previous work as muscle depleted with cachexia group with BMI less than 21 kg/m 2 and FFMI less than 16 with a mean FEV 1 of 28.1±10.52 which means that most of them are in stage IV but there was statistically significant increase after PRP as the mean FEV 1 reaches 40.39±13.81 [15].
Weight loss was particularly prevalent in COPD patients and was closely correlated with exercise capacity limitation, increased frequency of exacerbations, and decreased quality of life and mortality. Improvements in exercise performance, and quality of life and skeletal muscle function after exercise training in COPD patients are well reported. However, the effect of PRP on COPD patients with different body compositions has rarely been studied.
Previous studies hypothesized that FFM-depleted COPD patients are less likely to improve after pulmonary rehabilitation since exercise training can induce systemic inflammation and oxidative stress in COPD patients with muscle depletion [16].
Regarding FFMI the lowest mean values were in the cachectic group followed by the muscle depleted group and the highest value was in the nonmuscle depleted group with statistically significant difference between them before PRP but nonsignificant after PRP. So, these results agree with Jones et al. [15] as they found that patients who had sarcopenia had the same responses to pulmonary rehabilitation as those without muscle sarcopenia in terms of exercise performance (incremental shuttle walk) and quality of life (St. George's questionnaire). Tunsupon and Mador [17] found that body weight muscle depletion and muscle depletion had no effect on patients achieving the minimal clinically important difference for quality of life and exercise tolerance measures after PRP which is not in agreement with our results. Maltais et al. [18] performed aerobic exercise on patients with COPD and he found that COPD patients who had muscle depletion have weaker muscles than those who had not have muscle depletion.
In this study the lowest mean values of FEV 1 was found in the cachectic group, followed by the muscle depleted group and the highest value was in the non-muscle depleted group, regarding FEV 1 /FVC the lowest mean values were in the cachectic group, followed by the muscle depleted group and the highest value was in the nonmuscle depleted group. Criner et al. [19] found that there were statistically significant improvements of the mean values of FEV 1 , FEV 1 /FVC but there were improvements in 6MWT but not significant after 8 weeks of pulmonary rehabilitation.In our study, the lowest mean values of 6 MWT were found in the cachectic group followed by the muscle depleted group and the highest value was in the non-muscle depleted group. The highest mean values of dyspnea (mMRC) was found in the cachectic group, followed by the muscle depleted group and the highest value was in the nonmuscle depleted group. The lowest mean values of CAT score was found in the muscle depleted group followed by the cachectic group and the highest value was in the nonmuscle depleted group.
In the study of Troosters et al. [20], 100 patients were assigned to receive the full exercise training program.
Patients who completed the 6-month duration program of outpatient training resulted in significant and clinically relevant improvement in exercise performance, 6-minute walk distance, quality of life, and respiratory and peripheral muscle strength. In the study of Griffiths et al. [21] on 200 disabling chronic lung disease patients (the majority with COPD) who were assigned for a 6-week rehabilitation program also showed greater improvements in general and diseasespecific health status and walking ability.
In the study by Ali et al. [22] nine sessions of PR exercises in COPD patients with acute exacerbation produced statistically significant improvement in FEV 1 , 6MWT, exercise capacity, general well-being, and peak oxygen uptake.
In a study of Ries et al. [23] on 119 outpatients COPD with moderate to severe airflow obstruction were randomly assigned to an 8-week comprehensive pulmonary rehabilitation; there were significant improvement in clinical symptoms and exercise performance. Pulmonary rehabilitation improves COPD systemic manifestations and relieves dyspnea. These improvements are clinically important.

Study limitation
BIA is not a gold standard method for assessing body composition, but is safe and relatively available. The small number of patients is another important limitation of this study, which did not allow statistical analysis in some groups. Also, female participants were fewer due to the relatively low morbidity of COPD in women.

Conclusion
PRP improves different functional parameters, health status, and exercise capacity in COPD patients with a different body composition but there is significant improvement in functional severity and health status in COPD patients with muscle depleted with cachexia.