Body Composition and COPD: A New Perspective

Figures & data

Table 1 Conclusions Related to BMI

Author	Year	Study Design	Country, Latitude Degree	Parameters Under Study	Relevant Conclusion
R. Q. Graumam et al^Citation4	2018	Cross-sectional study	Brazil	Gender, age, smoking history, BMI, bone densitometry (DXA), lung function, limb lean body mass (ALM), bone mass index (SMI), fat mass index (FMI), vertebral fracture, Baecke questionnaire, laboratory tests	In COPD, the prevalence of low BMI was significantly higher in GOLD 3 and 4 than in GOLD 1 and 2, with approximately 42.2% of men and 20.8% of women with COPD having low BMI compared with 14.3% and 3.2% of men and women in the control group (p = 0.027)
Lisa D. M. Verberne et al^Citation5	2017	Cross-sectional study	Dutch	Age, sex, BMI, smoking, comorbidities, prescription drugs were associated	Obese patients had more comorbidities, and SABA prescriptions were significantly more frequent in overweight and obese patients than in normal-weight patients, and obese patients were significantly more likely to receive LAMA and LABA + ICS prescriptions
Florian Kirsch et al^Citation8	2020	Prospective Studies	Germany	Age, sex, smoking status, income, BMI, lung function, medication use, health care expenditure, quality of life, Charlson index, Pulmonary emphysema, DMP interruption, corticosteroid DDDs	Patients with a BMI of 30 or just above had the lowest health care expenditures, underweight and obese patients had the highest health care expenditures, and overweight (25 ≤ BMI < 30) and obesity (30 ≤ BMI < 35) were associated with reduced mortality and improved health-related quality of life.
Paul Stoll et al^Citation9	2016	Cross-sectional study	Japan	Age, sex, BMI, comorbidities, 5 and 8 year survival after discharge	Patients with BMI ≥ 25 kg/m2 had significantly higher 5-year and 8-year OS than patients with BMI < 25 kg/m2. Overweight patients (BMI > 25 kg/m2) hospitalized for acute exacerbation of COPD had lower all-cause in-hospital mortality compared with patients with BMI < 25 kg/m2.
Lingyi Yang et al^Citation10	2019	Prospective Studies	China	Lung function, mMRC score, 6-minute walk distance (6MWD), body weight, BMI, fat-free mass (FFM), fat mass (FM), lean-to-fat (LTF) ratio, skeletal muscle mass (SMM) and other body composite variables, annual number of exacerbations	In the subgroup of BMI < 25 kg/m2, a low LTF ratio was significantly associated with a reduced risk of acute exacerbation of COPD (OR = 4.528; P < 0.05, the cumulative incidence of acute exacerbation of COPD was significantly increased (P = 0.014),
Eun Kyung Kim et al^Citation11	2020	Prospective Studies	Korea	Age, gender, smoking, BMI, Charlson’s comorbidity score, pulmonary function, St George’s respiratory questionnaire score, emphysema index, CT air retention index and airway size, BMI, number of acute exacerbations of COPD, mortality, 6-minute walk distance (6MWD), mMRC score, medication history, smoking status	During the annual follow-up period, a decrease in the BMI group was associated with a significant increase in mortality. In this cohort, a 5.9% increase in the BMI group was observed to be associated with lower mortality (p = 0.004), emphysema index (B = −0.080, p < 0.001), serum hemoglobin (B = 0.333, P < 0.001), p = 0.009), serum creatinine (B = 1.955, p = 0.032) and serum protein (B = 0.763, p = 0.021) were independent factors associated with BMI.
Hye Jung Park et al^Citation12	2019	Prospective cohort study	Korea	Smoking, BMI, COPD incidence, COPD-free survival, and overall survival	Among never-smokers or light smokers, the incidence of COPD in the low BMI group (5.6–6.7%) was significantly higher than that in the other groups (2.8–4.7%). In subjects with smoking history ≥ 30 years, the incidence of COPD was higher in the low BMI group (20.1%) than in the other groups (8.4–12.4%). Compared with a low BMI, normal or above normal weight was significantly protective against developing COPD (hazard ratio, 0.609–0.739). Copd-free survival (HR 0.491–0.622) and overall survival (HR 0.440–0.585) were also better than those in patients with low BMI (both P < 0.0001).

Abbreviations: BMI, body mass index; COPD, chronic obstructive pulmonary disease; 6MWD, 6-minute walk distance; FFM, fat-free mass; FM, fat mass; LTF, lean-to-fat; SMM, skeletal muscle mass.

Table 2 Conclusions Related to WHR

Author	Year	Study Design	Country, Latitude Degree	Parameters Under Study	Relevant Conclusion
Chunlong Li et al^Citation16	2018	Cross-sectional study	China	Age, sex, education, occupations, tobacco use, alcohol consumption, physical activities, current diseases, medical treatment, inherited diseases, BMI, Smoking, alcohol consumption, physical activity, HOMA-IR, WHR, VAI, ZJU, APRI, FLI, HIS, TyG, Laboratory testso	The optimal cut-off point at WHR>0.50 yielded their high sensitivities (84.0% and 70.8%, respectively) with the maximum Youden index (0.476) in whole population. Similarly, the optimal cut-off points at WHR> 0.47 and WHR>0.53 resulted in reasonable sensitivity (75.5% and 72.8%, respectively) and specificity (63.8% and 53.4%, respectively) in lean and overweight/obese population, respectively.
Ibrahim Mahmoud et al^Citation17	2021	Cross-sectional study	Emirati	Sex, age, race, smoking habits, daily physical activity, anthropometric measurements and fingers (BMI, WC, WHR), Comorbidities, including hypertension, diabetes, dyslipidemia, assessed using systolic, diastolic blood pressure, fasting blood sample	Overweight/obesity identified by WC, WHR and BMI are predictors of hypertension, with ORs (95% CI) of 1.62 (1.35–1.96), 1.52 (1.27–1.83) and 1.44 (1.20–1.74), respectively.
Jiachen Li et al^Citation20	2020	Prospective cohort study	China	Age, sex, marital status, highest level of education), lifestyle (smoking, passive smoking, alcohol consumption, physical activity, diet, household air pollution) and medical history, height, weight, WC, hip circumference, WHR, WHtR, lung function, metabolic equivalent task hours (MET-h)	Overweight (BMI 24.0–<28.0 kg·m^2) and obesity (BMI ≥28.0 kg·m^2) were not associated with an increased risk after adjustment for waist circumference. A higher waist circumference (≥85 cm for males and ≥80 cm for females) was positively associated with COPD risk after adjustment for BMI, waist-to-hip ratio and waist-to-height ratio were positively related to COPD risk.
Gundula Behrens et al^Citation21	2014	Cross-sectional study	America	Age, sex, race distribution, marital status, education, smoking, NIH-AARP diet, medical history, BMI, WC, Hip, WHR, physical activity, smoking, COPD incidence	For waist circumference, only underweight remained positively associated with COPD (relative risk [RR] 1.56, 95% confidence interval [CI] 1.15–2.11). Larger waist circumference (highest v. normal categories, adjusted RR 1.72, 95% CI 1.37–2.16) and higher waist–hip ratio (highest v. normal categories, adjusted RR 1.46, 95% CI 1.23–1.73) were also positively associated with COPD, hip circumference (highest v. normal categories, adjusted RR 0.78, 95% CI 0.62–0.98) and physical activity (≥ 5 v. 0 times/wk, adjusted RR 0.71, 95% CI 0.63–0.79) were inversely associated with COPD.
Ahmad Jayedi et al^Citation23	2020	A systematic review and dose-response meta-analysis of prospective cohort studies		Location, age range or mean age (years), sex, number of participants, waist circumference, hip circumference, thigh circumference, waist-to-hip ratio, waist-to-height ratio, waist-to-thigh ratio, body adiposity index, body shape index, BMI, All-cause mortality	The risk of all cause mortality did not change for a waist circumference of 60–80 cm (hazard ratio80cm 1.01, 95% confidence interval 0.99 to 1.03) and then increased sharply and linearly (Pnonlinearity<0.001, n=23;). The analysis of men indicated a J shaped relation with the risk of all cause mortality, which was lowest at a waist circumference of 90 cm (hazard ratio90cm 0.96, 95% confidence interval 0.94 to 0.98), and then increased sharply and linearly (Pnonlinearity <0.001, n=16). Indices of central fatness including waist circumference, waist-to-hip ratio, waist-to-height ratio, waist-to-thigh ratio, body adiposity index, and A body shape index, independent of overall adiposity, were positively and significantly associated with a higher all cause mortality risk. Larger hip circumference and thigh circumference were associated with a lower risk.
Nina F. Caspersen et al^Citation32	2018	Cross-sectional study	Norwegian	Age, gender, height, smoking habits, weight, body mass index, waist-hip ratio, metabolic syndrome, obstructive sleep apnoea (OSA) and C-reactive protein, ADPN, lung function	The median (interquartile range) level of serum ADPN was 7.6 (5.4–10.4) mg/L. ADPN levels were positively associated with FVC % of predicted (beta 3.4 per SD adiponectin, p < 0.001)) in univariate linear regression analysis, but the association was attenuated in multivariate analysis (standardized beta 0.03, p = 0.573))
Yu-En Hsu et al^Citation33	2021	Cross-sectional study	China	Ex, age, histories of diabetes mellitus, smoking, hypertension, asthma and emphysema or bronchitis, levels of total cholesterol, LDL-C, HDL-C, diet, lifestyle factors, LAP, BRI, CI, BAI, AVI, BMI, WHR, WHtR	The results showed that the participants with high BMI (per 1 kg/m2; coefficient β, 0.303; p < 0.001), high WHR (per 1%; β, 0.123; p < 0.001), high WHtR (per 1%; β, 0.190; p < 0.001), high LAP (per 10; β, 0.245; p = 0.002), high BRI (per 1; β, 0.565; p < 0.001), high CI (per 0.1; β, 0.694; p = 0.005), high BAI (per 1; β, 0.263; p < 0.001), and high AVI (per 1; β, 0.296; p < 0.001) were significantly associated with a high FEV1/FVC.
Heng He et al^Citation35	2020	Prospective cohort study	China	Gender, age, city, family income, occupational hazard exposure, lifestyles, height, weight, body mass index, smoking status, drinking status, education levels, BMI, WC, WHR, WHtR, lung function test, Plasma CRP Measurements	Abdominal obesity indices (WC, WHR and WHtR) and lung function parameters, including forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) (all P<0.05). Each 1-unit increase in WC was associated with a 3.39 mL decrease in FEV1 and a 3.96 mL decrease in FVC (all P<0.05). Each 1% increase in WHR and WHtR was associated with a 5.42 mL and a 14.23 mL decrease in FEV1, and a 5.70 mL and a 16.92 mL decrease in FVC (all P<0.05).

Abbreviations: HOMA-IR, homeostasis model assessment of insulin resistance; WHR, waist circumstance-to-height ratio; VAI, visceral adiposity index; ZJU, Zhejiang University index; APRI, aspartate aminotransferase-to-platelet ratio index; FLI, fatty liver index; HIS, hepatic steatosis index; TyG, triglycerides and fasting blood glucose index; WC, waist circumference; WHtR, waist-to-Height Ratio; MET-h, metabolic equivalent task hours; BMI, body mass index; CRP, C-reactive protein; FEV1, Forced Expiratory Volume in the first second; FVC, Forced Vital Capacity; OSA, obstructive sleep apnoea; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; LAP, lipid accumulation product; BRI, body roundness index; CI, conicity index; BAI, body adiposity index; AVI, abdominal volume index.

Table 3 Conclusions Related to BFR

Author	Year	Study Design	Country, Latitude Degree	Parameters Under Study	Relevant Conclusion
Ryosuke Kawabata et al^Citation36	2020	Cross-sectional study	Japan	Gender, age, smoking status, weight, FVC, FEV1, BFP, SMI, BMI, VFA, WC, WHR	In the older female group, there was a significantly negative correlation between the predicted FVC% and body composition index (r =−0.139, p = 0.037 for body fat percentage; r = −0.138, p = 0.039 for body fat percentage of the trunk; r = −0.172, p = 0.010 for VFA).
Ohn G. Elliot et al^Citation37	2019	Cross-sectional study	Australian	Gender, age, ever smoked, BMI, weight, age at onset of asthma, duration of asthma, years, corticosteroid use, airway size and the area of adipose tissue within the airway wall	While adipose tissue was identified in airways from all subject groups, it was limited to the outer airway wall and was observed predominantly in large to medium sized airways (>6mm Pbm). Adipose tissue area/Pbm was positively correlated with BMI in all case groups and all airway size groups
Gwen Skloot et al^Citation41	2019	Cross-sectional study	America	Gender, age, weight, smoking status, BMI, lung function, allergy skin testing	The obese group was characterized by increased Mch reactivity, concentrated in small airways.

Abbreviations: BMI, body mass index; BFP, body fat percentage; WC, waist circumference; WHR, waist circumstance-to-height ratio; FEV1, Forced Expiratory Volume in the first second; FVC, Forced Vital Capacity; SMI, skeletal muscle mass index; VFA, Visceral fat area.

Table 4 Conclusions Related to VAT

Author	Year	Study Design	Country, Latitude Degree	Parameters Under Study	Relevant Conclusion
Isabelle K Vila et al^Citation42	2022	Randomized controlled trial	France	STING, cGAS, FADS2, delta-6 Desaturase, polyunsaturated fatty acids, interferon responses, cytosolic DNA	While revealing increased glucose uptake in the visceral adipose tissue (VAT), the brown adipose tissue (BAT), and a tendency (p = 0.08) in the subcutaneous adipose tissue (SAT), reflecting increased metabolic activity in adipose tissues.
Lucia Baila-Rueda et al^Citation43	2022	Cross-sectional study	Spain	Adipose tissue, 24S-hydroxycholesterol, 27-hydroxycholesterol, oxysterols and cholesterol, total cholesterol, triglycerides, and HDL cholesterol, Apolipoprotein A1, apolipoprotein B, lipoprotein (a), insulin, leptin, glucose, glycated hemoglobin (HbA1c), and high-sensitivity C-reactive protein (hs-CRP) were also measured	Women with higher BMI had lower HDL cholesterol (P = 0.033) and apolipoprotein A1 (P = 0.043) and higher insulin (P = 0.037), HOMA-IR (P = 0.008), and HbA1c (P = 0.024). An inverse correlation between visceral adipose tissue cholesterol concentration and serum total cholesterol (Spearman’s coefficient −0.221).
Justin C Brown et al^Citation44	2018	Cross-sectional study	America	Age, height, weight, WC, thigh circumferences, apVAT, BMI, WC	apVAT accounted for more variance in biomarkers of inflammation than BMI (R2=3.8%; P<0.001), WC (R2=3.1%; P<0.001), and BMI+WC (R2=2.9%; P<0.001). apVAT accounted for more variance in biomarkers of lipid metabolism than BMI (R2=2.9–9.2%; P<0.001), WC (R2= 2.9–5.2%; P<0.001), and BMI+WC (R2=2.4–4.1%: P 0.01).
Lin Ding et al^Citation45	2017	Cross-sectional study	China	Age, gender, smoking and drinking status, family history of CAD, educational attainment, height, weight, WC, BMI, physical activity, hypertension, dyslipidemia, and diabetes, VFA, γ-glutamyltranspeptidase (GGT), SAT, liver fat accumulation; subclinical coronary atherosclerosis, 75-goral glucose tolerance test (OGTT)	Most indicators of fat accumulation such as BMI, waist circumference, visceral fat areas, and GGT levels increased significantly with increasing coronary stenosis (all P < 0.01), except for subcutaneous fat areas which were similar among groups (P = 0.487). One-SD increase in BMI, waist circumference, log (visceral fat areas), and log (GGT levels) was associated with 10%, 3%, 66%, and 55% increase in risks of having <50% coronary stenosis, respectively.
Ryuko Furutate et al^Citation46	2011	Cross-sectional study	Japan	Weight, height, comorbidities, smoking status, WC, BMI. Fat-free mass (FFM) and fat mass (FM), FFMI, lung function, Arterial blood gases, mMRC, The 6-minute walk test, Analysis of emphysema, VFA, SAT, triglyceride, high-density lipoprotein (HDL)-cholesterol, fasting blood glucose	The COPD group (n = 101) had a higher smoking index than the control group (n = 62). The COPD group had a larger VFA than the control group. VFA was positively correlated with the MMRC scale score (P = 0.013, Rho = 0.252).
Paula Duarte de Oliveira et al^Citation50	2017	Prospective cohort study	Brazil	Gender, skin, birth weight, maternal smoking during pregnancy, schooling, family socioeconomic level, smoking at 30 years, self-reported wheezing in last year, any kind of corticosteroid use in the last 3 months, habitual physical activity, total fat mass, SAT and VATthicknesses	Women had higher total fat mass compared to men (37.3 versus 24.5%); on the other hand, men had higher mean VAT than women (6.9 versus 4.9 cm). Concerning the spirometry, men had mean FEV1 and FVC 1.1 L and 1.3 L, respectively, higher than women.
Yide Wang et al^Citation52	2021	Cross-sectional study	China	Gender, age and education level, smoking status, medical history, lung function, BMI, Visceral adipose index (VAI)	Males having a significantly higher VAI than females: 13.17 ± 3.91 vs 7.58 ± 2.65, The piecewise linear spline models indicated a significant thresh-old effect between lung function and VAI in the general population and the males population, showing an inverted U-shaped curve. But there was no significant association between VAI and lung function in females. FEV1% predicted and FVC% predicted increased with the increase of VAI (β 0.76; 95% CI 0.30, 1.21) and (β 0.50; 95% CI 0.06, 0.94) in males with VAI ≤ 14, while FEV1% predicted and FVC% predicted decreased with the increase of VAI (β −1.17; 95% CI-1.90, −0.45) and (β −1.36; 95% CI - 2.08, - 0.64) in males with VAI ≥ 15.
Alvar Agustí et al^Citation55	2012	Cohort studies	Spain	Lung function, smoking status, BMI, FFMI, 6 MWD, BODE index. Circulating WBC count, IL-6, IL-8 and TNF-α	On average the WBC count and levels ofCRP, IL-6 and fibrinogen were significantly higher in COPD patients than in smokers with normal lung function and nonsmokers, whereas IL-8 and TNF-α values were higher in smokers without COPD. In patients with COPD, the WBC count and the serum levels of CRP, IL-6 and fibrinogen, but not those of IL-8 and TNF-α, tended to increase with the severity of airflow limitation.
Damien Viglino et al^Citation58	2020	Prospective study	Canada	Age, gender, smoking status, weight, height, WC, Pittsburgh Sleep Quality Index, hip circumferences, glucose, lipid profiles, lung function, VAT, Blood sample and biochemical analysis	Triglycerides, total/HDL cholesterol ratio and HOMA-IR were positively associated with the three indices of adiposity (BMI, waist-to-hip ratio and VAT area) in individuals with COPD and controls. (all regression lines with a p<0.05). The COPD 2+ status was associated with a VAT area>75th percentile (OR = 2.27, CI95% 1.00;5.15, p = 0.05).

Abbreviations: STING, stimulator of interferon genes; cGAS, Cyclic GMP-AMP synthetase; FADS2, Polyclonal Antibody to Fatty Acid Desaturase 2; VAT,⁴² visceral adipose tissue; BAT, the brown adipose tissue; SAT,⁴² subcutaneous adipose tissue; HbA1c, glycated hemoglobin; hs-CRP, high-sensitivity C-reactive protein; BMI, body mass index; HDL, high-density lipoprotein; VAT,^44,46 Visceral fat; WC, waist circumference; FFM, fat-free mass; FM, fat mass; FFMI, Fat-free mass index; SAT,⁴⁶ subcutaneous fat; VFA, Visceral fat area;6 MWD, Six Minute Walk Distance; IL-6, interleukin 6; IL-8, interleukin 8; TNF-α, Tumor necrosis factor –α.

Table 5 Conclusions Related to FFMI

Author	Year	Study Design	Country, Latitude Degree	Parameters Under Study	Relevant Conclusion
Afsane Ahmad et al^Citation72	2021	Cross-sectional study	Iran	Age, educational degree, job circumstances, smoking habits, type of tobacco used and age of onset, smoking status, medical history, researchers. Spirometery test, weight, weight loss%, dietary intake, gastrointestinal symptoms, functional capacity, respiratory stress, physical examination, calf circumference (CC), FFM, FFMI	The results of univariate analysis showed muscle mass (p=0.036), total protein (p=0.043), FFM (p=0.047), FFMI (p=0.007), SGA (p=0.029), right handgrip strength (p=0.004) and left hand grip strength (p=0.023) were associated with FEV1. In addition, the results of multivariate analysis demonstrated low values of FFMI (p=0.005) and right handgrip strength (p=0.042) were the main detrimental factors for FEV1. The results of multivariate analysis were confirmed by stepwise model.
Jamie R Chua et al^Citation73	2019	Cross-sectional study	Philippines	Demographic, BMI, health information, body composition, grip strength, six-minute walking distance, FEV1, FEV1/FVC, PIF, PEF, CAT	Sarcopenic COPD patients had statistically significant reduced peak inspiratory flow (r= −0.6074, P value 0.0001), peak expiratory flow (r= −0.3993, P value 0.0144), hand grip strength (r= −0.3751, P value 0.0007), and CAT score (r= −0.3751, P value 0.0157) compared to non-sarcopenic patients.ow FFMI had statistically significant reduction in PIF (r= −0.5791, P value 0.0002), PEF (r= −0.4475, P value 0.0055), and hand grip strength (r= −0.4560, P value 0.0027), however low CAT score (r= −0.3422, P value 0.0285).
M. FEKETE et al^Citation75	2021	Cross-sectional study	Hungary	Weight, BMI, FFM, Malnutrition Universal Screening Tool (MUST), body mass, body fat percentage, muscle percentage, water content, 6MWD, Spirometry, quality of life, the Saint George’s Respiratory Questionnaire (SGRQ-C), mMRC, CAT	Respiratory distress was more frequent in patients with low FFMI compared to those with normal FFMI (FEV1ref%: 38.9 versus 48.6, P 5 0.023), FFMI was significantly correlated with FEV1 (r 5 0.370, P < 0.001) and 6MWD as well (r 5 0.531, P <0.001), as shown in Table 6. We found a statistically significant relationship between CAT points and FFMI (r=5 0.4906, P 5=0.0003) and CAT points with SMMI (r=5 0.4532, P 5=0.0009).
Ester Marco et al^Citation76	2018	Prospective cohort study	Spain	Age, sex, smoking history, the Mini Nutritional Assessment Short Form (MNA-SF), BMI, FFMI, the number of admissions and days of stay during the follow up period, mMRC, 6 MWT, lung function, body composition	The total number of days spent in the hospital during this period was significantly higher in patients with malnutrition: median (P25, P75) of 18 (1, 53.5) days in malnourished patients, compared to in front of 9 (3, 20.5) days in patients without malnutrition (p ¼ 0.041).
HIANG PING CHAN et al^Citation80	2016	Prospective cohort study	Singapore	Gender, race, age, FEV1, FVC, BMI, airflow obstruction, St George’s Respiratory Questionnaire and age (BOSA), 10-point index (BOSA index), all-cause mortality, SGRQ	Mortality increases with worse BOSA grades, and that race and gender did not affect mortality.
Paula Portal Teixeira et al^Citation82	2022	Prospective cohort study	Brazil	Age, gender, ethnicity, education levels, smoking habit and morbidity history, FFMI, calf circumference (CC), adductor muscle pollicis thickness (AMPT), C-reactive protein (CRP), mMRC	Low FFMI, and CC predicted malnutrition (low CC; OR = 4.6; 95% CI, 2.2–9.7 and low FFMI; OR = 8.8, 95% CI, 3.7–20.8).
Zinka Matkovic et al^Citation85	2017	Cross-sectional study	Spain	Age, sex, smoking history, treatment recorded, COPD exacerbations in the previous year, BMI, WC, hip, calf circumference (CC), WHR, mid-upper arm circumference (MUAC), triceps skin fold (TSF), mid-arm muscle circumference (MAMC)	Regarding nutritional status, patients with low exercise capacity had a lower LMI, FFMI, BMC, BMD (p < 0.01), andT-score (p < 0.05). Similar to patients with low exercise capacity, patients with low physical activity (7128 steps/day) were significantly older, had worse lung function, a higher CAT score and mMRC dyspnoea grade, more frequent exacerbations and worse health related quality of life. They also had a slower gait speed and shorter 6MWD (p < 0.01).

Abbreviations: CC, calf circumference; FFM, fat-free mass; FM, fat mass; FFMI, Fat-free mass index; FEV1, Forced Expiratory Volume in the first second; FVC, Forced Vital Capacity; PIF peak inspiratory flow; PEF, peak expiratory flow; BMI, body mass index; COPD, chronic obstructive pulmonary disease; MUST, Malnutrition Universal Screening Tool; 6 MWD, Six Minute Walk Distance; SGRQ-C, the Saint George’s Respiratory Questionnaire; MNA-SF, the Mini Nutritional Assessment Short Form; AMPT, adductor muscle pollicis thickness; CRP, C-reactive protein; MUAC, mid-upper arm circumference; TSF, triceps skin fold; MAMC, mid-arm muscle circumference; LMI, lean mass index; BMC, bone mass content; BMD, bone mineral density.

Table 6 Conclusions Related to Body Water

Author	Year	Study Design	Country, Latitude Degree	Parameters Under Study	Relevant Conclusion
Takahiro Yoshikawa et al^Citation94	2012	Cross-sectional study	Japan	Age, plasma, high molecular weight (HMW), adiponectin. ICW, ECW, ECW/ICW ratio, physical examinations, anthropometric, measurements, BMI, assessment of lung function, blood sampling	Regarding the state of cellular hydration, the plasma levelsof total adiponectin were inversely correlated with the ECW/ICW ratio and positively with ICW values in patients with COPD. TNF-α levels were closely correlated with total adiponectin levels in COPD patients (r = 0.75, P <0.001).
E.M. Baarends et al^Citation100	1997	Cross-sectional study	Netherlands	Age, lung function, BMI, TBW, ECW, ICW, FFM, FM%, ECW/TBW	The transfer factor of the lung for carbon monoxide (TL, CO) intrathoracic gas volume (ITGV), maximal expiratory and inspiratory mouth pressure, forced expiratory volume in one second (FEV1), FFM-index (FFM/height2), body mass index (weight/height2) and ICW-index correlated strongly (p<0.01) to peak oxygen consumption (V ‘O2). The ratio ECW/ICW correlated only weakly, but significantly, with peak V ‘O2 (r=−0.25, p<0.05). The results of this study further more indicate that severe FFM depletion is related to a blunted tidal volume response to peak exercise, a decreased peak oxygen pulse and an early anaerobic metabolism in patients with COPD.
Francesca de Blasioa et al^Citation101	2017	Cross-sectional study	Italy	Age, height, weight, BMI, 4 m gait speed, lung function, FFM, FFMI, FM, SM, Albumin, C-reactive protein, 250kHz/5 kHz, Ph A, Albumin	The overall prevalence of malnutrition and sarcopenia was 19.8% and 24.0% respectively, increasing with disease severity. The prevalence of sarcopenia was significantly higher in patients with malnutrition (71.2% vs 12.3%; p < 0.001), especially in those with systemic inflammation (cachectic patients) (85.7% vs 61.3%; p < 0.001). Malnourished patients with sarcopenia had a significant reduction in BMI, fat-free mass and HGScompared to non-sarcopenic patients. Finally, impedance ratio significantly increased and phase angle decreased in patients with severe sarcopenia and in cachectic patients.
Roohi Chhabra et al^Citation102	2021	Prospective cohort study	British	Age, gender, Dialysis months, No BP meds, Clinical Frailty score, Davies grade, weight, BMI, TBW, ECW, ICW, FFM, FM%, ECW/TBW	More patients in the lower predialysis serum sodium cohort had diabetes, greater frailty scores, higher CRP, and higher ratios of both ECW/ICW and ECW/TBW, with lower serum creatnine, LMI and right arm lean mass, and muscle strength. ECW/TBW (0.409 ± 0.016 vs 0.402 ± 0.016, p < 0.01), C reactive protein (CRP) (9 (4–6) vs 5 (2–12) g/L, p < 0.05), CFS (5 (4–6) vs 4 (3–6), p <0.05) were higher.

Abbreviations: HMW, high molecular weight; ICW, intracellular water; ECW, extracellular water; BMI, body mass index; TBW, total body water; FFM, fat-free mass; FM, fat mass; SM, Skeletal Muscle; PhA, phase angle; LMI, lean mass index; CFS, Clinical Frailty score; CRP, C-reactive protein.

Table 7 Conclusions Related to PhA

Author	Year	Study Design	Country, Latitude Degree	Parameters Under Study	Relevant Conclusion
Giliane Belarmino et al^Citation107	2017	Prospective Study	Brazil	Age, weight, height, Severe ascites (%), Model for endstage liver disease score, Encephalopathy (%), BMI, Midarm muscle circumference (cm), IL-6/IL-10 ratio (pg/mL), Handgrip strength (kg), Albumin (g/dL)	Patients from the PA > 4.9° group were younger and had higher MAMC, albumin, and ND-HGS values and lower severe ascites and encephalopathy incidences, IL-6/IL-10 ratios, and CRP levels than did patients from the PA ≤ 4.9° group. The PA ≤ 4.9° group were significantly more likely to die, as demonstrated by Kaplan-Meier curves.
Büntzel J et al^Citation108	2019	Prospective Study	Germany	Gender, age, BMI, SD, PA, Median survival (mo)	Patients with a PA>5° showed a significantly better overall survival (p=0.016; Figure 1). Median survival in this group was 51.16 months (range=7.02–116.79 months), while median survival of malnourished patients was 13.84 months (range=0.69–125.19 months).
M. Dittmar1 et al^Citation112	2015	Cross-sectional study	British	Age, weight, height, BMI, Resistanc, PhA, the total body potassium measurement, 5, 50 and 100 kHz he resistance, reactance and phase angle at three frequencies	The phase angle at 100 kHz strongly correlated with total body potassium (r = 0.70, P = 0.001). The phase angle at 100kHz discriminated more strongly between patients with Type 2 diabetes and control subjects than did the phase angle at 50 kHz. Phase angle ratios better discriminated between patients and control subjects than phase angles alone (phase angle at 5 kHz/ phase angle at 50 kHz ratio, P = 1.51 9 10 16; phase angle at 5kHz/phase angle at 100 kHz ratio, P = 2.13 9 10).
Laurence Genton et al^Citation113	2016	Retrospective study	Switzerland	Age, weight, height, BMI, PhA, impedance, resistance, reactance, FFM, CIRS, Comorbidities, medication, lung function	When replacing sex-specific phase angle quartiles by sex-specific FFMI quartiles in models 1 and 2, the R2 (95% CI) decreased from 15.6 (11.4, 27.2) to 8.6 (3.8, 16.5) in women and from 21.5 (17.1, 29.2) to 14.2 (9.4, 20.2) in men. The addition of sex-specific FFMI quartiles to models 1 and 2 led to an R2 (95% CI) of 15.1 (11.7, 28.0) in women and 21.3 (17.4, 29.7) in men. Thus, the phase angle better predicts mortality than BIA-derived FFMI, and the addition of FFMI to phase angle does not improve the Cox regression models. Kaplan-Meier analyses 160 showed the higher risk of mortality with lower phase angle or 161 standardized phase angle quartiles
F de Blasio et al^Citation118	2017	Cross-sectional study	Italy	Age, sex, height, weight, BMI, FEV1, Impedance, Bioimpedance index, PhA, Handgrip strength, FFMI, FM, FFM, BODE index	An inverse correlation between PhA and BODE index was observed both in males (r=- 0.343, Po0.001) and females (r=−0.358, Po0.01), whereas a marked decline across GOLD stages was observed only in males (5.37 ± 0.89, 5.00 ± 0.92 and 4.82 ± 0.99 degrees in stages I/II, III and IV, respectively). With respect to respiratory muscle strength, there was in both genders a significant association of MIP or MEP with BIA estimates of FFM, and also with PhA (for MEP only in males).
Nathalie Martínez-Luna et al^Citation118	2022	Cross-sectional study	America	Age, sex, height, weight, diabetes, Hypertension, smoking statue, Heart failure, Hospitalization previous year, BMI, lung function, FImpedance, Bioimpedance index, PhA, Handgrip strength, FFMI, FM, FFM, SMMI, BODE index, Exercise tolerance	A linear regression adjusted model showed associations between body mass index, fat-free mass, skeletal muscle mass index, appendicular skeletal muscle mass index, and phase angle (PhA), and sarcopenia with FEV1 (%). As regards FVC (%), PhA and exercise tolerance had positive associations.

Abbreviations: BMI, body mass index; PA, prealbumin; PhA, phase angle; FFM, fat-free mass; FM, fat mass; FEV1, Forced Expiratory Volume in the first second; FVC, Forced Vital Capacity.

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