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Pulmonary function and functional capacity cut-off point to establish sarcopenia and dynapenia in patients with COPD

ABSTRACT

Objective

To establish a cut-off point for clinical and functional variables to determinate sarcopenia and dynapenia in COPD patients, and to analyze the impact of skeletal muscle dysfunction (SMD) on these variables.

Methods

Cross-sectional study, screened COPD patients for sarcopenia or dynapenia through low muscle mass and hand grip strength (HGS). Clinical variables: pulmonary function, respiratory muscle strength and functional capacity (FC). The precision of the variables in determining points of predictive cut-off for sarcopenia or dynapenia were performed using the Receiver Operating Characteristic curve and two-way analysis of variance.

Results

20 COPD patients stratified for sarcopenia (n = 11) and dynapenia (n = 07). Sarcopenia group presented lower lean mass and lower maximal inspiratory pressure (MIP), decreased HGS, reduced FC (p<0.050). Dynapenia group presented reduced MIP, lower HGS and walked a shorter distance at Incremental shuttle walk test (ISWT) (p<0.050). We found cut-off points of forced expiratory volume in one second (FEV1), MIP and maximal expiratory pressure (MEP) and ISWT. It is possible to identify sarcopenia or dynapenia in these patients. We found the coexistence of the conditions (SMD effect) in COPD – reduction in the distance in the ISWT (p = 0.002) and %ISWT (p = 0.017).

Conclusion

In moderate to very severe COPD patients the sarcopenia could be predicted by FEV1 (%predicted) < 52, MIP < 73 cmH2O, MEP < 126 cmH2O and distance traveled of < 295 m in ISWT. Whereas dynapenia could be predicted by FEV1 < 40%, MIP < 71 cmH2O, MEP < 110 cmH2O and distance of < 230 m traveled in ISWT.

Keywords:
Sarcopenia; Chronic obstructive pulmonary disease; Musculoskeletal system

RESUMO

Objetivo

Estabelecer ponto de corte entre as variáveis clínicas e funcionais para avaliar a prevalência de sarcopenia e dinapenia em pacientes com Doença Pulmonar Obstrutiva Crônica (DPOC), além de analisar o impacto da Disfunção Muscular Esquelética (DME) nestas variáveis.

Métodos

Realizado estudo transversal com pacientes diagnosticados com DPOC para determinar sarcopenia ou dinapenia por meio do índice de baixa massa muscular e Força de Preensão Palmar (FPP). Avaliadas a função pulmonar, força muscular respiratória e capacidade funcional (CF). A precisão das variáveis na determinação dos pontos de corte previstos para as doenças em questão foi obtida a partir da curva Receiver Operating Characteristic (ROC) e de uma análise bidirecional da variância.

Resultados

Ao final da análise, obtiveram-se 20 pacientes com DPOC estratificados por sarcopenia (n = 11) e dinapenia (n = 07). O grupo com sarcopenia apresentou menor massa magra e menor pressão inspiratória máxima (PImáx), diminuição da Força de Preensão Palmar (FPP) e redução da CF (p<0,050). O grupo com dinapenia apresentou redução da PImáx, menor FPP e menor distância percorrida no teste Incremental Shuttle Walk (ISWT) (p<0,050). Foram encontrados pontos de corte no Volume Expiratório Forçado (VEF1) durante o primeiro segundo na PImáx, na Pressão Expiratória Máxima (PEmáx) e no ISWT, o que possibilitou identificar sarcopenia ou dinapenia nestes pacientes. A partir destes resultados, foi possível encontrar coexistência das condições (efeito DME) na DPOC: redução da distância no ISWT (p = 0,002) e % ISWT (p = 0,017).

Conclusões

Em pacientes com DPOC moderada a muito grave, a sarcopenia pode ser prevista pelo VEF1 (% previsto) <52, PImáx <73 cm H2O, PEmáx <126 cm H2O e distância percorrida de <295 metros no ISWT. Já a dinapenia pode ser prevista pelo VEF1 <40%, PImáx <71 cm H2O, PEmáx <110 cm H2O e distância de <230 metros percorrida no ISWT.

Descritores:
Sarcopenia; Doença pulmonar obstrutiva crônica; Sistema musculoesquelético

INTRODUCTION

Chronic Obstructive Pulmonary Disease (COPD) is characterized by a persistent airflow limitation initially associated with abnormal inflammatory response in the airways and lungs.(11 GOLD: Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of COPD [Internet]. Wisconsin: GOLD; 2018 [cited 2018 July 22]. Available from: https://goldcopd.org/wp-content/uploads/2017/11/GOLD-2018-v6.0-FINAL-revised-20-Nov_WMS.pdf
https://goldcopd.org/wp-content/uploads/...
) Secondarily, its progression reflects on multisystemic symptoms and the presence of comorbidities such as skeletal muscle dysfunctions (SMD), obstructive sleep apnea, cardiovascular disease, metabolic syndrome, osteoporosis, mental disorders and lung cancer.(22 Chatila WM, Thomashow BM, Minai OA, Criner GJ, Make BJ. Comorbidities in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2008;5(4):549-55. http://dx.doi.org/10.1513/pats.200709-148ET. PMid:18453370.
http://dx.doi.org/10.1513/pats.200709-14...
,33 Jaitovich A, Barreiro E. Skeletal muscle dysfunction in Chronic Obstructive Pulmonary Disease (COPD): what we know and can do for our patients. Am J Respir Crit Care Med. 2018;198(2):175-86. http://dx.doi.org/10.1164/rccm.201710-2140CI. PMid:29554438.
http://dx.doi.org/10.1164/rccm.201710-21...
) Systematic inflammation in COPD increases the presence of inflammatory mediators on bloodstream, promoting oxidative stress, consequently resulting on protein degradation, causing SMD.(44 Byun MK, Cho EN, Chang J, Ahn CM, Kim HJ. Sarcopenia correlates with systemic inflammation in COPD. Int J Chron Obstruct Pulmon Dis. 2017;12:669-75. http://dx.doi.org/10.2147/COPD.S130790. PMid:28255238.
http://dx.doi.org/10.2147/COPD.S130790...

5 Kalyani RR, Corriere M, Ferrucci L. Age-related and disease-related muscle loss: the effect of diabetes, obesity, and other diseases. Lancet Diabetes Endocrinol. 2014;2(10):819-29. http://dx.doi.org/10.1016/S2213-8587(14)70034-8. PMid:24731660.
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-66 Gayan-Ramirez G, Decramer M. Mechanisms of striated muscle dysfunction during acute exacerbations of COPD. J Appl Physiol. 2013;114(9):1291-9. http://dx.doi.org/10.1152/japplphysiol.00847.2012. PMid:23372146.
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) Nutritional imbalance and hypoxemia are also potential contributors for this condition, which results in a poor prognosis independent of lung function.(77 Maltais F, Decramer M, Casaburi R, Barreiro E, Burelle Y, Debigaré R, et al. An official American Thoracic Society/European Respiratory Society statement: update on limb muscle dysfunction in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2014;189(9):e15-62. http://dx.doi.org/10.1164/rccm.201402-0373ST. PMid:24787074.
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)

SMD is composed by peripheral muscle weakness, a shift from type I and II to a higher presence of type II fibers and muscular atrophy. COPD patients usually have decreased tolerance to physical exercise and difficulties in performing activities of daily living. Hence studying skeletal muscle function, structure and its dysfunction in this population is important because its repercussions bring to low exercise performance, poor health status and premature mortality.(77 Maltais F, Decramer M, Casaburi R, Barreiro E, Burelle Y, Debigaré R, et al. An official American Thoracic Society/European Respiratory Society statement: update on limb muscle dysfunction in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2014;189(9):e15-62. http://dx.doi.org/10.1164/rccm.201402-0373ST. PMid:24787074.
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,88 Barreiro E, Gea J. Molecular and biological pathways of skeletal muscle dysfunction in chronic obstructive pulmonary disease. Chron Respir Dis. 2016;13(3):297-311. http://dx.doi.org/10.1177/1479972316642366. PMid:27056059.
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)

Age-related loss of muscle strength is known as dynapenia,(99 Clark BC, Manini TM. What is dynapenia? Nutrition. 2012;28(5):495-503. http://dx.doi.org/10.1016/j.nut.2011.12.002. PMid:22469110.
http://dx.doi.org/10.1016/j.nut.2011.12....
) which leads to functional impairment of the skeletal muscle system and is associated with diminished physical performance.(1010 Clark BC, Manini TM. Sarcopenia ≠ dynapenia. J Gerontol A Biol Sci Med Sci. 2008;63(8):829-34. http://dx.doi.org/10.1093/gerona/63.8.829. PMid:18772470.
http://dx.doi.org/10.1093/gerona/63.8.82...
) Loss of skeletal muscle mass is referred as sarcopenia(1111 Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, et al. Sarcopenia: European consensus on definition and diagnosis. Report of the European Working Group on Sarcopenia in Older People. Age Ageing. 2010;39(4):412-23. http://dx.doi.org/10.1093/ageing/afq034. PMid:20392703.
http://dx.doi.org/10.1093/ageing/afq034...
) and its etiology could have genetic, physiological, and environmental factors.(1212 Woo J. Sarcopenia. Clin Geriatr Med. 2017;33(3):305-14. http://dx.doi.org/10.1016/j.cger.2017.02.003. PMid:28689564.
http://dx.doi.org/10.1016/j.cger.2017.02...
) It is noteworthy that there is no global consensus on the term sarcopenia.(1313 Mitchell WK, Williams J, Atherton P, Larvin M, Lund J, Narici M. Sarcopenia, dynapenia, and the impact of advancing age on human skeletal muscle size and strength; a quantitative review. Front Physiol. 2012;3:260. http://dx.doi.org/10.3389/fphys.2012.00260. PMid:22934016.
http://dx.doi.org/10.3389/fphys.2012.002...
) Both conditions are linked to reduction in muscle performance leading to exercise intolerance and sedentary behaviors.(1414 Neves T, Lopes MMB, Souza MGC, Ferriolli E, Fett CA, Fett WCR. Sarcopenia versus dynapenia: functional performance and physical disability in cross sectional study. J Aging Res Clin Pract. 2018;7:60-8.) It is already known that sarcopenia could coexist with other disorders,(1515 Jeejeebhoy KN. Malnutrition, fatigue, frailty, vulnerability, sarcopenia and cachexia: overlap of clinical features. Curr Opin Clin Nutr Metab Care. 2012;15(3):213-9. http://dx.doi.org/10.1097/MCO.0b013e328352694f. PMid:22450775.
http://dx.doi.org/10.1097/MCO.0b013e3283...
) but the presence and prevalence of the overlapping between dynapenia and sarcopenia is still unknown.

The prevalence of sarcopenia in stable COPD patients is around 15%, which increased with age and GOLD stages.(1616 Jones SE, Maddocks M, Kon SS, Canavan JL, Nolan CM, Clark AL, et al. Sarcopenia in COPD: prevalence, clinical correlates and response to pulmonary rehabilitation. Thorax. 2015;70(3):213-8. http://dx.doi.org/10.1136/thoraxjnl-2014-206440. PMid:25561517.
http://dx.doi.org/10.1136/thoraxjnl-2014...
) The prevalence of dynapenia in COPD patients needs to be investigated. It is important to emphasize that COPD is characterized by two different phenotypes that have their own particularities, which we should take in account when thinking on how much sarcopenia and dynapenia are related to these phenotypes.(1717 McNicholas WT. COPD-OSA overlap syndrome: evolving evidence regarding epidemiology, clinical consequences, and management. Chest. 2017;152(6):1318-26. http://dx.doi.org/10.1016/j.chest.2017.04.160. PMid:28442310.
http://dx.doi.org/10.1016/j.chest.2017.0...
) Therefore, our aim was to establish a cut-off point for clinical and functional variables to determinate sarcopenia and dynapenia in COPD patients and to analyze the impact of skeletal muscle dysfunction on the evaluated variables. We hypothesized that in COPD patients, sarcopenia and dynapenia could be predicted by reduced functional capacity, respiratory muscle strength and airway obstruction.

METHODS

Study design

This was a cross-sectional study performed on a convenience non-probability sample, conducted in the Santa Cruz Hospital’s Cardiorespiratory Rehabilitation Program (Santa Cruz do Sul, RS, Brazil). The sample of our study was constituted of patients who attend the pneumology outpatient clinic of the Santa Cruz Hospital for follow-up and treatment of their conditions and were requested to join the Cardiorespiratory Rehabilitation Program through the pulmonologist or general practitioner referral. The Research was approved by the Research Ethics Committee of University of Santa Cruz do Sul, protocol n. 1.514.705. All volunteers signed an informed consent statement prior to participation.

Subjects and selection

Subjects with clinical diagnosis of COPD confirmed by pulmonary function test, adequate cognition, no disease exacerbation 30 days prior to the study who signed the informed consent statement were included in the study. The exclusion criteria were musculoskeletal or neurological disorders that affected the locomotor system in such a way that would impede participation in the research protocol, clinical diagnosis of lung cancer, current alcoholism, arrhythmias, uncontrolled metabolic disease, or electrocardiogram alterations.

Measurements

The research was conducted in an acclimated laboratory at a temperature of 22 °C and relative humidity between 50% and 60%, during the morning (between 8 a.m. to 12 a.m.). Subject’s clinical characteristics were reviewed and recorded including age, sex, height, weight and medications used.

Dynapenia screening

Hand-grip strength (HGS) was measured to evaluate muscle strength (Jamar Hydraulic Dynamometer, Bolingbrook, IL, USA). To perform the maneuver, volunteers were sitting on a standard height chair without armrest with their shoulder adducted, elbow flexed at 90°, forearm in neutral position, and wrists with 15° extension.(1818 Desrosiers J, Bravo G, Hébert R, Dutil E. Normative data for grip Strength of elderly men and women. Am J Occup Ther. 1995;49(7):637-44. http://dx.doi.org/10.5014/ajot.49.7.637. PMid:7573334.
http://dx.doi.org/10.5014/ajot.49.7.637...
) Participants were asked to grasp the dynamometer at their maximal power. Three attempts on both hands were performed with a one-minute rest between each of them. The mean value of each hand was used in the analysis. We considered dynapenia when our patients presented cut-off values of < 30 kg/f for men and < 20 kg/f for women.(1919 Lauretani F, Russo CR, Bandinelli S, Bartali B, Cavazzini C, Di Iorio A, et al. Age-associated changes in skeletal muscles and theireffect on mobility: an operational diagnosis of sarcopenia. J Appl Physiol. 2003;95(5):1851-60. http://dx.doi.org/10.1152/japplphysiol.00246.2003. PMid:14555665.
http://dx.doi.org/10.1152/japplphysiol.0...
)

Sarcopenia screening

The skeletal muscle mass was assessed by the appendicular skeletal muscle mass (ASM) and defined skeletal muscle mass index (SMI) as ASM/height2 (kg/m2).(2020 Baumgartner RN, Koehler KM, Gallagher D, Romero L, Heymsfield SB, Ross RR, et al. Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol. 1998;147(8):755-63. http://dx.doi.org/10.1093/oxfordjournals.aje.a009520. PMid:9554417.
http://dx.doi.org/10.1093/oxfordjournals...
) Sarcopenia was diagnosed according to the criteria proposed by the European Working Group for Sarcopenia in Older People.(1111 Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, et al. Sarcopenia: European consensus on definition and diagnosis. Report of the European Working Group on Sarcopenia in Older People. Age Ageing. 2010;39(4):412-23. http://dx.doi.org/10.1093/ageing/afq034. PMid:20392703.
http://dx.doi.org/10.1093/ageing/afq034...
) Were considered sarcopenic those patients with low muscle mass defined as SMI below 7.26 kg/m2 for men and below 5.45 kg/m2 for women.(1111 Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, et al. Sarcopenia: European consensus on definition and diagnosis. Report of the European Working Group on Sarcopenia in Older People. Age Ageing. 2010;39(4):412-23. http://dx.doi.org/10.1093/ageing/afq034. PMid:20392703.
http://dx.doi.org/10.1093/ageing/afq034...
)

To evaluate the lean mass, patients’ body composition was assessed by means of electrical bioimpedance with Biodynamics® (model 420, international version 5.1). The exam was performed according to the National Institutes of Health Technology Assessment Conference statement.(2121 American Society for Clinical Nutrition. Bioelectrical impedance analysis in body composition measurement: National Institutes of Health Technology Assessment Conference. Am J Clin Nutr. 1996;64(3, Suppl):387S-532S. PMid:8928699.)

Pulmonary function test

To assess pulmonary function a digital spirometer (Microloop®, MK8, Care Fusion, Hoechberg, Germany) was used. The test was performed in accordance to the American Thoracic Society recommendations,(2222 Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, et al. Standardisation of spirometry. Eur Respir J. 2005;26(2):319-38. http://dx.doi.org/10.1183/09031936.05.00034805. PMid:16055882.
http://dx.doi.org/10.1183/09031936.05.00...
) and the results were interpreted according to the values predicted by Pereira et al.(2323 Pereira CAC, Sato T, Rodrigues SC. New reference values for forced spirometry in white adults in Brazil. J Bras Pneumol. 2007;33(4):397-406. http://dx.doi.org/10.1590/S1806-37132007000400008. PMid:17982531.
http://dx.doi.org/10.1590/S1806-37132007...
) The variables analyzed were: forced expiratory volume in 1 s (FEV1), and the FEV1/FVC ratio. Airflow limitation was categorized in agreement to the Global Initiative for Chronic Obstructive Lung Disease 2018 recommendations, where patients were classified as mild (GOLD I), moderate (GOLD II), severe (GOLD III), or very severe (GOLD IV).(11 GOLD: Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of COPD [Internet]. Wisconsin: GOLD; 2018 [cited 2018 July 22]. Available from: https://goldcopd.org/wp-content/uploads/2017/11/GOLD-2018-v6.0-FINAL-revised-20-Nov_WMS.pdf
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)

Respiratory muscle strength

Respiratory muscle strength (RMS) was evaluated through digital manometer (MDI®, MVD300, Porto Alegre, Brazil), where we obtained measures of the maximum inspiratory pressure (MIP) and the maximum expiratory pressure (MEP). MIP was obtained after the individual expired to the residual volume and carried out the inspiration until total lung capacity. For the measurement of the MEP, the patient underwent an inspiration to total lung capacity, expiring until the residual volume. The values were later compared with those described in the literature for Brazilian population(2424 Neder JA, Andreoni S, Lerario MC, Nery LE. Reference values for lung function tests. II. Maximal respiratory pressures and voluntary ventilation. Braz J Med Biol Res. 1999;32(6):719-27. http://dx.doi.org/10.1590/S0100-879X1999000600007. PMid:10412550.
http://dx.doi.org/10.1590/S0100-879X1999...
) and expressed as a percentage of predicted values. Respiratory muscle weakness was determined for a MIP of < 60 cmH2O.(2525 Beaumont M, Mialon P, Ber-Moy CL, Lochon C, Péran L, Pichon R, et al. Inspiratory muscle training during pulmonary rehabilitation in chronic obstructive pulmonary disease. Chron Respir Dis. 2015;12(4):305-12. http://dx.doi.org/10.1177/1479972315594625. PMid:26170421.
http://dx.doi.org/10.1177/14799723155946...
)

Functional capacity

The incremental shuttle walking test (ISWT) aims to assess one’s performance considering the individuals’ limiting symptoms used to evaluate functional capacity as described in Singh et al.(2626 Singh SJ, Morgan MD, Scott S, Walters D, Hardman AE. Development of a shuttle walking test of disability in patients with chronic airways obstruction. Thorax. 1992;47(12):1019-24. http://dx.doi.org/10.1136/thx.47.12.1019. PMid:1494764.
http://dx.doi.org/10.1136/thx.47.12.1019...
) The test has 12 stages with one minute each, with initial velocity of 0.5 m/s, with each minute being added 0.17 m/s (equivalent to 10 m/min). There was provided a standardized verbal command at the end of each stage to inform the individual of increasing walking speed. The walking speed is determined by two distinct types of beeps: a single beep indicating a change of direction, and a triple (beep) signal that indicates a change of direction and stage. The percentage of the predicted walked distance ISWT (% predicted) was calculated considering sex, age, height and weight of each patient according to Dourado et al.(2727 Dourado VZ, Guerra RLF, Tanni SE, Antunes LCO, Godoy I. Reference values for the incremental shuttle walk test in healthy subjects: from the walk distance to physiological responses. J Bras Pneumol. 2013;39(2):190-7. http://dx.doi.org/10.1590/S1806-37132013000200010. PMid:23670504.
http://dx.doi.org/10.1590/S1806-37132013...
)

Statistical analyses

Data were analyzed using the Sigmaplot® statistical package (version 11.0, Systat Software Inc., San Jose, CA, USA). Data were tested for normality through the Shapiro-Wilk test and presented descriptively as mean and STD (parametric) or as median and minimum and maximum interval (non-parametric). The analyses between the groups were performed through Student T test or Mann Whitney.

The precision of the clinical variables, pulmonary function (FEV1% predicted), respiratory muscle strength (MIP) and functional capacity (ISWT) in determining points of predictive cut-off sarcopenia and dynapenia were performed using the Receiver Operating Characteristic (ROC) curves.(2828 Erdreich LS, Lee ET. Use of relative operating characteristic analysis in epidemiology: a method for dealing with subjective judgement. Am J Epidemiol. 1981;114(5):649-62. http://dx.doi.org/10.1093/oxfordjournals.aje.a113236. PMid:7304595.
http://dx.doi.org/10.1093/oxfordjournals...
) The total area under the ROC curve was determined between FEV1 (% predicted), MIP, ISWT, and sarcopenia and dynapenia indexes. The greater area under the ROC curve represented greater discriminatory power of clinical variables to establish sarcopenia or dynapenia in individuals with COPD.(2929 Schisterman EF, Faraggi D, Reiser B, Trevisan M. Statistical inference for the area under the receiver operating characteristic curve in the presence of random measurement error. Am J Epidemiol. 2001;154(2):174-9. http://dx.doi.org/10.1093/aje/154.2.174. PMid:11447052.
http://dx.doi.org/10.1093/aje/154.2.174...
) The 95% confidence interval (95% CI) was used to determine the ability of the clinical variables to predict sarcopenia and dynapenia, with the lower limit being greater than 0.50.(2424 Neder JA, Andreoni S, Lerario MC, Nery LE. Reference values for lung function tests. II. Maximal respiratory pressures and voluntary ventilation. Braz J Med Biol Res. 1999;32(6):719-27. http://dx.doi.org/10.1590/S0100-879X1999000600007. PMid:10412550.
http://dx.doi.org/10.1590/S0100-879X1999...
) Subsequently, the cut-off points of the clinical variables that obtained significant areas under the ROC curve, with the respective values of sensitivity and specificity, balanced among themselves. Values lower than 60% were identified.

The results were compared using two-way analysis of variance on ranks with post-hoc Bonferroni, in order to identify statistically significant differences in: (i) functional capacity; and (ii) pulmonary function. For these analyses, subjects were categorized according to SMD effect (dynapenia vs sarcopenia) and Non SMD effect (non dynapenia vs non sarcopenia). Residuals were evaluated under the assumptions of normality, constant variance, and independence. P ≤ 0.05 was considered significant.

RESULTS

A total of 20 subjects were enrolled in the study. Of them, 11 were stratified with sarcopenia, 7 with dynapenia and 7 with overlapping between the conditions. In COPD patients with sarcopenia there were found lower lean mass and lower MIP, decreased HGS and reduced functional capacity than non-sarcopenia group. The patients with dynapenia presented reduced MIP, lower HGS and walked a shorter distance in the ISWT, when compared with non-dynapenia group (Table 1). There were no significant differences of the groups for age, BMI, pulmonary function, GOLD stages and MEP. It is important to highlight that we did not find any significant difference between overlapping and dynapenia and sarcopenia groups in isolation.

Table 1
COPD patients’ clinical characteristics stratified by sarcopenia and dynapenia.

The cut-off points, the areas under the ROC curve and 95% CI of clinical variables, as well as the sensitivity and specificity of the clinical variables as predictors of sarcopenia and dynapenia are showed in Table 2. According to the prediction model, FEV1 < 52%, MIP < 73 cmH2O, MEP < 126 cmH2O identified sarcopenia in these patients and FEV1 < 40%, MIP < 71 cmH2O, MEP < 110 cmH2O identified dynapenia. The distance walked on the ISWT was significantly able to determine the presence of sarcopenia and dynapenia in patients with COPD, with walked distance of 295 and 230 m respectively. There was established as cut-off point according to the adopted sensitivity and specificity.

Table 2
Cut-off values, sensitivity and specificity of variable clinics with prediction of sarcopenia and dynapenia in COPD patients.

When applying two-way ANOVA, there was found that COPD patients with dynapenia and sarcopenia (SMD effect) presented a reduction in the distance walked in the ISWT (p = 0.002) and the %ISWT (p = 0.017) (Figure 1), demonstrating the impact of SMD on the functional capacity of these patients. We emphasize that there were not significant results for FEV1.

Figure 1
Comparison of functional capacity and FEV1 in COPD patients with MSD and without MSD. #p <0.050 for MSD. FEV1: forced expiratory volume in one second; ISWT: Incremental shuttle walk test; MSD: muscular skeletal dysfunction. (A) Comparison between FEV1 (L/s) of MSD and non-MSD groups; (B) Comparison between% FEV1 of MSD and non-MSD groups; (C) Comparison between ISWT (m) of MSD and non-MSD groups; (D) Comparison between% ISWT of MSD and non-MSD groups.

DISCUSSION

COPD patients with sarcopenia or dynapenia present reduced inspiratory muscular strength, handgrip strength and distance walked in the ISWT. COPD patients with sarcopenia also presented a reduction in lean mass. According to ROC curve, it was possible to establish that COPD patients with FEV1 (%pred) < 52%, MIP < 73 cmH2O, MEP < 126 cmH2O identified sarcopenia; and FEV1 < 40%, MIP < 71 cmH2O, MEP < 110 cmH2O identified dynapenia. Furthermore, a distance walked in the ISWT of 295 and 230 m can determine sarcopenia or dynapenia, respectively.

SMD is associated with diminished physical performance and functional capacity. Moreover, skeletal muscle impairment could provoke physiological, metabolic and functional repercussions.(3030 Tieland M, Trouwborst I, Clark BC. Skeletal muscle performance and ageing. J Cachexia Sarcopenia Muscle. 2018;9(1):3-19. http://dx.doi.org/10.1002/jcsm.12238. PMid:29151281.
http://dx.doi.org/10.1002/jcsm.12238...
,3131 Bone AE, Hepgul N, Kon S, Maddocks M. Sarcopenia and frailty in chronic respiratory disease. Chron Respir Dis. 2017;14(1):85-99. http://dx.doi.org/10.1177/1479972316679664. PMid:27923981.
http://dx.doi.org/10.1177/14799723166796...
) In COPD patients, the SMD affects both ventilatory and non-ventilatory muscle groups, contributing to greater energy expenditure for the individual to execute his activities of daily living, it also leads to decreased quality of life and the aftermath is a poor prognosis.(33 Jaitovich A, Barreiro E. Skeletal muscle dysfunction in Chronic Obstructive Pulmonary Disease (COPD): what we know and can do for our patients. Am J Respir Crit Care Med. 2018;198(2):175-86. http://dx.doi.org/10.1164/rccm.201710-2140CI. PMid:29554438.
http://dx.doi.org/10.1164/rccm.201710-21...
) Our study is in congruence with these findings, where we found an impact on handgrip and respiratory muscle strength as well as in functional capacity on both patients with sarcopenia or dynapenia.

SMD pathophysiology is complex and involves fiber damage and catabolic events that worsen with ageing and the presence of comorbidities.(3030 Tieland M, Trouwborst I, Clark BC. Skeletal muscle performance and ageing. J Cachexia Sarcopenia Muscle. 2018;9(1):3-19. http://dx.doi.org/10.1002/jcsm.12238. PMid:29151281.
http://dx.doi.org/10.1002/jcsm.12238...
) Byun et al.(44 Byun MK, Cho EN, Chang J, Ahn CM, Kim HJ. Sarcopenia correlates with systemic inflammation in COPD. Int J Chron Obstruct Pulmon Dis. 2017;12:669-75. http://dx.doi.org/10.2147/COPD.S130790. PMid:28255238.
http://dx.doi.org/10.2147/COPD.S130790...
) found correlation between sarcopenia, old age, low body mass index, presence of comorbidities and systemic inflammation in COPD patients. Therefore, considering that our sample was composed by elderly subjects, we can hypothesize that muscle wasting in our patients was due to natural physiological reasons, like an imbalance between muscle protein synthesis and muscle protein breakdown and changes associated with COPD consequences, such as chronic inflammation and functional decline. It is important to emphasize that the loss of 1% of lean mass is equivalent to a reduction of 3% in muscle strength in elderly, something that could have an impact on one’s functionality.(2727 Dourado VZ, Guerra RLF, Tanni SE, Antunes LCO, Godoy I. Reference values for the incremental shuttle walk test in healthy subjects: from the walk distance to physiological responses. J Bras Pneumol. 2013;39(2):190-7. http://dx.doi.org/10.1590/S1806-37132013000200010. PMid:23670504.
http://dx.doi.org/10.1590/S1806-37132013...
)

Sarcopenia and dynapenia are two conditions related to muscle mass and its function, and for identifying them there are several methods that could be used. Bone et al.,(3131 Bone AE, Hepgul N, Kon S, Maddocks M. Sarcopenia and frailty in chronic respiratory disease. Chron Respir Dis. 2017;14(1):85-99. http://dx.doi.org/10.1177/1479972316679664. PMid:27923981.
http://dx.doi.org/10.1177/14799723166796...
) in a review paper, listed handgrip strength and low gait speed as instruments for defining sarcopenia. Handgrip measurement has the advantage of being simple and easy and sometimes used as an index of muscular strength for the whole body. When it comes to muscle mass evaluation we used bioelectrical impedance analysis, considered by Maddocks et al.(3232 Maddocks M, Kon SS, Jones SE, Canavan JL, Nolan CM, Higginson IJ, et al. Bioelectrical impedance phase angle relates to function, disease severity and prognosis in stable chronic obstructive pulmonary disease. Clin Nutr. 2015;34(6):1245-50. http://dx.doi.org/10.1016/j.clnu.2014.12.020. PMid:25597016.
http://dx.doi.org/10.1016/j.clnu.2014.12...
) a more practical tool for this purpose. There are other methods used for muscle mass assessment as seen in Bone et al.,(3131 Bone AE, Hepgul N, Kon S, Maddocks M. Sarcopenia and frailty in chronic respiratory disease. Chron Respir Dis. 2017;14(1):85-99. http://dx.doi.org/10.1177/1479972316679664. PMid:27923981.
http://dx.doi.org/10.1177/14799723166796...
) who cited dual X-ray absorptiometry and computational tomography. Specifically to determinate dynapenia, Morley et al.(3333 Morley JE, Abbatecola AM, Argiles JM, Baracos V, Bauer J, Bhasin S, et al. Sarcopenia with limited mobility: an international consensus. J Am Med Dir Assoc. 2011;12(6):403-9. http://dx.doi.org/10.1016/j.jamda.2011.04.014. PMid:21640657.
http://dx.doi.org/10.1016/j.jamda.2011.0...
) mentioned evaluating walking speed, walking distance and stair climbing as screening tools. Whilst for identifying sarcopenia in COPD patients, most studies used Six-minute walk test for functional capacity evaluation, to our knowledge no study has used ISWT for this purpose.(3434 Limpawattana P, Inthasuwan P, Putraveephong S, Boonsawat W, Theerakulpisut D, Sawanyawisuth K. Sarcopenia in chronic obstructive pulmonary disease: a study of prevalence and associated factors in the Southeast Asian population. Chron Respir Dis. 2018;15(3):250-7. http://dx.doi.org/10.1177/1479972317743759. PMid:29186972.
http://dx.doi.org/10.1177/14799723177437...

35 Cebron LN, Schols AM, van den Borst B, Beijers RJ, Kosten T, Omersa D, et al. Sarcopenia in advanced COPD affects cardiometabolic risk reduction by short-term high-intensity pulmonary rehabilitation. J Am Med Dir Assoc. 2016;17(9):814-20. http://dx.doi.org/10.1016/j.jamda.2016.05.002. PMid:27321867.
http://dx.doi.org/10.1016/j.jamda.2016.0...
-3636 Costa TM, Costa FM, Moreira CA, Rabelo LM, Boguszewski CL, Borba VZ. Sarcopenia in COPD: relationship with COPD severity and prognosis. J Bras Pneumol. 2015;41(5):415-21. http://dx.doi.org/10.1590/S1806-37132015000000040. PMid:26578132.
http://dx.doi.org/10.1590/S1806-37132015...
)

To date, there is still no consensus on measurement tools or diagnostic cut-off to determinate these two conditions, but it is known that diagnosis could be done by assessing muscle mass and functional performance.(55 Kalyani RR, Corriere M, Ferrucci L. Age-related and disease-related muscle loss: the effect of diabetes, obesity, and other diseases. Lancet Diabetes Endocrinol. 2014;2(10):819-29. http://dx.doi.org/10.1016/S2213-8587(14)70034-8. PMid:24731660.
http://dx.doi.org/10.1016/S2213-8587(14)...
) The diversity of methods available to measure these variables could lead to several cut-off as well underestimate the presence of this condition in COPD patients. We emphasize that this is a relevant and original study where we evaluated sarcopenia and dynapenia in moderate to very severe COPD patients. With a pulmonary function test, through FEV1 (%pred) < 52 and assessing physical performance by means of ISWT, the distance traveled of < 295 m is able to predict sarcopenia, and a distance in ISWT of < 230 m is able to predict dynapenia.

Our findings are important because they allow clinical practitioners to apply feasible methods to assess sarcopenia and dynapenia on their routine, like a spirometry and a 10 m hall to perform ISWT. Additionally, the results demonstrate that a careful evaluation of these patients is required, as well as a future focus on SMD based mechanisms and its relationship with activity of daily living execution, physical activity levels and quality of life in a COPD population.

Some limitations pointed out are due to our strict inclusion and exclusion criteria, resulting in a number of subjects that might be considered small. We emphasize that our results should be considered only for patients with COPD. This study is of clinical relevance since SMD in COPD impacts on anatomical, physiological and functional systems. Identifying these conditions could help health care professionals to assess in a feasible and workable way, to understand and treat patients with specifically interventions (e.g multidisciplinary rehabilitation programs), it is already known that physical exercise can reverse sarcopenia in COPD patients and improve the condition in older adults(3737 Landi F, Marzetti E, Martone AM, Bernabei R, Onder G. Exercise as a remedy for sarcopenia. Curr Opin Clin Nutr Metab Care. 2014;17(1):25-31. PMid:24310054.). Regarding nutritional treatment strategies there is still a lack of specific recommendations.(3838 Cruz-Jentoft AJ, Kiesswetter E, Drey M, Sieber CC. Nutrition, frailty, and sarcopenia. Aging Clin Exp Res. 2017;29(1):43-8. http://dx.doi.org/10.1007/s40520-016-0709-0. PMid:28155181.
http://dx.doi.org/10.1007/s40520-016-070...
) Knowing that skeletal muscles perform essential functions for the whole organism, we highlight the importance of early recognition of these disorders for patients’ risk stratification and prevention, which may reduce the development of comorbidities, delay functional decline and improve prognosis in patients with chronic obstructive pulmonary disease.

In conclusion, this study was able to give variables’ cut-off points for identifying or predicting sarcopenia and dynapenia in moderate to very severe COPD patients. Moreover, these SMD cause negative impact on the peripheral muscular strength and functional capacity. Sarcopenia could be predicted by FEV1 (%predicted) < 52, MIP < 73 cmH2O, MEP < 126 cmH2O and distance traveled of < 295 m in ISWT. Whereas, dynapenia could be predicted by FEV1 < 40%, MIP < 71 cmH2O, MEP < 110 cmH2O and distance of < 230 m traveled in ISWT.

  • Study carried out in the Programa de Reabilitação Cardiorrespiratória, Hospital Santa Cruz, Santa Cruz do Sul (RS) Brasil.
  • Financial support: Financial support was received from the University of Santa Cruz do Sul – UNISC, Santa Cruz Hospital; project nº 88881.062123/2014-01; FAPESP, project nº 2018/03233-0 and 2015/26501-1.

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Publication Dates

  • Publication in this collection
    17 Oct 2019
  • Date of issue
    2019

History

  • Received
    15 Aug 2018
  • Accepted
    26 Feb 2019
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