Hipermetabolismo e alterações musculares na doença pulmonar obstrutiva crônica
DOI:
https://doi.org/10.33233/fb.v11i6.1458Resumo
Introdução: Durante a evolução da Doença Pulmonar Obstrutiva Crônica (DPOC) há desequilíbrio no metabolismo que leva a intolerância aos esforços. Cerca de 25% dos pacientes com DPOC desenvolvem caquexia, fato que está associado com o aumento do catabolismo e a redução da sobrevida. Objetivo: Discutir a influência da ação dos mediadores inflamatórios e sua relação com o uso crônico de corticosteróides sobre o metabolismo dos indivíduos com DPOC. Método: Foram cotejados e discutidos artigos da literatura atual publicados em revistas de circulação internacional, com alto índice de impacto. Resultados: O processo catabólico nos pacientes com DPOC é regulado eminentemente pela liberação de mediadores inflamatórios e hormônios em resposta ao stress. Devido ao baixo nível energético celular ocorre sinalização para a neoglicogênese, anaplerose e cataplerose, levando ao maior consumo de aminoácidos como substrato energético. O indivíduo com DPOC apresenta redução da atividade de enzimas oxidativas e glicolíticas, com consequente diminuição da produção de ATP. Isso aumenta sinergicamente o stress físico e contribui para a instalação da fadiga e morte. Desta forma, a inflamação crônica decorrente da diminuição de hormônios anabólicos circulantes, associada ao aumento de sinalizadores catabólicos, induz a progressão da DPOC, que é exacerbada pelo uso crônico de corticosteróides. Conclusão: A cooperação entre o catabolismo e a inflamação são os principais agentes causadores das alterações musculoesqueléticas na DPOC. Durante a DPOC o desequilíbrio do suprimento energético resulta na perda de massa ponderal e diminuição da capacidade laboral causada pela associação de fatores como: 1) a inflamação sistêmica; 2) o uso de fármacos; 3) o elevado turnover protéico e 4) a ineficiência mecânico-metabólica dos músculos respiratórios, em um processo sinérgico que pode acelerar o estado de insuficiência respiratória. O entendimento destes processos e modelos terapêuticos para diminuírem sua progressão passam a ser metas no tratamento da DPOC.
Palavras-chave: inflamação, catabolismo, suplementos dietéticos, gliconeogênese, exercício.Â
Referências
Eid AA, Ionescu AA, Nixon LS, Lewis-Jenkins V, Matthes SB, Griffiths TL, Shale DJ. Inflammatory response and body composition in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001;164:1414-8.
Engelen MPKJ, Schols AMWJ, Baken WC, Wesseling GJ, Wouters EFM. Nutritional depletion in relation to respiratory and peripheral skeletal muscle function in out-patients with COPD. Eur Respir J 1994;7:1793-7.
Engelen MPKJ, Schols AMWJ, Does JD, Wouters EFM. Skeletal muscle weakness is associated with wasting of extremity fat-free mass but not with airflow obstruction in patients with chronic obstructive pulmonary disease. Am J Clin Nutr 2000;71:733-8.
Maltais F, LeBlanc P, Whittom F, Simard C, Marquis K, Bélanger M, Breton MJ, Jobin J. Oxidative enzyme activities of the vastus lateralis muscle and the functional status in patients with COPD. Thorax 2000;55:848-53.
Pouw EM, Koerts-de Lang E, Gosker HR, Freling G, van der Vusse, EFM Wouters, Schols AMWJ. Muscle metabolic status in patients with severe COPD with and without long-term predinisolone. Eur Respir J 2000;16:247-52.
Salueda J, GarcÃa-Palmer F, Wiesner RJ, Tarraga S, Harting I, Tomás P, et al. Cytochrome oxidase activity and mitochondrial gene expression in skeletal muscle of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;1557:1413-7.
Creutzberg EC, Wouters EFM, Vanderhoven-Augustin IML, Dentener MA, Schols AMW. Disturbances in leptin metabolism are related to energy imbalance during acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000;162:1239-45.
Saudny-Unterberger H, Martin JG, Gray-Donald K. Impact of nutritional support on functional status during an acute exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1997;156:794-9.
Schols AMWJ, Wesseling G, Kester ADM, de Vries G, Mostert R, Slangen J, et al. Dose dependent increased mortality risk in COPD patients treated with oral gkucocorticoids. Eur Respir J 2001;17:337-42.
Gayan-Ramirez G, Vanderhoydonc F, Verhoeven G, Decramer M. Acute treatment with corticosteroids decreases IGF-1 and IGF-2 expression in the rat diaphragm and gatrocnemius. Am J Respir Crit Care Med 1999;159:283-9.
Strle K, Broussard SR, McCusker RH, Shen W-H, Johnson RW, Freund GG, Dantzer R, Kelley KW. Proinflammatory cytokine impairment of insulin-like growth factor I-induced protein synthesis in skeletal muscle myoblasts requires ceramides. Endocrinology 2004;145(10):4592-602.
Baarends EM, Schols AMWJ, Akkermans MA, Wouters EFM. Decreased mechanical efficiency in clinically stable patients with COPD. Thorax 1997;52:981-6.
Palange P, Forte S, Onorati P, Paravati V, Manfredi F, Serra P, Carlone S. Effect of reduced body weight on muscle aerobic capacity in patients with COPD. Chest 1998;114:12-8.
Pouw EM, Schols AMWJ, van der Vusse GJ, Wouters EFM. Elevated inosine monophosphate levels in resting muscle of patients with stable chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;157:453-7.
Pouw EM, Schols AMWJ, Deutz NEP, Wouters EFM. Plasma and muscle amino acid levels in relation to resting energy expenditure and inflammation in stable chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;158:797-801.
Broekhuizen R, Wouters EFM, Creutzberg EC, Weling-Scheepers CAPM, Schols AMWJ. Polyunsaturated fatty acids improve exercise capacity in chronic obstructive pulmonary disease. Thorax 2005;60:376-82.
Burdet L, de Muralt R, Schutz Y, Richard C, Fitting JW. Administration of growth hormone to underweight patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1997;156:1800-6.
Fujimoto K, Matsuzawa Y, Yamaguchi S, Koizumi T, Kubo K. Benefits of oxygen on exercise performance and pulmonary hemodynamics in patients with COPD with mild hypoxemia. Chest 2002;122:457-63.
Fuld JP, Kilduf LP, Neder JA, Pitsiladis Y, Lean MEJ, Ward SA, Cotton MM. Creatine supplementation during pulmonary rehabilitation in chronic obstructive pulmonary disease. Thorax 2005;60;531-7.
Sala E, Roca J, Marrades RM, Alonso J, Gonzalez de Suso JM, Moreno A, et al. Effects of endurance training on skeletal muscle bioenergetics in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999;159:1726-34.
Vogiatzis I, Williamsom AF, Miles J, Taylor IA. Physiological response to moderate exercise workloads in a pulmonary rehabilitation program in patients with varying degrees of airflow obstruction. Chest 1999;116:1200-7.
Engelen MPKJ, Deutz NEP, Wouters EFM, Schols AMWJ. Enhanced levels of whole-body protein turnover in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000;162:1488-92.
Baarends EM, Schols AMWJ, Westerterp KR, Wouters EFM. Total daily energy expenditure relative to energy expenditure in clinically stable patients with COPD. Thorax 1997;52:780-5.
Cohen RI, Marzouk K, Berkoski P, O`Donnel CP, Polotsky VY, Scharf SM. Body composition and resting energy expenditure in clinically stable, non-weight-losing patients with severe emphysema. Chest 2003;124:1365-72.
Mannix ET, Manfredi F, Farher MO. Elevated O2 cost of ventilation contributes to tissue wasting in COPD. Chest 1999;115:708-13.
Chung KF. Cytokines in chronic obstructive pulmonary disease. Eur Respir J 2001;18(34):50-9.
Creutzberg EC, Schols AMW, Weling-Scheepers CAPM, Buurman WA, Wouters EFM. Characterization of nonresponse to high caloric oral nutrition therapy in depleted patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000;161:745-52.
Dentener MA, Creuztberg EC, Schols AMWJ, Mantovani A, van’t Veer C, Buurman WA, Wouters EFM. Systemic anti–inflammatory mediators in COPD: increase in soluble interleukin 1 receptor II during treatment of exacerbations. Thorax 2001;56:721-6.
Debigaré R, Marquis K, Côté CH, Tremblay RR, Michaud A, LeBlanc P, et al. Catabolic/anabolic balance and muscle wasting in patients with COPD. Chest 2003;124:83-9.
Schols AMW, Creutzberg EC, Buurman WA, Campfield LA, Saris WHM, Wouters, EFM. Plasma leptin is related to proinflammtory status and dietary intake in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999; 160(4); 1220-6.
Grunfeld C, Zhao C, Fuller J, Pollock A, Moser A, Friedman J, Feingold KR. Endotoxin and cytokines induce expression of leptin, the ob gene product, in hamster. J Clin Invest 1996;97(9):2152-7.
Straub RH, Konecna L, Hrach S, Rothe G, Kreutz M, Schölmerich J, et al. Serum dehydroepiandrosterona (DHEA) and DHEA sulfate are negatively correlated with serum interleukin-6 (IL-6), and DHEA inhibits IL-6 secretion from mononuclear cells in man in vitro: possible link between endocrinosenescence and immunosenescence. J Clin Endocrinol Metab 1998;83;2012-7.
Straub RH, Schuld A, Mullington J, Haack M, Schölmerich J, Pollmächer T. The endotoxin-induced increase of cytokines is followed by an increase of cortisol relative to dehydroepiandrosterone (DHEA) in healthy male subjects. J Endocrinol 2002;175:467-74.
Peschon JJ, Torrance DS, Stocking KL, Glaccum MB, Otten C, Willis CR, et al. TNF receptor-deficient mice reveal divergent roles for p55 and p75 in several models of inflammation. J Immunol 1998;160:943-52.
Churg A, Dai J, Xie C, Wright JL. Tumor necrosis Factor-α is central to acute cigarette smoke-induced inflammation and connective tissue breakdown. Am J Respir Crit Care Med 2002;166:849-54.
Takabatake N, Nakamura H, Abe S, Inque S, Hino T, Saito H, et al. The relationship between chronic hypoxemia and activation of the tumor necrosis factor–α system in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000;161:1179-84.
Takabatake N, Nakamura H, Abe S, Hino T, Saito H, Yuki , et al. Circulating leptin in patient with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999;159:1215-19.
Bourke M, Casseti A, Villa A, Fadlon E, Coletta F, Mantovani A. IL-1 scavenging by type II IL-1 decoy receptor in human neutrophils. J Immunol 2003;170:5999-6005.
Gabay C, Smith MF, Eidlen D, Arend WP. Interleukin receptor antagonist (IL-1Ra) is an acute - phase protein. J Clin Invest 1997;99:2930-40.
Grube BJ, Cochane CG, Ye RD, Green CE, McPhail ME, Ulevitch RJ, et al. Lipopolysaccharide binding protein expression in primary human hepatocytes and HepG2 hepatoma cells. J Biol Chem 1994;269:8477-82.
Engelen MPKJ, Deutz NEP, Mostert R, Wouters EFM , Schols AMWJ. Response of whole-body protein and urea turnover to exercise differs between patients with chronic pulmonary obstructive disease with and without emphysema. Am J Clin Nut 2003;77:868-74.
Dahl M, Tybjaerg-hansen, Vestbo J, Lange P, Nordestgaard BG. Elevated plasma fibrinogen associated with reduced pulmonary function and increased risk of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001;164(6):1008-11.
Li H, He G, Chu H, Zhao L, Yu H. A step-wise application of methylprednisolone versus dexamethasone in the treatment of acute exacerbations of COPD. Respirology 2003;8:199-204.
Amaya-Villar R, Garnacho-Montero J, GarcÃa-GarmendÃa JL, Madrazo-Osuna J, Garnacho-Montero MC, Luque R, et al. Steroid-induced myopathy in patients intubated due to exacerbation of chronic obstructive pulmonary disease. Intensive Care Med 2005;31(1):157-61.
Hopkinson NS, Man WD-C, Dayer MJ, Ross ET, Nickol AH, Hart N, et al. Acute effect of oral steroids on muscle function in chronic obstructive pulmonary disease. Eur Respir J 2004;24:137-42.
Dekhuijzen PNR, van Balkom RHH. Steroid-induced change in the respiratory muscles: its relevance in patients with obstructive airways disease. Respir Med 1994;88:335-41.
Rice KL, Rubins JB, Lebahn F, Parenti CM, Duane PG, Kuskowski M, et al. Withdrawal of chronic systemic corticosteroids in patients with COPD. Am J Respir Crit Care Med 2000;162:174-8.
Gosker HR, van Mameren H, van Dijik PJ, Engelen MPKJ, van der Vusse GJ, Wouters EFM, et al. Skeletal muscle fibre-type shifting and metabolic profile in patients with chronic obstructive pulmonary disease. Eur Respir J 2002;19:617-25.
Downloads
Publicado
Edição
Seção
Licença
Autores que publicam nesta revista concordam com os seguintes termos:
Autores mantém os direitos autorais e concedem à revista o direito de primeira publicação, com o trabalho simultaneamente licenciado sob a Licença Creative Commons Attribution 4.0 que permite o compartilhamento do trabalho com reconhecimento da autoria e publicação inicial nesta revista.
Autores têm autorização para distribuição não-exclusiva da versão do trabalho publicada nesta revista (ex.: publicar em repositório institucional ou como capítulo de livro), com reconhecimento de autoria e publicação inicial nesta revista.
