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Nan Y, Zhou Y, Dai Z, Yan T, Zhong P, Zhang F, Chen Q, Peng L. Role of nutrition in patients with coexisting chronic obstructive pulmonary disease and sarcopenia. Front Nutr 2023; 10:1214684. [PMID: 37614743 PMCID: PMC10442553 DOI: 10.3389/fnut.2023.1214684] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Accepted: 07/24/2023] [Indexed: 08/25/2023] Open
Abstract
Chronic obstructive pulmonary disease (COPD) is one of the most common chronic diseases in the elderly population and is characterized by persistent respiratory symptoms and airflow obstruction. During COPD progression, a variety of pulmonary and extrapulmonary complications develop, with sarcopenia being one of the most common extrapulmonary complications. Factors that contribute to the pathogenesis of coexisting COPD and sarcopenia include systemic inflammation, hypoxia, hypercapnia, oxidative stress, protein metabolic imbalance, and myocyte mitochondrial dysfunction. These factors, individually or in concert, affect muscle function, resulting in decreased muscle mass and strength. The occurrence of sarcopenia severely affects the quality of life of patients with COPD, resulting in increased readmission rates, longer hospital admission, and higher mortality. In recent years, studies have found that oral supplementation with protein, micronutrients, fat, or a combination of nutritional supplements can improve the muscle strength and physical performance of these patients; some studies have also elucidated the possible underlying mechanisms. This review aimed to elucidate the role of nutrition among patients with coexisting COPD and sarcopenia.
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Affiliation(s)
- Yayun Nan
- Department of Ningxia Geriatrics Medical Center, Ningxia People’s Hospital, Yinchuan, China
| | - Yuting Zhou
- Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Ziyu Dai
- Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Ting Yan
- Department of Ningxia Geriatrics Medical Center, Ningxia People’s Hospital, Yinchuan, China
| | - Pingping Zhong
- Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Fufeng Zhang
- Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Qiong Chen
- Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Linlin Peng
- Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
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2
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Yen A, Westover KD. Case Report: Resolution of radiation pneumonitis with androgens and growth hormone. Front Oncol 2022; 12:948463. [PMID: 36091134 PMCID: PMC9449808 DOI: 10.3389/fonc.2022.948463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Accepted: 07/18/2022] [Indexed: 11/30/2022] Open
Abstract
Radiation pneumonitis (RP) occurs in some patients treated with thoracic radiation therapy. RP often self-resolves, but when severe it is most commonly treated with corticosteroids because of their anti-inflammatory properties. Androgens and human growth hormone (HGH) also have anti-inflammatory and healing properties in the lung, but have not been studied as a remedy for RP. Here we present a case of corticosteroid-refractory RP that resolved with androgen and HGH-based therapy.
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van Bakel SIJ, Gosker HR, Langen RC, Schols AMWJ. Towards Personalized Management of Sarcopenia in COPD. Int J Chron Obstruct Pulmon Dis 2021; 16:25-40. [PMID: 33442246 PMCID: PMC7800429 DOI: 10.2147/copd.s280540] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Accepted: 12/21/2020] [Indexed: 12/13/2022] Open
Abstract
The awareness of the presence and consequences of sarcopenia has significantly increased over the past decade. Sarcopenia is defined as gradual loss of muscle mass and strength and ultimately loss of physical performance associated with aging and chronic disease. The prevalence of sarcopenia is higher in chronic obstructive pulmonary disease (COPD) compared to age-matched controls. Current literature suggests that next to physical inactivity, COPD-specific alterations in physiological processes contribute to accelerated development of sarcopenia. Sarcopenia in COPD can be assessed according to current guidelines, but during physical performance testing, ventilatory limitation should be considered. Treatment of muscle impairment can halt or even reverse sarcopenia, despite respiratory impairment. Exercise training and protein supplementation are currently at the basis of sarcopenia treatment. Furthermore, effective current and new interventions targeting the pulmonary system (eg, smoking cessation, bronchodilators and lung volume reduction surgery) may also facilitate muscle maintenance. Better understanding of disease-specific pathophysiological mechanisms involved in the accelerated development of sarcopenia in COPD will provide new leads to refine nutritional, exercise and physical activity interventions and develop pharmacological co-interventions.
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Affiliation(s)
- Sophie I J van Bakel
- NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre +, Department of Respiratory Medicine, Maastricht, The Netherlands
| | - Harry R Gosker
- NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre +, Department of Respiratory Medicine, Maastricht, The Netherlands
| | - Ramon C Langen
- NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre +, Department of Respiratory Medicine, Maastricht, The Netherlands
| | - Annemie M W J Schols
- NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre +, Department of Respiratory Medicine, Maastricht, The Netherlands
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Kang MJ. Recent Advances in Molecular Basis of Lung Aging and Its Associated Diseases. Tuberc Respir Dis (Seoul) 2020; 83:107-115. [PMID: 32185913 PMCID: PMC7105435 DOI: 10.4046/trd.2020.0003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2020] [Revised: 02/05/2020] [Accepted: 02/19/2020] [Indexed: 12/26/2022] Open
Abstract
Aging is often viewed as a progressive decline in fitness due to cumulative deleterious alterations of biological functions in the living system. Recently, our understanding of the molecular mechanisms underlying aging biology has significantly advanced. Interestingly, many of the pivotal molecular features of aging biology are also found to contribute to the pathogenesis of chronic lung disorders such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis, for which advanced age is the most crucial risk factor. Thus, an enhanced understanding of how molecular features of aging biology are intertwined with the pathobiology of these aging-related lung disorders has paramount significance and may provide an opportunity for the development of novel therapeutics for these major unmet medical needs. To serve the purpose of integrating molecular understanding of aging biology with pulmonary medicine, in this review, recent findings obtained from the studies of aging-associated lung disorders are summarized and interpreted through the perspective of molecular biology of aging.
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Affiliation(s)
- Min Jong Kang
- Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
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Abdulai RM, Jensen TJ, Patel NR, Polkey MI, Jansson P, Celli BR, Rennard SI. Deterioration of Limb Muscle Function during Acute Exacerbation of Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med 2019; 197:433-449. [PMID: 29064260 DOI: 10.1164/rccm.201703-0615ci] [Citation(s) in RCA: 67] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Important features of both stable and acute exacerbation of chronic obstructive pulmonary disease (COPD) are skeletal muscle weakness and wasting. Limb muscle dysfunction during an exacerbation has been linked to various adverse outcomes, including prolonged hospitalization, readmission, and mortality. The contributing factors leading to muscle dysfunction are similar to those seen in stable COPD: disuse, nutrition/energy balance, hypercapnia, hypoxemia, electrolyte derangements, inflammation, and drugs (i.e., glucocorticoids). These factors may be the trigger for a downstream cascade of local inflammatory changes, pathway process alterations, and structural degradation. Ultimately, the clinical effects can be wide ranging and include reduced limb muscle strength. Current therapies, such as pulmonary/physical rehabilitation, have limited impact because of low participation rates. Recently, novel drugs have been developed in similar disorders, and learnings from these studies can be used as a foundation to facilitate discovery in patients hospitalized with a COPD exacerbation. Nevertheless, investigators should approach this patient population with knowledge of the limitations of each intervention. In this Concise Clinical Review, we provide an overview of acute muscle dysfunction in patients hospitalized with acute exacerbation of COPD and a strategic approach to drug development in this setting.
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Affiliation(s)
- Raolat M Abdulai
- 1 Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts.,2 Respiratory, Inflammation, and Autoimmunity, Early Clinical Development, IMED Biotech Unit, AstraZeneca, Boston, Massachusetts
| | - Tina Jellesmark Jensen
- 3 Respiratory, Inflammation, and Autoimmunity, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden
| | - Naimish R Patel
- 2 Respiratory, Inflammation, and Autoimmunity, Early Clinical Development, IMED Biotech Unit, AstraZeneca, Boston, Massachusetts.,4 Beth Israel Deaconess Hospital, Boston, Massachusetts
| | - Michael I Polkey
- 5 National Institute for Health Research, Respiratory Biomedical Research Unit at the Royal Brompton Hospital and Imperial College London, London, United Kingdom
| | - Paul Jansson
- 3 Respiratory, Inflammation, and Autoimmunity, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden
| | - Bartolomé R Celli
- 1 Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts.,6 Harvard Medical School, Boston, Massachusetts
| | - Stephen I Rennard
- 7 Pulmonary and Critical Care Medicine, University of Nebraska Medical Center, Omaha, Nebraska; and.,8 Clinical Discovery Unit, Early Clinical Development, IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom
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Lakhdar R, Rabinovich RA. Can muscle protein metabolism be specifically targeted by nutritional support and exercise training in chronic obstructive pulmonary disease? J Thorac Dis 2018; 10:S1377-S1389. [PMID: 29928520 PMCID: PMC5989103 DOI: 10.21037/jtd.2018.05.81] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Accepted: 05/08/2018] [Indexed: 12/18/2022]
Abstract
Chronic obstructive pulmonary disease (COPD) associates with several extra-pulmonary effects. Muscle dysfunction and wasting is one of the most prominent extra-pulmonary effects and contributes to exercise limitation and health related quality of life (HRQoL), morbidity as well as mortality. The loss of muscle mass is characterised by an impaired balance between protein synthesis (anabolism) and protein breakdown (catabolism) which relates to nutritional disturbances, muscle disuse and the presence of a systemic inflammation, among other factors. Current approaches to reverse skeletal muscle dysfunction and wasting attain only modest improvements. The development of new therapeutic strategies aiming at improving skeletal muscle dysfunction and wasting are needed. This requires a better understanding of the underlying molecular pathways responsible for these abnormalities. In this review we update recent research on protein metabolism, nutritional depletion as well as physical (in)activity in relation to muscle wasting and dysfunction in patients with COPD. We also discuss the role of nutritional supplementation and exercise training as strategies to re-establish the disrupted balance of protein metabolism in the muscle of patients with COPD. Future areas of research and clinical practice directions are also addressed.
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Affiliation(s)
- Ramzi Lakhdar
- ELEGI Colt Laboratory, MRC Centre for Inflammation Research, The Queen’s Medical Research Institute, University of Edinburgh, Scotland, UK
| | - Roberto A. Rabinovich
- ELEGI Colt Laboratory, MRC Centre for Inflammation Research, The Queen’s Medical Research Institute, University of Edinburgh, Scotland, UK
- Respiratory Medicine Department, Royal Infirmary of Edinburgh, Scotland, UK
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7
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Kozhevnikova SA, Budnevskiy AV, Malysh EJ, Ovsyannikov ES. Endocrine glands and their hormones with
anabolic properties: influence on the course and outcomes of chronic obstructive pulmonary disease. ACTA ACUST UNITED AC 2017. [DOI: 10.18821/0023-2149-2017-95-519-523] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Chronic obstructive pulmonary disease (COPD) affects not only the lungs and respiratory tract but also other organs and systems. Systemic manifestations of COPD include endocrine disorders involving pituitary, gonads, and adrenals. However, diagnostics and characteristic of combined endocrine dysfunction in COPD are often disregarded. Several studies have demonstrated the influence of hormonal profile on the clinical course and outcome of COPD. In this review article, we consider the relationship between hormones with anabolic properties produced in endocrine glands (pituitary, gonads, adrenals) and COPD with special reference to the effect of COPD on endocrine dysfunction by hypoxemia, hypercapnia, systemic inflammation, and intake of glucocorticosteroids. Also discussed is the strong influence of endocrine disorders on COPD via decreased protein anabolism, increased protein catabolism, non-enzymatic glycosylation, abnormal control of breathing, decreases in respiratory and limb-muscle mass, worsening of respiratory mechanics, impairment of cardiac function and fluid balance disorders. Numerous clinical studies demonstrated high frequency of COPD combined with dysfunctions of endocrine glands (pituitary, gonads, adrenals) producing anabolic effect. Common risk factors and pathogenetic mechanisms as well as direct hormonal effects increase COPD morbidity; adversely affect the clinical course, outcome and prognosis of the disease. Most patients with COPD and endocrine diseases are in need of replacement, stimulation, inhibitory or blocking hormonal therapy in addition to standard medical treatment of the underlying disease. It is concluded that management of patients with COPD and endocrine dysfunction requires an individually-based approach based on better understanding mechanisms of the above associations, the development of modern medication and drug-free therapeutic modalities.
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Abstract
Background: Exercise limitation is a hallmark of chronic obstructive pulmonary disease (COPD) and is integral to the associated impaired health status of these patients. The poor exercise tolerance is multifactorial in origin, relating to airflow obstruction, disadvantageous lung mechanics, reduced oxygen delivery and skeletal muscle dysfunction. A number of interventions have been studied to determine whether they can impact on exercise performance. The most evidence-based of these is exercise training, which along with other approaches, both previously investigated and putative, are discussed in this review.
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Affiliation(s)
- J P Fuld
- Department of Respiratory Medicine, Monklands Hospital, Airdrie, UK.
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9
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Ribeiro JS, Maciel JVB, Knop LAH, Machado MÂN, Grégio AMT, Camargo ES. Effect of growth hormone in experimental tooth movement. Braz Dent J 2015; 24:503-7. [PMID: 24474293 DOI: 10.1590/0103-6440201302286] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2013] [Accepted: 10/10/2013] [Indexed: 11/22/2022] Open
Abstract
The aim of this study was to evaluate, by histological analysis, the effect of growth hormone (GH) on periodontal ligament and alveolar bone during experimental tooth movement in rats. Eighty male Wistar rats divided into control (C) and experimental (E) groups were examined after 3, 7, 14 and 21 days under controlled climate conditions. Orthodontic force (30 cN) was applied on the maxillary first molar by an orthodontic appliance. Group E received 0.1 IU/kg/day of GH and Group C received 0.5 mL/kg/day of saline. The samples were processed and evaluated under optical microscopy and polarized light microscopy. The Kruskal Wallis test was applied to compare the intergroup variables at 5% significance level. Group E presented a larger number of osteoclasts on the 3rd and 7th days and Howship lacunae on the 3 rd day, a smaller number of blood vessels and greater amount of mature collagen on the 3 rd and 7 th days than Group C (p<0.05). It was concluded that GH accelerated and intensified bone resorption and produced delay in immature collagen formation during experimental tooth movement.
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Affiliation(s)
- Jucienne Salgado Ribeiro
- Dentistry Graduate Program/Orthodontics, PUCPR - Catholic University of Paraná, CuritibaPR, Brazil
| | | | | | | | | | - Elisa Souza Camargo
- Dentistry Graduate Program/Orthodontics, PUCPR - Catholic University of Paraná, CuritibaPR, Brazil
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10
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Guidelines for the Evaluation and Treatment of Muscle Dysfunction in Patients With Chronic Obstructive Pulmonary Disease. ACTA ACUST UNITED AC 2015. [DOI: 10.1016/j.arbr.2015.04.027] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Barreiro E, Bustamante V, Cejudo P, Gáldiz JB, Gea J, de Lucas P, Martínez-Llorens J, Ortega F, Puente-Maestu L, Roca J, Rodríguez-González Moro JM. Guidelines for the evaluation and treatment of muscle dysfunction in patients with chronic obstructive pulmonary disease. Arch Bronconeumol 2015; 51:384-95. [PMID: 26072153 DOI: 10.1016/j.arbres.2015.04.011] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2014] [Revised: 03/24/2015] [Accepted: 04/23/2015] [Indexed: 01/09/2023]
Abstract
In patients with chronic obstructive pulmonary disease (COPD), skeletal muscle dysfunction is a major comorbidity that negatively impacts their exercise capacity and quality of life. In the current guidelines, the most recent literature on the various aspects of COPD muscle dysfunction has been included. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) scale has been used to make evidence-based recommendations on the different features. Compared to a control population, one third of COPD patients exhibited a 25% decline in quadriceps muscle strength, even at early stages of their disease. Although both respiratory and limb muscles are altered, the latter are usually more severely affected. Numerous factors and biological mechanisms are involved in the etiology of COPD muscle dysfunction. Several tests are proposed in order to diagnose and evaluate the degree of muscle dysfunction of both respiratory and limb muscles (peripheral), as well as to identify the patients' exercise capacity (six-minute walking test and cycloergometry). Currently available therapeutic strategies including the different training modalities and pharmacological and nutritional support are also described.
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Affiliation(s)
- Esther Barreiro
- Servei de Pneumologia, Unitat de Recerca en Múscul i Aparell Respiratori (URMAR), IMIM-Hospital del Mar, CEXS, Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona (PRBB), Barcelona, España; CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, España.
| | - Víctor Bustamante
- Hospital Universitario Basurto, Osakidetza, Departamento de Medicina, Universidad del País Vasco, Bilbao, España; Servicio de Neumología y Unidad de Investigación, Hospital de Cruces, Universidad del País Vasco , Barakaldo, España
| | - Pilar Cejudo
- Servicio de Neumología y Unidad de Investigación, Hospital de Cruces, Universidad del País Vasco , Barakaldo, España
| | - Juan B Gáldiz
- CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, España; Hospital Universitario Basurto, Osakidetza, Departamento de Medicina, Universidad del País Vasco, Bilbao, España
| | - Joaquim Gea
- Servei de Pneumologia, Unitat de Recerca en Múscul i Aparell Respiratori (URMAR), IMIM-Hospital del Mar, CEXS, Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona (PRBB), Barcelona, España; CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, España
| | - Pilar de Lucas
- Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Hospital Universitario Virgen del Rocío, Sevilla, España
| | - Juana Martínez-Llorens
- Servei de Pneumologia, Unitat de Recerca en Múscul i Aparell Respiratori (URMAR), IMIM-Hospital del Mar, CEXS, Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona (PRBB), Barcelona, España; CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, España
| | - Francisco Ortega
- CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, España; Servicio de Neumología y Unidad de Investigación, Hospital de Cruces, Universidad del País Vasco , Barakaldo, España
| | - Luis Puente-Maestu
- Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Hospital Universitario Virgen del Rocío, Sevilla, España
| | - Josep Roca
- CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, España; Servicio de Neumología, Hospital General Gregorio Marañón, Universidad Complutense de Madrid, Madrid, España; Servei de Pneumologia, Hospital Clínic de Barcelona, Barcelona, España
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Meal pattern of male rats maintained on amino acid supplemented diets: the effect of tryptophan, lysine, arginine, proline and threonine. Nutrients 2014; 6:2509-22. [PMID: 24988289 PMCID: PMC4113753 DOI: 10.3390/nu6072509] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2013] [Revised: 04/24/2014] [Accepted: 06/03/2014] [Indexed: 01/05/2023] Open
Abstract
The macronutrient composition of the diet has been shown to affect food intake, with proteins having distinct effects. The present study investigated the effect of diet supplementation with individual amino acids (tryptophan, lysine, arginine, proline and threonine) on meal pattern among male rats. Meal pattern and body weight were monitored for two weeks. Proline and threonine had minimal effects on meal pattern, while the most pronounced changes were observed in the tryptophan group. Both tryptophan and lysine decreased overall food intake, which was translated into a reduction in body weight. The reduced food intake of the tryptophan group was associated with an increase in meal size, intermeal intervals (IMI) and meal time and a decrease in meal number. The decrease in the food intake of the lysine group was associated with a reduction in both IMI and meal number, and this was accompanied by an increase in meal time. Arginine increased meal number, while decreasing IMI. Proline and threonine had a minimal effect on meal pattern. Lysine seems to increase satiety, and arginine seems to decrease it, while tryptophan seems to increase satiety and decrease satiation. Accordingly, changes in meal patterns are associated with the type of amino acid added to the diet.
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Maltais F, Decramer M, Casaburi R, Barreiro E, Burelle Y, Debigaré R, Dekhuijzen PNR, Franssen F, Gayan-Ramirez G, Gea J, Gosker HR, Gosselink R, Hayot M, Hussain SNA, Janssens W, Polkey MI, Roca J, Saey D, Schols AMWJ, Spruit MA, Steiner M, Taivassalo T, Troosters T, Vogiatzis I, Wagner PD. 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:e15-62. [PMID: 24787074 DOI: 10.1164/rccm.201402-0373st] [Citation(s) in RCA: 730] [Impact Index Per Article: 66.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Limb muscle dysfunction is prevalent in chronic obstructive pulmonary disease (COPD) and it has important clinical implications, such as reduced exercise tolerance, quality of life, and even survival. Since the previous American Thoracic Society/European Respiratory Society (ATS/ERS) statement on limb muscle dysfunction, important progress has been made on the characterization of this problem and on our understanding of its pathophysiology and clinical implications. PURPOSE The purpose of this document is to update the 1999 ATS/ERS statement on limb muscle dysfunction in COPD. METHODS An interdisciplinary committee of experts from the ATS and ERS Pulmonary Rehabilitation and Clinical Problems assemblies determined that the scope of this document should be limited to limb muscles. Committee members conducted focused reviews of the literature on several topics. A librarian also performed a literature search. An ATS methodologist provided advice to the committee, ensuring that the methodological approach was consistent with ATS standards. RESULTS We identified important advances in our understanding of the extent and nature of the structural alterations in limb muscles in patients with COPD. Since the last update, landmark studies were published on the mechanisms of development of limb muscle dysfunction in COPD and on the treatment of this condition. We now have a better understanding of the clinical implications of limb muscle dysfunction. Although exercise training is the most potent intervention to address this condition, other therapies, such as neuromuscular electrical stimulation, are emerging. Assessment of limb muscle function can identify patients who are at increased risk of poor clinical outcomes, such as exercise intolerance and premature mortality. CONCLUSIONS Limb muscle dysfunction is a key systemic consequence of COPD. However, there are still important gaps in our knowledge about the mechanisms of development of this problem. Strategies for early detection and specific treatments for this condition are also needed.
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Hermans G, De Jonghe B, Bruyninckx F, Van den Berghe G, Cochrane Neuromuscular Group. Interventions for preventing critical illness polyneuropathy and critical illness myopathy. Cochrane Database Syst Rev 2014; 2014:CD006832. [PMID: 24477672 PMCID: PMC7390458 DOI: 10.1002/14651858.cd006832.pub3] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Critical illness polyneuropathy or myopathy (CIP/CIM) is a frequent complication in the intensive care unit (ICU) and is associated with prolonged mechanical ventilation, longer ICU stay and increased mortality. This is an interim update of a review first published in 2009 (Hermans 2009). It has been updated to October 2011, with further potentially eligible studies from a December 2013 search characterised as awaiting assessment. OBJECTIVES To systematically review the evidence from RCTs concerning the ability of any intervention to reduce the incidence of CIP or CIM in critically ill individuals. SEARCH METHODS On 4 October 2011, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, and EMBASE. We checked the bibliographies of identified trials and contacted trial authors and experts in the field. We carried out an additional search of these databases on 6 December 2013 to identify recent studies. SELECTION CRITERIA All randomised controlled trials (RCTs), examining the effect of any intervention on the incidence of CIP/CIM in people admitted to adult medical or surgical ICUs. The primary outcome was the incidence of CIP/CIM in ICU, based on electrophysiological or clinical examination. Secondary outcomes included duration of mechanical ventilation, duration of ICU stay, death at 30 and 180 days after ICU admission and serious adverse events from the treatment regimens. DATA COLLECTION AND ANALYSIS Two authors independently extracted the data and assessed the risk of bias in included studies. MAIN RESULTS We identified five trials that met our inclusion criteria. Two trials compared intensive insulin therapy (IIT) to conventional insulin therapy (CIT). IIT significantly reduced CIP/CIM in the screened (n = 825; risk ratio (RR) 0.65, 95% confidence interval (CI) 0.55 to 0.77) and total (n = 2748; RR 0.70, 95% CI 0.60 to 0.82) population randomised. IIT reduced duration of mechanical ventilation, ICU stay and 180-day mortality, but not 30-day mortality compared with CIT. Hypoglycaemia increased with IIT but did not cause early deaths.One trial compared corticosteroids with placebo (n = 180). The trial found no effect of treatment on CIP/CIM (RR 1.27, 95% CI 0.77 to 2.08), 180-day mortality, new infections, glycaemia at day seven, or episodes of pneumonia, but did show a reduction of new shock events.In the fourth trial, early physical therapy reduced CIP/CIM in 82/104 evaluable participants in ICU (RR 0.62. 95% CI 0.39 to 0.96). Statistical significance was lost when we performed a full intention-to-treat analysis (RR 0.81, 95% CI 0.60 to 1.08). Duration of mechanical ventilation but not ICU stay was significantly shorter in the intervention group. Hospital mortality was not affected but 30- and 180-day mortality results were not available. No adverse effects were noticed.The last trial found a reduced incidence of CIP/CIM in 52 evaluable participants out of a total of 140 who were randomised to electrical muscle stimulation (EMS) versus no stimulation (RR 0.32, 95% CI 0.10 to 1.01). These data were prone to bias due to imbalances between treatment groups in this subgroup of participants. After we imputed missing data and performed an intention-to-treat analysis, there was still no significant effect (RR 0.94, 95% CI 0.78 to 1.15). The investigators found no effect on duration of mechanical ventilation and noted no difference in ICU mortality, but did not report 30- and 180-day mortality.We updated the searches in December 2013 and identified nine potentially eligible studies that will be assessed for inclusion in the next update of the review. AUTHORS' CONCLUSIONS There is moderate quality evidence from two large trials that intensive insulin therapy reduces CIP/CIM, and high quality evidence that it reduces duration of mechanical ventilation, ICU stay and 180-day mortality, at the expense of hypoglycaemia. Consequences and prevention of hypoglycaemia need further study. There is moderate quality evidence which suggests no effect of corticosteroids on CIP/CIM and high quality evidence that steroids do not affect secondary outcomes, except for fewer new shock episodes. Moderate quality evidence suggests a potential benefit of early rehabilitation on CIP/CIM which is accompanied by a shorter duration of mechanical ventilation but without an effect on ICU stay. Very low quality evidence suggests no effect of EMS, although data are prone to bias. Strict diagnostic criteria for CIP/CIM are urgently needed for research purposes. Large RCTs need to be conducted to further explore the role of early rehabilitation and EMS and to develop new preventive strategies.
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Affiliation(s)
- Greet Hermans
- KU LeuvenDepartment of Cellular and Molecular MedicineHerestraat 49, 3000 LeuvenLeuvenBelgium
| | - Bernard De Jonghe
- Centre Hospitalier de Poissy‐Saint‐GermainRéanimation Médico‐Chirurgicale10 rue du Champ Gaillard, F‐78300PoissyFrance
| | - Frans Bruyninckx
- KU Leuven, University HospitalsPhysical Medicine and RehabilitationHerestraat 49, 3000LeuvenBelgium
| | - Greet Van den Berghe
- KU Leuven, University HospitalsDepartment of Intensive Care MedicineHerestraat 49,3000LeuvenBelgium
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Hermans G, De Jonghe B, Bruyninckx F, Van den Berghe G. Interventions for preventing critical illness polyneuropathy and critical illness myopathy. THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS 2014. [PMID: 24477672 DOI: 10.1002/14651858.cd006832] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Critical illness polyneuropathy or myopathy (CIP/CIM) is a frequent complication in the intensive care unit (ICU) and is associated with prolonged mechanical ventilation, longer ICU stay and increased mortality. This is an interim update of a review first published in 2009 (Hermans 2009). It has been updated to October 2011, with further potentially eligible studies from a December 2013 search characterised as awaiting assessment. OBJECTIVES To systematically review the evidence from RCTs concerning the ability of any intervention to reduce the incidence of CIP or CIM in critically ill individuals. SEARCH METHODS On 4 October 2011, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, and EMBASE. We checked the bibliographies of identified trials and contacted trial authors and experts in the field. We carried out an additional search of these databases on 6 December 2013 to identify recent studies. SELECTION CRITERIA All randomised controlled trials (RCTs), examining the effect of any intervention on the incidence of CIP/CIM in people admitted to adult medical or surgical ICUs. The primary outcome was the incidence of CIP/CIM in ICU, based on electrophysiological or clinical examination. Secondary outcomes included duration of mechanical ventilation, duration of ICU stay, death at 30 and 180 days after ICU admission and serious adverse events from the treatment regimens. DATA COLLECTION AND ANALYSIS Two authors independently extracted the data and assessed the risk of bias in included studies. MAIN RESULTS We identified five trials that met our inclusion criteria. Two trials compared intensive insulin therapy (IIT) to conventional insulin therapy (CIT). IIT significantly reduced CIP/CIM in the screened (n = 825; risk ratio (RR) 0.65, 95% confidence interval (CI) 0.55 to 0.77) and total (n = 2748; RR 0.70, 95% CI 0.60 to 0.82) population randomised. IIT reduced duration of mechanical ventilation, ICU stay and 180-day mortality, but not 30-day mortality compared with CIT. Hypoglycaemia increased with IIT but did not cause early deaths.One trial compared corticosteroids with placebo (n = 180). The trial found no effect of treatment on CIP/CIM (RR 1.27, 95% CI 0.77 to 2.08), 180-day mortality, new infections, glycaemia at day seven, or episodes of pneumonia, but did show a reduction of new shock events.In the fourth trial, early physical therapy reduced CIP/CIM in 82/104 evaluable participants in ICU (RR 0.62. 95% CI 0.39 to 0.96). Statistical significance was lost when we performed a full intention-to-treat analysis (RR 0.81, 95% CI 0.60 to 1.08). Duration of mechanical ventilation but not ICU stay was significantly shorter in the intervention group. Hospital mortality was not affected but 30- and 180-day mortality results were not available. No adverse effects were noticed.The last trial found a reduced incidence of CIP/CIM in 52 evaluable participants out of a total of 140 who were randomised to electrical muscle stimulation (EMS) versus no stimulation (RR 0.32, 95% CI 0.10 to 1.01). These data were prone to bias due to imbalances between treatment groups in this subgroup of participants. After we imputed missing data and performed an intention-to-treat analysis, there was still no significant effect (RR 0.94, 95% CI 0.78 to 1.15). The investigators found no effect on duration of mechanical ventilation and noted no difference in ICU mortality, but did not report 30- and 180-day mortality.We updated the searches in December 2013 and identified nine potentially eligible studies that will be assessed for inclusion in the next update of the review. AUTHORS' CONCLUSIONS There is moderate quality evidence from two large trials that intensive insulin therapy reduces CIP/CIM, and high quality evidence that it reduces duration of mechanical ventilation, ICU stay and 180-day mortality, at the expense of hypoglycaemia. Consequences and prevention of hypoglycaemia need further study. There is moderate quality evidence which suggests no effect of corticosteroids on CIP/CIM and high quality evidence that steroids do not affect secondary outcomes, except for fewer new shock episodes. Moderate quality evidence suggests a potential benefit of early rehabilitation on CIP/CIM which is accompanied by a shorter duration of mechanical ventilation but without an effect on ICU stay. Very low quality evidence suggests no effect of EMS, although data are prone to bias. Strict diagnostic criteria for CIP/CIM are urgently needed for research purposes. Large RCTs need to be conducted to further explore the role of early rehabilitation and EMS and to develop new preventive strategies.
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Affiliation(s)
- Greet Hermans
- Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, 3000 Leuven, Leuven, Belgium
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Pan L, Wang M, Xie X, Du C, Guo Y. Effects of anabolic steroids on chronic obstructive pulmonary disease: a meta-analysis of randomised controlled trials. PLoS One 2014; 9:e84855. [PMID: 24427297 PMCID: PMC3888411 DOI: 10.1371/journal.pone.0084855] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2013] [Accepted: 11/19/2013] [Indexed: 11/25/2022] Open
Abstract
Background Anabolic steroids are known to improve body composition and muscle strength in healthy people. However, whether anabolic steroids improve the physical condition and function in patients with chronic obstructive pulmonary disease (COPD) remains undetermined. A meta-analysis was conducted to review the current evidence regarding the effects of anabolic steroids on COPD patients. Methods A comprehensive literature search of PubMed and EMBASE was performed to identify randomised controlled trials that examine the effects of anabolic steroids on COPD patients. Weighted mean differences (WMDs) with 95% confidence intervals were calculated to determine differences between anabolic steroid administration and control conditions. Results Eight eligible studies involving 273 COPD patients were identified in this meta-analysis. Significant improvements were found in body weight (0.956 kg), fat-free mass (1.606 kg), St. George's Respiratory Questionnaire total score (−6.336) and symptom score (−12.148). The apparent improvements in maximal inspiratory pressure (2.740 cmH2O) and maximal expiratory pressure (12.679 cmH2O) were not significant. The effects on handgrip strength, forced expiratory volume in one second (FEV1), predicted FEV1 percent, PaO2, PaCO2 and six-min walk distance were negative, with WMDs of −0.245 kg, −0.096 L/sec, −1.996% of predicted, −1.648 cmHg, −0.039 cmHg and −16.102 meters, respectively. Conclusions Limited evidence available from the published literature suggests that the benefit of anabolic steroids on COPD patients cannot be denied. However, further studies are needed to identify the specific benefits and adverse effects of anabolic steroids on COPD patients and to determine the optimal populations and regimes of anabolic steroids in COPD patients.
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Affiliation(s)
- Lei Pan
- Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Binzhou Medical University, Binzhou, China
| | - Manyuan Wang
- School of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Xiaomei Xie
- Department of Radiotherapy, Xuzhou Central Hospital, Affiliated Xuzhou Hospital of Medical College of Southeast University, Xuzhou, China
| | - Changjun Du
- Department of Respiratory Medicine, Xuzhou Central Hospital, Affiliated Xuzhou Hospital of Medical College of Southeast University, Xuzhou, China
| | - Yongzhong Guo
- Department of Respiratory Medicine, Xuzhou Central Hospital, Affiliated Xuzhou Hospital of Medical College of Southeast University, Xuzhou, China
- * E-mail: .
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Spruit MA, Singh SJ, Garvey C, ZuWallack R, Nici L, Rochester C, Hill K, Holland AE, Lareau SC, Man WDC, Pitta F, Sewell L, Raskin J, Bourbeau J, Crouch R, Franssen FME, Casaburi R, Vercoulen JH, Vogiatzis I, Gosselink R, Clini EM, Effing TW, Maltais F, van der Palen J, Troosters T, Janssen DJA, Collins E, Garcia-Aymerich J, Brooks D, Fahy BF, Puhan MA, Hoogendoorn M, Garrod R, Schols AMWJ, Carlin B, Benzo R, Meek P, Morgan M, Rutten-van Mölken MPMH, Ries AL, Make B, Goldstein RS, Dowson CA, Brozek JL, Donner CF, Wouters EFM. An official American Thoracic Society/European Respiratory Society statement: key concepts and advances in pulmonary rehabilitation. Am J Respir Crit Care Med 2013; 188:e13-64. [PMID: 24127811 DOI: 10.1164/rccm.201309-1634st] [Citation(s) in RCA: 2320] [Impact Index Per Article: 193.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Pulmonary rehabilitation is recognized as a core component of the management of individuals with chronic respiratory disease. Since the 2006 American Thoracic Society (ATS)/European Respiratory Society (ERS) Statement on Pulmonary Rehabilitation, there has been considerable growth in our knowledge of its efficacy and scope. PURPOSE The purpose of this Statement is to update the 2006 document, including a new definition of pulmonary rehabilitation and highlighting key concepts and major advances in the field. METHODS A multidisciplinary committee of experts representing the ATS Pulmonary Rehabilitation Assembly and the ERS Scientific Group 01.02, "Rehabilitation and Chronic Care," determined the overall scope of this update through group consensus. Focused literature reviews in key topic areas were conducted by committee members with relevant clinical and scientific expertise. The final content of this Statement was agreed on by all members. RESULTS An updated definition of pulmonary rehabilitation is proposed. New data are presented on the science and application of pulmonary rehabilitation, including its effectiveness in acutely ill individuals with chronic obstructive pulmonary disease, and in individuals with other chronic respiratory diseases. The important role of pulmonary rehabilitation in chronic disease management is highlighted. In addition, the role of health behavior change in optimizing and maintaining benefits is discussed. CONCLUSIONS The considerable growth in the science and application of pulmonary rehabilitation since 2006 adds further support for its efficacy in a wide range of individuals with chronic respiratory disease.
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Gea J, Martínez-Llorens J, Barreiro E. [Nutritional abnormalities in chronic obstructive pulmonary disease]. Med Clin (Barc) 2013; 143:78-84. [PMID: 24054776 DOI: 10.1016/j.medcli.2013.05.040] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2013] [Accepted: 05/30/2013] [Indexed: 10/26/2022]
Abstract
Nutritional abnormalities are associated with chronic obstructive pulmonary disease with a frequency ranging from 2 to 50%, depending on the geographical area and the study design. Diagnostic tools include anthropometry, bioelectrical impedance, dual energy radioabsortiometry and deuterium dilution, being the body mass and the lean mass indices the most frequently used parameters. While the most important consequences of nutritional abnormalities are muscle dysfunction and exercise limitation, factors implicated include an imbalance between caloric intake and consumption, and between anabolic and catabolic hormones, inflammation, tobacco smoking, poor physical activity, hypoxemia, some drugs and aging/comorbidities. The most important molecular mechanism for malnutrition associated with chronic obstructive pulmonary disease appears to be the mismatching between protein synthesis and breakdown. Among the therapeutic measures proposed for these nutritional abnormalities are improvements in lifestyle and nutritional support, although the use of anabolic drugs (such as secretagogues of the growth hormone) offers a new therapeutic strategy.
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Affiliation(s)
- Joaquim Gea
- Servicio de Neumología, Hospital del Mar-IMIM, Barcelona, España; Departamento de Ciencias Experimentales y de la Salud (CEXS), Universitat Pompeu Fabra, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Bunyola, Mallorca, España.
| | - Juana Martínez-Llorens
- Servicio de Neumología, Hospital del Mar-IMIM, Barcelona, España; Departamento de Ciencias Experimentales y de la Salud (CEXS), Universitat Pompeu Fabra, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Bunyola, Mallorca, España
| | - Esther Barreiro
- Servicio de Neumología, Hospital del Mar-IMIM, Barcelona, España; Departamento de Ciencias Experimentales y de la Salud (CEXS), Universitat Pompeu Fabra, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Bunyola, Mallorca, España
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Mechanism and novel therapeutic approaches to wasting in chronic disease. Maturitas 2013; 75:199-206. [PMID: 23664695 DOI: 10.1016/j.maturitas.2013.03.014] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2013] [Accepted: 03/20/2013] [Indexed: 11/21/2022]
Abstract
Cachexia is a multifactorial syndrome defined by continuous loss of skeletal muscle mass - with or without loss of fat mass - which cannot be fully reversed by conventional nutritional support and which may lead to progressive functional impairment and increased death risk. Its pathophysiology is characterized by negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism. Muscle wasting is encountered in virtually all chronic disease states in particular during advanced stages of the respective illness. Several pre-clinical and clinical studies are ongoing to ameliorate this clinical problem. The mechanisms of muscle wasting and cachexia in chronic diseases such as cancer, chronic heart failure, chronic obstructive pulmonary disease and chronic kidney disease are described. We discuss therapeutic targets and such potential modulators as appetite stimulants, selective androgen receptor modulators, amino acids and naturally occurring peptide hormones.
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Ferreira IM, Brooks D, White J, Goldstein R. Nutritional supplementation for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2012; 12:CD000998. [PMID: 23235577 PMCID: PMC11742366 DOI: 10.1002/14651858.cd000998.pub3] [Citation(s) in RCA: 106] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND Individuals with chronic obstructive pulmonary disease (COPD) and low body weight have impaired pulmonary status, reduced diaphragmatic mass, lower exercise capacity and higher mortality than those who are adequately nourished. Nutritional support may be useful for their comprehensive care. OBJECTIVES To assess the impact of nutritional support on anthropometric measures, pulmonary function, respiratory and peripheral muscles strength, endurance, functional exercise capacity and health-related quality of life (HRQoL) in COPD.If benefit is demonstrated, to perform subgroup analysis to identify treatment regimens and subpopulations that demonstrate the greatest benefits. SEARCH METHODS We identified randomised controlled trials (RCTs) from the Cochrane Airways Review Group Trials Register, a handsearch of abstracts presented at international meetings and consultation with experts. Searches are current to April 2012. SELECTION CRITERIA Two review authors independently selected trials for inclusion, assessed risk of bias and extracted the data. Decisions were made by consensus. DATA COLLECTION AND ANALYSIS We used post-treatment values when pooling the data for all outcomes, and change from baseline scores for primary outcomes. We used mean difference (MD) to pool data from studies that measured outcomes with the same measurement tool and standardised mean difference (SMD) when the outcomes were similar but the measurement tools different. We contacted authors of the primary studies for missing data.We established clinical homogeneity prior to pooling. We presented the results with 95% confidence intervals (CI) in the text and in a 'Summary of findings' table. MAIN RESULTS We included 17 studies (632 participants) of at least two weeks of nutritional support. There was moderate-quality evidence (14 RCTs, 512 participants, nourished and undernourished) of no significant difference in final weight between those who received supplementation and those who did not (MD 0.69 kg; 95% CI -0.86 to 2.24). Pooled data from 11 RCTs (325 undernourished patients) found a statistically significant weight gain (MD 1.65 kg; 95% CI 0.14 to 3.16) in favour of supplementation; three RCTs (116 mixed population) found no significant difference between groups (MD -1.28 kg; 95% CI -6.27 to 3.72). However, when analysed as change from baseline, there was significant improvement with supplementation: 14 RCTs (five of which had imputed SE), MD 1.62 kg (95% CI 1.27 to 1.96 ); 11 RCTs (malnourished), MD 1.73 kg (95% CI 1.29 to 2.17) and three RCTs (mixed), MD 1.44 kg (95% CI 0.68 to 2.19).There was low-quality evidence from five RCTs (six comparisons, 287 participants) supporting a significant improvement from baseline for fat-free mass/fat-free mass index (SMD 0.57; 95% CI 0.04 to 1.09), which was larger for undernourished patients (three RCTs, 125 participants; SMD 1.08; 95% CI 0.70 to 1.47). There was no significant change from baseline noted for adequately nourished patients (one RCT, 71 participants; SMD 0.27; 95% CI -0.20 to 0.73), or for a mixed population (two RCTs, 91 participants; SMD -0.05; 95% CI -0.76 to 0.65).There was moderate-quality evidence from two RCTs (91 mixed participants) that nutritional supplementation significantly improved fat mass/fat mass index from baseline (SMD 0.90; 95% CI 0.46 to 1.33).There was low-quality evidence (eight RCTs, 294 participants) of an increase in mid-arm muscle circumference change (MAMC; MD 0.29; 95% CI 0.02 to 0.57).There was low-quality evidence (six RCTs, 125 participants) of no significant difference in change from baseline scores for triceps measures (MD 0.54; 95% CI -0.16 to 1.24).There was low-quality evidence (five RCTs, 142 participants) of no significant difference between groups in the six-minute walk distance (MD 14.05 m; 95% CI -24.75 to 52.84), 12-minute walk distance or in shuttle walking. However, the pooled change from baseline for the six-minute walk distance was significant (MD 39.96 m; 95% CI 22.66 to 57.26).There was low-quality evidence (seven RCTs, 228 participants) that there was no significant difference between groups in the forced expiratory volume in one second (FEV(1); SMD -0.01; 95% CI -0.31 to 0.30) when measured in litres or percentage predicted.There was low-quality evidence (nine RCTs, 245 participants) of no significant between group difference in maximum inspiratory pressure (MIP; MD 3.54 cm H(2)O; 95% CI -0.90 to 7.99), but those who received supplementation had a higher maximum expiratory pressure (MEP; MD 9.55 cm H(2)O; 95% CI 2.43 to 16.68). For malnourished patients (seven RCTs, 189 participants), those with supplementation had significantly better MIP (MD 5.02; 95% CI 0.29 to 9.76) and MEP (MD 12.73; 95% CI 4.91 to 20.55).There was low-quality evidence (four RCTs, 130 participants) of no significant difference in HRQoL total score (SMD -0.36; 95% CI -0.77 to 0.06) when pooling results from both the St George's Respiratory Questionnaire (SGRQ) and the Chronic Respiratory Questionnaire (CRQ).Two trials (67 participants) used the SGRQ to measure individual domains of activity, impact and symptoms. At the end of treatment, the pooled total SGRQ score was both statistically and clinically significant (MD -6.55; 95% CI -11.7 to -1.41). The three RCTs (123 participants) that used the CRQ to measure the change in individual domains (dyspnoea, fatigue, emotion, mastery), found no significant difference between groups. AUTHORS' CONCLUSIONS We found moderate-quality evidence that nutritional supplementation promotes significant weight gain among patients with COPD, especially if malnourished. Nourished patients may not respond to the same degree to supplemental feeding. We also found a significant change from baseline in fat-free mass index/fat-free mass, fat mass/fat mass index, MAMC (as a measure of lean body mass), six-minute walk test and a significant improvement in skinfold thickness (as measure of fat mass, end score) for all patients. In addition, there were significant improvements in respiratory muscle strength (MIP and MEP) and overall HRQoL as measured by SGRQ in malnourished patients with COPD.These results differ from previous reviews and should be considered in the management of malnourished patients with COPD.
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Affiliation(s)
- Ivone M Ferreira
- Asthma and Airways Centre, Toronto Western Hospital, Toronto, Canada.
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Sakuma K, Yamaguchi A. Sarcopenia and cachexia: the adaptations of negative regulators of skeletal muscle mass. J Cachexia Sarcopenia Muscle 2012; 3:77-94. [PMID: 22476916 PMCID: PMC3374017 DOI: 10.1007/s13539-011-0052-4] [Citation(s) in RCA: 92] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2011] [Accepted: 11/08/2011] [Indexed: 12/25/2022] Open
Abstract
Recent advances in our understanding of the biology of muscle, and how anabolic and catabolic stimuli interact to control muscle mass and function, have led to new interest in the pharmacological treatment of muscle wasting. Loss of muscle occurs as a consequence of several chronic diseases (cachexia) as well as normal aging (sarcopenia). Although many negative regulators [Atrogin-1, muscle ring finger-1, nuclear factor-kappaB (NF-κB), myostatin, etc.] have been proposed to enhance protein degradation during both sarcopenia and cachexia, the adaptation of mediators markedly differs among these conditions. Sarcopenic and cachectic muscles have been demonstrated to be abundant in myostatin- and apoptosis-linked molecules. The ubiquitin-proteasome system (UPS) is activated during many different types of cachexia (cancer cachexia, cardiac heart failure, chronic obstructive pulmonary disease), but not many mediators of the UPS change during sarcopenia. NF-κB signaling is activated in cachectic, but not in sarcopenic, muscle. Some studies have indicated a change of autophagic signaling during both sarcopenia and cachexia, but the adaptation remains to be elucidated. This review provides an overview of the adaptive changes in negative regulators of muscle mass in both sarcopenia and cachexia.
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Affiliation(s)
- Kunihiro Sakuma
- Research Center for Physical Fitness, Sports and Health, Toyohashi University of Technology, 1-1 Hibarigaoka, Tenpaku-cho, Toyohashi, 441-8580, Japan,
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Ahasic AM, Zhai R, Su L, Zhao Y, Aronis KN, Thompson BT, Mantzoros CS, Christiani DC. IGF1 and IGFBP3 in acute respiratory distress syndrome. Eur J Endocrinol 2012; 166:121-9. [PMID: 22004906 PMCID: PMC3757506 DOI: 10.1530/eje-11-0778] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
OBJECTIVE IGF1 and its most abundant binding protein, IGF-binding protein 3 (IGFBP3), have been implicated in fibrotic lung diseases and persistent acute respiratory distress syndrome (ARDS) due to profibrogenic and antiapoptotic activity. Whether circulating levels of IGF1 and IGFBP3 are altered in ARDS and whether they predict progression of and survival from ARDS remains unknown. This study aims to characterize the circulating levels of IGF1 and IGFBP3 in patients at risk for ARDS in relation to i) development of ARDS and ii) mortality among ARDS cases. DESIGN In this case-cohort study, consecutive patients with risk factors for ARDS admitted to the intensive care unit were enrolled and followed prospectively for the development of ARDS. Cases were followed for all-cause mortality through day 60. Of the 2397 patients enrolled in the parent study, plasma samples were available in 531 (22%) patients (356 controls and 175 cases) from early in presentation. Total plasma IGF1 and IGFBP3 levels were measured. RESULTS After adjusting for relevant clinical covariates including severity of illness, IGF1 and IGFBP3 levels were significantly lower in ARDS cases than in controls (odds ratio (OR), 0.58; P=0.006; OR, 0.57; P=0.0015 respectively). Among the ARDS cases, IGF1 and IGFBP3 levels were significantly lower in the 78 (45%) non-survivors (hazard ratio (HR), 0.70; P=0.024; HR, 0.69; P=0.021 respectively). CONCLUSIONS Lower circulating levels of IGF1 and IGFBP3 were independently associated with ARDS case status. Furthermore, lower levels were associated with mortality among the ARDS cases. These data support the role of the IGF pathway in ARDS.
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Affiliation(s)
- Amy M Ahasic
- Section of Pulmonary and Critical Care Medicine, Department of Medicine, Yale University School of Medicine, 300 Cedar Street, PO Box 208057, New Haven, Connecticut 06520-8057, USA.
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Gullett NP, Hebbar G, Ziegler TR. Update on clinical trials of growth factors and anabolic steroids in cachexia and wasting. Am J Clin Nutr 2010; 91:1143S-1147S. [PMID: 20164318 PMCID: PMC2844687 DOI: 10.3945/ajcn.2010.28608e] [Citation(s) in RCA: 71] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
This article and others that focused on the clinical features, mechanisms, and epidemiology of skeletal muscle loss and wasting in chronic diseases, which include chronic kidney disease, cancer, and AIDS, were presented at a symposium entitled "Cachexia and Wasting: Recent Breakthroughs in Understanding and Opportunities for Intervention," held at Experimental Biology 2009. The clinical and anabolic efficacy of specific growth factors and anabolic steroids (eg, growth hormone, testosterone, megestrol acetate) in malnutrition and other catabolic states has been the subject of considerable research during the past several decades. Research on the effects of these agents in cachexia or wasting conditions, characterized by progressive loss of skeletal muscle and adipose tissue, focused on patients with AIDS in the early 1990s, when the devastating effects of the loss of body weight, lean body mass, and adipose tissue were recognized as contributors to these patients' mortality. These same agents have also been studied as methods to attenuate the catabolic responses observed in cancer-induced cachexia and in wasting induced by chronic obstructive pulmonary disease, congestive heart failure, renal failure, and other conditions. This article provides an updated review of recent clinical trials that specifically examined the potential therapeutic roles of growth hormone, testosterone, oxandrolone, and megestrol acetate and emerging data on the orexigenic peptide ghrelin, in human cachexia and wasting.
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Affiliation(s)
- Norleena P Gullett
- Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA, USA
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Rabinovich RA, Vilaró J. Structural and functional changes of peripheral muscles in chronic obstructive pulmonary disease patients. Curr Opin Pulm Med 2010; 16:123-33. [PMID: 20071991 PMCID: PMC2920417 DOI: 10.1097/mcp.0b013e328336438d] [Citation(s) in RCA: 61] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
PURPOSE OF REVIEW The purpose of this review is to identify new advances in our understanding of skeletal muscle dysfunction in patients with chronic obstructive pulmonary disease (COPD). RECENT FINDINGS Recent studies have confirmed the relevance of muscle dysfunction as an independent prognosis factor in COPD. Animal studies have shed light on the molecular mechanisms governing skeletal muscle hypertrophy/atrophy. Recent evidence in patients with COPD highlighted the contribution of protein breakdown and mitochondrial dysfunction as pathogenic mechanisms leading to muscle dysfunction in these patients. SUMMARY COPD is a debilitating disease impacting negatively on health status and the functional capacity of patients. COPD goes beyond the lungs and incurs significant systemic effects among which muscle dysfunction/wasting is one of the most important. Muscle dysfunction is a prominent contributor to exercise limitation, healthcare utilization and an independent predictor of morbidity and mortality. Gaining more insight into the molecular mechanisms leading to muscle dysfunction/wasting is key for the development of new and tailored therapeutic strategies to tackle skeletal muscle dysfunction/wasting in COPD patients.
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Affiliation(s)
- Roberto A Rabinovich
- ELEGI Laboratory, Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.
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Kim HC, Lee GD, Hwang YS. Skeletal Muscle Dysfunction in Patients with Chronic Obstructive Pulmonary Disease. Tuberc Respir Dis (Seoul) 2010. [DOI: 10.4046/trd.2010.68.3.125] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Affiliation(s)
- Ho Cheol Kim
- Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Korea
- Gyeongsang Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Gi Dong Lee
- Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Young Sil Hwang
- Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Korea
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Zs-Nagy I. Is consensus in anti-aging medical intervention an elusive expectation or a realistic goal? Arch Gerontol Geriatr 2009; 48:271-5. [PMID: 19269702 DOI: 10.1016/j.archger.2009.02.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2007] [Revised: 01/29/2009] [Accepted: 02/03/2009] [Indexed: 10/21/2022]
Abstract
One of the biggest scandals of the recent history of medicine is the conflict of views between the gerontological establishment and the American Academy of Anti-Aging Medicine (A4M). The style used in that discussion was really rough and unusual. On the one hand, according to some representatives of the American Medical Associations (AMA), the use of human growth hormone (hGH) for anti-aging medical interventions is illegal, criminal, and requires persecution. On the other hand, A4M is of the opinion that all this is "...filled with incorrect, misplaced references and studies, and multiple basic scientific errors, in an apparent attempt to damage the anti-aging medical profession...". It is evident that in the frame of a short article is impossible to treat all the relevant aspects of this complicated story. Nevertheless, this Editorial attempts to point out the main results obtained so far, together with the most important issues of theoretical feasibility of the hGH replacement therapy (hGHRT). The comprehensive explanation of the aging process called "membrane hypothesis of aging" (MHA) offers a solid basis for the interpretation of the observed beneficial effects of the hGH through its practically ubiquitous membrane receptors, and the species specificity of this peptide hormone. The specific activation of these receptors stimulates the membrane transport functions, rehydrates the intracellular colloids, allowing to speed up the protein synthesis and turnover, and activates a great number of cellular functions, all observed so far. The facts known about the adult growth hormone deficiency (AGHD) syndrome, and the beneficial effects of hGHRT in all aspects of this pathology suggest that aging may generally be considered as an AGHD syndrome. If this concept is accepted by most of the gerontologists, we can resolve practically all problems involved in the above outlined controversies. All this requires an independent, open-minded approach to the problem, and pushes us to a better understanding of the results of theoretical aging research. This approach may open a new, realistic way to the development of efficient anti-aging medical interventions.
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Gayan-Ramirez G, Decramer M. Réhabilitation respiratoire des patients souffrant de bronchopneumopathie chronique obstructive. Presse Med 2009; 38:452-61. [DOI: 10.1016/j.lpm.2008.12.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2008] [Accepted: 12/15/2008] [Indexed: 11/28/2022] Open
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Hermans G, De Jonghe B, Bruyninckx F, Van den Berghe G. Interventions for preventing critical illness polyneuropathy and critical illness myopathy. Cochrane Database Syst Rev 2009:CD006832. [PMID: 19160304 DOI: 10.1002/14651858.cd006832.pub2] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
BACKGROUND Critical illness polyneuro-and/or myopathy (CIP/CIM) is an important and frequent complication in the intensive care unit (ICU), causing delayed weaning from mechanical ventilation. It may increase ICU stay and mortality. OBJECTIVES To examine the ability of any intervention to prevent the occurrence of CIP/CIM. SEARCH STRATEGY We searched the Cochrane Neuromuscular Disease Group Trials Register (October 2007), MEDLINE (January 1950 to April 2008), EMBASE (January 1980 to October 2007), checked bibliographies and contacted trial authors and experts in the field. SELECTION CRITERIA All randomised controlled trials (RCTs), examining the effect of any intervention on the incidence of CIP/CIM in adult medical or surgical ICU patients. The primary outcome measure was the incidence of CIP/CIM after at least seven days in ICU, based on electrophysiological or clinical examination. DATA COLLECTION AND ANALYSIS Two authors independently extracted the data. MAIN RESULTS Three out of nine identified trials, provided data on our primary outcome measure. Two trials examined the effects of intensive insulin therapy versus conventional insulin therapy. Eight hundred and twenty-five out of 2748 patients randomised, were included in the analysis. The incidence of CIP/CIM was significantly reduced with intensive insulin therapy in the population screened for CIP/CIM (relative risk (RR) 0.65, 95% confidence interval (CI) 0.55 to 0.78) and in the total population randomised (RR 0.60, 95% CI 0.49 to 0.74). Duration of mechanical ventilation, duration of ICU stay and 180-day mortality but not 30-day mortality, were significantly reduced with intensive insulin therapy, in both the total and the screened population. Intensive insulin therapy significantly increased hypoglycaemic events and recurrent hypoglycaemia. Death within 24 hours of the hypoglycaemic event was not different between groups. The third trial examined the effects of corticosteroids versus placebo in 180 patients with prolonged acute respiratory distress syndrome. No significant effect of corticosteroids on CIP/CIM was found (RR 1.09, 95% CI 0.53 to 2.26). No effect on 180-day mortality, new serious infections and glycaemia at day seven was found. A trend towards fewer episodes of pneumonia and reduction of new events of shock was shown. AUTHORS' CONCLUSIONS Substantial evidence shows that intensive insulin therapy reduces the incidence of CIP/CIM, the duration of mechanical ventilation, duration of ICU stay and 180-day mortality. There was a significant associated increase in hypoglycaemia. Further research needs to identify the clinical impact of this and strategies need to be developed to reduce the risk of hypoglycaemia. Limited evidence shows no significant effect of corticosteroids on the incidence of CIP/CIM, or on any of the other secondary outcome measures, except for a significant reduction of new episodes of shock. Strict diagnostic criteria for the purpose of research should be defined. Other interventions should be investigated in randomised controlled trials.
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Affiliation(s)
- Greet Hermans
- Department of General Internal Medicine, Medical Intensive Care Unit, Catholic University of Leuven, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Leuven, Belgium
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Wouters EF, Celis MP, Breyer MK, Rutten EP, Graat-Verboom L, Spruit MA. Co-morbid manifestations in COPD. ACTA ACUST UNITED AC 2007. [DOI: 10.1016/j.rmedu.2007.08.003] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Graham MR, Baker JS, Evans P, Kicman A, Cowan D, Hullin D, Davies B. Short-term recombinant human growth hormone administration improves respiratory function in abstinent anabolic-androgenic steroid users. Growth Horm IGF Res 2007; 17:328-335. [PMID: 17512232 DOI: 10.1016/j.ghir.2007.04.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2007] [Revised: 04/01/2007] [Accepted: 04/03/2007] [Indexed: 10/23/2022]
Abstract
OBJECTIVES To determine whether 6 days recombinant human growth hormone (rhGH) administration, in an abstinent anabolic-androgenic steroid (AAS) using group had any respiratory, endurance exercise and biochemical effects compared with an abstinent AAS control group. METHODS Male subjects (n=48) were randomly divided, using a single blind procedure into two groups: (1) control group (C) n=24, means+/-SD, age 32+/-11 years; height 1.8+/-0.06 m; (2) rhGH using group (0.019 mg kg(-1) day(-1)) (GH) n=24, means+/-SD, age 32+/-9 years; height 1.8+/-0.07 m. Anthropometry, respiratory muscle function and endurance exercise were investigated. Respiratory measurements examined, were forced expiratory volume in one second, forced vital capacity, maximum inspiratory pressure and maximum expiratory pressure. Endurance exercise was assessed by measuring peak oxygen uptake (VO(2)peak). Biochemical analysis included; haemoglobin, packed cell volume, glucose, sodium, urea, creatinine, total protein, albumin, testosterone and insulin like growth factor-I (IGF-I). RESULTS Forced expiratory volume in one second/forced vital capacity, maximum inspiratory pressure, maximum expiratory pressure, and IGF-I significantly increased compared with the control group (all P<0.05). Body mass index, fat free mass index, peak oxygen uptake, maximum inspiratory pressure, maximum expiratory pressure, IGF-I and serum sodium significantly increased, whilst body fat, total protein and albumin, significantly decreased within the GH group (all P<0.017). CONCLUSION The findings of this study indicated that short-term high dose rhGH increased aerobic performance and respiratory muscle strength in former AAS users.
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Affiliation(s)
- Michael R Graham
- Health and Exercise Science Research Unit, Faculty of Health Sport and Science, University of Glamorgan, Pontypridd, Wales, United Kingdom.
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Villaça DS, Lerario MC, Dal Corso S, Neder JA. Novas terapias ergogênicas no tratamento da doença pulmonar obstrutiva crônica. J Bras Pneumol 2006; 32:66-74. [PMID: 17273571 DOI: 10.1590/s1806-37132006000100013] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2005] [Accepted: 06/16/2005] [Indexed: 04/19/2023] Open
Abstract
A doença pulmonar obstrutiva crônica é considerada, atualmente, uma doença sistêmica, cujas alterações estruturais e metabólicas podem levar à disfunção muscular esquelética. Esta afeta negativamente o desempenho muscular respiratório e periférico, a capacidade funcional, a qualidade de vida relacionada à saúde e mesmo a sobrevida. A indicação de suplementação de substâncias ergogênicas para pacientes com doença pulmonar obstrutiva crônica baseia-se no fato de que estas drogas podem evitar, ou minimizar, o catabolismo e/ou estimular a síntese protéica, diminuindo a depleção de massa muscular e aumentando a capacidade de exercício. A presente revisão sumariza o conhecimento disponível acerca da utilização de esteróides anabolizantes, creatina, L-carnitina, aminoácidos de cadeia ramificada e hormônio de crescimento em pacientes com doença pulmonar obstrutiva crônica. A vantagem do uso dessas substâncias ergogênicas parece residir no aumento da massa magra e/ou na indução de modificações bioenergéticas. Nesse contexto, a maior experiência acumulada é com os esteróides anabolizantes. Entretanto, os benefícios clínicos em relação à melhora da capacidade de exercício e força muscular, bem como os efeitos na morbimortalidade, não foram, até a presente data, consistentemente demonstrados. A suplementação ergogênica pode vir a se constituir numa ferramenta adjuvante para o tratamento de pacientes com doença pulmonar obstrutiva crônica avançada, especialmente naqueles com depleção muscular e/ou fraqueza periférica.
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Affiliation(s)
- Debora Strose Villaça
- Setor de Função Pulmonar e Fisiologia Clínica do Exercício, Universidade Federal de São Paulo, São Paulo, Brazil
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Abstract
Trauma, sepsis, and surgery are associated with global hypercatabolism and a negative nitrogen balance. When critical illness is prolonged the relentless loss of lean tissue becomes functionally important. Protein catabolism in the critically ill patient is associated with complex changes in the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis. Many small clinical studies indicate that treatment with recombinant human (rh) GH would be a safe and effective means of limiting the deleterious effects of the catabolic response. Unexpectedly, however, two large prospective randomized controlled trials (PRCTs) demonstrated that administration of rhGH to long-stay critically ill adults increases morbidity and mortality. Some progress has been made in understanding the mechanisms underlying this observation.
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Affiliation(s)
- Teng Teng Chung
- Department of Endocrinology, 5th Floor, King George V Building, St. Bartholomew's Hospital, West Smithfield, London EC1A 7BE, UK
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Tivesten A, Isgaard J. Cardiovascular and Respiratory Systems. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2005; 567:149-66. [PMID: 16370139 DOI: 10.1007/0-387-26274-1_6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
- Asa Tivesten
- Research Center for Endocrinology and Metabolism, Department of Internal Medicine, Sahlgrenska Academy at the University of Göteborg, Sweden
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Nagaya N, Itoh T, Murakami S, Oya H, Uematsu M, Miyatake K, Kangawa K. Treatment of Cachexia With Ghrelin in Patients With COPD. Chest 2005; 128:1187-93. [PMID: 16162705 DOI: 10.1378/chest.128.3.1187] [Citation(s) in RCA: 205] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
STUDY OBJECTIVES Ghrelin is a novel growth hormone (GH)-releasing peptide that also induces a positive energy balance by decreasing fat utility and stimulating feeding through GH-independent mechanisms. We investigated whether ghrelin improves cachexia and functional capacity in patients with COPD. METHODS This is an open-label pilot study. Human ghrelin (2 microg/kg bid) was IV administered to seven cachectic patients with COPD for 3 weeks. Food intake, body composition, muscle strength, exercise capacity, pulmonary function, and sympathetic nerve activity were examined before and after ghrelin therapy. RESULTS A single administration of ghrelin markedly increased serum GH (21-fold). Three-week treatment with ghrelin resulted in a significant increase in mean (+/- SEM) body weight (49.3 +/- 3.6 to 50.3 +/- 3.8 kg; p < 0.05). Food intake was significantly increased during ghrelin therapy. Ghrelin increased lean body mass and peripheral and respiratory muscle strength. Ghrelin significantly increased Karnofsky performance status score and the distance walked in 6 min (370 +/- 30 to 432 +/- 35 m; p < 0.05), although it did not significantly alter pulmonary function. Ghrelin attenuated the exaggerated sympathetic nerve activity, as indicated by a marked decrease in plasma norepinephrine level (889 +/- 123 to 597 +/- 116 pg/mL; p < 0.05). CONCLUSIONS These preliminary results suggest that repeated administration of ghrelin improves body composition, muscle wasting, functional capacity, and sympathetic augmentation in cachectic patients with COPD.
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Affiliation(s)
- Noritoshi Nagaya
- Department of Internal Medicine, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
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Schols AMWJ, Broekhuizen R, Weling-Scheepers CA, Wouters EF. Body composition and mortality in chronic obstructive pulmonary disease. Am J Clin Nutr 2005. [DOI: 10.1093/ajcn/82.1.53] [Citation(s) in RCA: 465] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Affiliation(s)
- Annemie MWJ Schols
- From the Department of Respiratory Medicine, University of Maastricht, Maastricht, Netherlands (AMWJS, RB, and EFW) and the Asthma Centre Hornerheide, Horn, Netherlands (CAW)
| | - Roelinka Broekhuizen
- From the Department of Respiratory Medicine, University of Maastricht, Maastricht, Netherlands (AMWJS, RB, and EFW) and the Asthma Centre Hornerheide, Horn, Netherlands (CAW)
| | - Clarie A Weling-Scheepers
- From the Department of Respiratory Medicine, University of Maastricht, Maastricht, Netherlands (AMWJS, RB, and EFW) and the Asthma Centre Hornerheide, Horn, Netherlands (CAW)
| | - Emiel F Wouters
- From the Department of Respiratory Medicine, University of Maastricht, Maastricht, Netherlands (AMWJS, RB, and EFW) and the Asthma Centre Hornerheide, Horn, Netherlands (CAW)
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Ferreira IM, Brooks D, Lacasse Y, Goldstein RS, White J. Nutritional supplementation for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2005:CD000998. [PMID: 15846608 DOI: 10.1002/14651858.cd000998.pub2] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND Low body weight in patients with chronic obstructive pulmonary disease (COPD) is associated with an impaired pulmonary status, reduced diaphragmatic mass, lower exercise capacity and higher mortality rate when compared to adequately nourished individuals with this disease. Nutritional support may therefore be a useful part of their comprehensive care. OBJECTIVES To conduct a systematic review of randomised controlled trials (RCTs) to clarify whether nutritional supplementation (caloric supplementation for at least 2 weeks) improved anthropometric measures, pulmonary function, respiratory muscle strength and functional exercise capacity in patients with stable COPD. SEARCH STRATEGY Randomized controlled trials (RCTs) were identified from the Cochrane Airways Group register of RCTs, a hand-search of abstracts presented at international meetings and consultation with experts. Searches are current as of March 2004. SELECTION CRITERIA Two reviewers independently selected trials for inclusion, assessed quality and extracted the data. DATA COLLECTION AND ANALYSIS Within each trial and for each outcome, we calculated an effect size. The effect sizes were then pooled by a random-effects model. Homogeneity among the effect sizes was also tested. MAIN RESULTS Eleven studies recruiting 352 participants met the inclusion criteria. Eight papers were considered as high quality. Two studies were double-blinded. For each of the outcomes studied, the effect of nutritional support was small: the 95% confidence intervals around the pooled effect sizes all included zero. The effect of nutritional support was homogeneous across studies. AUTHORS' CONCLUSIONS Nutritional support had no significant effect on anthropometric measures, lung function or exercise capacity in patients with stable COPD.
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Affiliation(s)
- I M Ferreira
- St Catherines, Ontario, 76 Roehampton Avenue, Canada, L2M 7W5.
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Chen S, Wang HT, Yang B, Fu YR, Ou QJ. Protective effects of recombinant human growth hormone on cirrhotic rats. World J Gastroenterol 2004; 10:2894-7. [PMID: 15334695 PMCID: PMC4572127 DOI: 10.3748/wjg.v10.i19.2894] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To investigate the effects and molecular mechanisms of recombinant human growth hormone (rhGH) on protecting liver function and alleviating portal hypertension of liver cirrhotic rats.
METHODS: Liver cirrhosis of male Sprague-Dawley rats was induced by administration of thioacetamide. The rats with or without liver cirrhosis were randomly divided into four groups. Group A consisted of the normal rats was treated with normal saline (NS), group B consisted of the normal rats was treated with rhGH, group C consisted of cirrhotic rats was treated with NS, and group D consisted of cirrhotic rats was treated with rhGH. The rats of different groups were subcutaneously injected with 0.5 mL of NS or 333 ng/kg of rhGH daily for 7 d. After treatments, the following parameters were examined, including GH-binding capacity (RT) by 125I-hGH binding, growth hormone receptor mRNA(GHR mRNA) expression by RT-PCR, relative content of collagen (RCC) by histomorphomertry, and level of malon-dialdehyde (MDA) and superoxide dismutase (SOD) in liver tissue by thiobarbituric acid reaction and pyrogallic acid self-oxidation, respectively. Serum albumin (ALB), alanine transaminase (ALT) and portal vein pressure (PVP) were also examined.
RESULTS: rhGH up-regulated both the GH-binding capacity (RT) and the expression of GHR mRNA in vivo. RT in group A (72 ± 12 fmol/mg protein) was significantly higher than that in group C (31 ± 4 fmol/mg protein) (P < 0.05). RT in group B (80 ± 9 fmol/mg protein) increased markedly compared to group A (P < 0.05). RT in group D (40 ± 7 fmol/mg protein) raised remarkably compared with group C (P < 0.05), but less than that in group A, and there was no significant GH binding affinity contrast (Kd) change. The GHR mRNA level (iOD, pixel) in group A (29 ± 3) was significantly higher than that in group C (23 ± 3) (P < 0.05). GHR mRNA levels were significantly raised in group B (56 ± 4) and group D (42 ± 8) compared with groups A and C (29 ± 3 and 23 ± 3, respectively) (P < 0.05). Compared with the normal liver, MDA level was higher and SOD level was lower in cirrhotic livers. After rhGH treatment, MDA level was significantly declined to 12.0 ± 2.2 nmol/mg protein and SOD was raised to 1029 ± 76 U/mg protein in group D (P < 0.05). ALB levels in groups B and D (42 ± 7 g/L and 37 ± 7 g/L, respectively) were significantly raised compared with those in groups A and C (35 ± 5 g/L and 29 ± 4 g/L, respectively) (P < 0.05). ALT level was markedly lower in group D (69 ± 7 U/L) compared to group C (89 ± 15 U/L) (P < 0.05), and close to group A (61 ± 10 U/L). RCC in group C (22.30% ± 3.86%) was significantly higher than that in group A (1.14% ± 0.21%) and group D (14.70% ± 2.07%) (P < 0.05). In addition, rhGH markedly alleviated portal hypertension in liver cirrhotic rats (group D vs C, 9.3 ± 1.5 cmH2O vs 14.4 ± 2.0 cmH2O) (P < 0.05).
CONCLUSION: Pharmacological doses of rhGH can increase RT and GHR mRNA expression, ameliorate liver functions, repress fibrosis and decline portal hypertension, suggesting it has potentially clinical usage as a hepatotropic factor.
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Affiliation(s)
- Shuang Chen
- Department of General Surgery, Sun Yat-Sen Memorial Hospital, the Second Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong Province, China.
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Jansen M, Darby I, Abribat T, Dubreuil P, Ferdinandi ES, Hardy JG. Pulmonary delivery of TH9507, a growth hormone releasing factor analogue, in the dog. Int J Pharm 2004; 276:75-81. [PMID: 15113616 DOI: 10.1016/j.ijpharm.2004.02.012] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2003] [Revised: 02/11/2004] [Accepted: 02/12/2004] [Indexed: 11/25/2022]
Abstract
A modified growth hormone releasing factor (GRF; TH9507), a 44 amino acid peptide analogue of natural human growth hormone releasing factor, is being developed for the treatment of age-associated conditions resulting from diminished growth hormone (GH) secretion. The inhalation route of administration is being considered as an alternative to subcutaneous injection. A study was undertaken in dogs to investigate the absorption of TH9507 following pulmonary delivery. Male beagle dogs were administered TH9507 by intratracheal dry powder insufflation and subcutaneous injection at doses of approximately 375 and 38microg/kg, respectively. In a separate study, male and female dogs received 100microg/kg intravenously. Blood samples were collected at selected sampling times after dosing and plasma levels of TH9507 were measured by radioimmunoassay. The bioavailability by the inhaled route was 41% relative to subcutaneous dosing, with an absolute bioavailability estimated at 13%. No significant difference was observed for the terminal half-life of TH9507 after intratracheal (39min) and subcutaneous (26min) administrations. The mean residence time (MRT) was greater following intratracheal administration (74min versus 52min; P<0.01). These data indicate that the delivery of the TH9507 by the inhalation route may provide a suitable alternative to subcutaneous injection.
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Affiliation(s)
- Mendel Jansen
- Quadrant Drug Delivery Limited, 1 Mere Way, Ruddington, Nottingham NG11 6JS, UK
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Abstract
Poor nutritional status is associated with an increased incidence of morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). While a number of factors have been shown to produce tissue catabolism, no single mechanism has been clearly identified as a primary cause for weight loss in patients with severe COPD. Without a clear understanding of the aetiology of weight loss, therapeutic strategies to reverse this process have historically been unsuccessful. A review of recent studies allows consideration of a model of mechanisms of weight loss. This model includes multiple pathways that may be activated singly or simultaneously to cause loss of weight, specifically lean body mass. These include energy imbalances, elevated levels of cytokines, tissue hypoxia and the effects of cocorticosteroid therapy. To date, interventional studies that have looked at newer pharmacotherapies such as growth hormone and anabolic steroids in patients with COPD who are losing weight have not demonstrated reversal of weight loss or improvement in nutritional status. Currently, early identification of patients at risk for weight loss and aggressive nutritional supplementation coupled with an exercise programme has demonstrated the greatest benefit. However, with increasing understanding of the mechanisms that may be implicated, new targets for therapies are being identified. Of particular research interest are molecules such as leukotrienes, hormones, tumour necrosis factor-alpha and acute-phase proteins, which are noted to be elevated in some patients with COPD-associated weight loss. Currently, inhibitors to some of these inflammatory substances are used therapeutically in other chronic illnesses such as rheumatoid arthritis and cancer cachexia. Future research may investigate their usefulness in COPD and direct new therapies that target the processes contributing to weight loss in these patients.
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Affiliation(s)
- Jean K Berry
- University of Illinois at Chicago, College of Nursing, 60612-7350, USA.
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42
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Abstract
Androgens are known to have a role in the body fat, muscle size, muscle performance and physical function differences seen between hypogonadal and eugonadal men. The results of investigations into effects of testosterone on body composition, fat metabolism and muscle anabolism are reviewed here. Testosterone dose-response relationships are presented in studies of the effects of physiologic and supraphysiologic doses with and without exercise in young hypogonadal men, older men with low testosterone levels and in chronic illness states.
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Affiliation(s)
- Shalender Bhasin
- Division of Endocrinology, Metabolism and Molecular Medicine, Charles R. Drew University of Medicine and Science, 1731 E. 120th Street, Los Angeles, CA 90059, USA.
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Cicoira M, Kalra PR, Anker SD. Growth hormone resistance in chronic heart failure and its therapeutic implications. J Card Fail 2003; 9:219-26. [PMID: 12815572 DOI: 10.1054/jcaf.2003.23] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
BACKGROUND In recent years the administration of recombinant human growth hormone (GH) has received great attention. This review compares the potential of this therapeutic intervention in heart failure with that in other diseases where wasting is commonly seen. The pathophysiologic importance of GH and insulin-like growth factor (IGF)-I in these conditions will be discussed. METHODS AND RESULTS Abnormalities of the GH-IGF-I axis play an important role in the development of cachexia in chronic illnesses. GH resistance is a major determinant of the wasting process, acting through several different mechanisms: increased catabolism, impaired anabolism, and enhanced apoptosis in peripheral tissues. GH therapy has been evaluated in chronic heart failure (CHF); acquired GH resistance may explain the general lack of therapeutic success in the majority of studies. The assessment of plasma levels of GH, IGF-I, and, in particular, GH binding protein may help to guide dosing of GH for CHF patients. CONCLUSIONS GH resistance might be overcome by use of intermittent or higher doses of GH, or alternatively by combining GH with IGF-I. Randomized studies of GH therapy in catabolic states, with targeted dosing and longer duration of treatment are required to fully assess the safety and efficacy of this treatment approach.
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Wang HT, Chen S, Wang J, Ou QJ, Liu C, Zheng SS, Deng MH, Liu XP. Expression of growth hormone receptor and its mRNA in hepatic cirrhosis. World J Gastroenterol 2003; 9:765-70. [PMID: 12679928 PMCID: PMC4611446 DOI: 10.3748/wjg.v9.i4.765] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the expression of growth hormone receptor (GHR) and mRNA of GHR in cirrhotic livers of rats with the intension to find the basis for application of recombinant human growth hormone (rhGH) to patients with liver cirrhosis.
METHODS: Hepatic cirrhosis was induced in Sprague-Dawley rats by administration of thioacetamide intraperitoneally for 9-12 weeks. Collagenase IV was perfused in situ for isolation of hepatocytes. The expression of GHR and its mRNA in cirrhotic livers was studied with radio-ligand binding assay, RT-PCR and digital image analysis.
RESULTS: One class of specific growth hormone-binding site, GHR, was detected in hepatocytes and hepatic tissue of cirrhotic livers. The binding capacity of GHR (RT, fmol/mg protein) in rat cirrhotic liver tissue (30.8 ± 1.9) was significantly lower than that in normal control (74.9 ± 3.9) at the time point of the ninth week after initiation of induction of cirrhosis (n = 10, P < 0.05), and it decreased gradually along with the accumulation of collagen in the process of formation and development of liver cirrhosis (P < 0.05). The number of binding sites (× 104/cell) of GHR on rat cirrhotic hepatocytes (0.86 ± 0.16) was significantly lower than that (1.28 ± 0.24) in control (n = 10, P < 0.05). The binding affinity of GHR among liver tissue, hepatocytes of various groups had no significant difference (P > 0.05). The expression of GHR mRNA (riOD, pixel) in rat cirrhotic hepatic tissues (23.3 ± 3.1) was also significantly lower than that (29.3 ± 3.4) in normal control (n = 10, P < 0.05).
CONCLUSION: The growth hormone receptor was expressed in a reduced level in liver tissue of cirrhotic rats, and lesser expression of growth hormone receptors was found in a later stage of cirrhosis. The reduced expression of growth hormone receptor was partly due to its decreased expression on cirrhotic hepatocytes and the reduced expression of its mRNA in cirrhotic liver tissue.
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Affiliation(s)
- Hong-Tao Wang
- Department of Hepato-biliary Surgery, Sun Yat-Sen Memorial Hospital, the Second Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong Province, China.
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45
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Abstract
A number of hormones, including hypothalamic neuropeptides acting as neurotransmitters and neuromodulators in the CNS, are involved in the physiologic regulation of breathing and participate in adjustment of breathing in disease. In addition to central effects, some hormones also control breathing at peripheral chemoreceptors or have local effects on the lungs and airways. Estrogen and progesterone seem to protect from sleep-disordered breathing, whereas testosterone may predispose to it. Progesterone and thyroxine have long been known to stimulate respiration. More recently, several hormones such as corticotropin-releasing hormone and leptin have been suggested to act as respiratory stimulants. Somatostatin, dopamine, and neuropeptide Y have a depressing effect on breathing. Animal models and experimental human studies suggest that also many other hormones may be involved in respiratory control.
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Affiliation(s)
- Tarja Saaresranta
- Department of Pulmonary Diseases, Turku University Central Hospital, Kiinamyllynkatu 4-8, FIN-20520 Turku, Finland.
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46
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Iioka Y, Tatsumi K, Sugito K, Moriya T, Kuriyama T. Effects of insulin-like growth factor on weight gain in chronic hypoxic rats. J Cardiovasc Pharmacol 2002; 39:636-42. [PMID: 11973406 DOI: 10.1097/00005344-200205000-00003] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Chronic hypoxemia has been suggested as the cause of weight loss in malnourished patients with chronic obstructive pulmonary disease. Insulin-like growth factor I (IGF-I) is believed to improve nitrogen balance and have anabolic effects, and it has been proposed as one of the mediators of vascular smooth muscle proliferation. The aim of this study was to assess the effects of IGF-I administration on the nutritional status and pulmonary vasculature in normoxic and chronic hypoxic rats. Twenty rats were randomly assigned to the normoxic (n = 10) and chronic hypoxic groups (n = 10). They received daily subcutaneous injections of either 3.2 mg/kg of recombinant human IGF-I (rhIGF-I) or isotonic saline (control group) for 3 weeks. Body weight was greater in IGF-I-treated rats compared with vehicle-treated rats, especially during the early and late stages of chronic hypoxic exposure, whereas similar weight gain was observed between IGF-I- and vehicle-treated normoxic rats. In addition, IGF-I treatment increased serum total protein and albumin at the end of hypoxic exposure. However, IGF-I had no additive effects on the degree of pulmonary hypertension. These results indicated that IGF-I promoted anabolism under chronic exposure to hypoxia, whereas no adverse effect was observed in the development of pulmonary hypertension.
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Affiliation(s)
- Yoshinori Iioka
- Department of Respirology, Graduate School of Medicine, Chiba University, Japan
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47
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Roerig JL, Mitchell JE, Myers TC, Glass JB. Pharmacotherapy and medical complications of eating disorders in children and adolescents. Child Adolesc Psychiatr Clin N Am 2002; 11:365-85, xi. [PMID: 12109326 DOI: 10.1016/s1056-4993(01)00012-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
In this article, the authors cover two areas of interest regarding eating disorders in childhood and adolescence: (1) the detection of eating disorders in medical practice and their medical complications and (2) the psychopharmacologic treatment of patients with eating disorders.
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Affiliation(s)
- James L Roerig
- Neuropsychiatric Research Institute, 700 First Avenue South, PO Box 1415, Fargo, ND 58103, USA
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48
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Abstract
Prolonged length of stay is the major challenge for modern intensive care because of the associated morbidity and the impact on resource utilization. Severe trauma or infection is associated with a catabolic response, which is characterized by increased protein turnover and negative nitrogen balance. Severe catabolism leads to end-organ dysfunction and muscular weakness, prolonging the need for mechanical ventilation. Catabolism cannot be prevented with standard parenteral or enteral nutritional formulas. In order to prevent the complications of catabolism in intensive care patients, recombinant growth hormone has been applied as an experimental therapy for two decades in patients requiring parenteral nutrition and in patients with respiratory failure. Administration of recombinant growth hormone has resulted in positive nitrogen balance, and studies in mechanically ventilated patients suggest that it may shorten the need for ventilatory support. In contrast to the results of these relatively small studies, a recent multinational randomized controlled trial revealed that the administration of recombinant growth hormone (with doses 10-20 times higher than used for replacement therapy) increases mortality of critically ill patients. The excessive mortality in patients treated with recombinant growth hormone was related to infections and development of multiple organ failure, leading to the conclusion that administration of high doses of recombinant growth hormone cannot be recommended for critically ill patients. This review reinforces that conclusion.
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Affiliation(s)
- Esko Ruokonen
- Critical Care Research Program, Department of Anesthesiology and Intensive Care, Kuopio University Hospital, Kuopio, Finland
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49
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Ferreira IM, Brooks D, Lacasse Y, Goldstein RS, White J. Nutritional supplementation for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2002:CD000998. [PMID: 11869582 DOI: 10.1002/14651858.cd000998] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND Low body weight in patients with chronic obstructive pulmonary disease (COPD) is associated with an impaired pulmonary status, reduced diaphragmatic mass, lower exercise capacity and higher mortality rate when compared to adequately nourished individuals with this disease. Nutritional support may therefore be a useful part of their comprehensive care. OBJECTIVES To conduct a systematic review of randomized controlled trials (RCTs) to clarify whether nutritional supplementation (caloric supplementation for at least 2 weeks) improved anthropometric measures, pulmonary function, respiratory muscle strength and functional exercise capacity in patients with stable COPD. SEARCH STRATEGY Randomized controlled trials (RCTs) were identified from the Cochrane Airways Group register of RCTs, a hand-search of abstracts presented at international meetings and consultation with experts. SELECTION CRITERIA Two reviewers independently selected trials for inclusion, assessed quality and extracted the data. DATA COLLECTION AND ANALYSIS Within each trial and for each outcome, we calculated an effect size. The effect sizes were then pooled by a random-effects model. Homogeneity among the effect sizes was also tested. MAIN RESULTS From 272 references, nine RCTs were ultimately included. Six papers were considered as high quality and only two studies were double-blinded. For each of the outcomes studied, the effect of nutritional support was small: the 95% confidence intervals around the pooled effect sizes all included zero. The effect of nutritional support was homogeneous across studies. An additional search conducted in August 2001 did not identify further studies. REVIEWER'S CONCLUSIONS Nutritional support had no significant effect on anthropometric measures, lung function or exercise capacity in patients with stable COPD.
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Affiliation(s)
- I M Ferreira
- Respiratory Division, University of Toronto, 82 Buttonwood, Toronto, Ontario, Canada, M6M 2J5.
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50
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Akner G, Cederholm T. Treatment of protein-energy malnutrition in chronic nonmalignant disorders. Am J Clin Nutr 2001; 74:6-24. [PMID: 11451713 DOI: 10.1093/ajcn/74.1.6] [Citation(s) in RCA: 168] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Protein-energy malnutrition (PEM) is common in connection with chronic disease and is associated with increased morbidity and mortality. Because the risk of PEM is related to the degree of illness, the causal connections between malnutrition and a poorer prognosis are complex. It cannot automatically be inferred that nutritional support will improve the clinical course of patients with wasting disorders. We reviewed studies of the treatment of PEM in cases of chronic obstructive pulmonary disease, chronic heart failure, stroke, dementia, rehabilitation after hip fracture, chronic renal failure, rheumatoid arthritis, and multiple disorders in the elderly. Several methodologic problems are associated with nutrition treatment studies in chronically ill patients. These problems include no generally accepted definition of PEM, uncertain patient compliance with supplementation, and a wide range of outcome variables. Avail-able treatment studies indicate that dietary supplements, either alone or in combination with hormonal treatment, may have positive effects when given to patients with manifest PEM or to patients at risk of developing PEM. In chronic obstructive pulmonary disease, nutritional treatment may improve respiratory function. Nutritional therapy of elderly women after hip fractures may speed up the rehabilitation process. When administered to elderly patients with multiple disorders, diet therapy may improve functional capacity. The data regarding nutritional treatment of the conditions mentioned above is still inconclusive. There is still a great need for randomized controlled long-term studies of the effects of defined nutritional intervention programs in chronically ill and frail elderly with a focus on determining clinically relevant outcomes.
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Affiliation(s)
- G Akner
- Departments of Geriatric Medicine at Karolinska Hospital and Huddinge University Hospital, Stockholm, Sweden
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