New treatments for chronic obstructive pulmonary disease using ergogenic aids

Chronic obstructive pulmonary disease is currently considered a systemic disease, presenting structural and metabolic alterations that can lead to skeletal muscle dysfunction. This negatively affects the performance of respiratory and peripheral muscles, functional capacity, health-related quality of life and even survival. The decision to prescribe ergogenic aids for patients with chronic obstructive pulmonary disease is based on the fact that these drugs can avert or minimize catabolism and stimulate protein synthesis, thereby reducing the loss of muscle mass and increasing exercise tolerance. This review summarizes the available data regarding the use of anabolic steroids, creatine, L-carnitine, branched-chain amino acids and growth hormones in patients with chronic obstructive pulmonary disease. The advantage of using these ergogenic aids appears to lie in increasing lean muscle mass and inducing bioenergetic modifications. Within this context, most of the data collected deals with anabolic steroids. However, to date, the clinical benefits in terms of increased exercise tolerance and muscle strength, as well as in terms of the effect on morbidity and mortality, have not been consistently demonstrated. Dietary supplementation with substances of ergogenic potential might prove to be a valid adjuvant therapy for treating patients with advanced chronic obstructive pulmonary disease, especially those presenting loss of muscle mass or peripheral muscle weakness.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.Universidade Federal de São Paulo (UNIFESP) Setor de Função Pulmonar e Fisiologia Clínica do ExercícioUniversidade Federal de São Paulo (UNIFESP)UNIFESP, Setor de Função Pulmonar e Fisiologia Clínica do ExercícioUNIFESPSciEL

Strength and endurance of the respiratory and handgrip muscles after the use of flunisolide in normal subjects

Objective: To evaluate the effects of the inhaled flunisolide upon the strength and endurance of the respiratory and peripheral muscles of normal subjects.Design: A randomized, double blind and placebo-controlled study.Setting: A university-affiliated teaching hospital.Participants: Thirteen normal volunteers selected from a graduation course.Intervention: Subjects were randomly allocated to receive a placebo or corticosteroid (flunisolide) to be inhaled twice a day for 4 weeks. After 2 weeks of a washout period, subjects who were receiving the placebo, received flunisolide and vise versa for another 4-week period.Measurements and results: Spirometry was used to define the volunteers as being normal in terms of pulmonary function. During the study, subjects performed tests of respiratory muscle function (strength and endurance), measurements of handgrip strength and endurance and anthropometric measurements. Muscle strength was measured each week while muscle endurance was measured every 2 weeks. There was no significant difference in the maximal inspiratory and expiratory pressure and handgrip strength during weeks 1-4 when the subjects used either flunisolide or placebo. However, we observed an increase in the endurance time of the respiratory and handgrip muscles in the 4th week of both flunisolide and placebo use, what may be considered due to a learning effect.Conclusion: Inhalation of flunisolide by normal subjects for 1 month does not cause any acute or clinically perceived effect in the peripheral or respiratory muscles. (C) 2007 Published by Elsevier B.V.Universidade Federal de São Paulo, Resp Div, BR-04023062 São Paulo, BrazilUniv Fed Bahia, Div Resp, Ufba, BA, BrazilUniv Metropolitana Santos, Resp Div, São Paulo, BrazilUniversidade Federal de São Paulo, Resp Div, BR-04023062 São Paulo, BrazilWeb of Scienc

Evaluation of prone position associated with CPAP in newborn preterm

The aim of this study was to evaluate clinical variables in new born preterm infants (NBPT) in the prone position (PP) associated with CPAP. A cross sectional study in NBPT with CPAP at the intensive care unit was done. Variables: heart rate (HR), respiratory rates (RR), SpO2, respiratory distress quantify by Silverman and Andersen (BSA) bulletin (which the higher level means worst respiratory distress) were assessed. The protocol was conducted in five phases. In phase I, HR, RR, SpO2, and BSA were evaluated in supine position. In phases II, III, IV and V the same variables were evaluated as phase I, at 5, 15, 30 and 60 min, respectively, after phase I. Following the phase I, the RNPT was positioned at the PP. We performed repeated analysis of variance to compare all the variables studied in five phases, and used the Bonferroni test for post hoc analysis. Statistical significance was considered when pO objetivo deste estudo foi avaliar os benefícios nas variáveis clínicas do decúbito ventral (DV) associado a pressão positiva contínua nas vias aéreas (CPAP), em recém-nascido pré-termo (RNPT). Foi feito um estudo transversal em RNPT com utilização do CPAP internados na unidade de terapia intensiva (UTI). As frequências cardíaca (FC) e respiratória (FR), SpO2, quantificação do desconforto respiratório pelo boletim de Silverman e Andersen (BSA: quanto maior o valor, pior o desconforto respiratório) foram avaliados em cinco fases. Na fase I foram avaliadas a FC, FR, SpO2 e BSA em decúbito supino. Nas fases II, III, IV e V foram coletadas as mesmas variáveis da fase I após 5, 15, 30 e 60 min, respectivamente. O RNPT foi posicionado em DV logo após a fase I. Foi realizada análise de variância repetida para comparação entre todas as variáveis estudadas nas cinco fases, e utilizado-se teste de Bonferroni para análise post hoc. Foi considerada significância estatística quando

A symptom-limited incremental step test determines maximum physiological responses in patients with chronic obstructive pulmonary disease

Background: Step tests have been used to evaluate exercise tolerance and effort-related hypoxemia in different diseases. A symptom-limited incremental step test (IST) has never been tested in COPD patients.Aim: To compare maximal physiological responses between an IST and cardiopulmonary exercise testing (CPET), to test the reproducibility of the IST on different days, and to provide a predict equation to estimate VO2 from the IST in patients with COPD.Material and methods: At the same day, thirty-four patients (VEF1 46 +/- 14% of pred) underwent a CPET on cycle ergometer and the first 151 (IST-1) (1 h apart). After 2-5 days, patients repeated the IST (IST-2). Pulmonary gas exchange was measured during all tests.Results: Peak VO2 was significantly higher in IST-1 and IST-2 than in CEPT (Mean +/- SD: 1.19 +/- 0.39 L, 1.20 +/- 0.40 L, 1.07 +/- 0.35 L) with no difference for ventilation (VE), heart rate (HR), and perception of effort. ISTs were highly reproducible, with significant intraclass correlation coefficient (CCI [95% confidence interval]) for number of steps (0.98[0.95-0.99]), VO2 (0.99 [0.98-0.99]), VE (0.97[0.93-0.99]), HR (0.92[0.81-0.97]), and SpO(2) (0.96[0.90-0.98]). Desaturation was significantly higher for IST-1 and IST-2 compared with cycling (Mean +/- SD: -6 +/- 5%, -6 +/- 4%, - 3 +/- 3%). Number of steps and patient weight explained 81% of the variance in peak VO2 (p < 0.001).Conclusion: A symptom-limited incremental step test, externally paced, elicits maximal cardiopulmonary and metabolic responses, and is well tolerated and reproducible in patients with COPD. (C) 2013 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ Nove Julho UNINOVE, Postgrad Program Rehabil Sci, BR-01504001 São Paulo, BrazilFed Univ São Paulo UNIFESP, Dept Med, Div Resp Dis, São Paulo, BrazilUniv Fed Juiz de Fora, Human Physiol Dept, Juiz de Fora, MG, BrazilFed Univ São Paulo UNIFESP, Dept Med, Div Resp Dis, São Paulo, BrazilFAPESP: 2010/09732-6Web of Scienc

Neuromuscular electrical stimulation improves exercise tolerance in chronic obstructive pulmonary disease patients with better preserved fat-free mass

BACKGROUND: High-frequency neuromuscular electrical stimulation increases exercise tolerance in patients with advanced chronic obstructive pulmonary disease (COPD patients). However, it is conceivable that its benefits are more prominent in patients with better-preserved peripheral muscle function and structure. OBJECTIVE: To investigate the effects of high-frequency neuromuscular electrical stimulation in COPD patients with better-preserved peripheral muscle function. Design: Prospective and cross-over study. METHODS: Thirty COPD patients were randomly assigned to either home-based, high-frequency neuromuscular electrical stimulation or sham stimulation for six weeks. The training intensity was adjusted according to each subject's tolerance. Fat-free mass, isometric strength, six-minute walking distance and time to exercise intolerance (Tlim) were assessed. RESULTS: Thirteen (46.4%) patients responded to high-frequency neuromuscular electrical stimulation; that is, they had a post/pre &#916; Tlim >10% after stimulation (unimproved after sham stimulation). Responders had a higher baseline fat-free mass and six-minute walking distance than their seventeen (53.6%) non-responding counterparts. Responders trained at higher stimulation intensities; their mean amplitude of stimulation during training was significantly related to their fat-free mass (r = 0.65; p<0.01). Logistic regression revealed that fat-free mass was the single independent predictor of Tlim improvement (odds ratio [95% CI] = 1.15 [1.04-1.26]; p<0.05). CONCLUSIONS: We conclude that high-frequency neuromuscular electrical stimulation improved the exercise capacity of COPD patients with better-preserved fat-free mass because they tolerated higher training stimulus levels. These data suggest that early training with high-frequency neuromuscular electrical stimulation before tissue wasting begins might enhance exercise tolerance in patients with less advanced COPD

Expression of matrix metalloproteinases -2 and -9 in saliva from patients with chronic obstructive pulmonary disease

The increased expression of matrix metalloproteinases (MMP) is considered a key factor in the development of chronic obstructive pulmonary disease (COPD). This study aimed at assessing expression levels of MMP-2 and MMP-9 in saliva from patients with COPD, comparing them to those of healthy subjects, thus assessing the feasibility of characterizing specific biomarkers for COPD. Patients with COPD (n=16) and healthy controls (n=9) were selected; both groups submitted to spirometry and to collection of saliva samples. Saliva levels of MMP-2 and MMP-9 were determined by Western blot. MMP-2 and MMP-9 levels were significantly higher in COPD patients than in control subjects. In COPD patients, a moderate, negative correlation was found between MMP-2 concentration and forced expiatory volume at the first second (r= -0.582; p=0.014). These findings open new perspectives to study specific biomarkers in saliva to predict and monitor airway obstruction in COPD patients.O aumento da expressão das metaloproteinases da matriz extracelular (MPM) é considerado um importante fator no desenvolvimento da doença pulmonar obstrutiva crônica (DPOC). O presente estudo teve como objetivo avaliar os níveis de expressão da MPM-2 e MPM-9 na saliva de pacientes com DPOC em comparação com indivíduos saudáveis, verificando a viabilidade de usar a saliva para a caracterização de biomarcadores específicos em DPOC. Foram selecionados pacientes com DPOC (n=16) e controles saudáveis (n=9). Em ambos os grupos foram realizados teste espirométrico e obtidas amostras de saliva de cada indivíduo. Os níveis de MPM-2 e MPM-9 na saliva foram determinados pela técnica Western blot. A MPM-2 e a MPM-9 foram significativamente maiores em pacientes com DPOC do que no grupo de indivíduos saudáveis. Foi encontrada moderada correlação negativa entre a concentração de MPM-2 e o volume expiratório forçado no primeiro segundo (r= -0,582, p=0,014) em pacientes com DPOC. Estes resultados abrem novas perspectivas para o estudo específico de biomarcadores na saliva para predizer e monitorar a obstrução ao fluxo aéreo em pacientes com DPOC

The pattern and timing of breathing during incremental exercise: a normative study

Clinical evaluation of the pattern and timing of breathing during submaximal exercise can be valuable for the identification of the mechanical ventilatory consequences of different disease processes and for assessing the efficacy of certain interventions.Sedentary individuals (60 male/60 female, aged 20-80 yrs) were randomly selected from >8,000 subjects and submitted to ramp incremental cycle ergometry. Tidal volume (V-T)/ resting inspiratory capacity, respiratory frequency, total respiratory time (Trot), inspiratory time (T-I), expiratory time (T-E), duty cycle (TI/Ttot) and mean inspiratory flow (V-T/T-I) were analysed at selected submaximal ventilatory intensities.Senescence and female sex were associated with a more tachypnoeic breathing pattern during isoventilation. the decline in T-tot was proportional to the TI and TE P reductions, i.e. T-I/T-tot was remarkably constant across age strata, independent of sex. the pattern, but not timing, of breathing was also influenced by weight and height; a set of demographically and anthropometrically based prediction equations are therefore presented.These data provide a frame of reference for assessing the normality of some clinically useful indices of the pattern and timing of breathing during incremental cycle ergometry in sedentary males and females aged 20-80 yrs.Universidade Federal de São Paulo, Pulmonary Funct & Clin Exercise Physiol Unit, Div Resp, Dept Med,Paulista Sch Med, BR-04020050 São Paulo, BrazilUniv Glasgow, Ctr Exercise Sci & Med, Inst Biol & Life Sci, Glasgow, Lanark, ScotlandUniversidade Federal de São Paulo, Pulmonary Funct & Clin Exercise Physiol Unit, Div Resp, Dept Med,Paulista Sch Med, BR-04020050 São Paulo, BrazilWeb of Scienc

A step test to assess exercise-related oxygen desaturation in interstitial lung disease

A 6-min step test (6MST) may constitute a practical method for routinely assessing effort tolerance and exercise-related oxyhaemoglobin desaturation (ERD) in the primary care of patients with interstitial lung disease.In total, 31 patients (19 males) with idiopathic pulmonary fibrosis I and chronic hypersensitivity pneumonia were submitted, on different days, to two 6MSTs. Physiological responses were compared with those found on maximal and submaximal cycle ergometer tests at the same oxygen uptake I Chronic breathlessness was also determined, as measured by the baseline dyspnoea index (BDI).Responses to 6MST were highly reproducible: 1.3 +/- 2.0 steps(.)min(-1), +/- 5 beats(.)min(-1) (cardiac frequency), +/- 50 mL(.)min(-1) (V'O-2), +/- 7 L(.)min(-1) (minute ventilation) and +/- 2% (arterial oxygen saturation measured by pulse oximetry (Sp,O-2)). the number of steps climbed in 6 min was correlated to peak V'O-2 and the BDI. There were significant associations among the tests in relation to presence (change in Sp,O-2 between rest and exercise >= 4%) and severity (Sp,O-2 < 88%) of ERD. Four patients, however, presented ERD only in response to 6MST. Resting diffusing capacity of the lung for carbon monoxide and alveolar-arterial oxygen tension difference were the independent predictors of the number of steps climbed.A single-stage, self-paced 6-min step test provided reliable and reproducible estimates of exercise capacity and exercise-related oxyhaemoglobin desaturation in interstitial lung disease patients.UNIFESP, EPM, Dept Med,SEFICE, Div Resp,Pulm Funct & Clin Exercise Physiol Unit, BR-04020050 São Paulo, BrazilUNIFESP, EPM, Dept Med,SEFICE, Div Resp,Pulm Funct & Clin Exercise Physiol Unit, BR-04020050 São Paulo, BrazilWeb of Scienc