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1.
Rev Port Pneumol (2006) ; 23(5): 266-272, 2017.
Article in English | MEDLINE | ID: mdl-28579149

ABSTRACT

The six minute walk test (6MWT) is a standardized test that provides information on exercise capacity in patients with COPD. It is considered a submaximal test in opposition to incremental cardiopulmonary exercise tests (CPET) that provide valuable information on all the systems involved in exercise. OBJECTIVES: 1. To compare the perceptive, physiological responses and degree of dynamic hyperinflation during two exercise tests: the 6MWT and the incremental CPET on a treadmill. 2. To evaluate how dyspnea is related to dynamic hyperinflation (DH) and other functional parameters in both tests. METHODS: 29 stable COPD male patients, age 68±5.8 years, mean post-bronchodilator FEV1 57±11%, were recruited. To evaluate dynamic hyperinflation, inspiratory capacity (IC) was measured at rest and upon completing each one of the tests. At the same time, perceived dyspnea and leg discomfort were rated on specific modified Borg scales. RESULTS: The mean walk distance in 6MWT was 494±88m. The Borg scale rating for shortness of breath upon completing the test was 4.7±2, whilst 2.9±2 for leg discomfort. IC changed from 2.53±0.63l before to 2.34±0.60l after completion of the test. In the treadmill CPET, maximal oxygen consumption (V˙O2max) was 21.8±5mL/kg/min with 6.6±2 dyspnea and 4.3±2 leg discomfort on Borg scales. IC changed from 2.17±0.53l to 1.20±0.43l. CONCLUSIONS: Dynamic hyperinflation occurs in male COPD patients during submaximal exercise such as the 6MWT. This phenomenon is more pronounced after incremental CPET on a treadmill. Despite being dyspnea the dominant limiting symptom for both tests, we observed different physiological responses.


Subject(s)
Dyspnea/physiopathology , Exercise Test , Pulmonary Disease, Chronic Obstructive/physiopathology , Walk Test , Aged , Aged, 80 and over , Dyspnea/etiology , Exercise Test/methods , Humans , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/complications , Time Factors
2.
Arch. bronconeumol ; 51(8)Aug. 2015.
Article in English | BIGG - GRADE guidelines | ID: biblio-965199

ABSTRACT

La disfunción muscular de pacientes con enfermedad pulmonar obstructiva crónica (EPOC) constituye una de las comorbilidades más importantes, con repercusiones negativas en su capacidad de ejercicio y calidad de vida. En la presente normativa se ha resumido la literatura publicada más recientemente sobre los diferentes aspectos del tema y se ha utilizado también la escala Grading of Recommendations Assessment, Development, and Evaluation (GRADE) de recomendaciones sobre el grado de evidencia de las diferentes propuestas de la normativa. Respecto a una población control, se estima que en un tercio de los pacientes EPOC la fuerza del cuádriceps es un 25% inferior incluso en estadios precoces de su enfermedad. Aunque tanto los músculos respiratorios como los de las extremidades están alterados, estos últimos suelen verse mayormente afectados. Diversos factores y mecanismos biológicos están involucrados en la disfunción muscular de los pacientes. Se proponen diversas pruebas para evaluar y diagnosticar el grado de afectación de los músculos respiratorios y de las extremidades (periféricos), así como identificar la capacidad de esfuerzo de los pacientes (prueba de marcha de 6min y cicloergometría). Se describen también las posibles estrategias terapéuticas vigentes que incluyen las diversas modalidades de entrenamiento y de soporte farmacológico y nutricional.(AU)


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.(AU)


Subject(s)
Humans , Muscle Weakness/therapy , Pulmonary Disease, Chronic Obstructive , Oxygen/therapeutic use , Spirometry , Steroids/therapeutic use , Breathing Exercises , Growth Hormone-Releasing Hormone/therapeutic use , Nutritional Support , Electrodiagnosis , Exercise Therapy , Ghrelin/therapeutic use , Helium/therapeutic use
3.
Biochim Biophys Acta ; 1842(2): 175-85, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24215713

ABSTRACT

BACKGROUND: Loss of quadriceps muscle oxidative phenotype (OXPHEN) is an evident and debilitating feature of chronic obstructive pulmonary disease (COPD). We recently demonstrated involvement of the inflammatory classical NF-κB pathway in inflammation-induced impairments in muscle OXPHEN. The exact underlying mechanisms however are unclear. Interestingly, IκB kinase α (IKK-α: a key kinase in the alternative NF-κB pathway) was recently identified as a novel positive regulator of skeletal muscle OXPHEN. We hypothesised that inflammation-induced classical NF-κB activation contributes to loss of muscle OXPHEN in COPD by reducing IKK-α expression. METHODS: Classical NF-κB signalling was activated (molecularly or by tumour necrosis factor α: TNF-α) in cultured myotubes and the impact on muscle OXPHEN and IKK-α levels was investigated. Moreover, the alternative NF-κB pathway was modulated to investigate the impact on muscle OXPHEN in absence or presence of an inflammatory stimulus. As a proof of concept, quadriceps muscle biopsies of COPD patients and healthy controls were analysed for expression levels of IKK-α, OXPHEN markers and TNF-α. RESULTS: IKK-α knock-down in cultured myotubes decreased expression of OXPHEN markers and key OXPHEN regulators. Moreover, classical NF-κB activation (both by TNF-α and IKK-ß over-expression) reduced IKK-α levels and IKK-α over-expression prevented TNF-α-induced impairments in muscle OXPHEN. Importantly, muscle IKK-α protein abundance and OXPHEN was reduced in COPD patients compared to controls, which was more pronounced in patients with increased muscle TNF-α mRNA levels. CONCLUSION: Classical NF-κB activation impairs skeletal muscle OXPHEN by reducing IKK-α expression. TNF-α-induced reductions in muscle IKK-α may accelerate muscle OXPHEN deterioration in COPD.


Subject(s)
I-kappa B Kinase/metabolism , Muscle Fibers, Skeletal/metabolism , Muscle, Skeletal/metabolism , NF-kappa B/metabolism , Aged , Animals , Blotting, Western , Cell Line , Female , Gene Expression Regulation/drug effects , Humans , I-kappa B Kinase/genetics , Male , Mice , Middle Aged , Muscle Fibers, Skeletal/drug effects , Muscle, Skeletal/drug effects , NF-kappa B/genetics , Oxidation-Reduction/drug effects , Phenotype , Pulmonary Disease, Chronic Obstructive/genetics , Pulmonary Disease, Chronic Obstructive/metabolism , Pulmonary Disease, Chronic Obstructive/physiopathology , Quadriceps Muscle/metabolism , Quadriceps Muscle/physiopathology , RNA Interference , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/drug effects , Signal Transduction/genetics , Signal Transduction/physiology , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/pharmacology
4.
FASEB J ; 24(12): 5052-62, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20807714

ABSTRACT

Chronic obstructive pulmonary disease (COPD) is characterized by weight loss, muscle wasting (in advanced disease ultimately resulting in cachexia), and loss of muscle oxidative phenotype (oxphen). This study investigates the effect of inflammation (as a determinant of muscle wasting) on muscle oxphen by using cell studies combined with analyses of muscle biopsies of patients with COPD and control participants. We analyzed markers (citrate synthase, ß-hydroxyacyl-CoA dehydrogenase, and cytochrome c oxidase IV) and regulators (PGC-1α, PPAR-α, and Tfam) of oxphen in vastus lateralis muscle biopsies of patients with advanced COPD and healthy smoking control participants. Here 17 of 73 patients exhibited elevated muscle TNF-α mRNA levels. In these patients, significantly lower mRNA levels of all oxidative markers/regulators were found. Interestingly, these patients also had a significantly lower body mass index and tended to have less muscle mass. In cultured muscle cells, mitochondrial protein content and myosin heavy chain isoform I (but not II) protein and mRNA levels were reduced on chronic TNF-α stimulation. TNF-α also reduced mitochondrial respiration in a nuclear factor kappaB (NF-κB) -dependent manner. Importantly, TNF-α-induced NF-κB activation decreased promoter transactivation and transcriptional activity of regulators of mitochondrial biogenesis and muscle oxphen. In conclusion, these results demonstrate that TNF-α impairs muscle oxphen in a NF-κB-dependent manner.


Subject(s)
Cachexia/metabolism , Muscle, Skeletal/metabolism , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/pharmacology , Animals , Blotting, Western , Cell Line , Citrate (si)-Synthase/metabolism , DNA-Binding Proteins/metabolism , Electron Transport Complex IV/metabolism , Electrophoretic Mobility Shift Assay , Enzyme-Linked Immunosorbent Assay , Heat-Shock Proteins/metabolism , Humans , Hydro-Lyases/metabolism , Mice , Mitochondrial Proteins/metabolism , Muscle, Skeletal/drug effects , NF-kappa B/genetics , NF-kappa B/metabolism , PPAR alpha/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Pulmonary Disease, Chronic Obstructive/metabolism , Transcription Factors/metabolism , Tumor Necrosis Factor-alpha/genetics
5.
J Anim Physiol Anim Nutr (Berl) ; 94(6): e393-401, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20662962

ABSTRACT

Skeletal muscle dysfunction is a common systemic manifestation in several prevalent diseases. Predictive values are useful tools for the diagnosis and prognosis of diseases. In experimental animals, no reference values of muscle function evaluation have been so far reported. The objective was to obtain predictive values of maximal inspiratory pressure (MIP) and grip strength measurements in healthy rats. In 70 healthy rats, MIP and grip strength were measured in vivo weekly for five consecutive weeks using non-invasive methodologies. Three ranges of rat body weights (250-299, 300-349 and 350-399 g) and lengths (37.0-41.0, 41.1-42.0 and 42.1-44.0 cm) were established. MIP and grip strength measurements falling within the ranges of weight 350-399 and 300-349 g and length 42.1-44.0 cm were significantly greater than values falling within 250-299 g and 37.0-41.0 cm ranges respectively. Specific weight- and length-percentile distributions for MIP and grip strength measurements were calculated. As significant direct correlations were observed between rat weights and lengths and either MIP or grip strength measurements, regression equations relating all these variables were also determined. Skeletal muscle dysfunction is frequently associated with highly prevalent conditions. The significant predictive equations described for both MIP and grip strength measurements will enable scientists to better estimate the respiratory and peripheral muscle dysfunctions of laboratory animals, especially when conducting follow-up and/or intervention investigations.


Subject(s)
Body Weight/physiology , Muscle Strength/physiology , Muscle, Skeletal/physiology , Animals , Male , Oxygen Consumption , Rats , Rats, Wistar
6.
Pulm Pharmacol Ther ; 23(5): 438-44, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20416390

ABSTRACT

NVA237 is a novel once-daily inhaled long-acting muscarinic antagonist administered via a dry powder inhaler. This randomized, double-blind, placebo-controlled study evaluated the safety, tolerability and bronchodilator efficacy of two doses of NVA237 (100 and 200 microg), versus placebo, in patients with moderate-to-severe COPD (forced expiratory volume in 1s [FEV(1)]>or=30% and <80% predicted and FEV(1)/forced vital capacity [FVC]<0.7, 30 min after inhalation of 80 microg ipratropium bromide). After appropriate washout periods, patients were randomized to treatment with NVA237 100 microg (n=92), NVA237 200 microg (n=98) or placebo (n=91) for 28 days. The primary objective was evaluation of safety, with efficacy measures included as secondary objectives. NVA237 was generally well tolerated and associated with a frequency and distribution of adverse events similar to placebo. Serious adverse events were uncommon and there was no evidence of adverse cardiovascular effects or unexpected events. Trough FEV(1) was significantly higher in those receiving NVA237 compared with placebo. For NVA237 100 microg the differences were 131 and 161 mL on Days 1 and 28, respectively (p<0.05), and for NVA237 200 microg the differences were 146 and 151 mL on Days 1 and 28, respectively (p<0.05). Peak FEV(1), FEV(1) at all timepoints up to 24h after dosing, and FEV(1) area under the curve during 5 min-5 h post-dosing were also significantly higher in both NVA237 groups, compared with placebo. Patients receiving NVA237 required fewer daily puffs of rescue medication and had a higher percentage of days on which rescue medication was not required. Overall, the present study provides further evidence of the safety, tolerability and bronchodilator efficacy of once-daily treatment with NVA237 100 and 200 microg in patients with moderate-to-severe COPD.


Subject(s)
Bronchodilator Agents/therapeutic use , Glycopyrrolate/therapeutic use , Muscarinic Antagonists/therapeutic use , Pulmonary Disease, Chronic Obstructive/drug therapy , Administration, Inhalation , Aged , Aged, 80 and over , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/adverse effects , Double-Blind Method , Drug Administration Schedule , Female , Glycopyrrolate/administration & dosage , Glycopyrrolate/adverse effects , Humans , Male , Middle Aged , Muscarinic Antagonists/administration & dosage , Muscarinic Antagonists/adverse effects , Nebulizers and Vaporizers
7.
Thorax ; 63(2): 100-7, 2008 Feb.
Article in English | MEDLINE | ID: mdl-17875568

ABSTRACT

BACKGROUND: Systemic proinflammatory cytokines and oxidative stress have been described in association with peripheral muscle wasting and weakness of patients with severe chronic obstructive pulmonary disease (COPD), but their expression in skeletal muscle is unknown. The objectives of the present study were to determine muscle protein levels of selected cytokines in patients with COPD and to study their relationships with protein carbonylation as a marker of oxidative stress, quadriceps function and exercise capacity. METHODS: We conducted a cross sectional study in which 36 cytokines were detected using a human antibody array in quadriceps specimens obtained from 19 patients with severe COPD and seven healthy controls. Subsequently, selected cytokines (tumour necrosis factor (TNF)alpha, TNFalpha receptors I and II, interleukin (IL) 6, interferon gamma, transforming growth factor (TGF) beta and vascular endothelial growth factor (VEGF)), as well as protein carbonylation (oxidative stress index) were determined using an enzyme linked immunosorbent assay (ELISA) in all muscles. RESULTS: Compared with controls, the vastus lateralis of patients with COPD showed significantly lower protein ELISA levels of TNFalpha, which positively correlated with their quadriceps function, TNFalpha receptor II and VEGF. Protein ELISA levels of IL6, interferon gamma and TGFbeta did not differ between patients and controls. Quadriceps protein carbonylation was greater in patients and inversely correlated with quadriceps strength among them. CONCLUSIONS: These findings do not support the presence of a proinflammatory environment within the quadriceps muscles of clinically and weight stable patients with severe COPD, despite evidence for increased oxidative stress and the presence of muscle weakness.


Subject(s)
Cytokines/metabolism , Pulmonary Disease, Chronic Obstructive/metabolism , Quadriceps Muscle/metabolism , Aged , Biomarkers/metabolism , Biopsy, Needle , Cross-Sectional Studies , Enzyme-Linked Immunosorbent Assay , Humans , Immunohistochemistry , Male , Microarray Analysis , Middle Aged , Muscle Weakness/metabolism , Muscle Weakness/physiopathology , Oxidative Stress/physiology
8.
Eur Respir J ; 30(2): 223-31, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17459895

ABSTRACT

Leptin is a powerful stimulant of ventilation in rodents. In humans, resistance to leptin has been consistently associated with obesity. Raised leptin levels have been reported in subjects with sleep apnoea or obesity-hypoventilation syndrome. The aim of the present study was to assess, by multivariate analysis, the possible association between respiratory centre impairment and levels of serum leptin. In total, 364 obese subjects (body mass index >or=30 kg.m(-2)) underwent the following tests: sleep studies, respiratory function tests, baseline and hypercapnic response (mouth occlusion pressure (P(0.1)), minute ventilation), fasting leptin levels, body composition and anthropometric measures. Subjects with airways obstruction on spirometry were excluded. Out of the 346 subjects undergoing testing, 245 were included in the current analysis. Lung volumes, age, log leptin levels, end-tidal carbon dioxide tension, percentage body fat and minimal nocturnal saturation were predictors for baseline P(0.1). The hypercapnic response test was performed by 186 subjects; log leptin levels were predictors for hypercapnic response in males, but not in females. Hyperleptinaemia is associated with a reduction in respiratory drive and hypercapnic response, irrespective of the amount of body fat. These data suggest the extension of leptin resistance to the respiratory centre.


Subject(s)
Hypercapnia/physiopathology , Hypoventilation/physiopathology , Leptin/blood , Obesity/physiopathology , Respiratory Mechanics/physiology , Adult , Body Composition , Chi-Square Distribution , Female , Humans , Hypercapnia/blood , Hypoventilation/blood , Linear Models , Male , Obesity/blood , Polysomnography , Respiratory Function Tests , Statistics, Nonparametric
9.
J Appl Physiol (1985) ; 100(2): 555-63, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16195391

ABSTRACT

We hypothesized that resistive breathing of moderate to high intensity might increase diaphragm oxidative stress, which could be partially attenuated by antioxidants. Our objective was to assess the levels of oxidative stress in the dog diaphragm after respiratory muscle training of a wide range of intensities and whether N-acetyl-cysteine (NAC) might act as an antioxidant. Twelve Beagle dogs were anesthetized with 1% propophol, tracheostomized, and subjected to continuous inspiratory resistive breathing (IRB) (2 h/day for 2 wk). They were further divided into two groups (n = 6): NAC group (oral NAC administration/24 h for 14 days) and control group (placebo). Diaphragm biopsies were obtained before (baseline biopsy) and after (contralateral hemidiaphragm) IRB and NAC vs. placebo treatment. Oxidative stress was evaluated in all diaphragm biopsies through determination of 3-nitrotyrosine immunoreactivity, protein carbonylation, hydroxynoneal protein adducts, Mn-SOD, and catalase, using immunoblotting and immunohistochemistry. Both protein tyrosine nitration and protein carbonylation were directly related to the amount of the respiratory loads, and NAC treatment abrogated this proportional rise in these two indexes of oxidative stress in response to increasing inspiratory loads. A post hoc analysis revealed that only the diaphragms of dogs subjected to high-intensity loads showed a significant increase in both protein tyrosine nitration and carbonylation, which were also significantly reduced by NAC treatment. These results suggest that high-intensity respiratory loading-induced oxidative stress may be neutralized by NAC treatment during IRB in the canine diaphragm.


Subject(s)
Acetylcysteine/pharmacology , Diaphragm/drug effects , Oxidative Stress/drug effects , Work of Breathing/physiology , Acetylcysteine/administration & dosage , Animals , Antioxidants/administration & dosage , Antioxidants/pharmacology , Diaphragm/metabolism , Dogs , Male , Muscle Fatigue , Protein Carbonylation , Proteins/metabolism , Respiration , Tyrosine/analogs & derivatives , Tyrosine/metabolism
10.
Eur Respir J ; 26(6): 1032-9, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16319332

ABSTRACT

The antioxidant N-acetylcysteine (NAC) prevented sepsis-induced diaphragmatic dysfunction. As an indirect antioxidant NAC was shown to induce superoxide dismutase (SOD) activity in immune cells from endotoxaemic mice. The aim of this study was to assess whether NAC acts as an indirect antioxidant by inducing manganese (Mn)-SOD activity in the diaphragms of endotoxaemic rats, while preventing muscle dysfunction. A controlled study was conducted, in which protein carbonylation, Mn-SOD, catalase, and 3-nitrotyrosine immunoreactivity were detected using immunoblotting and immunohistochemistry in rat diaphragms. Six groups were studied for 24 h after a saline (control) or lipopolysaccharide (LPS; 20 mg.kg-1) i.p. injection in the absence and presence of NAC pre-treatment (either 1.5 or 3 mmol.kg(-1).24 h-1 for 7 days, oral administration). Diaphragm mitochondrial Mn-SOD activity and respiratory muscle function were also determined. Within 24 h, LPS induced maximal inspiratory pressure reduction, increasing diaphragmatic protein carbonylation and nitration. Pre-treatment with 3 mmol.kg-1 NAC clearly increased muscle Mn-SOD protein content and activity in both LPS- and saline-injected animals, while reducing protein carbonylation and nitration, and partially preventing the LPS-induced respiratory muscle dysfunction. Data produced from this study indicate that high doses of N-acetylcysteine induces manganese superoxide dismutase, as well as preserves its activity, possibly by preventing nitration of critical tyrosine residues of the enzyme.


Subject(s)
Acetylcysteine/pharmacology , Sepsis/drug therapy , Sepsis/enzymology , Superoxide Dismutase/metabolism , Analysis of Variance , Animals , Biopsy, Needle , Diaphragm/drug effects , Diaphragm/pathology , Disease Models, Animal , Immunohistochemistry , Male , Probability , Random Allocation , Rats , Rats, Sprague-Dawley , Reference Values , Risk Factors , Sensitivity and Specificity , Sepsis/pathology , Superoxide Dismutase/drug effects
11.
Eur Respir J ; 24(1): 129-36, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15293615

ABSTRACT

The aims of this study were to investigate whether the impairment in endurance of limb muscles is a general finding in chronic obstructive pulmonary disease (COPD) patients, affecting even those with mild-to-moderate disease or relatively normal physical activity. In addition, this study aimed to determine the physiopathology of exhaustion in local endurance tests and whether the reduction in quadriceps endurance can be predicted from muscle strength measurements. A total of 75 volunteers were assigned to one of two groups according to pulmonary function tests: COPD patients or healthy age-matched controls. Functional assessment included both quadriceps strength (maximum voluntary contraction (QMVC)), and quadriceps endurance (contractions against a load equivalent to 10% QMVC until task failure or for up to a limiting time of 30 min (QTlim)). COPD patients showed a decrease of approximately 43%, in QMVC and approximately 77% in QTlim compared with controls. Task failure occurred only in COPD patients and was due to muscle fatigue, since limiting symptoms were associated with a decrease in the median frequency of quadriceps electromyographical signal and a reversible decrease in QMVC. The impairment in skeletal muscle endurance was present even in patients with mild-to-moderate airflow obstruction and individuals with relatively normal physical activity, and was irrespective of lung function variables, anthropometrical data or quadriceps strength. Peripheral muscle endurance was impaired in chronic obstructive pulmonary disease patients, even in those with relatively normal physical activity and mild-to-moderate airflow obstruction. This impairment associated with an early onset of muscle fatigue and could not be predicted from the severity of the disease or the reduction in quadriceps strength.


Subject(s)
Muscle Fatigue/physiology , Muscle Weakness/etiology , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/diagnosis , Age Distribution , Aged , Case-Control Studies , Cross-Sectional Studies , Electromyography , Female , Hand Strength/physiology , Humans , Incidence , Linear Models , Lower Extremity , Male , Middle Aged , Muscle Weakness/epidemiology , Muscle, Skeletal/physiology , Musculoskeletal Physiological Phenomena , Physical Endurance , Probability , Reference Values , Respiratory Function Tests , Risk Assessment , Severity of Illness Index , Sex Distribution
12.
Arch Bronconeumol ; 38(7): 311-6, 2002 Jul.
Article in Spanish | MEDLINE | ID: mdl-12199930

ABSTRACT

BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) has been implicated in loss of muscle mass in chronic obstructive pulmonary disease and other consumptive processes. TNF-alpha production would be related to inflammation arising from pulmonary disease itself or, alternatively, from smoking, and would be carried to the muscle through the blood stream. However, it has also been suggested that TNF-alpha may be expressed directly in muscle tissue. Regardless the site of production of TNF-alpha, its relation to subsequent muscle damage is unclear. OBJECTIVE: We studied the expression of TNF-alpha and an interleukin inhibitor of its production (IL-10) in the main respiratory muscles and a peripheral muscle in the dog. METHOD: Nine young, male Beagle dogs were included. From all animals we obtained a biopsy of the diaphragm (Dph) and external intercostal (ExtI) muscles and a leg muscle (internal vastus of the quadriceps, IntV). TNF-alpha and IL-10 gene expressions were measured through the analysis of messenger RNA levels, using reverse transcription and polymerase chain reaction. We also assessed sarcolemmal damage using intracellular fibronectin detection (immunohistochemistry). RESULTS: The expression of both cytokines showed wide interindividual variability. On the one hand, TNF-alpha (was very low in Dph and ExtI (0.02 0.03 and 0.05 0.06 a.u., respectively), but relatively high in the IntV (0.14 0.08 a.u.). IL-10 expression, on the other hand was low in the Dph (0.06 0.05 a.u.) and slightly higher in the ExtI (2.7 1.9 a.u., p < 0.01) and IntV (1.6 1.7 a.u.). Sarcolemmal damage was minimal in all three muscles and was related to TNF-alpha expression in the peripheral muscle (r = 0.682, p < 0.05). CONCLUSIONS: 1) TNF-alpha and IL-10 appear to be constitutively expressed within the skeletal muscle in dogs. 2) Basal TNF-alpha expression is lower in respiratory muscles than in peripheral muscles. 3) The expression in the latter is related to membrane damage.


Subject(s)
Interleukin-10/genetics , Muscle, Skeletal/metabolism , Respiratory Muscles/metabolism , Sarcolemma/genetics , Tumor Necrosis Factor-alpha/genetics , Animals , Diaphragm/metabolism , Dogs , Gene Expression , Immunohistochemistry , Inflammation/complications , Intercostal Muscles/metabolism , Interleukin-10/blood , Interleukin-10/metabolism , Male , Muscle, Skeletal/chemistry , Pulmonary Disease, Chronic Obstructive/complications , Reverse Transcriptase Polymerase Chain Reaction , Sarcolemma/metabolism , Sarcolemma/pathology , Smoking/adverse effects , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/metabolism
13.
Arch Bronconeumol ; 38(6): 272-7, 2002 Jun.
Article in Spanish | MEDLINE | ID: mdl-12106553

ABSTRACT

BACKGROUND: The dog is one of the most widely used animals in studies of respiratory physiopathology, mainly because of its physiological characteristics. However, ethical and legal constraints are placed on the use of some species in our context. OBJECTIVE: We studied the underlying structural features of respiratory and peripheral muscles in the beagle dog in order to suggest reference values for future studies. METHOD: Fourteen young beagles were selected. Samples were taken from the costal diaphragm (DFG), external intercostal (EI) and vastus medialis (VM) muscles. We analyzed fiber percentages and sizes (immunohistochemistry, using myosin heavy chain [MyHC (monoclonal antibodies), percentages and absolute number of MyHC isoforms (electrophoresis and ELISA), and level of membrane damage (immunohistochemistry, using anti-fibronectin monoclonal antibodies). RESULTS: In the EI muscle, type I fibers were larger (by 20%) than type II fibers. Fibers resistant to fatigue (type I) predominated greatly over fast contraction fibers (type II) in all three muscles analyzed (DFG 57% 11% vs. 45% 12%; EI 58% 5% vs. 43% 5%; and VM 70% 8% vs. 34% 7 %). Few hybrid fibers (co-expression of fast and slow MyHC) were found and their percentages were similar in all three muscles. The absolute expression of MyHC was greater in the VM than in the respiratory muscles, with a relative predominance of the MyHC I isoform in the DFG and VM muscles and a similar tendency in the EI muscle. Membrane damage was very slight in all three muscles. CONCLUSIONS: The phenotype characteristics of respiratory and peripheral muscles in the beagle correspond to what we would expect functionally for a breed initially selected for hunting, with minimal lesions under normal circumstances, a predominance of fibers and proteins that are resistant to fatigue, and larger fibers in the EI, a muscle that plays a role in respiration in dogs.


Subject(s)
Dogs/anatomy & histology , Muscle, Skeletal/anatomy & histology , Respiratory Muscles/anatomy & histology , Animals , Data Interpretation, Statistical , Diaphragm/anatomy & histology , Diaphragm/physiology , Immunohistochemistry , Intercostal Muscles/anatomy & histology , Intercostal Muscles/physiology , Muscle Fatigue/physiology , Muscle Fibers, Skeletal/cytology , Muscle Fibers, Skeletal/physiology , Muscle, Skeletal/physiology , Phenotype , Reference Values , Respiratory Muscles/physiology
14.
Eur J Clin Invest ; 32(6): 443-7, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12059990

ABSTRACT

BACKGROUND: The use of Procion orange dye (POD) is one of the most widely accepted techniques to assess sarcolemmal damage. This phenomenon has been related to functional adaptation in skeletal muscles. The POD method includes intravenous injection of this colorant in vivo, enabling its identification inside those fibres with membrane leaks (fluorescence). However, the safety of the use of POD has not been proven. AIM: This study was designed to compare POD with a safer alternative, involving the identification of intracellular fibronectin using specific antibodies. METHOD: Eight Swiss mice were submitted to electrical stimulation of the lower limbs at different frequencies (10-80 Hz). Subsequently, the POD solution was infused, and samples from the vastus medialis muscle were obtained 24 h later. Samples were processed and serial sections were analysed using immunohistochemistry (monoclonal antibodies against fibronectin) and epifluorescence microscopy. RESULTS: Ninety-eight per cent of the fibres were equally classified by both techniques, which in addition showed good correlation (percentages of damaged fibres, r = 0.998, P < 0.001) and concordance (R1 = 0.82) in quantitative terms. CONCLUSIONS: Although the two techniques compared here are based on different principles, both are comparable in assessing sarcolemmal damage. This would facilitate comparisons between human and experimental studies. In addition, the fibronectin technique appears to be a suitable alternative for long-term studies including repeated biopsies.


Subject(s)
Fibronectins/metabolism , Fluorescent Dyes/metabolism , Sarcolemma/ultrastructure , Staining and Labeling/methods , Triazines/metabolism , Animals , Electric Stimulation , Humans , Mice , Muscle Contraction/physiology , Muscle Fibers, Skeletal/cytology , Muscle, Skeletal/cytology , Muscle, Skeletal/metabolism , Sarcolemma/metabolism
15.
Arch Bronconeumol ; 38(5): 204-8, 2002 May.
Article in Spanish | MEDLINE | ID: mdl-12028927

ABSTRACT

BACKGROUND: Spirometry can be considered a routine way to evaluate patients with respiratory complaints, both inside and outside the hospital setting. OBJECTIVE: To assess the quality of spirometry in a public health care area with respect to two factors: the technicians' performance and the calibration of spirometers. MATERIAL AND METHOD: Four health care clinics were studied. Four technicians participated and the four spirometers were tested at different volumes (calibration syringes 1L and 3L) and different flows (explosive decompression). Eight patients with COPD participated in the study of inter-technician variability. RESULTS: Agreement among the technicians was very high: 0.98-0.99 for FEV1 and 0.91-0.98 for FVC. The mean results obtained by the technicians were: FEV1 = 2.15 0.03, range 2.20-2.14; FVC = 3.25 0.05, range 3.30-3.21 (ns). Volumetric readings from the spirometers were correct for the 1I calibration syringe, but 2 out of 4 spirometers lost linearity with the 3I calibration syringe. One spirometer gave readings out of range for all flow levels, and 2 out of 4 spirometers were out of range at low flows. CONCLUSIONS: 1. Results obtained by different technicians were not significantly different and there was high agreement among them, confirming that performance of spirometry was good. 2. The spirometers showed poor linearity at low flows.


Subject(s)
Public Health , Spirometry/standards , Aged , Analysis of Variance , Calibration , Confidence Intervals , Forced Expiratory Volume , Humans , Middle Aged , Outpatients , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/physiopathology , Quality of Health Care , Spain , Vital Capacity
16.
Arch Bronconeumol ; 37(11): 489-94, 2001 Dec.
Article in Spanish | MEDLINE | ID: mdl-11734138

ABSTRACT

OBJECTIVE: To shorten hospital stays of patients with exacerbated chronic obstructive pulmonary disease (COPD) or asthma by way of a home care program and to assess whether the program increased the number of readmissions. METHODS: Patients admitted due to COPD exacerbation or asthma who did not need critical care and were discharged before the fourth day. A registered nurse experienced with respiratory disease patients and in regular contact with the pneumologist who supervised the program made follow-up home care visits to give instructions and check compliance with treatment. RESULTS: Sixty-nine patients enrolled in the program, 53 with COPD and 16 with asthma. A mean 7.2 home care visits per patient were made. The mean hospital stay was 3.69 ( 0.5 days for patients receiving home care and 7.89 ( 5 days for those who received no home care (p < 0.005). Severity of COPD in terms of age, FEV1 and PaO2 was similar in both groups, as follows: FEV1 was 39.4 12% and PaO2 66.3 7,7% for patients receiving home care; FEV1 was 40.6 ( 12% and PaO2 was 64.3 ( 7% for those receiving no home care (ns). The mean hospital stay overall for both groups was 7.4 (4.9 days; the mean hospital stay for the same diseases in the same previous the year before the study was 8.3 ( 5.5 (p < 0.05). The rate of readmissions for new exacerbations within 30 days of discharge was 4.3% (3/69) in the group receiving home care and 7.2% (29/401) among patients receiving only hospital care (ns.). A questionnaire survey at the end of the program showed satisfaction to be very high. CONCLUSIONS: A program of home care provided by a registered nurse experienced with respiratory diseases allows mean hospital stay to be reduced without increasing the number of readmissions within 30 days, with high patient satisfaction.


Subject(s)
Asthma/therapy , Home Care Services , Patient Discharge , Pulmonary Disease, Chronic Obstructive/therapy , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Patient Discharge/statistics & numerical data , Patient Satisfaction , Time Factors
17.
Arch Bronconeumol ; 36(10): 557-62, 2000 Nov.
Article in Spanish | MEDLINE | ID: mdl-11149198

ABSTRACT

BACKGROUND: If techniques for studying respiratory muscle function are easy to use and well tolerates by patients, they can be used routinely. Measuring mouth twitches (TwM) using either bilateral anterior or posterior magnetic stimulation meets both criteria. SUBJECTS AND METHODS: We studied 16 healthy subjects. TwM was measured using bilateral anterior (TwMA) and posterior (TwMP) stimulation. Ten stimuli were applied for each technique for each subject. Five subjects repeated the test was repeated on a different day. RESULTS: The mean TwMA in healthy subjects was 21.07 +/- 4.4 cmH2O (range 13.72-30.11); the mean TwMP was 21.12 +/- 5.9 cmH2O (range 12.7-35.7) (NS). The mean difference was 2.8 +/- 2.5 cmH2O, while the ratio TwMP/PImax was 0.15 (range 0.08-0.10) and TwMA/PImax was 0.14 (range 0.07-0.15). The correlation between the two technique was 0.8. The patients who underwent testing twice had a mean TwMA of 20 cmH2O on the first day and 10.18 cmH2O on the second (NS). The coefficient of variation (CoV%) was 5.9% for TwMA and 7.2% for TwMP. CONCLUSIONS: The two techniques for measuring TwM give similar results and coefficients of variation in healthy subjects; either technique can be used. Variation from one testing day to another is low.


Subject(s)
Diaphragm/physiology , Electromagnetic Phenomena , Physical Stimulation/methods , Adult , Analysis of Variance , Female , Humans , Male , Manometry/methods , Mouth , Respiratory Physiological Phenomena , Sex Factors , Spirometry
18.
Arch Bronconeumol ; 35(11): 529-34, 1999 Dec.
Article in Spanish | MEDLINE | ID: mdl-10687036

ABSTRACT

INTRODUCTION: The rate of readmission among asthmatic emergency patients varies. In 1991 we observed a 9% rate of readmission following emergency room release. Studies of the number of readmissions or request for medical care are used as the basis for recommendations for releasing patients from hospital emergency care. No studies have assessed disease stability following release or factors related to stability. OBJECTIVES: To assess the course of disease and clinical stability of patients in the period immediately following release from emergency room care. To determine factors that might predict such stability. to determine the rate of readmission in the month following release after applying a treatment protocol and release criteria, with follow-up examination 72 h later. MATERIAL AND METHODS: Prospective, descriptive study with follow-up 72 h and one month after release. SETTING: Emergency and pneumology departments of a general hospital. PERIOD: six months. PATIENTS: 82 asthmatic patients released from the emergency room. RESULTS: Two patients (2.43% were readmitted. At the first follow-up visit (72 h) 81 patients (98.78%) were seen. At the second visit, 66 patients (80.5%) were examined. We observed stability in 70.3% of patients at 72 h and in 86.4% after on month. Stability was statistically related to whether peak expiratory flow greater or less than 70% (76.92% stable versus 46.66% unstable) (p < 0.05). No other clinical, epidemiological or treatment variables recorded upon release were found to influence stability. CONCLUSIONS: 1) A large proportion of patients are in stable condition 72 h after release. 2) When peak expiratory flow upon release is > 70%, stability is significantly increased 72 h later. 3) Our 2.43% rate of readmission one month after release is very low. 4) No differences in stability were seen to be related to oral corticoid prescription upon release.


Subject(s)
Asthma/therapy , Patient Readmission , Acute Disease , Adrenal Cortex Hormones/therapeutic use , Adult , Asthma/drug therapy , Asthma/physiopathology , Data Interpretation, Statistical , Emergencies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Peak Expiratory Flow Rate , Time Factors
19.
Arch Bronconeumol ; 34(2): 82-6, 1998 Feb.
Article in Spanish | MEDLINE | ID: mdl-9580518

ABSTRACT

The diaphragm is the main inspiratory muscle. It is composed of two parts, the costal and crural, with both anatomical and functional differences. The general morphometric characteristics of the diaphragm have been described in various species but homogeneity throughout the muscle has not been adequately studied. The aim of this study was to evaluate the fiber phenotype of various parts of the diaphragm. The entire diaphragm muscles of five New Zealand rabbits were removed and each was divided into quarters. The specimens were processed for morphometry (hematoxyllineosin stains, NADH-TR and ATPase at pH levels of 4.2, 4.6 and 9.4). For each portion we measured percent and size of fibers, expressing the latter as minimum diameter (Dm), measured area (Ar) and calculated area (Ac). Left and right diaphragm hemispheres (20 portions examined) were similar for fiber percentages and sizes. For left and right halves, respectively 50 +/- 2 and 51 +/- 4% of fibers were type I; type I Dm measurements were 38 +/- 5 and 41 +/- 4 microns; type I Ar values were 1798 +/- 481 and 2030 +/- 390 micron 2; type I Ac values were 1181 +/- 360 and 1321 +/- 382 micron 2; type II Dm values were 46 +/- 4 and 46 +/- 5 microns; type II Ar values were 2466 +/- 388 micron 2 and 2539 +/- 456 micron 2; type II Ac data were 1642 +/- 255 and 1655 +/- 382 micron 2. We likewise found no differences between costal and crural portions of the muscle (n = 20). For costal and crural portions, respectively, 50 +/- 3 and 50 +/- 2% of fibers were type I; type I Dm sizes were 39 +/- 5 and 40 +/- 4 microns; type I Ar measurements were 1859 +/- 521 and 1964 +/- 365 micron 2; type I Ac figures were 1231 +/- 317 and 1266 +/- 288 micron 2; type II Dm were 47 +/- 4 and 44 +/- 3 microns; type II Ar were 2563 +/- 481 and 2430 +/- 331 micron 2; type II Ac were 1729 +/- 373 and 1557 +/- 212 micron 2. Type II fibers, however, were somewhat larger than type I fibers in all portions (p = 0.001). New Zealand rabbit diaphragm muscle has similar percentages of slow and rapid contraction fibers. The size is not different from that observed in other species of mammals of similar size. Fiber type proportions are similar throughout the muscle, with more type II fibers present in all areas. The morphometric characters, therefore, suggest an homogeneous throughout the diaphragm, suggesting homogeneous response of the muscle to usual loads, and also suggesting the possibility of proposing longitudinal morphometric studies using this species as a model.


Subject(s)
Diaphragm/anatomy & histology , Muscle Fibers, Skeletal/cytology , Animals , Data Interpretation, Statistical , Diaphragm/cytology , Histological Techniques , Male , Muscle Contraction , Phenotype , Rabbits , Staining and Labeling
20.
Arch Bronconeumol ; 33(10): 503-8, 1997 Nov.
Article in Spanish | MEDLINE | ID: mdl-9453817

ABSTRACT

To establish the diagnostic yield of computerized tomography (CT) in pleural effusions with no presumed diagnosis arising from standard clinical examination. A prospective protocol study enrolling all cases of effusion admitted to our hospital between January 1994 through July 1995 without a presumed diagnosis after initial testing that included thoracocentesis. Twenty-two patients were enrolled. All were given a CT scan as well as other complementary examinations considered appropriate and were referred to our outpatient clinic for follow-up. The CT images were read by an expert radiologist and their contribution was classified as "diagnostic", "suggestive" or "nil". A definitive etiologic diagnosis was achieved in 14 cases (8 neoplasms, 4 benign due to asbestos, 1 tuberculosis and 1 pulmonary embolism). The CT contribution was nil in 13 cases (59%), "diagnostic" in 6 (2 mesotheliomas, 1 hypernephroma, 1 lymphoma, 1 adenocarcinoma of the colon and another of the ovary) and "suggestive" in 3 (2 benign due to asbestos and 1 lymphoma). Positive information was obtained in 9 cases (41%). CT gives good yield in the investigation of pleural effusions with no presumed diagnosis and should be made available to this group of patients before other more invasive procedures are resorted to. It is especially useful for detecting neoplastic disease of the upper abdomen, mesothelioma and sings of unsuspected exposure to asbestos.


Subject(s)
Pleural Effusion/etiology , Tomography, X-Ray Computed , Aged , Carcinoma, Renal Cell/complications , Female , Humans , Kidney Neoplasms/complications , Lymphoma, Non-Hodgkin/complications , Male , Mesothelioma/complications , Ovarian Neoplasms/complications , Pleural Effusion/diagnostic imaging , Pleural Neoplasms/complications , Prospective Studies
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