[Changes in respiratory and peripheral muscle function in asthmatic children: effects of inhaled corticoids]. / Cambios en la función muscular respiratoria y periférica en niños asmáticos: efectos de los corticoides inhalados.

INTRODUCTION: Asthma is the most common chronic disease in children and adolescents. The intermittent mechanical overloads during crises can lead to functional changes in the respiratory muscles, which experience adaptation phenomena. This article attempts to evaluate the respiratory and peripheral muscle state in asthmatic children who receive inhaled corticoids, and to find out if there is an association between muscle function and respiratory function. PATIENTS AND METHODS: The study involved 12 children over 7-years old with asthma and treated with inhaled corticoids for at least 2 years at intermediate doses (budesonide >or=400 microg, or fluticasone >or=200 microg) and 7 healthy control children paired by age. The following were determined: forced spirometry, static lung volumes, airway resistance, maximum inspiratory and expiratory pressures, peripheral musculo-skeletal function, and body composition using bioimpedance measurements. RESULTS: The anthropometric, nutritional variables and peripheral muscle function were similar in both groups. The asthmatic children showed signs of air trapping, lung hyperinflation, and higher maximum inspiratory pressure values. CONCLUSIONS: No evidence was found that continuous high doses of inhaled steroids lead to a deterioration in respiratory or peripheral muscle function in asthmatic children. On the other hand, signs were found of respiratory muscle adaptation to the long-term overload of persistent asthma. The so-called "training effect" seems to be limited only to the inspiratory muscles.

Mortality of COPD patients infected with multi-resistant Pseudomonas aeruginosa: a case and control study.

BACKGROUND: The incidence of infections caused by multiresistant Pseudomonas aeruginosa (MDRP) is increasing, especially in critically ill patients. The relevance of MDRP in the prognosis of chronic obstructive pulmonary disease (COPD) acute exacerbation in patients admitted to the hospital's general ward is not well known. PATIENTS AND METHODS: Case and control study. Cases were patients admitted for COPD acute exacerbation in which a MDRP was isolated from spontaneous sputum. MDRP was defined as the absence of susceptibility to three or more antibiotic families (betalactams, quinolones, carbapenems and aminoglycosides). Patients currently or previously admitted to the intensive care unit (ICU), who had a recent surgery, neoplasia or immunosuppressive treatment were excluded from the study. Patients from the control group were admitted for COPD acute exacerbation and matched 1:1 with each case-patient in terms of age, sex, date of admission and degree of airway obstruction. Pseudomonas aeruginosa susceptible to all antimicrobials or other microorganisms was isolated from sputum. RESULTS: During the study period (2000-2005), 50 case-patients and 50 controls were included. Crude mortality at 2 years was 60% for the case-patients and 28% for the control group. In the logistic regression analysis adjusted for age, FEV(1) and number of previous hospital admissions, MDRP infection was associated to an increased mortality in comparison to patients without MDRP (OR = 6.2; IC 95%: 1.7-22.1; p < 0.01). CONCLUSIONS: In COPD patients admitted to the general ward, acute exacerbation with MDRP in sputum was associated with higher mortality.

Upregulation of pro-inflammatory cytokines in the intercostal muscles of COPD patients.

Muscle dysfunction is a characteristic feature of chronic obstructive pulmonary disease (COPD). Recent studies suggest that cytokines may operate as local regulators of both muscle function and regeneration. The aim of the present study was to characterise the expression of different cytokines in the external intercostal muscle of COPD. Muscle biopsies were obtained from 25 stable COPD patients and eight healthy controls. Local tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, -6 and -10 expressions (real-time PCR and ELISA), sarcolemmal damage (immunohistochemistry), and the transcript levels of CD18 were assessed. Muscle TNF-alpha and IL-6 transcripts were significantly higher in COPD patients compared with controls, and IL-1beta and sarcolemmal damage showed a strong tendency in the same direction. Similar results were observed at protein level. The CD18 panleukocyte marker was similar in COPD and controls. Respiratory muscle function was impaired in COPD patients and it correlated to both the severity of lung function impairment and TNF-alpha muscle expression. Chronic obstructive pulmonary disease is associated with the upregulation of pro-inflammatory cytokines in the intercostal muscles. This phenomenon might be involved in respiratory muscle dysfunction.

Mitochondrial dysfunction in COPD patients with low body mass index.

Patients with chronic obstructive pulmonary disease (COPD) show abnormal adaptations of skeletal muscle redox status after exercise training. Increased skeletal muscle oxidative stress in COPD patients may prompt mitochondrial dysfunction. The present study explores the association between body composition and mitochondrial respiration in seven COPD patients with low body mass index (BMI(L)), eight COPD patients with normal body mass index (BMI(N)) and seven healthy controls. All of them underwent a vastus lateralis biopsy in which muscle structure, in vitro mitochondrial respiratory function, uncoupling protein 3 (UCP3) mRNA expression and glutathione levels in both isolated mitochondria and the whole muscle were determined. Mitochondrial respiratory function (assessed by acceptor control ratio (ACR)) was impaired in BMI(L) (2.2+/-0.6) compared with both BMI(N) (5.3+/-1.3) and controls (8.2+/-1.3). ACR significantly correlated with arterial oxygen tension and with muscle endurance but it showed a negative association with exercise-induced increase in blood lactate levels. UCP3 mRNA expression was reduced in BMI(L) patients. In conclusion, chronic obstructive pulmonary disease patients with low body mass index show electron transport chain dysfunction, which may contribute to low muscle endurance in the current subgroup of patients.

[Physiologic particularities of muscle impairments in the patient with COPD]. / Particularidades fisiopatológicas de las alteraciones musculares en el paciente con EPOC.

Patients with chronic obstructive pulmonary disease (COPD) frequently have skeletal muscle dysfunction, of either respiratory muscles or those located of the limbs. This dysfunction may appear even at relatively early stages and it conditions symptoms and patient's quality of life. In the case of respiratory muscles, factors that seem to determine muscle dysfunction are, particularly, changes in thorax configuration and an unbalance between decreased energy availability and increased energy demands by the muscle. However, respiratory muscles show signs of structural and metabolic adaptation to this situation, partially compensating the above-mentioned deleterious effects. However, at muscles of the limbs, particularly of the lower limbs, dysfunction seems to be essentially due to deconditioning by physical activity reduction. Structural changes in these muscles are involutional in nature. At both respiratory and peripheral muscles, other factors such as nutritional impairments, inflammation, oxidative stress, some drugs, and the presence of comorbidity seem to play a relevant role. All of them will condition both dysfunction and structural changes, which will be heterogeneous for the different muscle groups in each patient.

Wood smoke exposure and risk of chronic obstructive pulmonary disease.

It was hypothesised that wood smoke exposure could be a risk factor for chronic obstructive pulmonary disease (COPD) in Spain. The present study was designed as a case-control study of 120 females requiring hospitalisation during 2001-2003 at Hospital del Mar (Barcelona, Spain). Cases were recruited from hospital records as females who had been admitted for an exacerbation of COPD. Controls were obtained from pulmonary function test laboratory consultations prior to a surgical intervention. All patients answered a standardised questionnaire. Exposure to wood or charcoal smoke was strongly associated with COPD after adjusting for age and smoking. The association between length of exposure and COPD suggested a dose-response pattern. Intensity of exposure in both summer and winter was also related to COPD. Wood or charcoal alone independently increased risk of COPD (odds ratio (OR) 1.8 and 1.5, respectively), but only the combination of both was statistically significant (OR 4.5). In conclusion, the present study shows a strong association between wood or charcoal smoke exposure and chronic obstructive pulmonary disease, supporting its existence not only in developing countries, but also in European countries, such as Spain. Further studies assessing whether this association also exists in other European societies are warranted.

Relevance of assessing quadriceps endurance in patients with COPD.

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.

[Analysis of respiratory muscle structure and tumor necrosis and insulin-like growth factor expression in chronic obstructive pulmonary disease: are samples valid if obtained during thoracotomy performed because of localized pulmonary neoplasia?]. / Análisis estructual y expresión de los factores de necrosis tumoral y crecimiento insulina-like en los músculos respiratorios de pacientes con EPOS. Son válidas las muestras obtenidas en el curso de una toracotomía por neoplasia pulmonar localizada?

OBJECTIVE: Various methods have been used to obtain samples to study the structure of human respiratory muscles and the expression of diverse substances in them. Samples are most often obtained from autopsies, from muscle biopsies during thoracotomy performed because of a localized pulmonary lesion (TLL), and from ambulatory thoracoscopic biopsy in patients free of comorbidity (AT). The disadvantage of the first 2 of these methods lies in the possibility of interference from factors related to the patient's death in the first case or from the disease that necessitated surgery in the second. Although AT is free from the disadvantages of the other 2 methods, it is impossible to obtain samples of the diaphragm the principal respiratory muscle with this procedure. The objective of this study was to analyze the fibrous structure of the external intercostal muscle of patients with chronic obstructive pulmonary disease and to quantify the expression of the principal inflammatory cytokine tumor necrosis factor alpha (TNF-alpha)- and of insulin-like growth factor (IGF-1) in the same muscle, comparing the results obtained with TLL and AT samples. METHODS: Prospective and consecutive samples were taken of the external intercostal muscle (fifth space, anterior axillary line) in 15 patients with chronic obstructive pulmonary disease (mean [SD] age 66 [6] years; forced expiratory volume in 1 second 49% [9%] of predicted; PaO2 75 [9] mm Hg). Samples were taken during TLL (8 patients, all with pulmonary neoplasms but carefully selected in order to rule out systemic effects) or TA (7 patients). Patients with serious comorbidity were excluded from the second group. Samples were processed for structural analysis of fibers (immunohistochemical and enzymatic histochemical) and genetic expression of TNF-alpha and IGF-1 (real-time polymerase chain reaction). RESULTS: No differences in the structure of fibers were found between the 2 groups. No differences were observed in the expression of TNF-alpha or IGF-1. CONCLUSIONS: Using rigorous criteria, the TLL method appears to be suitable for studying the structural characteristics and expression of inflammatory cytokines and growth factors in the external intercostal muscle. Moreover, it can also be inferred that TLL is probably also useful for obtaining samples of the diaphragm, a muscle which cannot currently be sampled by any alternative method.

Glutathione and glutamate levels in the diaphragm of patients with chronic obstructive pulmonary disease.

Recently, decreased glutamate (Glu) and reduced glutathione (GSH) levels were reported in the quadriceps femoris of patients with chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate whether Glu and GSH levels are also modified in the diaphragm of these patients. Nine male COPD patients (forced expiratory volume in one second (FEV1) range 28-68% of the predicted value) and seven male patients with normal pulmonary function (mean +/- SD FEV1 86 +/- 3% pred) submitted to thoracotomy were included. Biopsy specimens were taken from the diaphragm (both groups) and the quadriceps femoris (COPD group alone) in order to assess fibre size, myosin heavy chain expression, GSH levels and amino acid profile. The COPD group was characterised by preserved fibre size, a higher proportion of type I fibres (mean +/- SEM 70 +/- 3 versus 26 +/- 4%), and higher Glu and GSH content in the diaphragm compared to the quadriceps muscle. However, Glu and GSH levels were similar in diaphragm from the COPD and control groups. Glu level correlated with GSH level in both muscles. No significant correlation was found between Glu or GSH level and fibre size or proportions. This study shows that glutamate and reduced glutathione levels are preserved in the diaphragm of chronic obstructive pulmonary disease patients. Alterations in glutamate and reduced glutathione metabolism are muscle-specific in chronic obstructive pulmonary disease, affecting the quadriceps femoris but not the diaphragm. Glutamate and reduced glutathione levels are strongly interrelated in both muscles, independent of fibre type distribution and fibre size.

Structure and function of the respiratory muscles in patients with COPD: impairment or adaptation?

Respiratory muscles are essential to alveolar ventilation. These muscles work against increased mechanical loads due to airflow limitation and geometrical changes of the thorax derived from pulmonary hyperinflation. Respiratory muscle fibres show several degrees of impairment in cellular and subcellular structures which, in many cases, are proportional to the severity of the disease and accompanying conditions (ageing, deconditioning, starvation, comorbidity). This structural impairment translates, from the functional point of view, to a loss of strength (capacity to generate tension) and an increased susceptibility to failure in the face of a particular load (early onset of fatigue). On the other hand, there is accumulating evidence that the diaphragm and other respiratory muscles are also able to express adaptive changes in response to the chronic mechanical load imposed by the disease. In most cases, impairment and adaptation of the respiratory muscles reaches a balance that permits enough ventilation for patients' survival. However, this balance can be altered for additional increments of the mechanical or metabolic load on the muscles (e.g. abdominal or thoracic surgeries, pneumonia, pulmonary embolism, etc.). Moreover, loss of balance is not always associated with extreme situations. Many patients develop ventilatory failure and require hospital admission even if the cause of the exacerbation is less dramatic (bronchial infections, pain of any nature, electrolyte disturbances, etc.). Although the physiopathology of chronic obstructive pulmonary disease exacerbations is multifactorial, the above-mentioned fragility suggests the existence of a "fragile balance" between respiratory muscle overload and respiratory muscle adaptations. Assessment of respiratory muscle function through specific tests evaluating the strength and endurance could offer valuable information about this particular susceptibility to muscle imbalance. Identification of patients possessing a fragile respiratory muscle balance could have important implications for the application of specific strategies such as respiratory muscle training, nutrition, or anabolic treatment.

Gastro-oesophageal reflux in mechanically ventilated patients: effects of an oesophageal balloon.

Gastro-oesophageal reflux (GOR) and bronchoaspiration of gastric content are risk factors linked with ventilator-associated pneumonia. This study was aimed at evaluating the effect of a nasogastric tube (NGT) incorporating a low-pressure oesophageal balloon on GOR and bronchoaspiration in patients receiving mechanical ventilation. Fourteen patients were studied in a semi-recumbent position for 2 consecutive days. Inflation or deflation of the oesophageal balloon was randomised. Samples of blood, gastric content, and oropharyngeal and bronchial secretions were taken every 2 h over a period of 8 h. A radioactively labelled nutritional solution was continuously administered through the NGT. The magnitude of both the GOR and bronchoaspiration was measured by radioactivity counting of oropharyngeal and bronchial secretion samples, respectively. Inflation of the oesophageal balloon resulted in a significant decrease of both GOR and bronchoaspiration of gastric content. This protective effect was statistically significant from 4 h following inflation throughout the duration of the study. This study demonstrates that an inflated oesophageal balloon delays and decreases gastro-oesophageal and bronchial aspiration of gastric content in patients carrying a nasogastric tube and receiving enteral nutrition during mechanical ventilation. Although the method was found to be safe when applied for 8 h, longer times should be considered with caution.

[Fiber-optic bronchoscopic biopsy of bronchial smooth muscle. Efficacy of the technique in individuals with normal lung function and patients with COPD]. / Biopsia de músculo liso bronquial mediante fibrobroncoscopia. Eficacia de la técnica en individuos con función pulmonar normal y en pacientes con EPOC.

BACKGROUND AND OBJECTIVES: The epithelium and airway smooth muscles of patients with chronic obstructive pulmonary disease (COPD) or bronchial asthma undergo certain structural changes that are probably related to increased expression of inflammatory molecules and cell growth factors. Studying the relation between disease and changes in bronchial smooth muscle is difficult if investigation is restricted to samples from autopsies or thoracotomies. This study was designed to evaluate the probability of obtaining bronchial smooth muscle by endoscopic bronchial biopsy in patients with COPD and from individuals with normal lung function, the relation of disease to bronchial epithelial histology, and the potential usefulness of studying airway muscle remodeling events. METHODS: Forty-two patients undergoing diagnostic fiberoptic bronchoscopy were enrolled. Bronchial biopsies were taken systematically from the lobar and segmental dividing ridges. The epithelial structure was analyzed by conventional histology. The smooth muscle was identified by immunohistochemistry (anti-desmin antibody assay) and Western-blot analysis (anti-desmin, actin and myosin antibodies). RESULTS: Sixty-nine percent of the biopsies contained bronchial smooth muscle. The probability of obtaining smooth muscle was higher in segmental than in lobar biopsies (72 vs 30%, p < 0.05). This probability was unrelated to the presence of COPD or to signs of epithelial inflammation. The fragments allowed us to use electrophoresis to identify protein structures (myosin, actin, desmin) involved in muscle remodeling processes. CONCLUSIONS: Endoscopic biopsy of the bronchi allows us to obtain bronchial smooth muscle samples in a large percentage of patients, particularly when performed on segmental bronchi. The technique may be useful for future studies examining the processes of airway smooth muscle remodeling.

Procion orange tracer dye technique vs. identification of intrafibrillar fibronectin in the assessment of sarcolemmal damage.

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.

Expiratory muscle endurance in chronic obstructive pulmonary disease.

BACKGROUND: A reduction in expiratory muscle (ExM) endurance in patients with chronic obstructive pulmonary disease (COPD) may have clinically relevant implications. This study was carried out to evaluate ExM endurance in patients with COPD. METHODS: Twenty three patients with COPD (FEV(1) 35 (14)% predicted) and 14 matched controls were studied. ExM endurance was assessed using a method based on the use of an expiratory threshold valve which includes two steps. In step 1 the load is progressively increased (50 g every 2 minutes) until task failure is reached, and the pressure generated against the highest tolerated load is defined as the maximal expiratory sustainable pressure (Pthmax). In step 2 subjects breathe against a submaximal constant load (80% of Pthmax) and the time elapsed until task failure is termed the expiratory endurance time (Tth(80)). In addition, the strength of peripheral muscles (handgrip, HGS) and respiratory muscles (maximal inspiratory and expiratory pressures, PImax and PEmax, respectively) was evaluated. RESULTS: Patients with COPD had lower ExM strength and endurance than controls: PEmax 64 (19)% predicted v 84 (14)% predicted (mean difference 20%; 95% confidence intervals (CI) 14 to 39); Pthmax 52 (27) v 151 (46) cm H(2)O (mean difference 99, 95% CI 74 to 123); and Tth(80) 9.4 (6.3) v 14.2 (7.4) min (mean difference 4.8, 95% CI 1.0 to 10.4; p<0.01 for all). Interestingly, ExM endurance directly correlated with both the severity of airways obstruction (Pthmax with FEV(1), r=0.794, p<0.01) and the reduction in strength observed in different muscle groups (Pthmax with HG, PImax or PEmax, r=0.550, p<0.05; r=0.583, p<0.001; and r=0.584, p<0.001, respectively). CONCLUSIONS: ExM endurance is decreased in patients with COPD. This impairment is proportional to the severity of the disease and is associated with lower strength in different muscle groups. This suggests that systemic effects are implicated in the impairment observed in ExM function.

[Low-weight syndrome associated with COPD in our setting]. / Síndrome de bajo peso asociado a la EPOC en nuestro medio.

UNLABELLED: The high prevalence of chronic obstructive pulmonary disease (COPD) has considerable economic and health-related impact. The consequences arise largely from limitations on a patient's activity and shortened life expectancy. Low body weight has recently been implicated as a factor affecting limitations. Although the reason is not clear, weight loss appears to affect many patients (from 25 to 35% in different series), at least in Europe and North America. However, the situation is thought to be different in the Mediterranean area. OBJECTIVE: To estimate the prevalence of the low weight syndrome in patients with COPD in our area. METHODS: COPD patient characteristics monitored by our laboratory over the last two years (2000 and 2001) were reviewed. RESULTS: The prevalence of a body mass index (BMI) less than 20 kg/m2 was only 6.6% among the 3,126 patients studied. That percentage fell to 3.1% with a cutoff of 18 kg/m2. The figure was even more striking if we consider that half the patients had severe disease (FEV1 < 50% of reference). BMI was directly related to FEV1/FC and CO transfer. CONCLUSIONS: These results suggest that COPD patients in our geographic area have characteristics that distinguish them from those previously described in other countries. Specifically, the prevalence of low weight syndrome in our area appears to be lower. However, larger studies should be performed to confirm this finding.

Expiratory muscle endurance in middle-aged healthy subjects.

To evaluate expiratory muscle endurance in middle-aged healthy subjects using incremental as well as constant expiratory loads, 14 healthy volunteers (51 +/- 16 years) were submitted to a specific endurance test, which was performed breathing against a threshold valve, and was divided into two parts. In part I, the load was progressively increased (50 g each 2 min) until task failure occurred. The mean mouth pressure generated against the highest load held for at least 60 sec was defined as the maximal expiratory sustainable pressure (Pth(max)). In part II, each subject breathed against a constant submaximal expiratory load (80% Pth(max)) until task failure occurred (expiratory endurance time or Tth(80)). Both parts of the test were repeated 24-48 h later. Progressive expiratory loading induced a linear increase in mouth expiratory pressure and the Pth(max) obtained was 141 +/- 43 cm H(2)O, representing 74 +/- 28% of the maximal expiratory pressure (PE(max)). Under constant loads, the Tth(80) was 17 +/- 9 min. At the end-point of both parts, the tension time index for expiratory muscles was dramatically increased (>0.25), and both EMG central frequency and PE(max) were decreased with no changes in maximal inspiratory pressure or inspiratory capacity. Extreme dyspnea was present in most of the subjects but no complications were observed. The endurance of expiratory muscles can be easily assessed in healthy subjects using this method, which has acceptable reproducibility and tolerance.

Injury of the human diaphragm associated with exertion and chronic obstructive pulmonary disease.

Injury of the diaphragm may have clinical relevance having been reported in cases of sudden infant death syndrome or fatal asthma. However, examination of diaphragm injury after acute inspiratory loading has not been reported. The purpose of this study was to determine whether an acute inspiratory overload induces injury of the human diaphragm and to determine if diaphragm from chronic obstructive pulmonary disease (COPD) is more susceptible to injury. Eighteen patients with COPD and 11 control patients with normal pulmonary function (62 +/- 10 yr) undergoing thoracotomy or laparotomy were studied. A threshold inspiratory loading test was performed prior to surgery in a subset of seven patients with COPD and five control patients. Samples of the costal diaphragm were obtained during surgery and processed for electron microscopy analysis. Signs of sarcomere disruption were found in all diaphragm samples. The range of values of sarcomere disruption was wide (density: 2-45 abnormal areas/100 microm(2); area fractions: 1.3-17.3%), significantly higher in diaphragm from patients with COPD (p < 0.05) and with the greatest injury after inspiratory loading. We conclude that sarcomere disruption is common in the human diaphragm, is more evident in patients with COPD, and is higher after inspiratory loading, especially in the diaphragm of those with COPD.

Structural and functional changes in the skeletal muscles of COPD patients: the "compartments" theory.

This review focuses on the structural and functional changes occurring in respiratory as well as peripheral muscles in COPD patients. These changes are particular for each muscle territory or compartment. Respiratory muscles predominantly undergo structural adaptive changes. However, they have to do their job in unfavourable mechanical conditions and thus their function is impaired. Peripheral muscles have to be grouped in at least two different compartments: upper and lower limb muscles. The structure and function are relatively preserved in the former, due to the maintenance of some daily activities involving the arms or even the use of some of these muscles in the ventilatory effort. Lower limb muscles in contrast undergo involute structural changes which result in an impairment in their function and in the global exercise capacity of the individual. Deconditioning due to a reduction in daily activities secondary to ventilatory impairment is probably the driving factor for these changes. Although the level of activity appears to be the main determining factor in changes occurring in different territories, this would be modulated by other local and systemic factors, such as inflammation, oxidative stress, drugs and nutritional abnormalities.