Reduction of disease activity, corticosteroids use, and healthcare resource utilisation in patients with systemic lupus erythematosus treated with belimumab in clinical practice settings: OBSErve Spain multicentre study / Reducción de la actividad de la enfermedad, el uso de corticosteroides y recursos sanitarios en pacientes con lupus eritematoso sistémico tratados con belimumab en práctica clínica real: estudio multicéntrico OBSErve España

Introduction and objectives: This OBSErve Spain study, a part of the international OBSErve programme, evaluated belimumab real-world use and effectiveness following 6 months of treatment in patients with active systemic lupus erythematosus (SLE) in clinical practice in Spain. Materials and methods: In this retrospective, observational study (GSK Study 200883), eligible patients with SLE receiving intravenous belimumab (10mg/kg) had their disease activity (physician assessed), SELENA-SLEDAI scores, corticosteroid use, and healthcare resource utilisation (HCRU), assessed after 6 months of treatment versus index (belimumab initiation) or 6 months pre-index. Results: Overall, 64 patients initiated belimumab, mainly due to ineffectiveness of previous treatments (78.1%) and to reduce corticosteroid use (57.8%). Following 6 months of treatment, 73.4% of patients achieved ≥20% overall clinical improvement, while only 3.1% of patients worsened. Mean (standard deviation, SD) SELENA-SLEDAI score decreased from 10.1 (6.2) at index to 4.5 (3.7) 6 months post-index. HCRU decreased from 6 months pre-index to 6 months post-index, with fewer hospitalisations (10.9% vs 4.7% patients) and ER visits (23.4% vs 9.4% patients). Mean (SD) corticosteroid dose decreased from 14.5 (12.5)mg/day at index to 6.4 (5.1)mg/day 6 months post-index. Conclusions: Patients with SLE receiving belimumab for 6 months in real-world clinical practice in Spain experienced clinical improvements and a reduction in HCRU and corticosteroid dose.(AU)

Introducción y objetivos: El estudio OBSErve España, que forma parte del programa internacional OBSErve, evaluó el uso y la eficacia de belimumab en la práctica clínica real española tras seis meses de tratamiento en pacientes con lupus eritematoso sistémico (LES) activo. Materiales y métodos: En este estudio observacional y retrospectivo (GSK Study 200883) fue evaluada la respuesta clínica, la actividad de la enfermedad (puntuación SELENA-SLEDAI), el uso de corticosteroides y los recursos sanitarios utilizados de los pacientes con LES que recibieron belimumab intravenoso (10mg/kg), al inicio y tras seis meses de tratamiento. Resultados: En total 64 pacientes iniciaron belimumab, principalmente por ineficacia de los tratamientos previos (78,1%) y para reducir los corticoides (57,8%). Después de seis meses de tratamiento, 73,4% de los pacientes lograron una mejoría clínica general de ≥20%, mientras que solo 3,1% de los pacientes empeoró. La puntuación media (desviación estándar, DE) de SELENA-SLEDAI disminuyó de 10,1 (6,2) a 4,5 (3,7). Los recursos sanitarios utilizados disminuyeron con menos hospitalizaciones (10,9 vs. 4,7%) y visitas a urgencias (23,4 vs. 9,4%). La dosis media (DE) de corticosteroides disminuyó de 14,5 (12,5mg/día) a 6,4 (5,1mg/día). Conclusiones: Los pacientes con LES que recibieron belimumab durante seis meses en la práctica clínica real en España experimentaron mejoras clínicas y una reducción de la dosis de corticosteroides y recursos sanitarios utilizados.(AU)

Reduction of disease activity, corticosteroids use, and healthcare resource utilisation in patients with systemic lupus erythematosus treated with belimumab in clinical practice settings: OBSErve Spain multicentre study.

INTRODUCTION AND OBJECTIVES: This OBSErve Spain study, a part of the international OBSErve programme, evaluated belimumab real-world use and effectiveness following 6 months of treatment in patients with active systemic lupus erythematosus (SLE) in clinical practice in Spain. MATERIALS AND METHODS: In this retrospective, observational study (GSK Study 200883), eligible patients with SLE receiving intravenous belimumab (10mg/kg) had their disease activity (physician assessed), SELENA-SLEDAI scores, corticosteroid use, and healthcare resource utilisation (HCRU), assessed after 6 months of treatment versus index (belimumab initiation) or 6 months pre-index. RESULTS: Overall, 64 patients initiated belimumab, mainly due to ineffectiveness of previous treatments (78.1%) and to reduce corticosteroid use (57.8%). Following 6 months of treatment, 73.4% of patients achieved ≥20% overall clinical improvement, while only 3.1% of patients worsened. Mean (standard deviation, SD) SELENA-SLEDAI score decreased from 10.1 (6.2) at index to 4.5 (3.7) 6 months post-index. HCRU decreased from 6 months pre-index to 6 months post-index, with fewer hospitalisations (10.9% vs 4.7% patients) and ER visits (23.4% vs 9.4% patients). Mean (SD) corticosteroid dose decreased from 14.5 (12.5)mg/day at index to 6.4 (5.1)mg/day 6 months post-index. CONCLUSIONS: Patients with SLE receiving belimumab for 6 months in real-world clinical practice in Spain experienced clinical improvements and a reduction in HCRU and corticosteroid dose.

Injury of peripheral muscles in smokers with chronic obstructive pulmonary disease.

Muscle injury has clinical relevance in diseased individuals because it is associated with muscle dysfunction in terms of decreased strength and/or endurance. This study was aimed at answering three questions: whether the presence of chronic obstructive pulmonary disease (COPD) is associated with peripheral muscle injury; whether muscle injury is associated with some of the relevant functional impairment in the muscles; and whether muscle injury can be solely justified by deconditioning. Twenty-one male COPD patients were eligible for the study. Seven healthy volunteers recruited from the general population were included as controls. Function of the quadriceps muscle was assessed through specific single-leg exercise (strength and endurance). Cellular (light microscopy) and subcellular (electron microscopy) techniques were used to evaluate muscle injury on biopsies from the vastus lateralis muscle. Signs of injury were found in muscles from both control and COPD patients, not only in cases showing severe airflow obstruction but also in the mild or moderate stages of the disease. Current smoking and presence of COPD were significantly associated with increased injury of the muscle as assessed by light and electron microscopy techniques. The authors conclude that peripheral muscle injury is evident in mild, moderate, and severe stages of COPD even in the absence of respiratory failure, hypercapnia, chronic steroid treatment, low body weight, or some coexisting disease. These findings support the theory that systemic factors with deleterious effect are acting on peripheral muscles of smokers with COPD, increasing the susceptibility of the muscle fibers to membrane and sarcomere injury.

Does oxidative stress modulate limb muscle atrophy in severe COPD patients?

Oxidative stress may differentially regulate protein loss within peripheral muscles of severe chronic obstructive pulmonary disease (COPD) patients exhibiting different body composition. Oxidation levels of proteins, myosin heavy chain (MyHC) and myonuclei, superoxide anion, antioxidants, actin, creatine kinase, carbonic anhydrase-3, ubiquitin-proteasome system, redox-signalling pathways, inflammation and muscle structure, and damage were quantified in limb muscles of severe COPD patients with and without muscle wasting, and in sedentary controls. Compared with controls, in the quadriceps of muscle-wasted COPD patients, levels of protein carbonylation, oxidation of MyHC and myonuclei, superoxide anion production, superoxide dismutase, total protein ubiquinitation, E2(14k), atrogin-1, FoxO1 and p65 were higher, while content of MyHC, creatine kinase, carbonic anhydrase-3, myogenin, and fast-twitch fibre size were decreased. Importantly, in nonwasted COPD patients, where MyHC was more oxidised than in controls, its content was preserved. Muscle inflammation and glutathione levels did not differ between patients and controls. In all patients, muscle structure abnormalities were increased, while muscle force and exercise capacity were reduced. In severe COPD, while muscle oxidative stress increases regardless of their body composition, protein ubiquitination and loss of MyHC were enhanced only in patients exhibiting muscle atrophy. Oxidative stress does not seem to directly modulate muscle protein loss in these patients.

Clinical correlates of apathy in patients recently diagnosed with Parkinson's disease: the ANIMO study.

OBJECTIVE: Little is known about apathy in the early stages of Parkinson's disease (PD). We determined the clinical correlates of apathy in a large representative sample of patients recently diagnosed with PD (ANIMO study). METHODS: PD patients, diagnosed within 2 years of inclusion, were recruited in 102 outpatient clinics situated in 82 populations throughout Spain. Apathy was quantified using the Lille Apathy Rating Scale (LARS). Clinical comparisons and correlations were performed using nonparametric tests. Regression analyses were used to test the association of clinical variables with apathy. RESULTS: We recruited 557 PD patients (60.3% men) with a mean age of 68.8 ± 9.7 years, and UPDRS motor score of 21.1 ± 10.8. Apathy only was diagnosed in 186 (33.4%), and apathy and depression in 215 patients (38.6%). Patients with higher comorbidity (OR = 1.10, 95% CI 1.01-1.20, p = 0.001), motor impairment (OR = 1.07, 95% CI 1.03-1.10, p < 0.0001), and lower education (OR = 2.16, 95% CI 1.21-3.85, p = 0.009) had higher odds of having apathy, in contrast to patients living in a rural environment (OR = 0.35, 95% CI 0.32-0.85, p = 0.01), and left predominant PD motor laterality (OR = 0.34, 95% CI 0.13-0.88, p = 0.01). LARS scores were significantly correlated with UPDRS motor scores (r(s) = 0.44, p < 0.001), predominantly with axial score (r(s) = 0.43, p < 0.001). CONCLUSIONS: In PD, apathy is a very common and disabling nonmotor symptom separable from depression. Patients living in a rural environment, with lower comorbidity and motor impairment, higher education background, and left predominant PD motor laterality are at lower risk of suffering from apathy.

Impact of apathy on health-related quality of life in recently diagnosed Parkinson's disease: the ANIMO study.

The impact of apathy on health-related quality of life (HRQOL) in recently diagnosed Parkinson's disease (PD) has not been systematically investigated. The objective of this cross-sectional survey (ANIMO study) was to examine the contribution of apathy to HRQOL in a Spanish sample of recently diagnosed PD patients. PD patients, diagnosed within 2 years of inclusion, were recruited at 102 outpatient clinics in 82 communities throughout Spain. Apathy was quantified using the Lille Apathy Rating Scale and HRQOL with the EuroQol-5D questionnaire. A mean EuroQol-5D index score of 0.89 obtained from population references in Spain was used as the cutoff for this study. The relationship between apathy and the dichotomized EuroQol-5D index score (<0.89 [lower HRQOL] vs ≥0.89 [reference]) was examined using multiple logistic regression analysis, adjusting for sociodemographic and clinical variables. We consecutively recruited 557 patients (60.3% men) with a mean age of 68.8 ± 9.7 years. Apathy was diagnosed in 291 (52.2%) and was related to problems in each of the EuroQoL dimensions. Apathetic PD patients showed EuroQol-5D index scores significantly lower than those without apathy (0.64 vs 0.83). In an adjusted model, apathetic PD patients were 2.49 times more likely to have lower HRQOL than nonapathetic patients (odds ratio, 2.49; 95% confidence interval, 1.49-4.15, P < 0.01). Apathy is very common in those with recently diagnosed PD and is one of the major clinical determinants of HRQOL in this disease. It should be one of the primary concerns among clinicians who provide treatment to individuals affected by PD.

Global muscle dysfunction as a risk factor of readmission to hospital due to COPD exacerbations.

UNLABELLED: Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with several modifiable (sedentary life-style, smoking, malnutrition, hypoxemia) and non-modifiable (age, co-morbidities, severity of pulmonary function, respiratory infections) risk factors. We hypothesise that most of these risk factors may have a converging and deleterious effects on both respiratory and peripheral muscle function in COPD patients. METHODS: A multicentre study was carried out in 121 COPD patients (92% males, 63 ± 11 yr, FEV(1), 49 ± 17%pred). Assessments included anthropometrics, lung function, body composition using bioelectrical impedance analysis (BIA), and global muscle function (peripheral muscle (dominant and non-dominant hand grip strength, HGS), inspiratory (PI(max)), and expiratory (PE(max)) muscle strength). GOLD stage, clinical status (stable vs. non-stable) and both current and past hospital admissions due to COPD exacerbations were included as covariates in the analyses. RESULTS: Respiratory and peripheral muscle weakness were observed in all subsets of patients. Muscle weakness, was significantly associated with both current and past hospitalisations. Patients with history of multiple admissions showed increased global muscle weakness after adjusting by FEV(1) (PE(max), OR = 6.8, p < 0.01; PI(max), OR = 2.9, p < 0.05; HGSd, OR = 2.4, and HGSnd, OR = 2.6, p = 0.05). Moreover, a significant increase in both respiratory and peripheral muscle weakness, after adjusting by FEV(1), was associated with current acute exacerbations. CONCLUSIONS: Muscle dysfunction, adjusted by GOLD stage, is associated with an increased risk of hospital admissions due to acute episodes of exacerbation of the disease. Current exacerbations further deteriorate muscle dysfunction.

Citocinas inflamatorias y factores de reparaci¨®n en los m¨²sculos intercostales de pacientes con EPOC grave / Inflammatory Cytokines and Repair Factors in the Intercostal Muscles of Patients With Severe COPD

Introducci¨®nLas acciones locales de las citocinas en los m¨²sculos de los pacientes con enfermedad pulmonar obstructiva cr¨®nica (EPOC) se hallan sometidas a debate. El objetivo del presente estudio ha sido analizar las relaciones entre su expresi¨®n y la activaci¨®n gen¨¦tica de programas de reparaci¨®n muscular.Pacientes y m¨¦todosSe incluy¨® en el estudio a 25 pacientes con EPOC grave en situaci¨®n estable. Se les realiz¨® una biopsia del m¨²sculo intercostal externo, donde se evaluaron los signos de lesi¨®n muscular (morfometr¨ªa), la infiltraci¨®n de c¨¦lulas inflamatorias (inmunohistoqu¨ªmica) y la expresi¨®n de genes seleccionados (t¨¦cnica de reacci¨®n en cadena de la polimerasa en tiempo real) correspondientes a las propias citocinas ¡ªfactor de necrosis tumoral alfa (TNF-¦Á) y sus receptores 1 y 2 (TNFR1 y TNFR2), e interleucinas-1¦Â, 6 y 10¡ª, un marcador panleucocitario (CD18) y mol¨¦culas clave en las v¨ªas de reparaci¨®n-miog¨¦nesis (Pax7, M-Caderina y Mio-D).ResultadosLa expresi¨®n de TNFR2 se relacion¨® directamente con la funci¨®n muscular inspiratoria (representada por la presi¨®n inspiratoria m¨¢xima sostenible; r=0,496, p<0,05), mientras que la expresi¨®n de CD18 se relacion¨® inversamente con ella (r=−0,462, p<0,05). Por otra parte, la expresi¨®n de los 2 receptores del TNF-¦Á se relacion¨® directamente con la de las mol¨¦culas clave de las v¨ªas de reparaci¨®n analizadas (TNFR1 con Pax7, r=0,650, y M-Caderina, r=0,678, ambas con p<0,001; TNFR2 con Pax7, r=0,395, M-Caderina, r=0,409, y Mio-D, r=0,418, con p<0,05 en todas).ConclusionesLa expresi¨®n de los receptores del TNF-¦Á guarda una estrecha relaci¨®n tanto con la activaci¨®n de los programas de miog¨¦nesis como con la propia funci¨®n muscular inspiratoria. Este hecho refuerza nuestra hip¨®tesis de que algunas citocinas locales participan en la reparaci¨®n de los m¨²sculos respiratorios en los pacientes con EPOC(AU)

ObjectiveThere is disagreement regarding the local action of cytokines in the respiratory muscles of patients with chronic obstructive pulmonary disease (COPD). The objective of this study was to analyze the relationships between cytokine expression and genetic activation of the mechanisms of muscle repair.Patients and methodsTwenty-five patients with severe COPD and in stable condition were enrolled in the study. We performed a biopsy of the external intercostal muscle of the patients and analyzed the specimen for signs of muscle lesion (morphometry), infiltration of inflammatory cells (immunohistochemistry), and expression of selected genes (real-time polymerase chain reaction technique) corresponding to the cytokines (tumor necrosis factor ¦Á [TNF-¦Á] and its type 1 and 2 receptors [TNFR1 and TNFR2], and interleukin [IL] 1¦Â, IL-6, and IL-10), a pan-leukocyte marker (CD18), and key molecules in the repair-myogenesis pathways (Pax7, M-cadherin, and MyoD).ResultsExpression of TNFR2 is directly related to inspiratory muscle function (represented by maximum sustainable inspiratory pressure; r=0.496; P<.05), whereas expression of CD18 is inversely related (r=0.462; P<.05). Moreover, expression of the 2 TNF-¦Á receptors was directly related to that of the key molecules of the repair pathways analyzed (TNFR1 to Pax7 [r=0.650; P<.001] and M-cadherin [r=0.678; P<.001]; TNFR2 to Pax7 [r=0.395; P<.05], M-cadherin [r=0.409; P<.05], and MyoD [r=0.418; P<.05]).ConclusionsExpression of TNF-¦Á receptors bears a close relationship both to activation of the myogenesis programs and to inspiratory muscle function. This reinforces our hypothesis that some local cytokines take part in the repair of respiratory muscles in patients with COPD(AU)

[Inflammatory cytokines and repair factors in the intercostal muscles of patients with severe COPD]. / Citocinas inflamatorias y factores de reparación en los músculos intercostales de pacientes con EPOC grave.

OBJECTIVE: There is disagreement regarding the local action of cytokines in the respiratory muscles of patients with chronic obstructive pulmonary disease (COPD). The objective of this study was to analyze the relationships between cytokine expression and genetic activation of the mechanisms of muscle repair. PATIENTS AND METHODS: Twenty-five patients with severe COPD and in stable condition were enrolled in the study. We performed a biopsy of the external intercostal muscle of the patients and analyzed the specimen for signs of muscle lesion (morphometry), infiltration of inflammatory cells (immunohistochemistry), and expression of selected genes (real-time polymerase chain reaction technique) corresponding to the cytokines (tumor necrosis factor alpha [TNF-alpha] and its type 1 and 2 receptors [TNFR1 and TNFR2], and interleukin [IL] 1beta, IL-6, and IL-10), a pan-leukocyte marker (CD18), and key molecules in the repair-myogenesis pathways (Pax7, M-cadherin, and MyoD). RESULTS: Expression of TNFR2 is directly related to inspiratory muscle function (represented by maximum sustainable inspiratory pressure; r=0.496; P<.05), whereas expression of CD18 is inversely related (r=0.462; P<.05). Moreover, expression of the 2 TNF-alpha receptors was directly related to that of the key molecules of the repair pathways analyzed (TNFR1 to Pax7 [r=0.650; P<.001] and M-cadherin [r=0.678; P<.001]; TNFR2 to Pax7 [r=0.395; P<.05], M-cadherin [r=0.409; P<.05], and MyoD [r=0.418; P<.05]). CONCLUSIONS: Expression of TNF-alpha receptors bears a close relationship both to activation of the myogenesis programs and to inspiratory muscle function. This reinforces our hypothesis that some local cytokines take part in the repair of respiratory muscles in patients with COPD.

Sustained CTL activation by murine pulmonary epithelial cells promotes the development of COPD-like disease.

Chronic obstructive pulmonary disease (COPD) is a lethal progressive lung disease culminating in permanent airway obstruction and alveolar enlargement. Previous studies suggest CTL involvement in COPD progression; however, their precise role remains unknown. Here, we investigated whether the CTL activation receptor NK cell group 2D (NKG2D) contributes to the development of COPD. Using primary murine lung epithelium isolated from mice chronically exposed to cigarette smoke and cultured epithelial cells exposed to cigarette smoke extract in vitro, we demonstrated induced expression of the NKG2D ligand retinoic acid early transcript 1 (RAET1) as well as NKG2D-mediated cytotoxicity. Furthermore, a genetic model of inducible RAET1 expression on mouse pulmonary epithelial cells yielded a severe emphysematous phenotype characterized by epithelial apoptosis and increased CTL activation, which was reversed by blocking NKG2D activation. We also assessed whether NKG2D ligand expression corresponded with pulmonary disease in human patients by staining airway and peripheral lung tissues from never smokers, smokers with normal lung function, and current and former smokers with COPD. NKG2D ligand expression was independent of NKG2D receptor expression in COPD patients, demonstrating that ligand expression is the limiting factor in CTL activation. These results demonstrate that aberrant, persistent NKG2D ligand expression in the pulmonary epithelium contributes to the development of COPD pathologies.

[Determination of maximal diaphragm strength in chronic obstructive pulmonary disease: cervical magnetic stimulation versus traditional sniff maneuver]. / Fuerza máxima del diafragma en la EPOC: estimulación magnética cervical frente a la clásica maniobra de inhalación forzada.

OBJECTIVE: Magnetic stimulation of the diaphragm allows its strength to be assessed. The clinical applications of this technique are becoming more widespread given that the patient's cooperation is not required. The aim of the present study was to compare this inhalation technique with traditional voluntary forced inspiration (sniff test) in a group of patients with chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: Sixteen men with moderate-to-severe COPD were studied (mean [SD] forced expiratory volume in 1 second, 35% [15%] of the reference value). For all patients, the maximal transdiaphragmatic pressure (a measure of the contractility of the muscle) was determined at peak inspiration and during cervical magnetic stimulation. RESULTS: A moderate correlation between measurements with the 2 techniques was observed. The value obtained with stimulation was approximately 20% of that obtained with the sniff maneuver (22 [7] cm H2O vs 97 [27] cm H2O, respectively). The stimulation technique yielded an intraindividual coefficient of variability of 12% (7%) and an interindividual one of 33% (6%). Very similar values for these coefficients were obtained with the sniff maneuver. Qualitative analysis of the stimulation technique showed it to have a high sensitivity (89%) for diagnosing muscle weakness, with few false negatives. In contrast, specificity was very low (43%), and false positives for muscle weakness were relatively common. The overall effectiveness of the prediction was acceptable (69%). CONCLUSIONS: Cervical magnetic stimulation appears to be a good clinical option for ruling out diaphragm weakness. It is particularly indicated in patients with limited capacity for understanding instructions or those unable to cooperate.

Fuerza máxima del diafragma en la EPOC: estimulación magnética cervical frente a la clásica maniobra de inhalación forzada / Determination of maximal diaphragm strength in Chronic Obstructive Pulmonary Disease: cervical magnetic stimulation ersus traditional sniff maneuver

Objetivo: La estimulación magnética del diafragma es una técnica que permite evaluar la fuerza de este músculo. Dado que obvia la necesidad de colaboración del paciente, va extendiendo progresivamente su aplicación clínica. El objetivo del presente estudio ha sido comparar esta técnica de estimulación con la clásica de inhalación voluntaria forzada (sniff) en un grupo de pacientes con enfermedad pulmonar obstructiva crónica (EPOC). Pacientes y métodos: Se estudió a 16 pacientes varones con EPOC de moderada a grave (valor medio ± desviación estándar del volumen espiratorio forzado en el primer segundo del 35 ± 15% del valor de referencia). En todos ellos se obtuvo la presión máxima del diafragma (expresión de la fuerza contráctil del músculo) por maniobras de inhalación voluntaria máxima y de estimulación cervical magnética. Resultados: Se observó una relación moderada entre ambas técnicas, siendo los valores obtenidos con estimulación de aproximadamente un 20% de los obtenidos con la maniobra voluntaria (97 ± 27 y 22 ± 7 cmH2O, respectivamente). La técnica de estimulación mostró unos coeficientes de variabilidad intraindividual del 12 ± 7%, e interindividual del 33 ± 6%, muy similares a los del método de inhalación. El análisis cualitativo de la técnica de estimulación para el diagnóstico de debilidad muscular mostró una elevada sensibilidad (89%), con escasos falsos negativos. Por el contrario, su especificidad fue muy baja (43%), con una tasa relativamente elevada de sobrediagnósticos. La eficacia de la predicción resultó globalmente aceptable (69%). Conclusiones: La técnica de estimulación magnética cervical se muestra como una buena opción clínica para descartar debilidad del diafragma, con indicación sobre todo en pacientes con poca capacidad de comprensión o incapacidad de colaboración

Objective: Magnetic stimulation of the diaphragm allows its strength to be assessed. The clinical applications of this technique are becoming more widespread given that the patient's cooperation is not required. The aim of the present study was to compare this inhalation technique with traditional voluntary forced inspiration (sniff test) in a group of patients with chronic obstructive pulmonary disease (COPD). Patients and methods: Sixteen men with moderate-to-severe COPD were studied (mean [SD] forced expiratory volume in 1 second, 35% [15%] of the reference value). For all patients, the maximal transdiaphragmatic pressure (a measure of the contractility of the muscle) was determined at peak inspiration and during cervical magnetic stimulation. Results: A moderate correlation between measurements with the 2 techniques was observed. The value obtained with stimulation was approximately 20% of that obtained with the sniff maneuver (22 [7] cm H2O vs 97 [27] cm H2O, respectively). The stimulation technique yielded an intraindividual coefficient of variability of 12% (7%) and an interindividual one of 33% (6%). Very similar values for these coefficients were obtained with the sniff maneuver. Qualitative analysis of the stimulation technique showed it to have a high sensitivity (89%) for diagnosing muscle weakness, with few false negatives. In contrast, specificity was very low (43%), and false positives for muscle weakness were relatively common. The overall effectiveness of the prediction was acceptable (69%). Conclusions: Cervical magnetic stimulation appears to be a good clinical option for ruling out diaphragm weakness. It is particularly indicated in patients with limited capacity for understanding instructions or those unable to cooperate

Aging, sex differences, and oxidative stress in human respiratory and limb muscles.

Oxidative stress is involved in the sarcopenia of aging muscles. On the grounds that ventilatory muscles are permanently active, and their activity may even increase with aging, we hypothesized that the levels of oxidative stress would probably be increased in the external intercostals of elderly healthy individuals. We conducted a case-control study in which reactive carbonyl groups, malondialdehyde-protein adducts, 3-nitrotyrosine immunoreactivity, Mn-superoxide dismutase (Mn-SOD), and catalase were detected using immunoblotting in external intercostals and quadriceps (open muscle biopsies) obtained from 12 healthy elderly and 12 young individuals of both sexes. In elderly subjects, reactive carbonyls, malondialdehyde-protein adducts, 3-nitrotyrosine, Mn-SOD, and catalase were significantly greater in the external intercostals than in the young controls. A post hoc analysis, in which men and women from both groups were analyzed separately, revealed that the external intercostals of elderly women, but not those of elderly men, showed significantly increased levels of reactive carbonyls, malondialdehyde-protein adducts, 3-nitrotyrosine, and Mn-SOD compared to those of control females. This study suggests that differences in muscle activity might explain the differential pattern of oxidative stress observed in human respiratory and limb muscles with aging as well as the likely existence of a sex-related regulation of this phenomenon in these muscles.

[Global muscle dysfunction and exacerbation of COPD: a cohort study]. / Disfunción muscular global durante la exacerbación de la EPOC: un estudio de cohortes.

BACKGROUND AND OBJECTIVE: The purpose of this study was to evaluate on a prospective fashion the effects of clinical relapses of chronic obstructive pulmonary disease (COPD) on both peripheral and respiratory skeletal muscle functions. PATIENTS AND METHOD: We included 49 patients (males, 63 [11] years) who were assigned to three cohorts: a) COPD patients who were hospitalized in a conventional ward because of a relapse of their disease; b) patients hospitalized in conventional wards because of another lung disease or a pulmonary nodule; and c) COPD patients whose disease was stabilized (outpatients). Sequential measurements were made by means of anthropometry, serum biochemistry and body bioimpedance (BIA). In COPD patients with a disease relapse, we assessed changes in the function of peripheral muscles [force (Fhand) and resistance (Tlimhand) of hands], inspiratory muscles (PImax) and respiratory muscles (PEmax). RESULTS: Patients were evaluated during a 6 [2] days period. Patients with a COPD relapse displayed a global and progressive functional muscle impairment, which was expressed as a decrease of PEmax (17 [12]%), F hand-D (6 [9]%), F hand-ND (7 [8]%), Tlim hand-D (28 [26]%) and Tlim hand-ND (23 [16]%). These changes showed a linear trend. BIA exhibited a loss of lean mass (7 [6]%, p < 0.05) which would have been unnoticeable if only the body weight was quantified. Pneumonia cases showed similar changes in BIA. On the other hand, the cohort of patients with stable COPD did not have changes in both muscle function and BIA. CONCLUSIONS: COPD exacerbation is associated with an acute and global impairment of the function of respiratory and peripheral skeletal muscles. It is possible that these changes are related to an acute loss of muscular mass (proteolysis). This muscle dysfunction is not detected if only the inspiratory muscular function is evaluated--possibly because of the coexistence of transitory mechanic factors.