Blas Rojo

Daily physical activity in patients with chronic obstructive pulmonary disease is mainly associated with dynamic hyperinflation.

RATIONALE Although the major limitation to exercise performance in patients with COPD is dynamic hyperinflation, little is known about its relation to daily physical activity. OBJECTIVES To analyze the contribution of dynamic hyperinflation, exercise tolerance, and airway oxidative stress to physical activity in patients with COPD. METHODS In a cross-sectional study, we included 110 patients with moderate to very severe COPD. Daily physical activity was measured using a triaxial accelerometer providing a mean of 1-minute movement epochs as vector magnitude units (VMU). Patients performed the 6-minute walk test, incremental exercise test with measurement of breathing pattern and operating lung volumes, and constant-work rate test at 75% of maximal work rate. MEASUREMENTS AND MAIN RESULTS Using the GOLD stage and BODE index, we determined arterial blood gases, lung volumes, diffusing capacity, and biomarkers in exhaled breath condensate. Daily physical activity was lower in the 89 patients who developed dynamic hyperinflation than in the 21 who did not (n =161 [SD 70] vs. n = 288 [SD 85] VMU; P = 0.001). Physical activity was mainly related to distance walked in 6 minutes (r = 0.72; P = 0.001), Vo(2) (r = 0.63; P = 0.001), change in end-expiratory lung volume during exercise (r = -0.73; P = 0.001), endurance time (r = 0.61; P = 0.001), and 8-isoprostane in exhaled breath condensate (r = -0.67; P = 0.001). In a multivariate linear regression analysis using VMU as a dependent variable, dynamic hyperinflation, change in end-expiratory lung volume, and distance walked in 6 minutes were retained in the prediction model (r(2) = 0.84; P = 0.001). CONCLUSIONS Daily physical activity of patients with COPD is mainly associated with dynamic hyperinflation, regardless of severity classification.

Prognostic Value of the Objective Measurement of Daily Physical Activity in Patients With COPD

BACKGROUND Subjective measurement of physical activity using questionnaires has prognostic value in COPD. However, their lack of accuracy and large individual variability limit their use for evaluation on an individual basis. We evaluated the capacity of the objective measurement of daily physical activity in patients with COPD using accelerometers to estimate their prognostic value. METHODS In 173 consecutive subjects with moderate to very severe COPD, daily physical activity was measured using a triaxial accelerometer providing a mean of 1-min movement epochs as vector magnitude units (VMUs). Patients were evaluated by lung function testing and 6-min walk, incremental exercise, and constant work rate tests. Patients were followed for 5 to 8 years, and the end points were all-cause mortality, hospitalization for COPD exacerbation, and annual declining FEV(1). RESULTS After adjusting for relevant confounders, a high VMU decreased the mortality risk (adjusted hazard ratio [HR], 0.986; 95% CI, 0.981-0.992), and in a multivariate model, comorbidity, endurance time, and VMU were retained as independent predictors of mortality. The time until first admission due to COPD exacerbation was shorter for the patients with lower levels of VMU (adjusted HR, 0.989; 95% CI, 0.983-0.995). Moreover, patients with higher VMU had a lower hospitalization risk than those with a low VMU (adjusted incidence rate ratio, 0.099; 95% CI, 0.033-0.293). In contrast, VMU was not identified as an independent predictor of the annual FEV(1) decline. CONCLUSION The objective measurement of the daily physical activity in patients with COPD using an accelerometer constitutes an independent prognostic factor for mortality and hospitalization due to severe exacerbation.

Monocytes from Cystic Fibrosis Patients Are Locked in an LPS Tolerance State: Down-Regulation of TREM-1 as Putative Underlying Mechanism

Cystic Fibrosis (CF) is an inherited pleiotropic disease that results from abnormalities in the gene that codes for the chloride channel, Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). CF patients are frequently colonized by several pathogens, but the mechanisms that allow colonization in spite of apparently functional immune systems are incompletely understood. In this paper we show that blood peripheral monocytes isolated from CF patients are found in an endotoxin tolerance state, yet this is not due to a deficient TLR activation. On the other hand, levels of the amplifier of inflammatory responses, TREM-1 (Triggering Receptor Expressed on Myeloid cells), are notably down-regulated in monocytes from patients, in comparison to those extracted from healthy volunteers. Furthermore, the soluble form of TREM-1 (sTREM-1) was not detected in the sera of patients. Additionally, and in strict contrast to patients who suffer from Chronic Obstructive Pulmonary Disease (COPD), CF monocytes challenged ex vivo with LPS neither up-regulated membrane-anchored TREM-1 nor sTREM-1. Finally, similar levels of PGE2 expression and p65 translocation into the nucleus were found in both patients and healthy volunteers, thus suggesting that TREM-1 regulation is neither controlled by PGE2 levels nor by p65 activation in this case. However, PU.1 translocation into the nucleus was significantly higher in CF monocytes than in controls, suggesting a role for this transcription factor in the control of TREM-1 expression. We conclude that down-regulation of TREM-1 expression in cystic fibrosis patients is at least partly responsible for the endotoxin tolerance state in which their monocytes are locked.

CPAP effect on recurrent episodes in patients with sleep apnea and myocardial infarction

BACKGROUND Obstructive sleep apnea (OSA) is linked to increased cardiovascular risk, but the association between OSA and myocardial infarction (MI) remains controversial. Our objectives were to compare the frequency of OSA in patients with acute MI and in a population-based sample of control subjects, and to evaluate the impact of CPAP on recurrent MI and coronary revascularization. METHODS Case-control study with a 6-year follow-up of the case cohort. 192 acute MI patients and 96 matched control subjects without coronary artery disease (CAD) (ratio 2:1). After overnight polysomnography, CPAP was recommended if apnea-hypopnea index (AHI) ≥ 5, and a mean daily use >3.5h/day was considered necessary to maintain the treatment. Lipids, fasting glucose, blood pressure, spirometry, comorbidity and current treatment were also registered. End-points were recurrent MI or need of revascularization. RESULTS OSA was an independent predictor of MI, with odds ratio 4.9 (95% confidence interval [CI] 2.9-8.3, p=0.017). 63 MI patients without OSA, 52 untreated patients with OSA and 71 OSA patients treated with CPAP were included in the follow-up study. After adjustment for confounding factors, treated OSA patients had a lower risk of recurrent MI (adjusted hazard ratio 0.16 [95%CI 0.03-0.76, p=0.021]) and revascularization (adjusted hazard ratio 0.15 [95%CI 0.03-0.79, p=0.025]) than untreated OSA patients, and similar to non-OSA patients. CONCLUSION Mild-severe OSA is an independent risk factor for MI. Risk of recurrent MI and revascularization was lower in OSA patients who tolerated CPAP.

Recording the Daily Physical Activity of COPD Patients With an Accelerometer: An Analysis of Agreement and Repeatability

OBJECTIVE The purpose of this study was to assess the agreement between different measurements of mean daily physical activity taken over a week in chronic obstructive pulmonary disease (COPD) patients with an accelerometer and to analyze the medium-term repeatability of these measurements. PATIENTS AND METHODS The study enrolled 12 healthy control subjects and 23 patients with stable COPD (mean [SD] forced expiratory volume in 1 second [FEV1] of 45% [13%] of predicted and a ratio of FEV1 to forced vital capacity of 53% [13%]). Accelerometer output, measured in vector magnitude units, was recorded in a physical activity log for a 1-week period. The results were then analyzed to compare output for a conventional recording period (Friday to Sunday) to that for 2 other periods (Monday to Wednesday and Tuesday to Thursday). The measurements were repeated 3 to 5 weeks later. RESULTS Activity counts were lower in the COPD patients than in the control subjects (184 [99] vs 314 [75]; P < .001). In the COPD patients, the results for the Friday to Sunday period correlated well with the results for both the Monday to Wednesday period (95% confidence interval, -29.21 to 28.81) and the Tuesday to Thursday period (95% confidence interval, -32.13 to 28.43). There were no significant differences in terms of medium-term repeatability of accelerometer readings between the COPD group and the control group (repeatability coefficient of 11.2% [4.6%] and 8.5% [4.7%], respectively). CONCLUSIONS Both agreement between the different measurements of physical activity taken during a 1-week period and medium-term repeatability for COPD patients and control subjects were very good.

Diferencias en función de la gravedad de la atenuación pulmonar en varones con EPOC

BACKGROUND AND OBJECTIVES We compare the inspiratory and expiratory regional lung densities between different levels of COPD severity (as assessed by the GOLD scale and by the BODE index), and to assess the relationship between regional lung densities and functional lung parameters. PATIENTS AND METHODS Fifty-five stable moderate-severe COPD men were selected. Functional evaluation included dyspnoea scale, blood gases, spirometry, plethysmography, diffusing capacity and six-minute walk test. Severity was classified according the GOLD scale and the BODE index. High resolution computed tomography (HRCT) scans of the entire lung at full inspiration and two sections at full expiration were obtained. Densitometry software was used to calculate the densities of the lung areas. RESULTS Inspiratory and expiratory mean lung densities (MLD) of the lower lobes were significantly lower in very severe and severe COPD patients than in moderate patients. In contrast, we only found differences between the upper lobe MLD values of moderate and severe COPD patients. Inspiratory and expiratory HRCT densities were similar among all BODE quartiles, for both the upper and lower lobes. In a multiple regression analysis, airway obstruction parameters were mainly related to the expiratory MLD of the lower lobes, whereas lung hyperinflation parameters were predicted by the inspiratory MLD of the lower lobes. Lastly, diffusion capacity was independently related to the expiratory/inspiratory MLD of the lower lobes and to the inspiratory MLD of the upper lobes. CONCLUSIONS There are differences in lung attenuation measurements by HRCT between the varying levels of COPD severity as assessed by the GOLD scale.

Severity Related Differences in Lung Attenuation in Men With COPD

Abstract Background and objectives We compare the inspiratory and expiratory regional lung densities between different levels of COPD severity (as assessed by the GOLD scale and by the BODE index), and to assess the relationship between regional lung densities and functional lung parameters. Patients and methods Fifty-five stable moderate-severe COPD men were selected. Functional evaluation included dyspnoea scale, blood gases, spirometry, plethysmography, diffusing capacity and six-minute walk test. Severity was classified according the GOLD scale and the BODE index. High resolution computed tomography (HRCT) scans of the entire lung at full inspiration and two sections at full expiration were obtained. Densitometry software was used to calculate the densities of the lung areas. Results Inspiratory and expiratory mean lung densities (MLD) of the lower lobes were significantly lower in very severe and severe COPD patients than in moderate patients. In contrast, we only found differences between the upper lobe MLD values of moderate and severe COPD patients. Inspiratory and expiratory HRCT densities were similar among all BODE quartiles, for both the upper and lower lobes. In a multiple regression analysis, airway obstruction parameters were mainly related to the expiratory MLD of the lower lobes, whereas lung hyperinflation parameters were predicted by the inspiratory MLD of the lower lobes. Lastly, diffusion capacity was independently related to the expiratory/inspiratory MLD of the lower lobes and to the inspiratory MLD of the upper lobes. Conclusions There are differences in lung attenuation measurements by HRCT between the varying levels of COPD severity as assessed by the GOLD scale.

Evaluación funcional respiratoria (obstrucción y atrapamiento)

La disminucion del calibre de las vias aereas y la perdida de retraccion elastica del parenquima pulmonar favorecen el desarrollo de obstruccion al flujo aereo en pacientes con enfermedad pulmonar obstructiva cronica (EPOC). La espirometria continua siendo el procedimiento de primera eleccion para la evaluacion de la obstruccion de forma rutinaria. Sin embargo, el analisis de la curva flujo-volumen a volumen corriente o la tecnica de presion espiratoria negativa permiten detectar de forma temprana a pacientes con limitacion al flujo aereo espiratorio. La dificultad para completar el vaciamiento alveolar origina atrapamiento aereo e hiperinsuflacion, tanto estatica como dinamica. Este fenomeno, que guarda una relacion mas estrecha con la disnea y la tolerancia al ejercicio que la obstruccion al flujo aereo, puede evaluarse mediante la determinacion de los volumenes pulmonares estaticos. Sin embargo, la capacidad inspiratoria, obtenida de una espirometria lenta, proporciona una estimacion indirecta de la magnitud de la hiperinsuflacion, mas sencilla y reproducible.