Rodolfo Alvarez-Sala

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.

Prospective comparison of helical CT with angiography in pulmonary embolism: global and selective vascular territory analysis. Interobserver agreement.

Abstract. The objective of this prospective study was to evaluate the sensitivity, specificity, positive and negative predictive values, and interobserver agreement in the diagnosis of pulmonary embolism with helical CT, compared with pulmonary angiography, for both global results and for selective vascular territories. Helical CT and pulmonary angiography were performed on 66 consecutive patients with clinical suspicion of pulmonary embolism. The exams were blindly interpreted by a vascular radiologist and by two independent thoracic radiologists. Results were analyzed for the final diagnosis as well as separately for 20 different arterial territories in each patient. Pulmonary angiography revealed embolism in 25 patients (38%); 48% were main, 28% lobar, 16% segmental, and 8% subsegmental. The sensitivity, specificity, and positive and negative predictive values of helical CT for observer 1 were, respectively, 91, 81.5, 75, and 94%; in 7.5% of the patients the exam was considered indeterminate. For observer 2 the values were, respectively, 88, 86, 81.5, and 91%; in 9% of the patients the exam was considered indeterminate. Main arteries were considered as non-valuable in 0–0.8%, the lobar in 1.5%, the segmental in 7.5–8.5%, and the subsegmental in 55–60%. Interobserver agreement for the final diagnosis was 80% (kappa 0.65). For each vascular territory, this was 98% (kappa 0.91) for main arteries, 92% (kappa 0.78) for lobar arteries, 79% (kappa 0.56) for segmental arteries, and 59% (kappa 0.21) for subsegmental arteries. Helical CT is a reliable method for pulmonary embolism diagnosis, with good interobserver agreement for main, lobar, and segmental territories. Worse results are found for subsegmental arteries, with high incidence of non-valuable branches and poor interobserver agreement.

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.

Pathophysiologic Mechanisms of Cardiovascular Disease in Obstructive Sleep Apnea Syndrome

Obstructive sleep apnea syndrome (OSAS) is a highly prevalent sleep disorder, characterized by repeated disruptions of breathing during sleep. This disease has many potential consequences including excessive daytime sleepiness, neurocognitive deterioration, endocrinologic and metabolic effects, and decreased quality of life. Patients with OSAS experience repetitive episodes of hypoxia and reoxygenation during transient cessation of breathing that provoke systemic effects. Furthermore, there may be increased levels of biomarkers linked to endocrine-metabolic and cardiovascular alterations. Epidemiological studies have identified OSAS as an independent comorbid factor in cardiovascular and cerebrovascular diseases, and physiopathological links may exist with onset and progression of heart failure. In addition, OSAS is associated with other disorders and comorbidities which worsen cardiovascular consequences, such as obesity, diabetes, and metabolic syndrome. Metabolic syndrome is an emerging public health problem that represents a constellation of cardiovascular risk factors. Both OSAS and metabolic syndrome may exert negative synergistic effects on the cardiovascular system through multiple mechanisms (e.g., hypoxemia, sleep disruption, activation of the sympathetic nervous system, and inflammatory activation). It has been found that CPAP therapy for OSAS provides an objective improvement in symptoms and cardiac function, decreases cardiovascular risk, improves insulin sensitivity, and normalises biomarkers. OSAS contributes to the pathogenesis of cardiovascular disease independently and by interaction with comorbidities. The present review focuses on indirect and direct evidence regarding mechanisms implicated in cardiovascular disease among OSAS patients.

Lung volume reference values for women and men 65 to 85 years of age.

RATIONALE In elderly subjects, static lung volumes are interpreted using prediction equations derived from primarily younger adult populations. OBJECTIVES To provide reference equations for static lung volumes for European adults 65 to 85 years of age and to compare the predicted values of this sample with those from other studies including middle-aged adults. We compare the lung volumes by plethysmography and helium dilution in elderly subjects. METHODS Reference equations were derived from a randomly selected sample from the general population of 321 healthy never-smoker subjects 65 to 85 years of age. Spirometry and lung volume determinations by plethysmography and multibreath helium equilibration method were performed following the American Thoracic Society/European Respiratory Society recommendations. Reference values and lower and upper limits of normal were derived using a piecewise polynomial model. MEASUREMENTS AND MAIN RESULTS Plethysmography provided higher values than the dilutional method for all lung volumes, with wide limits of agreement. In addition to height, our reference equations confirm the age- and body size dependence of lung volumes in older subjects. Practically all the estimations performed by extrapolating reference equations of middle-aged adults overpredicted the true lung volumes of our healthy elderly volunteers. Middle-aged reference equations classify subjects as being below the total lung capacity lower limit of normal between 17.9 and 62.5% of the women and between 12.5 and 42.2% of the men of the current study. CONCLUSIONS These results underscore the importance of using prediction equations appropriate to the origin, age, and height characteristics of the subjects being studied.

The clinical value of neuron-specific enolase as a tumor marker in bronchoalveolar lavage

Background. Neuron‐specific enolase (NSE) is used in the staging and monitoring of responses to therapy and the detection of recurrences in lung cancer. The diagnostic value of NSE has been under discussion. This may be because NSE usually has been studied in the sera of patients with bronchogenic carcinoma and not in the bronchoalveolar lavage (BAL).

Evolution of the COPD Assessment Test score during chronic obstructive pulmonary disease exacerbations: determinants and prognostic value.

BACKGROUND An adequate evaluation of exacerbations is a primary objective in managing patients with chronic obstructive pulmonary disease (COPD). OBJECTIVES To define the profile of health status recovery during severe exacerbations of COPD using the COPD Assessment Test (CAT) questionnaire and to evaluate its prognostic value. METHODS Forty-five patients with previous COPD diagnoses who were hospitalized due to severe exacerbation(s) were included in the study. These patients were treated by their respective physicians following current recommendations; health status was assessed daily using the CAT questionnaire. The CAT score, spirometry and recurrent hospitalizations were recorded one and three months after hospital discharge. RESULTS Global initiative for chronic Obstructive Lung Disease (GOLD) stage was an independent determinant for increased CAT score during the first days of exacerbation with respect to postexacerbation values. From hospitalization day 5, the CAT score was similar to that obtained in the stable phase. Body mass index, GOLD stage and education level were related to health status recovery pattern. CAT score increase and the area under the curve of CAT recovery were inversely related to the forced expiratory volume in 1 s achieved three months after discharge (r=-0.606; P<0.001 and r=-0.532; P<0.001, respectively). Patients with recurrent hospitalizations showed higher CAT score increases and slower recovery. CONCLUSIONS The CAT detects early health status improvement during severe COPD exacerbations. Its initial worsening and recovery pattern are related to lung function and recurrent hospitalizations.

Computerized physician order entry in the cardiac intensive care unit: effects on prescription errors and workflow conditions.

PURPOSES To evaluate the effects of a computerized physician order entry (CPOE) system in the cardiac intensive care unit by detecting prescription errors (PEs) and also to assess the impact on working conditions. METHODS A longitudinal, prospective, before-after study was conducted during the periods before and after the implementation of the CPOE system. Clinical pharmacists were responsible for the registration, description and classification of PEs, and their causes and severity, according to an international taxonomy. Professionals were also surveyed for their opinion, concerns, and level of satisfaction. RESULTS A total of 470 treatment orders containing 5729 prescriptions were evaluated. The CPOE resulted in a marked reduction in the number of PEs: error rate was 44.8% (819 errors among 1829 prescriptions) with handwritten orders and 0.8% (16 among 2094 prescriptions) at the final electronic phase (P < .001). Lapses were the main cause of error in both prescription methods. Most errors did not reach the patients. Errors related with the computerized system were scarce. Most users were satisfied with many aspects of this technology, although a higher workload was reported. CONCLUSIONS Computerized physician order entry in the cardiac intensive care unit proved to be a safe and effective strategy in reducing PEs and was globally well received by professionals.

RevisiónPrescripción electrónica asistida como nueva tecnología para la seguridad del paciente hospitalizadoComputerized physician order entry as a new technology for patients’ safety

Concern about patient safety is a priority in the quality policy of health systems. In the pharmacotherapeutic process, from prescription to administration of drugs, failures that cause unwanted effects in patients may occur. This is especially common in patients with multiple pathologies and polypharmacy, common in medical specialities services. To analyze and identify the causes that trigger medical errors is essential to prevent their occurrence. In this context, computerized physician order entry appear as an attractive tool for ensuring patients safety.

Epidemiological and Pathogenic Relationship between Sleep Apnea and Ischemic Heart Disease

Obstructive sleep apnea is recognized as having high prevalence and causing remarkable cardiovascular risk. Coronary artery disease has been associated with obstructive sleep apnea in many reports. The pathophysiology of coronary artery disease in obstructive sleep apnea patients probably includes the activation of multiple mechanisms, as the sympathetic activity, endothelial dysfunction, atherosclerosis, and systemic hypertension. Moreover, chronic intermittent hypoxia and oxidative stress have an important role in the pathogenesis of coronary disease and are also fundamental to the development of atherosclerosis and other comorbidities present in coronary artery diseases such as lipid metabolic disorders. Interestingly, the prognosis of patients with coronary artery disease has been associated with obstructive sleep apnea and the severity of sleep disordered breathing may have a direct relationship with the morbidity and mortality of patients with coronary diseases. Nevertheless, treatment with CPAP may have important effects, and recent reports have described the benefits of obstructive sleep apnea treatment on the recurrence of acute heart ischaemic events in patients with coronary artery disease.