Raúl Galera

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.

Effect of Continuous Positive Airway Pressure on Glycemic Control in Patients with Obstructive Sleep Apnea and Type 2 Diabetes. A Randomized Clinical Trial

RATIONALE Obstructive sleep apnea (OSA) is a risk factor for type 2 diabetes that adversely impacts glycemic control. However, there is little evidence about the effect of continuous positive airway pressure (CPAP) on glycemic control in patients with diabetes. OBJECTIVES To assess the effect of CPAP on glycated hemoglobin (HbA1c) levels in patients with suboptimally controlled type 2 diabetes and OSA, and to identify its determinants. METHODS In a 6-month, open-label, parallel, and randomized clinical trial, 50 patients with OSA and type 2 diabetes and two HbA1c levels equal to or exceeding 6.5% were randomized to CPAP (n = 26) or no CPAP (control; n = 24), while their usual medication for diabetes remained unchanged. MEASUREMENTS AND MAIN RESULTS HbA1c levels, Homeostasis Model Assessment and Qualitative Insulin Sensitivity Check Index scores, systemic biomarkers, and health-related quality of life were measured at 3 and 6 months. After 6 months, the CPAP group achieved a greater decrease in HbA1c levels compared with the control group. Insulin resistance and sensitivity measurements (in noninsulin users) and serum levels of IL-1β, IL-6, and adiponectin also improved in the CPAP group compared with the control group after 6 months. In patients treated with CPAP, mean nocturnal oxygen saturation and baseline IL-1β were independently related to the 6-month change in HbA1c levels (r(2) = 0.510, P = 0.002). CONCLUSIONS Among patients with suboptimally controlled type 2 diabetes and OSA, CPAP treatment for 6 months resulted in improved glycemic control and insulin resistance compared with results for a control group. Clinical trial registered with www.clinicaltrials.gov (NCT01801150).

Dynamic Hyperinflation, Arterial Blood Oxygen, and Airway Oxidative Stress in Stable Patients With COPD

BACKGROUND There is considerable evidence that oxidative stress is increased in patients with COPD, although little information is available about its relationship with the structural and functional alterations produced by COPD. In this study, we evaluated the relationship between 8-isoprostane in exhaled breath condensate (EBC) of stable patients with COPD and the main parameters of the disease (such as dyspnea), stages of severity, lung parenchyma densities, lung function impairment, and exercise tolerance in order to identify the predictors of airway oxidative stress. METHODS In a cross-sectional study, we included 76 men with moderate to very severe COPD. 8-Isoprostane levels in EBC were measured by enzyme immunoassay. Regional lung densities were measured by lung densitometry with high-resolution CT scanning. Arterial blood gas levels, lung volumes, and diffusing capacity were determined. Patients performed a 6-min walk test and an incremental exercise test with measurement of breathing pattern and operating lung volumes. RESULTS Significant severity-related differences in 8-isoprostane were identified according to the BMI, obstruction, dyspnea, and exercise (BODE) index. 8-Isoprostane levels were related to smoking intensity, lung densities in expiration, static lung volumes, PaO(2), diffusion capacity, distance walked in 6 min, peak oxygen uptake, and anaerobic threshold. Concentration of 8-isoprostane was higher in the 60 patients (79%) who developed dynamic hyperinflation than in the remaining 16 (21%) who did not. In a multivariate linear regression analysis using 8-isoprostane as a dependent variable, end-expiratory lung volume change and PaO(2) were retained in the prediction model (r(2) = 0.734, P < .001). CONCLUSIONS In stable patients with COPD, oxygen level and dynamic hyperinflation are related to airway oxidative stress.

Prediction Equations for Single-Breath Diffusing Capacity in Subjects Aged 65 to 85 Years

BACKGROUND In senior subjects, diffusing capacity of the lung for carbon monoxide (Dlco) is interpreted using prediction equations derived from primarily younger adult populations. Our objectives were to provide reference equations for single-breath Dlco for a cohort of healthy, never-smoking, white, European adults between 65 and 85 years of age and to compare the predicted values of this sample with those from other studies involving middle-aged adults. METHODS Reference equations were derived from a randomly selected sample from the general population of 431 healthy never smoker subjects aged 65 to 85 years (262 women and 169 men). Spirometry, lung volume determinations by plethysmography, and single-breath Dlco (corrected for hemoglobin) were performed following the American Thoracic Society/European Respiratory Society guidelines. Reference values and lower and upper limits of normal were derived using a piecewise polynomial model. RESULTS In addition to age, our reference equations confirmed the height and body size dependence of Dlco and diffusing capacity for alveolar volume (Dlco/Va) in older subjects. Practically all of the reference values obtained by extrapolating reference equations of middle-aged adults underestimated the true diffusing capacity of the healthy elderly volunteers. Middle-aged reference equations underestimated Dlco by 2.1% to 22.3% in women and 2.8% to 37.8% in men. In addition, Dlco/Va was overestimated up to 18% and 39.8% in women and men, respectively, whereas other equations underestimated Dlco/Va up to 22.2% and 11.9% in women and men, respectively. CONCLUSIONS These results underscore the importance of using prediction equations appropriate to the origin and age characteristics of the subjects being studied.

Classification of Airflow Limitation Based on z-Score Underestimates Mortality in Patients with Chronic Obstructive Pulmonary Disease

&NA; Rationale: Global Lung Function Initiative recommends reporting lung function measures as z‐score, and a classification of airflow limitation (AL) based on this parameter has recently been proposed. Objectives: To evaluate the prognostic capacity of the AL classifications based on z‐score or percentage predicted of FEV1 in patients with chronic obstructive pulmonary disease (COPD). Methods: A cohort of 2,614 patients with COPD recruited outside the hospital setting was examined after a mean (± SD) of 57 ± 13 months of follow‐up, totaling 10,322 person‐years. All‐cause mortality was analyzed, evaluating the predictive capacity of several AL staging systems. Measurements and Main Results: Based on Global Initiative for Chronic Obstructive Lung Disease guidelines, 461 patients (17.6%) had mild, 1,452 (55.5%) moderate, 590 (22.6%) severe, and 111 (4.2%) very severe AL. According to z‐score classification, 66.3% of patients remained with the same severity, whereas 23.7% worsened and 10.0% improved. Unlike other staging systems, patients with severe AL according to z‐score had higher mortality than those with very severe AL (increase of risk by 5.2 and 3.9 times compared with mild AL, respectively). The predictive capacity for 5‐year survival was slightly higher for FEV1 expressed as percentage of predicted than as z‐score (area under the curve: 0.714‐0.760 vs. 0.649‐0.708, respectively). A severity‐dependent relationship between AL grades by z‐score and mortality was only detected in patients younger than age 60 years. Conclusions: In patients with COPD, the AL classification based on z‐score predicts worse mortality than those based on percentage of predicted. It is possible that the z‐score underestimates AL severity in patients older than 60 years of age with severe functional impairment.

Does airway hyperresponsiveness monitoring lead to improved asthma control

The current guidelines recommend an approach to asthma management based on asthma control, rather than asthma severity. Although several specific questionnaires have been developed and control criteria have been established based on clinical guidelines, the evaluation of asthma control is still not optimal. In general, these indicators provide adequate assessment of current control, but they are more limited when estimating future risk. There is much evidence demonstrating the persistence of airway inflammation and airway hyperresponsiveness (AHR) in patients with total control. Therefore, the objective of this review was to analyse the possible role of AHR monitoring as an instrument for assessing asthma control. We will evaluate its capacity as an indicator for future risk, both for estimating the possibility of clinical deterioration and loss of lung function or exacerbations. Furthermore, its relationship with inhaled corticosteroid treatment will be analysed, while emphasizing its capacity for predicting response and adjusting dosage, as well as information about the capability of AHR for monitoring treatment. Last of all, we will discuss the main limitations and emerging opportunities of AHR as an assessment instrument for asthma control.

Identification of non-coding genetic variants in samples from hypoxemic respiratory disease patients that affect the transcriptional response to hypoxia

A wide range of diseases course with an unbalance between the consumption of oxygen by tissues and its supply. This situation triggers a transcriptional response, mediated by the hypoxia inducible factors (HIFs), that aims to restore oxygen homeostasis. Little is known about the inter-individual variation in this response and its role in the progression of disease. Herein, we sought to identify common genetic variants mapping to hypoxia response elements (HREs) and characterize their effect on transcription. To this end, we constructed a list of genome-wide HIF-binding regions from publicly available experimental datasets and studied the genetic variability in these regions by targeted re-sequencing of genomic samples from 96 chronic obstructive pulmonary disease and 144 obstructive sleep apnea patients. This study identified 14 frequent variants disrupting potential HREs. The analysis of the genomic regions containing these variants by means of reporter assays revealed that variants rs1009329, rs6593210 and rs150921338 impaired the transcriptional response to hypoxia. Finally, using genome editing we confirmed the functional role of rs6593210 in the transcriptional regulation of EGFR. In summary, we found that inter-individual variability in non-coding regions affect the response to hypoxia and could potentially impact on the progression of pulmonary diseases.

Patrón pulmonar intersticial unilateral como primera manifestación de una endocarditis bacteriana

Infective endocarditis (IE) refers to the set of clinical and pathological alterations accompanying an infection of the endocardium, particularly in the cardiac valves. It may be caused by countless bacterial and fungal strains. Depending on the course of the disease, it may be classified as acute or sub-acute; the latter form progresses more slowly and is associated with previously abnormal valves and prior infections. We report the case of a woman who had been experiencing fever and dyspnoea for a month and whose radiology images showed a unilateral interstitial pattern compatible with pulmonary oedema of cardiogenic origin caused by bacterial endocarditis. Our search of medical literature revealed only one published case of a radiography showing a unilateral interstitial pattern due to heart failure. The 49-year old female patient was admitted to our unit for the first time for study of constitutional symptoms including loss of 8kg in one month and fever. Relevant factors in her personal history were discoid lupus on the lower lip, hypoacusia and smoking (one pack/ day smoker for 18 years). She was not taking any habitual treatments. During the time she was admitted to our centre, physical examination was normal except for pulmonary auscultation, which detected crackling sounds in the left hemithorax, and cardiac auscultation, which detected a pansystolic murmur at 90Lpm. Additional procedures included the following: blood work showing haemoglobin at 10mg/dl, white blood cell count 6,620/μl, platelet count 614,000/μl, fibrinogen 628mg/dl, sedimentation rate 86mm/h, C-reactive protein 118mg/dl and rheumatoid factor 8.5 U/ ml (positive). All other immunological studies were normal. In the tumour marker study, CA-125 was at 43 U/ml. Biochemical analysis revealed abnormal liver function, with alanine aminotransferase (ALAT) at 126 U/l, aspartate aminotransferase (AST) at 85 U/l, gamma-glutamyl transpeptidase (GGT) at 67 U/l and lactate dehydrogenase (LDH) at 607 U/l. Functional respiratory tests showed a forced vital capacity (FVC) of 2.22L (77%), forced expired volume in one second (FEV1) of 1.36L (55%), FEV1/FVC of 60% and baseline oxygen saturation of 90%. No significant abnormalities were found in the bronchoscopy; cytological examination of bronchial aspirate and bronchoalveolar lavage were negative, and there were no other microbiological findings. The chest radiography showed loss of volume in the left hemithorax, areas with a groundglass appearance and others with an interstitial pattern. Inspection with a high-resolution CT showed small bilateral pleural effusion, signs of pulmonary hypertension, decreased left hemithorax volume with widespread pulmonary involvement, interlobular and Table 1 Duke-Durack Criteria

Small airway dysfunction in smokers with stable ischemic heart disease

Background A higher prevalence of airflow limitation (AL) has been described in patients with ischemic heart disease (IHD). Although small airway dysfunction (SAD) is an early feature of AL, there is little information about its occurrence in IHD patients. Our objective was to describe the prevalence of SAD in IHD patients, while comparing patient-related outcomes and future health risk among IHD patients with AL, SAD and normal lung function. Methods In 118 consecutive smoking patients with stable IHD, comorbidities, utilization of healthcare resources, current treatment, blood biochemistry and health status were recorded. SAD was evaluated by impulse oscillometry, and pre- and post-bronchodilator spirometry was performed. Results The prevalence of AL and SAD were 20.3 (95% CI, 13.1–27.6%) and 26.3% (95% CI, 18.3–34.2%), respectively. Compared to the normal lung function group, patients with SAD and without AL had lower spirometric values, poorer quality of life and higher levels of C-reactive protein (CRP), as well as increased cardiovascular risk and more vascular age. In patients with normal spirometry, the presence of SAD was independently associated with pack-years, HDL-cholesterol and CRP levels. Conclusion In patients with IHD, the presence of SAD is common and that it is associated with reduced health status and increased future cardiac risk.

The effect of treatment for sleep apnoea on determinants of blood pressure control

Our aim was to assess the effect of continuous positive airway pressure (CPAP) on the nocturnal evolution of peripheral chemosensitivity, renin–angiotensin–aldosterone system activity, sympathetic tone and endothelial biomarkers in obstructive sleep apnoea (OSA) patients with isolated nocturnal hypertension (INH) or day–night sustained hypertension (D-NSH). In a crossover randomised trial, 32 OSA patients newly diagnosed with hypertension and without antihypertensive treatment were randomly assigned to 12 weeks of CPAP or sham CPAP. Peripheral chemosensitivity was evaluated before and after sleep using the hypoxic withdrawal test (%ΔVI). At baseline, D-NSH patients showed higher %ΔVI before sleep and higher levels of aldosterone and diurnal catecholamines. CPAP only reduced the nocturnal increase of %ΔVI in INH patients (6.9%, 95% CI 1.0–12.8%; p=0.026). CPAP-induced change from baseline in %ΔVI after sleep was 7.5% (95% CI 2.6–12.2%, p=0.005) in the INH group and 5.7% (95% CI 2.2–9.3%, p=0.004) in the D-NSH group. In contrast, %ΔVI before sleep only decreased with CPAP in the D-NSH patients (3.0%, 95% CI 0.5–5.6%; p=0.023). In conclusion, CPAP reduces the nocturnal increase of peripheral chemosensitivity experienced by INH patients and corrects the high daytime sensitivity of patients with D-NSH. Differences in response to CPAP between these patients can help better understand the mechanisms of perpetuation of hypertension in sleep apnoea. Peripheral chemosensitivity justifies differences in nocturnal–diurnal blood pressure in patients with sleep apnoea http://ow.ly/ntYr30eFU0b