Showing papers by "Judith Garcia-Aymerich published in 2011"

Antibiotics for exacerbations of chronic obstructive pulmonary disease

Abstract: Background Many patients with an exacerbation of chronic obstructive pulmonary disease (COPD) are treated with antibiotics. However, the value of antibiotics remains uncertain as systematic reviews and clinical trials have shown conflicting results. Objectives To assess the effects of antibiotics in the management of acute COPD exacerbations on treatment failure as observed between seven days and one month after treatment initiation (primary outcome) and on other patient-important outcomes (mortality, adverse events, length of hospital stay). Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and other electronically available databases up to September 2012. Selection criteria Randomised controlled trials (RCTs) in people with acute COPD exacerbations comparing antibiotic therapy and placebo with a follow-up of at least seven days. Data collection and analysis Two review authors independently screened references and extracted data from trial reports. We kept the three groups of outpatients, inpatients and patients admitted to the intensive care unit (ICU) separate for benefit outcomes and mortality because we considered them to be clinically too different to be summarised in one group. We considered outpatients to have a mild to moderate exacerbation, inpatients to have a severe exacerbation and ICU patients to have a very severe exacerbation. Where outcomes or study details were not reported we requested missing data from the authors of the primary studies. We calculated pooled risk ratios (RR) for treatment failure, Peto odds ratios (OR) for rare events (mortality and adverse events) and weighted mean differences (MD) for continuous outcomes using fixed-effect models. We used GRADE to assess the quality of the evidence. Main results Sixteen trials with 2068 participants were included. In outpatients (mild to moderate exacerbations), there was evidence of low quality that antibiotics did statistically significantly reduce the risk for treatment failure between seven days and one month after treatment initiation (RR 0.75; 95% CI 0.60 to 0.94; I2 = 35%) but they did not significantly reduce the risk when the meta-analysis was restricted to currently available drugs (RR 0.80; 95% CI 0.63 to 1.01; I2 = 33%). Evidence of high quality showed that antibiotics statistically significantly reduced the risk of treatment failure in inpatients with severe exacerbations (ICU not included) (RR 0.77; 95% CI 0.65 to 0.91; I2 = 47%) regardless of whether restricted to current drugs. The only trial with 93 patients admitted to the ICU showed a large and statistically significant effect on treatment failure (RR 0.19; 95% CI 0.08 to 0.45; high-quality evidence). Evidence of low-quality from four trials in inpatients showed no effect of antibiotics on mortality (Peto OR 1.02; 95% CI 0.37 to 2.79). High-quality evidence from one trial showed a statistically significant effect on mortality in ICU patients (Peto OR 0.21; 95% CI 0.06 to 0.72). Length of hospital stay (in days) was similar in the antibiotics and placebo groups except for the ICU study where antibiotics statistically significantly reduced length of hospital stay (mean difference -9.60 days; 95% CI -12.84 to -6.36 days). One trial showed no effect of antibiotics on re-exacerbations between two and six weeks after treatment initiation. Only one trial (N = 35) reported health-related quality of life but did not show a statistically significant difference between the treatment and control group. Evidence of moderate quality showed that the overall incidence of adverse events was higher in the antibiotics groups (Peto OR 1.53; 95% CI 1.03 to 2.27). Patients treated with antibiotics experienced statistically significantly more diarrhoea based on three trials (Peto OR 2.62; 95% CI 1.11 to 6.17; high-quality evidence). Authors' conclusions Antibiotics for COPD exacerbations showed large and consistent beneficial effects across outcomes of patients admitted to an ICU. However, for outpatients and inpatients the results were inconsistent. The risk for treatment failure was significantly reduced in both inpatients and outpatients when all trials (1957 to 2012) were included but not when the analysis for outpatients was restricted to currently used antibiotics. Also, antibiotics had no statistically significant effect on mortality and length of hospital stay in inpatients and almost no data on patient-reported outcomes exist. These inconsistent effects call for research into clinical signs and biomarkers that help identify patients who benefit from antibiotics and patients who experience no effect, and in whom downsides of antibiotics (side effects, costs and multi-resistance) could be avoided.

Identification and prospective validation of clinically relevant chronic obstructive pulmonary disease (COPD) subtypes

Abstract: Background Chronic obstructive pulmonary disease (COPD) is increasingly considered a heterogeneous condition. It was hypothesised that COPD, as currently defined, includes different clinically relevant subtypes. Methods To identify and validate COPD subtypes, 342 subjects hospitalised for the first time because of a COPD exacerbation were recruited. Three months after discharge, when clinically stable, symptoms and quality of life, lung function, exercise capacity, nutritional status, biomarkers of systemic and bronchial inflammation, sputum microbiology, CT of the thorax and echocardiography were assessed. COPD groups were identified by partitioning cluster analysis and validated prospectively against cause-specific hospitalisations and all-cause mortality during a 4 year follow-up. Results Three COPD groups were identified: group 1 (n¼126, 67 years) was characterised by severe airflow limitation (postbronchodilator forced expiratory volume in 1 s (FEV1) 38% predicted) and worse performance in most of the respiratory domains of the disease; group 2 (n¼125, 69 years) showed milder airflow limitation (FEV1 63% predicted); and group 3 (n¼91, 67 years) combined a similarly milder airflow limitation (FEV1 58% predicted) with a high proportion of obesity, cardiovascular disorders, diabetes and systemic inflammation. During follow-up, group 1 had more frequent hospitalisations due to COPD (HR 3.28, p<0.001) and higher all-cause mortality (HR 2.36, p¼0.018) than the other two groups, whereas group 3 had more admissions due to cardiovascular disease (HR 2.87, p¼0.014). Conclusions In patients with COPD recruited at their first hospitalisation, three different COPD subtypes were identified and prospectively validated: ‘severe respiratory COPD’, ‘moderate respiratory COPD’, and ‘systemic COPD’.

Lung function impairment, COPD hospitalisations and subsequent mortality

Abstract: Background Hospitalisations and their sequelae comprise key morbidities in the natural history of chronic obstructive pulmonary disease (COPD). A study was undertaken to examine the associations between lung function impairment and COPD hospitalisation, and COPD hospitalisation and mortality. Methods The analysis included a population-based sample of 20 571 participants with complete demographic, lung function, smoking, hospitalisation and mortality data, with 10-year median follow-up. Participants were classified by prebronchodilator lung function according to the modified Global Initiative on Obstructive Lung Disease (GOLD) criteria. Hospitalisations were defined by the presence of a COPD discharge diagnosis (ICD-9 codes 490–496). Incidence rate ratios (IRR) of COPD admissions and hazard ratios (HR) of mortality with respective 95% CI were calculated, adjusted for potential confounders. Results The prevalence of modified GOLD categories was normal (36%), restricted (15%), GOLD stage 0 (22%), GOLD stage 1 (13%), GOLD stage 2 (11%) and GOLD stages 3 or 4 (3%). Adjusted IRRs (and 95% CI) indicated an increased risk of COPD hospitalisation associated with each COPD stage relative to normal lung function: 4.7 (3.7 to 6.1), 2.1 (1.6 to 2.6), 3.2 (2.6 to 4.0), 8.0 (6.4 to 10.0) and 25.5 (19.5 to 33.4) for the restricted, GOLD stage 0, GOLD stage 1, GOLD stage 2 and GOLD stages 3 or 4, respectively. Hospitalisation for COPD increased the risk of subsequent mortality (HR 2.7, 95% CI 2.5 to 3.0), controlling for severity, number of prior hospitalisations and other potential confounders. The increase in mortality associated with admission was very similar across the modified GOLD stages. Conclusions COPD severity was associated with a higher rate of severe exacerbations requiring hospitalisation, although severe exacerbations at any stage were associated with a higher risk of short-term and long-term all-cause mortality.

Anti-tissue antibodies are related to lung function in chronic obstructive pulmonary disease.

Abstract: Rationale: Chronic obstructive pulmonary disease (COPD) is a multicomponent disease. Autoimmunity can contribute to the pathogenesis of COPD.Objectives: This study investigates the prevalence of circulating antinuclear antibodies (ANA) and anti-tissue (AT) antibodies, two common markers of autoimmunity, in COPD and their relationship with several components of the disease.Methods: We determined lung function, the serum titers of ANA and AT by immunofluorescence, and the serum levels of C-reactive protein (CRP) by high sensitivity nephelometry in 328 patients with clinically stable COPD and in 67 healthy controls recruited in the PAC-COPD study. Multiple linear and logistic regression analysis was used to analyze results.Measurements and Main Results: The prevalence of abnormal ANA and AT titers was 34% and 26% in patients and 3% and 6% in controls, respectively. Levels of AT greater than or equal to 1:320 were seen in 21% of patients with COPD and were independently associated with the severity of airflow...

WITHDRAWN: Antibiotics for exacerbations of chronic obstructive pulmonary disease.

Abstract: Background Most patients with an exacerbation of chronic obstructive pulmonary disease (COPD) are treated with antibiotics However the value of their use remains uncertain Some controlled trials of antibiotics have shown benefit (Berry 1960; Pines 1972) while others have not (Elmes 1965b; Nicotra 1982) Objectives To conduct a systematic review of the literature estimating the value of antibiotics in the management of acute COPD exacerbations Search strategy We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2005, issue 4) which contains the Acute Respiratory Infections Group's Specialized Register; MEDLINE (1966 to December 2005); EMBASE (1974 to December 2005); Web of Science (December 2005), and other electronically available databases Selection criteria Randomised controlled trials (RCTs) in patients with acute COPD exacerbations comparing antibiotic (for a minimum of five days) and placebo Data collection and analysis Data were analysed using Review Manager software Continuous data were analysed using weighted mean differences (WMD) and 95% confidence intervals (CI) Relative risks (RR) (and 95% CI) were calculated for all dichotomous data Where appropriate, number needed to treat to benefit (NNT) and 95% CI were calculated Main results Eleven trials with 917 patients were included Ten trials used increased cough, sputum volume and purulence diagnostic criteria for COPD exacerbation Eight-hundred and fifty-seven patients provided data for outcomes including mortality, treatment failure, increased sputum volume, sputum purulence, PaCO(2), PaO(2), peak flow and adverse events Antibiotic therapy regardless of antibiotic choice significantly reduced mortality (RR 023; 95% CI 010 to 052 with NNT of 8; 95% CI 6 to 17), treatment failure (RR 047; 95% CI 036 to 062 with NNT of 3; 95% CI 3 to 5) and sputum purulence (RR 056; 95% CI 041 to 077 with NNT of 8; 95% CI 6 to 17) There was a small increase in risk of diarrhoea with antibiotics (RR 286; 95% CI 106 to 776) Antibiotics did not improve arterial blood gases and peak flow Authors' conclusions This review shows that in COPD exacerbations with increased cough and sputum purulence antibiotics, regardless of choice, reduce the risk of short-term mortality by 77%, decrease the risk of treatment failure by 53% and the risk of sputum purulence by 44%; with a small increase in the risk of diarrhoea These results should be interpreted with caution due to the differences in patient selection, antibiotic choice, small number of included trials and lack of control for interventions that influence outcome, such as use of systemic corticosteroids and ventilatory support Nevertheless, this review supports antibiotics for patients with COPD exacerbations with increased cough and sputum purulence who are moderately or severely ill

Validity of instruments to measure physical activity may be questionable due to a lack of conceptual frameworks: a systematic review

Abstract: Guidance documents for the development and validation of patient-reported outcomes (PROs) advise the use of conceptual frameworks, which outline the structure of the concept that a PRO aims to measure. It is unknown whether currently available PROs are based on conceptual frameworks. This study, which was limited to a specific case, had the following aims: (i) to identify conceptual frameworks of physical activity in chronic respiratory patients or similar populations (chronic heart disease patients or the elderly) and (ii) to assess whether the development and validation of PROs to measure physical activity in these populations were based on a conceptual framework of physical activity. Two systematic reviews were conducted through searches of the Medline, Embase, PsycINFO, and Cinahl databases prior to January 2010. In the first review, only 2 out of 581 references pertaining to physical activity in the defined populations provided a conceptual framework of physical activity in COPD patients. In the second review, out of 103 studies developing PROs to measure physical activity or related constructs, none were based on a conceptual framework of physical activity. These findings raise concerns about how the large body of evidence from studies that use physical activity PRO instruments should be evaluated by health care providers, guideline developers, and regulatory agencies.

Opportunities and challenges in the Genetics of COPD 2010: An international COPD Genetics conference report

Abstract: Chronic obstructive pulmonary disease (COPD) is defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) as a disease state characterized by airflow limitation that is not fully reversible (1). Cigarette smoking is the most important risk factor for the development of COPD. Although the dose-response relationship between cigarette smoking and pulmonary function is well-established, there is considerable variability in the reduction in FEV1 among smokers with similar smoking exposures (2, 3). The low percentage of variance in pulmonary function explained by smoking suggests that there could be genetic differences in susceptibility to the effects of cigarette smoking (4, 5). In addition to genetic factors, other environmental determinants such as indoor biomass smoke exposure can be important risk factors for COPD (6). A small percentage of COPD patients (estimated at 1-2%) inherit severe alpha-1 antitrypsin (AAT) deficiency, which proves that genetic factors can in-fluence COPD susceptibility. The discovery of AAT deficiency was a major factor in the development of the Protease-Antiprotease Hypothesis for COPD, which has been one of the prevailing models of disease pathogenesis for more than 40 years. With the substantial impact of AAT deficiency on our understanding of COPD pathogenesis, it was natural to hope that the identification of other COPD susceptibility genes would lead to similar novel insights into COPD. Until recently, however, progress in the identification of additional genetic risk factors for COPD has been slow. To facilitate the development of such research, a meeting of COPD genetics investigators was held on July 13-14,2010 in Boston. The goals of the meeting were: To review the current state of COPD genetics research; To discuss existing study populations for COPD genetics research throughout the world; To consider opportunities for collaborations between different COPD research groups through an International COPD Genetics Consortium; To recognize challenges in building COPD genetics collaborations and to discuss them openly; and, To develop a framework for future collaborative studies. Current status of COPD genetics research Many candidate gene association studies have been performed over the past 40 years, but the results have been largely inconsistent. These inconsistencies likely relate to a variety of methodological issues, including small sample sizes, variable definitions of case and control groups, failure to adjust for multiple statistical testing, and inadequate adjustments for population stratification and smoking exposure. Most of the studies describing COPD-associated polymorphisms were performed in White populations (7). A meta-analysis of 20 polymorphisms in 12 candidate genes involved in the protease-antiprotease balance and several an-tioxidant pathways showed that, after combining independent studies, many of these candidate genes had no association with COPD (8). Another factor likely impeding the progress of identifying COPD susceptibility genes is the lack of accurate phenotypic characterization of this complex and heterogeneous disease. Airflow limitation determined by spirometry has been the most common approach to classify and monitor the disease. Structural changes of the lung including emphysema and small airway obstruction are the primary processes that affect lung function (9), but they are not easily discernable with the simple spirometric measures commonly used for phe-notyping COPD. Recent advances in characterizing pathologic changes such as emphysema and remodeling of the small and large airways by quantitative analyses of image data from multidetector computed tomography (CT), together with physiological testing, have been helpful to differentiate COPD phenotypes (emphysema-predominant, airway-predominant, or mixed)(10). Study populations that have chest CT data may help to better identify COPD-associated genetic variations (11). Other potentially relevant COPD phenotypes, such as cachexia and low exercise capacity, have not been widely analyzed in COPD genetic studies. Perhaps the greatest problem in the candidate gene era of COPD genetic studies was improper candidate gene selection, which reflects our limited understanding of COPD pathogenesis. However, the application of genome-wide association studies (GWAS), which provide an unbiased and comprehensive search throughout the genome for common susceptibility loci, has changed the landscape of COPD genetics. Based on GWAS, three genetic loci have been unequivocally associated with COPD susceptibility, located on chromosome 4 near the HHIP gene, on chromosome 4 in the FAM13A gene, and on chromosome 15 in a block of genes which contains several components of the nicotinic acetyl-choline receptor as well as the IREB2 gene. In 2009, a series of studies provided convincing support for these three genetic loci in COPD susceptibility. Pillai and colleagues found genome-wide significant associations of the CHRNA3/CHRNA5/IREB2 region to COPD (12). DeMeo and colleagues performed gene expression studies of normal vs. COPD lung tissues followed by genetic association analysis of COPD (13), suggesting that at least one of the key COPD genetic determinants in the chromosome 15 GWAS region was IREB2. In the Framingham Heart Study (14), the HHIP region was associated with FEV1/FVC at genome-wide significance with replication of the effect on FEV1/FVC demonstrated in an independent sample drawn from the Family Heart Study, and this same region nearly reached genome-wide significance with COPD susceptibility in the Pillai paper (12). Recently, two papers published in Nature Genetics from large general population samples have provided strong support for the association of HHIP SNPs with FEV1/FVC (15, 16). One of these articles, from the CHARGE Consortium, also found evidence for association of FEV1/FVC with the FAM13A locus (15), which has been strongly associated with COPD susceptibility (17). Moreover, several case-control studies from other European populations have replicated these findings by confirming significant associations to the chromosome 15q25 locus (CHRNA3/CHRNA5/IREB2) (18, 19), chromosome 4q31 locus (HHIP) (20, 21), and chromosome 4q22 locus (FAM13 A) (22). Thus, the frustration of inconsistent genetic association results in COPD from the beginning of the last decade has been replaced by optimism regarding the likely importance of the IREB2/CHRNA3/CHRNA5, HHIP, and FAM13A loci in COPD susceptibility.

Validation of the Yale Physical Activity Survey in Chronic Obstructive Pulmonary Disease Patients

Abstract: Background Patients with chronic obstructive pulmonary disease (COPD) perform limited physical activity. Surprisingly, there is a lack of research in COPD about the validity of physical activity questionnaires. Our aim was to validate the Yale Physical Activity Survey in COPD patients in order to quantify and classify their levels of physical activity. Methods 172 COPD patients from 8 university hospitals in Spain wore an accelerometer (SenseWear® Pro2 Armband) for 8 days and answered the questionnaire 15 days later. Statistical analyses used to compare both tools measures included: (i) Spearman's correlation coefficient, (ii) intraclass correlation coefficient (ICC) and Bland–Altman plots, (iii) distribution of accelerometer measurements according to tertiles of the questionnaire, and (iv) receiver operating characteristic (ROC) curves to detect sedentary patients. Results 94% of participants were men, 28% were active smokers and 7% were currently working. Mean (standard deviation) age was 70 (8) years, mean post-bronchodilator FEV1 was 52 (15)% predicted, and median (p25–p75) steps taken was 5702 (3273–9253) steps per day−1. Spearman correlations were low to moderate (from 0.29 to 0.52, all P Conclusions The Yale Physical Activity Survey may be a valid tool to classify, but not to quantify, physical activity performed by COPD patients. The summary index of this questionnaire, based on seven short questions, shows the best validity properties. This suggests that it should be considered as a screening tool to identify patients at risk for sedentarism.

Validación del cuestionario de actividad física de Yale en pacientes con enfermedad pulmonar obstructiva crónica

Abstract: Introduccion Los pacientes con enfermedad pulmonar obstructiva cronica (EPOC) se caracterizan por una actividad fisica limitada. Sorprendentemente, apenas se dispone de investigacion sobre los cuestionarios para medir la actividad fisica en la EPOC. El objetivo del presente estudio fue validar el cuestionario Yale Physical Activity Survey en pacientes con EPOC. Metodos Un total de 172 pacientes de 8 hospitales universitarios espanoles usaron un acelerometro (SenseWear®PrO2Armband) durante 8 dias y contestaron el cuestionario. Los analisis estadisticos de comparacion de ambos instrumentos incluyeron: a) correlacion de Spearman; b) coeficiente de correlacion intraclase (CCI) y graficos de Bland-Altman; c) distribucion de las medidas del acelerometro segun los terciles del cuestionario, y d) la curva receiver operating characteristic (ROC) para detectar a los pacientes sedentarios. Resultados El 94% de los participantes eran hombres, el 28% eran fumadores y el 7% eran trabajadores activos; la edad media (±DE) fue de 70 (8) anos, el volumen espiratorio medio en el primer segundo (VEMS) posbroncodilatador fue de 52 (15) como porcentaje del valor de referencia, y la mediana (p25-p75) de pasos fue de 5.702 (3.273-9.253) pasos/dia. Las correlaciones de Spearman fueron debiles o moderadas (desde 0,29 hasta 0,52, todas las p<0,001). Los CCI mostraron concordancias debiles (desde 0,34 hasta 0,40, todas las p<0,001). Los graficos de Bland-Altman mostraron una gran variabilidad en la concordancia. Se encontraron diferencias significativas en las medidas del acelerometro segun los terciles del cuestionario (todas las p<0,001). El area bajo la curva ROC para identificar el sedentarismo fue de 0,71 (intervalo de confianza del 95%: 0,63-0,79). Conclusion El cuestionario Yale Physical Activity Survey es una herramienta valida para clasificar la actividad fisica que realizan los pacientes con EPOC, pero no para cuantificarla. El indice resumen del cuestionario, originado de tan solo 7 preguntas, muestra los mejores resultados de validez, sugiriendo que deberia considerarse un instrumento de cribado para identificar a los pacientes que corren riesgo de sedentarismo.

The investigation of asthma phenotypes.

Abstract: PURPOSE OF REVIEW: Asthma is a heterogeneous disease constituted by overlapping separate syndromes. This review discusses recent published data relevant to asthma and severe asthma classification, resting either on the 'candidate' approach based on criteria chosen by experts or on the 'exploratory' approach based on unsupervised statistical methods. RECENT FINDINGS: Following the 'candidate' approach, groups of experts recently reviewed the classification of severe asthma to be applicable in low-income, milddle-income, and high-income countries and provided a systematic algorithm to diagnose severe refractory asthma. The concept of asthma endotypes involving different biological mechanisms has recently being proposed. Results from the 'exploratory' approach support the clinical heterogeneity in severe asthma and the need for new approaches for the classification of asthma severity. The novel childhood and adult asthma phenotypes recently identified using the exploratory approach were supported by first evidence of validity (replication in independent studies, assessment of their discriminative properties, and effect on clinical prognosis). SUMMARY: Research on asthma phenotypes has increased exponentially in the last year. The main focus has been on severe asthma, likely due to its clinical and socioeconomic burden. Interestingly, many of the phenotypes identified are stable across populations and methodological approaches. Further analyses on the asthma phenotypes are needed to address their stability over time and their relevance from clinical and etiological perspectives.