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Association of oxidative stress markers and C-reactive protein with multidimensional indexes in COPD.

To evaluate the oxidative stress and the C-reactive protein (CRP) in chronic obstructive pulmonary disease (COPD) patients and their correlation between the severity of the disease according to GOLD criteria and multidimensional indexes such as BODE index. A blood sample was collected for thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase, glutathione (GSH), homocysteine (HCY) and CRP analysis from 45 stable COPD patients. Lung function, body nutritional status, dyspnea and 6-min walk test (6MWT) were evaluated.

Patients with GOLD stage IV presented a higher value for the TBARS than stage I patients (4.47 + 1.58 versus 2.27 + 1.04 nmol/mL, p < 0.05). CRP was higher for GOLD IV (2.46 + 3.68 mg/dL) than other stages (GOLD I: 0.39 + 0.25, GOLD II: 0.39 + 0.18 and GOLD III: 0.48 + 0.36 mg/dL, p < 0.05). Oxidative stress markers measured as TBARS presented a negative correlation between forced expiratory volume in the first second (FEV(1)) post bronchodilatador (% predicted; r = -0.39, p = 0.01) and positive correlations with Modified Medical Research Council Scale (MMRC) dyspnea index (r = 0.40, p = 0.01), multidimensional index (r = 0.49, p = 0.001) and BODE index (r = 0.51, p = 0.001).

Dynamic hyperinflation, arterial blood oxygen and airway oxidative stress in stable COPD patients.

There is considerable evidence that oxidative stress is increased in patients with COPD, although little information is available about its relation with the structural and functional alterations produced by COPD. We evaluate the relationship between 8-isoprostane in exhaled breath condensate (EBC) of stable COPD patients and the main parameters of the disease such as dyspnoea, 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 males with moderate to very severe COPD. 8-isoprostane levels in EBC were measured by EIA. Regional lung densities were measured by lung densitometry with high resolution computed tomography. Arterial blood gases, lung volumes and diffusing capacity were determined. Patients performed a six-minute 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 BODE index. 8-isoprostane levels were related to smoking intensity, lung densities in expiration, static lung volumes, PaO(2), diffusion capacity, distance walked in six minutes, 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 who did not (21%). 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<0.001).

CONCLUSION: In stable COPD patients, oxygen level and dynamic hyperinflation are related to airway oxidative stress.

Association of SERPINE2 with Asthma.

The "Dutch hypothesis" suggests that asthma and COPD have common genetic determinants. SERPINE2 is a gene that has been previously associated with COPD. We sought to determine whether SERPINE2 is associated with asthma and asthma-related phenotypes.

METHODS: We measured the association of 39 SERPINE2 single nucleotide polymorphisms (SNPs) with asthma-related phenotypes in 655 parent-child trios of the Childhood Asthma Management Program, and we measured the association of 19 SERPINE2 SNPs with asthma in a case-control design of 359 CAMP probands and 846 population controls. We attempted to replicate primary asthma-related phenotype findings in one independent population and primary asthma affection status findings in two independent populations. We compared association results with CAMP proband expression quantitative trait loci (eQTL).

RESULTS: Nine of 39 SNPs had p-values <0.05 for at least one phenotype in CAMP, and two of these replicated in an independent population of 426 childhood asthmatics. Six of 19 SNPs had p-values <0.05 for association with asthma in CAMP/Illumina. None of these replicated in two independent populations. The eQTL revealed that five SNPs associated with asthma in CAMP/Illumina and one SNP associated with FEV(1) in CAMP are strongly correlated with SERPINE2 expression levels. Comparison of results to previous COPD studies identified five SNPs that have been associated with both asthma- and COPD-related phenotypes.

CONCLUSIONS: Our results weakly support SERPINE2 as a Dutch Hypothesis candidate gene via nominally significant associations with asthma and related traits. Further study of SERPINE2 is necessary to verify its involvement in asthma and COPD.

The Best on Infections, update from the 2010 ERS Conference.

Respiratory tract infections and tuberculosis are among the leading reasons for seeking medical care. In this report the most recent advances in the field of clinical research and basic sciences of respiratory infections and tuberculosis are presented through the analysis of some of the best abstracts presented at the 20(th) ERS Congress in Barcelona and their subsequent publications in major journals.

The role of viruses in COPD exacerbations, the importance of new biomarkers in the management and risk assessment of LRTIs, new modalities of treatment of respiratory infections as well as new tools for the diagnosis of latent and active tuberculosis in special subgroups of patients (children, immunocompromised individuals), and the new epidemiological threat of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis cases are discussed.

The 2010 NICE COPD Guidelines: how do they compare with the GOLD guidelines?

The UK National Institute for Health and Clinical Excellence (NICE) has produced a 2010 partial update of its original 2004 Guidelines on COPD management. The definition of airflow obstruction has been altered to a post-bronchodilator FEV1/FVC ratio < 0.7 and the severity of airflow obstruction has been similarly aligned with the Global initiative for Obstructive Lung Disease (GOLD) guideline definition. However, patients with GOLD Stage 1 (i.e. FEV1 predicted > 80%) must be symptomatic for a diagnosis of COPD to be made under the new NICE criteria.

Recent large scale trials have resulted in a new inhaled pharmacotherapy algorithm which includes early use of inhaled corticosteroid/long-acting β2-agonist combination therapy for patients with an FEV1 < 50% predicted. In spite of an apparent emphasis on pharmacotherapy, both GOLD and NICE Guidelines emphasise that COPD is a multi-system disease requiring a multidimensional approach to treatment. In particular, the importance of smoking cessation and pulmonary rehabilitation is reiterated, the latter not only being of use in managing stable disease but also following hospital discharge.

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