Effect of a rehabilitation-based chronic disease management program targeting severe COPD exacerbations on readmission patterns.

BACKGROUND: Pulmonary rehabilitation (PR) is recommended after a severe COPD exacerbation, but its short- and long-term effects on health care utilization have not been fully established. AIMS: The aims of this study were to evaluate patient compliance with a chronic disease management (CDM) program incorporating home-based exercise training as the main component after a severe COPD exacerbation and to determine its effects on health care utilization in the following year. MATERIALS AND METHODS: COPD patients with a severe exacerbation were included in a case-cohort study at admission. An intervention group participated in a nurse-supervised CDM program during the 2 months after discharge, comprising of home-based PR with exercise components directly supervised by a physiotherapist, while the remaining patients followed usual care. RESULTS: Nineteen of the twenty-one participants (90.5%) were compliant with the CDM program and were compared with 29 usual-care patients. Compliance with the program was associated with statistically significant reductions in admissions due to respiratory disease in the following year (median [interquartile range]: 0 [0-1] vs 1 [0-2.5]; P=0.022) and in days of admission (0 [0-7] vs 7 [0-12]; P=0.034), and multiple linear regression analysis confirmed the protective effect of the CDM program (ß coefficient -0.785, P=0.014, and R2=0.219). CONCLUSION: A CDM program incorporating exercise training for COPD patients without limiting comorbidities after a severe exacerbation achieves high compliance and reduces admissions in the year following after the intervention.

FDG-PET parameters predicting mediastinal malignancy in lung cancer.

BACKGROUND: Staging of mediastinal lymph nodes in non-small cell lung cancer (NSCLC) is mandatory. The maximum Standard Uptake Value (SUVmax) obtained using F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) is the best non-invasive technique available for this evaluation, but its performance varies from center to center. The aim of the present study was to identify FDG-PET predictors of mediastinal malignancy that are able to minimize intercenter variability and improve the selection of subsequent staging procedures. METHOD: A multicenter study of NSCLC patients staged through FDG-PET and endobronchial ultrasonography with needle aspiration (EBUS-NA) was performed using therapeutic surgery with systematic nodal dissection as gold standard. Intercenter variability and predictive power for mediastinal malignancy of different FDG-PET measures were assessed, as well as the role of these measures for selecting additional staging procedures. RESULTS: One hundred and twenty-one NSCLC patients, of whom 94 (72%) had ≥1 hypermetabolic spots in the mediastinum, were included in the study. Mean SUVmax of the primary tumor was 12.3 (SD 6.3), and median SUVmax of the highest hypermetabolic spots in the mediastinum was 3.9 (IQR 2.4-7). Variability of FDG-PET measures between hospitals was statistically significant (p = 0.016 and p < 0.001 respectively), but lost significance when SUVmax in the mediastinum was expressed as a ratio or a subtraction from the primary tumor (SUVmax mediastinum/tumor, p = 0.083; and SUVmax mediastinum - tumor, p = 0.428 respectively). SUVmax mediastinum/tumor showed higher accuracy in the ROC analysis (AUC 0.77 CI 0.68-0.85, p < 0.001), and showed predictive power for mediastinal malignancy when using a 0.4 cutoff (OR 6.62, 95%CI 2.98-14.69). Sensitivities and negative predictive values of clinical staging through EBUS-NA attained values ranging between 57% and 92% after FDG-PET, which improved with additional techniques when the tumor had a diameter >3 cm and/or a SUVmax mediastinum/tumor ratio >0.4. CONCLUSION: The SUVmax mediastinum/tumor ratio is a good predictor of regional tumor extension in NSCLC. This measure is not influenced by intercenter variability and has an accuracy of over 70% for the identification of malignancy when using a 0.4 cutoff.

Aberrant gene methylation and bronchial dysplasia in high risk lung cancer patients.

INTRODUCTION: The risk for lung cancer is incremented in high degree dysplasia (HGD) and in subjects with hypermethylation of multiple genes. We sought to establish the association between them, as well as to analyze the DNA aberrant methylation in sputum and in bronchial washings (BW). METHODS: Cross sectional study of high risk patients for lung cancer in whom induced sputum and autofluorescence bronchoscopy were performed. The molecular analysis was determined on DAPK1, RASSF1A and p16 genes using Methylation-specific PCR. RESULTS: A total of 128 patients were enrolled in the study. Dysplasia lesions were found in 79 patients (61.7%) and high grade dysplasia in 20 (15.6%). Ninety eight patients out of 128 underwent molecular analysis. Methylation was observed in bronchial secretions (sputum or BW) in 60 patients (61.2%), 51 of them (52%) for DAPK1, in 20 (20.4%) for p16 and in three (3.1%) for RASSF1A. Methylated genes only found in sputum accounted for 38.3% and only in BW in 41.7%, and in both 20.0%. In the 11.2% of the patients studied, HGD and a hypermethylated gene were present, while for the 55.1% of the sample only one of both was detected and for the rest of the subjects (33.6%), none of the risk factors were observed. CONCLUSIONS: Our data determines DNA aberrant methylation panel in bronchial secretions is present in a 61.2% and HGD is found in 15.6%. Although both parameters have previously been identified as risk factors for lung cancer, the current study does not find a significative association between them. The study also highlights the importance of BW as a complementary sample to induced sputum when analyzing gene aberrant methylation.

Bronchial microbiome of severe COPD patients colonised by Pseudomonas aeruginosa.

The bronchial microbiome in severe COPD during stability and exacerbation in patients chronically colonised by Pseudomonas aeruginosa (PA), has not been defined. Our objective was to determine the characteristics of the bronchial microbiome of severe COPD patients colonised and not colonised by P. aeruginosa and its changes during exacerbation. COPD patients with severe disease and frequent exacerbations were categorised according to chronic colonisation by P. aeruginosa. Sputum samples were obtained in stability and exacerbation, cultured, and analysed by 16S rRNA gene amplification and pyrosequencing. Sixteen patients were included, 5 of them showing chronic colonisation by P. aeruginosa. Pseudomonas genus had significantly higher relative abundance in stable colonised patients (p = 0.019), but no significant differences in biodiversity parameters were found between the two groups (Shannon, 3 (2-4) vs 3 (2-3), p = 0.699; Chao1, 124 (77-159) vs 140 (115-163), p = 0.364). In PA-colonised patients bronchial microbiome changed to a microbiome similar to non-PA-colonised patients during exacerbations. An increase in the relative abundance over 20 % during exacerbation was found for Streptococcus, Pseudomonas, Moraxella, Haemophilus, Neisseria, Achromobacter and Corynebacterium genera, which include recognised potentially pathogenic microorganisms, in 13 patients colonised and not colonised by P. aeruginosa with paired samples. These increases were not identified by culture in 5 out of 13 participants (38.5 %). Stable COPD patients with severe disease and PA-colonised showed a similar biodiversity to non-PA-colonised patients, with a higher relative abundance of Pseudomonas genus in bronchial secretions. Exacerbation in severe COPD patients showed the same microbial pattern, independently of previous colonisation by P. aeruginosa.

Representativeness of nodal sampling with endobronchial ultrasonography in non-small-cell lung cancer staging.

The objective of our study was to determine the procedure-related requirements of mediastinal node sampling with endobronchial ultrasonography with real-time transbronchial needle aspiration (EBUS-TBNA) that would provide negative predictive value (NPV) for the identification of stage III disease in non-small-cell lung cancer (NSCLC) high enough to consider the technique equivalent to cervical mediastinoscopy. Representative EBUS-TBNA was defined as a sampling procedure obtaining satisfactory samples from normal nodes in regions 4R, 4L and 7 or diagnosing malignancy in mediastinal nodes. NPV was estimated using the results of postsurgical staging in patients who underwent surgery as a reference. Two-hundred ninety-six patients staged with EBUS-TBNA were included. Representative samples from regions 4R, 4L and 7 showing nonmalignant cytology were obtained from 98 patients (33.1%) and EBUS-TBNA detected N2/N3 disease in 150 (50.7%). Accordingly, an EBUS-TBNA procedure accomplishing the representativeness criteria required for sampling was attained in 248 of the participating patients (83.8%). The NPV of the procedure in this setting was 93.6%, with false-negative results only found in 5 patients, four of them with nodal metastasis out of the reach of EBUS-TBNA (regions 5, 8 and 9). In conclusion, representative sampling of regions 4R, 4L and 7 is achieved in more than 80% of patients staged using EBUS-TBNA, and in the procedures that attain this requirement a NPV >90% for mediastinal malignancy is reached, a figure equivalent to cervical mediastinoscopy.

Beclomethasone/formoterol in the management of COPD: a randomised controlled trial.

OBJECTIVES: To evaluate the effect of beclomethasone/formoterol versus budesonide/formoterol (non-inferiority) and versus formoterol (superiority) in patients with severe stable chronic obstructive pulmonary disease (COPD). METHODS: A double-blind, double-dummy, randomised, active-controlled, parallel-group study. After 4 weeks run-in with ipratropium/salbutamol (40/200 µg, three times daily) patients were randomised to receive beclomethasone/formoterol (200/12 µg pressurised metered dose inhaler), budesonide/formoterol (400/12 µg dry powder inhaler) or formoterol (12 µg dry powder inhaler) twice daily for 48 weeks. Co-primary efficacy variables were change from baseline to 48 weeks in pre-dose morning forced expiratory volume in 1 s (FEV(1)) and mean rate of COPD exacerbations. RESULTS: Of 718 patients randomised, 703 (232 beclomethasone/formoterol, 238 budesonide/formoterol, 233 formoterol) were in the ITT analysis. Improvement in pre-dose morning FEV(1) was 0.077 L, 0.080 L and 0.026 L for beclomethasone/formoterol, budesonide/formoterol and formoterol respectively (LS mean from the ANCOVA model). Beclomethasone/formoterol was not inferior to budesonide/formoterol (95% CI of the difference -0.052, 0.048) and superior to formoterol (p = 0.046). The overall rate of COPD exacerbations/patient/year was similar and not statistically significantly different among treatments (beclomethasone/formoterol 0.414, budesonide/formoterol 0.423 and formoterol 0.431). Quality of life and COPD symptoms improved in all groups and use of rescue medication decreased. Safety profiles were as expected and treatments well-tolerated. CONCLUSIONS: Beclomethasone/formoterol (400/24 µg) treatment for 48 weeks improved pulmonary function, reduced symptoms compared to formoterol, was safe and well-tolerated in patients with severe stable COPD. Neither of the long-acting ß2-agonist/inhaled corticosteroid combinations affected the low exacerbation rate seen in this population.

Variability and effects of bronchial colonisation in patients with moderate COPD.

Sputum and lung function were periodically assessed in stable moderate chronic obstructive pulmonary disease (COPD) outpatients to determine relationships between bronchial colonisation and inflammation. Relationships between potentially pathogenic microorganism (PPM) typology, bronchial inflammation (neutrophilia, tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-8, IL-10 and IL-12) and post-bronchodilator decline in forced expiratory volume in 1 s (FEV(1)) were analysed. PPMs periodically showing the same molecular profile using pulse field gel electrophoresis were considered long-term persistent. Bronchial colonisation was observed in 56 out of 79 follow-up examinations (70.9%) and was mainly due to Haemophilus influenzae, Pseudomonas aeruginosa and enterobacteria (n = 47). These PPMs were all related to sputum neutrophilia (p< or =0.05, Chi-squared test), and H. influenzae was related to higher levels of IL-1beta (p = 0.005) and IL-12 (p = 0.01), with a dose-response relationship (Spearman's correlation coefficient of 0.38 for IL-1beta (p = 0.001), and of 0.32 for IL-12 (p = 0.006)). Haemophilus parainfluenzae was not associated with an identifiable inflammatory response. Long-term persistence of the same strain was observed in 12 examinations (21.4%), mainly due to P. aeruginosa or enterobacteria. A neutrophilic bronchial inflammatory response was associated with a statistically significant decline in FEV(1) during follow-up (OR 2.67, 95% CI 1.07-6.62). A load-related relationship to bronchial inflammation in moderate COPD was observed for colonisation by H. influenzae, but not for colonisation by H. parainfluenzae.

Endobronchial ultrasound-guided transbronchial needle aspiration for identifying EGFR mutations.

The presence of somatic mutations of the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene in patients with advanced nonsmall cell lung cancer (NSCLC) correlates with a good response to tyrosine kinase inhibitors. The usefulness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the detection of EGFR mutations in cells recovered from malignant mediastinal nodes in patients with NSCLC was assessed. All patients with lung adenocarcinoma or unspecified NSCLC referred for staging with EBUS-TBNA were included. Nodes with a short-axis diameter of >5 mm were sampled, and genomic DNA from metastatic tumour cells was obtained for analysis of exons 19 and 21. The impact of sampling on management was assessed. EGFR gene analysis of the EBUS-TBNA sample was feasible in 26 (72.2%) out of the 36 patients with lymph node metastasis. Somatic mutations of the EGFR gene were detected in tissue obtained through EBUS-TBNA in two (10%) out of 20 patients with metastasic lung adenocarcinoma. Malignant tissue samples obtained by EBUS-TBNA from patients with nodal metastasis of NSCLC are suitable for the detection of EGFR mutations in most cases, and this technique demonstrates mutated neoplastic cells in a tenth of patients with adenocarcinoma.

e-Learning strategies in occupational legal medicine based on problem solving through "CASUS" system.

The use of online teaching tools facilitate the incorporation of self-learning methods. With a view to encouraging convergence in teaching tools and methods in Occupational Legal Medicine, an initiative was set up within the classes of Legal and Forensic Medicine at Saragossa University, as part of the EU funded NetWoRM project, which has been led since 1999 by Ludwig-Maximilians-Universität in Munich (Germany). The interest of medical students in Occupational Legal Medicine has so far been low and in addition different aspects complicate the teaching of Occupational Legal Medicine at medical schools: One reason for the low interest is the limited availability of bedside teaching, one of the students' most favourite and effective way to learn. The reason for that is that most medical schools with occupational departments only have outpatient clinics. "Interesting" patients who be need for educational purposes are therefore only available for a limited part of the day. However, in order to recognize and prevent occupational disorders each medical student and physician needs profound clinical knowledge in Occupational Legal Medicine. This project has proven to be highly efficient in permitting the creation and validation of teaching tools which cover and improve the traditional training of the Occupational Legal Medicine programme imparted in the degree of Medicine.

Efficacy of moxifloxacin in the treatment of bronchial colonisation in COPD.

This study was designed to investigate the efficacy of moxifloxacin for the eradication of bacterial colonisation of the airways in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). Out of 119 stable patients with COPD screened, 40 (mean age 69 yrs, mean forced expiratory volume in 1 s 50% predicted) were colonised with potentially pathogenic microorganisms (PPMs) and were included in a randomised, double-blind, placebo-controlled trial with moxifloxacin 400 mg daily for 5 days. Eradication rates were 75% with moxifloxacin and 30% with placebo at 2 weeks (p = 0.01). Bacterial persistence at 8 weeks was still higher (not significantly) in the placebo arm (five (25%) out of 20 versus one (5%) out of 20; p = 0.18). The frequencies of acquisition of a new PPM were high and similar in both treatment groups; consequently, the prevalence of colonisation at 8 weeks was also similar between treatment arms. No difference was found in the number of patients with exacerbations during the 5-month follow-up. Only the acquisition of a new PPM during follow-up showed a statistically significant relationship with occurrence of an exacerbation. Moxifloxacin was effective in eradicating PPMs in patients with positive sputum cultures. However, most patients were recolonised after 8 weeks of follow-up. Acquisition of a new strain of bacteria was associated with an increased risk of developing an exacerbation.

Tratamiento antimicrobiano de la agudización de la EPOC: Documento de Consenso 2007 / Antimicrobial treatment of COPD deterioration: Consensus Document 2007

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Guía SEPAR para el tratamiento del tabaquismo en la empresa / SEPAR guide for treatment of smoking habit in the work sites

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Effect of smoking on skin elastic fibres: morphometric and immunohistochemical analysis.

BACKGROUND: It has been established during recent years that smoking is an independent risk factor for the development of premature facial wrinkling. The underlying mechanism is not well known, but elastic fibres of the dermis seem to be the major target of smoke components. OBJECTIVES: To determine quantitative and qualitative changes of the dermal elastic tissue of non-sun-exposed skin induced by smoking, as well as the possible mechanisms responsible for them. METHODS: Sixty-nine patients were recruited (20 nonsmokers, 19 former smokers and 30 smokers). Using static morphometry and immunohistochemistry and lectin staining we analysed elastic fibres of the dermis and their major components, elastin and microfibrillar component. RESULTS: Significantly higher values for the number of elastic fibres mm(-2) and the percentage of the area filled by them in the reticular dermis were found in smokers. Cumulative tobacco dose showed statistically significant correlations with both morphological parameters (Spearman's rank correlation coefficient). Immunohistochemistry demonstrated that the two main components of elastic fibres were altered in smokers. Plasma protease inhibitors and lectin staining were negative in all the samples. CONCLUSIONS: Smoking is an independent risk factor for the increase of elastic fibres in the reticular dermis of nonexposed skin, and it acts on their two main structural components, elastin and microfibrillar component. This increase in the area of elastic fibres in smokers is not due to newly synthesized elastic material, but to their degradation, as occurs in solar elastosis and which acts in an additive manner.

Reported occupational respiratory diseases in Catalonia.

OBJECTIVES: A voluntary surveillance system was implemented in Catalonia (Spain) to ascertain the feasibility, incidence, and characteristics of occupational respiratory diseases and compare them with those of the compulsory official system. METHODS: In 2002, in collaboration with the Occupational and Thoracic Societies of Catalonia, occupational and chest physicians and other specialists were invited to report, on a bimonthly basis, newly diagnosed cases of occupational respiratory diseases. Information requested on each case included diagnosis, age, sex, place of residence, occupation, suspected agent, and physician's opinion on the likelihood that the condition was work related. Compulsory official system data derived from statistics on work related diseases for possible disability benefits declared by insurance companies, which are responsible for declaring these diseases to the Autonomous Government of Catalonia. RESULTS: Of 142 physicians seeing patients with occupational respiratory diseases approached, 102 (74%) participated. Three hundred and fifty nine cases were reported, of which asthma (48.5%), asbestos related diseases (14.5%), and acute inhalations (12.8%) were the most common. Physicians rated 63% of suspected cases as highly likely, 28% as likely, and 8% as low likelihood. The most frequent suspected agents reported for asthma were isocyanates (15.5%), persulphates (12.1%), and cleaning products (8.6%). Mesothelioma (5.9%) was the most frequent diagnosis among asbestos related diseases. The number of acute inhalations reported was high, with metal industries (26%), cleaning services (22%), and chemical industries (13%) being the most frequently involved. The frequency of occupational respiratory diseases recorded by this voluntary surveillance system was four times higher than that reported by the compulsory official system. CONCLUSIONS: The compulsory scheme for reporting occupational lung diseases is seriously underreporting in Catalonia. A surveillance programme based on voluntary reporting by physicians may provide better understanding of the incidence and characteristics of these diseases. Persulphates and cleaning products, besides isocyanates, were the most reported causes of occupational asthma. Metal industries and cleaning services were the occupations most frequently involved in acute inhalations with a remarkably high incidence in our register.

Analysis of forced wheezes in asthma patients.

BACKGROUND: Spirometric parameters can be normal in many stable asthma patients, making a diagnosis difficult at certain times in the course of disease. OBJECTIVES: The present study aims to find differences and similarities in the acoustic characteristics of forced wheezes among asthma patients with and without normal spirometric values. METHODS: Eleven chronic asthma patients (8 men/3 women) with moderate-to-severe airway obstruction (FEV1 48.4%), 9 stable asthma patients (6 males/3 females) with normal spirometry (FEV1 84.0%) and a positive methacholine test and 14 healthy subjects (8/6) were enrolled in the study. A contact sensor was placed on the trachea, and wheezes were detected by a modified Shabtai-Musih algorithm in a time-frequency representation. RESULTS: More wheezes were recorded in obstructive asthma patients than in stable asthma and control subjects: nonstable asthma 13.6 (13.3), stable asthma 3.5 (3.0) and control subjects 2.5 (2.1). The mean frequency of all wheezes detected was higher in control subjects than in either stable or non-stable asthma patients. The change in the total number of wheezes after terbutaline inhalation was more pronounced in nonstable asthma patients than in stable asthmatics and control subjects. CONCLUSIONS: This study confirms that wheeze recording during forced expiratory maneuvers can be a complementary measure to spirometry to identify asthma patients.

Colonización bronquial en la enfermedad pulmonar obstructiva crónica: algo se esconde debajo de la alfombra / Bronchial colonization in chronic obstructive pulmonary disease: what´s hiding under the rug

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[Respiratory diseases in European farmers-II. Part of the European farmers' project]. / Atemwegs- und Lungenerkrankungen in der Europäischen Landwirtschaft - Teil 2: Ergebnisse der europäischen Landwirtschaftsstudie -

BACKGROUND: The aim of the European Farmers' Project was to estimate the prevalence of respiratory diseases in farmers across Europe. Furthermore, risk factors for respiratory symptoms in different parts of agricultural production should be assessed. METHODS: In the first part of the study, 7496 farmers from four European countries answered a written questionaire. Of these, 229 were visited at their farms in the second part of the survey. On site, spirometry, allergy tests, as well exposure measurements were performed. RESULTS: Farmers with animal production had a significantly lower prevalence of allergic diseases than the general population. In contrast, the prevalence of chronic phlegm was higher in animal farmers. Organic dust toxic syndrome (ODTS) was a major predictor of chronic bronchitis. It was indicated that allergens found in the working environment could be transfered to the living environment of the farmer. Poor ventilation as well as high temperatures inside the animal buildings were shown to have a negative impact on respiratory symptoms and lung function parameters. CONCLUSION: Animal farmers are at high risk of chronic bronchitis. Intervention studies on the efficacy of different types of ventilation are now warranted. Furthermore, prospective studies on the associaton between ODTS and COPD should be done.