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Laura Millares,1–3 Sara Martí,2,4 Carmen Ardanuy,2,4 Josefina Liñares,2,4 Salud Santos,2,5 Jordi Dorca,5 Marian García-Nuñez,1–3,6 Sara Quero,3,6 Eduard Monsó2,7,8 1Department of Respiratory Medicine, Fundació Parc Taulí, Sabadell, Spain; 2CIBER de Enfermedades Respiratorias, CIBERES, Bunyola, Spain; 3Universitat Autònoma de Barcelona, Esfera UAB, Barcelona, Spain; 4Department of Microbiology, Hospital Universitari de Bellvitge-Universitat de Barcelona-IDIBELL, L’Hospitalet de Llobregat, Spain; 5Department of Respiratory Medicine, Hospital Universitari de Bellvitge-Universitat de Barcelona-IDIBELL, L’Hospitalet de Llobregat, Spain; 6Infectious Diseases Unit, Fundació Insitut d’Investigació GermansTrias i Pujol, Badalona, Spain; 7Department of Respiratory Medicine, Hospital Universitari Parc Taulí, Sabadell, Spain; 8Department of Medicine, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain Background: The bronchial mucosa is protected by a specialized immune system focused on the prevention of colonization and infection by potentially pathogenic microorganisms (PPMs). Immunoglobulin A (IgA) is the principal antibody involved in this mechanism. A defective immune barrier may facilitate the recurrent presence of PPMs in COPD.Purpose: The aim of this study was to determine IgA-mediated bronchial specific immune responses against Pseudomonas aeruginosa in stable patients with severe disease.Methods: COPD patients with good-quality sputum samples obtained during stability were included and classified according to the presence or absence of chronic bronchial colonization by P. aeruginosa. Levels of specific IgA for P. aeruginosa in sputum were determined by ELISA and expressed as ratios, using the pooled level of 10 healthy subjects as reference (optical density450 patient/control).Results: Thirty-six stable COPD patients were included, 15 of whom had chronic colonization by P. aeruginosa. Levels of specific IgA against P. aeruginosa in stable non-colonized patients were lower than those in healthy subjects (IgA ratio: median =0.15 [interquartile range {IQR} 0.05–0.36]). Colonized patients had higher levels, (1.56 [IQR 0.59–2.79]) (p

Miguel Gallego,1–3 Xavier Pomares,1,3 Silvia Capilla,4 Maria Angeles Marcos,5,6 David Suárez,7 Eduard Monsó,1–3,* Concepción Montón1,8,* 1Department of Respiratory Medicine, Hospital de Sabadell, Institut Universitari Parc Taulí-UAB, Sabadell, 2Universitat Autònoma de Barcelona, Esfera UAB, Barcelona, 3CIBER de Enfermedades Respiratorias, CIBERES, Bunyola, 4Laboratory of Microbiology, Institut Universitari Parc Taulí-UAB, Sabadell, 5Department of Clinical Microbiology, Hospital Clínic, 6ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic, Universitat de Barcelona, Barcelona, 7Epidemiology and Assessment Unit, Fundació Parc Taulí, Universitat Autònoma de Barcelona, Sabadell, 8Health Services Research on Chronic Diseases Network-REDISSEC, Galdakao, Spain *These authors contributed equally to this work Background: C-reactive protein (CRP) measurement has proven valuable for detecting exacerbations, but its usefulness in predicting etiology remains controversial. Likewise, its potential value as a marker of severity, which is well established in patients with pneumonia, remains unproven in chronic obstructive pulmonary disease (COPD) exacerbations. Methods: A cohort study of 118 patients with severe COPD and acute infectious exacerbations were included and followed up over 1 year. Episodes of exacerbations meeting Anthonisen’s criteria type I–II were evaluated, analyzing the etiology and inflammatory response as measured by CRP in blood. Results: A total of 380 episodes were recorded. Full microbiological analysis was available in 265 samples. Haemophilus influenzae was the most commonly isolated bacteria and rhinovirus the most common virus. Median CRP levels from the 265 episodes were higher in the cases with positive cultures for bacteria (58.30 mg/L, interquartile range [IQR] 21.0–28.2) than in episodes only positive for viruses (37.3 mg/L, IQR 18.6–79.1) and cases negative for any microorganism (36.4 mg/L, IQR 10.8–93.7) (P100 mg/L (OR: 4.23, 95% CI: 2.12–8.44) were independent predictors after adjustment for baseline characteristics. Conclusion: CRP level was higher in bacterial infections, especially when H. influenzae and S. pneumoniae were isolated. CRP values >100 mg/L were associated with a fourfold increased risk of hospital admission. Therefore, CRP blood levels may be a useful biomarker in the management of exacerbations appearing in patients with severe disease. Keywords: COPD exacerbations, C-reactive protein, viruses, hospital admission

Xavier Pomares1, Concepción Montón1, Mateu Espasa2, Jordi Casabon1, Eduard Monsó1,3, Miguel Gallego1,31Pneumology Service, 2Laboratory Service, Corporació Parc Taulí, Universitat Autònoma de Barcelona, Sabadell, Spain; 3Ciber de Enfermedades Respiratorias – CibeRes, Bunyola, SpainBackground: The aim of this study was to determine whether long-term intermittent azithromycin therapy reduces the frequency of exacerbation in severe chronic obstructive pulmonary disease (COPD).Methods: We retrospectively investigated the clinical benefits of long-term azithromycin (500 mg orally three times per week) over 12 months in patients with severe COPD and a minimum of four acute exacerbations (AECOPD) per year or chronic bronchial colonization by Pseudomonas aeruginosa, comparing the number of AECOPD, hospitalizations due to respiratory disease, days of hospital stay, and bacterial infections during azithromycin treatment and in the year prior to this therapy.Results: Twenty patients who completed the 12-month treatment period were analyzed. No clinically significant adverse events were observed during azithromycin treatment. Compared with baseline data, azithromycin therapy significantly reduced the number of AECOPD (2.8 ± 2.5 versus 6.8 ± 2.8, P < 0.001), hospitalizations (1.4 ± 1.5 versus 3.6 ± 1.4, P < 0.001), and cumulative annual days of hospital stay (25 ± 32.2 versus 43.7 ± 21.4, P = 0.01). The improvement was particularly significant in patients with exacerbations caused by common potentially pathogenic microorganisms, who had 70% fewer AECOPD and hospitalizations. Patients colonized by P. aeruginosa had reductions of 43% in AECOPD and 47% in hospitalizations.Conclusion: Long-term azithromycin is well tolerated and associated with significant reductions in AECOPD, hospitalizations, and length of hospital stay in patients with severe COPD.Keywords: azithromycin, chronic obstructive pulmonary disease, exacerbation, macrolides

Abstract Background Haemophilus influenzae is the most common colonizing bacteria of the bronchial tree in chronic obstructive pulmonary disease (COPD), and positive cultures for this potentially pathogenic microorganism (PPM) has been associated with local inflammation changes that may influence the relationships between H. influenzae and the bronchial mucosa. Methods A cross-sectional analysis of stable COPD patients enrolled in the Phenotype and Course of Chronic Obstructive Pulmonary Disease (PAC-COPD) Study, focusing on bronchial colonization by H. influenzae, was performed. Specific IgA against the PPM was measured by optical density, and metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) using ELISA in sputum samples. Levels in patients colonized by H. influenzae and non-colonized patients were compared. Results Sputum supernatant for the measurement of specific IgA against H. influenzae was available from 54 stable COPD patients, who showed levels of specific IgA significantly lower in colonized (n=21) than in non-colonized patients (n=33) (15 [4-37] versus 31 [10-75], p=0.033, Mann-Whitney U test). Proenzyme MMP-9 was measured in 44 patients, and it was higher in colonized (n=12, 1903 [1488-6699] ng/ml) than in non-colonized patients (n=32, 639 [373-972] ng/ml) (p Conclusions Clinically stable COPD patients colonized by H. influenzae had lower levels of specific IgA against the microorganism and higher values of the active form of MMP-9 in their sputum supernatant than non-colonized patients. Bronchial colonization by H. influenzae may cause structural changes in the extracellular matrix through a defective defense and the production of active metalloproteinases.

Abstract Since the development of endobronchial ultrasound-guided real-time needle aspiration (EBUS-rt-TBNA) no false positive (FP) cases have been described. We present the first FP case for EBUS-rt-TBNA secondary to a carcinoma in situ (CIS) in the bronchial point of puncture. A 66-years-old male was referred to our Institution because of a mass in left lower lobe. The bronchoscopy did not show any endobronchial lesion. The cytology of the washing confirmed an unspecified non-small cell lung cancer. An EBUS-rt-TBNA for staging was carried out. No mediastinal nodes over 5 mm length were found but one single left hilar node at station 11 L was sampled. The cytology of the TBNA showed lymphocytes and neoplastic squamous cells. The patient underwent thoracotomy. On the surgical specimen no metastasis on any of the nodes resected were detected but a CIS on the bronchial resection margin was described. A bronchial biopsy confirmed CIS on the bronchial stump. The reported case depicts an unusual situation, we consider EBUS-rt-TBNA an accurate technique if minimal requirements are met

Abstract Background Conventional smears of samples obtained by endobronchial ultrasound with real-time transbronchial needle aspiration (EBUS-TBNA) have proven useful in lung cancer staging, but the value of additional information from cell-block processing of EBUS-TBNA samples has only been marginally investigated. This study focussed on the contribution of cell block analysis to the diagnostic yield in lung cancer. Methods Patients referred for lung cancer diagnosis and/or staging by means of EBUS-TBNA were enrolled, the adequacy of the obtained samples for preparing cell blocks was assessed, and the additional pathologic or genetic information provided from cell block analysis was examined. Results In 270 lung cancer patients referred for EBUS-TBNA (mean age, 63.3 SD 10.4 years) 697 aspirations were performed. Cell blocks could be obtained from 334 aspirates (47.9%) and contained diagnostic material in 262 (37.6%) aspirates, providing information that was additional to conventional smears in 50 of the 189 samples with smears that were non-diagnostic, corresponding 21 of these blocks to malignant nodes, and allowing lung cancer subtyping of 4 samples. Overall, cell blocks improved the pathologic diagnosis attained with conventional smears in 54 of the 697 samples obtained with EBUS-TBNA (7.7%). Cell blocks obtained during EBUS-TBNA also made epithelial growth factor receptor mutation analysis possible in 39 of the 64 patients with TBNA samples showing metastatic adenocarcinoma (60.1%). Overall, cell blocks provided clinically significant information for 83 of the 270 patients participating in the study (30.7%). Conclusions Cell-block preparation from EBUS-TBNA samples is a simple way to provide additional information in lung cancer diagnosis. Analysis of cell blocks increases the diagnostic yield of the procedure by nearly seven per cent and allows for genetic analysis in a sixty per cent of the patients with metastatic adenocarcinoma.

Abstract Background Bacterial colonisation in chronic obstructive pulmonary disease (COPD) contributes to airway inflammation and modulates exacerbations. We assessed risk factors for bacterial colonisation in COPD. Methods Patients with stable COPD consecutively recruited over 1 year gave consent to provide a sputum sample for microbiologic analysis. Bronchial colonisation by potentially pathogenic microorganisms (PPMs) was defined as the isolation of PPMs at concentrations of ≥102 colony-forming units (CFU)/mL on quantitative bacterial culture. Colonised patients were divided into high (>105 CFU/mL) or low (5 CFU/mL) bacterial load. Results A total of 119 patients (92.5% men, mean age 68 years, mean forced expiratory volume in one second [FEV1] [% predicted] 46.4%) were evaluated. Bacterial colonisation was demonstrated in 58 (48.7%) patients. Patients with and without bacterial colonisation showed significant differences in smoking history, cough, dyspnoea, COPD exacerbations and hospitalisations in the previous year, and sputum colour. Thirty-six patients (62% of those colonised) had a high bacterial load. More than 80% of the sputum samples with a dark yellow or greenish colour yielded PPMs in culture. In contrast, only 5.9% of white and 44.7% of light yellow sputum samples were positive (P < 0.001). Multivariate analysis showed an increased degree of dyspnoea (odds ratio [OR] = 2.63, 95% confidence interval [CI] 1.53-5.09, P = 0.004) and a darker sputum colour (OR = 4.11, 95% CI 2.30-7.29, P < 0.001) as factors associated with the presence of PPMs in sputum. Conclusions Almost half of our population of ambulatory moderate to very severe COPD patients were colonised with PPMs. Patients colonised present more severe dyspnoea, and a darker colour of sputum allows identification of individuals more likely to be colonised.

Introduction: Chronic obstructive pulmonary disease (COPD) progression is variable and affects several disease domains, including decline in lung function, exercise capacity, muscle strength, and health status as well as changes in body composition. We aimed to assess the longitudinal association of physical activity (PA) with these a priori selected components of disease progression., Methods: We studied 114 COPD patients from the PAC-COPD cohort (94% male, mean [SD], 70 yr [8 yr] of age, 54 [16] forced expiratory volume in 1 s % predicted) at baseline and 2.6 yr (0.6 yr) later. Baseline PA was assessed by accelerometry. Multivariable general linear models were built to assess the association between PA and changes in lung function, functional exercise capacity, muscle strength, health status, and body composition. All models were adjusted for confounders and the respective baseline value of each measure., Results: Per each 1000 steps higher baseline PA, forced expiratory volume in 1 s declined 7 mL less (P < 0.01), forced vital capacity 9 mL less (P = 0.03) and carbon monoxide diffusing capacity 0.10 mL·min·mm Hg less (P = 0.04), while the St George's Respiratory Questionnaire symptom domain deteriorated 0.4 points less (P = 0.03), per year follow-up. Physical activity was not associated with changes in functional exercise capacity, muscle strength, other domains of health status or body composition., Conclusions: Higher PA is associated with attenuated decline in lung function and reduced health status (symptoms domain) deterioration in moderate-to-very severe COPD patients.

Intrathoracic lymph node enlargement is a common finding in patients with extrathoracic malignancies. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a technique that is commonly used for lung cancer diagnosis and staging but that has not been widely investigated for the diagnosis of enlarged mediastinal and lobar lymph nodes in patients with extrathoracic malignancies. We conducted a retrospective study of 117 patients with extrathoracic malignancies who underwent EBUS-TBNA for diagnosis of intrathoracic lymph node enlargement from October 2005 to December 2009 and compared the EBUS-TBNA findings with the final diagnoses. EBUS-TBNA diagnosed mediastinal metastases in 51 of the 117 (43.6 %) cases and gave an alternate diagnosis or ruled out the presence of malignancy in 35 (56.4 %). Fourteen of these 35 patients underwent further surgical investigation, while the remaining 21 had clinical and radiological follow-up for 18 months. No false negatives were found in the surgery group. In the follow-up group, 13 patients had stable or regressive lymphadenopathy, and eight developed clinicoradiological progression and were assumed to have been false negatives by EBUS-TBNA. The sensitivity and negative predictive value of EBUS-TBNA were 86.4 and 75 %, respectively. Immunohistochemical staining (IHC) was performed in 80.4 % of the samples obtained by EBUS-TBNA. In samples obtained from ten patients with metastatic breast cancer, estrogen receptor expression was successfully assessed in eight patients and progesterone receptor and human epidermal growth factor receptor 2 in four. EBUS-TBNA is an accurate procedure for the diagnosis of thoracic lymph node metastases in patients with extrathoracic malignancies and should be an initial diagnostic tool in these patients. Furthermore, EBUS-TBNA can obtain high-quality specimens from metastatic lymph nodes for use in molecular analyses.

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.

Farmers are known to be at high risk from the development of occupational airway disease. The first stage of the European farmers' study has shown that pig farmers in Denmark and Germany, poultry farmers in Switzerland and greenhouse workers in Spain were at highest risk for work-related respiratory symptoms. Therefore, the aim of this study was to determine exposure levels at relevant farm workplaces. Dust and endotoxin levels as well as microbiological concentrations were determined in 213 crop and animal farming environments by personal sampling. The highest total dust concentrations were found in poultry houses in Switzerland with median concentrations of 7.01 mg/m(3). The median airborne endotoxin concentrations in total dust ranged between 0.36 ng/m(3) in Spanish greenhouses and 257.58 ng/m(3) in poultry houses in Switzerland. Likewise, the highest median concentrations of total (2.0 x (7) cells/m(3)) and active fungi (4.4 x (5) cfu/m(3)) have been found in Swiss poultry houses. The predominant fungus taxa discovered in poultry houses were Eurotium spp. and thermophilic fungi. Cladosporium and Botrytis were mainly detected in greenhouses. The exposure level found in this study might put the farmers at risk from respiratory diseases.

The aim of the European Farmers' Project was to determine prevalence and risk factors of respiratory diseases in farmers across Europe. A cross-sectional study in 7 centres was carried out. In the first stage of the study, nearly 8,000 farmers in Denmark, Germany, Switzerland, the UK, and Spain answered a standardised questionnaire on farming characteristics and respiratory symptoms. The second stage of the study included exposure assessment and lung function measurements in 4 of the centres. Within the group of farmers, pig farmers were at high risk of asthma-like syndrome as compared to farmers keeping other kinds of animals. Among plant farmers, greenhouse workers were at higher risk for symptoms of asthma. The prevalence of symptoms of allergies were significantly lower among animal farmers as compared to the population of the European Community Respiratory Health Survey. In contrast, animal farmers had a significantly higher prevalence of symptoms of chronic bronchitis. The major risk factor for respiratory symptoms was shown to be ventilation of the animal houses and greenhouses. Intervention studies are now warranted to test the effectiveness of improved ventilation on respiratory health. The reasons for the low prevalence of allergic diseases among farmers are currently under study.

The study included 17 patients with facial paralysis (FP) (10 male, 7 female) aged 47.6 +/- 21.0 years. Twelve of the 17 patients had Bell's palsy. The other causes of FP were as follows: one, polyradiculoneuritis; one, war injury; one, cerebrovascular accident; one, sarcoidosis; and one, dermatomyositis. Spirometry and maximal respiratory pressures (PImax and PEmax) were performed with three different techniques: without holding the lips, with patient holding lips, and with technician holding lips. We observed significant differences for PImax and PEmax among the three methods. There were no differences for spirometric values. In nine of the patients with Bell's palsy, PImax, PEmax, and spirometry tests were repeated two months after the first determination. With respect to the first determination, the values of Pmax-w/v holding lips increased, yet spirometric values were similar. In conclusion, PImax and PEmax can be an index of clinical FP evolution. Spirometric maneuvers can be performed with either patient or technician holding lips to ensure a perfect seal between lips and mouthpiece.