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Background: Interstitial lung diseases (ILDs) have a major impact on survival and quality of life but only a small percentage of patients are referred for palliative care (PC).Objective: To assess the impact of early PC referral on hospital admissions, emergency department visits, and place of death in the last year of life.Design: This is a single-center retrospective observational study.Setting/Subjects: Subjects were patients with ILDs who attended the respiratory department of Hospital Santa Creu i Sant Pau (Barcelona, Spain) between 2011 and 2019.Results: Of the 51 included patients, 45% received early PC referral. Logistic regression indicated that early PC referral was independently associated with a lower risk of hospital admissions in the last year of life (OR = 0.16; 95% CI 0.03-0.75; p = 0.02) and a lower risk of dying in hospital (OR = 0.11; 95% CI 0.02-0.5; p = 0.009).Conclusion: Early PC referral reduces the need for hospitalization and enables domiciliary death.

This study aimed to describe real-life microbiological testing of adults hospitalised with community-acquired pneumonia (CAP) and to assess concordance with the 2007 Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) and 2011 European Respiratory Society (ERS) CAP guidelines. This was a cohort study based on the Global Initiative for Methicillin-resistant Staphylococcus aureus Pneumonia (GLIMP) database, which contains point-prevalence data on adults hospitalised with CAP across 54 countries during 2015. In total, 3702 patients were included. Testing was performed in 3217 patients, and included blood culture (71.1%), sputum culture (61.8%), Legionella urinary antigen test (30.1%), pneumococcal urinary antigen test (30.0%), viral testing (14.9%), acute-phase serology (8.8%), bronchoalveolar lavage culture (8.4%) and pleural fluid culture (3.2%). A pathogen was detected in 1173 (36.5%) patients. Testing attitudes varied significantly according to geography and disease severity. Testing was concordant with IDSA/ATS and ERS guidelines in 16.7% and 23.9% of patients, respectively. IDSA/ATS concordance was higher in Europe than in North America (21.5% versus 9.8%; p, Testing practices vary based on geography and disease severity, and IDSA/ATS/ERS testing recommendations are rarely followed http://ow.ly/80Iy30lxo1c

RationaleRecently a frequent exacerbator phenotype has been described in bronchiectasis, but the underlying biological mechanisms are unknown. Antimicrobial peptides (AMPs) are important in host defence against microbes but can be proinflammatory in chronic lung disease.ObjectivesTo determine pulmonary and systemic levels of AMP and their relationship with disease severity and future risk of exacerbations in bronchiectasis.MethodsA total of 135 adults with bronchiectasis were prospectively enrolled at three European centres. Levels of cathelicidin LL-37, lactoferrin, lysozyme and secretory leucocyte protease inhibitor (SLPI) in serum and sputum were determined at baseline by ELISA. Patients were followed up for 12 months. We examined the ability of sputum AMP to predict future exacerbation risk.Measurements and main resultsAMP levels were higher in sputum than in serum, suggesting local AMP release. Patients with more severe disease at baseline had dysregulation of airway AMP. Higher LL-37 and lower SLPI levels were associated with Bronchiectasis Severity Index, lower FEV1 (forced expiratory volume in 1 s) and Pseudomonas aeruginosa infection. Low SLPI levels were also associated with the exacerbation frequency at baseline. During follow-up, higher LL-37 and lower SLPI levels were associated with a shorter time to the next exacerbation, whereas LL-37 alone predicted exacerbation frequency over the next 12 months.ConclusionsPatients with bronchiectasis showed dysregulated sputum AMP levels, characterised by elevated LL-37 and reduced SLPI levels in the frequent exacerbator phenotype. Elevated LL-37 and reduced SLPI levels are associated with Pseudomonas aeruginosa infection and can predict future risk of exacerbations in bronchiectasis.

Objective: To investigate the prognostic impact of early readmission (30 days) on hospitalized patients with Interstitial Lung Disease (ILD). Methods: Observational study analysing a cohort of patients hospitalized in a respiratory ward at a University Hospital. Demographic, clinical data and survival status were collected from patients' records. Early readmission was defined as hospitalization within 30 days after patient's discharge. The primary outcome was 90-day and 1-year all-cause mortality.Results: Between 2013 to 2016, a total of 2.238 patients were admitted to the respiratory ward and 98 (%) had a diagnosis of ILD. Among them, 74 patients were discharged (25% in-hospital mortality). Early readmission was observed in 15 cases (20.2%). Early readmitted patients were more frequently current smokers (20% vs. 2%, p=0.02). After a multivariate analysis, early readmission was found to be independently associated with 90-day and 1 year mortality (Odds Ratio (OR) 17.6, 95% Confidence Interval (CI) 4.5-69-2, p=0.001 and OR 4.5; 95CI 1.3-15.2, p=0.01, respectively).Conclusion: In patients with ILD, early readmission after hospitalization increases both short-term and long term mortality. Thus, preventing early readmission after discharge from hospital admission may have an impact in the clinical course of ILD patients. Further studies are required to identify factors contributing to early readmission.

Objective: To investigate the prognostic impact of early readmission (30 days) on hospitalized patients with Interstitial Lung Disease (ILD). Methods: Observational study analysing a cohort of patients hospitalized in a respiratory ward at a University Hospital. Demographic, clinical data and survival status were collected from patients’ records. Early readmission was defined as hospitalization within 30 days after patient’s discharge. The primary outcome was 90-day and 1-year all-cause mortality. Results: Between 2013 to 2016, a total of 2.238 patients were admitted to the respiratory ward and 98 (%) had a diagnosis of ILD. Among them, 74 patients were discharged (25% in-hospital mortality). Early readmission was observed in 15 cases (20.2%). Early readmitted patients were more frequently current smokers (20% vs. 2%, p=0.02). After a multivariate analysis, early readmission was found to be independently associated with 90-day and 1 year mortality (Odds Ratio (OR) 17.6, 95% Confidence Interval (CI) 4.5-69-2, p=0.001 and OR 4.5; 95CI 1.3-15.2, p=0.01, respectively). Conclusion: In patients with ILD, early readmission after hospitalization increases both short-term and long term mortality. Thus, preventing early readmission after discharge from hospital admission may have an impact in the clinical course of ILD patients. Further studies are required to identify factors contributing to early readmission.

Rationale: Airway colonization by Potentially Pathogenic Microorganisms ( PPM) in bronchiectasis is associated with worse clinical outcomes. The electronic nose is a non-invasive technology capable of distinguishing volatile organic compounds ( VOC) in exhaled breath. We aim to explore if an electronic nose can reliably discriminate airway bacterial colonization in patients with bronchiectasis. Methods: Seventy-three clinically stable bronchiectasis patients were included. PPM presence was determined using sputum culture. Exhaled breath was collected in Tedlar bags and VOC breath-prints were detected by the electronic nose Cyranose 320(R). Raw data was reduced to three factors with principal component analysis. Univariate ANOVA followed by post-hoc least significant difference test was performed with these factors. Patients were then classified using linear canonical discriminant analysis. Cross-validation accuracy values were defined by the percentage of correctly classified patients. Results: Forty-one (56%) patients were colonized with PPM. Pseudomonas aeruginosa ( n=27, 66%) and Haemophilus influenzae ( n=7, 17%) were the most common PPM. VOC breath-prints from colonized and non-colonized patients were significantly different ( accuracy of 72%, AUROC 0.75, p < 0.001). VOC breath-prints from Pseudomonas aeruginosa colonized patients were significantly different from those of patients colonized with other PPM ( accuracy of 89%, AUROC 0.97, p < 0.001) and non-colonized patients ( accuracy 73%, AUROC 0.83, p=0.007). Conclusions: An electronic nose can accurately identify VOC breath-prints of clinically stable bronchiectasis patients with airway bacterial colonization, especially in those with Pseudomonas aeruginosa.

Background: Pseudomonas aeruginosa (PA) is a common microorganism related to severe exacerbations in Chronic Obstructive Pulmonary Disease (COPD). However, their role in COPD patients with frequent hospitalized exacerbations (FHE) is not well described. Objectives: We aimed to determine prevalence, risk factors, susceptibility patterns and impact on outcomes of PA in COPD patients with FHE. Methods: Prospective observational multicentre study that included COPD patients with FHE. The cohort was stratified in 2 groups according to the presence or absence of PA isolation in sputum. Patients were followed up for 12 months. Results: We enrolled 207 COPD patients with FHE. In 119 patients (57%), a valid sputum culture was collected. Of them, PA was isolated in 21 patients (18%). The risk factors associated with PA were prior use of systemic corticosteroids (OR 3.3, 95% CI 1.2–9.7, p = 0.01) and prior isolation of PA (OR 4.36, 95% CI 1.4–13.4, p < 0.01). Patients with PA had an increased risk of having ≥3 readmissions (OR 4.1, 95% CI 1.3–12.8, p = 0.01) and higher PA isolation rate (OR 7.7, 95% CI 2.4–24.6, p < 0.001) during the follow-up period. In 14 patients (67%), PA was resistant to at least one antibiotic tested. PA persisted in the sputum in 70% of patients. Conclusions: The presence of PA was related to 3 or more readmissions during the 1-year follow-up and PA persisted in the sputum despite an appropriate antibiotic treatment. This finding suggested an important role of PA in the course of the disease of COPD patients with FHE.

Background: Pseudomonas aeruginosa (PA) is a common microorganism related to severe exacerbations in Chronic Obstructive Pulmonary Disease (COPD). However, their role in COPD patients with frequent hospitalized exacerbations (FHE) is not well described. Objectives: We aimed to determine prevalence, risk factors, susceptibility patterns and impact on outcomes of PA in COPD patients with FHE. Methods: Prospective observational multicentre study that included COPD patients with FHE. The cohort was stratified in 2 groups according to the presence or absence of PA isolation in sputum. Patients were followed up for 12 months. Results: We enrolled 207 COPD patients with FHE. In 119 patients (57%), a valid sputum culture was collected. Of them, PA was isolated in 21 patients (18%). The risk factors associated with PA were prior use of systemic corticosteroids (OR 3.3, 95% CI 1.2-9.7, p = 0.01) and prior isolation of PA (OR 4.36, 95% CI 1.4-13.4, p < 0.01). Patients with PA had an increased risk of having ≥3 readmissions (OR 4.1, 95% CI 1.3-12.8, p = 0.01) and higher PA isolation rate (OR 7.7, 95% CI 2.4-24.6, p < 0.001) during the follow-up period. In 14 patients (67%), PA was resistant to at least one antibiotic tested. PA persisted in the sputum in 70% of patients. Conclusions: The presence of PA was related to 3 or more readmissions during the 1-year follow-up and PA persisted in the sputum despite an appropriate antibiotic treatment. This finding suggested an important role of PA in the course of the disease of COPD patients with FHE.

Respiratory infections are a major cause of global mortality and morbidity. In recent years, an increased incidence of multidrug-resistant (MDR) Gram-negative bacteria (GNB) has been described. Microorganisms such as Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae or Acinetobacter baumannii have been identified as causative pathogens of different respiratory tract infections. Several studies have detected MDR-GNB in patients with community-acquired and nosocomial pneumonia. Furthermore, MDR-GNB have also been isolated in patients with chronic obstructive pulmonary disease and bronchiectasis having acute or chronic bronchial infection. Prevalence varies depending on the geographical area but MDR-GNB has been reported in the Asia-Pacific region, Europe and the United States, reaching rates of 70% in hospital-acquired infection. The presence of MDR-GNB has been related to poor clinical outcomes, including increased mortality, although data regarding this relationship are limited. This is probably linked to inappropriate selection of empiric antibiotic treatment; this poses a threat of widespread resistance. GNB antibiotic resistance and the absence of new antibiotics are a major concern given limited treatment options; an aspect that deserves future research. We review current literature, highlight prevalence of MDR-GNB in different respiratory infections and explore their impact on clinical outcomes.

Background For still unclear reasons, chronic airway infection often occurs in patients with Chronic Obstructive Pulmonary Disease (COPD), particularly in those with more severe airflow limitation. Fatty-acid binding protein 4 (FABP4) is an adipokine involved in the innate immune response against infection produced by alveolar macrophages (Mɸ). We hypothesized that airway levels of FABP4 may be altered in COPD patients with chronic airway infection. Methods In this prospective and controlled study we: (1) compared airway FABP4 levels (ELISA) in induced sputum, bronchoalveolar lavage fluid (BALF) and plasma samples in 52 clinically stable COPD patients (65.2 ± 7.9 years, FEV1 59 ± 16% predicted) and 29 healthy volunteers (55.0 ± 12.3 years, FEV1 97 ± 16% predicted); (2) explored their relationship with the presence of bacterial airway infection, defined by the presence of potentially pathogenic bacteria (PPB) at ≥103 colony-forming units/ml in BALF; (3) investigated their relationship with the quantity and proportion of Mɸ in BALF (flow cytometry); and, (4) studied their relationship with the severity of airflow limitation (FEV1), GOLD grade and level of symptoms (CAT questionnaire). Results We found that: (1) airway levels of FABP4 (but not plasma ones) were reduced in COPD patients vs. controls [219.2 (96.0–319.6) vs. 273.4 (203.1–426.7) (pg/ml)/protein, p = 0.03 in BALF]; (2) COPD patients with airway infection had lower sputum FABP4 levels [0.73 (0.35–15.3) vs. 15.6 (2.0–29.4) ng/ml, p = 0.02]; (3) in COPD patients, the number and proportion of Mɸ were positively related with FABP4 levels in BALF; (4) BALF and sputum FABP4 levels were positively related with FEV1, negatively with the CAT score, and lowest in GOLD grade D patients. Conclusions Airway FABP4 levels are reduced in COPD patients, especially in those with airway infection and more severe disease. The relationship observed between Mɸ and airway FABP4 levels supports a role for FABP4 in the pathogenesis of airway infection and disease severity in COPD.

Community-acquired pneumonia (CAP) is a leading cause of hospitalization, morbidity, and mortality. Despite advances in antibiotic treatments, mortality among patients with CAP is still high. For this reason, interest has been focused on nonantibiotic therapeutic measures directed to the host response rather than the microorganism. The development of an efficacious adjunctive treatment has important implications for reducing mortality in CAP. Some clinical studies performed in the last decade have shown a clinically beneficial effect of corticosteroids, possibly by diminishing local and systemic inflammatory host response. Recent meta-analyses showed faster resolution of symptoms, shorter time to clinically stability, reduction of mechanical ventilation needed, and reduction of mortality in the most severe population, although some methodological limitations must be taken into account. In addition, some studies using statins also suggested improved outcomes due to its anti-inflammatory effect in CAP, although this requires further research. Other adjunctive therapies such as immunoglobulins and stem cells are being explored, but are not yet in the stage of clinical trials. In summary, the use of corticosteroids and other adjuvant treatments are promising in CAP, but more studies are needed to determine their impact on mortality.

Background and objective Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) due to Pseudomonas aeruginosa (PA) are associated with worse outcomes. PA antibiotic resistance is important to determine treatment and may influence clinical outcomes. The aim was to study clinical characteristics and outcomes in patients with AECOPD associated with PA based on their antibiotic resistance. Methods This was a prospective observational study including all patients with AECOPD and positive PA sputum culture admitted in a respiratory ward in a tertiary hospital in Barcelona during 2013–2014. PA was defined as resistant (PA-R) when the antibiogram showed ≥1 resistance. Results Four hundred one patients with AECOPD were evaluated. Of them, 54 (13%) had a positive PA sputum culture. Eighty-two per cent were men, median age was 77 (SD 7) years old and FEV1 was less than 36% (SD 17) of predicted value. PA-R was isolated in 35 patients (66%), and PA-sensitive (PA-S) was isolated in 18 (34%) patients. No differences were found in demographics, lung function and comorbidities among groups. PA-R patients were more likely exposed to prior oral corticosteroids (77% vs 44%, P = 0.03) and antibiotics (77% vs 31%, P = 0.01), respectively. AECOPD patients associated with PA-S were more likely to die at 30 days (odds ratio 13.53, 95% confidence interval: 1.14–69.56, P = 0.03) and 90 days (odds ratio 7.09, 95% confidence interval: 1.33–37.89, P = 0.02), respectively. Conclusion Pseudomonas aeruginosa-resistant affects patients with severe AECOPD and previous use of corticosteroids and antibiotics. The presence of PA-S is associated with higher mortality. These results may suggest increased virulence in PA-S strains causing acute infections.

Rationale: The principal underlying inhaled antibiotic treatment in bronchiectasis is that airway bacterial load drives inflammation, and therefore antibiotic treatment will reduce symptoms. Objectives: To determine the relationship between bacterial load and clinical outcomes, assess the stability of bacterial load over time, and test the hypothesis that response to inhaled antibiotics would be predicted by baseline bacterial load. Methods: We performed three studies. Studies 1 and 2 were prospective studies including adults with bronchiectasis. Study 3 was a post hoc analysis of a randomized trial of inhaled aztreonam. A priori patients were divided into low (= 10(7) cfu/g) using quantitative sputum culture. Measurements and Main Results: Bacterial load was a stable trait associated with worse quality of life and more airway inflammation in studies 1, 2, and 3. In study 3, patients with high bacterial load showed an improvement in the primary endpoint (Quality of Life-Bronchiectasis-Respiratory Symptoms Score at Week 4) in favor of aztreonam (mean difference of 9.7 points; 95% confidence interval, 3.4-16.0; P = 0.003). The proportion of patients who achieved an increase above the minimum clinically important difference was higher in the aztreonam group at Week 4 (63% vs. 37%; P = 0.01) and at Week 12 (62% vs. 38%; P = 0.01) only in high bacterial load patients. Conclusions: Improvement of quality of life with inhaled aztreonam was only evident in patients with high bacterial load. Bacterial load may be a useful biomarker of severity of disease and treatment response.

La enfermedad pulmonar obstructiva crónica (EPOC) es una enfermedad prevalente que genera un gran impacto social y sanitario. Las agudizaciones de la enfermedad son la causa más importante de admisión hospitalaria, gasto sanitario y mortalidad, siendo las infecciones bronquiales la causa más frecuente de agudización. La infección por P. aeruginosa se ha asociado a peores resultados clínicos en diferentes enfermedades respiratorias. En la EPOC, se aísla de forma frecuente en las agudizaciones graves que requieren de ingreso hospitalario. Además en los últimos años se ha apreciado un aumento en el patrón de resistencias a los antibióticos más utilizados. Sin embargo, el impacto de la infección bronquial por P.aeruginosa y sus patrones de resistencia en pacientes con EPOC y agudizaciones frecuentes no está bien establecido. La hipótesis que nos planteamos es que los pacientes con EPOC y agudizaciones graves por P. aeruginosa tienen peores resultados clínicos, presentando una mayor tasa de readmisión hospitalaria y que el patrón de resistencia microbiológica tiene un impacto en el pronóstico. Es por ello que el objetivo de esta tesis es evaluar el impacto de P. aeruginosa y su patrón de resistencias en las agudizaciones de EPOC que requieren de ingreso hospitalario. Con esta premisa se diseñaron dos estudios prospectivos en los que se incluyeron pacientes con agudizaciones graves de EPOC. En el primer estudio se incluyeron solo los pacientes con EPOC y cultivo de esputo positivo al ingreso para P. aeruginosa y se evaluaron resultados clínicos en función del patrón de resistencia. Este estudio concluye que los pacientes EPOC ingresados por una agudización con aislamiento de P. aeruginosa en el cultivo de esputo tienen diferentes resultados en función del patrón de resistencia a antibióticos. Los pacientes con P. aeruginosa multisensible presentaban mayor mortalidad comparados con los que tenían un patrón de resistencia a antibióticos, y permanecían en la vía aérea a pesar de recibir un correcto tratamiento antibiótico, sugiriendo distintas formas de virulencia en función del patrón de resistencias. En el segundo estudio se reclutaron pacientes con agudización grave de EPOC independientemente del aislamiento microbiológico. Posteriormente se evaluaron prevalencia, factores de riesgo e impacto en resultados, del grupo de pacientes con aislamiento de P.aeruginosa al compararlo con aquellos en los que no se aislaban MPP. Este estudio concluye que el aislamiento de P. aeruginosa juega un papel importante en la evolución de los pacientes con EPOC, aumentando el porcentaje de readmisiones por agudización y persistiendo en el esputo durante el seguimiento. La conclusión global de este trabajo es que las agudizaciones graves de EPOC debidas a P.aeruginosa presentan peores resultados clínicos, asociándose a un mayor número de readmisiones hospitalarias y se han observado diferencias en la evolución clínica de los pacientes en función del patrón de resistencia antibiótica. Chronic obstructive pulmonary disease (COPD) is a prevalent disease that generates a great social and health impact. The exacerbations of the disease are the most important cause of hospital admission, health expenditure and mortality, with bronchial infections being the most frequent cause of exacerbation. P. aeruginosa infection has been associated with poorer clinical outcomes in different respiratory diseases. In COPD, it is frequently isolated in severe exacerbations that require hospital admission. In addition, in recent years there has been an increase in the pattern of resistance to the most commonly used antibiotics. However, the impact of bronchial infection due to P. aeruginosa and its resistance patterns in patients with COPD and frequent exacerbations is not well established. The hypothesis that we propose is that patients with COPD and exacerbations due to P. aeruginosa have poorer clinical results, presenting a greater hospital readmission and that the pattern of microbiological resistance has an impact on outcomes. That is why the objective of this thesis is to evaluate the impact of P. aeruginosa and its pattern of resistance in exacerbations of COPD who required hospital admission. In accordance with this premise, two prospective studies were designed in which patients with severe exacerbations of COPD. In the first study, only patients with COPD and positive sputum culture at admission for P. aeruginosa were included and clinical results were evaluated according to the resistance pattern. The first study concludes that COPD patients admitted for an exacerbation with isolation of P. aeruginosa in sputum culture have different results depending on the pattern of resistance to antibiotics. Patients with multisensible P. aeruginosa had higher mortality compared to those who had a pattern of resistance to antibiotics, who stayed in the airway despite receiving a correct antibiotic treatment, suggesting different forms of virulence depending on the pattern of resistance. In the second study, patients with severe exacerbation and COPD were enrolled regardless of microbiological isolation. Subsequently, prevalence, risk factors and impact on the results of the group of patients with P. aeruginosa isolation were evaluated when compared to those in which MPP was not isolated. This work concludes that the isolation of P. aeruginosa plays an important role in the evolution of patients with COPD, increasing the percentage of readmissions due to exacerbation and persisting in the sputum during follow-up. The overall conclusion of this study is that severe exacerbations of COPD due to P.aeruginosa present worse clinical results, being associated with a greater number of hospital readmissions and differences in the clinical evolution of patients have been observed depending on the pattern of antibiotic resistance.

Introduction: Hospital readmissions are critical in the natural history of severe COPD patients. However, its prediction is complicated in clinical practice. The electronic nose is a non-invasive technology capable of distinguish volatile organic compounds (VOC) breath-prints in exhaled breath. Objective: We aim to explore if an electronic nose can reliably predict the presence of future hospital readmissions in admitted patients with Chronic Obstructive Pulmonary Disease (COPD) and frequent severe exacerbations. Methods: Eighty-eight hospitalized COPD patients with two ore more severe exacerbations in the previous year were included. On admission, clinical, functional, microbiological and laboratory data were recorded. During the first 24 hours of admission, exhaled breath was collected in Tedlar bags and VOCs breath-prints were detected by the commercially available electronic nose Cyranose 320®. Cross-validation accuracy was assessed using principal component reduction analysis (PCA). Patients were followed during 90 days after discharge. Results: Seventeen patients (19%) were readmitted at 30-days, and 33 patients (37%) were readmitted at 90-days. No clinical differences on admission were observed among patients who were readmitted or not. However, VOC breath-prints were different among both groups. In predicting 30-day readmission, the accuracy was of 87.5%, sensitivity of 90% and specificity of 76.5% (AUROC 0.85, p Conclusions: An electronic nose may identify admitted severe COPD patients at risk of 30-day and 90-day readmission. Suported by SEPAR, FUCAP.

Background and objective Secreted mucins play a key role in antibacterial defence in the airway, but have not previously been characterized in non-cystic fibrosis (CF) bronchiectasis patients. We aim to investigate the relationship between secreted mucins levels and the presence of bacterial colonization due to potentially pathogenic microorganisms (PPM) in the airways of stable bronchiectasis patients. Methods Clinically stable bronchiectasis patients were studied prospectively at two centres. Patients with other pulmonary conditions were excluded. Spontaneous sputum was subject to bacterial culture, and secreted mucins (MUC2, MUC5AC and MUC5B) were measured in sputum supernatants by ELISA. Results A total of 50 patients were included. PPM were identified from sputum samples in 30 (60%), with Pseudomonas aeruginosa (n = 10) and Haemophilus influenzae (n = 10) as the most common PPM. There were no baseline differences among airway colonized and non-colonized patients. Patients with airways colonized by PPM presented higher levels of airway MUC2. No differences in MUC5AC levels were found among groups, whereas MUC5B levels were undetectable. Patients with P. aeruginosa colonization expressed the highest levels of MUC2. High levels of MUC2 and MUC5AC are also correlated with disease severity using the Bronchiectasis Severity Index. Conclusions Airway MUC2 levels were higher in bronchiectasis patients colonized with PPM compared with those without airway colonization, especially in patients with P. aeruginosa. These findings suggest that airway-secreted mucins levels may play a role in the pathogenesis of airway infection in non-CF bronchiectasis.

Rationale Respiratory infections are common after strenuous exercise, when salivary immunity may be altered. We aim to investigate changes in salivary immunity after a marathon and its relationship with lower respiratory tract infections (LRTI) in healthy non-elite marathon runners. Methods Forty seven healthy marathon runners (28 males and 19 females) who completed the 42.195 km of the 2016 Barcelona marathon were studied. Saliva and blood samples were collected the day before the marathon and two days after the end of the race. Salivary IgA, antimicrobial proteins (lactoferrin, lysozyme) and chemokines (Gro alpha, Gro beta, MCP-1) were determined using ELISA kits in saliva supernatant. Blood biochemistry and haemogram were analyzed in all participants. The presence of LRTI was considered in those runners who reported infectious lower respiratory tract symptoms during a minimum of 3 consecutive days in the 2 weeks after the race. Results Eight participants (17%) presented a LRTI during the 2 weeks of follow-up. Higher lysozyme levels were detected after the race in runners with LRTI when compared with those without infection. A decrease in salivary lysozyme, Gro alpha and Gro beta levels after the race were observed in those runners who did not develop a LRTI when compared to basal levels. Salivary Gro alpha levels correlated with basophil blood counts, and salivary lysozyme levels correlated with leukocyte blood counts. Conclusions LRTI are common after a marathon race in non-elite healthy runners. Changes in salivary antimicrobial proteins and chemokines are related to the presence of LRTI and correlate with systemic defense cells, which suggest an important role of salivary immunity in the development of LRTI in non-elite marathon runners.

Respiratory infections are a major cause of global mortality and morbidity. In recent years, an increased incidence of multidrug-resistant (MDR) Gram-negative bacteria (GNB) has been described. Microorganisms such as Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae or Acinetobacter baumannii have been identified as causative pathogens of different respiratory tract infections. Several studies have detected MDR-GNB in patients with community-acquired and nosocomial pneumonia. Furthermore, MDR-GNB have also been isolated in patients with chronic obstructive pulmonary disease and bronchiectasis having acute or chronic bronchial infection. Prevalence varies depending on the geographical area but MDR-GNB has been reported in the Asia-Pacific region, Europe and the United States, reaching rates of 70% in hospital-acquired infection. The presence of MDR-GNB has been related to poor clinical outcomes, including increased mortality, although data regarding this relationship are limited. This is probably linked to inappropriate selection of empiric antibiotic treatment; this poses a threat of widespread resistance. GNB antibiotic resistance and the absence of new antibiotics are a major concern given limited treatment options; an aspect that deserves future research. We review current literature, highlight prevalence of MDR-GNB in different respiratory infections and explore their impact on clinical outcomes.

Respiratory infections are a major cause of global mortality and morbidity. In recent years, an increased incidence of multidrug-resistant (MDR) Gram-negative bacteria (GNB) has been described. Microorganisms such as Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae or Acinetobacter baumannii have been identified as causative pathogens of different respiratory tract infections. Several studies have detected MDR-GNB in patients with community-acquired and nosocomial pneumonia. Furthermore, MDR-GNB have also been isolated in patients with chronic obstructive pulmonary disease and bronchiectasis having acute or chronic bronchial infection. Prevalence varies depending on the geographical area but MDR-GNB has been reported in the Asia-Pacific region, Europe and the United States, reaching rates of 70% in hospital-acquired infection. The presence of MDR-GNB has been related to poor clinical outcomes, including increased mortality, although data regarding this relationship are limited. This is probably linked to inappropriate selection of empiric antibiotic treatment; this poses a threat of widespread resistance. GNB antibiotic resistance and the absence of new antibiotics are a major concern given limited treatment options; an aspect that deserves future research. We review current literature, highlight prevalence of MDR-GNB in different respiratory infections and explore their impact on clinical outcomes.

Background Identification of chronic Pseudomonas aeruginosa (PA) infection is important in the management of bronchiectasis, but requires repeated sputum sampling. We hypothesized that serum anti-PA IgG antibodies could diagnose chronic PA infection at a single visit. Methods Clinically stable bronchiectasis patients were studied prospectively. Chronic PA infection was defined as 2 or more positive sputum samples at least 3 months apart and/or failure to clear PA following eradication treatment. Baseline serum anti-PA IgG was determined by a validated ELISA kit. Results A total of 408 patients were included. Sixty of them (14.7%) had chronic PA infection and had higher anti-PA IgG levels (median 6.2 vs. 1.3 units, p

Identification of chronic Pseudomonas aeruginosa (PA) infection is important in the management of bronchiectasis, but requires repeated sputum sampling. We hypothesized that serum anti-PA IgG antibodies could diagnose chronic PA infection at a single visit.Clinically stable bronchiectasis patients were studied prospectively. Chronic PA infection was defined as 2 or more positive sputum samples at least 3 months apart and/or failure to clear PA following eradication treatment. Baseline serum anti-PA IgG was determined by a validated ELISA kit.A total of 408 patients were included. Sixty of them (14.7%) had chronic PA infection and had higher anti-PA IgG levels (median 6.2 vs. 1.3 units, p 0.001). Antibody levels showed direct significant correlations with exacerbation frequency, the bronchiectasis severity index and sputum inflammatory markers. Fifty-seven patients with chronic PA infection had a positive test, giving 95% sensitivity, 74.4% specificity and AUROC of 0.87. During follow-up, 38 patients had a new PA isolation. Eradication at 12 months was achieved in 89.5% of subjects with a negative antibody test and 15.8% of patients with a positive test.Anti-PA IgG test is highly accurate to detect chronic PA infection in bronchiectasis patients. In addition, it may be a marker of disease severity and treatment response.

INTRODUCTION: Severe exacerbations are key events in the natural history of bronchiectasis. However, data on patients9 characteristics and outcomes is scarce. OBJECTIVE: To assess clinical characteristics and outcomes in hospitalized patients with bronchiectasis exacerbations. METHODS: Prospective observational study conducted on consecutive adults with bronchiectasis admitted to a respiratory ward of a tertiary university hospital because of an exacerbation during 2013-2015. Patients with pneumonia were excluded. RESULTS: Among 60 patients enrolled, median (±SD) age was 74±13 years and FEV1 (% predicted) was 44±17%. Baseline median Bronchiectasis Severity Index was 15 (±4) points and FACED score was 4 (±1). Acute respiratory failure was present in 62% of patients. Length of stay was 8 (±5) days. 10 patients (17%) were readmitted before 30-days of hospital discharge and 20 (34%) before 90-days. Three patients died before 90-days of follow-up. Pseudomonas aeruginosa: (PA) was the most common microorganism isolated in 17 (28%) of the subjects. Patients with PA had lower FEV 1 (37±12% vs. 48±18%, p=0.02), a higher number of exacerbations in the previous year (2.6±2.3 vs. 1.1±1.7, p=0.07) and a higher rate of chronic PA infection (47% vs. 5%, p=0.001) in comparison to those without PA. No differences in clinical outcomes evaluated were found among groups. CONCLUSIONS: Acute exacerbations of bronchiectasis requiring hospitalization affect patients with severe disease and are associated with a higher rate of readmissions. PA is the most common causative microorganism and affects patients with chronic PA colonization and previous exacerbations. However, its presence is not related with worse outcomes.

Introduction and objective Itraconazole is an antifungal imidazole used for the treatment of aspergillosis. Evidence supporting the association between itraconazole and the onset of congestive heart failure (CHF) is limited and is based on cases reported after drug market release. Case report We report the case of a 76-year-old man with hypertension and COPD GOLD D who experienced heart failure after receiving a new line of treatment with itraconazole. The patient's symptoms resolved completely after the drug's withdrawal and initiation of treatment with diuretic therapy. Using validated algorithms, we concluded that there was a probable association between itraconazole and the onset of CHF. Conclusions The association between the administration of itraconazole and the onset of CHF is difficult to prove. Further observational studies are needed to assess this association. However, based on the available evidence, we should consider this possible adverse effect and even contraindicate this treatment in patients with a structural heart disease.

Community-acquired pneumonia (CAP) is a leading cause of hospitalization, morbidity, and mortality. Despite advances in antibiotic treatments, mortality among patients with CAP is still high. For this reason, interest has been focused on nonantibiotic therapeutic measures directed to the host response rather than the microorganism. The development of an efficacious adjunctive treatment has important implications for reducing mortality in CAP. Some clinical studies performed in the last decade have shown a clinically beneficial effect of corticosteroids, possibly by diminishing local and systemic inflammatory host response. Recent meta-analyses showed faster resolution of symptoms, shorter time to clinically stability, reduction of mechanical ventilation needed, and reduction of mortality in the most severe population, although some methodological limitations must be taken into account. In addition, some studies using statins also suggested improved outcomes due to its anti-inflammatory effect in CAR although this requires further research. Other adjunctive therapies such as immunoglobulins and stem cells are being explored, but are not yet in the stage of clinical trials. In summary, the use of corticosteroids and other adjuvant treatments are promising in CAR but more studies are needed to determine their impact on mortality.

Purpose of review Identification of patients with multidrug-resistant (MDR) pathogens at initial diagnosis is essential for the appropriate selection of empiric treatment of patients with pneumonia coming from the community. The term Healthcare-Associated Pneumonia (HCAP) is controversial for this purpose. Our goal is to summarize and interpret the data addressing the association of MDR pathogens and community-onset pneumonia. Recent findings Most recent clinical studies conclude that HCAP risk factor does not accurately identify resistant pathogens. Several risk factors related to MDR pathogens, including new ones that were not included in the original HCAP definition, have been described and different risk scores have been proposed. The present review focuses on the most recent literature assessing the importance of different risk factors for MDR pathogens in patients with pneumonia coming from the community. These included generally MDR risk factors, specific risk factors related to methicillin-resistant Staphylococcus aureus or Pseudomonas aeruginosa and clinical scoring systems develop to assess the MDR risk factors and its application in clinical practice. Different MDR risk factors and prediction scores have been recently developed. However, further research is needed in order to help clinicians in distinguishing between different MDR pathogens causing pneumonia.

Background and objectiveAcute exacerbations of chronic obstructive pulmonary disease (AECOPD) due to Pseudomonas aeruginosa (PA) are associated with worse outcomes. PA antibiotic resistance is important to determine treatment and may influence clinical outcomes. The aim was to study clinical characteristics and outcomes in patients with AECOPD associated with PA based on their antibiotic resistance. MethodsThis was a prospective observational study including all patients with AECOPD and positive PA sputum culture admitted in a respiratory ward in a tertiary hospital in Barcelona during 2013-2014. PA was defined as resistant (PA-R) when the antibiogram showed 1 resistance. ResultsFour hundred one patients with AECOPD were evaluated. Of them, 54 (13%) had a positive PA sputum culture. Eighty-two per cent were men, median age was 77 (SD 7) years old and FEV1 was less than 36% (SD 17) of predicted value. PA-R was isolated in 35 patients (66%), and PA-sensitive (PA-S) was isolated in 18 (34%) patients. No differences were found in demographics, lung function and comorbidities among groups. PA-R patients were more likely exposed to prior oral corticosteroids (77% vs 44%, P=0.03) and antibiotics (77% vs 31%, P=0.01), respectively. AECOPD patients associated with PA-S were more likely to die at 30 days (odds ratio 13.53, 95% confidence interval: 1.14-69.56, P=0.03) and 90 days (odds ratio 7.09, 95% confidence interval: 1.33-37.89, P=0.02), respectively. ConclusionPseudomonas aeruginosa-resistant affects patients with severe AECOPD and previous use of corticosteroids and antibiotics. The presence of PA-S is associated with higher mortality. These results may suggest increased virulence in PA-S strains causing acute infections. Pseudomonas aeruginosa (PA) plays an important role in AECOPD. However, the impact of PA resistance patterns on clinical outcomes is not clear. Our study demonstrates that the presence of PA-sensitive is associated with higher mortality.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) due to Pseudomonas aeruginosa (PA) are associated with worse outcomes. PA antibiotic resistance is important to determine treatment and may influence clinical outcomes. The aim was to study clinical characteristics and outcomes in patients with AECOPD associated with PA based on their antibiotic resistance.This was a prospective observational study including all patients with AECOPD and positive PA sputum culture admitted in a respiratory ward in a tertiary hospital in Barcelona during 2013-2014. PA was defined as resistant (PA-R) when the antibiogram showed ≥1 resistance.Four hundred one patients with AECOPD were evaluated. Of them, 54 (13%) had a positive PA sputum culture. Eighty-two per cent were men, median age was 77 (SD 7) years old and FEV1 was less than 36% (SD 17) of predicted value. PA-R was isolated in 35 patients (66%), and PA-sensitive (PA-S) was isolated in 18 (34%) patients. No differences were found in demographics, lung function and comorbidities among groups. PA-R patients were more likely exposed to prior oral corticosteroids (77% vs 44%, P = 0.03) and antibiotics (77% vs 31%, P = 0.01), respectively. AECOPD patients associated with PA-S were more likely to die at 30 days (odds ratio 13.53, 95% confidence interval: 1.14-69.56, P = 0.03) and 90 days (odds ratio 7.09, 95% confidence interval: 1.33-37.89, P = 0.02), respectively.Pseudomonas aeruginosa-resistant affects patients with severe AECOPD and previous use of corticosteroids and antibiotics. The presence of PA-S is associated with higher mortality. These results may suggest increased virulence in PA-S strains causing acute infections.

Introduction: Acute Exacerbations of Chronic Obstructive Pulmonary disease (AECOPD) due to Pseudomonas aeruginosa (PA) are associated with worse outcomes. PA antibiotic resistance is important to determine treatment. Objectives: To study clinical characteristics and outcomes in patients with AECOPD due to PA based on their antibiotic resistance. Methods: Prospective observational study including all patients with AECOPD due to PA admitted in a Respiratory ward in a tertiary hospital in Barcelona during 2013-2014. Resistant PA (PA-R) was defined when ≥1 class of antibiotics were resistant on the antibiogram. Results: 401 patients with AECOPD were evaluated. Of them, 53 (13%) had a positive PA sputum culture. 82% were men, median age (± SD) 77 (±7) years old and FEV1 36 (±17) % of predicted. PA-R was isolated in 35 patients (66%).No differences in demographics, lung function and comorbidities among patients with PA-R and PA-sensible (PA-S) were found, except that patients with PA-R had received more prior oral steroids (80% vs 44%, p = 0.009) and antibiotics (65% vs 33%, p = 0.02) PA persistence after adequate treatment was higher in the PA-R group (82% vs 50%, p = 0.04). However, patients with PA-R had lower 30-day and 90-day mortality when compared to patients with PA –S (3% vs 22%, p = 0.02, and 9% vs 33%, p= 0.02, respectively). Conclusions: PA-R affects patients with severe COPD and previous use of steroids and antibiotics. Persistent PA-R strains were found in follow-up sputum samples. However, the presence of sensitive PA is associated with higher mortality. These results may reflect a contrast between acute infections caused by PA-S and chronic colonization with PA-R.

Resumen Introduccion y objetivo Itraconazol es un antifungico imidazolico para el tratamiento de la aspergilosis. La evidencia que respalda la asociacion entre itraconazol y el desarrollo de insuficiencia cardiaca congestiva (ICC) es limitada y se basa en los casos notificados poscomercializacion del farmaco. Caso clinico Presentamos el caso de un varon de 76 anos, hipertenso, con EPOC GOLD D, que presenta un inicio de insuficiencia cardiaca tras la introduccion de tratamiento con itraconazol. Tras la retirada del farmaco y tratamiento diuretico muestra resolucion completa del cuadro clinico. Tras utilizar varios algoritmos validados sobre causalidad de efectos adversos se concluyo como probable la asociacion entre itraconazol y el desarrollo de ICC en este caso. Conclusiones La asociacion entre la administracion de itraconazol y el desarrollo de ICC es una relacion causal dificil de demostrar. Son necesarios estudios observacionales dirigidos a evaluar tal asociacion. No obstante, con la evidencia disponible debemos considerar la posibilidad de dicho efecto adverso e incluso valorar la contraindicacion en pacientes con antecedentes de cardiopatia estructural.

Background and objective: Secreted mucins play a key role in antibacterial defence in the airway, but have not previously been characterized in non-cystic fibrosis (CF) bronchiectasis patients. We aim to investigate the relationship between secreted mucins levels and the presence of bacterial colonization due to potentially pathogenic microorganisms (PPM) in the airways of stable bronchiectasis patients. Methods: Clinically stable bronchiectasis patients were studied prospectively at two centres. Patients with other pulmonary conditions were excluded. Spontaneous sputum was subject to bacterial culture, and secreted mucins (MUC2, MUC5AC and MUC5B) were measured in sputum supernatants by ELISA. Results: A total of 50 patients were included. PPM were identified from sputum samples in 30 (60%), with Pseudomonas aeruginosa (n = 10) and Haemophilus influenzae (n = 10) as the most common PPM. There were no baseline differences among airway colonized and non-colonized patients. Patients with airways colonized by PPM presented higher levels of airway MUC2. No differences in MUC5AC levels were found among groups, whereas MUC5B levels were undetectable. Patients with P. aeruginosa colonization expressed the highest levels of MUC2. High levels of MUC2 and MUC5AC are also correlated with disease severity using the Bronchiectasis Severity Index. Conclusions: Airway MUC2 levels were higher in bronchiectasis patients colonized with PPM compared with those without airway colonization, especially in patients with P. aeruginosa. These findings suggest that airway-secreted mucins levels may play a role in the pathogenesis of airway infection in non-CF bronchiectasis.

Secreted mucins play a key role in antibacterial defence in the airway, but have not previously been characterized in non-cystic fibrosis (CF) bronchiectasis patients. We aim to investigate the relationship between secreted mucins levels and the presence of bacterial colonization due to potentially pathogenic microorganisms (PPM) in the airways of stable bronchiectasis patients.Clinically stable bronchiectasis patients were studied prospectively at two centres. Patients with other pulmonary conditions were excluded. Spontaneous sputum was subject to bacterial culture, and secreted mucins (MUC2, MUC5AC and MUC5B) were measured in sputum supernatants by ELISA.A total of 50 patients were included. PPM were identified from sputum samples in 30 (60%), with Pseudomonas aeruginosa (n = 10) and Haemophilus influenzae (n = 10) as the most common PPM. There were no baseline differences among airway colonized and non-colonized patients. Patients with airways colonized by PPM presented higher levels of airway MUC2. No differences in MUC5AC levels were found among groups, whereas MUC5B levels were undetectable. Patients with P. aeruginosa colonization expressed the highest levels of MUC2. High levels of MUC2 and MUC5AC are also correlated with disease severity using the Bronchiectasis Severity Index.Airway MUC2 levels were higher in bronchiectasis patients colonized with PPM compared with those without airway colonization, especially in patients with P. aeruginosa. These findings suggest that airway-secreted mucins levels may play a role in the pathogenesis of airway infection in non-CF bronchiectasis.