Salivary immunity and lower respiratory tract infections in non-elite marathon runners

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Antimicrobial peptides, disease severity and exacerbations in bronchiectasis

Rationale: Recently 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. Objectives: To determine pulmonary and systemic levels of AMP and their relationship with disease severity and future risk of exacerbations in bronchiectasis. Methods: A 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 results: AMP 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. Conclusions: Patients 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

Pseudomonas aeruginosa en la enfermedad pulmonar obstructiva crónica; papel de los patrones de resistencia e impacto en las agudizaciones graves.

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

Pseudomonas aeruginosa en la enfermedad pulmonar obstructiva crónica; papel de los patrones de resistencia e impacto en las agudizaciones graves.

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

Pseudomonas aeruginosa en la enfermedad pulmonar obstructiva crónica : papel de los patrones de resistencia e impacto en las agudizaciones graves /

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

Drug related problems in clinical practice : a cross-sectional study on their prevalence, risk factors and associated pharmaceutical interventions

Drug-related problems (DRP) cause preventable negative health outcomes, especially during hospital admissions. The aim of our study was to examine the prevalence and characteristics of DRP in regular clinical pharmacy, as well as to determine those factors associated with a higher risk of DRP in the hospital setting. We analyzed data from a standardized registry database of regular pharmacy practice (2015- 2016). DRP were classified according to the Pharmaceutical Care Network Europe v6.2 classification. Cross-sectional data were obtained from 1602 adults admitted to medical wards. Crude and adjusted binary logistic regressions were performed to identify associations between potential risk factors and DRP. Overall DRP prevalence was high across medical specialties (45,1%), in a population characterized by advanced age, polypharmacy and multimorbidity. Problems leading to DRP were mainly classified into two domains (effectiveness and adverse reactions), being drug and dose selection the most frequent causes. Interventions were accepted and DRP were totally or partially solved in 74.1% and 4.81% of cases, respectively. In the adjusted model polypharmacy, allergies, BMI > 25 kg/m2 and clearance < 30 mL/min were associated with a higher risk of DRP. The participation of clinical pharmacists into multidisciplinary teams promotes the detection and solution of DRP. Polypharmacy, obesity, renal impairment and allergy are associated with a higher risk of DRP during admission

Salivary immunity and lower respiratory tract infections in non-elite marathon runners

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