Relación de Citoquinas y Biomarcadores como patrones de inflamación y etiología de la neumonía adquirida en la comunidad"

La neumonía adquirida en la comunidad (NAC) es una enfermedad respiratoria infecciosa muy prevalente y de elevada mortalidad que desencadena inflamación sistémica. Las últimas investigaciones analizan la respuesta inflamatoria y han observado que la infección por determinados microorganismos se caracterizaría por un "patrón" de respuesta inflamatoria. Nuestro estudio analizó la diferente etiología de la NAC y la respuesta inflamatoria (PCR, PCT y citocinas). Concluyó que las NAC causadas por microorganismo conocido presentan un "patrón" de inflamación específico (S. pneumoniae eleva la PCT e IL-6, la Legionella aumenta la PCR), y que la respuesta está incrementada en presencia de bacteriemia.La pneumònia adquirida a la comunitat (NAC) és una malaltia respiratòria infecciosa molt prevalent i d'elevada mortalitat que desencadena inflamació sistémica. Les últimes investigacions analitzen la resposta inflamatòria i han observat que la infecció per determinats microorganismes es caracteritzaria per un "patró" de resposta inflamatòria. El nostre estudi va analitzar la diferent etiología de la NAC i resposta inflamatòria (PCR, PCT i citocines). Va concloure que les NAC causades per microorganisme conegut presenten un "patró" d'inflamació específic (S. pneumoniae eleva la PCT i IL-6, la Legionella augmenta la PCR), i que la resposta està incrementada en presencia de bacteriemia

Predicting treatment failure in patients with community acquired pneumonia: a case-control study

INTRODUCTION: Treatment failure in community-acquired-pneumonia (CAP) patients is associated with a high mortality rate, and therefore are a matter of great concern in clinical management. Those patients have increased mortality and are a target population for randomized clinical trials. METHODS: A case-control study was performed in patients with CAP (non-failure cases vs. failure cases, discriminating by late and early failure). CRP, PCT, interleukin 1, 6, 8 and 10 and TNF were determined at days 1 and 3 of hospitalization. RESULTS: A total of 253 patients were included in this study where 83 patients presented treatment failure. Of these, 40 (48.2%) had early failure. A discriminative effect was found for a higher CURB-65 score among late failure patients (p = 0.004). A significant increase on day 1 of hospitalization in CRP (p < 0.001), PCT (p = 0.004), IL-6 (p < 0.001) and IL-8 (p = 0.02), and a decrease in IL-1 (p = 0.06) in patients with failure was observed compared with patients without failure. On day 3, only the increase in CRP (p < 0.001), PCT (p = 0.007) and IL-6 (p < 0.001) remained significant. Independent predictors for early failure were higher IL-6 levels on day 1 (OR = 1.78, IC = 1.2-2.6) and pleural effusion (OR = 2.25, IC = 1.0-5.3), and for late failure, higher PCT levels on day 3 (OR = 1.60, IC = 1.0-2.5), CURB-65 score ≥ 3 (OR = 1.43, IC = 1.0-2.0), and multilobar involvement (OR = 4.50, IC = 2.1-9.9). CONCLUSIONS: There was a good correlation of IL-6 levels and CAP failure and IL-6 & PCT with late CAP failure. Pleural effusion and multilobar involvement were simple clinical predictors of early and late failure, respectively

Systemic Inflammation during and after Bronchiectasis Exacerbations: Impact of Pseudomonas aeruginosa

Bronchiectasis is a chronic structural disease associated with exacerbations that provoke systemic inflammation. We aimed to evaluate the systemic acute proinflammatory cytokine and its biomarker profiles during and after exacerbations and its relationship with the severity of episode, microbiological findings, and the bronchiectasis severity index. This prospective observational study compared exacerbation and stable groups. Cytokine (interleukins (IL)-17a, IL-1β, IL-6, IL 8; tumor necrosis factor-alpha (α)) and high-sensitivity C-reactive protein (hsCRP) levels were determined by multiplex analysis on days 1, 5, 30, and 60 in the exacerbation group and on day 1 in the stable group. We recruited 165 patients with exacerbations, of which 93 were severe (hospitalized). Proinflammatory systemic IL-17a, IL-1β, IL-8, and tumor necrosis factor-α levels increased similarly on days 1 and 5 in severe and non-severe episodes, but on day 30, IL-17a, IL-8, and IL-6 levels were only increased for severe exacerbations. The highest IL-17a level occurred in patients with chronic plus the acute isolation of Pseudomonas aeruginosa. At 30 days, severe exacerbations were independently associated with higher levels of IL-17 (Odds ratio (OR) 4.58), IL-6 (OR 4.89), IL-8 (OR 3.08), and hsCRP (OR 6.7), adjusted for age, the bronchiectasis severity index, and treatment duration. Exacerbations in patients with chronic P. aeruginosa infection were associated with an increase in IL-17 and IL-6 at 30 days (ORs 7.47 and 3.44, respectively). Severe exacerbations elicit a higher systemic proinflammatory response that is sustained to day 30. Patients with chronic P. aeruginosa infection had impaired IL-17a reduction. IL-17a could be a useful target for measuring systemic inflammation

Predictors of severe sepsis among patients hospitalized for community-acquired pneumonia

Background Severe sepsis, may be present on hospital arrival in approximately one-third of patients with community-acquired pneumonia (CAP). Objective To determine the host characteristics and micro-organisms associated with severe sepsis in patients hospitalized with CAP. Results We performed a prospective multicenter cohort study in 13 Spanish hospital, on 4070 hospi- talized CAP patients, 1529 of whom (37.6%) presented with severe sepsis. Severe sepsis CAP was independently associated with older age ( > 65 years), alcohol abuse (OR, 1.31; 95% CI, 1.07 - 1.61), chronic obstructive pulmonary disease (COPD) (OR, 1.75; 95% CI, 1.50 - 2.04) and renal disease (OR, 1.57; 95% CI, 1.21 - 2.03), whereas prior antibiotic treat- ment was a protective factor (OR, 0.62; 95% CI, 0.52 - 0.73). Bacteremia (OR, 1.37; 95% CI, 1.05 - 1.79), S pneumoniae (OR, 1.59; 95% CI, 1.31 - 1.95) and mixed microbial etiology (OR, 1.65; 95% CI, 1.10 - 2.49) were associated with severe sepsis CAP. Conclusions CAP patients with COPD, renal disease and alcohol abuse, as well as those with CAP due to S pneumonia or mixed micro-organisms are more likely to present to the hospital with severe sepsis

Relación de Citoquinas y Biomarcadores como patrones de inflamación y etiología de la neumonía adquirida en la comunidad”

La neumonía adquirida en la comunidad (NAC) es una enfermedad respiratoria infecciosa muy prevalente y de elevada mortalidad que desencadena inflamación sistémica. Las últimas investigaciones analizan la respuesta inflamatoria y han observado que la infección por determinados microorganismos se caracterizaría por un “patrón” de respuesta inflamatoria. Nuestro estudio analizó la diferente etiología de la NAC y la respuesta inflamatoria (PCR, PCT y citocinas). Concluyó que las NAC causadas por microorganismo conocido presentan un “patrón” de inflamación específico (S. pneumoniae eleva la PCT e IL-6, la Legionella aumenta la PCR), y que la respuesta está incrementada en presencia de bacteriemia.La pneumònia adquirida a la comunitat (NAC) és una malaltia respiratòria infecciosa molt prevalent i d´elevada mortalitat que desencadena inflamació sistémica. Les últimes investigacions analitzen la resposta inflamatòria i han observat que la infecció per determinats microorganismes es caracteritzaria per un “patró” de resposta inflamatòria. El nostre estudi va analitzar la diferent etiología de la NAC i resposta inflamatòria (PCR, PCT i citocines). Va concloure que les NAC causades per microorganisme conegut presenten un “patró” d´inflamació específic (S. pneumoniae eleva la PCT i IL-6, la Legionella augmenta la PCR), i que la resposta està incrementada en presencia de bacteriemia

Características clínicas, etiológicas y pronóstico de los pacientes con neumonía adquirida en la comunidad (NAC) y sepsis grave al ingreso

La neumonía adquirida en la comunidad (NAC) es un tipo infección respiratoria con elevada tasa de complicaciones y mortalidad sobre todo en los casos que asocian sepsis grave, siendo un problema grave de salud a nivel mundial. En la práctica clínica actual, el reconocimiento del paciente con NAC y sepsis grave o fallo de órgano al ingreso hospitalario es un reto ya que existen dificultades a la hora de identificar a la población de riesgo pudiendo pasar desapercibidos para el clínico. La identificación precoz de la gravedad de la sepsis y fallo de órgano es vital a la hora de instaurar una mejor monitorización clínica y manejo terapéutico del paciente. Este trabajo ha pretendido caracterizar e identificar de forma precoz la gravedad y etiología causal de la sepsis grave y fallo de órgano en los pacientes de mayor riesgo que ingresan por NAC. Para ello se llevó a cabo un estudio prospectivo y multicéntrico en 13 hospitales españoles, recogiéndose los factores de riesgo asociados al huésped, los resultados microbiológicos, el impacto de las complicaciones y mortalidad de la NAC con sepsis grave y fallo de órgano. El primer trabajo evaluó las diferentes comorbilidades del paciente y los microorganismos causales de la NAC, obteniendo un perfil de diferentes características de los episodios más graves de NAC con sepsis grave. El segundo artículo estudió las NAC estructurándola por grupos de riesgo de presentación de fallo de órgano y su asociación con las diferentes comorbilidades, etiología causal e impacto en la mortalidad. Los resultados de esta tesis han permitido ampliar los conocimientos y la mejor caracterización del grupo de pacientes con peor evolución y pronóstico con NAC, pudiendo identificar de forma más específica los microorganismos causales en los episodios más graves, el impacto en la mortalidad y el fallo de órgano más frecuente asociado. Las conclusiones a las que han llevado los resultados de esta tesis suponen una mejora para la práctica diaria del clínico, siendo de utilidad en la toma de decisiones a nivel clínico tanto en el tratamiento como en el manejo del paciente. Además, propicia nuevas hipótesis de investigación en cuanto a mejoría del manejo terapéutico y monitorización de los pacientes de mayor gravedad con NAC.Community adquired pneumonia (CAP) is a respiratory infection with higher rate of complications and increased mortality, especially in those cases associated with severe sepsis which is a serious health problem worldwide. Recognition of patients with CAP and severe sepsis or organ failure on admission is a challenge in the current clinical practice, since there are several difficulties in identifying the population at risk and they may go unnoticed by the clinician who could delay further specific attention. It is important an early identification of the severity of sepsis and organ failure in order to establish a closer monitoring of the evolution the first hours at admission and to improve therapeutic management. This study had aimed to characterize and early identify the severity of sepsis and organ failure in higher risk patients admitted to hospital by CAP. Thus we performed a prospective multicenter study in 13 Spanish hospitals. Data that were collected were: risk factors associated with the host, results of microbiological studies, the impact of different complications and mortality due to CAP with severe sepsis or different organ failure. The first study evaluated the different comorbidities and etiological microorganisms of CAP, with the result of various specific characteristics for CAP with severe sepsis. The second article studied CAP depending on number of organ failure, and structured groups of patients with different risk of presentation showing that each group presented different comorbidities, causal microorganisms and mortality. The results of this thesis has widen the knowledge and the best characterization of the group of patients with worse evolution and prognosis. We can identify more specifically the causal microorganisms of the most severe episodes, the impact on mortality and the most frequent organ failure associated with CAP. The conclusions of this thesis lead us to improve the daily clinical practice, and has been a useful tool to take clinical decisions in treatment, monitoring and in the management of patients. In addition, it fosters new research hypotheses regarding improvement in clinical, therapeutic management and monitoring those patients with greater severity CAP

Características clínicas, etiológicas y pronóstico de los pacientes con neumonía adquirida en la comunidad (NAC) y sepsis grave al ingreso

La neumonía adquirida en la comunidad (NAC) es un tipo infección respiratoria con elevada tasa de complicaciones y mortalidad sobre todo en los casos que asocian sepsis grave, siendo un problema grave de salud a nivel mundial. En la práctica clínica actual, el reconocimiento del paciente con NAC y sepsis grave o fallo de órgano al ingreso hospitalario es un reto ya que existen dificultades a la hora de identificar a la población de riesgo pudiendo pasar desapercibidos para el clínico. La identificación precoz de la gravedad de la sepsis y fallo de órgano es vital a la hora de instaurar una mejor monitorización clínica y manejo terapéutico del paciente. Este trabajo ha pretendido caracterizar e identificar de forma precoz la gravedad y etiología causal de la sepsis grave y fallo de órgano en los pacientes de mayor riesgo que ingresan por NAC. Para ello se llevó a cabo un estudio prospectivo y multicéntrico en 13 hospitales españoles, recogiéndose los factores de riesgo asociados al huésped, los resultados microbiológicos, el impacto de las complicaciones y mortalidad de la NAC con sepsis grave y fallo de órgano. El primer trabajo evaluó las diferentes comorbilidades del paciente y los microorganismos causales de la NAC, obteniendo un perfil de diferentes características de los episodios más graves de NAC con sepsis grave. El segundo artículo estudió las NAC estructurándola por grupos de riesgo de presentación de fallo de órgano y su asociación con las diferentes comorbilidades, etiología causal e impacto en la mortalidad. Los resultados de esta tesis han permitido ampliar los conocimientos y la mejor caracterización del grupo de pacientes con peor evolución y pronóstico con NAC, pudiendo identificar de forma más específica los microorganismos causales en los episodios más graves, el impacto en la mortalidad y el fallo de órgano más frecuente asociado. Las conclusiones a las que han llevado los resultados de esta tesis suponen una mejora para la práctica diaria del clínico, siendo de utilidad en la toma de decisiones a nivel clínico tanto en el tratamiento como en el manejo del paciente. Además, propicia nuevas hipótesis de investigación en cuanto a mejoría del manejo terapéutico y monitorización de los pacientes de mayor gravedad con NAC.Community adquired pneumonia (CAP) is a respiratory infection with higher rate of complications and increased mortality, especially in those cases associated with severe sepsis which is a serious health problem worldwide. Recognition of patients with CAP and severe sepsis or organ failure on admission is a challenge in the current clinical practice, since there are several difficulties in identifying the population at risk and they may go unnoticed by the clinician who could delay further specific attention. It is important an early identification of the severity of sepsis and organ failure in order to establish a closer monitoring of the evolution the first hours at admission and to improve therapeutic management. This study had aimed to characterize and early identify the severity of sepsis and organ failure in higher risk patients admitted to hospital by CAP. Thus we performed a prospective multicenter study in 13 Spanish hospitals. Data that were collected were: risk factors associated with the host, results of microbiological studies, the impact of different complications and mortality due to CAP with severe sepsis or different organ failure. The first study evaluated the different comorbidities and etiological microorganisms of CAP, with the result of various specific characteristics for CAP with severe sepsis. The second article studied CAP depending on number of organ failure, and structured groups of patients with different risk of presentation showing that each group presented different comorbidities, causal microorganisms and mortality. The results of this thesis has widen the knowledge and the best characterization of the group of patients with worse evolution and prognosis. We can identify more specifically the causal microorganisms of the most severe episodes, the impact on mortality and the most frequent organ failure associated with CAP. The conclusions of this thesis lead us to improve the daily clinical practice, and has been a useful tool to take clinical decisions in treatment, monitoring and in the management of patients. In addition, it fosters new research hypotheses regarding improvement in clinical, therapeutic management and monitoring those patients with greater severity CAP

Características clínicas, etiológicas y pronóstico de los pacientes con neumonía adquirida en la comunidad (NAC) y sepsis grave al ingreso /

La neumonía adquirida en la comunidad (NAC) es un tipo infección respiratoria con elevada tasa de complicaciones y mortalidad sobre todo en los casos que asocian sepsis grave, siendo un problema grave de salud a nivel mundial. En la práctica clínica actual, el reconocimiento del paciente con NAC y sepsis grave o fallo de órgano al ingreso hospitalario es un reto ya que existen dificultades a la hora de identificar a la población de riesgo pudiendo pasar desapercibidos para el clínico. La identificación precoz de la gravedad de la sepsis y fallo de órgano es vital a la hora de instaurar una mejor monitorización clínica y manejo terapéutico del paciente. Este trabajo ha pretendido caracterizar e identificar de forma precoz la gravedad y etiología causal de la sepsis grave y fallo de órgano en los pacientes de mayor riesgo que ingresan por NAC. Para ello se llevó a cabo un estudio prospectivo y multicéntrico en 13 hospitales españoles, recogiéndose los factores de riesgo asociados al huésped, los resultados microbiológicos, el impacto de las complicaciones y mortalidad de la NAC con sepsis grave y fallo de órgano. El primer trabajo evaluó las diferentes comorbilidades del paciente y los microorganismos causales de la NAC, obteniendo un perfil de diferentes características de los episodios más graves de NAC con sepsis grave. El segundo artículo estudió las NAC estructurándola por grupos de riesgo de presentación de fallo de órgano y su asociación con las diferentes comorbilidades, etiología causal e impacto en la mortalidad. Los resultados de esta tesis han permitido ampliar los conocimientos y la mejor caracterización del grupo de pacientes con peor evolución y pronóstico con NAC, pudiendo identificar de forma más específica los microorganismos causales en los episodios más graves, el impacto en la mortalidad y el fallo de órgano más frecuente asociado. Las conclusiones a las que han llevado los resultados de esta tesis suponen una mejora para la práctica diaria del clínico, siendo de utilidad en la toma de decisiones a nivel clínico tanto en el tratamiento como en el manejo del paciente. Además, propicia nuevas hipótesis de investigación en cuanto a mejoría del manejo terapéutico y monitorización de los pacientes de mayor gravedad con NAC.Community adquired pneumonia (CAP) is a respiratory infection with higher rate of complications and increased mortality, especially in those cases associated with severe sepsis which is a serious health problem worldwide. Recognition of patients with CAP and severe sepsis or organ failure on admission is a challenge in the current clinical practice, since there are several difficulties in identifying the population at risk and they may go unnoticed by the clinician who could delay further specific attention. It is important an early identification of the severity of sepsis and organ failure in order to establish a closer monitoring of the evolution the first hours at admission and to improve therapeutic management. This study had aimed to characterize and early identify the severity of sepsis and organ failure in higher risk patients admitted to hospital by CAP. Thus we performed a prospective multicenter study in 13 Spanish hospitals. Data that were collected were: risk factors associated with the host, results of microbiological studies, the impact of different complications and mortality due to CAP with severe sepsis or different organ failure. The first study evaluated the different comorbidities and etiological microorganisms of CAP, with the result of various specific characteristics for CAP with severe sepsis. The second article studied CAP depending on number of organ failure, and structured groups of patients with different risk of presentation showing that each group presented different comorbidities, causal microorganisms and mortality. The results of this thesis has widen the knowledge and the best characterization of the group of patients with worse evolution and prognosis. We can identify more specifically the causal microorganisms of the most severe episodes, the impact on mortality and the most frequent organ failure associated with CAP. The conclusions of this thesis lead us to improve the daily clinical practice, and has been a useful tool to take clinical decisions in treatment, monitoring and in the management of patients. In addition, it fosters new research hypotheses regarding improvement in clinical, therapeutic management and monitoring those patients with greater severity CAP

Systemic inflammatory pattern of patients with community-acquired pneumonia with and without COPD

Background: Several clinical studies have evaluated the role of COPD in patients with communityacquired pneumonia (CAP). We investigated the systemic inflammatory response of patients with CAP (CAP + COPD) and patients without associated COPD (CAP only). Methods: Clinical, microbiologic, and immunologic data were collected from 367 prospective patients on admission to hospital during a 3-year period. Comparative analyses were performed between patients with CAP + COPD (n = 117) and those with CAP only (n + 250) and between patients with and without domiciliary use of inhaled corticosteroids (ICSs) and oral corticosteroids. Results: Detailed characteristics of clinical severity and prognosis (mortality on hospitalization and at 30 and 90 days) were similar between the CAP + COPD and CAP-only groups. The readmission rate and the frequency of previous pneumonia were higher in the group of patients with CAP + COPD. On day 1 (admission to hospital), patients with CAP + COPD had significantly lower serum levels of tumor necrosis factor-α, IL-1, and IL-6 compared with the CAP-only group; levels of the remaining inflammatory biomarkers (C-reactive protein, procalcitonin, IL-8, and IL-10) were similar at days 1 and 3. The exclusion of patients with domiciliary use of ICS and oral corticosteroids confirmed lower levels of TNF-α on day 1 in patients with CAP + COPD. Finally, lower levels of IL-6 were found only among those patients with COPD who were currently using ICS. Conclusions: Our prospective study demonstrates a different, disease-specific, early inflammatory pattern between patients with CAP with and without associated COPD. These findings are not completely corticosteroid mediated. © 2013 American College of Chest Physicians

Pneumonic and nonpneumonic exacerbations of COPD: Inflammatory response and clinical characteristics

Background: Community-acquired pneumonia (CAP) is a frequent event in patients with COPD, although it is not currently considered an acute exacerbation of COPD (AECOPD). To our knowledge, no studies have compared the inflammatory response of patients with COPD who develop CAP or AECOPD. The aim of our study was to compare clinical and evolutive manifestations and biologic signaling of AECOPD and CAP + COPD. Methods: Prospective data were collected from 249 consecutively hospitalized patients with COPD. Comparative analyses were performed in patients with AECOPD (n = 133) and patients with CAP + COPD (n = 116). Measures of clinical characteristics, blood biomarkers, and evolution were recorded on admission, after 3 and 30 days, and in a follow-up period of 30 days, 90 days, and 1 year. Results: Patients with CAP + COPD had higher FEV 1 compared with patients with COPD without pneumonia. In-hospital and long-term outcomes (1 year) were similar for both populations. However, patients with AECOPD had more readmissions, and patients with CAP had more prior episodes of pneumonia. At day 1 and day 3, patients with CAP + COPD had significantly (P < .001) higher serum levels of C-reactive protein (CRP), procalcitonin, tumor necrosis factor-α, and IL-6. Repetition of the analyses after stratifying patients based on severity of disease, current inhaled pharmacotherapy, and noninfectious AECOPD cause confirmed higher levels of the same biomarkers in patients with CAP + COPD. Chills, pleuritic pain, sputum purulence, and CRP levels at day 1 were independent clinical predictors of CAP + COPD. Conclusions: Our study confirms that two different clinical and inflammatory profiles exist in hospitalized patients with COPD in response to CAP (stronger response) and AECOPD, although with similar short-term and long-term outcomes. © 2013 American College of Chest Physicians