Relationship between Respiratory Microbiome and Systemic Inflammatory Markers in COPD: A Pilot Study.

The respiratory microbiome may influence the development and progression of COPD by modulating local immune and inflammatory events. We aimed to investigate whether relative changes in respiratory bacterial abundance are also associated with systemic inflammation, and explore their relationship with the main clinical COPD phenotypes. Multiplex analysis of inflammatory markers and transcript eosinophil-related markers were analyzed on peripheral blood in a cohort of stable COPD patients (n = 72). Respiratory microbiome composition was analyzed by 16S rRNA microbial sequencing on spontaneous sputum. Spearman correlations were applied to test the relationship between the microbiome composition and systemic inflammation. The concentration of the plasma IL-8 showed an inverted correlation with the relative abundance of 17 bacterial genera in the whole COPD cohort. COPD patients categorized as eosinophilic showed positive relationships with blood eosinophil markers and inversely correlated with the degree of airway obstruction and the number of exacerbations during the previous year. COPD patients categorized as frequent exacerbators were enriched with the bacterial genera Pseudomonas which, in turn, was positively associated with the severity of airflow limitation and the prior year's exacerbation history. The associative relationships of the sputum microbiome with the severity of the disease emphasize the relevance of the interaction between the respiratory microbiota and systemic inflammation.

Proyecto de biomarcadores y perfiles clínicos personalizados en la enfermedad pulmonar obstructiva crónica (proyecto BIOMEPOC) / The BIOMEPOC Project: Personalized Biomarkers and Clinical Profiles in Chronic Obstructive Pulmonary Disease

La enfermedad pulmonar obstructiva crónica (EPOC) es una entidad de presentación heterogénea. Por ello, se han intentado perfilar diferentes fenotipos y endotipos, que permitirían un manejo más diferenciado. El objetivo del proyecto Biomarcadores en la EPOC (BIOMEPOC) es identificar biomarcadores sanguíneos útiles para tipificar mejor a los enfermos. Se analizarán datos clínicos y muestras sanguíneas en un grupo de pacientes y controles sanos. El proyecto constará de fases de prospección y de validación. Se realizarán determinaciones analíticas sanguíneas con técnicas convencionales y de diversas ciencias «ómicas» (transcriptómica, proteómica y metabolómica). Las primeras se realizarán orientadas por hipótesis, mientras que con las segundas se realizará una exploración sin dicho condicionante. Finalmente se realizará un análisis multinivel. En el momento actual se han reclutado 269 pacientes y 83 controles, y se está iniciando el procesamiento de muestras. Con los resultados obtenidos se espera identificar nuevos biomarcadores que, en solitario o combinados, permitan una mejor tipificación de los pacientes

Chronic obstructive pulmonary disease (COPD) is an entity with a heterogeneous presentation. For this reason, attempts have been made to characterize different phenotypes and endotypes to enable a more individualized approach. The aim of the Biomarkers in COPD (BIOMEPOC) project is to identify useful biomarkers in blood to improve the characterization of patients. Clinical data and blood samples from a group of patients and healthy controls will be analyzed. The project will consist of an exploration phase and a validation phase. Analytical parameters in blood will be determined using standard techniques and certain ‘omics’ (transcriptomics, proteomics, and metabolomics). The former will be hypothesis-driven, whereas the latter will be exploratory. Finally, a multilevel analysis will be conducted. Currently, 269 patients and 83 controls have been recruited, and sample processing is beginning. Our hope is to use the results to identify new biomarkers that, alone or combined, will allow a better characterization of patients

The BIOMEPOC Project: Personalized Biomarkers and Clinical Profiles in Chronic Obstructive Pulmonary Disease. / Proyecto de biomarcadores y perfiles clínicos personalizados en la enfermedad pulmonar obstructiva crónica (proyecto BIOMEPOC).

Chronic obstructive pulmonary disease (COPD) is an entity with a heterogeneous presentation. For this reason, attempts have been made to characterize different phenotypes and endotypes to enable a more individualized approach. The aim of the Biomarkers in COPD (BIOMEPOC) project is to identify useful biomarkers in blood to improve the characterization of patients. Clinical data and blood samples from a group of patients and healthy controls will be analyzed. The project will consist of an exploration phase and a validation phase. Analytical parameters in blood will be determined using standard techniques and certain 'omics' (transcriptomics, proteomics, and metabolomics). The former will be hypothesis-driven, whereas the latter will be exploratory. Finally, a multilevel analysis will be conducted. Currently, 269 patients and 83 controls have been recruited, and sample processing is beginning. Our hope is to use the results to identify new biomarkers that, alone or combined, will allow a better characterization of patients.

Oral Low-dose Theophylline on Top of Inhaled Fluticasone-Salmeterol Does Not Reduce Exacerbations in Patients With Severe COPD: A Pilot Clinical Trial.

BACKGROUND: COPD is characterized by chronic inflammation. In vitro and ex vivo observations suggest that this inflammatory response is partially resistant to the effect of corticosteroids and that low-dose theophylline can restore this response via enhancement of histone deacetylase (HDAC) activity. Whether this occurs in vivo and what its potential clinical consequences are is unclear. OBJECTIVES: The objective of this trial was to determine whether low-dose theophylline on top of inhaled long-acting ß2-agonists and inhaled corticosteroids (ICS) in patients with COPD (1) enhances HDAC activity and the antiinflammatory effects of ICS in vivo, (2) reduces the concentration of inflammatory markers, and (3) reduces exacerbation frequency. METHODS: In this prospective, double-blind, placebo-controlled clinical trial, we randomized patients with COPD (FEV1 < 50% predicted plus at least one hospitalization due to exacerbation in the previous year) to ICS plus theophylline 100 mg bid or matched placebo. We determined the following at baseline and at the end of 52 weeks of follow-up: (1) HDAC activity in blood monocytes and sputum macrophages, (2) the concentration of several inflammatory markers (IL-8, IL-6, IL-1ß, and tumor necrosis factor -α) in serum and sputum supernatant, and (3) the rates of exacerbations and adverse effects. RESULTS: Seventy patients were randomized-36 to theophylline and 34 to placebo. HDAC activity and inflammatory marker levels were not different in the two arms either at baseline or after 52 weeks. Likewise, the rate of exacerbations during follow-up was similar in both groups. CONCLUSIONS: The combination of low-dose oral theophylline and ICS did not enhance the antiinflammatory properties of ICS in vivo or influence exacerbation rate. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01599871; URL: www.clinicaltrials.gov.

Actividad de una unidad de cuidados respiratorios intermedios dependiente de un servicio de neumología / Activity of an Intermediate Respiratory Care Unit Attached to a Respiratory Medicine Department

Introducción y objetivo: El desarrollo de la ventilación no invasiva (VNI) ha aumentado la complejidad de los pacientes ingresados en los servicios de neumología. Por ello, en España y Europa se están incorporando unidades especiales para el seguimiento y tratamiento de pacientes con enfermedades respiratorias graves: las unidades de cuidados respiratorios intermedios (UCRI). El objetivo del presente estudio ha sido describir la actividad de una UCRI dependiente de un servicio de neumología. Esta información puede ser un punto de referencia útil que facilite la implementación de las UCRI en otros hospitales del Sistema Nacional de Salud español. Métodos: De enero a diciembre de 2006, ambos inclusive, se recogió de forma prospectiva y sistemática la actividad realizada en la UCRI del Hospital Universitario Son Dureta. Resultados: Ingresaron 206 pacientes, cuya edad media (±desviación estándar) era de 65±14 años. Los Servicios de Urgencias y Neumología y la Unidad de Cuidados Intensivos (UCI) aportaron, respectivamente, el 67, el 14 y el 12% de todos los ingresos. Los principales diagnósticos de ingreso fueron: agudización de la enfermedad pulmonar obstructiva crónica (EPOC, con 97 casos; 47,1%), neumonía (n=39; 18,9%) e insuficiencia cardíaca (n=17; 8,2%). Del total de pacientes, 121 (59%) precisaron VNI. La estancia media fue de 5±5 días. El 79,1% recibió el alta a camas de hospitalización convencional del propio Servicio de Neumología, el 7,8% requirió ingreso posterior en la UCI y el 9,7% falleció. De los pacientes con agudización de la EPOC (edad media: 66,5±10 años; estancia media: 4,6±4,5 días), el 67% precisó VNI, el 7,2% requirió un ingreso posterior en la UCI y el 8,2% falleció(AU)

Conclusiones: En nuestro país es viable la creación de una UCRI dependiente del servicio de neumología. Estas unidades permiten desarrollar una alta actividad asistencial con un bajo porcentaje de fracasos terapéuticos. La agudización de la EPOC fue el diagnóstico de ingreso más habitual en nuestra UCRI, y la necesidad de tratamiento con VNI, el criterio de ingreso más frecuente(AU)

Background and objectiveWith the development of noninvasive ventilation (NIV), patients with increasingly complex needs have been admitted to respiratory medicine departments. For this reason, such departments in Spain and throughout Europe have been adding specialized respiratory intermediate care units (RICUs) for monitoring and treating patients with severe respiratory diseases. The aim of the present study was to describe the activity of such a RICU. The description may be of use in facilitating the setting up of RICUs in other hospitals of the Spanish National Health Service. MethodsA systematic record of activity carried out in the RICU of the Hospital Universitario Son Dureta between January and December 2006 was kept prospectively. ResultsOf 206 patients with a mean (SD) age of 65 (14) years admitted to the unit, 67% came from the emergency department, 14% from the respiratory medicine department, and 12% from the intensive care unit (ICU). The most common admission diagnoses were exacerbated chronic obstructive pulmonary disease (COPD) (n=97, 47.1%), pneumonia (n=39, 18.9%), heart failure (n=17, 8.2%), and pulmonary vascular diseases (n=18, 8.7%). One hundred twenty-one patients (59%) required NIV. Mean length of stay in the RICU was 5 (5) days. Patients were discharged to the conventional respiratory ward in 79.1% of the cases; 7.8% required subsequent admission to the ICU, and 9.7% died. Of the patients with exacerbated COPD (mean age, 66.5 [10] years; mean length of stay, 4.6 [4.5] days), 67% required NIV, 7.2% required subsequent admission to the ICU, and 8.2% died. ConclusionsThe creation of a RICU by a respiratory medicine department is viable in Spain. Such units make it possible to treat a large number of patients with a low rate of therapeutic failures. Exacerbated COPD was the most common diagnosis on admission to our RICU, and the need for NIV the most common criterion for admission(AU)

[Activity of an intermediate respiratory care unit attached to a respiratory medicine department]. / Actividad de una unidad de cuidados respiratorios intermedios dependiente de un servicio de neumología.

BACKGROUND AND OBJECTIVE: With the development of noninvasive ventilation (NIV), patients with increasingly complex needs have been admitted to respiratory medicine departments. For this reason, such departments in Spain and throughout Europe have been adding specialized respiratory intermediate care units (RICUs) for monitoring and treating patients with severe respiratory diseases. The aim of the present study was to describe the activity of such a RICU. The description may be of use in facilitating the setting up of RICUs in other hospitals of the Spanish National Health Service. METHODS: A systematic record of activity carried out in the RICU of the Hospital Universitario Son Dureta between January and December 2006 was kept prospectively. RESULTS: Of 206 patients with a mean (SD) age of 65 (14) years admitted to the unit, 67% came from the emergency department, 14% from the respiratory medicine department, and 12% from the intensive care unit (ICU). The most common admission diagnoses were exacerbated chronic obstructive pulmonary disease (COPD) (n=97, 47.1%), pneumonia (n=39, 18.9%), heart failure (n=17, 8.2%), and pulmonary vascular diseases (n=18, 8.7%). One hundred twenty-one patients (59%) required NIV. Mean length of stay in the RICU was 5 (5) days. Patients were discharged to the conventional respiratory ward in 79.1% of the cases; 7.8% required subsequent admission to the ICU, and 9.7% died. Of the patients with exacerbated COPD (mean age, 66.5 [10] years; mean length of stay, 4.6 [4.5] days), 67% required NIV, 7.2% required subsequent admission to the ICU, and 8.2% died. CONCLUSIONS: The creation of a RICU by a respiratory medicine department is viable in Spain. Such units make it possible to treat a large number of patients with a low rate of therapeutic failures. Exacerbated COPD was the most common diagnosis on admission to our RICU, and the need for NIV the most common criterion for admission.

[Impact of an on-duty pulmonologist on the activity of a respiratory medicine department]. / Impacto de la presencia de un neumólogo de guardia sobre la actividad de un servicio de neumología.

OBJECTIVE: To evaluate the impact on health care and clinical management of 24-hour coverage by an on-site pulmonologist in a respiratory medicine department. METHODS: In February 2004, a new respiratory medicine 24-hour duty service was started in our hospital. The activity of the on-duty pulmonologist during the following 12 months was systematically and prospectively recorded. The results were put into perspective by comparing the number of monthly admissions and the mean length of stay during the study period with those of the previous 12-month period. RESULTS: During the study period, the on-duty pulmonologist received a mean (SD) of 9.02 (5.27) emergency calls every day, performed 202 diagnostic or therapeutic interventions, and discharged 342 patients. During this period, 1305 patients were admitted to the department (mean length of stay, 8.1 days), whereas in the previous 12 months, with no on-site pulmonologist, 1680 patients were admitted (mean length of stay, 9.0 days). This represents a 22.3% reduction in the annual number of admissions and a reduction in the mean stay by almost 1 day (0.9 days). CONCLUSIONS: The provision of an on-duty pulmonologist was efficient because it facilitated patient turnaround.

Impacto de la presencia de un neumólogo de guardia sobre la actividad de un servicio de neumología / Impact of an on-duty pulmonologist on the activity of a respiratory medicine department

OBJETIVO: Analizar qué impacto asistencial y de gestión clínica tiene la implantación de guardias de presencia física continuada en un servicio de neumología. MÉTODOS: En febrero de 2004 se introdujeron las guardias de neumología en el Hospital Universitario Son Dureta. Durante un año, hasta enero de 2005, se recogió de forma prospectiva y sistemática la actividad realizada por el/la neumólogo/a de guardia. Con objeto de situar estos resultados en perspectiva, se ha comparado el número de ingresos mensuales y su estancia media durante los 12 meses en que se ha dispuesto de guardia de neumología y los 12 meses inmediatamente anteriores. RESULTADOS: Durante los 12 meses evaluados, el/la neumólogo/a de guardia recibió una media ± desviación estándar de 9,02 ± 5,27 avisos urgentes cada día, realizó 202 técnicas diagnósticas/terapéuticas y dio de alta a 342 pacientes. Durante este período ingresaron en el servicio 1.305 pacientes (estancia media: 8,1 días), mientras que en los 12 meses previos, sin guardia de la especialidad, habían ingresado en el servicio 1.680 pacientes (estancia media: 9,0 días); esto supone una reducción del 22,3% del número anual de ingresos y una disminución de la estancia media de los pacientes ingresados de prácticamente un día (0,9 días). CONCLUSIONES: La implantación de guardias de neumología ha sido una medida eficiente, que ha contribuido a agilizar la rotación de los pacientes ingresados

OBJECTIVE: To evaluate the impact on health care and clinical management of 24-hour coverage by an on-site pulmonologist in a respiratory medicine department. METHODS: In February 2004, a new respiratory medicine 24-hour duty service was started in our hospital. The activity of the on-duty pulmonologist during the following 12 months was systematically and prospectively recorded. The results were put into perspective by comparing the number of monthly admissions and the mean length of stay during the study period with those of the previous 12-month period. RESULTS: During the study period, the on-duty pulmonologist received a mean (SD) of 9.02 (5.27) emergency calls every day, performed 202 diagnostic or therapeutic interventions, and discharged 342 patients. During this period, 1305 patients were admitted to the department (mean length of stay, 8.1 days), whereas in the previous 12 months, with no on-site pulmonologist, 1680 patients were admitted (mean length of stay, 9.0 days). This represents a 22.3% reduction in the annual number of admissions and a reduction in the mean stay by almost 1 day (0.9 days). CONCLUSIONS: The provision of an on-duty pulmonologist was efficient because it facilitated patient turnaround