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.

Relationship between the respiratory microbiome and the severity of airflow limitation, history of exacerbations and circulating eosinophils in COPD patients.

BACKGROUND: The respiratory microbiome is altered in COPD patients but its relationship with core components of the disease, such as the severity of airflow limitation, the frequency of exacerbations or the circulating levels of eosinophils, is unclear. METHODS: Cross-sectional study comprising 72 clinically stable COPD patients (mean age 68 [SD 7.9] years; FEV1 48.7 [SD 20.1]% of reference) who provided spontaneous sputum samples for 16S rRNA gene amplification and sequencing. The microbiome composition was analysed with QIIME. RESULTS: We observed that: (1) more severe airflow limitation was associated with reduced relative abundance (RA) of Treponema and an increase in Pseudomonas; (2) patients with ≥2 exacerbations the previous year showed a significantly different bacterial community with respect to non-exacerbators (p = 0.014), with changes in 13 genera, including an increase of Pseudomonas, and finally, (3) peripheral eosinophils levels ≥2% were associated with more diverse microbiome [Chao1 224.51 (74.88) vs 277.39 (78.92) p = 0.006; Shannon 3.94 (1.05) vs 4.54 (1.06) p = 0.020], and a significant increase in the RAs of 20 genera. CONCLUSION: The respiratory microbiome in clinically stable COPD patients varies significantly according to the severity of airflow limitation, previous history of exacerbations and circulating eosinophils levels.

Predictors of one-year mortality after hospitalization for an exacerbation of COPD.

BACKGROUND: Hospitalization for a severe exacerbation of COPD (eCOPD) is an important event in the natural history of COPD. Identifying factors related to mortality 1 year after hospitalization could help determine interventions to reduce mortality. METHODS: In a prospective, observational, multicentre study, we evaluated data from two cohorts: the Spanish audit of hospital COPD exacerbation care (our derivation sample) and the Spanish cohort of the European audit of COPD exacerbation care (our validation sample). The endpoint was all-cause mortality. Mortality was determined by local research managers of the participating hospitals and matched the official national index records in Spain. RESULTS: In the multivariate analysis, factors independently related to an increase in mortality were older age, cardio-cerebro-vascular and/or dementia comorbidities, PaCO2 > 55 mmHg measured at emergency department arrival, hospitalizations for COPD exacerbations in the previous year, and hospital characteristics. The area under the receiver-operating curve for this model was 0.75 in the derivation cohort and 0.76 in the validation cohort. CONCLUSION: One-year mortality following the index hospitalization for an exacerbation of COPD was related to clinical characteristics of the patient and of the index event, previous events of similar severity, and characteristics of the hospital where the patient was treated.

Risk of death and readmission of hospital-admitted COPD exacerbations: European COPD Audit.

Studies report high in-hospital and post-discharge mortality of chronic obstructive pulmonary disease (COPD) exacerbations varying depending upon patient characteristics, hospital resources and treatment standards. This study aimed to investigate the patient, resource and organisational factors associated with in-hospital and 90-day post-discharge mortality and readmission of COPD exacerbations within the European COPD Audit. The audit collected data of COPD exacerbation admissions from 13 European countries.On admission, only 49.7% of COPD patients had spirometry results available and only 81.6% had blood gases taken. Using logistic regression analysis, the risk associated with in-hospital and post-discharge mortality was higher age, presence of acidotic respiratory failure, subsequent need for ventilatory support and presence of comorbidity. In addition, the 90-day risk of COPD readmission was associated with previous admissions. Only the number of respiratory specialists per 1000 beds, a variable related to hospital resources, decreased the risk of post-discharge mortality.The European COPD Audit identifies risk factors associated with in-hospital and post-discharge mortality and COPD readmission. Addressing the deficiencies in acute COPD care such as making spirometry available and measuring blood gases and providing noninvasive ventilation more regularly would provide opportunities to improve COPD outcomes.

Molecular and clinical diseasome of comorbidities in exacerbated COPD patients.

The frequent occurrence of comorbidities in patients with chronic obstructive pulmonary disease (COPD) suggests that they may share pathobiological processes and/or risk factors.To explore these possibilities we compared the clinical diseasome and the molecular diseasome of 5447 COPD patients hospitalised because of an exacerbation of the disease. The clinical diseasome is a network representation of the relationships between diseases, in which diseases are connected if they co-occur more than expected at random; in the molecular diseasome, diseases are linked if they share associated genes or interaction between proteins.The results showed that about half of the disease pairs identified in the clinical diseasome had a biological counterpart in the molecular diseasome, particularly those related to inflammation and vascular tone regulation. Interestingly, the clinical diseasome of these patients appears independent of age, cumulative smoking exposure or severity of airflow limitation.These results support the existence of shared molecular mechanisms among comorbidities in COPD.

Predictive factors of severe multilobar pneumonia and shock in patients with influenza.

PURPOSE: To identify risk factors present at admission in adult patients hospitalised due to influenza virus infection during the 2009/10 and 2010/11 seasons--including whether infection was from pandemic or seasonal influenza A infections--that were associated with the likelihood of developing severe pneumonia with multilobar involvement and shock. METHODS: Prospective cohort study. Patients hospitalised due to influenza virus infection were recruited. We collected information on sociodemographic characteristics, pre-existing medical conditions, vaccinations, toxic habits, previous medications, exposure to social environments, and EuroQoL-5D (EQ-5D). Severe pneumonia with multilobar involvement and/or shock (SPAS) was the primary outcome of interest. We constructed two multivariate logistic regression models to explain the likelihood of developing SPAS and to create a clinical prediction rule for developing SPAS that includes clinically relevant variables. RESULTS: Laboratory-confirmed A(H1N1)pdm09, EQ-5D utility score 7 days before admission, more than one comorbidity, altered mental status, dyspnoea on arrival, days from onset of symptoms, and influenza season were associated with SPAS. In addition, not being vaccinated against seasonal influenza in the previous year, anaemia, altered mental status, fever and dyspnoea on arrival at hospital, difficulties in performing activities of daily living in the previous 7 days, and days from onset of symptoms to arrival at hospital were related to the likelihood of SPAS (area under the curve value of 0.75; Hosmer-Lemeshow p value of 0.84). CONCLUSIONS: These variables should be taken into account by physicians evaluating a patient affected by influenza as additional information to that provided by the usual risk scores.

A Pilot Study on Proteomic Predictors of Mortality in Stable COPD.

Chronic Obstructive Pulmonary Disease (COPD) is the third leading cause of global mortality. Despite clinical predictors (age, severity, comorbidities, etc.) being established, proteomics offers comprehensive biological profiling to obtain deeper insights into COPD pathophysiology and survival prognoses. This pilot study aimed to identify proteomic footprints that could be potentially useful in predicting mortality in stable COPD patients. Plasma samples from 40 patients were subjected to both blind (liquid chromatography-mass spectrometry) and hypothesis-driven (multiplex immunoassays) proteomic analyses supported by artificial intelligence (AI) before a 4-year clinical follow-up. Among the 34 patients whose survival status was confirmed (mean age 69 ± 9 years, 29.5% women, FEV1 42 ± 15.3% ref.), 32% were dead in the fourth year. The analysis identified 363 proteins/peptides, with 31 showing significant differences between the survivors and non-survivors. These proteins predominantly belonged to different aspects of the immune response (12 proteins), hemostasis (9), and proinflammatory cytokines (5). The predictive modeling achieved excellent accuracy for mortality (90%) but a weaker performance for days of survival (Q2 0.18), improving mildly with AI-mediated blind selection of proteins (accuracy of 95%, Q2 of 0.52). Further stratification by protein groups highlighted the predictive value for mortality of either hemostasis or pro-inflammatory markers alone (accuracies of 95 and 89%, respectively). Therefore, stable COPD patients' proteomic footprints can effectively forecast 4-year mortality, emphasizing the role of inflammatory, immune, and cardiovascular events. Future applications may enhance the prognostic precision and guide preventive interventions.

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.

Understanding variation in length of hospital stay for COPD exacerbation: European COPD audit.

Chronic obstructive pulmonary disease (COPD) care across Europe has high heterogeneity with respect to cost and the services available. Variations in length of stay (LOS) may be attributed to patient characteristics, resource and organisational characteristics, and/or the so-called hospital cluster effect. The European COPD Audit in 13 countries included data from 16 018 hospitalised patients. The recorded variables included information on patient and disease characteristics, and resources available. Variables associated with LOS were evaluated by a multivariate, multilevel analysis. Mean±sd LOS was 8.7±8.3 days (median 7 days, interquartile range 4-11 days). Crude variability between countries was reduced after accounting for clinical factors and the clustering effect. The main factors associated with LOS being longer than the median were related to disease or exacerbation severity, including GOLD class IV (OR 1.77) and use of mechanical ventilation (OR 2.15). Few individual resource variables were associated with LOS after accounting for the hospital cluster effect. This study emphasises the importance of the patients' clinical severity at presentation in predicting LOS. Identifying patients at risk of a long hospital stay at admission and providing targeted interventions offers the potential to reduce LOS for these individuals. The complex interactions between factors and systems were more important that any single resource or organisational factor in determining differences in LOS between hospitals or countries.

Results from an audit feedback strategy for chronic obstructive pulmonary disease in-hospital care: a joint analysis from the AUDIPOC and European COPD audit studies.

BACKGROUND: Clinical audits have emerged as a potential tool to summarize the clinical performance of healthcare over a specified period of time. However, the effectiveness of audit and feedback has shown inconsistent results and the impact of audit and feedback on clinical performance has not been evaluated for COPD exacerbations. In the present study, we analyzed the results of two consecutive nationwide clinical audits performed in Spain to evaluate both the in-hospital clinical care provided and the feedback strategy. METHODS: The present study is an analysis of two clinical audits performed in Spain that evaluated the clinical care provided to COPD patients who were admitted to the hospital for a COPD exacerbation. The first audit was performed from November-December 2008. The feedback strategy consisted of personalized reports for each participant center, the presentation and discussion of the results at regional, national and international meetings and the creation of health-care quality standards for COPD. The second audit was part of a European study during January and February 2011. The impact of the feedback strategy was evaluated in term of clinical care provided and in-hospital survival. RESULTS: A total of 94 centers participated in the two audits, recruiting 8,143 admissions (audit 1∶3,493 and audit 2∶4,650). The initially provided clinical care was reasonably acceptable even though there was considerable variability. Several diagnostic and therapeutic procedures improved in the second audit. Although the differences were significant, the degree of improvement was small to moderate. We found no impact on in-hospital mortality. CONCLUSIONS: The present study describes COPD hospital care in Spanish hospitals and evaluates the impact of peer-benchmarked, individually written and group-oral feedback strategy on the clinical outcomes for treating COPD exacerbations. It describes small to moderate improvements in the clinical care provided to COPD patients with no impact on in-hospital mortality.

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

Clinical audit of COPD patients requiring hospital admissions in Spain: AUDIPOC study.

BACKGROUNDS: AUDIPOC is a nationwide clinical audit that describes the characteristics, interventions and outcomes of patients admitted to Spanish hospitals because of an exacerbation of chronic obstructive pulmonary disease (ECOPD), assessing the compliance of these parameters with current international guidelines. The present study describes hospital resources, hospital factors related to case recruitment variability, patients' characteristics, and adherence to guidelines. METHODOLOGY/PRINCIPAL FINDINGS: An organisational database was completed by all participant hospitals recording resources and organisation. Over an 8-week period 11,564 consecutive ECOPD admissions to 129 Spanish hospitals covering 70% of the Spanish population were prospectively identified. At hospital discharge, 5,178 patients (45% of eligible) were finally included, and thus constituted the audited population. Audited patients were reassessed 90 days after admission for survival and readmission rates. A wide variability was observed in relation to most variables, hospital adherence to guidelines, and readmissions and death. Median inpatient mortality was 5% (across-hospital range 0-35%). Among discharged patients, 37% required readmission (0-62%) and 6.5% died (0-35%). The overall mortality rate was 11.6% (0-50%). Hospital size and complexity and aspects related to hospital COPD awareness were significantly associated with case recruitment. Clinical management most often complied with diagnosis and treatment recommendations but rarely (<50%) addressed guidance on healthy life-styles. CONCLUSIONS/SIGNIFICANCE: The AUDIPOC study highlights the large across-hospital variability in resources and organization of hospitals, patient characteristics, process of care, and outcomes. The study also identifies resources and organizational characteristics associated with the admission of COPD cases, as well as aspects of daily clinical care amenable to improvement.

La auditoría clínica y su circunstancia / Clinical audit: Why, where and how?

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[Clinical audit of patients admitted to hospital in Spain due to exacerbation of COPD (AUDIPOC study): method and organisation]. / Auditoria clínica de los pacientes hospitalizados por exacerbación de EPOC en España (estudio AUDIPOC): método y organización del trabajo.

BACKGROUND: There is little information regarding the clinical management of hospital inpatients diagnosed with exacerbation of Chronic Obstructive Pulmonary Disease (COPD). AUDIPOC is a clinical audit dealing with the clinical management of COPD in Spain. OBJECTIVES: To examine the adequacy and validity of the instruments used to measure the variables proposed by AUDIPOC Spain (Preliminary Study) and to verify the viability of AUDIPOC in a complex environment with hospitals of different sizes, resources, and organizational layout (Pilot Study). MATERIALS AND METHODS: The Preliminary Study took place in 4 hospitals and studied 213 cases. The Pilot Study took place in 30 hospitals of 6 Autonomous Communities (i.e. Regions) and studied 1203 cases. RESULTS: The results of both studies contributed to the improvement of the design, methods and organization of the AUDIPOC work. Some of the improvements include better training of those responsible at a hospital level, a new classification of hospitals, the incorporation of new variables and the creation of a Bureau for the Coordination and Management of the Project. CONCLUSIONS: The AUDIPOC study is viable. It aims to recruit 10000 patients across 142 hospitals from all the Regions of Spain.

Auditoria clínica de los pacientes hospitalizados por exacerbación de EPOC en España (estudio AUDIPOC): método y organización del trabajo / Clinical Audit of Patients Admitted to Hospital in Spain due to Exacerbation of COPD (AUDIPOC Study): Method and Organisation

AntecedentesExiste poca información sobre el manejo clínico de pacientes ingresados en hospitales públicos españoles con un diagnóstico de exacerbación de enfermedad pulmonar obstructiva crónica. AUDIPOC es una auditoría clínica sobre el manejo de exacerbación de EPOC en España.ObjetivosValidar la adecuación y validez de los instrumentos de medición de las variables propuestas en AUDIPOC España (estudio preliminar) y verificar su viabilidad en un medio complejo con hospitales de tamaño, recursos y organización diferentes (estudio piloto).Material y métodosEl estudio preliminar se realizó en 4 hospitales y 213 casos. El estudio piloto en 30 hospitales de 6 comunidades autónomas y 1.203 casos.ResultadosLos resultados de ambos estudios contribuyeron a mejorar el diseño y los métodos y organización del estudio AUDIPOC, incluyendo un mejor entrenamiento de los responsables hospitalarios, una nueva clasificación de hospitales, la incorporación de nuevas variables y la creación de una oficina de coordinación y gestión del proyecto.ConclusionesEl estudio AUDIPOC es viable y prevé reclutar 10.000 pacientes en 142 hospitales de todas las Comunidades Autónomas(AU)

BackgroundThere is little information regarding the clinical management of hospital inpatients diagnosed with exacerbation of Chronic Obstructive Pulmonary Disease (COPD). AUDIPOC is a clinical audit dealing with the clinical management of COPD in Spain.ObjectivesTo examine the adequacy and validity of the instruments used to measure the variables proposed by AUDIPOC Spain (Preliminary Study) and to verify the viability of AUDIPOC in a complex environment with hospitals of different sizes, resources, and organizational layout (Pilot Study).Materials and methodsThe Preliminary Study took place in 4 hospitals and studied 213 cases. The Pilot Study took place in 30 hospitals of 6 Autonomous Communities (i.e. Regions) and studied 1203 cases.ResultsThe results of both studies contributed to the improvement of the design, methods and organization of the AUDIPOC work. Some of the improvements include better training of those responsible at a hospital level, a new classification of hospitals, the incorporation of new variables and the creation of a Bureau for the Coordination and Management of the Project.ConclusionsThe AUDIPOC study is viable. It aims to recruit 10000 patients across 142 hospitals from all the Regions of Spain(AU)