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BackgroundThe 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.MethodsCross-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.ResultsWe 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.ConclusionThe respiratory microbiome in clinically stable COPD patients varies significantly according to the severity of airflow limitation, previous history of exacerbations and circulating eosinophils levels., This study was funded by FIS PI15/00167 and PI15/02042 from Instituto de Salud Carlos III (ISCIII), SAF 2014-54371 (FEDER) from Ministerio de Economia y Competitividad, Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR), Laboratorios Menarini S. A, Fundacio Pla Armengol and Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias (CIBERES). CIBERES is an initiative of the ISCIII.; This work was also supported by grants from Agencia de Gestio d'Ajuts Universitaris i de Recerca-Generalitat de Catalunya (2017 GRC-716).

[ES] 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., [EN] 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 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.

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.

Background Previous studies have demonstrated significant variability in the processes of care and outcomes of chronic obstructive pulmonary disease (COPD) exacerbations. The AUDIPOC is a Spanish nationwide clinical audit that identified large between-hospital variations in care and clinical outcomes. Here, we test the hypothesis that these variations can be attributed to either patient characteristics, hospital characteristics and/or the so-called hospital-clustering effect, which indicates that patients with similar characteristics may experience different processes of care and outcomes depending on the hospital to which they are admitted. Methods A clinical audit of 5178 COPD patients consecutively admitted to 129 Spanish public hospitals was performed, with a 90-day follow-up. Multilevel regression analysis was conducted to model the probability of patients experiencing adverse outcomes. For each outcome, an empty model (with no independent variables) was fitted to assess the clustering effect, followed by a model adjusted for the patient- and hospital-level covariables. The hospital-clustering effect was estimated using the intracluster correlation coefficient (ICC); the cluster heterogeneity was estimated with the median odds ratio (MOR), and the coefficients of predictors were estimated with the odds ratio (OR). Results In the empty models, the ICC (MOR) for inpatient mortality and the follow-up mortality and readmission were 0.10 (1.80), 0.08 (1.65) and 0.01 (1.24), respectively. In the adjusted models, the variables that most represented the patients’ clinical conditions and interventions were identified as outcome predictors and further reduced the hospital variations. By contrast, the resource factors were primarily unrelated with outcomes. Conclusions This study demonstrates a noteworthy reduction in the observed crude between-hospital variation in outcomes after accounting for the hospital-cluster effect and the variables representing patient's clinical conditions. This emphasises the predictor importance of the patients’ clinical conditions and interventions, and understates the impacts of hospital resources and organisational factors. Authors thank all participating institutions for their willingness to contribute to medical research aimed at reducing medical practice variations, improving the quality of care provided. Supported by the Spanish Ministry of Health, Instituto de Salud Carlos III, FIS project numbers: PI07/90129, PI07/90309, PI07/90486, PI07/90503, PI07/90516, PI07/90721, PI08/90129, PI08/90578, PI08/90251, PI08/90529, PI08/90129, PI07/90403, PI08/90447, PI08/90457, PI08/90486 and PI08/90550, the Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES) and the Spanish Society of Respiratory and Thoracic Surgey (SEPAR).

Introduction and objectives The major cost to health services of COPD care is hospital admission for exacerbation. Reducing length of stay (LOS) will reduce cost, yet there is wide variability across patients and hospitals. We test the hypothesis that these variations may be attributed to either patient characteristics, hospital characteristics and/or the so-called hospital-clustering effect, which indicates that patients with similar characteristics may experience different processes of care and outcomes depending on the hospital to which they are admitted. Methods The European COPD Audit which was carried out in 432 hospitals from 13 countries, included data from 16,018 patients admitted over an 8 week period. The recorded variables included information on the patient and disease characteristics, resources available and clinical practice. Variables in each category associated with LOS were evaluated by a multivariate multilevel analysis and expressed as odds ratios (OR). Results Mean LOS was 8.7 days (median: 7, standard deviation: 8.3, interquartile range: 4–11). Factors associated with an LOS higher than the median (see figure) were clinical with the highest impact in patients with use of mechanical ventilation (OR: 4.74) and higher oxygen flows (OR 2.63). In-hospital treatments, comorbidities and patient-related variables including GOLD class IV (OR 1.77) were also significant. These relationships were maintained with respect to longer LOS (> 21 days). Neither the day of admission, nor any of the resource variables were associated with significant differences in LOS. The crude variability of LOS between the different countries was reduced after accounting for these clinical factors and the clustering effect. Conclusions This study demonstrates a noteworthy reduction in the observed crude inter-hospital variation in LOS after accounting for the hospital-cluster effect and patient related variables. This emphasises the predictor importance of the patients’ clinical conditions and interventions, and understates the impacts of hospital resources and organisational factors. This “real-life” reflection may highlight some valid learning points that may help us to determine which achievable strategies are most relevant to improve outcomes.