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PLoS One. 2012; 7(7): e42156.
Published online Jul 31, 2012. doi:  10.1371/journal.pone.0042156
PMCID: PMC3418048

Clinical Audit of COPD Patients Requiring Hospital Admissions in Spain: AUDIPOC Study

Joan A. Caylà, Editor

Abstract

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.

Introduction

The existence of variations in clinical practice and clinical appropriateness has been recognized for decades [1]. Two methods, both developed in the late 1980s, of exploring and dealing with these variations are Evidence-Based Medicine and Clinical Audits [2], [3]. These approaches are of particular relevance for the development of evidence-based clinical practice guidelines and the generation of real-life information that may eventually feed-back to the further refinement of guidelines [4].

Chronic Obstructive Pulmonary Disease (COPD) is a major health problem of increasing incidence. COPD is currently the 5th most common cause of death in the world, with the World Health Organization (WHO) predicting that it will rank 4th by 2030 [5]. In Spain, the prevalence of COPD is about 10% of the adult population [6]. Many COPD patients suffer episodes of exacerbation (ECOPD) during the course of their disease which impact negatively on their health status and prognosis, and constitute a major portion of the total health care costs of the disease [7]-.

Two British multicentre COPD clinical audits reported wide variability in interventions and outcomes. [8], [9] Other smaller audits have followed [10], [11], showing wide variations between different hospitals and between different countries in patient care, which is frequently not consistent with published guidelines. Interestingly, considerable variation in case recruitment and characteristics of cases across hospitals has also been described. This variations have been traditionally associated to temporal and geographical factors [12 14]. However, no studies have been carried out to assess the importance of these variations and the factors associated to them. Identifying organizational or clinical factors potentially associated with the admission to hospital and diagnosis of COPD cases (“case recruitment”) may therefore be of interest in efforts to improve the quality of health care afforded to such patients.

This paper presents for the first time the results of the AUDIPOC study, a national clinical audit carried out in Spain that sought to: 1) describe hospital resources and organizational patterns of hospitals in Spain delivering care for patients with ECOPD 2) analyse the variability among hospitals in COPD case recruitment and associated factors; 3) describe patient characteristics, clinical interventions and outcomes, both at the patient and hospital level; and 4) inform on the adequacy of care as per current clinical practice guidelines.

Methods

Study Design and Ethics

The methods of the AUDIPOC study have been described in detail elsewhere [15]. Briefly, AUDIPOC is a cross-sectional study with prospective case ascertainment of consecutive ECOPD hospital admissions from November 1st to December 31st, 2008, and retrospective data gathering from medical records. Patients were followed-up for 90 days after hospital admission with a view to include in the analysis two clinically relevant outcomes: mortality (in-hospital and out-hospital) and readmissions. The ethics committee of each participating hospital approved the study protocol. Due to the non-interventional nature of the study and the need of blindly evaluating the clinical performance, an informed consent was waived.

Participating Hospitals

All 225 acute care hospitals of the public Spanish National Health System listed in the 2008 Registry of the Ministry of Health [16] were invited to participate. Each hospital’s catchment population was estimated from the proportion of the corresponding regional population census (January 1st, 2009) that was assigned for admission to that particular hospital [17].

Ascertainment of Cases

The inclusion of patients in the AUDIPOC study followed a two-step process. First, clinical notes of all cases hospitalized by the Emergency Department (ED) were reviewed daily to identify one or more of 13 clinical conditions compatible with the diagnosis of ECOPD (table 1); these patients were labelled as interim ECOPD cases. Second, these cases were reassessed at hospital discharge against a list of definite inclusion and exclusion criteria (table 1) to identify cases with a clinical diagnosis of ECOPD, that were labelled as definite ECOPD cases [15].

Table 1
Provisional and definitive inclusion and exclusion criteria.

Data Acquisition and Processing

Hospitalization and follow-up data were obtained from clinical records and entered into a web-based application that was monitored daily to identify errors, inconsistencies and missing values during the audit. Once the audit had ended, two quality controls were established. Firstly, independent auditors re-entered data for 28 relevant variables for a random sample of 1897 patients (15% of all interim cases). Secondly, after a preliminary data description that was made to identify extreme values and inconsistencies, the database entered a data cleaning process [18]. Those values considered extreme or found to have inconsistencies with other related variables were sent to local investigators to check and send back the correct value.

Guidelines Adherence Evaluation

The main recommendations regarding hospital care of ECOPD patients were identified from three different guidelines (GOLD 2010 [19], NICE 2010 [20] and SEPAR/ALAT 2009 [21]), and the degree of compliance with these recommendations was investigated in the AUDIPOC database.

Statistical Analysis

Results at a patient level are presented as percentages or medians, interquartile ranges (IQR) and ranges, as appropriate. Results at a hospital level are presented as medians IQR and ranges of data grouped for all patients within each hospital (i.e. clustered). Inter-rater agreement between the initial set of data and the re-entered by independent auditors was calculated as Cohen’s kappa coefficient. Between-hospital variability in case recruitment was modelled using Bayesian multivariate analysis [22], [23]. Bayesian analysis is a method of statistical inference that allows the investigator to explicitly incorporate the distribution of prior beliefs and expert knowledge (prior probability distribution) concerning parameters such as means, variances and regression coefficients underlying random variables, with the currently observed data and the assumed probability model to obtain posterior probability distributions. To determine which hospital resource and organizational related attributes were associated with the variable “ratio of observed to expected number of interim cases,” we used a Poisson probability regression model. For the “proportion of interim cases ultimately considered definite cases,” a binomial probability regression model was fitted.

The above models were built allowing for the quantification of the extra-variability in the response variables via a random effects term. Uninformative prior distributions were used to assign prior probabilities to all values for each parameter, including the regression coefficients and the variance associated with the hospital-level random effects term. The Markov Chain Monte Carlo (MCMC) method was used [24], to simulate posterior distributions of all parameters in the final model. In order to maximize the quality of the sampling of the posterior distributions, one million iterations were run for each of the two models; one half to verify convergence, and the other half for statistical inference. Results were expressed with the mean posterior probability and its 25–75% limits of credibility, and with an estimated average Odds Ratio. These credible intervals indicate that the true population parameter lies in this interval with a probability of 50%.

Results

A total of 11,564 interim ECOPD cases were hospitalized during the study period. At discharge, 5,178 patients fulfilled all the inclusion and none of the exclusion criteria and were therefore included in the audit as definite ECOPD cases. Not-included cases were slightly older (78 vs. 75 yrs.), more often females (47 vs. 12%) and were less frequently diagnosed on admission with conditions related to COPD (20 vs. 80%) or at discharge with a primary diagnosis of COPD (18 vs. 82%). Regarding the internal consistency of the data recorded, it is of note that the inter-rater agreement was high, with 68% of Cohen’s kappa coefficients >0.61 and only one <0.40 (Table S1 in the online Appendix).

Characteristics of Participating Hospitals

A total of 129 hospitals (57% of all those potentially eligible) from all 17 Spanish regions participated in the AUDIPOC study. The proportion of participating hospitals and the regional population coverage varied across regions (Table 2). We estimated that the AUDIPOC study covered a total population of 31,744,972, representing about 70% of the Spanish population.

Table 2
Participating hospitals and population coverage by region.

Table 3 shows the inter-hospital variation regarding hospital resources and organization of care. The size of the catchment population, the number of hospital beds and the total number of hospital admissions varied widely (about 20-fold) between participating hospitals. These inter-hospital differences increased further (60-fold) for the number of ECOPD admissions in the year prior to the audit, total number of faculty physicians (50-fold) and total number of pulmonologists in the faculty (30- fold). There was a 10-fold variation between hospitals in relation to the number of internists.

Table 3
Characteristics of participating hospitals (N = 129).

Analysis of Hospital Variability in Case Recruitment

Table 4 displays the mean and 50% credible intervals of the posterior distribution of regression coefficients in the final models, as well as the corresponding average odds ratio (OR). The positive/negative signs in front of their values indicate the same/opposite direction of effects. The number of interim ECOPD cases recruited was positively associated with variables somehow related to COPD awareness such as number of cases admitted in the year prior to the study, existence of a COPD clinical management protocol, or the availability of respiratory physicians in the ED. By contrast they were negatively associated with variables related to hospital size and complexity, including case-mix index, number of beds, existence of an early discharge scheme or domiciliary hospitalisation, number of respiratory physicians, or being a university-affiliated hospital (Table 4, upper panel). On the other hand, the proportion of interim cases that became definite was positively associated with hospital size and complexity and negatively associated with hospital COPD awareness (exceptions were university affiliated and medical training hospitals, for which the probability of an interim case becoming definite decreased) (Table 4, lower panel). Interestingly, both the number of interim ECOPD cases and the proportion of definite cases rose with the availability of hospital documents in electronic format. In any case, a large component of the hospital-related variance in the number of interim ECOPD cases recruited initially (calculated as a 45-fold change) and the proportion of interim cases that become definite (calculated as a 17-fold change) remained unexplained by the models fitted (Table 4).

Table 4
Multivariate Bayesian analysis showing posterior distributions for the regression coefficients associated with recruitment hospital performance.

Characteristics of Audited Patients

Table 5 presents the main clinical characteristics, interventions and outcomes of the 5,178 patients included in the audit, at different time points and at both the patient and hospital levels. Additional information can be found in the online supplement (Table S2 in the online Appendix). There was large variability in patient characteristics, interventions and outcomes across hospitals. Gender, age, smoking status, comorbidity, general health status (e.g. performance status), anaemia, peripheral oedema, serum albumin and creatinine levels and the frequency and severity of respiratory failure (Table S2 in the online Appendix) varied widely between patients treated in different hospitals. Further differences between hospitals were observed in relation to the availability of spirometric data, arterial blood gas analysis at the ED, and prescription of oxygen therapy, ventilation support, antibiotics, systemic/inhaled steroids, long-acting ß2 agonists (LABA) and long-acting muscarinic antagonists (LAMA), as well as for other treatments (Table 5). In-hospital mortality ranged from 0 to 35% (median  = 4.5%, IQR  = 1.3–7.7%). Length of stay (LOS) ranged from 4 to 65 days (median  = 8 days, IQR  = 7–10 days) and all-cause hospital readmissions from 0 to 62% (median 34%, IQR 28–42%). Mortality during follow-up ranged from 0 to 38% (median 6%, IQR 2–9%) and the overall mortality across hospitals ranged from 0 to 50% (median 12%, IQR 8–15%).

Table 5
Selected patient characteristics, clinical interventions and outcomes. Estimation at patient level and at hospital level.

Compliance with Clinical Practice Guidelines

Compliance with clinical practice guidelines is summarised in Table 6 (with further information available in Table S3 in the online Appendix). Although considerable variability at the hospital level was also observed, compliance with recommendations regarding diagnosis or in- hospital treatment revealed high standards of care. In contrast, the level of information included in the final discharge report was not of a high standard, since recommendations related to general health practices and life-style improvements were given in written form to less than 50% of discharged patients (Table 6).

Table 6
Guideline statements related to clinical findings GOLD (2010)/NICE (2009)/SEPAR-ALAT (2009).

Discussion

This is the first national clinical audit of patients hospitalized in Spain because of ECOPD. Given the high percentage of population coverage the results should provide an accurate description of the clinical characteristics of ECOPD cases, current clinical practice models, and outcomes of ECOPD treatment in Spain. Further, our results identify the hospital characteristics associated with the admission of ECOPD patients and confirm, for the Spanish National Health System, previous findings on different health-care systems concerning the variability of available resources, clinical presentation and outcomes of patients admitted to these hospitals. Finally, our study provides novel information relating to the degree of actual compliance with international guidelines. Taken together, a proactive approach to the management of this information should contribute to improvements in organizational aspects of care given to COPD patients.

Previous Studies

Most previous ECOPD audits included small samples of patients or hospitals, or focused on particular aspects of clinical care. Further to this, those studies involving large numbers of patients were mainly based on administrative databases [25][27]. To our knowledge, only two other nationwide clinical audits of patients hospitalized with ECOPD, and which involved the prospective recruitment of cases and collection of patient clinical record-based data, have been published to date. Both of these studies were carried out in the United Kingdom. The first was performed in 2003 and included 234 participating hospitals and 7514 patients. Median inpatient mortality was 7% (between-hospital IQR 3%–11%), total mortality was 15% (IQR 9%–21%), median LOS was 6 days (IQR 3–11 days) and the re-hospitalization rate was 31% (IQR 22%–40%) [8]. The second study, undertaken in 2008 and which included 232 participating hospitals and 9716 patients, reported similar updated results [9]. Overall, the results of these two studies are in keeping with those of AUDIPOC. Minor differences may be related to the distinctiveness of the British and Spanish health systems as well as to differences in the inclusion criteria used in the respective studies.

Interpretation of Findings

The general clinical profile of the patients included in the AUDIPOC study corresponded mostly to that of elderly persons (a third of whom were still smokers) with a history of previous ECOPD hospitalizations and frequent comorbidities (mostly cardiovascular). At the ED they complained of increased dyspnoea with purulent sputum. By and large, treatment during hospitalization and at discharge followed international recommendations (Tables 6 and S3). There were, however, relatively few documented interventions aimed at promoting smoking cessation, an active life-style (including rehabilitation prescription) and/or influenza or pneumococcal vaccination. Importantly, re-hospitalizations were frequent and there was remarkably high all-cause mortality (11.6%).

A more detailed analysis of our results, however, showed that there were marked variations across hospitals in terms of patient characteristics, process of care, adherence to guidelines (Tables 6 and S3), and outcomes. Although part of this variability can be explained by the relatively small number of cases provided by some hospitals, it is more likely due to one or more of the following: (1) heterogeneity of the participating hospitals in terms of size, resources and organization, case recruitment, complexity of health care delivery, (2) heterogeneity of the disease itself [28] as well as diversity of interventions undertaken; (3) thoroughness and accuracy of clinical record data collection; or (4) other, still unidentified, factors not included in the analysis, such as those related to geographical location [14]. In order to gain further insight into the relative contribution of each of these, we first investigated what hospital resources and organizational variables could be identified to explain the recruitment of ECOPD cases into the audit. To this end, we used a Bayesian approach because of its flexibility to study complex models and databases, and the fact that it generates posterior probability distributions that facilitate the interpretation of regression coefficients [29]. This identified a number of explanatory variables that seem to act in opposing directions with respect to the number of interim COPD cases and the proportion of definite cases (Table 4). Hospital size and complexity attributes were associated with admitting fewer interim cases and selecting more definite cases from these (i.e. a more refined selection strategy), whilst the COPD awareness dimension facilitates the admission of more interim cases and selection of fewer definite cases (i.e. a less refined selection strategy). The association of access to electronic/digital information with the number of interim and definite cases suggests that the use of information technologies may increase the identification of cases and, possibly, improve the audit process. In any case, a large component of hospital-related variance remained unexplained, suggesting that the clinical profile of patients included in the study also varied markedly across hospitals. Differences in reported outcomes could also be due to discretionary patterns in the process of care itself. To this extent, an exhaustive study of these variations might offer the best chance for resolving potential differences in quality of treatment provided to ECOPD patients.

Finally, our study provides novel information on the degree of real-life compliance with international guidelines which, overall, was acceptable. The study identified, however, that general recommendations concerning a healthy life-style, such as detailed instructions on how to stop smoking, how to improve nutrition or undertake more daily physical activity, or the provision of information concerning the advantages of influenza and pneumococcal vaccination, were often not provided. This issue has been recently audited and specific national recommendations have been issued [30], [31].

Strengths and Limitations

The application of strict inclusion/exclusion criteria has likely resulted in the inclusion in the AUDIPOC study of a relatively “pure” ECOPD cohort, with few patients incorrectly included. As such, the study’s results can be generalized to all patients admitted with ECOPD. An additional strength of this study is that the auditors were reasonably consistent in their re-entering of data, thus supporting the quality of the data retrieving and entry process (Table S1). On the other hand, however, a potential limitation of this study, which is intrinsic to any clinical audit, is that medical charts were used as the data source, so some missing and inconsistent values were unavoidable. To address this limitation, a thorough process of database screening and editing was undertaken and the number of extreme or inconsistent values was notably reduced. However, missing data values still remained that tended to cluster in related variables, thus contributing to cross-correlation among them and rendering the multivariate analysis particularly challenging.

Conclusions

The AUDIPOC study is the first national audit on patients hospitalized in Spain because of ECOPD. Our results confirm previous studies from other countries and show significant variability in terms of the resources and organization of hospitals, process of care and outcomes. The study also identifies for the first time a number of resources and organizational characteristics of hospitals that may influence the routine admission of COPD cases for hospitalization, pinpointing therefore to several improvable organizational aspects. The issue of compliance with clinical practice guidelines in real life was also addressed, with some aspects that are amenable to improvement of daily clinical care also identified.

Supporting Information

Table S1

Consistency analysis of variables included in the study.

(DOCX)

Table S2

Additional patient characteristics, clinical interventions and outcomes. Estimations at patient level and at hospital level.

(DOCX)

Table S3

Additional guidelines assessment.

(DOCX)

Acknowledgments

AUDIPOC Spain Study Group

Steering Group. POZO RODRIGUEZ, Francisco. Neumología, Hospital 12 de Octubre. Madrid. CIBERES. CASTRO ACOSTA, Ady Angélica. CIBERES y Unidad de Epidemiología Clínica, Hospital Universitario 12 de octubre. Madrid. BOUKICHOU ABDELKADER, Nisa Lic. CC y TT. Estadísticas. Investigador CIBERES y Unidad de Epidemiología Clínica, Hospital Universitario 12 de octubre. Madrid. ESTEBAN GARCIA-NAVAS, Sara Investigador CIBERES Unidad de Epidemiología Clínica, Hospital Universitario 12 de octubre. Madrid.

Scientific Committee. POZO RODRÍGUEZ, Francisco. AGUSTÍ, Alvar. Neumología, Instituto Cardiotorácico Hospital Clinic, Barcelona. ÁLVAREZ MARTÍNEZ, Carlos José. Neumología, Hospital 12 de Octubre. Madrid. CAPELASTEGUI SAIZ, Alberto. Neumología, Barakaldo. Bilbao. ESTEBAN GONZÁLEZ, Cristóbal. Neumología, Hospital de Galdakao. Vizcaya. HERNÁNDEZ CARCERENY, Carme. Neumología, Hospital Clinic. Barcelona. IZQUIERDO ALONSO, José Luis. Neumología, Hospital de Guadalajara. LOPEZ CAMPOS, José Luis. Neumología, Hospital Universitario Virgen del Rocío. Sevilla. MELERO MORENO, Carlos. Neumología, Hospital Universitario 12 de octubre. Madrid.

Coordinators by Region and Hospital

Andalucia. REGIONAL COORDINATOR: José Luis López Campos. Neumología, Hospital Universitario Virgen del Rocío. HOSPITAL COORDINATORS: Almería, Complejo Hospitalario Torrecárdenas: José Calvo Bonachera. Cádiz, Hospital de La Línea de la Concepción: Armando Falces Sierra, Hospital General de Jerez de la Frontera: Gregorio Soto Campos, Hospital Puerta del Mar: Fernando Romero Valero y Isidro Blanco Sáez, Hospital Puerto Real: Jesús Sánchez Gómez. Hospital Universitario Reina Sofía: Marisol Arenas de la Riva y María Jesús Cobos Ceballos. Granada: Hospital Universitario San Cecilio: Alicia Conde Valero. Huelva: Hospital Infanta Elena: Rosa Vázquez Oliva y Fernando Hernández Utrera. Hospital Juan Ramón Jiménez: Rut Ayerbe García. Jaén: Centro Hospitalario Ciudad de Jaén: Bernardino Alcázar Navarrete. E.P.H.A.G. Alto Guadalquivir (Andujar): Juan Manuel Bravo Santervás. Málaga: Hospital Costa del Sol: José Fernández Guerra. Hospital Comarcal de Vélez Málaga: Carlos Rueda, Hospital Regional Carlos Haya: José Luis de la Cruz Ríos. Hospital Serranía de Ronda: Francisco José Cabello Rueda. Hospital Virgen de la Victoria: Francisco Marín Sánchez. Sevilla: Hospital de la Merced – Osuna: José Pérez Ronchel. Hospital Universitario Virgen del Rocío: José Luis López Campos. Hospital Universitario Valme: Inmaculada Alfageme Michavila. ARAGÓN: REGIONAL COORDINATOR: Luis Borderías. Neumología, Hospital San Jorge de Huesca, José Manuel Gascón Pelegrín. Neumología, Hospital Miguel Servet. Zaragoza, Instituto Aragonés de Salud: Anselmo López y Mónica Torrijos HOSPITAL COORDINATORS: Hospital Clínico Universitario Lozano Bleza: Joaquín Carlos Costán Galicia. Hospital Miguel Servet: Salvador Bello Dronda, Andrés Sánchez Barón y José Manuel Gascón Pelegrín. Hospital San Jorge de Huesca: Luis Borderías. CANARIAS: REGIONAL COORDINATOR Ana Velázquez Benítez. H Ntra Señora de la Candelaria. José Gabriel Julia. Neumología, Hospital Dr Negrín HOSPITAL COORDINATORS: Las Palmas: Hospital Dr Negrín: Carlos Cabrera López. Lanzarote: Hospital Dr José Molina Orosa, Lanzarote: Javier Navarro Esteva. Santa Cruz de Tenerife: HM Nuestra Señora de Candelaria: Magdalena Alonso, Ruth Pitti, José Batista y Orlando Acosta Fernández. Hospital Universitario de Tenerife: José Antonio Gullón. CANTABRIA: REGIONAL COORDINATOR Ramón Agüero Balbín. Neumología, Hospital Marqués de Valdecilla. Cantabria: Hospital de Laredo: Miguel Zabaleta Murguiondo. Hospital Marqués de Valdecilla: Beatriz Abascal Bolado y Ramón Agüero Balbín. Hospital Sierrallana: Mar García Pérez. CASTILLA LA MANCHA: REGIONAL COORDINATOR Jose Celdran Gil. Neumología, Hospital Nuestra Señora del Prado de Talavera. Jesús Fernández Francés. Neumología, Hospital de Guadalajara. HOSPITAL COORDINATORS: Albacete: Hospital de Albacete: Ana Isabel Tornero. Ciudad Real: Hospital La Mancha Centro (ALCAZAR): Gloria Francisco. Hospital Manzanares. Fernando Pedraza y Marisi Verdugo. Cuenca: Hospital Virgen de la Luz de Cuenca: María José Peirón. Guadalajara: Hospital de Guadalajara: Jesús Fernández Francés y José Luis Izquierdo. Soria: Complejo Asistencial de Soria, H Santa Bárbara: José Luis Orcastegui Candial Toledo: Hospital Nuestra Señora del Prado de Talavera: José Celdrán. Hospital Virgen de la Luz de Toledo: Encarnación López Gabaldón. CASTILLA Y LEÓN: REGIONAL COORDINATOR Jesús Reyes Hernández Hernández. Neumología, Hospital Nuestra señora de Sonsoles. HOSPITAL COORDINATORS: Ávila: H Nuestra señora de Sonsoles: José Eugenio Alonso Muñoz y Eugenio Trujillo Santos. Burgos: Complejo Hospitalario de Burgos: Luis Rodríguez Pascual. Hospital Santiago Apóstol de Miranda de Ebro: Esteban Pascual Pablo. Hospital Santos Reyes Aranda de Duero: Pedro Cancelo Suárez. León: Complejo Asistencial de León: Ana José Seco García. Hospital del Bierzo: Juan Ortiz De Saracho y Bobo. Palencia: Complejo Asistencial de Palencia: María Ángeles Fernández Jorge. Salamanca: Complejo hospitalario de Salamanca: Rosa Cordovilla Pérez. Segovia: Hospital General de Segovia: Graciliano Estrada Trigueras. Soria: Complejo Asistencial de Soria, Hospital Santa Bárbara: José Luis Orcastegui Candial. Valladolid: Hospital Clínico Universitario: Carlos Disdier y Enrique Macías Fernández. Hospital Río Hortera: Félix del Campo Matías. Zamora: Complejo Hospitalario de Zamora. Hospital de Benavente: Carmen Fernández García, Cecilia Alonso Medievilla y María Victoria Domínguez Rodríguez. CATALUÑA: REGIONAL COORDINATOR Carlos Martínez Rivera. Neumología, Hospital Universitari Germans Trias i Pujol. Eduard Monsó Molas. Neumología, Hospital Universitari Germans Trias i Pujol. HOSPITAL COORDINATORS: Barcelona: Hospital Clinic Barcelona: Néstor Soler Porcar, Carmen Hernández. Hospital Comarcal de Ĺalt Penedés,Vilefrance de Penedés: Nuria Rodríguez Lázaro. Hospital del Mar: Joaquim Gea, Roser Pedreny y Sergi Pascual. Hospital General de Vic: Fernando Ruiz Mori. Hospital San Pau: Antonio Antón y Virginia Pajares Ruiz. Virginia Pajares Ruiz. Hospital Universitari Germans Trias i Pujol: Eduard Monsó Molas e Ignasi Garcia Olivé. Hospital Vall d´Hebron: Esther Rodríguez Fernández. Hospital Viladecans: Joan Anton Lloret Queraltó, Mercedes Palau Benavent y Nuria Celorrio Jiménez. Gerona (Girona): Hospital Universitario Doctor Josep Trueta: Manuel Haro Estarriol. Lérida (Lleida): Hospital Arnau: Ferrán Barbé. H General Par Sanitari Sant Joan de Déu: Luis Lores Obradors, H Parc Taulí de Sabadell: Eduard Monso, H Joan XXIII de Tarragona: Leonardo Esteban. MADRID: REGIONAL COORDINATOR. Julio Ancochea Bermúdez. Neumología, Hospital de la Princesa. Carlos Melero Moreno y Carlos José Álvarez Martínez. Neumología, Hospital Universitario 12 de Octubre. HOSPITAL COORDINATORS: Madrid. H. 12 OCTUBRE: Virginia Pérez González. Hospital Clínico San Carlos: Gema Rodríguez Trigo. Hospital de la Princesa: Enrique Zamora García. Hospital de Tajo, Aranjuez: José. Fernando González Torralba. Hospital de Valdemoro: Rocío García García. Hospital El Escorial: Francisco Gómez Rico. Hospital Fundación Alcorcón: Bárbara Steen. Eva De Higes Martínez. Mercedes Izquierdo Patrón y Ángela Ramos Pinedo. Hospital Gómez Ulla: Javier Jareño, Ignacio Granda Uribe y Sergio Campos Téllez. Hospital Gregorio Marañón: José de Miguel Rodríguez González Moro y Jorge García. Hospital Infanta Cristina, Parla: Beatriz Jara Chinarro, María Teresa Río Ramírez. Hospital Infanta Sofía: Raúl Moreno Zabaleta, Maria Teresa Ramírez Prieto y Blas Rojo Moreno Arrones. Hospital La Paz: Francisco García Río y Sergio Alcolea Batres. Hospital Puerta de Hierro: Rosa Malo de Molina Ruíz, Antolín López Viña y Pietat Ussetti. Hospital Ramón y Cajal: Esteban Pérez Rodríguez y Salvador Díaz Lobato. Hospital Infanta Leonor: Carmen Matesanz Ruíz, Maria Jesus Buendia. Hospital Sureste Arganda del Rey: Sergio Salgado Aranda. Fundación Jiménez Díaz: Germán Peces-Barba. Hospital de Getafe: Ma Antonia Juretschke Moragues. Hospital Príncipe de Asturias Alcalá Henares: Soledad Alonso Viteri. Hospital de Móstoles: Dolores Álvaro. Hospital Severo Ochoa de Leganés: Asunción Perpina. Hospital del Henares: Ma Ángeles Ruíz-Cobos. C.F.NAVARRA: REGIONAL COORDINATOR. Javier Hueto Perez de Heredia. Neumología, Complejo Hospitalario de Navarra. HOSPITAL COORDINATORS: Hospital Virgen del Camino: Pilar Cebollero Rivas y Joan Boldú Mitjans. Hospital de Navarra: Jalil Abú-Shams y Victor Manuel Eguía Astibia. Hospital Garcia Orcoyen de Estella: Idoya Pascal Martínez. Hospital Reina Sofía de Tudela: José Antonio Cascante Rodrigo y José Javier Lorza Blasco. C. VALENCIANA: REGIONAL COORDINATOR Pablo Catalán Serra y Juan José Soler Cataluña. Neumología, Hospital de Requena. HOSPITAL COORDINATORS: Alicante: Hospital de Elda: Alejandro Muñoz. Hospital de Orihuela: José Manuel Querol. Hospital de San Joan: Eusebi Chiner Vives y Adaluz Andreu Rodríguez. Hospital de Torrevieja: Esther Pastor. Castellón de la Plana: Hospital de la Magdalena: Khaled Bdeir Egnayem Hospital de La Plana: Luis Miravet. Hospital General de Castellón: Margarita Marín Royo. Valencia: Hospital Clínico Valencia: María Cruz González Villaescusa. Hospital de Requena: Pablo Catalán Serra y Juan José Soler Cataluña. Hospital Dr Peset: Estrella Fernández Fabrellas, Ángela Cervera Juan, Alberto Herrerón Silvestre y Alfonso Martinez Martínez. Hospital Francés de Borja, Gandia: Concha Pellicer Ciscar. Hospital de la Rivera: Elsa Naval Sendra. Hospital Sagunto: Eva Martínez Moragón. Hospital Universitario la Fe: Montserrat León Fábregas. EXTREMADURA: REGIONAL COORDINATOR Juan Antonio Riesco Miranda. Neumología, Hospital de Cáceres. HOSPITAL COORDINATORS: Badajoz: Hospital Infanta Cristina de Badajoz: José Antonio Gutierrez Lara, Fernando Fuentes. Cáceres: Hospital de Cáceres: Juan Antonio Riesco Miranda. Hospital de Plasencia: Miguel Ángel Hernández Mezquita. Mérida: Hospital de Mérida: Germán García Vinuesa. GALICIA: REGIONAL COORDINATOR Alberto Fernández Villar. Neumología, Complejo Hospitalario de Vigo. Juan Suárez Antelo. Neumología, Complejo Hospitalario Universitario A Coruña. HOSPITAL COORDINATORS: La Coruña (A Coruña): Complejo Hospitalario Universitario A Coruña: Juan Suarez Antelo. FPH Barbanza: Emilio Manuel Padin Paz. Hospital de Conxo - Santiago de Compostela: Jesús Suarez Martinez. Lugo: Hospital Comarcal Burela: Sonia Paredes Vila. Hospital Xeral, Lugo: Rafael Golpe Gómez y Luis Pérez de Llano. Orense (Ourense): CH Ourense: Pedro Marcos, Carlos Vilariño Pombo y Jose Manuel García Pazos. Pontevedra: Hospital provincial de Pontevedra: Adolfo Baloira. Hospital Xeral, Vigo: Alberto Fernández Villar y Cristina Represas Represas. Hospital do Meixoero, Vigo: Manuel Nuñez Delgado. Hospital Povisa: Maria Dolores Corbacho Abelaira. Hospital Xeral, Vigo: Marta Nuñez Fernandez. ISLAS BALEARES: REGIONAL COORDINATOR Borja García-Cosío. Neumología, Hospital Son Espases. HOSPITAL COORDINATORS: Palma de Mallorca: Hospital Comarcal de Inca: Elena Laserna Martinez. Hospital de Manacor: Rosa Maria Irigaray Canals. Hospital de San Llatzer: Salvador Pons Vivas. Hospital Son Espases: Borja Garcia Cosio. Menorca: Hospital Mateu Orfila: Jordi Guerrero. Ibiza: Hospital Can Misses, Ibiza: Alvaro De Astorza y Antonio Cascales García. LA RIOJA: REGIONAL COORDINATOR Manuel Barrón Medrano. Neumología, Hospital de la Rioja. HOSPITAL COORDINATORS: La Rioja: Fundación Hospital de Calahorra: Susana Chic Palacin y Manuel Barron Medrano. Hospital De La Rioja: Carlos Ruiz Martínez y Manuel Barron Medrano. PAIS VASCO: REGIONAL COORDINATOR Cristóbal Esteban González. Neumología, Hospital de Galdakao. HOSPITAL COORDINATORS: Álava: H de Santiago: Ma Ines Carrascosa. H Txagorritxu: Laura Tomas. Guipuzcoa (Guipuzkoa): H Bidasoa: Jose Antonio Miguel Arce, Ma Asunción Celaya y Silvia Dorronsoro. H Donostia: Ma Rosa Berdejo, Mónica Rayón y Gabriel Zubillaga Garmendia. Hospital de Mendaro: José Ignacio Royo, Susana Chic Palacin y Nicolás Gurrutxaga. H de Mondragón: Iñaki Peña y Mikel Temprano Gogenola. H Zumarraga: Silvia Dorronsoro, Cristina Estirado y Raquel Sánchez. Vizcaya (Bizkaia): H Basurto: Miren Begoña Salinas y Igor Iturbe. H Cruces: José Ma Antoñana y Pilar Marin. H Galdakao: Alberto Capelastegui, Cristóbal Esteban y Mikel Egurrola. H San Eloy: Juan Manuel Nuñez, Jesús Camino y Luis Alberto Ruiz Iturriaga. PRINCIPADO DE ASTURIAS: REGIONAL COORDINATOR Cristina Martinez. Neumología, Hospital Universitario Central de Asturias. HOSPITAL COORDINATORS: Hospital Universitario Central de Asturias: Marta García Clemente, Aida Quero Martínez y Cristina Martínez, Hospital de Cabueñes Gijón: Teresa Pascual Pascual y Concepción Díaz Sánchez. Hospital del Oriente-Arriondas: Blanca Requejo Mañana. Hospital Fundación Jove: Benigno Del Busto Lorenzo. Hospital San Agustín, Avilés: Fernando Álvarez Navascues y Marta García Clemente. Hospital Valle del Nalón Langreo: Hortensia Canto Argiz. REGION DE MURCIA: REGIONAL COORDINATOR. Juan Miguel Sánchez Nieto. Neumología, Hospital General Universitario Morales Meseguer. HOSPITAL COORDINATORS: Hospital de los Arcos: Damián Melia Alvarado, Jose A Ros Lucas, Nuria Castejón Piña y Ada Luz Andreu Rodríguez. Hospital General Universitario Morales Meseguer: Roberto Bernabeu Mora, Juan Miguel Sánchez Nieto y Maria Loreto Alemany Frances. Hospital Universitario Santa Lucía: Pilar Berlinches Acin y Inés Bernal Belijar. Hospital U Reina Sofía: Carlos Orts Arqueros, Maria Jesus Aviles Ingles y Pedro Méndez Martinez.

Information Managers by Region.

ANDALUCÍA: Cinta Olmedo Rivas, Zulema Palacios Hidalgo, Juan Emilio Hurtado Ayuso, José María García Jiménez, Pilar Cuéllar, Adolfo Domenech del Río, Francisco Canales Cid, Francisco Luis Gil Muñoz, Domingo Jesús García Aguilar, Francisco Pérez Grimaldi, Antonia Soto Venegas, Mónica Martín Rebollo, Jesús Flores González, Ignacio Casado Moreno, Víctor Navarro Pérez, Virginia Rodríguez Martínez, Leonor Núñez Basallote, Alejandro Segado Soriano, Isidro Blanco Sáez, Ma Paz Martínez Cortés, Aida García Cuesta, Pablo Pérez Navarro. ARAGÓN: Andrés Sánchez Barón, Helena Briz Muñoz y Laura Anoro Abenoza. CANARIAS: Baltasar Gómez Rueda, Carlos Cabrera López, Javier Navarro, Purificación Ramírez, Orlando Acosta, Cristina Cabrera Lacalzada, José Antonio Gullón Blanco y Luisa Eiroa González. CANTABRIA: Beatriz Abascal Bolado, Carlos Amado Diago y Miguel Iglesias Heras. CASTILLA LA- MANCHA: Gloria Francisco, Ruth Cicuendez Trilla, Ana Isabel Tornero, Encarnación Fernández Robledo, David Alfaro Tercero, Javier Callejas González, Sergio García Castillo, Marisi Verdugo, Rosario Vargas González, Ma Eugenia Casado López, José María Peñas Herrero, Belén Arnalich Jiménez, Arturo Martínez Martínez, Raúl Hidalgo Carvajal, Isabel García San José, Javier Quiles Lapuerta, Alberto Nistal Rodríguez, Ma Antonia Sepúlveda, Elisabeth Guzmán Robles, Juan Pablo Rodríguez Gallego, Galo Fernández Zapata, Yamilex Urbano Aranda y Beatriz Cadavid Rodríguez. CASTILLA Y LEÓN: José Ángel Tapias del Pozo, Marco Budiño Sánchez, Belén Moreno de Vega Herrero, Ana Parra Ulloa, Eva Rodríguez Beltrán, Victoria Hernández Jiménez, Luis Rodríguez Pascual, Cristina Pérez, Ana del Riego Balledor, José Luis Delgado, Esteban Pascual de Pablo, Javier Niso, Ana J. Seco García, Silvia Fernández Huerga, Virginia Serrano Gutiérrez, Rafael Castrodeza Sanz, Emilio Juárez Moreno, Iria Vidal García, Julio César Oblanca, José Antonio Iglesias Guerra, Tomás Ruiz Albi, Rosa Cordovilla Pérez, José María González Ruiz, Juan Vitelio Márquez, Ma José Bernabé Barrios, Ruth García García, Manuel Cantera Maortua, María Cepeda Alonso, Sonia Martín Rodríguez, Isabel Ramos Cancelo, Margarita Carrera, Purificación Sánchez, Rosa Iban Ochoa, Julio de Frutos Arribas, Ana Sánchez Fernández, Ana Andrés Blanco, Ainhoa Arroyo, María González San Pedro, Rosa Pajares Mediavilla, Carmen Paredes Arranz, Francisco Javier Pagán Buzo, Marta Arroyo Cozar, Santiago Juarros Martínez, Jorge Arana Ruiz, Laura Fernández Concellon, Juan Carlos Sánchez Rodríguez, Cecilia Alonso Medievilla, Carmen Fernández García, Teresa Garrote, Anselma Fernández Testa, Cristina Martín Gómez, Ma Victoria Domínguez Rodríguez, Miguel Martín-Luquero Ibañez, Cristina García Melón, Carmen del Río Fernández, Jaime Sanabria, Ángela Peñaloza, Noelia Fernández Núñez, David Vielba Dueñas, Concepción Carrancio Lomas y Miguel Iglesias Heras. CATALUÑA: Laia Seto Gort, Gemma Rubies, Eva Ribes, Anna Segura, Montserrat Buireu, Gabriel Celedón, Ma Elena Olmeda Arcos, Esther Rodríguez González, Virgina Pajares Ruiz, Antonio Antón, Roser Pedreny, Gladis Sabater Talaverano, Silvia Valls Pradó, Eva Tapia Melechon, Ángeles Barrio Guirado, Milagros Gándara Sanz, David Lobillo López, Eugenia Bueno Portela, Ramona Hervás, Eva Salinas y Teresa Boada Muñoz. MADRID: Miriam Aguilar Pérez, Pedro Daniel Benavides Mañas, Andrea Trisán Alonso, Cristina Martín, Gonzalo Segrelles, Celia Pinedo, Ascensión Hernando Sanz, Dita Dita Kopecna, Magdalena Alonso Plasencia, Celia Zamarro García, Vicente Gómez del Olmo, Allan Charles San Cerna, Diana Sánchez Mellado, Carolin Wagner Strücvinez, Francisco Gómez Rico, Blas Rojo Moreno Arrones, Amparo Sanz Cabrera, Pilar de Andrés Ruzafa, José González Torralba, Rodrigo Alonso Moralejo, Claudia Llontop, Elizabeth Martínez Cerón, Beatriz Gil Marín, Mercedes Izquierdo Patrón, Ángela Ramos Pinedo, Eva de Higes Martínez, Raquel Pérez Rojo, Teresa Bilbao-Goyoaga Arenas, Natividad Quílez Ruiz-Rico, David Lin Trinidad, Sandra Pelícano, José Fernández, Mónica Gómez García, María Piñeiro Martínez, Patricia Minguez Clemente, Manuel Valle Falcones, Belén Arnalich Jiménez, Álvaro Casanova Espinosa, Eva de Santiago Delgado, Pilar Alba, María del Valle Somiedo, Sara Yamamoto, José Andrés García Romero de Tejada, Rosa Mar Gómez Púnter, Alicia Ferreira, Antonio Ruiz, Concepción Losada, Esther Alonso Peces, Gerardo Vázquez, Julio Flores, María Vázquez Mezquita, Olga Navarrete y Silvia Sánchez. C.F. NAVARRA: Tamara Gutiérrez Urra y María Hernández Bonaca. C. VALENCIANA: Miren Azcune, Belén Safont, Magnolia Nieto, Giuliana Rissi, Jorge Pinel, Daniel Martínez, María Meseguer, Montserrat León Fabregas, Marta Salud Palop Cervera, Ma José Selfa, Irene Valero, Alfonso Martínez, Ricardo Peris, Mónica Abdilla Bonias, Vicenta Cresencio Pérez, Cristina Pérez de la Blanca Muñoz, Silvia Rodríguez Mercadal, Lourdes Sánchez Sánchez, Alejandro Muñoz, Justo Grau Delgado, Esther Pastor, Ana Gutiérrez Rubio, María Encarnación barroso Medel, Julio Blázquez Encinar, Yolanda Calero Amaro, Cristina Senent Español, Ana Camarasa, Khaled, Javier Guimera Monserrat, Ma José Bueso Fabra, Ma Carmen Aguar Benito, Ion Cociu, Juan Guallar, Juan Antonio Royo, Germán Llavador, Manuel Modesto, José Norberto Sancho Chust, Estrella Fernández-Fabrellas, Anna Santabasilisa, Susana Herrera, Rubén Lera, Cristina Miralles, Belén Orosa, Inmaculada Lluch Tortajada, Alfonso Martínez, Juliana Rissi, Paola Lisseth Ordoñez Gómez, Erick Leonardo Monclou Garzón, Ma Dolores Martínez Pitarch y Lucía Gil Maneu. EXTREMADURA: Amparo Sanz Cabrera, Belén Morcillo Lozano, José Antonio Marín Torrado, Estefania Molina Ortiz, Ma José Antona Rodríguez, José Carlos Serrano Rebollo, María Díaz Jiménez, Estefanía García Ledesma, Rafael Villasaña, Lourdes Cañón Barroso, Elena Badarán, Ma José López Jiménez, Alfonso García Guisado, Miriam Torres González, Miguel Ángel Hernández Mezquita, Vanesa Hidalgo Sierra y María Teresa Lainez Lazcoz. GALICIA: Javier J. Mariñas Dávila, Guillermo Rodríguez Martínez, Emilio Manuel Padin Paz, Jesús Suárez Martínez, Antonio Mazaira Riocabo, Araceli Álvarez Álvarez, Rafael Golpe Gómez, Marta Núñez Fernández, José Manuel García Pazos, Carlos Vilariño Pombo, Marta García Carrero, Mari Luz Santalla Martínez, Manuel Tumbeiro Novoa, María Reyes Ceresuela Gómez, Pedro Jorge Marcos Rodríguez, Gloria Rey García, Ana Medeiro Domínguez, Jesús González Ayude, Isaura Parente Lamelas, María Isabel Botana Rial, Virginia Leiro Fernández, Fernando Iglesias Río y Ana Cobas Paz. ISLAS BALEARES: David Blanquer Escribano, Ma José Cons González, Rocío Córdova Díaz, Álvaro de Astorza Vergara, Marissa Escobar Povedano, Jorge Guerrero y Elena Laserna Martínez. LA RIOJA: Rosana Tejedor Romera, María V. Bonilla y Francisco San Juan. PRINCIPADO DE ASTURIAS: Roberto Fernández Mellado, Nuria Rodríguez Núñez, Luis Sota Yoldi, Montserrat Barreiros, Arancha Cano, Concepción Díaz Sánchez, Blanca Requejo Mañana, Benigno del Busto Lorenzo, Hortensia Canto Argiz, Evaristo Lombardero Rico, Manuel Villanueva Montes, Ana Pando Sandoval y Francisco Julián López González. REGIÓN DE MURCIA: María Jesús Avilés Inglés, Pedro Méndez Martínez, Daniela Rosillo Castro, Antonio Mellado Fernández, Francisco Manuel Vallejo Auñon, Juan Luis de la Torre Alvarado, Carmen Aguayo Jiménez, Julia Guardiola Martínez, Consolación Alcalde Rumayol, Elena Paya Peñalver, Daniel Palazón Fernández, Pedro García Torres, Manuel Castilla Martínez, Rubén Andújar Espinosa, Olga Meca Birlanga, Beatriz Gálvez Martínez y Carlos Castillo Quintanilla.

Central Coordination. We are grateful to the staff of QUODEM Consultores SL (www.quodem.com) for their assistance in the design, construction and maintenance of the web-based application, and to Nisa Boukichou Abdelkader and Juan Dorado for their invaluable help in the editing of the database, and to Sra Esteban for her editing work.

Funding Statement

This work was supported by Fondo de Investigación Sanitaria (FIS), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (PI 08/90129, PI 90486, PI08/90578, PI 07/90503, PI 08/90251, PI 07/90516, PI 08/90529, PI 07/90309, PI 08/90457, PI 08/90129, PI 07/90721, PI 08/90550, PI08/90447, PI07/90403, PI 08/90486), Spanish Respiratory Society (SEPAR) and CIBER de Enfermedades Respiratorias (CIBERES). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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