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Athlete's heart encompasses multiple physiological cardiac adaptations, although less is known at atrial level. How sex may influence the type and extent of atrial adaptations to exercise stimuli is also unknown. Our objective was to compare gender differences of echocardiographic atrial function indices in response to exercise in endurance athletes (EAs).Highly trained ( 10 h/week) endurance athletes performed a maximal cardiopulmonary exercise test (CPET). Echocardiographic evaluation was performed at rest and immediately after exercise. Atria analysis consisted of standard and speckle-tracking echocardiographic assessment of atrial dimensions and contractile, reservoir, and conduit functions with myocardial deformation.80 EAs (55% women) were enrolled and performed excellent CPET (129.6% of predicted VOIn highly trained EAs, women have similar or even lower atrial dimensions remodelling compared to men, but better function based on reservoir and conduit strain values both at rest and in response to exercise. This phenomenon should be confirmed in larger studies and its potential role in the development of supraventricular arrhythmias, addressed in a specifically designed protocol.

Moderate to extreme prematurity is associated with lower lung function in adults1 while evidence is poorer and controversial for late prematurity.2 Likewise, the potential long-term impact on adult lung function of being born small for gestational age (SGA) at term is not well established since most previous studies in this field have been done in groups with participants enrolled by birthweight and not by SGA per se.2 This may be important because not all infants born SGA have experienced intrauterine growth restriction (IUGR) and, the other way round, early IUGR does not necessarily bring fetal growth down below the 10th percentile (the definition of SGA). We recently showed that young adults born SGA at term had markedly reduced exercise capacity, mostly of cardiovascular origin.3 In particular, they showed lower maximal workload, peak oxygen consumption and oxygen pulse, as well as higher minute ventilation/carbon dioxide production equivalent at the anaerobic threshold, than age-matched controls.3 Here, we extend and complement these previously published observations3 with the analysis of pulmonary physiology (spirometry and carbon monoxide diffusing capacity [DLCO]) and the measurement of circulatory markers of abnormal lung development, including surfactant protein A and D (SP-A and SP-D) and club cell protein 16 (CC16). We conducted an ambispective, controlled, cohort study whose detailed methodology has been published elsewhere.3 Briefly, from the birth records of our institution, we identified individuals born at term (≥37 weeks of gestation) between 1975 and 1995 with either appropriate weight for gestational age (AGA) or SGA (

[EN] Background: Frequently used reference values for clinical exercise testing have been derived from non-random samples and some with poorly defined maximal criteria. Our objective was to obtain population based reference values for peak oxygen uptake ( ̇VO2 ) and work rate (WR) for cardiopulmonary exercise testing in a representative sample of Caucasian Spanish men and women. Methods: 182 men and women, 20–85 years old, were included and exercised on cycle-ergometer to exhaustion. ( ̇VO2 ) and WR were measured. The equations obtained from this sample were validated in an independent cohort of 69 individuals, randomly sampled form the same population. Then a final equation merging the two cohorts (=251) was produced. Results: Height, sex and age resulted predictive of both ̇VO2 peak and WR. Weight and physical activity added very little to the accuracy to the equations. The formulas ̇VO2 peak = 0.017 · height (cm) − 0.023 · age (years) + 0.864 · sex (female = 0/male = 1) ± 179 l min−1 , and peak WR = 1.345 · height (cm) − 2.074 · age (years) + 76.54 · sex (female = 0/male = 1) ± 21.2 W were the best compromise between accuracy and parsimony. Conclusions: This study provides new and accurate ̇VO2 peak and WR rate reference values for individuals of European Spanish descent, [ES] Antecedentes: Los valores de referencia utilizados con frecuencia para las pruebas de esfuerzo clínicas derivan de muestras no aleatorias y los criterios máximos para algunos de ellos están mal definidos. Nuestro objetivo fue obtener valores de referencia basados en la población general para el consumo máximo de oxígeno (VO 2 ) y la carga de trabajo (CT) para las pruebas de ejercicio cardiopulmonar a partir de una muestra representativa de varones y mujeres caucásicos españoles. Métodos: Se incluyeron 182 varones y mujeres, de entre 20 y 85 a ̃nos, que realizaron ejercicio en el cicloergómetro hasta el agotamiento. Se midieron el VO 2 y la CT. Las ecuaciones obtenidas de esta muestra se validaron en una cohorte independiente de 69 individuos, seleccionados aleatoriamente de la misma población. A continuación, se creó una ecuación final que fusionó las dos cohortes (n = 251). Resultados: La altura, el sexo y la edad resultaron predictivos tanto del ̇VO2 máximo como de la CT. El peso y la actividad física contribuyeron muy poco a la precisión de las ecuaciones. Las fórmulas ̇VO2 máximo = 0,017 × altura (cm) − 0,023 × edad (a ̃nos) + 0,864 × sexo (mujer = 0/varón = 1) ± 179 L × min−1 ; y CT máxima = 1,345 × altura (cm) − 2,074 × edad (a ̃nos) + 76,54 × sexo (mujer = 0/varón = 1) ± 21,2 W fueron el mejor equilibrio entre precisión y parsimonia. Conclusiones: Este estudio proporciona valores de referencia del ̇VO 2 máximo y la CT nuevos y precisos para personas de ascendencia espa ̃nola europea., This study was supported by a SEPAR (Sociedad Española de Neumología y Cirugía Torácica/Spanish society of Pulmonology and Thoracic Surgery) grant and NEUMOMADRD (Sociedad Madrileña de Neumología y Cirugía Torácica/Madrilenian Society of Pulmonology and Thoracic Surgery) research award.

Background: Evidence suggests lungs as the organ most affected by coronavirus disease 2019 (COVID-19). The literature on previous coronavirus infections reports that patients may experience persistent impairment in respiratory function after being discharged. Our objective was to determine the prevalence of restrictive pattern, obstructive pattern and altered diffusion in patients post-COVID-19 infection and to describe the different evaluations of respiratory function used with these patients. Methods: A systematic review was conducted in five databases. Studies that used lung function testing to assess post-infection COVID-19 patients were included for review. Two independent reviewers analysed the studies, extracted the data and assessed the quality of evidence. Results: Of the 1973 reports returned by the initial search, seven articles reporting on 380 patients were included in the data synthesis. In the sensitivity analysis, we found a prevalence of 0.39 (CI 0.24–0.56, p

Background Current techniques for measuring absolute lung volumes rely on bulky and expensive equipment and are complicated to use for the operator and the patient. A novel method for measurement of absolute lung volumes, the MiniBox method, is presented. Research Question Across a population of patients and healthy participants, do values for total lung capacity (TLC) determined by the novel compact device (MiniBox, PulmOne Advanced Medical Devices, Ltd.) compare favorably with measurements determined by traditional whole body plethysmography? Study Design and Methods A total of 266 participants (130 men) and respiratory patients were recruited from five global centers (three in Europe and two in the United States). The study population comprised individuals with obstructive (n = 197) and restrictive (n = 33) disorders as well as healthy participants (n = 36). TLC measured by conventional plethysmography (TLCPleth) was compared with TLC measured by the MiniBox (TLCMB). Results TLC values ranged between 2.7 and 10.9 L. The normalized root mean square difference (NSD) between TLCPleth and TLCMB was 7.0% in healthy participants. In obstructed patients, the NSD was 7.9% in mild obstruction and 9.1% in severe obstruction. In restricted patients, the NSD was 7.8% in mild restriction and 13.9% in moderate and severe restriction. No significant differences were found between TLC values obtained by the two measurement techniques. Also no significant differences were found in results obtained among the five centers. Interpretation TLC as measured by the novel MiniBox system is not significantly different from TLC measured by conventional whole body plethysmography, thus validating the MiniBox method as a reliable method to measure absolute lung volumes.

A workshop “Electronic Health Records and Pulmonary Function Data: Developing an Interoperability Roadmap” was held at the American Thoracic Society 2019 International Conference. “Interoperability” is defined as is the ability of different information-technology systems and software applications to directly communicate, exchange data, and use the information that has been exchanged. At present, pulmonary function test (PFT) equipment is not required to be interoperable with other clinical data systems, including electronic health records (EHRs). For this workshop, we assembled a diverse group of experts and stakeholders, including representatives from patient-advocacy groups, adult and pediatric general and pulmonary medicine, informatics, government and healthcare organizations, pulmonary function laboratories, and EHR and PFT equipment and software companies. The participants were tasked with two overarching Aobjectives: 1) identifying the key obstacles to achieving interoperability of PFT systems and the EHR and 2) recommending solutions to the identified obstacles. Successful interoperability of PFT data with the EHR impacts the full scope of individual patient health and clinical care, population health, and research. The existing EHR–PFT device platforms lack sufficient data standardization to promote interoperability. Cost is a major obstacle to PFT–EHR interoperability, and incentives are insufficient to justify the needed investment. The current vendor–EHR system lacks sufficient flexibility, thereby impeding interoperability. To advance the goal of achieving interoperability, next steps include identifying and standardizing priority PFT data elements. To increase the motivation of stakeholders to invest in this effort, it is necessary to demonstrate the benefits of PFT interoperability across patient care and population health.

Pulmonary function testing was performed in 3 bottlenose dolphins Tursiops truncatus (1 female and 2 males) under managed care during a 2 yr period to assess whether these data provide diagnostic information about respiratory health. Pulmonary radiographs and standard clinical testing were used to evaluate the pulmonary health of each dolphin. The female dolphin (F1) had evidence of chronic pulmonary fibrosis, and 1 male (M2) developed pneumonia during the study. Pulmonary function data were collected from maximal respiratory efforts in water and from spontaneous breaths while beached. From these data, the flow-volume relationship, the flow measured between 25 and 75% of the expired vital capacity (mid forced expiratory flow, FEF25%-75%), and the percent of the vital capacity (VC) at the peak expiratory flow (%VCPEF), were evaluated and compared with the diagnostic assessment. For maximal respiratory manoeuvres in water, there were no differences in FEF25%-75% or %VCPEF, and the flow-volume relationship showed a consistent pattern for F1. Additionally, FEF25%-75% and %VCPEF decreased by 27 and 52%, respectively, and the flow-volume relationship showed clear flow limitations with emerging disease in M2. While spontaneously breathing on land, M2 also showed a 49% decrease in %VCPEF and changes in the flow-volume relationship, indicating flow limitations following the development of pneumonia. Based on these preliminary results, we suggest that pulmonary function testing should be given more attention as a non-invasive and possibly adjunctive diagnostic tool to evaluate lung health of dolphins under managed care and in the wild.

BackgroundFew studies have investigated the collaborative potential between artificial intelligence (AI) and pulmonologists for diagnosing pulmonary disease. We hypothesised that the collaboration between a pulmonologist and AI with explanations (explainable AI (XAI)) is superior in diagnostic interpretation of pulmonary function tests (PFTs) than the pulmonologist without support.MethodsThe study was conducted in two phases, a monocentre study (phase 1) and a multicentre intervention study (phase 2). Each phase utilised two different sets of 24 PFT reports of patients with a clinically validated gold standard diagnosis. Each PFT was interpreted without (control) and with XAI's suggestions (intervention). Pulmonologists provided a differential diagnosis consisting of a preferential diagnosis and optionally up to three additional diagnoses. The primary end-point compared accuracy of preferential and additional diagnoses between control and intervention. Secondary end-points were the number of diagnoses in differential diagnosis, diagnostic confidence and inter-rater agreement. We also analysed how XAI influenced pulmonologists’ decisions.ResultsIn phase 1 (n=16 pulmonologists), mean preferential and differential diagnostic accuracy significantly increased by 10.4% and 9.4%, respectively, between control and intervention (pConclusionA collaboration between a pulmonologist and XAI is better at interpreting PFTs than individual pulmonologists reading without XAI support or XAI alone.

Coronavirus disease 2019 (COVID-19) has negatively affected the delivery of respiratory diagnostic services across the world due to the potential risk of disease transmission during lung function testing. Community prevalence, reoccurrence of COVID-19 surges and the emergence of different variants of SARS-CoV-2 have impeded attempts to restore services. Finding consensus on how to deliver safe lung function services for both patients attending and for staff performing the tests are of paramount importance.This international statement presents the consensus opinion of 23 experts in the field of lung function and respiratory physiology balanced with evidence from the reviewed literature. It describes a robust roadmap for restoration and continuity of lung function testing services during the COVID-19 pandemic and beyond.Important strategies presented in this consensus statement relate to the patient journey when attending for lung function tests. We discuss appointment preparation, operational and environmental issues, testing room requirements including mitigation strategies for transmission risk, requirement for improved ventilation, maintaining physical distance and use of personal protection equipment. We also provide consensus opinion on precautions relating to specific tests, filters, management of special patient groups and alternative options to testing in hospitals.The pandemic has highlighted how vulnerable lung function services are and forces us to re-think how long-term mitigation strategies can protect our services during this and any possible future pandemic. This statement aspires to address the safety concerns that exist and provide strategies to make lung function tests and the testing environment safer when tests are required.

The 6-min walking distance (6MWD) is often used to assess prognosis in pulmonary arterial hypertension (PAH) patients. Whether or not changes in arterial oxygen saturation (SpOAmbispective study that includes 137 patients with PAH: 38 idiopathic/heritable (i/h PAH), 42 with connective tissue disease (CTD-PAH), 34 with porto-pulmonary hypertension (PoPH), 21 with HIV-associated PAH and 2 with pulmonary venous occlusive disease (PVOD). Patients were characterized and, treated according to international recommendations, and were followed-up for 5 years. To integrate SpO(1) during follow-up, 40 patients died (29.2%); (2) results confirmed the prognostic value of the 6MWD (AUC 0.913 [IQR 0.868-0.958]; p 0.0001), original DDR (AUC 0.923 [0.881-0.966]; p 0.001), New DDR (AUC 0.917 [0.872-0.961], p 0.001), and DSP (AUC 0.914 [0.869-0.959], p 0.001); and, (3) neither the original or new DDR or DSP added significant prognostic value to 6MWD in these patients.Consideration of three different composite indices of arterial oxygenation changes during exercise does not add prognostic value to that of the 6MWD in patients with PAH.

Background The mechanisms underlying the high interindividual variability demonstrated for right-ventricular (RV) adaptation to exercise have not yet been identified, but different pulmonary vascular adaptations among individuals could be involved. Pulmonary transit of agitated saline (PTAS) during exercise has been demonstrated to be a good estimator of vascular reserve. Aim The aim of this study was to evaluate the presence of PTAS among endurance athletes (EAs) of both sexes and its influence on RV adaptation to exercise. Methods A total of 100 highly trained EAs performed a maximal cardiopulmonary exercise test. Bi-ventricular functional and structural characteristics as well as PTAS were evaluated at baseline and at peak exercise. Athletes were distributed between two groups based on the amount of PTAS during exercise as high (HTPAS; >12 bubbles) and low (LPTAS; ≤12 bubbles). Results Overall, 11 EAs exhibited an intra-cardiac shunt at rest and 1 met the criteria for chronic pulmonary disease and were excluded from the study. Among the remaining 88 EAs (51% women), 47 (53%) athletes were classified as HPTAS and 41 (47%) as LPTAS. HPTAS capability was associated with significantly larger RV contractile reserve, larger pulmonary vascular reserve and an enhanced maximal exercise capacity. On multivariate analysis, females were the only independent correlate of the HPTAS capability. Conclusion In highly trained endurance athletes, a HPTAS capability during exercise corresponded to an increase in pulmonary vascular and RV contractile reserves as well as an enhanced maximal exercise capacity. The long-term clinical or performance implications of the absence or presence of pulmonary shunting, and the subsequent RV afterload increase while performing exercise, remains to be determined.

This document is updated technical standards of European Respiratory Society (ERS) and American Thoracic Society (ATS) for single-breath carbon monoxide diffusing capacity measurement. The previous version of this document was published in 2005. Both terms used to describe the uptake of carbon monoxide in the lungs, DLCO (diffusing capacity) and TLCO (transfer factor), are equally valid, but the term DLCO is used in this document. The document was developed by joint ATS/ERS taskforce and was based on a survey of published evidence. Expert opinion was used for issues for which evidence was not available or was insufficient. Principal changes in the technical standards are related to new systems with rapidly responding gas analyzers for carbon monoxide. Additional materials are available at erj.ersjournals.com. Adopted from: Graham B.L., Brusasco V., Burgos F., Cooper B.G., Jensen R., Kendrick A., MacIntyre N.R., Thompson B.R., Wanger J. 2017 ERS/ATS standards for single-breath carbon monoxide uptake in the lung. Eur. Respir. J. 2017; 49 (1): pii: 1600016. DOI: 10.1183/13993003.00016-2016.

AIM We hypothesize that training-induced changes in muscle oxygen saturation (StO2 ) assessed by near-infrared spectroscopy (NIRS) during constant work rate cycling exercise (CWRE) may be a useful marker of the effects of training at 'vastus medialis' of the quadriceps in patients with chronic obstructive pulmonary disease (COPD). METHODS Incremental exercise [peak oxygen uptake (VO2 )] and CWRE at 70% pretraining peak VO2 , before and after 8-w training, were done in 10 healthy age-matched subjects (H) [80% men, 65(11) years, FEV1 105(14)%] and 16 COPD patients [94% men, 70(5) years, FEV1 46(11) %] encompassing the entire spectrum of disease severity, recruited in the outpatient clinics. NIRS was used to assess StO2 in the 'vastus medialis' of the left quadriceps. RESULTS Pretraining CWRE decreased StO2 (P

IMPORTANCE: Being born small for gestational age (SGA), approximately 10% of all births, is associated with increased risk of cardiovascular mortality in adulthood, but mechanistic pathways are unclear. Cardiac remodeling and dysfunction occur in fetuses SGA and children born SGA, but it is uncertain whether and how these changes persist into adulthood. OBJECTIVE: To evaluate baseline cardiac function and structure and exercise capacity in young adults born SGA. DESIGN, SETTING, AND PARTICIPANTS: This cohort study conducted from January 2015 to January 2018 assessed a perinatal cohort born at a tertiary university hospital in Spain between 1975 and 1995. Participants included 158 randomly selected young adults aged 20 to 40 years born SGA (birth weight below the 10th centile) or with intrauterine growth within standard reference ranges (controls). Participants provided their medical history, filled out questionnaires regarding smoking and physical activity habits, and underwent incremental cardiopulmonary exercise stress testing, cardiac magnetic resonance imaging, and a physical examination, with blood pressure, glucose level, and lipid profile data collected. EXPOSURE: Being born SGA. MAIN OUTCOMES AND MEASURES: Cardiac structure and function assessed by cardiac magnetic resonance imaging, including biventricular end-diastolic shape analysis. Exercise capacity assessed by incremental exercise stress testing. RESULTS: This cohort study included 81 adults born SGA (median age at study, 34.4 years [IQR, 30.8-36.7 years]; 43 women [53%]) and 77 control participants (median age at study, 33.7 years [interquartile range (IQR), 31.0-37.1 years]; 33 women [43%]). All participants were of White race/ethnicity and underwent imaging, whereas 127 participants (80% of the cohort; 66 control participants and 61 adults born SGA) completed the exercise test. Cardiac shape analysis showed minor changes at rest in right ventricular geometry (DeLong test z, 2.2098; P = .02) with preserved cardiac function in individuals born SGA. However, compared with controls, adults born SGA had lower exercise capacity, with decreased maximal workload (mean [SD], 180 [62] W vs 214 [60] W; P = .006) and oxygen consumption (median, 26.0 mL/min/kg [IQR, 21.5-33.5 mL/min/kg vs 29.5 mL/min/kg [IQR, 24.0-36.0 mL/min/kg]; P = .02). Exercise capacity was significantly correlated with left ventricular mass (ρ = 0.7934; P

Case Reports

The aim of this study was to assess the impact of personalized prehabilitation on postoperative complications in high-risk patients undergoing elective major abdominal surgery.Prehabilitation, including endurance exercise training and promotion of physical activity, in patients undergoing major abdominal surgery has been postulated as an effective preventive intervention to reduce postoperative complications. However, the existing studies provide controversial results and show a clear bias toward low-risk patients.This was a randomized blinded controlled trial. Eligible candidates accepting to participate were blindly randomized (1:1 ratio) to control (standard care) or intervention (standard care + prehabilitation) groups. Inclusion criteria were: i) age70 years; and/or, ii) American Society of Anesthesiologists score III/IV. Prehabilitation covered 3 actions: i) motivational interview; ii) high-intensity endurance training; and promotion of physical activity. The main study outcome was the proportion of patients suffering postoperative complications. Secondary outcomes included the endurance time (ET) during cycle-ergometer exercise.We randomized 71 patients to the control arm and 73 to intervention. After excluding 19 patients because of changes in the surgical plan, 63 controls and 62 intervention patients were included in the intention-to-treat analysis. The intervention group enhanced aerobic capacity [ΔET 135 (218) %; P0.001), reduced the number of patients with postoperative complications by 51% (relative risk 0.5; 95% confidence interval, 0.3-0.8; P = 0.001) and the rate of complications [1.4 (1.6) and 0.5 (1.0) (P = 0.001)] as compared with controls.Prehabilitation enhanced postoperative clinical outcomes in high-risk candidates for elective major abdominal surgery, which can be explained by the increased aerobic capacity.

Forced spirometry testing is gradually becoming available across different healthcare tiers including primary care. It has been demonstrated in earlier work that commercially available spirometers are not fully able to assure the quality of individual spirometry manoeuvres. Thus, a need to expand the availability of high-quality spirometry assessment beyond specialist pulmonary centres has arisen. In this paper, we propose a method to select and optimise a classifier using supervised learning techniques by learning from previously classified forced spirometry tests from a group of experts. Such a method is able to take into account the shape of the curve as an expert would during visual inspection. We evaluated the final classifier on a dataset put aside for evaluation yielding an area under the receiver operating characteristic curve of 0.88 and specificities of 0.91 and 0.86 for sensitivities of 0.60 and 0.82. Furthermore, other specificities and sensitivities along the receiver operating characteristic curve were close to the level of the experts when compared against each-other, and better than an earlier rules-based method assessed on the same dataset. We foresee key benefits in raising diagnostic quality, saving time, reducing cost, and also improving remote care and monitoring services for patients with chronic respiratory diseases in the future if a clinical decision support system with the encapsulated classifier is to be integrated into the work-flow of forced spirometry testing.

Aims: Endurance athletes develop cardiac remodeling to cope with increased cardiac output during exercise. This remodeling is both anatomical and functional and shows large interindividual variability. In this study, we quantify local geometric ven-tricular remodeling related to long-standing endurance training and assess its relationship with cardiovascular performance during exercise.Methods: We extracted 3D models of the biventricular shape from end-diastolic cine magnetic resonance images acquired from a cohort of 89 triathlon athletes and 77 healthy sedentary subjects. Additionally, the athletes underwent cardio-pulmonary exercise testing, together with an echocardiographic study at baseline and few minutes after maximal exercise. We used statistical shape analysis to identify regional bi-ventricular shape differences between athletes and non-athletes.Results: The ventricular shape was significantly different between athletes and controls (p < 1e−6). The observed regional remodeling in the right heart was mainly a shift of the right ventricle (RV) volume distribution towards the right ventricular infundibulum, increasing the overall right ventricular volume. In the left heart, there was an increment of left ventricular mass and a dilation of the left ventricle. Within athletes, the amount of such remodeling was independently associated to higher peak oxygen pulse (p < 0.001) and weakly with greater post-exercise RV free wall longitudinal strain (p = 0.03).Conclusions: We were able to identify specific bi-ventricular regional remodeling induced by long-lasting endurance training. The amount of remodeling was associated with better cardiopulmonary performance during an exercise test. This study was partially supported by the Spanish Ministry of Economy and Competitiveness (Grant DEP2013-44923-P, TIN2014-52923-R; Maria de Maeztu Units of Excellence Programme—MDM-2015-0502), el Fondo Europeo de Desarrollo Regional (FEDER), the European Union under the Horizon 2020 Programme for Research, Innovation (Grant agreement No. 642676 CardioFunXion) and Erasmus+Programme (Framework Agreement number: 2013-0040), “la Caixa” Foundation (LCF/PR/GN14/10270005, LCF/PR/GN18/10310003), Instituto de Salud Carlos III (PI14/00226, PI15/00130, PI17/00675) integrated in the “Plan Nacional I+D+I” and AGAUR 2017 SGR Grant no. 1531.

Background Comprehensive assessment of integrated care deployment constitutes a major challenge to ensure quality, sustainability and transferability of both healthcare policies and services in the transition toward a coordinated service delivery scenario. To this end, the manuscript articulates four different protocols aiming at assessing large-scale implementation of integrated care, which are being developed within the umbrella of the regional project Nextcare (2016–2019), undertaken to foster innovation in technologically-supported services for chronic multimorbid patients in Catalonia (ES) (7.5 M inhabitants). Whereas one of the assessment protocols is designed to evaluate population-based deployment of care coordination at regional level during the period 2011–2017, the other three are service-based protocols addressing: i) Home hospitalization; ii) Prehabilitation for major surgery; and, iii) Community-based interventions for frail elderly chronic patients. All three services have demonstrated efficacy and potential for health value generation. They reflect different implementation maturity levels. While full coverage of the entire urban health district of Barcelona-Esquerra (520 k inhabitants) is the main aim of home hospitalization, demonstration of sustainability at Hospital Clinic of Barcelona constitutes the core goal of the prehabilitation service. Likewise, full coverage of integrated care services addressed to frail chronic patients is aimed at the city of Badalona (216 k inhabitants). Methods The population-based analysis, as well as the three service-based protocols, follow observational and experimental study designs using a non-randomized intervention group (integrated care) compared with a control group (usual care) with a propensity score matching method. Evaluation of cost-effectiveness of the interventions using a Quadruple aim approach is a central outcome in all protocols. Moreover, multi-criteria decision analysis is explored as an innovative method for health delivery assessment. The following additional dimensions will also be addressed: i) Determinants of sustainability and scalability of the services; ii) Assessment of the technological support; iii) Enhanced health risk assessment; and, iv) Factors modulating service transferability. Discussion The current study offers a unique opportunity to undertake a comprehensive assessment of integrated care fostering deployment of services at regional level. The study outcomes will contribute refining service workflows, improving health risk assessment and generating recommendations for service selection. Trials registration NCT03130283 (date released 04/06/2018), NCT03768050 (date released 12/05/2018), NCT03767387 (date released 12/05/2018). Electronic supplementary material The online version of this article (10.1186/s12913-019-4174-2) contains supplementary material, which is available to authorized users.

Background Some patients with COPD report frequent acute exacerbations (AECOPD) of the disease (FE), whereas others suffer them infrequently (IE). Because the current diagnosis of exacerbation relies on patient9s perception of increased symptoms (mostly dyspnoea), we hypothesised that dyspnoea perception might be different in COPD patients with FE (≥2 exacerbations or 1 hospitalisation due to AECOPD in the previous year) or IE (≤1 exacerbation in the previous year), AECOPD being defined by the institution antibiotics and/or steroids treatment, or hospital admission. Objective To test the hypothesis that dyspnoea perception is increased in FE and/or decreased in IE with COPD. Methods We compared the perception of dyspnoea (Borg scale), mouth occlusion pressure 0.1 s after the onset of inspiration (P 0.1 ) and ventilatory response to hypercapnia (ΔV E /ΔP ET CO 2 ) in 34 clinically stable COPD patients with FE (n=14) or IE (n=20), with similar age, gender, body mass index and degree of airflow limitation. As a reference, we studied a group of age-matched healthy volunteers (n=10) with normal spirometry. Results At rest, P 0.1 was higher in FE than IE and controls (p Conclusions Dyspnoea perception during CO 2 rebreathing is enhanced in FE and blunted in IE. These differences may contribute to the differential rate of reported exacerbations in FE and IE. Trial registration number NCT02113839.

Background Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with limited response to currently available therapies. Alveolar type II (ATII) cells act as progenitor cells in the adult lung, contributing to alveolar repair during pulmonary injury. However, in IPF, ATII cells die and are replaced by fibroblasts and myofibroblasts. In previous preclinical studies, we demonstrated that ATII-cell intratracheal transplantation was able to reduce pulmonary fibrosis. The main objective of this study was to investigate the safety and tolerability of ATII-cell intratracheal transplantation in patients with IPF. Methods We enrolled 16 patients with moderate and progressive IPF who underwent ATII-cell intratracheal transplantation through fiberoptic bronchoscopy. We evaluated the safety and tolerability of ATII-cell transplantation by assessing the emergent adverse side effects that appeared within 12 months. Moreover, pulmonary function, respiratory symptoms, and disease extent during 12 months of follow-up were evaluated. Results No significant adverse events were associated with the ATII-cell intratracheal transplantation. After 12 months of follow-up, there was no deterioration in pulmonary function, respiratory symptoms, or disease extent. Conclusions Our results support the hypothesis that ATII-cell intratracheal transplantation is safe and well tolerated in patients with IPF. This study opens the door to designing a clinical trial to elucidate the potential beneficial effects of ATII-cell therapy in IPF.

Table S3. Prehabilitation protocol. (DOCX 28 kb)

Annex 1 - Method for ASsessment of Telemedicine (mini-MAST). (DOCX 22 kb)

Table S2. Home Hospitalization protocol. (DOCX 35 kb)

Table S1. Population-based protocol. (DOCX 26 kb)

A patient with ischemic myocardiopathy who had undergone resynchronization therapy was admitted to the authors' institution with progressive dyspnea. Echocardiography demonstrated a left ventricular ejection fraction (LVEF) of 25%, with a massive mitral regurgitation (MR) secondary to anterior leaflet prolapse and posterior leaflet restriction. Despite intensive medical treatment, the patient developed cardiogenic shock and required mechanical ventilation, inotropic support and intra-aortic balloon pumping. The patient was rejected for surgery due to the high operative risk, but subsequently underwent a successful percutaneous repair with two MitraClip® devices. Immediately after the intervention there was a progressive improvement that allowed the patient to be discharged, such that the clinical outcome was favorable at the six-month follow up (NYHA class II/IV). This case report describes the benefits of minimally invasive therapy in selected patients who are at very high surgical risk and who, despite being in a critical condition and with low LVEF, experience an outstanding clinical improvement following the resolution of a massive MR.

Background: Technology-supported integrated care services can enhance clinical management of chronic patients. But, the role of an electronic Personal Health Folder (ePHF) and mobile technology (mHealth) to facilitate behavioral change is not clear. Objective: To assess the impact of an intervention supported by mHealth on behavioral aspects and health status in obstructive sleep apnea patients. Methods: One arm pilot study. Inclusion criteria: 25-70 yrs, BMI 27-35 kg/m2, apnea-hypopnea index > 15/h treated or not by CPAP. Intervention: i) Motivational interview; ii) 1-m supervised endurance training program; followed by, iii) a 2-m period of promotion of physical activity (PA) in the community supported by a mHealth tool and Fitbit®. Motivational aspects for PA, health status (SF36) and anthropometry measurements were assessed at baseline and at 3 m. Results: 15 out of 16 patients completed the study. mHealth tool usability by patients and professionals was well accepted. Motivational aspects towards PA showed a positive change after 3 months, namely: autodetermination [5.4 (0.54) vs 5.6 (0.59) p=0.011]; action planning [6.5 (0.44) vs 6.1 (0.46); p=0.002] and vitality [4.8 (0.39) vs 5.1 (0.47); p=0.001]. Neck and hip diameter (cm) diminished (43.3 vs 42.5 p=0.04 and 108 vs 107; p Conclusions: The mHealth supported intervention showed a positive impact on motivation for PA and anthropometry measurements. The ePHF may play a central role to ensure interoperability of mHealth with electronic medical records. Supported by S4H (EIT-Health)

Dual-chamber (DDD) pacing has been used for treatment of patients with hypertrophic obstructive cardiomyopathy (HOCM). Due to inconclusive results in prior trials, current guidelines assign DDD pacing a class IIb indication in selected patients. Prior observations indicate that lack of clinical improvement may result from suboptimal effect of DDD pacing with non-physiological AV intervals due to fusion of intrinsic and paced QRS complex. The Triple Chamber Pacing in Hypertrophic Obstructive Cardiomyopathy Patients (TRICHAMPION) trial is a prospective, randomized, single-blinded, multicenter study to investigate the benefit of atrial synchronous biventricular pacing (CRT-P) in highly symptomatic HOCM patients with severe left ventricular outflow tract (LVOT) obstruction who are not candidates for ablative therapies. AV node ablation is used as key tool to optimize AV intervals in patients with QRS fusion. The primary endpoint is the percentage of patients with symptomatic improvement at 12 months, defined as improvement of New York Heart Association functional class, in the Minnesota Living with Heart Failure Questionnaire score and increased cardiopulmonary exercise endurance. The aim of the TRICHAMPION trial is to investigate the benefit of optimized atrial synchronous biventricular pacing in absence of QRS fusion in highly symptomatic HOCM patients with severe LVOT obstruction who are not candidates for ablative therapies.

Background: Community pharmacies (CP) have access to subjects at high-risk of suffering Chronic Obstructive Pulmonary Disease (COPD). We investigated if a COPD case finding program in CP could be a new strategy to reduce COPD underdiagnosis. Methods: Prospective, cross-sectional, descriptive, uncontrolled, remotely supported study in 100 CP in Barcelona, Spain. Pharmacists were trained in a four-day workshop on spirometry and COPD, and each was provided with a spirometer for 12 weeks. The program included questionnaires and forced spirometry measurements, whose quality was controlled and monitored by web-assistance. Findings: Overall 2295 (73.5%), of 3121 CP customers invited to participate in the program accepted, and 1.456 (63.4%) were identified as "high risk" for COPD using the GOLD questionnaire. Only 33 could not conduct spirometry, and a pre-bronchodilator airflow limitation (FEV1/FVC ratio

Protocol for regional implementation of collaborative self-management services to promote physical activity. This file includes the specific details of each of the three protocols described in the main manuscript. (DOC 531 kb)

Background The relationship between airway hyperresponsiveness (AHR) and obesity, a low-grade systemic inflammatory condition, remains largely unknown. It is established that AHR to indirect stimuli is associated with active airway inflammation. The objectives were to investigate the rate of AHR to mannitol in obese subjects and its changes 1 year after bariatric surgery (BS). Methods We enrolled 58 candidates to BS severely obese (33 nonsmokers and 25 smokers) without history of asthma and 20 healthy, nonobese participants and related AHR to functional findings and serum and exhaled biomarkers. Results Before surgery, AHR was observed in 16 (28 %) obese with the provocation doses of mannitol to induce a 15 % fall in FEV1 (PD15) of (geometric mean [95 % CI]) 83 (24–145) mg. Compared to control participants, obese participants had lower spirometric values and higher serum and exhaled biomarkers (p