Personalized Respiratory Medicine: Exploring the Horizon, Addressing the Issues. Summary of a BRN-AJRCCM Workshop Held in Barcelona on June 12, 2014.

This Pulmonary Perspective summarizes the content and main conclusions of an international workshop on personalized respiratory medicine coorganized by the Barcelona Respiratory Network (www.brn.cat)and the AJRCCM in June 2014. It discusses (1) its definition and historical, social, legal, and ethical aspects; (2) the view from different disciplines, including basic science, epidemiology, bioinformatics,and network/systems medicine; (3) the bottlenecks and opportunities identified by some currently ongoing projects; and (4) the implications for the individual, the healthcare system and the pharmaceutical industry. The authors hope that, although it is not a systematic review on the subject,this document can be a useful reference for researchers, clinicians, healthcare managers, policy-makers,and industry parties interested in personalized respiratory medicine

Mortality prediction in chronic obstructive pulmonary disease comparing the GOLD 2015 and GOLD 2019 staging: a pooled analysis of individual patient data

In 2019, The Global Initiative for Chronic Obstructive Lung Disease (GOLD) modified the grading system for patients with COPD, creating 16 subgroups (1A–4D). As part of the COPD Cohorts Collaborative International Assessment (3CIA) initiative, we aim to compare the mortality prediction of the 2015 and 2019 COPD GOLD staging systems. We studied 17 139 COPD patients from the 3CIA study, selecting those with complete data. Patients were classified by the 2015 and 2019 GOLD ABCD systems, and we compared the predictive ability for 5-year mortality of both classifications. In total, 17 139 patients with COPD were enrolled in 22 cohorts from 11 countries between 2003 and 2017; 8823 of them had complete data and were analysed. Mean±sd age was 63.9±9.8 years and 62.9% were male. GOLD 2019 classified the patients in milder degrees of COPD. For both classifications, group D had higher mortality. 5-year mortality did not differ between groups B and C in GOLD 2015; in GOLD 2019, mortality was greater for group B than C. Patients classified as group A and B had better sensitivity and positive predictive value with the GOLD 2019 classification than GOLD 2015. GOLD 2015 had better sensitivity for group C and D than GOLD 2019. The area under the curve values for 5-year mortality were only 0.67 (95% CI 0.66–0.68) for GOLD 2015 and 0.65 (95% CI 0.63–0.66) for GOLD 2019

Correlation between work impairment, scores of rhinitis severity and asthma using the MASK-air (R) App

Background In allergic rhinitis, a relevant outcome providing information on the effectiveness of interventions is needed. In MASK-air (Mobile Airways Sentinel Network), a visual analogue scale (VAS) for work is used as a relevant outcome. This study aimed to assess the performance of the work VAS work by comparing VAS work with other VAS measurements and symptom-medication scores obtained concurrently. Methods All consecutive MASK-air users in 23 countries from 1 June 2016 to 31 October 2018 were included (14 189 users; 205 904 days). Geolocalized users self-assessed daily symptom control using the touchscreen functionality on their smart phone to click on VAS scores (ranging from 0 to 100) for overall symptoms (global), nose, eyes, asthma and work. Two symptom-medication scores were used: the modified EAACI CSMS score and the MASK control score for rhinitis. To assess data quality, the intra-individual response variability (IRV) index was calculated. Results A strong correlation was observed between VAS work and other VAS. The highest levels for correlation with VAS work and variance explained in VAS work were found with VAS global, followed by VAS nose, eye and asthma. In comparison with VAS global, the mCSMS and MASK control score showed a lower correlation with VAS work. Results are unlikely to be explained by a low quality of data arising from repeated VAS measures. Conclusions VAS work correlates with other outcomes (VAS global, nose, eye and asthma) but less well with a symptom-medication score. VAS work should be considered as a potentially useful AR outcome in intervention studies.Peer reviewe

Large-scale external validation and comparison of prognostic models: an application to chronic obstructive pulmonary disease

Background: External validations and comparisons of prognostic models or scores are a prerequisite for their use in routine clinical care but are lacking in most medical fields including chronic obstructive pulmonary disease (COPD). Our aim was to externally validate and concurrently compare prognostic scores for 3-year all-cause mortality in mostly multimorbid patients with COPD. Methods: We relied on 24 cohort studies of the COPD Cohorts Collaborative International Assessment consortium, corresponding to primary, secondary, and tertiary care in Europe, the Americas, and Japan. These studies include globally 15,762 patients with COPD (1871 deaths and 42,203 person years of follow-up). We used network meta-analysis adapted to multiple score comparison (MSC), following a frequentist two-stage approach; thus, we were able to compare all scores in a single analytical framework accounting for correlations among scores within cohorts. We assessed transitivity, heterogeneity, and inconsistency and provided a performance ranking of the prognostic scores. Results: Depending on data availability, between two and nine prognostic scores could be calculated for each cohort. The BODE score (body mass index, airflow obstruction, dyspnea, and exercise capacity) had a median area under the curve (AUC) of 0.679 [1st quartile-3rd quartile = 0.655-0.733] across cohorts. The ADO score (age, dyspnea, and airflow obstruction) showed the best performance for predicting mortality (difference AUC(ADO) - AUC(BODE) = 0.015 [95% confidence interval (CI) = - 0.002 to 0.032]; p = 0.08) followed by the updated BODE (AUCBODE updated - AUCBODE = 0.008 [95% CI = -0.005 to +0.022]; p = 0.23). The assumption of transitivity was not violated. Heterogeneity across direct comparisons was small, and we did not identify any local or global inconsistency. Conclusions: Our analyses showed best discriminatory performance for the ADO and updated BODE scores in patients with COPD. A limitation to be addressed in future studies is the extension of MSC network meta-analysis to measures of calibration. MSC network meta-analysis can be applied to prognostic scores in any medical field to identify the best scores, possibly paving the way for stratified medicine, public health, and research

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Identification and prospective validation of clinically relevant chronic obstructive pulmonary disease (COPD) subtypes

Background Chronic obstructive pulmonary disease (COPD) is increasingly considered a heterogeneous condition. It was hypothesised that COPD, as currently defined, includes different clinically relevant subtypes. Methods To identify and validate COPD subtypes, 342 subjects hospitalised for the first time because of a COPD exacerbation were recruited. Three months after discharge, when clinically stable, symptoms and quality of life, lung function, exercise capacity, nutritional status, biomarkers of systemic and bronchial inflammation, sputum microbiology, CT of the thorax and echocardiography were assessed. COPD groups were identified by partitioning cluster analysis and validated prospectively against cause-specific hospitalisations and all-cause mortality during a 4 year follow-up. Results Three COPD groups were identified: group 1 (n ¼ 126, 67 years) was characterised by severe airflow limitation (postbronchodilator forced expiratory volume in 1 s (FEV 1 ) 38% predicted) and worse performance in most of the respiratory domains of the disease; group 2 (n ¼ 125, 69 years) showed milder airflow limitation (FEV 1 63% predicted); and group 3 (n ¼ 91, 67 years) combined a similarly milder airflow limitation (FEV 1 58% predicted) with a high proportion of obesity, cardiovascular disorders, iabetes and systemic inflammation. During follow-up, group 1 had more frequent hospitalisations due to COPD (HR 3.28, p < 0.001) and higher all-cause mortality (HR 2.36, p ¼ 0.018) than the other two groups, whereas group 3 had more admissions due to cardiovascular disease (HR 2.87, p ¼ 0.014). Conclusions In patients with COPD recruited at their first hospitalisation, three different COPD subtypes were identified and prospectively validated:"severe respiratory COPD","moderate respiratory COPD", and"systemic COPD

Can digital mobility assessment enhance the clinical assessment of disease severity in Parkinson's disease?

Background: Real-world walking speed (RWS) measured using wearable devices has the potential to complement the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) for motor assessment in Parkinson's disease (PD). Objective: Explore cross-sectional and longitudinal differences in RWS between PD and older adults (OAs), and whether RWS was related to motor disease severity cross-sectionally, and if MDS-UPDRS III was related to RWS, longitudinally. Methods: 88 PD and 111 OA participants from ICICLE-GAIT (UK) were included. RWS was evaluated using an accelerometer at four time points. RWS was aggregated within walking bout (WB) duration thresholds. Between-group-comparisons in RWS between PD and OAs were conducted cross-sectionally, and longitudinally with mixed effects models (MEMs). Cross-sectional association between RWS and MDS-UPDRS III was explored using linear regression, and longitudinal association explored with MEMs. Results: RWS was significantly lower in PD (1.04 m/s) in comparison to OAs (1.10 m/s) cross-sectionally. RWS significantly decreased over time for both cohorts and decline was more rapid in PD by 0.02 m/s per year. Significant negative relationship between RWS and the MDS-UPDRS III only existed at a specific WB threshold (30 to 60 s, β= - 3.94 points, p = 0.047). MDS-UPDRS III increased significantly by 1.84 points per year, which was not related to change in RWS. Conclusion: Digital mobility assessment of gait may add unique information to quantify disease progression remotely, but further validation in research and clinical settings is needed.This work is also supported by the Innovative Medicines Initiative 2 Joint Undertaking (IMI2 JU) project Mobilise-D that has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No. 820820. This JU receives support from the European Union’s Horizon 2020 research and innovation program and the European Federation of Pharmaceutical Industries and Associations (EFPIA). Content in this publication reflects the authors’ view and neither IMI nor the European Union, EFPIA, or any Associated Partners are responsible for any use that may be made of the information contained herein

Positive health effects of the natural outdoor environment in typical populations in different regions in Europe (PHENOTYPE): a study programme protocol

Introduction: Growing evidence suggests that close contact with nature brings benefits to human health and well-being, but the proposed mechanisms are still not well understood and the associations with health remain uncertain. The Positive Health Effects of the Natural Outdoor environment in Typical Populations in different regions in Europe (PHENOTYPE) project investigates the interconnections between natural outdoor environments and better human health and well-being. Aims and methods: The PHENOTYPE project explores the proposed underlying mechanisms at work (stress reduction/restorative function, physical activity, social interaction, exposure to environmental hazards) and examines the associations with health outcomes for different population groups. It implements conventional and new innovative high-tech methods to characterise the natural environment in terms of quality and quantity. Preventive as well as therapeutic effects of contact with the natural environment are being covered. PHENOTYPE further addresses implications for land-use planning and green space management. The main innovative part of the study is the evaluation of possible short-term and long-term associations of green space and health and the possible underlying mechanisms in four different countries (each with quite a different type of green space and a different use), using the same methodology, in one research programme. This type of holistic approach has not been undertaken before. Furthermore there are technological innovations such as the use of remote sensing and smartphones in the assessment of green space. Conclusions: The project will produce a more robust evidence base on links between exposure to natural outdoor environment and human health and well-being, in addition to a better integration of human health needs into land-use planning and green space management in rural as well as urban areas.This research is receiving funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no: 282996 (ENV.2011.1.2.3-2) (Positive effects of natural environment for human health and well-being) Duration 1 January 2012 – 31 December 201

Urban environment and physical activity and capacity in patients with chronic obstructive pulmonary disease

Background: Physical activity and exercise capacity are key prognostic factors in chronic obstructive pulmonary disease (COPD) but their environmental determinants are unknown. Objectives: To test the association between urban environment and objective physical activity, physical activity experience and exercise capacity in COPD. Methods: We studied 404 patients with mild-to-very severe COPD from a multi-city study in Catalonia, Spain. We measured objective physical activity (step count and sedentary time) by the Dynaport MoveMonitor, physical activity experience (difficulty with physical activity) by the Clinical visit-PROactive (C-PPAC) instrument, and exercise capacity by the 6-min walk distance (6MWD). We estimated individually (geocoded to the residential address) population density, pedestrian street length, slope of terrain, and long-term (i.e., annual) exposure to road traffic noise, nitrogen dioxide (NO2) and particulate matter (PM2.5). We built single- and multi-exposure mixed-effects linear regressions with a random intercept for city, adjusting for confounders. Results: Patients were 85% male, had mean (SD) age 69 (9) years and walked 7524 (4045) steps/day. In multi-exposure models, higher population density was associated with fewer steps, more sedentary time and worse exercise capacity (-507 [95% CI: 1135, 121] steps, +0.2 [0.0, 0.4] h/day and -13 [-25, 0] m per IQR). Pedestrian street length related with more steps and less sedentary time (156 [9, 304] steps and -0.1 [-0.1, 0.0] h/day per IQR). Steeper slope was associated with better exercise capacity (15 [3, 27] m per IQR). Higher NO2 levels related with more sedentary time and more difficulty in physical activity. PM2.5 and noise were not associated with physical activity or exercise capacity. Discussion: Population density, pedestrian street length, slope and NO2 exposure relate to physical activity and capacity of COPD patients living in highly populated areas. These findings support the consideration of neighbourhood environmental factors during COPD management and the attention to patients with chronic diseases when developing urban and transport planning policies