Automated Quantification of QT-Intervals by an Algorithm: A Validation Study in Patients with Chronic Obstructive Pulmonary Disease.

Study Objectives: To assess the diagnostic accuracy of a purpose-designed QTc-scoring algorithm versus the established hand-scoring in patients with chronic obstructive pulmonary disease (COPD) undergoing sleep studies. Methods: We collected 62 overnight electrocardiogram (ECG) recordings in 28 COPD patients. QT-intervals corrected for heart rate (QTc, Bazett) were averaged over 1-min periods and quantified, both by the algorithm and by cursor-assisted hand-scoring. Hand-scoring was done blinded to the algorithm-derived results. Bland-Altman statistics and confusion matrixes for three thresholds (460, 480, and 500ms) were calculated. Results: A total of 32944 1-min periods and corresponding mean QTc-intervals were analysed manually and by computer. Mean difference between manual and algorithm-based QTc-intervals was -1ms, with limits of agreement of -18 to 16ms. Overall, 2587 (8%), 357 (1%), and 0 QTc-intervals exceeding the threshold 460, 480, and 500ms, respectively, were identified by hand-scoring. Of these, 2516, 357, and 0 were consistently identified by the algorithm. This resulted in a diagnostic classification accuracy of 0.98 (95% CI 0.98/0.98), 1.00 (1.00/1.00), and 1.00 (1.00/1.00) for 460, 480, and 500ms, respectively. Sensitivity was 0.97, 1.00, and NA for 460, 480, and 500ms, respectively. Specificity was 0.98, 1.00, and 1.00 for 460, 480, and 500ms, respectively. Conclusion: Overall, 8% of nocturnal 1-min periods showed clinically relevant QTc prolongations in patients with stable COPD. The automated QTc-algorithm accurately identified clinically relevant QTc-prolongations with a very high sensitivity and specificity. Using this tool, hospital sleep laboratories may identify asymptomatic patients with QTc-prolongations at risk for malignant arrhythmia, allowing them to consult a cardiologist before an eventual cardiac event.

Low-load blood flow restriction strength training in patients with COPD: a randomised single-blind pilot study.

OBJECTIVE: The objective of this study is to compare the effectiveness of lower limb low-load blood flow restriction training (LL-BFRT) with high-load strength training (HL-ST) as part of an outpatient pulmonary rehabilitation programme on leg strength in patients with chronic obstructive pulmonary disease (COPD). METHODS: Participants were randomised to LL-BFRT or HL-ST (24 sessions). LL-BFRT was done at 30% 1-repetition maximum (1-RM) with 70% arterial occlusion pressure. HL-ST was done at 70% 1-RM. Primary outcome was isometric strength of knee extensors and flexors. Secondary outcomes were 1-RM, functional exercise capacity, physical activity, symptom burden and health-related quality of life. Perceptions of dyspnoea and leg fatigue were recorded after every exercise. We compared groups with t-tests. RESULTS: We included 30 participants (13 women, 17 men, 64 (9) years, forced expiratory volume in 1 s 47 (18)% pred.), 24 completed the study. Isometric knee extensor strength improved to a clinically relevant degree in both legs in both groups (LL-BFRT: right leg 9 (20) Nm, left leg 10 (18) Nm; HL-ST: right leg 15 (26) Nm, left leg 16 (30) Nm, data are mean (SD)), without statistically significant or clinically relevant between-group differences (right leg mean difference= -6.4, 95% CI= -13.20 to 25.92 Nm, left leg mean difference= -5.6, 95% CI= -15.44 to 26.55 Nm). 1 min sit-to-stand test performance improved to a clinically relevant degree only in the LL-BFRT group (4 (4) vs 1 (5) repetitions). Interestingly, physical activity improved to a clinically relevant degree only in the LL-BFRT group (1506 (2441) vs -182 (1971) steps/day). LL-BFRT lowered perceived in-exercise dyspnoea and increased leg fatigue compared with HL-ST in the initial 12 trainings. CONCLUSION: In patients with stable COPD undergoing outpatient pulmonary rehabilitation, LL-BFRT was not superior to HL-ST in improving leg strength. LL-BFRT led to similar strength gains as HL-ST while reducing perceptions of dyspnoea in the initial training phase. TRIAL REGISTRATION NUMBER: NCT04151771.

Inhaled salbutamol induces leanness in well-trained healthy females but not males during a period of endurance training: a randomised controlled trial.

Introduction: Many athletes use short-acting inhaled ß2-agonists multiple times weekly during training sessions to prevent exercise-induced bronchoconstriction, but it is unclear if treatment impairs training outcomes. Herein, we investigated performance adaptations in well-trained females and males training with prior inhalation of salbutamol. Methods: 19 females and 21 males with maximal oxygen uptake (V'O2max) of 50.5±3.3 and 57.9±4.9 mL·min-1·kg-1, respectively, participated in this double-blinded, placebo-controlled, parallel-group study. We randomised participants to placebo or salbutamol inhalation (800-1600 µg·training day-1) for 6 weeks of combined endurance (1× per week) and high-intensity interval training (2× per week). We assessed participants' body composition, V'O2max and muscle contractile function, and collected vastus lateralis muscle biopsies. Results: Salbutamol induced a sex-specific loss of whole-body fat mass (sex×treatment: p=0.048) where only salbutamol-treated females had a fat mass reduction compared to placebo (-0.8 kg at 6 weeks; 95% CI: -0.5 to -1.6; p=0.039). Furthermore, salbutamol-treated females exhibited a repartitioning effect, lowering fat mass while gaining lean mass (p=0.011), which was not apparent for males (p=0.303). Salbutamol negatively impacted V'O2max in both sexes (treatment main effect: p=0.014) due to a blunted increase in V'O2max during the initial 4 weeks of the intervention. Quadriceps contractile strength was impaired in salbutamol-treated females (-39 N·m; 95% CI: -61 to -17; p=0.002) compared to placebo at 6 weeks. Muscle electron transport chain complex I-V abundance increased with salbutamol (treatment main effect: p=0.035), while content of SERCAI, ß2-adrenoceptor and desmin remained unchanged. Conclusion: Inhaled salbutamol appears to be an effective repartitioning agent in females but may impair aerobic and strength-related training outcomes.

Characterisation of the acute hypoxic response using breathing variability parameters: A pilot study in humans.

PURPOSE: We aimed to investigate respiratory rate variability (RRV) and tidal volume (Vt) variability during exposure to normobaric hypoxia (i.e., reduction in the fraction of inspired oxygen - FiO2), and the association of the changes in RRV and Vt variability with the changes in pulse oxygen saturation (SpO2). METHODS: Thirty healthy human participants (15 females) were exposed to: (1) 15-min normoxia, (2) 10-min hypoxia simulating 2200 m, (3) 10-min hypoxia simulating 4000 m, (4) 10-min hypoxia simulating 5000 m, (5) 15-min recovery in normoxia. Linear regression modelling was applied with SpO2 (dependent variable) and the changes in RRV and Vt variability (independent variables), controlling for FiO2, age, sex, changes in heart rate (HR), changes in HR variability (HRV), and changes in minute ventilation (VE). RESULTS: When modelling breathing parameter variability as root-mean-square standard deviation (RMSSD), a significant independent association of the changes in RRV with the changes in SpO2 was found (B = -4.3e-04, 95% CI = -8.3e-04/-2.1e-05, p = 0.04). The changes in Vt variability showed no significant association with the changes in SpO2 (B = -1.6, 95% CI = -5.5/2.4, p = 0.42). When modelling parameters variability as SD, a significant independent association of the changes in RRV with the changes in SpO2 was found (B = -8.2e-04, 95% CI = -1.5e-03/-9.4e-05, p = 0.03). The changes in Vt variability showed no significant association with the changes in SpO2 (B=1.4, 95% CI = -5.8/8.6, p = 0.69). CONCLUSION: Higher RRV is independently associated with lower SpO2 during acute hypoxic exposure, while Vt variability parameters are not. Therefore, RRV may be a potentially interesting parameter to characterize individual responses to acute hypoxia.

The effects of standardised versus individualised seat height on 1-minute sit-to-stand test performance in healthy individuals: a randomised crossover trial.

PURPOSE: We aimed to (i) investigate differences in 1-minute sit-to-stand test (1MSTST) performance (i.e., the number of repetitions) between a standardised modality (i.e., starting from a conventional chair with 46 cm seat height) and an individualised modality (i.e., starting with a knee joint flexion angle of 90°), and to (ii) quantify the influence of tibia and femur length on 1MSTST performance. METHODS: Healthy participants were recruited for this randomised crossover study, performing each 1MSTST modality twice in a randomised order. The primary outcome was the number of repetitions in the 1MSTST. Secondary endpoints were the acute responses in peripheral oxygen saturation, heart rate, and leg fatigue and dyspnoea. Additionally, we investigated correlations of performance with knee extensor strength in both modalities. RESULTS: Thirty participants were recruited and completed the study. They achieved significantly less repetitions in the standardised 1MSTST compared to the individualised 1MSTST (B = - 12.1, 95% confidence interval [95% CI] = - 14.8/- 9.4, p < 0.001). We found a significant effect of femur length on 1MSTST performance (B = - 1.6, 95% CI = - 2.6/- 0.7, p = 0.01), tibia length showed significant interaction with the 1MSTST modality (B = 1.2, 95% CI = 0.2/2.2, p = 0.03). CONCLUSION: An individualisation of the 1MSTST starting position to 90° knee flexion angle leads to more repetitions compared to the traditional starting position. The higher repetition count is explained by controlling for differences in tibia length. We recommend individualisation of the 1MSTST, enabling more valid comparisons across populations and study samples. TRIAL REGISTRATION NUMBER: http://www. CLINICALTRIALS: gov , NCT04772417. TRIAL REGISTRATION DATE: February 26, 2021.

Validation of a small cough detector.

Research question: The assessment of cough frequency in clinical practice relies predominantly on the patient's history. Currently, objective evaluation of cough is feasible with bulky equipment during a brief time (i.e. hours up to 1 day). Thus, monitoring of cough has been rarely performed outside clinical studies. We developed a small wearable cough detector (SIVA-P3) that uses deep neural networks for the automatic counting of coughs. This study examined the performance of the SIVA-P3 in an outpatient setting. Methods: We recorded cough epochs with SIVA-P3 over eight consecutive days in patients suffering from chronic cough. During the first 24 h, the detector was validated against cough events counted by trained human listeners. The wearing comfort and the device usage were assessed using a questionnaire. Results: In total, 27 participants (mean±sd age 50±14 years) with either chronic unexplained cough (n=12), COPD (n=4), asthma (n=5) or interstitial lung disease (n=6) were studied. During the daytime, the sensitivity of SIVA-P3 cough detection was 88.5±2.49% and the specificity was 99.97±0.01%. During the night-time, the sensitivity was 84.15±5.04% and the specificity was 99.97±0.02%. The wearing comfort and usage of the device was rated as very high by most participants. Conclusion: SIVA-P3 enables automatic continuous cough monitoring in an outpatient setting for objective assessment of cough over days and weeks. It shows comparable sensitivity or higher sensitivity than other devices with fully automatic cough counting. Thanks to its wearing comfort and the high performance for cough detection, it has the potential for being used in routine clinical practice.

Mapping the landscape of lung cancer breath analysis: A scoping review (ELCABA).

Lung cancer is the leading cause of cancer death worldwide due to its late-stage detection. Lung cancer screening, including low-dose computed tomography (low-dose CT), provides an initial clinical solution. Nevertheless, further innovations and refinements would help to alleviate remaining limitations. The non-invasive, gentle, and fast nature of breath analysis (BA) makes this technology highly attractive to supplement low-dose CT for an improved screening algorithm. However, BA has not taken hold in everyday clinical practice. One reason might be the heterogeneity and variety of BA methods. This scoping review is a comprehensive summary of study designs, breath analytical methods, and suggested biomarkers in lung cancer. Furthermore, this synthesis provides a framework with core outcomes for future studies in lung cancer BA. This work supports future research for evidence synthesis, meta-analysis, and translation into clinical routine workflows.

Criterion Validity and Test-Retest Reliability of a Modified Version of the International Physical Activity Questionnaire-Short Form (IPAQ-SF) in Kidney Transplant Recipients.

Introduction: Accelerometry, the clinically valued standard of physical activity monitoring, has limited acceptance in transplantation rehabilitation; therefore, the International Physical Activity Questionnaire (IPAQ) self-report instrument is widely used. However, while the IPAQ's repeatability is good, its criterion validity is unsatisfactory. We hypothesized that adding a concise oral introduction would help overcome this shortfall. Materials and Methods: This is a secondary analysis of a RCT in a sample of kidney transplant recipients that underwent observational follow-up. We assessed criterion validity of our modified version of the four-item IPAQ-Short Form (mIPAQ-SF) via Pearson, and test-retest reliability via intraclass correlation coefficients. The main difference in the new version is an oral pre-measurement introduction to the questionnaire's concepts. We compared our results with those of published studies. Results: Post-kidney-transplantation data of 92 patients were analyzed. Across the four IPAQ-SF/mIPAQ-SF items, values of correlations between mIPAQ-SF responses and accelerometry records ranged from 0.07 (min in vigorous activity) to 0.35 (min in moderate activity) for criterion validity, and from 0.19 (days with moderate activity) to 0.58 (min in moderate activity) for test-retest reliability. Discussion: Regarding moderate-to-vigorous physical activity, mIPAQ-SF self-reports' correlations to accelerometry records improved considerably on those of the IPAQ-SF (r = 0.18 vs. r = 0.33), i.e., improved criterion validity. We therefore conclude that a pre-measurement oral explanation of key IPAQ-SF/mIPAQ concepts enhances criterion validity regarding self-reported moderate-to-vigorous physical activity.

Increasing Daily Physical Activity and Its Effects on QTc Time in Severe to Very Severe COPD: A Secondary Analysis of a Randomised Controlled Trial.

Approximately, half of COPD patients die from cardiovascular diseases. A prolongation of cardiac repolarization (measured as QTc interval) is associated with cardiovascular events or cardiovascular deaths in populations of older adults and COPD. One way to reduce the QTc could be to increase physical activity (PA). We investigated whether QTc can be reduced by an increase in PA in patients with severe COPD. This is a secondary outcome analysis from a randomized controlled trial investigating the effects of a 3 months pedometer based program to improve PA. 12-lead ECG was assessed at baseline and after 3 months. We measured PA using a validated triaxial accelerometer. Data were analyzed from 59 participants. Multiple regression modeling, including adjustment for baseline QTc, sex, QT prolonging medications, BMI, smoking status and FEV1%, showed no evidence for an association between an improvement of ≥15% PA and QTc reduction. A 15% improvement in PA according to step counts over 3 months seems not to reduce QTc interval by its MCID of 20 ms in patients with severe to very severe COPD.

A Scoping Review on Outcomes and Outcome Measurement Instruments in Rehabilitative Interventions for Patients with Haematological Malignancies Treated with Allogeneic Stem Cell Transplantation.

RATIONALE: Allogeneic hematopoietic stem cell transplantation (HSCT) is associated with increased treatment-related mortality, loss of physical vitality, and impaired quality of life. Future research will investigate the effects of multidisciplinary rehabilitative interventions in alleviating these problems. Nevertheless, published studies in this field show considerable heterogeneity in selected outcomes and the outcome measurement instruments used. The purpose of this scoping review is to provide an overview of the outcomes and outcome measurement instruments used in studies examining the effects of rehabilitative interventions for patients treated with allogeneic HSCT. METHODS: We conducted a scoping review that included randomized controlled trials, pilot studies, and feasibility studies published up to 28 February 2022. RESULTS: We included n = 39 studies, in which n = 84 different outcomes were used 227 times and n = 125 different instruments were used for the measurements. CONCLUSIONS: Research in the field of rehabilitation for patients with haematological malignancies treated with allogeneic HSCT is hampered by the excess outcomes used, the inconsistent outcome terminology, and the inconsistent use of measurement instruments in terms of setting and timing. Researchers in this field should reach a consensus with regard to the use of a common terminology for the outcomes of interest and a homogeneity when selecting measurement instruments and measurement timing methods.

Shape your career: opportunities for Early Career Members in 2022 and the experience of applying for an ERS fellowship.

In this article, we present the @EuroRespSoc opportunities for ECMs (@EarlyCareerERS) in the upcoming year and describe the experience of applying for an ERS Fellowship, with the key steps and challenges identified https://bit.ly/3nz5KlO.

Multisensory Home-Monitoring in Individuals With Stable Chronic Obstructive Pulmonary Disease and Asthma: Usability Study of the CAir-Desk.

BACKGROUND: Research integrating multisensory home-monitoring in respiratory disease is scarce. Therefore, we created a novel multisensory home-monitoring device tailored for long-term respiratory disease management (named the CAir-Desk). We hypothesize that recent technological accomplishments can be integrated into a multisensory participant-driven platform. We also believe that this platform could improve chronic disease management and be accessible to large groups at an acceptable cost. OBJECTIVE: This study aimed to report on user adherence and acceptance as well as system functionality of the CAir-Desk in a sample of participants with stable chronic obstructive pulmonary disease (COPD) or asthma. METHODS: We conducted an observational usability study. Participants took part in 4 weeks of home-monitoring with the CAir-Desk. The CAir-Desk recorded data from all participants on symptom burden, physical activity, spirometry, and environmental air quality; data on sputum production, and nocturnal cough were only recorded for participants who experienced symptoms. After the study period, participants reported on their perceptions of the usability of the monitoring device through a purpose-designed questionnaire. We used descriptive statistics and visualizations to display results. RESULTS: Ten participants, 5 with COPD and 5 with asthma took part in this study. They completed symptom burden questionnaires on a median of 96% (25th percentile 14%, 75th percentile 96%), spirometry recordings on 55% (20%, 94%), wrist-worn physical activity recordings on 100% (97%, 100%), arm-worn physical activity recordings on 45% (13%, 63%), nocturnal cough recordings on 34% (9%, 54%), sputum recordings on 5% (3%, 12%), and environmental air quality recordings on 100% (99%, 100%) of the study days. The participants indicated that the measurements consumed a median of 13 (10, 15) min daily, and that they preferred the wrist-worn physical activity monitor to the arm-worn physical activity monitor. CONCLUSIONS: The CAir-Desk showed favorable technical performance and was well-accepted by our sample of participants with stable COPD and asthma. The obtained insights were used in a redesign of the CAir-Desk, which is currently applied in a randomized controlled trial including an interventional program.

Real-Time Monitoring of Metabolism during Exercise by Exhaled Breath.

Continuous monitoring of metabolites in exhaled breath has recently been introduced as an advanced method to allow non-invasive real-time monitoring of metabolite shifts during rest and acute exercise bouts. The purpose of this study was to continuously measure metabolites in exhaled breath samples during a graded cycle ergometry cardiopulmonary exercise test (CPET), using secondary electrospray high resolution mass spectrometry (SESI-HRMS). We also sought to advance the research area of exercise metabolomics by comparing metabolite shifts in exhaled breath samples with recently published data on plasma metabolite shifts during CPET. We measured exhaled metabolites using SESI-HRMS during spiroergometry (ramp protocol) on a bicycle ergometer. Real-time monitoring through gas analysis enabled us to collect high-resolution data on metabolite shifts from rest to voluntary exhaustion. Thirteen subjects participated in this study (7 female). Median age was 30 years and median peak oxygen uptake (VO2max) was 50 mL·/min/kg. Significant changes in metabolites (n = 33) from several metabolic pathways occurred during the incremental exercise bout. Decreases in exhaled breath metabolites were measured in glyoxylate and dicarboxylate, tricarboxylic acid cycle (TCA), and tryptophan metabolic pathways during graded exercise. This exploratory study showed that selected metabolite shifts could be monitored continuously and non-invasively through exhaled breath, using SESI-HRMS. Future studies should focus on the best types of metabolites to monitor from exhaled breath during exercise and related sources and underlying mechanisms.

Personalization of Conversational Agent-Patient Interaction Styles for Chronic Disease Management: Two Consecutive Cross-sectional Questionnaire Studies.

BACKGROUND: Conversational agents (CAs) for chronic disease management are receiving increasing attention in academia and the industry. However, long-term adherence to CAs is still a challenge and needs to be explored. Personalization of CAs has the potential to improve long-term adherence and, with it, user satisfaction, task efficiency, perceived benefits, and intended behavior change. Research on personalized CAs has already addressed different aspects, such as personalized recommendations and anthropomorphic cues. However, detailed information on interaction styles between patients and CAs in the role of medical health care professionals is scant. Such interaction styles play essential roles for patient satisfaction, treatment adherence, and outcome, as has been shown for physician-patient interactions. Currently, it is not clear (1) whether chronically ill patients prefer a CA with a paternalistic, informative, interpretive, or deliberative interaction style, and (2) which factors influence these preferences. OBJECTIVE: We aimed to investigate the preferences of chronically ill patients for CA-delivered interaction styles. METHODS: We conducted two studies. The first study included a paper-based approach and explored the preferences of chronic obstructive pulmonary disease (COPD) patients for paternalistic, informative, interpretive, and deliberative CA-delivered interaction styles. Based on these results, a second study assessed the effects of the paternalistic and deliberative interaction styles on the relationship quality between the CA and patients via hierarchical multiple linear regression analyses in an online experiment with COPD patients. Patients' sociodemographic and disease-specific characteristics served as moderator variables. RESULTS: Study 1 with 117 COPD patients revealed a preference for the deliberative (50/117) and informative (34/117) interaction styles across demographic characteristics. All patients who preferred the paternalistic style over the other interaction styles had more severe COPD (three patients, Global Initiative for Chronic Obstructive Lung Disease class 3 or 4). In Study 2 with 123 newly recruited COPD patients, younger participants and participants with a less recent COPD diagnosis scored higher on interaction-related outcomes when interacting with a CA that delivered the deliberative interaction style (interaction between age and CA type: relationship quality: b=-0.77, 95% CI -1.37 to -0.18; intention to continue interaction: b=-0.49, 95% CI -0.97 to -0.01; working alliance attachment bond: b=-0.65, 95% CI -1.26 to -0.04; working alliance goal agreement: b=-0.59, 95% CI -1.18 to -0.01; interaction between recency of COPD diagnosis and CA type: working alliance goal agreement: b=0.57, 95% CI 0.01 to 1.13). CONCLUSIONS: Our results indicate that age and a patient's personal disease experience inform which CA interaction style the patient should be paired with to achieve increased interaction-related outcomes with the CA. These results allow the design of personalized health care CAs with the goal to increase long-term adherence to health-promoting behavior.

Blood-Flow-Restricted Strength Training Combined With High-Load Strength and Endurance Training in Pulmonary Rehabilitation for COPD: A Case Report.

OBJECTIVE: The purpose of this report is to describe the case of a patient with chronic obstructive pulmonary disease (COPD) who was load compromised and being referred for outpatient pulmonary rehabilitation. Low-load blood flow restriction strength training (LL-BFRT) was applied to prepare for and increase tolerability of subsequently applied high-load strength training. METHODS (CASE DESCRIPTION): A 62-year-old woman with COPD GOLD 2 B presented with severe breathlessness. Lower limb strength was severely reduced while functional exercise capacity was preserved. The patient was severely load compromised and had high risk to be intolerant of the high training loads required to trigger the desired adaptations. LL-BFRT was applied during the first 12 training sessions and high-load strength training in the subsequent 12 training sessions of the rehabilitation program. Endurance training on a cycle ergometer was performed throughout the program. RESULTS: Symptom burden in the COPD assessment test was reduced by 6 points (40%). Lower limb strength improved by 95.3 Nm (521%) and 88.4 Nm (433%) for the knee extensors and by 33.8 Nm (95%) and 56 Nm (184%) for the knee flexors, respectively. Functional exercise capacity improved by 44 m (11%) in the 6-minute walk test and 14 repetitions (108%) in the 1-minute sit-to stand test. The patient did not experience any adverse events related to the exercise training. CONCLUSION: Clinically relevant changes were observed in both strength-related functional and self-reported outcomes. The achievements translated well into daily living and enabled functioning according to the patients' desires. LL-BFRT was reported to be well tolerated and implementable into an outpatient pulmonary rehabilitation program. IMPACT: The description of this case encourages the systematic investigation of LL-BFRT in COPD. LL-BFRT has the potential to increase benefits as well as tolerability of strength training in pulmonary rehabilitation. Consideration of the physiological changes achieved through LL-BFRT highlights potential in targeting peripheral muscle dysfunction in COPD.

Longitudinal Smartphone-Based Post-hospitalisation Symptom Monitoring in SARS-CoV-2 Associated Respiratory Failure: A Multi-Centre Observational Study.

Background: We aimed to longitudinally monitor the recovery in breathlessness, symptom burden, health-related quality-of-life, and mental health status in individuals hospitalised due to SARS-CoV-2 associated respiratory failure. Methods: Individuals hospitalised due to SARS-CoV-2 associated respiratory failure were recruited at hospital discharge in three participating centres. During the 90 day follow-up, European Quality of Life-5 Dimensions-5 Levels Instrument (EQ-5D-5L), modified Medical Research Council (mMRC) Dyspnoea Scale, COPD Assessment Test (CAT), and weekly Hospital Anxiety and Depression Scale (HADS) questionnaires were assessed using a smartphone application. The results were presented using descriptive statistics and graphics. Linear mixed models with random intercept were fitted to analyse differences of intensive-care unit status on the recovery course in each outcome. Results: We included 58 participants, 40 completed the study. From hospital discharge until 90 days post-discharge, EQ-5D-5L index changed from 0.83 (0.66, 0.92) to 0.96 (0.82, 1.0), VAS rating on general health status changed from 62 (50, 75) % to 80 (74, 94) %, CAT changed from 13 (10, 21) to 7 (3, 11) points, mMRC changed from 1 (0, 2) to 0 (0, 1) points, HADS depression subscale changed from 6 (4, 9) to 5 (1, 6) points, HADS anxiety subscale changed from 7 (3, 9) to 2 (1, 8) points. Differences in the recovery courses were observed between intensive-care and ward participants. Participants that were admitted to an intensive-care unit during their hospitalisation (n = 16) showed increases in CAT, mMRC, HADS scores, and decreases in EQ-5D-5L 30 days after hospital discharge. Conclusion: Being admitted to an ICU led to statistically significant reductions in recovery in the EQ-5D-5L and the CAT. Furthermore, the flare-up in symptom burden and depression scores, accompanied by an attenuated recovery in HrQoL and general health status in the ICU-group suggests that a clinical follow-up 1 month after hospital discharge can be recommended, evaluating further treatments. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT04365595].

A few more steps lead to improvements in endothelial function in severe and very severe COPD.

INTRODUCTION: Cardiovascular disease is among the most prevalent concomitant chronic diseases in COPD. Physical activity (PA) modifies endothelial function and is commonly impaired in COPD. However, studies directly investigating the effects of increased PA on endothelial function in COPD are lacking. We investigated the effect of changes in PA on endothelial function in patients with severe to very severe COPD. Furthermore, we determined which variables modify this effect. MATERIALS AND METHODS: This is a secondary outcome analysis from a randomised controlled trial investigating the effects of combined PA counselling and pedometer-based feedback in COPD. We analysed the change in PA based on three visits during one year. We measured PA using a validated triaxial accelerometer, and endothelial function using flow-mediated dilation. RESULTS: Data was analysed from 54 patients, which provided 101 change scores. Multiple regression modelling, including adjustment for baseline step count, showed strong evidence for an association between changes in flow-mediated dilation and changes in PA (p < 0.001). The analysis of several effect modificators showed no evidence of any influence on the interaction between PA and endothelial function: smoking status (p = 0.766), severity of airflow obstruction (p = 0.838), exacerbation frequency (p = 0.227), lung diffusion capacity of carbon monoxide % pred. (p = 0.735). CONCLUSION: We found strong evidence that increasing steps per day ameliorates the heavily impaired endothelial function in patients with severe and very severe COPD. Further studies should examine which factors influence this relationship in a positive or negative manner.

Long-Term Effects of Pedometer-Based Physical Activity Coaching in Severe COPD: A Randomized Controlled Trial.

Background and Objective: Limited evidence on long-term effects of physical activity programs in COPD is available. The aim of the study was to investigate the effects of a three-month program combining physical activity counselling and pedometer-based feedback in addition to usual care, followed by a nine-month unsupervised observation period as compared to usual care in participants with severe to very severe COPD. Methods: Participants were randomized to either a control group receiving usual care or an intervention group receiving motivational support, an activity diary with an individual step count goal (ie, an increase of ≥15% from baseline) and a pedometer in addition to usual care. The intervention ended after three months and an unsupervised observational period followed until twelve months. Primary outcome was daily step count after one year. Results: Seventy-four participants were included, 61 (82%) completed the study. Linear regression modelling, adjusted for baseline step count, showed no significant difference in change in step count after 12 months between the groups (Β = 547.33, 95% CI = -243.55/1338.20). Conclusion: A three-month program combining physical activity counselling and pedometer-based feedback in addition to usual care does not attenuate the declining course of physical activity in participants with severe and very severe COPD during a long term follow-up of one year as compared to usual care. This result was primarily determined by the low intervention response rates to the combined program. Clinical Trial Registration: www.ClinicalTrials.gov, NCT03114241.

A Telemonitoring and Hybrid Virtual Coaching Solution "CAir" for Patients with Chronic Obstructive Pulmonary Disease: Protocol for a Randomized Controlled Trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is one of the most common disorders in the world. COPD is characterized by airflow obstruction, which is not fully reversible. Patients usually experience breathing-related symptoms with periods of acute worsening and a substantial decrease in the health-related quality-of-life. Active and comprehensive disease management can slow down the progressive course of the disease and improve patients' disabilities. Technological progress and digitalization of medicine have the potential to make elaborate interventions easily accessible and applicable to a broad spectrum of patients with COPD without increasing the costs of the intervention. OBJECTIVE: This study aims to develop a comprehensive telemonitoring and hybrid virtual coaching solution and to investigate its effects on the health-related quality of life of patients with COPD. METHODS: A monocentric, assessor-blind, two-arm (intervention/control) randomized controlled trial will be performed. Participants randomized to the control group will receive usual care and a CAir Desk (custom-built home disease-monitoring device to telemonitor disease-relevant parameters) for 12 weeks, without feedback or scores of the telemonitoring efforts and virtual coaching. Participants randomized to the intervention group will receive a CAir Desk and a hybrid digital coaching intervention for 12 weeks. As a primary outcome, we will measure the delta in the health-related quality of life, which we will assess with the St. George Respiratory Questionnaire, from baseline to week 12 (the end of the intervention). RESULTS: The development of the CAir Desk and virtual coach has been completed. Recruitment to the trial started in September 2020. We expect to start data collection by December 2020 and expect it to last for approximately 18 months, as we follow a multiwave approach. We expect to complete data collection by mid-2022 and plan the dissemination of the results subsequently. CONCLUSIONS: To our knowledge, this is the first study investigating a combination of telemonitoring and hybrid virtual coaching in patients with COPD. We will investigate the effectiveness, efficacy, and usability of the proposed intervention and provide evidence to further develop app-based and chatbot-based disease monitoring and interventions in COPD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04373070; https://clinicaltrials.gov/ct2/show/NCT04373070. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/20412.

Arterial Stiffness Increases Over Time in Relation to Lung Diffusion Capacity: A Longitudinal Observation Study in COPD.

Background: Cardiovascular events are, after cancer, the most common cause of death in COPD patients. Arterial stiffness is an independent predictor of all-cause mortality and cardiovascular events. Several cross-sectional studies have confirmed increased arterial stiffness in patients with COPD. Various mechanisms in the development of arterial stiffness in COPD such as reduced lung function or systemic inflammation have been proposed. However, clinical predictors of arterial stiffness that had been reported in cross-sectional studies have not yet been confirmed in a longitudinal setting. We have assessed the course of augmentation index (AIx) - a measure of systemic arterial stiffness - and possible predictors in a cohort of COPD patients over a period of up to 7 years. Methods: COPD patients underwent annual AIx measurement by applanation tonometry for a maximum duration of 7 years. Additionally, we performed annual assessments of lung function, blood gases, systemic inflammation, serum lipids and blood pressure. Associations between the course of AIx and potential predictors were investigated through a mixed effect model. Results: Seventy-six patients (mean (SD) age 62.4 (7.1), male 67%) were included. The AIx showed a significant annual increase of 0.91% (95% CI 0.21/1.60) adjusted for baseline. The change in diffusion capacity (DLco), low-density lipoprotein (LDL), and high-sensitivity c-reactive protein (hsCRP) was independently associated with the increasing evolution of AIx (Coef. - 0.10, p<0.001, Coef. 1.37, p=0.003, and Coef. 0.07, p=0.033, respectively). Conclusion: This study demonstrated a meaningful increase in arterial stiffness in COPD over time. A greater annual increase in arterial stiffness was associated with the severity of emphysema (measured by DLco), systemic inflammation, and dyslipidaemia. Clinical Trial Registration: www.ClinicalTrials.gov, NCT01527773.