Effects of Asthma on the Performance of Activities of Daily Living: A Retrospective Study.

The study aim was to identify the most problematic self--reported activities of daily living (ADLs). In a retrospective study, 1935 problematic ADLs were reported by 538 clients with 95% experiencing two or more problematic ADLs. Problematic ADLs were assessed by occupational therapists using the Canadian Occupational Performance Measure with walking (67%), household activities (41%), and climbing the stairs (41%) identified as the most prevalent problematic ADLs. Significant but weak associations were found between clinical determinants (e.g. physical, psychosocial) and problematic ADLs. The wide variety of problematic ADLs and the absence of a strong association with clinical determinants emphasizes the need for using individualized interview-based performance measures in clients with asthma.

Impact and timing of pulmonary rehabilitation in patients undergoing bronchoscopic lung volume reduction with endobronchial valves: A multicentre randomized controlled trial in patients with severe emphysema.

BACKGROUND AND OBJECTIVE: Both bronchoscopic lung volume reduction with endobronchial valves (BLVR-EBV) and pulmonary rehabilitation (PR) are effective treatments for improving exercise capacity and patient-reported outcomes in patients with severe Chronic Obstructive Pulmonary Disease (COPD). According to current recommendations, all BLVR-EBV patients should have undergone PR first. Our aim was to study the effects of PR both before and after BLVR-EBV compared to BLVR-EBV alone. METHODS: We included patients with severe COPD who were eligible for BLVR-EBV and PR. Participants were randomized into three groups: PR before BLVR-EBV, PR after BLVR-EBV or BLVR-EBV without PR. The primary outcome was change in constant work rate cycle test (CWRT) endurance time at 6-month follow-up of the PR groups compared to BLVR-EBV alone. Secondary endpoints included changes in 6-minute walking test, daily step count, dyspnoea and health-related quality of life. RESULTS: Ninety-seven participants were included. At 6-month follow-up, there was no difference in change in CWRT endurance time between the PR before BLVR-EBV and BLVR-EBV alone groups (median: 421 [IQR: 44; 1304] vs. 787 [123; 1024] seconds, p = 0.82) or in any of the secondary endpoints, but the PR after BLVR-EBV group exhibited a smaller improvement in CWRT endurance time (median: 107 [IQR: 2; 573], p = 0.04) and health-related quality of life compared to BLVR-EBV alone. CONCLUSION: The addition of PR to BLVR-EBV did not result in increased exercise capacity, daily step count or improved patient-reported outcomes compared to BLVR-EBV alone, neither when PR was administered before BLVR-EBV nor when PR was administered after BLVR-EBV.

Relationship between Volitional and Non-Volitional Quadriceps Muscle Endurance in Patients with Chronic Obstructive Pulmonary Disease.

Volitional assessment of quadriceps muscle endurance is clinically relevant in patients with chronic obstructive pulmonary disease (COPD). However, studies that determine the construct validity of volitional tests by comparing them to non-volitional measures are lacking. Therefore, the aim of the current study is to evaluate the correlation between volitional and non-volitional quadriceps muscle endurance in patients with COPD. Quadriceps muscle endurance was evaluated in twenty-six patients with COPD. A volitional isometric and a volitional isokinetic protocol were performed on a computerised dynamometer to determine the isometric time and isokinetic work fatigue index, respectively. Non-volitional assessment of quadriceps muscle endurance was evaluated using repetitive electrical stimulations to establish the isometric muscle force decline. Sixteen patients (61 ± 8 years, 63% male, FEV1 47 (32-53)%) performed all three quadriceps endurance tests conforming to pre-defined test criteria. Both volitional isometric time and isokinetic work fatigue index did not significantly correlate with non-volitional muscle force decline (both p > 0.05). There was a strong correlation between volitional isometric time and isokinetic work fatigue index (rho = -0.716, p = 0.002). To conclude, this study suggests that volitional measures evaluate partly different aspects of quadriceps muscle endurance compared to non-volitional measures. Accordingly, these outcome measures cannot be used interchangeably.

Sleep Hypoventilation is Common in Diurnal Normocapnic COPD Patients with Severe or Very Severe Obstruction and is Not Associated with Body Mass Index.

Sleep hypoventilation (SH) is common in COPD patients with diurnal hypercapnia, however there are little data on the presence of SH in COPD patients with diurnal normocapnia. In this study the prevalence of SH in stable normocapnic COPD patients with severe or very severe obstruction (GOLD stages III and IV) was evaluated across body mass index (BMI) classes and associations between SH and body composition measures were explored. A total of 56 diurnal normocapnic COPD patients, of whom 17 normal-weight (COPDNW), 18 overweight (COPDOW) and 21 obese (COPDOB), underwent polysomnography to objectify SH and bioelectrical impedance analysis to assess body composition. The overall prevalence of SH was 66.1% and was not different across BMI classes. Logistic regression models indicated that SH was not associated with waist-to-hip ratio, body fat percentage and fat-free mass index. Our data indicate that SH is common in diurnal normocapnic COPD patients with severe or very severe obstruction and is not associated with BMI or body composition.

Frequency and Functional Consequences of Low Appendicular Lean Mass and Sarcopenic Obesity in Patients with Asthma Referred for Pulmonary Rehabilitation.

INTRODUCTION: One of the most prominent extrapulmonary manifestations in patients with chronic respiratory disease is changes in body weight and composition. However, the frequency and functional consequences of low appendicular lean mass (ALM) or sarcopenic obesity (SO) in patients with asthma are largely unknown. Therefore, the aim of the current study was to assess the frequency and functional consequences of low appendicular lean mass index (ALMI) and SO in patients with asthma. METHODS: A retrospectively analyzed cross-sectional study was conducted in 687 patients with asthma (60% female, 58 ± 13 years, FEV1 76 ± 25% pred) referred for comprehensive pulmonary rehabilitation (PR). Body composition, pulmonary function, exercise capacity, quadriceps muscle function, and quality of life were assessed. Patients were classified as presenting low ALMI according to the 10th percentiles of age-sex-body mass index (BMI)-specific reference values and as having SO according to the diagnostic procedure proposed by the 2022 ESPEN/EASO consensus. In addition, clinical outcomes between patients with normal and low ALMI or with and without SO were compared. RESULTS: The frequency of patients classified as low ALMI was 19%, whereas 45% of the patients were obese. Among the obese patients, 29% had SO. In patients with normal weight, those with low ALMI were younger and had worse pulmonary function, exercise capacity and quadriceps muscle function than those with normal ALMI (all p < 0.05). Overweight patients with low ALMI presented poorer pulmonary function and quadriceps muscle function (both strength and total work capacity). In obese class I patients, those with low ALMI showed lower quadriceps strength and maximal oxygen uptake acquired during cardiopulmonary exercise testing. Both male and female patients with SO showed lower quadriceps muscle function and reduced maximal exercise capacity compared to non-SO asthma patients. CONCLUSION: Approximately one in five asthma patients presented low ALM when age-sex-BMI-specific ALMI cutoffs were applied. Obesity is common among patients with asthma referred for PR. Among the obese patients, a significant proportion presented SO. Low ALM and SO were associated with worse functional outcomes.

Longitudinal Analysis of Quadriceps Muscle Strength in Patients with Previous COVID-19 Hospitalization and in Patients with Post-Acute Sequelae following Mild COVID-19.

Muscle weakness is a prominent symptom in post-acute sequelae of COVID-19 (PASC). However, few studies have objectively and longitudinally assessed muscle strength after varying COVID-19 severity grades. This observational study aimed to explore the prevalence, determinants, and 1.5 years change of quadriceps muscle weakness in 98 patients discharged from COVID-19 hospitalization and in 50 patients with PASC following mild COVID-19. Isometric quadriceps maximal voluntary contraction (MVC) was assessed on a computerized dynamometer at three visits. Also, in a subgroup of 14 post-COVID-19 patients with quadriceps muscle weakness, muscle thickness and echo intensity were determined by muscle ultrasound of nine upper and lower extremity muscles. Muscle weakness was found in 59% of post-hospitalized patients and in 65% of those with PASC following mild COVID-19 at ~14 weeks after acute COVID-19. Whereas during ~1.5 years follow-up MVC modestly improved, muscle weakness prevalence remained unchanged. Hospital length of stay and diabetes mellitus were identified as possible predictors of muscle weakness following COVID-19 hospitalization. No predictors could be identified in those with PASC following mild COVID-19. Ultrasound outcomes revealed no large structural abnormalities. In conclusion, clinically relevant muscle weakness is common after COVID-19 and its long-term improvement is poor. Future studies with relevant control groups are warranted to confirm our data.

Isokinetic testing of quadriceps function in COPD: feasibility, responsiveness, and minimal important differences in patients undergoing pulmonary rehabilitation.

BACKGROUND: Isokinetic testing of peripheral muscle function is valid and reliable in patients with chronic obstructive pulmonary disease (COPD). OBJECTIVE: To evaluate whether and to what extent isokinetic testing of quadriceps function meets pre-defined test criteria in patients with COPD; to determine the response to pulmonary rehabilitation (PR), and to calculate minimal important differences (MIDs) of isokinetic quadriceps function. METHODS: Retrospective analysis of 2033 patients with COPD (age: 65±9 years, body mass index: 26±6 kg/m2, FEV1: 49±22% predicted) who followed a comprehensive PR program. Pre and post PR isokinetic quadriceps function was assessed with 30 maximal extension-flexion contractions at an angular speed of 90°/s on a computerized dynamometer. The chosen anchors were 6-min walk test and COPD assessment test. RESULTS: Pre PR, 27% of the patients performed the isokinetic test incorrectly. In male and female patients with a correct pre and post PR isokinetic test, peak torque (Δ=10±13 Nm or 9% and Δ=7±9 Nm or 10%, respectively) and total work (Δ=263±270 J or 14% and Δ=198±190 J or 15%, respectively) improved significantly. There was no change in work fatigue index following PR. Using distribution-based calculations, MID estimates for peak torque and total work ranged between 6-7 Nm and 97-135 J in males and between 4-5 Nm and 62-99 J in females. CONCLUSIONS: Based on the current test criteria, three in four patients with COPD performed the isokinetic quadriceps test correctly during baseline PR assessment. Furthermore, peak torque and total work, but not work fatigue index, were responsive to PR and sex-specific MIDs were established.

Patient activation is a treatable trait in patients with chronic airway diseases: An observational study.

Background: Self-management is key for reducing the burden of disease in chronical illness. However, applying self-management presupposes behavioral change. Sufficient knowledge, skills, confidence and motivation to make the needed behavior changes are important prerequisites. During the past years the Integral Diagnostic Trajectory was developed for patients with asthma or COPD which aims to identify treatable traits and activating patients for self-management. Objective: In the present study the effects of the Integral Diagnostic Trajectory on the Patient Activation Measure (PAM®) were examined. In addition, predictive variables for PAM baseline scores and change scores were sought. Materials and methods: A total of 241 patients with asthma or COPD referred to the pulmonologist at the Radboud university medical center, location Dekkerswald, Nijmegen were included. Patient activation was measured before the first visit and after the intervention with the 13-item PAM®. Additional, patient characteristics and health status were measured with the Nijmegen Clinical Screening Instrument (NCSI), modified Medical Research Council (mMRC), Asthma Control Questionnaire (ACQ), and COPD Clinical Questionnaire (CCQ). Results: Fifty percent of the patients with asthma and seventy percent of the patients with COPD had low levels of activation at baseline (PAM level 1-2). Baseline PAM scores could be explained in patients with asthma for 7% by number of severe problems in health status. And for 18% in patients with COPD by number of severe problems, age and employment status. After the intervention both groups significantly improved on the PAM (T0: 56.0 ± 13.1 vs. T1:63.3 ± 14.0 in asthma, and T0: 50.0 ± 8.8 vs. 58.4 ± 11.1 in COPD). Multivariate stepwise regression analysis showed that only 24% of the change in score could be explained by baseline PAM score and being employed in patients with asthma, and 18% of the variance in change score could be predicted by baseline PAM score in COPD. Conclusion: The present study showed that low level of activation is a common feature in patients with asthma and COPD. With a relatively short and seemingly simple intervention patients can reach higher levels of patient activation, which is a prerequisite for adopting self-management techniques in daily life.

Long-term cognitive performance and its relation to anti-inflammatory therapy in a cohort of survivors of severe COVID-19.

Background and objectives: Long-term cognitive performance data in former critically ill COVID-19 patients are sparse. Current evidence suggests that cognitive decline is related to neuroinflammation, which might be attenuated by COVID-19 related anti-inflammatory therapies. The objective of this prospective cohort study was to study long term cognitive outcomes following severe COVID-19 and the relation to anti-inflammatory therapies. Methods: Prospective observational cohort of patients that survived an intensive care unit (ICU) admission due to severe COVID-19. Six months after hospital discharge, we extensively assessed both objective cognitive functioning and subjective cognitive complaints. Furthermore, patients were stratified in cohorts according to their anti-inflammatory treatment (i.e. no immunomodulatory therapy, dexamethasone, or both dexamethasone and interleukin-6 receptor antagonist tocilizumab). Results: 96 patients were included (March 2020-June 2021, median [IQR] age 61 [55-69] years). 91% received invasive mechanical ventilation, and mean ± SD severity-of-disease APACHE-II-score at admission was 15.8 ± 4.1. After 6.5 ± 1.3 months, 27% of patients scored cognitively impaired. Patients that did or did not develop cognitive impairments were similar in ICU-admission parameters, clinical course and delirium incidence. Patients with subjective cognitive complaints (20%) were more likely women (61% vs 26%), and had a shorter ICU stay (median [IQR] 8 [5-15] vs 18 [9-31], p = 0.002). Objective cognitive dysfunction did not correlate with subjective cognitive dysfunction. 27% of the participants received dexamethasone during intensive care admission, 44% received additional tocilizumab and 29% received neither. Overall occurrence and severity of cognitive dysfunction were not affected by anti-inflammatory therapy, although patients treated with both dexamethasone and tocilizumab had worse executive functioning scores (Trail Making Test interference) than patients without anti-inflammatory treatment (T-score 40.3 ± 13.5 vs 49.1 ± 9.3, p = 0.007). Discussion: A relevant proportion of critically ill COVID-19 patients shows deficits in long-term cognitive functioning. Apart from more pronounced executive dysfunction, overall, anti-inflammatory therapy appeared not to affect long-term cognitive performance. Our findings provide insight in long-term cognitive outcomes in patients who survived COVID-19, that may facilitate health-care providers counseling patients and their caregivers.

Persistent Exertional Dyspnea and Perceived Exercise Intolerance After Mild COVID-19: A Critical Role for Breathing Dysregulation?

OBJECTIVE: After mild COVID-19, a subgroup of patients reported post-acute-phase sequelae of COVID-19 (PASC) in which exertional dyspnea and perceived exercise intolerance were common. Underlying pathophysiological mechanisms remain incompletely understood. The purpose of this study was to examine outcomes from cardiopulmonary exercise testing (CPET) in these patients. METHODS: In this observational study, participants were patients who were referred for the analysis of PASC after mild COVID-19 and in whom CPET was performed after standard clinical workup turned out unremarkable. Cardiocirculatory, ventilatory, and metabolic responses to and breathing patterns during exercise at physiological limits were analyzed. RESULTS: Twenty-one patients (76% women; mean age = 40 years) who reported severe disability in physical functioning underwent CPET at 32 weeks (interquartile range = 22-52) after COVID-19. Mean peak O2 uptake was 99% of predicted with normal anaerobic thresholds. No cardiovascular or gas exchange abnormalities were detected. Twenty of the 21 patients (95%) demonstrated breathing dysregulation (ventilatory inefficiency [29%], abnormal course of breathing frequency and tidal volume [57%], absent increase of end-tidal Pco2 [57%], and abnormal resting blood gases [67%]). CONCLUSION: Breathing dysregulation may explain exertional dyspnea and perceived exercise intolerance in patients with PASC after mild COVID-19 and can be present in the absence of deconditioning. This finding warrants further study on the levels of neural control of breathing and muscle function, and simultaneously provides a potential treatment opportunity. IMPACT: This study contributes to the understanding of persistent exertional dyspnea and perceived exercise intolerance following mild COVID-19, which is vital for the development of effective rehabilitation strategies.

Patients with Chronic Obstructive Pulmonary Disease Can Accurately Perform Home-Based Measurements of Inspiratory Capacity and Dynamic Hyperinflation.

Home-based lung function measurements can be used to capture day-to-day variations in symptoms in patients with chronic obstructive pulmonary disease (COPD). Although dynamic hyperinflation (DH) is clinically relevant, existing home-based measurements do not include its assessment. DH can be measured through inspiratory capacity (IC) measurements before and after metronome-paced tachypnea test (MPT). The goal of this study is to determine the accuracy of unsupervised home-based IC and DH measurements in COPD.Sixteen COPD patients performed IC and DH measurements during 4 home visits. Visit 1 was considered a training session. During all visits supervised and unsupervised IC at rest (ICREST) and after MPT (ICMPT) were measured. DH was calculated as the difference between ICREST and ICMPT, and as a percentage of ICREST. Bland-Altman analyses and ANOVA tests were performed to determine the effect of supervision and repeated measures over time.The biases between supervised and unsupervised ICREST, ICMPT, ΔIC and ΔIC% were 0.007 L, 0.007 L, 0 mL and -0.09% in the last visit, respectively. Limits of agreement of ICREST and ΔIC% decreased from ±0.261 mL to ±0.201 mL, and from ±13.84% to ±10.81% between visit 1 and 4, respectively. No significant effect of supervision or over time was found.After a robust training and a learning phase, COPD patients are able to perform IC measurements in an accurate manner in both rest and after MPT. This yield accurate assessment of DH, in an unsupervised home-based setting.

Skeletal muscle alterations in patients with acute Covid-19 and post-acute sequelae of Covid-19.

Skeletal muscle-related symptoms are common in both acute coronavirus disease (Covid)-19 and post-acute sequelae of Covid-19 (PASC). In this narrative review, we discuss cellular and molecular pathways that are affected and consider these in regard to skeletal muscle involvement in other conditions, such as acute respiratory distress syndrome, critical illness myopathy, and post-viral fatigue syndrome. Patients with severe Covid-19 and PASC suffer from skeletal muscle weakness and exercise intolerance. Histological sections present muscle fibre atrophy, metabolic alterations, and immune cell infiltration. Contributing factors to weakness and fatigue in patients with severe Covid-19 include systemic inflammation, disuse, hypoxaemia, and malnutrition. These factors also contribute to post-intensive care unit (ICU) syndrome and ICU-acquired weakness and likely explain a substantial part of Covid-19-acquired weakness. The skeletal muscle weakness and exercise intolerance associated with PASC are more obscure. Direct severe acute respiratory syndrome coronavirus (SARS-CoV)-2 viral infiltration into skeletal muscle or an aberrant immune system likely contribute. Similarities between skeletal muscle alterations in PASC and chronic fatigue syndrome deserve further study. Both SARS-CoV-2-specific factors and generic consequences of acute disease likely underlie the observed skeletal muscle alterations in both acute Covid-19 and PASC.

Short Physical Performance Battery: Response to Pulmonary Rehabilitation and Minimal Important Difference Estimates in Patients With Chronic Obstructive Pulmonary Disease.

OBJECTIVE: To determine the response to a pulmonary rehabilitation (PR) program and minimal important differences (MIDs) for the Short Physical Performance Battery (SPPB) subtests and SPPB summary score in patients with chronic obstructive pulmonary disease (COPD). DESIGN: Retrospective analysis using distribution- and anchor-based methods. SETTING: PR center in the Netherlands including a comprehensive 40-session 8-week inpatient or 14-week outpatient program. PARTICIPANTS: A total of 632 patients with COPD (age, 65±8y; 50% male; forced expiratory volume in the first second=43% [interquartile range, 30%-60%] predicted). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Baseline and post-PR results of the SPPB, consisting of 3 balance standing tests, 4-meter gait speed (4MGS), and 5-repetition sit-to-stand (5STS). The chosen anchors were the 6-Minute Walk Test and COPD Assessment Test. Patients were stratified according to their SPPB summary scores into low-performance, moderate-performance, and high-performance groups. RESULTS: 5STS (∆=-1.14 [-4.20 to -0.93]s) and SPPB summary score (∆=1 [0-2] points) improved after PR in patients with COPD. In patients with a low performance at baseline, balance tandem and 4MGS significantly increased as well. Based on distribution-based calculations, the MID estimates ranged between 2.19 and 6.33 seconds for 5STS and 0.83 to 0.96 points for SPPB summary score. CONCLUSIONS: The 5STS and SPPB summary score are both responsive to PR in patients with COPD. The balance tandem test and 4MGS are only responsive to PR in patients with COPD with a low performance at baseline. Based on distribution-based calculations, an MID estimate of 1 point for the SPPB summary score is recommended in patients with COPD. Future research is needed to confirm MID estimates for SPPB in different centers.

Correlates of variability in endurance shuttle walk test time in patients with chronic obstructive pulmonary disease.

BACKGROUND: The endurance shuttle walk test (ESWT) is used to evaluate exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). The recommended pre-intervention tolerated duration (Tlim) is between 3-8 minutes for optimal interpretation of treatment effects. However, this window may be exceeded and factors determining ESWT Tlim are not completely understood. Therefore, we aimed to determine whether pulmonary function, physical and incremental shuttle walk test (ISWT) performance measures are associated with ESWT Tlim in COPD patients. METHODS: Assessment data from patients eligible for pulmonary rehabilitation was retrospectively analyzed. Inclusion criteria were: diagnosis of COPD and complete data availability regarding ESWT and ISWT. Patients performed an ESWT at 85% of ISWT speed and were divided into three groups (ESWT Tlim: <3 minutes, 3-8 minutes, >8 minutes). Subject characteristics, severity of complaints, pulmonary function, physical capacity and activity, exercise tolerance and quadriceps muscle strength were evaluated. RESULTS: 245 COPD patients (FEV1 38 (29-52)% predicted) were included. Median ESWT Tlim was 6.0 (3.7-10.3) minutes, 41 (17%) patients walked <3 minutes and 80 (33%) patients walked >8 minutes. Body mass index, maximal oxygen consumption, Tlim on constant work rate cycle test, physical activity level, maximal ISWT speed, dyspnoea Borg score at rest and increase of leg fatigue Borg score during ISWT independently predicted Tlim in multivariate regression analysis (R2 = 0.297, p<0.001). CONCLUSION: This study reported a large variability in ESWT Tlim in COPD patients. Secondly, these results demonstrated that next to maximal ISWT speed, other ISWT performance measures as well as clinical measures of pulmonary function, physical capacity and physical activity were independent determinants of ESWT Tlim. Nevertheless, as these determinants only explained ~30% of the variability, future studies are needed to establish whether additional factors can be used to better adjust individual ESWT pace in order to reduce ESWT Tlim variability.

Comprehensive Health Assessment 3 Months After Recovery From Acute Coronavirus Disease 2019 (COVID-19).

BACKGROUND: Long-term health sequelae of coronavirus disease 2019 (COVID-19) may be multiple but have thus far not been systematically studied. METHODS: All patients discharged after COVID-19 from the Radboud University Medical Center, Nijmegen, the Netherlands, were consecutively invited to a multidisciplinary outpatient facility. Also, nonadmitted patients with mild disease but with symptoms persisting >6 weeks could be referred by general practitioners. Patients underwent a standardized assessment including measurements of lung function, chest computed tomography (CT)/X-ray, 6-minute walking test, body composition, and questionnaires on mental, cognitive, health status, and quality of life (QoL). RESULTS: 124 patients (59 ±â€…14 years, 60% male) were included: 27 with mild, 51 with moderate, 26 with severe, and 20 with critical disease. Lung diffusion capacity was below the lower limit of normal in 42% of discharged patients. 99% of discharged patients had reduced ground-glass opacification on repeat CT imaging, and normal chest X-rays were found in 93% of patients with mild disease. Residual pulmonary parenchymal abnormalities were present in 91% of discharged patients and correlated with reduced lung diffusion capacity. Twenty-two percent had low exercise capacity, 19% low fat-free mass index, and problems in mental and/or cognitive function were found in 36% of patients. Health status was generally poor, particularly in the domains functional impairment (64%), fatigue (69%), and QoL (72%). CONCLUSIONS: This comprehensive health assessment revealed severe problems in several health domains in a substantial number of ex-COVID-19 patients. Longer follow-up studies are warranted to elucidate natural trajectories and to find predictors of complicated long-term trajectories of recovery.

Treatable traits qualifying for nonpharmacological interventions in COPD patients upon first referral to a pulmonologist: the COPD sTRAITosphere.

INTRODUCTION: The present study assessed the prevalence of nine treatable traits (TTs) pinpointing nonpharmacological interventions in patients with COPD upon first referral to a pulmonologist, how these TTs co-occurred and whether and to what extent the TTs increased the odds having a severely impaired health status. METHODS: Data were collected from a sample of 402 COPD patients. A second sample of 381 patients with COPD was used for validation. Nine TTs were assessed: current smoking status, activity-related dyspnoea, frequent exacerbations <12 months, severe fatigue, depressed mood, poor physical capacity, low physical activity, poor nutritional status and a low level of self-management activation. For each TT the odds ratio (OR) of having a severe health status impairment was calculated. Furthermore, a graphic representation was created, the COPD sTRAITosphere, to visualise TTs prevalence and OR. RESULTS: On average 3.9±2.0 TTs per patient were observed. These TTs occurred relatively independently of each other and coexisted in 151 unique combinations. A significant positive correlation was found between the number of TTs and Clinical COPD Questionnaire total score (r=0.58; p<0.001). Patients with severe fatigue (OR: 8.8), severe activity-related dyspnoea (OR: 5.8) or depressed mood (OR: 4.2) had the highest likelihood of having a severely impaired health status. The validation sample corroborated these findings. CONCLUSIONS: Upon first referral to a pulmonologist, COPD patients show multiple TTs indicating them to several nonpharmacological interventions. These TTs coexist in many different combinations, are relatively independent and increase the likelihood of having a severely impaired health status.

Beta-alanine supplementation in patients with COPD receiving non-linear periodised exercise training or neuromuscular electrical stimulation: protocol of two randomised, double-blind, placebo-controlled trials.

INTRODUCTION: Exercise intolerance is common in patients with chronic obstructive pulmonary disease (COPD) and, although multifactorial, it is largely caused by lower-limb muscle dysfunction. Research has shown that patients with severe to very severe COPD have significantly lower levels of muscle carnosine, which acts as a pH buffer and antioxidant. Beta-alanine (BA) supplementation has been shown to consistently elevate muscle carnosine in a variety of populations and may therefore improve exercise tolerance and lower-limb muscle function. The primary objective of the current studies is to assess the beneficial effects of BA supplementation in enhancing exercise tolerance on top of two types of exercise training (non-linear periodised exercise (NLPE) training or neuromuscular electrical stimulation (NMES)) in patients with COPD. METHODS AND ANALYSIS: Two randomised, double-blind, placebo-controlled trials have been designed. Patients will routinely receive either NLPE (BASE-TRAIN trial) or NMES (BASE-ELECTRIC trial) as part of standard exercise-based care during their 8-to-10 week pulmonary rehabilitation (PR) programme. A total of 222 patients with COPD (2×77 = 154 patients in the BASE-TRAIN trial and 2×34 = 68 patients in the BASE-ELECTRIC trial) will be recruited from two specialised PR centres in The Netherlands. For study purposes, patients will receive 3.2 g of oral BA supplementation or placebo per day. Exercise tolerance is the primary outcome, which will be assessed using the endurance shuttle walk test (BASE-TRAIN) or the constant work rate cycle test (BASE-ELECTRIC). Furthermore, quadriceps muscle strength and endurance, cognitive function, carnosine levels (in muscle), BA levels (in blood and muscle), markers of oxidative stress and inflammation (in blood, muscles and lungs), physical activity and quality of life will be measured. ETHICS AND DISSEMINATION: Both trials were approved by CMO Regio Arnhem-Nijmegen, The Netherlands (NL70781.091.19. and NL68757.091.19). TRIAL REGISTRATION NUMBER: NTR8427 (BASE-TRAIN) and NTR8419 (BASE-ELECTRIC).