Construct validity of the Post-COVID-19 Functional Status Scale in adult subjects with COVID-19.

BACKGROUND: An increasing number of subjects are recovering from COVID-19, raising the need for tools to adequately assess the course of the disease and its impact on functional status. We aimed to assess the construct validity of the Post-COVID-19 Functional Status (PCFS) Scale among adult subjects with confirmed and presumed COVID-19. METHODS: Adult subjects with confirmed and presumed COVID-19, who were members of an online panel and two Facebook groups for subjects with COVID-19 with persistent symptoms, completed an online survey after the onset of infection-related symptoms. The number and intensity of symptoms were evaluated with the Utrecht Symptom Diary, health-related quality of life (HrQoL) with the 5-level EQ-5D questionnaire, impairment in work and activities with the Work Productivity and Activity Impairment questionnaire and functional status with the PCFS Scale. RESULTS: 1939 subjects were included in the analyses (85% women, 95% non-hospitalized during infection) about 3 months after the onset of infection-related symptoms. Subjects classified as experiencing 'slight', 'moderate' and 'severe' functional limitations presented a gradual increase in the number/intensity of symptoms, reduction of HrQoL and impairment in work and usual activities. No differences were found regarding the number and intensity of symptoms, HrQoL and impairment in work and usual activities between subjects classified as experiencing 'negligible' and 'no' functional limitations. We found weak-to-strong statistical associations between functional status and all domains of HrQoL (r: 0.233-0.661). Notably, the strongest association found was with the 'usual activities' domain of the 5-level EQ-5D questionnaire. CONCLUSION: We demonstrated the construct validity of the PCFS Scale in highly-symptomatic adult subjects with confirmed and presumed COVID-19, 3 months after the onset of symptoms.

Severe Fatigue in Long COVID: Web-Based Quantitative Follow-up Study in Members of Online Long COVID Support Groups.

BACKGROUND: Fatigue is the most commonly reported symptom in patients with persistent complaints following COVID-19 (ie, long COVID). Longitudinal studies examining the intensity of fatigue and differentiating between physical and mental fatigue are lacking. OBJECTIVE: The objectives of this study were to (1) assess the severity of fatigue over time in members of online long COVID peer support groups, and (2) assess whether members of these groups experienced mental fatigue, physical fatigue, or both. METHODS: A 2-wave web-based follow-up study was conducted in members of online long COVID peer support groups with a confirmed diagnosis approximately 3 and 6 months after the onset of infectious symptoms. Demographics, COVID-19 diagnosis, received health care (from medical professionals or allied health care professionals), fatigue (Checklist Individual Strength-subscale subjective fatigue [CIS-Fatigue]; 8-56 points), and physical and mental fatigue (self-constructed questions; 3-21 points) were assessed. Higher scores indicated more severe fatigue. A CIS-Fatigue score ≥36 points was used to qualify patients as having severe fatigue. RESULTS: A total of 239 patients with polymerase chain reaction/computed tomography-confirmed COVID-19 completed the survey 10 weeks (SD 2) and 23 weeks (SD 2) after onset of infectious symptoms, respectively (T1 and T2). Of these 239 patients, 198 (82.8%) were women; 142 (59.4%) had no self-reported pre-existing comorbidities; 208 (87%) self-reported being in good health before contracting COVID-19; and 62 (25.9%) were hospitalized during acute infection. The median age was 50 years (IQR 39-56). The vast majority of patients had severe fatigue at T1 and T2 (n=204, 85.4%, and n=188, 78.7%, respectively). No significant differences were found in the prevalence of normal, mild, and severe fatigue between T1 and T2 (P=.12). The median CIS-Fatigue score was 48 points (IQR 42-53) at T1, and it decreased from T1 to T2 (median change: -2 points, IQR -7 to 3; P<.001). At T1, a median physical fatigue score of 19 points (IQR 16-20) and a median mental fatigue score of 15 points (IQR 10-17) were reported; these scores were lower at T2 for physical but not for mental fatigue (median change for physical fatigue -1 point, IQR -3 to 0, P<.001; median change for mental fatigue 0 points, IQR -3 to 3, P=.52). At the time of completing the follow-up survey, 194/239 (81.2%) and 164/239 (68.6%) of all patients had received care from at least one medical professional and one allied health care professional, respectively. CONCLUSIONS: Fatigue in members of online long COVID support groups with a confirmed COVID-19 diagnosis decreases from 10 to 23 weeks after onset of symptoms. Despite this, severe fatigue remains highly prevalent. Both physical and mental fatigue are present. It remains unclear whether and to what extent fatigue will resolve spontaneously in the longer term. TRIAL REGISTRATION: Netherlands Trial Register NTR8705; https://www.trialregister.nl/trial/8705.

Symptoms and quality of life before, during, and after a SARS-CoV-2 PCR positive or negative test: data from Lifelines.

This study evaluates to what extent symptoms are present before, during, and after a positive SARS-CoV-2 polymerase chain reaction (PCR) test, and to evaluate how the symptom burden and quality of Life (QoL) compares to those with a negative PCR test. Participants from the Dutch Lifelines COVID-19 Cohort Study filled-out as of March 2020 weekly, later bi-weekly and monthly, questions about demographics, COVID-19 diagnosis and severity, QoL, and symptoms. The study population included those with one positive or negative PCR test who filled out two questionnaires before and after the test, resulting in 996 SARS-CoV-2 PCR positive and 3978 negative participants. Nearly all symptoms were more often reported after a positive test versus the period before the test (p < 0.05), except fever. A higher symptom prevalence after versus before a test was also found for nearly all symptoms in negatives (p < 0.05). Before the test, symptoms were already partly present and reporting of nearly all symptoms before did not differ between positives and negatives (p > 0.05). QoL decreased around the test for positives and negatives, with a larger deterioration for positives. Not all symptoms after a positive SARS-CoV-2 PCR test might be attributable to the infection and symptoms were also common in negatives.

Physical and mental fatigue in people with non-communicable chronic diseases.

BACKGROUND: Fatigue is frequently reported in people with a non-communicable chronic disease. More insight in the nature of this symptom may enhance targeted treatment of fatigue. In this study, we aimed to gain more insight in the prevalence of different types of fatigue and in current prescribed treatment strategies to reduce fatigue in non-communicable chronic diseases. METHODS: People with non-communicable chronic diseases were contacted via public, non-profit, disease-specific health funds and patient associations and invited to complete a web-based survey. The survey included a general question about the experience ("Do you now or have you ever had complaints of fatigue?") and nature of fatigue (physically/mentally/combination), the Checklist Individual Strength-subscale subjective fatigue (CIS-Fatigue; 8-56 points), self-constructed questions for the distinction between physical and mental fatigue (both 3-21 points) and questions on prescribed treatments for fatigue. RESULTS: In total, 4199 participants (77% females) completed the online survey. 3945 participants (94.0%) reported experiencing fatigue, of which 64.4% reported a combination of both physical and mental fatigue. Median CIS-Fatigue score was 41 (32-48) points, with 68% of the participants reporting severe fatigue (≥36 points). Median scores for physical and mental fatigue were 15 (11-18) and 12 (8-16) points, respectively. In 55% of the participants, fatigue was only occasionally or never discussed with the healthcare professional, and only 23% of the participants were prescribed a treatment for fatigue. Participants often reported no effect or even an increase in fatigue after treatment. CONCLUSIONS: Findings indicate that both physical and mental fatigue are often experienced simultaneously in people with non-communicable chronic diseases, but can also occur separately. Fatigue is often only occasionally or never discussed, let alone treated, highlighting the need to raise awareness among healthcare professionals. Future studies are needed to gain more insight in underlying factors of fatigue in non-communicable chronic diseases, its impact on daily life and development and evaluation of targeted treatment strategies.Key messages:Both physical and mental fatigue are frequently present in people with non-communicable chronic diseases.Fatigue is often only occasionally or never discussed during consultation with the physician, highlighting the need to raise awareness among healthcare professionals for adequate screening and evaluating of fatigue in people with non-communicable chronic diseases.Only less than a quarter of the people with non-communicable chronic diseases who reported to experience fatigue were prescribed a treatment for fatigue, which was often experienced as ineffective.

The prevalence and related factors of fatigue in patients with COPD: a systematic review.

BACKGROUND: Fatigue is a distressing symptom in patients with COPD. Little is known about the factors that contribute to fatigue in COPD. This review summarises existing knowledge on the prevalence of fatigue, factors related to fatigue and the instruments most commonly used to assess fatigue in COPD. METHODS: Pubmed, PsycINFO, EMBASE, Cochrane and CINAHL databases were searched for studies from inception up to 7 January 2020 using the medical subject headings "COPD" and "Fatigue". Studies were reviewed in accordance with PRISMA guidelines. RESULTS: 196 studies were evaluated. The prevalence of fatigue ranged from 17-95%. Age (r=-0.23 to r=0.27), sex (r=0.11), marital status (r=-0.096), dyspnoea (r=0.13 to r=0.78), forced expiatory volume in 1 s % predicted (r=-0.55 to r=-0.076), number of exacerbations (r=0.27 to r=0.38), number of comorbidities (r=0.10), number of medications (r=0.35), anxiety (r=0.36 to r=0.61), depression (r=0.41 to r=0.66), muscle strength (r=-0.78 to r=-0.45), functional capacity (r=-0.77 to r=-0.14) and quality of life (r=0.48 to r=0.77) showed significant associations with fatigue. CONCLUSIONS: Fatigue is a prevalent symptom in patients with COPD. Multiple physical and psychological factors seem to be associated with fatigue. Future studies are needed to evaluate these underlying factors in integral analyses in samples of patients with COPD.

The Impact of Post-COVID-19 Syndrome on Self-Reported Physical Activity.

Background: A subgroup of patients recovering from COVID-19 experience persistent symptoms, decreased quality of life, increased dependency on others for personal care and impaired performance of activities of daily living. However, the long-term effects of COVID-19 on physical activity (PA) in this subgroup of patients with persistent symptoms remain unclear. Methods: Demographics, self-reported average time spent walking per week, as well as participation in activities pre-COVID-19 and after three and six months of follow-up were assessed in members of online long-COVID-19 peer support groups. Results: Two hundred thirty-nine patients with a confirmed COVID-19 diagnosis were included (83% women, median (IQR) age: 50 (39-56) years). Patients reported a significantly decreased weekly walking time after three months of follow-up (three months: 60 (15-120) min. vs. pre-COVID-19: 120 (60-240) min./week; p < 0.05). Six months after the onset of symptoms walking time was still significantly lower compared to pre-COVID-19 but significantly increased compared to three months of follow-up (three months: 60 (15-120) min. vs. six months: 90 (30-150) min.; p < 0.05). Conclusions: Patients who experience persistent symptoms after COVID-19 may still demonstrate a significantly decreased walking time six months after the onset of symptoms. More research is needed to investigate long-term consequences and possible treatment options to guide patients during the recovery fromCOVID-19.

Fatigue in patients with chronic disease: results from the population-based Lifelines Cohort Study.

(1) To evaluate the prevalence of severe and chronic fatigue in subjects with and without chronic disease; (2) to assess to which extent multi-morbidity contributes to severe and chronic fatigue; and (3) to identify predisposing and associated factors for severe and chronic fatigue and whether these are disease-specific, trans-diagnostic, or generic. The Dutch Lifelines cohort was used, including 78,363 subjects with (n = 31,039, 53 ± 12 years, 33% male) and without (n = 47,324, 48 ± 12 years, 46% male) ≥ 1 of 23 chronic diseases. Fatigue was assessed with the Checklist Individual Strength-Fatigue. Compared to participants without a chronic disease, a higher proportion of participants with ≥ 1 chronic disease were severely (23% versus 15%, p < 0.001) and chronically (17% versus 10%, p < 0.001) fatigued. The odds of having severe fatigue (OR [95% CI]) increased from 1.6 [1.5-1.7] with one chronic disease to 5.5 [4.5-6.7] with four chronic diseases; for chronic fatigue from 1.5 [1.5-1.6] to 4.9 [3.9-6.1]. Multiple trans-diagnostic predisposing and associated factors of fatigue were found, explaining 26% of variance in fatigue in chronic disease. Severe and chronic fatigue are highly prevalent in chronic diseases. Multi-morbidity increases the odds of having severe and chronic fatigue. Several trans-diagnostic factors were associated with fatigue, providing a rationale for a trans-diagnostic approach.

Recovery from COVID-19: a sprint or marathon? 6-month follow-up data from online long COVID-19 support group members.

BACKGROUND: It remains unknown whether and to what extent members of online "long COVID" peer support groups remain symptomatic and limited over time. Therefore, we aimed to evaluate symptoms in members of online long COVID peer support groups up to 6 months after the onset of coronavirus disease 2019 (COVID-19)-related symptoms. METHODS: Demographics, symptoms, health status, work productivity, functional status and health-related quality of life were assessed about 3 and 6 months after the onset of COVID-19-related symptoms in members of online long COVID peer support groups. RESULTS: Data from 239 patients with a confirmed COVID-19 diagnosis (83% women; median (interquartile range) age 50 (39-56) years) were analysed. During the infection, a median (interquartile range) of 15 (11-18) symptoms was reported, which was significantly lower 3 and 6 months later: 6 (4-9) and 6 (3-8), respectively (p<0.05). From 3 to 6 months follow-up, the proportion of patients without symptoms increased from 1.3% to only 5.4% (p<0.001). Patients also reported a significantly improved work productivity (work absenteeism and presenteeism: 73% versus 52% and 66% versus 60%, respectively), self-reported good health (9.2% versus 16.7%), functional status (mean±sd Post-COVID-19 Functional Status scale: 2.4±0.9 versus 2.2±1.0) and health-related quality of life (all p<0.05). CONCLUSION: Although patients with confirmed COVID-19, who were all members of online long COVID peer support groups, reported significant improvements in work productivity, functional status and quality of life between 3 and 6 months follow-up, these data clearly highlight the long-term impact of COVID-19, as approximately 6 months after the onset of COVID-19-related symptoms a large proportion still experienced persistent symptoms, a moderate-to-poor health, moderate-to-severe functional limitations, considerable loss in work productivity, and/or an impaired quality of life. Action is needed to improve the management and healthcare of these patients.

Care Dependency in Non-Hospitalized Patients with COVID-19.

BACKGROUND: A large sample of "mild" COVID-19 patients still experience multiple symptoms months after being infected. These persistent symptoms are associated with many clinically relevant outcomes, including poor health status and impaired functional status. To date, no information is available about care dependency. Therefore, we aimed to explore the level of care dependency and the need for assistance with personal care in non-hospitalized COVID-19 patients. METHODS: Members of two Facebook groups for COVID-19 patients with persistent complaints in The Netherlands and Belgium, and from a panel of people who registered at a website of the Lung Foundation Netherlands, were assessed for demographics, pre-existing comorbidities, health status, and symptoms. In addition, patients were asked about their dependence on others for personal care before and after the infection. The level of care dependency was assessed with the Care Dependency Scale (CDS) in members of the Belgian Facebook group (n = 210). RESULTS: The data of 1837 non-hospitalized patients (86% women; median (IQR) age: 47 (38-54)) were analyzed. Only a small proportion of patients needed help with personal care before COVID-19, but the care need increased significantly after the infection (on average 79 ± 17 days after the onset of symptoms; 7.7% versus 52.4%, respectively; p < 0.05). The patients had a median (IQR) CDS score of 72 (67-75) points, and 31% of the patients were considered as care-dependent (CDS score ≤ 68 points). CONCLUSIONS: COVID-19 has an important impact on care dependency in non-hospitalized patients. About three months after the onset of symptoms, a considerable proportion of non-hospitalized patients were to some degree dependent on others for personal care. This indicates that the impact of COVID-19 on patients' daily lives is tremendous, and more attention is needed to identify optimal treatment strategies to restore patients' independency.

Generic and Respiratory-Specific Quality of Life in Non-Hospitalized Patients with COVID-19.

The impact of coronavirus disease 2019 (COVID-19) on quality of life appears to be highly underestimated, especially in patients who have not been admitted to the hospital. Therefore, our aim was to assess respiratory-specific quality of life in addition to generic quality of life in former patients with confirmed/suspected COVID-19 who have never been admitted to the hospital. Members of an online Belgian social support group for patients with confirmed/suspected COVID-19 with persistent complaints, completed an online survey. The five-level EQ-5D (EQ-5D-5L) and the Clinical COPD Questionnaire (CCQ) were used to assess generic and respiratory-specific quality of life, respectively. Data of 210 non-hospitalized patients (88% women, 45 ± 11 years, 79 ± 17 days after symptom onset) were included in the analyses. Mean EQ-5D index and visual analogue scale (EQ-VAS) score was 0.62 ± 0.19 and 50.71 ± 18.87, respectively, with 40% of the patients demonstrating an EQ-5D index that was below the fifth percentile of normative values, indicating poor generic quality of life. The mean CCQ score was 2.01 ± 0.98 points, while 123 respondents (59%) had a total score ≥1.9 points, indicating poor respiratory-specific quality of life. The correlation between EQ-5D index score/EQ-VAS score and CCQ total score was moderate (r = -0.524 and r = -0.374; both p < 0.001). In conclusion, both generic and respiratory-specific quality of life are affected in non-hospitalized patients with COVID-19, approximately three months after the onset of symptoms. The combined use of the EQ-5D and the CCQ could identify the broad impact of COVID-19 on quality of life.

Persistent symptoms 3†months after a SARS-CoV-2 infection: the post-COVID-19 syndrome?

BACKGROUND: Many patients with COVID-19 did not require hospitalisation, nor underwent COVID-19 testing. There is anecdotal evidence that patients with "mild" COVID-19 may complain about persistent symptoms, even weeks after the infection. This suggests that symptoms during the infection may not resolve spontaneously. The objective of this study was to assess whether multiple relevant symptoms recover following the onset of symptoms in hospitalised and nonhospitalised patients with COVID-19. METHODS: A total of 2113 members of two Facebook groups for coronavirus patients with persistent complaints in the Netherlands and Belgium, and from a panel of people who registered on a website of the Lung Foundation Netherlands, were assessed for demographics, pre-existing comorbidities, health status, date of symptoms onset, COVID-19 diagnosis, healthcare utilisation, and the presence of 29 symptoms at the time of the onset of symptoms (retrospectively) and at follow-up (mean±sd 79±17 days after symptoms onset). RESULTS: Overall, 112 hospitalised patients and 2001 nonhospitalised patients (confirmed COVID-19, n=345; symptom-based COVID-19, n=882; and suspected COVID-19, n=774) were analysed. The median number of symptoms during the infection reduced significantly over time (median (interquartile range) 14 (11-17) versus 6 (4-9); p<0.001). Fatigue and dyspnoea were the most prevalent symptoms during the infection and at follow-up (fatigue: 95% versus 87%; dyspnoea: 90% versus 71%). CONCLUSION: In previously hospitalised and nonhospitalised patients with confirmed or suspected COVID-19, multiple symptoms are present about 3 months after symptoms onset. This suggests the presence of a "post-COVID-19 syndrome" and highlights the unmet healthcare needs in a subgroup of patients with "mild" or "severe" COVID-19.

Pulmonary Rehabilitation Reduces Subjective Fatigue in COPD: A Responder Analysis.

To date, it remains unknown which patients report a clinically-relevant improvement in fatigue following pulmonary rehabilitation (PR). The purpose of this study was to identify and characterize these responders. Demographics, lung function, anxiety (anxiety subscale of the 90-item symptom checklist (SCL-90-A)), depression (Beck depression inventory for primary care (BDI-PC)), exercise tolerance (six-minute walking distance test (6MWD)), and health status (Nijmegen clinical screening instrument (NCSI)) were assessed before and after a 12-week PR programme. Fatigue was assessed using the checklist individual strength (CIS)-Fatigue. Patients with a decline ≥ 10 points (minimally clinically important difference, MCID) on the CIS-Fatigue were defined as responders. Chronic obstructive pulmonary disease (COPD) patients (n = 446, 61 ± 9 years, 53% male, forced expiratory volume in 1 s (FEV1) 43% ± 18% predicted, 75% severe fatigue) were included. Mean change in fatigue after PR was 10 ± 12 points (p < 0.01) and exceeded the MCID. In total, 56% were identified as fatigue responders. Baseline CIS-Fatigue (45 ± 7 vs. 38 ± 9 points, respectively, p < 0.001) and health-related quality-of-life (HRQoL; p < 0.001) were different between responders and non-responders. No differences were found in demographics, baseline anxiety, depression, lung function, 6MWD, and dyspnoea (p-values > 0.01). Responders on fatigue reported a greater improvement in anxiety, depression, 6MWD, dyspnoea (all p-values < 0.001), and most health status parameters. PR reduces fatigue in COPD. Responders on fatigue have worse fatigue and HRQoL scores at baseline, and are also likely to be responders on other outcomes of PR.

ERS statement on standardisation of cardiopulmonary exercise testing in chronic lung diseases.

The objective of this document was to standardise published cardiopulmonary exercise testing (CPET) protocols for improved interpretation in clinical settings and multicentre research projects. This document: 1) summarises the protocols and procedures used in published studies focusing on incremental CPET in chronic lung conditions; 2) presents standard incremental protocols for CPET on a stationary cycle ergometer and a treadmill; and 3) provides patients' perspectives on CPET obtained through an online survey supported by the European Lung Foundation. We systematically reviewed published studies obtained from EMBASE, Medline, Scopus, Web of Science and the Cochrane Library from inception to January 2017. Of 7914 identified studies, 595 studies with 26 523 subjects were included. The literature supports a test protocol with a resting phase lasting at least 3 min, a 3-min unloaded phase, and an 8- to 12-min incremental phase with work rate increased linearly at least every minute, followed by a recovery phase of at least 2-3 min. Patients responding to the survey (n=295) perceived CPET as highly beneficial for their diagnostic assessment and informed the Task Force consensus. Future research should focus on the individualised estimation of optimal work rate increments across different lung diseases, and the collection of robust normative data.

Fatigue is highly prevalent in patients with COPD and correlates poorly with the degree of airflow limitation.

BACKGROUND: The objective of this study was to compare fatigue levels between subjects with and without COPD, and to investigate the relationship between fatigue, demographics, clinical features and disease severity. METHODS: A total of 1290 patients with COPD [age 65 ± 9 years, 61% male, forced expiratory volume in 1 s (FEV1) 56 ± 19% predicted] and 199 subjects without COPD (age 63 ± 9 years, 51% male, FEV1 112 ± 21% predicted) were assessed for fatigue (Checklist Individual Strength-Fatigue), demographics, clinical features and disease severity. RESULTS: Patients with COPD had a higher mean fatigue score, and a higher proportion of severe fatigue (CIS-Fatigue score 35 ± 12 versus 21 ± 11 points, p < 0.001; 49 versus 10%, p < 0.001). Fatigue was significantly, but poorly, associated with the degree of airflow limitation [FEV1 (% predicted) Spearman correlation coefficient = -0.08, p = 0.006]. Multiple regression indicated that 30% of the variance in fatigue was explained by the predictor variables. CONCLUSIONS: Severe fatigue is prevalent in half of the patients with COPD, and correlates poorly with the degree of airflow limitation. Future studies are needed to better understand the physical, psychological, behavioural, and systemic factors that precipitate or perpetuate fatigue in COPD.

Fatigue is Highly Prevalent in Patients with Asthma and Contributes to the Burden of Disease.

The 2018 update of the Global Strategy for Asthma Management and Prevention does not mention fatigue-related symptoms. Nevertheless, patients with asthma frequently report tiredness, lack of energy, and daytime sleepiness. Quantitative research regarding the prevalence of fatigue in asthmatic patients is lacking. This retrospective cross-sectional study of outpatients with asthma upon referral to a chest physician assessed fatigue (Checklist Individual Strength-Fatigue (CIS-Fatigue)), lung function (spirometry), asthma control (Asthma Control Questionnaire (ACQ)), dyspnea (Medical Research Council (MRC) scale), exercise capacity (six-minute walk test (6MWT)), and asthma-related Quality-of-Life (QoL), Asthma Quality of Life Questionnaire (AQLQ) during a comprehensive health-status assessment. In total, 733 asthmatic patients were eligible and analyzed (47.4 ± 16.3 years, 41.1% male). Severe fatigue (CIS-Fatigue ≥ 36 points) was detected in 62.6% of patients. Fatigue was not related to airflow limitation (FEV1, ρ = -0.083); was related moderately to ACQ (ρ = 0.455), AQLQ (ρ = -0.554), and MRC (ρ = 0.435; all p-values < 0.001); and was related weakly to 6MWT (ρ = -0.243, p < 0.001). In stepwise multiple regression analysis, 28.9% of variance in fatigue was explained by ACQ (21.0%), MRC (6.5%), and age (1.4%). As for AQLQ, 42.2% of variance was explained by fatigue (29.8%), MRC (8.6%), exacerbation rate (2.6%), and age (1.2%). Severe fatigue is highly prevalent in asthmatic patients; it is an important determinant of disease-specific QoL and a crucial yet ignored patient-related outcome in patients with asthma.

Fatigue in patients with chronic obstructive pulmonary disease: protocol of the Dutch multicentre, longitudinal, observational FAntasTIGUE study.

INTRODUCTION: Fatigue is the second most common symptom in patients with chronic obstructive pulmonary disease (COPD). Despite its high prevalence, fatigue is often ignored in daily practice. For this reason, little is known about the underlying determinants of fatigue in patients with COPD. The primary objectives of this study are to chart the course of fatigue in patients with COPD, to identify the physical, systemic, psychological and behavioural factors that precipitate and perpetuate fatigue in patients with COPD, to evaluate the impact of exacerbation-related hospitalisations on fatigue and to better understand the association between fatigue and 2-year all-cause hospitalisation and mortality in patients with COPD. The secondary aim is to identify diurnal differences in fatigue by using ecological momentary assessment (EMA). This manuscript describes the protocol of the FAntasTIGUE study and gives an overview of the possible strengths, weaknesses and clinical implications. METHODS AND ANALYSIS: A 2-year longitudinal, observational study, enrolling 400 patients with clinically stable COPD has been designed. Fatigue, the primary outcome, will be measured by the subjective fatigue subscale of the Checklist Individual Strength (CIS-Fatigue). The secondary outcome is the day-to-day/diurnal fatigue, registered in a subsample (n=60) by EMA. CIS-Fatigue and EMA will be evaluated at baseline, and at 4, 8 and 12 months. The precipitating and perpetuating factors of fatigue (physical, psychological, behavioural and systemic) will be assessed at baseline and at 12 months. Additional assessments will be conducted following hospitalisation due to an exacerbation of COPD that occurs between baseline and 12 months. Finally, at 18 and 24 months the participants will be followed up on their fatigue, number of exacerbations, exacerbation-related hospitalisation and survival. ETHICS AND DISSEMINATION: This protocol was approved by the Medical research Ethics Committees United, Nieuwegein, the Netherlands (NL60484.100.17). TRIAL REGISTRATION NUMBER: NTR6933; Pre-results.

Changes in physical activity and sedentary behaviour following pulmonary rehabilitation in patients with COPD.

A more profound investigation about the responses in activity levels following pulmonary rehabilitation (PR) in patients with COPD is needed. We aimed to describe groups of patients with COPD according to patterns of change in physical activity and sedentary behaviour following PR. 90 patients with COPD (60% male; mean age 67 ± 8; median FEV1 47 (32-62) %pred) completed a comprehensive PR programme. A triaxial accelerometer was used to assess the time in sedentary behaviour, light activities and moderate-to-vigorous physical activity (MVPA). Additionally, exercise capacity, quality of life, and symptoms of anxiety and depression were assessed before and after PR. Six groups with different patterns of change in physical activity and sedentary behaviour were identified. The two most prevalent patterns were represented by good responders (increase in physical activity and reduction in sedentary behaviour, 34%) and poor responders (decrease in physical activity and increase in sedentary behaviour, 30%). Good responders had greater improvements in six-minute walk distance (6MWD) and symptoms of depression than poor responders (P < 0.05 for all). Strong correlation was found between changes in sedentary behaviour and changes in light activities (rs = -0.89; P < 0.0001). Changes in 6MWD correlated fairly with changes in sedentary behaviour (rs = -0.26), light activities (rs = 0.25), and MVPA (rs = 0.24); P < 0.05 for all. Different patterns of change in activity levels following PR can be found in patients with COPD. Focusing on light physical activities might be a potential strategy to make patients less sedentary, but for this to be achieved prior (or at least parallel) improvements in functional capacity seem to be necessary.

What is the impact of impaired left ventricular ejection fraction in COPD after adjusting for confounders?

BACKGROUND: It remains unknown whether and to what extent impaired left ventricular ejection fraction (LVEF) affects physical and psychological status in COPD. We aimed to compare health outcome measures between COPD patients with and without impaired LVEF after adjusting for age, sex, BMI and FEV1. METHODS: Impaired LVEF was defined as values <50%. 85 COPD patients with impaired LVEF and 85 COPD patients with normal LVEF were matched for sex, age, BMI and FEV1. Exercise capacity, quadriceps muscle function, functional mobility, inflammatory status, health status, care dependency, and mood disorders were cross-sectionally assessed. RESULTS: Patients with impaired LVEF had shorter 6-minute walk distance (mean -59 (95% confidence interval: -94, -25)m), lower symptom-limited peak oxygen uptake (-131 (-268, 7)ml/min), weaker quadriceps muscles (-12 (-20, -3)Nm) and had more symptoms of anxiety (+2 (1, 3) points) and depression (+1 (0, 2) points) than those with normal LVEF (all P<0.05). Health status was not statistically different between groups (P>0.05). CONCLUSIONS: Impaired LVEF has a clear impact on physical and psychological status in patients with COPD, even after adjusting for confounders. This reinforces the importance of assessing and treating cardiac problems in COPD.