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Fatigue as a relevant outcome in patients with COPD

Authors: Yvonne M.J. Goërtz1, Zjala Ebadi2, Maarten Van Herck3.

1 Department of Research and Education, Ciro, Centre of Expertise for Chronic Organ Failure, Horn, NM 6085, The Netherlands.

2 Radboud University Medical Center, Radboud Institute for Health Sciences, Department of Medical Psychology, 6525 GA Nijmegen, The Netherlands.

3 REVAL - Rehabilitation Research Center, BIOMED - Biomedical Research Institute, Faculty of Rehabilitation Sciences, Hasselt University, Diepenbeek, Belgium.


People diagnosed with chronic conditions, including chronic obstructive pulmonary disease (COPD), experience a myriad of symptoms. Fatigue, defined as “a subjective, unpleasant symptom which incorporates total body feelings ranging from tiredness to exhaustion creating an unrelenting overall condition which interferes with individuals’ ability to function to their normal capacity” (Ream & Richardson, 1997), is ranked by people with moderate to severe COPD as the second most prominent and disabling symptom, and it significantly and adversely affects quality of life (Blinderman, Homel, Billings, Tennstedt, & Portenoy, 2009; Goertz et al., 2018). In contrast with a prevalence rate of 10% in elderly people without COPD, severe and clinically relevant fatigue (which is defined as a score 36 points on the subscale subjective fatigue of the Checklist Individual Strength) is experienced by half of stable outpatients with COPD (Goertz et al., 2019). Despite being a predictor of poorer health outcomes and highly prevalent, fatigue remains to date often under-reported by people with COPD. A reason for this might be that patients believe it to be a natural consequence of their disease (Stridsman, Skar, Hedman, Ronmark, & Lindberg, 2015). Moreover, fatigue is also under-diagnosed and under-treated by healthcare professionals (Janssen, Spruit, Uszko-Lencer, Schols, & Wouters, 2011). This might be due to the underrepresentation of fatigue questions in commonly used health status assessment tools (Stridsman et al., 2018). Another reason may be that fatigue is a poorly understood symptom, and the previously mentioned definition of fatigue, although broad, does not reflect the complexity of this symptom. Not to mention, the underlying causes of fatigue in COPD remain elusive. Consequently, therapeutic approaches aimed at reducing fatigue in COPD are lacking. Of note, management of COPD is still rather focused on relieving respiratory symptoms.


A longitudinal study on the course of fatigue in 77 stable outpatients with moderate to severe COPD found that the prevalence of severe fatigue doubled after four years follow-up despite standard COPD care (cfr. treatment as usual: education, smoking cessation, optimal medication prescription, counselling regarding exercise and physical activity; Figure 1). Of note, lung function parameters did not significantly differ between baseline and follow-up (Peters et al., 2011).

 image 1


Treatment strategies such as exercise training (Arslan & Oztunc, 2016), self-management programs (Mitchell et al., 2014) and cognitive behaviour therapy (Luk, Gorelik, Irving, & Khan, 2017) etc., have been shown to reduce fatigue in people with COPD, but on their own, these strategies only benefit a limited number of people. This is probably due to the multifactorial nature of fatigue (Spruit, Vercoulen, Sprangers, & Wouters, 2017). Therefore, a holistic approach, such as a comprehensive pulmonary rehabilitation (PR) program (Spruit et al., 2013), seems the most appropriate choice to reduce fatigue. A Cochrane review on the effectiveness of PR in people with COPD (McCarthy et al., 2015) demonstrated a clinically relevant moderate-certainty evidence that PR relieves fatigue (mean difference [95% CI] in the fatigue subscale of the Chronic Respiratory Disease Questionnaire 0.68 [0.45 to 0.92]; 19 trials on 1291 participants). Similar results were found in a recent published paper of the FAntasTIGUE consortium. A multidisciplinary inpatient PR program, that included 446 participants with moderate-to-very severe COPD, was able to decrease the prevalence of severe fatigue from 75% to 33% after PR (Figure 2). But although PR is an effective strategy to reduce fatigue in patients with COPD on group level, not everyone reports a minimal clinical improvement following PR despite room to improvement (Van Herck et al., 2019). This emphasizes the need for personalized medicine based upon a comprehensive assessment of possible contributing factors of fatigue.

 image 2


Up to now only few studies investigated possible factors that contribute to increased fatigue (Al-shair et al., 2011; Baghai-Ravary et al., 2009; Breukink et al., 1998; Gift & Shepard, 1999; Goertz et al., 2019; Kapella, Larson, Patel, Covey, & Berry, 2006; Kentson et al., 2016; Lewko, Bidgood, & Garrod, 2009; Matura, Malone, Jaime-Lara, & Riegel, 2018; Woo, 2000). Although it is expected that multiple factors play a role in the cause of fatigue in people with COPD, these few studies did not include all possible factors that contribute to increased fatigue (Spruit et al., 2017). Currently, a large multicentre, longitudinal, observational (FAntasTIGUE) study in patients with COPD is investigating all physical, psychological, behavioural, and systemic factors that contribute to fatigue in people with COPD (Goertz et al., 2018). This study is likely to identify underlying factors and empower health professionals to prescribe the optimal treatment, at the optimal time, for each individual. We look forward to, in the near future, informing you about the findings of this study.


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