Fatigue in Chronic Respiratory Diseases: Theoretical Framework and Implications For Real-Life Performance and Rehabilitation

Abstract

Fatigue is a primary disabling symptom in chronic respiratory diseases (CRD) with major clinical implications. However, fatigue is not yet sufficiently explored and is still poorly understood in CRD, making this symptom underdiagnosed and undertreated in these populations. Fatigue is a dynamic phenomenon, particularly in such evolving diseases punctuated by acute events which can, alone or in combination, modulate the degree of fatigue experienced by the patients. This review supports a comprehensive inter-disciplinary approach of CRD-related fatigue and emphasizes the need to consider both its performance and perceived components. Most studies in CRD evaluated perceived fatigue as a trait characteristic using multidimensional scales, providing precious information about its prevalence and clinical impact. However, these scales are not adapted to understand the complex dynamics of fatigue in real-life settings and should be augmented with ecological assessment of fatigue. The state level of fatigue must also be considered during physical tasks as severe fatigue can emerge rapidly during exercise. CRD patients exhibit alterations in both peripheral and central nervous systems and these abnormalities can be exacerbated during exercise. Laboratory tests are necessary to provide mechanistic insights into how and why fatigue develops during exercise in CRD. A better knowledge of the neurophysiological mechanisms underlying perceived and performance fatigability and their influence on real-life performance will enable the development of new individualized countermeasures. This review aims first to shed light on the terminology of fatigue and then critically considers the contemporary models of fatigue and their relevance in the particular context of CRD. This article then briefly reports the prevalence and clinical consequences of fatigue in CRD and discusses the strengths and weaknesses of various fatigue scales. This review also provides several arguments to select the ideal test of performance fatigability in CRD and to translate the mechanistic laboratory findings into the clinical practice and real-world performance. Finally, this article discusses the dose-response relationship to training and the feasibility and validity of using the fatigue produced during exercise training sessions in CRD to optimize exercise training efficiency. Methodological concerns, examples of applications in selected diseases and avenues for future research are also provided.

Keywords: chronic obstructive pulmonary disease; cystic fibrosis; ecological momentary assessment; exercise training; muscle function; obstructive sleep apnea; perceived fatigability; performance fatigability.

Figure 1

(A) Performance and perceived fatigability concept is adapted and modified from Enoka and Duchateau (2016). The domains of perceived and performance fatigability are controlled by different factors acting at a micro- and macro-level. (B) Consequences of fatigue on patient's life. (C) Modulating factors which can influence the respective weight of each factor contributing to fatigue. (D) A better knowledge of the determinants of fatigue will permit to design new individualized strategies with the aim to increase acute muscle loading during a given exercise training session and counteract the negative influences of fatigue (see text for details). CRD, chronic respiratory diseases; Perf feedback, performance feedback; sarcolemmal AP, Sarcolemmal action potential.

Figure 2

An important clinical application of the measurement of performance fatigability is to evaluate the acute muscle fatigability following an exercise rehabilitation session as a surrogate of efficient muscle loading. Such technique may help identifying future responders and non-responders to an exercise program of several weeks/months. Patients who exhibit fatigue [e.g., reduction in the amplitude of the potentiated twitch (Tw_p) elicited by femoral magnetic nerve stimulation] following an acute exercise session can be classified as responders to the intervention and are more likely to develop positive adaptations following the whole program than patients who do not exhibit fatigue. For these latter, the next step is to identify the factors preventing the development of acute muscle fatigue on an individual basis. The proposed inter-disciplinary approach should permit to evaluate the relative influence of physiological, psychological and sociological factors. Various alternatives strategies can be offered to trigger optimal muscle loading. The effectiveness of some of these strategies to produce acute muscle fatigue remains to be confirmed, as well as the potential additional benefits of incorporating a concomitant cognitive component to these strategies. The current list is thus proposed as an initial framework that should be modified and/or completed according to future experimental results. A given exercise strategy may be effective over a short time period. However, it may become less effective in the long term. Thus, regular acute muscle fatigability assessments should be performed with the aim to adjust training modalities if necessary and then promote long-term adherence and health benefits. Treadmill and cycling exercise illustrations were modified from Smart Servier Medical Art on April 2018, available online at https://smart.servier.com/category/general-items/equipment/, licensed under the CC BY 3.0 license. MVC, maximal voluntary contraction; NMES, neuromuscular electrical stimulation; PA, physical activity; ROF, rating-of-fatigue.