Unraveling fatigue in fibrotic interstitial lung disease: perceived and performance mechanisms

Background: Fatigue can be defined as a disabling symptom for which perceived and performance fatigability interact to limit physical functioning. Most patients (70%) with fibrotic interstitial lung disease (f-ILD) seek medical advice due to fatigue. It is unknown whether sensations of fatigue (perceived) relate to changes in neuromuscular mechanisms (performance fatigability) in f-ILD. Methods: Sixteen patients (13 men, 73±8 years, 10 with idiopathic pulmonary fibrosis) completed a constant-load (60% peak) cycle test to symptom limitation. Magnetic nerve stimulation, the Fatigue Severity Scale (FSS) and Rating-of-Fatigue (ROF) scale assessed quadriceps neuromuscular fatigability [peripheral and central components: post-exercise falls in potentiated twitch (∆Tw) and voluntary activation (∆VA)], trait and state levels of perceived fatigability, respectively. Patients were classified as less or more fatigued using their FSS and ROF scores (median sample score cut-off). Results: Patients completed 44±19 kJ of external work on average. Performance fatigability did not correlate with FFS scores (p>0.05). Due to less work performed (30±12 vs 59±12 kJ, p<0.001), more fatigued patients had greater ROF scores (0.10±0.03 vs 0.24±0.08 ROF units/kJ, p=0.001) at exercise cessation. When adjusted for work, ΔTw was larger in more fatigued patients: -0.72±0.13 vs -0.38±0.20%/kJ (p=0.001); ROF scores and ΔTw strongly correlated (r= -0.80; p<0.001). However, ΔVA did not correlate with ROF scores (p>0.05). Conclusion: Interventions improving peripheral factors of performance fatigability on exertion may prove valuable to decrease heightened perceived fatigability in f-ILD, since both seem closely related.