Severe fatigue in uncontrolled asthma: impact of alpine altitude climate rehabilitation and predictive factors for persistent severe fatigue

<bold>Background:</bold> Fatigue is a major concern for patients with severe asthma and tied to poor asthma control. This study investigates the impact of multidisciplinary pulmonary rehabilitation in the alpine altitude climate (AACT) on fatigue and identifies factors contributing to persistent severe fatigue. <bold>Methods:</bold> 420 patients with severe, uncontrolled asthma, referred for AACT (2007- 2018), underwent a systematic assessment including: subjective fatigue (CIS-Fatigue), psychopathology (SCL90), asthma control (ACQ6), health-related quality of life (AQLQ), spirometry, FeNO, blood eosinophil counts, atopic status, oral corticosteroid (OCS) use, comorbidities, and exercise capacity. <bold>Results:</bold> At baseline, 91% of patients reported severe fatigue (CIS-F ≥36). Eleven weeks of AACT led to significant improvements in CIS-F (median(IQR) 50(11) to 27(21)) and ACQ6 (3.0(1.3) to 1.2(1.3)), and all conventional asthma outcomes. However, 27% of patients experienced persistent severe fatigue at the end of AACT, correlating with less improvement in asthma outcomes. Multivariable regression analysis identified daily OCS use, sleeping problems, higher baseline fatigue score, and older age as independent predictors of persistent severe fatigue. <bold>Discussion:</bold> This is the first major cohort study investigating the impact of rehabilitation on fatigue in severe asthma. It shows that multidisciplinary Alpine Altitude Climate Treatment results in recovered fatigue and improved asthma control in most patients. Maintenance OCS, sleeping problems, more fatigue at baseline, and older age predict persistent severe fatigue, emphasizing the need for targeted treatment strategies.