Severe Fatigue in Uncontrolled Asthma: Contributing Factors and Impact of Rehabilitation

Abstract

Background: Fatigue is a major concern for patients with severe asthma.

Objective: This observational study aims to assess fatigue severity and associated factors, to explore the effect of pulmonary rehabilitation on fatigue, and to investigate which factors predict persistent severe fatigue.

Methods: Patients with severe, uncontrolled asthma referred for alpine altitude climate treatment (AACT) between 2007 and 2018 were systematically assessed before and after rehabilitation regarding clinical, inflammatory, functional, and psychological characteristics. Fatigue severity was assessed by Checklist Individual Strength (CIS-Fatigue). Multivariable regression analyses were used to identify factors associated with fatigue severity and persistence.

Results: A total of 420 patients were assessed, of whom 91% reported severe fatigue (CIS-Fatigue ≥36). Stepwise multiple regression explained 35% of variance in initial fatigue severity. Significant contributing factors were higher Asthma Control Questionnaire (ACQ) (36%), sleeping problems (21%), female sex (19%), reflux (12%), and lower fractional exhaled nitric oxide (12%). AACT led to significant improvements in CIS-Fatigue (median [IQR] 50 [11] to 27 [21]) (P < .001), ACQ (3.0 [1.3] to 1.2 [1.3]) (P < .001), and other asthma outcomes. However, 27% of patients reported persistent severe fatigue, correlating with less improvement in asthma outcomes. Daily oral corticosteroid use (odds ratio [OR] [95% confidence interval (CI)]: 2.4 [1.4-4.1]), sleeping problems (OR [95% CI]: 2.7 [1.6-4.5]), initial very severe fatigue (OR [95% CI]: 3.1 [1.6-6.3]), and older age (OR [95% CI]: 1.02 [1.0-1.04]) were independent predictors of persistent severe fatigue.

Conclusions: Severe fatigue is highly prevalent in patients with severe, uncontrolled asthma. AACT results in recovered fatigue and improved asthma control in most patients. Predicting factors of persistent fatigue suggest exploring the effect of targeted treatment strategies beyond the asthma domain.

Keywords: Alpine; Fatigue; Pulmonary rehabilitation; Severe asthma.