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

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.

Effect of dietary interventions on markers of type 2 inflammation in asthma: A systematic review.

INTRODUCTION: Type 2 (T2) inflammation is a key mechanism in the pathophysiology of asthma. Diet may have immunomodulatory effects, and a role for diet in T2 inflammation has been suggested in the literature. Indeed, diet and food allergies play a role in children with atopic asthma, but less is known about diet in relation to adult asthma, which is often non-atopic. OBJECTIVE: To review the effect of dietary interventions on markers of T2 inflammation in adults with asthma. METHODS: The databases PubMed, Embase, Cochrane Library, and CINAHL were searched for eligible studies until December 2022. We included studies of all types of foods, nutrients, diets or supplements, either as an exposure or as an intervention, in adults and adolescents with asthma. Outcomes of interest included the T2 biomarkers FeNO, eosinophils, IL-4, IL-5, IL-13, eosinophil cationic protein and eosinophil peroxidase. The methodological quality of eligible studies was systematically evaluated, and the results were summarised according to dietary clusters. RESULTS: The systematic search identified studies on the dietary clusters antioxidants (n = 14), fatty acids, (n = 14), Mediterranean-style diets (n = 5), phytotherapy (n = 7), prebiotics & probiotics (n = 8), vitamin D (n = 7), and other dietary factors (n = 5). Studies within the phytotherapy and omega-3 poly-unsaturated fatty acids (PUFA) clusters showed possible improvements in T2 inflammation. Furthermore, we found little evidence for an effect of antioxidants, prebiotics & probiotics, and Mediterranean-style diets on T2 inflammation. However, heterogeneity in study protocols, methodological shortcomings and limited power of almost all studies make it difficult to fully determine the impact of different dietary approaches on T2 inflammation in asthma. CONCLUSIONS: Overall, the current evidence does not support a specific dietary intervention to improve T2 inflammation in asthma. Interventions involving phytotherapy and omega-3 PUFA currently have the best evidence and warrant further evaluation in well-designed and adequately powered studies, while taking into account T2-high phenotypes of asthma.

Long-Term Weight Changes After Starting Anti-IL-5/5Ra Biologics in Severe Asthma: The Role of Oral Corticosteroids.

BACKGROUND: Many patients with severe asthma are overweight or obese, often attributed to unintentional weight gain as a side effect of oral corticosteroids (OCSs). Anti-IL-5/5Ra biologics significantly reduce OCS use, but their long-term effects on weight are unknown. OBJECTIVES: To examine (1) weight change up to 2 years after anti-IL-5/5Ra initiation in subgroups on the basis of maintenance OCS use at start of treatment and (2) whether cumulative OCS exposure before or changes in OCS exposure during treatment are related to weight change. METHODS: Real-world data on weight and cumulative OCS dose from adults included in the Dutch Registry of Adult Patients with Severe asthma for Optimal DIsease management before and at least 2 years after starting anti-IL-5/5Ra were analyzed using linear mixed models and linear regression analyses. RESULTS: For the included 389 patients (55% female; mean body mass index, 28 ± 5 kg/m2; 58% maintenance OCS), mean weight decreased -0.27 kg/y (95% CI, -0.51 to -0.03; P = .03), with more weight loss in patients with maintenance OCS use than in those without maintenance OCS use (-0.87 kg/y [95% CI, -1.21 to -0.52; P < .001] vs +0.54 kg/y [0.26 to 0.82; P < .001]). Greater weight loss at 2 years was associated with higher cumulative OCS dose in the 2 years before anti-IL-5/5Ra initiation (ß = -0.24 kg/g; 95% CI, -0.38 to -0.10; P < .001) and, independently, greater reduction in cumulative OCS dose during follow-up (ß = 0.27 kg/g; 95% CI, 0.11 to 0.43; P < .001). CONCLUSIONS: Anti-IL-5/5Ra therapy is associated with long-term weight reduction, especially in patients with higher OCS exposure before treatment and those able to reduce OCS use during treatment. However, the effect is small and does not apply to all patients, and so additional interventions seem necessary if weight change is desired.