Using the 6-min walk test to assess the clinical response to mepolizumab and conventional therapy in severe eosinophilic asthma

Abstract

Background: Severe asthma limits exercise to avoid respiratory symptoms. The objective of the present study was to investigate the role of the 6-min walk test (6MWT) in severe asthma.

Methods: Consecutive patients with severe eosinophilic asthma were enrolled. A 6MWT was performed before and after 12 months. Inhaled therapy dose, oral corticosteroids dose, pulmonary function tests, eosinophil blood count, fractional exhaled nitric oxide (F_eNO), Asthma Control Test (ACT) score and responses to the Asthma Quality of Life Questionnaire (AQLQ) were also recorded.

Results: Of the 22 patients enrolled, 13 were treated with mepolizumab 100 mg every 4 weeks in addition to conventional therapy and nine with conventional therapy only. The majority of the patients were treated with high-dose inhaled corticosteroids/long-acting β-agonists/long-acting muscarinic receptor antagonists, while approximately half were on continuous oral corticosteroids. After 12 months, the mepolizumab group only showed a significant improvement in pulmonary function tests (percentage forced expiratory volume in 1 s and percentage forced expiratory flow at 25-75% forced vital capacity (FEF_25-75%), both p<0.001; percentage forced vital capacity, p<0.01) and clinical laboratory parameters (eosinophil count, F_eNO measured at a flow rate of 50 mL·s^-1, ACT and AQLQ, p<0.001). No significant changes in the proportion of patients using continuous oral corticosteroids and high-dose inhaled corticosteroids/long-acting β-agonists/long-acting muscarinic receptor antagonists were observed in either group (p>0.05). By paired comparisons, statistically significant improvements of the mean 6-min walk distance (6MWD) were observed in the mepolizumab (p<0.001) and conventional therapy (p<0.01) groups, while no improvement was seen in dyspnoea Borg scale, heart rate, percentage oxygen saturation or systolic and diastolic blood pressure. 6MWD showed significant direct correlations with ACT (r=0.5998, p<0.001), AQLQ (r=0.3978, p=0.009) and FEF_25-75% (r=0.3589, p=0.017).

Conclusions: The 6MWT could complement severe asthma assessment and be relevant in evaluating the objective response to treatment, including biological therapies like mepolizumab.

FIGURE 1

Paired comparisons in the a) mepolizumab group (before and after mepolizumab) and b) conventional therapy group of the 6-min walk distance (6MWD) data, Borg dyspnoea scale, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and peripheral oxygen saturation (S_pO2) in ambient air at baseline (T0) and after 1 year of observation (T1). **: p<0.01; ***: p<0.001.

FIGURE 2

a) Individual 6-min walk distance (6MWD) in the studied patients. Red line refers to the minimal important difference (25 m) conventionally used as a cut-off. b–d) Correlations between 6MWD pulling together data from baseline and after 1 year of observation of the 22 patients studied (n=44) and forced expiratory volume at 25–75% of the forced vital capacity (FEF_25-75%) (b), Asthma Quality of Life Questionnaire (AQLQ) score (c) and Asthma Control Test (ACT) score (d). Correlations were calculated with the Spearman's method and reported in the figure as R and p-value. 95% CI and details can be found in supplementary table S1.