Lower baseline FEV1 is associated with greater FEV1 improvement after tiotropium add-on in uncontrolled asthma

Abstract

Long-acting muscarinic antagonists (LAMAs) have been suggested as an additional treatment option for asthmatics inadequately controlled by inhaled corticosteroids and long-acting beta-agonists, though the specific patient characteristics that predict optimal LAMA responsiveness remain unclear. This study aims to identify predictors of response to tiotropium, one of LAMAs, in adult asthma patients. A retrospective analysis of 111 patients treated with tiotropium at a tertiary hospital (2009-2018) and a prospective study involving 18 patients were conducted. Response was defined as forced expiratory volume in 1 second (FEV1) improvement (≥10% predicted or ≥ 100 mL) or absence of exacerbations. In the retrospective study, while overall FEV1 changes were minimal (-10 mL, -0.33%), FEV1 responders (n = 21) showed significant increases (340 mL, 10.3%; P < .001). FEV1 responders had lower baseline FEV1 compared to nonresponders (44.6 ± 13.0 vs 53.5 ± 15.5%; P = .031), and those with exacerbations had significantly lower baseline FEV1 (51.1 ± 18.2 vs 63.2 ± 25.7%; P = .008). In multivariate analysis, baseline FEV1 < 50% predicted remained an independent predictor of a positive FEV1 response (OR 3.5, 95% CI 1.1-11.6, P = .037). The prospective study confirmed similar trends; FEV1 responders had lower baseline FEV1 (55.0 ± 17.5% vs 72.0 ± 16.7%; P = .04) and showed greater FEV1 improvements. Other factors, including eosinophil counts, immunoglobulin E levels, asthma-chronic obstructive pulmonary disease overlap, and smoking status, were not significant predictors of response. Tiotropium improved lung function, particularly in patients with lower baseline FEV1. Identifying such predictors can optimize patient selection for LAMA therapy. Further large-scale studies are needed to refine these findings.

Keywords: asthma; long-acting muscarinic antagonists; lung function; predictors; tiotropium.

Figure 1.

Flowchart of the retrospective cohort. Study population was defined as asthma patients who received tiotropium add-on therapy at least twice between 2010 and 2020 (N = 111). Among them, 60 patients had available 1-year follow-up spirometry and were further classified into FEV1 responders (≥100 mL or ≥ 10% improvement) and nonresponders. The remaining 51 patients without follow-up spirometry were included only in baseline and clinical comparisons. FEV1 = forced expiratory volume in 1 second.

Figure 2.

Changes in FEV1 (%) after 1 year of tiotropium treatment (the retrospective study). Tiotropium response was defined by 2 criteria: ≥ 100 mL or ≥ 10% improvement in FEV1 after 1 year, or absence of exacerbations during the year. Exacerbation was defined as any unscheduled outpatient visit, emergency department visit, or hospitalization due to asthma. FEV1 = forced expiratory volume in 1 second.