Tiotropium Add-On and Treatable Traits in Asthma-COPD Overlap: A Real-World Pilot Study

Abstract

Purpose

The ‘treatable traits’ strategy for patients with chronic inflammatory airway diseases, especially asthma and chronic obstructive pulmonary disease (COPD), is a focus of interest, because it implements precision and personalized medicine. Asthma-COPD overlap (ACO), a phenotype involving both asthma and COPD, is an important disease entity because patients with ACO have significantly worse outcomes, conferring greater economical and social burdens. Some guidelines for ACO recommend add-on therapy of long-acting muscarinic antagonists to inhaled corticosteroids and long-acting β₂ agonists. However, this approach is based on extrapolation from patients with asthma or COPD alone. Consequently, a ‘treatable traits’ approach suitable for ACO remains obscure.

Methods

A 12-week open-label cross-over pilot study was conducted in patients with ACO to investigate the effect of tiotropium bromide (TIO) 5 µg/day add-on therapy to fluticasone propionate/formoterol fumarate (FP/FM) 500/20 µg/day compared with FP/FM 500/20 µg/day alone. A 4-week run-in period and two 4-week treatment periods were included.

Results

A total of 18 male patients with stable ACO participated in this pilot study. All patients were ex-smokers. Mean values ± standard deviation (SD) for forced expiratory volume in 1 second (FEV₁) were 1.21 ± 0.49 L after the run-in period, 1.20 ± 0.51 L after the FP/FM combination therapy period, and 1.30 ± 0.48 L after the TIO add-on therapy to FP/FM period. FEV₁ values after the TIO add-on therapy FP/FM period were significantly higher than those after the run-in period (p < 0.01).

Conclusion

TIO add-on therapy to FP/FM in patients with ACO, considered difficult to treat because of the presence of both asthma and COPD, resulted in improvements in lung function parameters in this real-world pilot study, indicating the potential value of TIO add-on therapy as a “treatable traits” option for standard treatment for ACO.

Keywords:

• treatable trait
• asthma-COPD overlap
• tiotropium
• fluticasone
• formoterol
• triple therapy

Abbreviations

ACO, asthma-COPD overlap; ACQ, asthma control questionnaire; AHR, airway hyperresponsiveness; ANOVA, analysis of variance; ASK-12, adherence status with knowledge-12; BDR, bronchodilator response; CAT, COPD assessment test; COPD, chronic obstructive pulmonary disease; DPI, dry powder inhalation; FEF_25–75, forced expiratory flow at 25%–75%; FeNO, fractional exhaled nitric oxide; FEV₁, forced expiratory volume in 1 s; FOT, forced oscillation technique; FP, fluticasone propionate; FM, formoterol fumarate; FVC, forced vital capacity; ICS, inhaled corticosteroid; IgE, immunoglobulin E; LABA, long-acting β₂ agonist; LAMA, long-acting muscarinic antagonist; MEF, maximum expiratory flow rate; MEF₂₅, maximum expiratory flow rate at 25% forced vital capacity; MEF₅₀, maximum expiratory flow rate at 50% forced vital capacity; pMDI, pressurized metered-dose inhaler; M3, muscarinic receptor type 3; SD, standard deviation; SMI, Soft Mist™ inhaler; TIO, tiotropium bromide; UMIN, University Hospital Medical Information Network; VC, vital capacity.

Data Sharing Statement

The clinical study data used to support the findings of this study are available from the corresponding author upon request.

Ethics Approval and Informed Consent

The study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the Ethics Committee of Kansai Medical University (approval no. 2017315). Written informed consent was obtained from all patients prior to participation.

Acknowledgment

The authors thank Alison Sherwin, PhD, from Edanz for editing a draft of this manuscript.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that they have no competing interests in this work.