Clinical Implications of Peak Inspiratory Flow in COPD: Post Hoc Analyses of the TRONARTO Study

Abstract

Background

In patients with COPD, inhalation ability should be assessed when considering inhaler choice. To evaluate whether the soft mist inhaler (SMI) is suitable for COPD patients irrespective of inhalation ability, the TRONARTO study investigated the efficacy of dual long-acting bronchodilator therapy delivered via the Respimat^® SMI on lung function in patients with COPD stratified by inhalation ability. Tiotropium/olodaterol delivered via the SMI was effective both in patients with peak inspiratory flow (PIF) <60 L/min and PIF ≥60 L/min, measured against medium-low resistance.

Methods

This congress compilation summarizes post hoc analyses from the TRONARTO study presented at the annual American Thoracic Society 2022 and European Respiratory Society 2022 meetings. These analyses evaluated PIF in over 200 patients, with PIF measurements taken daily at home for 4 weeks, and in the clinic at baseline, Weeks 2 and 4.

Results

Overall, 57.9% of patients had a PIF range (difference between lowest and highest PIF measurements) <20 L/min (12.4% of patients had PIF range <10 L/min). At-home PIF range decreased over the study period, suggesting that inhaler training/repeated PIF measurements may help to make patients’ inspiratory effort more consistent. Some patient characteristics correlated with lower PIF (female gender, shorter stature, more severe disease, worse airflow obstruction) and lower PIF range (more severe disease). PIF measurements differed between medium-low and high-resistance settings, highlighting the importance of measuring PIF at the resistance of a patient’s inhaler. PIF correlated poorly with spirometry measurements.

Conclusion

As indicated in COPD management guidelines, choice of inhaler is essential to optimize pharmacologic therapies for COPD. Poor inspiratory ability should be viewed as a treatable trait that can help to inform inhaler choice. Inhaler training and consideration of PIF (if patients use a dry powder inhaler) can reduce patient-to-inhaler mismatch, with potential consequences for health status and exacerbation risk.

Keywords:

• COPD
• dry powder inhaler
• DPI
• PIF
• suboptimal
• congress
• variability
• characteristics

Abbreviations

COPD, chronic obstructive pulmonary disease; DPI, dry powder inhaler; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; GOLD, Global Initiative for Chronic Obstructive Lung Disease; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist; PIF, peak inspiratory flow; pMDI, pressurized metered-dose inhaler; SE, standard error; SMI, soft mist inhaler; TIO/OLO, tiotropium/olodaterol.

Data Sharing Statement

To ensure independent interpretation of clinical study results and enable authors to fulfil their role and obligations under the ICMJE criteria, Boehringer Ingelheim grants all external authors access to relevant clinical study data. In adherence with the Boehringer Ingelheim Policy on Transparency and Publication of Clinical Study Data, scientific and medical researchers can request access to clinical study data after publication of the primary manuscript and secondary analyses in a peer-reviewed journals and regulatory and once reimbursement activities are completed, normally within 1 year after the marketing application has been granted by major Regulatory Authorities. Researchers should use the https://vivli.org/ link to request access to study data and visit https://www.mystudywindow.com/msw/datasharing for further information.

Ethics Approval and Informed Consent

The TRONARTO study protocol was reviewed and approved by the respective independent review boards and ethics committees of the participating sites: 26 in Germany and the United States of America beginning January 8, 2020 and ending September 29, 2020 (for full details, see Supplementary Table 1). The TRONARTO study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. All patients provided written informed consent.

Consent for Publication

All authors provide their consent for publication of this manuscript and all related contents. All patients provided their informed consent when entering the TRONARTO study.

Acknowledgments

These post hoc analyses were sponsored by Boehringer Ingelheim International GmbH. Medical writing assistance, in the form of the preparation and revision of the manuscript, was supported financially by Boehringer Ingelheim and provided by Paul Todd, PhD, at Meditech Media, under the authors’ conceptual direction and based on feedback from the authors.

Author Contributions

The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors. All authors 1) made a significant contribution to the work reported, whether through conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; 2) took part in drafting, revising or critically reviewing the article; 3) gave final approval of the version to be published; 4) agreed on the journal to which the article was submitted; and 5) agreed to be accountable for all aspects of the work. The authors received no compensation related to the development of the manuscript.

Disclosure

MBD reports research grants from the National Institutes of Health, Department of Defense, American Lung Association, Boehringer Ingelheim, Midmark and Teva unrelated to this work. He reports personal consulting fees from Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, Teva, Midmark, Verona, Optimum Patient Care, Chiesi, Becker Pharma and Polarean unrelated to this work. HW reports grants, personal fees and other support from Boehringer Ingelheim during the conduct of the study. Outside the submitted work, HW received grants, personal fees and other support from AstraZeneca, Chiesi, Bayer, Boehringer Ingelheim, GlaxoSmithKline, Sanofi, and Novartis. JR is an employee of Syneos Health working on behalf of Boehringer Ingelheim. AG, RE-S and AS are employees of Boehringer Ingelheim. DAM reports fees for advisory boards from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Teva, Theravance, Verona and Viatris; royalties from Salem Media Group – COPD: Answers to Your Questions (2015); work with pharmaceutical companies on the use of BDI/TDI; participation in speaker’s bureau for AstraZeneca, Boehringer Ingelheim and Teva; and https://www.donaldmahler.com – an educational website for those with COPD and their families. The authors report no other conflicts of interest in this work.