Identifying critical inhalation technique errors in Dry Powder Inhaler use in patients with COPD based on the association with health status and exacerbations: findings from the multi-country cross-sectional observational PIFotal study
Authors: Kocks Janwillem , Bosnic-Anticevich Sinthia , van Cooten Joyce , Correia de Sousa Jaime , Cvetkovski Biljana , Dekhuijzen Richard , Dijk Lars , Garcia Pardo Marina , Gardev Asparuh , Gawlik Radosław , van der Ham Iris , Janse Ymke , Lavorini Federico , Maricoto Tiago , Meijer Jiska , Metz Boyd , Price David , Roman Rodriguez Miguel , Schuttel Kirsten , Stoker Nilouq , Tsiligianni Ioanna , Usmani Omar , Voorham Jaco , Leving Marika T. 
Published: August 2023

Abstract
Background
Correct inhaler use depends on a complex interplay of factors, including device preparation and generating sufficient inspiratory flow. It is currently unknown which inhalation technique errors can be considered critical in Chronic Obstructive Pulmonary Disease (COPD) patients on Dry Powder Inhaler (DPI) maintenance therapy.

Objective
To investigate the association between inhalation technique errors and health status or exacerbations in patients with COPD. Additionally, the association between the number of errors and COPD outcomes was determined.

Methods
The PIFotal study is a cross-sectional multi-country observational study in a primary care setting, including 1434 COPD patients aged ≥ 40 years (50.1% female; mean age 69.2 yrs) using a DPI for their maintenance therapy. Inhalation technique was video recorded and scored by two independent researchers using inhaler-specific checklists. Health status was assessed with two questionnaires; the Clinical COPD Questionnaire (CCQ) and the COPD Assessment Test (CAT). The number of moderate and severe exacerbations in the past 12 months was recorded. Critical errors were identified based on their association with health status or exacerbations through multi-level prediction models adjusted for identified confounding.

Results
Errors in inhalation technique steps ‘Breathe in’, ‘Hold breath’, and ‘Breathe out calmly after inhalation’ were significantly associated with poorer CCQ and CAT outcomes and thus deemed critical. None of the errors were significantly associated with moderate exacerbations. Patients with errors ‘Preparation’, ‘Hold inhaler in correct position during inhalation’, and ‘Breathe in’ had significantly more severe exacerbations, and therefore these errors were also deemed critical. 81.3% of patients with COPD made at least one critical error. Specific combinations of errors were associated with worse outcomes. The more inhalation technique errors identified, the poorer the health status and the higher the exacerbation rate.

Conclusion
In this study, we identified multiple critical inhalation technique errors in COPD patients using DPIs each associated with poorer outcomes. Explorative analysis revealed that specific combinations of errors may be of clinical relevance, especially those related to the inhalation manoeuvre. COPD outcomes worsened with increasing error count. These results warrant further prospective longitudinal studies to establish the effect of correcting these errors on COPD control.

Trial registration
https://clinicaltrials.gov/ct2/show/NCT04532853 (31/08/2020)