Effectiveness of digital inhaled therapy management and respiratory muscle training in moderate to severe COPD patients: study protocol for a randomized controlled, assessor-blinded, multicenter trial

BACKGROUND: Digital inhaler therapy management can help patients promote adherence and correct inhaler techniques. Poor inhaler technique and suboptimal adherence contribute to COPD exacerbations, uncontrolled symptoms, and a progressive decline in pulmonary function. Digital Inhaled Therapy Management (DITM) platforms can provide standardized technique training, objective adherence monitoring, and real-time feedback. Respiratory Muscle Training is a recommended component of pulmonary rehabilitation that can improve respiratory muscle strength and exercise tolerance. Whether DITM and IMT, alone or in combination, reduce exacerbations and improve patient-reported and physiologic outcomes compared with usual care remains uncertain. METHODS: This is a 1-year, multicenter, open-label, assessor-blinded, randomized, parallel-group superiority trial with participants randomly allocated to four arms (1:1:1:1): DITM, IMT, DITM + IMT, and usual care (verbal inhaler education). Adults ≥ 40 years with COPD per GOLD 2024, FEV1%pred < 60, symptomatic burden (e.g., CAT ≥ 10 and/or mMRC ≥ 2), and high risk of exacerbation (≥ 2 moderate or ≥ 1 severe in past 12 months) will be enrolled (N = 410). Follow-up contacts occur at 3, 6, and 12 months. The primary outcome timepoint is the cumulative 12-month rate of moderate-to-severe COPD exacerbations,with severe events defined as COPD-related hospitalizations, the 3-and 6-month contacts are used for event ascertainment and not as separate primary timepoint. Secondary outcomes include time to first moderate-to-severe exacerbation, CAT, mMRC, SGRQ-C, spirometry, inspiratory muscle strength (MIP/MEP), 6-min walk test, and device-derived metrics of inhaler adherence and technique. Analyses will follow intention-to-treat principles, using negative binomial or Poisson regression for exacerbation rates, Cox models for time-to-event outcomes, and mixed-effects models for repeated continuous outcomes. DISCUSSION: This trial will evaluate the effectiveness of DITM and IMT-alone and combined-on exacerbations, symptoms, and function in high-risk COPD. Findings may inform integration of digital self-management and inspiratory muscle training into routine COPD care. TRIAL REGISTRATION: ClinicalTrials.gov NCT06958666; registered in July 2025. Ethics approved was obtained from the Ethics Committee of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine (Approval No. 20250119).