This paper presents a study undertaken to evaluate the sensor systems that were shortlisted to be used in the development of a portable respiratory-gated transcutaneous auricular vagus nerve stimulation (taVNS) system. To date, all published studies assessing respiratory-gated taVNS have been performed in controlled laboratory environments. This limitation arises from the reliance on non-portable sensing equipment, which poses significant logistical challenges. Therefore, we recognised a need to develop a portable sensor system for future research, enabling participants to perform respiratory-gated stimulation conveniently from their homes. This study aimed to measure the accuracy of an in-ear and a fingertip-based photoplethysmography (PPG) sensor in measuring cardiac vagal tone relevant heart rate variability (HRV) parameters of root mean square of successive R-R interval differences (RMSSDs) and the high-frequency (HF) component of HRV. Thirty healthy participants wore the prototype sensor equipment and the gold standard electrocardiogram (ECG) equipment to record beat-to-beat intervals simultaneously during 10 min of normal breathing and 10 min of deep slow breathing (DSB). Additionally, a stretch sensor was evaluated to measure its accuracy in detecting exhalation when compared to the gold standard sensor. We used Bland–Altman analysis to establish the agreement between the prototypes and the ECG system. Intraclass correlation coefficients (ICCs) were calculated to establish consistency between the prototypes and the ECG system. For the stretch sensor, the true positive rate (TPR), false positive rate (FPR), and false negative rate (FNR) were calculated. Results indicate that while ICC values were generally good to excellent, only the fingertip-based sensor had an acceptable level of agreement in measuring RMSSDs during both breathing phases. Only the fingertip-based sensor had an acceptable level of agreement during normal breathing in measuring HF-HRV. The study highlights that a high correlation between sensors does not necessarily translate into a high level of agreement. In the case of the stretch sensor, it had an acceptable level of accuracy with a mean TPR of 85% during normal breathing and 95% during DSB. The results show that the fingertip-based sensor and the stretch sensor had acceptable levels of accuracy for use in the development of the respiratory-gated taVNS system.

Introduction/objectives: Rheumatoid arthritis is a chronic autoimmune disease that primarily affects the joints, causing pain, inflammation, and long-term joint damage. Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising non-pharmacological intervention for managing pain and inflammation, particularly when delivered in the exhalation phase of respiration. However, until now, the lack of portable equipment has meant the respiratory phase effects have not been evaluated outside of the laboratory or in a home setting. The primary goal of this study was to determine the feasibility of a future clinical trial of home-based respiratory-gated taVNS in people with rheumatoid arthritis. Methods: This was a single-arm, non-randomised feasibility trial involving 12 individuals with active rheumatoid arthritis. Participation involved 12 respiratory-gated taVNS sessions at home and three laboratory visits for outcome assessments (day 1, day 8, and day 15). Feasibility outcomes focused on recruitment rate, intervention adherence, acceptability questionnaires, and adverse events. In addition, outcome measures related to pain, psychological distress, and key inflammatory biomarkers were assessed. Results: Feasibility outcomes demonstrated an acceptable recruitment rate, high adherence (90% session completion), excellent usability (9/10), and acceptability (average score 66%, general score 87%), with no severe treatment-emergent adverse events. While single-armed and not powered to determine efficacy, medium to large pre- to post-intervention reductions in pain interference, grip pain intensity, psychological distress, and tumour necrosis factor-alpha levels were observed, with minimal changes in other outcomes. Conclusion: An adequately powered, randomised controlled trial of home-based respiratory-gated taVNS in people with rheumatoid arthritis is feasible and safe. Key Points • To the best of our knowledge, this study is the first to evaluate the feasibility of homebased respiratory-gated (RG) transcutaneous auricular vagus nerve stimulation (taVNS) for the treatment of rheumatoid arthritis (RA). • Feasibility outcomes demonstrated high adherence and excellent usability ratings with few treatment-emergent adverse events reported. • Home-based RG taVNS using the developed system is safe and feasible to evaluate in an adequately powered, controlled trial.