To Örebro University

BACKGROUND: Chronic cough markedly impairs health-related quality of life (HRQoL). The Leicester Cough Questionnaire (LCQ) is widely used to assess cough burden across physical, psychological, and social domains; however, no validated Danish version is available.

MATERIALS AND METHODS: The LCQ was translated and culturally adapted into Danish in accordance with COSMIN guidelines and was approved by the original developers. Forty-two clinically stable patients with chronic cough (mean age 70.8 years; 67% male) completed baseline and retest questionnaires at a median of 28 days (IQR 21-42). Internal consistency was examined with Cronbach's alpha. Test-retest reliability was assessed using intraclass correlation coefficients (ICC), standard error of measurement (SEM), and minimal detectable change (MDC).

RESULTS: The LCQ-DK demonstrated excellent internal consistency (Cronbach's alpha = 0.96 total; 0.84-0.92 domains). Test-retest reliability was high (ICC = 0.90, 95% CI: 0.79-0.95 total; 0.86-0.89 domains). SEM was 1.14 points (8%) and MDC 3.16 points (23%) for the total score. No floor or ceiling effects were seen for the total score, though ceiling effects up to 12% occurred within domains.

CONCLUSION: The LCQ-DK demonstrates high reliability following cross-cultural adaptation and supports group-level assessment of HRQoL in Danish-speaking patients with chronic cough for clinical and research use.

RATIONALE: Patients with COPD on long-term oxygen therapy (LTOT) have an unmet need for oxygen adjustments during sleep, rest, and activity, documented by continuous monitoring of oxygen saturation (SpO2). While emerging technology enables automated adjustments, its feasibility in home settings remains uncertain. This randomized crossover trial evaluated the feasibility and preliminary effects of continuous automated oxygen titration at home.

METHODS: The intervention period involved four days of automated oxygen titration targeting a SpO2 of 90-94% using a Bluetooth-connected electronic device and wrist pulse oximeter, forming a closed-loop system. Oxygen flow (0.9-6.8 L/min) was continuously adjusted based on SpO2. During the control period, patients received their usual fixed dose oxygen. Feasibility was defined as time with automated titration, time within target SpO2 and patient acceptance. Additionally, health status was measured using the Clinical COPD Questionnaire (CCQ, minimal important difference 0.4).

RESULTS: Twelve patients (8 men, mean (SD) age 72.9 (5.5) years) on LTOT with an oxygen dose of 2.0 (0.8) L/min were included. Each patient provided more than 217,000 paired SpO2 and oxygen flow data points. Oxygen flow was automatically adjusted for a median of 77 h (IQR 68.0-84.3), covering 83% of the time. Time within target SpO2 increased from 52% (42-63) to 86% (75-90) during the intervention. All patients used the full available flow range. The CCQ score improved by 0.74 (0.47) points; p < 0.001.

CONCLUSION: Automated oxygen titration is feasible in the home setting, achieving more time with normoxia, but it required a wide flow range and continuous SpO2 monitoring. The patients reported a clinically relevant reductions in COPD symptoms measured with CCQ. The clinical importance of controlling SpO2 needs to be examined in a larger study.

BACKGROUND: Minimising hypoxaemia during submaximal walking tests has a positive effect on exercise capacity and dyspnoea in patients with chronic obstructive pulmonary disease (COPD) on long-term oxygen therapy (LTOT). However, the impact of optimising oxygenation during everyday tasks remains unexplored. Therefore, we investigated the effects of maintaining a target saturation on activities of daily living (ADL) using automated oxygen titration compared with conventional fixed oxygen flow.

METHODS: In a double-blinded, randomised crossover trial, patients with COPD on LTOT performed two GlittreADL tests to assess the functional capacity of everyday activities using (1) their fixed oxygen dose and (2) an adjusted flow from 0 to 8 L/min targeting a peripheral oxygen saturation (SpO2) of 90-94%. A closed-loop device automatically titrated the oxygen based on information from a Bluetooth wrist pulse oximeter.

RESULTS: 31 patients (mean±SD age: 72.8±5.9 years, forced expiratory volume in 1 s of % predicted: 36.7±12.7) were included. The patients reduced the time to perform the ADL test by median (IQR) 38 (12-73) s, p<0.001, using automated titration compared with the fixed oxygen flow. The oxygen flow in the automated arm more than tripled to 5.4 (4.1-6.8) versus 1.6 (1.1-2.1) L/min (fixed) during the test, p<0.001, while the time spent within SpO2-target was increased from 19% to 49%, p=0.002. Correspondingly, the patients experienced less dyspnoea (BorgCR10); 5 (3-7) versus 6 (4-8), p<0.001, in favour of the automated oxygen titration.

CONCLUSIONS: Improving oxygenation and extending the time spent within target saturation reduced dyspnoea and improved functional capacity in ADL in patients with COPD on LTOT.

TRIAL REGISTRATION NUMBER: NCT05553847.

Patients with COPD on long-term oxygen therapy (LTOT) often experience fluctuations in oxygen demand during walking, daily activities, and rest. Conventional fixed-dose oxygen therapy fails to adequately meet these dynamic needs, leading to episodes of hypoxemia that may negatively impact dyspnea, exercise endurance, and overall quality of life. Automated oxygen titration systems, have the potential to optimize oxygen delivery by adjusting flow rates in real time based on oxygen saturation (SpO₂).

This thesis consists of four studies evaluating the feasibility, efficacy and patient experience of reducing hypoxemia using automated oxygen titration in patients with COPD on LTOT across walking, activities of daily living (ADL), and in the home environment. 

Two randomized crossover trials, one randomized crossover feasibility trial and a qualitative interview study were conducted. Oxygen flow was adjusted to maintain SpO₂ between 90-94% and compared to usual fixed-dose oxygen.

Automated titration significantly increased time spent within target saturation and reduced episodes of hypoxemia compared to usual oxygen dose. It required a wide flow range and continuous monitoring. The improvements in oxygenation were associated with increased walking distance, enhanced ADL performance, and reduced dyspnea. At home, improving SpO₂ proved feasible, with high patient acceptance and it seemed to positively affect self-reported health. Patients described more ease daily functioning and expressed optimism about the technology.

The present study included the first patients with COPD on long-term oxygen therapy who experienced second-by-second oxygen adjustments in their homes based on oxygen saturation. A device capable of automatically titrating the patient's oxygen was installed in the patients' home aiming at increasing the time spent within target saturation. We explored patients' experiences with this automated home oxygen titration, focusing on how maintaining target saturation affected daily life. Semi-structured interviews were conducted with eight men and four women after installation. Systematic text condensation was used in the analysis. Three main themes emerged from patient narratives: (1) "This is my life" - Patients preferred maintaining stable oxygen saturation, associating hypoxemia with dyspnea, discomfort, and difficulties with daily tasks. (2) "Getting the oxygen, I need" - Many patients reported improved ability to perform daily activities when oxygen was automatically adjusted. (3) "New technology gives hope for my life" - Patients expressed optimism about the potential of home-based technology, offering suggestions to improve usability, mainly by reducing concentrator noise. Our findings suggested high acceptability of the automated oxygen in the patients' home, as they believed it to increase the time spend with sufficient oxygen, especially during daily activities. Integrating patient insights is essential for implementation and acceptance of automated home oxygen therapy.

Background: Minimizing hypoxemia during submaximal test has a positive effect on exercise capacity and dyspnea in patients with COPD on long-term oxygen therapy (LTOT). However, the impact of optimizing oxygenation during everyday tasks remains unexplored. Therefore, we investigated the effects of maintaining a target saturation on Activities of Daily Living (ADL) using an automated oxygen system compared to conventional fixed oxygen flow.

Methods: In a double-blinded, randomized crossover trial, 31 patients with COPD on LTOT performed two Glittre-ADL tests to assess the functional performance of everyday activities using a) an adjusted flow from 0-8 L/min targeting a SpO2 of 90-94% and b) their fixed oxygen dose. An electronic device (O2matic HOT) automatically titrated the oxygen based on information from a Bluetooth wrist pulse oximeter.

Results: The patients reduced the time to perform the ADL-test by median (IQR) 38 (12-73) seconds, p<0.001, using automated titration compared to the fixed oxygen flow. The oxygen flow in the automated arm more than tripled to 5.4 (4.1 – 6.8) L/min vs. 1.6 (1.1-2.1) L/min (fixed) during the test, p<0.001, while the time spend within SpO2-target was increased from 24% to 47%, p<0.001. Correspondingly, the patients experienced less dyspnea (BorgCR10); 5 (3-7) vs. 6 (4-8), p<0.001. Twenty-seven (87%) patients exceeded the minimal clinical important difference (MCID) in either the change of dyspnea score or time difference to complete the ADL-test.

Conclusions: Extending the time spent within target saturation reduced dyspnea and improved functional performance in activities of daily living in patients with COPD on LTOT.

Introduction: Automated oxygen titration (AutOx) is a new technology which could give patients with chronic respiratory failure the opportunity of personalized oxygen treatment. AutOx has been tested in a safe environment but never in a real life setting for several days in the patient's home.

Aim: To investigate the setup of automated oxygen in the home of patients with chronic respiratory failure in a pilot study.

Methods: A new device, O2matic HOT, was connected to a high-flow concentrator which could provide for up to 10 l/min. Patients wore a Nonin WristOx pulse oximeter, connected via bluetooth to the O2matic HOT. In a closed-loop circuit oxygen flow was titrated based on oxygen saturation (SpO2). Patients were encouraged to wear the pulse oximeter as much as possible, also during activity. Data was sent to a cloud solution.

Results: Two patients tested the setup for each 4 days. Pulse oximeter signal was achieved for 78.3 to 78.9 % of the time, with 272,399 paired observations of SpO2 and oxygen flow for patient 1 and 262,568 observations for patient 2. SpO2 was in target interval (90-94 %) in 94.8 % of the time for patient 1 and 84.7 % of the time for patient 2. Oxygen flow was median 1.3 l/min (2.5-97.5 % percentile: 1.0-5.9 l/min) for patient 1 and median 0.6 l/min (2.5-97.5 % percentile: 0.5-6.7 l/min) for patient 2.

Discussion: It is possible to titrate oxygen flow in a home setting and achieve almost perfect control of SpO2, but it requires major adjustments in oxygen flow. The clinical importance of controlling SpO2 is not clear, but dyspnea and endurance has been shown to improve with titrated oxygen. Further studies will be needed to examine the feasibility of automated oxygen titration at home.

The need for oxygen increases with activity in patients with COPD and on long-term oxygen treatment (LTOT), leading to periods of hypoxemia, which may influence the patient's performance. This study aimed to evaluate the effect of automated oxygen titration compared to usual fixed-dose oxygen treatment during walking on dyspnea and endurance in patients with COPD and on LTOT. In a double-blinded randomised crossover trial, 33 patients were assigned to use either automated oxygen titration or the usual fixed-dose in a random order in two walking tests. A closed-loop device, O2matic delivered a variable oxygen dose set with a target saturation of 90-94%. The patients had a home oxygen flow of (mean ± SD) 1.6 ± 0.9 L/min. At the last corresponding isotime in the endurance shuttle walk test, the patients reported dyspnea equal to median (IQR) 4 (3-6) when using automated oxygen titration and 8 (5-9) when using fixed doses, p < 0.001. The patients walked 10.9 (6.5-14.9) min with automated oxygen compared to 5.5 (3.3-7.9) min with fixed-dose, p < 0.001. Walking with automated oxygen titration had a statistically significant and clinically important effect on dyspnea. Furthermore, the patients walked for a 98% longer time when hypoxemia was reduced with a more well-matched, personalised oxygen treatment.

Rationale Patients with COPD on long-term oxygen therapy (LTOT) have an unmet need for oxygen adjustments during sleep, rest, and activity, documented by continuous monitoring of oxygen saturation. While emerging technology enables automated adjustments, its feasibility in home settings remains uncertain. This randomized crossover trial evaluated the feasibility and preliminary effects of continuous automated oxygen titration in the homes of patients on LTOT.

Methods The intervention involved four days of automated oxygen titration targeting a SpO₂ of 90-94% using a Bluetooth-connected electronic device and wrist pulse oximeter, forming a closed-loop system. Oxygen flow (0.9-6.8 L/min) was continuously adjusted based on SpO₂. During the control period, patients received their usual fixed dose oxygen. Feasibility was defined as successful automated titration time and time spent with normoxia. Changes in health status were measured using the Clinical COPD Questionnaire (CCQ).

Results Twelve patients on LTOT (2.0±0.8 L/min) were included, with more than 217,000 paired SpO2 and oxygen flow data points collected per patient. Oxygen flow was automatically adjusted for a median (IQR) of 77 (68.0–84.3) hours, covering 83% of the time. Time within target saturation increased significantly from 52% (42–63) to 86% (75–90) during intervention, with all patients utilizing the full available flow range. The CCQ score improved by 0.74±0.47 points, p <0.001.

Conclusion Automated home oxygen titration is feasible, achieving more time with normoxia, but it required a wide flow range and continuous monitoring. The patients reported notable reductions in COPD symptoms.