Improvement of Sleep in COPD Patients Through Inhalation Management Education by Nurse.

●Research participants, eligibility criteria, and exclusion criteria The study will include stable COPD patients who are outpatients at Kumamoto University Hospital, Kounan Hospital, or Iwakuni City Nishiki Central Hospital, which specialize in internal and respiratory medicine. Eligible participants must meet all of the following criteria and must not meet any exclusion criteria.

【Eligibility Criteria】

• Aged 20 years or older at the time of informed consent.
• Prescribed inhaled medications and have used them continuously for at least one month.
• No prior experience with inhalation therapy required.
• No hospitalization for COPD exacerbation within one month prior to study enrollment.
• Patients with obstructive sleep apnea (OSAS) overlap syndrome (OVS) receiving nasal continuous positive airway pressure (CPAP) therapy are eligible if their symptoms are stable, as determined by a physician after CPAP initiation.
• Able to operate a device such as an Android tablet, iPad, or computer; if not, participation is still acceptable if a caregiver can operate the device.
• Individuals deemed to be in a stable condition by a physician and who have obtained permission.

【exclusion criterias】

• Presence of other respiratory diseases such as asthma or interstitial pneumonia.
• Presence of advanced cancer, including lung cancer.
• Restricted chest movement due to chest deformity or trauma
• Sleep-disordered breathing with a central apnea-hypopnea index (AHI) exceeding 50%.
• Sleep-disordered breathing with a central AHI of more than half
• Diagnosis of dementia or other psychiatric disorders.

• Registration of study subjects The attending physician at the collaborating research institution will refer patients who meet the eligibility criteria for the study, and the principal investigator or research collaborator will obtain the patient's consent directly. The purpose and significance of the study, the methods, and ethical considerations will be explained verbally and in writing, and written consent will be obtained. After obtaining consent, a study subject identification code will be assigned, and the study subject will be registered in this study.
• Allocation method A stratified block allocation will be performed using gender (male, female) and severity classification (GOLD Grade 1, 2, 3, 4) as allocation factors. The allocation of study participants to each treatment group will be conducted by Makiko Yamamoto at the Department of Basic Nursing Science, Kumamoto University Graduate School of Nursing.

Following the pre-established random allocation table, participants will be sequentially assigned to each treatment group in the order of case registration, and a registration confirmation form will be issued, indicating the participant's registration number and treatment group. The allocation table will be retained by the allocation officer and will not be disclosed to the principal investigator or co-investigators.

●Sample size Target number of participants (Total: 34 cases) Intervention group: 17 cases Control group: 17 cases Number of participants expected to enroll(Total: 60 cases) Intervention group: 30 cases Control group: 30 cases There are no previous studies measuring the effect of inhalation management education on sleep quality. In previous studies, the average PSQI score for COPD patients was 8.3-11.5 points, and the PSQI cutoff value is 5.5 points. Assuming a change of 5.0 points in the average PSQI-J score after 3 months in the intervention group, the sample size required to maintain a two-sided test (significance level 5%) with 80% power is 17 cases per group. Considering that many participants are elderly and may have difficulty continuing to use computers or video conferencing tools, a higher dropout rate than usual is anticipated. Therefore, 30 participants per group, totaling 60 participants, will be enrolled in the study.

●Criteria for exclusion from analysis The definition of the analysis population is as follows.

-Full Analysis Set (FAS) The FAS consists of all study subjects who provided informed consent, excluding the following study subjects.

• Cases that do not meet the primary eligibility criteria (e.g., diagnosed with a disease outside the scope of the study, or found to have violated objectively determinable selection or exclusion criteria) • Cases with no post-randomization measurements -The population compliant with the study protocol (Per Protocol Set: PPS)

The PPS is defined as the FAS excluding the following subjects:

• Cases with unavailable measurements of the primary endpoint

• Cases with major protocol violations (e.g., allocation errors, failure to meet eligibility criteria, non-compliance with medication)

This study will clearly identify the breakdown of cancellations and dropouts by compiling data on the number of registered subjects who were excluded from the analysis population and the reasons for their exclusion, broken down by analysis population.

●Analysis and statistical methods for verifying evaluation items Statistical analysis will be performed using JMP Pro 18, with a significance level set at 5%.

-Analysis of primary endpoints Primary endpoint: Change in PSQI-J at 3 months before and after the educational intervention The primary endpoint will be analyzed using the FAS. The change in PSQI-J scores will be calculated for each group, and independent t-tests will be performed to compare groups at a significance level (two-sided) of 5%. A similar analysis will be conducted using PPS as the analysis population as a secondary analysis.

-Using FAS as the analysis population, the difference in the mean change in JESS, Japanese CAT, and HADS scores between groups will be analyzed using a paired t-test at a significance level of 5%. Similar analyses will also be conducted using PPS as the analysis population.

In this study, baseline data for the primary outcome measure, PSQI, were missing at study registration. If PSQI-J was measured within one month of baseline (prior to the first intervention), that data was used to impute baseline data for PSQI-J. This method of data imputation may result in the presence of data from different measurement time points at baseline.

However, since the PSQI-J reflects sleep quality over the past month and no interventions were conducted during that period, this method of data supplementation is considered appropriate. For other items, missing values will not be supplemented.

Information on patients obtained at baseline from participants who withdrew from the study or withdrew their consent will be used for analysis if consent is obtained from the participants themselves, as it constitutes valuable data on inhalation techniques, inhalation education, and methods for current COPD patients.

●Criteria for discontinuing participation in research The principal investigator or co-investigator shall terminate the study if they determine that it is impossible to continue the study for any of the following reasons.

<Termination Criteria>

• If a research subject withdraws from the study or revokes their consent

• If it is determined after registration that the subject no longer meets the eligibility criteria (inclusion/exclusion criteria)
• If the subject requires emergency hospitalization and treatment due to worsening of the underlying disease
• If the study cannot be continued due to worsening of complications
• If the study cannot be continued due to adverse events
• If the study is terminated
• If the physician determines that termination of the study is appropriate for other reasons

Inclusion criteria

• Individuals aged 20 years or older at the time of consent.
• Individuals who have been prescribed inhaled medications and have been using them continuously for more than one month.
• Prior experience with inhalation instruction is not required.
• Individuals who have not been hospitalized within one month prior to study participation due to exacerbation of COPD.
• Individuals with obstructive sleep apnea syndrome (OSAS) who are receiving treatment with continuous positive airway pressure (CPAP) therapy are eligible, provided that the physician determines that symptoms are stable following CPAP initiation.
• Participants must be able to operate devices such as Android, iPad, or computer. However, if a caregiver can operate the device, the participant's inability to do so is acceptable.
• Participants must be in a stable condition as determined by a physician and have obtained permission to participate.

Exclusion criteria

• Suffering from other respiratory diseases such as asthma or interstitial pneumonia
• Suffering from advanced cancer, including lung cancer
• Restricted chest movement due to chest deformity or trauma
• Suffering from diseases that cause respiratory distress, such as heart disease
• Suffering from sleep-disordered breathing with a central AHI of more than 50%
• Diagnosed with dementia or mental illness