Below is a detailed description of the proposed pilot interventional study which will be carried out among 60 participants in urban Mysore, India.

An adapted Chronic Care Model (CCM) will be used in the study to support enhanced health outcomes. The constructs of the CCM will help us design the study instruments for data collection, improve outcomes from the research and guide data analysis and interpretation of results. The chronic care model (CCM) is an evidence-based framework that can support enhanced health outcomes among patients with chronic medical conditions. The constructs of the CCM (Fig 1) include self-management support, community resources, healthcare organization, decision support, delivery system redesign and clinical information systems. Reinforcing self-management among hypertensive patients in this sense, adhering to lifestyle recommendations not only increases self-efficacy but can improve relevant physiologic outcomes. 

Study Participant Enrolment

Leveraging Public Health Research Institute of India’s (PHRII) existing community relationships, health education and recruitment meetings will be held throughout Mysore. Information describing the purpose of the study will be provided, including eligibility criteria, and study activities. Individuals expressing interest in the study will be screened based on inclusion and exclusion criteria. To be included, participants must be 60 years or older, having hypertension, residing in urban Mysore district/Mysore city for six or more months with no plans to shift residence during the next 14 weeks, having a systolic BP level over 140 mm Hg; and able to give informed consent and complete all study procedures including a medical examination, assessment of their respiratory muscle strength, and an interviewer-administered survey. Hypertension will be diagnosed if, when measured twice on different days, systolic blood pressure on both readings is ≥140 mmHg and/or diastolic blood pressure on both readings is ≥90 mmHg. Exclusion criteria will include having a cognitive disability that makes them unable to perform the IMST training; reported history of uncontrolled cardiac arrhythmias; circulatory shock; acute ischemic heart disease; acute respiratory failure; neuromuscular disease or myopathies; or diaphragmatic paresis or paralysis, ear problems, hospitalization in the prior past three months, any hospitalization for respiratory illness in the last 6 months, having loose teeth/dentures or other oral health issues, any history of smoking in the last ten years and having any condition that might pose a risk for undergoing study procedures including inspiratory pressure testing. A brief survey will be used to collect demographic information from potential participants who declined enrollment to assess any systematic biases in participant recruitment. Prior to data collection, potential participants will undergo an informed consent process. Study staff will explain the study purpose, read the informed consent document verbatim, describe all study procedures, and answer any questions from potential participants. To be included in the study, potential participants must provide written informed consent. A total of 60 eligible participants will be enrolled into the study. Consenting participants will be enrolled into the intervention group (total n=30) or a comparison group (total n=30). This pragmatic study design will help us understand the effectiveness of Inspiratory Muscle Strength Training (IMST) in real-life conditions. The study protocol has been approved by the Institutional Ethics Review Board at PHRII.

Identifiable Personal Information During Screening

Basic demographic information will be collected using a standardized form during the screening process and towards the end of the study, the data gathered from the screening phase will be analyzed to determine whether non-participants differed from study participants in some significant and systematic way. Contact information and personal identifiable information used for recruitment purposes will be kept separate from the study data. These data will only be used for maintaining study participation logs to avoid duplication of subjects. Only research team members will have access to this information. Hard copies will be kept in a locked file.

Experimental vs. Standard Procedures

Inspiratory Muscle Strength Training (IMST) is a novel lifestyle intervention that aims to improve the function of the respiratory muscles through specific breathing exercises. Although it is not a standard means to treat blood pressure, recent studies have shown that it lowers blood pressure in a safe and feasible manner, even among older adults with decreased lung function. The primary aim of this proposed study is to assess IMST’s preliminary effectiveness on blood pressure and observe its effect on aging measures. Upon obtaining informed consent, a study staff member will ask participants to provide some basic information such as age, occupation, and other general information and conduct a short survey on their medical history. The participants’ blood pressure will be recorded, and level of lung functioning will be measured using a spirometry test and Maximum Inspiratory Pressure (PIMAX) recorded. Participants will then be taught to use a simple breathing device that creates resistance when they breathe through it, called an Inspiratory Muscle Strength Trainer. The participants will be asked to breathe using this device 5 times a day, each time taking 6 breaths followed by a minute of rest. They will be asked to repeat this activity for 5 days a week for the next 14 weeks. The first two weeks will be considered a training period where the resistance on the device will be set to 15% (low-resistance) of the participant’s MIP, which will allow the participants to get used breathing with the trainer. After the first two weeks, in the intervention group the resistance will be progressively increased to 55% (for 2 weeks), 65% (for the next 2 weeks) and 75% (for the last 8 weeks) of the participant’s PIMAX. The comparison group will continue at low-resistance for 12 weeks. Research staff will monitor the weekly progress of the study participants, obtain blood pressure measurements every two weeks and record other aging measures at mid-point (6 weeks of intervention) and at the endline (12 weeks of intervention). These measurements and the breathing exercise will be stopped anytime participants feel uncomfortable or anxious. If a participant has a blood pressure measurement of 140/90 mmHg or more at any point in the study or if they feel unwell during any of the study procedures, they will be referred to the local public hospital and a research team member will accompany them. 

Drugs/Devices

The study will use the POWERbreathe inspiratory muscle training (IMST) device. The IMST device is a small, handheld device which provides resistance against inhalation and for the purpose of this study, each participant will be given an IMST device and will be trained in how to take deep breaths with the device placed in their mouths. The device will be tailored to each participant’s inspiratory strength and overall medical condition. A dial allows for increasing the resistance of the device. In this study, participants will receive a pulmonary function test to assess maximal inspiratory pressures (PI max) produced at the mouth during static efforts. The device offers resistance when breathing in, and this is adjusted using a spring-loaded valve. In this study, participants will perform 30 inspiratory maneuvers (5 sets of 6, 1‐minute rest between sets), 5 days per week, for 12 weeks.

Cleaning the device and disinfection protocol: The following instructions will be provided orally and in writing to the participants. These instructions have been taken from the device website as different types of IMST devices have different protocols. 

“Your POWERbreathe breathing trainer will be exposed to saliva during use and we recommend that you clean it frequently to keep it hygienic and in good working order. It is recommended that you rinse your device after each use in warm running water and allow it to dry before your next training session.

Once a week, you may soak your POWERbreathe breathing device for about ten minutes in warm water that contains a mild soap. After cleansing, hold the IMT device upside down under a running tap so that water can run through the device to rinse it thoroughly. Shake off excess water and leave on a clean towel to dry. 

If further cleaning is necessary, such as if saliva is sticking the device together making it difficult to use, you may disassemble your device into its main component parts only (mouthpiece, main body, handle cover) and clean as above. Please be careful not lose any of the components and always refer to instructions provided by the study team when disassembling your device.”

Data Collection Instruments   

Data will be collected using a standardized questionnaire. Blood pressure will also be recorded by trained nurses. Blood pressure will be recorded every two weeks and other data will be recorded at baseline, 6 weeks and 12 weeks of intervention. Participant names and cell phone numbers will be collected on a locator form to allow for collection of information on adherence and safety during the study. This form will be stored separately from other study documents in a locked cabinet accessible only to study staff. Following a standardized protocol, training and support will be provided to participants on the proper use of the POWERbreathe K3 IMST device and proper adherence to the intervention for five days each week for 12 weeks. Baseline data on participants’ medical history, hypertensive status, inspiratory muscle strength and other sociodemographic variables will be obtained. A follow-up schedule involving regular assessments of blood pressure, inspiratory muscle strength, and overall health status will be carried out at baseline and visits at weeks 2, 4, 6, 8, 10 and 12. For the first month, participants will receive bi-weekly calls to check adherence, answer any questions, and encourage adherence. We will compare the outcomes of the participants in the IMST intervention with others in the community who have similar hypertension measures but are not using the POWERbreathe K3 IMST device at high resistance. To monitor the trend of the primary outcome (SBP), two blood pressure (BP) measurements will be obtained at baseline and averaged for each participant with the use of a digital Omron blood pressure monitor HEM-1040 observing the standardized protocol provided by the manufacturer with regards cuff size, application, body position and time intervals between measurements. This procedure will also be observed for subsequent BP measurements every two weeks until the 12^th week post-enrollment. 

Data Management and Analysis

The Primary outcomes for this study will be changes in measures of systolic and diastolic blood pressure from baseline to end of intervention and between intervention and comparison groups. Potential mediators include demographics, socioeconomic status, and comorbidities (depression, obesity, diabetes). Generalized linear mixed modeling techniques will be used to determine if IMST improves BP.The data collection instruments will be reviewed for completeness following, which quantitative data will be entered into a secured laptop, and the paper instruments will be stored in office cabinets under lock and key; both the laptop and cabinet will be accessible to me and my mentors only. Data quality checks will be programmed into the data collection templates to minimize data entry errors. Cleaned data will be analyzed using SAS statistical software version 17.0. Categorical demographic variables will be presented as frequencies and percentages, while continuous variables will be presented as means and standard deviations. Students’ t-test and ANOVA will be used to test the association between continuous variables, while Pearson’s chi-square tests will be employed to assess relationships between categorical variables. A linear-mixed effects model will be used to determine the effect of the intervention. Statistical significance will be set at p<0.05.