Translational Potential of High-resistance Imst
The ability of high-resistance IMST to improve CV function while overcoming multiple barriers to adherence suggests it has potential for public health implementation. However, investigation of high-resistance IMST has been limited to the clinical research setting. Initial translational evidence for IMST outside of the controlled research environment is available for low- to moderate-resistance IMST protocols of various durations. Accordingly, for the purposes of this review, we will summarize findings on adherence, safety, tolerability, feasibility, and implementation outcomes from home-based, low- or moderate-resistance IMST trials, as these studies provide key insights regarding potential efficacy and challenges for translating high-resistance IMST to the public health arena. We acknowledge that dissemination, implementation, and full-scale public health translation have their own frameworks and deep science structure. In this Perspective for Progress, the focus is on translating initial findings on physiological efficacy and providing a broad overview of future areas of research. As such, a full discussion of framework models is outside the scope of this review.
An important aspect of translating IMST out of the clinical setting and into the public health sector is an understanding of the methods by which investigators could track the progression of individuals through an IMST intervention without study team interaction. Some studies have had participants perform completely unsupervised, home-based IMST with adherence self-reported through diaries.[90–93] Although a useful design in its simplicity, self-reporting adherence in physical diaries runs the risk of subjects losing their diaries, or incorrectly or incompletely filling them out, as has been reported in an IMST trial using this strategy. Other studies have scheduled weekly phone calls with subjects to track adherence, monitor progress, and assist with altering the training intensity for those in the experimental groups.[92,93,95] Regular phone calls allow researchers to track participants more accurately through the intervention compared with training diaries. However, participants may feel more accountable when they are required to regularly report intervention adherence to investigators and therefore may be more motivated to adhere to IMST than they otherwise would under unsupervised settings. Accordingly, regular contact with the research team, even when done remotely, may bias participant adherence and limit the translational knowledge gained from this type of design.
To overcome these issues, IMST training devices that automatically record and store training data have been used. Internal data storage allows for objective recording of intervention adherence and progression (e.g., changes in training load or achieved inspiratory volumes during training sessions).[95,96] Although these recordings overcome certain research limitations associated with self-reported information, objective documentation of training data does not help with IMST translation and implementation per se.
Web-based platforms have been used to implement IMST outside of the clinic. In one study, patients with chronic obstructive pulmonary disease (COPD) were assigned to 12 wk of home-based IMST with or without Internet-based feedback. After each training session, the Internet-based feedback group self-reported their rating of perceived exertion; in response, these participants would receive suggestions for adjusting their training intensity. Participants in the no-feedback group reported adherence via paper diaries and did not receive training-related suggestions. Although no direct, verbal communication was made between participants and investigators, those in the web-based feedback group exhibited higher rates of adherence to IMST than those not receiving feedback (87% vs 67% of prescribed training sessions completed). This finding supports the role of accountability via eHealth strategies for promoting adherence to home-based IMST.
Currently, studies investigating the efficacy of time-efficient, high-resistance IMST have used either daily or weekly in-person instructional and supervised sessions.[58,65–68] These studies have all demonstrated the excellent safety and tolerability (i.e., ability to tolerate any side effects to maintain participation) profile of high-resistance IMST. However, due to the regular supervision of training sessions, the feasibility of users effectively progressing through an unsupervised home-based high-resistance IMST intervention is unknown.
Importantly, small feasibility trials for home-based, moderate-resistance IMST were performed in clinical populations,[96,98] and provided initial insight on the ability of individuals to perform an IMST intervention without researcher oversight. In one study, adults with stable COPD performed 8 wk of moderate-resistance IMST (60% PIMAX, 30 breaths twice per day, 5 d·wk−1), with one session supervised in person. After this 8-wk run in period, participants continued training completely unsupervised, 3 d·wk−1, for an additional 18 wk. Seven of the 10 subjects enrolled completed the entire intervention. IMST was found to be acceptable, with most participants expressing confidence in their skill and ability to use the IMST device and perform the intervention. Additionally, adherence during the unsupervised sessions was high (91% of prescribed training sessions completed), but ranged from 22% to 162%, indicating low use by certain participants but a desire to perform more than the prescribed number of training sessions by other participants. This suggests home-based IMST is feasible in this population and warrants a larger trial.
In another trial assessing the feasibility and tolerability of IMST in patients recovering from pneumonia, subjects performed IMST twice daily for 9 wk at 50% PIMAX with weekly supervised training sessions. IMST was safe, with side effects of training reported in only 15 of 1183 training sessions. Importantly, side effects did not prevent further training, indicating the IMST intervention was tolerable. Patient-reported acceptability of IMST, such as finding IMST to be an attractive or agreeable intervention, was 99.4%.
In studies reporting adherence to home-based IMST interventions, participants in the experimental (IMST) groups completed 76% to 91% of assigned training sessions.[90,92,94,96,97] Notably, the populations enrolled in these studies included healthy older adults, adults with stable COPD, patients with heart failure, and stroke survivors. This broad range of populations investigated suggests implementation of home-based IMST is feasible across groups with varying health statuses and physical limitations.
Finally, clinic-based studies assessing time-efficient, high-resistance IMST have reported high rates of adherence, with at least 94% of prescribed training sessions completed.[58,65–68] However, whether adherence to high-resistance IMST remains high when performed at-home, without regular supervision, requires investigation. Critically, whether unsupervised, high-resistance IMST programs can effectively improve CV function has not been determined.
Potential for Digital Health Technologies to Advance IMST
Although available studies support the translational potential of high-resistance IMST as an adherable intervention, a crucial limitation to date is that all current studies have used investigator-led instruction on how to perform IMST. Indeed, that there is no current route for administering and disseminating high-resistance IMST outside of the clinical research setting is a serious limiting factor for public health translation.
As discussed, digital health technologies are effective for delivering aerobic exercise interventions and are acceptable for use by midlife and older populations. Although not yet tested, digital health technologies also are likely to be effective tools to deliver and monitor high-resistance IMST interventions. For example, a majority of adults in America, including over three quarters of midlife and older adults, own a smartphone, which is kept on their person at most times. As such, high-resistance IMST could effectively be delivered through a smartphone app without appreciably altering user burden.
However, even with increasing smartphone ownership, there will still be barriers to technology uptake among midlife/older adults. Internet connection issues could pose a barrier to adherence. In fact, ~25% of adults 50 yr and older report having problems connecting to the internet. However, a greater proportion of adults younger than 50 yr (33%) report internet connection issues. This suggests internet connection is a general infrastructure barrier and not an issue of aging per se. Barriers related to technology adoption, such as physical and mental challenges or lack of comfort or familiarity with technology, also can impact older adults (age, ≥65 yr), with visual, cognitive, motor skills, and literacy barriers becoming more prevalent with increasing age.[101,102] Recently, there has been a trend toward teaching older adults technology skills, and more focus has been placed on user-centered technology design for older adults.[47,104] Incorporating these steps focused on increasing usability by older adults will be critical in the app design phase.
IMST devices that wirelessly pair with a smartphone app to deliver a high-resistance IMST intervention could be developed. Such apps could include features such as video instructions for IMST device use and training technique, training prompts or reminders, wireless data transfer between the app and device, and a user-tailored algorithm to automatically instruct and guide users through a high-resistance IMST intervention for improving CV function. The app also could pair with wireless home BP monitors and integrate this information with the IMST data to track changes in BP across the intervention period and notify users if their BP classification changes (e.g., if SBP dropped from the stage 1 hypertension into the elevated range).
Although such automated digital features will aid with effective uptake of high-resistance IMST, it is important to consider that reliance on expensive equipment has the potential to exacerbate current health disparities. Therefore, it will be crucial that any eventual app for delivering high-resistance IMST effectively works with more affordable, mechanical (i.e., non-digital) IMST devices that do not have the ability to automatically sync with a smartphone. Individuals using a mechanical IMST device will have to manually input training information into the accompanying smartphone app, which may decrease convenience. However, the cost difference between digital and mechanical IMST devices can be substantial, so the ability to use more affordable, mechanical IMST devices in conjunction with an app will reduce overall financial burden and make IMST accessible to a broader range of users.
Overall, leveraging the growing field of digital health technologies is likely to be an effective way to speed the dissemination and implementation of high-resistance IMST from the clinical research setting into the public health domain as a feasible strategy for improving CV aging.
Future Directions for Translating IMST Toward Public Health
Available evidence suggests high-resistance IMST performed in a clinical research setting is efficacious for improving CV function, particularly lowering SBP, and for promoting adherence in midlife and older adults. These encouraging initial results support initiating further translational research on high-resistance IMST with the ultimate goal of improving public health (Figure 4).
Translational potential for progress of high-resistance inspiratory muscle strength training (IMST) toward public health implementation. BP, blood pressure; CV, cardiovascular; RCT, randomized controlled trial.
As most studies to date have been small, proof-of-concept trials, the next step is to conduct larger, appropriately powered safety and efficacy trials to more definitively establish the CV health benefits of high-resistance IMST. Such larger trials in midlife and older adults (NCT05000515, NCT04848675), patients with obstructive sleep apnea (NCT04932447), and patients with chronic kidney disease (NCT04911491) have recently begun and will start to fill this knowledge gap. However, trials in additional patient populations with BP-associated risk, such as patients with glaucoma or mild cognitive impairment, also are warranted. Although the focus has primarily been on midlife and older adults, high-resistance IMST should also be considered for use in children with conditions associated with above-normal BP and increased lifetime risk of CVD, such as those with youth-onset type 2 diabetes mellitus. In addition, as high-resistance IMST only requires use of the respiratory muscles, it may be accessible for groups with physical limitations that restrict whole body exercise. Accordingly, high-resistance IMST should be assessed for improving CV function in those with spinal cord injury, orthopedic injuries, frail older adults, adults with excessive adiposity, or other conditions associated with elevated risk for CVD due to increased sedentary behavior.
A majority of ongoing trials are all using a similar high-resistance IMST paradigm (i.e., 30 breaths per day, 75% PIMAX, 5–6 d·wk−1). However, whether this commonly prescribed protocol represents the most efficacious high-resistance, low-repetition IMST intervention for improving CV function has not been determined. Additional trials will be needed to identify the optimal high-resistance IMST protocol that elicits the greatest CV health benefits, or find the minimal effective dose of high-resistance IMST for improving CV function, by modulating the training frequency, training time of day, intensity, and number of breaths per session. The larger sample sizes afforded by these clinical trials will also provide key information on the effectiveness of high-resistance IMST for improving CV function in important subgroups. For example, larger clinical trials should enable us to gather evidence as to whether the effectiveness of IMST varies based on sex, initial BP, medication status, or whether other important subject characteristics influence responsiveness.
If the efficacy of high-resistance IMST for improving CV aging is established in these appropriately powered clinical trials, the next step would be to perform pragmatic studies examining the comparative or added effectiveness of IMST to established therapies. Indeed, it will be important to compare the BP-lowering effects of high-resistance IMST to established lifestyle strategies, such as aerobic exercise or dietary sodium restriction, and to approved pharmacotherapies, to determine the equivalence (or superiority/inferiority) of IMST to current interventions. As high-resistance IMST is a time-efficient intervention, it also holds promise as an additive therapy. Thus, similar trials where IMST is performed in addition to current lifestyle strategies to see if there are added CV health benefits, will be important. Additionally, trials adding IMST to pharmacotherapy regimens can determine whether IMST decreases the number of medications or dose necessary to achieve BP control.
Such pragmatic trials will pave the way for multisite clinical trials with longer follow-up periods assessing the impact of high-resistance IMST on CV events, such as myocardial infarction and all-cause mortality. Multisite trials should include both healthy adults and those with established CVD to determine the ability of high-resistance IMST to both prevent and treat CVD.
If the clinical efficacy of high-resistance IMST for improving CV function and decreasing disease risk is established, and the results of comparative effectiveness trials support equivalency (or better) versus alternative strategies, uncovering effective avenues for dissemination and implementation of IMST will become important. As discussed, high-resistance IMST has qualities that suggest it would be acceptable for uptake and to promote adherence in real world settings. However, minimal data supporting this hypothesis are available.
Digital health technologies are a promising strategy for dissemination and implementation of high-resistance IMST. However, before such tools can be made available to the public, the efficacy of high-resistance IMST delivered via digital health technologies for improving CV function will need to be established. This will require first collecting input from potential users on the appropriateness, feasibility, and acceptability of receiving high-resistance IMST through proposed digital health technologies, such as smartphone apps, to create a vehicle to deliver IMST that is usable by the target population. Next, high-resistance IMST delivered via the digital health approach will need to be compared with researcher-supervised, clinic-based IMST for lowering BP and improving vascular function to ensure efficacy.
Once the efficacy of technology-delivered, high-resistance IMST for improving CV function is established, dissemination and implementation research can begin. Of particular importance will be testing digital health technologies for delivering IMST in underserved populations, such as in urban/rural settings or to racial and ethnic minorities who do not traditionally receive equitable access to health care. In addition, cost-benefit analyses will be needed to determine the health care and economic impact of uptake of high-resistance IMST. Such information will offer health care providers and insurance companies the information needed to determine the viability of providing free or reduced-price access to IMST devices and the accompanying digital health delivery system. Working with providers, along with underserved groups, will be critical for providing equal access to high-resistance IMST for all who may benefit from this promising lifestyle intervention.
Exerc Sport Sci Rev. 2022;50(3):107-117. © 2022 American College of Sports Medicine