Chronic obstructive pulmonary disease (COPD) is a progressive respiratory condition characterized by chronic bronchitis and emphysema [1]. It is the third-leading cause of death worldwide [2] and is responsible for high levels of health care use because of frequent respiratory exacerbations [3]. Individuals with COPD experience significant airflow obstruction and dynamic hyperinflation of the lungs, leading to symptoms of dyspnea, sputum production, chronic cough, and fatigue [1]. Skeletal muscle dysfunction, comprising decreased muscular strength and endurance, is also a common consequence of COPD and is driven by a combination of several mechanisms, including muscle atrophy, altered fiber type, and impaired metabolism [4]. Collectively, these changes contribute to diminished exercise capacity, limitations in activities of daily living (ADLs), and reduced health-related quality of life (HRQL) among individuals with COPD [5].

A growing body of research has demonstrated the presence of limitations across several domains of cognition among individuals with COPD [6]. Decreases in attention, memory, and visual-motor processing have been commonly reported [6-8]. The underlying mechanisms of cognitive impairment among individuals with COPD are complex and have been attributed in part to neural tissue hypoxemia and systemic inflammation [9,10].

Recent studies have indicated that COPD is associated with impaired dual-tasking performance [11,12]. Dual tasking, the performance of 2 tasks simultaneously, is an important aspect of executive function and is often required for the performance of routine daily activities, such as walking and talking. The performance of a cognitive task (eg, spelling words backward) while carrying out a physical task (ie, usual-paced walking) can result in decrements in cognitive or physical performance (eg, walking speed or distance) owing to competing attentional demands. Dual task decrements (difference between dual and single task performance) are often more pronounced in those with existing cognitive impairments or neurological conditions compared with those without these disorders [13,14]. Indeed, increased dual task decrements for both motor [12,15] and cognitive [16] performance have been found among people with COPD compared with healthy individuals [17]. There is emerging evidence indicating that cognitive-motor dual task performance impairment among patients with COPD is related to alterations in markers of prefrontal cortex neural activity and inefficiency, which may impede the executive function needed to plan one’s day [11,12,17]. Thus, combined cognitive-physical training may be a good strategy to improve neural efficiency in patients with COPD who may have a range of executive functional capacities. Cognitive training targeting attention, memory, executive functioning, and speed of processing when combined with physical exercise training may provide the neuroplasticity to derive synergistic benefits on the performance of ADLs and physical function [18-20].

Pulmonary rehabilitation is considered a primary management approach for moderate to severe COPD and has been shown to reduce dyspnea and increase exercise capacity, leading to improvements in daily function and HRQL among individuals with COPD [21]. To date, pulmonary rehabilitation strategies have typically focused on education (eg, medication management, breathing techniques, and stress reduction) and physical training (ie, aerobic and strength exercises) [21,22]. Currently, cognitive training is not included in most pulmonary rehabilitation programs despite evidence that cognitive impairments are common among individuals with COPD and are associated with greater functional limitations, decreased HRQL, and increased health care use in this population [8,23].

Several barriers limit engagement in pulmonary rehabilitation for people with COPD, including factors related to the environment (eg, travel and wait times), knowledge (eg, referral processes), and beliefs (eg, perceived benefits) [24]. Recently, accessibility has been further complicated by the COVID-19 pandemic. For these reasons, there is increasing interest in home-based pulmonary rehabilitation programs as an alternative strategy for COPD management compared with center-based pulmonary rehabilitation programs [25-27]. Several studies have demonstrated the safety and feasibility of remote telerehabilitation interventions for patients with COPD, with high levels of compliance with home training and no adverse events [28-30]. There is meta-analytic evidence from systematic reviews also indicating that the effects of home-based pulmonary rehabilitation interventions are similar to those of traditional outpatient programs for outcomes including dyspnea [26,27], exercise capacity [26,31], and HRQL [26,31], potentially offering increased accessibility to those with travel restrictions [32]. However, most studies on telerehabilitation for COPD have required study assessments to be conducted in person, and none have included remote assessment of functional testing, cognitive assessments, or dual task performance, a knowledge gap that this study hopes to address [27].

The specific aims of this study are to evaluate the feasibility (ie, recruitment rate, program adherence, attrition, safety, and participant satisfaction) of an 8-week individualized, home-based cognitive-physical training program for patients with moderate to severe COPD and derive preliminary estimates of cognitive-physical training intervention efficacy on measures of cognitive and physical function, dual task performance, ADL, and HRQL. We hypothesize that it will be feasible to safely recruit patients with COPD into a home-based cognitive-physical training program with 75% adherence and high satisfaction ratings with the prescribed training. We also hypothesize that the cognitive-physical training group will demonstrate greater beneficial effects on cognitive function, dual task performance, ADL, and HRQL compared with the physical training group.

This is a pilot randomized controlled trial (RCT) to assess the feasibility of a full-scale, adequately powered RCT evaluating a home-based combined cognitive-physical training program for patients with moderate to severe COPD. The study takes place at the University Health Network (UHN) in Toronto, Ontario, Canada, but has been expanded to include recruitment from community respirology clinics not affiliated with the UHN.

Research ethics approval was obtained through the research ethics board of the UHN (study ID: 21-5336), and the study has been registered at ClinicalTrials.gov (NCT05140226). Informed consent will be obtained from participants before study enrollment.

The study sample will consist of older adults (aged ≥50 years) with a clinical and spirometric diagnosis of moderate to severe COPD (postbronchodilator forced expiratory volume in the first second [FEV₁]/forced vital capacity of <0.70 [or lower limit of normal of FEV1/forced vital capacity] and FEV₁=30%-79%). Participants will be required to have access to a reliable internet connection and be able to mobilize independently and safely with or without a walking aid. Exclusion criteria include the following: (1) current participation in supervised in-person or an internet-based pulmonary rehabilitation program; (2) COPD exacerbation in the previous 3 months to ensure clinical stability; (3) presence of cardiovascular, neurological, or musculoskeletal conditions that could interfere with the safe performance of study procedures (eg, unstable coronary artery disease, heart failure, stroke, myopathy, or moderate to severe arthritis); (4) severe cognitive impairment ascertained through chart review or self-report (eg, severe dementia or inability to perform ADLs independently); (5) medical instability (eg, hepatic dysfunction, metabolic abnormality, or active infection); (6) overt psychiatric disorder or substance abuse; (7) current use of home oxygen therapy; (8) insufficient English fluency to carry out testing and training; and (9) being listed for lung transplantation.

Participants will be recruited during routine visits to outpatient respirology clinics at UHN in Toronto, Ontario, Canada, and local respirology clinics. Clinic personnel within the circle of care will introduce the study to patients with COPD and ask if they are interested in participating. If interested, a member of the research team will then contact the potential participant to screen for eligibility criteria, review study procedures, and obtain informed consent. The study recruitment poster will also be provided to medical personnel at local respirology clinics who will introduce the study to patients with COPD and instruct them to contact the research team if they are interested in pursuing study participation.

The study timeline is shown in Figure 1. After completing consent procedures, participants will receive a package by mail containing the following study equipment: Fitbit Charge 4 device (Fitbit Inc), foot peddler (VANGONA D2 pedal exerciser), pulse oximeter, resistance bands (Thera-Band), measuring tape, and exercise manual. They will also receive an email with instructions on how to access the internet-based appointment platform (Microsoft Teams; Microsoft Corp) on their devices. Following receipt of study materials, participants in both groups will be booked for a 45-minute videoconferencing familiarization session. During the familiarization session, participants will be introduced to the study equipment and software, their safety in performing remote physical testing will be assessed, and study assessment procedures will be explained. Furthermore, appropriate equipment setup for remote testing will be determined, and participants will have the opportunity to practice the physical assessment tests. After the familiarization session, participants will be booked for the baseline assessment session (1 hour) to complete the assessment measures described in the following sections.

After the baseline assessment, participants will be randomized to either the cognitive-physical training (intervention) group or the physical training (control) group using a 1:1 ratio. Randomization will be performed using shuffled opaque envelopes containing the group assignment. Given the pilot stage of this research and the nature of exercise interventions, group allocation will be known to the research team, exercise professionals, and study participants.

Our research team is trained in the study processes, measurement protocols, and institutional requirements. We have received peer review comments from the Canadian Lung Association (Multimedia Appendix 1) and incorporated this feedback into the study protocol. Standard operating procedures are in place for all study procedures. The research team will make every effort to have participants complete all study elements, and incomplete or missing data will not be imputed. All participants will be closely supervised by the exercise professional, who will support adherence and accurate data collection.

As per national and institutional research guidelines, all participants will be given a unique study ID to be used in place of their name for all study data. Physical data collection forms and data collected from questionnaires will be kept in a cabinet in the principal investigator’s office under lock and key. Electronic data will be stored on a password-protected research server. Once data collection is complete, deidentified data will be exported to statistical software for analysis.

COPD is associated with several physical and cognitive impairments contributing to limitations in daily activities that often involve the simultaneous performance of a physical (eg, walking) and cognitive (eg, talking) task, known as dual tasking. The benefits of pulmonary rehabilitation in reducing COPD symptoms and improving daily function are well established [21], and it is known to be feasible and effective when delivered remotely in the home environment via telehealth [26,27,31]. However, traditional pulmonary rehabilitation programs typically focus mainly on physical exercise training without addressing cognitive function despite evidence that many patients with COPD have some cognitive limitations, which can contribute to greater functional limitation, increased health care use, and decreased HRQL [6,23]. Patients with COPD with cognitive limitations are also at increased risk of noncompletion of pulmonary rehabilitation [59], suggesting that a better understanding of cognitive limitations and approaches to improve cognition may lead to better adherence and outcomes. However, to date, no studies have examined a pulmonary rehabilitation approach that specifically combines both physical and cognitive training. Therefore, this protocol describes a pilot RCT that is entirely internet based and home based and combines cognitive and physical training in patients with COPD with the aim of further improving daily function and HRQL beyond traditional pulmonary rehabilitation approaches.

Cortical activity is essential for all motor performance, ranging from complex activities to basic ADLs; thus, the benefits derived from cognitive training can be obtained even in those with normal cognition [60]. Cognitive training has been shown to be more effective in those completing a physical exercise intervention as the neural network is primed for neuroplasticity. Thus, cognitive training may be a complementary strategy in conjunction with physical exercise to improve dual tasking in patients with COPD, which is often required during routine daily activities (eg, talking or avoiding obstacles while walking). COPD is associated with impaired dual-tasking performance, manifested as changes in dual task gait properties, including reduced gait speed [12] and increased gait variability [15]. There is also evidence from our group that loss of neural automaticity may be an underlying mechanism contributing to slower gait speed among individuals with COPD [11]. Collectively, these changes suggest that cognitive limitations may arise from increased attentional demands and neural inefficiency, which may contribute to decreased cognitive and physical performance in COPD [17]. Although traditional pulmonary rehabilitation does not appear to improve dual task gait in patients with COPD [15], cognitive training is known to produce distinct benefits on dual task reaction time [61] and has been shown to independently improve measures of functional mobility among healthy older adults [62]. Therefore, the addition of cognitive training may help improve neural efficiency and attentional capacity in patients with COPD, leading to improvements in dual-tasking ability that may translate to better performance in daily activities and HRQL and reduction in the risk of falls.

Clinical practice guidelines established by several leading organizations recommend cognitive training as a strategy to decrease the risk of cognitive decline (World Health Organization; American Academy of Neurology; National Academies of Sciences, Engineering, and Medicine; and Agency for Healthcare Research and Quality) [63-66]. These recommendations were largely established based on strong scientific evidence in the form of meta-analyses showing both near and far transfer effects from cognitive training in older community-dwelling adults, those with mild cognitive impairment, and those with dementia [67-71]. BrainHQ by Posit Science is a computerized cognitive training platform offering game-based exercises that target the speed and accuracy of information processing across the domains of attention, memory, spatial navigation, executive function, and emotional processing. In the largest RCT on cognitive training to date involving 2832 healthy older adults, speed-of-processing training on BrainHQ was found to improve cognitive and functional performance to a greater extent than other forms of memory or reasoning training, which translated to a reduction in risk of impairments in daily activity performance and an increase in reported quality of life that remained at follow-up of 5 to 10 years [72]. BrainHQ training resulted in improved visual processing speed and accuracy, and these improvements were associated with improved balance and smaller decrements in dual task gait speed among older adults [73,74], which has important implications for patients with COPD who are at risk of falls [42]. To our knowledge, this study will be the first to explore BrainHQ cognitive training in a population of individuals with chronic lung disease.

Given the breadth of impairments associated with COPD and the complexity of routine daily activities, the rehabilitation approach described in this paper combining physical exercise with cognitive training targeting attention, memory, executive functioning, and speed of processing may offer the flexibility to further improve daily function and reduce the risk of falls in patients with COPD beyond physical training alone. Notably, the cognitive training modality to be implemented in this study is distinct from the proposed dual task outcome measure, supporting the potential transfer of gains to a variety of daily activities.

There are several strengths to this study. The physical training program and assessments were specifically designed to support feasibility and safety in the home environment. All participants will be provided with exercise training equipment (foot peddler, resistance bands, Fitbit, and pulse oximeter), which will improve safety and accessibility and standardize physical training and assessments. This study is novel as it provides a new approach to remote assessments of aerobic endurance (ie, foot peddler), functional outcomes, and cognitive assessment and training as part of a home-based pulmonary rehabilitation program for patients with COPD [27]. Our protocol may optimize not only accessibility but also outcomes in home-based pulmonary rehabilitation programs. The use of commercially available software programs (Fitbit, Physiotec, and BrainHQ) supports the future clinical translation of this work as these and other similar programs may be used by clinicians and patients looking to integrate cognitive-physical training into pulmonary rehabilitation programs. Furthermore, the chosen cognitive training platform (BrainHQ) has the largest evidence base and, to our knowledge, is the only brain training program that meets all the National Academy of Medicine criteria for cognitive training [29,30]. Our specific cognitive training protocol was designed in consultation with neuropsychology and cognitive science experts to specifically target common areas of deficit among individuals with COPD.

We also acknowledge that there are limitations to the design of this study. Given the small sample size, we will be unable to adjust the analyses for potential confounders such as medications (opiates, sedatives, or corticosteroids) or COPD exacerbations; however, these factors will be tracked throughout the study period to explore their influence on selected outcomes. This study will be conducted entirely remotely, and therefore, we are unable to prospectively measure specific tests of outcomes such as pulmonary function (ie, spirometry) or neural activity (ie, functional near-infrared spectroscopy). However, some of this information will be derived from chart review or will require future study. Furthermore, cognitive assessments will be completed independently at home, and differences in device or screen size (ie, computer vs tablet) may influence the results. Participants who do not have access to a suitable device will be provided with a tablet for the duration of the study. Owing to the nature of the training intervention and internet-based environment, blinding of participants and the exercise professional is not possible, thus creating a risk of bias. Furthermore, most of the physical training measures and intensity will be ascertained through self-report, which may not be as accurate as if they were captured electronically from the training devices.

A partly supervised, home-based, telehealth cognitive-physical training program may be an accessible intervention to improve cognitive function and further address dual-tasking abilities in people living with COPD. Evaluating the feasibility and effect estimates is a critical first step to inform future clinical trials evaluating this approach and its effects on physical and cognitive function, ADL performance, and HRQL.