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Chronic obstructive pulmonary disease (COPD) is a heterogeneous chronic lung condition often accompanied by comorbidities and systemic manifestations that affect the person’s clinical condition and prognosis and often require specific treatment. Therefore, the management of COPD extends beyond treatment for the lungs per se. Pulmonary rehabilitation (PR) should be considered as part of person-centered management, and supervised exercise training is a core component of this intervention. PR exercise training parameters (e.g., frequency, intensity, time, and type) should be individualized to maximize each individual’s functional gains while targeting systemic manifestations and comorbidities. This manuscript presents evidence-based tailored recommendations for optimizing exercise interventions for people with COPD and comorbidities that significantly affect prognosis (e.g., mortality, hospitalizations) including cardiovascular disease (CVD) (e.g., chronic coronary syndrome, heart failure), CVD risk factors (e.g., type 2 diabetes mellitus [T2DM], hypertension), and sarcopenia. To achieve these goals, existing guidelines and evidence for exercise training in COPD, CVD, CVD risk factors, and sarcopenia have been reviewed to identify synergies between PR and cardiac rehabilitation, as well as the treatment of T2DM and sarcopenia. In addition, we provided clinical cases to illustrate how PR can be adapted to accommodate specific comorbidities. These examples offer practical guidance for tailoring exercise prescriptions within PR programs to address the unique needs of people with COPD and clinically relevant comorbidities, thereby enhancing overall treatment effectiveness and optimizing health outcomes.

Background: Extrapulmonary manifestations including cognitive impairment, reduced muscle and cardiovascular function is common in COPD. While high-intensity exercise offers extrapulmonary benefits, its implementation in COPD is challenging. This randomised cross-over trial examined the feasibility and physiological responses of a novel supramaximal high-intensity interval-training (SupraHIIT) protocol compared to moderate-intensity continuous training (MICT) in people with COPD and matched healthy controls (HCs).

Methods: Sixteen people with COPD and 16 HCs performed SupraHIIT and MICT. SupraHIIT consisted of 10x6 sec intervals at ≈150% and ≈200% of maximum aerobic power (MAP), while MICT was performed for 20 min at 60% of MAP. Outcomes were exercise intensity, change in exerkines, feasibility, and cardiorespiratory demand of the modalities.

Results: SupraHIIT was feasible and enabled up to a 3.5-fold increase in external exercise intensity compared to MICT (184±66 and 245±88 watt versus 71±22 watt in COPD, p<0.001). All participants could complete SupraHIIT which was the preferred modality in both groups (p<0.01) while 5/16 participants with COPD interrupted MICT due to intolerable dyspnea or exhaustion (p=0.005). Both modalities increased plasma brain-derived neurotrophic factor (pBDNF) by an average of 59% (range 30%-87%, p<0.05). When normalised for duration at target power, SupraHIIT produced a 5–10-fold greater increase than MICT. Both modalities lead to a variable response in other exerkines including clusterin, lactate, hepatocyte growth factor and interleukin-6.

Conclusion: In COPD, short duration SupraHIIT is more feasible and enables markedly higher external exercise intensities than MICT. By elevating pBDNF and other potentially beneficial exerkines, it shows potential for extrapulmonary benefits.

Background Cognitive impairment is increasingly recognized as an extrapulmonary manifestation of COPD, yet little is known across cognitive domains and associations with exercise capacities and inflammation remain underexplored.

Aims and objectives: To compare cognitive function in COPD and age-, sex- and physical activity matched healthy controls (HCs) and examine associations with exercise performance and systemic inflammation.

Methods: Multi-domain cognitive function was assessed at baseline in 44 individuals with COPD and 39 matched HCs. Correlations of exercise performance including CPET Wpeak and anaerobic capacity (Borg cycle strength test [BCST Wpeak]) and inflammation were analysed.

Results: COPD participants exhibited lower cognitive function across most domains compared to HCs (Table 1). In COPD, BCST Wpeak correlated with trail making tests ([TMT] TMT-A: r=-.43; TMT-B: r=-.32; p<0.05)) visual processing (VP1: r=.43; p<0.05) and memory (PAL: r=.35; p<0.05), while CPET Wpeak showed no associations. Higher fibrinogen levels correlated with poorer TMT-B and PAL1 performance (r=.38 & r=-.40; p<0.05).

Conclusion: Cognitive impairment spans across multiple domains in COPD, even in those with relatively preserved fitness and lung function. Cognitive deficits were associated to anaerobic, but not aerobic exercise capacity and were associated with systemic inflammation in some, but not all domains.

Introduction: Resistance training (RT) is crucial in pulmonary rehabilitation to counteract muscle dysfunction in COPD. However, knowledge about how progression of RT volume is associated with changes in muscle function and functional capacity in COPD is limited.

Method: This secondary analysis from a multicenter RCT included 57 COPD patients (70±7 yrs, FEV1% 49±21, 58% male) who performed 8 weeks of either RT to improve muscle strength or to non-linear periodized resistance training (NLPRT) focusing on muscle strength and muscle endurance. Assessment of muscle strength, muscle endurance and functional capacity (1–Minute Sit-To-Stand, Endurance Shuttle Walk Test, and Unsupported Upper Limb Exercise Test) were conducted at baseline and after 8 weeks. Progression of training volume (set x reps x load) was calculated as the percentage change from week one to week eight.

Results: Significant associations were found between training volume progression and muscle endurance for both RT (r=.48) and NLPRT (r=.64). Significant associations were also identified between progression of training volume and muscle strength for RT (r=.50) and NLPRT (r=.52) (all <0.05). Progression of training volume was not associated with changes in functional capacity.

Discussion: The result from this study indicates that the progression of resistance training volume over time is associated with greater effects on muscle endurance and muscle strength in people with COPD.

Accurate prescription of supramaximal exercise requires exercise tests covering the intensity domain between maximal aerobic and peak power output. All-out tests are commonly used for this objective but are considered challenging for people with chronic obstructive pulmonary disease (COPD) due to the extreme physiological demand. The modified Borg cycle strength test (mBCST), previously used in older adults to achieve supramaximal intensities, might be a suitable alternative in people with COPD. We aimed to determine the feasibility of the mBCST in people with COPD and to compare the physiological response with that of healthy older adults. Eighteen people with COPD and 16 age-, sex- and physical activity-matched healthy adults performed a cardiopulmonary exercise test and a mBCST. The mBCST is an incremental test [30 s:30 s cycling:rest; with individualized starting load and step size (15-50 W)] with end-of-test criteria of a rating of perceived exertion of >= 17 or cadence of <75 RPM for >5 s. Feasibility was assessed using a framework covering the aim, interpretability, familiarity, duration, scoring/completion complexity, costs and safety. Measurements of external exercise intensity, rating of perceived exertion, symptoms and cardiorespiratory demand were obtained. The mBCST was deemed feasible according to the feasibility framework. Expressed relative to the cardiopulmonary exercise test, all participants reached supramaximal external exercise intensities during the mBCST [COPD, 145 (125-168)%; healthy, 154 (148-163)%], without differences in intensity or physiological response between groups (p > 0.05). The mBCST is feasible in people with COPD and enables supramaximal external exercise intensities, with similar physiological response to healthy older adults. The mBCST could be considered when selecting an exercise test to prescribe supramaximal exercise.

Background: A novel concept of controlled, short-duration supramaximal HIIT enables 3-4 times higher exercise intensities with reduced dyspnea, compared to moderate-intensity continuous training (MICT) in people with COPD. However, its effects on neurotrophic factors and brain health are yet to be investigated. We aimed to examine the acute response of neurotrophic factors to supramaximal HIIT and MICT in people with COPD.

Methods: Sixteen people with mild to severe COPD (75±6 years; 73±13 FEV1%pred) underwent supramaximal HIIT (comprising 10x6 sec intervals interspersed with 54 sec rest) and MICT (20 min at 60% CPET Wpeak). Supramaximal HIIT was performed at two intensities (HIIT60% and HIIT80%). We measured plasma levels of brain-derived neurotrophic factor (BDNF), irisin, cathepsin B and clusterin pre- and post- exercise.

Results: BDNF increased after both HIIT and MICT (Fig 1). Clusterin increased during HIIT80% (19940 [−35900 to 49600] ng/mL, +11%, p=0.01) and MICT (23390 [−5060 to 51010] ng/mL, +12%, p=0.03), but not HIIT60% (−1100 [−10060 to 113600] ng/mL, -1%, p=0.85). No changes were seen in irisin or cathepsin B.

Conclusion: For the first time, we showed that in COPD, supramaximal HIIT induces a similar increase in BDNF as MICT, with half the exercise duration. Supramaximal HIIT might be a viable exercise modality in COPD, while its long-term effects on brain health remain to be investigated.

Background: Beyond being a pulmonary disease, chronic obstructive pulmonary disease (COPD) presents with extrapulmonary manifestations including reduced cognitive, cardiovascular, and muscle function. While exercise training is the cornerstone in the non-pharmacological treatment of COPD, there is a need for new exercise training methods due to suboptimal adaptations when following traditional exercise guidelines, often applying moderate-intensity continuous training (MICT). In people with COPD, short-duration high-intensity interval training (HIIT) holds the potential to induce a more optimal stimulus for training adaptations while circumventing the ventilatory burden often associated with MICT in people with COPD. We aim to determine the effects of supramaximal HIIT and MICT on extrapulmonary manifestations in people with COPD compared to matched healthy controls.

Methods: COPD-HIIT is a prospective, multi-centre, randomized, controlled trial with blinded assessors and data analysts, employing a parallel-group designed trial. In phase 1, we will investigate the effects and mechanisms of a 12-week intervention of supramaximal HIIT compared to MICT in people with COPD (n = 92) and matched healthy controls (n = 70). Participants will perform watt-based cycling two to three times weekly. In phase 2, we will determine how exercise training and inflammation impact the trajectories of neurodegeneration, in people with COPD, over 24 months. In addition to the 92 participants with COPD performing HIIT or MICT, a usual care group (n = 46) is included in phase 2. In both phases, the primary outcomes are a change from baseline in cognitive function, cardiorespiratory fitness, and muscle power. Key secondary outcomes include change from baseline exercise tolerance, brain structure, and function measured by MRI, neuroinflammation measured by PET/CT, systemic inflammation, and intramuscular adaptations. Feasibility of the interventions will be comprehensively investigated.

Discussion: The COPD-HIIT trial will determine the effects of supramaximal HIIT compared to MICT in people with COPD and healthy controls. We will provide evidence for a novel exercise modality that might overcome the barriers associated with MICT in people with COPD. We will also shed light on the impact of exercise at different intensities to reduce neurodegeneration. The goal of the COPD-HIIT trial is to improve the treatment of extrapulmonary manifestations of the disease.

Background: Breathlessness is common in the population and can be related to a range of medical conditions. We aimed to evaluate the burden of breathlessness related to different medical conditions in a middle-aged population.

Methods: Cross-sectional analysis of the population-based Swedish CArdioPulmonary bioImage Study of adults aged 50–64 years. Breathlessness (modified Medical Research Council [mMRC] ≥ 2) was evaluated in relation to self-reported symptoms, stress, depression; physician-diagnosed conditions; measured body mass index (BMI), spirometry, venous haemoglobin concentration, coronary artery calcification and stenosis [computer tomography (CT) angiography], and pulmonary emphysema (high-resolution CT). For each condition, the prevalence and breathlessness population attributable fraction (PAF) were calculated, overall and by sex, smoking history, and presence/absence of self-reported cardiorespiratory disease.

Results: We included 25,948 people aged 57.5 ± [SD] 4.4; 51% women; 37% former and 12% current smokers; 43% overweight (BMI 25.0–29.9), 21% obese (BMI ≥ 30); 25% with respiratory disease, 14% depression, 9% cardiac disease, and 3% anemia. Breathlessness was present in 3.7%. Medical conditions most strongly related to the breathlessness prevalence were (PAF 95%CI): overweight and obesity (59.6–66.0%), stress (31.6–76.8%), respiratory disease (20.1–37.1%), depression (17.1–26.6%), cardiac disease (6.3–12.7%), anemia (0.8–3.3%), and peripheral arterial disease (0.3–0.8%). Stress was the main factor in women and current smokers.

Conclusion: Breathlessness mainly relates to overweight/obesity and stress and to a lesser extent to comorbidities like respiratory, depressive, and cardiac disorders among middle-aged people in a high-income setting—supporting the importance of lifestyle interventions to reduce the burden of breathlessness in the population.

Introduction: Resistance training (RT) is a key component of pulmonary rehabilitation for people with COPD; however, whether the effects of RT could be optimized by utilizing the exercise principle of non-linear periodization is yet to be determined.

Method: An international multicenter RCT was conducted across three countries. Fifty-seven people with COPD (70+7 yrs, FEV1% 49+21, 58% male) were randomized to 8 weeks of RT designed per current COPD guidelines to improve muscle strength or to non-linear periodized resistance training (NLPRT) designed to improve muscle strength [4 weeks] but also muscle endurance [4 weeks]. Outcomes included muscle strength, muscle endurance, functional exercise capacity (1-minute sit-to-stand [1-STS], endurance shuttle walk test [ESWT], Unsupported Upper Limb Exercise test [UULEX]), and disease-specific quality of life (QoL). Intention-to-treat (ITT) analysis was utilized, and Cohen's D Effect Sizes [ES] were calculated.

Result: ITT analysis demonstrated that NLPRT resulted in more pronounced effects on muscle strength (+33% vs. +21%, ES 0.928), muscle endurance (+147% vs. +50%, ES 1.080), ESWT (+168m vs. +36m, ES 0.592), 1-STS (+4 STS vs. 1 STS, ES 0.864), UULEX (+142sec vs. + 42sec, ES=0.819) (all p<0.05) when compared to RT. Both NLPRT and RT resulted in clinically relevant improvements in QoL without differences between modalities.

Conclusion: These results indicate that 8 weeks of NLPRT yields significantly better outcomes in various dimensions of muscle function and functional capacity when compared to 8 weeks of traditional RT. Consequently, this suggests a potential need for reevaluating and updating current RT guidelines to incorporate these findings.