A pilot study on the feasibility and effectiveness of treadmill-based perturbations for assessing and improving walking stability in chronic obstructive pulmonary disease

  • Christopher McCrum
    Correspondence
    Corresponding author at: Department of Nutrition and Movement Sciences, Maastricht University, PO Box 616, Maastricht, 6200, MD, the Netherlands.
    Affiliations
    Department of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, the Netherlands
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  • Anouk W. Vaes
    Affiliations
    Research and Development, CIRO, Horn, the Netherlands
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  • Jeannet M. Delbressine
    Affiliations
    Research and Development, CIRO, Horn, the Netherlands
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  • Maud Koopman
    Affiliations
    Research and Development, CIRO, Horn, the Netherlands

    Department of Respiratory Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, the Netherlands
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  • Wai-Yan Liu
    Affiliations
    Department of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, the Netherlands

    Research and Development, CIRO, Horn, the Netherlands

    Department of Orthopaedic Surgery, Máxima Medical Center, Eindhoven, the Netherlands

    Department of Orthopaedic Surgery, Catharina Hospital, Eindhoven, the Netherlands
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  • Paul Willems
    Affiliations
    Department of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, the Netherlands
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  • Author Footnotes
    1 Joint last authors.
    Kenneth Meijer
    Footnotes
    1 Joint last authors.
    Affiliations
    Department of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, the Netherlands
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  • Author Footnotes
    1 Joint last authors.
    Martijn A. Spruit
    Footnotes
    1 Joint last authors.
    Affiliations
    Research and Development, CIRO, Horn, the Netherlands

    Department of Respiratory Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, the Netherlands
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  • Author Footnotes
    1 Joint last authors.
Open AccessPublished:November 21, 2021DOI:https://doi.org/10.1016/j.clinbiomech.2021.105538

      Highlights

      • Treadmill-based gait perturbations are feasible in people with COPD.
      • People with COPD do not show large deficits in reactive gait stability.
      • People with COPD demonstrate some but reduced adaptability to perturbations.
      • Perturbation-based balance training may be considered for people with COPD.

      Abstract

      Background

      Falls risk is elevated in chronic obstructive pulmonary disease (COPD). However, there is a lack of evidence regarding the contributing factors. Here, we examined the feasibility of, and initial responses to, large walking perturbations in COPD, as well as the adaptation potential of people with COPD to repeated walking perturbations that might indicate potential for perturbation-based balance training in COPD.

      Methods

      12 participants with COPD undergoing inpatient pulmonary rehabilitation and 12 age-gender-matched healthy control participants walked on an instrumented treadmill and experienced repeated treadmill-belt acceleration perturbations (leading to a forward balance loss). Three-dimensional motion capture was used to quantify the stability of participants body position during perturbed walking. Feasibility, stability following the initial perturbations and adaptation to repeated perturbations were assessed.

      Findings

      Using perturbations in this manner was feasible in this population (no harness assists and participants completed the minimum number of perturbations). No clear, specific deficit in reactive walking stability in COPD was found (no significant effects of participant group on stability or recovery step outcomes). There were mixed results for the adaptability outcomes which overall indicated some adaptability to repeated perturbations, but not to the same extent as the healthy control participants.

      Interpretation

      Treadmill-based perturbations during walking are feasible in COPD. COPD does not appear to result in significant deficits in stability following sudden perturbations and patients do demonstrate some adaptability to repeated perturbations. Perturbation-based balance training may be considered for fall prevention in research and practice in people with COPD.

      Keywords

      1. Introduction

      Chronic obstructive pulmonary disease (COPD) is characterised by long-term respiratory symptoms and airflow limitation but also by many non-pulmonary features and comorbidities (
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      ). COPD leads to impaired balance performance in typical balance tests (
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      • Chueiro Jr., M.
      • Maia R.Q.
      • Ganança F.F.
      • Castro A.A.
      • Nascimento O.A.
      • Jardim J.R.
      Comparative postural control in COPD patients and healthy individuals during dynamic and static activities.
      ;
      • Roig M.
      • Eng J.J.
      • Macintyre D.L.
      • Road J.D.
      • Reid W.D.
      Postural control is impaired in people with COPD: an observational study.
      ;
      • Singh S.S.
      • Bhat A.
      • Mohapatra A.K.
      • Manu M.K.
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      Comparison of reaction time and functional balance in chronic obstructive pulmonary disease and healthy participants.
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      • Avram C.
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      • Petrescu L.
      • Timar B.
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      ) as well as differences in movement variability and stability during walking compared to healthy participants (
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      Differences in walking pattern during 6-min walk test between patients with COPD and healthy subjects.
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      • Wouters E.F.M.
      • Meijer K.
      Spatiotemporal gait characteristics in patients with COPD during the gait real-time analysis interactive lab-based 6-minute walk test.
      ;
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      • Schmid K.K.
      • Meijer K.
      • Spruit M.A.
      • Yentes J.M.
      Subjects with COPD walk with less consistent organization of movement patterns of the lower extremity.
      ;
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      • Berton D.C.
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      Limiting factors in walking performance of subjects with COPD.
      ;
      • Yentes J.M.
      • Sayles H.
      • Meza J.
      • Mannino D.M.
      • Rennard S.I.
      • Stergiou N.
      Walking abnormalities are associated with COPD: an investigation of the NHANES III dataset.
      ;
      • Yentes J.M.
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      • Blanke D.
      • Romberger D.J.
      • Rennard S.I.
      • Stergiou N.
      Gait mechanics in patients with chronic obstructive pulmonary disease.
      ). However, many fall risk factors are interrelated in COPD, making conclusions about the origin of balance and walking deficits, as well as falls, in COPD difficult (
      • Beauchamp M.K.
      • Sibley K.M.
      • Lakhani B.
      • Romano J.
      • Mathur S.
      • Goldstein R.S.
      • Brooks D.
      Impairments in systems underlying control of balance in COPD.
      ;
      • Janssens L.
      • Brumagne S.
      • McConnell A.K.
      • Claeys K.
      • Pijnenburg M.
      • Burtin C.
      • Janssens W.
      • Decramer M.
      • Troosters T.
      Proprioceptive changes impair balance control in individuals with chronic obstructive pulmonary disease.
      ;
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      • Guglielmetti S.
      • Giardini M.
      • Grasso M.
      • Giordano C.
      • Schieppati M.
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      Gait abnormalities of COPD are not directly related to respiratory function.
      ;
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      • Anderson G.P.
      • Clark R.A.
      • Thompson M.
      • Clarke S.
      • Baker T.
      • Irving L.B.
      • Denehy L.
      Balance and falls in acute exacerbation of chronic obstructive pulmonary disease: a prospective study.
      ;
      • Ozalevli S.
      • Ilgin D.
      • Narin S.
      • Akkoclu A.
      Association between disease-related factors and balance and falls among the elderly with COPD: a cross-sectional study.
      ;
      • Porto E.F.
      • Pradella C.O.
      • Rocco C.M.
      • Chueiro Jr., M.
      • Maia R.Q.
      • Ganança F.F.
      • Castro A.A.
      • Nascimento O.A.
      • Jardim J.R.
      Comparative postural control in COPD patients and healthy individuals during dynamic and static activities.
      ;
      • Roig M.
      • Eng J.J.
      • Road J.D.
      • Reid W.D.
      Falls in patients with chronic obstructive pulmonary disease: a call for further research.
      ;
      • Tudorache E.
      • Oancea C.
      • Avram C.
      • Fira-Mladinescu O.
      • Petrescu L.
      • Timar B.
      Balance impairment and systemic inflammation in chronic obstructive pulmonary disease.
      ).
      One issue preventing mechanistic links between fall risk factors and real falls in COPD is the lack of investigation into responses to large mechanical balance disturbances during walking (like slips and trips), which represent the most common causes of falls in the general older population (
      • Berg W.P.
      • Alessio H.M.
      • Mills E.M.
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      Circumstances and consequences of falls in independent community-dwelling older adults.
      ;
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      • Kaufman K.R.
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      The circumstances, orientations, and impact locations of falls in community-dwelling older women.
      ;
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      A Trip to Remember: Assessing and Improving Walking Stability in Older Adults.
      ;
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      • Musiol R.J.
      • Witham E.K.
      • Metter E.J.
      Falls in young, middle-aged and older community dwelling adults: perceived cause, environmental factors and injury.
      ). Singh et al. (
      • Singh S.S.
      • Bhat A.
      • Mohapatra A.K.
      • Manu M.K.
      • Vaishali K.
      Comparison of reaction time and functional balance in chronic obstructive pulmonary disease and healthy participants.
      ) reported slower stepping reaction times in people with COPD (PwCOPD) versus control participants and Beauchamp et al. (
      • Beauchamp M.K.
      • Sibley K.M.
      • Lakhani B.
      • Romano J.
      • Mathur S.
      • Goldstein R.S.
      • Brooks D.
      Impairments in systems underlying control of balance in COPD.
      ) also found slower reaction and completion times during a forward lean-and-release task. As reduced muscle strength is often considered a potential risk factor for falls, studies in healthy older adults with reduced muscle strength may also provide insight into falls in PwCOPD. Lower limb muscle strength, power and quality have been associated with falls in older adults (
      • Cattagni T.
      • Scaglioni G.
      • Laroche D.
      • Van Hoecke J.
      • Gremeaux V.
      • Martin A.
      Ankle muscle strength discriminates fallers from non-fallers.
      ;
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      The relationship between muscle quality and incidence of falls in older community-dwelling women: An 18-month follow-up study.
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      ;
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      Explosive power and asymmetry in leg muscle function in frequent fallers and non-fallers aged over 65.
      ) and associations have been reported between lower limb muscle strength and lab-assessed balance recovery performance following lean-and-release (
      • Carty C.P.
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      ;
      • Carty C.P.
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      • Mills P.M.
      • Barrett R.S.
      Lower limb muscle moments and power during recovery from forward loss of balance in male and female single and multiple steppers.
      ;
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      Lower extremity strength plays only a small role in determining the maximum recoverable lean angle in older adults.
      ;
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      Age-related deficit in dynamic stability control after forward falls is affected by muscle strength and tendon stiffness.
      ;
      • Karamanidis K.
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      Age-related degeneration in leg-extensor muscle-tendon units decreases recovery performance after a forward fall: compensation with running experience.
      ), trip (
      • Epro G.
      • McCrum C.
      • Mierau A.
      • Leyendecker M.
      • Brüggemann G.P.
      • Karamanidis K.
      Effects of triceps surae muscle strength and tendon stiffness on the reactive dynamic stability and adaptability of older female adults during perturbed walking.
      ;
      • Pavol M.J.
      • Owings T.M.
      • Foley K.T.
      • Grabiner M.D.
      Influence of lower extremity strength of healthy older adults on the outcome of an induced trip.
      ;
      • Pijnappels M.
      • Bobbert M.F.
      • van Dieen J.H.
      Push-off reactions in recovery after tripping discriminate young subjects, older non-fallers and older fallers.
      ;
      • Pijnappels M.
      • van der Burg P.J.
      • Reeves N.D.
      • van Dieen J.H.
      Identification of elderly fallers by muscle strength measures.
      ) and slip (
      • Ding L.
      • Yang F.
      Muscle weakness is related to slip-initiated falls among community-dwelling older adults.
      ) perturbations. However, associations have generally been small-to-moderate, and strength training does not seem to be effective as a stand-alone intervention to reduce falls in older adults (
      • Sherrington C.
      • Fairhall N.J.
      • Wallbank G.K.
      • Tiedemann A.
      • Michaleff Z.A.
      • Howard K.
      • Clemson L.
      • Hopewell S.
      • Lamb S.E.
      Exercise for preventing falls in older people living in the community.
      ). As opposed to strength training alone, interventions including dynamic stepping and perturbation-based balance tasks appear very effective at reducing falls (
      • McCrum C.
      • Gerards M.H.G.
      • Karamanidis K.
      • Zijlstra W.
      • Meijer K.
      A systematic review of gait perturbation paradigms for improving reactive stepping responses and falls risk among healthy older adults.
      ;
      • Okubo Y.
      • Schoene D.
      • Lord S.R.
      Step training improves reaction time, gait and balance and reduces falls in older people: a systematic review and meta-analysis.
      ;
      • Sherrington C.
      • Fairhall N.J.
      • Wallbank G.K.
      • Tiedemann A.
      • Michaleff Z.A.
      • Howard K.
      • Clemson L.
      • Hopewell S.
      • Lamb S.E.
      Exercise for preventing falls in older people living in the community.
      ) and may be feasible in clinical settings (
      • Gerards M.H.G.
      • McCrum C.
      • Mansfield A.
      • Meijer K.
      Perturbation-based balance training for falls reduction among older adults: current evidence and implications for clinical practice.
      ). However, the feasibility of large balance disturbances during treadmill walking has not yet been examined in the COPD population. Feasibility may be limited by the ability of PwCOPD to walk for extended periods of time, limiting the number of perturbations that can be applied. Similarly, it is unknown if COPD leads to specific deficits in the performance of such tasks, over and above those seen with ageing. In particular, if PwCOPD show a lack of adaptability to repeated perturbations, then the feasibility of the approach as a training method may be questioned.
      To address these gaps, we aimed to: 1) Examine the feasibility of treadmill-based walking perturbations in PwCOPD; 2) Determine if the stability-normalised walking speed approach developed previously (
      • McCrum C.
      • Willems P.
      • Karamanidis K.
      • Meijer K.
      Stability-normalised walking speed: a new approach for human gait perturbation research.
      ) would allow for valid patient-control comparisons of perturbed walking stability as previously shown for healthy young and older adults (
      • McCrum C.
      • Karamanidis K.
      • Willems P.
      • Zijlstra W.
      • Meijer K.
      Retention, savings and interlimb transfer of reactive gait adaptations in humans following unexpected perturbations.
      ;
      • McCrum C.
      • Karamanidis K.
      • Grevendonk L.
      • Zijlstra W.
      • Meijer K.
      Older adults demonstrate interlimb transfer of reactive gait adaptations to repeated unpredictable gait perturbations.
      ); 3) Examine the responses to large walking perturbations in COPD to determine if large deficits may exist; and 4) Evaluate the adaptation potential of PwCOPD to repeated walking perturbations. Regarding aims 3 and 4, we tentatively hypothesised that PwCOPD would exhibit lower stability and would require more recovery steps following novel perturbations but would demonstrate improvement with perturbation repetition.

      2. Methods

      2.1 Participants

      Twelve PwCOPD and 12 age-gender-matched healthy control participants were planned for this pilot study. PwCOPD were recruited during the first week of the inpatient pulmonary rehabilitation programme at Ciro (Horn, The Netherlands), prior to which, they completed an intake assessment, including measurements of isometric and isokinetic knee extension torque (Biodex Systems 3, Biodex Medical Systems Inc., New York, NY, USA; (
      • Sillen M.J.
      • Franssen F.M.
      • Delbressine J.M.
      • Vaes A.W.
      • Wouters E.F.
      • Spruit M.A.
      Efficacy of lower-limb muscle training modalities in severely dyspnoeic individuals with COPD and quadriceps muscle weakness: results from the DICES trial.
      ;
      • Sillen M.J.H.
      • Franssen F.M.E.
      • Vaes A.W.
      • Delbressine J.M.L.
      • Wouters E.F.M.
      • Spruit M.A.
      Metabolic load during strength training or NMES in individuals with COPD: results from the DICEStrial.
      )), a post-bronchodilator lung function test (MS/PFT Body Pro, CareFusion Netherlands B.V.), measurement of body composition (whole-body dual-energy x-ray absorptiometry, Lunar iDXA, GE Healthcare–enCORE v14, Madison, WI, USA), mobility tests (Tinetti-test (
      • Tinetti M.E.
      Performance-oriented assessment of mobility problems in elderly patients.
      ) and Short Physical Performance Battery (
      • Guralnik J.M.
      • Simonsick E.M.
      • Ferrucci L.
      • Glynn R.J.
      • Berkman L.F.
      • Blazer D.G.
      • Scherr P.A.
      • Wallace R.B.
      A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission.
      )) and two six-minute walk tests (
      • American Thoracic Society
      ATS statement: guidelines for the six-minute walk test.
      ). Inclusion criteria were a diagnosis of COPD (FEV1/FVC < 0.70), clinically stable (no exacerbation of COPD within four weeks of participating), completed the six-minute walk test without stopping and without assistive devices, no supplemental oxygen use and age 50–80 years old. Healthy participants were recruited via Ciro and were age-gender-matched to the PwCOPD. Inclusion criteria were no known musculoskeletal disease, condition or injury affecting walking or balance, no history of balance problems, dizziness or walking difficulties and the ability to walk non-stop at a comfortable speed for 30 min. Participants provided written informed consent prior to participating. The study was approved by the Medical Research Ethics Committees United (NL61317.100.17) and was performed according to the Declaration of Helsinki.

      2.2 Aims assessment

      Aim 1 was assessed by the number of perturbations completed by the PwCOPD (up to 10) and the number of “falls” (significant harness support) during the perturbations. A target of five perturbations was the threshold for feasibility, based on previous work (
      • Epro G.
      • McCrum C.
      • Mierau A.
      • Leyendecker M.
      • Brüggemann G.P.
      • Karamanidis K.
      Effects of triceps surae muscle strength and tendon stiffness on the reactive dynamic stability and adaptability of older female adults during perturbed walking.
      ;
      • McCrum C.
      • Eysel-Gosepath K.
      • Epro G.
      • Meijer K.
      • Savelberg H.H.
      • Brüggemann G.P.
      • Karamanidis K.
      Deficient recovery response and adaptive feedback potential in dynamic gait stability in unilateral peripheral vestibular disorder patients.
      ;
      • Pai Y.C.
      • Yang F.
      • Bhatt T.
      • Wang E.
      Learning from laboratory-induced falling: long-term motor retention among older adults.
      ). Aim 2 was assessed by the percentage of participants whose mean margin of stability (MoS) of the final 10 steps prior to the first perturbation was within one SD of the target 0.15 m (see Methods section). Aim 3 was assessed by comparing stability during the recovery steps and by the number of steps needed to return to steady-state walking following the first perturbation to each leg between PwCOPD and controls. Aim 4 was assessed by the change in stability from the start to the end of the perturbation protocol and by the change in the number of recovery steps needed following these perturbations.

      2.3 Experimental procedure

      Measurements were performed using the Gait Real-time Analysis Interactive Lab (Motekforce Link, Amsterdam, The Netherlands), which includes a dual-belt force plate-instrumented split-belt treadmill (1000 Hz), a 10-camera motion capture system (100 Hz; Vicon Motion Systems, Oxford, UK) and a virtual environment providing optic flow. A safety harness was always used. Eight retroreflective markers were attached to anatomical landmarks (C7, sacrum, left and right lateral epicondyle of the humerus, left and right trochanter and left and right hallux).
      Following explanation, trials of 1.5 min were completed at speeds of 0.6 m/s up to 1.4 m/s to familiarise participants with the setup and to determine which speeds were feasible. Measured trials were then conducted at speeds of 0.6 m/s up to 1.4 m/s (increased by 0.2 m/s every 2 min). The procedure was stopped when the participant was not able to continue, as assessed by the participant or investigator (e.g. due to discomfort, fatigue, or an inability to maintain walking at the prescribed speed).
      During a rest period, data from the preceding trials were analysed and the participant's stability-normalised walking speed was determined for use in the subsequent perturbation trial (details described elsewhere (
      • McCrum C.
      • Karamanidis K.
      • Willems P.
      • Zijlstra W.
      • Meijer K.
      Retention, savings and interlimb transfer of reactive gait adaptations in humans following unexpected perturbations.
      ;
      • McCrum C.
      • Willems P.
      • Karamanidis K.
      • Meijer K.
      Stability-normalised walking speed: a new approach for human gait perturbation research.
      ;
      • McCrum C.
      • Karamanidis K.
      • Grevendonk L.
      • Zijlstra W.
      • Meijer K.
      Older adults demonstrate interlimb transfer of reactive gait adaptations to repeated unpredictable gait perturbations.
      )). Briefly, the mean anteroposterior MoS at foot touchdown of the final 10 steps of each completed walking trial (0.6 m/s to 1.4 m/s) were used to determine the walking speed that would result in MoS of 0.15 m for the individual.
      The walking perturbation trial then started with two minutes unperturbed walking at the stability-normalised walking speed. Ten unilateral treadmill belt acceleration perturbations were then applied, each occurring every 30–90s. These comprised of a 3 m/s2 acceleration of the corresponding belt until it reached 180% of the walking speed while the other belt maintained the stability-normalised walking speed. Accelerations were triggered when the hallux marker of the to-be-perturbed limb became anterior to that of the stance limb (i.e. if the right leg was to be perturbed, the acceleration started on the right belt during mid-swing of the right leg so that the belt was already moving faster when the foot touched down). The belt decelerated at the same rate when the perturbed limb left the ground (toe-off). The first and last acceleration perturbed the right leg, while the second to ninth perturbed the left leg. Participants were told that they would complete a walking balance challenge and to try to continue walking as normally as possible; they were unaware of the specifics of the perturbations and no warnings or cues were given.

      2.4 Data processing

      Data processing was conducted in MATLAB (2016a, The MathWorks, Inc., Natick). The three-dimensional coordinates of the markers were filtered using a low pass second order Butterworth filter (zero-phase) with a 12 Hz cut-off frequency. Foot touchdown and toe-off were determined using a combined marker (
      • Zeni Jr., J.A.
      • Richards J.G.
      • Higginson J.S.
      Two simple methods for determining gait events during treadmill and overground walking using kinematic data.
      ) and force plate (50 N threshold) method as previously described (
      • McCrum C.
      • Lucieer F.
      • van de Berg R.
      • Willems P.
      • Perez Fornos A.
      • Guinand N.
      • Karamanidis K.
      • Kingma H.
      • Meijer K.
      The walking speed-dependency of gait variability in bilateral vestibulopathy and its association with clinical tests of vestibular function.
      ). The anteroposterior MoS at the instant of foot touchdown were calculated as defined by Hof et al. (
      • Hof A.L.
      • Gazendam M.G.
      • Sinke W.E.
      The condition for dynamic stability.
      ). The MoS is an instantaneous measure of the stability of the body configuration in terms of the centre of mass and base of support boundary relationship, accounting for centre of mass velocity during walking., This was done by subtracting the anteroposterior position of the extrapolated centre of mass (XCoM) from that of the anterior boundary of the base of support (anterior hallux marker), both relative to the posterior hallux marker, using the XCoM formula adapted for our reduced kinematic model (
      • Süptitz F.
      • Moreno Catala M.
      • Brüggemann G.P.
      • Karamanidis K.
      Dynamic stability control during perturbed walking can be assessed by a reduced kinematic model across the adult female lifespan.
      ). The MoS was calculated for: baseline for each perturbation (mean MoS of the eleventh to second last step before each perturbation; Base); the final step before each perturbation (Pre); and the first eight recovery steps following each perturbation (Post1–8). Within these eight analysed recovery steps, the number of steps to return to Base stability (defined as within 0.05 m of the MoS value of Base for each individual) following the perturbation was determined.

      2.5 Statistics

      To examine the effect of COPD on the MoS during the first perturbation to each leg (Pert1R and Pert2L), a two-way repeated measures ANOVA with group (COPD or Control) and step (repeated measures: Base, Pre, Post1–8) as factors was conducted, alongside Mann-Whitney tests to compare the number of recovery steps needed by each group. Adaptation potential following repeated perturbations was analysed for each group separately using two-way ANOVAs with perturbation number (repeated measures) and step (repeated measures: Base, Pre, Post1–8) combined with Wilcoxon signed rank tests for the number of recovery steps. The analysis of adaptation potential was conducted in two ways. A conservative approach compared the steps following the first left leg perturbation with the latest perturbation that all participants could complete (Pert2L vs. Pert4L). An intention to treat approach compared the first left leg perturbation with the final left leg perturbation completed by each individual participant (Pert2L vs. PertFINALL). Significance was set at α = 0.05. Analyses were performed in GraphPad Prism version 8.4.3 for Windows (GraphPad Software, LLC, San Diego, California, USA).

      3. Results

      3.1 Participants

      Fifteen PwCOPD participated as three PwCOPD were excluded from the analysis and replaced due to technical problems leading to insufficient data-quality (errors due to a force plate issue and problematic reflections). The 12 included PwCOPD were age and gender matched with 12 healthy control participants (maximum age difference of four years). Participant characteristics are presented in Table 1. Seven and 11 PwCOPD could not complete the measurements at the fourth (1.2 m/s) and fifth (1.4 m/s) speeds, respectively, because of dyspnoea and/or fatigue. One healthy participant stopped during the last speed, due to not being able to achieve the prescribed walking speed without running.
      Table 1Participant characteristics and intake assessment outcomes.
      COPD (n = 12)Healthy (n = 12)
      Mean ± SDMinimumMaximumMean ± SDMinimumMaximum
      Male gender50%N/AN/A50%N/AN/A
      Age (yr.)66.1 ± 8.5547966.9 ± 7.75378
      BMI (kg/m2)26.8 ± 6.019.539.226.9 ± 2.922.633.2
      FFMI (kg/m2)17.3 ± 2.314.519.6
      6MWD (m)427 ± 70327569
      6MWD (%pred)
      Based on reference values by Troosters et al. (Troosters et al., 1999).
      67.9 ± 8.854.080.0
      FEV1 (%pred)
      Based on reference values by Quanjer et al. (Quanjer et al., 2012).
      51.7 ± 23.324.893.7
      FEV1/FVC (%)36.3 ± 11.619.459.8
      TLC (%pred)
      Based on reference values of Stocks and Quanjer (Stocks and Quanjer, 1995).
      117.4 ± 16.280.9139.0
      RV (%pred)
      Based on reference values of Stocks and Quanjer (Stocks and Quanjer, 1995).
      144.7 ± 41.281.5219.5
      Quadriceps isometric peak torque (Nm)
      %pred based on reference values by Borges (Borges, 1989), n = 9 due to contra-indications for the test in three participants.
      129.8 ± 30.483.5170.8
      Quadriceps isokinetic peak torque (Nm)
      %pred based on reference values by Borges (Borges, 1989), n = 9 due to contra-indications for the test in three participants.
      101.8 ± 23.461.9131.0
      Quadriceps isokinetic peak torque (%pred)
      %pred based on reference values by Borges (Borges, 1989), n = 9 due to contra-indications for the test in three participants.
      76.3 ± 18.349.7107.4
      SPPB total score (points)11 ± 1912
      Tinetti total score (points)
      : n = 10 due to missing data for two participants; FFMI: Fat Free Mass Index; 6MWD: 6 Minute Walk Distance;FEV1: Forced Expiratory Volume in 1st second; FVC: Forced Vital Capacity; TLC: Total Lung Capacity; RV: Residual Volume; SPPB: Short Physical Performance Battery; %pred: Percentage of predicted value.
      28 ± 12628
      a Based on reference values by Troosters et al. (
      • Troosters T.
      • Gosselink R.
      • Decramer M.
      Six minute walking distance in healthy elderly subjects.
      ).
      b Based on reference values by Quanjer et al. (
      • Quanjer P.H.
      • Stanojevic S.
      • Cole T.J.
      • Baur X.
      • Hall G.L.
      • Culver B.H.
      • Enright P.L.
      • Hankinson J.L.
      • Ip M.S.
      • Zheng J.
      • Stocks J.
      Multi-ethnic reference values for spirometry for the 3–95-yr age range: the global lung function 2012 equations.
      ).
      c Based on reference values of Stocks and Quanjer (
      • Stocks J.
      • Quanjer P.H.
      Reference values for residual volume, functional residual capacity and total lung capacity. ATS workshop on lung volume measurements. Official statement of the European respiratory society.
      ).
      d %pred based on reference values by Borges (
      • Borges O.
      Isometric and isokinetic knee extension and flexion torque in men and women aged 20–70.
      ), n = 9 due to contra-indications for the test in three participants.
      e : n = 10 due to missing data for two participants; FFMI: Fat Free Mass Index; 6MWD: 6 Minute Walk Distance;FEV1: Forced Expiratory Volume in 1st second; FVC: Forced Vital Capacity; TLC: Total Lung Capacity; RV: Residual Volume; SPPB: Short Physical Performance Battery; %pred: Percentage of predicted value.

      3.2 Feasibility of using walking perturbations and the stability-normalised walking speed in people with COPD

      The PwCOPD completed an average of 8.2 walking perturbations before stopping. 11 of 12 PwCOPD completed at least five perturbations with one patient stopped after the fourth. No participants required significant harness support to catch them and prevent a fall. Nine out of 12 PwCOPD and 10 out of 12 controls were within 1 SD of the targeted MoS value of 0.15 m and all were within 0.05 m (Fig. 1).
      Fig. 1
      Fig. 1Means and SDs of the final 10 steps prior to the first perturbation for each individual.

      3.3 Responses to large walking perturbations in people with COPD

      For the first perturbation to each leg (Pert1R and Pert2L), two-way repeated measures ANOVAs with group and step as factors did not reveal significant effects of group (Fig. 2; Pert1R: F(1,22) = 0.8269, P = 0.3730; Pert2L: F(1, 22) = 0.1793, P = 0.6761). Analysis of the number of recovery steps needed to return to MoS values within 5 cm of Base showed that PwCOPD needed a median of 6 steps for both Pert1R and Pert2L, whereas the controls required a median of 5 steps (Fig. 3). These differences were not significant (Mann-Whitney test: P = 0.18 and P = 0.4).
      Fig. 2
      Fig. 2Median and 95% confidence intervals (with individual data points) of the anteroposterior margins of stability (MoS AP) during the first perturbation to each leg (Pert1R and Pert2L, respectively) including unperturbed walking prior to each perturbation (Base), the final step prior to each perturbation (Pre) and the first eight recovery steps following the perturbations (Post1–8) for the COPD and control groups.
      Fig. 3
      Fig. 3Medians and individual data points for the number of recovery steps required following the first perturbation to each leg (Pert1R and Pert2L, respectively) for the COPD and control groups.

      3.4 Adaptation potential following repeated perturbations in people with COPD

      The first participant with COPD to stop, stopped after Pert4L. The conservative analysis (Pert2L vs. Pert4L) did not show a significant effect of perturbation repetition (F(1,11) = 0.8069, P = 0.3883) (Fig. 4). A Wilcoxon signed rank test on the number of recovery steps also did not reveal a significant change from Pert2L to Pert4L but a one-step improvement in the median was seen (Fig. 5). The intention to treat analysis (Pert2L vs. PertFINALL) did not show a significant perturbation repetition effect (F(1, 11) = 3.709, P = 0.0803) although a medium effect was observed post hoc (partial η2 = 0.079) which, together with a significant difference between perturbations at Post3 (Sidak's multiple comparisons test: P = 0.0464) are suggestive of an effect not detected due to the small sample size (Fig. 4). A significant perturbation number by step interaction was found (F(9, 99) = 2.851, P = 0.0050) indicating that the stepping behaviour was generally altered. A non-significant, two-step improvement in the median number of recovery steps was seen (Fig. 5).
      Fig. 4
      Fig. 4Median and 95% confidence intervals (with individual data points) of the anteroposterior margins of stability (MoS AP) during the first and third perturbation to the left leg (left panel; conservative analysis; Pert2L and Pert4L, respectively) and during the first and final (for each individual) perturbation to the left leg (right panel; intention to treat analysis; Pert2L and PertFINALL, respectively) including unperturbed walking prior to each perturbation (Base), the final step prior to each perturbation (Pre) and the first eight recovery steps following the perturbations (Post1–8) for the COPD and control groups. *: Significant difference (Sidak's multiple comparisons test: P = 0.0464).
      Fig. 5
      Fig. 5Medians and individual data points for the number of recovery steps required following the first perturbation to the left leg (Pert2L), the last perturbation to the left leg that all participants completed (Pert4L) and the final perturbation to the left leg that each individual participant completed (PertFINALL) for the people with COPD.

      3.5 Additional post hoc analyses of the control group

      To provide further context for the adaptation potential results in the PwCOPD, we additionally analysed the adaptation from Pert2L to Pert9L in the matched control group. A two-way repeated measures ANOVA with perturbation number (Pert2L vs. Pert9L) and step as factors resulted in a significant perturbation repetition effect (F(1, 11) = 11.02, P = 0.0068) and a significant perturbation number by step interaction (F(9, 99) = 3.816, P = 0.0004) on the MoS (Fig. 6). Sidak's multiple comparisons test found a significant difference between perturbations at Post3 (P < 0.0001). When comparing the final perturbation for each group together in a similar manner to the first perturbations, the two-way repeated measures ANOVA with group (COPD vs. Control) and step as factors does not reveal a significant difference (F(1, 22) = 2.670, P = 0.1165), although this is a small effect (partial η2 = 0.032). A comparison of the recovery steps needed during the final perturbation between groups did not reveal a significant difference (Median of 4 steps in each group; Mann-Whitney test: P = 0.6337).
      Fig. 6
      Fig. 6Median and 95% confidence intervals (with individual data points) of the anteroposterior margins of stability (MoS AP) during the first and final perturbation to the left leg (Pert2L and Pert9L, respectively) including unperturbed walking prior to each perturbation (Base), the final step prior to each perturbation (Pre) and the first eight recovery steps following the perturbations (Post1–8) for the control group. *: Significant difference at Post3 (Sidak's multiple comparisons test: P < 0.0001).

      4. Discussion

      This study addressed the feasibility and potential effects of treadmill-based balance perturbations during walking in PwCOPD. Treadmill-based perturbations were feasible for PwCOPD. We found no significant differences between PwCOPD and matched control participants in stability or the number of recovery steps needed following novel perturbations, leading us to reject our hypothesis. Our hypothesis of significant improvement following repeated perturbations in PwCOPD was only partly supported.
      Such perturbations seem feasible in this population as all participants recovered balance without significant harness support and almost all participants could complete the minimum number of perturbations deemed necessary for beneficial adaptations. Larger perturbations (including those initially requiring harness support) might lead to greater training effects (
      • Liu X.
      • Bhatt T.
      • Pai Y.C.
      Intensity and generalization of treadmill slip training: high or low, progressive increase or decrease?.
      ;
      • Wang Y.
      • Wang S.
      • Lee A.
      • Pai Y.C.
      • Bhatt T.
      Treadmill-gait slip training in community-dwelling older adults: mechanisms of immediate adaptation for a progressive ascending-mixed-intensity protocol.
      ;
      • Yang F.
      • Wang T.Y.
      • Pai Y.C.
      Reduced intensity in gait-slip training can still improve stability.
      ) but feasibility and safety should be examined for COPD. However, high magnitudes are not necessary to improve fall-resisting skills (
      • Lee A.
      • Bhatt T.
      • Pai Y.C.
      Generalization of treadmill perturbation to overground slip during gait: effect of different perturbation distances on slip recovery.
      ;
      • Liu X.
      • Bhatt T.
      • Pai Y.C.
      Intensity and generalization of treadmill slip training: high or low, progressive increase or decrease?.
      ;
      • Yang F.
      • Wang T.Y.
      • Pai Y.C.
      Reduced intensity in gait-slip training can still improve stability.
      ), so this is not a barrier for implementation. Additionally, a shorter wash-out time could be applied in practice, allowing more perturbations before fatigue or dyspnoea onset.
      Our second aim was to determine if the stability-normalised walking speed approach developed previously (
      • McCrum C.
      • Willems P.
      • Karamanidis K.
      • Meijer K.
      Stability-normalised walking speed: a new approach for human gait perturbation research.
      ) would allow for valid patient-control comparisons of perturbed walking stability in a similar manner as previously shown for healthy young and older adults (
      • McCrum C.
      • Karamanidis K.
      • Willems P.
      • Zijlstra W.
      • Meijer K.
      Retention, savings and interlimb transfer of reactive gait adaptations in humans following unexpected perturbations.
      ;
      • McCrum C.
      • Karamanidis K.
      • Grevendonk L.
      • Zijlstra W.
      • Meijer K.
      Older adults demonstrate interlimb transfer of reactive gait adaptations to repeated unpredictable gait perturbations.
      ). Nine of 12 PwCOPD and 10 of 12 controls were within 1 SD of the targeted MoS of 0.15 m and all were within 0.05 m. These percentages of the samples (75% and 83%) are similar to previous studies in healthy young (83%) and older adults (82%) (
      • McCrum C.
      • Karamanidis K.
      • Willems P.
      • Zijlstra W.
      • Meijer K.
      Retention, savings and interlimb transfer of reactive gait adaptations in humans following unexpected perturbations.
      ;
      • McCrum C.
      • Willems P.
      • Karamanidis K.
      • Meijer K.
      Stability-normalised walking speed: a new approach for human gait perturbation research.
      ;
      • McCrum C.
      • Karamanidis K.
      • Grevendonk L.
      • Zijlstra W.
      • Meijer K.
      Older adults demonstrate interlimb transfer of reactive gait adaptations to repeated unpredictable gait perturbations.
      ), indicating that this procedure can also be used with PwCOPD.
      We found no clear deficit in reactive walking stability in PwCOPD over and above that seen with ageing. Muscle strength-related differences in walking stability following perturbations have previously been reported (
      • Ding L.
      • Yang F.
      Muscle weakness is related to slip-initiated falls among community-dwelling older adults.
      ;
      • Epro G.
      • McCrum C.
      • Mierau A.
      • Leyendecker M.
      • Brüggemann G.P.
      • Karamanidis K.
      Effects of triceps surae muscle strength and tendon stiffness on the reactive dynamic stability and adaptability of older female adults during perturbed walking.
      ;
      • Pavol M.J.
      • Owings T.M.
      • Foley K.T.
      • Grabiner M.D.
      Influence of lower extremity strength of healthy older adults on the outcome of an induced trip.
      ) but we did not see significant group differences during the initial perturbations, despite our PwCOPD having lower quadriceps isokinetic peak torque than would be expected based on age (
      • Borges O.
      Isometric and isokinetic knee extension and flexion torque in men and women aged 20–70.
      ). Despite these lack of differences, the lack of effectiveness of resistance exercise alone for falls reduction (
      • Sherrington C.
      • Fairhall N.J.
      • Wallbank G.K.
      • Tiedemann A.
      • Michaleff Z.A.
      • Howard K.
      • Clemson L.
      • Hopewell S.
      • Lamb S.E.
      Exercise for preventing falls in older people living in the community.
      ) and the more severe consequences of falls in PwCOPD (particularly due to increased prevalence of osteoporosis and fractures (
      • de Luise C.
      • Brimacombe M.
      • Pedersen L.
      • Sørensen H.T.
      Chronic obstructive pulmonary disease and mortality following hip fracture: a population-based cohort study.
      ;
      • Graat-Verboom L.
      • Wouters E.F.
      • Smeenk F.W.
      • van den Borne B.E.
      • Lunde R.
      • Spruit M.A.
      Current status of research on osteoporosis in COPD: a systematic review.
      ;
      • Regan E.A.
      • Radcliff T.A.
      • Henderson W.G.
      • Cowper Ripley D.C.
      • Maciejewski M.L.
      • Vogel W.B.
      • Hutt E.
      Improving hip fractures outcomes for COPD patients.
      ;
      • Sarkar M.
      • Bhardwaj R.
      • Madabhavi I.
      • Khatana J.
      Osteoporosis in chronic obstructive pulmonary disease.
      ;
      • Schnell K.
      • Weiss C.O.
      • Lee T.
      • Krishnan J.A.
      • Leff B.
      • Wolff J.L.
      • Boyd C.
      The prevalence of clinically-relevant comorbid conditions in patients with physician-diagnosed COPD: a cross-sectional study using data from NHANES 1999–2008.
      )), together with the promising results in step and perturbation training in other groups (for example, healthy older adults and people with Parkinson's or stroke; (
      • Gerards M.H.G.
      • McCrum C.
      • Mansfield A.
      • Meijer K.
      Perturbation-based balance training for falls reduction among older adults: current evidence and implications for clinical practice.
      ;
      • Mansfield A.
      • Wong J.S.
      • Bryce J.
      • Knorr S.
      • Patterson K.K.
      Does perturbation-based balance training prevent falls? Systematic review and meta-analysis of preliminary randomized controlled trials.
      ;
      • McCrum C.
      • Gerards M.H.G.
      • Karamanidis K.
      • Zijlstra W.
      • Meijer K.
      A systematic review of gait perturbation paradigms for improving reactive stepping responses and falls risk among healthy older adults.
      ;
      • Okubo Y.
      • Schoene D.
      • Lord S.R.
      Step training improves reaction time, gait and balance and reduces falls in older people: a systematic review and meta-analysis.
      )) might justify further research in PwCOPD.
      We found no significant effect of perturbation repetition on stability in PwCOPD, although a non-significant but potentially meaningful effect was observed. A significant step by perturbation interaction was found, indicating an altered step behaviour following perturbation repetition. The number of recovery steps needed reduced by two (potentially meaningful) but this was not significant. It is well established that healthy older adults can adapt and improve their responses to perturbations with repetition (
      • Bohm S.
      • Mademli L.
      • Mersmann F.
      • Arampatzis A.
      Predictive and reactive locomotor adaptability in healthy elderly: a systematic review and meta-analysis.
      ;
      • Karamanidis K.
      • Epro G.
      • McCrum C.
      • König M.
      Improving trip- and slip-resisting skills in older people: perturbation dose matters.
      ;
      • McCrum C.
      • Gerards M.H.G.
      • Karamanidis K.
      • Zijlstra W.
      • Meijer K.
      A systematic review of gait perturbation paradigms for improving reactive stepping responses and falls risk among healthy older adults.
      ). This raises the question of whether PwCOPD have reduced adaptability or perhaps whether the specific perturbation protocol used here was not sufficient to trigger adaptation. Our perturbation protocol did have participants walk at a higher MoS and, therefore, a slower walking speed than our previous studies (
      • McCrum C.
      • Karamanidis K.
      • Willems P.
      • Zijlstra W.
      • Meijer K.
      Retention, savings and interlimb transfer of reactive gait adaptations in humans following unexpected perturbations.
      ;
      • McCrum C.
      • Karamanidis K.
      • Grevendonk L.
      • Zijlstra W.
      • Meijer K.
      Older adults demonstrate interlimb transfer of reactive gait adaptations to repeated unpredictable gait perturbations.
      ), perhaps resulting in less difficulty recovering balance (
      • Krasovsky T.
      • Lamontagne A.
      • Feldman A.G.
      • Levin M.F.
      Effects of walking speed on gait stability and interlimb coordination in younger and older adults.
      ;
      • Pavol M.J.
      • Owings T.M.
      • Foley K.T.
      • Grabiner M.D.
      Gait characteristics as risk factors for falling from trips induced in older adults.
      ). To check this, we analysed the adaptation from Pert2L to Pert9L in our control group and did find a larger and significant improvement in the MoS values. Therefore, the protocol was sufficient to trigger the expected adaptations. This leaves three possibilities: that the reduced number of perturbations by the PwCOPD led to suboptimal adaptation; that fatigue and/or dyspnoea may have negatively influenced adaptation; or that PwCOPD are inherently less adaptable to walking perturbations. The evidence is mixed on whether local lower limb muscle fatigue effects kinematic parameters during balance recovery (
      • Mademli L.
      • Arampatzis A.
      • Karamanidis K.
      Dynamic stability control in forward falls: postural corrections after muscle fatigue in young and older adults.
      ;
      • Papa E.V.
      • Foreman K.B.
      • Dibble L.E.
      Effects of age and acute muscle fatigue on reactive postural control in healthy adults.
      ;
      • Parijat P.
      • Lockhart T.E.
      Effects of quadriceps fatigue on the biomechanics of gait and slip propensity.
      ;
      • Qu X.
      • Xie Y.
      • Hu X.
      • Zhang H.
      Effects of fatigue on balance recovery from unexpected trips.
      ;
      • Toebes M.J.
      • Hoozemans M.J.
      • Dekker J.
      • van Dieën J.H.
      Effects of unilateral leg muscle fatigue on balance control in perturbed and unperturbed gait in healthy elderly.
      ). However, no studies have examined adaptation to repeated perturbations and it is unclear how these fatigue protocols relate to walking-related fatigue experienced by PwCOPD. We do not think that inherently less adaptability in PwCOPD, independent of fatigue and perturbation repetitions, is likely, as this usually only manifests with pathology of the sensory or nervous systems (
      • Karamanidis K.
      • Epro G.
      • McCrum C.
      • König M.
      Improving trip- and slip-resisting skills in older people: perturbation dose matters.
      ;
      • Martelli D.
      • Luo L.
      • Kang J.
      • Kang U.J.
      • Fahn S.
      • Agrawal S.K.
      Adaptation of stability during perturbed walking in Parkinson's disease.
      ;
      • McCrum C.
      • Eysel-Gosepath K.
      • Epro G.
      • Meijer K.
      • Savelberg H.H.
      • Brüggemann G.P.
      • Karamanidis K.
      Deficient recovery response and adaptive feedback potential in dynamic gait stability in unilateral peripheral vestibular disorder patients.
      ;
      • Moreno Catala M.
      • Woitalla D.
      • Arampatzis A.
      Reactive but not predictive locomotor adaptability is impaired in young Parkinson's disease patients.
      ;
      • Rand M.K.
      • Wunderlich D.A.
      • Martin P.E.
      • Stelmach G.E.
      • Bloedel J.R.
      Adaptive changes in responses to repeated locomotor perturbations in cerebellar patients.
      ), which were not apparent in our participants. In summary, it seems likely that PwCOPD require an increased number of perturbation repetitions and possibly more rest during the sessions or shorter, more frequent sessions to reduce the potential influence of fatigue and/or dyspnoea.
      Some limitations should be highlighted. Our results concern a small group of PwCOPD and may not generalise to all PwCOPD (particularly those with frailty and more severe mobility impairment). Our participants could complete a six-minute walk test, did not use supplemental oxygen and had a mean SPPB score of 11 (range of 9–12); a substantial number of PwCOPD score 9 or less (
      • Mohan D.
      • Benson V.S.
      • Allinder M.
      • Galwey N.
      • Bolton C.E.
      • Cockcroft J.R.
      • MacNee W.
      • Wilkinson I.B.
      • Tal-Singer R.
      • Polkey M.I.
      Short Physical Performance Battery: What Does Each Sub-Test Measure in Patients with Chronic Obstructive Pulmonary Disease? Chronic Obstructive Pulmonary Diseases (Miami, Fla.).
      ;
      • Stoffels A.A.F.
      • De Brandt J.
      • Meys R.
      • van Hees H.W.H.
      • Vaes A.W.
      • Klijn P.
      • Burtin C.
      • Franssen F.M.E.
      • van den Borst B.
      • Sillen M.J.H.
      • Wouters E.F.M.
      • Janssen D.J.A.
      • Spruit M.A.
      Phenotypic characteristics of patients with chronic obstructive pulmonary disease after stratification for the short physical performance battery summary score.
      ). Our control group was not thoroughly screened like the patients, so precise group differences (e.g. lung function) are unknown. Selection bias may have influenced the findings, as patients with concern about balance and falls may not have volunteered. Finally, we would like to highlight that while we have used the MoS as a measure of stability, there are other approaches to quantifying stability during such tasks and it is currently unclear which would be most appropriate in a clinical setting (
      • Bruijn S.M.
      • Meijer O.G.
      • Beek P.J.
      • van Dieën J.H.
      Assessing the stability of human locomotion: a review of current measures.
      ;
      • Grabiner M.D.
      • Kaufman K.R.
      Developing and establishing biomechanical variables as risk biomarkers for preventable gait-related falls and assessment of intervention effectiveness.
      ;
      • Rieger M.M.
      • Papegaaij S.
      • Steenbrink F.
      • Pijnappels M.
      • van Dieën J.H.
      Development of a balance recovery performance measure for gait perturbation training based on the center of pressure.
      ).

      5. Conclusions

      Using treadmill-based perturbations during walking is feasible in PwCOPD, given appropriate walking speeds and perturbation intensities are selected. COPD does not appear to result in significant deficits in reactive walking stability and patients do demonstrate some adaptability to repeated perturbations (albeit not to the extent of healthy control participants). We recommend that perturbation-based balance training be considered as an option for fall prevention in future research and practice in PwCOPD and that the role of fatigue in balance control and adaptation following larger walking perturbations be further investigated.

      Conflicts of interest

      None.

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