Effects of Inspiratory Muscle Training on Shortness of Breath (Dyspnea) and Postural Control in Patients With COPD
Condition: Copd; Inspiratory Muscle Weakness
MeSH terms: Muscle Weakness; Dyspnea; Respiratory Aspiration
Study type: Interventional

Summary: 
      Shortness of breath (dyspnea) is an important symptom during physical exertion in patients
      with chronic obstructive pulmonary disease (COPD) and is related to respiratory muscle
      weakness. Dyspnea is a multidimensional sensation. The sensory perceptual domain (perceived
      dyspnea intensity) has been study extensively. The perception of respiratory distress
      (unpleasantness of dyspnea) has not received as much attention. Inspiratory muscle training
      (IMT) has been shown to improve inspiratory muscle function and reduce dyspnea intensity.
      Balance impairments increasing the risk of falling is another recognized problem in patients
      with COPD. Postural balance has been shown to be especially impaired in patients with COPD
      who have pronounced respiratory muscle weakness. Improvements in respiratory muscle function
      might improve balance control in patients. Respiratory Muscle Metaboreflex is known as
      respiratory muscle work during exercise reflexively induces sympathetically mediated
      vasoconstrictor activity, there by compromising blood flow and oxygen delivery to active limb
      and respiratory muscles.

      Eight weeks of controlled IMT is hypothesized to reduce both intensity as well as
      unpleasntness domain of dyspnea perception, improve postural control and improves blood flow
      and oxygen delivery to limb muscles in patients with COPD who have pronounced respiratory
      muscle weakness.
    

Detailed description: 
      The purpose of this clinical trial is to elucidate mechanisms of dyspnea relief and
      improvements in postural control after inspiratory muscle training (IMT) in patients with
      COPD.

      An endurance cycle exercise test (Constant work rate (CWR) test) will be used to evaluate
      dyspnea intensity and unpleasantness at comparable breathing efforts, at comparable work
      rates on the cycle ergometer, before and after IMT. Patients will be performing a CWR test at
      75% of the peak work rate achieved during a maximal incremental cardiopulmonary exercise test
      (CPET). Before, during and after CWR cycling tests patients will rate their intensity of
      dyspnea, unpleasantness of dyspnea, breathing related-anxiety and leg discomfort using a
      modified 10- point Borg scale. Patients will be asked to report qualitative descriptors of
      dyspnea at the end of the CWR cycling test. Maximum duration of the CWR test will be recorded
      and levels of minute ventilation will be registered continuously throughout the exercise
      protocol. With this endurance exercise test the investigators will be able to assess changes
      in the onset of dyspnea (intensity and unpleasantness) and the performance in endurance
      exercise before and after IMT.

      Surface electromyography (EMG), and a multipair esophageal electrode catheter system will be
      used during CWR exercise to evaluate respiratory muscle recruitment, respiratory effort and
      neural drive to the different respiratory muscles. The catheter will be inserted to
      continuously record Pes (esophageal pressure), Pgas (gastric pressure) and EMGdi
      (electromyogram of the diaphragm muscle). PesMax (maximal esophageal pressure), PgasMax
      (maximal gastric pressure) and PdiMax (maximal transdiaphragmatic pressure) will be obtained
      during maximal sniff and cough maneuvers. Transcutaneous surface electromyography (sEMG)
      techniques will be applied to scalene, sternocleidomastoid and parasternal intercostal
      muscles to register neural drive to these respiratory muscles. With this measurements, the
      investigators will be able to assess whether there are any changes in respiratory muscle
      recruitment patterns and respiratory neural drive to the different respiratory muscles after
      IMT.

      During exercise 'Respiratory Muscle Metaboreflex' will lead to sympathetically mediated
      vasoconstriction of limb locomotor muscle, less blood and oxygen supply to active limbs
      muscle there by locomotor muscle fatigue occurred. Quadriceps twitch forces evoked by
      magnetic stimulation of femoral nerve will be assessed to measure locomotor muscle fatigue at
      identical exercise time points during CWR test before and after the intervention. With this
      technique, the investigators will be able to assess whether the onset of locomotor muscle
      fatigue is delayed after IMT.

      An isocapnic hyperpnea trial will be performed to assess respiratory muscle perfusion,
      dyspnea intensity and unpleasantness, respiratory muscle recruitment pattern, respiratory
      effort and neural respiratory drive without the work of locomotor muscle before and after
      IMT. Patients will be asked to maintain a targeted minute ventilation pattern equal to their
      breathing frequency, tidal volume and minute ventilation recorded at rest and during the
      final minute of constant load exercise test (at ~75% WRpeak). Experimenters will provide
      verbal guidance to patients to adjust the rate and depth of their breathing such that the
      target ventilation will be obtained and maintained constant within ±5%. Isocapnia will be
      maintained by having subjects inspire from a Douglas bag containing 5% CO2, 21% O2, balance
      N2 that will be connected to a two-way non-rebreathing valve (model 2700, Hans Rudolph) by a
      piece of tubing.

      Loaded breathing tests will be performed to assess dyspnea intensity and unpleasantness,
      respiratory muscle recruitment patterns, respiratory effort and neural respiratory drive.
      Patients will be asked to breathe through a tapered flow resistive loading (TFRL) device
      (powerbreathe KH1) as long as they can (3-7 minutes), the resistance will be set at 50% of
      patients' PImax. Heart rate, oxygen saturation, and number of breaths will be monitored.
      Before and after the test Borg dyspnea, inspiratory effort and unpleasantness will be
      recorded. The test will be repeated after 8 weeks of IMT, at the same resistance. Borg
      dyspnea, inspiratory effort and unpleasantness will be recorded at time limit of pre-training
      and at the symptom limit. The longest time for post training can be up to 15 minutes.

      Respiratory (i.e., intercostal, scalene and abdominal) and locomotor muscle blood flow index
      (i.e., vastus lateralis) will be simultaneously measured during isocapnic hyperpnea trials as
      well as during CWR test (at 75% of the peak work rate) before and after IMT according to a
      previously established method using Near-Infrared Spectroscopy (NIRS) and indocyanine green
      (ICG). Respiratory (i.e., intercostal, scalene, abdominal) and locomotor muscle (i.e., vastus
      lateralis) oxygen delivery will be calculated by multiplying blood flow index to arterial
      oxygen content, the latter will be calculated non-invasively by pulse oximetry. Respiratory
      (i.e., intercostal, scalene, abdominal) and locomotor muscle (i.e., vastus lateralis) oxygen
      saturation (Stio2) - an index of oxygen availability reflecting the balance between oxygen
      supply and demand-, will be recorded continuously during the trial by NIRS.

      A noninvasive technique for studying the neural processing of respiratory sensations will be
      used to assess changes in the affective unpleasantness component of dyspnea during a
      standardized loaded breathing task. Electroencephalography (EEG) will be used to measure
      respiratory related evoked potentials (RREPs) during loaded and unloaded breathing. The RREP
      recorded from EEG is a measurement of cerebral cortical activity, which is elicited by the
      activation of lung and muscle mechanoreceptors due to short inspiratory occlusions. Patients
      will be wearing EEG sensors [129 channel system, Electrical Geodesics Inc., Eugene, USA] and
      breathe through a breathing circuit with a non-rebreathing valve via a mouthpiece. The
      inspiration will be interrupted briefly for 150 milliseconds every two to six breaths by
      activation of the occlusion valve with pressurized air, which induces the RREP. Patients will
      be rating their perceived intensity and unpleasantness of dyspnea and intensity of occlusion
      on a Borg scale while inspiratory load and occlusion will be applied via a breathing valve.
      This method will be used to assess if there is less unpleasantness associated with a giving
      level of dyspnea elicited by a resistive breathing task and whether these changes are
      correlated with changes in the central processing of the dyspnea sensation.

      To evaluate postural balance, displacement of the center of pressure (CoP) in will be
      estimated from the raw force plate data using the equation: CoP = Mx/Fz (medio-lateral) and
      CoP=My/Fz (anterior-posterior). CoP will be measured during upright standing with and without
      vision, on stable and unstable (foam pad) support surface. During some conditions, local
      muscle vibration on ankle and/or back muscles will be applied to evaluate the role of
      proprioception in postural control. Furthermore, in some conditions a repetitive ballistic
      arm movement will be asked to evaluate the effect of a internal perturbation on postural
      control. Root mean square values of the CoP displacements will be used for the analysis of
      postural stability measures and mean values will be calculated for the vibration trials to
      analyze the expected directional effect. A ratio of the CoP displacements of the ankle
      muscles vibration trial regard to the back muscles vibration trial will be calculated to
      determine the proprioceptive postural control strategy.

      A sample size of 16 participants for intervention group and 8 for control group are required
      to detect a difference of one unit in dyspnea Borg-10 scale, assuming a SD of 1 unit in the
      change in dyspnea score between pre and post measurements (power 80%, level of significance
      p<0.05). These estimates are based on previous work on dyspnea during exercise. Therefore 24
      clinically stable COPD patients with inspiratory muscle weakness (PiMax<70% predicted or
      <60cmH2O) and dyspnea symptoms (BDI<7) will be included. Patients who are unable to perform
      exercise testing will be excluded.

      Patients will perform daily training consisting of two training sessions of 30 breaths
      (intensity ~50% of PiMax; 4-5 minutes per session). One session per week will be performed
      supervised at the research center. IMT will be performed using an electronic tapered flow
      resistive loading (TFRL) device [POWERbreath®KH1, HaB International Ltd., Southam, UK] for 8
      weeks. The PiMax will be measured every week in order to increase the appropriate training
      intensity to around 50% of the PiMax at that moment. The sham group will perform IMT at an
      inspiratory load that is not expected to improve inspiratory muscle function (intensity <10%
      of baseline PiMax; unchanged throughout the protocol).

      Differences in primary and secondary outcomes between groups after 8 weeks of IMT will be
      compared adjusting for baseline differences in an analysis of covariance (ANCOVA).
    

Intervention name(s): Inspiratory Muscle Strength Training; Inspiratory Muscle Endurance Training
Intervention type(s): Procedure; Procedure
Intervention description(s): IMT will be performed using a variable flow resistive loading device (POWERbreathe®KH1, HaB International Ltd., Southam, UK). The device is able to store training parameters of up to 40 sessions. Most training sessions during this RCT will be performed by patients at their homes without supervision. The intervention group (strength IMT) will perform two daily sessions of 30 breaths. Measurements of Pi,max will be performed every week and training loads will be increased continuously to maintain at least 40-50% of the actual Pi,max values. Each week, one training session will be performed under supervision. Training load will be increased during this session.; IMT will be performed using a variable flow resistive loading device (POWERbreathe®KH1, HaB International Ltd., Southam, UK). The device is able to store training parameters of up to 40 sessions. Most training sessions during this RCT will be performed by patients at their homes without supervision. The sham group (endurance IMT) will perform three daily sessions of 30 breaths and will train at a constant inspiratory load of no more than 10% of their initial Pi,max. Each week, one training session will be performed under supervision.
Other intervention name(s): Electronic Variable Flow Resistive Loading IMT Device; POWERbreathe®KH1, HaB International Ltd., Southam, UK; Electronic Variable Flow Resistive Loading IMT Device; POWERbreathe®KH1, HaB International Ltd., Southam, UK
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Inspiratory muscle training; COPD; Dyspnea; Balance