Effect of respiratory muscle training on load sensations in people with chronic tetraplegia: a secondary analysis of a randomised controlled trial.

STUDY DESIGN: Secondary analysis of a randomised controlled trial. OBJECTIVES: Our primary study showed that increasing inspiratory muscle strength with training in people with chronic (>1 year) tetraplegia corresponded with reduced sensations of breathlessness when inspiration was loaded. This study investigated whether respiratory muscle training also affected the respiratory sensations for load detection and magnitude perception. SETTING: Independent research institute in Sydney, Australia. METHODS: Thirty-two adults with chronic tetraplegia participated in a 6-week, supervised training protocol. The active group trained the inspiratory muscles through progressive threshold loading. The sham group performed the same protocol with a fixed threshold load (3.6 cmH2O). Primary measures were load detection threshold and perceived magnitudes of six suprathreshold loads reported using the modified Borg scale. RESULTS: Maximal inspiratory pressure (PImax) increased by 32% (95% CI, 18-45) in the active group with no change in the sham group (p =  0.51). The training intervention did not affect detection thresholds in the active (p =  0.24) or sham (p =  0.77) group, with similar overall decreases in Borg rating of 0.83 (95% CI, 0.49-1.17) in active and 0.72 (95% CI, 0.32-1.12) in sham group. Increased inspiratory muscle strength reduced slope magnitude between Borg rating and peak inspiratory pressure (p =  0.003), but not when pressure was divided by PImax to reflect contraction intensity (p =  0.92). CONCLUSIONS: Training reduces the sensitivity of load sensations for a given change in pressure but not for a given change in contraction intensity.

The reliability of inspiratory resistive load magnitude and detection testing.

OBJECTIVES: To assess the test-retest reliability of inspiratory load detection and load magnitude perception tests in healthy volunteers. DESIGN: Cohort of convenience. SETTING: Respiratory physiology laboratory. PARTICIPANTS: Twenty healthy adults. INTERVENTIONS: On two separate occasions participants performed tests of inspiratory loading. Participants breathed through custom made resistive tubing and were asked to indicate when they detected a different resistance during inspiration. In a second test participants rated the magnitude of presented inspiratory loads using the modified Borg score. MAIN OUTCOME MEASURES: Intra-class Correlation Coefficient (ICC2,1) values for repeated tests of inspiratory load detection threshold and load magnitude rating. RESULTS: ICC2,1 values ranged from 0.657-0.786 for load detection testing and 0.739 to 0.969 for rating of load magnitude. CONCLUSIONS: The tests are simple and reliable measures of inspiratory load detection and magnitude rating. They can be used in future research to determine the effectiveness of interventions to reduce the effort of breathing in health and disease.

Impact of respiratory muscle training on respiratory muscle strength, respiratory function and quality of life in individuals with tetraplegia: a randomised clinical trial.

BACKGROUND: Respiratory complications remain a leading cause of morbidity and mortality in people with acute and chronic tetraplegia. Respiratory muscle weakness following spinal cord injury-induced tetraplegia impairs lung function and the ability to cough. In particular, inspiratory muscle strength has been identified as the best predictor of the likelihood of developing pneumonia in individuals with tetraplegia. We hypothesised that 6 weeks of progressive respiratory muscle training (RMT) increases respiratory muscle strength with improvements in lung function, quality of life and respiratory health. METHODS: Sixty-two adults with tetraplegia participated in a double-blind randomised controlled trial. Active or sham RMT was performed twice daily for 6 weeks. Inspiratory muscle strength, measured as maximal inspiratory pressure (PImax) was the primary outcome. Secondary outcomes included lung function, quality of life and respiratory health. Between-group comparisons were obtained with linear models adjusting for baseline values of the outcomes. RESULTS: After 6 weeks, there was a greater improvement in PImax in the active group than in the sham group (mean difference 11.5 cmH2O (95% CI 5.6 to 17.4), p<0.001) and respiratory symptoms were reduced (St George Respiratory Questionnaire mean difference 10.3 points (0.01-20.65), p=0.046). Significant improvements were observed in quality of life (EuroQol-Five Dimensional Visual Analogue Scale 14.9 points (1.9-27.9), p=0.023) and perceived breathlessness (Borg score 0.64 (0.11-1.17), p=0.021). There were no significant improvements in other measures of respiratory function (p=0.126-0.979). CONCLUSIONS: Progressive RMT increases inspiratory muscle strength in people with tetraplegia, by a magnitude which is likely to be clinically significant. Measurement of baseline PImax and provision of RMT to at-risk individuals may reduce respiratory complications after tetraplegia. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN 12612000929808).

Genioglossus motor unit activity in supine and upright postures in obstructive sleep apnea.

This study investigated whether a change in posture affected the activity of the upper-airway dilator muscle genioglossus in participants with and without obstructive sleep apnea (OSA). During wakefulness, a monopolar needle electrode was used to record single motor unit activity in genioglossus in supine and upright positions to alter the gravitational load that causes narrowing of the upper airway. Activity from 472 motor units was recorded during quiet breathing in 17 males, nine of whom had OSA. The mean number of motor units for each participant was 11.8 (SD 3.4) in the upright and 16.0 (SD 4.2) in the supine posture. For respiratory-modulated motor units, there were no significant differences in discharge frequencies between healthy controls and participants with OSA. Within each breath, genioglossus activity increased through the recruitment of phasic motor units and an increase in firing rate, with an overall increase of ~6 Hz (50%) across both postures and participant groups. However, the supine posture did not lead to compensatory increases in the peak discharge frequencies of inspiratory and expiratory motor units, despite the increase in gravitational load on the upper airway. Posture also had no significant effect on the discharge frequency of motor units that showed no respiratory modulation during quiet breathing. We postulate that, in wakefulness, any increase in genioglossus activity to compensate for the gravitational effects on the upper airway is achieved primarily through the recruitment of additional motor units in both healthy controls and participants with OSA.

Abdominal functional electrical stimulation to assist ventilator weaning in critical illness: a double-blinded, randomised, sham-controlled pilot study.

BACKGROUND: For every day a person is dependent on mechanical ventilation, respiratory and cardiac complications increase, quality of life decreases and costs increase by > $USD 1500. Interventions that improve respiratory muscle function during mechanical ventilation can reduce ventilation duration. The aim of this pilot study was to assess the feasibility of employing an abdominal functional electrical stimulation (abdominal FES) training program with critically ill mechanically ventilated patients. We also investigated the effect of abdominal FES on respiratory muscle atrophy, mechanical ventilation duration and intensive care unit (ICU) length of stay. METHODS: Twenty critically ill mechanically ventilated participants were recruited over a 6-month period from one metropolitan teaching hospital. They were randomly assigned to receive active or sham (control) abdominal FES for 30 min, twice per day, 5 days per week, until ICU discharge. Feasibility was assessed through participant compliance to stimulation sessions. Abdominal and diaphragm muscle thickness were measured using ultrasound 3 times in the first week, and weekly thereafter by a blinded assessor. Respiratory function was recorded when the participant could first breathe independently and at ICU discharge, with ventilation duration and ICU length of stay also recorded at ICU discharge by a blinded assessor. RESULTS: Fourteen of 20 participants survived to ICU discharge (8, intervention; 6, control). One control was transferred before extubation, while one withdrew consent and one was withdrawn for staff safety after extubation. Median compliance to stimulation sessions was 92.1% (IQR 5.77%) in the intervention group, and 97.2% (IQR 7.40%) in the control group (p = 0.384). While this pilot study is not adequately powered to make an accurate statistical conclusion, there appeared to be no between-group thickness changes of the rectus abdominis (p = 0.099 at day 3), diaphragm (p = 0.652 at day 3) or combined lateral abdominal muscles (p = 0.074 at day 3). However, ICU length of stay (p = 0.011) and ventilation duration (p = 0.039) appeared to be shorter in the intervention compared to the control group. CONCLUSIONS: Our compliance rates demonstrate the feasibility of using abdominal FES with critically ill mechanically ventilated patients. While abdominal FES did not lead to differences in abdominal muscle or diaphragm thickness, it may be an effective method to reduce ventilation duration and ICU length of stay in this patient group. A fully powered study into this effect is warranted. TRIAL REGISTRATION: The Australian New Zealand Clinical Trials Registry, ACTRN12617001180303. Registered 9 August 2017.

Reflex response to airway occlusion in human inspiratory muscles when recruited for breathing and posture.

Briefly occluding the airway during inspiration produces a short-latency reflex inhibition in human inspiratory muscles. This occlusion reflex seems specific to respiratory muscles; however, it is not known whether the reflex inhibition has a uniform effect across a motoneuron pool when a muscle is recruited concurrently for breathing and posture. In this study, participants were seated and breathed through a mouthpiece that occluded inspiratory airflow for 250 ms at a volume threshold of 0.2 liters. The reflex response was measured in the scalene and sternocleidomastoid muscles during 1) a control condition with the head supported in space and the muscles recruited for breathing only, 2) a postural condition with the head unsupported and the neck flexors recruited for both breathing and to maintain head posture, and 3) a large-breath condition with the head supported and the volume threshold raised to between 0.8 and 1.0 liters to increase inspiratory muscle activity. When normalized to its preocclusion mean, the reflex response in the scalene muscles was not significantly different between the large-breath and control conditions, whereas concomitant recruitment of these muscles for posture control reduced the reflex response by half compared with the control condition. A reflex response occurred in sternocleidomastoid when it contracted phasically as an accessory muscle for inspiration during the large-breath condition. These results indicate that the occlusion reflex does not produce a uniform effect across the motoneuron pool and that afferent inputs for this reflex most likely act via intersegmental networks of premotoneurons rather than at a motoneuronal level. NEW & NOTEWORTHY In this study, we investigated the effect of nonrespiratory activity on the reflex response to brief sudden airway occlusions in human inspiratory muscles. We show that the reflex inhibition in the scalene muscles was not uniform across the motoneuron pool when the muscle was recruited concurrently for breathing and postural control. The reflex had a larger effect on respiratory-driven motoneurons than those recruited to maintain head posture.

Inspiratory pre-motor potentials during quiet breathing in ageing and chronic obstructive pulmonary disease.

KEY POINTS: A cortical contribution to breathing, as indicated by a Bereitschaftspotential (BP) in averaged electroencephalographic signals, occurs in healthy individuals when external inspiratory loads are applied. Chronic obstructive pulmonary disease (COPD) is a condition where changes in the lung, chest wall and respiratory muscles produce an internal inspiratory load. These changes also occur in normal ageing, although to a lesser extent. In the present study, we determined whether BPs are present during quiet breathing and breathing with an external inspiratory load in COPD compared to age-matched and young healthy controls. We demonstrated that increased age, rather than COPD, is associated with a cortical contribution to quiet breathing. A cortical contribution to inspiratory loading is associated with more severe dyspnoea (i.e. the sensation of breathlessness). We propose that cortical mechanisms may be engaged to defend ventilation in ageing with dyspnoea as a consequence. ABSTRACT: A cortical contribution to breathing is determined by the presence of a Bereitschaftspotential, a low amplitude negativity in the averaged electroencephalographic (EEG) signal, which begins ∼1 s before inspiration. It occurs in healthy individuals when external inspiratory loads to breathing are applied. In chronic obstructive pulmonary disease (COPD), changes in the lung, chest wall and respiratory muscles produce an internal inspiratory load. We hypothesized that there would be a cortical contribution to quiet breathing in COPD and that a cortical contribution to breathing with an inspiratory load would be linked to dyspnoea, a major symptom of COPD. EEG activity was analysed in 14 participants with COPD (aged 57-84 years), 16 healthy age-matched (57-87 years) and 15 young (18-26 years) controls during quiet breathing and inspiratory loading. The presence of Bereitschaftspotentials, from ensemble averages of EEG epochs at Cz and FCz, were assessed by blinded assessors. Dyspnoea was rated using the Borg scale. The incidence of a cortical contribution to quiet breathing was significantly greater in participants with COPD (6/14) compared to the young (0/15) (P = 0.004) but not the age-matched controls (6/16) (P = 0.765). A cortical contribution to inspiratory loading was associated with higher Borg ratings (P = 0.007), with no effect of group (P = 0.242). The data show that increased age, rather than COPD, is associated with a cortical contribution to quiet breathing. A cortical contribution to inspiratory loading is associated with more severe dyspnoea. We propose that cortical mechanisms may be engaged to defend ventilation with dyspnoea as a consequence.

Influence of respiratory mechanics and drive on genioglossus movement under ultrasound imaging.

METHODS: Twenty healthy subjects (10 males, age 28±5 years [mean ± SD]) lay supine, awake, with the head in a neutral position. Ventilation was monitored with inductance bands. Real-time B-mode ultrasound movies were analysed. We measured genioglossus motion (i) during spontaneous breathing, voluntary targeted breathing (normal tidal volume Vt), and voluntary hyperpnoea (at 1.5Vt and 2 Vt); (ii) during inspiratory flow resistive loading; (iii) with changes in end-expiratory lung volume (EELV). RESULTS: Average peak inspiratory displacement of the infero-posterior region of genioglossus was 0.89±0.56 mm; 1.02±0.88 mm; 1.27±0.70 mm respectively for voluntary Vt, and during voluntary hyperpnoea at 1.5Vt and 2Vt. A change in genioglossus motion was observed with increased Vt. During increasing inspiratory resistive loading, the genioglossus displaced less anteriorly (p = 0.005) but more inferiorly (p = 0.027). When lung volume was altered, no significant changes in genioglossus movement were observed (p = 0.115). CONCLUSION: In healthy subjects, we observed non-uniform heterogeneous inspiratory motion within the inferoposterior part of genioglossus during spontaneous quiet breathing with mean peak displacement between 0.5-2 mm, with more displacement in the posterior region than the anterior. This regional heterogeneity disappeared during voluntary targeted breathing. This may be due to different neural drive to genioglossus during voluntary breathing. During inspiratory resistive loading, the observed genioglossus motion may serve to maintain upper airway patency by balancing intraluminal negative pressure with positive pressure generated by upper airway dilatory muscles. In contrast, changes in EELV were not accompanied by major changes in genioglossus motion.

Feedforward consequences of isometric contractions: effort and ventilation.

The onset of voluntary muscle contractions causes rapid increases in ventilation and is accompanied by a sensation of effort. Both the ventilatory response and perception of effort are proportional to contraction intensity, but these behaviors have been generalized from contractions of a single muscle group. Our aim was to determine how these relationships are affected by simultaneous contractions of multiple muscle groups. We examined the ventilatory response and perceived effort of contraction during separate and simultaneous isometric contractions of the contralateral elbow flexors and of an ipsilateral elbow flexor and knee extensor. Subjects made 10-sec contractions at 25, 50, and 100% of maximum during normocapnia and hypercapnia. For simultaneous contractions, both muscle groups were activated at the same intensities. Ventilation was measured continuously and subjects rated the effort required to produce each contraction. As expected, ventilation and perceived effort increased proportionally with contraction intensity during individual contractions. However, during simultaneous contractions, neither ventilation nor effort reflected the combined muscle output. Rather, the ventilatory response was similar to when contractions were performed separately, and effort ratings showed a small but significant increase for simultaneous contractions. Hypercapnia at rest doubled baseline ventilation, but did not affect the difference in perceived effort between separate and simultaneous contractions. The ventilatory response and the sense of effort at the onset of muscle activity are not related to the total output of the motor pathways, or the working muscles, but arise from cortical regions upstream from the motor cortex.

Human intersegmental reflexes from intercostal afferents to scalene muscles.

NEW FINDINGS: What is the central question of this study? The aim was to determine whether specific reflex connections operate between intercostal afferents and the scalene muscles in humans, and whether these connections operate after a clinically complete cervical spinal cord injury. What is the main finding and its importance? This is the first description of a short-latency inhibitory reflex connection between intercostal afferents from intercostal spaces to the scalene muscles in able-bodied participants. We suggest that this reflex is mediated by large-diameter afferents. This intercostal-to-scalene inhibitory reflex is absent after cervical spinal cord injury and may provide a way to monitor the progress of the injury. Short-latency intersegmental reflexes have been described for various respiratory muscles in animals. In humans, however, only short-latency reflex responses to phrenic nerve stimulation have been described. Here, we examined the reflex connections between intercostal afferents and scalene muscles in humans. Surface EMG recordings were made from scalene muscles bilaterally, in seven able-bodied participants and seven participants with motor- and sensory-complete cervical spinal cord injury (median 32 years postinjury, range 5 months to 44 years). We recorded the reflex responses produced by stimulation of the eighth or tenth left intercostal nerve. A short-latency (∼38 ms) inhibitory reflex was evident in able-bodied participants, in ipsilateral and contralateral scalene muscles. This bilateral intersegmental inhibitory reflex occurred in 46% of recordings at low stimulus intensities (at three times motor threshold). It was more frequent (in 75-85% of recordings) at higher stimulus intensities (six and nine times motor threshold), but onset latency (38 ± 9 ms, mean ± SD) and the size of inhibition (23 ± 10%) did not change with stimulus intensity. The reflex was absent in all participants with spinal cord injury. As the intercostal-to-scalene reflex did not increase with larger stimulus intensities, it is likely to be mediated by large-diameter intercostal muscle afferents. This is the first demonstration of an intercostal-to-scalene reflex. As the reflex requires intact spinal connections, it may be a useful marker for recovery of thoracic or cervical spinal injury.

Short-latency inhibitory reflex responses to inspiratory loading of the scalene muscles are impaired in spinal cord injury.

NEW FINDINGS: What is the central question of this study? The aim was to determine whether the reflex inhibition in the electromyographic activity of scalene muscles in response to inspiratory muscle loading is present in individuals with cervical spinal cord injury and to examine whether the intercostal muscle afferents are critical for genesis of the reflex. What is the main finding and its importance? The lack of reflex inhibition in response to inspiratory loading in individuals with complete cervical spinal cord injury suggests that the reflex critically requires input from intercostal afferents and/or an intact intersegmental neural network. In healthy individuals, transient loading of inspiratory muscles with a brief inspiratory occlusion produces a short-latency inhibitory response (IR) in the electromyographic activity of scalene muscles at ∼40 ms, followed by an excitatory response (ER). It has been argued that this reflex plays a protective role in neuromuscular control of the inspiratory muscles and that it is co-ordinated by spinal segmental or supraspinal circuits. In this study, the reflex response to airway occlusion was recorded bilaterally from scalene muscles in 14 subjects and from the right costal diaphragm in seven subjects with spinal cord injury [SCI, C4-C6; American Spinal Injury Association (ASIA) Impairment Scale (AIS) A]. The incidence, latency and size of the reflex were compared with previously published data from able-bodied subjects. Only two subjects with SCI showed an IR, and six subjects had an ER. Latencies to the onset and peak of the IR and ER were 5-50 ms longer than in able-bodied subjects. However, when reflexes were identified, their size in individuals with SCI was similar to that of control subjects. We conclude that afferents from the scalene muscles and diaphragm are insufficient in most subjects with SCI to evoke the usual inhibition to airway occlusion and that input from chest wall afferents below the spinal cord lesion may be important for genesis of the short-latency inhibition in the able-bodied subjects.

Electrical stimulation of abdominal muscles to produce cough in spinal cord injury: effect of stimulus intensity.

BACKGROUND: Surface electrical stimulation of the abdominal muscles, with electrodes placed in the posterolateral position, combined with a voluntary cough can assist clearance of airway secretions in individuals with high-level spinal cord injury (SCI). OBJECTIVE: To determine whether an increase in stimulus intensity of the trains of electrical stimuli delivered to the expiratory muscles has an increasing effect on a stimulated voluntary cough and to determine at which stimulus intensity a plateau of cough peak expiratory flow occurs. METHODS: In 7 healthy individuals with a SCI at and above C7, gastric pressure (P(ga)), esophageal pressure (P(es)), peak expiratory cough flow (PEF(cough)), and expiratory volume were measured as participants coughed voluntarily with simultaneous trains of electrical stimuli delivered over the abdominal muscles (50 Hz, 1-s duration). The intensity of the stimulation was increased incrementally. RESULTS: A plateau in PEF(cough) occurred in all 7 individuals at a mean of 211 ± 29 mA (range 120-360 mA). Peak values reached for P(ga), P(es), and PEF(cough) were 83.0 ± 8.0 cm H2O, 66.1 ± 5.6 cm H2O, and 4.0 ± 0.4 l/s respectively. CONCLUSIONS: The plateau in expiratory cough flow that was associated with increasing expiratory pressures is indicative of dynamic airway compression. This suggests that the evoked cough will be effective in creating more turbulent airflow to further assist in dislodging mucus and secretions.

Abdominal muscle training can enhance cough after spinal cord injury.

BACKGROUND: Respiratory complications in people with high-level spinal cord injury (SCI) are a major cause of morbidity and mortality, particularly because of a reduced ability to cough as a result of abdominal muscle paralysis. OBJECTIVE: . We investigated the effect of cough training combined with functional electrical stimulation (FES) over the abdominal muscles for 6 weeks to observe whether training could improve cough strength. METHODS: Fifteen SCI subjects (C4-T5) trained for 6 weeks, 5 days per week (5 sets of 10 coughs per day) in a randomized crossover design study. Subjects coughed voluntarily at the same time as a train of electrical stimulation was delivered over the abdominal muscles via posterolaterally positioned electrodes (50 Hz, 3 seconds). Measurements were made of esophageal (Pes) and gastric (Pga) expiratory pressures and the peak expiratory flow (PEFcough) produced at the 3 time points of before, during, and after the training. RESULTS: During voluntary coughs, FES cough stimulation improved Pga, Pes, and PEFcough acutely, 20-fold, 4-fold, and 50%, respectively. Six weeks of cough training significantly increased Pga (37.1 ± 2.0 to 46.5 ± 2.9 cm H2O), Pes (35.4 ± 2.7 to 48.1 ± 2.9 cm H2O), and PEFcough (3.1 ± 0.1 to 3.6 ± 0.1 L/s). Cough training also improved pressures and flow during voluntary unstimulated coughs. CONCLUSIONS: FES of abdominal muscles acutely increases mechanical output in coughing in high-level SCI subjects. Six weeks of cough training further increases gastric and esophageal cough pressures and expiratory cough flow during stimulated cough maneuvers.

Increased ventilation does not impair maximal voluntary contractions of the elbow flexors.

Exercise performance is impaired by increased respiratory work, yet the mechanism for this is unclear. This experiment assessed whether neural drive to an exercising muscle was affected by cortically driven increases in ventilation. On each of 5 days, eight subjects completed a 2-min maximal voluntary contraction (MVC) of the elbow flexor muscles, followed by 4 min of recovery, while transcranial magnetic stimulation tested for suboptimal neural drive to the muscle. On 1 day, subjects breathed without instructions under normocapnia. During the 2-min MVC, ventilation was approximately 3.5 times that at rest. On another day, subjects breathed without instruction under hypercapnia. During the 2-min MVC, ventilation was approximately 1.5 times that on the normocapnic day. On another 2 days under normocapnia, subjects voluntarily matched their breathing to the uninstructed breathing under normocapnia and hypercapnia using target feedback of the rate and inspiratory volume. On a fifth day under normocapnia, the volume feedback was set to each subject's vital capacity. On this day, ventilation during the 2-min MVC was approximately twice that on the uninstructed normocapnic day (or approximately 7 times rest). The experimental manipulations succeeded in producing voluntary and involuntary hyperpnea. However, maximal voluntary force, fatigue and voluntary activation of the elbow flexor muscles were unaffected by cortically or chemically driven increases in ventilation. Results suggest that any effects of increased respiratory work on limb exercise performance are not due to a failure to drive both muscle groups optimally.

Panic attacks and perception of inspiratory resistive loads in chronic obstructive pulmonary disease.

RATIONALE: Panic attacks are common in chronic obstructive pulmonary disease (COPD), and the prevalence of panic disorder is at least 10 times higher than in the general population. In the current study, we examined resistive load perception in patients with COPD with and without panic attacks. OBJECTIVES: We tested competing hypotheses, based on conflicting results of earlier studies, that those patients with COPD with panic attacks or panic disorder would show either heightened or blunted perception of dyspnea as the magnitude of inspiratory resistive loads increased. METHODS: We compared 20 patients with COPD with panic attacks or panic disorder, 20 patients without panic, and 20 healthy, age-matched subjects using an inspiratory resistive load-testing protocol. MEASUREMENTS AND MAIN RESULTS: We administered a diagnostic interview for panic attacks and panic disorder. We measured perceived dyspnea in response to increasing inspiratory resistive loads (modified Borg scale) and several respiratory variables. Dyspnea ratings increased linearly for all groups as the size of resistive loads increased. No significant differences were found between groups on the respiratory variables. Patients with COPD with panic attacks or panic disorder rated their level of dyspnea significantly higher than did other subjects. CONCLUSIONS: Patients with COPD with panic attacks showed heightened sensitivity to inspiratory loads. The result reinforces the influence of psychological factors on symptom perception in this disease.