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Respiratory Investigation Unit, Department of Medicine, Queen's University, Kingston, Ontario, Canada K7L 2V7
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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We
mimicked important mechanical and ventilatory aspects of restrictive
lung disorders by employing chest wall strapping (CWS) and dead space
loading (DS) in normal subjects to gain mechanistic insights into
dyspnea causation and exercise limitation. We hypothesized that
thoracic restriction with increased ventilatory stimulation would evoke
exertional dyspnea that was similar in nature to that experienced in
such disorders. Twelve healthy young men [28 ± 2 (SE) yr of
age] completed pulmonary function tests and maximal cycle
exercise tests under four conditions, in randomized order: 1)
control, 2) CWS to 60% of vital capacity, 3) added DS
of 600 ml, and 4) CWS + DS. Measurements during exercise
included cardiorespiratory parameters, esophageal pressure, and Borg
scale ratings of dyspnea. Compared with control, CWS significantly
reduced the tidal volume response to exercise, increased dyspnea
intensity at any given work rate or ventilation, and thus limited
exercise performance. DS stimulated ventilation but had minimal effects
on dyspnea and exercise performance. Adding DS to CWS further increased
dyspnea by 1.7 ± 0.6 standardized Borg units (P = 0.012) and
decreased exercise performance (total work) by 21 ± 6% (P = 0.003) over CWS alone. Across conditions, increased dyspnea intensity
correlated best with decreased resting inspiratory reserve volume
(r = 
0.63, P < 0.0005). Dyspnea
during CWS was described primarily as "inspiratory difficulty"
and "unsatisfied inspiration," similar to restrictive disorders.
In conclusion, severe dyspnea and exercise intolerance were provoked in
healthy normal subjects when tidal volume responses were constrained in
the face of increased ventilatory drive during exercise.
dyspnea; exercise; mechanisms
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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IN MANY CARDIOPULMONARY DISORDERS, restrictive mechanical constraints on tidal volume (VT) expansion during exercise may contribute to exertional dyspnea and exercise intolerance (31). Restrictive mechanical abnormalities are the hallmark of disorders of the chest wall (i.e., kyphoscoliosis, pleural disease, neuromuscular disease, and abdominal distension), as well as infiltrative parenchymal diseases (i.e., interstitial lung disease). Similarly, restrictive mechanics occur in advanced chronic obstructive pulmonary disease, since VT is constrained as a consequence of dynamic lung hyperinflation (31, 35). Restrictive disorders are characterized by high ratios of VT to inspiratory capacity (IC) and relative tachypnea at low levels of exercise (31). We previously postulated that resting mechanical restriction and a restricted mechanical response to a given or excessive respiratory drive during exercise give rise to important qualitative dimensions of exertional dyspnea such as "unsatisfied inspiratory effort" and "shallowness" of breathing, which are characteristic of restrictive disorders (32, 33).
The effects of physical restriction in disease are compounded in many instances by a concomitant increase in respiratory drive due to, for example, the ventilatory stimulation effects of high physiological dead space. The coexistence of mechanical restriction and increased respiratory drive during exercise may hasten ventilatory limitation and the onset of intolerable dyspnea, which together limit exercise performance. In the disease state, it is difficult to evaluate the relative importance of mechanical loading and increased ventilatory demand and how these interrelate to contribute to dyspnea and exercise intolerance. Therefore, to gain new insights into the relative importance of these factors in restrictive disorders, we examined the effects of mechanical restriction and dead space loading, alone and in combination, on the quality and intensity of dyspnea, dynamic ventilatory mechanics, and exercise performance in normal healthy individuals.
Twelve healthy, young men undertook symptom-limited, incremental cycle exercise under four conditions, in random order: 1) unloaded control, 2) chest wall strapping (CWS) to reduce vital capacity (VC) to 60% predicted, 3) dead space loading (DS) with 600 ml of added dead space, and 4) CWS + DS. First, we studied the effects of CWS on dyspnea, exercise tolerance, ventilatory mechanics, and breathing pattern and determined the primary physiological contributing factors. Second, we compared the effects of ventilatory stimulation by DS under control conditions and conditions of mechanical restriction (CWS) to examine the sensory consequences of DS when subjects are deprived of the normal compensatory responses to this intervention. Finally, we compared the quality and intensity of dyspnea under all four conditions while we accounted for the level of ventilation, breathing pattern, respiratory effort [tidal esophageal pressure (Pes) swings relative to maximum inspiratory pressure (PImax), Pes/PImax], and the prevailing ventilatory constraints.
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Study Design
This was a single-center, controlled study. After hospital/university research ethics approval was obtained, subjects gave informed consent and entered the study on a staggered basis. Initial screening consisted of medical history, complete pulmonary function testing, familiarization with all testing procedures and questionnaires, and initial adjustment of the restriction vest such that the VC was ~50-60% of baseline. During experimental visits, subjects performed four symptom-limited maximal cycle exercise tests, randomized to order: control, CWS, DS, and CWS + DS. Subjects avoided caffeine and heavy meals
4 h before testing and avoided alcohol and major physical
exertion entirely on the day of each visit. All visits were conducted
at the same time of day for each subject.
Subjects
Subjects included 12 healthy male volunteers between 20 and 40 yr of age. Exclusion criteria included preexisting cardiac or pulmonary disease, inability to exercise because of neuromuscular or musculoskeletal disease, use of medications that may modify sensation of dyspnea, other potential causes of dyspnea, a smoking history of >5 pack-yr, or overweight (body mass index26 kg/m2).
CWS
A customized canvas restriction vest or corsetlike strap was adjusted to fit just beneath the axillae and around the chest to envelop the rib cage. The desirable degree of volume restriction was achieved by tightening a number of buckles at the back while subjects expired to residual volume (RV); a quick-release Velcro strap was present at the front for safety reasons. The extent of volume reduction during CWS was measured in a body plethysmograph after10 min of acclimatization to
the tightened chest strap.
DS
A dead space of 600 ml was added to the breathing circuit by using a length of 35-mm tubing connected to a Hans Rudolph low-resistance two-way nonrebreathing valve. The resistance added to the circuit was minimal at <1.0 cmH2O for a flow rate of 100 l/min (which approximates the level of ventilation at peak exercise). This methodology has been shown by others to consistently stimulate ventilation during exercise (28).Pulmonary Function Testing
Routine spirometry (6200 Autobox DL, SensorMedics, Yorba Linda, CA) was performed before exercise testing in accordance with recommended techniques (19). Functional residual capacity (FRC) and specific airway resistance (sRaw) were determined by constant-volume body plethysmography (6200 Autobox DL). Predicted normal values for spirometry, lung volumes, and sRaw were those of Morris and associates (30), Goldman and Becklake (20), and Briscoe and Dubois (7), respectively.Maximum inspiratory mouth pressures (MIP) from FRC and maximum expiratory mouth pressures (MEP) from TLC were measured with a standard mouthpiece and a direct-reading dial pressure gauge (Magnehelic, Dwyer Instruments, Michigan City, IN). Values for MIP were compared with the predicted normal values of Hamilton and co-workers (22).
Symptom Evaluation
Dyspnea, or breathing discomfort, was defined to subjects as "difficulty breathing," leg discomfort as "the level of difficulty experienced during pedaling," and inspiratory/expiratory difficulty as "the difficulty experienced while breathing in (and out)." Before exercise testing, subjects were familiarized with the modified Borg scale (6), and its end points were anchored such that zero represented "no breathing (leg) discomfort" and 10 was "the most severe breathing (leg) discomfort that they had ever experienced or could imagine experiencing." Subjects rated the intensity of their perceived breathing discomfort, inspiratory difficulty, expiratory difficulty, and leg discomfort by pointing to the Borg scale at rest, at every stage of exercise, and at peak exercise. On exercise cessation, subjects were asked to verbalize their main reason(s) for stopping exercise and to select qualitative descriptors of their peak exertional dyspnea by using a questionnaire modified from Simon et al. (37). In this questionnaire, subjects were specifically asked to "circle all applicable descriptors of your uncomfortable awareness of breathing" from a list of 15 possible descriptor phrases.Exercise Testing
During initial screening, a progressive cycle exercise test was performed for familiarization purposes to a symptom-limited maximum, as described in a previous publication (32). In experimental visits, cycle exercise tests were performed in a similar manner, with an incremental protocol increasing the work rate by 25 W every 3 min.Exercise tests were conducted on an electronically braked cycle ergometer (Ergometrics 800S, SensorMedics, Anaheim, CA) with use of a SensorMedics Vmax229 cardiopulmonary exercise testing system. With nasal passages occluded by a noseclip, subjects breathed through a mouthpiece attached to a low-resistance flow transducer adjusted and fixed at a comfortable height for each subject. An additional setup was integrated into the system to measure flow rates and Pes for the assessment of ventilatory mechanics (see below). Electrocardiography and pulse oximetry were carried out continuously, and blood pressure was taken by auscultation at rest, at the end of each stage of exercise, at peak exercise, and during recovery from exercise. Changes in end-expiratory lung volume (EELV) were estimated from IC maneuvers performed at rest, at every stage of exercise, and at peak exercise (with the assumption that TLC does not change with exercise). Techniques for performing and accepting IC measurements have been previously described (33, 34).
All exercise tests were terminated at the point of exhaustion or symptom limitation. For exercise tests with CWS, the restriction vest was adjusted 10 min before the start of the test and kept on throughout exercise. Exercise tests with DS included the 600-ml dead space as part of the mouth valve setup. Exercise responses were compared with the predicted normal values of Jones (25).
Breathing pattern analysis. Flow and integrated volume were recorded continuously during exercise testing. Tidal flow-volume curves at rest and at peak exercise were constructed for each subject and placed within their respective maximal flow-volume envelopes according to coinciding IC measurements. For this analysis, maximal flow-volume loops were performed at rest and immediately after exercise. The presence or absence of flow limitation was determined by comparing tidal expiratory flow rates with those of the maximal envelope at isovolume.
Lung mechanics: measurement and analysis. Pes was recorded continuously at rest and during exercise with use of a balloon-tipped catheter system. A 10-cm latex balloon containing 0.5 ml of air and connected by a polyethylene catheter to a Validyne differential pressure transducer was positioned according to an accepted technique (4). Concurrently with measurement periods at rest and peak exercise, maximum inspiratory maneuvers against an occluded airway at EELV were performed to obtain maximum values for Pes (PImax). The tension-time index of the inspiratory muscles was calculated as the product of mean inspiratory Pes/PImax and the inspiratory duty cycle (5). Finally, an index of neuromechanical coupling was calculated as the ratio of Pes/PImax to standardized VT (VT/predicted VC).
Statistical Analysis
Values are means ± SE. The conventional level of statistical significance of 0.05 was used for all analyses. Qualitative descriptors of breathlessness were analyzed as frequency statistics; group comparisons were made using Fisher's exact test. Measurements at rest, at peak exercise, and at a standardized level of exercise [the highest equivalent work rate (HEWR) that each subject completed in all exercise tests] were evaluated. Exercise-response slopes were studied using linear regression analysis of data sets from each individual. Exercise performance was evaluated as peak exercise capacity [i.e., maximum work rate (WRmax)] and as total work performed (i.e., total cumulative work). Summary statistics under each condition were compared using ANOVA for repeated measures.To examine associations between changes in exercise performance in
response to the different testing conditions and possible contributing
factors, regression analysis was performed across experimental
conditions; regressions were not performed within each condition
because of lack of power with a small sample size (n = 12) and
lack of variation in imposed levels of lung restriction [i.e., a
homogeneous reduction in forced vital capacity (FVC)]. Pearson's
correlations were performed using the percent change in total work (and
change in WRmax) as the dependent variable and various
measurements at rest and at a standardized level of exercise as
independent variables: resting spirometry [forced expiratory
volume in 1 s (FEV1)/FVC], operational lung volumes [IC, inspiratory reserve volume (IRV), VT/IC],
gas exchange [arterial O2 saturation
(SaO2) and fraction of end-tidal
CO2], ventilation (
E), breathing pattern (breathing
frequency and VT), respiratory mechanics
(Pes/PImax and PImax),
an index of neuromechanical dissociation (ratio of
Pes/PImax to VT/predicted VC), and
Borg ratings of symptom intensity (dyspnea, inspiratory difficulty, and
expiratory difficulty). Stepwise multiple regression analysis was then
carried out to establish the best predictive equation for this change;
resultant models were reestimated with significant predictors only.
Finally, possible predictors of change in exertional breathlessness at a standardized level of exercise (
BorgHEWR) were
evaluated similarly.
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Subjects
All 12 subjects successfully completed pulmonary function and exercise testing under each of the experimental conditions; however, two subjects did not have Pes measurements for the DS testing because of intolerance of the esophageal catheter. All subjects were nonsmokers, except one who had a <5 pack-yr smoking history. Subjects had normal baseline pulmonary function and exercise capacity (Table 1).
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Chest Wall Restriction
Application of CWS to the selected level of restriction resulted in significant changes in resting lung volumes (Table 1, Figs. 1 and 2) but had little effect on forced expiratory flow rates at a given lung volume (Fig. 1). The 35 ± 2% reduction in FVC was largely accomplished by reducing TLC with minimal reduction in RV. The 36 ± 2% reduction in IC resulted from reductions in TLC and FRC, with a resultant decrease in resting IRV by 45 ± 2% or 1.31 ± 0.07 liters. sRaw fell during CWS, while specific conductance increased significantly (Table 1).
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Exercise performance was significantly curtailed during testing with
CWS (Table 2, Fig.
3): the peak work rate achieved fell by
15 ± 1% (P < 0.01), and the total cumulative work
performed fell by 28 ± 3% (P < 0.01). Although peak
E was not different from control, levels
were increased at HEWR by 11.0 l/min (P < 0.01; Table
3) and at rest by 2.4 l/min (P < 0.05; Table 4). The increase in
E was directly related to the increase in
O2 consumption
(O2; r = 0.78, P = 0.003) and CO2 production
(CO2; r = 0.77, P = 0.003), such that
E/O2
and
E/CO2
slopes were superimposed under both conditions. The reduction in IC and IRV during CWS resulted in mechanical constraints on VT
expansion during exercise and a significantly more rapid and shallow
breathing pattern. There was no significant dynamic hyperinflation
throughout exercise with CWS (Fig. 2), although tidal expiratory flow
rates were closer to the maximal envelope during exercise: at HEWR, midtidal expiratory flows reached 34 ± 3 and 69 ± 6% of the
maximal flow at isovolume during control and CWS exercise, respectively (P < 0.0005).
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Respiratory effort (Pes/PImax) was elevated
throughout exercise for any given work rate (Table 3) or
E (Fig. 4)
because of an increase in tidal Pes and a decrease in
PImax. The increase in
Pes/PImax, combined with the significant
reduction in VT, resulted in increases in the ratio of
Pes/PImax to VT/predicted VC at
rest (P = 0.10) and throughout exercise (P < 0.05;
Fig. 3).
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Dyspnea intensity was significantly increased at any given work rate or
E (Figs. 3 and 4). This increase
correlated strongly with the increase in Borg ratings of inspiratory
difficulty (r = 0.87, P < 0.0005). In contrast to the
control condition, subjects predominantly described their exertional
dyspnea during CWS with phrases such as "breathing in requires more
effort" (83%) or those related to the sense of unsatisfied
inspiration: "I cannot get enough air in" (67%), "I cannot
take a deep breath in" (67%), and "my breath does not go in all
the way" (67%; Table 5). Although the
chest strap also imposed a general sense of chest tightness, subjects
reported that this did not change from rest to peak exercise.
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DS
The addition of a 600-ml dead space to the breathing circuit had relatively neutral effects on exercise tolerance and exertional dyspnea (Fig. 5). Breathing with added DS resulted in increases inE at rest and at any
given work rate during exercise that were comparable to those in the
CWS condition; however, there was no significant change in the peak
work rate achieved during exercise with added DS. Physiological changes
at rest and throughout exercise also included increases in end-tidal
CO2, VT, and tidal flow rates, with little
change in respiratory timing (Tables 2-4). Although tidal
Pes/PImax increased significantly during
exercise with DS, the ratio of Pes/PImax to
VT/predicted VC was not different from control at a given
work rate (Table 3) or E (Fig. 4).
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Compared with control, dyspnea intensity was only modestly elevated for
a given work rate during exercise with DS but did not change
significantly when expressed as a function of
E (Fig. 5). In the latter relationship,
dyspnea and E increased together along
the same slope with added DS. Qualitative descriptors of exertional
dyspnea during DS were not significantly different from control: the
primary descriptors chosen were "my breathing requires more work"
(75%), and "my breathing is heavy" (67%; Table 5).
CWS + DS
Adding DS to the restricted CWS condition resulted in more profound reductions in exercise tolerance: peak work rate fell by an additional 14 ± 4% (P = 0.005), while total work fell by an additional 21 ± 6% (P = 0.003) over CWS alone. Physiological responses to exercise were generally similar to those of CWS alone, although changes in several variables were larger (Fig. 3): increases inE, breathing frequency,
VT-to-inspiratory time ratio, VT-to-expiratory time ratio, tidal maximum expiratory flow rate, tidal Pes,
Pes/VT, and end-tidal CO2 were significantly
greater at HEWR, as were reductions in IRV and
SaO2 (Table 3). However, measurements of breathing frequency, VT, Pes/PImax,
and Pes/VT were not different from those with CWS alone
when they were expressed as a function of
E (Fig. 4).
Compared with CWS alone, there was a significant additional increase in
Borg ratings of dyspnea (by 1.7 ± 0.6, P = 0.012) and
inspiratory difficulty (by 2.2 ± 0.06, P = 0.003) at HEWR; i.e., slopes of Borg dyspnea ratings over work rate were further heightened by adding DS to the CWS condition (Fig. 3). However, slopes
of Borg dyspnea ratings over E were not
changed by the addition of DS to the restricted CWS condition, such
that increases in dyspnea were directly proportional to increases in
ventilation (Fig. 4). Similar to CWS alone, increased dyspnea intensity
was primarily related to increased inspiratory difficulty (r = 0.93, P < 0.0005). The addition of DS to CWS did not alter
the qualitative nature of dyspnea from that of CWS alone (Table 5).
During exercise with CWS + DS, four subjects showed O2
desaturation of 4%, to 
90% (the lowest being 83%). These
subjects did not experience a significantly greater increase in
exertional dyspnea intensity or reduction in exercise performance than
those who did not desaturate. However, there was a tendency toward a different selection of dyspnea descriptors at the end of exercise: those who desaturated were more likely to note that their "work" of breathing was increased (P = 0.08) and that their breathing felt more rapid (P = 0.08) and shallow (P = 0.08);
there were no differences in the selection frequency of other
descriptors such as "hunger" or "suffocation."
Correlates of Exercise Performance and Exertional Dyspnea
In response to all interventions (DS, CWS, CWS + DS), reductions in exercise performance from the control condition correlated best with increases in the intensity of inspiratory difficulty: 1) percent change () in total work correlated with inspiratory BorgHEWR (r = 0.72, P < 0.0005; Fig. 6), and 2)
%WRmax also correlated best with inspiratory
BorgHEWR (r = 0.72, P < 0.0005).
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With no imposed restrictions on the VT response, the
intensity and quality of dyspnea during exercise with DS were similar to the unloaded control test. We therefore analyzed the correlates of
inspiratory difficulty within CWS conditions only (with and without
DS), with corrections performed to account for repeated tests within
subjects. Changes in standardized Borg ratings of inspiratory
difficulty during constrained exercise (CWS with and without DS)
correlated best with the resting IRV normalized as a percentage of
predicted TLC (r2 = 0.43, r = 0.66,
P < 0.0005; Fig. 6), such that exertional dyspnea was most
severe when mechanical constraints on VT expansion were
greatest; after repeated testing in subjects was taken into account,
resting IRV continued to account for 43% of the variance in
inspiratory BorgHEWR (P < 0.0005). Note how
added DS increased the effects of imposed CWS (Fig. 6).
After repeated testing within subjects and the resting IRV were
accounted for, changes in various parameters measured during exercise
also contributed significantly to the variance in inspiratory BorgHEWR: these included changes in concurrent exercise
measurements of IRV/predicted TLC (P = 0.012) and
VT/IC (P = 0.024). Similar relationships were found
with standardized ratings of exertional dyspnea intensity in general.
Finally, changes in exertional symptom intensity (BorgHEWR
for dyspnea or inspiratory difficulty) did not correlate significantly
(P > 0.1) with alterations in
SaO2, end-tidal CO2,
Pes/PImax, or other Pes-derived measurements.
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Mechanical Effects of Thoracic Restriction and DS
Using CWS, we successfully contracted lung volumes to mimic a moderately severe restrictive disorder (33). IC and VC were reduced by over one-third of the control value, primarily as a result of TLC reduction. In keeping with the results of other studies, thoracic restriction did not compromise maximal expiratory flow rates in the "effort-independent range" (8, 16, 26, 38). The preservation (or enhancement) of tidal expiratory flow rates at lower lung volumes was due in part to improved airway conductance. The imposed reduction of IC and IRV at rest resulted in serious constraints on VT expansion during exercise: VT/IC values were significantly increased and IRV was significantly diminished at submaximal exercise levels compared with control, with a greater reliance on tachypnea to increase ventilation. Significant expiratory flow limitation did not occur, despite lower operational lung volumes, with consequent avoidance of increased EELV. This obviated further attenuation of the already restricted VT response during exercise.In keeping with the results of a recent study by Harty et al. (23),
submaximal ventilation during CWS was increased compared with control.
This increase was directly proportional to the increase in
O2 and
CO2 in our study. During CWS,
tidal Pes swings increased significantly from rest to peak exercise,
but this increase was likely attenuated by the adoption of the rapid
shallow breathing pattern, which is an effective compensatory strategy
for elastic loading. The net mechanical consequence of CWS, however,
was reduced VT expansion for a greater inspiratory effort
compared with control (Fig. 4). Thus the relationship between effort
and displacement (VT expressed as a percentage of predicted
VC) during CWS increased significantly compared with control at
submaximal levels of exercise. In association with the increased
ventilatory constraints, inspiratory difficulty intensified and
exercise was curtailed.
The ventilatory responses to DS in our subjects were similar to those
reported in previous studies (29, 39): submaximal E increased by ~20%, mainly as a
result of an increase in VT. Although VT was
larger at rest and throughout exercise than in control, peak
E was similar to control, and there were
adequate reserves of volume (IRV) and no significant ventilatory
limitation at end exercise. Pes/VT values remained similar
to control from rest to peak exercise, suggesting close coupling
between the increased inspiratory effort and thoracic displacement.
Despite increases in ventilation that were comparable to those in the
CWS condition, DS did not curtail exercise performance significantly
and resulted in only small increases in inspiratory difficulty at
submaximal levels of exercise.
CWS + DS had additive effects on dyspnea and exercise limitation (Fig. 6). The ventilatory stimulatory effects of added DS were evident even at rest: VT was increased, the IRV was diminished, and the ratio of end-inspiratory lung volume to TLC was 80% during resting breathing. Because of the additional ventilatory stimulation, VT expanded earlier in exercise to its relatively low maximum volume. Thus, at the reduced peak exercise level, severe ventilatory volume constraints were evident: the end-inspiratory lung volume-to-TLC ratio was 92%. At a standardized work rate during combined loading, VT represented, on average, 85% of the diminished IC and breathing frequency was greatly accelerated. During CWS + DS, maximal expiratory flow rates were maintained over the operating VT range, and EELV did not increase during exercise.
CWS + DS resulted in greater gas exchange abnormalities than CWS alone. CWS + DS caused a significant decrease in SaO2 and increase in end-tidal CO2 toward the end of progressive exercise, which likely reflected decompensation of the respiratory system with some degree of alveolar hypoventilation. This would be expected when severe mechanical restriction occurs in the face of excessive chemical drive. It is noteworthy that the significant, albeit small, increase in end-tidal CO2 (i.e., reflecting an increase in the estimated arterial PCO2 of 3 cmH2O) occurred, despite large increases in ventilation. Other potential explanations for arterial O2 desaturation during exercise with CWS + DS included increased ventilation-perfusion abnormalities due to atelectasis and increased right-to-left shunting (16, 26, 38). However, in the absence of direct measurements of arterial gases, a definitive conclusion about mechanisms of hypoxemia could not be made.
Physiological Correlates of Dyspnea During Thoracic Restriction
Chest strapping imperfectly mimics the intrinsic mechanical loads of restrictive disorders and best approximates disorders characterized by reduced chest wall compliance. Moreover, the acute imposition of thoracic restriction in health does not reflect the chronic sensory effects of restrictive loading in disease. Nevertheless, CWS did faithfully reproduce some of the mechanical effects of disease at rest and during exercise (i.e., reduced IC, increased VT/IC, relative tachypnea, and increased Pes/VT). In concurrence with the study of Harty et al. (23), CWS induced severe exertional dyspnea that was qualitatively similar in some important respects to that previously described in restrictive disorders (i.e., inspiratory difficulty, unsatisfied inspiration, and shallow breathing) (33).As anticipated, CWS induced a perception of "chest tightness" in all subjects throughout rest and exercise. The imposition of the tight-fitting, inelastic chest strap resulted in very slight increases in dyspnea at rest (i.e., a Borg rating of 1 indicates "very slight"), but anecdotally the awareness of chest tightness did not intensify with exercise in our subjects. The source of this dyspnea at rest may reflect an awareness of increased impedance to thoracic expansion arising from altered lung and chest wall afferents or, alternatively, from stimulation of pulmonary receptors from atelectasis. Subjects could readily distinguish between any uncomfortable sensation that arose from wearing the tightened chest strap and the sensations of labored breathing and inspiratory difficulty that progressively increased during exercise.
The finding that dyspnea increased in conjunction with Pes/VT at any given ventilation during CWS compared with control (Fig. 5) suggests a central role for mechanical factors in dyspnea causation. The strong statistical correlation between changes in Borg ratings of inspiratory difficulty and measurements of volume restriction (i.e., IRV at rest and during exercise and VT/IC during exercise) supports this contention. Moreover, the qualitative descriptor choices of "inspiratory difficulty," "unsatisfied inspiration," and "shallow breathing" may reasonably be attributed to the diminished ability to expand the thorax appropriately during exercise. Increased intensity of dyspnea during CWS, compared with control at a standardized work rate, could not be explained by changes in Pes/PImax. This poor correlation probably reflects the effective compensatory strategies (i.e., rapid shallow breathing pattern) that subjects adopted to minimize transthoracic pressures and respiratory effort. Alternatively, Pes/PImax measurements may underestimate the total inspiratory effort expended, specifically, the effort required to overcome alterations in chest wall compliance and resistance during CWS.
In contrast to CWS, the increase in E
with DS loading resulted in only small increases in dyspnea at
submaximal exercise work rates: Borg dyspnea ratings increased from 2.5 to 3.1 units ("moderate" severity) at HEWR, directly in
proportion to the increase in E. Notably,
there were no significant changes from control in dyspnea or
Pes/VT at any given ventilation in response to added DS
(Fig. 4). As anticipated, dyspnea descriptors selected during exercise
with DS were identical to those during the unloaded control condition.
Thus, when the respiratory system is unimpeded, increased ventilatory
stimulation alone does not give rise to perceptions of inspiratory
difficulty or unsatisfied inspiration, likely because the relationship
of respiratory drive to thoracic displacement (or change in respired
volume) remains harmonious throughout most of exercise:
Pes/VT slopes were superimposed during control and DS conditions.
The addition of DS to CWS had dramatic consequences on dyspnea
intensity: Borg ratings increased from 4.3 ("somewhat severe") to
6.5 ("very severe") at a standardized work rate. Thus adding DS
to the CWS condition resulted in significant curtailment of exercise
performance (total work fell by an average of 21%) compared with the
addition of DS to the control condition, where exercise performance did
not change significantly. By examining
Borg/E slopes under all four conditions
at a standardized work rate, it is clear that the dyspnea increase
during CWS + DS is primarily the result of mechanical factors with
additional increases as a result of increased ventilation (Fig. 4).
Thus the effects of combined loading were additive. As in CWS
conditions, dyspnea intensity correlated strongly with the
physiological indexes of volume restriction and ventilation, but not
with Pes-derived indexes. Qualitative dimensions of dyspnea during CWS + DS are similar to those of CWS alone and likely reflect the effects
of mechanical restriction.
To what extent did greater gas exchange abnormalities during CWS + DS,
compared with CWS alone, contribute to increased exertional dyspnea?
The magnitude of induced gas exchange abnormalities (i.e., O2 desaturation and increased end-tidal CO2)
did not contribute significantly to increased dyspnea intensity in our
study subjects, even in those with more severe levels of O2
desaturation. Harty et al. (23) described similar mild arterial
O2 desaturation during CWS and found that administration of
supplemental O2 to some of these study subjects did not
influence dyspnea intensity, suggesting that mild hypoxemia did not
contribute to dyspnea causation. If unmeasured hypercarbia, as a result
of alveolar hypoventilation, occurred toward end exercise during CWS + DS, dyspnea intensity would be expected to increase exponentially for a
given ventilation. However, Borg/E slopes
remained superimposed and linear during CWS and CWS + DS, making this
possibility less likely. Additionally, perception of air hunger, which
is thought to arise directly as a result of increased arterial
PCO2 stimulation of respiratory drive
independent of the motor response (3), was not reported more frequently
at exercise cessation during CWS + DS than in control.
Possible Neurophysiological Mechanisms of Dyspnea During Mechanical Restriction
This study demonstrates that exertional dyspnea intensity during CWS correlates more closely with measures of volume restriction than with Pes-derived indexes. Our results add to those of a number of studies that have shown that if VT is constrained (either voluntarily or imposed) in the setting of increased ventilatory stimulation, respiratory discomfort is intensified (2, 11, 27, 36). This suggests that feedback related to thoracic volume importantly modulates unpleasant respiratory sensations. The precise source of the volume feedback information is undetermined but may involve a variety of mechanoreceptors in the thoracic cage and the intercostal muscles, which have been shown to project to the central cortex and contribute to kinesthesia and proprioception (2, 36).Vagal afferents are also potentially implicated in causing unpleasant respiratory sensations during thoracic restriction. Chest compression and lung deflation in animals and humans have previously been shown to stimulate ventilation via vagal afferent pathways originating within the lung (12, 13, 21). Thus physical volume restriction could potentially reduce the input from slowly adapting stretch receptors with resultant tachypnea, while it simultaneously increases the input from rapidly adapting vagal receptors, which increase respiratory drive and ventilation, thus contributing to dyspnea (1, 14). Lung atelectasis during CWS may have activated pulmonary receptors, resulting in altered afferent inputs via the vagus nerve. Vagally mediated influences have previously been implicated in contributing to unpleasant respiratory sensations when VT is constrained in quadriplegic patients, but the importance of the vagus in dyspnea causation in humans without chest wall deafferentation is uncertain (15, 27).
In contrast to the control condition with or without dead space, where the ratio of effort to VT response was constant throughout most of exercise, this ratio and dyspnea intensity were increased at any given ventilation during CWS (Fig. 4). These findings support the hypothesis that when the VT response is reduced compared with what is expected during increased inspiratory drive of exercise, respiratory discomfort occurs because of neuromechanical dissociation of the ventilatory pump. In other words, CWS gives rise to a disparity between increased respiratory drive sensed by corollary discharge (9, 10) and the impaired mechanical response of the respiratory system, which is conveyed via an abundance of proprioceptive mechanoreceptors throughout the respiratory tract (i.e., lungs, muscles, tendons, and joints of the chest wall) (40). This mismatch, which may be further aggravated under conditions of added chemical drive (i.e., DS), may contribute to the intensity of dyspnea and some of its qualitative dimensions, i.e., unsatisfied inspiratory effort. Support for the notion that neuromechanical or "efferent-reafferent" dissociation may form the neurophysiological basis of dyspnea has arisen from a number of previous publications (32, 33, 36).
In summary, exertional dyspnea intensity and exercise intolerance during elastic mechanical loading, with and without added DS, correlated best with physiological indexes of volume restriction. The addition of DS to the breathing circuit of exercising subjects whose ability to compensate (by increasing VT) was compromised by mechanical restriction had profound effects on dyspnea and exercise capacity. Thoracic restriction gave rise to discrete qualitative sensations of inspiratory difficulty, unsatisfied inspiration, and shallow breathing, which have been shown previously to characterize restrictive disorders. We postulated that such unpleasant respiratory sensations may ultimately have their physiological basis, at least in part, in impaired ability to increase lung volume and displace the thorax appropriately in the setting of increased ventilatory drive during exercise.
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ACKNOWLEDGEMENTS |
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This study was supported by Physicians' Services Incorporated Foundation and the Ontario Ministry of Health.
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FOOTNOTES |
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The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Address for reprint requests and other correspondence: D. E. O'Donnell, Richardson House, 102 Stuart St., Kingston General Hospital, Kingston, ON, Canada K7L 2V7 (E-mail: odonnell{at}post.queensu.ca).
Received 29 June 1999; accepted in final form 23 December 1999.
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REFERENCES |
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TOP
ABSTRACT
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METHODS
RESULTS
DISCUSSION
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