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Division of Respiratory and Critical Care Medicine, 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 compared
qualitative and quantitative aspects of perceived exertional dyspnea in
patients with interstitial lung disease (ILD) and normal subjects and
sought a physiological rationale for their differences. Twelve patients
with ILD [forced vital capacity = 64 ± 4 (SE)
%predicted] and 12 age-matched normal subjects performed
symptom-limited incremental cycle exercise tests with measurements of
dyspnea intensity (Borg scale), ventilation, breathing pattern,
operational lung volumes, and esophageal pressures (Pes). Qualitative
descriptors of dyspnea were selected at exercise cessation. Both groups
described increased "work and/or effort" and
"heaviness" of breathing; only patients with ILD described
"unsatisfied inspiratory effort" (75%), "increased
inspiratory difficulty" (67%), and "rapid breathing" (58%)
(P < 0.05 patients with ILD vs.
normal subjects). Borg-O2 uptake
(
O2) and Borg-ventilation
slopes were significantly greater during exercise in patients with ILD
(P < 0.01). At peak exercise, when
dyspnea intensity and inspiratory effort (Pes-to-maximal inspiratory
pressure ratio) were similar, the distinct qualitative perceptions of
dyspnea in patients with ILD were attributed to differences in dynamic
ventilatory mechancis, i.e., reduced inspiratory capacity, heightened
Pes-to-tidal volume ratio, and tachypnea. Factors contributing to
dyspnea intensity in both groups were also different: the best
correlate of the Borg-O2
slope in patients with ILD was the resting tidal volume-to-inspiratory
capacity ratio (r = 0.58, P < 0.05) and in normal subjects was
the slope of Pes-to-maximal inspiratory pressure ratio over
O2
(r = 0.60, P < 0.05).
respiratory sensation; respiratory mechanics; exercise
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INTRODUCTION |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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DYSPNEA AND EXERCISE INTOLERANCE are common in interstitial lung disease (ILD) and often progress inexorably as the disease advances. The mechanisms of exertional dyspnea in this condition are not clearly understood and are likely multifactorial (19). Ratings of exertional dyspnea have been shown to correlate with the level of ventilation when expressed in absolute terms or as a fraction of the ventilatory capacity (19, 21). It is also known that exertional dyspnea in ILD may be aggravated by hypoxemia (5) or by concomitant expiratory flow limitation (21). As in other chronic cardiopulmonary disorders, dyspnea intensity in ILD correlates with increased inspiratory muscle force requirements (relative to the force reserve) and the duration of contraction (19). Accordingly, it is postulated that the amplitude of central motor command output to the inspiratory muscles is increased because of the elastic load in ILD and that this, in turn, is consciously perceived as the sense of heightened effort, an integral component of the subjective experience of breathing discomfort (19).
It has recently become clear that dyspnea encompasses a number of qualitatively distinct sensations that vary in intensity and may be different within various pulmonary disorders and in health (20, 24, 25). For example, we recently found that in the majority of patients with chronic airflow limitation (CAL), inspiratory difficulty and the awareness of "unsatisfied inspiratory effort" were important qualitative aspects of exertional dyspnea; this was in contrast to an age-matched normal group that did not report these sensations even at the peak of exhaustive exercise (26). We postulated that unsatisfied inspiratory effort had its mechanical basis in the disparity between the respiratory effort expended during exercise and the mechanical response of the system, which is seriously impaired in CAL (26).
In ILD, the mechanical response of the respiratory system is similarly restricted: inspiratory capacity (IC) is reduced, tidal volume (VT) expansion is thereby constrained, and during exercise VT must "cycle" close to total lung capacity (TLC) on the upper nonlinear extreme of the contracted pressure-volume (P-V) relationship of the respiratory system. We speculated that, as in CAL, this impaired mechanical response in the setting of increased ventilatory demand would give rise to distinguishable qualitative descriptions of exertional dyspnea in patients with ILD when compared with healthy normal subjects.
We hypothesized 1) that exertional dyspnea is qualitatively and quantitatively different in patients with ILD and in age-matched normal subjects, 2) that qualitative differences can be explained by differences in dynamic ventilatory mechanics, and 3) that the factors contributing to exertional dyspnea intensity are different in ILD than in normal subjects. To test these hypotheses, we first compared the qualitative descriptors selected by both groups at the end of symptom-limited exercise and evaluated the dynamic ventilatory parameters at this point of comparison. Second, we examined the relationships between dyspnea intensity and various physiological variables throughout exercise in each of the study groups. Finally, we used multiple-regression analysis to determine and contrast the physiological factors contributing to dyspnea intensity in patients with ILD and in normal subjects.
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METHODS |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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Subjects
Subjects included 12 patients who had clinically stable ILD, were presently nonsmokers (2 exsmokers with 10 and 20 pack · yr histories had quit >10 and >20 yr before the study, respectively), and had pulmonary function tests showing a restrictive pattern [i.e., reduced lung volumes, forced vital capacity (FVC) <70% predicted] (Table 1). Specific diagnoses included idiopathic pulmonary fibrosis (n = 3); sarcoidosis (n = 2); rheumatoid arthritis (n = 3); scleroderma (n = 1); bronchiolitis obliterans and organizing pneumonia with polymyositis (n = 1); and interstitial pulmonary fibrosis resulting from acute respiratory distress syndrome (n = 1) and as a result of toxic lung damage (n = 1). Seven of twelve patients had their diagnosis confirmed with tissue biopsies, and no patient was on corticosteroid or immunosuppressive therapy at the time of the study. Five of twelve patients had radiographic interstitial patterns and pulmonary function test abnormalities indicative of lung restriction in association with collagen vascular disorders. Individuals with evidence of concurrent airflow obstruction [forced expiratory volume in 1 s (FEV1)/FVC < 100% predicted] or other diseases that could contribute to exertional dyspnea were excluded. A group of 12 healthy normal subjects reported in a previous study (26) was used for comparison purposes. These normal subjects underwent identical testing during the same time period and were well matched for age and anthropometric measurements (Table 1).
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Informed consent was obtained from all subjects, and study approval was received from the university and/or hospital research ethics board. In an initial screening visit, subjects were thoroughly familiarized with exercise testing and with all dyspnea scales and questionnaires. Subjects avoided caffeine and heavy meals for 4 h before testing and avoided major physical exertion entirely on the day of testing.
Dyspnea Evaluation
Dyspnea, or breathlessness, was defined as "the sensation of labored or difficult breathing." Chronic dyspnea was assessed with the modified Baseline Dyspnea Index (28). In the acute setting, the intensity of dyspnea was evaluated by using the Borg scale (4) during exercise testing. Before testing, the Borg scale was explained and its end points were anchored such that 0 indicated "no difficulty breathing" and 10 represented "the most severe (maximal) difficulty breathing that the subject had previously experienced or could imagine." By pointing to the Borg scale, subjects rated dyspnea at rest, every 2 min during exercise, and at peak exercise. We had postulated that, similar to CAL (26), the impaired mechanical response to exercise in patients with ILD would result in a distinct qualitative description of dyspnea characterized predominantly by inspiratory difficulty; to test this theory, we also used the Borg scale to rate the magnitude of "inspiratory difficulty" during exercise in the ILD group.Immediately after exercise cessation and the completion of mechanical measurements, subjects were asked the reason(s) for exercise termination (i.e., dyspnea, leg fatigue, both, or other). At this time, subjects were also asked to describe their sensation of breathing discomfort at peak exercise by selecting the most representative qualitative descriptors from a questionnaire (Table 2) that consisted of a list of descriptive phrases that we modified (7) from those of Simon and co-workers (24).
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Pulmonary Function Testing
Routine spirometry (6200 Autobox DL; SensorMedics, Yorba Linda, CA) was performed as recommended (13). Maximal inspiratory and expiratory mouth pressures measured at FRC and TLC, respectively, were assessed with a standard mouthpiece and a pressure manometer (Magnehelic; Dwyer Instruments, Michigan City, IN). In the patients with ILD, single-breath diffusing capacity for carbon monoxide (DLCO) and plethysmographic thoracic gas volume were also measured (6200 Autobox DL). Predicted normal values for spirometry, lung volumes, DLCO, and mouth pressures were those of Morris et al. (23), Goldman and Becklake (14), Gaensler and Wright (11) and Hamilton and et al. (15), respectively.Exercise Testing
Incremental symptom-limited cycle exercise tests were conducted as described previously (27). Esophageal pressure (Pes) was also recorded continuously at rest and throughout exercise by using a balloon-tipped catheter system as previously reported (26); however, Pes data were not obtained in four patients with ILD who could not tolerate balloon placement. Maximal inspiratory maneuvers against an occluded airway at the end of a normal expiration were performed to obtain values for maximum force-generating capacity [maximal inspiratory pressure (PImax)] at rest and within 30 s of exercise cessation. Because of the disruption of breathing pattern that we have found occurring after these maneuvers during exercise, especially in patients with severe lung disease, values for PImax at intermediate points during exercise were calculated at isovolume [i.e., at the concurrent dynamic end-expiratory lung volume (EELVdyn) as estimated by IC measurements (see below)] by linear interpolation between simultaneous PImax and EELV measurements taken at rest and at the end of exercise. All measurements of tidal Pes were subsequently compared with PImax at isovolume. The tension-time index for the inspiratory muscles (TTI = mean inspiratory Pes/PImax × TI/Ttot) (3), where TI and Ttot are inspiratory time and total time, respectively, and the inspiratory pressure-time integral (
Pes · dt) (22) were calculated and expressed per minute by multiplying by breathing frequency (f). Tidal P-V curves were examined, and dynamic elastance (Edyn) was calculated as
Pes/VT (i.e., the slope
between points of 0 flow at the onset of inspiration and at end
inspiration for each breath).
Assuming that TLC does not change during exercise in normal subjects (29) or in patients with ILD (21), changes in EELVdyn were estimated from IC measurements at rest, every 2 min during exercise, and at peak exercise. Satisfactory technique and reproducibility of IC maneuvers for each subject were established during an initial practice session at rest by evaluation of the consistency of volume and Pes measurements. To verify that TLC was attained with each IC maneuver during exercise, we confirmed that the peak inspiratory Pes during these maneuvers was similar to that at rest.
Flow, volume, Pes, and expiratory
CO2 and
O2 fraction signals were sampled
continuously at a rate of 100 Hz by using computer data-acquisition
software (CODAS; Dataq Instruments, Akron, OH) and stored for later
analysis. Computer software was used to calculate timing [f,
TI, expiratory time
(TE), Ttot],
VT, and flow
(VT/TI, VT/TE)
parameters for each breath. Minute ventilation
(E),
O2 uptake
(O2), and
CO2 output
(CO2) were calculated by
using standard formulas (17) at rest, each minute during exercise, and
at peak exercise for each subject. Exercise measurements were compared
with the predicted maximum values from Jones (17), and
E was compared with the maximal
ventilatory capacity (MVC) calculated by using the method of Killian et
al. (18). The latter method of estimating MVC takes into account the
individual's maximal VT and the
maximum rates at which this volume can be inspired and expired;
indirect estimates of MVC derived solely from
FEV1 are unreliable in this
population. The V-slope method (2) was used to estimate an
"anaerobic threshold" for each subject.
Tidal flow-volume curves were examined at a standardized
O2
(O2 std)
during exercise for each subject and placed within their respective
maximal envelopes according to coinciding IC measurements. Maximal
flow-volume loops performed immediately before exercise were used for
this analysis because they have been shown to be similar to those done
immediately after exercise (21) and because the performance of maximal
loops during exercise interferes with other measurements. Flow
limitation was determined by measuring the percentage of
VT that met or exceeded the
maximal expiratory flow-volume boundary (16) and by comparing tidal expiratory flow at 50% of VT
with that of the maximal envelope at isovolume. (Fig. 4)
Statistical Analysis
Results were expressed as means ± SE. A probability of P < 0.05 was accepted as significant for all analyses. Exercise-response slopes were expressed as means of slopes from linear regression analysis of individual subjects' data. Dyspnea "thresholds" were expressed as the x-intercepts of the relationships between Borg ratings and independent variables such asO2 and
E. Group data were compared by using
unpaired t-tests. Fisher exact tests were used to compare the selection frequencies of dyspnea descriptor clusters between groups.
To illustrate group differences during exercise, we evaluated responses
at a
O2 std,
i.e., 50% of the predicted maximum O2
(O2 max) was chosen
to represent a standardized metabolic load across groups because it
1) standardizes for age, gender, and
body size and 2) represents an
exercise stimulus of sufficient intensity to correspond with high
ventilatory levels. Values for Borg ratings and cardiorespiratory
parameters at 50% of the predicted O2 max were
calculated by linear interpolation between adjacent measurement points
for each subject.
To standardize for stimulus intensity (i.e., metabolic load during
exercise), the slope of Borg dyspnea ratings relative to O2 was used as the index of
exertional dyspnea. To determine the factors contributing to exertional
dyspnea intensity in each group, Pearson's correlation coefficients
were used to evaluate associations between the slope of Borg over
O2 (expressed as ml · kg
1 · min1)
and independent variables that included exercise-response slopes [E-O2,
E/MVC-O2,
CO2-O2,
arterial O2 saturation
(SaO2)-O2, heart rate-O2,
Pes/PImax-O2,
Pes/PImax-E,
and
Pes/VT-O2]; breathing pattern slopes (f-E,
VT/IC-E,
f-VT/IC,
f-VT/predicted VC), where VC is
vital capacity; expiratory airflow limitation (extent of
VT overlap on the maximal
flow-volume curve); and resting parameters
[FEV1, FVC, IC,
DLCO, f,
VT/IC, end-inspiratory lung volume (EILV)/TLC]. In patients with ILD, the same analysis was performed by using the slope of Borg ratings of inspiratory difficulty over O2 as the independent
variable. In each of the these analyses, significant variables were
selected by stepwise multiple-regression analysis to form the best
predictive equations for dyspnea intensity (i.e.,
Borg-O2 slopes). A further
analysis combining data from both groups was performed by using the
same variables noted above; to avoid the possibility that group
differences were responsible for the significance of any of these
relationships (i.e., association due to two discrete clusters of points
representing each group), each case was tested by adding "group"
(normal subjects = 0, patients with ILD = 1) as a possible covariate.
In this analysis, the group variable was tested as a possible covariate
by forcing it into the model sentence before stepping or fitting of the
model proceeded.
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RESULTS |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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Exertional Dyspnea
The patients with ILD exhibited severe exercise curtailment and stopped exercise primarily because of dyspnea, alone or in combination with leg fatigue (Tables 3 and 4). In contrast, the normal subjects had average exercise tolerance and stopped exercise mainly because of leg fatigue (Tables 3 and 4). Selection frequencies of the eight clusters describing exertional dyspnea in each group are shown in Fig. 1. Sensations of increased work and/or effort and heaviness of breathing were common to both groups. A significantly (P < 0.05) larger proportion of patients with ILD reported inspiratory difficulty (67%), "unrewarded inspiration" (75%) and "rapid breathing" (58%) than did normal subjects (17, 17, and 8%, respectively).
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Relationships between dyspnea and
O2 during exercise were
significantly different between patients with ILD and normal subjects (Fig. 2A,
Table 4): 1) slopes of Borg
ratings over O2 were greater
in patients with ILD than in normal subjects
(P < 0.001); 2) the onset or threshold of dyspnea
occurred at a much lower O2
in patients with ILD than in normal subjects
(P < 0.001); and
3) at a
O2 equivalent to the
breakpoint of exercise in patients with ILD, they experienced
"severe" dyspnea, whereas normal subjects had not yet attained a
noticeable level of respiratory difficulty (Borg < 0.5). Similar
results were obtained between dyspnea and E expressed as liters per minute or as
%MVC (Table 4). In patients with ILD, slopes of "overall"
dyspnea corresponded strongly with slopes of inspiratory difficulty
(r = 1.00, P < 0.0005; no difference between
slopes, P = 0.69) (Table 4).
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Physiological Exercise Responses
All but one of the normal subjects reachedO2 max on the basis of
criteria outlined by Jones (17); one overweight, deconditioned female
subject achieved a peak
O2 that was 98% of
that predicted but had significant cardiac and ventilatory reserves and
stopped exercise because of "moderate" leg fatigue only. In all
patients with ILD, exercise studies were symptom limited and a
"true" O2 max was
not attained (peak O2 = 76 ± 8% predicted).
Resting SaO2 was normal in both
groups, and there was no clinically significant desaturation in
the normal group during exercise (Table 3).
SaO2 fell by 4%
or more during exercise in six patients with ILD; however,
SaO2 fell below 90% (i.e., 83 and 87%,
respectively) in only two of these patients. Compared with the normal
group, the ILD group had a significantly
(P < 0.01) heightened ventilatory response to exercise (Fig. 2B).
Anaerobic thresholds were not significantly different between groups: a
detectable anaerobic threshold could be determined with confidence in
six patients with ILD at a O2
of 0.98 ± 0.05 l/min compared with 1.12 ± 0.08 l/min in the
12 normal subjects.
Breathing patterns and operational lung volumes. Patients with ILD had a significantly (P < 0.01) more rapid and shallow breathing pattern than did normal subjects (Fig. 2C). Although absolute VT at rest was comparable between groups (0.71 ± 0.05 and 0.75 ± 0.05 liter in patients with ILD and normal subjects, respectively), VT comprised a larger proportion of the significantly reduced IC in patients with ILD (43 ± 3%) compared with normal subjects (28 ± 2%; P < 0.001 between groups). With the increasing demands of exercise, increases in VT were progressively more truncated in patients with ILD such that increases in ventilation were achieved primarily by increasing f (Fig. 2C, Table 3): VT only increased by 0.46 ± 0.10 liter at peak exercise compared with the 1.54 ± 0.24-liter increase in VT in normal subjects.
The assumption that TLC did not change during exercise was supported by the fact that PImax at the peak of symptom-limited exercise did not change significantly from rest in either group. In addition, peak values of inspiratory Pes (an estimate of effort) did not change during sequential IC maneuvers, thereby validating the use of IC measurements throughout exercise to estimate changes in EELVdyn. Because EELVdyn did not change significantly during exercise in either group, the increase in VT during exercise was accomplished by increasing dynamic end-inspiratory lung volume (EILVdyn) (EILVdyn-EELVdyn + VT) (Figs. 3 and 4). Accordingly, VT expansion during exercise correlated significantly with the constraints of baseline IC (n = 24, r = 0.72, P < 0.001).
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Ventilatory mechanics.
Inspiratory effort was greater during exercise in patients with ILD
than in normal subjects, as shown by the elevated slope of the
relationship between tidal
Pes/PImax
and O2 (Fig.
2D) and the increased
Pes/PImax
at
O2 std
(Table 3); however, TTI and TTI/min in patients with ILD were not
different from normal subjects at
O2 std.
Throughout exercise, expiratory effort (Pes-to-maximal expiratory mouth
pressure ratio) was also greater in patients with ILD than in normal
subjects and was smaller than inspiratory effort in both groups (Table
3).
O2 std (P < 0.001); increased Edyn
(or
Pes/PImax-VT/IC)
correlated significantly with reduced IC (or increased
EILVdyn/TLC) at
O2 std
(P < 0.01).
At
O2 std,
tidal flow-volume curves did not approach their respective maximal
curves in five subjects from each of the normal and ILD groups. In the
remaining seven subjects in each group, tidal expiratory flow-volume
curves equaled or exceeded their maximal curves. In these latter
subjects, impingement occurred near EELVdyn over a mean of 53 ± 11 and 33 ± 11% of the VT in normal subjects and patients with ILD, respectively. At 50% of VT, the degree to which tidal
expiratory flow rates approached and/or impinged on their
respective maximal loops at isovolume was not different between groups
(82 ± 23 vs. 65 ± 14% in normal subjects and patients with
ILD, respectively).
Correlates of Dyspnea
Within the ILD group, Borg-O2
slopes failed to correlate significantly with any of the tested
parameters except the resting VT/IC
[Borg-O2 = 1.63(VT/IC) 
0.16; r = 0.58, P < 0.05] or its inverse,
IRV/IC (r = 0.58,
P < 0.05), where IRV is inspiratory reserve volume. Similarly, Borg-time slopes were best predicted by the
combination of resting VT/IC and
exertional slopes of f-time (r = 0.82, P = 0.007). None of the Pes-derived
measurements correlated significantly with dyspnea slopes in the eight
patients with ILD with mechanical measurements. Similarly, the closest
significant correlate of inspiratory
difficulty-O2 slopes in
patients with ILD was the resting
VT/IC
(r = 0.52, P = 0.12).
In normal subjects, Borg-O2
slopes correlated significantly with slopes of
Pes/PImax-O2
[Borg-O2 = 0.08 + 0.09 (Pes/PImax-O2); r = 0.60, P < 0.05] and
Pes/PImax-E
[Borg-O2 = 0.09 + 0.18(Pes/PImax-E); r = 62, P < 0.05] but did not
correlate with any other of the tested parameters. Stepwise
multiple-regression analysis of the combined data from all subjects
found that Borg-O2
slopes correlated best with slopes of
Pes/VT-O2
(P < 0.015) after the
group covariate, which alone predicted 42% of its variance:
Borg-O2 = 0.16 + 0.06 (Pes/VT-O2) + 0.39(group), n = 20, r2 = 0.60, P < 0.0005, was accounted for. None
of the variables measured at end exercise, including
VT/IC, correlated with any index
of exertional dyspnea.
Interestingly, exercise capacity
(O2 max expressed as
%predicted) correlated best with resting IC
(P = 0.002) and FVC
(P = 0.002), both expressed as
%predicted, after group was accounted for. By using stepwise
multiple-regression analysis, the slope of Borg dyspnea ratings over
O2 was added to the baseline
IC (%predicted) and the group covariate to form the best predictive equation for O2 max
(r2 = 0.70, P < 0.001).
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DISCUSSION |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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Exertional dyspnea was qualitatively and quantitatively different in patients with ILD and normal subjects. Although descriptions of increased effort and/or work and heaviness of breathing were common to both groups, only patients with ILD consistently selected descriptors that alluded to unsatisfied inspiratory effort, inspiratory difficulty, and rapidity of breathing. Increased sense of effort is pervasive during exercise in health and across the spectrum of cardiopulmonary diseases; in qualitative terms, it is nondiscriminatory (20). Mahler and co-workers (20), in a similar qualitative analysis of dyspnea in various lung diseases, also found that the descriptors denoting increased work and/or effort and rapid breathing were commonly selected by patients with ILD. In their study, in contrast with our results, unsatisfied inspiratory effort was not specifically identified as being representative of ILD. Differences between results of the two studies may be explained by the fact that the three descriptors included under the cluster heading unsatisfied inspiratory effort in our study (Table 1) were subsumed under the work and/or effort and "inhalation" clusters in the study of Mahler et al. (20). Another important methodological difference that could account for differences in results was that our study subjects selected descriptors immediately after symptom-limited exercise, whereas patients relied on recall of more remote exertional symptoms in the other study.
The finding that awareness of inspiratory difficulty and, in particular, unsatisfied inspiratory effort, is characteristic of ILD implies that patients with ILD receive peripheral sensory information that indicates to them that the mechanical response of the ventilatory system is insufficient or inappropriate for the effort expended. It is noteworthy that in an earlier study by Simon et al. (25), normal subjects challenged with elastic mechanical loading selected similar descriptors of breathlessness to those selected by our ILD group.
Clearly, the mechanical response in our group of patients with moderate ILD is seriously impaired compared with that in normal subjects. The resting IC in patients with ILD was significantly diminished and represents the narrow operating limits for VT expansion because EELVdyn did not decrease from rest to peak exercise; the IC strongly predicted the extent of VT expansion during exercise in both groups and correlated significantly with exercise capacity. VT/IC and EILV/TLC at rest and during exercise were greater in patients with ILD than in normal subjects, thus indicating the serious mechanical constraints on VT expansion in the face of increased ventilatory demand during exercise (Fig. 3). Given the reduced IC, VT must encroach on the upper nonlinear extreme of the respiratory system's P-V relationship. This contention is supported by our finding that the ratio of tidal Pes (effort) to VT (displacement) widened significantly from rest to peak exercise in patients with ILD. Although the sense of increased breathing effort was uniformly reported by all subjects at the breakpoint of exercise, the normal group rarely selected descriptors from the unsatisfied effort cluster to describe their breathing discomfort. In this group, VT expansion was not as restricted because the IC was considerably larger than in patients with ILD. Therefore, the relationship between effort and mechanical response remained harmonious throughout exercise: Pes/VT was unchanged, indicating that, unlike the ILD group, VT normally remains within the linear portion of the P-V relationship.
It is reasonable to assume that differences in the quality of dyspnea between patients with ILD and normal subjects fundamentally reflect differences in mechanical impedance and ventilatory demand. At the end of symptom-limited maximal exercise, when dyspnea intensity was similar in both groups, the qualitative differences that were evident could reasonably be attributed to differences in dynamic ventilatory mechanics. Thus the perceptions of inspiratory difficulty, unsatisfied inspiratory effort, and rapidity of breathing in patients with ILD were likely related to the significantly reduced IC, the heightened Pes/VT, and the tachypnea, respectively, that occurred at this point of comparison. Clearly, qualitative differences could not be attributed to differences in inspiratory effort (Pes/PImax), which was similar in both groups at end exercise.
Exertional dyspnea was quantitatively greater in patients with ILD than
in normal subjects when Borg ratings were expressed as a function of
O2 or
E. Between-group differences in these relationships suggest that dyspnea may have different physiological contributors in the two groups. Thus the finding that dyspnea ratings
were higher at a given E in patients with
ILD compared with normal subjects suggests that mechanical impedance is
important in ILD. Moreover, multiple-regression analysis identified
different contributing factors in each group. Pes-derived indexes
correlated strongly with dyspnea in normal subjects, whereas the
resting VT/IC was the main
independent contributor to the intensity of dyspnea and inspiratory
difficulty in patients with ILD. In other words, the mechanical
constraints on volume expansion (determined at rest) correlated best
with the rate of change of dyspnea during exercise in patients with
ILD. Furthermore, resting mechanics (i.e., IC, FVC) and dyspnea
intensity each contributed significantly to the variance in exercise
capacity in patients with ILD. Although our contention is that
restrictive mechanics shape exertional dyspnea intensity and that this
leads to exercise curtailment, another explanation is that abnormal
mechanics primarily limit exercise but do not directly give rise to
dyspnea; increasing dyspnea in this scenario merely reflects increasing
exercise intensity as it does in normal subjects. Given the strong
statistical interrelationships among mechanical derangements, exercise
capacity, and exertional dyspnea in patients with ILD, it is difficult,
if not impossible, to examine these factors in isolation.
In normal healthy subjects, impedance is low and effort is used to increase the velocity of shortening and the extent of inspiratory muscle contraction to displace the thorax during respiration. In accordance with previous studies, it is not surprising that Pes/PImax (which directly reflects the amplitude of central motor command output) correlated well with dyspnea intensity in our normal group. By contrast, in our ILD group, impedance was increased, thoracic displacement was diminished, velocity of shortening was relatively increased at low work rates, and compensatory strategies were likely in place to minimize intrathoracic pressure perturbations and the associated breathing discomfort (see below).
In contrast to the situation in normal subjects, Pes-derived indexes of inspiratory effort did not correlate with exertional dyspnea intensity in the ILD group. This may be because of the smaller sample size of the ILD group (n = 8) in which Pes measurements were available. However, all of the variables that correlated with Borg dyspnea ratings in the larger group (n = 12) continued to correlate strongly in the smaller sample. Therefore, even if the sample size were increased and Pes-derived measurements correlated significantly with dyspnea intensity, they would still not correlate as strongly as other volume-derived measurements (i.e., resting VT/IC).
Pes/PImax
was significantly increased at any given
O2 in patients with
ILD compared with normal subjects; however, the magnitude of this
increase was less than that reported in other pulmonary disorders
(e.g., CAL): although impeded in their action by elastic loading, the
inspiratory muscles were not working under a major mechanical
disadvantage, as is the case, for example, in CAL. In accordance with a
previous study (10),
PImax was
relatively well preserved in our ILD group. Thus, despite the increased
tidal Pes excursions, and notwithstanding some reduction in functional muscle strength because of the increased
VT/ TI,
Pes/PImax
was only moderately increased and TTI, a measure of the oxygen cost of
breathing, was comparable to normal at
O2 std
because of the relatively reduced
TI. The adoption of a rapid
shallow breathing pattern in patients with ILD served to minimize the
work required to attain a given ventilation and was therefore an
effective compensatory strategy for the elastic load (30, 31). Although
this breathing pattern response to exercise in patients with ILD may,
in part, be dictated by restrictive mechanics, there is also evidence
to suggest that it may be behaviorally modulated to minimize breathing discomfort during elastic loading (30, 31).
Our finding that Pes/PImax did not correlate with exertional dyspnea in patients with ILD differs from that in a previous study by Leblanc et al. (19) that reported significant correlations between the intensity of dyspnea and Pes-to-maximal inspiratory mouth pressure ratio in 20 patients with various cardiopulmonary disorders, including ILD, and normal subjects. A separate analysis of the ILD subgroup was not provided in that study and would be required for accurate comparison with our results because different sensory and mechanical factors could have contributed to the intensity and quality of dyspnea across cardiopulmonary diseases and in normal subjects.
Exertional dyspnea in patients with ILD did not correlate with the
extent of expiratory flow limitation at rest or during exercise.
Resting SaO2 values were normal in all
subjects, and SaO2 during exercise fell
significantly (i.e., 
4%) in only six patients with ILD and below
90% in only two of these patients. In addition, the resting
SaO2 and the extent of oxygen
desaturation during exercise did not contribute significantly to the
variance in exertional dyspnea in our group of patients with moderately severe ILD; therefore, hypoxia was unlikely to have contributed to
dyspnea causation in this group. However, our results are not generalizable to patients with ILD who have significant oxygen desaturation during exercise.
At peak exercise, when qualitative differences between groups were
recorded, Pes/VT was found to be
almost three times higher in patients with ILD than in normal subjects,
reflecting the increased elastic load. In the stepwise
multiple-regression analysis including both groups,
Pes/VT emerged as the best
predictor of exertional dyspnea; together with the group covariate,
the slopes of
Pes/VT-O2 accounted for 60% of the variance in
Borg-O2 slopes. The increased Pes/VT provides a potential
mechanical basis for some of its distinctive qualitative dimensions
(e.g., unsatisfied inspiratory effort). Inspiratory difficulty and
unsatisfied inspiratory effort in patients with ILD may have its
psychophysical basis in the conscious awareness of a mismatching
between expended effort and the mechanical response of the system that
is conveyed to consciousness by afferent feedback from multiple
mechanoreceptors (31). There is evidence that the sense of contractile
effort is the sensory expression of motor command output that is
conveyed to consciousness via central corollary discharge (8, 9, 12).
Unsatisfied effort may therefore have its neurophysiological basis in
altered afferent feedback from peripheral mechanoreceptors relative to
the magnitude of corollary discharge. Of the receptors available, those
in the ventilatory muscles (muscle spindles, Golgi tendon organs)
represent a potential proximal source of sensory feedback (31)
regarding effort-displacement mismatching. In this regard, Campbell et
al. (6, 7) originally proposed that the ability of humans to detect
imposed elastic loads depended on the perception of "length-tension inappropriateness"; this arises from the integration and central processing of signals conveying information about muscle lengthening (or volume change) via muscle spindles and joint receptors with those
conveying information about muscle tension development (or pressure)
via tendon organs. However, it is unlikely that the ventilatory muscles
are the exclusive source of dyspneogenic afferent signals; feedback
information concerning the extent of thoracic displacement for a given
neural activation or effort could equally arise from proprioceptive
mechanoreceptors in both the lung and chest wall (i.e., joint
receptors) that ascend via vagal, autonomic, and spinal pathways.
The remarkable similarity in choices of qualitative descriptors (i.e., inspiratory difficulty, unsatisfied inspiratory effort) for exertional dyspnea in patients with ILD and a previously studied group of patients with CAL raises the intriguing possibility that they share some common underlying mechanisms. In both conditions, IC was diminished and VT/IC was increased early in exercise; thus movement of the thoracic cage and lung was greatly restricted despite patients mustering considerable inspiratory efforts during exercise. In patients with CAL, the intensity of inspiratory difficulty was strongly related to the ratio of Pes/PImax to VT/VC. This ratio, a measure of the disparity between respiratory effort and thoracic displacement, is increased in patients with CAL compared with normal subjects because of dynamic hyperinflation that results in VT being positioned at the upper, nonlinear extreme of the respiratory system's P-V curve.
In summary, the qualitative descriptors of dyspnea recorded at the termination of symptom-limited exercise were different in patients with ILD than in normal subjects. Significant differences in dynamic ventilatory mechanics and breathing pattern may explain the distinctive qualitative perceptions of inspiratory difficulty, unsatisfied inspiratory effort, and rapidity of breathing found in ILD. The relationship between exertional dyspnea and ventilation was different in patients with ILD than normal subjects, and the physiological factors contributing to dyspnea (and inspiratory difficulty) in patients with ILD were different from those contributing to dyspnea in normal subjects: the intensity of exertional dyspnea in patients with ILD was more closely linked to the mechanical constraints on volume expansion than to indexes of inspiratory effort per se.
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ACKNOWLEDGEMENTS |
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D. E. O'Donnell holds a career scientist award from the Ontario Ministry of Health.
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FOOTNOTES |
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Parts of this study were presented at the American Lung Association/American Thoracic Society International Meeting (New Orleans, LA, May 1996).
Address for reprint requests: D. E. O'Donnell, Richardson House, 102 Stuart St., Kingston General Hospital, Kingston, Ontario, Canada K7L 2V7.
Received 23 December 1996; accepted in final form 2 February 1998.
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REFERENCES |
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Top
Abstract
Introduction
Methods
Results
Discussion
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