Effect of chest wall vibration on breathlessness in normal subjects HAROLD L. MANNING, ROBERT BASNER, JACK RINGLER, CAROLYN RAND, VLADIMIR FENCL, STEVEN E. WEINBERGER, J. WOODROW WEISS, AND RICHARD M. SCHWARTZSTEIN Charles A. Dana Research Institute and Harvard-Thorndike Laboratory of Beth Israel Hospital, Departments of Medicine, Beth Israel Hospital and Brigham and Women’s Hospital, and Department of Medicine, Harvard Medical School, Boston, Mussuchusetts 02115 MANNING, HAROLDL,, RUBERTBASNER,JACK RINGLER, onstrated
that out-of-phase
vibration
of the chest wall,
CAROLYN RAND,VLADIMIRFENCL,STEVEN E. WEINBERGER, i.e., inspiratory muscles in the upper rib cage during expiJ. WOODROW WEISS, AND RICHARDM. SCHWARTZSTEIN. Effect ration or expiratory muscles in the lower rib cage during of chmt wall vibration on breathhvwss in normal subjects. J. inspiration, may worsen breathlessness, and Sempik and
Appl. Physiol. 71(l): l75-181,1991.-This study evaluated the effect of chest wall vibration (115 Hz) on breathlessness. Breathlessnesswas induced in normal subjectsby a combination of hypercapnia and an inspiratory resistive load; both minute ventilation and end-tidal CO, were kept constant. Crossmodality matching was used to rate breathlessness.Ratings during intercostal vibration were expressedas a percentageof ratings during the cuntrol condition (either deltoid vibration or no vibration). To evaluate their potential contribution to any changesin breathlessness,we assessed several aspectsof ventilation, including chest wall configuration, functional residual capacity (FRC), and the ventilatory responseto steady-state hypercapnia. Intercostal vibration reducedbreathlessnessratings by 6.5 t 5.7% comparedwith deltoid vibration (P < 0.05) and by 7.0 & 8.3% comparedwith no vibration (P < 0.05). The reduction in breathlessnesswas accompanied by either no changeor negligiblechangein minute ventilation, tidal volume, frequency, duty cycle, compartmental ventilation, FRC, and the steady-state hypercapnic response.We concludethat chest wall vibration reducesbreathlessnessand speculatethat it may do so through stimulation of receptors in the chest wall. dyspnea; respiratory sensation; control of ventilation; hypercapnia; senseof effort
THE SENSATION of breathlessness
may be modulated by afferent information from a variety of sources. Schwartzstein et al. (30) demonstrated a reduction in breathlessness with flow of cold air against the face, which they hypothesized was due to stimulation of trigeminal nerve afferents. Other studies suggest that information from the airways (14,27) or chest wall (6,29, 31) may likewise alter respiratory sensation. Because previous investigators have shown that vibration is a potent stimulus to musculoskeletal receptors, including muscle spindles (5), tendon organs (3), and joint receptors (4), we hypothesized that through its effects on these receptors chest wall vibration would reduce the sensation of breathlessness induced in normal subjects. The timing and location of chest wall vibration may be important in determining the effect of this intervention on breathlessness. Homma et al. (19) have dem0161~‘7567/91$1.50
Patrick (32) found that vibration of the upper rib cage prolongs breath-holding time. Therefore we chose to study the effect of in-phase inspiratory muscle vibration (upper rib cage) on the breathlessness associated with hypercapnia and an inspiratory resistive load. Because previous work has also shown that chest wall vibration may alter ventilation (11, 15,18), we devised a protocol that would allow us to determine whether breathlessness, if present, were due merely to changes in either total ventilation or the pattern of ventilation or were independent of these variables. MElTHODS
Subjects We studied 13 male subjects aged 25-34 yr. By history, all subjects were free of pulmonary and cardiac disease. One subject had uncomplicated insulin-dependent diabetes mellitus but was otherwise healthy. None of the subjects was aware of the purpose of the study. The protocol was approved by the Committee on Clinical Investigations at Beth Israel Hospital. Informed consent was obtained from all subjects in accordance with the guidelines of this committee. Techniques Breathing circuit. Each subject was seated in a specially constructed straight-back chair that allowed position to be fixed. The subjects wore noseclips and breathed through an Otis-McKerrow valve connected to a Fleisch pneumotachograph (no. 3). Two three-way valves separated the inspiratory portion of the breathing circuit into two limbs, one of which contained a resistance (sintered filter) of 14 cmH,O 1-l. s, whereas the other contained no added resistance. Both inspiratory limbs of the circuit were connected to a differential manometer (Magnehelie), which was used to target minute ventilation (23). Measurement of respiratory variables. The relative contributions of the rib cage and abdominal compartments to total ventilation were measured by respiratory inductive plethysmography (Respitrace). Calibrations were l
Copyright 0 1991 the American Physiological Society
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176
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performed by the isovolume method at the beginning and at the end of each study. End-tidal CO, (PEQ~J was measured at the mouth with a mass spectrometer (Perkin Elmer 1100). Flow, PETITE, and Respitrace rib cage, abdomen, and sum signals were recorded continuously on a strip-chart recorder (Hewlett-Packard 7758B). Tidal volume (VT) was obtained by electrical integration (Hewlett-Packard 8815A) of the flow signal measured with the pneumotachograph. Inspiratory time (TI) and total respiratory cycle time (TT) were measured from the flow tracing. The percentage contribution to total ventilation of the rib cage compartment was obtained by dividing the amplitude of the rib cage signal by the sum of the rib cage plus abdominal signals. To determine changes in functional residual capacity (FRC), the sum signal from the Respitrace belts was converted to an absolute volume by calibrating it with the volume obtained by integration of the flow signal. Induction of breathlessness. We used a combination of hypercapnia and an inspiratory resistive load to induce breathlessness. Because of the great intersubject variability in hypercapnic responsiveness, different levels of PETIT, (range 46-60 Torr) were used for different subjects, based on the subject’s steady-state hypercapnic response (see below). For each subject, we estimated the PETIT, value that would produce a steady-state ventilation of -30 l/min. Vibration. Vibration was applied with two standard physiotherapy vibrators (Novafon), which were manually triggered during inspiration. The amplitude and frequency of vibration were 3 mm and 115 Hz, respectively. The vibrations were transmitted to the subjects through a hard plastic disk with a diameter of 25 mm. For intercostal vibration, the vibrators were applied bilaterally over the second or third parasternal spaces, and for deltoid vibration, the vibrators were applied bilaterally over the deltoid muscles. Throughout all the studies, the vibrators were applied by a single investigator, who attempted to maintain a constant force of application. The timing of vibration was determined from the flow signal displayed on a storage oscilloscope (Tektronics 5111). Assessment of breathlessness. Each subject was given the same instructions to read from a printed text. To conceal the purpose of the study, the instructions were phrased in the must general terms possible. The subject was told that we would measure various aspects of his breathing and that from time to time he would be asked to rate his breathlessness, which we defined as “an unpleasant or uncomfortable sensation of breathing.” The subject was also told that the inspired concentrations of CO, and/or 0, might vary and that periodically a vibrator would be applied to his shoulders or to his chest. We assessed breathlessness with a variation of the techniques of cross-modality matching (35, 36). A tape measure was held and slowly exposed by one of the investigators such that the markings on the tape were visible only to the investigators. The subject was instructed to think of the length of tape exposed as being propor-
because the subject was unaware of the actual length of the tape (183 cm), he was told to consider the tape to be infinite in length (the maximum length of tape actually exposed by any of the subjects was 37 cm). For each rating period the length of exposed tape (in cm) was recorded and was taken as the subject’s breathlessness rating for that period. Experimental Protocol (Fig 1) Protocol A. STEADY-STATE co2 RESPONSE. With the subject breathing air, CO, was added to the inspiratory limb of the circuit to raise the PETITE to 50 Torr. Ten minutes were allowed for partial CO, equilibration; during the next 10 min we alternated 1-min periods of intercostal vibration with 1-min periods of deltoid vibration. A 15-min rest period followed the hypercapnic response. BREATHLESSNESS. After 10 min of unloaded breathing at the PET,,, selected to produce an expired minute ventilation of -30 Urnin, the subject breathed through the inspiratory resistance for another 60 s, after which his ventilation was noted. Because some individuals may continue to increase ventilation after the first 10 min of hypercapnia, the subject was instructed to target his ventilation to a level -15% above that achieved spontaneously. This allowed ventilation to be kept constant and helped eliminate any need for the subject to suppress his ventilation during the subsequent trial periods. The subject was given another 60 s to become accustomed to the targeted level of ventilation, after which the rating periods began. Each rating period lasted 30 s; during the last 10 s of the period the subject was asked to rate his breathlessness. The rating periods were divided into groups of three, consisting of one rating period each for intercostal, deltoid, and no vibration. At the beginning of each group of ratings the tape measure was set at zero, but for the other two periods in the group the subject was instructed to adjust the length of tape relative to the previous rating. With this protocol, a comparison of nonadjacent rating periods required not only the subject’s ability to recall the intensity of a prior sensation but also his ability to recall the length of tape corresponding to that sensation. Because the tape measure was unmarked, the latter would have been an exceedingly difficult task. On the basis of these considerations and our experience in several pilot studies, we concluded that a meaningful comparison could be made only between stimuli presented in adjacent rating periods. A schedule was devised so that deltoid vibration and intercostal vibration were always presented in adjacent periods, although the order in which they were presented was varied randomly. A period of no vibration was included as the first or last stimulus in each group but, for reasons stated above, was not included in the analysis of protocoZ A. A formal comparison of intercostal vibration and no vibration was performed separately (see protocol B below). There were a total of 18 rating periods (6 groups of 3 rating periods). A second run of identical design but with a different randomized schedule was completed after another 150min
tional to his degree of breathlessness and was told to
rest.
signal when the appropriate length of tape had been exposed. The upper limit of the scale was not defined, and
Protocol B. The hypercapnic response was measured as in protocol A, except that we alternated 1-min periods of
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CHEST
PROTOCOL Part
f-
10 MINUTES state
= 50 mm Hg +
Part 2 (Breathlessness) Hypercapnia* + 30
of Sequence
Same
+
f-
ventilation
10 MINUTES + achieve steady state ventilation
SECONDS $
Deltoid
10 MINUTES + alternating one minute periods of intercostal and deltoid vibration
+ 1 MINUTE $ f 1 MINUTE $ addition of targeted -) Vibration load ventilation Sequence with load
+ 30 SECONDS $ Intercostal
L---
PROTOCOL
177
AND BREATHLESSNESS
achieve steady
(CO2 Response)
Example Vibration
VIBRATION
A
1
PETGO
WALL
Breathlessness
SECONDS $ No Vibration -b Reset Tape-) Measure
+ 30
Next Sequence
4
Rating -
B basic
design as Protocol
Part 1: Intercostal vibration Part 2: Vibration sequences
A, except: alternated with no vibration for 8 minutes. included only intercostal vibration and no vibration,
* Level of hypercapnia varied among subjects (see text) FIG. 1. Schematic outline of pro~w~k A and El. See text for details.
intercostal vibration with l-min periods of no vibration at all, for a total of 8 min. In the breathlessness portion of protocol B, only intercostal vibration and no vibration were compared; deltoid vibration was not included in protocol B. The rating periods were divided into groups of two, and for each group the order of presentation was randomly determined. The tape measure was reset at the end of each group. There were a total of 18 rating periods (9 groups of 2 rating periods each). Five subjects were studied in both protocols, another five were studied in only protocol A, and an additional three were studied in only protocol B. For subjects who participated in both protocols, the two portions of the study were always done on separate days. At the end of each protocol, subjects were asked to comment on their sensations during the study. Datu Analysis
During the steady-state hypercapnic response, respiratory variables were measured during the middle 30 s of every l-min period. During the breathlessness portion of the protocol, respiratory variables were measured during the first 20 s of each 30-s period. Mean breathlessness ratings for each subject were calculated from the individual rating periods for each of the conditions of the study. For all respiratory variables, data are expressed as means t SD. Comparisons between intercostal vibration and either deltoid vibration or no vibration were made using a paired t test. For each subject, the mean breathlessness rating during intercostal vibration was expressed as a percentage of the mean breathlessness rating during the control period (either deltoid vibration or no vibration). Comparisons of breathlessness ratings were made using the Wilcoxon sign-rank test. For rea-
sons already discussed, a comparison of intercostal vibration and no vibration was made only from the data in protocol B. Statistical calculations were done with the AppStats (Statsoft, Tulsa, OK) software package. P < 0.05 was considered significant. RESULTS Ventilutory Response to Steady-State Hypercupnia Protcml A. There were no significant differences between intercostal vibration and deltoid vibration for any of the measured ventilatory variables (Table 1). Protocol B. Inspired minute ventilation (VI) was significantly greater with intercostal vibration than with no vibration (34.7 t 14.3 vs. 33.9 t 14.5 Vmin, P < O.Ol), although the difference was extremely small in magnitude. Ventilation of the rib cage compartment was greater with no vibration than with intercostal vibration (67 t 10 vs. 63 t 12%, P < 0.05). There were no signifiTABLE 1. Ventilatory data from the steady-state hypercupnic response Protocol A
Protocol B
Intercostal
Deltoid
Intercostal
No vibration
VI, l/min f, min-l VT, liters
29.9213.3 19.7t7.1
Tr, s
1.66-t0.51 0.5o-to.05 6126
29.7t13.5 19.9t7.9 1.54tO.59 1.66kO.55 0.49t0.05 62t5
34.7-t-14.3* 21.5t6.4 1.63tO.40 1.48t0.34 0.49+0.03 63t12”
33.9*14.5* 20.4k6.1 1.64t0.35 1.48-+0.31 0.48kO.05 67tlO*
TI/TT
%RC
1.55-to.57
Values are group means t, SD. VI, inspired minute ventilation; f, frequency; VT, tidal volume; TI, inspiratory time; TI/TT, duty cycle; %RC, percentage of VI attributable to rib cage compartment. *P < 0.05.
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178
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PROTOCOL
VIBRATION
AND BREATHLESSNESS
PROTOCOL
A
B
110 (3 z Fr 100
SH
a a
FR DK J&m DO
v) cl3 y 90 to # 3 xt 80
EL
100
90
JK
a
W a
m 70 0
I
I
I
Deltoid
Intercostal
No Vibration
I
Intercostal
FIG. 2. Breathlessness ratings during intercostal vibration expressed as percentage of ratings during deltoid vibration and no vibration. Each symbol represents mean value of all breathlessness ratings from a single subject.
cant differences among any of the remaining variables (Table 1).
ventilatory
Assessment of Breathlessness Breathlessness ratings. Intercostal vibration reduced breathlessness ratings by 6.5 t 5.7% compared with deltoid vibration (protocol A, P < 0.05) and by 7.0 t 8.3% compared with no vibration (protocol B, P < 0.05) (Fig. 2). Ventilation data. Subjects were quite successful in targeting their ventilation. Inprotocol A, there was no significant difference in VI or in any other ventilatory parameter between deltoid vibration and intercostal vibration (Table 2). In protocol B, there was also no significant difference in VI between intercostal vibration and no vibration, although frequency was greater (21.7 k 7.2 vsI 20.3 t 6.3 min- ‘* P < 0.05) and VT wasless (1.63 t 0.46 vs. 1.71 t 0.46 liters, P < 0.05) with intercostal vibration (Table 2). There were no significant differences in any of the remaining ventilatory variables during protocol B. Subjective comments. Most of the subjects’ spontaneous comments focused on their breathing effort, with TABLE
protocol
VI, l/min f, min” VT,
liters
TI, s TI/TT %RC FRC Values capacity;
sample comments including “it seemed like I got a bigger breath with the vibration for the same effort,” “definitely easier to breathe at the target with chest vibration,” “with chest vibration had to work less to maintain the target,” and “vibration over my chest made it feel like there was less resistance at the end of my breath.” Although some subjects were unsure whether vibration had altered their breathlessness, several were quite convinced that intercostal vibration had reduced their breathlessness. One subject (PG) stated that intercostal vibration made his breathlessness worse and, in fact, was the only subject to have a higher breathlessness rating with intercostal vibration than with deltoid vibration. Subjects considered the magnitude of the effect of vibration on breathlessness to be slight to moderate. DISCUSSION
The principal finding of this study is that intercostal vibration reduced the breathlessness elicited by combined hypercapnia and inspiratory resistive loading. Breathlessness ratings were lower during intercostal vibration than during either no vibration or deltoid vibra2. Ventilatory data from breathlessness portion of tion. Previous studies have examined the effects of different during which minute ventilation was targeted sites of application and timing of a vibratory stimulus. Prutucul B Protocol A Homma et al. (19) elicited breathlessness in normal subjects by vibrating over the parasternal regions during exfntercostal Deltoid fnkcostal No viktion piration and over the lower intercostals during inspira29.Ok5.7 33.1-t5.7 32.7xk5.3 tion (out-of-phase vibration). 28.5+5.9 We chose to vibrate over 22.527.7 22.8~7.6 21.7k7.2" 20.3*6.3* the parasternal spaces because of the inspiratory action 1.37t0.31 1.35HI.30 1.63kO.46" 1.71t0.46* of the parasternal intercostal muscles (7), and in con1.75kO.47 1.82k0.43 1.76kO.41 1.75k0.43 trast to Homma et al. (17), we applied vibration during 0.59t,o.o3 0.58t0.03 0.61t,0.05 0.6lt0.05 67k7 68H3 inspiration (in phase) because of the finding that in65k6 66t6 0.02zkO.15 0.07~0.10 0.05zkO.16 0.05t0.17 phase vibration elicits a tonic vibration reflex in the underlying intercostal muscles (see below). are group means k SD. FRC, change in functional residual The vibrators used in our study were applied and trigother abbreviations as in Table 1. *P < 0.05.
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CHEST
WALL
VIBRATION
gered manually. Although we attempted to minimize variability by having a single investigator apply the vibrators in all studies, there undoubtedly was a brief lag between the subjects’ transitions between inspiration and expiration and the investigator’s triggering of the vibrators, as well as some slight intra- and intersubject variability in the force of application of the vibrators. Thus, although we believe that the reduction in breathlessness associated with intercostal vibration was due to inspiratory vibration, we cannot exclude the possibility that a very brief period of expiratory vibration may have contributed to the reduction in breathlessness. Expiratory vibration is unlikely to have this effect, however, given the work of Homma et al. (19), which suggests that out-of-phase vibration worsens breathlessness. One might argue that the reduction in breathlessness associated with intercostal vibration was due to a nonspecific effect of vibration, such as distraction. On this basis, however, one would predict that there would be no difference in breathlessness between intercostal vibration and deltoid vibration. In fact, relative to deltoid vibration, intercostal vibration significantly reduced breathlessness. Moreover, although only one of the two control conditions (deltoid vibration) offered a distraction, the magnitude of the reduction in breathlessness with intercostal vibration was similar whether the control condition was deltoid vibration or no vibration. Thus we believe that it is unlikely for the reduction in breathlessness associated with intercostal vibration to be due simply to distraction or to some other nonspecific effect of vibration. Chemical drive (Pco,) may alter breathlessness independently of changes in ventilation (1, Z), and ventilation may likewise alter breathlessness independently of changes in chemical drive (6,3l). We therefore adjusted the inspired CO, to keep PET,~~ constant during all rating periods, and by targeting ventilation, we maintained ventilation at a constant level. Although there were statistically significant differences in frequency and VT between intercostal vibration and no vibration, the magnitude of the difference was very small and is extremely unlikely to have produced the difference in breathlessness ratings. Respiratory sensation can also be altered by changes in lung volume (22) or by pattern of respiratory muscle activation (34,37). However, there was no significant difference in FRC among the three study conditions. Furthermore, although we did not assess the activation of specific muscles, compartmental ventilation, which reflects the pattern of activation of particular muscle groups, also did not differ among the study conditions. Thus we either controlled for or found no difference in the chemical and mechanical factors that previously have been shown to play a role in respiratory sensation, thereby making it reasonable to invoke intercostal vibration as the cause of the reduction in breathlessness. One mechanism by which intercostal vibration might reduce breathlessness is through a reduction in respiratory drive (medullary inspiratory neuron activity). Although the precise relation between medullary inspiratory neuron activity and breathlessness is uncertain, there is evidence that it is one of the determinants of
AND BREATHLESSNESS
179
breathlessness (2). Several lines of evidence from both animal and human studies indicate that intercostal vibration reduces respiratory drive (3, 4, 28). Vibration studies in humans have looked at indirect indices of medullary inspiratory neuron activity, such as tidal volume (11), diaphragm electromyogram (16), and breath-holding time (32). Taken together these studies suggest that chest wall vibration also reduces respiratory drive in humans. In our study we induced breathlessness with hypercapnia and an inspiratory resistive load. Because the work of Hida et al. (15) suggests that vibration alters the effect of hypercapnia on medullary inspiratory activity, we examined the effects of vibration on the ventilatory response to hypercapnia. In contrast to previous investigations (15,20,24), however, we found that neither limb muscle (deltoid) nor intercostal vibration had a sizable effect on the ventilatory response to steady-state hypercapnia (Table 1). Our finding of a trivial effect of intercostal vibration on the ventilatory response to hypercapnia conflicts with the findings of Hida et al. (15). They used a similar frequency, timing, and site of vibration and found an -70% increase in the ventilatory response to progressive hyperoxic hypercapnia, whereas we demonstrated only a 3% increase in ventilation during steady-state normoxic hypercapnia. Although the two studies utilized different techniques and conditions for assessing the ventilatory response to hypercapnia, this does not seem adequate to account for the widely disparate results obtained in the two studies. Thus, although we are unable to explain the lack of effect of vibration on the ventilatory response to hypercapnia, it appears that the reduction in breathlessness associated with intercostal vibration cannot be explained by a change in the relationship between medullary inspiratory neuron activity and hypercapnia. We were surprised that during intercostal vibration the rib cage compartment contributed less to total ventilation than during the no-vibration condition. The magnitude of the difference was small, however, and we can only speculate that the pressure of the vibrators on the rib cage during inspiration caused a slight decrease in rib cage expansion. The work of Schwartzstein et al. (31) and Chonan et al. (6) may bear on the interpretation of our results. Both groups of workers found that, at a constant level of hypercapnia, normal subjects had an increase in breathlessness when ventilation was voluntarily reduced below that achieved during free breathing. The authors (31) suggested that the increase in breathlessness may have been related to mismatch between the actual motion of the chest wall and/or lung and the level of motion expected on the basis of the outgoing motor command. Similar reasoning could be extended to the results of our study. During the breathlessness portion of the protocol, ventilation was similar to that achieved during free breathing (Tables 1 and 2), but the addition of the inspiratory resistance must have necessitated a substantial increase in the outgoing motor command to the inspiratory muscles. This may have resulted in discordance between afferent signals from the chest wall and/or lung and the efferent motor command. Although our study does not allow us to test this hypothesis, it is possible
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that chest wall vibration produced an increase in afferent information, thereby providing a better match between incoming sensory signals and outgoing motor commands and thus reducing breathlessness. Another possible mechanism by which intercostal vibration may have reduced breathlessness is through a decreased sense of effort. According to the theory proposed by Killian and co-workers (8,22), breathlessness is the sensation of respiratory muscle effort. On the basis of this theory, one would predict that those factors that reduce the sense of respiratory muscle effort would reduce breathlessness as well. As pointed out by Gandevia (9), there are many parallels between limb muscle sensation and respiratory sensation. There is substantial evidence supporting the notion that the sense of limb muscle effort results from perception of the cortical motor command to the muscle (9, 25). In situations where increased activation of the muscles is required to sustain a task (fatigue, partial paralysis), the sense of effort increases (12, 13). Similarly, when increased activation of the inspiratory muscles is required because of fatigue (10) or a disadvantageous length for tension development (22,34), the sense of effort increases. Of particular relevance to our study is the work of McCloskey et al. (26). Their experiments demonstrated that application of a lOO-Hz physiotherapy vibrator over the biceps tendon caused subjects to underestimate the force output of the biceps muscle. One interpretation of these findings is that vibration of the muscle tendon had a facilitory effect on the cu-motor neurons innervating the biceps (tonic vibration reflex), thereby requiring decreased activation by cortical motor centers, and producing a decreased sense of effort. A similar argument could be extended to our study. By targeting ventilation, we achieved similar ventilatory parameters in all study conditions. Because intercostal vibration has been shown to have a segmental facilitatory effect (33), a possible explanation for our results is that through facilitation of inspiratory motor neurons, intercostal vibration decreased the activation required from cortical centers, thereby decreasing the sense of effort associated with inspiration. Gandevia (9) has proposed an analogous explanation for the findings of Homma et al. (19), who reported that alternating out-of-phase vibration caused a sensation of breathlessness in normal subjects. Gandevia suggests that, in the study by Homma et al. (19), vibration of the expiratory intercostals caused reciprocal inhibition of the inspiratory intercostals and that, as a result, a greater voluntary motor command was required to activate the inspiratory motor neurons (9). One problem that arises in interpreting the study by Homma et al. (19) is that vibration caused an increase in breathing frequency and tidal volume and a shortening of inspiratory time (and presumably an increase in inspiratory flow rate). These factors may independently alter respiratory sensation (8, 21), making it difficult to ascertain whether breathlessness was due to vibration per se or merely to the increase in ventilation associated with vibration. Because of the many parallels already established between limb muscle and respiratory muscle sensation (9) and because most of the subjects’ spontaneous comments were concerned with the effort or work of breathing, we believe it possible that intercostal vibration
AND BREATHLESSNESS
caused a reduction in the sense of inspiratory muscle effort. Although the inspiratory resistance used in our study was modest, ventilation was high, and the effort of breathing through the resistance was almost certainly a component of the breathlessness experienced by our subjects. Thus, by decreasing the sense of inspiratory effort, vibration may have reduced breathlessness. For both the limb muscles and the respiratory muscles, there is conflicting evidence about the role played by specific receptors in mediating the effects of vibration (3,5, 11,25,28). Our study did not address the issue of which receptors were stimulated by vibration nor of which receptor( s) mediated the reduction in breathlessness caused by intercostal vibration. In summary, we found minimal effect of either deltoid or intercostal vibration on the ventilatory response to hypercapnia. Intercostal vibration reduced breathlessness and did so independently of any sizable changes in total ventilation, compartmental ventilation, or FRC. We speculate that a decrease in inspiratory effort sensation and an improved matching of afferent information from the chest wall with the outgoing respiratory motor command are the most likely mechanisms for the reduction in breathlessness. We thank Dr. Martha Teghtsoonian for assisting with the design of the study and Edwyna Von Gal for expert technical assistance. This study was supported by Pulmonary Specialized Center of Research Grant HL-19170 and Training Grant HL-07633 from the National Heart, Lung, and Blood Institute. Address for reprint requests: R. M. Schwartzstein, Pulmonary Unit, Beth Israel Hospital, 330 Brookline Ave., Boston, MA 02215. Received 26 December 1989; accepted in final form 26 February 1991. REFERENCES 1.
ADAMS, L., R. LANE, S. A. SHEA, A. COCKCROFT, AND A. Guz. Breathlessness during different forms of ventilatory stimulation: a study of mechanisms in normal subjects and respiratory patients. Clin. Sci. Lord.
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2. BANZETT, R. B., R. W. LANSING, M. B. REID, L. ADAMS, AND R. BROWN. ‘Air hunger’ arising from increased PCO~ in mechanically ventilated quadriplegics. Respir. Physiot. 76: 53-67, 1989. 3. BOLSER, D. C., B. B. LINDSEY, AND R. SHANNON. Medullary inspiratory activity: influence of intercostal tendon organs and muscle spindle endings. J. Appl. Physiol. 62: 1046-1056, 1987. 4. BOLSER, D. C., B+ G. LINDSEY, AND R. SHANNON. Respiratory pattern changes produced by intercostal muscle/rib vibration. J. Appl. Physiol. 64: 2458-2462, 1988. 5. BROWN, M. C, I. ENGBERG, AND P. B. C. MATTHEWS. The relative sensitivity to vibration of muscle receptors of the cat. J. Physiol. Lond. 192: 773-800,1967. 6. CHONAN, T., M. B. MULHOLLAND, N. S. CHERNIA~K, AND M. D. ALTOSE. Effects of voluntary constraining of thoracic displacement during hypercapnia. J. Appl. Physid. 63: 1822~1828,1987. 7. DE TROYER, A., AND S. KELLY. Chest wall mechanics in dogs with acute diaphragm paralysis. J. Appl. Physiol. 53: 373-379, 1982. 8. EL-MANSHAWI, A., K. J. KILLIAN, E. SUMMERS, AND N. L. JONES. Breathlessness during exercise with and without resistive loading. J. Appl.
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9. GANDEVIA, S. C. Neural mechanism underlying the sensation of breathlessness: kinesthetic parallels between respiratory and limb muscles. Awt. NZ J. Med. 18: 83-91, 1988. 10. GANDEVIA, S. C., K. J. KILLIAN, AND E. J. M. CAMPBELL. The effect of respiratory muscle fatigue on respiratory sensations. CEin. Sci. Lo&. 60: 463-466,198l. 11, GANDEVIA, S. C., AND D. I. MCCLOSKEY. Changes in the pattern of breathing caused by chest vibration. Respir. Physiol. 26: 163-171, 1976. 12. GANDEWA, S. C., AND D. I. MCCLOSKEY. Sensations of heaviness. Brain 100: 345-354, 1977.
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13. GANDEVIA, S. C., AND D. I. MCCLOSKEY. Changes in motor commands as shown by changes in perceived heaviness during partial curarization and peripheral muscle anaesthesia in man. J. physiol. Lmd. 272: 673-689,1977. 14. HAMILTON, R. D., A. J. WINNING, A. PERRY, AND A. Guz. Aerosol anesthesia increases hypercapnic ventilation and breathlessness in laryngectomized humans. J. Appl. Physiol. 63: 2286-2292,1987. 15. HIDA, W., R. SUSUKI, Y. KIKUCHI, C, SHINDOH, T, CHONAN, H. SASAKI, AND T. TAKISHIMA. Effect of local vibration on ventilatory response to hypercapnia in normal subjects. Bull. Eur. Physisp&d. Respir. 23: 227-232, 1987. 16. HOMMA, I. Inspiratory inhibitory reflex caused by the chest wall vibration in man. Respir. Physiot. 39: 345-53, 1980. 17. HOMMA, I., G. EKLUND, AND EL E. HAGIBARTH. Respiration in man affected by TVR contractions elicited in inspiratory and expiratory intercostal muscles. Respir. Physiol. 35: 335-348, 1978. 18. HoMMA,~., T. NAGAI, T, SAKAI, M. UHASHI, M. BEPPU,AND K. YONEINITU. Effect of chest wall vibration on ventilation in patients with spinal cord lesion. J, Appl. Physid. 50: 107-111, 1981. 19. HOMMA, I., T. OBATA, M. SIBUYA, AND M. UCHIDA. Gate mechanism in breathlessness caused by chest wall vibration in humans. J. Appt. Physiul. 56: 8-11,1984. 20. JAMMES,Y., M-J. MATHIOT, J.P. ROLLJLPREFAUT, F. BERTHELIN, C. GRIMAIJD, AND J. MILDEMILI. Ventilatory responses to muscular vibrations in healthy humans. J. Appl. Physiol. 51: 262269,198l. 21, KILLIAN, K. J., D. D. BUCENS, AND E. J. M. CAMPBELL. Effect of breathing patterns on the perceived magnitude of added loads to breathing. J. Appl. Physiol. 52: 578-584, 1982. 22. KILLIAN, K. J., S. C. GANDEVIA, E. SUMMERS, AND E. M. CAMPBELL. Effect of increased lung volume on perception of breathlessness, effort, and tension. J. Appl. Pbysid. 57: 686-691, 1984. 23. LEITH, D. E. Target device for regulating ventilation during voluntary hyperpnea. J. Appl. Physiok 55: 1932-1935,1983. 24. LEITNER, L. M., AND P. DEJOURS, Reflex increase in ventilation induced by vibrations applied to the triceps surae muscles in the cat. Respir. Physid. 12: 199-204, 1971. 25. MCCLOSKEY, D. I. Kinesthetic sensibility. Physid Reu, 58: 763820,1978.
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26, MCCLOSKEY, D. I., P. EBELING, AND CT.M. GOODWIN. Estimation of weights and tensions and apparent involvement of a “sense of effort.” Exp. Neural. 42: 220-232, 1974. 27. O’DONNELL, D. E., R. SANII, N. R. ANTHONISEN, AND M. YOIJNES. Effect of dynamic airway compression on breathing pattern and respiratory sensation in severe chronic obstructive pulmonary disease. Am. Rev. Respir. Dis. 135: 912-918, 1987. 28. REMMERS, J. E. Inhibition of inspiratory activity by intercostal muscle afferents. Respir. Physid. 10: 358-383, 1970. 29. REMMERS, J. E., J. G. BROOKS, AND S. M. TENNEY. Effect of controlled ventilation on the tolerable limit of hypercapnia. Respir. Physiol. 4: 78-90, 1968. 30. SCHWARTZSTEIN, R. M., K. LAHIVE, A. POPE, S. E. WEINBERGER, AND J. W. WEISS. Cold facial stimulation reduces breathlessness induced in normal subjects. Am. Rev. Respir. Dis. 136: 58-61,1987. 31. SCHWARTZSTEIN, R. M., P. M. SIMON, J. W. WEISS, V. FENCL, AND S. E. WEINBERGER. Breathlessness induced by dissociation between ventilation and chemical drive. Am. Rev. Respir. Dis. 139: 1231~1237,1989. 32. SEMPIK, A., AND J. M. PATRICK. The effect of thoracic vibration on ventilation and breath-holding in man. Respir. Physiol. 44: 381-91, 1980. 33. SHANNON, R. Reflexes from the respiratory muscles and costovertebral joints. In: Handbook of Physiology. The Respiratory System. Control of Breuthing. Bethesda, MD: Am. Physiol. Sot., 1986, sect. 3, vol. II, pt. 1, chapt. 13, p. 431-448. 34. STUBBING,D.G., E. H. RAMSDALE, K.J. KILLI.AN,AND E.J. M. CAMPBELL. Psychophysics of inspiratory muscle force. J. Appl. Physiol. 54: 12164221, 1983. 35. TEGHTSOONIAN, M., E. BECKER, AND B. EDELMAN. A psychophysical analysis of perceived satiety: its relation to consumatory behavior and degree of overweight. Appetite 2: 217-229,1981. 36. TIZGHTSOONIAN, M., E. BECKER, AND B. EDELMAN. The measurement of perceived satiety: a reply to comments on “A psychophysical analysis of perceived satiety.” Appetite 2: 245-249,198l. 37. WARD, M. E,, D. EIDELMAN, D. G. STUBBING, F. BELLEMARE, AND P. T. MACKLEM. Respiratory sensation and pattern of respiratory muscle activation during diaphragm fatigue. J. Appl. Physid. 65: 2181~2189,1989.
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that out-of-phase
vibration
of the chest wall,
CAROLYN RAND,VLADIMIRFENCL,STEVEN E. WEINBERGER, i.e., inspiratory muscles in the upper rib cage during expiJ. WOODROW WEISS, AND RICHARDM. SCHWARTZSTEIN. Effect ration or expiratory muscles in the lower rib cage during of chmt wall vibration on breathhvwss in normal subjects. J. inspiration, may worsen breathlessness, and Sempik and
Appl. Physiol. 71(l): l75-181,1991.-This study evaluated the effect of chest wall vibration (115 Hz) on breathlessness. Breathlessnesswas induced in normal subjectsby a combination of hypercapnia and an inspiratory resistive load; both minute ventilation and end-tidal CO, were kept constant. Crossmodality matching was used to rate breathlessness.Ratings during intercostal vibration were expressedas a percentageof ratings during the cuntrol condition (either deltoid vibration or no vibration). To evaluate their potential contribution to any changesin breathlessness,we assessed several aspectsof ventilation, including chest wall configuration, functional residual capacity (FRC), and the ventilatory responseto steady-state hypercapnia. Intercostal vibration reducedbreathlessnessratings by 6.5 t 5.7% comparedwith deltoid vibration (P < 0.05) and by 7.0 & 8.3% comparedwith no vibration (P < 0.05). The reduction in breathlessnesswas accompanied by either no changeor negligiblechangein minute ventilation, tidal volume, frequency, duty cycle, compartmental ventilation, FRC, and the steady-state hypercapnic response.We concludethat chest wall vibration reducesbreathlessnessand speculatethat it may do so through stimulation of receptors in the chest wall. dyspnea; respiratory sensation; control of ventilation; hypercapnia; senseof effort
THE SENSATION of breathlessness
may be modulated by afferent information from a variety of sources. Schwartzstein et al. (30) demonstrated a reduction in breathlessness with flow of cold air against the face, which they hypothesized was due to stimulation of trigeminal nerve afferents. Other studies suggest that information from the airways (14,27) or chest wall (6,29, 31) may likewise alter respiratory sensation. Because previous investigators have shown that vibration is a potent stimulus to musculoskeletal receptors, including muscle spindles (5), tendon organs (3), and joint receptors (4), we hypothesized that through its effects on these receptors chest wall vibration would reduce the sensation of breathlessness induced in normal subjects. The timing and location of chest wall vibration may be important in determining the effect of this intervention on breathlessness. Homma et al. (19) have dem0161~‘7567/91$1.50
Patrick (32) found that vibration of the upper rib cage prolongs breath-holding time. Therefore we chose to study the effect of in-phase inspiratory muscle vibration (upper rib cage) on the breathlessness associated with hypercapnia and an inspiratory resistive load. Because previous work has also shown that chest wall vibration may alter ventilation (11, 15,18), we devised a protocol that would allow us to determine whether breathlessness, if present, were due merely to changes in either total ventilation or the pattern of ventilation or were independent of these variables. MElTHODS
Subjects We studied 13 male subjects aged 25-34 yr. By history, all subjects were free of pulmonary and cardiac disease. One subject had uncomplicated insulin-dependent diabetes mellitus but was otherwise healthy. None of the subjects was aware of the purpose of the study. The protocol was approved by the Committee on Clinical Investigations at Beth Israel Hospital. Informed consent was obtained from all subjects in accordance with the guidelines of this committee. Techniques Breathing circuit. Each subject was seated in a specially constructed straight-back chair that allowed position to be fixed. The subjects wore noseclips and breathed through an Otis-McKerrow valve connected to a Fleisch pneumotachograph (no. 3). Two three-way valves separated the inspiratory portion of the breathing circuit into two limbs, one of which contained a resistance (sintered filter) of 14 cmH,O 1-l. s, whereas the other contained no added resistance. Both inspiratory limbs of the circuit were connected to a differential manometer (Magnehelie), which was used to target minute ventilation (23). Measurement of respiratory variables. The relative contributions of the rib cage and abdominal compartments to total ventilation were measured by respiratory inductive plethysmography (Respitrace). Calibrations were l
Copyright 0 1991 the American Physiological Society
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performed by the isovolume method at the beginning and at the end of each study. End-tidal CO, (PEQ~J was measured at the mouth with a mass spectrometer (Perkin Elmer 1100). Flow, PETITE, and Respitrace rib cage, abdomen, and sum signals were recorded continuously on a strip-chart recorder (Hewlett-Packard 7758B). Tidal volume (VT) was obtained by electrical integration (Hewlett-Packard 8815A) of the flow signal measured with the pneumotachograph. Inspiratory time (TI) and total respiratory cycle time (TT) were measured from the flow tracing. The percentage contribution to total ventilation of the rib cage compartment was obtained by dividing the amplitude of the rib cage signal by the sum of the rib cage plus abdominal signals. To determine changes in functional residual capacity (FRC), the sum signal from the Respitrace belts was converted to an absolute volume by calibrating it with the volume obtained by integration of the flow signal. Induction of breathlessness. We used a combination of hypercapnia and an inspiratory resistive load to induce breathlessness. Because of the great intersubject variability in hypercapnic responsiveness, different levels of PETIT, (range 46-60 Torr) were used for different subjects, based on the subject’s steady-state hypercapnic response (see below). For each subject, we estimated the PETIT, value that would produce a steady-state ventilation of -30 l/min. Vibration. Vibration was applied with two standard physiotherapy vibrators (Novafon), which were manually triggered during inspiration. The amplitude and frequency of vibration were 3 mm and 115 Hz, respectively. The vibrations were transmitted to the subjects through a hard plastic disk with a diameter of 25 mm. For intercostal vibration, the vibrators were applied bilaterally over the second or third parasternal spaces, and for deltoid vibration, the vibrators were applied bilaterally over the deltoid muscles. Throughout all the studies, the vibrators were applied by a single investigator, who attempted to maintain a constant force of application. The timing of vibration was determined from the flow signal displayed on a storage oscilloscope (Tektronics 5111). Assessment of breathlessness. Each subject was given the same instructions to read from a printed text. To conceal the purpose of the study, the instructions were phrased in the must general terms possible. The subject was told that we would measure various aspects of his breathing and that from time to time he would be asked to rate his breathlessness, which we defined as “an unpleasant or uncomfortable sensation of breathing.” The subject was also told that the inspired concentrations of CO, and/or 0, might vary and that periodically a vibrator would be applied to his shoulders or to his chest. We assessed breathlessness with a variation of the techniques of cross-modality matching (35, 36). A tape measure was held and slowly exposed by one of the investigators such that the markings on the tape were visible only to the investigators. The subject was instructed to think of the length of tape exposed as being propor-
because the subject was unaware of the actual length of the tape (183 cm), he was told to consider the tape to be infinite in length (the maximum length of tape actually exposed by any of the subjects was 37 cm). For each rating period the length of exposed tape (in cm) was recorded and was taken as the subject’s breathlessness rating for that period. Experimental Protocol (Fig 1) Protocol A. STEADY-STATE co2 RESPONSE. With the subject breathing air, CO, was added to the inspiratory limb of the circuit to raise the PETITE to 50 Torr. Ten minutes were allowed for partial CO, equilibration; during the next 10 min we alternated 1-min periods of intercostal vibration with 1-min periods of deltoid vibration. A 15-min rest period followed the hypercapnic response. BREATHLESSNESS. After 10 min of unloaded breathing at the PET,,, selected to produce an expired minute ventilation of -30 Urnin, the subject breathed through the inspiratory resistance for another 60 s, after which his ventilation was noted. Because some individuals may continue to increase ventilation after the first 10 min of hypercapnia, the subject was instructed to target his ventilation to a level -15% above that achieved spontaneously. This allowed ventilation to be kept constant and helped eliminate any need for the subject to suppress his ventilation during the subsequent trial periods. The subject was given another 60 s to become accustomed to the targeted level of ventilation, after which the rating periods began. Each rating period lasted 30 s; during the last 10 s of the period the subject was asked to rate his breathlessness. The rating periods were divided into groups of three, consisting of one rating period each for intercostal, deltoid, and no vibration. At the beginning of each group of ratings the tape measure was set at zero, but for the other two periods in the group the subject was instructed to adjust the length of tape relative to the previous rating. With this protocol, a comparison of nonadjacent rating periods required not only the subject’s ability to recall the intensity of a prior sensation but also his ability to recall the length of tape corresponding to that sensation. Because the tape measure was unmarked, the latter would have been an exceedingly difficult task. On the basis of these considerations and our experience in several pilot studies, we concluded that a meaningful comparison could be made only between stimuli presented in adjacent rating periods. A schedule was devised so that deltoid vibration and intercostal vibration were always presented in adjacent periods, although the order in which they were presented was varied randomly. A period of no vibration was included as the first or last stimulus in each group but, for reasons stated above, was not included in the analysis of protocoZ A. A formal comparison of intercostal vibration and no vibration was performed separately (see protocol B below). There were a total of 18 rating periods (6 groups of 3 rating periods). A second run of identical design but with a different randomized schedule was completed after another 150min
tional to his degree of breathlessness and was told to
rest.
signal when the appropriate length of tape had been exposed. The upper limit of the scale was not defined, and
Protocol B. The hypercapnic response was measured as in protocol A, except that we alternated 1-min periods of
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CHEST
PROTOCOL Part
f-
10 MINUTES state
= 50 mm Hg +
Part 2 (Breathlessness) Hypercapnia* + 30
of Sequence
Same
+
f-
ventilation
10 MINUTES + achieve steady state ventilation
SECONDS $
Deltoid
10 MINUTES + alternating one minute periods of intercostal and deltoid vibration
+ 1 MINUTE $ f 1 MINUTE $ addition of targeted -) Vibration load ventilation Sequence with load
+ 30 SECONDS $ Intercostal
L---
PROTOCOL
177
AND BREATHLESSNESS
achieve steady
(CO2 Response)
Example Vibration
VIBRATION
A
1
PETGO
WALL
Breathlessness
SECONDS $ No Vibration -b Reset Tape-) Measure
+ 30
Next Sequence
4
Rating -
B basic
design as Protocol
Part 1: Intercostal vibration Part 2: Vibration sequences
A, except: alternated with no vibration for 8 minutes. included only intercostal vibration and no vibration,
* Level of hypercapnia varied among subjects (see text) FIG. 1. Schematic outline of pro~w~k A and El. See text for details.
intercostal vibration with l-min periods of no vibration at all, for a total of 8 min. In the breathlessness portion of protocol B, only intercostal vibration and no vibration were compared; deltoid vibration was not included in protocol B. The rating periods were divided into groups of two, and for each group the order of presentation was randomly determined. The tape measure was reset at the end of each group. There were a total of 18 rating periods (9 groups of 2 rating periods each). Five subjects were studied in both protocols, another five were studied in only protocol A, and an additional three were studied in only protocol B. For subjects who participated in both protocols, the two portions of the study were always done on separate days. At the end of each protocol, subjects were asked to comment on their sensations during the study. Datu Analysis
During the steady-state hypercapnic response, respiratory variables were measured during the middle 30 s of every l-min period. During the breathlessness portion of the protocol, respiratory variables were measured during the first 20 s of each 30-s period. Mean breathlessness ratings for each subject were calculated from the individual rating periods for each of the conditions of the study. For all respiratory variables, data are expressed as means t SD. Comparisons between intercostal vibration and either deltoid vibration or no vibration were made using a paired t test. For each subject, the mean breathlessness rating during intercostal vibration was expressed as a percentage of the mean breathlessness rating during the control period (either deltoid vibration or no vibration). Comparisons of breathlessness ratings were made using the Wilcoxon sign-rank test. For rea-
sons already discussed, a comparison of intercostal vibration and no vibration was made only from the data in protocol B. Statistical calculations were done with the AppStats (Statsoft, Tulsa, OK) software package. P < 0.05 was considered significant. RESULTS Ventilutory Response to Steady-State Hypercupnia Protcml A. There were no significant differences between intercostal vibration and deltoid vibration for any of the measured ventilatory variables (Table 1). Protocol B. Inspired minute ventilation (VI) was significantly greater with intercostal vibration than with no vibration (34.7 t 14.3 vs. 33.9 t 14.5 Vmin, P < O.Ol), although the difference was extremely small in magnitude. Ventilation of the rib cage compartment was greater with no vibration than with intercostal vibration (67 t 10 vs. 63 t 12%, P < 0.05). There were no signifiTABLE 1. Ventilatory data from the steady-state hypercupnic response Protocol A
Protocol B
Intercostal
Deltoid
Intercostal
No vibration
VI, l/min f, min-l VT, liters
29.9213.3 19.7t7.1
Tr, s
1.66-t0.51 0.5o-to.05 6126
29.7t13.5 19.9t7.9 1.54tO.59 1.66kO.55 0.49t0.05 62t5
34.7-t-14.3* 21.5t6.4 1.63tO.40 1.48t0.34 0.49+0.03 63t12”
33.9*14.5* 20.4k6.1 1.64t0.35 1.48-+0.31 0.48kO.05 67tlO*
TI/TT
%RC
1.55-to.57
Values are group means t, SD. VI, inspired minute ventilation; f, frequency; VT, tidal volume; TI, inspiratory time; TI/TT, duty cycle; %RC, percentage of VI attributable to rib cage compartment. *P < 0.05.
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VIBRATION
AND BREATHLESSNESS
PROTOCOL
A
B
110 (3 z Fr 100
SH
a a
FR DK J&m DO
v) cl3 y 90 to # 3 xt 80
EL
100
90
JK
a
W a
m 70 0
I
I
I
Deltoid
Intercostal
No Vibration
I
Intercostal
FIG. 2. Breathlessness ratings during intercostal vibration expressed as percentage of ratings during deltoid vibration and no vibration. Each symbol represents mean value of all breathlessness ratings from a single subject.
cant differences among any of the remaining variables (Table 1).
ventilatory
Assessment of Breathlessness Breathlessness ratings. Intercostal vibration reduced breathlessness ratings by 6.5 t 5.7% compared with deltoid vibration (protocol A, P < 0.05) and by 7.0 t 8.3% compared with no vibration (protocol B, P < 0.05) (Fig. 2). Ventilation data. Subjects were quite successful in targeting their ventilation. Inprotocol A, there was no significant difference in VI or in any other ventilatory parameter between deltoid vibration and intercostal vibration (Table 2). In protocol B, there was also no significant difference in VI between intercostal vibration and no vibration, although frequency was greater (21.7 k 7.2 vsI 20.3 t 6.3 min- ‘* P < 0.05) and VT wasless (1.63 t 0.46 vs. 1.71 t 0.46 liters, P < 0.05) with intercostal vibration (Table 2). There were no significant differences in any of the remaining ventilatory variables during protocol B. Subjective comments. Most of the subjects’ spontaneous comments focused on their breathing effort, with TABLE
protocol
VI, l/min f, min” VT,
liters
TI, s TI/TT %RC FRC Values capacity;
sample comments including “it seemed like I got a bigger breath with the vibration for the same effort,” “definitely easier to breathe at the target with chest vibration,” “with chest vibration had to work less to maintain the target,” and “vibration over my chest made it feel like there was less resistance at the end of my breath.” Although some subjects were unsure whether vibration had altered their breathlessness, several were quite convinced that intercostal vibration had reduced their breathlessness. One subject (PG) stated that intercostal vibration made his breathlessness worse and, in fact, was the only subject to have a higher breathlessness rating with intercostal vibration than with deltoid vibration. Subjects considered the magnitude of the effect of vibration on breathlessness to be slight to moderate. DISCUSSION
The principal finding of this study is that intercostal vibration reduced the breathlessness elicited by combined hypercapnia and inspiratory resistive loading. Breathlessness ratings were lower during intercostal vibration than during either no vibration or deltoid vibra2. Ventilatory data from breathlessness portion of tion. Previous studies have examined the effects of different during which minute ventilation was targeted sites of application and timing of a vibratory stimulus. Prutucul B Protocol A Homma et al. (19) elicited breathlessness in normal subjects by vibrating over the parasternal regions during exfntercostal Deltoid fnkcostal No viktion piration and over the lower intercostals during inspira29.Ok5.7 33.1-t5.7 32.7xk5.3 tion (out-of-phase vibration). 28.5+5.9 We chose to vibrate over 22.527.7 22.8~7.6 21.7k7.2" 20.3*6.3* the parasternal spaces because of the inspiratory action 1.37t0.31 1.35HI.30 1.63kO.46" 1.71t0.46* of the parasternal intercostal muscles (7), and in con1.75kO.47 1.82k0.43 1.76kO.41 1.75k0.43 trast to Homma et al. (17), we applied vibration during 0.59t,o.o3 0.58t0.03 0.61t,0.05 0.6lt0.05 67k7 68H3 inspiration (in phase) because of the finding that in65k6 66t6 0.02zkO.15 0.07~0.10 0.05zkO.16 0.05t0.17 phase vibration elicits a tonic vibration reflex in the underlying intercostal muscles (see below). are group means k SD. FRC, change in functional residual The vibrators used in our study were applied and trigother abbreviations as in Table 1. *P < 0.05.
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gered manually. Although we attempted to minimize variability by having a single investigator apply the vibrators in all studies, there undoubtedly was a brief lag between the subjects’ transitions between inspiration and expiration and the investigator’s triggering of the vibrators, as well as some slight intra- and intersubject variability in the force of application of the vibrators. Thus, although we believe that the reduction in breathlessness associated with intercostal vibration was due to inspiratory vibration, we cannot exclude the possibility that a very brief period of expiratory vibration may have contributed to the reduction in breathlessness. Expiratory vibration is unlikely to have this effect, however, given the work of Homma et al. (19), which suggests that out-of-phase vibration worsens breathlessness. One might argue that the reduction in breathlessness associated with intercostal vibration was due to a nonspecific effect of vibration, such as distraction. On this basis, however, one would predict that there would be no difference in breathlessness between intercostal vibration and deltoid vibration. In fact, relative to deltoid vibration, intercostal vibration significantly reduced breathlessness. Moreover, although only one of the two control conditions (deltoid vibration) offered a distraction, the magnitude of the reduction in breathlessness with intercostal vibration was similar whether the control condition was deltoid vibration or no vibration. Thus we believe that it is unlikely for the reduction in breathlessness associated with intercostal vibration to be due simply to distraction or to some other nonspecific effect of vibration. Chemical drive (Pco,) may alter breathlessness independently of changes in ventilation (1, Z), and ventilation may likewise alter breathlessness independently of changes in chemical drive (6,3l). We therefore adjusted the inspired CO, to keep PET,~~ constant during all rating periods, and by targeting ventilation, we maintained ventilation at a constant level. Although there were statistically significant differences in frequency and VT between intercostal vibration and no vibration, the magnitude of the difference was very small and is extremely unlikely to have produced the difference in breathlessness ratings. Respiratory sensation can also be altered by changes in lung volume (22) or by pattern of respiratory muscle activation (34,37). However, there was no significant difference in FRC among the three study conditions. Furthermore, although we did not assess the activation of specific muscles, compartmental ventilation, which reflects the pattern of activation of particular muscle groups, also did not differ among the study conditions. Thus we either controlled for or found no difference in the chemical and mechanical factors that previously have been shown to play a role in respiratory sensation, thereby making it reasonable to invoke intercostal vibration as the cause of the reduction in breathlessness. One mechanism by which intercostal vibration might reduce breathlessness is through a reduction in respiratory drive (medullary inspiratory neuron activity). Although the precise relation between medullary inspiratory neuron activity and breathlessness is uncertain, there is evidence that it is one of the determinants of
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breathlessness (2). Several lines of evidence from both animal and human studies indicate that intercostal vibration reduces respiratory drive (3, 4, 28). Vibration studies in humans have looked at indirect indices of medullary inspiratory neuron activity, such as tidal volume (11), diaphragm electromyogram (16), and breath-holding time (32). Taken together these studies suggest that chest wall vibration also reduces respiratory drive in humans. In our study we induced breathlessness with hypercapnia and an inspiratory resistive load. Because the work of Hida et al. (15) suggests that vibration alters the effect of hypercapnia on medullary inspiratory activity, we examined the effects of vibration on the ventilatory response to hypercapnia. In contrast to previous investigations (15,20,24), however, we found that neither limb muscle (deltoid) nor intercostal vibration had a sizable effect on the ventilatory response to steady-state hypercapnia (Table 1). Our finding of a trivial effect of intercostal vibration on the ventilatory response to hypercapnia conflicts with the findings of Hida et al. (15). They used a similar frequency, timing, and site of vibration and found an -70% increase in the ventilatory response to progressive hyperoxic hypercapnia, whereas we demonstrated only a 3% increase in ventilation during steady-state normoxic hypercapnia. Although the two studies utilized different techniques and conditions for assessing the ventilatory response to hypercapnia, this does not seem adequate to account for the widely disparate results obtained in the two studies. Thus, although we are unable to explain the lack of effect of vibration on the ventilatory response to hypercapnia, it appears that the reduction in breathlessness associated with intercostal vibration cannot be explained by a change in the relationship between medullary inspiratory neuron activity and hypercapnia. We were surprised that during intercostal vibration the rib cage compartment contributed less to total ventilation than during the no-vibration condition. The magnitude of the difference was small, however, and we can only speculate that the pressure of the vibrators on the rib cage during inspiration caused a slight decrease in rib cage expansion. The work of Schwartzstein et al. (31) and Chonan et al. (6) may bear on the interpretation of our results. Both groups of workers found that, at a constant level of hypercapnia, normal subjects had an increase in breathlessness when ventilation was voluntarily reduced below that achieved during free breathing. The authors (31) suggested that the increase in breathlessness may have been related to mismatch between the actual motion of the chest wall and/or lung and the level of motion expected on the basis of the outgoing motor command. Similar reasoning could be extended to the results of our study. During the breathlessness portion of the protocol, ventilation was similar to that achieved during free breathing (Tables 1 and 2), but the addition of the inspiratory resistance must have necessitated a substantial increase in the outgoing motor command to the inspiratory muscles. This may have resulted in discordance between afferent signals from the chest wall and/or lung and the efferent motor command. Although our study does not allow us to test this hypothesis, it is possible
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that chest wall vibration produced an increase in afferent information, thereby providing a better match between incoming sensory signals and outgoing motor commands and thus reducing breathlessness. Another possible mechanism by which intercostal vibration may have reduced breathlessness is through a decreased sense of effort. According to the theory proposed by Killian and co-workers (8,22), breathlessness is the sensation of respiratory muscle effort. On the basis of this theory, one would predict that those factors that reduce the sense of respiratory muscle effort would reduce breathlessness as well. As pointed out by Gandevia (9), there are many parallels between limb muscle sensation and respiratory sensation. There is substantial evidence supporting the notion that the sense of limb muscle effort results from perception of the cortical motor command to the muscle (9, 25). In situations where increased activation of the muscles is required to sustain a task (fatigue, partial paralysis), the sense of effort increases (12, 13). Similarly, when increased activation of the inspiratory muscles is required because of fatigue (10) or a disadvantageous length for tension development (22,34), the sense of effort increases. Of particular relevance to our study is the work of McCloskey et al. (26). Their experiments demonstrated that application of a lOO-Hz physiotherapy vibrator over the biceps tendon caused subjects to underestimate the force output of the biceps muscle. One interpretation of these findings is that vibration of the muscle tendon had a facilitory effect on the cu-motor neurons innervating the biceps (tonic vibration reflex), thereby requiring decreased activation by cortical motor centers, and producing a decreased sense of effort. A similar argument could be extended to our study. By targeting ventilation, we achieved similar ventilatory parameters in all study conditions. Because intercostal vibration has been shown to have a segmental facilitatory effect (33), a possible explanation for our results is that through facilitation of inspiratory motor neurons, intercostal vibration decreased the activation required from cortical centers, thereby decreasing the sense of effort associated with inspiration. Gandevia (9) has proposed an analogous explanation for the findings of Homma et al. (19), who reported that alternating out-of-phase vibration caused a sensation of breathlessness in normal subjects. Gandevia suggests that, in the study by Homma et al. (19), vibration of the expiratory intercostals caused reciprocal inhibition of the inspiratory intercostals and that, as a result, a greater voluntary motor command was required to activate the inspiratory motor neurons (9). One problem that arises in interpreting the study by Homma et al. (19) is that vibration caused an increase in breathing frequency and tidal volume and a shortening of inspiratory time (and presumably an increase in inspiratory flow rate). These factors may independently alter respiratory sensation (8, 21), making it difficult to ascertain whether breathlessness was due to vibration per se or merely to the increase in ventilation associated with vibration. Because of the many parallels already established between limb muscle and respiratory muscle sensation (9) and because most of the subjects’ spontaneous comments were concerned with the effort or work of breathing, we believe it possible that intercostal vibration
AND BREATHLESSNESS
caused a reduction in the sense of inspiratory muscle effort. Although the inspiratory resistance used in our study was modest, ventilation was high, and the effort of breathing through the resistance was almost certainly a component of the breathlessness experienced by our subjects. Thus, by decreasing the sense of inspiratory effort, vibration may have reduced breathlessness. For both the limb muscles and the respiratory muscles, there is conflicting evidence about the role played by specific receptors in mediating the effects of vibration (3,5, 11,25,28). Our study did not address the issue of which receptors were stimulated by vibration nor of which receptor( s) mediated the reduction in breathlessness caused by intercostal vibration. In summary, we found minimal effect of either deltoid or intercostal vibration on the ventilatory response to hypercapnia. Intercostal vibration reduced breathlessness and did so independently of any sizable changes in total ventilation, compartmental ventilation, or FRC. We speculate that a decrease in inspiratory effort sensation and an improved matching of afferent information from the chest wall with the outgoing respiratory motor command are the most likely mechanisms for the reduction in breathlessness. We thank Dr. Martha Teghtsoonian for assisting with the design of the study and Edwyna Von Gal for expert technical assistance. This study was supported by Pulmonary Specialized Center of Research Grant HL-19170 and Training Grant HL-07633 from the National Heart, Lung, and Blood Institute. Address for reprint requests: R. M. Schwartzstein, Pulmonary Unit, Beth Israel Hospital, 330 Brookline Ave., Boston, MA 02215. Received 26 December 1989; accepted in final form 26 February 1991. REFERENCES 1.
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