Quality of Dyspnea in Bronchoconstriction Differs from External Resistive Loads MARILYN L. MOY, J. WOODROW WEISS, DAVID SPARROW, ELLIOT ISRAEL, and RICHARD M. SCHWARTZSTEIN Divisions of Pulmonary and Critical Care Medicine, Departments of Medicine, Beth Israel Deaconess Medical Center and Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts; VA Normative Aging Study, and Department of Medicine, Boston University School of Medicine, Boston, Massachusetts
To test the hypothesis that patients perceive the same quality of dyspnea during mild bronchoconstriction and external resistive loads, we studied subjects with asthma under two conditions: (1) during methacholine bronchoprovocation to mimic the bronchospasm of mild asthma and (2) while breathing on a circuit to which was added a range of external resistors to mimic the mechanical load of mild asthma. During each of these stimuli, respiratory variables, overall dyspnea intensity on a modified Borg scale, and the qualitative descriptors of breathlessness from a 19-item questionnaire were assessed. The “chest tightness” and “constriction” responses were significantly more frequent in the methacholine trials as compared with the external load trials (p ⬍ 0.0001). The “chest tightness” or “constriction” response was chosen during 92% of the 26 trials of methacholine bronchoconstriction compared with 3% of the 72 trials of breathing against the external resistors. Changes in functional residual capacity were not significantly different between the two conditions. We conclude that in mild asthma, the sensation of chest tightness is distinct from the sensation of work and effort and is not attributable to the mechanical load imposed on the respiratory system.
In individuals with asthma there is only a modest correlation between changes in lung function, as measured by FEV1, and symptoms of breathing discomfort. A controversy exists among researchers in this field regarding the source of the respiratory sensations in patients with asthma. Given the range of physiological mechanisms proposed for dyspnea (1, 2), investigators have postulated that airway resistance alone is not the primary derangement responsible for breathing discomfort associated with bronchospasm. A number of investigations have examined the dyspnea of asthma under varying conditions and utilizing different models of airway obstruction. Studies in patients challenged with doses of inhaled methacholine sufficient to produce moderate to severe airway obstruction have suggested that the dyspnea of asthma is characterized by the sensation of “an unsatisfied breath,” “unrewarded inspiratory effort,” or an “inability to get a deep breath” (3). These findings are similar to those in studies performed in patients with emphysema (4) and have been attributed to the mechanical load on the system, specifically hyperinflation, and to the experience of breathing at one extreme of the respiratory system’s pressure–volume curve (3, 4). These results, obtained in patients with moderate to severe airway obstruction, were associated with changes in functional residual capacity (FRC) that approximated 2 L.
(Received in original form July 28, 1999 and in revised form February 8, 2000) Supported in part by NIH/NHLBI Grant HL07427. Correspondence and requests for reprints should be addressed to Richard M. Schwartzstein, M.D., Division of Pulmonary and Critical Care Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215. E-mail:
[email protected] Am J Respir Crit Care Med Vol 162. pp 451–455, 2000 Internet address: www.atsjournals.org
In contrast to these findings, studies of patients with asthma who are questioned about the breathing discomfort they experience with their disease have revealed that the sensations of “chest tightness” or “constriction” are prominent (5–7). The discrepancy between the findings in studies of moderate to severe bronchoconstriction as compared with those in which patients completed dyspnea questionnaires may be due to the level of bronchoconstriction and accompanying hyperinflation under these different conditions. Furthermore, inhaled lidocaine has been shown to reduce the intensity of dyspnea resulting from chemically induced bronchoconstriction (8). These results suggest that information from pulmonary receptors rather than afferent feedback from stimulation of chest wall receptors by hyperinflation and mechanical loads may be important in giving rise to the sensations of breathlessness when only mild airway obstruction is provoked. This controversy is further fueled by the preliminary results of a study by Homma and coworkers (9) in which vibrators were applied to the chest wall of individuals with a history of asthma. In five subjects, chest wall vibration resulted in a sensation that was described as similar to the respiratory discomfort associated with an acute asthma attack. These results suggest that chest wall afferents may be the source of breathlessness in patients with asthma. Mild asthma is characterized by increased airway resistance in the absence of significant hyperinflation. If mechanical factors, specifically those associated with increased airway resistance, are responsible for the dyspnea of mild asthma, we postulated that the quality of breathing discomfort associated with mild bronchospasm would be the same as that associated with external resistive loads. To investigate this question, we studied the quality of dyspnea in patients with asthma in whom mild bronchospasm, at levels of airway obstruction not expected to produce significant hyperinflation, was induced by inhalation of methacholine. The quality of dyspnea was also assessed in these subjects while breathing on a circuit to which was added a range of external resistors to mimic the mechanical load of mild asthma. Finally, to systematically examine the qualitative aspects of the dyspnea associated with chest wall vibration, physiotherapy vibrators were applied to these subjects and the associated respiratory sensations were assessed.
METHODS Subjects We studied seven males and one female with a history of mild asthma as defined by the criteria of the American Thoracic Society (10) or based on a clinical history of wheezing without a significant smoking history (less than 10 pack-years). All subjects had stable lung function at the time of study. Exclusion criteria included FEV1 ⬍ 70% predicted and use of oral or inhaled corticosteroids. Subjects were instructed to withhold routine bronchodilators for the 24 h prior to the study. Written informed consent was obtained from all subjects according to the guidelines of the Committee on Clinical Investigations, Beth Israel Deaconess Medical Center.
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To simulate mild asthma, each subject underwent methacholine bronchoprovocation to mimic the bronchospasm of asthma without concomitant hyperinflation. While breathing on a circuit, each subject was also exposed to a range of external resistors to mimic the mechanical load of asthma. Six subjects underwent chest wall vibration. During each of these stimuli, respiratory variables, intensity of dyspnea, and the qualitative descriptors of breathlessness were assessed.
cycle time (Ttot) were measured from the flow tracing. Changes in FRC were determined by the magnetometers in the external loading experiments. Changes in FRC and airways resistance from baseline to maximal bronchoconstriction during the methacholine challenges were measured in the plethysmograph. End-tidal PCO2 was measured at the mouth with a mass spectrometer (Perkin-Elmer 1100 Medical Gas Analyzer, Pomona, CA). The relative contributions of the rib cage and abdominal compartments to total ventilation were measured with magnetometers.
Interventions
Assessment of Dyspnea
Methacholine bronchoprovocation. Test solutions of methacholine (Roche Laboratories, Nutley, NJ) were prepared prior to each study by serial dilution in filtered, sterilized phenolic buffered saline. Each bronchial inhalation challenge was performed in the standard manner described by Chai and coworkers (11). Aerosols were generated by De Vilbiss No. 646 nebulizer (De Vilbiss Respiratory Products, Somerset, PA) powered by compressed air at 20 psi and a RosenthalFrench dosimeter (Laboratory for Applied Immunology, Inc., Baltimore, MD) set at a delivery time of 0.6 s manually triggered at FRC. Each dose consisted of five inhalations of the test solution. In all studies, the diluent was administered as an initial test dose. Baseline airway resistance and FRC were measured by plethysmography. Successive doses of increasing concentration were delivered until the subject’s FEV1 was ⭐ 55% predicted or the subject rated breathlessness as ⭓ 4 (“somewhat strong”) on a modified Borg scale. Methacholine concentrations ranged from 0.025 to 25.0 mg/ml. Each administration of a dose was considered one trial of the methacholine challenge test (the number of trials per subject ranged from two to five). External resistive loads. Magnetometers (Magnetometer-NP-1400Q) were used to determine rib cage and abdominal movements and changes in lung volume. Each subject’s position was fixed in a rigid chair that kept him in a semirecumbent position. Changes in FRC were monitored utilizing the tidal tracing. The magnetometers were calibrated with the isovolume maneuver (12). A low-resistance breathing circuit with inspiratory and expiratory arms was used. Each trial began with 2 min of quiet breathing through a mouthpiece with no load to establish the baseline breathing pattern and FRC. Two valves were then turned, which added an inspiratory and expiratory load to the breathing circuit. Subjects breathed on the loads for 2 min. External resistive loads of three sizes, 63.2, 32.5, and 9.8 cm H2O/L/s (linear resistors at flow between 0.5 and 1.5 L/s) were applied in combination to both the inspiratory and expiratory limbs of the apparatus to produce nine sets of resistances. Each subject performed nine trials. The order in which subjects experienced the nine resistances was random. There was a minimum of 2 min of rest between trials, during which time the subjects came off the circuit. Vibration. Two standard physiotherapy vibrators (Novafon; Eldredge Resources, Inc., Murray, UT) were applied on either the right side of the chest over the third and seventh intercostal spaces or bilaterally over the lower rib cage at the seventh rib interspace. Control vibrations were applied bilaterally over the deltoid muscles. The vibration, with an amplitude and frequency of 3 mm and 115 Hz, respectively, was transmitted to the subjects via a hard plastic disk with a diameter of 25 mm. Vibration was applied “out of phase,” that is, during expiration on the muscles of inspiration at the third intercostal space and during inspiration on the muscles of exhalation at the lower rib cage. The vibrators were applied for 2 min. Subjects were asked if they had any breathing discomfort. If yes, they described the intensity and quality of the breathlessness. Each subject was also asked if the breathing discomfort was similar to the sensation associated with an asthma exacerbation.
Subjects were instructed to grade the overall intensity of their “breathing discomfort” by assigning a numerical value using a modified Borg scale (13). The quality of breathlessness was evaluated using the 19-item questionnaire of descriptors of dyspnea (Table 1) (14). One of five versions of the questionnaire, differing in the order in which the phrases were presented, was randomly used for each subject. The same version was used for a particular subject throughout the external resistive load and methacholine challenge protocols. Subjects answered the questionnaires while breathing on the mouthpiece during the external resistive load protocol. Following each combination of external resistive loads, subjects were asked if they had any “breathing discomfort or breathlessness.” If yes, they rated the overall intensity of dyspnea using the modified Borg scale. Then they were asked to select the phrases that best described the quality of breathlessness. If more than three phrases were chosen, the subject was asked to select the three that best described the breathing discomfort. Similarly, the overall intensity of breathing discomfort and quality of dyspnea were assessed during bronchoconstriction after each dose of methacholine.
Respiratory Variables Spirometry was measured with the use of a Collins Eagle Spirometer (Warren E. Collins, Inc., Braintree, MA). The best of three maneuvers in terms of FEV1 was used. Spirometry was measured after each dose of methacholine. Subjects breathed through a mouthpiece attached to a unidirectional valve (Rudolph valve) with inspiratory flow measured with a Fleisch No. 3 pneumotachograph and a differential pressure transducer (Validyne ⫾ 2 cm H2O; Validyne Corp., Northridge, CA). The flow signal was integrated by a respiratory integrator (Hewlett-Packard 8815A; Hewlett-Packard, Waltham, MA) for determination of tidal volume (VT) and minute ventilation (VE). Inspiratory time (TI) and total respiratory
Statistical Analysis To compare the external load interventions with the methacholine challenges, respiratory variables analyzed were those obtained at a matched overall intensity of breathlessness of “4” or “somewhat severe” on the modified Borg scale. For the instances when more than one external load trial matched in intensity with the methacholine trial, separate analyses were done using the lowest external load and the highest external load. Analysis of variance was used to determine overall differences among the three states: baseline, methacholine bronchoprovocation, and external loading. Pairwise comparisons were determined by parametric Neuman–Keul’s tests or nonparametric Friedman’s rank sum tests where appropriate. Change in FRC from baseline to external load was compared with change in FRC from baseline to bronchoconstriction using paired Student’s t-test. Significance was defined as p ⬍ 0.05 and results are presented as mean ⫾ standard deviation. A two-sample test for proportions with an adjustment for multiple observations per individual (15) was used to compare types of breathlessness experienced during methacholine trials and external resistive load trials. The two specific types of breathlessness analyzed were the
TABLE 1 DESCRIPTORS OF DYSPNEA I feel that my breathing is rapid. My breath does not go out all the way. My breath does not go in all the way. My breathing is shallow. My breathing requires effort. My breathing requires more work. I feel that I am smothering. I feel that I am suffocating. I feel a hunger for more air. I feel out of breath. I cannot get enough air. My chest feels tight. My chest is constricted. My breathing is heavy. I feel that I am breathing more. I cannot take a deep breath. I feel that my breath stops. I am gasping for breath. My breathing requires more concentration.
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Age (yr)
Duration of Asthma (yr)
Medications
Precipitating Factors of Asthma
Baseline FEV1 (L) (% pred )
⌬FEV1 (L) (%⌬)*
⌬FRC (L) (%⌬)*
23 35 23 32 26 22 20 22
19 33 17 10 25 22 7 19
-Agonists as needed -Agonists as needed -Agonists as needed -Agonists as needed -Agonists as needed -Agonists as needed -Agonist every day -Agonists as needed
Allergens, cold air, smoke Allergens, cold air, exercise Allergens, cold air, exercise Cold air, exercise Allergens, URI, cold air Allergens, URI, exercise Allergens, exercise Allergens, exercise
5.03 (100) 3.60 (79.6) 4.27 (102) 4.60 (89.6) 3.00 (90.0) 4.32 (107.0) 4.63 (98.3) 4.61 (104.0)
⫺1.72 (⫺34.4) ⫺1.27 (⫺36.3) ⫺0.70 (⫺16.4) ⫺1.98 (⫺42.3) ⫺1.51 (⫺49.0) ⫺1.68 (⫺39.6) ⫺2.02 (⫺42.8) ⫺2.26 (⫺51.3)
⫹0.31 (⫹5.0) ⫺0.16 (⫺4.0) ⫹0.47 (⫹13.3) ⫹1.57 (⫹49.8) ⫹1.23 (⫹56.4) ⫹1.70 (⫹54.8) ⫹0.92 (⫹24.9) ⫹0.78 (⫹23.3)
Definition of abbreviations: FRC ⫽ functional residual capacity; URI ⫽ upper respiratory infection. * Changes in FEV1 and FRC at maximal bronchoconstriction with methacholine when subjects rated dyspnea ⭓ 4 on modified Borg scale.
combined descriptors “work/effort” and the combined descriptors “tightness/constriction.” Each trial was classified into a binomial outcome (one of two possible types of breathlessness), ignoring trials when the subject chose both types or neither one.
RESULTS Eight subjects, one woman and seven men with age range 20– 35 yr, participated in the study. The subjects had been diagnosed with asthma for at least 7 yr. All subjects used inhaled -agonists and had normal baseline spirometry (Table 2). Table 2 shows that at maximal bronchoconstriction with methacholine, mild airway obstruction with varying degrees of hyperinflation (⌬FRC range ⫺ 0.16 to ⫹ 1.70 L) was achieved. There was no significant difference in respiratory variables, VT, VE, PETCO2, duty cycle (TI/Ttot), and mean inspiratory flow (VT/TI), measured during the external loads compared with the methacholine bronchoprovocation trials (Tables 3 and 4). FRC increased by 850 ml during methacholine trials and 350–380 ml with external loading (p ⫽ NS). To achieve a comparable intensity of dyspnea, external loads totaling 72.5– 97.5 cm H2O/L/s were needed to reproduce the discomfort of an internal airway resistance of 4.93 cm H2O/L/s. There was a trend toward greater relative contributions of the rib cage as compared with the abdominal compartments toward tidal volume with external loads as compared with methacholine challenge. The “chest tightness” and “constriction” responses in the methacholine trials were significantly more frequent than in the external load trials (two-sample test for proportions, p ⬍ 0.0001). The “chest tightness” or “constriction” response was chosen during 92% of the 26 trials of methacholine bronchoconstriction as compared with 3% of the 72 trials of breathing against the exter-
nal resistors (Table 5). The responses “work” and “effort” were chosen in 92% of the external load trials and in 54% of the methacholine bronchoconstriction trials. Figure 1 demonstrates that at low levels of bronchoconstriction and relatively normal FEV1, before significant airways resistance or hyperinflation developed, “chest tightness” was the predominant sensation noted by subjects. With increasing methacholine-induced bronchoconstriction, as lung function declined and hyperinflation increased, the sense of “effort and work” of breathing was noted along with “chest tightness.” Six of the eight subjects completed the vibration protocol. Three of the subjects experienced breathing discomfort with chest wall vibration. When asked to describe the quality of the breathing discomfort, two of these individuals used the phrase “constriction.” The remaining subject felt the discomfort was related to the pressure of the vibrators on the chest wall and was unlike his asthma. The small number of subjects precluded statistical analysis of these results.
DISCUSSION This study demonstrates that mild bronchoconstriction does not produce the same quality of dyspnea as do mechanical loads associated with external resistors in patients with mild asthma. Patients experience dyspnea described as a sensation of “chest tightness” during methacholine-induced bronchoconstriction, in the absence of significant dynamic hyperinflation and elastic loads. This sensation of “chest tightness” is essentially absent from descriptions of dyspnea associated with external resistive loading and is accompanied by the sensations of increased “work and effort” at moderate levels of bronchoconstriction. Thus, it appears
TABLE 3 RESPIRATORY VARIABLES MATCHED FOR EQUAL INTENSITY OF BREATHLESSNESS: LOW EXTERNAL LOAD*
Tidal volume L Duty cycle Minute ventilation L/min End-tidal PCO2, mm Hg Mean inspiratory flow, L/s Rib cage contribution to ventilation, % Change in functional residual capacity, L Airways resistance, cm H2O/L/s
Baseline
Exernal Resistors
Methacholine Bronchoconstriction
p Value
0.86 ⫾ 0.40 0.34 ⫾ 0.04 12.1 ⫾ 5.8 33.9 ⫾ 7.5 0.59 ⫾ 0.24‡ 63 ⫾ 12
1.09 ⫾ 0.76 0.39 ⫾ 0.06 10.5 ⫾ 6.0 35.4 ⫾ 8.0 0.44 ⫾ 0.18 66 ⫾ 14§ 0.35 ⫾ 1.20 72.5 ⫾ 36.9§
0.80 ⫾ 0.38 0.36 ⫾ 0.03 11.3 ⫾ 3.9 34.7 ⫾ 6.2 0.54 ⫾ 0.24 55 ⫾ 13 0.85 ⫾ 0.64 4.93 ⫾ 1.47
NS NS NS NS ⬍ 0.05 ⬍ 0.05 NS ⬍ 0.01
1.36 ⫾ 0.52‡
* For the instances when more than one external load trial matched in intensity with the methacholine trial, the lowest external load was analyzed. † p Value for overall analysis of variance. ‡ Significant difference between baseline and external resistor groups. § Significant difference between external resistor and methacholine bronchoconstriction groups.
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TABLE 4 RESPIRATORY VARIABLES MATCHED FOR EQUAL INTENSITY OF BREATHLESSNESS: HIGH EXTERNAL LOAD* Baseline Tidal volume, L Duty cycle Minute ventilation, L/min End-tidal PCO2, mm Hg Mean inspiratory flow, L/s Rib cage contribution to ventilation, % Change in functional residual capacity, L Airways resistance, cm H2O/L/s
0.84 ⫾ 0.35 0.35 ⫾ 0.05 12.5 ⫾ 6.4 34.1 ⫾ 8.1 0.59 ⫾ 0.26‡ 55 ⫾ 14 1.36 ⫾ 0.52‡
External Resistors
Methacholine Bronchoconstriction
p Value†
1.03 ⫾ 0.57 0.38 ⫾ 0.08 10.0 ⫾ 6.2 36.4 ⫾ 9.2 0.44 ⫾ 0.21 62 ⫾ 12 0.38 ⫾ 1.19 97.5 ⫾ 32.8§
0.80 ⫾ 0.38 0.36 ⫾ 0.03 11.3 ⫾ 3.9 34.7 ⫾ 6.2 0.54 ⫾ 0.24 55 ⫾ 13 0.85 ⫾ 0.64 4.93 ⫾ 1.47
NS NS NS NS ⬍ 0.05 NS NS ⬍ 0.001
* For the instances when more than one external load trial matched in intensity with the methacholine trial, the highest external load was analyzed. † p Value for overall analysis of variance. ‡ Significant difference between baseline and external resistor groups. § Significant difference between external resistor and methacholine bronchoconstriction groups.
that “chest tightness,” which is present at the earliest stages of bronchoconstriction, before significant airway resistance or hyperinflation develops, arises from one mechanism whereas the sense of “work and effort” is the result of a different mechanism. Chest wall vibration did not consistently produce sensations of chest “tightness.” That chest tightness is a distinct sensation arising from a mechanism other than dynamic hyperinflation and mechanical loading on the respiratory system is supported by other studies in the literature. Taguchi and coworkers (8) showed that the administration of inhaled lidocaine ameliorated the breathing discomfort arising from histamine-induced bronchoconstriction but not the dyspnea associated with external resistive loads. Furthermore, administration of an inhaled -agonist to patients presenting with acute spontaneous asthma reduced the intensity of chest tightness to a greater degree than the sensation of the work and effort of breathing (16). These findings in patients with mild asthma complement the studies published in the literature to date in which patients with more severe bronchoconstriction and concomitant hyperinflation were examined. Studies examining the effects of increasing lung volume on the sensation of dyspnea have suggested that the intensity of dyspnea with increasing lung volume is associated with increased effort (17). Furthermore Simon and coworkers (14) demonstrated with the language descriptors of dyspnea that when normal volunteers increased FRC by 1 L above their normal FRC, dyspnea was described predominantly as difficulty with exhalation and rapid breathing, but not as a sensation of tightness or constriction. Differences between the sensory experience of patients in this study and that of studies describing dyspnea as inspiratory difficulty (3, 4) are most likely due to differences in the severity of airway obstruction as well as the level of dynamic hyperinflation achieved. Subjects with chronic obstructive lung disease and asthma who experienced increases in functional
residual capacity (FRC) of 1–2 L with exercise (18) or inhalation of high doses of methacholine described dyspnea as an inability to get a deep breath or an awareness of “unsatisfied” inspiratory effort (3). Similarly, Kelsen and coworkers (19) showed that the sense of effort was significantly greater in patients with asthma exposed to methacholine-induced bronchoconstriction than in patients given external resistive loads. This significant difference in the sense of effort patterned the difference in the increase in FRC between the two groups of patients with asthma—that is, mean FRC at the highest dose of methacholine was 151% of control, whereas mean FRC with the severest external resistance was 107% of control. In contrast, our subjects did not note the sensation of inspiratory difficulty as a prominent feature of their dyspnea nor was the sensation of work and effort prominent in patients during methacholine-induced bronchoconstriction compared with the trials of external resistive loading. However, our goal was to study mild asthma and bronchoconstriction without hyperinflation. The changes in FRC at maximal bronchoconstriction with methacholine in the current study spanned a broad range; nevertheless, only three of the eight subjects experienced an increase in FRC of over 1 L during methacholine challenge.
TABLE 5 QUALITY OF BREATHLESSNESS*
“Chest tightness” or “constriction” “Work” or “effort”
External Resistors
Methacholine Bronchoconstriction
3 92
92 54
* Values represent the percentage of trials (n ⫽ 72 for external resistors, n ⫽ 26 for bronchoconstriction) under the conditions of external resistive loading and bronchoconstriction during which breathing discomfort was characterized by the phrases shown.
Figure 1. Percent of responses for each level of FEV1. Considering those responses when chest tightness and constriction and/or effort and work were chosen to describe the quality of breathlessness during methacholine inhalation, the quality of the sensation varied with the degree of airway obstruction. At mild degrees of airway obstruction, “chest tightness” or “constriction” was the primary sensation. At more intense levels of bronchoconstriction, the sense of “work” and “effort,” in addition to “tightness,” was used to characterize the breathing discomfort.
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Moy, Weiss, Sparrow, et al.: Quality of Dyspnea in Bronchoconstriction
Chest tightness was the predominant sensation perceived by subjects even at low levels of airway obstruction (Figure 1) when hyperinflation was minimal. All study subjects were patients with mild asthma who were naive to the protocol and the descriptors of dyspnea, making it unlikely that the results represent a learning effect or selection bias. The use of chemically induced bronchoconstriction and external resistive loads to model mechanical and sensory aspects of asthma is widely accepted and has been used in other studies (3, 8, 19). Nevertheless, factors such as airway inflammation may not be mimicked with these models. The use of an esophageal balloon to measure transpulmonary pressure in concert with a body plethysmograph would give more accurate measurements of airway resistance than those obtained in this study. However, the upper airway discomfort of the esophageal balloon may potentially confound the sensation of breathlessness being measured and was avoided in this investigation. The mean airway resistance of 4.93 cm H2O/L/s in the methacholine group is consistent with the mild level of airway obstruction achieved, with a mean change in FEV1 of only 1.64 L from a normal baseline of 4.26 L. During acute bronchoconstriction, the utility of airway resistance as an assessment of the severity of airway narrowing may be limited by airway closure. Nevertheless, other studies in the literature have also shown airway resistances at this level. Taguchi and coworkers (8) reported airway resistance (Raw) with histamine-induced bronchoconstriction as 3.0–3.3 cm H2O/L/s with a control value of 1.1 cm H2O/L/s in normal subjects. Fisher and coworkers (20) demonstrated in patients with asthma after exercise an airway resistance that ranged from 4.3 to 17.8 cm H2O/L/s. No spirometric data or intensity of dyspnea ratings were reported with these values of airway resistance. Two potential limitations of the methodology used require discussion. First, during acute bronchoconstriction, the endtidal PCO2 may underestimate PaCO2. Given our focus on the sensory aspects of asthma, our major concern would be that the subjects were unknowingly hypercapnic. In mild asthma, however, patients are typically eucapnic or mildly hypocapnic. Thus, the underestimation of the PaCO2 in these subjects is unlikely to be of a magnitude that would have a significant impact on the interpretation of the results. Second, the goal of the vibration protocol was to stimulate muscle spindles. The amplitude and frequency of the vibrators were assessed with the vibrators activated in isolation, i.e., not applied to a surface. It is possible that the effective frequency and amplitude transmitted to the muscle spindles are different than those applied at the chest wall. Nevertheless, the technique employed has been used by other investigators and found under different conditions to produce respiratory discomfort (9) or alleviate dyspnea (21, 22). In fact, Homma and coworkers (9) have shown that vibrations around 100 Hz induce the strongest sensations. In conclusion, multiple mechanisms likely lead to several distinct sensations of dyspnea in asthma. Mild bronchoconstriction is associated with the sensation of chest tightness whereas mechanical loads and dynamic hyperinflation are associated with sensations of work and effort and an inability to get a deep breath. We conjecture that the sensation of chest tightness originates from pulmonary receptors rather than chest wall muscles. Further studies are needed to pinpoint the specific origins of these sensations of dyspnea in patients with asthma.
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