Distinguishable Types of Dyspnea in Patients with Shortness of Breath 1- 3
PEGGY M. SIMON, RICHARD M. SCHWARTZSTEIN, J. WOODROW WEISS, VLADIMIR FENCL, MARTHA TEGHTSOONIAN, and STEVEN E. WEINBERGER Introduction
Dyspnea is perhaps the most common symptom felt by patients with pulmonary or cardiac disease. It frequently accompanies a variety of disorders that involve disturbances in gas exchange,pulmonary circulation, and respiratory mechanics, as well as disturbances in cardiovascular function. Current evidence suggests that there is no unique peripheral site that mediates dyspnea. Rather, receptors in the airways, diaphragm, and intercostal muscles, as well as the sense of respiratory effort, can all be involved (1-7). How these various types of information are relayed and processed by the central nervous system and perceived as breathlessness is still a subject of much debate. Although dyspnea is frequently considered a single sensation (1), the term "breathlessness" may alternatively encompass multiple sensations (8-11). We have previously demonstrated that normal volunteers in whom dyspnea was induced by various stimuli could distinguish different sensations of breathlessness (9). Furthermore, there was an association between these different sensations and the stimuli used to produce breathlessness. These findings led us to propose the existence of multiple types of dyspnea and to speculate that different mechanisms generate these distinguishable sensations. It is not known whether qualitative differences exist between the sensation(s) of breathlessness experienced by patients and those experienced by normal subjects. The present study was designed to test systematically, in a patient population, the hypothesis that breathlessness produced by various disease states encompasses multiple sensations. Furthermore, the goal was to refine and validate the questionnaire and preliminary classification structure developed in the earBer study in normal volunteers (9). Methods Subjects .. group of 53 patients with shortness of
SUMMARY Dyspnea frequently accompanies a variety of cardiopulmonary abnormalities. Although dyspnea Is often considered a single sensation, alternatively It may encompass multiple sensations that are not well explained by a single physiologic mechanism. To Investigate whether breathlessness experienced by patients represents more than one sensation, we studied 53 patients with one of the following seven conditions: pulmonary vascular disease, neuromuscular and chest wall disease, congestive heart failure, pregnancy, Interstitial lung disease, asthma, and chronic obstructive pulmonary disease. Patients were asked to choose descriptions of their sensatlon(s) of breathlessness from a dyspnea questionnaire listing 19descriptors. Cluster analysis was used to Identify natural groupings among the chosen descriptors. We found that patients could distinguish different sensations of breathlessness. In addition, we found an association between certain groups of descriptors and specific conditions producing dyspnea. These findings concur with those In an earlier study In normal volunteers In whom dyspnea was Induced by various stimuli. We conclude that different types of dyspnea exist In patients with a variety of cardiopulmonary abnormalities. Furthermore, different mechanisms may mediate these various sensations. AM REV RESPIR DIS 1990; 142:1009-1014
breath, who were followed in either the pulmonary clinic or hospitalized at Beth Israel Hospital, participated in the study. Patient diagnoses were determined by reviewof medical records. Only those patients whose breathlessness was thought to result from one of seven specific conditions were included. Patients with more than one condition were excluded from the study. The seven patient groups were as follows: six patients with pulmonary vascular disease (four with pulmonary embolic diseaseand two with primary pulmonary hypertension); five with neuromuscular and chest wall disease (one myasthenia gravis, one neurofibromatosis, one poliomyelitis, one kyphoscoliosis, and one amyotrophic lateral sclerosis); five with congestive heart failure (CHF) (one valvular heart disease, two acute pulmonary edema, one chronic CHF, and one dilated cardiomyopathy); five with pregnancy (first and second trimesters); nine with interstitial lung disease (three sarcoidosis and six idiopathic pulmonary fibrosis); seven with asthma; and 16 with chronic obstructive pulmonary disease (COPD). Patients were excluded from the interstitial lung disease group if they had coexistent obstructive abnormalities on pulmonary function testing. Patient characteristics are shown in table 1. Pulmonary function tests were not obtained during the evaluation or management of patients in the congestive heart failure, pulmonary vascular disease, and pregnancy groups, so those groups are not included in table 1. Informed consent was obtained in accordance with the guidelines of the Committee on ClinicalInvestigations, Beth IsraelHospital.
Protocol The questionnaire used for this study wasoriginally developed for our earlier work on normal volunteers with induced dyspnea (9). It consisted of a list of 19 descriptors (table 2), which was compiled from descriptions of breathlessness given by patients with cardiopulmonary disease and by normal volunteers in whom breathlessness was induced in a preliminary study. For each subject, one of five versions of the questionnaire was used; these versions differed in the order in which the descriptors were presented. The investigator administered the questionnaire to the patient by reading the 19descriptors. The patient was asked to indicate which of the descriptors applied to his or her "uncomfortable awareness of breathing." After the selection of all ap-
(Received in original form October 20, 1989 and in revised form June 6, 1990) 1 From the Charles A. Dana Research Institute and Harvard-Thorndike Laboratory of Beth Israel Hospital, the Departments of Medicine, Beth Israel Hospital and Brigham and Women's Hospital, the Department of Medicine, Harvard Medical School, Boston; and the Department of Psychology, Smith College, Northampton, Massachusetts. 2 Supported by Pulmonary Specialized Center of Research Grant No. HL-19170 and Training Grant No. HL-07633 from the National Heart, Lung, and Blood Institute, and by a grant from the Jack and Pauline Freeman Foundation. 3 Correspondence and requests for reprints should be addressed to StevenE. Weinberger, M.D., Pulmonary Unit, Beth Israel Hospital, 330 Brookline Avenue, Boston, MA 02215.
1009
SIMON, SCHWARTZSTEIN, WEISS, FENCL, TEGHTSOONIAN, AND WEINBERGER
1010 TABLE 1 CHARACTERISTICS OF PATIENTS· Age (yl)
FEV1 (L)
FVC (L)
FEV1/FVC
TLC (L)
OLeo
Numbert
(% predicted)
(% predicted)
(%)
(% predicted)
(% predicted)
Neuro
45 ± 18
4/5
0.99 ± 0.41 (39 ± 23)
1.23 ± 0.74 (39 ± 29)
86 ± 14
2.27 ± 1.34* (51 ± 29)
83 ± 10§
Inters
52 ± 22
6/9
1.71 ± 0.60 (60 ± 7)
1.97 ± 0.69 (50 ± 9)
94 ± 13
3.01 ± 0.61 (52 ± 8)
57 ± 22
Asthma
40 ± 13
617
1.69 ± 0.37 (54 ± 16)
3.24 ± 0.72 (77 ± 10)
53 ± 12
COPD
65 ± 10
15/16
0.92 ± 0.46 (39 ± 16)
1.91 ± 0.79 (58 ± 15)
49 ± 12
5.24 ± 1.3911 (98 ± 8)
57 ± 291
Disease States
Definmon of abbreviations: Neuro = neuromuscular and chest wall disease; Inters = interstitial lung disease. • Data presented as mean ± SO. Number of patients with available data on pulmonary functionltotal number of patients in the disease category, except when indicated. Data available in three of fIVe patients. § Data available in two of five patients. I Data available in nine of 16 patients. , Data available in 10 of 16 patients.
t
*
plicable qualifiers, the patient was asked to choose the best three descriptors. The patient was then instructed to grade the intensity of breathlessness by assigning a numerical value using a modified Borg scale (table 3).
Data Analysis A cluster analysis similar to the analysis used in a previous study by Simon and coworkers (9) was performed to evaluate the descriptors that the patients chose from the questionnaire to characterizetheir sensory experienceof dyspnea. If different types ofsensory experiences exist, there are differential associations among descriptors that are reflected in groupings of descriptors. Cluster analysis searches for and identifies these natural groupings or classes. Similarity coefficients form the basis of the analysis.A similarity coefficient for each pair of descriptors (i and J) was calculated by tabulating for each patient, whether he or she chose both i andj or neither i nor j. The value 1 was assigned if there was agreement in the choice of i and j; the value zero was assigned if there wasdisagreement in the choice. TABLE 2 LIST OF DESCRIPTORS
1. 2.
3. 4.
5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16.
17. 18. 19.
My breath does not go in all the way. My breathing requires effort. I feel that I am smothering. I feel a hunger for more air. My breathing is heavy. I cannot take a deep breath. I feel out of breath. My chest feels tight. My breathing requires more work. I feel that I am suffocating. I feel that my breath stops. I am gasping for breath. My chest is constricted. I feel that my breathing is rapid. My breathing is shallow. I feel that I am breathing more. I cannot get enough air. My breath does not go out all the way. My breathing requires more concentration.
From each patient's data, a 19 (descriptor) x 19 (descriptor) matrix was constructed whose entries weremeasures of the similarity between pairs (i, J) of descriptors. The individual similarity matrices for the 57 subjects were then collapsed into a single matrix by averaging similarity indices for each descriptor pair. The problem for data analysis was to find whether the descriptors form one or more groups in which the members of a group are more similar to each other than to descriptors not in the group. Cluster analysis is a useful method with a set of techniques for producing classifications from initially unclassified data. We chose to analyze our similarity data by a modification of the Jardine-Sibson method (12) contained in CLUSTAN (13). This method may be characterized briefly in the following way (14).Each descriptor is representedby a node on a graph. All pairs of nodes that correspond to descriptor pairs having a similarity index over some threshold value q are identified; then there is a search for the largest subsets of descriptors for which all pairs of nodes are connected. These are maximal complete subgraphs. All pairs of maximal complete subgraphs that intersect in at least k nodes are connected. When there are no more connections, the soTABLE 3 MODIFIED BORG SCALE· Number
Verbal Description
10 9 8
Severe
7 Moderate
4 3 2
Sligh!
The selection of particular k and q values is necessarily arbitrary and involvesa subjective assessment by the investigators to' find the "best" combination of values. When k = 2 and q = 0.811, the qualifiers clustered in a way that was most logical and provided the most discriminating information. When k = 2, overlap is allowed; for example, the descriptors "My breathing requires effort" and "My breathing requires more work" each belonged to more than one cluster. Using
~
.30
~ 25 en 20
~
15
r:
o-f----&l....,..'-LL.....L...&jf-&-l.L...LIJ'+-'L-&...L+--............- - + _ O~ ~3 ~4 ~5 ~6 o 0.1 RATIO
1
• Modified from reference 18.
Results
-
Moderately severe
6 5
o
lution is the Jardine-Sibson overlapping classification for these values of q and k. This analysis, unlike most classification techniques, allows a descriptor to belong to more than one cluster; the degree of overlap is controlled by setting the value of k, where k -1 specifies the number of descriptors that can be shared by two clusters. When k = 1, there is no overlap among clusters, and the method reduces to a single-linkage analysis. We allowed k to vary from 1 to 4 because it was possible that descriptors could occur in more than one cluster. The analysis also allows one to specify a threshold value q, which depends on the similarity coefficient, for accepting the inclusion of two descriptors in the same cluster. The analysis was run with q at all available levels from zero to 1.0. The extent to which the clusters emerging from this analysis characterized individual stimuli was evaluated in the following way. For each cluster the number of times the descriptors within it were chosen as the "best three" to describe a particular condition was divided by the product of the number of descriptors within that cluster and the number of patients with that particular condition. A cluster was considered to characterize a particular condition when this ratio was greater than 0.25. The mean (± SD) ratio characterizing the relationships between each cluster and each condition was 0.15 ± 0.14. Although any choice of a cutoff ratio for associating a cluster with a particular condition is arbitrary, the histogram of the ratios has a break around 0.25 (figure 1).
None
Fig. 1. Distribution of number of times each ratio (characterizing the association between a cluster and a disease condition) was chosen. Calculation of the ratio is described in the text.
1011
DISTINGUISHABLE TYPES OF DYSPNEA
these criteria, we found that eight qualifiers stood alone and the remaining 11 descriptors formed six clusters (table 4). Names were given for cluster identification. The first eight clusters listed are those involving single descriptors: "breath does not go in," "cannot take a deep breath," "breath stops," "gasping for breath," "rapid breathing," "breathing more," "breath does not go out," and ''breathing requires more concentration." These descriptors were not closely related to any other descriptors. Clusters 9 through 13 each appeared to group together synonyms: Cluster 9 describes a feeling of suffocating; Cluster 10,a hunger for more air; Cluster 11, heavy breathing; Cluster 12,effortful breathing; Cluster 13, a tight chest. Only Cluster 14 grouped disparate experiences: "breathing requires more work" and "breathing is shallow." The association between clusters and specific conditions is illustrated in table 5. 1\velve clusters were chosen at least once to characterize a particular condition. Clusters "stops" and "more" were not found to be closely associated with any particular condition; that is, their descriptors were infrequently chosen by patients with any ofthe sevenconditions. Clusters "exhalation," "concentration," and "tight" characterize asthma and are not shared with the other six conditions. "Heavy" characterizes both asthma and capo; however, capo also elicits "gasping," "hunger," and "effort," and asthma also elicits "deep." Neuromuscular-ehest wall diseaseand interstitial lung disease share "gasping," "effort," and "shallow" clusters, but in addition, neuromuscular-ehest wall disease elicits "heavy" and "in." "Rapid" is associated with both pulmonary vascular disease and CHF. "Suffocating," "hunger," and "heavy" clusters are also associated with CHF; pulmonary vascular disease also elicits the cluster "in." Dyspnea of pregnancy shares clusters with several of the other conditions. Dyspnea was experienced by patients whose underlying conditions were clinically very different. When we asked subjects to rate the intensity of their breathlessness, the mean intensity ratings for all seven conditions fell between 5 (moderate) and 8 (moderately severe)as shown in figure 2. As table 5 illustrates, the various conditions produced qualitatively different sensory experiences, with no two conditions exactly alike. There was no obvious relationship between the qualitative description of dyspnea and the quantitative intensity of the sensation
TABLE 4 CLUSTERS' Cluster Name
Descriptor
Descriptive Phrase
1.
In
2.
Deep
6
I cannot take a deep breath.
3.
Stops
11
I feel that my breath stops.
4.
Gasping
12
I am gasping for breath.
5.
Rapid
14
I feel that my breathing is rapid.
6.
More
16
I feel that I am breathing more.
7.
Exhalation
18
My breath does not go out all the way.
8.
Concentration
19
My breathing requires more concentration.
9.
Suffocating
3 10
I feel that I am smothering . I feel that I am suffocating .
10.
Hunger
4 7 17
I feel a hunger for more air. I feel out of breath. I cannot get enough air.
11.
Heavy
2 5
My breathing requires effort . My breathing is heavy.
12. Effort
2 7 9
My breathing requires effort . I feel out of breath. My breathing requires more work.
13. Tight
8 13
My chest feels tight. My chest is constricled.
14. Shallow
9 15
My breathing requires more work. My breathing is shallow.
My breath does not go in all the way.
• k = 2 (degree of overlap) and q = 0.811 (similarity level; see text).
TABLE 5 CLUSTERS ASSOCIATED WITH PARTICULAR CONDITIONS Clusters 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14.
In Deep Stops Gasping Rapid More Exhalation Concentration Suffocating Hunger Heavy Effort Tight Shallow
Descriptors
Vase
Neuro
1 6 11 12 14 16 18 19 3, 10 4,7,17 2,5 2, 7, 9 8,13 9, 15
X
X
CHF
Preg
Inters
X
COPD
X
X X
Asthma
X
X X X X
X X
X /X X
X X X
X
X X X
X X
X
DeflnltJon of abbreviations: Vasc - pulmonary vascular disease; Neuro = neuromuscular and chest wall disease; Preg = intersmial lung disease .
nancy ; Inters
10
Fig. 2. Grading of intensity of breathlessness (mean :I: SD) for each patient category. The modified Borg scale used to rate breathlessness is shown in table 3.
Neuro
CHF
Pro;
Inton
DISE,tlSE STATES
= preg-
1012
SIMON, SCHWARTZSTEIN, WEISS, FENCL, TEGHTSOONIAN, AND WEINBERGER
among the patient groups. For example, Cluster 2 ("deep") was shared by the patient groups with the highest (asthma) and the lowest (pregnancy) intensity of breathlessness (table 5 and figure 2). In contrast, the four patient categories with the highest intensity of breathlessness (CHF, interstitial disease, asthma, and COPO) had very different patterns of clusters describing the qualitative experience of breathlessness. Thus it is the quality of the sensation(s), not the quantity or intensity, that appears to be the distinguishing feature among the various dyspnea-producing conditions. Discussion
In this study, we found that patients with breathlessness resulting from a variety of pathophysiologic conditions experience qualitatively different sensations. Their choices of descriptors characterizing the symptom of dyspnea demonstrate a number of interesting features, which we call multiplicity, uniqueness, and sharing. Multiplicity. All seven conditions were characterized by more than one clusterat least two and as many as five. This strongly suggests that breathlessness is not a single sensation but a composite of severalsensations. Thus more than one pathophysiologic mechanism may be involved in the generation of dyspnea, even among patients within a particular diagnostic category. Uniqueness. Each condition was associated with a unique set of clusters. Although one cluster may characterize several conditions, no two conditions shared exactly the same set of clusters. Not only does breathlessness within a condition encompass multiple sensations, but also breathlessness in each condition is a different composite of sensations. For example, patients with congestive heart failure and interstitial lung disease both rated their breathlessness, on the average, as about 7 on a 10-point scale but chose different descriptors to characterize it: breathlessness in congestive heart failure was sensed as rapid and heavy breathing, a hunger for air, and a feeling of suffocating, whereas in interstitial lung disease it was sensed as effortful and shallow breathing and gasping for breath. Furthermore, the association between certain clusters and particular conditions makes sense from a pathophysiologic standpoint: the clusters "rapid," "suffocating," "hunger," and "heavy" were chosen to characterize congestive heart failure, whereas"deep," "exhalation," and ''tight'' wereamong the clusters associated with asthma.
TABLE 6 CLUSTERS IN NORMAL VOLUNTEERS WITH INDUCED DYSPNEA" Cluster Name
Descriptor
Descriptive Phrase
1. Rapid
14
I feel that my breathing is rapid.
2.
Exhalation
18
My breath does not go out all the way.
3. Concentration
19
My breathing requires concentration.
4. Shallow
1 6 15
My breath does not go in all the way. I cannot take a deep breath. My breathing is shallow.
5. Work 6. Suffocating
2 9
My breathing requires effort. My breathing requires more work.
13
I feel that I am smothering. My chest feels tight. I feel that I am suffocating. I feel that my breath stops. My chest is constricted.
7. Hunger
4 17
I feel a hunger for more air. I cannot get enough air.
8. Heavy
5 16
My breathing is heavy. I feel that I am breathing more.
9. Gasping
7 12
I feel out of breath. I am gasping for breath.
3 8 10 11
• Reproduced from reference 9.
Sharing. Whereas some clusters were associated with only one condition (e.g., "exhalation" with asthma and "suffocating" with congestive heart failure), others were shared by two or more conditions (e.g., "heavy" and "effort" were each shared by four conditions). Perhaps dyspnea is mediated by similar receptors or pathways in those conditions when there is sharing of clusters. For instance, J receptors are postulated to cause tachypnea in patients with such disorders as pneumonia, pulmonary emboli, and pulmonary edema (15). Wefound that "rapid" was shared by pulmonary vascular disease and congestive heart failure. These findings concur with those of the earlier study by Simon and coworkers (9) that showed that normal volunteers could distinguish different sensations of breathlessness induced by different respiratory stimuli, including breathholding, CO 2 inhalation, driven targeted ventilation (ventilation targeted to a levelbelow that dictated by chemical drive), resistiveand elastic loads, imposed patterns of breathing (decreased tidal volume and increased functional residual capacity), and exercise. Previous authors (8, 10, 11) have suggested that different types of dyspnea may exist, but this hypothesis had not been systematically studied. Furthermore, the study by Simon and coworkers (9) demonstrated an association between certain groups of descriptors and certain stimuli, again suggesting that the mechanisms mediating the sensations may be different.
These two studies taken in combination allow us to address the question of whether qualitative differences exist between the sensations of breathlessness experienced by patients and those of normal subjects. The list of clusters from the previous study in normal volunteers (9) is reproduced in table 6, and the associations with specific stimuli are shown in table 7. Similarities and differences were noted between the patient groups with dyspnea and the normal volunteers in whom dyspnea was induced. A greater number of clusters emerged in the study on patients than in the study on normal volunteers with induced dyspnea (14versus 9), primarily due to a greater number of single descriptor groups (8 versus 3; tables 4 and 6). The clusters "rapid," "exhalation," and "concentration" remained the same when the groups of descriptors werecompared between the two studies. In healthy volunteers (9), the clusters "suffocating" and "tight" were combined in a larger cluster. Otherwise, the clusters in the two studies were similar, frequently varying by one additional descriptor. Apart from slight differences in the clusters between the two studies, both resistive loading and COPO shared similar descriptor groups; however, several additional clusters characterized COPO (tables 5 and 7). Although one might expect similar sharing of clusters between elastic loading and interstitial disease, characteristic clusters differed. There was some similarity among clusters associated with interstitial disease and
1013
DISTINGUISHABLE TYPES OF DYSPNEA
TABLE 7 CLUSTERS ASSOCIATED WITH PARTICULAR STIMULI* BrHo
Cluster
Descriptors
Rapid Exhalation Concentration Shallow Work Suffocating 7. Hunger 8. Heavy 9. Gasping
14 18 19 1,6, 15 2, 9 3, 8, 10, 11, 13 4,17 5,16 7,12
1. 2. 3. 4. 5. 6.
=
CO2
DTV
Res
Elas
X X
VT
Exer
X X
X
X
X X
X X
FRC
X X
X
X X
=
= driven targeted ventilation; Res = decreased tidal volume; Exer =
imposition of decreased tidal volume (normal subjects instructed to limit tidal volume to 50% of baseline). That there was not complete concurrence between studies, with either the clusters or their relationship to dyspneaproducing conditions, is not surprising. One may expect that qualitative differences exist between breathlessness as a symptom of disease and as a sensation experienced by normal subjects. Furthermore, induction of dyspnea in the laboratory by a variety of stimuli, such as breathholding, CO2 inhalation, and resistive and elastic loading, does not exactly simulate the conditions responsible for dyspnea in patients. Previous authors (8, 16, 17) have suggested that dyspnea induced by exercise or by laboratory stimuli may be qualitatively different from that experienced by patients with underlying cardiopulmonary disorders. However, these possible differences have not been studied systematically before. It is also intriguing that the clusters chosen by patients with asthma and those with COPD were not more alike, considering that airflow obstruction is the functional consequence of both conditions. However, there are pathophysiologic features that also differ between these conditions, and these may be responsible for the differencesin sensation. For example, stimulation of irritant airway receptors may contribute to the sensation(s) experienced by asthmatic patients, whereas it may play a much less important role in patients with COPD. Alternatively, the loss of elastic recoil in many patients with COPD and/or differences in diaphragm position and function may also be responsible for differences in the sensory experience. One problem with the use of cluster analysis (and a limitation of this or any other study using this technique) is that there is no universal agreement about
what constitutes a cluster and about determining the most appropriate number of clusters (14). Subjective assessment in choosing cutoffs, which in practice define the limits of a cluster, is an unavoidable component of this method. Thus the ultimate criterion for making such decisions is the value judgment of the user, and the validity of clustersis judged qualitatively based on subjective evaluation and interpretability (14). Other choices of cutoffs - for k and q and for the ratio used to associate clusters with conditions - would have been possible. Those wechose appeared to make the most sense and provide the most logicalassociations. The present study in patients, taken in conjunction with the previous data obtained in the study of normal volunteers (9), allows us to evaluate further and to revise the questionnaire and the clusters characterizing breathlessness. Our goal was to simplify the questionnaire, deleting descriptors that did not appear to be helpful. Realizing that the utility of specific descriptors was not known when we
Definition of abbreviations: BrHo breathholding; CO2 steady-state hypercapnia; DTV load; Elas • elastic load; FRC increased functional residual capacity; VT exercise. • Reproduced from reference 9.
= resistive
=
started these investigations, we hoped to refine the questionnaire for future use. Based on the clusters found in these two studies, wereanalyzed the data after deleting four descriptors (Numbers 6, 11, 12,and 19from table 2) that did not cluster with other descriptors and were chosen infrequently or had little use in discriminating among sensations. Descriptor 11 ("I feel that my breath stops") was deleted because it was chosen infrequently by breathless patients. In the study of induced breathlessness in normal volunteers, Descriptor 11 was chosen almost exclusively with the stimulus of voluntary limitation of tidal volume, as one would expect. Descriptor 19("My breathing requires more concentration") was deleted because it was chosen both infrequently and in a nondiscriminating way in patients. In the study in normal volunteers, Descriptor 19was chosen primarily during tasks in which the subjects had to target their breathing, again as one would expect. Descriptors 6 ("I cannot take a deep breath") and 12("I am gasping for breath") were deleted for more subjective reasons. They did not cluster with other descriptors in the present study and did not add to the usefulness of revised Clusters 3 ("shallow") or 6 ("hunger"), respectively. In general, the revised clusters proposed in table 8 represented the authors' best attempt to combine the results obtained from both questionnaire studies: the earlier study in normal volunteers and the present study in patients. Because this revised questionnaire was created retrospectively and did involve subjective judgment by the investigators, it must be tested in a prospective fashion. Using this shortened list of 15descrip/
TABl.E 8 REVISED CLUSTERS Cluster Name
Descriptor
Descriptive Phrase
1. Rapid
14
I feel that my breathing is rapid.
2.
Exhalation
18
My breath does not go out all the way.
3.
Shallow
1 15
My breath does not go in all the way. My breathing is shallow.
4.
Work
5.
Suffocating
6.
Hunger
2 9
My breathing requires effort. My breathing requires more work.
3 10
I feel that I am smothering. I feel that I am suffocating.
4 7
17
I feel a hunger for more air. I feel out of breath. I cannot get enough air.
7. Tight
8 13
My chest feels tight. My chest is constricted.
8.
5 16
My breathing is heavy. I feel that I am breathing more.
Heavy
SIMON, SCHWARTZSTEIN, WEISS, FENCL, TEGHTSOONIAN, AND WEINBERGER
1014 TABLE 9
REVISED CLUSTERS ASSOCIATED WITH PARTICULAR CONDITIONS Clusters
1. Rapid 2.
3. 4. 5. 6. 7. 8.
Exhalation Shallow Work Suffocating Hunger Tight Heavy
Descriptors
Vase
14 18 1, 15 2,9
Neuro
X
CHF
Preg
Inters
Asthma
COPD
X X X
3, 10 4,7,17 8, 13 5,16
X X X
X
References
X
1. Burki NK. Dyspnea. Lung 1987; 165:269-77. 2. Altose MD. Dyspnea. Curr Pulmonol 1986; 7:199-226. 3. Killian KJ, Gandevia SC, Summers E, Campbell EJM. Effect of increased lung volume on perception of breathlessness, effort, and tension. J Appl Physiol 1984; 57:686-91. 4. El-Manshawi A, Killian KJ, Summers E, Jones NL. Breathlessness during exercise with and without resistive loading. J Appl Physiol 1986; 61: 896-905. 5. Chonan T, Mulholland MB, Cherniack NS, Altose MD. Effects of voluntary constraining of thoracic displacement during hypercapnia. J Appl Physiol 1987; 63:1822-8. 6. Schwartzstein RM, LaHive K, Pope A, Weinberger SE, Weiss JW. Cold facial stimulation reduces breathlessness induced in normal volunteers. Am Rev Respir Dis 1987; 136:58-61. 7. Schwartzstein RM, Simon PM, WeissJW, Fencl V, Weinberger SE. Breathlessness induced by dissociation between ventilation and chemical drive. Am Rev Respir Dis 1989; 139:1231-7. 8. Altose MD. Mechanisms of dyspnea. In: Montenegro HD, ed. Chronic obstructive pulmonary disease. New York: Churchill Livingstone, 1984; 117-40. 9. Simon PM, Schwartzstein RM, Weiss JW, et al. Distinguishable sensations of breathlessness induced in normal volunteers. Am Rev Respir Dis 1989; 140:1021-7. 10. Campbell EJM, Guz A. Breathlessness. In: Hornbein TF, ed. Regulation of breathing, Part II. New York: Marcel Dekker, 1981; 1181-95. 11. Noble MIM, Eisele JH, Trenchard D, Guz A. Effect of selective peripheral nerve blocks on respiratory sensations. In: Porter R, ed. Breathing: Hering-Breuer Centenary Symposium. London: JA Churchill, 1970; 233-46. 12. Jardine N, Sibson R. The construction of hierarchic and non-hierarchic classifications. Comp J 1968; 11:117-84. 13. WishartD. CLUSTAN, 3rded. Fife, Scotland: Computing Laboratory, Universityof St. Andrews, 1987; 1-250. 14. Everitt B. Cluster analysis. London: Heinemann Educational Books Ltd, 1974. 15. Wasserman K, Casaburi R. Dyspnea: physiological and pathophysiological mechanisms. Annu Rev Med 1988; 39:503-15. 16. Burki NK. Dyspnea. Clin Chest Med 1980; 1:47-55. 17. Campbell EJM, Howell JBL. The sensation of breathlessness. Br Med Bull 1963; 19:36-40. 18. Borg GAV. Psychological bases of perceived exertion. Med Sci Sports Exerc 1982; 14:377-81.
X
X X
X
For definition of abbreviations, see table 5.
tors, wealso propose a revisedlist of eight clusters that incorporate these descriptors. The proposed revisions are shown in table 8. The single-descriptor clusters "deep," "stops," "gasping," and "concentration" were not discriminating enough in the characterization of a particular clinical condition; therefore, they were eliminated in the revision. Clusters"work" and "heavy"from the study of normal volunteers (9) replaced "effort" and "heavy" from the patient study to eliminate overlap; the original clusters from these two studies varied by one descriptor (tables 4 and 6). Clusters "suffocating," "hunger," and ''tight'' from our present study remain the same in the revised list of clusters. An analysis of the associations among clusters and the sevendyspnea-producing conditions was repeated (see METHODS) using the eight revised clusters (table 8). The results are shown in table 9. The characterization of the dyspnea-producing conditions by the revised clusters appears more discriminating than that using the original 14 clusters. Of the eight clusters, four are associated with only one condition: "shallow" with neuromuscular-chest wall disease; "exhalation" and ''tight'' with asthma; and "suffocating" with CHF. The revised cluster "heavy" was not associated with any of the disease categories but is included in this list because it characterized the sensation experienced by normal volunteers in whom breathlessness was induced by exercise. The finding that exercise in normal indi-
these various sensations of breathlessness; additional future studies are needed to elucidate the mechanisms responsible for these different sensations.
viduals is described with a different cluster suggests that these individuals are experiencing a different and distinguishable sensation from any sensation of breathlessness due to disease. We recognize that cultural, socioeconomic, language, and educational backgrounds may influence the results found in a study like this, which is so dependent upon the use of language and the interpretation of subtleties in language. Although there were age differences among patient groups (table 1),there were no obvious language, educational, or socioeconomic differences to explain the results of the study. Nevertheless, wecannot absolutely exclude a possible contribution of these factors to the observed results. In summary, we have demonstrated that different types of dyspnea appear to exist in patients with a variety of cardiopulmonary abnormalities. We have also shown that some qualitative differences exist between the breathlessness experienced by patients with disease states and that experienced by normal subjects in the laboratory. From these data, a number of distinctive clusters can be discerned, with high discriminating value among diseases. Using the revised dyspnea questionnaire and a prospective, blinded approach, we plan to assess whether diagnoses can be predicted according to the pattern of responses chosen by a heterogeneous patient population. We hypothesize that several different mechanisms may be responsible for
PEGGY M. SIMON, RICHARD M. SCHWARTZSTEIN, J. WOODROW WEISS, VLADIMIR FENCL, MARTHA TEGHTSOONIAN, and STEVEN E. WEINBERGER Introduction
Dyspnea is perhaps the most common symptom felt by patients with pulmonary or cardiac disease. It frequently accompanies a variety of disorders that involve disturbances in gas exchange,pulmonary circulation, and respiratory mechanics, as well as disturbances in cardiovascular function. Current evidence suggests that there is no unique peripheral site that mediates dyspnea. Rather, receptors in the airways, diaphragm, and intercostal muscles, as well as the sense of respiratory effort, can all be involved (1-7). How these various types of information are relayed and processed by the central nervous system and perceived as breathlessness is still a subject of much debate. Although dyspnea is frequently considered a single sensation (1), the term "breathlessness" may alternatively encompass multiple sensations (8-11). We have previously demonstrated that normal volunteers in whom dyspnea was induced by various stimuli could distinguish different sensations of breathlessness (9). Furthermore, there was an association between these different sensations and the stimuli used to produce breathlessness. These findings led us to propose the existence of multiple types of dyspnea and to speculate that different mechanisms generate these distinguishable sensations. It is not known whether qualitative differences exist between the sensation(s) of breathlessness experienced by patients and those experienced by normal subjects. The present study was designed to test systematically, in a patient population, the hypothesis that breathlessness produced by various disease states encompasses multiple sensations. Furthermore, the goal was to refine and validate the questionnaire and preliminary classification structure developed in the earBer study in normal volunteers (9). Methods Subjects .. group of 53 patients with shortness of
SUMMARY Dyspnea frequently accompanies a variety of cardiopulmonary abnormalities. Although dyspnea Is often considered a single sensation, alternatively It may encompass multiple sensations that are not well explained by a single physiologic mechanism. To Investigate whether breathlessness experienced by patients represents more than one sensation, we studied 53 patients with one of the following seven conditions: pulmonary vascular disease, neuromuscular and chest wall disease, congestive heart failure, pregnancy, Interstitial lung disease, asthma, and chronic obstructive pulmonary disease. Patients were asked to choose descriptions of their sensatlon(s) of breathlessness from a dyspnea questionnaire listing 19descriptors. Cluster analysis was used to Identify natural groupings among the chosen descriptors. We found that patients could distinguish different sensations of breathlessness. In addition, we found an association between certain groups of descriptors and specific conditions producing dyspnea. These findings concur with those In an earlier study In normal volunteers In whom dyspnea was Induced by various stimuli. We conclude that different types of dyspnea exist In patients with a variety of cardiopulmonary abnormalities. Furthermore, different mechanisms may mediate these various sensations. AM REV RESPIR DIS 1990; 142:1009-1014
breath, who were followed in either the pulmonary clinic or hospitalized at Beth Israel Hospital, participated in the study. Patient diagnoses were determined by reviewof medical records. Only those patients whose breathlessness was thought to result from one of seven specific conditions were included. Patients with more than one condition were excluded from the study. The seven patient groups were as follows: six patients with pulmonary vascular disease (four with pulmonary embolic diseaseand two with primary pulmonary hypertension); five with neuromuscular and chest wall disease (one myasthenia gravis, one neurofibromatosis, one poliomyelitis, one kyphoscoliosis, and one amyotrophic lateral sclerosis); five with congestive heart failure (CHF) (one valvular heart disease, two acute pulmonary edema, one chronic CHF, and one dilated cardiomyopathy); five with pregnancy (first and second trimesters); nine with interstitial lung disease (three sarcoidosis and six idiopathic pulmonary fibrosis); seven with asthma; and 16 with chronic obstructive pulmonary disease (COPD). Patients were excluded from the interstitial lung disease group if they had coexistent obstructive abnormalities on pulmonary function testing. Patient characteristics are shown in table 1. Pulmonary function tests were not obtained during the evaluation or management of patients in the congestive heart failure, pulmonary vascular disease, and pregnancy groups, so those groups are not included in table 1. Informed consent was obtained in accordance with the guidelines of the Committee on ClinicalInvestigations, Beth IsraelHospital.
Protocol The questionnaire used for this study wasoriginally developed for our earlier work on normal volunteers with induced dyspnea (9). It consisted of a list of 19 descriptors (table 2), which was compiled from descriptions of breathlessness given by patients with cardiopulmonary disease and by normal volunteers in whom breathlessness was induced in a preliminary study. For each subject, one of five versions of the questionnaire was used; these versions differed in the order in which the descriptors were presented. The investigator administered the questionnaire to the patient by reading the 19descriptors. The patient was asked to indicate which of the descriptors applied to his or her "uncomfortable awareness of breathing." After the selection of all ap-
(Received in original form October 20, 1989 and in revised form June 6, 1990) 1 From the Charles A. Dana Research Institute and Harvard-Thorndike Laboratory of Beth Israel Hospital, the Departments of Medicine, Beth Israel Hospital and Brigham and Women's Hospital, the Department of Medicine, Harvard Medical School, Boston; and the Department of Psychology, Smith College, Northampton, Massachusetts. 2 Supported by Pulmonary Specialized Center of Research Grant No. HL-19170 and Training Grant No. HL-07633 from the National Heart, Lung, and Blood Institute, and by a grant from the Jack and Pauline Freeman Foundation. 3 Correspondence and requests for reprints should be addressed to StevenE. Weinberger, M.D., Pulmonary Unit, Beth Israel Hospital, 330 Brookline Avenue, Boston, MA 02215.
1009
SIMON, SCHWARTZSTEIN, WEISS, FENCL, TEGHTSOONIAN, AND WEINBERGER
1010 TABLE 1 CHARACTERISTICS OF PATIENTS· Age (yl)
FEV1 (L)
FVC (L)
FEV1/FVC
TLC (L)
OLeo
Numbert
(% predicted)
(% predicted)
(%)
(% predicted)
(% predicted)
Neuro
45 ± 18
4/5
0.99 ± 0.41 (39 ± 23)
1.23 ± 0.74 (39 ± 29)
86 ± 14
2.27 ± 1.34* (51 ± 29)
83 ± 10§
Inters
52 ± 22
6/9
1.71 ± 0.60 (60 ± 7)
1.97 ± 0.69 (50 ± 9)
94 ± 13
3.01 ± 0.61 (52 ± 8)
57 ± 22
Asthma
40 ± 13
617
1.69 ± 0.37 (54 ± 16)
3.24 ± 0.72 (77 ± 10)
53 ± 12
COPD
65 ± 10
15/16
0.92 ± 0.46 (39 ± 16)
1.91 ± 0.79 (58 ± 15)
49 ± 12
5.24 ± 1.3911 (98 ± 8)
57 ± 291
Disease States
Definmon of abbreviations: Neuro = neuromuscular and chest wall disease; Inters = interstitial lung disease. • Data presented as mean ± SO. Number of patients with available data on pulmonary functionltotal number of patients in the disease category, except when indicated. Data available in three of fIVe patients. § Data available in two of five patients. I Data available in nine of 16 patients. , Data available in 10 of 16 patients.
t
*
plicable qualifiers, the patient was asked to choose the best three descriptors. The patient was then instructed to grade the intensity of breathlessness by assigning a numerical value using a modified Borg scale (table 3).
Data Analysis A cluster analysis similar to the analysis used in a previous study by Simon and coworkers (9) was performed to evaluate the descriptors that the patients chose from the questionnaire to characterizetheir sensory experienceof dyspnea. If different types ofsensory experiences exist, there are differential associations among descriptors that are reflected in groupings of descriptors. Cluster analysis searches for and identifies these natural groupings or classes. Similarity coefficients form the basis of the analysis.A similarity coefficient for each pair of descriptors (i and J) was calculated by tabulating for each patient, whether he or she chose both i andj or neither i nor j. The value 1 was assigned if there was agreement in the choice of i and j; the value zero was assigned if there wasdisagreement in the choice. TABLE 2 LIST OF DESCRIPTORS
1. 2.
3. 4.
5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16.
17. 18. 19.
My breath does not go in all the way. My breathing requires effort. I feel that I am smothering. I feel a hunger for more air. My breathing is heavy. I cannot take a deep breath. I feel out of breath. My chest feels tight. My breathing requires more work. I feel that I am suffocating. I feel that my breath stops. I am gasping for breath. My chest is constricted. I feel that my breathing is rapid. My breathing is shallow. I feel that I am breathing more. I cannot get enough air. My breath does not go out all the way. My breathing requires more concentration.
From each patient's data, a 19 (descriptor) x 19 (descriptor) matrix was constructed whose entries weremeasures of the similarity between pairs (i, J) of descriptors. The individual similarity matrices for the 57 subjects were then collapsed into a single matrix by averaging similarity indices for each descriptor pair. The problem for data analysis was to find whether the descriptors form one or more groups in which the members of a group are more similar to each other than to descriptors not in the group. Cluster analysis is a useful method with a set of techniques for producing classifications from initially unclassified data. We chose to analyze our similarity data by a modification of the Jardine-Sibson method (12) contained in CLUSTAN (13). This method may be characterized briefly in the following way (14).Each descriptor is representedby a node on a graph. All pairs of nodes that correspond to descriptor pairs having a similarity index over some threshold value q are identified; then there is a search for the largest subsets of descriptors for which all pairs of nodes are connected. These are maximal complete subgraphs. All pairs of maximal complete subgraphs that intersect in at least k nodes are connected. When there are no more connections, the soTABLE 3 MODIFIED BORG SCALE· Number
Verbal Description
10 9 8
Severe
7 Moderate
4 3 2
Sligh!
The selection of particular k and q values is necessarily arbitrary and involvesa subjective assessment by the investigators to' find the "best" combination of values. When k = 2 and q = 0.811, the qualifiers clustered in a way that was most logical and provided the most discriminating information. When k = 2, overlap is allowed; for example, the descriptors "My breathing requires effort" and "My breathing requires more work" each belonged to more than one cluster. Using
~
.30
~ 25 en 20
~
15
r:
o-f----&l....,..'-LL.....L...&jf-&-l.L...LIJ'+-'L-&...L+--............- - + _ O~ ~3 ~4 ~5 ~6 o 0.1 RATIO
1
• Modified from reference 18.
Results
-
Moderately severe
6 5
o
lution is the Jardine-Sibson overlapping classification for these values of q and k. This analysis, unlike most classification techniques, allows a descriptor to belong to more than one cluster; the degree of overlap is controlled by setting the value of k, where k -1 specifies the number of descriptors that can be shared by two clusters. When k = 1, there is no overlap among clusters, and the method reduces to a single-linkage analysis. We allowed k to vary from 1 to 4 because it was possible that descriptors could occur in more than one cluster. The analysis also allows one to specify a threshold value q, which depends on the similarity coefficient, for accepting the inclusion of two descriptors in the same cluster. The analysis was run with q at all available levels from zero to 1.0. The extent to which the clusters emerging from this analysis characterized individual stimuli was evaluated in the following way. For each cluster the number of times the descriptors within it were chosen as the "best three" to describe a particular condition was divided by the product of the number of descriptors within that cluster and the number of patients with that particular condition. A cluster was considered to characterize a particular condition when this ratio was greater than 0.25. The mean (± SD) ratio characterizing the relationships between each cluster and each condition was 0.15 ± 0.14. Although any choice of a cutoff ratio for associating a cluster with a particular condition is arbitrary, the histogram of the ratios has a break around 0.25 (figure 1).
None
Fig. 1. Distribution of number of times each ratio (characterizing the association between a cluster and a disease condition) was chosen. Calculation of the ratio is described in the text.
1011
DISTINGUISHABLE TYPES OF DYSPNEA
these criteria, we found that eight qualifiers stood alone and the remaining 11 descriptors formed six clusters (table 4). Names were given for cluster identification. The first eight clusters listed are those involving single descriptors: "breath does not go in," "cannot take a deep breath," "breath stops," "gasping for breath," "rapid breathing," "breathing more," "breath does not go out," and ''breathing requires more concentration." These descriptors were not closely related to any other descriptors. Clusters 9 through 13 each appeared to group together synonyms: Cluster 9 describes a feeling of suffocating; Cluster 10,a hunger for more air; Cluster 11, heavy breathing; Cluster 12,effortful breathing; Cluster 13, a tight chest. Only Cluster 14 grouped disparate experiences: "breathing requires more work" and "breathing is shallow." The association between clusters and specific conditions is illustrated in table 5. 1\velve clusters were chosen at least once to characterize a particular condition. Clusters "stops" and "more" were not found to be closely associated with any particular condition; that is, their descriptors were infrequently chosen by patients with any ofthe sevenconditions. Clusters "exhalation," "concentration," and "tight" characterize asthma and are not shared with the other six conditions. "Heavy" characterizes both asthma and capo; however, capo also elicits "gasping," "hunger," and "effort," and asthma also elicits "deep." Neuromuscular-ehest wall diseaseand interstitial lung disease share "gasping," "effort," and "shallow" clusters, but in addition, neuromuscular-ehest wall disease elicits "heavy" and "in." "Rapid" is associated with both pulmonary vascular disease and CHF. "Suffocating," "hunger," and "heavy" clusters are also associated with CHF; pulmonary vascular disease also elicits the cluster "in." Dyspnea of pregnancy shares clusters with several of the other conditions. Dyspnea was experienced by patients whose underlying conditions were clinically very different. When we asked subjects to rate the intensity of their breathlessness, the mean intensity ratings for all seven conditions fell between 5 (moderate) and 8 (moderately severe)as shown in figure 2. As table 5 illustrates, the various conditions produced qualitatively different sensory experiences, with no two conditions exactly alike. There was no obvious relationship between the qualitative description of dyspnea and the quantitative intensity of the sensation
TABLE 4 CLUSTERS' Cluster Name
Descriptor
Descriptive Phrase
1.
In
2.
Deep
6
I cannot take a deep breath.
3.
Stops
11
I feel that my breath stops.
4.
Gasping
12
I am gasping for breath.
5.
Rapid
14
I feel that my breathing is rapid.
6.
More
16
I feel that I am breathing more.
7.
Exhalation
18
My breath does not go out all the way.
8.
Concentration
19
My breathing requires more concentration.
9.
Suffocating
3 10
I feel that I am smothering . I feel that I am suffocating .
10.
Hunger
4 7 17
I feel a hunger for more air. I feel out of breath. I cannot get enough air.
11.
Heavy
2 5
My breathing requires effort . My breathing is heavy.
12. Effort
2 7 9
My breathing requires effort . I feel out of breath. My breathing requires more work.
13. Tight
8 13
My chest feels tight. My chest is constricled.
14. Shallow
9 15
My breathing requires more work. My breathing is shallow.
My breath does not go in all the way.
• k = 2 (degree of overlap) and q = 0.811 (similarity level; see text).
TABLE 5 CLUSTERS ASSOCIATED WITH PARTICULAR CONDITIONS Clusters 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14.
In Deep Stops Gasping Rapid More Exhalation Concentration Suffocating Hunger Heavy Effort Tight Shallow
Descriptors
Vase
Neuro
1 6 11 12 14 16 18 19 3, 10 4,7,17 2,5 2, 7, 9 8,13 9, 15
X
X
CHF
Preg
Inters
X
COPD
X
X X
Asthma
X
X X X X
X X
X /X X
X X X
X
X X X
X X
X
DeflnltJon of abbreviations: Vasc - pulmonary vascular disease; Neuro = neuromuscular and chest wall disease; Preg = intersmial lung disease .
nancy ; Inters
10
Fig. 2. Grading of intensity of breathlessness (mean :I: SD) for each patient category. The modified Borg scale used to rate breathlessness is shown in table 3.
Neuro
CHF
Pro;
Inton
DISE,tlSE STATES
= preg-
1012
SIMON, SCHWARTZSTEIN, WEISS, FENCL, TEGHTSOONIAN, AND WEINBERGER
among the patient groups. For example, Cluster 2 ("deep") was shared by the patient groups with the highest (asthma) and the lowest (pregnancy) intensity of breathlessness (table 5 and figure 2). In contrast, the four patient categories with the highest intensity of breathlessness (CHF, interstitial disease, asthma, and COPO) had very different patterns of clusters describing the qualitative experience of breathlessness. Thus it is the quality of the sensation(s), not the quantity or intensity, that appears to be the distinguishing feature among the various dyspnea-producing conditions. Discussion
In this study, we found that patients with breathlessness resulting from a variety of pathophysiologic conditions experience qualitatively different sensations. Their choices of descriptors characterizing the symptom of dyspnea demonstrate a number of interesting features, which we call multiplicity, uniqueness, and sharing. Multiplicity. All seven conditions were characterized by more than one clusterat least two and as many as five. This strongly suggests that breathlessness is not a single sensation but a composite of severalsensations. Thus more than one pathophysiologic mechanism may be involved in the generation of dyspnea, even among patients within a particular diagnostic category. Uniqueness. Each condition was associated with a unique set of clusters. Although one cluster may characterize several conditions, no two conditions shared exactly the same set of clusters. Not only does breathlessness within a condition encompass multiple sensations, but also breathlessness in each condition is a different composite of sensations. For example, patients with congestive heart failure and interstitial lung disease both rated their breathlessness, on the average, as about 7 on a 10-point scale but chose different descriptors to characterize it: breathlessness in congestive heart failure was sensed as rapid and heavy breathing, a hunger for air, and a feeling of suffocating, whereas in interstitial lung disease it was sensed as effortful and shallow breathing and gasping for breath. Furthermore, the association between certain clusters and particular conditions makes sense from a pathophysiologic standpoint: the clusters "rapid," "suffocating," "hunger," and "heavy" were chosen to characterize congestive heart failure, whereas"deep," "exhalation," and ''tight'' wereamong the clusters associated with asthma.
TABLE 6 CLUSTERS IN NORMAL VOLUNTEERS WITH INDUCED DYSPNEA" Cluster Name
Descriptor
Descriptive Phrase
1. Rapid
14
I feel that my breathing is rapid.
2.
Exhalation
18
My breath does not go out all the way.
3. Concentration
19
My breathing requires concentration.
4. Shallow
1 6 15
My breath does not go in all the way. I cannot take a deep breath. My breathing is shallow.
5. Work 6. Suffocating
2 9
My breathing requires effort. My breathing requires more work.
13
I feel that I am smothering. My chest feels tight. I feel that I am suffocating. I feel that my breath stops. My chest is constricted.
7. Hunger
4 17
I feel a hunger for more air. I cannot get enough air.
8. Heavy
5 16
My breathing is heavy. I feel that I am breathing more.
9. Gasping
7 12
I feel out of breath. I am gasping for breath.
3 8 10 11
• Reproduced from reference 9.
Sharing. Whereas some clusters were associated with only one condition (e.g., "exhalation" with asthma and "suffocating" with congestive heart failure), others were shared by two or more conditions (e.g., "heavy" and "effort" were each shared by four conditions). Perhaps dyspnea is mediated by similar receptors or pathways in those conditions when there is sharing of clusters. For instance, J receptors are postulated to cause tachypnea in patients with such disorders as pneumonia, pulmonary emboli, and pulmonary edema (15). Wefound that "rapid" was shared by pulmonary vascular disease and congestive heart failure. These findings concur with those of the earlier study by Simon and coworkers (9) that showed that normal volunteers could distinguish different sensations of breathlessness induced by different respiratory stimuli, including breathholding, CO 2 inhalation, driven targeted ventilation (ventilation targeted to a levelbelow that dictated by chemical drive), resistiveand elastic loads, imposed patterns of breathing (decreased tidal volume and increased functional residual capacity), and exercise. Previous authors (8, 10, 11) have suggested that different types of dyspnea may exist, but this hypothesis had not been systematically studied. Furthermore, the study by Simon and coworkers (9) demonstrated an association between certain groups of descriptors and certain stimuli, again suggesting that the mechanisms mediating the sensations may be different.
These two studies taken in combination allow us to address the question of whether qualitative differences exist between the sensations of breathlessness experienced by patients and those of normal subjects. The list of clusters from the previous study in normal volunteers (9) is reproduced in table 6, and the associations with specific stimuli are shown in table 7. Similarities and differences were noted between the patient groups with dyspnea and the normal volunteers in whom dyspnea was induced. A greater number of clusters emerged in the study on patients than in the study on normal volunteers with induced dyspnea (14versus 9), primarily due to a greater number of single descriptor groups (8 versus 3; tables 4 and 6). The clusters "rapid," "exhalation," and "concentration" remained the same when the groups of descriptors werecompared between the two studies. In healthy volunteers (9), the clusters "suffocating" and "tight" were combined in a larger cluster. Otherwise, the clusters in the two studies were similar, frequently varying by one additional descriptor. Apart from slight differences in the clusters between the two studies, both resistive loading and COPO shared similar descriptor groups; however, several additional clusters characterized COPO (tables 5 and 7). Although one might expect similar sharing of clusters between elastic loading and interstitial disease, characteristic clusters differed. There was some similarity among clusters associated with interstitial disease and
1013
DISTINGUISHABLE TYPES OF DYSPNEA
TABLE 7 CLUSTERS ASSOCIATED WITH PARTICULAR STIMULI* BrHo
Cluster
Descriptors
Rapid Exhalation Concentration Shallow Work Suffocating 7. Hunger 8. Heavy 9. Gasping
14 18 19 1,6, 15 2, 9 3, 8, 10, 11, 13 4,17 5,16 7,12
1. 2. 3. 4. 5. 6.
=
CO2
DTV
Res
Elas
X X
VT
Exer
X X
X
X
X X
X X
FRC
X X
X
X X
=
= driven targeted ventilation; Res = decreased tidal volume; Exer =
imposition of decreased tidal volume (normal subjects instructed to limit tidal volume to 50% of baseline). That there was not complete concurrence between studies, with either the clusters or their relationship to dyspneaproducing conditions, is not surprising. One may expect that qualitative differences exist between breathlessness as a symptom of disease and as a sensation experienced by normal subjects. Furthermore, induction of dyspnea in the laboratory by a variety of stimuli, such as breathholding, CO2 inhalation, and resistive and elastic loading, does not exactly simulate the conditions responsible for dyspnea in patients. Previous authors (8, 16, 17) have suggested that dyspnea induced by exercise or by laboratory stimuli may be qualitatively different from that experienced by patients with underlying cardiopulmonary disorders. However, these possible differences have not been studied systematically before. It is also intriguing that the clusters chosen by patients with asthma and those with COPD were not more alike, considering that airflow obstruction is the functional consequence of both conditions. However, there are pathophysiologic features that also differ between these conditions, and these may be responsible for the differencesin sensation. For example, stimulation of irritant airway receptors may contribute to the sensation(s) experienced by asthmatic patients, whereas it may play a much less important role in patients with COPD. Alternatively, the loss of elastic recoil in many patients with COPD and/or differences in diaphragm position and function may also be responsible for differences in the sensory experience. One problem with the use of cluster analysis (and a limitation of this or any other study using this technique) is that there is no universal agreement about
what constitutes a cluster and about determining the most appropriate number of clusters (14). Subjective assessment in choosing cutoffs, which in practice define the limits of a cluster, is an unavoidable component of this method. Thus the ultimate criterion for making such decisions is the value judgment of the user, and the validity of clustersis judged qualitatively based on subjective evaluation and interpretability (14). Other choices of cutoffs - for k and q and for the ratio used to associate clusters with conditions - would have been possible. Those wechose appeared to make the most sense and provide the most logicalassociations. The present study in patients, taken in conjunction with the previous data obtained in the study of normal volunteers (9), allows us to evaluate further and to revise the questionnaire and the clusters characterizing breathlessness. Our goal was to simplify the questionnaire, deleting descriptors that did not appear to be helpful. Realizing that the utility of specific descriptors was not known when we
Definition of abbreviations: BrHo breathholding; CO2 steady-state hypercapnia; DTV load; Elas • elastic load; FRC increased functional residual capacity; VT exercise. • Reproduced from reference 9.
= resistive
=
started these investigations, we hoped to refine the questionnaire for future use. Based on the clusters found in these two studies, wereanalyzed the data after deleting four descriptors (Numbers 6, 11, 12,and 19from table 2) that did not cluster with other descriptors and were chosen infrequently or had little use in discriminating among sensations. Descriptor 11 ("I feel that my breath stops") was deleted because it was chosen infrequently by breathless patients. In the study of induced breathlessness in normal volunteers, Descriptor 11 was chosen almost exclusively with the stimulus of voluntary limitation of tidal volume, as one would expect. Descriptor 19("My breathing requires more concentration") was deleted because it was chosen both infrequently and in a nondiscriminating way in patients. In the study in normal volunteers, Descriptor 19was chosen primarily during tasks in which the subjects had to target their breathing, again as one would expect. Descriptors 6 ("I cannot take a deep breath") and 12("I am gasping for breath") were deleted for more subjective reasons. They did not cluster with other descriptors in the present study and did not add to the usefulness of revised Clusters 3 ("shallow") or 6 ("hunger"), respectively. In general, the revised clusters proposed in table 8 represented the authors' best attempt to combine the results obtained from both questionnaire studies: the earlier study in normal volunteers and the present study in patients. Because this revised questionnaire was created retrospectively and did involve subjective judgment by the investigators, it must be tested in a prospective fashion. Using this shortened list of 15descrip/
TABl.E 8 REVISED CLUSTERS Cluster Name
Descriptor
Descriptive Phrase
1. Rapid
14
I feel that my breathing is rapid.
2.
Exhalation
18
My breath does not go out all the way.
3.
Shallow
1 15
My breath does not go in all the way. My breathing is shallow.
4.
Work
5.
Suffocating
6.
Hunger
2 9
My breathing requires effort. My breathing requires more work.
3 10
I feel that I am smothering. I feel that I am suffocating.
4 7
17
I feel a hunger for more air. I feel out of breath. I cannot get enough air.
7. Tight
8 13
My chest feels tight. My chest is constricted.
8.
5 16
My breathing is heavy. I feel that I am breathing more.
Heavy
SIMON, SCHWARTZSTEIN, WEISS, FENCL, TEGHTSOONIAN, AND WEINBERGER
1014 TABLE 9
REVISED CLUSTERS ASSOCIATED WITH PARTICULAR CONDITIONS Clusters
1. Rapid 2.
3. 4. 5. 6. 7. 8.
Exhalation Shallow Work Suffocating Hunger Tight Heavy
Descriptors
Vase
14 18 1, 15 2,9
Neuro
X
CHF
Preg
Inters
Asthma
COPD
X X X
3, 10 4,7,17 8, 13 5,16
X X X
X
References
X
1. Burki NK. Dyspnea. Lung 1987; 165:269-77. 2. Altose MD. Dyspnea. Curr Pulmonol 1986; 7:199-226. 3. Killian KJ, Gandevia SC, Summers E, Campbell EJM. Effect of increased lung volume on perception of breathlessness, effort, and tension. J Appl Physiol 1984; 57:686-91. 4. El-Manshawi A, Killian KJ, Summers E, Jones NL. Breathlessness during exercise with and without resistive loading. J Appl Physiol 1986; 61: 896-905. 5. Chonan T, Mulholland MB, Cherniack NS, Altose MD. Effects of voluntary constraining of thoracic displacement during hypercapnia. J Appl Physiol 1987; 63:1822-8. 6. Schwartzstein RM, LaHive K, Pope A, Weinberger SE, Weiss JW. Cold facial stimulation reduces breathlessness induced in normal volunteers. Am Rev Respir Dis 1987; 136:58-61. 7. Schwartzstein RM, Simon PM, WeissJW, Fencl V, Weinberger SE. Breathlessness induced by dissociation between ventilation and chemical drive. Am Rev Respir Dis 1989; 139:1231-7. 8. Altose MD. Mechanisms of dyspnea. In: Montenegro HD, ed. Chronic obstructive pulmonary disease. New York: Churchill Livingstone, 1984; 117-40. 9. Simon PM, Schwartzstein RM, Weiss JW, et al. Distinguishable sensations of breathlessness induced in normal volunteers. Am Rev Respir Dis 1989; 140:1021-7. 10. Campbell EJM, Guz A. Breathlessness. In: Hornbein TF, ed. Regulation of breathing, Part II. New York: Marcel Dekker, 1981; 1181-95. 11. Noble MIM, Eisele JH, Trenchard D, Guz A. Effect of selective peripheral nerve blocks on respiratory sensations. In: Porter R, ed. Breathing: Hering-Breuer Centenary Symposium. London: JA Churchill, 1970; 233-46. 12. Jardine N, Sibson R. The construction of hierarchic and non-hierarchic classifications. Comp J 1968; 11:117-84. 13. WishartD. CLUSTAN, 3rded. Fife, Scotland: Computing Laboratory, Universityof St. Andrews, 1987; 1-250. 14. Everitt B. Cluster analysis. London: Heinemann Educational Books Ltd, 1974. 15. Wasserman K, Casaburi R. Dyspnea: physiological and pathophysiological mechanisms. Annu Rev Med 1988; 39:503-15. 16. Burki NK. Dyspnea. Clin Chest Med 1980; 1:47-55. 17. Campbell EJM, Howell JBL. The sensation of breathlessness. Br Med Bull 1963; 19:36-40. 18. Borg GAV. Psychological bases of perceived exertion. Med Sci Sports Exerc 1982; 14:377-81.
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For definition of abbreviations, see table 5.
tors, wealso propose a revisedlist of eight clusters that incorporate these descriptors. The proposed revisions are shown in table 8. The single-descriptor clusters "deep," "stops," "gasping," and "concentration" were not discriminating enough in the characterization of a particular clinical condition; therefore, they were eliminated in the revision. Clusters"work" and "heavy"from the study of normal volunteers (9) replaced "effort" and "heavy" from the patient study to eliminate overlap; the original clusters from these two studies varied by one descriptor (tables 4 and 6). Clusters "suffocating," "hunger," and ''tight'' from our present study remain the same in the revised list of clusters. An analysis of the associations among clusters and the sevendyspnea-producing conditions was repeated (see METHODS) using the eight revised clusters (table 8). The results are shown in table 9. The characterization of the dyspnea-producing conditions by the revised clusters appears more discriminating than that using the original 14 clusters. Of the eight clusters, four are associated with only one condition: "shallow" with neuromuscular-chest wall disease; "exhalation" and ''tight'' with asthma; and "suffocating" with CHF. The revised cluster "heavy" was not associated with any of the disease categories but is included in this list because it characterized the sensation experienced by normal volunteers in whom breathlessness was induced by exercise. The finding that exercise in normal indi-
these various sensations of breathlessness; additional future studies are needed to elucidate the mechanisms responsible for these different sensations.
viduals is described with a different cluster suggests that these individuals are experiencing a different and distinguishable sensation from any sensation of breathlessness due to disease. We recognize that cultural, socioeconomic, language, and educational backgrounds may influence the results found in a study like this, which is so dependent upon the use of language and the interpretation of subtleties in language. Although there were age differences among patient groups (table 1),there were no obvious language, educational, or socioeconomic differences to explain the results of the study. Nevertheless, wecannot absolutely exclude a possible contribution of these factors to the observed results. In summary, we have demonstrated that different types of dyspnea appear to exist in patients with a variety of cardiopulmonary abnormalities. We have also shown that some qualitative differences exist between the breathlessness experienced by patients with disease states and that experienced by normal subjects in the laboratory. From these data, a number of distinctive clusters can be discerned, with high discriminating value among diseases. Using the revised dyspnea questionnaire and a prospective, blinded approach, we plan to assess whether diagnoses can be predicted according to the pattern of responses chosen by a heterogeneous patient population. We hypothesize that several different mechanisms may be responsible for
