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whereas predominant scrolls are found in those cells that contain only tryptase (5). A further explanation for the discrepancy between our observations and those of Heard and colleagues is the major difference in the source of bronchial tissue. Although the studies by Heard and colleagues were conducted in apparently "normal" airway tissue, the normality of their sample must be questioned. The tissue from all three lung preparations came from surgical resection specimens from patients with lung cancer. We have recently found that histamine and tryptase concentrations in bronchoalveolar lavage (BAL) are significantly elevated in patients with bronchial carcinoma by comparison with patients investigated for hemoptysis in whom no lung disease was found (mean ± SD = 3.16 ± 0.82 versus 0.82 ± 0.14 ng/ml for histamine, and 4.06 ± 0.32 versus 1.85 ± 0.22 ng/ml for tryptase (Walls AF), unpublished data), suggesting that increased mast cell degranulation is also a feature of cancer. Furthermore, one of us has shown that co-culture of mast cells and tumor cells results in the release of granule proteoglycans (6). A probable history of smoking (possibly with bronchitis), the effects of general anesthesia, acute tissue hypoxia related to arterial clamping prior to resection, and the fact that the biopsy samples were not fixed immediately may provide a further explanation for the observed degranulation changes in their study. We are unable to comment on Dr. Heard's current study on mast cells in asthma because no information is given on the control group and the drugs used for premedication for bronchoscopy. Finally, our comparative ultrastructural study of mast cells in asthmatic and healthy control subjects is in agreement with the overwhelming evidence of elevated mast cell products (tryptase, histamine) (7,8) in BAL and the bronchodilator action of potential and selective Hj-receptor antagonists (9). DJUKANOVIC Wn..LIAM R. ROCHE STEPHEN T. HOLGATE ANDREW F. WALLS PETER H. HOWARTH

to associate particular types of dyspnea with specific stimuli in normal subjects (1) and subjects with specific diseases (2). One type of dyspnea not addressed in either article is that associated with anxiety. Clinically, anxiety-induced "dyspnea" is important because it is not associated with organic disease as are other types of dyspnea, a very important distinction to patients concerned about their health. Yet it has an identifiable etiology and the diagnosis is often helpful therapeutically. Anxious patients often complain that "I cannot get a deep enough breath," a sensation that they describe as shortness of breath and which in turn physicians often label "dyspnea." This and other complaints are quite similar to the authors' descriptors "I cannot take a deep breath" and "My breath does not go in all the way." The first of these descriptors was actually eliminated by the authors as being of little value in discriminating the types of dyspnea in the diseases studied; however, it is strongly suggestive of anxiety-induced dyspnea and should therefore be included among those indicative of clinically important disorders. It might be well to include anxiety-induced dyspnea among disorders studied in the future. DANIEL H. SIMMONS, M.D., PH.D.

University of California at Los Angeles School of Medicine Los Angeles, CA 1. Simon PM, SchwartzsteinRM, Weiss JW, et al. Distinguishable sensations of breathlessness induced in normal volunteers. Am Rev Respir Dis 1989; 140:1021-7.

2. Simon PM, Schwartzstein RM, Weiss JW, et al. Distinguishable types

of dyspnea in patients with shortness of breath. Am Rev Respir Dis 1990; 142:1009-14.

RATKO

Faculty of Medicine University of Southampton Southampton, UK 1. Friedman MM, KalinerM. Ultrastructural changes in human skin mast cellsduring antigen-induced degranulation in vivo.J AllergyClin Immunol 1988; 82:998-1005.

2. Dvorak AM, Mihm MC, Dvorak HF. Degranulation of basophilic leukocytes in allergic contact dermatitis reactions in man. J Immunol 1976; 116:687-95.

3. Dvorak AM, SchulmanES, PetersSP, et al. ImmunoglobulinE-mediated degranulation of isolated human lung mast cells.Lab Invest 1985; 53:45-56. 4. Heard B, Dewar A, Nunn AJ, Kay AB. Heterogeneous ultrastructure of human bronchial mast cells:morphometric subdivisionof celltypes and evidence for a degranulation gradient. Am J RespirCellMolBioi 1990; 3:71-8. 5. Craig SS,SchechterNM, SchwartzLB.Ultrastructuralanalysisof maturing human mast cells in situ. Lab Invest 1989; 60:147-57. 6. Roche WR. Mast cells and tumor angiogenesis. The tumor-related release of an endothelial growth factor from mast cells. Int J Cancer 1985; 36:721-8.

7. Wenze1-SE~ Fowler AA, Schwartz LB. Activation of pulmonary mast cellsby bronchoalveolar allergenchallenge: in vivo releaseof histamine and tryptase in atopic subjects with and without asthma. Am Rev Respir Dis 1988; 137:1002-8.

8. Casale TB, Wood D, Richerson HB, et al. Elevated bronchoalveolar lavagefluid histaminelevels in allergic asthmaticsare associated withmethacholine bronchial hyperresponsiveness. J Clin Invest 1987; 79:1197-203. 9. Rafferty P, Holgate ST. Terfenadine(Seldane) is a potent and selective histamine HI-receptor antagonist in asthmatic airways. Am Rev Respir Dis

From the Authors: We thank Dr. Simmons for his comments. The breathlessness associated with anxiety or emotional factors, like that of breathlessness seen in "normal" subjects who exercise, may exist in the absence of cardiopulmonary pathology. It has been classified clinically by terms such as the "hyperventilation syndrome" or "psychogenic dyspnea." Burns and Howell (1) were among the first to characterize the respiratoryaspects of this syndrome. They emphasized the acute onset of the symptom, the "fluctuating and recurrent episodes of breathlessness," the tendency to describe the discomfort as "difficulty in getting air in," and the "disproportionate" intensity of the breathlessness given the level of lung pathology. Other symptoms associated with this syndrome include dizziness, visual disturbances, paresthesias, and chest pain and may in part be related to acute hypocapnia (2). Our anecdotal experience with patients suffering from the hyperventilation syndrome confirms the observations of Dr. Simmons. These patients often describe sensations such as, "I cannot get enough air," or "I cannot get a deep enough breath." However, we have not yet had the opportunity to study these patients systematically. It is possible these individuals will choose descriptors that fall within the clusters "shallow" (my breath does not go in all the way) or "hunger" (I cannot get enough air) which include phrases similar to "I cannot get a deep enough breath." We agree with Dr. Simmons that it would be interesting to include these patients in future studies and hope to be able to do so. PEGGY M. SIMON, M.D.

J. WOODROW WEISS, M.D.

1987; 135:181-4.

CLASSIFYING TYPES OF DYSPNEA

STEVEN E. WEINBERGER, M.D. RICHARD M. SCHWARTZSTEIN, M.D.

To the Editor:

1. Bums BH, Howell JBL. Disproportionately severe breathlessness in chronic bronchitis. Q J Med 1969; 38:277-94. 2. Lum LC. Hyperventilation: the tip and the iceberg. J Psychosom Res

Simon and colleagues are to be congratulated for their attempts

1975; 19:375-83.

Classifying types of dyspnea.

1201 whereas predominant scrolls are found in those cells that contain only tryptase (5). A further explanation for the discrepancy between our obser...
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