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Histamine Receptors in the Lung
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-~lilliE CHEST editorials ---=-
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VOLUME 82 I NUMBER 2 I AUGUST, 1982
Histamine Receptors in the Lung The precise pathogenesis of asthma remains elu · sive. It is clearly multifactoral; the patient who wheezes only after a viral infection is different from the wheezing child with a strong family history of asthma, or from the factory worker who develops wheezing after exposure to wood dust. Furthermore, development of effective pharmacotherapy has been multifaceted. The major concentration in recent years has been on more effective use of methylxanthines and steroids, as well as the use of more specific beta-adrenergic agents. Although therapy with antihistamines has long been known to have some effect on airflow obstruction in asthma, antihistamines have not attained a prominent role in our understanding of the pathophysiology or treatment of this disorder. Recent work by a number of investigators has revived interest in the role of antihistamines in asthma. Animal and in vitro human studies have demonstrated the presence of H, and H2 receptors in the lung through the use of specific receptor antagonists. 1•2 In this issue of Chest (see page 143), Schachter and colleagues provide clinical evidence for the presence of H2 receptors in asthmatic patients, confirming recent work by Nathan et al. 3 The exact relationship between pulmonary H, and H2 receptors remains unclear. It appears that H, receptors have a predominant bronchoconstrictive effect, while H2 receptors modulate bronchodilatation. The effect of H, receptors is usually dominant, but the problem is one of balance. That is, there may be a block or deficiency of H 2 receptors in asthmatic patients rather than a greater number of H, receptors. Also, the effective proportion of each receptor probably varies in the same patient in different clinical settings. The work of Schachter and colleagues supports this concept as they were unable to demonstrate H2 mediated bronchodilatation in normal subjects. Animal studies have shown conversion of some H2 receptors to H, receptors during hypersensitization, 4 but it is not yet known if this happens in man. One's receptor status is therefore not likely to be a static defect, but intimately tied to the clinical setting. This interplay must be further defined before
this new information can be applied clinically. Although probably not useful in every asthmatic patient, therapy directed at histamine receptors has great promise for selected individuals. We may be able to exploit the relationship of H, and H2 receptors much as we have for beta, and beta2 adrenergic receptors. For example, H2 agonist aerosols may provide useful bronchodilatation. Specific H 1 antagonists may be useful in certain patients and are already being tested in clinical trials. Whether or not the information provided by Schachter and colleagues leads to new clinically therapeutic agents, this line of investigation will certainly improve our understanding of the pathophysiology of asthma. ]ames R. Myers, M.D. Providence, Rhode Island Providence VA Medical Center, Brown University. REFERENCES
Chand N. Distribution and classification of airway histamine receptors : The physiological significance of histamine H 2 -receptors. Advanced Pharm Chemother 1980; 17:10-31 2 Dunlop LS, Smith AP. The effect of histamine antagonists or antigen-induced contractions of sensitized human bronchus in vitro. Br J Pharmacal 1977; 59 :475 3 Nathan RA, Segall N, Schocket AL. A comparison of the actions of H 1 and H 2 antihistamines on histamine-induced bronchoconstriction and cutaneous wheal response in asthmatic patients.] Allerg Clin Immunol 1981; 67 : 17177 4 Chand N, Altura BM . Distribution of histamine receptor in mammalian airway smooth muscle cells. Cell Bioi 1979; 83 :237 (suppl)
Tuberculosis in Refugees from Southeast Asia Approximately 500,000 refugees from Southeast Asia have been admitted into the United States since 1975. Tuberculosis is prevalent in this population, and as such, has been a source of overrea~ tion in some areas of high resettlement density. Tuberculosis can represent a differential diagnosis CHEST I 82 I 2 I AUGUST, 1982
133
-~lilliE CHEST editorials ---=-
--------"
VOLUME 82 I NUMBER 2 I AUGUST, 1982
Histamine Receptors in the Lung The precise pathogenesis of asthma remains elu · sive. It is clearly multifactoral; the patient who wheezes only after a viral infection is different from the wheezing child with a strong family history of asthma, or from the factory worker who develops wheezing after exposure to wood dust. Furthermore, development of effective pharmacotherapy has been multifaceted. The major concentration in recent years has been on more effective use of methylxanthines and steroids, as well as the use of more specific beta-adrenergic agents. Although therapy with antihistamines has long been known to have some effect on airflow obstruction in asthma, antihistamines have not attained a prominent role in our understanding of the pathophysiology or treatment of this disorder. Recent work by a number of investigators has revived interest in the role of antihistamines in asthma. Animal and in vitro human studies have demonstrated the presence of H, and H2 receptors in the lung through the use of specific receptor antagonists. 1•2 In this issue of Chest (see page 143), Schachter and colleagues provide clinical evidence for the presence of H2 receptors in asthmatic patients, confirming recent work by Nathan et al. 3 The exact relationship between pulmonary H, and H2 receptors remains unclear. It appears that H, receptors have a predominant bronchoconstrictive effect, while H2 receptors modulate bronchodilatation. The effect of H, receptors is usually dominant, but the problem is one of balance. That is, there may be a block or deficiency of H 2 receptors in asthmatic patients rather than a greater number of H, receptors. Also, the effective proportion of each receptor probably varies in the same patient in different clinical settings. The work of Schachter and colleagues supports this concept as they were unable to demonstrate H2 mediated bronchodilatation in normal subjects. Animal studies have shown conversion of some H2 receptors to H, receptors during hypersensitization, 4 but it is not yet known if this happens in man. One's receptor status is therefore not likely to be a static defect, but intimately tied to the clinical setting. This interplay must be further defined before
this new information can be applied clinically. Although probably not useful in every asthmatic patient, therapy directed at histamine receptors has great promise for selected individuals. We may be able to exploit the relationship of H, and H2 receptors much as we have for beta, and beta2 adrenergic receptors. For example, H2 agonist aerosols may provide useful bronchodilatation. Specific H 1 antagonists may be useful in certain patients and are already being tested in clinical trials. Whether or not the information provided by Schachter and colleagues leads to new clinically therapeutic agents, this line of investigation will certainly improve our understanding of the pathophysiology of asthma. ]ames R. Myers, M.D. Providence, Rhode Island Providence VA Medical Center, Brown University. REFERENCES
Chand N. Distribution and classification of airway histamine receptors : The physiological significance of histamine H 2 -receptors. Advanced Pharm Chemother 1980; 17:10-31 2 Dunlop LS, Smith AP. The effect of histamine antagonists or antigen-induced contractions of sensitized human bronchus in vitro. Br J Pharmacal 1977; 59 :475 3 Nathan RA, Segall N, Schocket AL. A comparison of the actions of H 1 and H 2 antihistamines on histamine-induced bronchoconstriction and cutaneous wheal response in asthmatic patients.] Allerg Clin Immunol 1981; 67 : 17177 4 Chand N, Altura BM . Distribution of histamine receptor in mammalian airway smooth muscle cells. Cell Bioi 1979; 83 :237 (suppl)
Tuberculosis in Refugees from Southeast Asia Approximately 500,000 refugees from Southeast Asia have been admitted into the United States since 1975. Tuberculosis is prevalent in this population, and as such, has been a source of overrea~ tion in some areas of high resettlement density. Tuberculosis can represent a differential diagnosis CHEST I 82 I 2 I AUGUST, 1982
133