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Catecholamines and the Lung
CHEST VOLUME 69 I NUMBER 5 I MAY, 1976
EDITORIALS
is usually depressed in obstructive pulmonary diseases. In the anesthetized dog, Sackner et al have demonstrated clearly that both aerosol isoproterenol and carbuterol increase tracheal mucous velocity above mean baseline values of 3.7 to 4.6 mm/min. Increased duration of action for three hours was detected only with the larger dose of carbuterol. It is likely that a similar effect occurs in man when reduced mucous velocity due to underlying pulmonary disease is present. As the authors speculate, this action of ,82-adrenergic agonists may result in another antiallergic effect by enhancing removal of antigenic fragments. While ,82-adrenergic drugs are referred to as bronchodilators, the antiallergic effects of inhibition of release of mediators from mast cells and enhanced removal of antigenic fragments may contribute to their therapeutic effectiveness.
Catecholamines and the Lung modifications of catecholamines have led Structural to the introduction of several agents for clinical use with more selective ,82-adrenergic activity and prolonged duration of action. Terbutaline, salbutamol, and carbuterol have the identical side-chain tertiary butyl substituent of the imine nitrogen believed to be responsible for the keyhold fit into the cell membrane receptor. 1 Each differs in the modification of the catechol nucleus responsible for resistance to catechol-0-methyltransferase and increased duration of action. Sulmefanol and fenoterol are compounds under investigation with extensive sidechain modifications that appear to offer even more ,82-adrenergic selectivity than the tertiary butyl substituent. The beneficial effects of catecholamines administered parenterally or locally to patients with reversible pulmonary obstruction (asthmatic bronchitis) are not limited to bronchodilation. It appears to be well established that ,82-adrenergic agonists and methylxanthines are antiallergic in that they inhibit antigen-induced release of histamine, slow-reacting substance of anaphylaxis, and eosinophil chemotactic factor of anaphylaxis from human peripheral leukocytes and pulmonary tissues in vitro. 2 In addition, the study by Sackner et al in this issue (see page 593) demonstrates the stimulatory effect of isoproterenol and carbuterol upon tracheal mucous velocity in intact anesthetized dogs, with the use of a cinematic method utilizing the fiberoptic bronchoscope and Teflon disks. The mucociliary apparatus is responsible for removing particles greater than 2~t to 3~t in diameter which implant on the bronchial tree. A ner-ve mechanism controlling the cilia in man's respiratory tract has not been identified, but the beats are coordinated metachronally, beating successively, one after the other. 3 In man, external measurements of radioactive tracers indicate that transport rates are between 10 and 20 rom/minute, so that 9 percent of the material deposited on the mucosa is physically cleared in less than one hour. 4 This transport system
Michael H. Grieco, M.D. o New York 0
Director, R. A. Cooke Institute of Allergy the Roosevelt Hospital, and Associate Professor of Clini~ Medicine, Columbia University College of Physicians and Surgeons.
Reprint requests: Dr. Grieco, Roosevelt Hospital, 445 West 58th Street, New York Cityl0019 REFERENCES
1 Leifer KN, Wittig HJ: The P2-sympathomimetic aerosols in the treatment of asthma. Ann Allergy 35:69, 1975 2 Orange RP : Immunopharmacological aspects of bronchial • asthma. Clin Allergy 3:521-537, 1973 3 Okeson GC, Divertie MB: Cilia and bronchial clearance: The effects of pharmacologic agents and disease. Mayo Clin Proc 45:361-373, 1970 4 Green GM: In defense of the lung. Am Rev Respir Dis 102:691-703, 1970
Kar+agener's Syndrome: A Pediatric Responsibility
K artagener's syndrome ( KS) is viewed by most
physicians as an interesting but uncommon triad. Since its eponymic dubbing in 1933, 1 more than 400 cases have been reported of the association of situs inversus totalis, sinusitis, and bronchiectasis. In recent times, this journal has seen fit to publish
573
EDITORIALS
is usually depressed in obstructive pulmonary diseases. In the anesthetized dog, Sackner et al have demonstrated clearly that both aerosol isoproterenol and carbuterol increase tracheal mucous velocity above mean baseline values of 3.7 to 4.6 mm/min. Increased duration of action for three hours was detected only with the larger dose of carbuterol. It is likely that a similar effect occurs in man when reduced mucous velocity due to underlying pulmonary disease is present. As the authors speculate, this action of ,82-adrenergic agonists may result in another antiallergic effect by enhancing removal of antigenic fragments. While ,82-adrenergic drugs are referred to as bronchodilators, the antiallergic effects of inhibition of release of mediators from mast cells and enhanced removal of antigenic fragments may contribute to their therapeutic effectiveness.
Catecholamines and the Lung modifications of catecholamines have led Structural to the introduction of several agents for clinical use with more selective ,82-adrenergic activity and prolonged duration of action. Terbutaline, salbutamol, and carbuterol have the identical side-chain tertiary butyl substituent of the imine nitrogen believed to be responsible for the keyhold fit into the cell membrane receptor. 1 Each differs in the modification of the catechol nucleus responsible for resistance to catechol-0-methyltransferase and increased duration of action. Sulmefanol and fenoterol are compounds under investigation with extensive sidechain modifications that appear to offer even more ,82-adrenergic selectivity than the tertiary butyl substituent. The beneficial effects of catecholamines administered parenterally or locally to patients with reversible pulmonary obstruction (asthmatic bronchitis) are not limited to bronchodilation. It appears to be well established that ,82-adrenergic agonists and methylxanthines are antiallergic in that they inhibit antigen-induced release of histamine, slow-reacting substance of anaphylaxis, and eosinophil chemotactic factor of anaphylaxis from human peripheral leukocytes and pulmonary tissues in vitro. 2 In addition, the study by Sackner et al in this issue (see page 593) demonstrates the stimulatory effect of isoproterenol and carbuterol upon tracheal mucous velocity in intact anesthetized dogs, with the use of a cinematic method utilizing the fiberoptic bronchoscope and Teflon disks. The mucociliary apparatus is responsible for removing particles greater than 2~t to 3~t in diameter which implant on the bronchial tree. A ner-ve mechanism controlling the cilia in man's respiratory tract has not been identified, but the beats are coordinated metachronally, beating successively, one after the other. 3 In man, external measurements of radioactive tracers indicate that transport rates are between 10 and 20 rom/minute, so that 9 percent of the material deposited on the mucosa is physically cleared in less than one hour. 4 This transport system
Michael H. Grieco, M.D. o New York 0
Director, R. A. Cooke Institute of Allergy the Roosevelt Hospital, and Associate Professor of Clini~ Medicine, Columbia University College of Physicians and Surgeons.
Reprint requests: Dr. Grieco, Roosevelt Hospital, 445 West 58th Street, New York Cityl0019 REFERENCES
1 Leifer KN, Wittig HJ: The P2-sympathomimetic aerosols in the treatment of asthma. Ann Allergy 35:69, 1975 2 Orange RP : Immunopharmacological aspects of bronchial • asthma. Clin Allergy 3:521-537, 1973 3 Okeson GC, Divertie MB: Cilia and bronchial clearance: The effects of pharmacologic agents and disease. Mayo Clin Proc 45:361-373, 1970 4 Green GM: In defense of the lung. Am Rev Respir Dis 102:691-703, 1970
Kar+agener's Syndrome: A Pediatric Responsibility
K artagener's syndrome ( KS) is viewed by most
physicians as an interesting but uncommon triad. Since its eponymic dubbing in 1933, 1 more than 400 cases have been reported of the association of situs inversus totalis, sinusitis, and bronchiectasis. In recent times, this journal has seen fit to publish
573