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The use of antihistamines in patients with asthma
Position statement The use of antihistamines with asthma
Antihistamines relieve the nasal discharge, sneezing, and itching of allergic rhinitis’; however, they have beenconsideredto be ineffective in the treatment of asthma. This may be because(1) other chemical mediators contribute to the asthmatic response, (2) there are mechanismsthat causebronchial obstruction not responsiveto antihistamines, and (3) it is difficult to reach effective cellular concentrations of antihistamines in the lung with sedatingantihistamineswithout causing adverseeffects.2.3 Nevertheless, antihistamines have been demonstratedto result in modest bronchodilation in patientswith asthma.4“oIn addition they have beendemonstratedto increasethe threshold for bronchoconstriction after challenge with histamine,i’-‘3 exercise,14-16 and, to a lesser extent, allergens,I7 but not methacholine.13.‘xIn many of these studies, the beneficial effects of antihistamines are clearly dose related. Effective treatment of allergic rhinitis to facilitate filtration, warming, and humidification of inspired air appears especially desirable in patients who have asthma.Most patients with asthmatolerate concurrent treatment with antihistamines without obvious adhowever, there are reports of hyverse effects7”9,20; droxyzine, brompheniramine, and diphenhydramine causing airway obstruction in a few patients with asthma.2’,22 A history of breathing difficulty after antihistamine administration should arouse suspicion. However, only pulmonary function testing, before and after the administration of antihistamines to patients who are not receiving bronchodilators, can objectively identify those patients who are subject to this adverse effect, Antihistamine-induced airway obstruction appearsto be a result of bronchoconstriction, rather than mucus retention, since it is reversible after bronchodilator administration. Although antihistamines are not first-line drugs for the treatment of asthma, they should not be withheld from patients with asthma who require treatment for concomitant disorders, such as allergic rhinitis, allergic dermatoses,and urticaria. The traditional labeling for antihistamines includes the statement “antihistamines should not be used to
in patients
treat lower respiratory tract symptoms m&ding asthma.“23The American Academy of Allergy and Immunology recommendsthat this labeling be revised to reflect the current knowledge that antihistamines are not contraindicatedin patients with asthma,unless an adversereaction hasbeenpreviously demonstrated. R. Michael Sly, MD, and James P. Kemp, MD, Chairmen American Academy of Allergy and Immunoio~y Committee on Drugs John A. Andersczn. MD C. Wurren Bierman, MD Milan L. Rrandon, MD Herbert A. Bronstein, MD Earl B. &-own, MD Paul Chervinsky, MD Frederick C. Cogen. MD Robert J. Dockhorn, MD James G. Euston, MD Constantine .I. FaRiers, MD b-a Frnegold, MD Sidney Friedlaender, MD Cl$ton Furukawa, MD Sherwin A. Giliman, MD Leonard S. Girsh, MD Israel Glazer, MD Nathan I. Handebnan. MD Paul J. Hannaway, MD Leslie Hendeies. PharmD William E. Hermance, MD Gregon: 1. Kadler-, MD Roger M. Katz, MD Herbert S. Kaufman, MD AUun Knight, MD Daniet Kordansky, MD Richard A. Krl~rnbo~~~MD James M. Labraico, MD Gilbert Larwf13 MD Robert hi, Land. MD Richard L. London, MD Lloyd D. Mayer, MD William D. McKee, MD Eli 0. Seltzer, MD
482 Committee on drugs
J. ALLERGY
Jerome Miller, MD Shirley Murphy, MD Richard A. Nicklas, MD Irwin Rappaport, MD Michael S. Rowe, MD Diane E. Schuller, MD Allen T. Segal, MD Gail G. Shapiro, MD Sheldon C. Siegel, MD Peter E. Siegler, MD F. Estelle R. Simons, MD Paul L. Sutton, MD Stanley J. SzeJler, MD Andor Szentivanyi, .MD James I. Tennenbaum, MD Donald L. Thruston, MD Raymond E. Tobey, MD Miles Weinberger, MD Michael J. Welch, MD Thomas R. Woehler, MD Minoru Yamate, MD Burton Zweiman, MD REFERENCES 1. SecherC, Kirkegaard J, Borum P, MaanssonA, Osterhammel P, Mygind N. Significance of H, and H* receptorsin the human nose: rationale for topical use of combined antihistaminepreparations. J ALLERGYCLIN IMMIJNOL1982;70:211-18. 2. Michelson AL, Lowell FC. Antihistaminic drugs. N Engl J Med 1958;258:994-1000. 3. Chai H. Antihistamines and asthma. Chest 1980;78:420-2. 4. Heurich A, Sousa-PozaM, Lyons HA. Bronchodilator effects of hydroxyzine hydrochloride. Respiration 1972;29:135-8. 5. Groggins RC, Milner AD, Stokes GM. The bronchodilator effects of chlorpheniramine in childhood asthma. Br J Dis Chest 1979;73:297-301. 6. Popa VT. Effect of an H, blocker, chlorpheniramine, on inhalation tests with histamine and allergen in allergic asthma. Chest 1980;78:442-51. 7. Lewiston NJ, JohnsonS, Sloan E. Effect of antihistamine on
CLIN. IMMUNOL. SEPTEMBER 1988
pulmonary function of children with asthma. J Pediatr 1982; 101:458-60. 8. Holgate ST, Emanuel MB, Howarth PH. Astemizole and other H,-antihistaminic drug treatment of asthma. J ALLERGYCLIN IMMLJNOL 1985;76:375-80. 9. Cookson WOCM. Bronchodilator action of the antihistamine terfenadine. Br J Clin Pharmacol 1987;24:120-1. 10. Popa VT. Bronchodilating activity of an H, blocker, chlorpheniramine. J ALLERGYCLIN IMMUNOL1977;59:54-63. 11. Brik A, Tashkin DP, Gong H Jr, Dauphinee B, Lee E. Effect of cetirizine, a new histamine H, antagonist, on airway dynamicsandresponsivenessto inhaled histaminein mild asthma. J ALLERGYCLIN IMMUNOL1987;80:51-6. 12. Hartmann V, MagnussenH, Holle JP, Schuler E. Modulation of histamine-inducedbronchoconstrictionwith inhaled, oral, and intravenousclemastine in normal and asthmatic subjects. Thorax 1981;36:737-40. 13. Rafferty P, Holgate ST. Terfenadine(Seldane)is a potent and selective histamine H,-receptor antagonist in asthmatic airways. Am Rev Respir Dis 1987;135:181-4. 14. Hardy JPR, Nogrady SG. Effect of an inhaled antihistamine in exercise-inducedasthma. Thorax 1980;35:675-9. 15. Pate1KR. Terfenadine in exercise-inducedasthma. Br Med J 1984;288:1496-7. 16. Clee MD, Ingram CG, Reid PC, RobertsonAS. The effect of astemizole on exercise-induced asthma. Br J Dis Chest 1984;78:180-3. 17. ChanTB, SheltonDM, Eiser NM. Effect of an oral H,-receptor antagonist, terfenadine, on antigen-inducedasthma. Br J Dis Chest 1986;80:375-84. 18. Pate1KR. Effect of terfenadineon methacholine-inducedbronchoconstriction in asthma. J ALLERGYCLIN IMMUNOL1987; 79:355-8. 19. Karlin JM. The use of antihistaminesin asthma. AM Allergy 1972;30:342-7. 20. Karlin JM. The useof antihistaminesin allergic disease.Pediatr Clin North Am 1975;22:157-62. 21. Schuller DE. Adverse effects of brompheniramine on pulmonary function in a subsetof asthmaticchildren. J ALLERGY CLIN IMMlJNOL 1983;72:175-9. 22. Schuller DE. The spectrum of antihistamines adversely affecting pulmonary function in asthmatic children. J ALLERGY CLIN IMMIJNOL1983;71:147. 23. Physicians’ Desk Reference.Oradell, N.J.: Medical Economics Co, Inc, 1986.
Antihistamines relieve the nasal discharge, sneezing, and itching of allergic rhinitis’; however, they have beenconsideredto be ineffective in the treatment of asthma. This may be because(1) other chemical mediators contribute to the asthmatic response, (2) there are mechanismsthat causebronchial obstruction not responsiveto antihistamines, and (3) it is difficult to reach effective cellular concentrations of antihistamines in the lung with sedatingantihistamineswithout causing adverseeffects.2.3 Nevertheless, antihistamines have been demonstratedto result in modest bronchodilation in patientswith asthma.4“oIn addition they have beendemonstratedto increasethe threshold for bronchoconstriction after challenge with histamine,i’-‘3 exercise,14-16 and, to a lesser extent, allergens,I7 but not methacholine.13.‘xIn many of these studies, the beneficial effects of antihistamines are clearly dose related. Effective treatment of allergic rhinitis to facilitate filtration, warming, and humidification of inspired air appears especially desirable in patients who have asthma.Most patients with asthmatolerate concurrent treatment with antihistamines without obvious adhowever, there are reports of hyverse effects7”9,20; droxyzine, brompheniramine, and diphenhydramine causing airway obstruction in a few patients with asthma.2’,22 A history of breathing difficulty after antihistamine administration should arouse suspicion. However, only pulmonary function testing, before and after the administration of antihistamines to patients who are not receiving bronchodilators, can objectively identify those patients who are subject to this adverse effect, Antihistamine-induced airway obstruction appearsto be a result of bronchoconstriction, rather than mucus retention, since it is reversible after bronchodilator administration. Although antihistamines are not first-line drugs for the treatment of asthma, they should not be withheld from patients with asthma who require treatment for concomitant disorders, such as allergic rhinitis, allergic dermatoses,and urticaria. The traditional labeling for antihistamines includes the statement “antihistamines should not be used to
in patients
treat lower respiratory tract symptoms m&ding asthma.“23The American Academy of Allergy and Immunology recommendsthat this labeling be revised to reflect the current knowledge that antihistamines are not contraindicatedin patients with asthma,unless an adversereaction hasbeenpreviously demonstrated. R. Michael Sly, MD, and James P. Kemp, MD, Chairmen American Academy of Allergy and Immunoio~y Committee on Drugs John A. Andersczn. MD C. Wurren Bierman, MD Milan L. Rrandon, MD Herbert A. Bronstein, MD Earl B. &-own, MD Paul Chervinsky, MD Frederick C. Cogen. MD Robert J. Dockhorn, MD James G. Euston, MD Constantine .I. FaRiers, MD b-a Frnegold, MD Sidney Friedlaender, MD Cl$ton Furukawa, MD Sherwin A. Giliman, MD Leonard S. Girsh, MD Israel Glazer, MD Nathan I. Handebnan. MD Paul J. Hannaway, MD Leslie Hendeies. PharmD William E. Hermance, MD Gregon: 1. Kadler-, MD Roger M. Katz, MD Herbert S. Kaufman, MD AUun Knight, MD Daniet Kordansky, MD Richard A. Krl~rnbo~~~MD James M. Labraico, MD Gilbert Larwf13 MD Robert hi, Land. MD Richard L. London, MD Lloyd D. Mayer, MD William D. McKee, MD Eli 0. Seltzer, MD
482 Committee on drugs
J. ALLERGY
Jerome Miller, MD Shirley Murphy, MD Richard A. Nicklas, MD Irwin Rappaport, MD Michael S. Rowe, MD Diane E. Schuller, MD Allen T. Segal, MD Gail G. Shapiro, MD Sheldon C. Siegel, MD Peter E. Siegler, MD F. Estelle R. Simons, MD Paul L. Sutton, MD Stanley J. SzeJler, MD Andor Szentivanyi, .MD James I. Tennenbaum, MD Donald L. Thruston, MD Raymond E. Tobey, MD Miles Weinberger, MD Michael J. Welch, MD Thomas R. Woehler, MD Minoru Yamate, MD Burton Zweiman, MD REFERENCES 1. SecherC, Kirkegaard J, Borum P, MaanssonA, Osterhammel P, Mygind N. Significance of H, and H* receptorsin the human nose: rationale for topical use of combined antihistaminepreparations. J ALLERGYCLIN IMMIJNOL1982;70:211-18. 2. Michelson AL, Lowell FC. Antihistaminic drugs. N Engl J Med 1958;258:994-1000. 3. Chai H. Antihistamines and asthma. Chest 1980;78:420-2. 4. Heurich A, Sousa-PozaM, Lyons HA. Bronchodilator effects of hydroxyzine hydrochloride. Respiration 1972;29:135-8. 5. Groggins RC, Milner AD, Stokes GM. The bronchodilator effects of chlorpheniramine in childhood asthma. Br J Dis Chest 1979;73:297-301. 6. Popa VT. Effect of an H, blocker, chlorpheniramine, on inhalation tests with histamine and allergen in allergic asthma. Chest 1980;78:442-51. 7. Lewiston NJ, JohnsonS, Sloan E. Effect of antihistamine on
CLIN. IMMUNOL. SEPTEMBER 1988
pulmonary function of children with asthma. J Pediatr 1982; 101:458-60. 8. Holgate ST, Emanuel MB, Howarth PH. Astemizole and other H,-antihistaminic drug treatment of asthma. J ALLERGYCLIN IMMLJNOL 1985;76:375-80. 9. Cookson WOCM. Bronchodilator action of the antihistamine terfenadine. Br J Clin Pharmacol 1987;24:120-1. 10. Popa VT. Bronchodilating activity of an H, blocker, chlorpheniramine. J ALLERGYCLIN IMMUNOL1977;59:54-63. 11. Brik A, Tashkin DP, Gong H Jr, Dauphinee B, Lee E. Effect of cetirizine, a new histamine H, antagonist, on airway dynamicsandresponsivenessto inhaled histaminein mild asthma. J ALLERGYCLIN IMMUNOL1987;80:51-6. 12. Hartmann V, MagnussenH, Holle JP, Schuler E. Modulation of histamine-inducedbronchoconstrictionwith inhaled, oral, and intravenousclemastine in normal and asthmatic subjects. Thorax 1981;36:737-40. 13. Rafferty P, Holgate ST. Terfenadine(Seldane)is a potent and selective histamine H,-receptor antagonist in asthmatic airways. Am Rev Respir Dis 1987;135:181-4. 14. Hardy JPR, Nogrady SG. Effect of an inhaled antihistamine in exercise-inducedasthma. Thorax 1980;35:675-9. 15. Pate1KR. Terfenadine in exercise-inducedasthma. Br Med J 1984;288:1496-7. 16. Clee MD, Ingram CG, Reid PC, RobertsonAS. The effect of astemizole on exercise-induced asthma. Br J Dis Chest 1984;78:180-3. 17. ChanTB, SheltonDM, Eiser NM. Effect of an oral H,-receptor antagonist, terfenadine, on antigen-inducedasthma. Br J Dis Chest 1986;80:375-84. 18. Pate1KR. Effect of terfenadineon methacholine-inducedbronchoconstriction in asthma. J ALLERGYCLIN IMMUNOL1987; 79:355-8. 19. Karlin JM. The use of antihistaminesin asthma. AM Allergy 1972;30:342-7. 20. Karlin JM. The useof antihistaminesin allergic disease.Pediatr Clin North Am 1975;22:157-62. 21. Schuller DE. Adverse effects of brompheniramine on pulmonary function in a subsetof asthmaticchildren. J ALLERGY CLIN IMMlJNOL 1983;72:175-9. 22. Schuller DE. The spectrum of antihistamines adversely affecting pulmonary function in asthmatic children. J ALLERGY CLIN IMMIJNOL1983;71:147. 23. Physicians’ Desk Reference.Oradell, N.J.: Medical Economics Co, Inc, 1986.