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WHO POSITION PAPER ON ORAL (SUBLINGUAL) IMMUNOTHERAPY
drug should be given to a child undergoing a severe asthmatic attack and who doesn’t respond to the combination of beta-mimetics and glucocorticoids. We know that aminophylline, the ethylene diamine salt of theophylline, is a weaker bronchodilator than betaadrenoceptor agonists, and it may not increase beta-mimetic-induced bronchodilation. Although its mode of action is uncertain, some possible modes of action include adenosine antagonism, prostaglandin antagonism, release of beta-adrenergic agonists, and enhancement of binding of cAMP to a cAMP-binding protein. There is some evidence that aminophylline has other longer-acting antiasthmatic effects. It can inhibit both immediate and latephase asthmatic responses to allergenic challenge and sometimes reduces bronchial hyperresponsiveness. It also enhances the contractility of the fatigued diaphragm and mucociliary clerens. In order to determine the role of aminophylline in the management of acute asthma, we made a prospective study including 28 children at Hacettepe University Children’s Hospital in 1993.2 We compared the efficacy of aminophylline with corticosteroids in the treatment of moderate asthma exacerbations that were unresponsive to beta-mimetics. The outcome variables were duration of symptoms and hospital stay. Our results suggested that corticosteroids speed the resolution of exacerbations refractory to bronchodilators better than aminophylline. We concluded that aminophylline should not be used in the early treatment of moderate acute asthma attack, but might provide some additive benefit to inhaled beta-agonists in severe exacerbations that didn’t respond to beta-mimetics and glucocorticoids. We believe that attempts to provide a better and faster control of moderateto-severe attacks should continue by compare to the additive therapeutic effects of aminophylline with ipratropium bromide or leukotriene antagonists.
VOLUME 83, NOVEMBER, 1999
NAZAN TOMAC¸, MD Doktor Sami Ulus Children’s Hospital Ankara, Turkey REFERENCES 1. Nuhog˘ lu Y, Dai A, Barlan IB, Bas¸aran M. Efficacy of aminophylline in the treatment of acute asthma exacerbation in children. Ann Allergy Asthma Immunol 1998;80:395–398. 2. Tomac¸ N, Sarac¸lar Y, Tuncer A, Adalıog˘ lu G, Cengizlier R. Efficacy of intravenously administered theophylline in children with moderate asthma attacs. C¸ocuk Sag˘ lıg˘ ı ve Hastalıkları Dergisi 1996;39:423–30.
Response: In her letter, Dr. Tomac¸ shared our conclusion that there is no additive effect of theophylline in the treatment of acute asthma attack in children. On the other hand, it is hard to draw any conclusion regarding the effect of theophylline on acute severe asthma since neither our nor their study1 included children with severe attack. There is certainly a need for better therapeutic modalities in this respect. YONCA NUHG¨LU, MD; IS¸ıL B BARLAN, MD; AND M MU¨JDAT BAS¸ARAN, MD Marma Ra University Hospital Department of Pediatrics Division of Pediatric Allergy/Immunology Istanbul, Turkey REFERENCE 1. Tomac¸ N, Sarac¸lar Y, Tuncer A, et al. Efficacy of intravenously administered theophylline in children with moderate asthma attacks. C ¸ ocuk sag˘ lıg˘ ı ve Hastalıkları Dergisi 1996;39:423– 430.
WHO POSITION PAPER ON ORAL (SUBLINGUAL) IMMUNOTHERAPY To the Editor: This month I was thrilled to receive the World Health Organization report on their most recent Position Paper on immunotherapy. On page 23, paragraph 6.4 states:
“Properly controlled, well-designed studies employing sublingual and intranasal immunotherapy provide evidence that this form of therapy may be a viable alternative to parenteral injection therapy to treat allergic airway diseases.” I published two papers in Annals of Allergy1,2 in 1969 and 1970 on the oral (sublingual) treatment of foods and inhalants. In over 30 years using these techniques, I can be sure from outcome studies that it works very well. In the original WHO Position Paper, enteric-coated capsule oral immunotherapy was not recommended because clinical improvement did not occur until at least 12 months of treatment. Significant adverse reactions occurred related to very high doses. “Sublingualswallow” is differentiated from oral capsule immunotherapy. Properly controlled, well-designed studies showed “clinical efficacy” without significant risk of systemic side effects. This is an important distinction that was not apparent in the summary statement published in the Annals of Allergy, Asthma, and Immunology. The oral (sublingual-swallow) method of immunotherapy has been shown to be effective in 18 controlled studies. DAVID L. MORRIS, MD, ABAI Allergy Associates La Crosse, Wisconsin REFERENCES 1. Morris DL. Use of sublingual antigen in diagnosis and treatment of food allergy. Ann Allergy 1969;27:289 –294. 2. Morris DL. Treatment of respiratory disease with ultra-small doses of antigens. Ann Allergy 1970;28:494 –500. 3. Morris DL. Intradermal testing and sublingual desensitization for nickel. Cutis 1998;61:129 –132.
Response: The WHO Position Paper, “Allergen Immunotherapy: Therapeutic Vaccines for Allergic Diseases” was an international consensus statement on allergen immunotherapy. Many drafts were circulated among the 22 international committee members to assure that a
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VOLUME 83, NOVEMBER, 1999
NAZAN TOMAC¸, MD Doktor Sami Ulus Children’s Hospital Ankara, Turkey REFERENCES 1. Nuhog˘ lu Y, Dai A, Barlan IB, Bas¸aran M. Efficacy of aminophylline in the treatment of acute asthma exacerbation in children. Ann Allergy Asthma Immunol 1998;80:395–398. 2. Tomac¸ N, Sarac¸lar Y, Tuncer A, Adalıog˘ lu G, Cengizlier R. Efficacy of intravenously administered theophylline in children with moderate asthma attacs. C¸ocuk Sag˘ lıg˘ ı ve Hastalıkları Dergisi 1996;39:423–30.
Response: In her letter, Dr. Tomac¸ shared our conclusion that there is no additive effect of theophylline in the treatment of acute asthma attack in children. On the other hand, it is hard to draw any conclusion regarding the effect of theophylline on acute severe asthma since neither our nor their study1 included children with severe attack. There is certainly a need for better therapeutic modalities in this respect. YONCA NUHG¨LU, MD; IS¸ıL B BARLAN, MD; AND M MU¨JDAT BAS¸ARAN, MD Marma Ra University Hospital Department of Pediatrics Division of Pediatric Allergy/Immunology Istanbul, Turkey REFERENCE 1. Tomac¸ N, Sarac¸lar Y, Tuncer A, et al. Efficacy of intravenously administered theophylline in children with moderate asthma attacks. C ¸ ocuk sag˘ lıg˘ ı ve Hastalıkları Dergisi 1996;39:423– 430.
WHO POSITION PAPER ON ORAL (SUBLINGUAL) IMMUNOTHERAPY To the Editor: This month I was thrilled to receive the World Health Organization report on their most recent Position Paper on immunotherapy. On page 23, paragraph 6.4 states:
“Properly controlled, well-designed studies employing sublingual and intranasal immunotherapy provide evidence that this form of therapy may be a viable alternative to parenteral injection therapy to treat allergic airway diseases.” I published two papers in Annals of Allergy1,2 in 1969 and 1970 on the oral (sublingual) treatment of foods and inhalants. In over 30 years using these techniques, I can be sure from outcome studies that it works very well. In the original WHO Position Paper, enteric-coated capsule oral immunotherapy was not recommended because clinical improvement did not occur until at least 12 months of treatment. Significant adverse reactions occurred related to very high doses. “Sublingualswallow” is differentiated from oral capsule immunotherapy. Properly controlled, well-designed studies showed “clinical efficacy” without significant risk of systemic side effects. This is an important distinction that was not apparent in the summary statement published in the Annals of Allergy, Asthma, and Immunology. The oral (sublingual-swallow) method of immunotherapy has been shown to be effective in 18 controlled studies. DAVID L. MORRIS, MD, ABAI Allergy Associates La Crosse, Wisconsin REFERENCES 1. Morris DL. Use of sublingual antigen in diagnosis and treatment of food allergy. Ann Allergy 1969;27:289 –294. 2. Morris DL. Treatment of respiratory disease with ultra-small doses of antigens. Ann Allergy 1970;28:494 –500. 3. Morris DL. Intradermal testing and sublingual desensitization for nickel. Cutis 1998;61:129 –132.
Response: The WHO Position Paper, “Allergen Immunotherapy: Therapeutic Vaccines for Allergic Diseases” was an international consensus statement on allergen immunotherapy. Many drafts were circulated among the 22 international committee members to assure that a
423