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Specific immunotherapy in asthma
REVUE FRAN~AISE D'ALLERGOLOGIE ET D'IMMUNOLOGIE CtINIQUE
Specific immunotherapy in asthma M. BOUSQUET
KEY-WORDS: Asthma immunotherapy,
-
Rhinitis
-
Specific
MOTS-CLI~S: Asthme - Rhinite - Immunothtrapie sp~cifique.
Asthma and allergies are a m o n g the most common chronic diseases. The role of inhalant allergens has been clearly demonstrated in the pathogenesis of asthma and other conditions such as allergic rhinitis. Specific immunotherapy (SIT) was introduced for the treatment of asthma in 1918 by Dr Robert A. Cooke and is still controversial. The role of inhalant allergens has been clearly demonstrated in the pathogenesis of asthma [1, 2], but the importance of specific immunotherapy (SIT) in its treatment is still controversial [3,4] despite a recent meta-analysis [5]. Guidelines and indications for i m m u n o t h e r a p y with inhalant allergens have been published within the past years [6-12]. A WHO Position Paper on SIT published in 1998 [13] defines indications for asthma. Asthma is an inflammatory disease in which allergic triggers are often involved (especially in young asthmatics) although they are not always the major cause of inflammation. It is proposed that allergen avoidance, i m m u n o l o g i c a n d antiinflammatory treatments should be associated but
after a long course of the disease, inflammation becomes a major cause of symptorfis suggesting that the immunologic treatment should then be replaced by anti-inflammatory drugs. The natural history of asthma in children is not completely known but a large proportion of children with episodic mild asthma will outgrow their symptoms within several years whereas in those with a more severe form of the disease, asthma will persist later in life. However, allergen avoidance and SIT are the only treatments that may affect the natural course of allergic diseases.
Clinique des Maladies Respiratoires, H6pital Arnaud de Villeneuve, CHU, MontpeUier, (France). Correspondence : Pr. J. Bousquet, Clinique des Maladies Respiratoires, Htpital Arnaud de ViUeneuve, CHU, 371, Avenue Doyen Gaston Giraud, 34295 MONTPELLIER Cedex 5, (France). Interasma Marrakech' 98.
Guidelines or indications for immunotherapy with inhalant allergens have been published within the past years. These reports provide guidelines for a b e t t e r u n d e r s t a n d i n g a n d indications for the use of allergen immunotherapy. However, none of them represent a consensus report of representatives from various parts of the world [8] and some reports address specific issues on one of the target organs in relation to asthma or rhinitis. Therefore, physicians and scientists from
BOUSQUET J. - Specific immunotherapy in asthma. Rev. ft. Aller8ol., 1998, 38 (7S), $269-$271.
© Expansion Scientifique Publications, 1998
• j BOVSQ~T/
$270
various parts of the world convened at the W H O headquarters in Geneva, January 27-29, 1997 to review the science of and indications for allergen immunotherapy [13]. The panel entitled this position staternent <
IMPORTANCE OF STANDARDIZED ALLERGENS
The quality of the allergen vaccine is critical for both diagnosis and treatment. Where possible, standardized vaccines of known potency and shelflife should be used. The most common vaccines used in clinical allergy practice are now available as s t a n d a r d i z e d p r o d u c t s or are p e n d i n g standardization. T h e m e a s u r e m e n t of major allergens for standardization is now a realistic and desirable goal which should be e n c o u r a g e d making it possible to administer a defined amount of allergen during SIT.
MECHANISMS
Recent studies have provided insight into the mechanisms of this form of treatment. Whereas earlier work focused on circulating antibody and effector cells, recent studies suggest that these changes may be secondary to an influence of IT on T cell response to allergen. Most work has e x a m i n e d allergen injection i m m u n o t h e r a p y rather than IT by altemative routes. Mechanisms are likely to be heterogeneous depending on the nature of the allergen, the site of allergy, the route, dose and duration of immunotherapy, the use of different adjuvants and, not least, the genetic status of the host.
Parietaria and mountain cedar as well as house dust mite vaccines (for review see [13]). Fewer studies have found that immunotherapy is effective for patients allergic to cat, Alternaria and Cladosporium. A meta-analysis of clinical trials of allergen immunotherapy demonstrated that it is effective for treatment of asthma [5J. Asthma appears to be a significant risk factor for systemic reactions during SIT, thus, only patients with controlled asthma should receive SIT. Properly controlled, well designed studies employing high dose sublingual-swallow and intranasal immunotherapy provide evidence that this fonn o f t h e r a p y may be a viable alternative to parenteral injection therapy in the treatment of allergic airways disease (Mailing, submitted). F u r t h e r studies n e e d to be d o n e to fully characterize the most appropnate patients, the optimal therapeutic target dose, and the degree of effectiveness as c o m p a r e d to c o n v e n t i o n a l injection immunotherapy.
INDICATIONS
Most patients with allergic asthma present rhinitis or rhino-conjunctivitis, however, the indications for immunotherapy in asthma and rhinitis have been separated in some guidelines and this artificial separation has led to unresolved questions [14,15], possibly because the IgEmediated reaction has not been considered as a multiple organ involvement. It is t h e r e f o r e important to consider immunotherapy based on the allergen sensitization rather than on a particular disease manifestation. Guidelines suggest that SIT should be considered in patients with moderate to severe rhinitis uncontrolled by usual drugs and mild asthma [13].
EFFICACY AND SAFETY
In allergic rhinitis [13], immunotherapy is indicated for subjects: 1. in w h o m a n t i h i s t a m i n e s a n d topical medications insufficiently control symptoms, 2. who do not wish to be on pharmacotherapy, 3. in w h o m p h a r m a c o t h e r a p y produces undesirable side effects, 4. who do not desire to receive a long-term pharmacologic treatment.
Controlled studies demonstrate that allergen i m m u n o t h e r a p y is effective for patients with allergic rhinitis/conjunctivitis and allergic asthma. hnmunotherapy is effective treatment for many pollen species including grasses, ragweed,
In allergic asthma [13] immunotherapy is indicated for subjects: 1. who do not present a severe form of the disease. FEV1 levels should be over 70% from Rev.fr. AllergoL, 1998, 38, 7S
$271
/ SPECIFIC IMMUNOTHERAPY IN ASTHMA •
predicted values after adequate pharmacologic treatment, 2. in whom symptoms are not adequately controlled by allergen avoidance and pharmacologic treatment,
3. who have both nasal and bronchial symptoms, 4. who do not wish to be on long-term pharmacotherapy, 5. in whom p h a r m a c o t h e r a p y produces undesirable side effects.
REFERENCES
1. Platts-Mills T.A., Sporik R.B., Chapman M.D., Heymann P.W. - The role of domestic allergens. Ciba Found Symp. 1997, 206, 173-185. 2. Reid MJ., Moss R.B., Hsu Y.E, KwasnickiJ.M., Commerford T.M., Nelson B.L. - Seasonal asthma in northern California: allergic causes and efficacy of immunotherapy. J. Allergy Clin. Immunol., 1986, 78,590-600. 3. BousquetJ., Hejjaoui A., Michel EB. - Specific immunotherapy in asthma. J. Allergy Clin. ~mmunol., 1990, 86, 292-305. 4. Adkinson N. Jr., Eggleston EA., Eney D., et al. - A controlled trial of i m m u n o t h e r a p y for asthma in allergic children [see comments]. N. Engl.J. Med., 1997, 336, 324-331. 5. Abramson M.J., Puy R.M., Weiner J.M. - Is allergen i m m u n o t h e r a p y effective in asthma? A meta-analysis of randomized controlled trials [see comments]. Am. J. Respir. Oit. Care Med., 1995, 151, 969-974. 6. The current status of allergen immunotherapy (hyposensitisation). Report of a WHO/IUIS working group. Allergy, 1989, 44, 369-379. 7. Current status of allergen immunotherapy. Shortenedwersion of a World Health Organisation/International Union of Immunological Societies Working Group Report. Lancet, 1989,1, 259-261.
mmm
Rev. fr. Allergol., 1998, 38, 7S
8. Mailing H., Weeke B. - Immunotherapy. Position Paper of the European Academy of Allergy and Clinical Immunology. Allergy, 1993, 48, suppl. 14, 9-35. 9. International Consensus Report on Diagnosis and Management of Asthma. International Asthma Management Project. Allergy, 1992, 47, 1-61. 10. Global strategy for asthma management and prevention. WHO/NHLBI workshop report. In: National Institutes of Health, National Heart, Lung and Blood Institute, Publication Number 95-3659, 1995: 11. Frew AJ. - Injection immunotherapy. British Society for Allergy and Clinical Immunology Working Party. BMJ., 1993, 307, 919-923. 12. Nicklas R., Bernstein I., Blessing-Moore J., et al. - Practice parameters for allergen immunotherapy. J. Allergy Clin. kmmunoL, 1996, 6, 1001-1011. 13. BousquetJ., Lockey R. Malling H. - WHO Position Paper. Allergen Immunotherapy: TherapeuticVaccines for allergic diseases. 1998. 14. Norman E - Is there a role for immunotherapy in the treatment of asthma? Yes. Am.J. Respir Crit. Care Med., 1996, 154, 1225-1228. 15. Barnes P. - Is there a role for immunotherapy in the treatment of asthma? No. Am.J. Respir. Crit. Care Med.,1996, 154, 1227-1288.
Specific immunotherapy in asthma M. BOUSQUET
KEY-WORDS: Asthma immunotherapy,
-
Rhinitis
-
Specific
MOTS-CLI~S: Asthme - Rhinite - Immunothtrapie sp~cifique.
Asthma and allergies are a m o n g the most common chronic diseases. The role of inhalant allergens has been clearly demonstrated in the pathogenesis of asthma and other conditions such as allergic rhinitis. Specific immunotherapy (SIT) was introduced for the treatment of asthma in 1918 by Dr Robert A. Cooke and is still controversial. The role of inhalant allergens has been clearly demonstrated in the pathogenesis of asthma [1, 2], but the importance of specific immunotherapy (SIT) in its treatment is still controversial [3,4] despite a recent meta-analysis [5]. Guidelines and indications for i m m u n o t h e r a p y with inhalant allergens have been published within the past years [6-12]. A WHO Position Paper on SIT published in 1998 [13] defines indications for asthma. Asthma is an inflammatory disease in which allergic triggers are often involved (especially in young asthmatics) although they are not always the major cause of inflammation. It is proposed that allergen avoidance, i m m u n o l o g i c a n d antiinflammatory treatments should be associated but
after a long course of the disease, inflammation becomes a major cause of symptorfis suggesting that the immunologic treatment should then be replaced by anti-inflammatory drugs. The natural history of asthma in children is not completely known but a large proportion of children with episodic mild asthma will outgrow their symptoms within several years whereas in those with a more severe form of the disease, asthma will persist later in life. However, allergen avoidance and SIT are the only treatments that may affect the natural course of allergic diseases.
Clinique des Maladies Respiratoires, H6pital Arnaud de Villeneuve, CHU, MontpeUier, (France). Correspondence : Pr. J. Bousquet, Clinique des Maladies Respiratoires, Htpital Arnaud de ViUeneuve, CHU, 371, Avenue Doyen Gaston Giraud, 34295 MONTPELLIER Cedex 5, (France). Interasma Marrakech' 98.
Guidelines or indications for immunotherapy with inhalant allergens have been published within the past years. These reports provide guidelines for a b e t t e r u n d e r s t a n d i n g a n d indications for the use of allergen immunotherapy. However, none of them represent a consensus report of representatives from various parts of the world [8] and some reports address specific issues on one of the target organs in relation to asthma or rhinitis. Therefore, physicians and scientists from
BOUSQUET J. - Specific immunotherapy in asthma. Rev. ft. Aller8ol., 1998, 38 (7S), $269-$271.
© Expansion Scientifique Publications, 1998
• j BOVSQ~T/
$270
various parts of the world convened at the W H O headquarters in Geneva, January 27-29, 1997 to review the science of and indications for allergen immunotherapy [13]. The panel entitled this position staternent <
IMPORTANCE OF STANDARDIZED ALLERGENS
The quality of the allergen vaccine is critical for both diagnosis and treatment. Where possible, standardized vaccines of known potency and shelflife should be used. The most common vaccines used in clinical allergy practice are now available as s t a n d a r d i z e d p r o d u c t s or are p e n d i n g standardization. T h e m e a s u r e m e n t of major allergens for standardization is now a realistic and desirable goal which should be e n c o u r a g e d making it possible to administer a defined amount of allergen during SIT.
MECHANISMS
Recent studies have provided insight into the mechanisms of this form of treatment. Whereas earlier work focused on circulating antibody and effector cells, recent studies suggest that these changes may be secondary to an influence of IT on T cell response to allergen. Most work has e x a m i n e d allergen injection i m m u n o t h e r a p y rather than IT by altemative routes. Mechanisms are likely to be heterogeneous depending on the nature of the allergen, the site of allergy, the route, dose and duration of immunotherapy, the use of different adjuvants and, not least, the genetic status of the host.
Parietaria and mountain cedar as well as house dust mite vaccines (for review see [13]). Fewer studies have found that immunotherapy is effective for patients allergic to cat, Alternaria and Cladosporium. A meta-analysis of clinical trials of allergen immunotherapy demonstrated that it is effective for treatment of asthma [5J. Asthma appears to be a significant risk factor for systemic reactions during SIT, thus, only patients with controlled asthma should receive SIT. Properly controlled, well designed studies employing high dose sublingual-swallow and intranasal immunotherapy provide evidence that this fonn o f t h e r a p y may be a viable alternative to parenteral injection therapy in the treatment of allergic airways disease (Mailing, submitted). F u r t h e r studies n e e d to be d o n e to fully characterize the most appropnate patients, the optimal therapeutic target dose, and the degree of effectiveness as c o m p a r e d to c o n v e n t i o n a l injection immunotherapy.
INDICATIONS
Most patients with allergic asthma present rhinitis or rhino-conjunctivitis, however, the indications for immunotherapy in asthma and rhinitis have been separated in some guidelines and this artificial separation has led to unresolved questions [14,15], possibly because the IgEmediated reaction has not been considered as a multiple organ involvement. It is t h e r e f o r e important to consider immunotherapy based on the allergen sensitization rather than on a particular disease manifestation. Guidelines suggest that SIT should be considered in patients with moderate to severe rhinitis uncontrolled by usual drugs and mild asthma [13].
EFFICACY AND SAFETY
In allergic rhinitis [13], immunotherapy is indicated for subjects: 1. in w h o m a n t i h i s t a m i n e s a n d topical medications insufficiently control symptoms, 2. who do not wish to be on pharmacotherapy, 3. in w h o m p h a r m a c o t h e r a p y produces undesirable side effects, 4. who do not desire to receive a long-term pharmacologic treatment.
Controlled studies demonstrate that allergen i m m u n o t h e r a p y is effective for patients with allergic rhinitis/conjunctivitis and allergic asthma. hnmunotherapy is effective treatment for many pollen species including grasses, ragweed,
In allergic asthma [13] immunotherapy is indicated for subjects: 1. who do not present a severe form of the disease. FEV1 levels should be over 70% from Rev.fr. AllergoL, 1998, 38, 7S
$271
/ SPECIFIC IMMUNOTHERAPY IN ASTHMA •
predicted values after adequate pharmacologic treatment, 2. in whom symptoms are not adequately controlled by allergen avoidance and pharmacologic treatment,
3. who have both nasal and bronchial symptoms, 4. who do not wish to be on long-term pharmacotherapy, 5. in whom p h a r m a c o t h e r a p y produces undesirable side effects.
REFERENCES
1. Platts-Mills T.A., Sporik R.B., Chapman M.D., Heymann P.W. - The role of domestic allergens. Ciba Found Symp. 1997, 206, 173-185. 2. Reid MJ., Moss R.B., Hsu Y.E, KwasnickiJ.M., Commerford T.M., Nelson B.L. - Seasonal asthma in northern California: allergic causes and efficacy of immunotherapy. J. Allergy Clin. Immunol., 1986, 78,590-600. 3. BousquetJ., Hejjaoui A., Michel EB. - Specific immunotherapy in asthma. J. Allergy Clin. ~mmunol., 1990, 86, 292-305. 4. Adkinson N. Jr., Eggleston EA., Eney D., et al. - A controlled trial of i m m u n o t h e r a p y for asthma in allergic children [see comments]. N. Engl.J. Med., 1997, 336, 324-331. 5. Abramson M.J., Puy R.M., Weiner J.M. - Is allergen i m m u n o t h e r a p y effective in asthma? A meta-analysis of randomized controlled trials [see comments]. Am. J. Respir. Oit. Care Med., 1995, 151, 969-974. 6. The current status of allergen immunotherapy (hyposensitisation). Report of a WHO/IUIS working group. Allergy, 1989, 44, 369-379. 7. Current status of allergen immunotherapy. Shortenedwersion of a World Health Organisation/International Union of Immunological Societies Working Group Report. Lancet, 1989,1, 259-261.
mmm
Rev. fr. Allergol., 1998, 38, 7S
8. Mailing H., Weeke B. - Immunotherapy. Position Paper of the European Academy of Allergy and Clinical Immunology. Allergy, 1993, 48, suppl. 14, 9-35. 9. International Consensus Report on Diagnosis and Management of Asthma. International Asthma Management Project. Allergy, 1992, 47, 1-61. 10. Global strategy for asthma management and prevention. WHO/NHLBI workshop report. In: National Institutes of Health, National Heart, Lung and Blood Institute, Publication Number 95-3659, 1995: 11. Frew AJ. - Injection immunotherapy. British Society for Allergy and Clinical Immunology Working Party. BMJ., 1993, 307, 919-923. 12. Nicklas R., Bernstein I., Blessing-Moore J., et al. - Practice parameters for allergen immunotherapy. J. Allergy Clin. kmmunoL, 1996, 6, 1001-1011. 13. BousquetJ., Lockey R. Malling H. - WHO Position Paper. Allergen Immunotherapy: TherapeuticVaccines for allergic diseases. 1998. 14. Norman E - Is there a role for immunotherapy in the treatment of asthma? Yes. Am.J. Respir Crit. Care Med., 1996, 154, 1225-1228. 15. Barnes P. - Is there a role for immunotherapy in the treatment of asthma? No. Am.J. Respir. Crit. Care Med.,1996, 154, 1227-1288.