Specific Immunotherapy Useful for Childhood Seasonal Allergic Asthma
News Author: Anthony J. Brown, MD
CME Author: Penny Murata, MD
March 10, 2006 — Specific immunotherapy appears to be a safe and effective treatment for children with seasonal allergic asthma sensitized to grass pollen, according to a report in the Journal of Allergy and Clinical Immunology for February.
"We currently have no curative therapy for asthma — specific immunotherapy has the potential for curing allergic asthma," lead author Dr. Graham Roberts told Reuters Health. "This study demonstrates that it is both efficacious and safe within a pediatric population."
Several reports have shown specific immunotherapy to safely reduce the symptoms of allergic rhinoconjunctivitis in children and adults, but its role as treatment for allergic asthma is less clear. Conflicting results have been obtained in adults and there are little data regarding specific immunotherapy for grass pollen–induced asthma in children.
In a randomized, placebo-controlled study, Dr. Roberts, from the Southampton University Hospital NHS Trust in the UK, and colleagues assessed the benefits of specific immunotherapy over two pollen seasons in 35 children with grass pollen–induced asthma. To be eligible for the study, the children had to require at least 200 micrograms of inhaled beclomethasone equivalent per day.
Alutard SQ grass pollen (Phleum pratense) was used for specific immunotherapy and was given in increasing doses, from 10 to 100,000 SQ-U, over eight visits, which took several weeks to complete. Each grass pollen injection was pretreated with topical anesthetic cream and loratadine. The children, who were between the ages of 3 and 16 years, were observed for 60 minutes after each injection.
Histamine was included in the placebo injections to mimic the skin reactions of the active treatment and maintain blinding, the report indicates.
The main outcome measure, the authors note, was the asthma symptom–medication score during the second pollen season. In addition, cutaneous, conjunctival, and bronchial reactivity to the allergen were determined as was the degree of airway inflammation.
Compared with placebo, specific immunotherapy lead to a significant reduction in the asthma symptom–medication score (P = 0.04), the authors state. Moreover, specific immunotherapy appeared to reduce all three types of allergen reactivity (P < 0.05 for all).
By contrast, sputum eosinophil and exhaled nitric oxide testing suggested no difference in airway inflammation between the groups. The authors note that this was despite the fact that patients in the specific immunotherapy group had reduced their steroid dose to half of that in control patients. Thus, specific immunotherapy may have had an antiinflammatory effect.
Specific immunotherapy appeared to be well tolerated with no serious side effects observed and no treatment withdrawals due to adverse events, the investigators point out.
Dr. Roberts emphasized that appropriate patient selection is critical for specific immunotherapy to work.
"Good candidates have summer asthma and often hay fever. They should have a positive skin prick test to the grass pollen allergy and positive serum specific IgE to it," he said. Importantly, the children should have no significant asthma symptoms from other allergens or unstable asthma during the winter when treatment tapering occurs.
The New findings extend those of a recent study in which immunotherapy reduced the symptoms of rhinoconjunctivitis in children and helped prevent progression from hay fever to asthma, the authors note.
J Allergy Clin Immunol. 2006;117:263-268
Learning Objectives for This Educational Activity
Upon completion of this activity, participants will be able to:
Describe the efficacy of specific immunotherapy in the treatment of children with grass pollen–induced asthma.
Identify adverse effects of specific immunotherapy in the treatment of children with grass pollen-induced asthma.
Clinical Context
Immunotherapy has been reported to be effective in the treatment of adults with allergic asthma. In the August 12, 1999, issue of The New England Journal of Medicine, Durham and colleagues found that in adults with allergic rhinitis, specific immunotherapy leads to decreased need for corticosteroid therapy. However, in the July 1993 issue of the Journal of Allergy Clinical Immunology, Reid and colleagues presented concerns about the adverse effects of specific immunotherapy in patients with asthma. A study of children with seasonal allergies, reported by Moller and colleagues in the February 2002 Journal of Allergy Clinical Immunology, found that immunotherapy decreases rhinoconjunctivitis symptoms and the development of asthma.
The current study is a randomized, double-blind, placebo-controlled trial to evaluate (1) the efficacy of grass pollen–specific immunotherapy using measures of asthma symptoms; cutaneous, conjunctival, and bronchial allergen reactivity; lung function; and airway inflammation (exhaled nitric oxide, sputum eosinophilia) and (2) the safety of specific immunotherapy in children with asthma induced by grass pollen (P. Pratense) for 2 grass pollen seasons.
Study Highlights
39 children aged 3 to 16 years with the following criteria were enrolled: grass pollen–induced asthma requiring at least 200 μg of inhaled beclomethasone daily; positive skin prick, specific IgE, and conjunctival provocation test results. After 4 patients withdrew or were excluded, data for 35 subjects were analyzed during 2 grass pollen seasons.
Exclusion criteria included previous grass pollen immunotherapy, perennial asthma requiring inhaled corticosteroids, perennial allergic rhinitis, or sensitization to household pet.
18 children were randomized to receive specific immunotherapy with P. pratense pollen preparation for 8 visits for standard updosing and approximately 6-week intervals for maintenance injections; 17 children received histamine-containing placebo. All received pretreatment with loratidine and topical anesthetic cream.
The groups were similar in sex, mean age, weight, height, severity of summer asthma symptoms, and median daily inhaled beclomethasone dose during previous summer. There appeared to be differences in ethnicity, severity of summer rhinoconjunctivitis symptoms, atopic dermatitis, and symptoms on exposure to tree pollen, house dust mites, and animal hair and dander (P values were not reported).
Subjects completed symptom-medication diary during 2 grass pollen seasons: asthma symptoms of wheezing, coughing, shortness of breath, tight chest, and breathing problems while exercising were rated on scale of 0 (no symptoms) to 3 (severe symptoms). Rescue medications (with assigned scores) were allowed for hay fever and asthma symptoms.
Primary outcome data for 1783 (86%) of possible 2065 days during second pollen season showed significant reduction in asthma symptom–medication score for specific immunotherapy group vs placebo group (median, 0.5 vs 1.0; P = .04). There was no significant difference in corticosteroid or inhaled bronchodilator use between the 2 groups.
Skin prick, conjunctival provocation, and bronchial provocation tests with increasing concentrations of P. pratense allergen at baseline and after pollen season showed significant increase in allergen required to cause reaction in the specific immunotherapy vs placebo group.
Lung function measured by portable spirometers twice daily in 13 specific immunotherapy subjects and 16 placebo subjects showed normal baseline function and forced expiratory volume in 1 second was less than 85% of predicted value for one third of second season for both groups.
Exhaled nitric oxide measured every 4 weeks during second season in 9 specific immunotherapy subjects and 14 placebo subjects during second season showed no difference in highest value for both groups.
Induced sputum samples from 6 specific immunotherapy subjects and 10 placebo subjects during peak of second season showed no difference in number of eosinophils per gram of sputum.
Of 54 adverse events, 34 were reported by 13 (72%) of specific immunotherapy subjects and 20 were reported by 7 (41%) of placebo subjects. Of 24 local adverse effects (including pruritis, pain, or swelling), 13 occurred in specific immunotherapy group and 11 in placebo group. Of 30 systemic events (mostly eczema, urticaria, or rhinoconjunctivitis), 21 occurred in specific immunotherapy group and 9 in placebo group. Of 7 mild pulmonary events, 4 occurred in specific immunotherapy group and 3 in placebo group; 2 occurred more than 1-hour postinjection. No subjects withdrew due to adverse events.
2 (57%) of 35 subjects withdrew prior to second season: 1 due to needle phobia and 1 due to family reasons.
Pearls for Practice
In children with grass pollen–induced asthma, specific immunotherapy improves the asthma symptom–medication score and allergen sensitivity in the skin, eyes, and lungs; specific immunotherapy shows no effect on lung function or allergic airway inflammation.
In children with grass pollen–induced asthma treated with specific immunotherapy, adverse events included local, systemic, and pulmonary effects, none of which required discontinuation of treatment.
Saludos Cordiales
Dr. José Manuel Ferrer Guerra
CME Author: Penny Murata, MD
March 10, 2006 — Specific immunotherapy appears to be a safe and effective treatment for children with seasonal allergic asthma sensitized to grass pollen, according to a report in the Journal of Allergy and Clinical Immunology for February.
"We currently have no curative therapy for asthma — specific immunotherapy has the potential for curing allergic asthma," lead author Dr. Graham Roberts told Reuters Health. "This study demonstrates that it is both efficacious and safe within a pediatric population."
Several reports have shown specific immunotherapy to safely reduce the symptoms of allergic rhinoconjunctivitis in children and adults, but its role as treatment for allergic asthma is less clear. Conflicting results have been obtained in adults and there are little data regarding specific immunotherapy for grass pollen–induced asthma in children.
In a randomized, placebo-controlled study, Dr. Roberts, from the Southampton University Hospital NHS Trust in the UK, and colleagues assessed the benefits of specific immunotherapy over two pollen seasons in 35 children with grass pollen–induced asthma. To be eligible for the study, the children had to require at least 200 micrograms of inhaled beclomethasone equivalent per day.
Alutard SQ grass pollen (Phleum pratense) was used for specific immunotherapy and was given in increasing doses, from 10 to 100,000 SQ-U, over eight visits, which took several weeks to complete. Each grass pollen injection was pretreated with topical anesthetic cream and loratadine. The children, who were between the ages of 3 and 16 years, were observed for 60 minutes after each injection.
Histamine was included in the placebo injections to mimic the skin reactions of the active treatment and maintain blinding, the report indicates.
The main outcome measure, the authors note, was the asthma symptom–medication score during the second pollen season. In addition, cutaneous, conjunctival, and bronchial reactivity to the allergen were determined as was the degree of airway inflammation.
Compared with placebo, specific immunotherapy lead to a significant reduction in the asthma symptom–medication score (P = 0.04), the authors state. Moreover, specific immunotherapy appeared to reduce all three types of allergen reactivity (P < 0.05 for all).
By contrast, sputum eosinophil and exhaled nitric oxide testing suggested no difference in airway inflammation between the groups. The authors note that this was despite the fact that patients in the specific immunotherapy group had reduced their steroid dose to half of that in control patients. Thus, specific immunotherapy may have had an antiinflammatory effect.
Specific immunotherapy appeared to be well tolerated with no serious side effects observed and no treatment withdrawals due to adverse events, the investigators point out.
Dr. Roberts emphasized that appropriate patient selection is critical for specific immunotherapy to work.
"Good candidates have summer asthma and often hay fever. They should have a positive skin prick test to the grass pollen allergy and positive serum specific IgE to it," he said. Importantly, the children should have no significant asthma symptoms from other allergens or unstable asthma during the winter when treatment tapering occurs.
The New findings extend those of a recent study in which immunotherapy reduced the symptoms of rhinoconjunctivitis in children and helped prevent progression from hay fever to asthma, the authors note.
J Allergy Clin Immunol. 2006;117:263-268
Learning Objectives for This Educational Activity
Upon completion of this activity, participants will be able to:
Describe the efficacy of specific immunotherapy in the treatment of children with grass pollen–induced asthma.
Identify adverse effects of specific immunotherapy in the treatment of children with grass pollen-induced asthma.
Clinical Context
Immunotherapy has been reported to be effective in the treatment of adults with allergic asthma. In the August 12, 1999, issue of The New England Journal of Medicine, Durham and colleagues found that in adults with allergic rhinitis, specific immunotherapy leads to decreased need for corticosteroid therapy. However, in the July 1993 issue of the Journal of Allergy Clinical Immunology, Reid and colleagues presented concerns about the adverse effects of specific immunotherapy in patients with asthma. A study of children with seasonal allergies, reported by Moller and colleagues in the February 2002 Journal of Allergy Clinical Immunology, found that immunotherapy decreases rhinoconjunctivitis symptoms and the development of asthma.
The current study is a randomized, double-blind, placebo-controlled trial to evaluate (1) the efficacy of grass pollen–specific immunotherapy using measures of asthma symptoms; cutaneous, conjunctival, and bronchial allergen reactivity; lung function; and airway inflammation (exhaled nitric oxide, sputum eosinophilia) and (2) the safety of specific immunotherapy in children with asthma induced by grass pollen (P. Pratense) for 2 grass pollen seasons.
Study Highlights
39 children aged 3 to 16 years with the following criteria were enrolled: grass pollen–induced asthma requiring at least 200 μg of inhaled beclomethasone daily; positive skin prick, specific IgE, and conjunctival provocation test results. After 4 patients withdrew or were excluded, data for 35 subjects were analyzed during 2 grass pollen seasons.
Exclusion criteria included previous grass pollen immunotherapy, perennial asthma requiring inhaled corticosteroids, perennial allergic rhinitis, or sensitization to household pet.
18 children were randomized to receive specific immunotherapy with P. pratense pollen preparation for 8 visits for standard updosing and approximately 6-week intervals for maintenance injections; 17 children received histamine-containing placebo. All received pretreatment with loratidine and topical anesthetic cream.
The groups were similar in sex, mean age, weight, height, severity of summer asthma symptoms, and median daily inhaled beclomethasone dose during previous summer. There appeared to be differences in ethnicity, severity of summer rhinoconjunctivitis symptoms, atopic dermatitis, and symptoms on exposure to tree pollen, house dust mites, and animal hair and dander (P values were not reported).
Subjects completed symptom-medication diary during 2 grass pollen seasons: asthma symptoms of wheezing, coughing, shortness of breath, tight chest, and breathing problems while exercising were rated on scale of 0 (no symptoms) to 3 (severe symptoms). Rescue medications (with assigned scores) were allowed for hay fever and asthma symptoms.
Primary outcome data for 1783 (86%) of possible 2065 days during second pollen season showed significant reduction in asthma symptom–medication score for specific immunotherapy group vs placebo group (median, 0.5 vs 1.0; P = .04). There was no significant difference in corticosteroid or inhaled bronchodilator use between the 2 groups.
Skin prick, conjunctival provocation, and bronchial provocation tests with increasing concentrations of P. pratense allergen at baseline and after pollen season showed significant increase in allergen required to cause reaction in the specific immunotherapy vs placebo group.
Lung function measured by portable spirometers twice daily in 13 specific immunotherapy subjects and 16 placebo subjects showed normal baseline function and forced expiratory volume in 1 second was less than 85% of predicted value for one third of second season for both groups.
Exhaled nitric oxide measured every 4 weeks during second season in 9 specific immunotherapy subjects and 14 placebo subjects during second season showed no difference in highest value for both groups.
Induced sputum samples from 6 specific immunotherapy subjects and 10 placebo subjects during peak of second season showed no difference in number of eosinophils per gram of sputum.
Of 54 adverse events, 34 were reported by 13 (72%) of specific immunotherapy subjects and 20 were reported by 7 (41%) of placebo subjects. Of 24 local adverse effects (including pruritis, pain, or swelling), 13 occurred in specific immunotherapy group and 11 in placebo group. Of 30 systemic events (mostly eczema, urticaria, or rhinoconjunctivitis), 21 occurred in specific immunotherapy group and 9 in placebo group. Of 7 mild pulmonary events, 4 occurred in specific immunotherapy group and 3 in placebo group; 2 occurred more than 1-hour postinjection. No subjects withdrew due to adverse events.
2 (57%) of 35 subjects withdrew prior to second season: 1 due to needle phobia and 1 due to family reasons.
Pearls for Practice
In children with grass pollen–induced asthma, specific immunotherapy improves the asthma symptom–medication score and allergen sensitivity in the skin, eyes, and lungs; specific immunotherapy shows no effect on lung function or allergic airway inflammation.
In children with grass pollen–induced asthma treated with specific immunotherapy, adverse events included local, systemic, and pulmonary effects, none of which required discontinuation of treatment.
Saludos Cordiales
Dr. José Manuel Ferrer Guerra
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