Untitled

Sublingual Immunotherapy to House Dust
Mite in Pediatric Patients With
Allergic Rhinitis and Asthma:
A Retrospective Analysis of Clinical Course
Over a 3-Year Follow-up Period
Y Nuhoglu,1 SS Ozumut,2 C Ozdemir,1 M Ozdemir, C Nuhoglu,3 M Erguven2 1 Department of Pediatric Allergy, SB Istanbul Goztepe Training and Research Hospital, Istanbul, Turkey2 Department of Pediatrics, SB Istanbul Goztepe Training and Research Hospital, Istanbul, Turkey3 Department of Pediatrics, Haydarpasa Numune Training and Research Hospital Istanbul, Turkey ■ Abstract
Background and objective: Specifi c allergen immunotherapy is believed to be the only treatment able to change the natural history of allergic airway diseases. Sublingual immunotherapy (SLIT) is especially preferred because of its easy application and safety. The aim of this study was to describe the effect of SLIT in pediatric patients who have allergic airway disease.
Methods: Children with asthma and rhinitis who were allergic to house dust mite were evaluated. The effect on clinical course of 3 years of SLIT with 50 % Dermatophagoides pteronyssinus and 50 % Dermatophagoides farinae in a standardized extract was assessed retrospectively. Results: The records of 39 patients (23 boys, 16 girls) were studied. The mean (± SD) age for starting SLIT was 8.8 ± 2.3 years. The mean number of acute asthma attacks at the onset of the disease was 8.18 ± 3.05. The mean number of attacks after 3 years of SLIT was 0.44 ± 0.79. There was a statistically signifi cant difference in the number of acute asthma attacks before and after therapy (P < .001). Complete clinical remission of asthma was recorded in 37 (95%) patients. Similarly, complete clinical remission of allergic rhinitis was recorded in 32 (82%) patients.
Conclusion: This retrospective study shows that SLIT is effective in children who have allergic airway disease which cannot be controlled effectively with allergen avoidance measures only.
Key words: Sublingual immunotherapy. Asthma. Children.
■ Resumen
Antecedentes y objetivo: Se cree que la inmunoterapia específi ca es el único tratamiento que puede cambiar la historia natural de las enfermedades respiratorias de origen alérgico. La inmunoterapia sublingual (ITSL) se prefi ere especialmente debido a la facilidad de administración y seguridad. El objetivo del estudio fue describir el efecto de la ITSL en pacientes pediátricos con enfermedad de las vías respiratorias de origen alérgico.
Métodos: Se evaluó a niños con asma y rinitis, alérgicos al ácaro del polvo doméstico. Se valoró retrospectivamente el efecto en la trayec-toria clínica de 3 años de ITSL con un 50 % de Dermatophagoides pteronyssinus y un 50 % de Dermatophagoides farinae en un extracto estandarizado. Resultados: Se estudiaron las historias clínicas de 39 pacientes (23 niños y 16 niñas). La media de edad (± SD) para empezar la ITSL fue de 8,8 ± 2,3 años. El promedio de ataques de asma agudos al inicio de la enfermedad era de 8,18 ± 3,05. El promedio de ataques a los tres años de tratamiento con ITSL fue de 0,44 ± 0,79. La diferencia en la cantidad de ataques de asma agudos antes y después de este tratamiento fue estadísticamente signifi cativa (P < 0,001). En 37 de los pacientes (95 %) se registró la remisión clínica completa del asma. De forma similar, en 32 de los pacientes (82 %) se registró la remisión clínica completa de la rinitis alérgica.
Conclusión: Este estudio retrospectivo demuestra que la ITSL es efectiva para el tratamiento pediátrico de enfermedades respiratorias de origen alérgico que no pueden controlarse únicamente con la aplicación de medidas para evitar la exposición a los alérgenos.
Palabras clave: Inmunoterapia sublingual. Asma. Niños.
J Investig Allergol Clin Immunol 2007; Vol. 17(6): 375-378 Sublingual Immunotherapy to Mites in Children Introduction
are described. The patients visit the outpatient clinic every 3 months and a pediatric allergist records the number of acute Allergic airway disease has been effectively controlled in asthma attacks lasting more than 24 hours and resolved with many pediatric patients with inhaled and nasal corticosteroids bronchodilator treatment, as noted in the patientsʼ diary cards. during recent decades. Disease activity usually starts again If the patient is having an acute attack at the time of the routine after the cessation of these drugs, however, if the underlying visit, as detected during the pediatric allergistʼs examination, allergy is not controlled. The reaction to inhalant allergens can that is also recorded in the fi le. After at least 6 months of using only be achieved with appropriate allergen avoidance measures anti-infl ammatory medication and allergen avoidance, if a and specifi c immunotherapy, which is believed to be the only patientʼs symptoms are not completely controlled, pulmonary treatment method that can change the natural history of the function tests are performed and SLIT is prescribed for patients disease. In this respect; subcutaneous immunotherapy has been who have a forced expiratory volume in 1 second (FEV ) widely applied and has been shown to be effective in reducing above 70 %. The patients receive SLIT for 3 years. At the symptoms [1]. However, uncommon but severe and nearly fatal same time, anti-infl ammatory medication is also prescribed systemic reactions have begun to worry physicians [2] and and the dose is arranged according to clinical progress as noted repeated injections have led to serious complaints especially in visits once in every 3 months with the pediatric allergist. among children [3]. Thus, alternative routes of immunotherapy When the patient does not have any acute asthma attacks or have been proposed. Among them, sublingual immunotherapy allergic rhinitis symptoms during the previous year, the anti- (SLIT), by which oral tolerance is induced at mucosal surfaces, infl ammatory medication is stopped. When the patient still has been gaining the confi dence of practitioners because of does not have any symptoms for at least 6 months with no its good safety profi le and its effectiveness in the context of anti-infl ammatory medication, they are accepted as being in We report clinical outcomes in a group of pediatric patients The main outcome measures for this study of patients with allergic rhinitis and asthma who had been treated with undergoing those procedures were the number of acute asthma attacks that had been recorded before and after SLIT and the rate of complete remission.
A standardized extract of house dust mites (50% D pteronyssinus/50 % D farinae) (Stallergenes) was used. Twenty drops of the solution (100 index of reactivity [IR]) Children who attended the outpatient clinic with allergic was placed under the tongue for 3 minutes on 3 alternate mild-to-moderate asthma and allergic rhinitis were studied retrospectively. The asthma diagnosis was made according The comparison of the number of acute asthma attacks to American Thoracic Society criteria [5], on the basis of before and after SLIT was made with the Wilcoxon signed- recurrent cough, wheeze, and chest tightness that reversed spontaneously or with bronchodilator therapy. The severity was reported according to the guidelines of the Global Initiative for Asthma [6]. Allergic rhinitis was diagnosed if the patient had at least 1 rhinitis symptom (stuffi ness, rhinorrhea, sneezing) for more than 1 hour a day on most of the days of the The records of 39 patients (23 boys and 16 girls) were week. The patients were monosensitized to house dust mites studied. The mean (± SD) age at the onset of the fi rst signs and (Dermatophagoides pteronyssinus and Dermatophagoides farinae). A skin prick test was performed on each patient with the most common aeroallergen solutions (Stallergenes SA, Antony Cedex, France). A multi-test applicator (Hollister- Stier Laboratories, Spokane, Washington, USA) was used during the procedure. A wheal diameter of more than 3 mm In our outpatient allergy clinic the number of acute asthma attacks reported by the patient is recorded at the time of diagnostic interview, before any anti-infl ammatory medication is started. An attack is defi ned as cough, wheeze, and dyspnea that persisted for more than 24 hours and that was resolved with bronchodilator treatment. If the severity of asthma is mild, moderate or severe and persistent the patients are treated with inhaled budesonide and nasal budesonide for their allergic rhinitis if present. The inhaled budesonide dose is 200 μg twice daily and the nasal budesonide dose is 50 μg for each nostril twice daily. At the same time allergen avoidance measures (no Mean ( ± SD) number of acute asthma attacks per year before and after sublingual immunotherapy (SLIT) carpets in the home and use of allergy control barrier bedding) J Investig Allergol Clin Immunol 2006; Vol. 17(6): 375-378 symptoms of allergic airway disease was 3.6 ± 2.5 years and the the good clinical outcomes, even though those investigators mean age at the time of diagnosis was 8.1 ± 2.1 years. The mean achieved signifi cant clinical progress only after 4 years. We age upon beginning SLIT was 8.8 ± 2.3 years. The severity of observed a signifi cant difference with respect to symptoms asthma was assessed as mild-to-moderate persistent.
after 3 years of therapy. Our study analyzed pediatric patients, The mean number of acute asthma attacks reported for however, and the age factor might have been the reason for the previous year at the time of diagnosis (with no anti- the discrepancy, as response to immunotherapy is stated to be infl ammatory medication) was 8.18 ± 3.05. The mean number better in younger patients in whom allergen-specifi c memory of attacks after 3 years of SLIT (with no anti-infl ammatory type 2 helper T cells are not well established and are more medication) was 0.44 ± 0.79. There was a statistically signifi cant difference in the number of acute asthma attacks The long-term effect of SLIT was investigated in an open, before and after therapy (P < .0001) (fi gure). Complete clinical controlled, observational study which included 60 mite- remission of asthma was recorded in 37 (95 %) patients. sensitive asthmatic children aged from 3 to 17 years old [8]. Similarly, complete clinical remission of allergic rhinitis was SLIT was given for 4 to 5 years and the children were followed recorded in 32 (82 %) patients. No signifi cant side effects for 10 years, at which time there was a signifi cant reduction in the prevalence of asthma, use of asthma medication and a signifi cant increase in peak expiratory fl ow rate in the SLIT group compared with the control group. Although our study Discussion
was not placebo controlled and the duration was shorter, the results with respect to asthma remission seem to be similar. In this study we observed a signifi cant effect of SLIT on One other study by Bahceciler and colleagues [15] enrolled pediatric patients with allergic rhinitis and mild-to-moderate 15 children with allergic rhinitis and asthma due to house dust asthma with ongoing symptoms despite adequate avoidance mites in a placebo controlled manner. The investigators used measures and adequate anti-infl ammatory therapy. These low-dose SLIT (100 IR) for 6 months and found a signifi cant results are consistent with evidence that SLIT is an effective reduction in the daily asthma score in the therapy group in method of desensitization in allergic rhinitis (level of evidence comparison with the placebo group. In our study the same 1A) [7] and asthma (level of evidence, 1B) [8]). It is especially dose of allergen was used with longer treatment duration. The preferred in children with immunoglobulin (Ig) E mediated comparison of clinical status was made within the same group, diseases because of its good safety profi le [9]. However, yet both studies report symptom improvement after therapy.
a meta-analysis published by the Cochrane Library on the Recently, Lue and colleagues [16] studied the effect of clinical effi cacy of SLIT in patients with rhinitis included 22 SLIT to D pteronyssinus and D farinae at a dose of 300 IR double-blind, placebo-controlled clinical trials and a total of (maximum cumulative dose, 41 824 IR) for 6 months in a group 979 patients failed to fi nd a clear relation between the duration of 36 pediatric patients in a double-blind, placebo controlled of treatment and clinical effi cacy due to insuffi cient data [10]. fashion. After treatment they observed signifi cant differences Similarly, the doses of allergen used in different SLIT studies in the nighttime asthma symptoms and specifi c IgG4 levels. was found to range from 3 to 5 times to 375 times the effective The authors had analyzed FEV both before and after therapy cumulative dose of subcutaneous immunotherapy when this and observed signifi cant improvement. Similarly, Niu and feature was analyzed by Canonica and Passalacqua [11] and colleagues [17] analyzed the effect of high-dose SLIT in no clear relation between the dose administered and clinical pediatric patients sensitized to house dust mites in a double-blind effi cacy was reported in that meta-analysis. We are reporting fashion. Symptom scores and lung function test parameters were the data of patients treated with a SLIT dose of 100 IR after compared. The authors reported a signifi cant difference with respect to both measures after SLIT treatment. Lung function A double-blind, placebo-controlled study conducted by tests were carried out only once before treatment in our study, Bousquet and colleagues [12] in adults with perennial asthma however. The assessment of clinical response in our study relied sensitive to house dust mites, in which SLIT with 300 IR was solely on the symptoms recorded on the patientsʼ diary cards and prescribed for 24 months, found that inhaled corticosteroid during the pediatric allergistʼs physical examination.
use was signifi cantly less after therapy. That study in adults In conclusion, this retrospective study with a 3-year was of a shorter duration than our study, yet our clinically follow-up of children with allergic airway disease treated with good results are similar to the good progress and less use of SLIT shows that this treatment could be an effective method inhaled corticosteroids they reported. A retrospective analysis for children whose asthma and rhinitis cannot be controlled of a group of adult patients with allergic rhinitis and bronchial hyperreactivity who had been treated with SLIT to house dust mites was reported by Marogna et al [13]. The investigators had divided the patients into 4 groups according to the duration of References
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