IgE and Allergen Immunotherapy in Allergic Children
Aim. Allergen immunotherapy (AIT) is indicated in IgE-mediated respiratory allergy. Recently, it has been reported that serum-specific IgE (sIgE) levels >10 kU/l may predict AIT efficacy in adults with allergic rhinitis. The aim of the present preliminary study was to investigate whether this cut-off could also be associated with perception of effective AIT in children with allergic asthma and/or rhinitis due to house dust mites (HDM).
Methods. A total of 31 allergic children (17 males; mean age of 12.5 years) with levels of serum sIgE to HDM >10 kU/l were evaluated. Eight allergic children (five males; mean age of 13.4 years) with levels of serum sIgE to HDM <10 kU/l were considered as control. All patients were treated with sublingual immunotherapy for 3 years with HDM allergen extract. Children's perception of AIT efficacy was assessed by visual analog scale (VAS), considering both symptom severity and drug use. Responder patients were defined with >6 VAS. Severity of nasal symptoms was assessed by nasal VAS, and asthma control was evaluated by asthma control test; both were considered before and after AIT.
Results. All children (but one) with sIgE >10 kU/l perceived AIT efficacy, whereas only one child with sIgE <10 kU/l perceived AIT benefit (p < 0.001). There was a strong relationship between perception of AIT efficacy by VAS and serum sIgE levels (r = 0.615; p < 0.001). Also, nasal VAS and asthma control tests significantly improved only in children with sIgE > 10 kU/l (p < 0.001 for both).
Conclusion. Allergen-sIgE assessment before AIT prescription might represent a useful tool to individuate potential responders.
Allergic disorders are characterized by an IgE-mediated reaction as a consequence of the exposure to a specific allergen. Thus, allergen-specific IgE (sIgE) production may be considered the hallmark of allergy, such as a sine qua non factor. At present, allergen immunotherapy (AIT) is the unique causal treatment for respiratory allergy. Indeed, successful AIT can induce a physiologic immune tolerance toward the causal allergen.
There is evidence, supported by many double-blind placebo-controlled trials and meta-analysis studies, that AIT is effective and safe. AIT indications and contraindications are clearly defined by relevant position papers. In particular, AIT is indicated in well-documented IgE-mediated respiratory allergy. However, no biomarker has yet been validated to be a good predictor of clinical response to AIT. Previously, changes in some cytokines were associated with successful AIT (including IL-4, IL-10, IL-12, IFN-γ and TGF-β), but they have not been clearly established markers for AIT response or for defining AIT responders. On the other hand, it was reported some years ago that the serum-sIgE/total IgE ratio may predict the clinical response to AIT in monosensitized patients to grass, Parietariajudaica, Oleaeuropea and house dust mites. In fact, high ratios (>16.2) were associated with an effective response. However, another study showed conflicting findings, such as patients with low serum-sIgE/total IgE ratio (<0.19) reporting better improvement than patients with high ratio, even though only at the second treatment year.
Conversely, a recent real-life experience reported that high serum-sIgE levels could predict response to AIT in 75 adults with allergic rhinitis (AR). AIT effectiveness was calculated considering both clinical improvement and drug use (prescribed on demand) reduction. Patients globally evaluated both parameters, reporting their perception by visual anaglog scale (VAS). After 3-year sublingual immunotherapy (SLIT), 63 patients (84%) were AIT responders. Serum-sIgE levels were significantly higher (p < 0.0001) in responder patients (median: 33.15 kU/l) than in nonresponder patients (median: 6.12 kU/l). More recently, a retrospective study was performed to confirm these preliminary findings. The study was conducted on 174 allergic patients treated with SLIT for 3 years. Responder patients were defined on the basis of a (VAS both for symptom and drug assessment) reduction of at least 30% compared with the baseline value. Response to SLIT was considered effective in 145 (83.3%) patients. A cut-off value (such as ≥9.74 kU/l) for serum-sIgE was able to discriminate effective from ineffective AIT, with 96.4% sensitivity, 100% specificity and 0.987 area under the receiver operating characteristic curve. Thus, this study concluded that sIgE level assessment before starting AIT might predict its efficacy in adult patients with allergic rhinitis.
VAS represents a simple quantitative measure commonly employed in assessing the perception of symptoms. VAS was deeply investigated and validated in allergic rhinitis and shown to significantly correlate with severity of rhinitis and quality of life after AIT, reflecting changes after treatment. Very recently, it has provided evidence that VAS is a practical, sensitive and valid tool to monitor the burden of allergic rhinitis in clinical practice. In particular, it has been suggested that changes in VAS >2 cm after treatment should be considered of clinical importance, highlighting the usefulness of measuring VAS in clinical practice for assessing nasal symptom severity. Another relevant issue is the patient's perception of AIT efficacy. In this regard, a multicenter trial showed that VAS could be a reliable tool to assess the patient's perception of AIT efficacy. More recently, another multicenter study, conducted on 199 patients with allergic rhinitis, demonstrated that patient's perception of symptom severity and drug use, assessed by VAS, may be a practical approach to evaluate AIT efficacy.
On the basis of these considerations, the present preliminary study has been performed to investigate whether a serum-sIgE level ≥10 kU/l, before starting AIT, could also be useful in allergic children to define AIT efficacy, considering the patient's perception assessed by VAS.
Abstract and Introduction
Abstract
Aim. Allergen immunotherapy (AIT) is indicated in IgE-mediated respiratory allergy. Recently, it has been reported that serum-specific IgE (sIgE) levels >10 kU/l may predict AIT efficacy in adults with allergic rhinitis. The aim of the present preliminary study was to investigate whether this cut-off could also be associated with perception of effective AIT in children with allergic asthma and/or rhinitis due to house dust mites (HDM).
Methods. A total of 31 allergic children (17 males; mean age of 12.5 years) with levels of serum sIgE to HDM >10 kU/l were evaluated. Eight allergic children (five males; mean age of 13.4 years) with levels of serum sIgE to HDM <10 kU/l were considered as control. All patients were treated with sublingual immunotherapy for 3 years with HDM allergen extract. Children's perception of AIT efficacy was assessed by visual analog scale (VAS), considering both symptom severity and drug use. Responder patients were defined with >6 VAS. Severity of nasal symptoms was assessed by nasal VAS, and asthma control was evaluated by asthma control test; both were considered before and after AIT.
Results. All children (but one) with sIgE >10 kU/l perceived AIT efficacy, whereas only one child with sIgE <10 kU/l perceived AIT benefit (p < 0.001). There was a strong relationship between perception of AIT efficacy by VAS and serum sIgE levels (r = 0.615; p < 0.001). Also, nasal VAS and asthma control tests significantly improved only in children with sIgE > 10 kU/l (p < 0.001 for both).
Conclusion. Allergen-sIgE assessment before AIT prescription might represent a useful tool to individuate potential responders.
Introduction
Allergic disorders are characterized by an IgE-mediated reaction as a consequence of the exposure to a specific allergen. Thus, allergen-specific IgE (sIgE) production may be considered the hallmark of allergy, such as a sine qua non factor. At present, allergen immunotherapy (AIT) is the unique causal treatment for respiratory allergy. Indeed, successful AIT can induce a physiologic immune tolerance toward the causal allergen.
There is evidence, supported by many double-blind placebo-controlled trials and meta-analysis studies, that AIT is effective and safe. AIT indications and contraindications are clearly defined by relevant position papers. In particular, AIT is indicated in well-documented IgE-mediated respiratory allergy. However, no biomarker has yet been validated to be a good predictor of clinical response to AIT. Previously, changes in some cytokines were associated with successful AIT (including IL-4, IL-10, IL-12, IFN-γ and TGF-β), but they have not been clearly established markers for AIT response or for defining AIT responders. On the other hand, it was reported some years ago that the serum-sIgE/total IgE ratio may predict the clinical response to AIT in monosensitized patients to grass, Parietariajudaica, Oleaeuropea and house dust mites. In fact, high ratios (>16.2) were associated with an effective response. However, another study showed conflicting findings, such as patients with low serum-sIgE/total IgE ratio (<0.19) reporting better improvement than patients with high ratio, even though only at the second treatment year.
Conversely, a recent real-life experience reported that high serum-sIgE levels could predict response to AIT in 75 adults with allergic rhinitis (AR). AIT effectiveness was calculated considering both clinical improvement and drug use (prescribed on demand) reduction. Patients globally evaluated both parameters, reporting their perception by visual anaglog scale (VAS). After 3-year sublingual immunotherapy (SLIT), 63 patients (84%) were AIT responders. Serum-sIgE levels were significantly higher (p < 0.0001) in responder patients (median: 33.15 kU/l) than in nonresponder patients (median: 6.12 kU/l). More recently, a retrospective study was performed to confirm these preliminary findings. The study was conducted on 174 allergic patients treated with SLIT for 3 years. Responder patients were defined on the basis of a (VAS both for symptom and drug assessment) reduction of at least 30% compared with the baseline value. Response to SLIT was considered effective in 145 (83.3%) patients. A cut-off value (such as ≥9.74 kU/l) for serum-sIgE was able to discriminate effective from ineffective AIT, with 96.4% sensitivity, 100% specificity and 0.987 area under the receiver operating characteristic curve. Thus, this study concluded that sIgE level assessment before starting AIT might predict its efficacy in adult patients with allergic rhinitis.
VAS represents a simple quantitative measure commonly employed in assessing the perception of symptoms. VAS was deeply investigated and validated in allergic rhinitis and shown to significantly correlate with severity of rhinitis and quality of life after AIT, reflecting changes after treatment. Very recently, it has provided evidence that VAS is a practical, sensitive and valid tool to monitor the burden of allergic rhinitis in clinical practice. In particular, it has been suggested that changes in VAS >2 cm after treatment should be considered of clinical importance, highlighting the usefulness of measuring VAS in clinical practice for assessing nasal symptom severity. Another relevant issue is the patient's perception of AIT efficacy. In this regard, a multicenter trial showed that VAS could be a reliable tool to assess the patient's perception of AIT efficacy. More recently, another multicenter study, conducted on 199 patients with allergic rhinitis, demonstrated that patient's perception of symptom severity and drug use, assessed by VAS, may be a practical approach to evaluate AIT efficacy.
On the basis of these considerations, the present preliminary study has been performed to investigate whether a serum-sIgE level ≥10 kU/l, before starting AIT, could also be useful in allergic children to define AIT efficacy, considering the patient's perception assessed by VAS.
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