Unmet Needs in Understanding Sublingual Immunotherapy to Grass Pollen

The lack of medication for allergy symptoms at the end of the last millennium has been the promoter of the idea of treating allergies as if you were treating an infectious disease, by vaccination prophylaxis. Two forms of AIT 1) subcutaneous immunotherapy (SCIT) and 2) sublingual immunotherapy (SLIT) are used in the world. Considerable interest has emerged in SLIT both scientifically and especially financially. SLIT is not a new treatment modality. First description dates back to 1900 when H. Curtis. It was relatively widely used until the late 1970’s mainly in US by homeopathic therapists

Assessment of a qualitative serological assay to screen for allergic sensitization in elderly subjects

We used a commercially available specific IgE qualitative serological assay to screen for allergic sensitization. Two hundred twenty-eight elderly subjects took part in the study. Skin-prick tests (SPTs) to a panel of relevant aeroallergens present in the study area were used as the diagnostic reference procedure (gold standard). Subjects with at least one positive SPT (≥3 mml n = 76) were considered to have developed an allergic sensitization. The qualitative assay correctly classified subjects as sensitized to an allergen or not sensitized in 257 of 288 cases (accuracy, 88.9%; 95% CI, 85.0-92.0%). The qualitative assay sensitivity was 70.0 (95% CI, 58.1-79.7) and specificity was 95.7 (95% CI, 92.1-98.0), positive predictive value (PPV) was 85.4 (95% CI, 85.1-93.4), negative predictive value (NPV) was 89.8 (95% CI, 85.1-93.4), positive likelihood ratio (LR(+)) was 16.5 (95% CI, 8.7-31.6), negative LR (LR(-)) was 0.31 (95% CI, 0.21-0.43), and the diagnostic odds ratio (DOR) was 52.2 (95% CI, 21.5-133.6). In the elderly subjects with respiratory symptoms, the qualitative assay correctly classified subjects as allergen sensitized or nonsensitized in 81 of 89 cases (accuracy, 91.0; 95% CI, 85.0-96.9). In this subgroup, the qualitative assay sensitivity was 94.6 (95% CI, 85.1-98.8), specificity was 84.8 (95% CI, 68.1-94.9), PPV was 91.3 (95% CI, 81.0-97.1), and NPV was 90.3 (95% CI, 74.2-97.9). LR(+) was 6.2 (95% CI, 3.0-14.2), LR(-) was 0.06 (95% CI, 0.02-0.17), and the DOR was 98.9 (95% CI, 18.0-621.4). The qualitative serological assay is a valuable tool for the diagnosis of allergic sensitization in a population of elderly subjects

Comparison between statistical and fuzzy approaches for improving diagnostic decision making in patients with chronic nasal symptoms

This paper compares a fuzzy model, expressed in rule-form, with a well known statistical approach (i.e. logistic regression model) for diagnostic decision making in patients with chronic nasal symptoms. The analyses were carried out using a database obtained from a questionnaire administered to 1359 patients with nasal symptoms containing personal data, clinical data and skin prick test (SPT) results. Both the fuzzy model and the logistic regression model developed were validated using a data set obtained from another medical institution. The accuracy of the two models in identifying patients with positive or negative SPT was similar. This study is a preliminary step to the creation of a software that primary care doctors can use to make a diagnostic decision, when deciding whether patients with nasal symptoms need allergy testing or not

Efficacy of grass pollen allergen sublingual immunotherapy tablets for seasonal allergic rhinoconjunctivitis: A systematic review and meta-analysis

IMPORTANCE: Randomized clinical trials (RCTs) and meta-analyses of sublingual immunotherapy (SLIT) for the treatment of seasonal allergic rhinoconjunctivitis (SARC) have shown a modest clinical benefit compared with placebo. Furthermore, indirect comparison by meta-analyses showed that subcutaneous immunotherapy is more effective than SLIT. Despite these data, SLIT has become the most prescribed treatment of SARC in Europe in recent years, and it was approved by the US Food and Drug Administration for the treatment of SARC to grass pollen in the United States on April 1, 2014. OBJECTIVE: To assess the efficacy and safety of the grass pollen sublingual tablets licensed as drugs in the treatment of patients with SARC to grass pollen. DATA SOURCES: Computerized bibliographic searches of MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov (from inception to April 30, 2014) were supplemented with a manual search of reference lists. STUDY SELECTION: Randomized clinical trials were included if they compared the grass pollen SLIT tablets approved by regulatory authorities in the European Union and the United States for SARC with placebo. DATA EXTRACTION AND SYNTHESIS: Data on populations, interventions, and outcomes were extracted from each RCT according to the intent-to-treat method by 2 independent observers and were combined using the method by DerSimonian and Laird. MAIN OUTCOMES AND MEASURES: The primary end point was the difference in the symptom score and medication score between SLIT and placebo. We pooled data using random-effects meta-analysis, with standardized mean differences (SMDs) and 95% CIs reported. RESULTS: Data were available in 13 RCTs for the symptom score (4659 patients) and in 12 RCTs for the medication score (4558 patients). We found a small treatment benefit in the symptom score (SMD, -0.28; 95% CI, -0.37 to -0.19; P < .001) and in the medication score (SMD, -0.24; 95% CI, -0.31 to -0.17; P < .001). Adverse events were reported in 1384 of 2259 patients (61.3%) receiving SLIT and in 477 of 2279 patients (20.9%) receiving placebo. Seven patients in the SLIT group reported treatment-related adverse events requiring epinephrine. CONCLUSIONS AND RELEVANCE: Findings show a small benefit of the grass pollen sublingual tablets in reducing symptoms and in decreasing the use of symptomatic medication (antihistamines and corticosteroids) in patients with SARC. Considering the low magnitude of the benefit, the convenience and easy administration do not seem to be sufficient reasons for the choice of SLIT

Bilateral striatal necrosis in two subjects with Aicardi-Goutières syndrome due to mutations in ADAR1 (AGS6)

Aicardi-Goutières syndrome (AGS) is a genetic inflammatory disease. The classic neuroradiological picture mimics that of congenital infections in that Aicardi-Goutières syndrome is characterized by leukoencephalopathy, brain atrophy and intracranial calcifications. To date, bilateral striatal necrosis has not been reported in patients with AGS. We report on two patients with clinical diagnosis of Aicardi-Goutières syndrome in which brain MRI and CT scans demonstrated bilateral striatal necrosis. The diagnosis of Aicardi-Goutières syndrome in these two patients was genetically confirmed after the recent discovery that mutations in the ADAR1 (AGS6) gene may cause Aicardi-Goutières syndrome. This is the first report of bilateral striatal necrosis in association with Aicardi-Goutières syndrome. These results expand the neuroradiological phenotype of Aicardi-Goutières syndrom

Sublingual immunotherapy with natural grass pollen extracts: An appraisal of the evidence

Many clinical studies have demonstrated that sublingual immunotherapy is effective against allergic symptoms, but caution must be exercised with these conclusions because of the wide variation among different studies in, for example, allergen dose used, type of treatment, patient selection and type of outcome measures. In order to overcome the inconsistency between the results of different studies and to assess the magnitude of the treatment effect, we performed a systematic review of double-blind, placebo-controlled, randomized clinical trials of grass pollen-specific immunotherapy for the treatment of seasonal allergic rhinoconjunctivitis in adults and children. Our conclusions were that sublingual immunotherapy (SLIT) with grass allergens improves rhinosinusitis symptoms and that it reduces the need for medications compared with placebo in adults. Further studies are needed to define the role of SLIT with grass allergens in children. © 2011 Future Medicine Ltd

Differences in the behavior of advanced glycation end products and advanced oxidation protein products in patients with allergic rhinitis.

BACKGROUND: The presence of oxidative stress in patients with asthma is well documented; however, the role of oxidative stress in allergic rhinitis has received less attention, although it is likely to be similar to that observed in patients with asthma. Advanced glycation end products (AGEs) and advanced oxidation protein products (AOPPs) are compounds formed by the transformation of macromolecules, including proteins, which can serve as densitometric markers of oxidative stress and inflammation in several diseases. OBJECTIVE: The aim of this study was to investigate the role of AGEs and AOPPs as new markers of oxidative stress and inflammation in patients affected by allergic rhinitis. METHODS: AGE and AOPP levels were determined in the sera of 25 patients with allergic rhinitis and 64 healthy controls. AGEs and AOPPs were detected using spectrofluorimetry and spectrophotometry, respectively. RESULTS: AGE levels in patients were significantly higher than those in controls (P < .0001). These levels were not affected by the presence of asthma. No statistically significant differences were found between AOPP levels in patients or controls (P = .38). CONCLUSIONS: Formation of AGEs and AOPPs may be accelerated in immunological and respiratory disorders such as asthma. Depending on the marker evaluated, the presence or absence of oxidative stress in allergic rhinitis is controversial. To our knowledge, this is the first study showing the possible involvement of AGEs in allergic rhinitis. The different behavior observed for these 2 biomarkers is very likely due to the activation of specific related biochemical pathways (eg, the myeloperoxidase pathway) associated with the condition under study

Analysis of a Database to Predict the Result of Allergy Testing in Vivo in Patients with Chronic Nasal Symptoms

Background: This article uses the logistic regression model for diagnostic decision making in patients with chronic nasal symptoms. We studied the ability of the logistic regression model, obtained by the evaluation of a database, to detect patients with positive allergy skin-prick test (SPT) and patients with negative SPT. The model developed was validated using the data set obtained from another medical institution. Methods: The analysis was performed using a database obtained from a questionnaire administered to the patients with nasal symptoms containing personal data, clinical data, and results of allergy testing (SPT). All variables found to be significantly different between patients with positive and negative SPT (p < 0.05) were selected for the logistic regression models and were analyzed with backward stepwise logistic regression, evaluated with area under the curve of the receiver operating characteristic curve. A second set of patients from another institution was used to prove the model. Results: The accuracy of the model in identifying, over the second set, both patients whose SPT will be positive and negative was high. The model detected 96% of patients with nasal symptoms and positive SPT and classified 94% of those with negative SPT. Conclusion: This study is preliminary to the creation of a software that could help the primary care doctors in a diagnostic decision making process (need of allergy testing) in patients complaining of chronic nasal symptoms