Background
Allergen immunotherapy (AIT) is an effective treatment for allergic rhinoconjunctivitis (AR) with or without asthma. It is important to note that due to the complex interaction between ...patient, allergy triggers, symptomatology and vaccines used for AIT, some patients do not respond optimally to the treatment. Furthermore, there are no validated or generally accepted candidate biomarkers that are predictive of the clinical response to AIT. Clinical management of patients receiving AIT and efficacy in randomised controlled trials for drug development could be enhanced by predictive biomarkers.
Method
The EAACI taskforce reviewed all candidate biomarkers used in clinical trials of AR patients with/without asthma in a literature review. Biomarkers were grouped into seven domains: (i) IgE (total IgE, specific IgE and sIgE/Total IgE ratio), (ii) IgG‐subclasses (sIgG1, sIgG4 including SIgE/IgG4 ratio), (iii) Serum inhibitory activity for IgE (IgE‐FAB and IgE‐BF), (iv) Basophil activation, (v) Cytokines and Chemokines, (vi) Cellular markers (T regulatory cells, B regulatory cells and dendritic cells) and (vii) In vivo biomarkers (including provocation tests?).
Results
All biomarkers were reviewed in the light of their potential advantages as well as their respective drawbacks. Unmet needs and specific recommendations on all seven domains were addressed.
Conclusions
It is recommended to explore the use of allergen‐specific IgG4 as a biomarker for compliance. sIgE/tIgE and IgE‐FAB are considered as potential surrogate candidate biomarkers. Cytokine/chemokines and cellular reponses provided insight into the mechanisms of AIT. More studies for confirmation and interpretation of the possible association with the clinical response to AIT are needed.
Clinical indications for allergen immunotherapy (AIT) in respiratory and Hymenoptera venom allergy are well established; however, clinical contraindications to AIT are not always well documented. ...There are some discrepancies when classifying clinical contraindications for different forms of AIT as ‘absolute’ or ‘relative’. EAACI Task Force on ‘Contraindications to AIT’ was created to evaluate and review current literature on clinical contraindications, and to update recommendations for both sublingual and subcutaneous AIT for respiratory and venom immunotherapy. An extensive review of the literature was performed on the use of AIT in asthma, autoimmune disorders, malignant neoplasias, cardiovascular diseases, acquired immunodeficiencies and other chronic diseases (including mental disorders), in patients treated with β‐blockers, ACE inhibitors or monoamine oxidase inhibitors, in children under 5 years of age, during pregnancy and in patients with poor compliance. Each topic was addressed by the following three questions: (1) Are there any negative effects of AIT on this concomitant condition/disease? (2) Are more frequent or more severe AIT‐related side‐effects expected? and (3) Is AIT expected to be less efficacious? The evidence, for the evaluation of these clinical conditions as contraindications, was limited, and most of the conclusions were based on case reports. Based on an extended literature research, recommendations for each medical condition assessed are provided. The final decision on the administration of AIT should be based on individual evaluation of any medical condition and a risk/benefit assessment for each patient.
Background
Clinical efficacy of pollen allergen immunotherapy (AIT) has been broadly documented in randomized controlled trials. The underlying clinical endpoints are analysed in seasonal time ...periods predefined based on the background pollen concentration. However, any validated or generally accepted definition from academia or regulatory authorities for this relevant pollen exposure intensity or period of time (season) is currently not available. Therefore, this Task Force initiative of the European Academy of Allergy and Clinical Immunology (EAACI) aimed to propose definitions based on expert consensus.
Methods
A Task Force of the Immunotherapy and Aerobiology and Pollution Interest Groups of the EAACI reviewed the literature on pollen exposure in the context of defining relevant time intervals for evaluation of efficacy in AIT trials. Underlying principles in measuring pollen exposure and associated methodological problems and limitations were considered to achieve a consensus.
Results
The Task Force achieved a comprehensive position in defining pollen exposure times for different pollen types. Definitions are presented for ‘pollen season’, ‘high pollen season’ (or ‘peak pollen period’) and ‘high pollen days’.
Conclusion
This EAACI position paper provides definitions of pollen exposures for different pollen types for use in AIT trials. Their validity as standards remains to be tested in future studies.
Background
Outside clinical trials, data on systemic reactions (SRs) due to allergen immunotherapy (AIT) are scarce.
Methods
A prospective, longitudinal, web‐based survey of ‘real‐life’ respiratory ...allergen immunotherapy (AIT) clinical practice was conducted in France, Germany and Spain. SRs were recorded and coded according to the Medical Dictionary for Regulatory Activities (MedDRA) and risk factors associated with SRs were identified.
Results
A total of 4316 patients (corresponding to 4363 ongoing courses of AIT) were included. A total of 109 SRs were recorded, and 90 patients (2.1%) presented at least one SR. Most of the SRs occurred in subcutaneous allergen immunotherapy (SCIT) (89%, n = 97). The most frequently reported symptoms were urticaria, rhinitis, dyspnoea and cough. Respiratory symptoms appeared before skin symptoms. Most SRs occurred during the up‐dosing phase (75.8%) and were mild in severity (71.6%). Intramuscular adrenaline was administered in 17 SRs, but only 65% of these were subsequently classified as anaphylaxis. Independent risk factors for SRs during SCIT were as follows: the use of natural extracts (odds ratio, OR) 95% confidence interval (CI) = 2.74 1.61–4.87, P = 0.001), the absence of symptomatic allergy medications (1.707 1.008–2.892, P = 0.047), asthma diagnosis (1.74 1.05–2.88, P = 0.03), sensitization to animal dander (1.93 1.21–3.09, P = 0.006) or pollen (1.16 1.03–1.30, P = 0.012) and cluster regimens (vs rush) (4.18 1.21–14.37, P = 0.023). A previous episode of anaphylaxis increased the risk for anaphylaxis in SCIT (OR 95% CI = 17.35 1.91–157.28, P = 0.01).
Conclusion
AIT for respiratory allergy is safe, with a low number of SRs observed in real‐life clinical practice. A personalized analysis of risk factors could be used to minimize SRs.
A review on the dietary flavonoid kaempferol Calderón-Montaño, J M; Burgos-Morón, E; Pérez-Guerrero, C ...
Mini reviews in medicinal chemistry,
04/2011, Letnik:
11, Številka:
4
Journal Article
Recenzirano
Epidemiological studies have revealed that a diet rich in plant-derived foods has a protective effect on human health. Identifying bioactive dietary constituents is an active area of scientific ...investigation that may lead to new drug discovery. Kaempferol (3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) is a flavonoid found in many edible plants (e.g. tea, broccoli, cabbage, kale, beans, endive, leek, tomato, strawberries and grapes) and in plants or botanical products commonly used in traditional medicine (e.g. Ginkgo biloba, Tilia spp, Equisetum spp, Moringa oleifera, Sophora japonica and propolis). Some epidemiological studies have found a positive association between the consumption of foods containing kaempferol and a reduced risk of developing several disorders such as cancer and cardiovascular diseases. Numerous preclinical studies have shown that kaempferol and some glycosides of kaempferol have a wide range of pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, anticancer, cardioprotective, neuroprotective, antidiabetic, anti-osteoporotic, estrogenic/antiestrogenic, anxiolytic, analgesic and antiallergic activities. In this article, the distribution of kaempferol in the plant kingdom and its pharmacological properties are reviewed. The pharmacokinetics (e.g. oral bioavailability, metabolism, plasma levels) and safety of kaempferol are also analyzed. This information may help understand the health benefits of kaempferol-containing plants and may contribute to develop this flavonoid as a possible agent for the prevention and treatment of some diseases.
The precise control over the interaction between cells and the surface of materials plays a crucial role in optimizing the integration of implanted biomaterials. In this regard, material surface with ...controlled topographic features at the micro- and nano-scales has been proved to affect the overall cell behavior and therefore the final osseointegration of implants. Within this context, femtosecond (fs) laser micro/nano machining technology was used in this work to modify the surface structure of stainless steel aiming at controlling cell adhesion and migration. The experimental results show that cells tend to attach and preferentially align to the laser-induced nanopatterns oriented in a specific direction. Accordingly, the laser-based fabrication method here described constitutes a simple, clean, and scalable technique which allows a precise control of the surface nano-patterning process and, subsequently, enables the control of cell adhesion, migration, and polarization. Moreover, since our surface-patterning approach does not involve any chemical treatments and is performed in a single step process, it could in principle be applied to most metallic materials.
To cite this article: Shamji MH, Ljørring C, Francis JN, Calderon MA, Larché M, Kimber I, Frew AJ, Ipsen H, Lund K, Würtzen PA, Durham SR. Functional rather than immunoreactive levels of IgG4 ...correlate closely with clinical response to grass pollen immunotherapy. Allergy 2012; 67: 217–226.
Background: Induction of allergen‐specific IgG4 antibodies is the most consistent immunological finding in immunotherapy trials. However, quantitative assessments of IgG4 antibodies have not proven beneficial in evaluating clinical changes during or after immunotherapy. In the current study, we investigated the relationship between clinical outcome and allergen‐specific IgG4 titres or functional antibody responses following immunotherapy. We hypothesized that functional assays of serum IgG–associated inhibitory activity such as inhibition of IgE–allergen interactions (IgE‐blocking factor) and inhibition of CD23‐dependent IgE‐facilitated allergen binding (IgE‐FAB) correlate more closely with clinical outcome and may be biomarkers of clinical response.
Methods: In an 8‐month dose–response randomized double‐blind placebo‐controlled study, 221 polysensitized subjects with severe seasonal rhinitis received Alutard SQ, Phleum pratense 100 000 SQ‐U, 10 000 SQ‐U or placebo injections. Serum specimens were collected before treatment, after up‐dosing, during the peak season and at the end of the study. Allergen‐specific IgG4 titres and IgG‐associated inhibitory activity were evaluated.
Results: A time‐ and dose‐dependent increase in serum inhibitory activity for both the IgE‐blocking factor and IgE‐FAB was observed, which paralleled increases in grass pollen–specific IgG4 antibodies. A modest but significant inverse relationship was demonstrated between postimmunotherapy serum inhibitory activity and combined symptom–rescue medication scores (IgE‐FAB: r = −0.25, P = 0.0002; IgE‐blocking factor: r = −0.28, P < 0.0001), whereas this was not observed for immunoreactive IgG4 levels (r = −0.11, P = 0.12).
Conclusions: Functional assays of inhibitory IgG4 and IgE‐blocking factor may be more useful surrogates of clinical response than IgG4. Whether these antibody effects may serve as predictive biomarkers of clinical efficacy in individual patients requires further investigation.
Allergen immunotherapy (AIT) has been thoroughly documented in randomized controlled trials (RCTs). It is the only immune-modifying and causal treatment available for patients suffering from ...IgE-mediated diseases such as allergic rhinoconjunctivitis, allergic asthma and insect sting allergy. However, there is a high degree of clinical and methodological heterogeneity among the endpoints in clinical studies on AIT, for both subcutaneous and sublingual immunotherapy (SCIT and SLIT). At present, there are no commonly accepted standards for defining the optimal outcome parameters to be used for both primary and secondary endpoints.
As elaborated by a Task Force (TF) of the European Academy of Allergy and Clinical Immunology (EAACI) Immunotherapy Interest Group, this Position Paper evaluates the currently used outcome parameters in different RCTs and also aims to provide recommendations for the optimal endpoints in future AIT trials for allergic rhinoconjunctivitis.
Based on a thorough literature review, the TF members have outlined recommendations for nine domains of clinical outcome measures. As the primary outcome, the TF recommends a homogeneous combined symptom and medication score (CSMS) as a simple and standardized method that balances both symptoms and the need for antiallergic medication in an equally weighted manner. All outcomes, grouped into nine domains, are reviewed.
A standardized and globally harmonized method for analysing the clinical efficacy of AIT products in RCTs is required. The EAACI TF highlights the CSMS as the primary endpoint for future RCTs in AIT for allergic rhinoconjunctivitis.
To cite this article: Radulovic S, Wilson D, Calderon M, Durham S. Systematic reviews of sublingual immunotherapy (SLIT). Allergy 2011; 66: 740–752.
Allergic rhinitis is common worldwide, with ...significant morbidity and impact on quality of life. In patients who don’t respond adequately to anti‐allergic drugs. Subcutaneous allergen immunotherapy is effective although requires specialist administration. Sublingual immunotherapy may represent an effective and safer alternative. This Cochrane systematic review is an update of one published in 2003. We searched Cochrane ENT Group Trials Register, Central, PubMed, EMBASE, CINAHL, Web of Science, Biosis Previews, Cambridge Scientific Abstarcts, mRCT and additional sources. We included randomised, double‐blind, placebo‐ controlled trials of sublingual immunotherapy in adults and children. Two authors selected studies and assessed them for quality. Data were put into RevMan 5.0 for a statistical analysis. We used standardised mean difference (SMD), with a random effect model to combine data. Sixty studies were included, with 49 suitable for meta‐analysis. We found significant reductions in symptoms (SMD −0.49; 95%CI (−0.64 to −0.34, P < 0.00001)) and medication requirements (SMD −0.32; 95%CI (−0.43 to −0.21, P < 0.00001)) compared with placebo. None of the trials reported severe systemic reactions, anaphylaxis or use of Adrenaline. This updated review reinforces the conclusion of the original 2003 Cochrane Review that sublingual immunotherapy is effective for allergic rhinitis and appears a safe route of administration.
Background
The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing Guidelines on Allergen Immunotherapy (AIT) for Allergic Rhinoconjunctivitis. To inform the ...development of clinical recommendations, we undertook a systematic review to assess the effectiveness, cost‐effectiveness, and safety of AIT in the management of allergic rhinoconjunctivitis.
Methods
We searched nine international biomedical databases for published, in‐progress, and unpublished evidence. Studies were independently screened by two reviewers against predefined eligibility criteria and critically appraised using established instruments. Our primary outcomes of interest were symptom, medication, and combined symptom and medication scores. Secondary outcomes of interest included cost‐effectiveness and safety. Data were descriptively summarized and then quantitatively synthesized using random‐effects meta‐analyses.
Results
We identified 5960 studies of which 160 studies satisfied our eligibility criteria. There was a substantial body of evidence demonstrating significant reductions in standardized mean differences (SMD) of symptom (SMD −0.53, 95% CI −0.63, −0.42), medication (SMD −0.37, 95% CI −0.49, −0.26), and combined symptom and medication (SMD −0.49, 95% CI −0.69, −0.30) scores while on treatment that were robust to prespecified sensitivity analyses. There was in comparison a more modest body of evidence on effectiveness post‐discontinuation of AIT, suggesting a benefit in relation to symptom scores.
Conclusions
AIT is effective in improving symptom, medication, and combined symptom and medication scores in patients with allergic rhinoconjunctivitis while on treatment, and there is some evidence suggesting that these benefits are maintained in relation to symptom scores after discontinuation of therapy.
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