Перейти к содержанию

switzerland on forex

speaking, opinion, obvious. advise you..

Рубрика: Safe moon token

J investing allergol clin immunol impact factor 2011 calendar

j investing allergol clin immunol impact factor 2011 calendar

Efficacy of sublingual allergen vaccination for respiratory allergy in children. Conclusions from one meta-analysis. J Invest Allergol Clin. J Investig Allergol Clin Immunol ; Vol. 31, Suppl. 1 while environmental factors vary greatly and can impact on J Clin Invest. ;. significant interruption in the immunotherapy schedule. PEF, Peak expiratory flow rate measurement. J ALLERGY CLIN IMMUNOL. JANUARY S16 COX ET AL. INVESTING IN CHARTER SCHOOLS If you are one. FunctionFox Ideal by ' professionals, FunctionFox helps keep your website to organize error 11. The default configuration for options provided mp3 information sites requires start the so you reach everywhere, to fix.

Indeed, SLIT increases the frequency of Th1 cells, although other studies were performed with different groups of patients, where an increase in peripheral blood Th1 cells was also reported. The percentages of Th2 cells and those of peripheral basophils were not affected. These findings may be directly related, as IL-4 and IL are both released from Th2 cells and are both responsible for the stimulation proliferation and differentiation of basophils in bone marrow. This lack of change may be associated with the permanent contact of cells with allergens used in SLIT.

One year of SLIT also did not decrease the percentage of activated basophils after allergen challenge. A similar observation was reported by Horak et al. They evaluated basophil activation through CDc antigen upregulation after 4 months of SLIT in a group of 45 adults sensitized to grass pollen.

There was no difference in CDc expression on basophils stimulated with grass pollen allergens before and after treatment, 33 while the same group also showed that basophil activation based on the detection of CDc is not indicative of immunotherapy efficacy.

Although it concerned a group of nine patients, a shift of CDc antigen expression on basophils from subjects sensitized to Japanese cedar pollen after rush immunotherapy was demonstrated, and it was postulated that these changes were a reliable marker of basophil desensitization and immunotherapy effectiveness.

We postulate that the decrease of Th1 cell susceptibility to apoptosis may play a crucial role in restoring the immunological balance between T-helper cells in atopic diseases. It is of interest that Frisella et al. In summary, the immune mechanisms leading to clinical tolerance after SLIT have not yet been fully elucidated. Although flow cytometric evaluation of basophil sensitivity to degranulation after allergen challenge is found to be a reliable method in allergy diagnosis, our results do not confirm previous reports that suggest a decrease of degranulation in response to short-term SLIT.

The shift from Th2 to Th1 response has been attributed to the action of immunoregulatory cells. However, an alternative approach of immunodeviation should be also taken into consideration. The authors declare that they do not have any conflicts of interest to report.

Pediatric Allergy, Immunology, and Pulmonology. Pediatr Allergy Immunol Pulmonol. Find articles by Olga Ciepiela. Find articles by Anna Zawadzka-Krajewska. Find articles by Frans van Overveld. Find articles by Marek Kulus. Find articles by Urszula Demkow. Author information Article notes Copyright and License information Disclaimer. Corresponding author. Received Jan 7; Accepted Feb 3. Copyright , Mary Ann Liebert, Inc.

This article has been cited by other articles in PMC. Abstract Objective: Allergen-specific immunotherapy SIT is the unique modifying treatment of atopic diseases. Introduction A llergen-specific immunotherapy SIT based on the administration of increasing doses of allergen is the unique treatment of atopic diseases modifying the immune response. Materials and Methods Patients and samples Twenty-five patients aged 8. Table 1. Parameter Study group Control group Age range, years 8. Open in a separate window.

Table 2. Basophil activation test All tests were carried out within 2 hours of blood collection, in accordance with the recommendation regarding the time between blood collection and processing the basophils. Statistical analysis The Wilcoxon matched pairs test was used to compare nonparametric data from patients before and after 1 year of SLIT. Results Basophil numbers and activation The frequency of basophils in peripheral blood was 0.

Basophil activation in asthmatic patients before and after 1 year of SLIT The mean fluorescence channel MFC of basophils stained with PE-conjugated monoclonal antibody against CDc in the sample incubated with PBS negative control was used as a marker of spontaneous degranulation. Discussion A flow cytometric basophil activation test based on the detection of surface activation markers is found to be a reliable test to confirm sensitization in allergic subjects.

Author Disclosure Statement The authors declare that they do not have any conflicts of interest to report. References 1. One-year follow-up of clinical and inflammatory parameters in children allergic to grass pollen receiving high-dose ultrarush sublingual immunotherapy. A randomized double-blind comparative study of sublingual immunotherapy for cedar pollinosis. Allergen-specific immunotherapy: which outcome measures are useful in monitoring clinical trials? Allergen immunotherapy and tolerance.

Allergen-specific immunotherapy in asthmatic children: from basis to clinical applications. Sublingual allergen immunotherapy: mode of action and its relationship with the safety profile. Allergy ; 67 — [ PubMed ] [ Google Scholar ]. Cox L. Sublingual immunotherapy in pediatric allergic rhinitis and asthma: efficacy, safety, and practical considerations.

Sublingual immunotherapy mechanisms of action: the role of Th1 response. Dendritic cells modification during sublingual immunotherapy in children with allergic symptoms to house dust mites. Moingeon P, Mascarell L. Induction of tolerance via the sublingual route: mechanisms and application.

Sublingual immunotherapy affects specific antibody and TGF-beta serum levels in patients with allergic rhinitis. Mechanisms of immunotherapy to aeroallergens. Mechanisms of allergen-specific immunotherapy. Clin Transl Allergy ; 2 Impact of sublingual immunotherapy on specific antibody levels in asthmatic children allergic to house dust mites. Sublingual immunotherapy induces ILproducing T regulatory cells, allergen specific T-cell tolerance, and immune deviation.

Effect of sublingual immunotherapy with grass monomeric allergoid on allergen-specific T-cell proliferation and interleukin 10 production. Sublingual immunotherapy with Dermatophagoides monomeric allergoid down-regulates allergen-specific immunoglobulin E and increases both interferon gamma and interleukinproduction. Sublingual Immunotherapy: past, present, paradigm for the future?

A review of the literature. Changing survival, memory cell compartment, and T-helper balance of lymphocytes between severe and mild asthma. Update on the performance and application of basophil activation tests. The usefulness of CDc expression measurement on basophils after activation with grass pollen and Dermatophagoides pteronyssinus antigens. Preliminary study. House dust mite sublingual immunotherapy: the role for transforming growth factor-beta and functional regulatory T-cells.

Allergy ; 61 — [ PubMed ] [ Google Scholar ]. The role of interleukin in the pathogenesis of bronchial asthma and other allergic diseases and in activation of basophils and mastocytes. Sublingual immunotherapy with Dermatophagoides monomeric allergoid down-regulate allergen-specific immunoglobulin E and increases both interferon gamma and interleukinproduction.

Sublingual immunotherapy for peanut allergy: clinical and immunologic evidence of desensitization. Specificity was allergen dependent, and in vitro tests reported a greater number of positive tests to mites than SPT.

Specific IgE had a high negative predictive value of negative test results. In patients with symptoms, SPT-positive and negative in vitro test may be due to difference in extract allergen composition. In contrast, two allergens of dog extract have showed SPT-negative and specific IgE-positive results against the extract. The number of sensitizations that can be missed if either of the testing methods are being used alone has been evaluated in a large multicentre study.

There is a considerable overlap of total IgE values in healthy and allergic subjects being total IgE a poor screening test for sensitization 61,62 level of evidence 1a, grade of recommendation A. Advantages of specific IgE testing: 1.

Automatic method. It uses natural or recombinants proteins or crude extracts. To assess monitoring sensitization and timing of natural exposure to allergen some cases. To use in patients in whom SPT cannot be performed. Disadvantages of specific IgE testing: 1. It detects low-affinity IgE that may have no clinical relevance. Molecular diagnosis: This is an in vitro method that measures specific IgE that binds to single allergenic protein components purified from natural sources or obtained by recombinant techniques or even peptide fragments of allergenic proteins rather than whole allergen extracts.

Molecular diagnosis can establish the probability of patient symptoms due to exposure to different allergen sources by the pattern of sensitization to different allergens. Molecular diagnosis has somewhat lower sensitivity of individual allergen diagnostics with respect to many allergens, and not everything that is possible to diagnose at present is sensible for use in routine diagnosis. However, molecular diagnosis avoids the recognition of low-affinity IgE in lower allergen amounts.

It is not clear if recombinant forms are equivalent with their natural forms. Purified natural allergens not recombinant molecules may contain glycoproteins CCD that could result positive due to cross-reactivity. When glycosylated allergen molecules are used as natural purified glycoproteins , specific IgE to CCD could drive a positive result in in vitro tests based on extracts and in tests based on allergenic molecules molecular diagnosis.

The recombinant forms of the proteins are not glycosylated but may theoretically result in improper folding of the allergen protein, driving a false negative result. These markers are able to detect N-glycans in most pollen sources. Therefore, positive result to natural glycoproteins allergen molecules with negative result to CCD markers would suggest sensitization to the protein e.

Positive result to CCD markers needs to demonstrate the biological activity of the specific IgE to protein. Singleplex and multiplex measurement platforms are available for identifying IgE against allergenic molecules in the molecular diagnosis. Singleplex consists of one assay per sample. The clinicians must choose those allergenic molecules necessary for an accurate diagnosis defined by patient's clinical history.

Taking into account that including a higher number of molecules increases the economic cost, clinicians must have to consider if it is better to use a multiplex test instead e. If more than 10 to 12 allergens are required for an accurate diagnosis using singleplex tests, then a multiplex test may be preferable for economic reasons 68 level of evidence 1b, grade of recommendation A. These platforms use panels of single allergens. The detection limit of these systems is usually 0.

Another important finding of this study is that the specific IgE values for the cross-reacting allergens are significantly lower than those of the major allergens, which could be regarded as the cause of sensitization to grasses. This reinforces the fact that to quantify specific IgE is also relevant in molecular diagnosis as quantification specific IgE may objectively establish associations between groups of allergens for diagnostic purposes 38 level of evidence 1b, grade of recommendation A.

However, higher or more frequent specific IgE has been observed with some molecules not commonly found in the environment. Noteworthy, Scala et al. It is able to exclude responses from low-affinity IgE. Multiplex platforms consist of multiple assays per sample with a broad array of pre-selected allergens on a chip independently of the clinical history. The Immuno-Solid phase Allergen Chip ISAC is the most comprehensive multiplex platform currently available, with more than commercial allergenic molecules from about 50 allergen sources.

The allergens are spotted in triplicate and covalently immobilized on the chip. Two negative spots are considered negative result. Results are reported within a range of 0. Although the ISAC results are similar with those obtained from singleplex platforms, they are not interchangeable. Both tests correlate well despite concordance of results vary between allergens tested 36,64,72 level of evidence 1b, grade of recommendation A. The concordance of results between allergens tested is lower for positive results than for negative results ImmunoCAP technology measures IgE binding under conditions of excess of immobilized allergen whereas ISAC uses low amounts of immobilized allergen allowing for competition with allergen-specific isotypes e.

ISAC is especially suited for use in patients with complex sensitization pattern or symptoms when sensitization to cross-reacting allergens is suspected and when both food and airborne allergens are involved level of evidence 1b, grade of recommendation A. Advantages of molecular diagnosis: 1. It assesses the appropriate and individualized indication for AIT and selects the optimal allergen s. It provides extensive sensitization profile.

It identifies sensitization patterns associated with prognostic outcomes assessment of severity of reaction associated with certain allergens. It predicts the risk of adverse reactions of AIT. It distinguishes between cross-reactivity and co-sensitization, and understands patient symptoms due to this phenomenon. It allows determining whether a single, a few closely related or several widely different allergen sources need to be considered. In the case of cross-reactive allergens, it gives information on potential sensitization and clinical reactions to several different sources, even unanticipated or potentially high risky allergens.

It tests a large number of allergens natural or recombinant molecules using a small amount of serum ISAC platform. It studies sensitization at early stage and progression to a clinical stage allowing knowing the sensitization or allergic march. Disadvantages of molecular diagnosis: 1. Not all allergenic sources are included. It is needed expansion of additional allergenic molecules. Interpretation of the results can be confused.

The clinical utility of many allergenic molecules needs further investigation. Guidelines for appropriate test interpretation are needed each time new molecule is discovered. Detection of some cross-reactive molecules without knowledge of their underlying mechanism causing cross-reactivity and symptom presentation. This method is a semi-quantitative and manual assay.

The results in ISAC platform are variable and therefore it is not recommended for monitoring disease or response to treatments. ImmunoCAP has less allergens molecules available. Molecular diagnosis is recommended as a third step when previous tests were inconclusive 38 level of evidence 1a, grade of recommendation A , although experienced clinicians may also use it as a second step test.

An algorithm using a panel of specific markers of allergen sources and a panallergen screening has been proposed to assess patients from southern Europe suitable for AIT based on extracts. If the results are positive to purified natural CCD-contained forms such as nCyn d 1 Bermuda grass , nCup a 1 cypress , nOle e 1 olive , nSal k 1 salwort and nArt v 1 mugwort , they suggest to rule out sensitization only to CCD or to elucidate concurrent sensitization to both glycosylated and protein parts.

Recently, a User's Guide for Molecular Allergology has been published by the European Academy of Allergy and Clinical Immunology which includes the interpretation of molecular diagnosis results in order to make a clinical decision about suitable AIT. In summary, molecular diagnosis allows determining the indication and the optimal allergen s for AIT because is able to distinguish between sensitization to specific unique molecule of an allergen source and sensitization to highly cross-reactive molecules.

The usefulness is high in poly-sensitized patients, with unclear symptoms related to exposure or without response to treatment. Mono-sensitized patients with a clear clinical history related to exposure could be diagnosed with in vivo , in vitro or both diagnostic tests based on allergen extracts.

The allergen molecules useful for identification of those patients best suited for AIT are depicted in Table 3. Specific IgE to the same major allergen used in extract standardization diagnostic and therapeutic would increase the potential response to AIT 76 level of evidence 1a, grade of recommendation A.

Although profilins and polcalcins can trigger symptoms, they are not presented in high quantity in extracts AIT. Sensitization to profilins rPhl p 12 and rBet v 2 and polcalcins rPhl p 7 and rBet v 4 are markers of cross-reactivity and representative of the entire group of homologous proteins except of Parietaria sp. Profilin and polcalcin grass are the most frequent cause of sensitization to panallergens with high cross-reactivity. In areas with high prevalence of birch pollen rBet v 4 and rBet v 2 can be used as markers of cross-reactivity not in Mediterranean regions.

Relevant inhalant allergen molecules for AIT. Several factors of the allergic diagnosis of respiratory diseases affect the treatment of allergy and specifically in the decision of AIT. Children initially mono-sensitized to mites become poly-sensitized more frequently than children mono-sensitized to pollens Although profilins sensitization is usually associated with mild or no clinical symptoms, some patients may develop more severe reactions.

Aeroallergen sensitization profiles and disease expression differ according to local exposures patterns characteristic of the geographical region and genetic differences. Results obtained with allergic tests have to be related to local population studied. Grass is the first sensitization pollen followed by Olea sp. The highest prevalence to Par j 1 Parietaria sp. In some areas, Pla l 1 is the second allergen after grass.

Bet v 1 is relevant only in Galicia. In contrast, most patients in dry semi-desert areas and on the Mediterranean coast lower pollen counts are poly-sensitized showing high specific IgE levels to both major allergens and panallergens. The GA2LEN skin test study showed that many allergens previously regarded as untypical for some regions in Europe have been underestimated, such as Olea sp.

Aeroallergen sensitization is strongly associated with rhinitis, asthma and conjunctivitis. There is a relationship between sensitization and disease severity with more severe symptoms in poly-sensitized patients than in mono-sensitized. Some allergen molecules have been associated with severe asthma in children such as Fel d 1 cat and Can f 5 dog Respiratory allergy was associated with both D. Poly-sensitization develops over time and is a risk for respiratory allergy e. However, there is not always a relationship between an increase in number of sensitizations and respiratory allergy; some infants with wheezing and sensitization will develop new sensitizations 5 years later without wheezing at this age.

Using both methods in vivo SPT and in vitro specific IgE have been recommended to investigate sensitization in young children as lower concordance is reported at young ages 58 level of evidence 2b, grade of recommendation B. Paediatric population that shared the same geographical area of adults could have different pattern of sensitization. In a population of 66 children from the centre of Spain mean age Sensitization to Ole e 1, Phl p 1 and Phl p 5 were present in A minority of patients recognized cross-reactivity to allergens.

Total IgE levels increase in the first 6 months of life and continue to increase in the next two years of life. Specific aeroallergen sensitizations can already be detected within the first year of life in a few children. Up to Most allergen extracts used in AIT contain standardized major allergens with minimal or variable amounts of minor allergens. Patients with sensitization to minor allergens alone will not receive sufficient amounts of allergen to improve their symptoms.

Thus, better AIT outcomes have been found in those patients sensitized to the specific unique allergens of birch or grass pollen compared to patients sensitized to only minor, cross-reactive allergens 88 level of evidence 1a, grade of recommendation A. Some allergen sensitization patterns may also predict the risk of AIT adverse reactions. Specific allergens markers of more severe symptoms in pollen allergy and increased risk of systemic reactions during AIT are Ole e 9 and LTP Ole e 7 79 level of evidence 1b, grade of recommendation B.

AIT may only be used in diseases where an IgE mediated allergy mechanism is central to its pathogenesis 76 level of evidence 1a, grade of recommendation A. Therefore, in addition to demonstrating allergic sensitization by skin tests or by determination of specific serum IgE, the existence of a correlation between sensitization with the clinical symptoms presented must be ensured.

Identifying the allergen responsible for the patient's symptoms is an essential requirement for prescribing treatment with immunotherapy 38,59 level of evidence 1a, grade of recommendation B. Given the current scientific evidence, the clinical histories for which this treatment is indicated are: rhinitis that is not controlled with the usual pharmacological treatment, allergic asthma and allergy to Hymenoptera venom 89 level of evidence 1a, grade of recommendation A.

AIT is indicated as an adjunct treatment to allergen avoidance measures and drug treatment. Normally, AIT is indicated in patients aged 5—50 years of age, although today it is increasingly recommended in patients under 5 years of age 90,91 level of evidence 2a, grade of recommendation B.

AIT has shown to be effective in children and is often well tolerated, although parents must always be relied on to properly follow the immunotherapy regimen. The decision to initiate AIT treatment may depend on several factors including, but not limited to, the availability of a suitable extract with properly documented efficacy, patient preferences and the degree of compliance predictable, medication needs, the degree of patient exposure, the response to the allergen avoidance measures and the existence of and response to side effects of different drugs.

Patients with atopic dermatitis and sensitization to inhalant allergens could also be assessed. Patients presenting with a specific IgE, confirmed by either SPT the most common and cost-effective method or by determination of serum specific IgE. There should also be a correlation between patient symptoms and a sensitization to the allergen exposed.

In the case of a patient presenting with positive SPT or specific IgE, but with symptoms that are not clinically consistent and unrelated to exposure, it would be considered an asymptomatic sensitization and therefore not indicated for AIT. Patients with insufficient symptom control despite pharmacological measures and allergen avoidance, who require high-dose therapy and experience side effects from the use of multiple drugs or wish to avoid prolonged drug treatment, may be possible candidates for AIT.

The patient's clinical response in terms of quality of life and responsiveness to other forms of treatment, such as avoidance of the allergen or to the pharmacological measures, should also be factors to consider in the decision to prescribe AIT. The severity and duration of symptoms should also be taken into account in assessing the need for AIT.

The severity of symptoms can be defined by subjective and objective parameters. Time lost from work, visits to the emergency room or doctor's office indirect costs and the response to pharmacotherapy are important objective indicators of the severity of the allergic disease. The symptoms that interfere with sleep, work or school performance are other factors to consider.

The presence of comorbidities must also be considered in the evaluation of a patient as a possible candidate for AIT. Patients with AR who suffer from sleep disturbances due to symptoms or whose symptoms interfere with work or school performance are particularly good candidates for AIT. Patients who experience adverse side effects from pharmacotherapy, such as nosebleeds with intranasal steroids or excessive drowsiness with antihistamines, and those who find the pharmacotherapy inconvenient or ineffective may also be suitable candidates for immunotherapy.

Patients with coexisting AR and asthma should be treated with an appropriate combination of allergen avoidance measures and drug treatment, but can also benefit from AIT. However, the asthmatic condition of the patient must be stabilized before administering AIT. For the AIT to be effective, the allergen responsible for the patient's symptoms should be identified and should be an essential requirement for the treatment with immunotherapy 38,59 level of evidence 1a, grade of recommendation B.

A correlation between symptoms, allergen exposure and the results of diagnostic tests should exist. The specific aeroallergen responsible for the symptoms should be identified through SPT, specific IgE and molecular diagnosis , especially in the case of poly-sensitized patients as it differentiates whether poly-sensitization is the result of a true sensitization to various pollens or the effect of cross-reactivity to panallergens 63,64,72,73,— level of evidence 2a, grade of recommendation B.

While SPT and specific IgE to extracts only detect the sensitizing source, the molecular diagnosis clearly identifies the responsible allergen. If a molecular diagnosis is not available, an individualized patient assessment based on the experience of the specialist prescribing the immunotherapy should be performed. Otherwise, the indication should be assessed individually.

This also applies in the case of allergen mixtures. Once the patient is considered eligible to receive AIT, the administration route must be selected: subcutaneously native or modified extract or sublingually drops or tablets. Depending on the type of AIT, a set of indications may also be established. Patients with AR and asthma during the period of maximum exposure to the allergen.

Poly-sensitized patients where AIT with mixtures of more than two allergenic extracts is considered to be used. Patients who have suffered systemic reactions with SCIT. Patients who have trouble adhering to SCIT or do not tolerate it. Identification of other triggering factors that might be involved in the symptoms. The stabilization and control of respiratory functions essential in patients with asthma. Availability of standardized or high quality allergenic extracts. Socioeconomic factors, such as cost or the patient's occupation.

In patients with asthma, the AIT can be used before administering inhaled corticosteroids ICS for patients with mild allergic asthma and concomitant AR. AIT is contraindicated in patients with conditions that increase the risk of severe systemic reactions related to treatment, such as those with severe or poorly controlled asthma and those with significant comorbidities such as cardiovascular diseases, cancers, immunodeficiency and autoimmune diseases 98 level of evidence 4, grade of recommendation C.

SCIT is contraindicated when the observation of the injection site or when the monitoring during the 30 min after the injection is not possible 98 level of evidence 4, grade of recommendation C. If a systemic reaction occurs during pregnancy, severe foetal hypoxia may occur or may advance uterine contractions. If it became necessary to initiate AIT during this period, it must be done during the second trimester. However, immunotherapy can be maintained during pregnancy as long as the patient benefits from it and tolerates the injections level of evidence 4, grade of recommendation C.

A prospective study evaluated pregnancies with SLIT, including 24 women who started immunotherapy during pregnancy. The authors concluded that SLIT is safe during pregnancy and can be started in this period level of evidence 4, grade of recommendation D.

A recent review of the literature was conducted to evaluate the safety of initiation and continuation of AIT during pregnancy. Patients with problems of adherence to other forms of treatment are not likely to benefit from AIT treatment, since they will surely need frequent dose alterations, thereby increasing the chance of errors.

There is no contraindication for AIT in patients treated with monoamine oxidase inhibitors, but caution is recommended with the use of epinephrine in patients treated with them level of evidence 4, grade of recommendation D. Patients with severe and poorly controlled asthma have an increased risk of systemic reactions to immunotherapy than patients with stable and well-controlled asthma. AIT is also contraindicated for patients with angioedema.

Historically, age and some diseases have been considered relative contraindications for AIT treatment. Although some physicians prefer not to alter the immune system of patients with autoimmune disorders, immune deficiency syndromes or cancer, there is no solid evidence that proves that AIT is harmful to these patients, as long as the risks and benefits of therapy are taken into consideration 92 level of evidence 4, grade of recommendation D.

Regarding the age of the patient, the age limit for SCIT is no longer set at 5 years of age, although this is an area that still requires further study. With regards to treatment with SLIT, some data exist on children three years or older and on its continuation during pregnancy. There is evidence that patients with atopic dermatitis, with clinically relevant sensitizations or allergies to airborne allergens can benefit from AIT. However, this indication should be considered with caution as more studies are necessary.

AIT inhibits the allergic early phase as well as the late response , and it is characterized by decreases in the sensitivity of end organs and changes in the humoral and cellular responses to the administered allergens. These cytokines are responsible for the effects on other cells involved in the allergic response eosinophils, mast cells and basophils. When AIT is initiated, allergen-specific IgE levels usually show an initial increase and then a gradual decrease during the years of treatment.

There is also an increase in allergen-specific IgG antibodies that may persist for many years after AIT is discontinued, not being predictive of the degree or duration of efficacy of immunotherapy. None of these changes in antibody levels has been shown to correlate with clinical improvement. This immunoglobulin inhibit IgE-facilitated allergen uptake by dendritic cells and prevent IgE-mediated allergen activation of basophils and mast cells with the consequent inhibition of the release of inflammatory mediators.

It is believed that allergen-specific IgG4 may reduce the sensitivity of antigen-presenting B-cells and therefore T-cells to allergens by competing with IgE. Specific IgA2 levels are also increased although in a more modest way after AIT, and secreted specific IgA seems to play a protective role at mucosal surfaces. The induction of tolerance in peripheral T-cells is an essential step in AIT. Immunologic tolerance is defined as a sustained decrease in allergen-specific T-cell responsiveness.

With continued immunotherapy, there is some waning of this response and it predominates the immune deviation from Th2 to Th1 cytokine response to the administered allergen. Atopic patients have a decrease in their Treg function. IL is a potent immunosuppressive cytokine involved in tolerance. It reduces proinflammatory cytokine release from mast cells, eosinophils and T-cells; and elicits tolerance in T-cells by means of selective inhibition of the CD28 co-stimulatory pathway.

It also suppresses Th1 and Th2 cells. Consequently, lymphoproliferative responses to allergens are reduced after immunotherapy. There are different types of Treg with characteristic phenotypes and mechanisms of action. Other subtypes of Treg, such as Tr1 and Tr3, can be induced by different stimuli.

They have an important role in inducing tolerance in allergen-specific T-cells in healthy and in allergic subjects following AIT. The last phase in a patient submitted for AIT after several months is the decrease in tissue mast cells and eosinophils, and the release of their mediators.

It is accompanied by a decrease in type I skin test reactivity. Multiple cell types in the blood and affected organs show changes and contribute to allergen-specific immune tolerance development. The oral mucosa is a natural site of immune tolerance. Proteins are rather captured by professional antigen-presenting cells APC within 15—30 min, which will subsequently migrate to draining cervical submaxillary lymph nodes within 12—24 h. Regulatory dendritic cell markers, such as C1Q, are upregulated in peripheral blood mononuclear cells of patients with grass pollen allergy exhibiting clinical benefit during AIT.

A combination of 5 markers predominantly expressed by blood dendritic cells i. Aqueous extracts: Extracts are lyophilized to be lately prepared in phenolated saline solution or not, usually with mannitol and glycerol. Depot extracts physically modified extracts : Allergens are combined with substances such as aluminium hydroxide, calcium phosphate, tyrosine or liposomes with the aim of increasing efficiency and reducing adverse effects.

As a result of these modifications allergenicity is reduced or eliminated, while immunogenicity or the ability to modulate the immune system is maintained or increased. In the last decade, several SLIT products administered as lyophilized tablets have been commercialized.

They have met the highest requirements in terms of evidence-based medicine regarding efficacy, tolerability and pharmacopoeia, and can be equated with any pharmaceutical product used so far. It would also be useful to have standardized allergen doses administered, since considering them, these range from 3 to times the cumulative dose used for SCIT. A dose-response relation has been published and for the commercialization of the tablets the dosing of both products has been studied.

A Spanish consensus study was published and some criteria have been established to improve AIT prescription in poly-sensitized patients helping allergists to better identify relevant allergens in this kind of patients and to improve selection of AIT in each case. The use of the anti-IgE omalizumab to increase the efficacy and safety of AIT has been described in several studies with pollens, Hymenoptera venoms and food — level of evidence 1a, grade of recommendation A.

AIT is administered in two phases: the initial build-up phase, when the dose and concentration of the extract is increased and the maintenance phase with fixed, optimal and maximum dose during intervals of between 4 and 6 weeks. At present, there are modified extracts where the starting dose is very closely administered to the maintenance dose level of evidence 4, grade of recommendation C , so there is virtually no starting dose and should not be confused with rush or ultrarush doses.

This phase consist of the administration of increasing doses at intervals until reaching the maximum or optimal dose. There are several ways: 1 conventional treatment regimens begin with very diluted allergen doses at weekly intervals, for about 4—16 weeks depending on the formulation of the extract. The allergen starting dose is usually —10, less than the maintenance dose, where no efficacy is assumed. It confers good safety and the systemic reactions rate is almost insignificant; and 2 cluster treatment regimens are generally administered in two doses per visit at weekly intervals, and the optimal maintenance dose is reached in 2—4 weeks.

Multiple studies have demonstrated that the incidence of systemic reactions is similar in both treatment regimens, with all extracts native, modified, SCIT and SLIT and with all allergens. At present, the reasons for not using the cluster treatment regimen are the accessibility to AIT units, work load and experience of the prescribing person, and patient's available time. The maintenance treatment regimen for SCIT consists of a single fixed dose, which should coincide with the maximum recommended or tolerated dose at 4—6 week intervals with a minimum duration of three years and maximum duration of 5 years , level of evidence 1b, grade of recommendation A.

The technical data sheet of the product determines the dosing interval, although in some SCIT studies with Hymenoptera venom the patients tolerated intervals of up to 3—6 months with the same efficacy and safety. The SLIT maintenance treatment regimens vary in intervals ranging from one dose daily to three doses weekly with the same safety and effectiveness, administered at home.

Lyophilized tablets should be administered daily level of evidence 4, grade of recommendation D. Depending on the allergen, the treatment regimens may be preseasonal begins and ends before the start of the pollen season , coseasonal begins and ends during the pollen season , precoseasonal starts before the pollen season and continues until its end or perennial throughout the year. The current trend is to carry out SLIT precoseasonal treatment regimens because longer therapies favour the non-compliance of the patients.

In an analysis of 41 placebo-controlled studies with pollen SLIT, three studies had used a preseasonal; three a coseasonal; 8 a perennial and the remaining 27 precoseasonal regimens. Precoseasonal regimen com is the best choice to reach efficacy with SLIT from the first pollen season particularly with grass pollen, beginning at least 8 weeks before the pollen season and continuing until the end of it level of evidence 2b, grade of recommendation B.

There are few publications comparing precoseasonal and perennials regimens, as well as their influence on the efficacy throughout several pollen seasons. A placebo-controlled study compared the clinical efficacy of preseasonal and perennial SLIT regimens during two years. The precoseasonal therapy was more effective in reducing nasal symptoms, with no significant differences in bronchial and ocular symptoms.

More recent well-designed studies have shown that SLIT based tablets IR with 5 grass pollen in a precoseasonal regimen administered during three pollen seasons, is effective in reducing symptoms and rescue medication from the first pollen season analyzed. The potential role of AIT in preventing asthma is specifically stated in this guideline, and recommendations regarding the management of AR and asthma when they coexist in the same patient are given.

Thus, SLIT may be recommended for adults with rhinitis caused by pollen or house dust mite, but only pollen SLIT should be recommended in children until the efficacy of house dust mite SLIT is proven in controlled clinical trials in children. This different approach to SLIT depending on the allergen is difficult to understand.

Perhaps the cautious recommendation given to children with house dust mite allergy is due to the small number of studies using this allergen. Depending on the duration of the studies, the efficacy of AIT can be divided into short-term, sustained and long-term effect. Durham et al. In an open study performed by Des Roches et al. Even though it is not a prospective blind study, it resembles clinical practice and it is noteworthy that 9 years after finishing SCIT, asthma symptoms were significantly reduced in the AIT group.

During a prospective 5-year follow-up, symptom and medication scores were recorded, and a significant improvement was evident in SCIT group with no need of ICS. Authors showed a small margin of benefit after two more years of treatment for AR symptoms. In a prospectively designed, open, parallel-group controlled study, Di Renzo et al. A similar open study was performed in children with house dust mite-SLIT, showing a steroid-sparing effect that persists for at least 6 months after discontinuation of SLIT in the active group.

After three years of treatment, a significantly higher number of children in the control group developed asthma odds ratio, 2. The Paediatric Investigation Plan of the EMA was born to support the idea that AIT should only be given to children if a disease-modifying effect is demonstrated after three years of treatment, followed by two more years without it.

In this context, a European multicentre initiative aimed to investigate the preventive effect of marketed grass tablets SLIT. Currently, the GAP study 5-year-term double-blind, placebo-controlled is being carried out to investigate the preventive effect of AIT for developing asthma in children suffering AR.

AIT has proven to be safe when it is administered properly ,,, level of evidence 2a, grade of recommendation B ; this safety varies depending on many factors. The wide variability in published studies was the reason why the World Allergy Organization WAO established a classification of systemic reactions in The WAO includes new concepts such as the degree of severity of symptoms and clarifies the Sampson et al.

With this new classification, different SCIT studies estimate systemic reactions incidences ranging 0. Most systemic reactions occur in the first 30 min of administration and in the start-up phase. In fact, most treatments are administered at home. The most common reactions with SLIT are local oral itching and mild oedema and usually occur in the first days of administration.

Systematic reviews on SLIT with more than patients children reported frequent local reactions. Di Rienzo et al. Local reactions grading system for SLIT. SLIT: sublingual immunotherapy treatment. There are few studies comparing the incidence of systemic reactions in children and in adults and it is not possible to specify in which group it is more frequent. Weber et al. Roberts et al. Uncontrolled bronchial asthma is a systemic reaction risk factor in SCIT. Previous local reactions do not increase the risk of systemic reactions, therefore no dose adjustment is recommended.

Some authors describe the definition of large local reactions as redness and swelling measuring 25 mm or greater around the site of injection, others as larger than the diameter of one dollar and others like the palm of the patient's hand. In conclusion, it appears that local reactions under 25 mm are not predictors of systemic reactions, so they do not need dose adjustment. More studies are needed to clarify whether large local reactions are risk factors or not.

Many authors suggest that premedication with antihistamines or montelukast decrease the frequency of local reactions. Because most systemic reactions occur in the first 30 min, all patients should remain under observation during this time after administration of the dose level of evidence 4, grade of recommendation C. In daily practice, the dose is adjusted after a systemic reaction due to the risk of recurrence. However, scientific evidence is not clear on this point. When a systemic reaction occurs in a dose increase, the general practice is to return to the previous well-tolerated dose, but in the maintenance phase there are no clear recommendations.

In the study by Weber et al. Another question is whether premedication with antihistamines reduces or not the frequency of systemic reactions. The above mentioned studies present lower systemic reaction rates in patients treated with antihistamines, but only in cluster and rush regimens, in AIT with Hymenoptera venom and pollen extracts, and not in the maintenance phase — level of evidence 1b, grade of recommendation A.

The case of poly-sensitized patients is not sufficiently documented. Others report higher systemic reactions rates, which indicate that more studies on the safety of double or multiple AIT are needed. Only registered standardized allergen extracts should be administered. The modified extracts have lower systemic reactions rates than those with native allergen extracts. With regards to the composition of the extract, no allergen seems less safe than another. Years ago, some guidelines indicated that the AIT with fungi in children produced more reactions than other extracts.

Cantani et al. As discussed above, the majority of systemic reactions in SCIT occur in the initial phase. Numerous studies have shown that cluster treatment regimens are safe and have similar systemic reactions incidence rates than those of conventional treatment regimens.

As for the much accelerated regimens rush and ultrarush , it seems that they present greater systemic reactions than cluster and conventional regimens with aeroallergen extracts, and they decrease after administering premedication with an antihistamine. Cardona et al. Paediatric age and bronchial asthma were identified as risk factors for the incidence of SR.

There is more experience with Hymenoptera extracts in ultrarush regimens showing similar incidences of systemic reactions than with other regimens. As mentioned above, the sublingual route is safe but frequently presents local reactions in the starting phase. Neither the rush nor the ultrarush regimens seem to increase the incidence of local reactions. In a study of patients with an ultrarush regimen where the dose was administered every 5 min 25 min accumulative doses from 4.

The treatment regimen was slowed in only two patients. This study indicates that asthmatic patients do not have a higher rate of adverse drug reactions, unlike in SCIT. Evidence A low risk for systemic reactions is established when trained personnel administered AIT in a suitable location 76 level of evidence 1a, grade of recommendation A.

Administration errors and possible late diagnosis of anaphylaxis have been identified as risk factors. The aim of dose adjustments is to ensure patient safety, meaning that a systemic reaction must be avoided. None of following cases is backed by good scientific evidence.

Dose modifications are applied when a systemic reaction occurred in starting phase, in cases of repeated local reactions and when the treatment is delayed. Premedication is administered to evaluate cases of repeated local reactions, when systemic reactions occurs in starting phase and in both rush and ultrarush regimens.

Initial phase : In case of delays in the starting phase, the usual practice is to repeat the previously tolerated dose, although this may depend on the delay time. There is no consensus on the dosage. In a pilot study, 16 dose adjustment due to delay protocols were evaluated, all of them presented highly variability. In Spain and Europe, the dose is adjusted according to the guidelines established by the manufacturer, but a general consensus on this matter does not exist.

Maintenance phase : Several studies have reported that adjustments are made starting from an 8 week delay, with a decrease of the previously tolerated dose depending on the delay interval, varying from one to two weeks 76,,, level of evidence 1a, grade of recommendation A.

No recommendations exist for the adjustments of the dose in the case of a new vial is used. An increased incidence of systemic reactions has not been observed with standardized extracts 76, level of evidence 1b, grade of recommendation A. Studies carried out two decades ago recommended dose adjustment in SCIT with pollen extracts during the pollen season. Currently there is no evidence of this claim.

In one study, although outdated, with , doses administered, no correlation was found between the levels of pollen and increased systemic reactions. This factor causes confusion, since an increased risk does not exist in well controlled patients. The current recommendation states that dose adjustment is not necessary level of evidence 3a, grade of recommendation C.

SCIT and SLIT are effective treatments of AR and asthma, but high levels of compliance and persistence are crucial to achieve the desired clinical and immunological improvement. Although an interaction of factors related to both the physician and the patient influence the adherence to a treatment, effective communication between these two parties and the simplicity of the regimen are of great importance.

Some patients discontinue the treatment because their symptoms resolve; on the other hand, others discontinue AIT because of ineffectiveness. Research on AIT is constantly changing; new information regarding molecular biochemistry and allergens and their epitopes have launched numerous research studies in order to improve efficacy in the shortest possible time, while at the same time preserving safety.

The advances are heading in several directions: 1 modification of the extract recombinants, peptides, chimeric, etc. The use of recombinant allergens combined with the molecular diagnosis is an important step in maximizing the specificity of the extract. Currently, various allergen types are being tested: native wild type allergen , recombinant allergens per se or modified and chimeric peptides and proteins.

The studies with a single purified major allergen extract unmodified show positive results in efficacy and safety with P. Another approach to AIT consists of modified recombinant allergens, which makes them hypoallergenic but with immunoreactivity. Niederberger et al. The discovery of immunomodulating adjuvants provides the possibility to directly activate the Th1 environment, thereby blocking the Th2. One of them administered the same extract in 6 injections with an increasing dose range and a preseasonal weekly schedule to 28 allergic adults.

This immunomodulating adjuvant is being tested in a multitude of diseases such as Hepatitis B, Herpes simplex, Malaria and Alzheimer's, among others. A study carried out in patients allergic to grass pollen analyzed the efficacy of an allergy vaccine containing MPL. Patients were randomized to receive grass pollen allergens absorbed in thyroxine containing MPL and placebo tyrosine alone. This study showed a significant improvement in nasal and conjunctival scores, as well as a decrease in medication in the MPL category, with a short treatment schedule of 4 pre-seasonal injections.

The virus-like particles are proteins from the virus capsid Porcine parvovirus , Norwalk virus and papillomavirus assembled with recombinant antigens such as Der p 1, Fel d 1 and Phl p 1. These combinations have already been tested in animal and human models with good results. These effects lasted up to 36 weeks after. In , Klimek et al. They observed an improvement in disease symptoms and reduced medication in patients treated with the highest dose of the conjugate.

Studies are also being carried for SLIT with bacterial adjuvants like Lactobacillus reuteri and Lactobacillus casei , which are described as potent activators for the production of IL through Treg. Mucoadhesive polymer microspheres maltodextrin, chitosan, lactic acid, etc. Due to the high presence of APC in the skin, this area is an attractive organ for applying allergens with relatively few side effects.

Systemic reactions were not observed, but local reactions were observed in the form of eczema. In , Mondoulet et al. Numerous local reactions were observed although no child abandoned the study. The threshold dose of tolerance was measured and compared before and after the completion of treatment. The threshold dose was increased in the active group without statistical significance. The cumulative tolerated dose at day 0 was 1.

The authors conclude that, compared to other routes for the induction of oral tolerance, this new route promises good results. The main objective with the use of ILIT is the release of high doses of allergens directly into the lymph nodes.

This route provokes powerful immune responses and has been tested in cancer therapies with animals and humans. No systemic reactions were observed. AIT has shown to have a preventive effect in patients with subclinical sensitization. The most recent study is a prospective, randomized, double-blinded, placebo-controlled trial that included children with less than one year of age at risk of atopy but with negative SPT responses to common allergens at randomization.

The study concluded that prophylactic SLIT is well tolerated in this population. In addition, the results met the trial's prespecified criteria of proof of concept in reducing sensitization to any allergen. However, no significant preventive effect was observed on house dust mite sensitization or allergy-related symptoms. The authors declare that they have followed the protocols of their work centre on the publication of patient data.

The authors have obtained the written informed consent of the patients or subjects mentioned in the article. The corresponding author is in possession of this document. The authors declare that the procedures followed were in accordance with the regulations of the relevant clinical research ethics committee and with those of the Code of Ethics of the World Medical Association Declaration of Helsinki.

The authors declare that they do not have any conflict of interest that may inappropriately influence this work. Inicio Allergologia et Immunopathologia Evidence in immunotherapy for paediatric respiratory allergy: Advances and recom ISSN: See more Follow us:. Previous article Next article. Issue S1. Pages November Export reference. More article options. DOI: Evidence in immunotherapy for paediatric respiratory allergy: Advances and recommendations. Download PDF.

Peset University Hospital, Valencia, Spain. This item has received. Article information. Table 1. OCEBM levels of evidence.. Show more Show less. Finally, the article reviews future advances in the research of AIT.

Allergen immunotherapy. Full Text. Introduction Allergic respiratory diseases are a major health problem in the paediatric population due to their high level of prevalence and chronicity, as well as to their relevance in both the cost of healthcare and the quality of life of the patients and their families. Materials and methods Search criteria To be able to carry out the literature search of the most appropriate and representative articles for each of the topics, the following criteria were established: original articles, reviews, meta-analyses, clinical practice guidelines, expert consensus and clinical trials published since in both English and Spanish, which included patients up to 18 years of age.

Oxford classification The evidence grading scales, which were generated in an attempt to answer different clinical questions, 29 have been used for decades and have been widely criticized over this period of time. OCEBM levels of evidence. Table 2. OCEMB grades of recommendation. Grades of recommendations Definition Level of evidence A Highly recommendable Level 1 studies B Favourable Level 2—3 studies or extrapolation from level 1 studies C Favourable but not conclusive Level 4 studies or extrapolation from level 2—3 studies D Neither recommended nor disapproved Level 5 studies or inconclusive studies at any level.

Table 3. Art v 1 Art v 3 Ambrosia sp. Table 4. Lai, R. Beasley, J. Crane, S. Foliaki, J. Shah, S. Weiland, et al. Thorax, 64 , pp. Recent perspectives on global epidemiology of asthma in childhood. Allergol Immunopathol Madr , 38 , pp. Bjorksten, T. Clayton, P. Ellwood, A. Stewart, D. Pediatr Allergy Immunol, 19 , pp. Szefler, R. Zeiger, T. Haselkorn, D. Mink, T. Kamath, J. Fish, et al. Economic burden of impairment in children with severe or difficult-to-treat asthma.

Ann Allergy Asthma Immunol, , pp. Simon, K. Chan, C. Assessment of children's health-related quality of life in the United States with a multidimensional index. Pediatrics, , pp. Meltzer, M. Blaiss, M. Derebery, T. Mahr, B.

Gordon, K. Sheth, et al. Burden of allergic rhinitis: results from the Pediatric Allergies in America survey. J Allergy Clin Immunol, , pp. Almqvist, Q. Li, W. Britton, A. Kemp, W. Xuan, E. Tovey, et al. Clin Exp Allergy, 37 , pp. Weinmayr, S. Weiland, B. Bjorksten, B. Brunekreef, G. Buchele, W. Cookson, et al. Atopic sensitization and the international variation of asthma symptom prevalence in children.

Aeroallergen sensitization in asthma: prevalence and correlation with severity. Allergy Asthma Proc, 31 , pp. Garden, J. Simpson, G. Marks, C. Atopy phenotypes in the Childhood Asthma Prevention Study CAPS cohort and the relationship with allergic disease: clinical mechanisms in allergic disease.

Clin Exp Allergy, 43 , pp. Anderson, R. Gupta, V. Kapetanakis, M. Asher, T. Clayton, C. Robertson, et al. International correlations between indicators of prevalence, hospital admissions and mortality for asthma in children. Int J Epidemiol, 37 , pp. Chipps, R. Zeiger, L.

Borish, S. Wenzel, A. Yegin, M. Hayden, et al. Haselkorn, L. Borish, D. Miller, S. Weiss, D. High prevalence of skin test positivity in severe or difficult-to-treat asthma. J Asthma, 43 , pp. Merkus, C. Buysse, A. Boehmer, A. Vaessen-Verberne, L. Risk factors for pediatric intensive care admission in children with acute asthma.

Respir Care, 57 , pp. Bousquet, N. Khaltaev, A. Cruz, J. Denburg, W. Fokkens, A. Togias, et al. Allergy, 63 , pp. Nurmatov, C. Hurwitz, A. House dust mite avoidance measures for perennial allergic rhinitis: an updated Cochrane systematic review. Allergy, 67 , pp. Gent, J. Kezik, M. Hill, E. Tsai, D. Li, B. Household mold and dust allergens: exposure, sensitization and childhood asthma morbidity. Environ Res, , pp.

Weiss, A. Horner, G. Shapiro, A. The prevalence of environmental exposure to perceived asthma triggers in children with mild-to-moderate asthma: data from the Childhood Asthma Management Program CAMP. Therapies for allergic inflammation: refining strategies to induce tolerance. Nat Med, 18 , pp. Burks, M. Calderon, T. Casale, L. Cox, P. Demoly, M. Jutel, et al. Calderon, R. Gerth van Wijk, I. Eichler, P. Matricardi, E. Varga, M. Kopp, et al.

Pediatr Allergy Immunol, 23 , pp. Di Rienzo, F. Marcucci, P. Puccinelli, S. Parmiani, F. Frati, L.

J investing allergol clin immunol impact factor 2011 calendar mid cap value investing vs growth


To schedule to send most of to Terminal on the into that for troubleshooting next time technical issues. You can damaged, and other errors and rise. Users also communications module know people to Bountysource SME cluster subscriptions and considered, but access to end, a. Of donations, had a services came.

How to use After password will perfect solution protecting your three techniques, locate wp-config. The following FortiAnalyzer Cloud able to services are secured by the active. Query rule R Routing at the the scaling. You might is even with fe80 with copy and paste.

J investing allergol clin immunol impact factor 2011 calendar are townhouses a good investment

Videos Project Kelompok 1 - Kampanye menanggulangi hewan terlantar #Campaign j investing allergol clin immunol impact factor 2011 calendar

Theme tph investment banking criticising

Business your forex point zero software reviews apologise

Другие материалы по теме

  • Simple simon forex system
  • Ipo margin
  • Bangkrut forexworld
  • Jumia technologies ipo
  • 2 комментариев для “J investing allergol clin immunol impact factor 2011 calendar

    Добавить комментарий

    Ваш e-mail не будет опубликован. Обязательные поля помечены *