Grading local side effects of sublingual immunotherapy for respiratory allergy: speaking the same language.

Sublingual immunotherapy (SLIT) is increasingly used worldwide. Despite its safety being well ascertained, there is no universally accepted system to grade and classify its adverse events (AEs). According to the literature, it seems reasonable to classify and grade systemic side effects by using the previously published World Allergy Organization recommendations. On the other hand, local side effects are the most frequent with SLIT, sometimes leading to its discontinuation. Therefore grading of the severity of local side effects was perceived as necessary for the purpose of uniform reporting, classification, and quantification of this aspect. A World Allergy Organization Taskforce, after examining the available literature and the postmarketing surveillance data, proposed a clinically based grading of the severity of local AEs caused by SLIT. The use of the Medical Dictionary for Regulatory Activities nomenclature for AEs was also included in this context. The proposed grading system for SLIT-induced local reactions is expected to improve and harmonize surveillance and reporting of the safety of SLIT.

100 years of immunotherapy: the Monaco charter. under the high patronage of His Serene Highness Prince Albert II of Monaco.

Aims of the Monaco Charter: (1) to present the current evidence on the efficacy and safety of allergen-specific immunotherapy (SIT) and to address the reasons for its underuse in clinical practice; (2) to develop strategies to increase the awareness about the benefits and the hazards of SIT in allergic patients, lay public and healthcare professionals not trained in allergy, and (3) to make SIT accessible and affordable to eligible patients.

Pediatric sublingual immunotherapy efficacy: evidence analysis, 2009-2012.

OBJECTIVE: To perform a structured analysis of the latest scientific evidence obtained for the clinical efficacy of sublingual immunotherapy (SLIT) in children. DATA SOURCES: PubMed, Embase, reference lists from reviews, and personal databases were reviewed for original articles on clinical trials with SLIT in patients younger than 18 years published from January 1, 2009, through December 31, 2012, using broad search and medical subject heading terms. STUDY SELECTIONS: Clinical trials, irrespective of their design, of SLIT in the treatment of respiratory and food allergy in patients 18 years or younger were selected. Clinical outcomes (symptom scores, medication use, provocation tests, pulmonary function tests, skin prick tests, and adverse events) and immunologic changes were tabulated. Quality of each trial and total quality of compounded evidence was analyzed with the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS: Of 56 articles, 29 met the inclusion criteria. New evidence is robust for the precoseasonal tablet and drop grass pollen SLIT efficacy in allergic rhinitis and scarce for seasonal asthma. Some evidence for Alternaria SLIT efficacy is appearing. For house dust mite (HDM) SLIT in asthma, there is high-quality evidence for medication reduction while maintaining symptom control; evidence for HDM SLIT efficacy in allergic rhinitis is of moderate-low quality. There is moderate evidence for efficacy of dual grass pollen-HDM SLIT after 12 months of treatment and 1 year after discontinuation. Specific provocation test results (nasal, skin) improve with grass pollen and HDM SLIT but nonspecific bronchial provocation testing does not. Food oral immunotherapy is more promising than food SLIT. Possible new surrogate markers have been reported. No anaphylaxis was found among 2469 treated children. CONCLUSION: Evidence for efficacy of SLIT in children with respiratory or food allergy is growing.

Allergy training and immunotherapy in Latin America: results of a regional overview.

BACKGROUND: One main practice gap in allergology that has been detected in several regions of the world is the application of specific immunotherapy (SIT). The prescription and practice of SIT should characterize allergologic specialists, but there are regional discrepancies in such practice. A detailed knowledge of the regulatory and legislation aspects and drawbacks would help improve and harmonize SIT practice. OBJECTIVE: To describe in Latin America the level of allergy training and the characteristics of the use of SIT, including the medical and legal aspects. METHODS: Three sources were used: a 24-item questionnaire sent to 22 allergologic leaders in 11 Latin American countries, 2 face-to-face meetings, and information from health authorities involved in the approval of medical substances. RESULTS: In 56% of countries, the specialty of allergology is a third-level care specialty and/or a subspecialty. Two countries have a special training program for pediatric allergists. Passing a board examination is mandatory in 3 countries, and recertification every 2 to 5 years occurs without examination. Sublingual and subcutaneous SITs are available in all Latin American countries. No legislation restricts SIT prescription and it can be performed by nonspecialists in 7 of 11 countries. In 90% of countries, allergists use allergen extracts from the United States (subcutaneous immunotherapy) and Europe (sublingual and subcutaneous immunotherapies), and 50% also manufacture extracts locally. Only 1 country has legal requirements for the quality of raw materials. CONCLUSION: The present analysis helps to identify gaps in the field of allergologic training and SIT in Latin America, many of them amendable.

Will sublingual immunotherapy offer benefit for asthma?

Evidence shows that sublingual immunotherapy (SLIT) is indicated in patients with allergic rhinitis (AR). In this article we discuss whether SLIT could offer benefit for children and adults with asthma.We reviewed individual trials on SLIT in asthmatic patients, but also asthma data reported in some SLIT trials conducted in AR patients. Findings were complemented with data from systematic reviews and metaanalysis on the subject since 2000 and some guidelines that mention immunotherapy for asthma treatment. In AR patients with concomitant persistent asthma, SLIT reduces medication needs while maintaining symptom control. This holds especially true for house dust mite SLIT. Data on pollen SLIT and lung symptom improvement with SLIT, however, are less convincing. Therefore, we suggest SLIT should be added as an optional add-on therapy for patients with asthma whenever a causative allergen has been demonstrated and AR is associated with asthma. For the future, SLIT should be studied in specifically designed asthma studies in allergic asthmatics without AR.

Diagnosis of occupational asthma: an update.

Work-related asthma (WRA) includes patients with sensitizer- and/or irritant-induced asthma in the workplace, as well as patients with preexisting asthma that is worsened by work factors. WRA is underdiagnosed; thus, the diagnosis is critical to prevent disease progression and its potential for morbidity and mortality. The interview is the first diagnostic tool to be used by physicians, and the question, "Does asthma improve away from work?" is of the highest sensitivity. However, history can show numerous false positives, and the relationships between asthma worsening and work should be confirmed by objective methods such as peak expiratory flow (PEF) at and away from work. PEF sensitivity and specificity can be enhanced in combination with nonspecific bronchial hyperresponsiveness to histamine/methacholine (NSBP) before and after 2 weeks at work and a similar period off work. Immunologic testing, especially skin prick test (SPT) or specific IgE, is useful for high molecular weight allergens and some low molecular weight agents. Other immunologic tests, as well as induced sputum, measurement of exhaled nitric oxide, exhaled breath condensate, and specific inhalation challenge (SIC) are methods that contribute to the diagnosis and are typically performed at specialized facilities. A diagnosis of occupational asthma (OA) should no longer be based on a compatible history only but should be confirmed by means of objective testing. SIC is the diagnostic gold standard. When SIC is not available, the combination of PEF measurement, NSBP test , a specific SPT, or specific IgE may be an appropriate alternative in diagnosing OA.

Diagnosis of allergy and asthma in childhood.

Childhood asthma is a widespread health problem because of its epidemic prevalence, as asthma affects more than 300 million people worldwide. Results from cross-sectional and cohort studies show that asthma starts in childhood in a large proportion of cases. A proper diagnosis is easier to make in adults and school-age children, as permanent changes in lung development, the strong impact of environmental factors on the airways, the immunologic maturity process, and the use of some diagnostic tools make asthma more difficult to diagnose in preschool children. This period of a child's life is an interesting challenge for pediatricians and specialists. The aim of the present review is to analyze the current knowledge regarding making an early and accurate asthma diagnosis and therefore deciding on the correct treatment to gain control over asthma symptoms and minimize health risks.

Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 revision.

BACKGROUND: Allergic rhinitis represents a global health problem affecting 10% to 20% of the population. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines have been widely used to treat the approximately 500 million affected patients globally. OBJECTIVE: To develop explicit, unambiguous, and transparent clinical recommendations systematically for treatment of allergic rhinitis on the basis of current best evidence. METHODS: The authors updated ARIA clinical recommendations in collaboration with Global Allergy and Asthma European Network following the approach suggested by the Grading of Recommendations Assessment, Development and Evaluation working group. RESULTS: This article presents recommendations about the prevention of allergic diseases, the use of oral and topical medications, allergen specific immunotherapy, and complementary treatments in patients with allergic rhinitis as well as patients with both allergic rhinitis and asthma. The guideline panel developed evidence profiles for each recommendation and considered health benefits and harms, burden, patient preferences, and resource use, when appropriate, to formulate recommendations for patients, clinicians, and other health care professionals. CONCLUSION: These are the most recent and currently the most systematically and transparently developed recommendations about the treatment of allergic rhinitis in adults and children. Patients, clinicians, and policy makers are encouraged to use these recommendations in their daily practice and to support their decisions.

Uniform definition of asthma severity, control, and exacerbations: document presented for the World Health Organization Consultation on Severe Asthma.

Asthma is a global health problem affecting around 300 million individuals of all ages, ethnic groups and countries. It is estimated that around 250,000 people die prematurely each year as a result of asthma. Concepts of asthma severity and control are important in evaluating patients and their response to treatment, as well as for public health, registries, and research (clinical trials, epidemiologic, genetic, and mechanistic studies), but the terminology applied is not standardized, and terms are often used interchangeably. A common international approach is favored to define severe asthma, uncontrolled asthma, and when the 2 coincide, although adaptation may be required in accordance with local conditions. A World Health Organization meeting was convened April 5-6, 2009, to propose a uniform definition of severe asthma. An article was written by a group of experts and reviewed by the Global Alliance against Chronic Respiratory Diseases review group. Severe asthma is defined by the level of current clinical control and risks as "Uncontrolled asthma which can result in risk of frequent severe exacerbations (or death) and/or adverse reactions to medications and/or chronic morbidity (including impaired lung function or reduced lung growth in children)." Severe asthma includes 3 groups, each carrying different public health messages and challenges: (1) untreated severe asthma, (2) difficult-to-treat severe asthma, and (3) treatment-resistant severe asthma. The last group includes asthma for which control is not achieved despite the highest level of recommended treatment and asthma for which control can be maintained only with the highest level of recommended treatment.

Metaanalysis of the efficacy of sublingual immunotherapy in the treatment of allergic asthma in pediatric patients, 3 to 18 years of age.

BACKGROUND: Recent studies have documented the efficacy and safety of sublingual immunotherapy (SLIT) in patients with rhinitis, but the value of this treatment in those with asthma is still debated. We evaluated the efficacy of SLIT in the treatment of allergic asthma in children by a metaanalysis of randomized, double-blind, and placebo-controlled (DBPC) clinical trials. METHODS: Electronic databases were searched up to May 31, 2006, for randomized DBPC trials assessing SLIT in pediatric cases of asthma. Effects on primary outcomes (ie, symptom scores and concomitant use of rescue medication) were calculated with standardized mean differences (SMDs) using the random-effects model. We performed the metaanalysis using a statistical software package (RevMan, 4.2.8; The Cochrane Collaboration; Oxford, UK), and we followed the recommendations of the Cochrane Collaboration and the Quality of Reporting of Metaanalyses guidelines. RESULTS: Seventy-three articles were identified and reviewed. Nine studies, all published after 1990, fulfilled the selection criteria. A total of 441 patients had a final assessment and were included in the analysis. Two hundred thirty-two patients received SLIT, and 209 patients received placebo. The results of the present analysis demonstrated a relevant heterogeneity due to widely differing scoring systems. Overall, there was a significant reduction in both symptoms (SMD - 1.14; 95% confidence interval [CI], - 2.10 to - 0.18; p = 0.02) and medication use (SMD, - 1.63; 95% CI, - 2.83 to - 0.44; p = 0.007) following SLIT. CONCLUSION: SLIT with standardized extracts reduces both symptom scores and rescue medication use in children with allergic asthma compared with placebo.

New perspectives in the treatment of allergic rhinitis and asthma in children.

PURPOSE OF REVIEW: Allergic rhinitis and asthma are some of the most prevalent chronic diseases in children. Meticulous evaluations of the therapeutic options and interventions are needed to control this burden. The central pathogenic mechanism is an immediate hypersensitivity reaction, followed by interventions in the allergic cascade. Once inflammation is established, potent anti-inflammatory agents or mediator antagonists could help control the phenomenon and reduce the characteristic symptoms related to severity. RECENT FINDINGS: Monoclonal antibody against IgE has demonstrated its efficacy in reducing the symptoms of asthma and rhinitis. In difficult-to-treat asthma patients it allows a reduction in the dose of inhaled steroids, the number of exacerbations, emergency visits and hospitalizations. Its broad implementation is limited by its high cost because adverse events are not a concern. Specific sublingual immunotherapy gave promising results in clinical trials, while modifying immunoglobulins and cytokine profiles, also inducing T-cell tolerance. Safety issues of subcutaneous immunotherapy have been surpassed by the sublingual route, with equivalent efficacy. The new inhaled steroid ciclesonide is effective in established inflammation, is activated only in the respiratory system, and has negligible systemic effects. SUMMARY: Robust evidence on the efficacy and safety of several novel therapies in rhinitis and asthma is available.

Why a registry of Chronic Urticaria (CUR) is needed.

Chronic urticaria (CU) has a major effect on patients' quality of life. While there have been progressive advances regarding its pathogenesis and treatment, much remains to be done. Registries of other chronic non-communicable diseases have shown many benefits, such as additional basic knowledge and management approaches to diabetes mellitus. Standards of care as well as diagnostic approaches can be elaborated and compared from different sites, using validated instruments. Registries in allergic diseases are also becoming well recognized, and the first registry on CU, accessible from SLaai's webpage, includes parameters for identification, evaluation and management. In our vision, informatics strategies have the potential to improve care for chronic illnesses such as CU. The registry represents a valid instrument from which to obtain a sufficient sample size for epidemiological studies and/or clinical research planning, including feasibility and potential enrollment. It can also provide invaluable data for adapting guidelines to local populations, as well as diagnostic approaches and cost-effective interventions in the context of organizational efforts to improve patient care.

Risk factors for asthma and atopy.

PURPOSE OF REVIEW: The aim of this article is to provide information on risk factors associated with the development of atopy and asthma in childhood. RECENT FINDINGS: Several gene polymorphisms have been associated with susceptibility to asthma and allergy; complex gene-environmental interactions, however, appear to play a key role in the development of the disease. Early life sensitization to aeroallergens, presence of atopic dermatitis or allergic rhinitis, maternal smoking during pregnancy and children's environmental exposure to tobacco smoke, lower respiratory tract infections with respiratory syncytial virus and potentially with other viruses including rhinovirus and metapneumovirus, exposure to air pollutants, several perinatal factors other than maternal smoking, are among factors associated with an increased risk for development of chronic asthma. SUMMARY: The prevalence of asthma and allergic diseases is increasing progressively. Those who are involved in the care of young children should be prepared to recognize risk factors for development of these diseases and to appreciate the role of gene-environment interactions. Preventive measures established at an early age may modify the natural history of asthma and other allergic diseases.

Sublingual immunotherapy in pediatric patients: beyond clinical efficacy.

PURPOSE OF REVIEW: Sublingual immunotherapy (SLIT) is widely used in several European countries. Many clinical trials and a meta-analysis presently support its efficacy, but limits and indications in pediatric age still need to be clarified. We review here the most recent literature on SLIT, with particular attention paid to the safety of children and to the additional clinical effects. RECENT FINDINGS: In addition to clinical trials, post-marketing surveillance studies have confirmed the optimal safety profile of SLIT in adults and children, including those below the age of 5 years. The most recent studies have shown that SLIT, identically to the subcutaneous route, has the potential to affect the immunological response to allergens. This is testified to by the facts that SLIT can prevent the onset of new sensitizations and maintain its beneficial effect for years after discontinuation. Moreover, it has been shown that SLIT can prevent the onset of asthma in children with rhinitis. SUMMARY: Due to its excellent safety, SLIT would be an optimal candidate for use in pediatric age groups, where the natural history of allergy can be to some extent modified. Nonetheless, formal and rigorous studies are needed to define its exact indication and dosage.

Four-year follow-up in children with moderate/severe uncontrolled asthma after withdrawal of a 1-year omalizumab treatment.

PURPOSE OF REVIEW: Allergic asthma, which is the most frequent asthma phenotype, is mainly a chronic inflammatory disease characterized by elevated serum IgE levels and specific-IgE against common allergens. A significant group of asthmatic children have uncontrolled moderate/severe symptoms despite the use of medium/high doses of inhaled corticosteroids (ICS) in combination with another controller. Asthma guidelines suggest omalizumab as an add-on therapy in these children and recent evidence has shown the efficacy and safety of this mAb against IgE. RECENT FINDINGS: Asthma cannot be cured and current available treatments are unable to modify the natural course of the disease. Recent studies have shown positive effects of omalizumab in reducing airway inflammation and remodelling. Herein, a 4-year follow-up of a group of children with moderate/severe uncontrolled asthma taking part in a randomized double blind placebo control with omalizumab is shown. After discontinuation of anti-IgE, children were followed up for 4 years. During the first 3 years of follow-up, they were completely free of asthma symptoms without any need of ICS or rescue medication. SUMMARY: The new evidence published and the clinical observation described herein generate the hypothesis that treatment with omalizumab could potentially modify the natural course of asthma. However, further studies are needed.

The international survey on the management of allergic rhinitis by physicians and patients (ISMAR).

Epidemiologic studies suggest that the prevalence of allergic rhinitis (AR) is rising worldwide. Several reports, in fact, indicate increasing trends in the prevalence of AR especially in developing countries, likely related to the environment and climate changes and the adoption of an urbanized Western lifestyle. The primary objective of the present study was to collect information about management in real-life settings, including a characterization of typical patients' profile referring to physicians, the disease features, the common approaches to diagnostic assessments and therapeutic decisions. This was an international, multicenter, cross-sectional study conducted in adults or children (≥6 years) suffering from rhinitis confirmed by physician's diagnosis for at least one year. The 234 physicians who participated in the study included a total of 2778 patients in Egypt, Mexico, Brazil, Colombia, Guatemala, Iran, Venezuela, Argentina, Israel, Kuwait and United Arab Emirates. It was found that clinical history was the selected tool to diagnose and categorize AR patients (97.1%), with less than half of patients undergoing allergy testing, may be explaining the scarce use of immunotherapy on management of disease. Out of 2776 patients, 93.4% had somehow received a recommendation to avoid allergens and irritant agent exposure. Notably, 91.4% were receiving at least one treatment at the time of the survey, mostly oral antihistamines (79.7%) and intranasal corticosteroids (66.3%). Oral antihistamines, intranasal steroids and decongestants were considered both safe and effective by patients and physicians, preferring oral and nasal route of administration. The ISMAR registry was designed according to the most accepted epidemiological recommendations, and provides interesting information regarding the management of rhinitis from a patient and physician points of view, with many similarities between the participating countries. Further efforts are required to better manage AR and its comorbidities.

Drug-Induced Anaphylaxis in Latin American Countries.

BACKGROUND: Information regarding the clinical features and management of drug-induced anaphylaxis (DIA) in Latin America is lacking. OBJECTIVE: The objective of this study was to assess implicated medications, demographics, and treatments received for DIA in Latin American patients referred to national specialty centers for evaluation. METHOD: A database previously used to compile information on drug-induced allergic reactions in 11 Latin American countries was used to identify and characterize patients presenting specifically with a clinical diagnosis of DIA. Information regarding clinical presentation, causative agent(s), diagnostic studies performed, treatment, and contributing factors associated with increased reaction severity was analyzed. RESULTS: There were 1005 patients evaluated for possible drug hypersensitivity reactions during the study interval, and 264 (26.3%) met criteria for DIA. DIA was more frequent in adults and in elderly females (N = 129 [76.6%] and N = 30 [75%], respectively) compared with children and/or adolescents (N = 21 [42.9%], P < .01). Severe DIA was less frequent with underlying asthma (N = 22 vs 35 [38.6% vs 61.4%], P < .05) or atopy (N = 62 vs 71 [43% vs 59% ], P < .01). Nonsteroidal anti-inflammatory drugs (NSAIDs) (N = 178 [57.8%]), beta-lactam antibiotics (N = 44 [14.3%]), and other antibiotics (N = 16 [5.2%]) were the most frequently implicated drug classes. Anaphylaxis was rated as severe in N = 133 (50.4%) and anaphylactic shock (AS) was present in N = 90 (34.1%). Epinephrine was only used in N = 73 (27.6%) overall, but in N = 70 (77.8%) of patients with AS. CONCLUSION: In Latin American patients referred for evaluation of DIA, NSAIDs and antibiotics were implicated in approximately 80% of cases. Most of these reactions were treated in the emergency department. Epinephrine was administered in only 27.6% of all cases, although more frequently for anaphylactic shock. Dissemination of anaphylaxis guidelines among emergency department physicians should be encouraged to improve management of DIA.