Abstract: Recombinant and purified allergens are currently available for determining specific IgE targeted to different allergenic components. In this way it is possible to diagnose the sensitization profile of each individual patient. The microarray technique makes it possible to determine specific IgE against multiple allergens simultaneously in one same patient, with a minimum amount of serum, and even allows the determination of IgG and IgM against the same allergens in one same serum sample. Microarray procedures are being developed not only for the determination of antibodies but also for cell activation tests. In addition, microarray technology will help explain cross-reactions, and will facilitate the evaluation of subjects in which skin tests cannot be performed. These techniques will allow a great step forward in the development of immunotherapy specifically targeted to the sensitizations found in each individual patient, yielding especially hypoallergenic forms of great immunogenic capacity, and thus improving the safety and efficacy of immunotherapy. Lastly, microarrays will improve our understanding of the physiopathology of allergic diseases.
Abstract: Allergic conjunctivitis is the most common form of ophthalmological allergy. Eye symptoms are one of the main and most frequent reasons for consultation among patients with allergic rhinoconjunctivitis, which in turn is the most common reason for visiting the allergologist, according to the Alergológica 2005 study. Itching is the key symptom of allergic conjunctivitis, and its relief is the principal objective of the broad range of treatment options available. Topical antihistamines with multiple actions (mast cell stabilization, and antiinflammatory and antihistaminic actions) are probably the best treatment option, thanks to their rapid action, safety and convenience of use. However, oral antihistamines (preferentially second generation drugs) can also play an important role, since they are of established efficacy and offer adequate treatment of the nasal symptoms that tend to accompany the ocular manifestations of allergic rhinoconjunctivitis. Models of allergic conjunctivitis are useful for investigational purposes and for advancing our knowledge of allergic reactions. Advances in the study of the physiopathology of ocular allergy allow us to introduce new therapeutic options for the management of such allergic reactions, thanks to the findings derived from models of this kind. The present review provides an update to the published data on allergic conjunctivitis and the current role of both topical and ocular antihistamines in treating the disorder.
Abstract: Pollinosis is defined as the appearance of respiratory symptoms (rhinoconjunctivitis and/or asthma) as a result of the inhalation of pollen to which the individual is sensitized. Pollen allergy becomes all the more relevant on taking into account that it may be responsible for the development of plant food allergy, or may even constitute the direct cause of esophageal, gastric and/or intestinal inflammation in the context of a digestive allergic process. Pollen can act as a source of allergens that induce primary sensitization in the host as a result of inhalation, with secondary allergy to plant foods containing shared allergens via a cross-reactivity mechanism. The observed pattern of plant food allergy depends on the dietary habits of the population in a given geographical setting, and on the pollination found in that setting. Pollinosis may account for the greater or lesser prevalence of allergy to certain plant foods, and for the severity of the associated reactions. Beyond the digestive tract inflammation that may result from allergy to a given food, pollinosis is also intrinsically able to generate a clinically relevant or irrelevant Th2-mediated inflammatory response at digestive level, and may even give rise to eosinophilic esophagitis. Inter-relation with the airway may also extend to the digestive tract as a consequence of the systemic response that characterizes allergic disease.
Abstract: The development of allergic rhinitis entails a complex interaction between genetic predisposition and environmental exposure to different factors, of which the most important is the implicated allergen. There is a clear hereditary component in allergic rhinitis that has been well corroborated by segregation studies and investigations in twins. From the strictly genetic perspective, it is believed that the disease may be the result of the interaction of different genetic alterations, each of which would contribute a small defect. In recent years, considerable attention has focused on the genes that may be implicated in allergic rhinitis. A number of genomic searches have been made, yielding different chromosomal associations--the most repeated being those involving chromosomes 2, 3, 4 and 9. Single-nucleotide polymorphism studies involving genes encoding for molecules implicated in the pathogenesis of allergic rhinitis have also been made. Such molecules comprise chemokines and their receptors, interleukins and their receptors, eosinophil peroxidase and leukotrienes, among others.
Abstract: BACKGROUND: Guidelines including level of evidence and grade of recommendation were recently published for chronic urticaria (CU). OBJECTIVES: To describe the therapeutic approach in patients with CU, and to depict how recent guidelines are implemented in the daily practice of management of CU. METHODS: We performed a cross-sectional multicentre study through a questionnaire answered by 139 specialists. In total, 695 patients were evaluated, mean+/-SD age 42.3+/-15 years, 62.1% women. Of the patients, 168 were treated by an allergist, 473 by a dermatologist and in 54 cases the specialist was not stated. The drug prescribed was the main variable, and chi2 and Fisher's tests were utilized for the statistical analysis. RESULTS: Nonsedating anti-H1 antihistamines taken regularly were the most common drugs prescribed, followed by nonsedating anti-H1 antihistamines taken as needed, corticosteroids, sedating antihistamines taken regularly, sedating antihistamines taken as needed, anti-H2 antihistamines, leukotriene antagonists, ciclosporin and doxepin. Nonsedating antihistamines plus corticosteroids was the most frequent drug combination prescribed. When comparing between allergists and dermatologists we found a positive and significant correlation only between prescription of cetirizine, dexchlorfeniramine, leukotriene antagonists and anti-H2 antihistamines and being treated by an allergist. A positive correlation was found with desloratadine and being seen by a dermatologist. We did not find any difference in CU management in the rest of the treatments studied. CONCLUSIONS: It is surprising that a large amount of sedating antihistamines was prescribed. In many instances these were prescribed as needed. This fact could have a negative impact on urticaria control and patient satisfaction. It seems difficult for the nonexpert to differentiate between CU and any kind of physical urticaria.
Abstract: Allergic rhinitis is presently the most common chronic disorder in the pediatric population. It can affect sleep at night and cause daytime sleepiness, with school absenteeism, "presenteeism" or inattention, mood disturbances and psychosocial problems. All this in turn can contribute to reduce school performance. The correct treatment of allergic rhinitis can improve school performance, though the first generation antihistamines have unacceptable central and anticholinergic effects that can actually worsen the situation. The second generation antihistamines constitute the drug treatment of choice for allergic rhinitis in children. Vasoconstrictors should not be used in pediatric patients, due to their unpredictable pharmacokinetics and very narrow therapeutic margin. Intranasal corticoids could improve school performance in some patients, by reducing nose block or congestion, the nocturnal sleep disturbances, and daytime sleepiness. Concrete studies of the impact of chromones, anticholinergic agents, antileukotrienes and immunotherapy upon school performance are lacking.
Abstract: In recent years it has been seen that the nervous and immune systems regulate each other reciprocally, thus giving rise to a new field of study known as psychoneuroimmunology. Stress is defined as a general body response to initially threatening external or internal demands, involving the mobilization of physiological and psychological resources to deal with them. In other words, stress is characterized by an imbalance between body demands and the capacity of the body to cope with them. The persistence of such a situation gives rise to chronic stress, which is the subject of the present study, considering its repercussions upon different organs and systems, with special emphasis on the immune system and--within the latter--upon the implications in relation to allergic disease. Activation of the neuroendocrine and sympathetic systems through catecholamine and cortisol secretion exerts an influence upon the immune system, modifying the balance between Th1/Th2 response in favor of Th2 action. It is not possible to affirm that chronic stress is intrinsically able to cause allergy, though the evidence of different studies suggests than in genetically susceptible individuals, such stress may favor the appearance of allergic disease on one hand, and complicate the control of existing allergy on the other.
Abstract: OBJECTIVES: The aim of this study was to develop a Spanish version of the Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) and to test its acceptability, reliability, validity, and sensitivity to change. METHODS: Forward and back translation by bilingual translators followed by pilot testing in patients with urticaria was used to adapt the questionnaire. The Spanish version of the CU-Q2oL was self-administered alongside the Skindex-29 in an observational, longitudinal, multicenter study. Feasibility was assessed by analyzing missing responses and ceiling and floor effects. Reliability was tested by examining internal consistency (Cronbach alpha). Construct validity was analyzed by examining convergent and discriminant validity with the Skindex-29 and by evaluating the ability of the CU-Q2oL to discriminate between patients according to a clinical classification of severity. Sensitivity to change was analyzed in a subgroup of patients who completed a second visit 4 weeks after baseline. RESULTS: A total of 695 patients were included in the analysis. Mean (SD) age was 42.4 (15.0) years and 62.1% of the sample was female. All of the items on the CU-Q2oL were answered by 91.9% of the sample. Over 15% of patients scored at the floor (best possible health) on 5 of the 6 dimensions. Cronbach alpha coefficients were > 0.80 for all dimensions of the CU-Q2oL, and 0.86 for the overall score. Construct validity was supported by correlations between the CU-Q2oL and the Skindex-29, which generally fulfilled hypotheses, and by the questionnaire's ability to discriminate between groups with different severities of urticaria.The questionnaire was sensitive to change, with an effect size of 1.0 for the overall score in patients reporting an improvement on the health transition scale. CONCLUSIONS: The Spanish version of the CU-Q2oL has shown satisfactory reliability, validity, and sensitivity to change. It is suitable for use as an outcome measure for chronic urticaria patients in clinical and research settings.
Abstract: BACKGROUND: Allergic Rhinitis and its Impact on Asthma (ARIA) differentiates mild from moderate/severe patients on the basis of 4 severity items. The high prevalence of moderate/severe patients suggests the need to differentiate between them. OBJECTIVES: To identify the categorization that maximizes discrimination between moderate and severe allergic rhinitis (AR) by using ARIA guidelines. METHODS: Observational, cross-sectional study. Clinical characteristics, nasal symptoms (Total Symptom Score 4), and health-related quality of life (HRQL; Rhinoconjunctivitis Quality of Life Questionnaire and Short Form 12) were assessed. The association of severity items (sleep, daily activities/sport, work/school, and troublesome symptoms) with symptoms and HRQL was analyzed using linear regression models. ANOVA and effect sizes were used to assess differences in symptoms and HRQL among groups defined by the number of affected ARIA items. RESULTS: Nontreated patients (N = 141) with moderate/severe AR were studied. All severity items showed a similar independent association with symptoms and HRQL scores, and there were no interaction effects, indicating that categorization of patients into moderate and severe could be based only on the number of items affected. Effect sizes were highest between patients with 4 affected ARIA items and those with 3, 2, or 1 affected item (effect sizes greater than 0.8 in all comparisons using Rhinoconjunctivitis Quality of Life Questionnaire and Short Form 12 Physical Composite Summary, and greater than 0.5 using the Total Symptom Score 4; P < .001). CONCLUSION: Using ARIA severity items, the criterion that best discriminates AR severity is considering moderate those with 1 to 3 affected items and severe those with 4. CLINICAL IMPLICATIONS: Discrimination between patients with moderate and severe AR should help to obtain homogeneous populations for both research and clinical purposes.
Abstract: OBJECTIVES: To develop and validate an instrument to measure health-related quality of life (HRQOL) specific to patients with allergic rhinitis (AR) and primarily for use in Spanish and Spanish-speaking populations. METHODS: An initial item pool was generated from literature review, focus groups with AR patients, and consultations with clinical experts. Item reduction was performed using clinimetric and psychometric approaches after administration of the item pool to 400 AR patients. The resulting instrument's internal consistency, test-retest (2-4 weeks) reliability, known groups and convergent validity, and sensitivity to change were tested in a longitudinal, observational, multicenter study in 210 AR patients who also completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). RESULTS: The new questionnaire took a mean (SD) of 7.1 (5.4) minutes to answer. Floor and ceiling effects were less than 15% on all dimensions. Cronbach's alpha values and intraclass correlation coefficient values for six of the sevendimensions and the overall score exceeded 0.70. Statistically significant differences (P < 0.01) were observed on all ESPRINT-28 dimensions and the overall score between patients with mild (mean overall score 1.97, SD 0.99), moderate (mean overall score 2.78, SD 0.88), and severe AR (mean overall score 3.89, SD 0.87). Patients with persistent AR had worse scores (P < 0.05) on all dimensions than patients with intermittent AR. Correlations between the ESPRINT-28 and the RQLQ were generally as expected. Effect sizes for score changes between the two study visits ranged from 0.96 to 1.76 for individual dimensions and the overall score. CONCLUSIONS: This new, Spanish-developed instrument to measure HRQOL in AR patients has shown good reliability, validity, and sensitivity to change. It has also proved easy to use and administer.
Abstract: Allergic rhinitis is an inflammatory disease of the nasal mucosa, caused by an IgE-mediated reaction after exposure to the allergen to which the patient is sensitized. Histamine is the most important preformed mediator released in the early stage of the allergic reaction, and also contributes to the late phase of the latter, exhibiting proinflammatory effects. Minimal persistent inflammation is a physiopathological phenomenon induced by the presence of an inflammatory cell infiltrate, together with ICAM-1 expression in the epithelial cells of the mucosa exposed to the allergen to which they are sensitized, in the absence of clinical symptoms. This molecule is considered to be an allergic inflammatory marker. The priming effect first described by Connell in 1968 consists of the reduction in the allergen concentration required to elicit a nasal hyper-response when performing a daily nasal exposure test. This implies that with natural exposure to inhaled allergens, small amounts of environmental allergen will maintain the patient symptoms, and thus of course minimal persistent inflammation. Considering the above, it is questionable whether antihistamines should be administered on a continuous basis or upon demand. The antihistamines, and fundamentally the second-generation drugs, have been shown to exert an antiinflammatory effect, and this effect is greater when the drug is administered continuously than when administered upon demand. Likewise, a reduction in treatment cost and an improvement in quality of life among patients treated on a continuous basis has been documented. However, no studies have been specifically designed to clarify the indication of treatment on a continuous basis or upon demand, as occurs in the GINA. As a result, the individualization of treatment according to the concrete characteristics of each patient seems to be the best approach, at least for the time being.
Abstract: It is well known that the prevalence of allergic diseases has increased in recent decades in the industrialized world. Exposure to environmental pollutants may partially account for this increased prevalence. In effect, air pollution is a growing public health problem. In Europe, the main source of air pollution due to particles in suspension is represented by motor vehicles--particularly those that use diesel fuel. Diesel exhaust particles (DEPs) are composed of a carbon core upon which high-molecular weight organic chemical components and heavy metals deposit. Over 80% of all DEPs are in the ultrafine particle range (< 0.1 pm in diameter). Air pollutants not only have a direct or indirect effect upon the individual, but also exert important actions upon aeroallergens. Pollen in heavily polluted zones can express a larger amount of proteins described as being allergenic. Through physical contact with the pollen particles, DEPs can disrupt the former, leading to the release of paucimicronic particles and transporting them by air--thus facilitating their penetration of the human airways. Climate change in part gives rise to variations in the temperature pattern characterizing the different seasons of the year. Thus, plants may vary their pollination calendar, advancing and prolonging their pollination period. In addition, in the presence of high CO2 concentrations and temperatures, plants increase their pollen output. Climate change may also lead to the extinction of species, and to the consolidation of non-native species--with the subsequent risk of allergic sensitization among the exposed human population. In conclusion, there is sufficient scientific evidence on the effect of air pollution upon allergens, increasing exposure to the latter, their concentration and/or biological allergenic activity.
Abstract: Chronic urticaria is highly prevalent in the general population, and while there are multiple treatments for the disorder, the results obtained are not completely satisfactory. The second-generation H1 antihistamines remain the symptomatic treatment option of choice. Depending on the different pharmacokinetics and H1 receptor affinity of each drug substance, different concentrations in skin can be expected, together with different efficacy in relation to the histamine-induced wheal inhibition test--though this does not necessarily have repercussions upon clinical response. The antiinflammatory properties of the H1 antihistamines could be of relevance in chronic urticaria, though it is not clear to what degree they influence the final therapeutic result. Before moving on to another therapeutic level, the advisability of antihistamine dose escalation should be considered, involving increments even above those approved in the Summary of Product Characteristics. Physical urticaria, when manifesting isolatedly, tends to respond well to H1 antihistamines, with the exception of genuine solar urticaria and delayed pressure urticaria. In some cases of chronic urticaria, the combination of H2 antihistamines may prove effective--though only with common liver metabolism (CYP3A4 isoenzyme-mediated) H1 antihistamines, due to the existence of mutual metabolic interferences. The role of leukotriene antagonists associated to antihistamines in application to chronic urticaria remains to be clearly defined.
Abstract: Drugs with antihistamine action are among the most commonly prescribed medicines in pediatrics. According to the International Medical Statistics (IMS), almost two million antihistamine units (in solution) for pediatric use were sold in Spain during 2006--at a cost of nearly 6 million euros. Of this amount, 34% corresponded to first-generation (or sedating) antihistamines. The difficulties inherent to research for drug development increase considerably when the pediatric age range is involved. The use of any medication in this age group must adhere to the strictest safety criteria, and must offer the maximum guarantees of efficacy. For this reason, detailed knowledge of the best scientific evidence available in relation to these aspects is essential for warranting drug use. The first-generation antihistamines have never been adequately studied for pediatric age groups, though they are still widely used in application to such patients. In contrast, studies in children have been made with the second-generation antihistamines, allowing us to know their safety profile, and such medicines are available at pediatric dosages that have been well documented from the pharmacological perspective. The present review affords an update to our most recent knowledge on antihistamine use in children, based on the best scientific evidence available.
Abstract: Epidemiological studies have revealed an association between pollution and allergic respiratory diseases. The main pollutants in this sense are nitric oxide, ozone, and particulate matter. The present review on one hand addresses the chemical characteristics of each of these three groups of pollutants and their main sources, and on the other examines their effects upon allergic respiratory diseases--placing special emphasis on the effects of diesel exhaust particles. For each of the pollutants, the underlying mechanisms capable of influencing allergic respiratory diseases are commented. Lastly, an evaluation is made of some of the genetic aspects related to the response to pollutants.
