House dust mite subcutaneous immunotherapy has sustained long-term effectiveness on allergic rhinitis and asthma: A 10-year follow-up.

BACKGROUND: Maintenance doses for allergen immunotherapy (AIT) have been recommended for at least 3 years but little data on long-term efficacy is available depending on AIT duration. To show sustained efficacy 10 years after completion of treatment with depigmented-polymerized house dust mite (dpg-pol HDM) allergen extract in adults with asthma and/or rhinoconjunctivitis. METHODS: Patients included in a double-blind placebo-controlled AIT study with dpg-pol HDM allergen extract were reviewed at completion of the perennial treatment and 10-year follow-up (10y-FU). Change in symptom and rescue medication score was the primary objective. Visual analog scale (VAS), asthma control test (ACT), and degree of disease control were the secondary objectives. A comparative analysis between patients who underwent AIT treatment for <3 years and ≥3 years was performed. RESULTS: Data from 31 patients (mean age 38 years) were available at 10y-FU. All had asthma and 29 had rhinoconjunctivitis at baseline. Twenty-three patients were treated ≥3 years and 8 for <3 years. Seventeen (55%) patients were asymptomatic at completion of AIT, with significant differences for nasal, conjunctival, and bronchial symptoms (p < .0001) compared with baseline only in those patients treated ≥3 years. Nine (52.9%) patients remained completely asymptomatic at 10y-FU, all were treated for ≥3 years. Moreover, significant reduction in the number of patients with rhinitis (p = .0117), conjunctivitis (p < .0001), and bronchial (p = .0005) symptoms was observed at 10y-FU compared with baseline only in the ≥3 years treated. Ten (32.3%) patients did not require any rescue medication at 10y-FU, all had been treated for ≥3 years. ACT at 10y-FU showed a good control of asthma (median 23.5; 95% IC[22.0, 25.0]). No significant differences were observed between VAS at end of treatment compared with VAS at 10y-FU. CONCLUSIONS: Sustained clinical efficacy is achieved 10 years after completion of depigmented-polymerized HDM, however, these findings were observed only if patients are treated for at least 3 years.

Effects of Exercise and Sleep Deprivation on Reaction Severity During Oral Peanut Challenge: A Randomized Controlled Trial.

BACKGROUND: The severity of allergic reactions to foods can vary markedly. Little is known of variations in reaction severity within or between individuals or the effects of cofactors. OBJECTIVE: We examined the effects of sleep deprivation and exercise and repeat challenges on the severity and patterns of allergic reactions to peanut. METHODS: In a randomized crossover study, adults with peanut allergy underwent 3 open peanut challenges in random order: with exercise after each dose, with sleep deprivation preceding challenge, and with no intervention. The primary outcome was eliciting dose, reported elsewhere. Reaction severity was a secondary outcome, evaluated using a weighted log-transformed numerical severity score. Analyses estimated the difference in severity between nonintervention challenge and challenges with exercise or sleep deprivation, adjusting for challenge order and using the highest dose tolerated by each individual across all their challenges. Symptom pattern reproducibility was assessed by comparing symptom sequences using pairwise sequence alignment to obtain a percentage match in symptom pattern. RESULTS: Eighty-one participants (mean age 25 y) completed at least 1 postbaseline challenge. Sleep deprivation, but not exercise, significantly increased severity score by 48% (95% CI 12%-84%; P = .009) compared with no intervention. A 38% increase in severity was observed between the first and the last postbaseline challenge (95% CI 1%-75%; P = .044). The average pairwise match of symptoms within individuals was 82.4% and across individuals was 78.3%. CONCLUSIONS: A novel severity score demonstrates that sleep deprivation and repeated challenges increase reaction severity. Understanding factors affecting severity is essential for effective risk management. We also show that symptom patterns in repeat peanut challenges are similar within and between individuals.

Safety and Effectiveness of a Single Multiallergen Subcutaneous Immunotherapy in Polyallergic Patients.

BACKGROUND: As the number of allergic sensitizations increases the severity of allergic respiratory diseases worsens. Multiple monoallergen immunotherapy can be accompanied by poor treatment adherence and high costs, single multiallergen immunotherapy needs to prove efficacy whilst maintaining a good safety profile. METHODS: Observational, retrospective, multicenter study using a 2-pollen single undiluted multiallergen subcutaneous immunotherapy (SCIT) in routine clinical practice in Spain. Patients with rhinoconjunctivitis, with/without controlled asthma, sensitized to grass, olive, Parietaria, Cupressus, plane tree and/or Salsola pollen were included. Primary and secondary clinical efficacy endpoints were quality of life (mini Rhinitis Quality of Life Questionnaire (miniRQLQ)) and visual analogue scale (VAS) respectively. All adverse events were documented. RESULTS: Ten centers included 97 patients, median age 32 years. SCIT treatment included combinations of grass mix with olive, Parietaria, Cupressus, plane tree or Salsola or olive with Parietaria, Cupressus or Salsola. The mean duration of SCIT was 1.8 years with a high treatment adherence (73%). Significant improvement in quality of life, nasal and ocular symptoms, activity limitations and practical problems (p< 0.0001) and other symptoms (p= 0.024) was observed. Most patients did not develop asthma-like symptoms and a significant improvement of all allergic symptom severity was perceived. VAS showed a significant improvement in rhinoconjunctivitis and asthma by patients and physicians. Twenty-nine patients experienced adverse reactions, 25 had local and 6 had systemic reactions. CONCLUSIONS: Single undiluted multiallergen SCIT treatment of two different pollens is efficacious and safe in both children and adults, showing that it is a suitable option for the treatment of polyallergic patients.

Delayed symptoms and orthostatic intolerance following peanut challenge.

BACKGROUND: Clinical reactions to Oral Food Challenge (OFC) in peanut-allergic individuals have been well-characterised, but rates and phenotypes of symptom recurrence beyond the first hour after objective symptoms are less well-characterised. OBJECTIVE: To evaluate the rate of new-onset symptoms occurring at least 1 h after stopping OFC in peanut-allergic children and adults undergoing peanut-OFC. METHODS: We prospectively collected data relating to adverse events following positive reactions at double-blind, placebo-controlled food challenges (DBPCFC) to peanut in children and adults evaluated for eligibility to participate in two clinical trials (NCT02149719, NCT02665793). The trials included people aged 8 to 45 with primary, IgE-mediated peanut allergy at DBPCFC. The challenge protocol included consumption of a light meal 1 h after reaction. RESULTS: A total of 121 participants (64 children, 57 adults) had immediate, objective symptoms at DBPCFC, 25 (17 children, 8 adults) with anaphylaxis. Thirty-three (27%) had progression or recurrence of symptoms ≥ 1 h after objective clinical reaction, of whom 8 developed anaphylaxis. In 23 cases, the onset of new symptoms was associated with consumption of a light meal. In eight cases, symptoms were limited to a symptomatic postural fall in blood pressure noted in preparation for discharge, without any other new features of an allergic reaction. CONCLUSIONS & CLINICAL RELEVANCE: Progressive or new-onset symptoms ≥1 h following initial allergic reaction at OFC are common and can include orthostatic hypotension. Recurrent symptoms may be temporally associated with food consumption.

Cardiovascular changes during peanut-induced allergic reactions in human subjects.

BACKGROUND: Food allergy is the most common cause of anaphylaxis. Changes in posture during acute reactions can trigger fatal outcomes, but the impact of allergic reactions on the cardiovascular system in nonfatal reactions remains poorly understood. OBJECTIVE: Our aim was to systematically evaluate changes in cardiovascular function during acute allergic reactions to peanut. METHODS: Participants underwent double-blind placebo-controlled food challenge to peanut as part of a clinical trial. Changes in hemodynamic parameters (heart rate, stroke volume, blood pressure, and peripheral blood flow) and electrocardiogram findings during food challenges were assessed using noninvasive continuous monitoring. RESULTS: A total of 57 adults (median age 24 years [interquartile range = 20-29]), 53% of whom were female, participated; 22 (39%) had anaphylaxis. Acute reactions were associated with significant changes in stroke volume (mean decrease of 4.2% [95% CI = 0.8-7.6; P = .03]), heart rate (mean increase 11.6% [95% CI = 8.4-14.8; P < .0001]), and peripheral blood flow (mean increase 19.7% [95% CI = 10.8-28.6; P < .0001]), irrespective of reaction severity. These changes were reproduced at a subsequent repeat peanut challenge in 26 participants, and could be reversed with administration of intravenous fluids which resulted in faster resolution of abdominal symptoms. CONCLUSIONS: In this first detailed human study of cardiovascular changes during food-induced allergic reactions, we found evidence for significant fluid redistribution, independent of reaction severity. This provides a sound rationale for optimizing venous return during significant allergic reactions to food. Finally, these data provide a new paradigm for understanding severity in anaphylaxis, in which poor outcomes may occur as a result of a failure in compensatory mechanisms.

Circulating Ara h 6 as a marker of peanut protein absorption in tolerant and allergic humans following ingestion of peanut-containing foods.

BACKGROUND: Bioaccessibility of food allergens may be a key determinant of allergic reactions. OBJECTIVE: To develop a protocol allowing the detection of the major peanut allergen, Ara h 6, in the bloodstream following ingestion of low amounts of peanut and to compare Ara h 6 bioaccessibility by food matrix. We further assessed for differences in absorption in healthy versus peanut-allergic volunteers. METHODS: A blood pretreatment combining acidic shock and thermal treatment was developed. This protocol was then applied to blood samples collected from human volunteers (n = 6, healthy controls; n = 14, peanut-allergic patients) at various time-points following ingestion of increasing levels of peanut incurred in different food matrices (cookies, peanut butter and chocolate dessert). Immunodetection was performed using an in-house immunoassay. RESULTS: An original pretreatment protocol was optimized, resulting in irreversible dissociation of human antibodies-Ara h 6 immune complex, thus rendering Ara h 6 accessible for its immunodetection. Ara h 6 was detected in samples from all volunteers following ingestion of 300-1000 mg peanut protein, although variations in the kinetics of passage were observed between individuals and matrices. Interestingly, in peanut-allergic subjects, Ara h 6 could be detected following ingestion of lower doses and at higher concentrations than in non-allergic volunteers. CONCLUSIONS AND CLINICAL RELEVANCE: The kinetics and intensity of Ara h 6 passage in bloodstream depend on both individual and food matrix. Peanut-allergic patients appear to demonstrate higher absorption rate, the clinical significance of which warrants further evaluation.

Reaction phenotypes in IgE-mediated food allergy and anaphylaxis.

OBJECTIVE: Food allergy encompasses a range of food hypersensitivities. Different clinical phenotypes for food allergy likely exist in much the same way as endotype discovery is now a major research theme in asthma. We discuss the emerging evidence for different reaction phenotypes (ie, symptoms experienced after allergen exposure in food allergic individuals) and their relevance for clinical practice. DATA SOURCES: Published and unpublished literature relating to reaction phenotypes in food allergy. STUDY SELECTIONS: Authors assessment of the available data. RESULTS: Food anaphylaxis may be pathophysiologically different than anaphylaxis caused by nonfood triggers. Currently, there are no robust, clinically useful predictors of severity in food allergy. It is likely that patient-specific reaction phenotypes exist in food allergy, which may affect the risk of severe anaphylaxis. Allergen immunotherapy may modulate these phenotypes. CONCLUSION: Data are emerging to confirm our clinical experience that many food allergic patients experience stereotypical symptoms after allergen exposure, both in the community and at supervised oral food challenge, in a manner that varies among patients. Integrating data sets from different cohorts and applying unbiased machine-based learning analyses may demonstrate specific food allergy endotypes in a similar way to asthma. Whether this results in improvements in patient management (eg, through facilitating risk stratification or affecting the decision to prescribe an epinephrine autoinjector and, perhaps, the number of devices) remains to be determined, but given our current inability to predict which patients are most at risk of severe food allergic reactions, this will clearly be an important area of research in the future.

Effect of sleep deprivation and exercise on reaction threshold in adults with peanut allergy: A randomized controlled study.

BACKGROUND: Peanut allergy causes severe and fatal reactions. Current food allergen labeling does not address these risks adequately against the burden of restricting food choice for allergic patients because of limited data on thresholds of reactivity and the influence of everyday factors. OBJECTIVE: We estimated peanut threshold doses for a United Kingdom population with peanut allergy and examined the effect of sleep deprivation and exercise. METHODS: In a crossover study, after blind challenge, participants with peanut allergy underwent 3 open peanut challenges in random order: with exercise after each dose, with sleep deprivation preceding challenge, and with no intervention. Primary outcome was the threshold dose triggering symptoms (in milligrams of protein). Primary analysis estimated the difference between the nonintervention challenge and each intervention in log threshold (as percentage change). Dose distributions were modeled, deriving eliciting doses in the population with peanut allergy. RESULTS: Baseline challenges were performed in 126 participants, 100 were randomized, and 81 (mean age, 25 years) completed at least 1 further challenge. The mean threshold was 214 mg (SD, 330 mg) for nonintervention challenges, and this was reduced by 45% (95% CI, 21% to 61%; P = .001) and 45% (95% CI, 22% to 62%; P = .001) for exercise and sleep deprivation, respectively. Mean estimated eliciting doses for 1% of the population were 1.5 mg (95% CI, 0.8-2.5 mg) during nonintervention challenge (n = 81), 0.5 mg (95% CI, 0.2-0.8 mg) after sleep, and 0.3 mg (95% CI, 0.1-0.6 mg) after exercise. CONCLUSION: Exercise and sleep deprivation each significantly reduce the threshold of reactivity in patients with peanut allergy, putting them at greater risk of a reaction. Adjusting reference doses using these data will improve allergen risk management and labeling to optimize protection of consumers with peanut allergy.

Mast cell activation test in the diagnosis of allergic disease and anaphylaxis.

BACKGROUND: Food allergy is an increasing public health issue and the most common cause of life-threatening anaphylactic reactions. Conventional allergy tests assess for the presence of allergen-specific IgE, significantly overestimating the rate of true clinical allergy and resulting in overdiagnosis and adverse effect on health-related quality of life. OBJECTIVE: To undertake initial validation and assessment of a novel diagnostic tool, we used the mast cell activation test (MAT). METHODS: Primary human blood-derived mast cells (MCs) were generated from peripheral blood precursors, sensitized with patients' sera, and then incubated with allergen. MC degranulation was assessed by means of flow cytometry and mediator release. We compared the diagnostic performance of MATs with that of existing diagnostic tools to assess in a cohort of peanut-sensitized subjects undergoing double-blind, placebo-controlled challenge. RESULTS: Human blood-derived MCs sensitized with sera from patients with peanut, grass pollen, and Hymenoptera (wasp venom) allergy demonstrated allergen-specific and dose-dependent degranulation, as determined based on both expression of surface activation markers (CD63 and CD107a) and functional assays (prostaglandin D2 and ß-hexosaminidase release). In this cohort of peanut-sensitized subjects, the MAT was found to have superior discrimination performance compared with other testing modalities, including component-resolved diagnostics and basophil activation tests. Using functional principle component analysis, we identified 5 clusters or patterns of reactivity in the resulting dose-response curves, which at preliminary analysis corresponded to the reaction phenotypes seen at challenge. CONCLUSION: The MAT is a robust tool that can confer superior diagnostic performance compared with existing allergy diagnostics and might be useful to explore differences in effector cell function between basophils and MCs during allergic reactions.

Epidemiology of Alcohol Abuse Among Spanish Immigrant Populations.

In recent years, the immigrant population has substantially increased in Spain. However, there is a lack of information in the knowledge of alcohol abuse among Spanish immigrants. We describe the epidemiology of alcohol abuse among foreign-born immigrants versus Spanish natives. We carried out a cross-sectional study that uses data from the European Survey of Health on the General Population of Spain of 2009. A sample of 22,188 subjects was analyzed (of whom, 3,162 were foreign). Proxies of problematic alcohol consumption were the prevalence of excessive average consumption and the prevalence of excessive episodic consumption (binge drinking). Descriptive analysis of the population, determination of area of origin with major alcohol consumption and related factors for each kind of consumption, separating immigrant and native population, were performed. The immigrant profile was heterogeneous, though predominantly aged between 35 and 54, and were living with their family and working. 3.4% of immigrants and 3.2% of natives were considered excessive drinkers; 8.9% and 10%, respectively, reported binge drinking in the last year. Immigrants from Northern and Western Europe, and Latin America, Andean countries had significantly a higher report of frequent alcohol consumption and/or binge drinking compared to native. On the contrary, born in Africa was a protective factor. Unemployment was the most relevant related factor, being more important in the immigrant population. The excessive alcohol consumption in immigrants is dissimilar; the interventions must be adapted to their social situation, environments and areas of origin.

A pesar del gran incremento de la población inmigrante en los últimos años, su uso de alcohol está poco estudiado. Se describe la epidemiología del consumo de riesgo de alcohol en la población inmigrante residente en España, frente a la nativa. Se emplearon datos de 22188 respondentes a la Encuesta Europea de Salud de 2009, de los que 3162 eran extranjeros. Como indicadores de consumo problemático se usó la prevalencia de consumo excesivo promedio y el consumo excesivo episódico. Se realizaron análisis descriptivo de la población, determinación de zonas de procedencia con mayor consumo de alcohol y factores relacionados para cada tipo de consumo separando población inmigrante de autóctona. El perfil sociodemográfico del inmigrante fue heterogéneo, aunque predominantemente de entre 35 y 54 años, que vive en familia y trabaja. Se consideraron bebedores excesivos promedio al 3,4% de los inmigrantes por el 3,2% de los nativos, y bebedores excesivos episódicos en el último año el 8,9% frente al 10%. Los inmigrantes procedentes de Europa del Norte y del Oeste, y América latina, países andinos, fueron aquellos que presentaron mayores razones de prevalencia de bebedores de riesgo que la población nativa. Por el contrario, proceder de África fue un factor protector. De los factores relacionados con un mayor consumo, destaca el desempleo, siendo más relevante en la población inmigrante. El consumo excesivo de alcohol en inmigrantes es muy heterogéneo, debiendo adecuarse las intervenciones sobre el mismo a su situación social, diferentes entornos y áreas de procedencia.

Epidemiología del abuso de alcohol entre la población inmigrante en España / Epidemiology of Alcohol Abuse Among Spanish Immigrant Populations

A pesar del gran incremento de la población inmigrante en los últimos años, su uso de alcohol está poco estudiado. Se describe la epidemiología del consumo de riesgo de alcohol en la población inmigrante residente en España, frente a la nativa. Se emplearon datos de 22188 respondentes a la Encuesta Europea de Salud de 2009, de los que 3162 eran extranjeros. Como indicadores de consumo problemático se usó la prevalencia de consumo excesivo promedio y el consumo excesivo episódico. Se realizaron análisis descriptivo de la población, determinación de zonas de procedencia con mayor consumo de alcohol y factores relacionados para cada tipo de consumo separando población inmigrante de autóctona. El perfil sociodemográfico del inmigrante fue heterogéneo, aunque predominantemente de entre 35 y 54 años, que vive en familia y trabaja. Se consideraron bebedores excesivos promedio al 3,4% de los inmigrantes por el 3,2% de los nativos, y bebedores excesivos episódicos en el último año el 8,9% frente al 10%. Los inmigrantes procedentes de Europa del Norte y del Oeste, y América latina, países andinos, fueron aquellos que presentaron mayores razones de prevalencia de bebedores de riesgo que la población nativa. Por el contrario, proceder de África fue un factor protector. De los factores relacionados con un mayor consumo, destaca el desempleo, siendo más relevante en la población inmigrante. El consumo excesivo de alcohol en inmigrantes es muy heterogéneo, debiendo adecuarse las intervenciones sobre el mismo a su situación social, diferentes entornos y áreas de procedencia

In recent years, the immigrant population has substantially increased in Spain. However, there is a lack of information in the knowledge of alcohol abuse among Spanish immigrants. We describe the epidemiology of alcohol abuse among foreign-born immigrants versus Spanish natives. We carried out a cross-sectional study that uses data from the European Survey of Health on the General Population of Spain of 2009. A sample of 22,188 subjects was analyzed (of whom, 3,162 were foreign). Proxies of problematic alcohol consumption were the prevalence of excessive average consumption and the prevalence of excessive episodic consumption (binge drinking). Descriptive analysis of the population, determination of area of origin with major alcohol consumption and related factors for each kind of consumption, separating immigrant and native population, were performed. The immigrant profile was heterogeneous, though predominantly aged between 35 and 54, and were living with their family and working. 3.4% of immigrants and 3.2% of natives were considered excessive drinkers; 8.9% and 10%, respectively, reported binge drinking in the last year. Immigrants from Northern and Western Europe, and Latin America, Andean countries had significantly a higher report of frequent alcohol consumption and/or binge drinking compared to native. On the contrary, born in Africa was a protective factor. Unemployment was the most relevant related factor, being more important in the immigrant population. The excessive alcohol consumption in immigrants is dissimilar; the interventions must be adapted to their social situation, environments and areas of origin

[Population-based studies on alcohol-related harm in Spain]. / Estudios poblacionales en España sobre daños relacionados con el consumo de alcohol.

Based on the review of scientific papers and institutional reports on the subject and analysis of some secondary data, we assess the alcohol-related harm in Spain between 1990 and 2011. In 2011 they could be attributable to alcohol, 10% of the total mortality of the population aged 15-64, and about 30% of deaths due to traffic accidents. Among the population aged 15-64 years at least 0.8% had alcohol use disorders, an additional 5% could have harmful alcohol consumption that would need clinical evaluation, and about 20% had had some acute alcohol intoxication (AAI) in the last year. The AAI accounted for approximately 0.5-1.1 % of hospital emergency visits. Social costs of alcohol could represent 1% of gross domestic product. The prevalence of alcohol-related harm was significantly higher in men than women, with a male/female ratio greater than three for alcohol-related mortality and serious injuries, and this situation has hardly changed in the last 20 years. Alcohol-related harm has followed a downward trend, except for AAI. In 1990-2011 the standardized mortality rates related to alcohol decreased by half. Large gaps in knowledge and uncertainties on alcohol-related harm in Spanish population, clearly justify the institutional support for the research in this field and the implementation of a comprehensive monitoring system.

Who and how many of the potential users would be willing to pay the current or a lower price of the HIV self-test? The opinion of participants in a feasibility study of HIV self-testing in Spain / ¿Quiénes y cuántos potenciales usuarios estarían dispuestos a pagar el precio actual o un precio menor de un autotest de VIH? Opinión de los participantes en un estudio de factibilidad del autotest de VIH en España

INTRODUCTION: We estimate the proportion of participants willing to pay the US price (€ 30) or € 20 for an HIV self-test and analyse their associated factors. METHODS: In a street-based testing program, 497 participants in a feasibility self-test study answered the question, "What would be the maximum price you would be willing to pay for a similar test to this one so you can use it at your convenience?" RESULTS: Only 17.9% would pay ≥ €30, while 40.0%, ≥ €20. In the logistic regression, paying more was associated with being tested outside the campuses and having paid or been paid for sex. CONCLUSION: In Spain, self-testing would not have an impact unless it became more affordable to potential users

INTRODUCCIÓN: Estimamos la proporción de participantes dispuestos a pagar por un autotest de VIH su precio en EEUU. (30 €), o 20 €, y analizamos factores asociados. MÉTODOS: En un programa de diagnóstico ofertado en la calle, 497participantes de un estudio de factibilidad del auto-test respondieron a la pregunta: ¿Cuál sería el precio máximo que estarías dispuesto a pagar por una prueba como esta para poder realizártela cuando estimaras oportuno?. RESULTADOS: El 17,9% pagaría ≥ 30 € y el 40,0% ≥ 20 €. En la regresión logística pagar más estuvo asociado con participar fuera de las universidades y haber pagado o sido pagado por sexo. CONCLUSIÓN: El autotest no tendrá impacto en España si su precio no disminuye a un valor más asequible para los potenciales usuarios

Who and how many of the potential users would be willing to pay the current or a lower price of the HIV self-test? The opinion of participants in a feasibility study of HIV self-testing in Spain.

INTRODUCTION: We estimate the proportion of participants willing to pay the US price (€30) or €20 for an HIV self-test and analyse their associated factors. METHODS: In a street-based testing program, 497 participants in a feasibility self-test study answered the question, "What would be the maximum price you would be willing to pay for a similar test to this one so you can use it at your convenience?" RESULTS: Only 17.9% would pay ≥€30, while 40.0%, ≥€20. In the logistic regression, paying more was associated with being tested outside the campuses and having paid or been paid for sex. CONCLUSION: In Spain, self-testing would not have an impact unless it became more affordable to potential users.

Misregulation of suppressors of cytokine signaling in eosinophilic esophagitis.

BACKGROUND: Several findings suggest that eosinophilic esophagitis (EoE) is strongly associated with atopy and allergen-driven, Th2-type immune responses, indicating the association of EoE with immune dysregulation. The objective of this study is to ascertain the molecular mechanism involved in EoE disease development a Th2 condition. METHODS: 25 patients with diagnosis of EoE and 17 non-EoE controls were recruited by the gastroenterology and allergy departments from three different hospitals. Transcription analysis of suppressors of cytokine signaling 1, 3, 5 (SOCS), interleukin-5 (IL), IL-13, eotaxin (CCL26), eoataxin receptor (CCR3), and mitogen-activated protein kinase 1 (MAPK1) was performed in esophageal biopsies by real time PCR. Western blot of ERK esophageal protein and additional measures of IL-5 and VEGF levels in serum were performed. RESULTS: The esophagus of EoE patients expresses and synthesizes high levels of SOCS1 and SOCS3 proteins (P < 0.05), and these expression correlated with levels of IL-5, IL-13, CCL26, CCR3, and MAPK1 genes. In addition, we demonstrate the implication of the ERK pathway (P < 0.001). CONCLUSIONS: SOCS proteins probably contribute to EoE pathogenesis by directly or indirectly inducing the Th2 profile, as well as by promoting the production of Th2 cytokines. All these findings further enhance our understanding of the mechanism of EoE, and accumulating evidence suggests that EoE pathogenesis is likely to be due to misregulation of immunological pathways.

Comparison of bronchial hyperresponsiveness to methacholine and adenosine and airway inflammation markers in patients with suspected asthma.

BACKGROUND: Bronchial hyperresponsiveness is usually measured by bronchial challenge test with direct (e.g., methacholine) and indirect (e.g., adenosine) agonists. There are few studies comparing both types of agents and they have had conflicting concordance. OBJECTIVE: We sought to compare the results of both tests in a population with symptoms suggestive of asthma so as to determine their relationship with bronchial inflammatory markers. METHODS: Seventy-nine patients whose age ranged from 14 to 81 years were recruited for this study. Challenge tests were performed using the tidal volume method. PC20 methacholine and PC15 and PC20 adenosine were calculated. Induced sputum and fraction of exhaled nitric oxide measurements were also performed. RESULTS: Atopy was found in 69% of the patients. Methacholine PC20 and adenosine PC15 were positive in 32 patients (40.5%), both having a sensitivity of 73%. Percentage of agreement was 45.45% and κ index was only 0.369. Adenosine PC20 elicited lower sensitivity and agreement. No correlation between methacholine PC20 and adenosine PC15 was observed. Higher fraction of exhaled nitric oxide values and sputum eosinophil counts were seen in patients with positive adenosine challenge results. The use of adenosine PC15 or PC20 did not alter the association with inflammatory markers. CONCLUSIONS: The concordance between both techniques was low. Methacholine is not a reliable predictor of hyperresponsiveness to adenosine, leading us to conclude that the two tests are complementary but not interchangeable in clinical practice. Additionally, responsiveness to the two bronchoconstrictor stimuli does not indicate presence of the same airway abnormality. Indirect stimuli provide a better reflection of bronchial inflammation.