Eosinophil-derived neurotoxin and clinical outcomes with mepolizumab in severe eosinophilic asthma

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Asthma diagnosis is not associated with obesity in a population of adults from Madrid

Background: Several studies have suggested a relationship between asthma and obesity; however, this relationship is unclear when obesity is compared with bronchial hyperresponsiveness to methacholine. Aim: To determine whether obesity is associated with a diagnosis of asthma. Methods: We conducted a cross-sectional study in a population of Spanish adults in the north of Madrid, Spain between 2003 and 2007. The patients included had experienced asthma symptoms during the previous year, but had a ratio of forced expiratory volume in the fi rst second of expiration (FEV1) to forced vital capacity (FVC) of >70%. Diagnosis was confi rmed by the presence of symptoms and demonstration of bronchial hyperresponsiveness to methacholine. Obesity was measured by body mass index (BMI). Adjusted odd ratios (OR) were obtained by logistic regression. Results: Of a total of 1424 patients included, 251 (17.6%) were diagnosed with asthma. These patients were younger (P<.001) and had lower BMI (P<.001) and lung function parameters (FEV1 and FEV1/FVC ratio) than individuals without asthma (P<.001). After adjusting the model for age, gender, baseline FEV1, and FEV1/FVC ratio, patients with overweight or obesity were not more frequently diagnosed with asthma than those with normal weight (OR, 0.848 [95% confi dence interval (CI), 0.59-1.20]; and OR, 0.616 [95% CI, 0.38-0.99], respectively). In addition, obese males were more frequently diagnosed with asthma than obese females (P<.041). Conclusions: In this study, obesity and overweight were not associated with a diagnosis of asthma based on the presence of consistent symptoms and demonstration of airway responsiveness to methacholineFundamento: Varios estudios sugieren que la obesidad es un factor de riesgo para padecer asma, lo que no siempre se confi rma cuando se compara la obesidad con la hiperreactividad bronquial (HRB) en pacientes con síntomas de asma. Objetivo: Determinar si la obesidad se asocia con el diagnóstico de asma, confi rmado por presencia de síntomas e HRB a metacolina. Pacientes y Métodos: Se realizó un estudio transversal en población adulta del Área Norte de Madrid entre 2003 y 2007. Se incluyeron sujetos que habían padecido síntomas de asma en el último año, con un FEV1/FVC>70% y que precisaban una prueba de metacolina para confi rmar el diagnóstico. La obesidad se defi nió según el índice de masa corporal (IMC). Se aplicó un modelo de regresión logística para calcular odd ratios (OR) ajustadas. Resultados: Se estudiaron 1.424 sujetos y se diagnosticaron de asma 251 sujetos (17,6%) que, comparados con los 1.173 no diagnosticados de asma, eran más jóvenes y presentaban un IMC y parámetros de función pulmonar (FEV1, FEV1/FVC) más bajos (p<0,001). Tras ajustar el modelo por edad, sexo, FEV1 basal y FEV1/FVC el diagnóstico de asma no fue más prevalente en los sujetos obesos o con sobrepeso que en los sujetos con peso normal (OR 0,848, IC95% 0,59-1,20 y OR 0,616, IC95% 0,38-0,99, respectivamente). El diagnóstico de asma fue más frecuente en hombres obesos que en mujeres obesas (p=0,041). Conclusiones: La obesidad y el sobrepeso no se asociaron con el diagnóstico de asma establecido por la presencia de síntomas e HRB a metacolinaThis research project was carried out with a grant from Fundación para la Investigación Biomédica del Hospital Universitario La Paz (FIBHULP

Asthma, obesity and diet

El asma y la obesidad son dos trastornos de gran impacto en la salud pública que han aumentado su prevalencia en los últimos años. Numerosos estudios han relacionado ambas entidades. La mayoría de los estudios prospectivos demuestran que la obesidad es un factor de riesgo para el diagnóstico “de novo” de asma. Además, los resultados de diversos estudios sugieren que así como la ganancia de peso aumenta el riesgo de asma, la pérdida mejora su evolución. En general, los estudios prospectivos encuentran una asociación positiva entre el índice de masa corporal (IMC) basal y el posterior desarrollo de asma, lo que sugiere que es el exceso de peso el que podría favorecer el desarrollo de asma, aunque estos resultados no son tan concluyentes cuando se estudia la asociación entre hiperreactividad bronquial con el IMC. Existen distintos factores que podrían explicar esta asociación. La obesidad es capaz de reducir la compliance pulmonar, los volúmenes pulmonares y el diámetro de de las vías respiratorias periféricas, así como alterar los volúmenes sanguíneos pulmonares y la relación ventilación- perfusión. Además, el aumento del funcionamiento normal del tejido adiposo en sujetos obesos conduce a un estado proinflamatorio sistémico, que produce un aumento de las concentraciones séricas de numerosas citoquinas, fracciones solubles de sus receptores y quimiocinas. Muchos de estos mediadores son sintetizados y secretados por células del tejido adiposo y reciben el nombre genérico de adipocinas, entre las que se incluyen IL-6, IL-10, eotaxina, TNF- , TGF- 1, PCR, leptina y adiponectina. Por último, se han identificado regiones específicas del genoma humano que están relacionadas tanto con el asma como con la obesidad. La mayoría de los estudios apuntan a que la obesidad es capaz de aumentar la prevalencia y la incidencia de asma, aunque este efecto parece ser moderado. El tratamiento de los asmáticos obesos debe incluir un programa de control de peso.Asthma and obesity have a considerable impact on public health and their prevalence has increased in recent years. Numerous studies have linked both disorders. Most prospective studies show that obesity is a risk factor for asthma and have found a positive correlation between baseline body mass index (BMI) and the subsequent development of asthma, although these results are not conclusive when studying the association between airway hyperresponsiveness with BMI. Furthermore, several studies suggest that whereas weight gain increases the risk of asthma, weight loss improves the course of the illness. Different factors could explain this association. Obesity is capable of reducing pulmonary compliance, lung volumes and the diameter of peripheral respiratory airways as well as affecting the volume of blood in the lungs and the ventilation-perfusion relationship. Furthermore, the increase in the normal functioning of adipose tissue in obese subjects leads to a systemic proinflammatory state, which produces a rise in the serum concentrations of several cytokines, the soluble fractions of their receptors and chemokines. Many of these mediators are synthesized and secreted by cells from adipose tissue and receive the generic name of adipokines, including IL-6, IL-10, eotaxin, TNF- , TGF- 1, PCR, leptin y adiponectin. Finally, specific regions of the human genome which are related to both asthma and obesity have been identified. Most studies point out that obesity is capable of increasing the prevalence and incidence of asthma, although this effect appears to be modest. The treatment of obese asthmatics must include a weight control progra

Evolution of occupational asthma: Does cessation of exposure really improve prognosis?

SummaryAimTo assess the evolution of occupational asthma (OA) depending on whether the patient avoids or continues with exposure to the offending agent.MethodsStudy in patients diagnosed with OA using a specific inhalation challenge. Patients underwent the following examinations on the same day: clinical interview, physical examination, forced spirometry, methacholine test and determination of total IgE. Clinical improvement, deterioration or no change were defined according to the changes seen on the GINA severity scale at the time of diagnosis.ResultsOf the 73 patients finally included, 55 had totally ended exposure and 18 continued to be exposed at work. Clinical improvement was observed in 47% of those who had terminated exposure and in 22% of those who remained exposed; clinical deterioration was observed in 14% and 17% respectively (p = 0.805). Logistical regression analysis, including the type of agent and the persistence or avoidance of exposure among the variables, did not show any predictive factors of clinical evolution. Similarly, the changes in FEV1 and in bronchial hyperresponsiveness were not associated with the avoidance or continuation of exposure to the causative agent.ConclusionsAvoiding exposure to the causative agent in patients with OA does not seem to improve prognosis in this disease. Despite these findings, there is insufficient evidence to recommend a change in current management guidelines

Efficacy and Safety of Reslizumab in Patients with Severe Asthma with Inadequate Response to Omalizumab : A Multicenter, Open-Label Pilot Study

Funding: This study was endorsed by the Asthma Research Program of the Spanish Respiratory Society (PII de Asma de SEPAR) supported by a grant from Teva Pharmaceutical Industries.Background: Patients with severe allergic and eosinophilic asthma could qualify for different biologic therapies. Objective: To evaluate the efficacy and safety of weight-based intravenous reslizumab dosing in patients who have previously failed therapy with omalizumab. Methods: We carried out a 24-week prospective, multicenter, open-label, single-group, self-controlled study in patients with severe eosinophilic asthma who had previously failed to respond to omalizumab. The main objective was to determine whether treatment with reslizumab significantly improved asthma symptoms assessed by the Asthma Control Test (ACT) at week 24. Secondary objectives were to evaluate symptoms at weeks 4 and 12, change in FEV at week 24, and the incidence of severe exacerbations over the study period. Results: Twenty-nine patients (62.1% women, median age, 50.8 years) were included in the study. The median ACT score significantly increased from 13.0 (interquartile range, 8.0-18.0) at baseline to 21.0 (interquartile range, 14.0-24.0) at 24 weeks (P =.002). Only 2 of 29 patients developed at least 1 severe exacerbation during follow-up and none of them required hospitalization. Overall, 15 of 25 patients (60%) were considered as being controlled (ACT score of ≥20 and no exacerbations) at week 24. The percentage of patients who were receiving daily systemic corticosteroids significantly decreased from 72.4% to 52.0% (P =.019). Adverse events were mostly moderate and within the range of previously reported side effects with reslizumab. Conclusion: Reslizumab is an effective and safe option for patients with severe eosinophilic asthma and a history of omalizumab failure

Antigenic Proteins Involved in Occupational Rhinitis 1 and Asthma Caused by Obeche Wood (Triplochiton Scleroxylon)

Background Obeche wood dust is a known cause of occupational asthma where an IgE-mediated mechanism has been demonstrated. Objective To characterize the allergenic profile of obeche wood dust and evaluate the reactivity of the proteins by in vitro, ex vivo and in vivo assays in carpenters with confirmed rhinitis and/or asthma Materials and methods An in-house obeche extract was obtained, and two IgE binding bands were purified (24 and 12 kDa) and sequenced by N-terminal identity. Specific IgE and IgG, basophil activation tests and skin prick tests (SPTs) were performed with whole extract and purified proteins. CCD binding was analyzed by ELISA inhibition studies. Results Sixty-two subjects participated: 12 with confirmed occupational asthma/rhinitis (ORA+), 40 asymptomatic exposed (ORA−), and 10 controls. Of the confirmed subjects, 83% had a positive SPT to obeche. There was a 100% recognition by ELISA in symptomatic subjects vs. 30% and 10% in asymptomatic exposed subjects and controls respectively (p<0.05). Two new proteins were purified, a 24 kDa protein identified as a putative thaumatin-like protein and a 12 kDa gamma-expansin. Both showed allergenic activity in vitro, with the putative thaumatin being the most active, with 92% recognition by ELISA and 100% by basophil activation test in ORA+ subjects. Cross-reactivity due to CCD was ruled out in 82% of cases. Conclusions Two proteins of obeche wood were identified and were recognized by a high percentage of symptomatic subjects and by a small proportion of asymptomatic exposed subjects. Further studies are required to evaluate cross reactivity with other plant allergens

Overall asthma control achieved with budesonide/formoterol maintenance and reliever therapy for patients on different treatment steps

<p>Abstract</p> <p>Background</p> <p>Adjusting medication for uncontrolled asthma involves selecting one of several options from the same or a higher treatment step outlined in asthma guidelines. We examined the relative benefit of introducing budesonide/formoterol (BUD/FORM) maintenance and reliever therapy (Symbicort SMART^®Turbuhaler^®) in patients previously prescribed treatments from Global Initiative for Asthma (GINA) Steps 2, 3 or 4.</p> <p>Methods</p> <p>This is a <it>post hoc </it>analysis of the results of five large clinical trials (>12000 patients) comparing BUD/FORM maintenance and reliever therapy with other treatments categorised by treatment step at study entry. Both current clinical asthma control during the last week of treatment and exacerbations during the study were examined.</p> <p>Results</p> <p>At each GINA treatment step, the proportion of patients achieving target levels of current clinical control were similar or higher with BUD/FORM maintenance and reliever therapy compared with the same or a higher fixed maintenance dose of inhaled corticosteroid/long-acting β₂-agonist (ICS/LABA) (plus short-acting β₂-agonist [SABA] as reliever), and rates of exacerbations were lower at all treatment steps in BUD/FORM maintenance and reliever therapy versus same maintenance dose ICS/LABA (P < 0.01) and at treatment Step 4 versus higher maintenance dose ICS/LABA (P < 0.001). BUD/FORM maintenance and reliever therapy also achieved significantly higher rates of current clinical control and significantly lower exacerbation rates at most treatment steps compared with a higher maintenance dose ICS + SABA (Steps 2-4 for control and Steps 3 and 4 for exacerbations). With all treatments, the proportion of patients achieving current clinical control was lower with increasing treatment steps.</p> <p>Conclusions</p> <p>BUD/FORM maintenance and reliever therapy may be a preferable option for patients on Steps 2 to 4 of asthma guidelines requiring a more effective treatment and, compared with other fixed dose alternatives, is most effective in the higher treatment steps.</p

Pre-asthma : a useful concept? A EUFOREA paper. Part 2—late onset eosinophilic asthma

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