Cost-effectiveness of omalizumab for the treatment of severe pediatric allergic asthma-Results of a real-life study in Spain.

BACKGROUND: Severe pediatric allergic asthma (SPAA) induces a huge economic burden in terms of direct, indirect, and intangible costs. The use of omalizumab for the treatment of these patients has produced a significant improvement in several clinical outcomes, but at the same time, the cost for the management of the disease has also increased. The aim of this report was to evaluate whether the use of omalizumab is cost-effective. METHODS: A sample of 426 children with SPAA from the ANCHORS (Asthma iN CHildren: Omalizumab in Real-life in Spain) study was used to calculate the incremental cost-effectiveness ratio (ICER) for the avoidance of moderate-to-severe exacerbations (MSE) and also for the improvement in childhood Asthma Control Test (c-ACT) or the Asthma Control Questionnaire (ACQ5). We retrospectively collected data on health encounters and drug consumption before and up to 6 years after the beginning of the treatment with omalizumab. RESULTS: The ICER per avoided MSE was €2107 after 1 year, and it consistently decreased to €656 in those followed up to 6 years. Similarly, the ICER for the minimally important difference in control tests showed a decrease from €2059 to €380 per each 0.5 points of improvement in ACQ5 and from €3141 to €2322 per each 3 points improvement in c-ACT, at years 1 and 6, respectively. CONCLUSION: The use of OMZ is a cost-effective option for most children with uncontrolled SPAA, especially those who have frequent exacerbations; the costs are progressively reduced in successive years of treatment.

Omalizumab outcomes for up to 6 years in pediatric patients with severe persistent allergic asthma.

BACKGROUND: Various studies have assessed omalizumab outcomes in the clinical practice setting but follow-up and/or number of patients included were limited. We aim to describe the long-term outcomes of pediatric patients with severe persistent allergic asthma receiving omalizumab in the largest real-life cohort reported to date. METHODS: ANCHORS was a multicenter, observational, retrospective cohort study conducted in 25 Pediatric Allergy and Pulmonology units in Spain. We collected data of patients < 18 years and initiating omalizumab between 2006 and 2018, from the year prior to omalizumab initiation to discontinuation or last available follow-up. The primary outcome was the evolution of the annual number of moderate-to-severe exacerbations compared with the baseline period. RESULTS: Of the 484 patients included, 101 (20.9%) reached 6 years of treatment. The mean ± standard deviation number of exacerbations decreased during the first year of treatment (7.9 ± 6.6 to 1.1 ± 2.0, P < .001) and remained likewise for up to 6 years. The other clinical parameters assessed also improved significantly during the first year and stabilized or continued to improve thereafter. The percentage of patients experiencing adverse events was consistently low, and the main reason for discontinuation was good disease evolution. CONCLUSION: In this large, long-term, observational study, moderate-to-severe exacerbations decreased significantly from the first year of treatment with omalizumab. The beneficial effect was maintained in the long term, along with a good safety profile. Our results position omalizumab as an effective long-term treatment in pediatric patients with severe persistent allergic asthma.

The impact of atmospheric pollutants on the prevalence of atopic eczema in 6-7-year-old schoolchildren in Spain; ISAAC Phase III.

Atopic Eczema (AE) is a chronic inflammatory skin disease that affects children and adults, and alters quality of life with a high morbidity rate and severe economic burden. The objective of the present work was to analyse specific atmospheric pollutants (O3, NO, PM10 and SO2) affecting the prevalence of diagnosed AE and its symptoms among 6-7-year-old schoolchildren.The participants included 21311 schoolchildren aged 6-7 years from 8 Spanish regions, whose parents completed the ISAAC Phase III questionnaire to ascertain AE diagnosis and symptoms. The mean levels (µg/m3) of O3, NO, PM10 (particles 10 micrometers or less in diameter) and SO2 were determined in each geographical area. Participating in this study.According to these mean levels, three levels of exposure to each pollutant were considered: level 1 (percentiles 0-25); level 2 (percentiles 26-74); level 3 (percentiles 75-100). Exposure to O3 was associated with increased prevalence of rashes (exposure level 2, Odds Ratio (OR): 1.22, 95% Confidence Interval (95%CI): 1.02-1.45; level 3 OR: 1.33, 95%CI: 1.10-1.61) and diagnosed AE (level 2, OR: 1.27, 95%CI: 1.17-1.39; level 3 OR: 1.27, 95%CI: 1.15-1.41). An association was found between the level of NO and a drop in the prevalence of diagnosed AE (exposure level 2, OR: 0.88, 95%CI: 0.81-0.95; level 3 OR: 0.85, 95%CI: 0.74-0.97). There was also an association between the highest exposure level to PM10 and a reduced prevalence of rashes (level 3 OR: 0.42, 95%CI: 0.22-0.81) and diagnosed AE (level 3 OR: 0.53, 95%CI: 0.38-0.75). Future studies into exposure to O3 and its relationship with allergic diseases may be conducted in order to prevent this association.

Is acetaminophen use associated with atopic eczema and other allergic diseases in adolescents?

Atopic Eczema (AE) is a chronic inflammatory skin disease that affects children and adults, and alters quality of life. Previous studies have suggested several socio-demographic and environmental factors related to the prevalence of AE and other allergic diseases, including acetaminophen use. In the present study, we report the rates of isolated AE, AE associated with asthma and AE associated with rhinitis among 13- to 14-year-old Spanish adolescents and the level of association of these conditions with the use of acetaminophen. We analyzed Spanish data from a cross-sectional Phase 3 study within ISAAC. A total of 28,717 adolescents completed the Phase 3 written questionnaire by answering questions for acetaminophen use and on asthma, rhinitis and AE symptoms.We observed an association between acetaminophen use and AE among the adolescents who had used acetaminophen in the previous month. Furthermore, the prevalence rate increased with the number of allergic processes: for AE alone, the adjusted Prevalence Ratio (aPR) was 1.81 and for AE associated with rhinitis or with asthma, aPRs were 2.20 and 3.03, respectively.We conclude that acetaminophen use in childhood may be an important factor associated with development and/or maintenance of AE and other allergic diseases.

Atopic dermatitis and indoor use of energy sources in cooking and heating appliances.

BACKGROUND: Atopic dermatitis (AD) prevalence has considerably increased worldwide in recent years. Studying indoor environments is particularly relevant, especially in industrialised countries where many people spend 80% of their time at home, particularly children. This study is aimed to identify the potential association between AD and the energy source (biomass, gas and electricity) used for cooking and domestic heating in a Spanish schoolchildren population. METHODS: As part of the ISAAC (International Study of Asthma and Allergies in Childhood) phase III study, a cross-sectional population-based survey was conducted with 21,355 6-to-7-year-old children from 8 Spanish ISAAC centres. AD prevalence, environmental risk factors and the use of domestic heating/cooking devices were assessed using the validated ISAAC questionnaire. Crude and adjusted odds ratios (cOR, aOR) and 95% confidence intervals (CIs) were obtained. A logistic regression analysis was performed (Chi-square test, p-value < 0.05). RESULTS: It was found that the use of biomass systems gave the highest cORs, but only electric cookers showed a significant cOR of 1.14 (95% CI: 1.01-1.27). When the geographical area and the mother's educational level were included in the logistic model, the obtained aOR values differed moderately from the initial cORs. Electric heating was the only type which obtained a significant aOR (1.13; 95% CI: 1.00-1.27). Finally, the model with all selected confounding variables (sex, BMI, number of siblings, mother's educational level, smoking habits of parents, truck traffic and geographical area), showed aOR values which were very similar to those obtained in the previous adjusted logistic analysis. None of the results was statistically significant, but the use of electric heating showed an aOR close to significance (1.14; 95% CI: 0.99-1.31). CONCLUSION: In our study population, no statistically significant associations were found between the type of indoor energy sources used and the presence of AD.

Early exposure to paracetamol or to antibiotics and eczema at school age: modification by asthma and rhinoconjunctivitis.

The association between early exposure to paracetamol or to antibiotics and eczema is conflicting. This study aims to know whether the early exposure to those drugs is associated with eczema at school age, and whether the strength of the association is modified by the presence of asthma or rhinoconjunctivitis. Children aged 6-7 (n = 13908) from the International Study of Asthma and Allergies in Childhood in Spain provided data about current asthma, rhinoconjunctivitis and eczema. Parent-reported information was also obtained on paracetamol and antibiotic consumption during the first year of life. Logistic regression analysis with eczema as outcome and including exposure to paracetamol or to antibiotics, together with possible confounders, was carried out in the whole sample of children and in five different strata: no respiratory symptom and any respiratory symptom further subdivided into: asthma with rhinoconjunctivitis, asthma without rhinoconjunctivitis and rhinoconjunctivitis without asthma. In the whole sample, exposure to paracetamol was associated with eczema (aOR 1.56 [1.36-1.80]) as was antibiotic consumption (aOR 1.66 [1.43-1.92]). These associations did not substantially change after additionally adjusting for the other drug. A similar pattern was found among children without respiratory symptoms. In children with symptoms, adjusting for the other drug modified the association with paracetamol (aOR from 1.32 [1.03-1.71] to 1.09 [0.83-1.43]) but did not change that with antibiotics (aOR from 1.80 [1.38-2.35] to 1.81 [1.37-2.39]). Early exposure to paracetamol or to antibiotics is associated with an increased prevalence of eczema at school age. Asthma and/or rhinoconjunctivitis substantially modifies this association.

Contaminación del aire y síntomas recientes de asma, rinitis alérgica y eccema atópico en escolares de 6 y 7 años / Air Pollution and Recent Symptoms of Asthma, Allergic Rhinitis, and Atopic Eczema in Schoolchildren Aged Between 6 and 7 Years

Introducción: El objetivo del estudio ha sido analizar la relación entre contaminantes del aire y la prevalencia de síntomas recientes de asma, rinitis alérgica y eccema atópico, en escolares de 6 y 7 años.Pacientes y métodos: La prevalencia de síntomas de enfermedades alérgicas recientes (últimos 12 meses) se obtuvo mediante el cuestionario del estudio ISAAC (International Study of Asthma and Allergies in Childhood) España, con la participación de 7 centros (Asturias, Barcelona, Bilbao, Cartagena, La Coruña, Madrid y Valencia) y 20.455 escolares de 6 y 7 años, durante 2002–2003. De los sistemas de detección de contaminantes de los centros citados se obtuvieron datos de las concentraciones anuales medias de dióxido de azufre (SO2), dióxido de nitrógeno (NO2), monóxido de carbono (CO) y total de partículas en suspensión.Resultados: La concentración media anual (CMA) de SO2 se asoció significativamente con una mayor prevalencia de asma grave reciente (odds ratio ajustada [ORa], nivel 3 sobre nivel 1 de contaminación=1,32; intervalo de confianza [IC] del 95%, 1,01–1,73), rinitis (ORa=1,56; IC del 95%, 1,39–1,75) y rinoconjuntivitis (ORa=1,70; IC del 95%, 1,45–2,00). La CMA de CO se asoció con una prevalencia más alta de rinitis (ORa=1,65; IC del 95%, 1,34–2,04), rinoconjuntivitis (ORa=1,76; IC del 95%, 1,31–2,37) y eccema atópico (ORa=1,55; IC del 95%, 1,17–2,04). Las CMA de NO2 y de total de partículas en suspensión presentaron asociaciones inversas con la prevalencia de tos seca nocturna.Conclusiones: Se indica qué contaminantes del aire, como SO2 y CO, incrementan el riesgo de síntomas recientes de asma y rinitis alérgica en escolares de 6 y 7 años de nuestro medio(AU)

Objective: The objective of the study was to analyze the relationship between air pollutants and the prevalence of recent symptoms of asthma, allergic rhinitis, and atopic eczema in schoolchildren aged between 6 and 7 years.Patients and Methods: The prevalence of recent (previous 12 months) symptoms of allergic diseases was obtained by means of the questionnaire of the International Study of Asthma and Allergies in Childhood (ISAAC), Spain, with the participation of 7 centers (Asturias, Barcelona, Bilbao, Cartagena, La Coruña, Madrid, and Valencia) and 20 455 schoolchildren aged between 6 and 7 years, from 2002 to 2003. The pollutant detection systems of the aforementioned centers provided the mean annual concentrations of sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and total suspended particulate matter.Results: The annual average concentration of SO2 showed a significant association with a higher prevalence of recent severe asthma (adjusted odds ratio [aOR] between level-1 and level-3 pollution, 1.32; 95% confidence interval [CI], 1.01–1.73), rhinitis (aOR, 1.56; 95% CI, 1.39–1.75), and rhinoconjunctivitis (aOR, 1.70; 95% CI, 1.45–2.00). The annual average concentration of CO was associated with a higher prevalence of rhinitis (aOR, 1.65; 95% CI, 1.34–2.04), rhinoconjunctivitis (aOR, 1.76; 95% CI, 1.31–2.37), and eczema (aOR, 1.55; 95% CI, 1.17–2.04). The annual average concentration for NO2 and total suspended particulate matter showed inverse associations with the prevalence of nocturnal dry cough.Conclusions: Findings suggest that air pollutants such as SO2 and CO increase the risk of recent symptoms of asthma and allergic rhinitis in schoolchildren aged between 6 and 7 years in Spain(AU)

[Air pollution and recent symptoms of asthma, allergic rhinitis, and atopic eczema in schoolchildren aged between 6 and 7 years]. / Contaminación del aire y síntomas recientes de asma, rinitis alérgica y eccema atópico en escolares de 6 y 7 años.

OBJECTIVE: The objective of the study was to analyze the relationship between air pollutants and the prevalence of recent symptoms of asthma, allergic rhinitis, and atopic eczema in schoolchildren aged between 6 and 7 years. PATIENTS AND METHODS: The prevalence of recent (previous 12 months) symptoms of allergic diseases was obtained by means of the questionnaire of the International Study of Asthma and Allergies in Childhood (ISAAC), Spain, with the participation of 7 centers (Asturias, Barcelona, Bilbao, Cartagena, La Coruña, Madrid, and Valencia) and 20 455 schoolchildren aged between 6 and 7 years, from 2002 to 2003. The pollutant detection systems of the aforementioned centers provided the mean annual concentrations of sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and total suspended particulate matter. RESULTS: The annual average concentration of SO2 showed a significant association with a higher prevalence of recent severe asthma (adjusted odds ratio [aOR] between level-1 and level-3 pollution, 1.32; 95% confidence interval [CI], 1.01-1.73), rhinitis (aOR, 1.56; 95% CI, 1.39-1.75), and rhinoconjunctivitis (aOR, 1.70; 95% CI, 1.45-2.00). The annual average concentration of CO was associated with a higher prevalence of rhinitis (aOR, 1.65; 95% CI, 1.34-2.04), rhinoconjunctivitis (aOR, 1.76; 95% CI, 1.31-2.37), and eczema (aOR, 1.55; 95% CI, 1.17-2.04). The annual average concentration for NO2 and total suspended particulate matter showed inverse associations with the prevalence of nocturnal dry cough. CONCLUSIONS: Findings suggest that air pollutants such as SO2 and CO increase the risk of recent symptoms of asthma and allergic rhinitis in schoolchildren aged between 6 and 7 years in Spain.

Influence of two different geo-climatic zones on the prevalence and time trends of asthma symptoms among Spanish adolescents and schoolchildren.

Few studies have focused on the long-term influence of the climate on the prevalence of asthma. The aim of this study is to establish the influence of geo-climatic conditions on the prevalence of asthma symptoms both in adolescents and schoolchildren, and to discover if this influence is associated with their time trends. Eight centres in Spain performed both ISAAC phases I (1994) and III (2002) in children 13-14 years old. Six of them also surveyed children 6-7 years old. For each age group and phase, about 3,000 children were surveyed per centre. This study examines the prevalence of current wheeze and severe current wheeze in two different geo-climatic zones, coast and plateau, considering their relative humidity and temperature range. In both age groups, the mean asthma prevalence on the coast, for phase I and III, was significantly higher than on the plateau. Living on the plateau was an independent protective factor for current wheeze and severe current wheeze for the two age groups. Within the coastal centres, the increase of the annual relative humidity was a statistical significant risk factor for current wheeze, the same trend existing for current severe wheeze. These effects were independent of the sex and of the phase of the study. The prevalence of asthma and severe asthma symptoms is more frequent on the coast of Spain as compared to the inner plateau. This finding was repeated both in 1994 and in 2002.

[Prevalence of atopic eczema and nutritional factors in 6-7 year old children]. / Prevalencia de dermatitis atópica y factores nutricionales en niños de 6-7 años.

OBJECTIVES: To describe the prevalence of atopic eczema (AE) and to find the characteristics of the diet of children with AE. DESIGN: Descriptive, transversal study. SETTING: Primary schools. MAIN MEASUREMENTS: The study used the standardized and validated questionnaire of the ISAAC phase III study, which finds the prevalence of AE in children and enables inter-centre comparison to be conducted. A questionnaire about food consumption was included. The prevalence ratio (PR) of AE and food consumption (95% confidence intervals) was calculated. RESULTS: A total of 28 448 children aged 6-7 were included in the study. The prevalence of clinically diagnosed AE was 15.35% in boys and 15.24% in girls. The foods most often consumed were: dairy and cereals, followed by rice, pasta, and eggs. The least consumed were: butter, margarine, and fast food. The PR for children who consumed pasta was (PR=1.35), seafood (PR=1.28), cereals (PR=1.26), eggs (PR=1.13), and meat (PR=1.09). CONCLUSIONS: The prevalence of AE in Spain was 15.3%, and was associated with food consumption. The consumption of dairy products, cereals, and olive oil was appropriate. The intake of fruit, vegetables, seafood, and legumes was below the recommended amounts. Future studies on the question are needed.

Prevalencia de dermatitis atópica y factores nutricionales en niños de 6-7 años / Prevalence of atopic eczema and nutritional factors in 6-7 year old children

Objetivo. Describir la prevalencia de dermatitis atópica (DA) y conocer las características de la dieta en niños con DA. Diseño. Estudio descriptivo, transversal. Emplazamiento. Centros escolares de educación primaria. Mediciones principales. Se realizó un estudio mediante la utilización del cuestionario validado y estandarizado del estudio ISAAC de fase III, que permite conocer la prevalencia de DA en niños y compararla entre centros. Se acompañó de una encuesta sobre consumo de alimentos. Se calcularon la razón de prevalencia (RP) de DA en relación con el consumo de alimentos y los intervalos de confianza del 95%. Resultados. Se incluyó en el estudio a un total de 28.448 niños de 6-7 años. La prevalencia de DA clínicamente diagnosticada fue del 15,35% en niños y del 15,24% en niñas. Los alimentos más consumidos fueron la leche y los cereales, seguidos del arroz, la pasta y los huevos. Los alimentos menos consumidos fueron la mantequilla, la margarina y la comida rápida. Se observó una razón de prevalencia de DA en los niños que consumían pasta (RP = 1,35), pescado (RP = 1,28), cereales (RP = 1,26), huevos (RP = 1,13) y carne (RP = 1,09). Conclusiones. La prevalencia de DA en España fue del 15,3% asociada con el consumo de alimentos. El consumo de lácteos, cereales y aceite de oliva es adecuado. La ingesta de fruta, verdura, pescado y legumbres es inferior a la aconsejada. Sería necesario realizar futuros estudios sobre el tema

Objectives. To describe the prevalence of atopic eczema (AE) and to find the characteristics of the diet of children with AE. Design. Descriptive, transversal study. Setting. Primary schools. Main measurements. The study used the standardized and validated questionnaire of the ISAAC phase III study, which finds the prevalence of AE in children and enables inter-centre comparison to be conducted. A questionnaire about food consumption was included. The prevalence ratio (PR) of AE and food consumption (95% confidence intervals) was calculated. Results. A total of 28 448 children aged 6-7 were included in the study. The prevalence of clinically diagnosed AE was 15.35% in boys and 15.24% in girls. The foods most often consumed were: dairy and cereals, followed by rice, pasta, and eggs. The least consumed were: butter, margarine, and fast food. The PR for children who consumed pasta was (PR=1.35), seafood (PR=1.28), cereals (PR=1.26), eggs (PR=1.13), and meat (PR=1.09). Conclusions. The prevalence of AE in Spain was 15.3%, and was associated with food consumption. The consumption of dairy products, cereals, and olive oil was appropriate. The intake of fruit, vegetables, seafood, and legumes was below the recommended amounts. Future studies on the question are needed

Asthma attributable to atopy: does it depend on the allergen supply?

The use of the population attributable fraction (PAF) of asthma owing to atopy has not been widely used in epidemiological studies on childhood asthma, especially to compare regions of the same country. The present study includes 1039 children from Cartagena, Spain (Mediterranean coast) and 663 from Madrid (centre of Spanish plateau) using the ISAAC phase II methodology (questionnaire and prick test to the most common allergens). While there were no differences in asthma symptoms between school children (aged 10-11 yr) from Madrid and Cartagena, atopy to any allergen was significantly higher in those from Madrid (40.9% vs. 29.3%, respectively, p < 0.0001). However, children from Madrid were mainly positive to pollen allergy whereas those from Cartagena were positive for mite allergy. PAF of all the different asthma symptoms owing to atopy (any positive skin test) and PAF of current wheezing owing to a more severe atopy (three positive wheals) were higher in children from Cartagena than those from Madrid (45.5% vs. 28.6% and 14.2% vs. 6.2%, respectively). Per cent of previous year wheezing attributable to atopy to specific allergens varied among those cities and was higher for D. pteronissinus, D. farinae, cat, and olive tree in children from Cartagena, and--conversely--higher for mixed grasses, mixed trees and Alternaria in those from Madrid. All of these differences remained significant even after adjusting for risk factors. PAF for asthma owing to atopy could be very different within the same country, probably depending on the allergen supply which may depend on environmental factors such as the climate.

[Time trends in prevalence of symptoms of allergic rhinitis in 13-14 year-old schoolchildren in 8 areas of Spain between 1993-1994 and 2001-2002 according to the International Study of Asthma and Allergies in Childhood (ISAAC)]. / Evolución temporal de la prevalencia de síntomas de rinitis alérgica en escolares de 13-14 años de 8 áreas españolas entre 1993-1994 y 2001-2002 según el Estudio Internacional sobre Asma y Alergias en la Infancia (ISAAC).

BACKGROUND AND OBJECTIVE: Our goal was to estimate the time trends in the prevalence of symptoms of allergic rhinitis (AR) and its geographic variations. POPULATION AND METHOD: During 2001-2002, the phase 3 of ISAAC study was carried out, and a comparison with the phase 1 (1993-1994) was done. This cross sectional study included 30,046 schoolchildren 13-14 years-old from 9 centers (Asturias, Barcelona, Bilbao, Cartagena, Castellon, Madrid, Pamplona, Valencia, and Valladolid). A questionnaire about rhinitis symptoms self-administered to schoolchildren was used at schools and institutes with a participation rate of 100% to 75.8%. RESULTS: A divergent time trend of AR prevalence symptoms was observed with a decrease in Barcelona and Bilbao, a stabilization in Cartagena, Pamplona, and Valencia, and an increase in Castellon; Madrid and Valladolid; however, there was an overall increase in nasal allergy. The prevalence of rhinoconjunctivitis in the past year (Prevalence Ratio [PR] = 1,13; 95% Confidence Interval [CI], 1.07-1.19) and nasal allergy ever (PR = 1.22; 95% CI, 1.15-1.30) increased after adjusting for gender, center and season change. The prevalence of rhinoconjunctivitis and nasal allergy varied according to centres, Madrid, Asturias, Cartagena and Bilbao exhibiting the higher prevalence. Taken as a whole, these data indicate a middle prevalence of AR when compared with other countries following an ISAAC methodology. CONCLUSIONS: Two patterns of time trend of prevalence of symptoms of AR were observed. The investigation of risk factors at local level could be important in order to undertake preventive measures.