Asthma diagnosis in infants and preschool children: a systematic review of clinical guidelines

Background and aim: The definition and diagnosis of asthma are the subject of controversy that is particularly intense in the case of individuals in the first years of life, due to reasons such as the difficulty of performing objective pulmonary function tests or the high frequency with which the symptoms subside in the course of childhood. Since there is no consensus regarding the diagnosis of asthma in preschool children, a systematic review has been carried out. Materials and methods: A systematic search was made of the clinical guidelines published in the last 10 years and containing information referred to the concept or diagnosis of asthma in childhood - including the first years of life (infants and preschool children). A series of key questions were established, and each selected guide was analyzed in search of answers to those questions. The review protocol was registered in the international prospective register of systematic reviews (PROSPERO), with registration number CRD42017074872. Results: Twenty-one clinical guidelines were selected: 10 general guides (children and adults), eight pediatric guides and three guides focusing on preschool children. The immense majority accepted that asthma can be diagnosed from the first years of life, without requiring pulmonary function tests or other complementary techniques. The response to treatment and the exclusion of other alternative diagnoses are key elements for establishing the diagnosis. Only one of the guides denied the possibility of diagnosing asthma in preschool children. Conclusions: There is generalized although not unanimous agreement that asthma can be diagnosed in preschool children

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Asthma diagnosis in infants and preschool children: a systematic review of clinical guidelines.

BACKGROUND AND AIM: The definition and diagnosis of asthma are the subject of controversy that is particularly intense in the case of individuals in the first years of life, due to reasons such as the difficulty of performing objective pulmonary function tests or the high frequency with which the symptoms subside in the course of childhood. Since there is no consensus regarding the diagnosis of asthma in preschool children, a systematic review has been carried out. MATERIALS AND METHODS: A systematic search was made of the clinical guidelines published in the last 10 years and containing information referred to the concept or diagnosis of asthma in childhood - including the first years of life (infants and preschool children). A series of key questions were established, and each selected guide was analyzed in search of answers to those questions. The review protocol was registered in the international prospective register of systematic reviews (PROSPERO), with registration number CRD42017074872. RESULTS: Twenty-one clinical guidelines were selected: 10 general guides (children and adults), eight pediatric guides and three guides focusing on preschool children. The immense majority accepted that asthma can be diagnosed from the first years of life, without requiring pulmonary function tests or other complementary techniques. The response to treatment and the exclusion of other alternative diagnoses are key elements for establishing the diagnosis. Only one of the guides denied the possibility of diagnosing asthma in preschool children. CONCLUSIONS: There is generalized although not unanimous agreement that asthma can be diagnosed in preschool children.

Allergological characterization of children treated with oral immunotherapy to egg

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Sublingual immunotherapy in children

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The influence of microorganisms in allergic diseases

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Waning protection of influenza vaccination during four influenza seasons, 2011/2012 to 2014/2015.

BACKGROUND: Concerns have been raised about intraseasonal waning of the protection conferred by influenza vaccination. METHODS: During four influenza seasons, we consecutively recruited individuals aged 18years or older who had received seasonal influenza vaccine and were subsequently admitted to the hospital for influenza infection, asassessed by reverse transcription polymerase chain reaction. We estimated the adjusted odds ratio (aOR) of influenza infection by date of vaccination, defined by tertiles, as early, intermediate or late vaccination. We used a test-negative approach with early vaccination as reference to estimate the aOR of hospital admission with influenza among late vaccinees. We conducted sensitivity analyses by means of conditional logistic regression, Cox proportional hazards regression, and using days between vaccination and hospital admission rather than vaccination date. RESULTS: Among 3615 admitted vaccinees, 822 (23%) were positive for influenza. We observed a lower risk of influenza among late vaccinees during the 2011/2012 and 2014/2015A(H3N2)-dominant seasons: aOR=0.68 (95% CI: 0.47-1.00) and 0.69 (95% CI: 0.50-0.95). We found no differences in the risk of admission with influenza among late versus early vaccinees in the 2012/2013A(H1N1)pdm09-dominant or 2013/2014B/Yamagata lineage-dominant seasons: aOR=1.18 (95% CI: 0.58-2.41) and 0.98 (95% CI: 0.56-1.72). When we restricted our analysis to individuals aged 65years or older, we found a statistically significant lower risk of admission with influenza among late vaccinees during the 2011/2012 and 2014/2015A(H3N2)-dominant seasons: aOR=0.61 (95% CI: 0.41-0.91) and 0.69 (95% CI: 0.49-0.96). We observed 39% (95% CI: 9-59%) and 31% (95% CI: 5-50%) waning of vaccine effectiveness among participants aged 65years or older during the two A(H3N2)-dominant seasons. Similar results were obtained in the sensitivity analyses. CONCLUSION: Waning of vaccine protection was observed among individuals aged 65years old or over in two A(H3N2)-dominant influenza seasons.

Evidence in immunotherapy for paediatric respiratory allergy: Advances and recommendations. Document of the Immunotherapy Working Group of the Spanish Society of Pediatric Clinical Immunology and Allergology (SEICAP)

Allergic respiratory diseases are major health problems in paediatric population due their high level of prevalence and chronicity, and to their relevance in the costs and quality of life. One of the most important risk factors for the development of airway diseases in children and adolescents is atopy. The mainstays for the treatment of these diseases are avoiding allergens, controlling symptoms, and preventing them through sustained desensitization by allergen immunotherapy (AIT). AIT is a treatment option that consists in the administration of increasing amounts of allergens to modify the biological response to them, inducing long-term tolerance even after treatment has ended. This treatment approach has shown to decrease symptoms and improve quality of life, becoming cost effective for a large number of patients. In addition, it is considered the only treatment that can influence the natural course of the disease by targeting the cause of the allergic inflammatory response. The aim of this publication is to reflect the advances of AIT in the diagnosis and treatment of allergic respiratory diseases in children and adolescents reviewing articles published since 2000, establishing evidence categories to support the strength of the recommendations based on evidence. The first part of the article covers the prerequisite issues to understand how AIT is effective, such as the correct etiologic and clinical diagnosis of allergic respiratory diseases. Following this, the article outlines the advancements in understanding the mechanisms by which AIT achieve immune tolerance to allergens. Administration routes, treatment regimens, dose and duration, efficacy, safety, and factors associated with adherence are also reviewed. Finally, the article reviews future advances in the research of AIT

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Evidence in immunotherapy for paediatric respiratory allergy: Advances and recommendations.

Allergic respiratory diseases are major health problems in paediatric population due their high level of prevalence and chronicity, and to their relevance in the costs and quality of life. One of the most important risk factors for the development of airway diseases in children and adolescents is atopy. The mainstays for the treatment of these diseases are avoiding allergens, controlling symptoms, and preventing them through sustained desensitization by allergen immunotherapy (AIT). AIT is a treatment option that consists in the administration of increasing amounts of allergens to modify the biological response to them, inducing long-term tolerance even after treatment has ended. This treatment approach has shown to decrease symptoms and improve quality of life, becoming cost effective for a large number of patients. In addition, it is considered the only treatment that can influence the natural course of the disease by targeting the cause of the allergic inflammatory response. The aim of this publication is to reflect the advances of AIT in the diagnosis and treatment of allergic respiratory diseases in children and adolescents reviewing articles published since 2000, establishing evidence categories to support the strength of the recommendations based on evidence. The first part of the article covers the prerequisite issues to understand how AIT is effective, such as the correct etiologic and clinical diagnosis of allergic respiratory diseases. Following this, the article outlines the advancements in understanding the mechanisms by which AIT achieve immune tolerance to allergens. Administration routes, treatment regimens, dose and duration, efficacy, safety, and factors associated with adherence are also reviewed. Finally, the article reviews future advances in the research of AIT.

Factors that increase wheezing risk in nursing infants in the first year of life

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PURPOSE: Juvenile systemic lupus erythematosus (JSLE) is a severe and chronic autoimmune disease of unknown origin. Inflammatory cytokines can play a pivotal role in the pathogenesis of JSLE, while their secretion is under genetic control. The current investigation was performed to analyse the associations of particular single nucleotide polymorphisms (SNPs) of interleukin-2 (IL-2) and interferon-gamma (IFN-γ) genes in a case control study. MATERIALS AND METHODS: The allele, genotype and haplotype frequencies of the polymorphic IL-2 (G/T at −330, rs2069762, and G/T at +166, rs2069763) and IFN-γ (A/T at +874, rs2430561) genes were estimated in 59 patients with JSLE by contrast with 140 healthy controls using polymerase chain reaction with sequence-specific primers method. RESULTS: Results of the analysed data revealed a negative allelic association for JSLE in IL-2 −330/T (P=0.02), as well as a positive allelic association for IL-2 −330/G (P=0.02). IL-2 GG genotype (−330) in the patient group was also significantly overrepresented (P<0.001), while IL-2 GT genotype (−330) was notably decreased in the patients with JSLE (P<0.001). Additionally, the frequency of IL-2 (−330, +166) GT haplotype was significantly higher in the patient group (P<0.001). CONCLUSION: IL-2 cytokine gene polymorphisms could affect individual susceptibility to JSLE and can take on the role of possible genetic markers for vulnerability to JSLE

Consenso para el abordaje del asma grave pediátrica en la práctica clínica habitual / Consensus-based approach for severe paediatric asthma in routine clinical practice

INTRODUCCIÓN: La identificación adecuada del paciente pediátrico con asma grave es esencial para su correcto manejo. Sin embargo, los criterios para definir el asma grave y las recomendaciones para su control varían mucho entre las distintas guías. MATERIAL Y MÉTODOS: Se elaboró una encuesta telemática para analizar las opiniones relativas a la definición y control del asma grave pediátrica. Para lograr un consenso se siguió una metodología Delphi modificada. Con los resultados se elaboraron recomendaciones prácticas. RESULTADOS: El cuestionario fue respondido por 11 neumólogos y alergólogos pediátricos expertos en asma grave. Hubo consenso en 50 de los 65 ítems planteados (76,92%). Se consideró que un paciente tiene asma grave si en el último año ha requerido 2 o más ciclos de corticoides orales, si requiere tratamiento diario con corticoides inhalados a dosis medias (con otra medicación controladora) o dosis altas (con o sin otra medicación controladora), si no responde a un tratamiento convencional optimizado, o si la enfermedad pone en riesgo su vida o deteriora gravemente su calidad de vida. La definición de asma grave también podría incluir a los pacientes que consumen recursos sanitarios de manera regular y justificada, o tienen factores psicosociales o ambientales que impiden su control. Para la monitorización, se recomienda usar cuestionarios específicos de población pediátrica (CAN o ACT). Respecto al tratamiento, se debería considerar el uso de omalizumab en un escalón anterior al de los corticoides orales. CONCLUSIONES: El presente trabajo ofrece recomendaciones consensuadas que pueden ser de utilidad en el manejo del asma grave pediátrica

INTRODUCTION: Accurate identification of paediatric patients with severe asthma is essential for an adequate management of the disease. However, criteria for defining severe asthma and recommendations for control vary among different guidelines. MATERIAL AND METHODS: An online survey was conducted to explore expert opinions about the definition and management of severe paediatric asthma. To reach a consensus agreement, a modified Delphi technique was used, and practice guidelines were prepared after the analysis of the results. RESULTS: Eleven paediatric chest disease physicians and allergy specialists with wide expertise in severe asthma responded to the survey. Consensus was reached in 50 out of 65 questions (76.92%). It was considered that a patient has severe asthma if during the previous year they have required 2 or more cycles of oral steroids, required daily treatment with medium doses of inhaled corticosteroids (with other controller medication) or high doses (with or without other controller medication), did not respond to optimised conventional treatment, or if the disease threatened the life of the patient or seriously impairs their quality of life. The definition of severe asthma may also include patients who justifiably use health resources on a regular basis, or have psychosocial or environmental factors impeding control. For monitoring, the use of questionnaires designed specifically for paediatric population, such as CAN or ACT, is recommended. As regards treatment, the use of omalizumab should be considered prior to the use of oral corticosteroids. CONCLUSIONS: This paper provides consensus recommendations that may be useful in the management of severe paediatric asthma

[Consensus-based approach for severe paediatric asthma in routine clinical practice]. / Consenso para el abordaje del asma grave pediátrica en la práctica clínica habitual.

INTRODUCTION: Accurate identification of paediatric patients with severe asthma is essential for an adequate management of the disease. However, criteria for defining severe asthma and recommendations for control vary among different guidelines. MATERIAL AND METHODS: An online survey was conducted to explore expert opinions about the definition and management of severe paediatric asthma. To reach a consensus agreement, a modified Delphi technique was used, and practice guidelines were prepared after the analysis of the results. RESULTS: Eleven paediatric chest disease physicians and allergy specialists with wide expertise in severe asthma responded to the survey. Consensus was reached in 50 out of 65 questions (76.92%). It was considered that a patient has severe asthma if during the previous year they have required 2 or more cycles of oral steroids, required daily treatment with medium doses of inhaled corticosteroids (with other controller medication) or high doses (with or without other controller medication), did not respond to optimised conventional treatment, or if the disease threatened the life of the patient or seriously impairs their quality of life. The definition of severe asthma may also include patients who justifiably use health resources on a regular basis, or have psychosocial or environmental factors impeding control. For monitoring, the use of questionnaires designed specifically for paediatric population, such as CAN or ACT, is recommended. As regards treatment, the use of omalizumab should be considered prior to the use of oral corticosteroids. CONCLUSIONS: This paper provides consensus recommendations that may be useful in the management of severe paediatric asthma.

Effectiveness of influenza vaccination programme in preventing hospital admissions, Valencia, 2014/15 early results.

Preliminary results for the 2014/15 season indicate low to null effect of vaccination against influenza A(H3N2)-related disease. As of week 5 2015, there have been 1,136 hospital admissions, 210 were due to influenza and 98% of subtype A strains were H3. Adjusted influenza vaccine effectiveness was 33% (range: 6-53%) overall and 40% (range: 13% to 59%) in those 65 years and older. Vaccination reduced by 44% (28-68%) the probability of admission with influenza.

Elevated advanced oxidation protein products (AOPPs) indicate metabolic risk in severely obese children.

BACKGROUND AND AIMS: The assessment of oxidative stress may aid in the identification of subsequent metabolic risk in obese children. The objective of this study was to determine whether the plasma level of advanced oxidation protein products, analyzed with a recently proposed modified assay that involves a delipidation step (mAOPPs), was related to metabolic risk factors (MRFs) in severely obese children. METHODS AND RESULTS: The plasma levels of mAOPPs were determined by spectrophotometry in 54 severely obese and 44 healthy children. We also measured lipid peroxidation biomarkers (thiobarbituric acid-reactive substances, malondialdehyde, and 8-isoprotane F(2α)) and sulfhydryl groups, a marker of antioxidant defense. Protein oxidation and lipid peroxidation markers were higher and sulfhydryl levels were lower in obese children compared with controls. Taking metabolic risk into account, obese children were subdivided according to the cutoff point (53.2 µmol/L) obtained for their mAOPPs values from the ROC curve. Anthropometric measures and the existence of hypertension did not differ between groups. The presence of dyslipidemia and insulin resistance was significantly higher in the group with higher mAOPPs levels. The highest levels of mAOPPs were found in the children with ≥3 MRFs. The level of mAOPPs was positively correlated with triglycerides and negatively correlated with high-density lipoprotein cholesterol. There was no correlation of this marker of protein oxidation with biomarkers of lipid peroxidation. CONCLUSION: The determination of mAOPPs in delipidated plasma is an easy way to evaluate protein oxidation. It may be useful in severely obese children for better cardiovascular risk assessment.

New factors of cardiometabolic risk in severely obese children: influence of pubertal status / Nuevos factores de riesgo cardiometabólico en niños con obesidad severa: influencia del estado puberal

The aim of this prospective study was to evaluate the utility of new biochemical markers to assess cardiometabolic risk in severely obese children and adolescents. A total of 107 subjects aged 7 to 14 years, were clinically assessed and anthropometric measures and percentage of fat mass by single frequency bioimpedance analysis were recorded. Of these, 44 were non-overweight and 63 severely obese (body mass index Z-score >2.5) which were stratified by Tanner stages. To estimate the metabolic risk the following variables were considered for analysis: Waist circumference/height >0.5, fasting glucose >100 mg/dL, triglycerides >110 mg/dL, HDL-C <40 mg/dL, and systolic or diastolic blood pressure >95th percentile for age and gender. Fasting insulinemia, apoprotein A1 and B, high-sensitive C-reactive protein, alanine aminotransferase, homocysteine, and folic and uric acids were determined. In severely obese children, metabolic risk was present more frequently in mid puberty. The normalized anthropometric parameters with respect to 50th percentile for age and gender did not differ in the presence of metabolic risk. Insulin resistance was an independent determinant of metabolic risk, adjusted by Tanner stages. Elevated high-sensitive C-reactive protein was noted without any effect of metabolic risk or pubertal stage. Homocysteine, apoprotein B, and alanine aminotransferase values increased with metabolic risk and were not influenced by puberty. Although insulin resistance remains the main factor influencing metabolic risk, biochemical markers as homocysteine, apoprotein B, and alanine aminotransferase, may be useful for identifying severe obese pubertal subjects particularly prone to comorbidities (AU)

El objetivo de este estudio prospectivo ha sido evaluar la utilidad de nuevos marcadores bioquímicos para evaluar el riesgo cardiometabólico en niños y adolescentes extremadamente obesos. Un total de 107 sujetos de entre 7 a 14 años, se valoraron clínicamente registrando sus medidas antropométricas y el porcentaje de masa grasa mediante bioimpedancia. De ellos, 44 presentaban un peso normal para su edad y género y 63 estaban gravemente obesos (puntuación Z del índice de masa corporal > 2,5), los cuales fueron estratificados por estadios de Tanner. Para valorar el riesgo metabólico se consideraron las siguientes variables: Circunferencia cintura/altura> 0,5, glucosa en ayunas >100 mg/dL, triglicéridos >110 mg/dL, HDL-C <40 mg/dL y presión arterial sistólica o diastólica > percentil 95 para edad y género. Se determinaron la insulinemia en ayunas, apoproteinas A1 y B, proteína C reactiva ultrasensible, alaninaminotransferasa, homocisteína y ácidos fólico y úrico. En los niños obesos severos, la presencia de factores de riesgo metabólico se producía con más frecuencia en la pubertad. Los parámetros antropométricos normalizados con respecto al percentil 50 para la edad y género no se diferenciaban según existiera o no mayor riego metabólico. La resistencia a la insulina fue un factor independiente de riesgo metabólico, ajustado por etapas de Tanner. La proteína C reactiva ultrasensible estaba elevada, sin relación con la mayor presencia de factores de riesgo del síndrome metabólico o la etapa puberal. La homocisteína, apoproteína B, y la alaninaminotransferasa se incrementaron con el riesgo metabólico y no fueron influidos por la pubertad. Aunque la resistencia a la insulina sigue siendo el principal factor que influye en el riesgo metabólico, los marcadores bioquímicos como la homocisteína, apoproteína B, y la alaninaminotransferasa, pueden ser útiles para identificar individuos con obesidad grave en etapa puberal predispuestos a padecer enfermedades relacionadas (AU)

Pulmonary agenesis: Importance of the diagnosis

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