RESUMEN
BACKGROUND: Diagnosing atopic dermatitis (AD) in infants is challenging. OBJECTIVES: To determine the incidence and persistence of eczema and AD in infants using the UK Working Party (UKWP) and Hanifin and Rajka (H&R) criteria. METHODS: A cohort of 1834 infants was examined clinically at 3, 6 and 12 months of age. AD was diagnosed by UKWP (3, 6 and 12 months) and H&R (12 months) criteria. Logistic regression models were used to assess the relationship between AD and eczema. RESULTS: Eczema was observed in 628 (34·2%) infants (n = 240, n = 359 and n = 329 at 3, 6 and 12 months, respectively), with AD diagnosed in 212 (33·7%) infants with any eczema and in 64/78 (82%) infants with eczema at all three visits. The odds of AD were lower with first presentation of eczema at 6 [odds ratio (OR) 0·33, 95% confidence interval (CI) 0·22-0·48] or 12 months (OR 0·49, 95% CI 0·32-0·74) than at 3 months, and higher in infants with eczema at three (OR 23·1, 95% CI 12·3-43·6) or two (OR 6·5, 95% CI 4·3-9·9) visits vs. one visit only. At 12 months, 156/329 (47·4%) fulfilled the UKWP and/or H&R criteria; 27 (8%) fulfilled the UKWP criteria only and 65 (20%) only the H&R criteria. Of the 129 infants who fulfilled the H&R criteria, 44 (34·1%) did not meet the itch criterion. CONCLUSIONS: Used in combination and at multiple timepoints, the UKWP and H&R criteria for AD may be useful in clinical research but may have limited value in most other clinical settings.
Asunto(s)
Dermatitis Atópica , Eccema , Estudios de Cohortes , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/epidemiología , Eccema/diagnóstico , Eccema/epidemiología , Humanos , Incidencia , Lactante , PruritoRESUMEN
BACKGROUND: Loss-of-function mutations in the skin barrier gene filaggrin (FLG) increase the risk of atopic dermatitis (AD), but their role in skin barrier function, dry skin and eczema in infancy is unclear. OBJECTIVES: To determine the role of FLG mutations in impaired skin barrier function, dry skin, eczema and AD at 3 months of age and throughout infancy. METHODS: FLG mutations were analysed in 1836 infants in the Scandinavian population-based PreventADALL study. Transepidermal water loss (TEWL), dry skin, eczema and AD were assessed at 3, 6 and 12 months of age. RESULTS: FLG mutations were observed in 166 (9%) infants. At 3 months, carrying FLG mutations was not associated with impaired skin barrier function (TEWL > 11·3 g m-2 h-1 ) or dry skin, but was associated with eczema [odds ratio (OR) 2·89, 95% confidence interval (CI) 1·95-4·28; P < 0·001]. At 6 months, mutation carriers had significantly higher TEWL than nonmutation carriers [mean 9·68 (95% CI 8·69-10·68) vs. 8·24 (95% CI 7·97-8·15), P < 0·01], and at 3 and 6 months mutation carriers had an increased risk of dry skin on the trunk (OR 1·87, 95% CI 1·25-2·80; P = 0·002 and OR 2·44, 95% CI 1·51-3·95; P < 0·001) or extensor limb surfaces (OR 1·52, 95% CI 1·04-2·22; P = 0·028 and OR 1·74, 95% CI 1·17-2·57; P = 0·005). FLG mutations were associated with eczema and AD in infancy. CONCLUSIONS: FLG mutations were not associated with impaired skin barrier function or dry skin in general at 3 months of age, but increased the risk for eczema, and for dry skin on the trunk and extensor limb surfaces at 3 and 6 months.
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Dermatitis Atópica , Eccema , Proteínas Filagrina/genética , Dermatitis Atópica/genética , Eccema/genética , Genotipo , Humanos , Lactante , Proteínas de Filamentos Intermediarios/genética , Proteínas de Filamentos Intermediarios/metabolismo , Mutación/genética , Piel/metabolismoAsunto(s)
Dermatitis Atópica/inmunología , Emolientes/administración & dosificación , Piel/patología , Pérdida Insensible de Agua/inmunología , Administración Cutánea , Mejilla , Dermatitis Atópica/patología , Dermatitis Atópica/prevención & control , Humanos , Lactante , Piel/efectos de los fármacos , Piel/inmunología , Pérdida Insensible de Agua/efectos de los fármacosRESUMEN
AIM: Inflammation is a major factor in the pathophysiology of bronchopulmonary dysplasia (BPD), and it contributes to accelerated telomere shortening and cellular ageing. This study aimed to determine its effect on telomere length and lung function in school-aged children born preterm with BPD. METHODS: We examined 29 children with BPD, born preterm in Stockholm county 1998-99, along with 28 children with allergic asthma born at term matched for age and gender. At 10 years of age, we measured relative telomere length (RTL) in blood by quantitative polymerase chain reaction, lung function by spirometry and inflammation by fractional exhaled nitric oxide and blood cytokines. RESULTS: RTL was not different in preterm born with BPD compared to term born children with asthma. The gender effect was strong in both groups; girls had significantly longer median RTL than boys (1.8 versus 1.5, p < 0.01). Short RTL was associated with low forced expiratory flow, also after adjusting for gender, but was not affected by severity of BPD or ongoing inflammation. CONCLUSION: Telomere length was similar in 10-year-old children born preterm with a history of BPD and term born children with allergic asthma. However, impaired lung function and male gender were associated with short telomeres.
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Asma/genética , Asma/fisiopatología , Displasia Broncopulmonar/genética , Displasia Broncopulmonar/fisiopatología , Recien Nacido Prematuro , Telómero/genética , Factores de Edad , Asma/inmunología , Estudios de Casos y Controles , Senescencia Celular/genética , Niño , Femenino , Estudios de Seguimiento , Humanos , Recién Nacido , Mediadores de Inflamación/análisis , Masculino , Pruebas de Función Respiratoria , Estudios Retrospectivos , Medición de Riesgo , Suecia , Nacimiento a TérminoRESUMEN
BACKGROUND: Multiple allergic sensitizations are common in persistent childhood asthma, and thorough assessment of allergy is crucial for optimal care of these children. Microarray testing offers opportunities for improved sIgE characterization, which has been projected to be useful in the management of multisensitized patients. OBJECTIVE: The aim of this study was to investigate the accuracy and information obtained by two microarray platforms applied on a well-characterized pediatric asthma cohort. METHODS: Seventy-one children were recruited from a nationwide Swedish study on severe childhood asthma. Severe (n = 40) and controlled (n = 31) asthmatics were assessed for allergic sensitization by two microarray systems (Microtest and ISAC) and by two standard diagnostic methods (ImmunoCAP and skin prick test). Data on clinical history, physical examination, spirometry, asthma control test, and doctor's diagnosis were collected. Results from the four diagnostic methods were analyzed and compared. RESULTS: A high prevalence of allergic sensitization was observed in this cohort. The pairwise concordance between two methods was 90-92% independently of methods compared. The sensitivity of the four methods against doctor's diagnosis was 0.77-0.88, and the specificity was 0.97-0.99. Microarray methods provided new information in 47% of the sensitized children in comparison with results obtained by standard diagnostic methods. CONCLUSION: The high prevalence of food and respiratory sensitization supports the clinical guideline recommendation that allergies should be evaluated in all children with suspected asthma. The microarray platforms studied here demonstrated acceptable accuracy and provided refined IgE characterization in 47% of the patients compared to standard extract-based methods.
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Alérgenos/inmunología , Asma/diagnóstico , Asma/inmunología , Hipersensibilidad/diagnóstico , Hipersensibilidad/inmunología , Análisis por Matrices de Proteínas/métodos , Adolescente , Asma/complicaciones , Niño , Manejo de la Enfermedad , Femenino , Humanos , Hipersensibilidad/complicaciones , Inmunoensayo/métodos , Inmunoensayo/normas , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Masculino , Análisis por Matrices de Proteínas/normas , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Pruebas Cutáneas/métodosRESUMEN
BACKGROUND: Information about severe reactions to foods in adolescence is limited. OBJECTIVE: To describe reactions to foods, including anaphylaxis, with regard to incidence, characteristics and associated risks, among 16-year-olds (adolescents) in a large, population-based birth cohort. METHODS: Parent-reported questionnaire data from ages 2-3 months, and 1, 2 and 16 years were used (N = 3153). Anaphylaxis at age 16 years was defined per NIAID/FAAN criteria. Immunoglobulin E (IgE) antibodies to 14 common food and inhalant allergens were analysed at ages 4 (n = 2283) and 16 years (n = 2510). Among adolescents with food-related symptoms (FRS) and for whom blood was available (n = 221), 25 additional food allergen extracts or allergen components were analysed. Associations between reactions to foods, and sensitization and allergic multimorbidity were investigated. RESULTS: In the 12 months prior to the 16-year assessment, 8.5% of adolescents had FRS. This included 0.8% (n = 24) adolescents who were classified as having anaphylaxis, yielding an incidence rate of 761/100 000 person-years. One-third of adolescents accessed health care during anaphylaxis. Allergic multimorbidity in infancy, as well as sensitization to foods and airborne allergens at age 4 years, was associated with an increased risk for FRS in adolescence. Peanuts and tree nuts were the most common culprit foods for anaphylaxis, and fruits and vegetables for non-anaphylactic reactions. Adolescents with anaphylaxis were significantly more likely to be sensitized to storage proteins (Ara h 2, Cor a 9, Cor a 14) and to be polysensitized to foods (P < 0.001 vs. non-anaphylactic reactions). CONCLUSIONS AND CLINICAL RELEVANCE: The incidence of food-induced anaphylaxis during adolescence in our population-based birth cohort is higher than previously reported. Adolescents with anaphylaxis differ from adolescents with non-anaphylactic FRS with regard to culprit foods and sensitization. Adolescents with previous anaphylaxis are likely to be polysensitized to foods, particularly tree nut and peanut storage proteins, and which warrants consideration at follow-up.
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Anafilaxia/epidemiología , Anafilaxia/etiología , Hipersensibilidad a los Alimentos/epidemiología , Alimentos/efectos adversos , Adolescente , Anafilaxia/diagnóstico , Anafilaxia/terapia , Niño , Preescolar , Comorbilidad , Epinefrina/administración & dosificación , Femenino , Estudios de Seguimiento , Hipersensibilidad a los Alimentos/diagnóstico , Hipersensibilidad a los Alimentos/inmunología , Hipersensibilidad a los Alimentos/terapia , Humanos , Inmunización , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Incidencia , Lactante , Masculino , Vigilancia de la Población , Riesgo , Evaluación de SíntomasRESUMEN
BACKGROUND: We have reported that increased fraction of exhaled nitric oxide (FeNO), a measure of TH2 -driven airway inflammation, and blood eosinophil count, a marker of systemic eosinophil inflammation, correlated with asthma attacks in a population-based study. OBJECTIVE: To investigate the relation between simultaneously elevated FeNO and serum eosinophil cationic protein (S-ECP) levels and asthma events among asthmatics. METHODS: Measurements of FeNO (elevated ≥ 25 ppb) and S-ECP (elevated ≥ 20 ng/mL) were performed in 339 adult asthmatics. Asthma events (attacks and symptoms) were self-reported. RESULTS: Simultaneously normal S-ECP and FeNO levels were found in 48% of the subjects. Subjects with simultaneously elevated S-ECP and FeNO (13% of the population) had a higher prevalence of asthma attacks in the preceding 3 months than subjects with normal S-ECP and FeNO (51% vs. 25%, P = 0.001). This was not found for subjects with singly elevated S-ECP (P = 0.14) or FeNO (P = 0.34) levels. Elevated S-ECP and FeNO levels were independently associated with asthma attacks in the preceding 3 months after adjusting for potential confounders (OR (95% CI) 4.2 (2.0-8.8). CONCLUSIONS: Simultaneously elevated FeNO and S-ECP levels were related to a higher likelihood of asthma attacks in the preceding 3 months. This indicates that there is a value in measuring both FeNO and systemic eosinophilic inflammation in patients with asthma to identify individuals at high risk of exacerbations. CLINICAL RELEVANCE: FeNO and S-ECP are markers for inflammation in asthma, but are dependent on different inflammatory pathways and weakly correlated. Simultaneous measurements of both offer better risk characterization of adult asthmatics.
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Asma/diagnóstico , Asma/metabolismo , Proteína Catiónica del Eosinófilo/sangre , Espiración , Óxido Nítrico/metabolismo , Adolescente , Adulto , Anciano , Asma/tratamiento farmacológico , Asma/epidemiología , Biomarcadores , Estudios Transversales , Progresión de la Enfermedad , Eosinófilos/inmunología , Eosinófilos/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Vigilancia de la Población , Pruebas de Función Respiratoria , Pruebas Cutáneas , Suecia/epidemiología , Evaluación de Síntomas , Adulto JovenRESUMEN
BACKGROUND: Some children with rhinovirus (RV) infections wheeze, but it is unknown whether this is due to more virulent strains of virus or differences in host immune responses. The aim of this study was to investigate the RV species-specific antibody responses measured at a follow-up visit in preschool children in relation to reported time with respiratory symptoms and the presence of different RV species during an acute episode of wheeze. METHOD: Nasopharyngeal swabs and blood samples were taken among 120 preschool children (<4 years of age) at an acute episode of wheeze and at a follow-up visit (median 11 weeks later). Nested PCR was used to detect different RV strains, and serum levels of IgG1 against purified recombinant VP1 proteins from representatives of the three RV species (RV-A, RV-B, and RV-C) were measured by ELISA. RESULTS: Rhinovirus was detected in 74% (n = 80/108) of the children at the acute visit, and RV-C was the most common subtype (n = 59/80, 74%). An increase in RV-specific IgG1 was seen in 61% (n = 73) of the children at follow-up, most frequently against RV-A (n = 61/73, 86%) irrespective of the RV strains detected by PCR. Increases in RV-specific IgG1 against RV-A or against RV-A and RV-C were significantly associated with more respiratory symptoms (p = 0.03, p = 0.007). CONCLUSION: Antibody response to recombinant RV VP1 proteins was associated with longer time with respiratory symptoms.
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Anticuerpos Antivirales/inmunología , Formación de Anticuerpos/inmunología , Infecciones por Picornaviridae/diagnóstico , Infecciones por Picornaviridae/inmunología , Ruidos Respiratorios/inmunología , Rhinovirus/inmunología , Preescolar , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Humanos , Inmunoglobulina G/inmunología , Lactante , Masculino , Infecciones por Picornaviridae/virología , Reacción en Cadena de la Polimerasa , Rhinovirus/genética , Índice de Severidad de la Enfermedad , SueciaRESUMEN
Asthma is a common chronic childhood disease with many different phenotypes that need to be identified. We analyzed a broad range of plasma proteins in children with well-characterized asthma phenotypes to identify potential markers of childhood asthma. Using an affinity proteomics approach, plasma levels of 362 proteins covered by antibodies from the Human Protein Atlas were investigated in a total of 154 children with persistent or intermittent asthma and controls. After screening, chemokine ligand 5 (CCL5) hematopoietic prostaglandin D synthase (HPGDS) and neuropeptide S receptor 1 (NPSR1) were selected for further investigation. Significantly lower levels of both CCL5 and HPGDS were found in children with persistent asthma, while NPSR1 was found at higher levels in children with mild intermittent asthma compared to healthy controls. In addition, the protein levels were investigated in another respiratory disease, sarcoidosis, showing significantly higher NPSR1 levels in sera from sarcoidosis patients compared to healthy controls. Immunohistochemical staining of healthy tissues revealed high cytoplasmic expression of HPGDS in mast cells, present in stroma of both airway epithelia, lung as well as in other organs. High expression of NPSR1 was observed in neuroendocrine tissues, while no expression was observed in airway epithelia or lung. In conclusion, we have utilized a broad-scaled affinity proteomics approach to identify three proteins with altered plasma levels in asthmatic children, representing one of the first evaluations of HPGDS and NPSR1 protein levels in plasma.
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Asma/sangre , Asma/diagnóstico , Quimiocina CCL5/sangre , Isomerasas/sangre , Receptores Acoplados a Proteínas G/sangre , Adolescente , Asma/metabolismo , Biomarcadores , Estudios de Casos y Controles , Quimiocina CCL5/metabolismo , Niño , Preescolar , Femenino , Humanos , Isomerasas/metabolismo , Masculino , Especificidad de Órganos , Receptores Acoplados a Proteínas G/metabolismo , Pruebas de Función RespiratoriaRESUMEN
BACKGROUND: Fractional exhaled nitric oxide (FeNO) has a potential clinical role in asthma management. Constitutive factors such as age, height and gender, as well as individual characteristics, such as IgE sensitization and smoking, affect the levels of FeNO in population-based studies. However, their effect on FeNO in subjects with asthma has been scarcely studied. OBJECTIVE: To study the effects on FeNO of these commonly regarded determinants, as demonstrated in healthy subjects, as well as menarche age and parental smoking, in a population of asthmatics. MATERIAL AND METHODS: Fractional exhaled nitric oxide was measured in 557 subjects with asthma from the Swedish GA(2) LEN study. Allergic sensitization was assessed by skin prick tests to most common aeroallergens. Upper airway comorbidities, smoking habits, smoking exposure during childhood and hormonal status (for women) were questionnaire-assessed. RESULTS: Male gender (P < 0.001), greater height (P < 0.001) and sensitization to both perennial allergens and pollen (P < 0.001) are related to higher FeNO levels. Current smoking (P < 0.001) and having both parents smoking during childhood, vs. having neither (P < 0.001) or only one parent smoking (P = 0.002), are related to lower FeNO. Women with menarche between 9 and 11 years of age had lower FeNO than those with menarche between 12 and 14 years of age (P = 0.03) or 15 and 17 years of age (P = 0.003). CONCLUSIONS AND CLINICAL RELEVANCE: Interpreting FeNO levels in clinical practice is complex, and constitutional determinants, as well as smoking and IgE sensitisation, are of importance in asthmatic subjects and should be accounted for when interpreting FeNO levels. Furthermore, menarche age and parental smoking during childhood and their effects on lowering FeNO deserve further studies.
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Asma/epidemiología , Asma/metabolismo , Espiración , Óxido Nítrico/metabolismo , Adulto , Asma/diagnóstico , Asma/inmunología , Biomarcadores , Pesos y Medidas Corporales , Comorbilidad , Femenino , Hormonas Esteroides Gonadales/metabolismo , Humanos , Inmunoglobulina E/inmunología , Masculino , Ciclo Menstrual , Persona de Mediana Edad , Polen , Pruebas de Función Respiratoria , Factores de Riesgo , Índice de Severidad de la Enfermedad , Pruebas Cutáneas , Espirometría , Suecia/epidemiologíaRESUMEN
BACKGROUND: Wheat is a common food causing allergy which has implications on the quality of life. The diagnosis of IgE-mediated wheat allergy is based on the clinical history and presence of IgE antibodies (IgE-Ab) in skin or blood, and the results of an oral food challenge which is time consuming and associated with risks. An improved diagnostic workup is needed for wheat allergy. The objective was to examine the relationship between wheat challenge, CD-sens and IgE-Ab to related allergens in wheat-allergic children and investigate if a combination of different markers could enhance the prediction of challenge outcome. METHOD: Twenty-four children (aged 1-15 years) with a wheat allergy diagnosis underwent an open wheat challenge. CD-sens and IgE-Ab to wheat, hydrolyzed wheat protein (HWP), ω-5 gliadin and timothy grass were analyzed and related to the challenge outcome. RESULTS: A positive challenge was seen in 12/24 children. Children reacting to the challenge had higher IgE-Ab concentrations to wheat, ω-5 gliadin and HWP (p < 0.01) and a tendency to higher wheat CD-sens values (p = 0.08) than nonreacting children. Combining wheat CD-sens >150 and IgE-Ab to wheat >20 kUA/l, or ω-5 gliadin >0.1 kUA/l predicted the challenge outcome in 83% of the patients. Most children with IgE-Ab to wheat also had IgE-Ab to timothy. Seven of 9 challenge-positive children had a positive CD-sens to HWP and IgE-Ab to HWP >8 kUA/l. CONCLUSION: Combining CD-sens and IgE-Ab to wheat or wheat components could be useful in the diagnosis and follow-up of wheat-allergic children.
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Alérgenos/inmunología , Basófilos/inmunología , Gliadina/inmunología , Inmunoglobulina E/sangre , Phleum/inmunología , Hipersensibilidad al Trigo , Adolescente , Biomarcadores/sangre , Pruebas de Provocación Bronquial , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Valor Predictivo de las Pruebas , Adulto JovenRESUMEN
Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on (ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re-evaluate and fine-tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype-specific treatment choices; however, this goal has not yet been achieved.
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Asma/diagnóstico , Asma/terapia , Adolescente , Asma/clasificación , Asma/prevención & control , Niño , Preescolar , Humanos , Lactante , Recién NacidoAsunto(s)
Asma , Sistema Respiratorio/fisiopatología , Rinitis Alérgica Perenne , Asma/diagnóstico , Asma/etiología , Asma/fisiopatología , Asma/terapia , Enfermedad Crónica , Desensibilización Inmunológica/métodos , Epigénesis Genética , Humanos , Inflamación/fisiopatología , Rinitis Alérgica Perenne/diagnóstico , Rinitis Alérgica Perenne/etiología , Rinitis Alérgica Perenne/fisiopatología , Rinitis Alérgica Perenne/terapia , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Information about acute reactions to foods among children is limited. OBJECTIVE: To describe the overall incidence of anaphylaxis in a paediatric emergency department (ED) setting and to describe reactions to foods in relation to sex and age, clinical characteristics and management. METHODS: In a review of medical records, children with ED visits at any of three paediatric hospitals in Stockholm County during 2007 were targeted. Inclusion criteria were any adverse reaction to foods or anaphylaxis. RESULTS: 383 children fulfilled the inclusion criteria of which 371 had had reactions to foods. The incidence of anaphylaxis was 32 per 100 000 person years irrespective of cause and food was involved in 92%. Tree nuts, particular cashew, and peanut were the most common eliciting foods, and in children under 3 years, reactions to these two food allergens were as common as reactions to milk and egg. Pollen-allergic children seemed to be admitted due to food-induced anaphylaxis more often during the deciduous tree pollen season compared with the rest of the year (P = 0.015). Symptoms from the lower airways occurred in 49% of children with anaphylaxis but without underlying asthma compared with 72% of children with anaphylaxis and asthma, P < 0.01. CONCLUSIONS AND CLINICAL RELEVANCE: Reactions to peanut and tree nuts are as common as reactions to milk and egg in early life. Concomitant exposure to airborne allergens seems to increase the risk of anaphylaxis to foods. Among children with anaphylaxis, wheeze is prevalent even in children without asthma diagnosis.
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Anafilaxia/epidemiología , Anafilaxia/etiología , Hipersensibilidad a los Alimentos/complicaciones , Distribución por Edad , Estudios de Casos y Controles , Niño , Preescolar , Comorbilidad , Servicios Médicos de Urgencia/estadística & datos numéricos , Femenino , Hipersensibilidad a los Alimentos/inmunología , Humanos , Incidencia , Lactante , Recién Nacido , MasculinoRESUMEN
BACKGROUND: Component-resolved allergy diagnostics enables the detection of crossreactive or species-specific allergen components. This study analysed Immunoglobulin E (IgE) profiles to single allergen components in relation to bronchial inflammation in severe childhood asthma. METHODS: Ninety-five schoolchildren were assessed, 39 with controlled mild-to-moderate asthma and 56 uncontrolled severe asthmatics. Allergen components (n = 111) of food allergens, pollen and perennial aeroallergens were analysed using an immunosolid-phase allergen chip. Blood eosinophils (10(9) × l(-1)), bronchial inflammation (FeNO, ppb), lung function (FEV(1)%) and bronchial hyper-responsiveness (BHR) (dose-response slope of methacholine challenge) were measured. RESULTS: A specific IgE response to more than three animal-derived components--lipocalin (nMus m 1, rEqu c 1, Fel d 4, rCan f 1, 2), kallikrein (rCan f 5) and secretoglobin (rFel d 1)--was more common among severe asthmatics compared to children with controlled asthma (n = 14 vs n = 3, P = 0.030). These subjects also displayed higher blood eosinophils (0.65 vs 0.39, P = 0.021), higher Fractional exhaled nitric oxide (38 ppb vs 25 ppb, P = 0.021) and increased BHR (112 vs 28, P = 0.002) compared to other severe asthmatics positive to fewer lipocalin/kallikrein/secretoglobin components. Among all sensitized subjects, there were correlations between specific IgE levels for rFel d 4 and nMus m 1 (r = 0.751, P ≤ 0.001) and for rFel d 4 and rEqu c 1 (r = 0.850, P ≤ 0.001). CONCLUSION: Multi-sensitization towards lipocalin, kallikrein and secretoglobin components is associated with increased bronchial inflammation in severe asthmatics. In addition, crossreactive patterns were observed between different lipocalin components.
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Alérgenos/inmunología , Asma/diagnóstico , Asma/inmunología , Inmunoglobulina E/inmunología , Calicreínas/inmunología , Lipocalinas/inmunología , Secretoglobinas/inmunología , Adolescente , Animales , Biomarcadores , Bronquitis/diagnóstico , Bronquitis/inmunología , Niño , Estudios Transversales , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: An association between asthma and antibiotic usage has been demonstrated, and the issue of reverse causation and confounding by indication is much debated. OBJECTIVE: Our aim was to study the association between different classes of antibiotics and prescription of asthma medication in a register-based cohort of all Swedish children, born between July 2005 and June 2009, ever treated with antibiotics. METHODS: Data on dispensed prescriptions of antibiotics (ATC-codes J01) and asthma medication (ATC-codes R03A-D) were requested from the Prescribed Drug Register. The association between dispensed prescriptions of different classes of antibiotics and asthma medication was analysed with Cox regression and a descriptive sequence symmetry analysis. RESULTS: In total, 211 192 children had received prescriptions of antibiotics. There was a strong association between prescription of antibiotics and prescription of asthma medication. The hazard ratios (HRs) for asthma medication associated with prescription of amoxicillin, penicillin, cephalosporin and macrolides (Gram-positive infections) were stronger than HRs associated with prescription of sulphonamides, trimethoprim and quinolones (urinary tract infections) and flucloxacillin (skin and soft tissue infections), e.g. first year HR = 2.27 (95% confidence intervals 2.17-2.37) as compared with HR = 1.04 (0.78-1.40). The HR associated with broad spectrum antibiotics was significantly higher than the narrow spectrum. CONCLUSIONS AND CLINICAL RELEVANCE: Our data suggest that the association between antibiotics and asthma is subject to either reverse causation or confounding by indication due to respiratory tract infections. This implies that careful consideration is required as to whether or not symptoms from the respiratory tract in early childhood should be treated with antibiotics or asthma medication.
Asunto(s)
Antiasmáticos/uso terapéutico , Antibacterianos/uso terapéutico , Asma/complicaciones , Asma/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/complicaciones , Sistema de Registros/estadística & datos numéricos , Infecciones del Sistema Respiratorio/complicaciones , Antibacterianos/clasificación , Preescolar , Estudios de Cohortes , Factores de Confusión Epidemiológicos , Femenino , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/microbiología , Humanos , Lactante , Recién Nacido , Masculino , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/microbiología , SueciaRESUMEN
There is a lack of high-quality evidence on what treatment should be used in children with properly characterised severe, therapy-resistant asthma. Data have to be largely extrapolated from trials in children with mild asthma, and adults with severe asthma. Therapeutic options can be divided into medications used in lower doses for children with less severe asthma, and those used in other paediatric diseases but not for asthma (for example, methotrexate). In the first category are high-dose inhaled corticosteroids (ICS) (≤ 2,000 µg · day(-1) fluticasone equivalent), oral prednisolone, the anti-immunoglobulin (Ig)E antibody omalizumab, high-dose long-acting ß(2)-agonists, low-dose oral theophylline and intramuscular triamcinolone. If peripheral airway inflammation is thought to be a problem, the use of fine-particle ICS or low-dose oral corticosteroids may be considered. More experimental therapies include oral macrolides, cyclosporin, cytotoxic drugs such as methotrexate and azathioprine, gold salts, intravenous infusions of Ig, subcutaneous ß(2)-agonist treatment and, in those sensitised to fungi, oral antifungal therapy with itraconazole or voriconazole. Those with recurrent severe exacerbations, particularly in the context of good baseline asthma control, are particularly difficult to treat; baseline control and lung function must be optimised with the lowest possible dose of ICS, and allergen triggers and exposures minimised. The use of high-dose ICS, leukotriene receptor antagonists or both at the time of exacerbations can be considered. There is no evidence regarding which therapeutic option to recommend. Better evidence is required for all these treatment options, underscoring the need for the international and co-ordinated approach which we have previously advocated.
Asunto(s)
Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Resistencia a Medicamentos , Medicina Basada en la Evidencia/métodos , Índice de Severidad de la Enfermedad , Antagonistas de Receptores Adrenérgicos beta 2/uso terapéutico , Antifúngicos/uso terapéutico , Niño , Humanos , Inmunosupresores/uso terapéuticoRESUMEN
AIM: To evaluate health-related quality-of-life (HR-QoL) and the asthma control test (ACT) in children with problematic severe asthma and those with controlled asthma and to identify whether clinical characteristics show correlations with these measurements. METHODS: This multicentre cross-sectional study included 93 children in total, 54 with problematic severe asthma and 39 age-matched with controlled asthma. Subjects completed the Paediatric Asthma Quality-of-Life Questionnaire as well as a standardized health questionnaire and the ACT. Objective measurements of exhaled nitric oxide, specific sensitization, pulmonary function and bronchial hyper-responsiveness to methacholine were also taken. RESULTS: HR-QoL was reduced in children with problematic severe asthma (5.4 vs. 6.7, p < 0.001), particularly for girls (5.1 vs. 5.6 for boys, p = 0.02), and their ACT scores were also lower (17 vs. 23, p < 0.001) compared with those of subjects with controlled asthma. A HR-QoL score <6.2 discriminated problematic severe asthma from controlled asthma with 85% sensitivity and 97% specificity, as did the ACT score <20 (79% sensitivity and 94% specificity). Objective measures and other clinical characteristics were weakly associated with HR-QoL or ACT score. CONCLUSION: Subjective measurements of HR-QoL and asthma control are both equally useful in differentiating children with problematic severe asthma from those with controlled asthma.
Asunto(s)
Asma/fisiopatología , Calidad de Vida , Pruebas de Función Respiratoria , Adolescente , Estudios de Casos y Controles , Niño , Estudios Transversales , Femenino , Humanos , Masculino , Observación , Índice de Severidad de la Enfermedad , Factores Sexuales , Perfil de Impacto de Enfermedad , Encuestas y Cuestionarios , SueciaRESUMEN
The aim of this update is to describe the paediatric highlights from the 2010 European Respiratory Society Annual Congress in Barcelona, Spain. Abstracts from the seven groups of the Paediatric Assembly (Respiratory physiology, Asthma and allergy, Cystic fibrosis, Respiratory infection and immunology, Neonatology and paediatric intensive care, Respiratory epidemiology and Bronchology) are presented in the context of the current literature.
Asunto(s)
Asma , Fibrosis Quística , Hipersensibilidad , Infecciones del Sistema Respiratorio , Asma/epidemiología , Asma/fisiopatología , Niño , Preescolar , Fibrosis Quística/epidemiología , Fibrosis Quística/fisiopatología , Humanos , Hipersensibilidad/epidemiología , Hipersensibilidad/fisiopatología , Lactante , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Pediatría , Respiración , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/inmunología , Infecciones del Sistema Respiratorio/fisiopatologíaRESUMEN
Assessment of problematic severe asthma in children should be performed in a step-wise manner to ensure an optimal approach. A four-step assessment scheme is proposed. First, a full diagnostic work-up is performed to exclude other diseases which mimic asthma. Secondly, a multi-disciplinary assessment is performed to identify issues that may need attention, including comorbidities. Thirdly, the pattern of inflammation is assessed, and finally steroid responsiveness is documented. Based upon these four steps an optimal individualised treatment plan is developed. In this article the many gaps in our current knowledge in all these steps are highlighted, and recommendations for current clinical practice and future research are made. The lack of good data and the heterogeneity of problematic severe asthma still limit our ability to optimise the management on an individual basis in this small, but challenging group of patients.