RESUMO
In the second of two linked articles, we describe the development in clinical as described by Clinical & Experimental Allergy and other journals in 2019. Epidemiology, clinical allergy, asthma and rhinitis are all covered. In this article, we described the development in the field of allergy as described by Clinical and Experimental Allergy in 2019. Epidemiology, clinical allergy, asthma and rhinitis are all covered.
Assuntos
Alérgenos/imunologia , Hipersensibilidade/imunologia , Sistema Imunitário/imunologia , Animais , Asma/epidemiologia , Asma/imunologia , Asma/metabolismo , Asma/terapia , Hipersensibilidade Alimentar/epidemiologia , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/metabolismo , Hipersensibilidade Alimentar/terapia , Humanos , Hipersensibilidade/epidemiologia , Hipersensibilidade/metabolismo , Hipersensibilidade/terapia , Sistema Imunitário/metabolismo , Prognóstico , Rinite Alérgica/epidemiologia , Rinite Alérgica/imunologia , Rinite Alérgica/metabolismo , Rinite Alérgica/terapia , Fatores de RiscoRESUMO
In the first of two linked articles, we describe the development in the mechanisms underlying allergy as described by Clinical & Experimental Allergy and other journals in 2019. Experimental models of allergic disease, basic mechanisms, clinical mechanisms and allergens are all covered.
Assuntos
Alérgenos/imunologia , Hipersensibilidade/imunologia , Sistema Imunitário/imunologia , Animais , Modelos Animais de Doenças , Humanos , Hipersensibilidade/metabolismo , Sistema Imunitário/metabolismoRESUMO
In this article, we describe developments in the field of clinical allergy as described by Clinical and Experimental Allergy in 2018; epidemiology, asthma and rhinitis, clinical allergy and allergens are all covered.
Assuntos
Alérgenos/imunologia , Asma/imunologia , Rinite/imunologia , Animais , Asma/patologia , Humanos , Rinite/patologiaRESUMO
In this article, we described the development in the field of allergy as described by Clinical and Experimental Allergy in 2017. Experimental models of allergic disease, basic mechanisms, clinical mechanisms, allergens, asthma and rhinitis and clinical allergy are all covered.
Assuntos
Estudos Clínicos como Assunto , Hipersensibilidade/epidemiologia , Pesquisa , Alérgenos/imunologia , Animais , Gerenciamento Clínico , Suscetibilidade a Doenças , História do Século XXI , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/etiologia , Hipersensibilidade/história , Fenótipo , Pesquisa/tendências , Fatores de RiscoRESUMO
In this article, we described the development in the field of allergy as described by Clinical and Experimental Allergy in 2016. Experimental models of allergic disease, basic mechanisms, clinical mechanisms, allergens, asthma and rhinitis, and clinical allergy are all covered.
Assuntos
Hipersensibilidade/etiologia , Alérgenos/imunologia , Animais , Gerenciamento Clínico , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/epidemiologia , Hipersensibilidade/terapia , ImunizaçãoRESUMO
It is well recognized that atopic sensitization is an important risk factor for asthma, both in adults and in children. However, the role of allergy in severe asthma is still under debate. The term 'Severe Asthma' encompasses a highly heterogeneous group of patients who require treatment on steps 4-5 of GINA guidelines to prevent their asthma from becoming 'uncontrolled', or whose disease remains 'uncontrolled' despite this therapy. Epidemiological studies on emergency room visits and hospital admissions for asthma suggest the important role of allergy in asthma exacerbations. In addition, allergic asthma in childhood is often associated with severe asthma in adulthood. A strong association exists between asthma exacerbations and respiratory viral infections, and interaction between viruses and allergy further increases the risk of asthma exacerbations. Furthermore, fungal allergy has been shown to play an important role in severe asthma. Other contributing factors include smoking, pollution and work-related exposures. The 'Allergy and Asthma Severity' EAACI Task Force examined the current evidence and produced this position document on the role of allergy in severe asthma.
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Alérgenos/imunologia , Asma/diagnóstico , Asma/etiologia , Hipersensibilidade/imunologia , Fatores Etários , Idade de Início , Animais , Asma/epidemiologia , Diagnóstico Diferencial , Exposição Ambiental , Humanos , Hipersensibilidade/complicações , Hipersensibilidade/epidemiologia , Hipersensibilidade/etiologia , Hipersensibilidade Imediata/complicações , Hipersensibilidade Imediata/imunologia , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Exposição por Inalação , Fenótipo , Índice de Gravidade de DoençaRESUMO
In the second of two papers, we describe developments in the field of clinical allergy as documented by Clinical and Experimental Allergy in 2015. Epidemiology, clinical allergy, asthma and rhinitis are all covered.
Assuntos
Hipersensibilidade/epidemiologia , Hipersensibilidade/etiologia , Alérgenos/imunologia , Animais , Asma/diagnóstico , Asma/epidemiologia , Asma/etiologia , Humanos , Hipersensibilidade/diagnóstico , Rinite/diagnóstico , Rinite/epidemiologia , Rinite/etiologiaRESUMO
In the first of two papers we described the development in the field of allergy mechanisms as described by Clinical and Experimental Allergy in 2015. Experimental models of allergic disease, basic mechanisms, clinical mechanisms and allergens are all covered. A second paper will cover clinical aspects.
Assuntos
Alergia e Imunologia/tendências , Hipersensibilidade/etiologia , Remodelação das Vias Aéreas , Alérgenos/imunologia , Animais , Modelos Animais de Doenças , Humanos , Hipersensibilidade/metabolismo , Hipersensibilidade/patologia , Hipersensibilidade/terapia , Sistema Imunitário/citologia , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Tolerância Imunológica , Imunoterapia , Inflamação/complicações , Inflamação/etiologia , Inflamação/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
BACKGROUND: Associations between vitamin D status and childhood asthma are increasingly reported, but direct causation and mechanisms underlying an effect remain unknown. We investigated the effect of early-life vitamin D deficiency on the development of murine neonatal allergic airways disease (AAD). METHODS: In utero and early-life vitamin D deficiency was achieved using a vitamin D-deficient diet for female mice during the third trimester of pregnancy and lactation. Offspring were weaned onto a vitamin D-deficient or vitamin D-replete diet, and exposure to intranasal house dust mite (HDM) or saline was commenced from day 3 of life for up to 6 weeks, when airway hyper-responsiveness (AHR), airway inflammation and remodelling were assessed. RESULTS: Neonatal mice that had in utero and early-life vitamin D deficiency had significantly increased pulmonary CD3(+) CD4(+) T1ST2(+) cells and reduced CD4(+) IL-10(+) cells. This effect was enhanced following HDM exposure. AHR in HDM-exposed mice was unaffected by vitamin D status. Introduction of vitamin D into the diet at weaning resulted in a significant reduction in serum IgE levels, reduced pulmonary eosinophilia and peri-bronchiolar collagen deposition. CONCLUSION: Peri-natal vitamin D deficiency alone has immunomodulatory effects including Th2 skewing and reduced IL-10-secreting T regulatory cells, exaggerated with additional allergen exposure. Vitamin D deficiency in early life does not affect AHR, but contributes to disease severity with worse eosinophilic inflammation and airway remodelling. Importantly, supplementation with vitamin D improves both of these pathological abnormalities.
Assuntos
Asma/imunologia , Hipersensibilidade/imunologia , Eosinofilia Pulmonar/imunologia , Células Th2/imunologia , Deficiência de Vitamina D/imunologia , Remodelação das Vias Aéreas , Animais , Animais Recém-Nascidos , Hiper-Reatividade Brônquica/imunologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Pulmão/imunologia , Camundongos , Camundongos Endogâmicos BALB CAssuntos
Asma , Pré-Escolar , Granulócitos , Humanos , Inflamação , Sons Respiratórios , Sistema RespiratórioRESUMO
BACKGROUND: The inflammatory phenotypes of severe asthma in adults may be reflected in peripheral blood. If this were true in children with severe therapy-resistant asthma (STRA), invasive tests could be avoided. At the moment there is no conclusive evidence in children. METHODS: All patients underwent blood tests, exhaled nitric oxide (FeNO), sputum induction, bronchoalveolar lavage (BAL) and endobronchial biopsy (EB). RESULTS: Sixty-three (71.6%) patients had a normal blood profile and only 1/88 had a combined blood eosinophilia and neutrophilia. 76/88 (86%) had normal blood eosinophils, but of these, 84% had airway eosinophilia in either BAL (n = 43;66%) or EB (n = 41;79%). In children with STRA blood eosinophilia was associated with airway eosinophilia. However, normal blood eosinophil levels did not exclude airway eosinophilic inflammation. CONCLUSIONS: Peripheral blood counts are not reliable in characterising airway inflammation in severe asthmatic children exposed to high dose steroid therapy, therefore bronchoscopy with BAL should be considered.
Assuntos
Asma/complicações , Asma/diagnóstico , Eosinofilia/complicações , Eosinófilos , Adolescente , Líquido da Lavagem Broncoalveolar/imunologia , Criança , Feminino , Humanos , Contagem de Leucócitos , Masculino , Neutrófilos , PrognósticoRESUMO
Asthma exacerbations and severe asthma are linked with high morbidity, significant mortality and high treatment costs. Recurrent asthma exacerbations cause a decline in lung function and, in childhood, are linked to development of persistent asthma. This position paper, from the European Academy of Allergy and Clinical Immunology, highlights the shortcomings of current treatment guidelines for patients suffering from frequent asthma exacerbations and those with difficult-to-treat asthma and severe treatment-resistant asthma. It reviews current evidence that supports a call for increased awareness of (i) the seriousness of asthma exacerbations and (ii) the need for novel treatment strategies in specific forms of severe treatment-resistant asthma. There is strong evidence linking asthma exacerbations with viral airway infection and underlying deficiencies in innate immunity and evidence of a synergism between viral infection and allergic mechanisms in increasing risk of exacerbations. Nonadherence to prescribed medication has been identified as a common clinical problem amongst adults and children with difficult-to-control asthma. Appropriate diagnosis, assessment of adherence and other potentially modifiable factors (such as passive or active smoking, ongoing allergen exposure, psychosocial factors) have to be a priority in clinical assessment of all patients with difficult-to-control asthma. Further studies with improved designs and new diagnostic tools are needed to properly characterize (i) the pathophysiology and risk of asthma exacerbations, and (ii) the clinical and pathophysiological heterogeneity of severe asthma.
Assuntos
Asma/diagnóstico , Asma/terapia , Animais , Asma/prevenção & controle , Progressão da Doença , Humanos , Guias de Prática Clínica como Assunto , Índice de Gravidade de DoençaRESUMO
The functional outcome in preschool severe wheezers with eosinophilic airway inflammation and increased reticular basement membrane (RBM) thickness is unknown. We investigated the relationship between airway pathology at age 2 yrs and lung function at age 4-6 yrs in previous severe wheezers. Severe wheezers previously investigated by endobronchial biopsy and healthy children aged 4-6 yrs were recruited. Lung clearance index (LCI), conducting zone ventilation inhomogeneity (S(cond)), acinar ventilation inhomogeneity by multiple-breath washout, plethysmographic-specific airway resistance and exhaled nitric oxide fraction (F(eNO)) were measured. Lung function was compared between wheezers and healthy controls, and in wheezers correlated with past RBM thickness and mucosal eosinophilia (EG2+ cells). 72 healthy controls and 28 previous severe wheezers were tested. Wheezers had significantly higher median LCI (6.8 versus 6.6; p=0.001) and S(cond) (0.046 versus 0.016; p<0.0005) than healthy controls. Past RBM thickness (r=0.474, p=0.047) and EG2+ cells (r=0.552, p=0.041) showed significant correlations with current F(eNO), but no correlations were seen between past RBM thickness and current lung function. RBM thickness and EG2+ cells at age 2 yrs show a significant positive association with F(eNO) at age 5 yrs. Although lung function was abnormal at age 5 yrs in severe wheezers, this did not correlate with past RBM thickness.
Assuntos
Pulmão/fisiologia , Sons Respiratórios/fisiopatologia , Asma/fisiopatologia , Membrana Basal/anatomia & histologia , Membrana Basal/fisiopatologia , Biópsia , Testes Respiratórios , Brônquios/fisiopatologia , Broncoscopia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Pulmão/patologia , Masculino , Óxido Nítrico/análise , Eosinofilia Pulmonar/fisiopatologia , Índice de Gravidade de DoençaRESUMO
This study describes the clinical characteristics and corticosteroid responsiveness of children with difficult asthma (DA). We hypothesised that complete corticosteroid responsiveness (defined as improved symptoms, normal spirometry, normal exhaled nitric oxide fraction (F(eNO)) and no bronchodilator responsiveness (BDR <12%)) is uncommon in paediatric DA. We report on 102 children, mean+/-sd age 11.6+/-2.8 yrs, with DA in a cross-sectional study. 89 children underwent spirometry, BDR and F(eNO) before and after 2 weeks of systemic corticosteroids (corticosteroid response study). Bronchoscopy was performed after the corticosteroid trial. Of the 102 patients in the cross-sectional study, 88 (86%) were atopic, 60 (59%) were male and 52 (51%) had additional or alternative diagnoses. Out of the 81 patients in the corticosteroid response study, nine (11%) were complete responders. Of the 75 patients with symptom data available, 37 (49%) responded symptomatically, which was less likely if there were smokers in the home (OR 0.31, 95% CI 0.02-0.82). Of the 75 patients with available spirometry data, 35 (46%) had normal spirometry, with associations being BAL eosinophilia (OR 5.43, 95% CI 1.13-26.07) and high baseline forced expiratory volume in 1 s (FEV(1)) (OR 1.08, 95% CI 1.02-1.12). Of these 75 patients, BDR data were available in 64, of whom 36 (56%) had <12% BDR. F(eNO) data was available in 70 patients, of whom 53 (75%) had normal F(eNO). Airflow limitation data was available in 75 patients, of whom 17 (26%) had persistent airflow limitation, which was associated with low baseline FEV(1) (OR 0.93, 95% CI 0.90-0.97). Only 11% of DA children exhibited complete corticosteroid responsiveness. The rarity of complete corticosteroid responsiveness suggests alternative therapies are needed for children with DA.
Assuntos
Corticosteroides/uso terapêutico , Asma/tratamento farmacológico , Adolescente , Adulto , Broncodilatadores/farmacologia , Criança , Estudos Transversais , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Óxido Nítrico/química , Óxido Nítrico/metabolismo , Fumar/efeitos adversos , Espirometria/métodos , Resultado do TratamentoAssuntos
Doenças do Sistema Imunitário/patologia , Pneumopatias/patologia , Doença Crônica , Meio Ambiente , Epitélio/patologia , Europa (Continente) , Fibrose/patologia , Predisposição Genética para Doença , Humanos , Sistema Imunitário , Doenças do Sistema Imunitário/complicações , Pneumopatias/complicações , Portugal , Doença Pulmonar Obstrutiva Crônica/patologia , Pneumologia/métodos , Pneumologia/organização & administração , Sociedades MédicasRESUMO
BACKGROUND: Whole airway wall thickening on high resolution computed tomography (HRCT) is reported to parallel thickening of the bronchial epithelial reticular basement membrane (RBM) in adult asthmatics. A similar relationship in children with difficult asthma (DA), in whom RBM thickening is a known feature, may allow the use of HRCT as a non-invasive marker of airway remodelling. We evaluated this relationship in children with DA. METHODS: 27 children (median age 10.5 [range 4.1-16.7] years) with DA, underwent endobronchial biopsy from the right lower lobe and HRCT less than 4 months apart. HRCTs were assessed for bronchial wall thickening (BWT) of the right lower lobe using semi-quantitative and quantitative scoring techniques. The semi-quantitative score (grade 0-4) was an overall assessment of BWT of all clearly identifiable airways in HRCT scans. The quantitative score (BWT %; defined as [airway outer diameter - airway lumen diameter]/airway outer diameter x100) was the average score of all airways visible and calculated using electronic endpoint callipers. RBM thickness in endobronchial biopsies was measured using image analysis. 23/27 subjects performed spirometry and the relationships between RBM thickness and BWT with airflow obstruction evaluated. RESULTS: Median RBM thickness in endobronchial biopsies was 6.7(range 4.6-10.0) microm. Median qualitative score for BWT of the right lower lobe was 1(range 0-1.5) and quantitative score was 54.3 (range 48.2-65.6)%. There was no relationship between RBM thickness and BWT in the right lower lobe using either scoring technique. No relationship was found between FEV1 and BWT or RBM thickness. CONCLUSION: Although a relationship between RBM thickness and BWT on HRCT has been found in adults with asthma, this relationship does not appear to hold true in children with DA.
Assuntos
Asma/patologia , Membrana Basal/patologia , Tomografia Computadorizada por Raios X , Adolescente , Asma/metabolismo , Asma/fisiopatologia , Membrana Basal/metabolismo , Biópsia , Brônquios/metabolismo , Brônquios/patologia , Brônquios/fisiopatologia , Criança , Pré-Escolar , Volume Expiratório Forçado , Humanos , EspirometriaRESUMO
There is little found in the published literature regarding the use of endobronchial biopsy (EBB) in children with cystic fibrosis (CF). One concern over the use of the technique may relate to safety, in particular increased risk of bleeding from a hypertrophied bronchial circulation. The aim of this retrospective study was to compare the safety of EBB in children with CF and those with other conditions, the most frequent of which included primary ciliary dyskinesia and recurrent lower respiratory tract infections. Case notes of all children undergoing EBB in our institution between February 2003 and May 2004 were reviewed. EBB was performed during 45 bronchoscopies in 42 CF patients (19 males, group mean age 7.13 +/- 4.48 years) and in 39 controls (20 males, group mean age 6.59 +/- 4.48 years). There were no significant differences between disease groups in the number, type, or severity of complications occurring during or in the first 12 hr after the procedure. We conclude that EBB performed as part of fibreoptic bronchoscopy (FOB) under general anaesthesia can be performed safely in children with CF, when both bronchoscopist and anaesthetist are suitably experienced. Studies of such samples would allow us to determine the early pathological changes in the CF airway and possibly find new treatments to prevent the progression to bronchiectasis and end stage airway destruction.
Assuntos
Biópsia/métodos , Brônquios/patologia , Broncoscopia , Fibrose Cística/patologia , Segurança , Anestesia Geral , Estudos de Casos e Controles , Criança , Feminino , Tecnologia de Fibra Óptica , Humanos , Masculino , Estudos RetrospectivosRESUMO
A child developed a bronchiolitis-like illness and was found to have mosaic Down's syndrome (diagnosed on karyotype) and also cystic fibrosis, diagnosed on the basis of a high sweat osmolality (247 mosmoles/kg sweat; normal, 62-137) and a homozygous delta F508 genotype. Despite two potentially life-threatening conditions, the child is doing well at the age of 7 years, despite pancreatic insufficiency.
Assuntos
Bronquiolite/patologia , Fibrose Cística/patologia , Síndrome de Down/patologia , Bronquiolite/diagnóstico , Bronquiolite/etiologia , Criança , Fibrose Cística/genética , Diagnóstico Diferencial , Síndrome de Down/genética , Feminino , Humanos , Mosaicismo , Prognóstico , Suor/químicaRESUMO
Deficient type I interferon-ß and type III interferon-λ induction by rhinoviruses has previously been reported in mild/moderate atopic asthmatic adults. No studies have yet investigated if this occurs in severe therapy resistant asthma (STRA). Here, we show that compared with non-allergic healthy control children, bronchial epithelial cells cultured ex vivo from severe therapy resistant atopic asthmatic children have profoundly impaired interferon-ß and interferon-λ mRNA and protein in response to rhinovirus (RV) and polyIC stimulation. Severe treatment resistant asthmatics also exhibited increased virus load, which negatively correlated with interferon mRNA levels. Furthermore, uninfected cells from severe therapy resistant asthmatic children showed lower levels of Toll-like receptor-3 mRNA and reduced retinoic acid inducible gene and melanoma differentiation-associated gene 5 mRNA after RV stimulation. These data expand on the original work, suggesting that the innate anti-viral response to RVs is impaired in asthmatic tissues and demonstrate that this is a feature of STRA.
Assuntos
Asma/genética , Asma/imunologia , Hipersensibilidade Imediata/genética , Hipersensibilidade Imediata/imunologia , Imunidade Inata/genética , Interferons/genética , Adolescente , Asma/metabolismo , Criança , Pré-Escolar , Proteína DEAD-box 58 , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Hipersensibilidade Imediata/metabolismo , Imunoglobulina E/imunologia , Helicase IFIH1 Induzida por Interferon , Interferon beta/genética , Interferon gama/genética , Interleucina-8/biossíntese , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/virologia , Masculino , Infecções por Picornaviridae/genética , Infecções por Picornaviridae/imunologia , Poli I-C/administração & dosagem , Poli I-C/imunologia , RNA Mensageiro/genética , Receptores Imunológicos , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/imunologia , Mucosa Respiratória/metabolismo , Mucosa Respiratória/virologia , Rhinovirus/imunologia , Fatores de Tempo , Receptor 3 Toll-Like/genética , Receptor 3 Toll-Like/metabolismoRESUMO
The management of young children with severe recurrent wheeze is difficult because symptoms are often refractory to conventional asthma therapy and other diagnoses must be excluded. The present authors aimed to evaluate the outcome of detailed, invasive investigations in such patients. Children aged between 3 months and 5 yrs with severe recurrent wheezing, who had been referred to a tertiary centre, underwent a protocol of investigations including a chest computed tomography scan, blood tests, nasal ciliary brushings, fibreoptic bronchoscopy, bronchoalveolar lavage (BAL), endobronchial biopsy and passage of an oesophageal pH probe. A total of 47 children (25 males) with a median age of 26 (range 5-58) months underwent investigation. Of these, 39% were atopic, two-thirds had evidence of gastro-oesophageal reflux and 37 out of 47 had an abnormal bronchoscopy. Findings included structural abnormalities (13 out of 37), excessive mucus (20 out of 37) and macroscopic inflammation (10 out of 37). BAL revealed bacterial growth in 12 out of 44 (27%) patients. Good quality endobronchial biopsies were obtained from 36 out of 46 (78%) patients; of these, 44% had tissue eosinophilia and 28% had a thickened reticular basement membrane. Additional investigations (including bronchoscopy) in young children with severe wheeze may help to identify positive diagnoses and provide information to support a clinical diagnosis of asthma. This hypothesis-generating work should form the basis of future interventional studies.