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1.
Clin Exp Allergy ; 48(4): 394-402, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29315919

RESUMO

BACKGROUND: The prevalence and time trends of food allergy change during childhood depending on the age of the child and the type of food. OBJECTIVE: To study prevalence and longitudinal trends in food allergy from birth to 18 years in an unselected birth cohort in the Isle of Wight. METHOD: Information on food allergy was collected at ages 1, 2, 4, 10 and 18 years from the Isle of Wight Birth Cohort (n = 1456). Skin prick testing (SPT) was performed at the age of 1 and 2 years in symptomatic children. At 4, 10 and 18 years of age, participants were tested to a panel of food and aeroallergens. Food allergy was diagnosed based on the criteria: symptoms suggestive of a typical IgE-mediated reaction and reaction <4 hours following exposure to a known food allergen. McNemar's test was used to determine significance of changes in prevalence over time. RESULTS: The prevalence of food allergy remained relatively constant in early childhood (5.3%, 4.4% and 5.0% at 1, 2 and 4 years, respectively), with significant decline at 10 years (2.3%, P < .001 vs 4 years) followed by significant rise at 18 years (4%, P = .02 vs 10 years). Cow's milk (1.6%-3.5%) and egg (1.1%-1.4%) were the most common allergens in the first 10 years with peanut (1%) and tree nuts (0.5%) becoming more prevalent beyond 10 years. Fruit and wheat allergy were less common at 10 years, and shellfish and kiwi emerged during adolescence. The prevalence of food allergy plus positive SPT was 1.3%, 0.8%, 0.8%, 0.9% and 2.2% at 1, 2, 4, 10 and 18 years, respectively. CONCLUSION: Food allergy is highly prevalent in infancy with partial resolution during late childhood. However, a number of children acquire new food allergy during adolescence resulting in a relatively higher prevalence at 18 years.


Assuntos
Hipersensibilidade Alimentar/epidemiologia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Inglaterra , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Prevalência
2.
Allergy ; 71(5): 661-70, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26714430

RESUMO

BACKGROUND: WHO guidelines advocate breastfeeding for 6 months, and EAACI guideline recommends exclusive breastfeeding for 4-6 months. However, evidence for breastfeeding to prevent asthma and allergic disease is conflicting. We examined whether following recommended breastfeeding guidelines alters the long-term risks of asthma, eczema, rhinitis or atopy. METHODS: The effect of nonexclusive (0, >0-6, >6 months) and exclusive breastfeeding (0, >0-4, >4 months) on repeated measures of asthma (10, 18 years), eczema, rhinitis, and atopy (1-or-2, 4, 10, 18 years) risks was estimated in the IoW cohort (n = 1456) using log-linear models with generalized estimating equations. The Food Allergy and Intolerance Research (FAIR) cohort (n = 988), also from the IoW, was examined to replicate results. RESULTS: Breastfeeding (any or exclusive) had no effect on asthma and allergic disease in the IoW cohort. In the FAIR cohort, any breastfeeding for >0-6 months protected against asthma at 10 years (RR = 0.50, 95% CI = 0.32-0.79, P = 0.003), but not other outcomes, whilst exclusive breastfeeding for >4 months protected against repeated rhinitis (RR = 0.36, 95% CI = 0.18-0.71, P = 0.003). Longer breastfeeding was protective against late-onset wheeze in the IoW cohort. CONCLUSION: The protective effects of nonexclusive and exclusive breastfeeding against long-term allergic outcomes were inconsistent between these colocated cohorts, agreeing with previous observations of heterogeneous effects. Although breastfeeding should be recommended for other health benefits, following breastfeeding guidelines did not appear to afford a consistent protection against long-term asthma, eczema, rhinitis or atopy. Further research is needed into the long-term effects of breastfeeding on allergic disease.


Assuntos
Aleitamento Materno , Hipersensibilidade/etiologia , Hipersensibilidade/prevenção & controle , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Guias como Assunto , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/epidemiologia , Lactente , Masculino , Exposição Materna , Avaliação de Resultados em Cuidados de Saúde , Gravidez , Sons Respiratórios/etiologia , Risco , Fatores Socioeconômicos , Fatores de Tempo
3.
Allergy ; 71(9): 1314-24, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26973132

RESUMO

BACKGROUND: Season of birth influences allergy risk; however, the biological mechanisms underlying this observation are unclear. The environment affects DNA methylation, with potentially long-lasting effects on gene expression and disease. This study examined whether DNA methylation could underlie the association between season of birth and allergy. METHODS: In a subset of 18-year-old participants from the Isle of Wight (IoW) birth cohort (n = 367), the risks of birth season on allergic outcomes were estimated. Whole blood epigenome-wide DNA methylation was measured, and season-associated CpGs detected using a training-and-testing-based technique. Validation method examined the 8-year-old Prevention and Incidence of Asthma and Mite Allergy (PIAMA) cohort. The relationships between DNA methylation, season of birth and allergy were examined. CpGs were analysed in IoW third-generation cohort newborns. RESULTS: Autumn birth increased risk of eczema, relative to spring birth. Methylation at 92 CpGs showed association with season of birth in the epigenome-wide association study. In validation, significantly more CpGs had the same directionality than expected by chance, and four were statistically significant. Season-associated methylation was enriched among networks relating to development, the cell cycle and apoptosis. Twenty CpGs were nominally associated with allergic outcomes. Two CpGs were marginally on the causal pathway to allergy. Season-associated methylation was largely absent in newborns, suggesting it arises post-natally. CONCLUSIONS: This study demonstrates that DNA methylation in adulthood is associated with season of birth, supporting the hypothesis that DNA methylation could mechanistically underlie the effect of season of birth on allergy, although other mechanisms are also likely to be involved.


Assuntos
Metilação de DNA , Hipersensibilidade/epidemiologia , Hipersensibilidade/etiologia , Estações do Ano , Adolescente , Criança , Pré-Escolar , Ilhas de CpG , Suscetibilidade a Doenças , Feminino , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Lactente , Recém-Nascido , Masculino , Exposição Materna , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Reprodutibilidade dos Testes
4.
J Hum Nutr Diet ; 29(6): 786-796, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27298213

RESUMO

BACKGROUND: Taste exposure in infancy is known to predict food preferences later in childhood. This is particularly relevant in children with cows' milk allergy who consume a substitute formula and/or a cows' milk exclusion (CME) diet early in life. This prospective study aimed to show whether there is a long-term effect of consuming a substitute formula and CME diet on taste preferences and dietary intake. METHODS: Children were predominantly recruited from two large birth cohort studies in the UK. Two groups were recruited: an experimental group of children who had consumed a CME diet during infancy and a control group who had consumed an unrestricted diet during infancy. Parents completed a food neophobia questionnaire and an estimated prospective food diary. Children completed a taste preference test and their growth was assessed. RESULTS: One hundred and one children with a mean age of 11.5 years were recruited (28 CME and 73 controls). Children in the CME group had a significantly higher preference for bitter taste than those in the control group (P < 0.05). There were significant differences between the groups with respect to the intake of some micronutrients, including riboflavin, iodine, sodium and selenium. Food neophobia did not differ between groups. Some 28% of the CME group were overweight/obese compared to 15% of the control group; however, this difference was not statistically significant. CONCLUSIONS: Consuming a substitute formula and/or a CME diet in infancy has a long-term effect on the preference for bitter taste. Differences exist with respect to the intake of some micronutrients, but not macronutrients. There was a nonsignificant trend towards being overweight and obese in children in the CME group.


Assuntos
Dieta/métodos , Ingestão de Alimentos , Preferências Alimentares/psicologia , Hipersensibilidade a Leite/psicologia , Paladar , Animais , Criança , Dieta/psicologia , Feminino , Humanos , Masculino , Leite , Estudos Prospectivos , Inquéritos e Questionários
5.
Thorax ; 70(6): 595-7, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25616486

RESUMO

Prenatal and peri-natal events play a fundamental role in health, development of diseases and ageing (Developmental Origins of Health and Disease (DOHaD)). Research on the determinants of active and healthy ageing is a priority to: (i) inform strategies for reducing societal and individual costs of an ageing population and (ii) develop effective novel prevention strategies. It is important to compare the trajectories of respiratory diseases with those of other chronic diseases.


Assuntos
Envelhecimento , Desenvolvimento Infantil , Doença Crônica/prevenção & controle , Desenvolvimento Fetal , Adulto , Idoso , Doença de Alzheimer/prevenção & controle , Asma/prevenção & controle , Depressão/prevenção & controle , Diabetes Mellitus/prevenção & controle , Comportamento Alimentar , Feminino , Humanos , Hipersensibilidade/prevenção & controle , Lactente , Recém-Nascido , Auditoria Médica , Pessoa de Meia-Idade , Osteoporose/prevenção & controle , Fatores de Risco
6.
Clin Exp Allergy ; 45(9): 1430-8, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25809555

RESUMO

BACKGROUND: While the prevalence of asthma in children is decreasing or remaining the same, time trends in the prevalence of rhinitis in children are not known. Understanding sensitisation trends may help inform about trends in asthma and rhinitis prevalence. OBJECTIVE: To assess time trends of wheeze, rhinitis and aero-allergen sensitisation prevalence at 10 years of age, we compared two birth cohorts established 12 years apart. To gain insight into differences in disease prevalence, we assessed association of family history, early life exposures and sensitisation with wheeze and rhinitis in each cohort. METHODS: The IoW (Isle of Wight) and FAIR (Food Allergy and Intolerance Research) unselected birth cohorts were established in 1989 and 2001 respectively in IoW. Identical ISAAC questionnaire and skin prick test data were collected and compared at 10 years of age. RESULTS: Over the 12-year period from 2001 to 2012, prevalence of lifetime wheeze, current wheeze and those ever treated for asthma decreased by 15.9% (45.5 vs. 29.6, P < 0.001), 3.9% (18.9 vs. 15, P = 0.020) and 8.2% (31.7 vs. 23.5, P = 0.001), respectively. Conversely, current rhinitis and lifetime rhinitis prevalence increased by 5.5% (22.6 vs. 28.1, P = 0.004) and 13% (18.6 vs. 31.7, P < 0.001), respectively. Atopic status remained stable; however, house dust mite (HDM) sensitisation decreased by 5.6% (19.2 vs. 13.6, P = 0.004) and grass sensitisation increased by 3.5% (12.9 vs. 16.4, P = 0.054). Male sex, parental history of asthma and HDM sensitisation were significantly associated with lifetime wheeze in both cohorts, while maternal smoking during pregnancy was a significant risk factor only in the earlier IoW cohort. Parental history of rhinitis and grass sensitisation was significantly associated with lifetime rhinitis in both cohorts, while HDM sensitisation was significant only for the IoW cohort. CONCLUSION: Contrasting changes were noted with falling wheeze and HDM sensitisation but rising rhinitis and grass sensitisation prevalence. Changing prevalence of aero-allergen sensitisations may explain the different time trends observed in these cohorts.


Assuntos
Asma/epidemiologia , Sons Respiratórios , Rinite Alérgica/epidemiologia , Criança , Feminino , Seguimentos , Humanos , Masculino , Prevalência , Estudos Prospectivos , Fatores Sexuais
7.
Allergy ; 70(9): 1062-78, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25913421

RESUMO

Allergic diseases [asthma, rhinitis and atopic dermatitis (AD)] are complex. They are associated with allergen-specific IgE and nonallergic mechanisms that may coexist in the same patient. In addition, these diseases tend to cluster and patients present concomitant or consecutive diseases (multimorbidity). IgE sensitization should be considered as a quantitative trait. Important clinical and immunological differences exist between mono- and polysensitized subjects. Multimorbidities of allergic diseases share common causal mechanisms that are only partly IgE-mediated. Persistence of allergic diseases over time is associated with multimorbidity and/or IgE polysensitization. The importance of the family history of allergy may decrease with age. This review puts forward the hypothesis that allergic multimorbidities and IgE polysensitization are associated and related to the persistence or re-occurrence of foetal type 2 signalling. Asthma, rhinitis and AD are manifestations of a common systemic immune imbalance (mesodermal origin) with specific patterns of remodelling (ectodermal or endodermal origin). This study proposes a new classification of IgE-mediated allergic diseases that allows the definition of novel phenotypes to (i) better understand genetic and epigenetic mechanisms, (ii) better stratify allergic preschool children for prognosis and (iii) propose novel strategies of treatment and prevention.


Assuntos
Alérgenos/imunologia , Hipersensibilidade/etiologia , Hipersensibilidade/metabolismo , Imunoglobulina E/imunologia , Transdução de Sinais , Especificidade de Anticorpos/imunologia , Comorbidade , Feminino , Predisposição Genética para Doença , Humanos , Hipersensibilidade/epidemiologia , Imunização , Fenótipo , Gravidez , Efeitos Tardios da Exposição Pré-Natal
8.
Pediatr Allergy Immunol ; 26(6): 503-8, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26111260

RESUMO

BACKGROUND: Cows' milk allergy (CMA) is the most common infant food allergy in the United Kingdom, requiring a strict exclusion diet. Feeding difficulties and fussy eating are also very common problems in young children and can negatively influence feeding and dietary intake in an infant with CMA. The aim of this study was to compare the levels of fussy eating and feeding difficulties in two groups of young children: a group consuming an exclusion diet for CMA and a control group of children consuming an unrestricted diet. METHOD: Participants were recruited from allergy and health visitor clinics on the Isle of Wight. Parents completed a number of questionnaires about their child's feeding behaviour. RESULTS: One hundred and twenty-six participants (mean age 13 months) were recruited. Participants consuming an exclusion diet for CMA had significantly higher scores for both fussy eating and feeding difficulties (p < 0.05), although overall both groups were within the normal range. A number of symptoms were found to be positively moderately correlated with higher feeding difficulty score (p < 0.05). A higher consumption of milk/milk substitute consumed per day was positively correlated to both feeding difficulties and fussy eating (p < 0.05). CONCLUSION: Participants consuming an exclusion diet for CMA have higher scores for feeding difficulties and fussy eating than those consuming an unrestricted diet; however, the majority of participants' scores were within the normal range and did not affect the growth.


Assuntos
Comportamento Alimentar , Preferências Alimentares , Comportamento do Lactente , Hipersensibilidade a Leite/dietoterapia , Estudos de Casos e Controles , Desenvolvimento Infantil , Pré-Escolar , Estudos Transversais , Inglaterra , Feminino , Humanos , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Testes Intradérmicos , Masculino , Hipersensibilidade a Leite/diagnóstico , Hipersensibilidade a Leite/imunologia , Estado Nutricional , Inquéritos e Questionários
9.
Clin Exp Allergy ; 44(5): 724-35, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24654674

RESUMO

BACKGROUND: Cluster analyses have enhanced understanding of the heterogeneity of both paediatric and adult wheezing. However, while adolescence represents an important transitional phase, the nature of young adult wheeze has yet to be clearly characterised. OBJECTIVES: To use cluster analysis to define, for the first time, clinically relevant young adult wheeze clusters in a longitudinal birth cohort. METHODS: K-means cluster analysis was undertaken among 309 currently wheezing subjects at 18 years in the Isle of Wight birth cohort (N = 1456). Thirteen disease-characterising clustering variables at 18 years were used. Resulting clusters were then further characterised by severity indices plus potential risk factors for wheeze development throughout the 1st 18 years of life. RESULTS: Six wheeze clusters were identified. Cluster 1 (12.3%) male-early-childhood-onset-atopic-wheeze-with-normal-lung-function had male predominance, normal spirometry, low bronchodilator reversibility (BDR), intermediate bronchial hyper-responsiveness (BHR), high atopy prevalence and more admissions. Cluster 2 (24.2%) early-childhood-onset-wheeze-with-intermediate-lung-function had no specific sex association, intermediate spirometry, BDR, BHR, more significant BTS step therapy and admissions. Cluster 3 (9.7%) female-early-childhood-onset-atopic-wheeze-with-impaired-lung-function showed female predominance, high allergic disease comorbidity, more severe BDR and BHR, greatest airflow obstruction, high smoking prevalence, higher symptom severity and admissions. Cluster 4 (19.4%) female-undiagnosed-wheezers had adolescent-onset non-atopic wheeze, low BDR and BHR, impaired but non-obstructed spirometry, high symptom frequency and highest smoking prevalence. Cluster 5 (24.6%) female-late-childhood-onset-wheeze-with-normal-lung-function showed no specific atopy association, normal spirometry, low BDR, BHR and symptom severity. Cluster 6 (9.7%) male-late-childhood-onset-atopic-wheeze-with-impaired-lung-function had high atopy and rhinitis prevalence, increased BDR and BHR, moderately impaired spirometry, high symptom severity and higher BTS step therapy. CONCLUSIONS AND CLINICAL RELEVANCE: Young adult wheeze is diverse and can be classified into distinct clusters. More severe clusters merit attention and are associated with childhood onset, atopy, impaired lung function and in some, smoking. Smoking-associated undiagnosed wheezers also merit recognition. Better understanding of young adult wheeze could facilitate better later adult respiratory health.


Assuntos
Sons Respiratórios/etiologia , Adolescente , Idade de Início , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Morbidade , Avaliação de Resultados da Assistência ao Paciente , Vigilância da População , Prevalência , Sons Respiratórios/diagnóstico , Fatores de Risco
10.
Clin Exp Allergy ; 44(9): 1170-8, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24708301

RESUMO

BACKGROUND: Allergic sensitization and filaggrin gene (FLG) variants are important risk factors for allergic disorders; however, knowledge on their individual and interactive effects on the coexistence of eczema, asthma, and rhinitis is lacking. OBJECTIVE: This study aimed at investigating the single and combined effects of allergic sensitization and FLG variants on the development of single and multiple allergic disorders. METHODS: The Isle of Wight birth cohort (n = 1456) has been examined at 1, 2, 4, 10, and 18 years of age. Repeated measurements of eczema, asthma, rhinitis, and skin prick tests were available for all follow-ups. FLG variants were genotyped in 1150 participants. Associations of allergic sensitization and FLG variants with single and multiple allergic disorders were tested in log-binomial regression analysis. RESULTS: The prevalence of eczema-, asthma-, and rhinitis-only ranged from 5.6% to 8.5%, 4.9% to 10.2%, and 2.5% to 20.4%, respectively, during the first 18 years of life. The coexistence of allergic disorders is common, with approximately 2% of the population reporting the comorbidity of 'eczema, asthma, and rhinitis' during the study period. In repeated measurement analyses, allergic sensitization and FLG variants, when analysed separately, were associated with having single and multiple allergic disorders. Of particular significance, their combined effect increased the risk of 'eczema and asthma' (RR = 13.67, 95% CI: 7.35-25.42), 'asthma and rhinitis' (RR = 7.46, 95% CI: 5.07-10.98), and 'eczema, asthma, and rhinitis' (RR = 23.44, 95% CI: 12.27-44.78). CONCLUSIONS AND CLINICAL RELEVANCE: The coexistence of allergic disorders is frequent, and allergic sensitization and FLG variants jointly increased risk of allergic comorbidities, which may represent more severe and complex clinical phenotypes. The interactive effect and the elevated proportion of allergic comorbidities associated with allergic sensitization and FLG variants emphasize their joint importance in the pathogenesis of allergic disorders.


Assuntos
Predisposição Genética para Doença , Variação Genética , Hipersensibilidade/epidemiologia , Hipersensibilidade/genética , Proteínas de Filamentos Intermediários/genética , Adolescente , Asma/epidemiologia , Asma/genética , Asma/imunologia , Criança , Pré-Escolar , Estudos de Coortes , Comorbidade , Eczema/epidemiologia , Eczema/genética , Eczema/imunologia , Feminino , Proteínas Filagrinas , Seguimentos , Genótipo , Humanos , Hipersensibilidade/imunologia , Lactente , Masculino , Razão de Chances , Prevalência , Rinite/epidemiologia , Rinite/genética , Rinite/imunologia , Fatores de Risco , Fatores Sexuais
11.
Allergy ; 69(5): 590-601, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24697491

RESUMO

Food allergy can have significant effects on morbidity and quality of life and can be costly in terms of medical visits and treatments. There is therefore considerable interest in generating efficient approaches that may reduce the risk of developing food allergy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Prevention and is part of the EAACI Guidelines for Food Allergy and Anaphylaxis. It aims to provide evidence-based recommendations for primary prevention of food allergy. A wide range of antenatal, perinatal, neonatal, and childhood strategies were identified and their effectiveness assessed and synthesized in a systematic review. Based on this evidence, families can be provided with evidence-based advice about preventing food allergy, particularly for infants at high risk for development of allergic disease. The advice for all mothers includes a normal diet without restrictions during pregnancy and lactation. For all infants, exclusive breastfeeding is recommended for at least first 4-6 months of life. If breastfeeding is insufficient or not possible, infants at high-risk can be recommended a hypoallergenic formula with a documented preventive effect for the first 4 months. There is no need to avoid introducing complementary foods beyond 4 months, and currently, the evidence does not justify recommendations about either withholding or encouraging exposure to potentially allergenic foods after 4 months once weaning has commenced, irrespective of atopic heredity. There is no evidence to support the use of prebiotics or probiotics for food allergy prevention.


Assuntos
Anafilaxia/prevenção & controle , Hipersensibilidade Alimentar/prevenção & controle , Prevenção Primária , Adulto , Aleitamento Materno , Criança , Pré-Escolar , Suplementos Nutricionais , Feminino , Humanos , Lactente , Fórmulas Infantis , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido , Masculino , Gravidez
12.
Allergy ; 69(5): 581-9, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24433563

RESUMO

BACKGROUND: Food allergies can have serious physical, social, and financial consequences. This systematic review examined ways to prevent the development of food allergy in children and adults. METHODS: Seven bibliographic databases were searched from their inception to September 30, 2012, for systematic reviews, randomized controlled trials, quasi-randomized controlled trials, controlled clinical trials, controlled before-and-after studies, interrupted time series studies, and prospective cohort studies. Experts were consulted for additional studies. There were no language or geographic restrictions. Two reviewers appraised the studies using appropriate tools. Data were not suitable for meta-analysis due to heterogeneity, so were narratively synthesized. RESULTS: Seventy-four studies were included, one-third of which were of high quality. There was no good evidence to recommend that pregnant or breastfeeding women should change their diet or take supplements to prevent allergies in infants at high or normal risk. There were mixed findings about the preventive benefits of breastfeeding for infants at high or normal risk, but there was evidence to recommend avoiding cow's milk and substituting with extensively or partially hydrolyzed whey or casein formulas for infants at high risk for the first 4 months. Soy milk and delaying the introduction of solid foods beyond 4 months did not have preventive benefits in those at high or normal risk. There was very little evidence about strategies for preventing food allergy in older children or adults. CONCLUSIONS: There is much to learn about preventing food allergy, and this is a priority given the high societal and healthcare costs involved.


Assuntos
Hipersensibilidade Alimentar/prevenção & controle , Prevenção Primária , Adulto , Aleitamento Materno , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Fórmulas Infantis , Recém-Nascido , Masculino , Gravidez
13.
J Eur Acad Dermatol Venereol ; 27(3): e420-3, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23003573

RESUMO

BACKGROUND: Loss-of-function variants within the filaggrin gene (FLG) are associated with a dysfunctional skin barrier that contributes to the development of eczema. Epigenetic modifications, such as DNA methylation, are genetic regulatory mechanisms that modulate gene expression without changing the DNA sequence. OBJECTIVES: To investigate whether genetic variants and adjacent differential DNA methylation within the FLG gene synergistically act on the development of eczema. METHODS: A subsample (n = 245, only females aged 18 years) of the Isle of Wight birth cohort participants (n = 1456) had available information for FLG variants R501X, 2282del4 and S3247X and DNA methylation levels for 10 CpG sites within the FLG gene. Log-binomial regression was used to estimate the risk ratios (RRs) of eczema associated with FLG variants at different methylation levels. RESULTS: The period prevalence of eczema was 15.2% at age 18 years and 9.0% of participants were carriers (heterozygous) of FLG variants. Of the 10 CpG sites spanning the genomic region of FLG, methylation levels of CpG site 'cg07548383' showed a significant interaction with FLG sequence variants on the risk for eczema. At 86% methylation level, filaggrin haploinsufficient individuals had a 5.48-fold increased risk of eczema when compared to those with wild type FLG genotype (P-value = 0.0008). CONCLUSIONS: Our novel results indicated that the association between FLG loss-of-function variants and eczema is modulated by DNA methylation. Simultaneously assessing the joint effect of genetic and epigenetic factors within the FLG gene further highlights the importance of this genomic region for eczema manifestation.


Assuntos
Metilação de DNA , Eczema/genética , Predisposição Genética para Doença , Proteínas de Filamentos Intermediários/genética , Adolescente , Estudos de Coortes , Feminino , Proteínas Filagrinas , Triagem de Portadores Genéticos , Humanos , Proteínas de Filamentos Intermediários/fisiologia
14.
Eur Respir J ; 39(4): 985-91, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21852333

RESUMO

Breastfeeding has been linked with increased forced vital capacity (FVC) in children but not in older adolescents. Our aim was to investigate the effects of breastfeeding duration and infant weight gain on FVC in both developmental periods. In a birth cohort, information on breastfeeding duration was collected at 1 and 2 yrs; spirometric tests were conducted at 10 and 18 yrs. To estimate the effect of breastfeeding duration on FVC at 18 yrs of age, we used linear models; to analyse repeated FVC measurements at 10 and 18 yrs of age, we used linear mixed models. Links between breastfeeding, infant weight gain and FVC at 10 and 18 yrs of age were analysed through path analyses. Among 808 breastfed children, 49% were breastfed for ≥ 4 months. At 18 yrs of age the augmenting effect of breastfeeding on FVC was reduced with increased height. Linear mixed models identified that breastfeeding duration was associated with increased FVC. Path analysis suggested a direct effect of breastfeeding on FVC at 10 yrs of age, but an indirect effect at 18 yrs of age via FVC at 10 yrs of age. Although inversely related to breastfeeding, a higher weight gain in infants led to taller adolescents and, in turn, resulted in increased FVC. In conclusion, a longer duration of breastfeeding contributes to lung health in childhood and adolescence.


Assuntos
Desenvolvimento do Adolescente , Aleitamento Materno/estatística & dados numéricos , Pneumopatias/prevenção & controle , Pulmão/fisiologia , Capacidade Vital , Adolescente , Criança , Desenvolvimento Infantil , Estudos de Coortes , Feminino , Humanos , Lactente , Modelos Lineares , Estudos Longitudinais , Pneumopatias/epidemiologia , Masculino , Fatores de Risco
15.
Clin Exp Allergy ; 42(10): 1501-9, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22994347

RESUMO

BACKGROUND: Skin prick testing (SPT) is fundamental to the practice of clinical allergy identifying relevant allergens and predicting the clinical expression of disease. There are only limited data on the natural history of SPT results over childhood and adolescence. OBJECTIVE: We aimed to describe the natural history of SPT and patterns of sensitization over childhood and adolescence. METHODS: The 1989 Isle of Wight birth cohort (1456 participants) was followed up at 1, 2, 4, 10 and 18 years. SPT was undertaken from 4 years. RESULTS: SPT was performed on 980 (80%), 1036 (75%) and 853 (65%) of participants at 4, 10 and 18 years. The prevalence of sensitization to any allergen at these time-points was 19.7%, 26.9% and 41.3% respectively. At each time-point, boys were significantly more likely to be sensitized (P < 0.016) and sensitization significantly increased over childhood and adolescence (average annual increase of 7%). Some children outgrew their sensitization. The rate of sensitization to most individual allergens increased over childhood and adolescence. A configural frequency analysis showed that whether an individual was sensitizated was relatively fixed over childhood and adolescence. Cluster analysis at 4 years demonstrated four major groups of individuals with similar co-sensitization to specific allergens. Children who were sensitized at age 4 years generally went onto become sensitized to additional allergens at 10 and 18 years. CONCLUSIONS AND CLINICAL RELEVANCE: Allergic sensitization continues to increase over childhood into adolescence although the majority of children who were not sensitized at 4 years remain non-sensitized throughout childhood and adolescence. The presence of sensitization at 4 years predicted later sensitization to additional allergens.


Assuntos
Alérgenos/imunologia , Hipersensibilidade/epidemiologia , Pele/imunologia , Adolescente , Animais , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Hipersensibilidade/etiologia , Hipersensibilidade/imunologia , Hipersensibilidade Imediata/epidemiologia , Hipersensibilidade Imediata/etiologia , Hipersensibilidade Imediata/imunologia , Lactente , Masculino , Prevalência , Fatores de Risco , Testes Cutâneos , Reino Unido/epidemiologia
16.
Clin Exp Allergy ; 42(12): 1697-723, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23181787

RESUMO

As in previous years, we felt it would be of value to our readership to summarize the new information provided by the authors who have published in Clinical and Experimental Allergy in 2011 and set this in the context of recent advances in our understanding of the pathogenesis and management of allergic disease in all its many manifestations. In 2011, about 210 articles were published in Clinical and Experimental Allergy including editorials, reviews, opinion articles, guidelines, letters, book reviews and of course at the heart of the journal, papers containing original data. As before, this review is divided into sections based on the way the journal is structured, although this year we have grouped together all the papers dealing with mechanisms of allergic disease, whether they involve patients (clinical mechanisms), pure in vitro studies (basic mechanisms) or animal models (experimental models), as we felt this was a more coherent way to deal with the subject. In the field of asthma and rhinitis, the relationship between airway inflammation and airway dysfunction was of perennial interest to investigators, as were phenotypes and biomarkers. Aspirin hypersensitivity appeared in studies in several papers and there was new interest in asthma in the elderly. The mechanisms involved in allergic disease describe advances in our understanding of T cell responses, the relationship between inflammation and disease, mast cell and basophil activation, steroid resistance and novel therapies. In the section dealing with epidemiology, studies seeking to identify risk factors for allergic disease including vitamin D are prominent, as once again are studies investigating gene-environment interactions. The clinical allergy section focuses on drug allergy, food allergy and immunotherapy. The area of oral immunotherapy for food allergy is well covered and we were grateful to Stephen Durham for guest editing an outstanding special issue on immunotherapy in the centenary year of Leonard Noon's pioneering work. Lastly, in the field of allergens, the interest in component-resolved diagnosis continues to grow and there are also articles describing important novel cultivars and the effect of food processing on the allergenic properties of foods. Another terrific year, full of important and high-quality work,which the journal has been proud to bring to the allergy community.


Assuntos
Asma/fisiopatologia , Asma/terapia , Hipersensibilidade/fisiopatologia , Hipersensibilidade/terapia , Idoso , Alérgenos/imunologia , Alérgenos/uso terapêutico , Animais , Asma/imunologia , Criança , Pré-Escolar , Modelos Animais de Doenças , Feminino , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/imunologia , Imunoterapia , Lactente , Masculino , Pessoa de Meia-Idade
18.
Clin Exp Allergy ; 41(6): 851-9, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21561494

RESUMO

BACKGROUND: Longitudinal studies of the natural history of childhood and adolescent rhinitis are lacking. OBJECTIVES: To investigate the natural history of rhinitis up to 18 years of age, and how that is influenced by gender and atopy. METHODS: The Isle of Wight birth cohort was recruited in 1989 (n=1456). Questionnaire data on nasal symptoms (rhinitis) were collected at 1, 2, 4, 10 and 18 years of age. To define atopy, skin prick tests were conducted at 4, 10 and 18 years. The 12-month period prevalence plus positive and negative transitions (defined as change in disease status in two consecutive study assessments) were stratified by gender and atopic status. RESULTS: Overall rhinitis prevalence increased from 5.4% at 4 years to 35.8% at 18 years (P<0.001), without gender difference. Atopic rhinitis prevalence increased steadily from 3.4% at 4 years to 27.3% at 18 years (P<0.001), was commoner in boys at 18 years (P=0.02) and associated with greater positive transition in boys from 10 to 18 years (P=0.01). Prevalence of non-atopic rhinitis also increased from 4 to 18 years (P=0.003) and was greater in girls at 18 years (P<0.001) reflecting higher female positive transition from 10 to 18 years (P<0.001). Non-atopic rhinitis negative transition (remission) was highest in early life and reduced in later childhood/adolescence. CONCLUSION: Atopic rhinitis becomes increasingly common as children grow into adolescents, with stronger associations to male gender. Non-atopic rhinitis shows a female predominance at 18 years as girls 'grow into' it more during adolescence. Our findings suggest differential gender effects on the increasing prevalence of both atopic and non-atopic rhinitis in adolescence. CLINICAL RELEVANCE: A better understanding of how gender and atopic status influence rhinitis during adolescence emerges from this study. Application of such knowledge could help to improve clinical recognition, judge prognosis and ultimately improve management of this common condition.


Assuntos
Rinite/epidemiologia , Rinite/imunologia , Adolescente , Fatores Etários , Asma/complicações , Asma/epidemiologia , Criança , Pré-Escolar , Progressão da Doença , Eczema/complicações , Eczema/epidemiologia , Feminino , Humanos , Incidência , Lactente , Estudos Longitudinais , Masculino , Prevalência , Rinite/complicações , Fatores Sexuais
20.
Clin Exp Allergy ; 40(12): 1776-84, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21059120

RESUMO

BACKGROUND: Trends in the prevalence of eczema in the course of childhood and adolescence are not clear although often a net remission during childhood is assumed. OBJECTIVES: To investigate the dynamics of change in eczema from 1 to 18 years in a prospective study and to understand the influence of gender and atopy. METHODS: Detailed information regarding eczema were collected at ages 1, 2, 4, 10 and 18 years from the 1989 Isle of Wight birth cohort (n=1456). Skin prick testing was performed at 4, 10 and 18 years of age. The 12-month period prevalence, positive and negative transitions (defined as change in disease status in two consecutive study assessments) were stratified by gender and atopic status. RESULTS: The period prevalence of eczema from birth to 18 years of age remained relatively constant (11.9-14.2%) with minimal remission. Up to 10 years of age, gender did not influence prevalence. From 10 to 18 years, eczema became more prevalent among girls (16.3% for girls vs. 8.3% for boys, P<0.001) as a result of a greater positive transition in girls (9.4% for girls vs. 4.3% for boys, P=0.001) and greater negative transition in boys (65.4% for boys vs. 50% for girls, P=0.04). The higher positive transition of eczema in girls was most pronounced for non-atopic eczema (5.9% for girls vs. 1.5% for boys, P=0.002). CONCLUSIONS: We found only a minimal reduction in the prevalence of eczema during childhood and adolescence. During adolescence, more girls develop eczema and more boys outgrow it suggesting a role for gender-specific pubertal factors.


Assuntos
Dermatite Atópica/epidemiologia , Eczema/epidemiologia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Inglaterra/epidemiologia , Feminino , Humanos , Lactente , Masculino , Prevalência , Fatores Sexuais
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