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1.
Handb Exp Pharmacol ; 268: 21-27, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34165634

RESUMO

The prevalences of allergic diseases, asthma, atopic dermatitis, allergic rhinitis and lately food allergy have been increasing over the last decades. It has been suggested that the prevalence of allergic diseases has reached a plateau in high income countries, while it is still on the rise in low and middle income countries. Generally, allergic diseases more often set on in childhood than in adulthood and affected children contribute more to the rise in allergic disease prevalence than affected adults. Epidemiological evidence suggests that not all atopic dermatitis and asthma cases are attributable to atopic sensitization. Indeed, mainly genetic association studies have prompted the unravelling of barrier dysfunction as a mainstay in the patho-mechanisms leading to atopic dermatitis and to asthma with atopic sensitization secondary to this dysfunction. Epidemiological research on risk and protective factors for allergic disease, acting against the background of genetic susceptibility, has produced an enormous body of evidence. Prominent observations are the 'sibling effect' and the 'farm effect' which gave rise to the 'hygiene hypothesis' and later the 'biodiversity hypothesis'. Future epidemiological research is required to evaluate and refine these hypotheses in light of the paradigm shift from atopic sensitization to barrier dysfunction with ever increasing options for environmental characterization, currently, e.g., 'omics'-techniques in microbiology and metabolism, and with ever increasing options for phenotyping of allergic techniques, including, e.g., high-resolution time series of symptoms using, e.g., sensing technologies.


Assuntos
Asma , Dermatite Atópica , Hipersensibilidade Alimentar , Adulto , Asma/epidemiologia , Asma/etiologia , Criança , Dermatite Atópica/epidemiologia , Dermatite Atópica/etiologia , Humanos , Prevalência , Fatores de Risco
2.
Environ Health Prev Med ; 26(1): 108, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34772333

RESUMO

The USA has a high burden of childhood asthma. Previous studies have observed associations between higher blood lead levels and greater hypersensitivity in children. The objective of the present study was to estimate the association between blood lead concentrations during early childhood and an asthma diagnosis between 48 and 72 months of age amongst a cohort with well-characterized blood lead concentrations. Blood lead concentrations were measured at 6, 12, 18, 24, 36, and 48 months of age in 222 children. The presence of an asthma diagnosis between 48 and 72 months was assessed using a questionnaire which asked parents or guardians whether they had been told by a physician, in the past 12 months, that their child had asthma. Crude and adjusted risk ratios (RR) of an asthma diagnosis were estimated for several parameterizations of blood lead exposure including lifetime average (6 to 48 months) and infancy average (6 to 24 months) concentrations. After adjustment for child sex, birthweight, daycare attendance, maternal race, education, parity, breastfeeding, income, and household smoking, age-specific or composite measures of blood lead were not associated with asthma diagnosis by 72 months of age in this cohort.


Assuntos
Asma/diagnóstico , Poluentes Ambientais/sangue , Chumbo/sangue , Asma/epidemiologia , Asma/etiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , New York/epidemiologia
3.
Artigo em Inglês | MEDLINE | ID: mdl-34769911

RESUMO

ICEES (Integrated Clinical and Environmental Exposures Service) provides a disease-agnostic, regulatory-compliant approach for openly exposing and analyzing clinical data that have been integrated at the patient level with environmental exposures data. ICEES is equipped with basic features to support exploratory analysis using statistical approaches, such as bivariate chi-square tests. We recently developed a method for using ICEES to generate multivariate tables for subsequent application of machine learning and statistical models. The objective of the present study was to use this approach to identify predictors of asthma exacerbations through the application of three multivariate methods: conditional random forest, conditional tree, and generalized linear model. Among seven potential predictor variables, we found five to be of significant importance using both conditional random forest and conditional tree: prednisone, race, airborne particulate exposure, obesity, and sex. The conditional tree method additionally identified several significant two-way and three-way interactions among the same variables. When we applied a generalized linear model, we identified four significant predictor variables, namely prednisone, race, airborne particulate exposure, and obesity. When ranked in order by effect size, the results were in agreement with the results from the conditional random forest and conditional tree methods as well as the published literature. Our results suggest that the open multivariate analytic capabilities provided by ICEES are valid in the context of an asthma use case and likely will have broad value in advancing open research in environmental and public health.


Assuntos
Asma , Exposição Ambiental , Asma/epidemiologia , Asma/etiologia , Humanos , Aprendizado de Máquina , Modelos Estatísticos
4.
Zhongguo Zhen Jiu ; 41(11): 1221-4, 2021 Nov 12.
Artigo em Chinês | MEDLINE | ID: mdl-34762374

RESUMO

OBJECTIVE: To compare the therapeutic effect on bronchial asthma between presence of skin reaction and the absence of skin reaction after acupoint application. METHODS: Sixty-one patients with bronchial asthma were treated with acupoint application during the hottest periods of summer ("dog days"). The acupoints included Dingchuan (EX-B 1), Feishu (BL 13), Xinshu (BL 15), Pishu (BL 20) and Shenshu (BL 23). The treatment was given once every 7 days, with the herbal plaster remained for 6 h each time, and 4 treatments were required totally. According to the local skin reaction after acupoint application, a skin reaction group (30 cases, 2 cases dropped off) and a non-skin reaction group (31 cases) were divided. Separately, before treatment and 1 year after treatment, using chronic disease management platform of asthma, the number of asthma attacks, the score of asthma control test (ACT) and the score of asthma quality of life questionnaire (AQLQ) were recorded online. Besides, the therapeutic effect was observed in the two groups 1 year after treatment. RESULTS: One year after treatment, the number of asthma attacks was reduced as compared with that before treatment in the patients of either group (P<0.001), the score of ACT and each domain in AQLQ, i.e. activity limitation, asthma symptoms, psychological state, reactions to stimuli and self-health care as well as the total scores of AQLQ were all increased as compared with those before treatment (P<0.001). The number of asthma attacks in the skin reaction group was less than the non-skin reaction group (P<0.05), the score of ACT and each domain of AQLQ and the total scores of AQLQ were all higher than the non-skin reaction group successively (P<0.05, P<0.01). The total effective rate was 82.1% (23/28) in the skin reaction group, better than 67.7% (21/31) in the non-skin reaction group (P<0.05). CONCLUSION: In treatment of acupoint application for bronchial asthma, the clinical therapeutic effect is better in the patients with local skin reaction after acupoint application. The chronic disease management platform of asthma is convenient for online evaluation.


Assuntos
Terapia por Acupuntura , Asma , Pontos de Acupuntura , Asma/etiologia , Asma/terapia , Gerenciamento Clínico , Humanos , Qualidade de Vida
5.
Int J Mol Sci ; 22(19)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34639020

RESUMO

A subset of adult-onset asthma patients attribute their symptoms to damp and moldy buildings. Symptoms of idiopathic environmental intolerance (IEI) may resemble asthma and these two entities overlap. We aimed to evaluate if a distinct clinical subtype of asthma related to damp and moldy buildings can be identified, to unravel its corresponding pathomechanistic gene signatures, and to investigate potential molecular similarities with IEI. Fifty female adult-onset asthma patients were categorized based on exposure to building dampness and molds during disease initiation. IEI patients (n = 17) and healthy subjects (n = 21) were also included yielding 88 study subjects. IEI was scored with the Quick Environmental Exposure and Sensitivity Inventory (QEESI) questionnaire. Inflammation was evaluated by blood cell type profiling and cytokine measurements. Disease mechanisms were investigated via gene set variation analysis of RNA from nasal biopsies and peripheral blood mononuclear cells. Nasal biopsy gene expression and plasma cytokine profiles suggested airway and systemic inflammation in asthma without exposure to dampness (AND). Similar evidence of inflammation was absent in patients with dampness-and-mold-related asthma (AAD). Gene expression signatures revealed a greater degree of similarity between IEI and dampness-related asthma than between IEI patients and asthma not associated to dampness and mold. Blood cell transcriptome of IEI subjects showed strong suppression of immune cell activation, migration, and movement. QEESI scores correlated to blood cell gene expression of all study subjects. Transcriptomic analysis revealed clear pathomechanisms for AND but not AAD patients. Furthermore, we found a distinct molecular pathological profile in nasal and blood immune cells of IEI subjects, including several differentially expressed genes that were also identified in AAD samples, suggesting IEI-type mechanisms.


Assuntos
Poluição do Ar em Ambientes Fechados , Asma/etiologia , Suscetibilidade a Doenças , Exposição Ambiental/efeitos adversos , Fungos , Perfilação da Expressão Gênica , Transcriptoma , Adulto , Células Sanguíneas/imunologia , Células Sanguíneas/metabolismo , Estudos de Casos e Controles , Citocinas/metabolismo , Feminino , Humanos , Imunofenotipagem , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Fatores de Risco
6.
Nat Cell Biol ; 23(10): 1060-1072, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34616019

RESUMO

Eosinophilic inflammation is a feature of allergic asthma. Despite mounting evidence showing that chromatin filaments released from neutrophils mediate various diseases, the understanding of extracellular DNA from eosinophils is limited. Here we show that eosinophil extracellular traps (EETs) in bronchoalveolar lavage fluid are associated with the severity of asthma in patients. Functionally, we find that EETs augment goblet-cell hyperplasia, mucus production, infiltration of inflammatory cells and expressions of type 2 cytokines in experimental non-infection-related asthma using both pharmaceutical and genetic approaches. Multiple clinically relevant allergens trigger EET formation at least partially via thymic stromal lymphopoietin in vivo. Mechanically, EETs activate pulmonary neuroendocrine cells via the CCDC25-ILK-PKCα-CRTC1 pathway, which is potentiated by eosinophil peroxidase. Subsequently, the pulmonary neuroendocrine cells amplify allergic immune responses via neuropeptides and neurotransmitters. Therapeutically, inhibition of CCDC25 alleviates allergic inflammation. Together, our findings demonstrate a previously unknown role of EETs in integrating immunological and neurological cues to drive asthma progression.


Assuntos
Asma/patologia , Líquido da Lavagem Broncoalveolar/imunologia , Eosinófilos/patologia , Armadilhas Extracelulares/fisiologia , Inflamação/patologia , Pulmão/patologia , Células Neuroendócrinas/patologia , Adulto , Animais , Asma/etiologia , Asma/metabolismo , Estudos de Casos e Controles , Eosinófilos/imunologia , Eosinófilos/metabolismo , Feminino , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Pulmão/imunologia , Pulmão/metabolismo , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células Neuroendócrinas/imunologia , Células Neuroendócrinas/metabolismo , Neutrófilos/imunologia , Neutrófilos/metabolismo , Neutrófilos/patologia , Proteína Quinase C-alfa/genética , Proteína Quinase C-alfa/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
7.
Immunol Allergy Clin North Am ; 41(4): 599-611, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34602231

RESUMO

Inner-city children with asthma are known to have high disease mortality and morbidity. Frequently, asthma in this high-risk population is difficult to control and more severe in nature. Several factors, including socioeconomic hardship, ability to access to health care, adherence to medication, exposure to certain allergens, pollution, crowd environment, stress, and infections, play an important role in the pathophysiology of inner-city asthma. Comprehensive control of home allergens and exposure to tobacco smoke, the use of immune based therapies, and school-based asthma programs have shown promising results in asthma control in this population.


Assuntos
Asma , Exposição Ambiental , Alérgenos , Asma/epidemiologia , Asma/etiologia , Asma/terapia , Criança , Exposição Ambiental/efeitos adversos , Humanos , Morbidade , População Urbana
9.
Allergy Asthma Proc ; 42(5): 400-402, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34474709

RESUMO

Background: On January 20, 2020, the first documented case of novel severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]) was reported in the United States. The U.S. Centers for Disease Control and Prevention continues to report more morbidity and mortality in adults than in children. Early in Pandemic, there was a concern that patients with asthma would be affected disproportionately from COVID-19, but this was not manifested. It is now recognized that angiotensin-converting enzyme 2 receptors that are used by the coronavirus for infection have low expression in children with atopy that may contribute to decreased infectivity in children who are atopic. There are several early reports of decreased emergency department (ED) visits for children with asthma. The authors previously reported a decrease in pediatric ED visits in the spring of 2020, which correlated with school closure. Objective: To determine if this trend of decreased ED visits for pediatric asthma was sustained throughout the first COVID-19 pandemic year. Methods: ED data from one inner city children's hospital were collected by using standard medical claims codes. Conclusion: We reported a sustained year of decreased ED visits for children with asthma in one pediatric ED in an inner-city hospital; this seemed to be secondary to school closure and decreased exposure to upper respiratory infections.


Assuntos
Asma , COVID-19/prevenção & controle , Progressão da Doença , Serviço Hospitalar de Emergência/tendências , Utilização de Instalações e Serviços/tendências , Doença Aguda , Adolescente , Asma/etiologia , Asma/fisiopatologia , Asma/terapia , Criança , Pré-Escolar , Exposição Ambiental/prevenção & controle , Exposição Ambiental/estatística & dados numéricos , Feminino , Humanos , Masculino , Michigan , Distanciamento Físico , Instituições Acadêmicas , Saúde da População Urbana
10.
BMJ Open ; 11(9): e046769, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475151

RESUMO

OBJECTIVES: The association between hypertensive disorders in pregnancy (HDP) and an increased risk of asthma in offspring remains controversial. No systematic review of this topic has been performed. The aim of this systematic review was to summarise the available evidence regarding the association between HDP and the risk of asthma in offspring. DESIGN: Systematic review and meta-analysis. METHODS: On the basis of a prepared protocol, a systematic search of PubMed, EMBASE, the Cochrane Library and Web of Science was performed using a detailed search strategy from the database inception to 17 January 2020. Cohort, case-control and cross-sectional studies published in English reporting the diagnoses of maternal HDP and asthma in offspring were included. The Meta-analysis of Observational Studies in Epidemiology guidelines were followed throughout the study. The estimated pooled ORs of HDP and asthma in offspring were calculated from the studies, and the meta-analysis was performed using random-effects models. RESULTS: Ten cohort studies involving a total of 6 270 430 participants were included. According to the Newcastle-Ottawa Scale, the overall methodological quality was good since 8 studies were of high quality and 2 studies were of moderate quality. After controlling for potential confounders, HDP was associated with a possible increased risk of asthma in offspring, with a pooled adjusted OR (aOR) of 1.19 (95% CI 1.12 to 1.26). The subgroup analyses according to HDP subgroups, sibling design, study quality, study location, offspring ages, singleton status, exposure assessment, outcome assessment and adjusted factors showed similar results. CONCLUSIONS: Exposure to HDP may be associated with an increased risk of asthma in offspring. Further research is needed to verify the results and determine whether the observed relationship is causal. PROSPERO REGISTRATION NUMBER: CRD42020148250.


Assuntos
Asma , Hipertensão Induzida pela Gravidez , Pré-Eclâmpsia , Asma/epidemiologia , Asma/etiologia , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Hipertensão Induzida pela Gravidez/epidemiologia , Gravidez
11.
Artigo em Inglês | MEDLINE | ID: mdl-34574732

RESUMO

OBJECTIVE: To determine the prevalence of cotton dust-related allergic asthma and associated factors among textile workers in Nam Dinh province, Vietnam. METHODS: A cross-sectional study was performed with 1082 workers in two textile garment companies using the asthma diagnostic criteria of the GINA (Global Initiative for Asthma) 2016 guidelines. RESULTS: Among study participants, 11.9% had suspected asthma symptoms, 7.4% were diagnosed with asthma, and 4.3% (3.6% in men and 4.5% in women) were diagnosed with cotton dust-related allergic asthma. Overweight, seniority more than 10 years, history of asthma, allergic rhinitis, family history of allergy, and exposure to cotton dust from more than one hour per day in the working environment were found to be important predictors of cotton dust-related allergic asthma among textile workers. CONCLUSIONS: Textile workers in two companies in Nam Dinh, Vietnam had a high prevalence of dust-related allergic asthma compared to estimates from the general population. There is a need to design appropriate measures of prevention, screening, and care for dust-related asthma in the textile industry. Further evaluation with better exposure assessment is necessary.


Assuntos
Asma , Doenças Profissionais , Exposição Ocupacional , Asma/epidemiologia , Asma/etiologia , Fibra de Algodão , Estudos Transversais , Poeira/análise , Feminino , Humanos , Masculino , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Prevalência , Indústria Têxtil , Têxteis , Vietnã/epidemiologia
12.
ScientificWorldJournal ; 2021: 8881390, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34566522

RESUMO

Air pollution has been associated with poor health outcomes and continues to be a risk factor for respiratory health in children. While higher particulate matter (PM) levels are associated with increased frequency of symptoms, lower lung function, and increase airway inflammation from asthma, the precise composition of the particles that are more highly associated with poor health outcomes or healthcare utilization are not fully elucidated. PM is measured quantifiably by current air pollution monitoring systems. To better determine sources of PM and speciation of such sources, a particulate matter (PM) source apportionment study, the Cleveland Multiple Air Pollutant Study (CMAPS), was conducted in Cleveland, Ohio, in 2009-2010, which allowed more refined assessment of associations with health outcomes. This article presents an evaluation of short-term (daily) and long-term associations between motor vehicle and industrial air pollution components and pediatric asthma emergency department (ED) visits by evaluating two sets of air quality data with healthcare utilization for pediatric asthma. Exposure estimates were developed using land use regression models for long-term exposures for nitrogen dioxide (NO2) and coarse (i.e., with aerodynamic diameters between 2.5 and 10 µm) particulate matter (PM) and the US EPA Positive Matrix Factorization receptor model for short-term exposures to fine (<2.5 µm) and coarse PM components. Exposure metrics from these two approaches were used in asthma ED visit prevalence and time series analyses to investigate seasonal-averaged short- and long-term impacts of both motor vehicles and industry emissions. Increased pediatric asthma ED visits were found for LUR coarse PM and NO2 estimates, which were primarily contributed by motor vehicles. Consistent, statistically significant associations with pediatric asthma visits were observed, with short-term exposures to components of fine and coarse iron PM associated with steel production. Our study is the first to combine spatial and time series analysis of ED visits for asthma using the same periods and shows that PM related to motor vehicle emissions and iron/steel production are associated with increased pediatric asthma visits.


Assuntos
Poluição do Ar/efeitos adversos , Asma/epidemiologia , Adolescente , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Asma/etiologia , Biomassa , Criança , Pré-Escolar , Exposição Ambiental/análise , Feminino , Combustíveis Fósseis , Humanos , Indústrias , Masculino , Ohio/epidemiologia , Material Particulado/efeitos adversos , Material Particulado/análise , Análise de Regressão , População Urbana , Emissões de Veículos
13.
Health Place ; 71: 102665, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34564025

RESUMO

This study tested the relationship of neighborhood crime as a driver of pediatric asthma diagnoses via the mechanism of toxic stress utilizing data from a police department, and pediatric clinic in a large urban city in the southwestern United States. Using structural equation modeling, a full mediation model of neighborhood crime as a driver of toxic stress resulting in increased asthma diagnoses fit the data well (Χ2 = 14.0, p =.371; df = 13; RMSEA = .028 [90% CI: 0.00, 0.102]; CFI: 0.995; SRMR = .053). Advocates should explore ways to reduce neighborhood crime to address toxic stress and asthma.


Assuntos
Asma , Características de Residência , Asma/epidemiologia , Asma/etiologia , Criança , Crime , Humanos , Modelos Estruturais , Polícia
14.
Sci Rep ; 11(1): 17788, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493738

RESUMO

Bile acid profiles are altered in obese individuals with asthma. Thus, we sought to better understand how obesity-related systemic changes contribute to lung pathophysiology. We also test the therapeutic potential of nitro-oleic acid (NO2-OA), a regulator of metabolic and inflammatory signaling pathways, to mitigate allergen and obesity-induced lung function decline in a murine model of asthma. Bile acids were measured in the plasma of healthy subjects and individuals with asthma and serum and lung tissue of mice with and without allergic airway disease (AAD). Lung function, indices of inflammation and hepatic bile acid enzyme expression were measured in obese mice with house dust mite-induced AAD treated with vehicle or NO2-OA. Serum levels of glycocholic acid and glycoursodeoxycholic acid clinically correlate with body mass index and airway hyperreactivity whereas murine levels of ß-muricholic acid and tauro-ß-muricholic acid were significantly increased and positively correlated with impaired lung function in obese mice with AAD. NO2-OA reduced murine bile acid levels by modulating hepatic expression of bile acid synthesis enzymes, with a concomitant reduction in small airway resistance and tissue elastance. Bile acids correlate to body mass index and lung function decline and the signaling actions of nitroalkenes can limit AAD by modulating bile acid metabolism, revealing a potential pharmacologic approach to improving the current standard of care.


Assuntos
Asma/metabolismo , Asma/fisiopatologia , Ácidos e Sais Biliares/metabolismo , Ácidos Graxos/fisiologia , Pulmão/fisiopatologia , Nitrocompostos/uso terapêutico , Obesidade/metabolismo , Ácidos Oleicos/uso terapêutico , Adolescente , Adulto , Animais , Antiasmáticos/uso terapêutico , Antígenos de Dermatophagoides/toxicidade , Asma/tratamento farmacológico , Asma/etiologia , Dieta Hiperlipídica/efeitos adversos , Avaliação Pré-Clínica de Medicamentos , Ácidos Graxos/química , Feminino , Volume Expiratório Forçado , Ácido Glicocólico/sangue , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/fisiopatologia , Hipersensibilidade Respiratória/induzido quimicamente , Hipersensibilidade Respiratória/tratamento farmacológico , Hipersensibilidade Respiratória/metabolismo , Magreza , Ácido Ursodesoxicólico/análogos & derivados , Ácido Ursodesoxicólico/sangue , Capacidade Vital , Adulto Jovem
15.
PLoS One ; 16(9): e0257531, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34547047

RESUMO

BACKGROUND: The use of antibiotics for treating infection in childhood and their association with increased risk of asthma remain controversial. Infants diagnosed with vesicoureteral reflux (VUR) belong to a unique population who are administered antibiotics for a long time and are susceptible to recurrent UTI. It is interesting to study the risk of asthma in these infants with or without VUR. METHODS: Taiwanese children born between 2000 and 2007 were enrolled in population-based birth cohort study. Participants diagnosed with VUR and UTI within first year were classified into four groups (VUR, UTI, VUR and UTI, and control). We calculated follow-up person-years for each participant from the index date until the asthma diagnosis, their withdrawal from the insurance system (because of death or loss to follow-up), or till the end of 2008. The risk of asthma was compared between the 4 cohorts by using Cox proportional hazards model analysis, adjusted hazard ratio (aHR), and 95% confidence interval (95% CI). RESULTS: Children diagnosed with VUR (n = 350), UTI (n = 15542), VUR and UTI (n = 1696), and randomly selected controls (n = 17588) were enrolled. The overall rate of incidence of asthma was found to be 1.64-fold, 1.45-fold, and 1.17-fold higher in the UTI, VUR/UTI, and VUR cohorts than in the controls (5.60, 5.07, and 4.10 vs. 3.17 per 100 person-years), respectively. After adjusting the potential factors, the overall risk of asthma remained the highest in UTI (aHR: 1.74, 95% CI : 1.65 to 1.80) followed by VUR/UTI (aHR: 1.56, 95% CI : 1.40 to 1.75) and VUR cohorts (aHR: 1.25, 95% CI: 0.96 to 1.62). The incidence of asthma was higher in boys than in girls. CONCLUSION: The nationwide retrospective cohort study demonstrated that short-term therapeutic dose of antibiotics for UTI in infants with or without VUR has a positive correlation with the prevalence of childhood asthma. Significant risk of childhood asthma was not observed when VUR cohort was exposed to long-term low-dose of prophylactic antibiotics.


Assuntos
Antibacterianos/uso terapêutico , Asma/diagnóstico , Infecções Urinárias/diagnóstico , Refluxo Vesicoureteral/diagnóstico , Asma/epidemiologia , Asma/etiologia , Criança , Pré-Escolar , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Incidência , Lactente , Masculino , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia , Infecções Urinárias/complicações , Infecções Urinárias/tratamento farmacológico , Refluxo Vesicoureteral/complicações
16.
Int J Mol Sci ; 22(15)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34360618

RESUMO

Activation of the Ca2+ activated Cl- channel TMEM16A is proposed as a treatment in inflammatory airway disease. It is assumed that activation of TMEM16A will induce electrolyte secretion, and thus reduce airway mucus plugging and improve mucociliary clearance. A benefit of activation of TMEM16A was shown in vitro and in studies in sheep, but others reported an increase in mucus production and airway contraction by activation of TMEM16A. We analyzed expression of TMEM16A in healthy and inflamed human and mouse airways and examined the consequences of activation or inhibition of TMEM16A in asthmatic mice. TMEM16A was found to be upregulated in the lungs of patients with asthma or cystic fibrosis, as well as in the airways of asthmatic mice. Activation or potentiation of TMEM16A by the compounds Eact or brevenal, respectively, induced acute mucus release from airway goblet cells and induced bronchoconstriction in mice in vivo. In contrast, niclosamide, an inhibitor of TMEM16A, blocked mucus production and mucus secretion in vivo and in vitro. Treatment of airway epithelial cells with niclosamide strongly inhibited expression of the essential transcription factor of Th2-dependent inflammation and goblet cell differentiation, SAM pointed domain-containing ETS-like factor (SPDEF). Activation of TMEM16A in people with inflammatory airway diseases is likely to induce mucus secretion along with airway constriction. In contrast, inhibitors of TMEM16A may suppress pulmonary Th2 inflammation, goblet cell metaplasia, mucus production, and bronchoconstriction, partially by inhibiting expression of SPDEF.


Assuntos
Anoctamina-1/metabolismo , Asma/patologia , Constrição Patológica/complicações , Fibrose Cística/patologia , Inflamação/patologia , Muco/metabolismo , Mucosa Respiratória/patologia , Animais , Anoctamina-1/genética , Asma/etiologia , Asma/metabolismo , Fibrose Cística/etiologia , Fibrose Cística/metabolismo , Células HEK293 , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Camundongos , Mucosa Respiratória/metabolismo
18.
BMJ Open ; 11(8): e045795, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34426461

RESUMO

INTRODUCTION: The hygiene hypothesis suggests that reduced exposure to microbes might have contributed to the increase in prevalence and incidence of asthma and allergy observed during the second half of the last century. Following this proposal, several studies have investigated the role of sibship size and birth order in the development of asthma and allergic diseases, but the underlying evidence is conflicting. The objective of the present systematic review will be to identify, critically appraise and synthesise previous primary studies investigating the association of sibship size and birth order with the risk of asthma and allergic diseases. METHODS AND ANALYSIS: The following databases will be searched: AMED, CABI, CINAHL, Embase, Google Scholar, OAIster, Open Access Theses and Dissertations, Open Grey, ProQuest Dissertations & Theses Global, PsycINFO, PubMed, SciELO, Scopus, Web of Science and WHO Global Index Medicus. Studies published up until 31 December 2020 will be eligible. There will be no restrictions by language and geographical location. Risk of bias in the included studies will be assessed using the Effective Public Health Practice Project quality assessment tool. The produced evidence will be synthesised narratively, and studies that present comparable numerical data will be included in meta-analyses using random effects model. ETHICS AND DISSEMINATION: Only data from the published literature will be included in this systematic review. Therefore, no ethical approval is required. The final review paper will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020207905.


Assuntos
Asma , Hipersensibilidade , Asma/epidemiologia , Asma/etiologia , Ordem de Nascimento , Humanos , Hipersensibilidade/epidemiologia , Metanálise como Assunto , Literatura de Revisão como Assunto , Revisões Sistemáticas como Assunto
19.
Cell Mol Life Sci ; 78(21-22): 6735-6744, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34459952

RESUMO

Kallikrein-related peptidases (KLKs) or kallikreins have been linked to diverse (patho) physiological processes, such as the epidermal desquamation and inflammation, seminal clot liquefaction, neurodegeneration, and cancer. Recent mounting evidence suggests that KLKs also represent important regulators of viral infections. It is well-established that certain enveloped viruses, including influenza and coronaviruses, require proteolytic processing of their hemagglutinin or spike proteins, respectively, to infect host cells. Similarly, the capsid protein of the non-enveloped papillomavirus L1 should be proteolytically cleaved for viral uncoating. Consequently, extracellular or membrane-bound proteases of the host cells are instrumental for viral infections and represent potential targets for drug development. Here, we summarize how extracellular proteolysis mediated by the kallikreins is implicated in the process of influenza (and potentially coronavirus and papillomavirus) entry into host cells. Besides direct proteolytic activation of viruses, KLK5 and 12 promote viral entry indirectly through proteolytic cascade events, like the activation of thrombolytic enzymes that also can process hemagglutinin, while additional functions of KLKs in infection cannot be excluded. In the light of recent evidence, KLKs represent potential host targets for the development of new antivirals. Humanized animal models to validate their key functions in viral infections will be valuable.


Assuntos
COVID-19/enzimologia , COVID-19/virologia , Interações entre Hospedeiro e Microrganismos/fisiologia , Calicreínas/metabolismo , SARS-CoV-2 , Viroses/enzimologia , Animais , Asma/etiologia , Coronavirus/genética , Coronavirus/patogenicidade , Coronavirus/fisiologia , Interações entre Hospedeiro e Microrganismos/genética , Humanos , Orthomyxoviridae/genética , Orthomyxoviridae/patogenicidade , Orthomyxoviridae/fisiologia , Infecções por Papillomavirus/enzimologia , Infecções por Papillomavirus/virologia , Infecções por Picornaviridae/complicações , Infecções por Picornaviridae/enzimologia , Infecções por Picornaviridae/virologia , Processamento de Proteína Pós-Traducional , Proteólise , Rhinovirus/patogenicidade , SARS-CoV-2/genética , SARS-CoV-2/patogenicidade , SARS-CoV-2/fisiologia , Infecção pelo Vírus da Varicela-Zoster/enzimologia , Infecção pelo Vírus da Varicela-Zoster/virologia , Proteínas Virais/genética , Proteínas Virais/metabolismo , Viroses/virologia , Internalização do Vírus
20.
Clin Chest Med ; 42(3): 497-506, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34353454

RESUMO

There are many unique aspects of asthma in women. Compared with men, women go through several hormonal stages over the life span-childhood, menarche, reproductive years, pregnancy, menopause, and postmenopause-and each affects asthma. Onset of asthma in women differs from men. Asthma in women is more often associated with obesity and women are over-represented among patients with severe asthma, including those being prescribed biologic therapies. Asthma affects fertility and pregnancy, and female hormone replacement therapy has been found to affect asthma onset as well as asthma severity. We explore the unique aspects of asthma in women.


Assuntos
Asma , Menopausa , Asma/epidemiologia , Asma/etiologia , Asma/terapia , Criança , Feminino , Humanos , Masculino , Menarca , Obesidade , Gravidez
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