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2.
Pediatrics ; 146(4)2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32934151

RESUMO

OBJECTIVES: Although the airway microbiota is a highly dynamic ecology, the role of longitudinal changes in airway microbiota during early childhood in asthma development is unclear. We aimed to investigate the association of longitudinal changes in early nasal microbiota with the risk of developing asthma. METHODS: In this prospective, population-based birth cohort study, we followed children from birth to age 7 years. The nasal microbiota was tested by using 16S ribosomal RNA gene sequencing at ages 2, 13, and 24 months. We applied an unsupervised machine learning approach to identify longitudinal nasal microbiota profiles during age 2 to 13 months (the primary exposure) and during age 2 to 24 months (the secondary exposure) and examined the association of these profiles with the risk of physician-diagnosed asthma at age 7 years. RESULTS: Of the analytic cohort of 704 children, 57 (8%) later developed asthma. We identified 4 distinct longitudinal nasal microbiota profiles during age 2 to 13 months. In the multivariable analysis, compared with the persistent Moraxella dominance profile during age 2 to 13 months, the persistent Moraxella sparsity profile was associated with a significantly higher risk of asthma (adjusted odds ratio, 2.74; 95% confidence interval, 1.20-6.27). Similar associations were observed between the longitudinal changes in nasal microbiota during age 2 to 24 months and risk of asthma. CONCLUSIONS: Children with an altered longitudinal pattern in the nasal microbiota during early childhood had a high risk of developing asthma. Our data guide the development of primary prevention strategies (eg, early identification of children at high risk and modification of microbiota) for childhood asthma. These observations present a new avenue for risk modification for asthma (eg, microbiota modification).


Assuntos
Asma/etiologia , Microbiota , Nariz/microbiologia , Aerococcaceae/isolamento & purificação , Fatores Etários , Asma/diagnóstico , Asma/microbiologia , Criança , Pré-Escolar , Feminino , Finlândia , Seguimentos , Perfilação da Expressão Gênica/métodos , Haemophilus/isolamento & purificação , Humanos , Incidência , Lactente , Recém-Nascido , Aprendizado de Máquina , Masculino , Microbiota/genética , Moraxella/isolamento & purificação , Análise Multivariada , Estudos Prospectivos , RNA Ribossômico 16S/genética , Infecções Respiratórias/complicações , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/microbiologia , Risco , Streptococcus/isolamento & purificação
3.
Medicine (Baltimore) ; 99(30): e21315, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791721

RESUMO

INTRODUCTION: There is evidence that caesarean section (CS) is associated with increased risk of childhood obesity, asthma, and coeliac disease. The gut microbiota of CS-born babies differs to those born vaginally, possibly due to reduced exposure to maternal vaginal bacteria during birth. Vaginal seeding is a currently unproven practice intended to reduce such differences, so that the gut microbiota of CS-born babies is similar to that of babies born vaginally. Our pilot study, which uses oral administration as a novel form of vaginal seeding, will assess the degree of maternal strain transfer and overall efficacy of the procedure for establishing normal gut microbiota development. METHODS AND ANALYSIS: Protocol for a single-blinded, randomized, placebo-controlled pilot study of a previously untested method of vaginal seeding (oral administration) in 30 CS-born babies. A sample of maternal vaginal bacteria is obtained prior to CS, and mixed with 5 ml sterile water to obtain a supernatant. Healthy babies are randomized at 1:1 to receive active treatment (3 ml supernatant) or placebo (3 ml sterile water). A reference group of 15 non-randomized vaginal-born babies are also being recruited. Babies' stool samples will undergo whole metagenomic shotgun sequencing to identify potential differences in community structure between CS babies receiving active treatment compared to those receiving placebo at age 1 month (primary outcome). Secondary outcomes include differences in overall gut community between CS groups (24 hours, 3 months); similarity of CS-seeded and placebo gut profiles to vaginally-born babies (24 hours, 1 and 3 months); degree of maternal vaginal strain transfer in CS-born babies (24 hours, 1 and 3 months); anthropometry (1 and 3 months) and body composition (3 months). ETHICS AND DISSEMINATION: Ethics approval by the Northern A Health and Disability Ethics Committee (18/NTA/49). Results will be published in peer-reviewed journals and presented at international conferences. REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12618000339257).


Assuntos
Cesárea/efeitos adversos , Microbiota/fisiologia , Placebos/administração & dosagem , Vagina/microbiologia , Adulto , Antropometria/métodos , Asma/epidemiologia , Asma/etiologia , Fenômenos Fisiológicos Bacterianos , Composição Corporal , Estudos de Casos e Controles , Doença Celíaca/epidemiologia , Doença Celíaca/etiologia , Parto Obstétrico/tendências , Fezes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Metagenômica/métodos , Microbiota/genética , Nova Zelândia/epidemiologia , Obesidade Pediátrica/epidemiologia , Obesidade Pediátrica/etiologia , Gravidez
4.
J Environ Public Health ; 2020: 6042146, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32831855

RESUMO

Few studies have investigated household interventions to enhance indoor air quality (IAQ) and health outcomes in relatively low-income communities. This study aims to examine the impact of the combined intervention with asthma education and air purifier on IAQ and health outcomes in the US-Mexico border area. An intervention study conducted in McAllen, Texas, between June and November 2019 included 16 households having children with asthma. The particulate matter (PM2.5) levels were monitored in the bedroom, kitchen, and living room to measure the IAQ for 7 days before and after the intervention, respectively. Multiple surveys were applied to evaluate changes in children's health outcomes. The mean PM2.5 levels in each place were significantly improved. Overall, they significantly decreased by 1.91 µg/m3 on average (p < 0.05). All surveys showed better health outcomes; particularly, quality of life for children was significantly improved (p < 0.05). This pilot study suggests that the combined household intervention might improve IAQ in households and health outcomes for children with asthma and reduce health disparities in low-income communities. Future large-scale studies are needed to verify the effectiveness of this household intervention to improve IAQ and asthma management.


Assuntos
Filtros de Ar/estatística & dados numéricos , Poluição do Ar em Ambientes Fechados/análise , Asma/etiologia , Saúde da Criança/estatística & dados numéricos , Educação em Saúde/estatística & dados numéricos , Criança , Feminino , Humanos , Masculino , Material Particulado/análise , Projetos Piloto , Qualidade de Vida , Texas
5.
Life Sci ; 259: 118191, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32777302

RESUMO

Numerous population studies conducted worldwide indicate that the prevalence of asthma is higher in obese versus lean individuals. It has been reported that sensitized lean mice has a better recovery of lung inflammation in asthma. Extracellular matrix (ECM) plays an essential role in the structural support of the lungs regulating the airways diameter, thus preventing its collapse during expiration. ECM renewal by metalloproteinase (MMPs) enzymes is critical for pulmonary biology. There seems to be an imbalance of MMPs activity in asthma and obesity, which can impair the lung remodeling process. In this study, we characterized the pulmonary ECM of obese and lean mice, non-sensitized and sensitized with ovalbumin (OVA). Pharmacological intervention was performed by using anti-TNF-α, and MMP-8 and MMP-9 inhibitors in obese and lean sensitized mice. Activity of MMPs was assessed by gelatinase electrophorese, western blotting and zymogram in situ. Unbalance of MMP-2, MMP-8, MMP-9 and MMP-12 was detected in lung tissue of OVA-sensitized obese mice, which was accompanied by high degradation, corroborating an excessive deposition of types I and III collagen in pulmonary matrix of obese animals. Inhibitions of TNF-α and MMP-9 reduced this MMP imbalance, clearly suggesting a positive effect on pulmonary ECM. Obese and lean mice presented diverse phenotype of asthma regarding the ECM compounds and the inhibition of MMPs pathway could be a good alternative to regulate the activity in ECM lungs of asthmatic obese individuals.


Assuntos
Asma/etiologia , Asma/metabolismo , Metaloproteases/metabolismo , Obesidade/complicações , Obesidade/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Líquido da Lavagem Broncoalveolar/citologia , Matriz Extracelular/metabolismo , Inflamação/metabolismo , Pulmão/patologia , Masculino , Metaloproteinase 8 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Ovalbumina/imunologia , Inibidores de Proteases/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores
6.
PLoS One ; 15(8): e0237769, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817718

RESUMO

Concerns exist that the positive association of physical activity with better lung function, which has been suggested in previous longitudinal studies in smokers, is due to reverse causation. To investigate this, we applied structural equation modeling (SEM), an exploratory approach, and marginal structural modeling (MSM), an approach from the causal inference framework that corrects for reverse causation and time-dependent confounding and estimates causal effects, on data from participants in the European Community Respiratory Health Survey (ECRHS, a multicentre European cohort study initiated in 1991-1993 with ECRHS I, and with two follow-ups: ECRHS II in 1999-2003, and ECRHS III in 2010-2014). 753 subjects who reported current smoking at ECRHS II, with repeated data on lung function at ECRHS I, II and III, physical activity at ECRHS II and III, and potential confounders at ECRHS I and II, were included in the analyses. SEM showed positive associations between physical activity and lung function in both directions. MSM suggested a protective causal effect of physical activity on lung function (overall difference in mean ß (95% CI), comparing active versus non-active individuals: 58 mL (21-95) for forced expiratory volume in one second and 83 mL (36-130) for forced vital capacity). Our results suggest bi-directional causation and support a true protective effect of physical activity on lung function in smokers, after accounting for reverse causation and time-dependent confounding.


Assuntos
Asma/terapia , Exercício Físico , Pulmão/fisiologia , Infecções Respiratórias/terapia , Adolescente , Adulto , Asma/etiologia , Asma/fisiopatologia , Peso Corporal/fisiologia , Dieta , Feminino , Volume Expiratório Forçado/fisiologia , Inquéritos Epidemiológicos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Fumantes , Fumar/efeitos adversos , Capacidade Vital/fisiologia , Adulto Jovem
7.
Environ Health Prev Med ; 25(1): 27, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32635895

RESUMO

BACKGROUND: Adjuvants used in inactivated vaccines often upregulate type 2 immunity, which is dominant in allergic diseases. We hypothesised that cumulative adjuvant exposure in infancy may influence the development of allergies later in life by changing the balance of type 1/type 2 immunity. We examined the relationship between immunisation with different vaccine types and later allergic disease development. METHODS: We obtained information regarding vaccinations and allergic diseases through questionnaires that were used in The Japan Environment and Children's Study (JECS), which is a nationwide, multicentre, prospective birth cohort study that included 103,099 pregnant women and their children. We examined potential associations between the initial vaccination before 6 months of age and symptoms related to allergies at 12 months of age. RESULTS: Our statistical analyses included 56,277 children. Physician-diagnosed asthma was associated with receiving three (aOR 1.395, 95% CI 1.028-1.893) or four to five different inactivated vaccines (aOR 1.544, 95% CI 1.149-2.075), compared with children who received only one inactivated vaccine. Similar results were found for two questionnaire-based symptoms, i.e. wheeze (aOR 1.238, 95% CI 1.094-1.401; three vaccines vs. a single vaccine) and eczema (aOR 1.144, 95% CI 1.007-1.299; four or five vaccines vs. a single vaccine). CONCLUSIONS: Our results, which should be cautiously interpreted, suggest that the prevalence of asthma, wheeze and eczema among children at 12 months of age might be related to the amount of inactivated vaccine exposure before 6 months of age. Future work should assess if this association is due to cumulative adjuvant exposure. Despite this possible association, we strongly support the global vaccination strategy and recommend that immunisations continue. TRIAL REGISTRATION: UMIN000030786 .


Assuntos
Hipersensibilidade/epidemiologia , Vacinas Virais/efeitos adversos , Asma/epidemiologia , Asma/etiologia , Estudos de Coortes , Dermatite Atópica/epidemiologia , Dermatite Atópica/etiologia , Feminino , Hipersensibilidade Alimentar/epidemiologia , Hipersensibilidade Alimentar/etiologia , Humanos , Hipersensibilidade/etiologia , Lactente , Recém-Nascido , Japão , Masculino , Vacinas de Produtos Inativados/efeitos adversos
8.
PLoS One ; 15(7): e0236806, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32730318

RESUMO

Adenotonsillectomy is a common paediatric surgery for treating obstructed breathing or recurrent inflammation; however, the long-term health consequences on the developing immune system are unknown. This study investigated the potential association between adenotonsillectomy and the development of asthma and upper respiratory infections (URI). This propensity score-matched retrospective cohort study utilized data from the National Sample Cohort 2002-2013. In the asthma cohort, we used a Cox-proportional hazards model to analyze the hazard ratio (HR) of adenotonsillectomy for asthma events. In the URI cohort, equivalence testing of postoperative visits for URI was performed. The margin of equivalence of the difference was set at -0.5-0.5. Asthma incidence was 66.97/1000 person-years in children who underwent adenotonsillectomy and 30.43/1000 person-years in those who did not. Adjusted asthma HRs were 2.25 (95% confidence interval, 1.96-2.57) in the adenotonsillectomy vs. non-adenotonsillectomy groups. In a subgroup analysis, children aged 5-9 years living in metropolitan areas showed a higher incidence of subsequent asthma than those of other ages and areas. However, any significant difference between the groups in terms of URI events in the 1-11-year postoperative period was not identified. Adenotonsillectomy in children is associated with an increased incidence of asthma, with no significant impact on postoperative visits for URI.


Assuntos
Adenoidectomia/efeitos adversos , Asma/epidemiologia , Infecções Respiratórias/epidemiologia , Tonsilectomia/efeitos adversos , Adolescente , Asma/etiologia , Asma/patologia , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , República da Coreia/epidemiologia , Infecções Respiratórias/etiologia , Infecções Respiratórias/patologia , Estudos Retrospectivos , Fatores de Risco
9.
Allergol. immunopatol ; 48(3): 237-243, mayo-jun. 2020. graf, tab
Artigo em Inglês | IBECS | ID: ibc-192025

RESUMO

BACKGROUND: Due to the high prevalence of recurrent wheezing in the pediatric population, it is important to be able to identify environmental risk factors that may affect the etiology of asthma in several regions. OBJECTIVE: to identify possible risk factors associated with asthma in children (9-12 years old) in Passo Fundo, Rio Grande do Sul, Brazil. MATERIAL AND METHODS: A total of 1003 school-age children were selected for the cross-sectional study by applying a standardized written questionnaire from the International Study of Asthma and Allergy, and a supplementary questionnaire (ISAAC phase II) was added to address personal, family and environmental factors. Of these, 125 children were excluded because they did not accept to do the skin prick test, resulting in a sample of 878. RESULTS: Independent risk factors associated with asthma were bronchiolitis before two years old [OR] = 3.11; 2.23-4.33, current rhinitis [0R] = 2.07; 1.43-3.0; sharing bedroom during the first year of life [OR] = 2.03; 1.36-3.04; atopy [OR] = 1,82; 1.26-2.50; use of paracetamol more than 12 times a year [OR] = 1.68; 1.20-2.31; use of antibiotics in the first six months of life [OR]=1,57 1;13-2.17; maternal asthma [OR] = 1.75; 1.05-2.78, having an indoor cat during the first year of life [OR] = 1.73, 1.07-2.78; premature birth [OR] = 1.60,1.02-2.50. CONCLUSIÓN: our results show that genetic backgrounds, environmental factors, premature birth, use of antibiotics before six months of life, using paracetamol once per month and the presence of co-morbidities such as rhinitis are the risk factors associated with asthma in Brazilian children


No disponible


Assuntos
Humanos , Masculino , Criança , Asma/epidemiologia , Instituições Acadêmicas/estatística & dados numéricos , Fatores de Risco , Brasil/epidemiologia , Asma/etiologia , Inquéritos e Questionários , Rinite/complicações , Estudos Transversais , Modelos Logísticos
10.
Rev Fac Cien Med Univ Nac Cordoba ; 77(2): 61-67, 2020 04 07.
Artigo em Espanhol | MEDLINE | ID: mdl-32558506

RESUMO

Objective: Evaluate the prevalence of asthma risk in subject of 13-14 years old that were exposed to volcanic ash. One year after the eruption of the Calbuco Volcano and in 2 cities with different degrees of exposure. Methods: Cross-sectional study was developed in subjects of 13-14 years old of two Patagonian cities: San Carlos de Bariloche and Cipolletti. The ISAAC questionnaire and video questionnaire was applied to determine asthma risk. Demographic and perception of exposure variables were assessed. Results: 511 subjects were surveyed in both cities. The prevalence of asthma at risk symptoms was higher in Bariloche 14% compared to Cipolletti 10%, but this difference was not statistically significant (p=0.32). A significant increase in the perception of volcanic ash exposure was reported 14% in Bariloche city vs. 6% in Cipolletti city, p<0.05. Conclusions: After 18 months of volcanic eruption with respiratory ash exposure and the lack of respiratory symptoms difference between two cities with different degree of exposure, this factor may not contribute to have a clinical impact in respiratory health.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Asma/epidemiologia , Asma/etiologia , Erupções Vulcânicas/efeitos adversos , Adolescente , Argentina/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Material Particulado/efeitos adversos , Prevalência , Fatores de Risco
11.
BMC Infect Dis ; 20(1): 387, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32473625

RESUMO

BACKGROUND: To compare the clinical characteristics of acute lower respiratory tract infections (ALRTIs) caused by respiratory syncytial virus (RSV) and human rhinovirus (HRV) and to explore the relationship between the development of recurrent wheezing/asthma and RSV/ HRV infections in infancy. METHODS: Retrospective study was conducted to compare the clinical characteristics of acute lower respiratory tract infections (ALRTIs). Hospitalized patients with ALRTIs from March 2007 to December 2016 were screened. Single RSV cases (s-RSV), single HRV cases (s-HRV), and cases who had co-infection with the two viruses were enrolled. Follow-up was performed to determine whether either specific respiratory virus infection was related to subsequent development of recurrent wheezing/asthma. RESULTS: The s-RSV children were the youngest (P = 0.021), they experienced the most serious condition (P < 0.001) and respiratory failure (P < 0.001), they also required highest demand of oxygen therapy (P < 0.001). And in s-RSV group, the incidence of development of recurrent wheezing was significantly higher in subgroup with the family history of wheezing than that without (P < 0.001). CONCLUSION: The s-RSV cases suffered from the worst severity of illness, respiratory failure and required highest demand of oxygen therapy. Recurrent wheezing was more common in s-RSV group with family history of wheezing than those without.


Assuntos
Asma/epidemiologia , Infecções por Picornaviridae/complicações , Infecções por Vírus Respiratório Sincicial/complicações , Infecções Respiratórias/complicações , Asma/etiologia , Criança , Pré-Escolar , Coinfecção/epidemiologia , Feminino , Humanos , Incidência , Lactente , Masculino , Infecções por Picornaviridae/epidemiologia , Sons Respiratórios/etiologia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Estudos Retrospectivos
12.
Artigo em Inglês | MEDLINE | ID: mdl-32512940

RESUMO

In the real world, dynamic changes in air pollutants and meteorological factors coexist simultaneously. Studies identifying the effects of individual pollutants on acute exacerbation (AE) of asthma may overlook the health effects of the overall combination. A comprehensive study examining the influence of air pollution and meteorological factors is required. Asthma AE data from emergency room visits were collected from the Taiwan National Health Insurance Research Database. Complete monitoring data for air pollutants (SO2; NO2; O3; CO; PM2.5; PM10) and meteorological factors were collected from the Environmental Protection Agency monitoring stations. A bi-directional case-crossover analysis was used to investigate the effects of air pollution and meteorological factors on asthma AE. Among age group divisions, a 1 °C temperature increase was a protective factor for asthma ER visits with OR = 0.981 (95% CI, 0.971-0.991) and 0.985 (95% CI, 0.975-0.994) for pediatric and adult patients, respectively. Children, especially younger females, are more susceptible to asthma AE due to the effects of outdoor air pollution than adults. Meteorological factors are important modulators for asthma AE in both asthmatic children and adults. When studying the effects of air pollution on asthma AE, meteorological factors should be considered.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Asma , Adolescente , Adulto , Poluentes Atmosféricos/toxicidade , Asma/etiologia , Criança , Feminino , Humanos , Masculino , Conceitos Meteorológicos , Material Particulado/toxicidade , Taiwan , Adulto Jovem
13.
PLoS One ; 15(5): e0231782, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32369487

RESUMO

RATIONALE: Severe early-life respiratory illnesses, particularly those caused by respiratory syncytial virus (RSV) and human rhinovirus (HRV), are strongly associated with the development of asthma in children. Puerto Rican children in particular have a strikingly high asthma burden. However, prior studies of the potential associations between early-life respiratory illnesses and asthma in Puerto Rican and other minority populations have been limited. OBJECTIVES: We sought to determine whether early-life respiratory illness was associated with asthma in Puerto Rican, Mexican American, and African American children. METHODS: Using a logistic regression analysis, we examined the association between early-life respiratory illnesses (report of upper respiratory infection (URI), pneumonia, bronchitis, and bronchiolitis/RSV) within the first two years of life and physician-diagnosed asthma after the age of two in a large cohort of Puerto Rican, Mexican American, and African American children. MEASUREMENTS AND MAIN RESULTS: While early-life respiratory illnesses were associated with greater asthma odds in Puerto Ricans, Mexican Americans, and African Americans, these associations were stronger among Puerto Rican children. Specifically, in Puerto Ricans, the odds was 6.15 (95% CI: 4.21-9.05) if the child reported at least one of the following respiratory illness: URI, pneumonia, bronchitis or bronchiolitis. The odds were also higher in Puerto Ricans when considering these conditions separately. CONCLUSIONS: We observed population-specific associations between early-life respiratory illnesses and asthma, which were especially significant and stronger in Puerto Ricans. Taken together with the known high burden of RSV in Puerto Rico, our results may help explain the high burden of asthma in Puerto Ricans.


Assuntos
Afro-Americanos/estatística & dados numéricos , Asma/epidemiologia , Hispano-Americanos/estatística & dados numéricos , Americanos Mexicanos/estatística & dados numéricos , Infecções Respiratórias/epidemiologia , Adolescente , Asma/etiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Modelos Logísticos , Masculino , Infecções Respiratórias/complicações , Infecções Respiratórias/virologia , Estados Unidos/etnologia , Adulto Jovem
14.
Ann Allergy Asthma Immunol ; 125(2): 156-162, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32454096

RESUMO

OBJECTIVE: To summarize the recent evidence in the treatment of viral-induced wheezing in the infant and preschool aged child. DATA SOURCES: Published literature obtained through PubMed database searches. STUDY SELECTIONS: Studies relevant to phenotypes and treatment of wheezing illnesses in infants and preschool children were included. RESULTS: Recurrent wheezing in preschool children is common and is frequently triggered by viral respiratory tract infections. Certain phenotypes may respond to treatments differently, depending on the risk factors identified. Inhaled corticosteroids, administered continuously or intermittently, reduce the risk of virus-induced wheezing episodes. The use of leukotriene modifying agents may have a role in wheezing episodes in a select group of preschool children. Early administration of azithromycin reduces the risk of severe lower respiratory tract illnesses in children. The effect of oral corticosteroids on wheezing episodes in young children varies by degree of episode severity. CONCLUSION: Recurrent viral-induced wheezing illnesses has been the focus of many clinical trials, which now provide an increasingly robust evidence base for management. Additional research is needed to define optimal strategies, to best match therapies to specific phenotypes and endotypes, and will eventually begin to include therapies directed specifically at the viral triggers.


Assuntos
Corticosteroides/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/prevenção & controle , Viroses/tratamento farmacológico , Asma/etiologia , Pré-Escolar , Humanos , Imunomodulação , Lactente , Fenótipo , Recidiva , Sons Respiratórios/etiologia , Risco , Viroses/complicações
17.
Neurology ; 94(16): e1726-e1737, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32217776

RESUMO

OBJECTIVE: To investigate the clinicopathologic features of eosinophilic granulomatosis with polyangiitis (EGPA)-associated neuropathy with a focus on the presence or absence of anti-neutrophil cytoplasmic antibodies (ANCAs). METHODS: We examined the clinical features and pathologic findings of sural nerve biopsy specimens from 82 patients with EGPA-associated neuropathy. Of these patients, 32.9% were myeloperoxidase (MPO)-ANCA positive, and 67.1% were MPO-ANCA negative. PR3-ANCA was negative in all of 78 examined patients. RESULTS: Upper limb symptoms were more frequently reported as initial neuropathic manifestations in the MPO-ANCA-positive group than in the MPO-ANCA-negative group (44.4% vs 14.6%, p < 0.01). The serum levels of C-reactive protein were significantly higher in the MPO-ANCA-positive group than in the MPO-ANCA-negative group (p < 0.05). Sural nerve biopsy specimens showed findings suggestive of vasculitis (i.e., destruction of vascular structures) in epineurial vessels; these results were seen more frequently in the MPO-ANCA-positive group than in the MPO-ANCA-negative group (p < 0.0001). Conversely, the numbers of eosinophils in the lumen of the epineurial vessels (p < 0.01) and epineurial vessels occluded by intraluminal eosinophils (p < 0.05) were higher in the MPO-ANCA-negative group than in the MPO-ANCA-positive group. Furthermore, the incidence of eosinophil infiltration in the endoneurium was higher in the MPO-ANCA-negative group than in the MPO-ANCA-positive group (p < 0.01). CONCLUSIONS: This study suggests that the pathogenesis of EGPA comprises at least 2 distinct mechanisms: ANCA-associated vasculitis resulting in ischemic effects and inflammation, which is prominent in MPO-ANCA-positive patients, and eosinophil-associated vascular occlusion leading to ischemia and eosinophil-associated tissue damage, which is conspicuous in MPO-ANCA-negative patients.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos/imunologia , Síndrome de Churg-Strauss/fisiopatologia , Debilidade Muscular/fisiopatologia , Nervos Periféricos/irrigação sanguínea , Doenças do Sistema Nervoso Periférico/fisiopatologia , Distúrbios Somatossensoriais/fisiopatologia , Idoso , Asma/etiologia , Síndrome de Churg-Strauss/complicações , Síndrome de Churg-Strauss/imunologia , Eletrodiagnóstico , Feminino , Humanos , Nefropatias/etiologia , Extremidade Inferior/inervação , Pneumopatias/etiologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Mieloblastina/imunologia , Condução Nervosa , Otorrinolaringopatias/genética , Nervos Periféricos/patologia , Doenças do Sistema Nervoso Periférico/etiologia , Doenças do Sistema Nervoso Periférico/imunologia , Doenças do Sistema Nervoso Periférico/patologia , Peroxidase/imunologia , Dermatopatias Vasculares/etiologia , Distúrbios Somatossensoriais/etiologia , Nervo Sural/patologia , Tomografia Computadorizada por Raios X , Extremidade Superior/inervação
18.
Scand J Immunol ; 91(5): e12865, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32185817

RESUMO

Plasmacytoid dendritic cells (pDCs) regulate immunity and promote tolerance in asthma. Notch signalling is a highly conserved pathway that regulates the immune response; however, its role in pDC-mediated asthmatic airway inflammation is unclear. This study clarified the effects of Notch signalling on pDC-mediated airway inflammation using murine models of ovalbumin-sensitized allergic asthma. RBP-J-deficient pDCs (RBP-J-/- pDCs) were co-cultured with naïve CD4+ T cells and supernatants and T cell subtypes were analysed. RBP-J-/- pDCs were intranasally transferred to the airways of ovalbumin-sensitized recipient mice. Lung samples of all mice were subjected to tests for histopathology, cytokine profile of bronchoalveolar lavage fluid, airway hyperactivity and expression of T helper type 1 (Th1)/Th2 cells, regulatory T cells and type 2 innate lymphoid cells (ILC2s). The results showed that pDCs with and without RBP-J deficiency significantly differed in expression levels of cluster of differentiation 83 (CD83), but not CD80, CD86 and major histocompatibility complex class II. Co-culturing pDCs with naïve T cells revealed a poorer immunosuppressive effect of RBP-J-/- pDCs. This may be attributed to the lower expression levels of inducible co-stimulator ligand and lower production of interleukin 10 in RBP-J-/- pDCs than in control pDCs, which impeded T cell activation and Treg suppression. RBP-J-/- pDCs were associated with high ILC2 expression and severe Th2 immune responses and airway inflammation. Therefore, Notch signalling is critical for pDC-dependent immunoregulation, and RBP-J deficiency reduces pDC-based immunosuppression via T cell activation and Th cell differentiation. Thus, this pathway may be a therapeutic target for pDC-based anti-asthma immunotherapy.


Assuntos
Diferenciação Celular , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Imunomodulação , Receptores Notch/metabolismo , Transdução de Sinais , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Animais , Asma/etiologia , Asma/metabolismo , Asma/patologia , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Suscetibilidade a Doenças , Feminino , Expressão Gênica , Humanos , Ligante Coestimulador de Linfócitos T Induzíveis/genética , Ligante Coestimulador de Linfócitos T Induzíveis/metabolismo , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Camundongos , Células Th2/imunologia , Células Th2/metabolismo
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