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2.
Nutrients ; 11(8)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31374861

RESUMO

Maternal diet during pregnancy plays a likely role in infant immune development through both direct nutrient specific immunomodulatory effects and by modulating the composition and metabolic activity of the maternal gut microbiome. Dietary fibers, as major substrates for microbial fermentation, are of interest in this context. This is the first study to examine maternal intakes of different fiber sub-types and subsequent infant allergic disease. In an observational study of 639 mother-infant pairs (all infants had a family history of allergic disease) we examined maternal intakes of total fiber, soluble fiber, insoluble fiber, resistant starch, and prebiotic fiber, by a semi-quantitative food frequency questionnaire at 36-40 weeks' gestation. Infants attended an allergy clinical assessment at 12 months of age, including skin prick testing to common allergens. Higher maternal dietary intakes of resistant starch were associated with reduced doctor diagnosed infant wheeze, adjusted odds ratio (aOR) 0.68 (95% CI 0.49, 0.95, p = 0.02). However, in contrast, higher maternal intakes of resistant starch were associated with higher risk of parent reported eczema aOR 1.27 (95% CI 1.09, 1.49, p < 0.01) and doctor diagnosed eczema aOR 1.19 (95% CI 1.01, 1.41, p = 0.04). In conclusion, maternal resistant starch consumption was differentially associated with infant phenotypes, with reduced risk of infant wheeze, but increased risk of eczema.


Assuntos
Dermatite Atópica/etiologia , Fibras na Dieta/administração & dosagem , Fibras na Dieta/efeitos adversos , Fenômenos Fisiológicos da Nutrição Materna , Estado Nutricional , Efeitos Tardios da Exposição Pré-Natal , Recomendações Nutricionais , Hipersensibilidade Respiratória/prevenção & controle , Adulto , Dermatite Atópica/diagnóstico , Feminino , Humanos , Lactente , Masculino , Gravidez , Fatores de Proteção , Hipersensibilidade Respiratória/diagnóstico , Hipersensibilidade Respiratória/etiologia , Sons Respiratórios , Medição de Risco , Fatores de Risco
3.
Rev Mal Respir ; 36(7): 889-901, 2019 Sep.
Artigo em Francês | MEDLINE | ID: mdl-31303366

RESUMO

Exposure to mould is a potential risk factor for asthma in both adults and children. In adult, the relation between exposure, sensitization and symptoms has been demonstrated in severe asthmatics sensitized to Alternaria. For children, exposure to mould in childhood is a risk factor for asthma in both atopic and non-atopic individuals. Exposure or sensitization to moulds are a risk factor for severe asthma and/or exacerbations in children. There appears to be a causal relationship between exposure and asthma. This link seems less significant in adults. However, in adults mould sensitive asthma seems to determine a phenotype of severe asthma associated with more marked obstructive lung disease. Moulds can stimulate either innate or the acquired immunity. They are responsible for a marked Th2 inflammation leading to more severe asthma. Besides the immunological mechanisms, toxic mechanisms can also intervene. It is therefore not correct to reduce the effect of moulds, particularly in respiratory symptoms, to only allergic mechanisms.


Assuntos
Poluição do Ar em Ambientes Fechados/efeitos adversos , Características da Família , Fungos , Pneumopatias Fúngicas/etiologia , Hipersensibilidade Respiratória , Adulto , Poluição do Ar em Ambientes Fechados/estatística & dados numéricos , Asma/epidemiologia , Asma/etiologia , Criança , Exposição Ambiental/efeitos adversos , Exposição Ambiental/estatística & dados numéricos , Humanos , Pneumopatias Fúngicas/epidemiologia , Material Particulado/efeitos adversos , Hipersensibilidade Respiratória/epidemiologia , Hipersensibilidade Respiratória/etiologia , Fatores de Risco
4.
Oxid Med Cell Longev ; 2019: 7450151, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31281589

RESUMO

Exposure to fine particulate matter (PM2.5) has been associated with lung inflammation and airway hyperresponsiveness (AHR). Transient receptor potential (TRP) vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) both may play important roles in lung inflammation and AHR. We investigated whether PM2.5-induced lung inflammation and AHR could be prevented by blocking TRPV1 and TRPA1 channels. Mice were injected intraperitoneally with AMG9810 (30 mg/kg, a TRPV1 antagonist) or A967079 (30 mg/kg, a TRPA1 antagonist) or their combination or vehicle (PBS) one hour before intranasal instillation of PM2.5 (7.8 mg/kg) or vehicle (PBS) for two consecutive days, and then the mice were studied 24 h later. All pretreatments inhibited PM2.5-induced AHR and inflammatory infiltration in the lung tissue and decreased inflammatory cytokine levels in the bronchoalveolar lavage fluid, together with oxidant levels in the lung. AMG9810 inhibited MFF expression and increased MFN2 expression while A967079 inhibited DRP1 expression and increased OPA1 expression; combined pretreatment reduced MFF and DPR1 expression and increased MFN2 and OPA1 expression. All pretreatments inhibited the activation of the TLR4/NF-κB pathway, while A967079 alone, and combined with AMG9810 also reduced the activation of the NLRP3/caspase-1 pathway. Both TRPV1 and TRPA1 channels play an important role in PM2.5-induced lung inflammation and AHR. However, inhibition of the TRPA1 channel or combined inhibition of TRPA1 and TRPV1 channels resulted in greater inhibitory effect on PM2.5-induced lung injury through regulating the mitochondrial fission/fusion proteins and inhibiting the TLR4/NF-κB and NLRP3/caspase-1 pathways.


Assuntos
Material Particulado/toxicidade , Pneumonia/etiologia , Hipersensibilidade Respiratória/etiologia , Canal de Cátion TRPA1/metabolismo , Canais de Cátion TRPV/metabolismo , Acrilamidas/farmacologia , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Líquido da Lavagem Broncoalveolar , Citocinas/metabolismo , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Dinâmica Mitocondrial/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Oximas/farmacologia , Tamanho da Partícula , Pneumonia/metabolismo , Pneumonia/patologia , Hipersensibilidade Respiratória/metabolismo , Hipersensibilidade Respiratória/patologia , Transdução de Sinais/efeitos dos fármacos , Canal de Cátion TRPA1/antagonistas & inibidores , Canal de Cátion TRPA1/biossíntese , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Cátion TRPV/biossíntese
5.
Am J Respir Cell Mol Biol ; 61(6): 702-712, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31144984

RESUMO

Obesity is a risk factor for asthma, especially nonatopic asthma, and attenuates the efficacy of standard asthma therapeutics. Obesity also augments pulmonary responses to ozone, a nonatopic asthma trigger. The purpose of this study was to determine whether obesity-related alterations in gut microbiota contribute to these augmented responses to ozone. Ozone-induced increases in airway responsiveness, a canonical feature of asthma, were greater in obese db/db mice than in lean wild-type control mice. Depletion of gut microbiota with a cocktail of antibiotics attenuated obesity-related increases in the response to ozone, indicating a role for microbiota. Moreover, ozone-induced airway hyperresponsiveness was greater in germ-free mice that had been reconstituted with colonic contents of db/db than in wild-type mice. In addition, compared with dietary supplementation with the nonfermentable fiber cellulose, dietary supplementation with the fermentable fiber pectin attenuated obesity-related increases in the pulmonary response to ozone, likely by reducing ozone-induced release of IL-17A. Our data indicate a role for microbiota in obesity-related increases in the response to an asthma trigger and suggest that microbiome-based therapies such as prebiotics may provide an alternative therapeutic strategy for obese patients with asthma.


Assuntos
Microbioma Gastrointestinal/fisiologia , Obesidade/complicações , Ozônio/toxicidade , Hipersensibilidade Respiratória/etiologia , Resistência das Vias Respiratórias , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Asma/etiologia , Asma/terapia , Celulose/administração & dosagem , Fibras na Dieta/administração & dosagem , Transplante de Microbiota Fecal , Feminino , Fermentação , Microbioma Gastrointestinal/efeitos dos fármacos , Vida Livre de Germes , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/genética , Obesidade/microbiologia , Obesidade/fisiopatologia , Pectinas/administração & dosagem , Pectinas/uso terapêutico , Receptores para Leptina/deficiência , Hipersensibilidade Respiratória/induzido quimicamente , Hipersensibilidade Respiratória/dietoterapia , Hipersensibilidade Respiratória/microbiologia
6.
Semin Immunopathol ; 41(3): 349-358, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30953160

RESUMO

CD69 is an activation marker on leukocytes. Early studies showed that the CD69+ cells were detected in the lung of patients with asthmatic and eosinophilic pneumonia, suggesting that CD69 might play crucial roles in the pathogenesis of such inflammatory diseases, rather than simply being an activation marker. Intensive studies using mouse models have since clarified that CD69 is a functional molecule regulating the immune responses. We discovered that Myosin light chain 9, 12a, 12b (Myl9/12) are ligands for CD69 and that platelet-derived Myl9 forms a net-like structure (Myl9 nets) that is strongly detected inside blood vessels in inflamed lung. CD69-expressing activated T cells attached to the Myl9 nets can thereby migrate into the inflamed tissues through a system known as the CD69-Myl9 system. In this review, we summarize the discovery of the CD69-Myl9 system and discuss how this system is important in inflammatory immune responses. In addition, we discuss our recent finding that CD69 controls the exhaustion status of tumor-infiltrating T cells and that the blockade of the CD69 function enhances anti-tumor immunity. Finally, we discuss the possibility of CD69 as a new therapeutic target for patients with intractable inflammatory disorders and tumors.


Assuntos
Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/metabolismo , Biomarcadores , Imunidade , Lectinas Tipo C/metabolismo , Cadeias Leves de Miosina/metabolismo , Animais , Antígenos CD/química , Antígenos CD/genética , Antígenos CD/imunologia , Antígenos de Diferenciação de Linfócitos T/química , Antígenos de Diferenciação de Linfócitos T/genética , Antígenos de Diferenciação de Linfócitos T/imunologia , Transformação Celular Neoplásica , Suscetibilidade a Doenças , Expressão Gênica , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Lectinas Tipo C/química , Lectinas Tipo C/genética , Lectinas Tipo C/imunologia , Ligantes , Terapia de Alvo Molecular , Cadeias Leves de Miosina/química , Cadeias Leves de Miosina/genética , Cadeias Leves de Miosina/imunologia , Neoplasias/etiologia , Neoplasias/metabolismo , Neoplasias/patologia , Ligação Proteica , Hipersensibilidade Respiratória/etiologia , Hipersensibilidade Respiratória/metabolismo , Hipersensibilidade Respiratória/patologia , Relação Estrutura-Atividade
7.
J Pediatr ; 209: 139-145.e1, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30902420

RESUMO

OBJECTIVE: To investigate the effect of vitamin D supplementation dose on allergic sensitization and allergic diseases in infants, and to evaluate whether vitamin D status in pregnancy and at birth are associated with infant allergy outcomes. STUDY DESIGN: Altogether, 975 infants participated in a randomized, controlled trial of daily vitamin D supplementation of 10 µg (400 IU) or 30 µg (1200 IU) from the age of 2 weeks. At 12 months of age, food and aeroallergen IgE antibodies were measured, and the occurrence of allergic diseases and wheezing were evaluated. RESULTS: We found no differences between the vitamin D supplementation groups in food (OR, 0.98; 95% CI, 0.66-1.46) or aeroallergen sensitization at 12 months (OR, 0.76; 95% CI,0.34-1.71). Allergic diseases or wheezing did not differ between groups, except for milk allergy which occurred more often in infants administered 30 µg vitamin D compared with the 10 µg dose (OR, 2.23; 95% CI, 1.00-4.96). Infants with high cord blood 25-hydroxyvitamin D (≥100 nmol/L) had a higher risk of food allergen sensitization compared with those with lower 25(OH)D concentration (75-99.9 nmol/L; OR, 2.00; 95% CI, 1.19-3.39). CONCLUSIONS: High-dose vitamin D supplementation did not prevent allergic sensitization, allergic diseases, or wheezing during the first year of life. In contrast, we observed an increased risk of milk allergy in infants randomized to higher vitamin D supplementation, and an increased risk of allergic sensitization in infants with high cord blood vitamin D status, indicating a possible adverse effect of high concentrations of vitamin D.


Assuntos
Suplementos Nutricionais , Hipersensibilidade Alimentar/prevenção & controle , Hipersensibilidade Respiratória/prevenção & controle , Vitamina D/administração & dosagem , Vitaminas/administração & dosagem , Alérgenos/efeitos adversos , Método Duplo-Cego , Feminino , Hipersensibilidade Alimentar/etiologia , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Hipersensibilidade Respiratória/etiologia , Falha de Tratamento , Vitamina D/sangue
8.
Am J Pathol ; 189(4): 762-772, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30711489

RESUMO

Increased angiogenesis is a characteristic feature of remodeling in asthmatic airways and stems from the imbalance between pro-angiogenic and anti-angiogenic factors. Surprisingly, the factors regulating this process in allergic asthma are poorly defined. Previously, we showed an important role of semaphorins 3E (Sema3E) in growth factor-induced airway smooth muscle proliferation and migration in vitro, and in down-regulating airway inflammation, T helper 2/T helper 17 cytokine response, mucus cell hyperplasia, and airway hyperresponsiveness in vivo. However, the role of Sema3E in airway angiogenesis is not fully understood. Here, we investigated the role of Sema3E in airway angiogenesis using a house dust mite (HDM) murine model of allergic asthma. Intranasal treatment with recombinant Sema3E significantly reduced the expression of angiogenesis markers within the airways of HDM-challenged mice compared with untreated mice. HDM-induced expression of vascular endothelial growth factor (VEGF) and VEGF receptor 2 protein were diminished substantially on Sema3E treatment. Interestingly, Sema3E-treated mice showed an enhanced expression of the negative regulator of angiogenesis, soluble VEGF receptor 1, compared with the untreated mice. These events were reversed in Sema3E-deficient mice at baseline or on HDM challenge. Taken together, this study provides the first evidence that Sema3E modulates angiogenesis in allergic asthmatic airways via modulating pro- and anti-angiogenic factors.


Assuntos
Asma/prevenção & controle , Proteínas do Citoesqueleto/fisiologia , Modelos Animais de Doenças , Inflamação/prevenção & controle , Proteínas de Membrana/fisiologia , Neovascularização Patológica/prevenção & controle , Pyroglyphidae/patogenicidade , Hipersensibilidade Respiratória/prevenção & controle , Remodelação das Vias Aéreas , Alérgenos/imunologia , Indutores da Angiogênese/imunologia , Indutores da Angiogênese/metabolismo , Animais , Asma/etiologia , Asma/patologia , Feminino , Inflamação/etiologia , Inflamação/patologia , Camundongos , Camundongos Knockout , Neovascularização Patológica/etiologia , Neovascularização Patológica/patologia , Hipersensibilidade Respiratória/etiologia , Hipersensibilidade Respiratória/patologia
9.
Redox Biol ; 22: 101129, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30735910

RESUMO

Protein disulfide isomerases (PDI) are a family of redox chaperones that catalyze formation or isomerization of disulfide bonds in proteins. Previous studies have shown that one member, PDIA3, interacts with influenza A virus (IAV) hemagglutinin (HA), and this interaction is required for efficient oxidative folding of HA in vitro. However, it is unknown whether these host-viral protein interactions occur during active infection and whether such interactions represent a putative target for the treatment of influenza infection. Here we show that PDIA3 is specifically upregulated in IAV-infected mouse or human lung epithelial cells and PDIA3 directly interacts with IAV-HA. Treatment with a PDI inhibitor, LOC14 inhibited PDIA3 activity in lung epithelial cells, decreased intramolecular disulfide bonds and subsequent oligomerization (maturation) of HA in both H1N1 (A/PR8/34) and H3N2 (X31, A/Aichi/68) infected lung epithelial cells. These reduced disulfide bond formation significantly decreased viral burden, and also pro-inflammatory responses from lung epithelial cells. Lung epithelial-specific deletion of PDIA3 in mice resulted in a significant decrease in viral burden and lung inflammatory-immune markers upon IAV infection, as well as significantly improved airway mechanics. Taken together, these results indicate that PDIA3 is required for effective influenza pathogenesis in vivo, and pharmacological inhibition of PDIs represents a promising new anti-influenza therapeutic strategy during pandemic and severe influenza seasons.


Assuntos
Infecções por Orthomyxoviridae/etiologia , Infecções por Orthomyxoviridae/metabolismo , Isomerases de Dissulfetos de Proteínas/genética , Mucosa Respiratória/enzimologia , Animais , Modelos Animais de Doenças , Suscetibilidade a Doenças , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Deleção de Genes , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Vírus da Influenza A/fisiologia , Camundongos , Camundongos Transgênicos , Infecções por Orthomyxoviridae/diagnóstico , Isomerases de Dissulfetos de Proteínas/metabolismo , Testes de Função Respiratória , Hipersensibilidade Respiratória/etiologia , Hipersensibilidade Respiratória/metabolismo , Hipersensibilidade Respiratória/fisiopatologia , Mucosa Respiratória/patologia , Mucosa Respiratória/virologia , Carga Viral
10.
Pulm Pharmacol Ther ; 55: 67-74, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30771475

RESUMO

In the general population, particularly in individuals with asthma, cough is a common symptom, often reported after exertion, although regular exercise may be associated with a reduction in the prevalence of cough. In athletes, exercise-induced cough is also a particularly frequent symptom. The main etiologies of cough in athletes are somewhat similar to non-athletes, including asthma/airway hyperresponsiveness, upper airways disorders such as allergic or non-allergic rhinitis, and exercise-induced laryngeal obstruction, although these conditions are more frequently observed in athletes. In these last, this symptom can also be related to the high ventilation and heat exchange experienced during exercise, particularly during exposure to cold/dry air or pollutants. However, gastroesophageal reflux, a common cause of cough in the general population, despite being highly prevalent in athletes, has not been reported as a main cause of cough in athletes. Cough may impair quality of life, sleep and exercise performance in the general population and probably also in athletes, although there are few data on this. The causes of cough should be documented through a systematic evaluation, the treatment adapted according to identified or most probable cough etiology and pattern of presentation, while respecting sports anti-doping regulations. More research is needed on exercise-induced persistent cough in the athlete to determine its pathophysiology, optimal management and consequences.


Assuntos
Atletas , Tosse/etiologia , Exercício Físico , Obstrução das Vias Respiratórias/complicações , Obstrução das Vias Respiratórias/etiologia , Asma Induzida por Exercício/complicações , Tosse/fisiopatologia , Humanos , Prevalência , Qualidade de Vida , Hipersensibilidade Respiratória/complicações , Hipersensibilidade Respiratória/etiologia
11.
J Med Entomol ; 56(2): 347-352, 2019 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-30462230

RESUMO

House dust mites (HDMs) are the major constituents of house dust (HD). HD and HDM sensitization is well documented worldwide. Storage mite (SM) sensitization is presently lacking from India. The present study evaluated the sensitization of both HDM and SM among 372 allergic rhinitis patients reported to the Allergy and Asthma Research Center of Kolkata metropolitan, India. HD samples were collected from the patients' home and analyzed for the major constituent mites. HD and six constituent mites Dermatophagoides pteronyssinus (DP), Dermatophagoides farina Hughes (Acari: Pyroglyphidae) (DF), Blomia tropicalis (BT), Acarus siro Linnaeus (Acari: Acaridae) (AS), Lepidoglyphus destructor (LD), and Tyrophagus putrescentiae (Schrank) (Acari: Acaridae) (TP) are tested for the allergenic potential through Skin Prick Test (SPT). Three SMs, namely AS, LD, and TP, were newly included in the mite SPT extract for the first time in Kolkata. In total, 330 patients showed significant positive SPT toward any one allergen tested. HD was the major elicitor exhibiting 92.42% response. Individuals of age group 15-40 were the worst sufferers. DF showed the highest sensitization (87.87%) among the dust mites. The SMs also contributed significantly to prove their sensitizing potential. SPT rates for AS, LD, and TP were 33, 25, and 18%, respectively. SPT grades and total Immunoglobulin E (IgE) were positively correlated for each of the allergens. Most of the patients were multi-sensitized (95%) and represented markedly high total IgE levels (>500 IU/ml). Three SMs proved to be significant allergens for the studied population. The sensitization toward these SMs is first time reported from India and can be recommended for inclusion of routine SPT for better outcome in the future.


Assuntos
Acaridae/imunologia , Pyroglyphidae/imunologia , Hipersensibilidade Respiratória/etiologia , Adolescente , Adulto , Animais , Feminino , Humanos , Imunoglobulina E/sangue , Índia/epidemiologia , Masculino , Hipersensibilidade Respiratória/sangue , Hipersensibilidade Respiratória/epidemiologia , Adulto Jovem
12.
Int Arch Allergy Immunol ; 178(2): 150-158, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30415264

RESUMO

BACKGROUND: Microbiota and human allergic airway diseases have been proven to be interrelated. Bacteria-derived extracellular vesicle (EV)s are known to play important roles in interbacterial and human-bacteria communications, but their relationship with allergies has not been examined yet. Urine EVs were investigated to determine whether they could be used as biomarkers for monitoring allergic airway diseases in children. METHODS: Subjects were 4 groups of chronic rhinitis (CR), allergic rhinitis (AR), atopic asthma (AS) and healthy controls. Single voided urine samples were collected. Urine EVs were isolated and their DNA was extracted for 16S-rDNA pyrosequencing. RESULTS: A total of 118 children participated in this study; 27, 39, 19, and 33 were in the CR, AR, AS, and control group, respectively. The AR had a significantly high Chao-1 index than that of controls. Principal component analysis revealed dysbiosis in the CR, AR, and AS compared to the controls. One phylum and 19 families and genera were significantly enriched or depleted in the disease groups compared to the controls; the Actinobacteria phylum and the Sphingomonadaceae family were more abundant in the AS and CR, the Comamonadaceae family, the Propionibacteraceae family, Propionibacterium and Enhydrobacter were more enriched in the CR, and the Methylobacteriaceae family and Methylobacterium were more abundant in each disease group, while the Enterobacteriaceae family was depleted in each disease group. CONCLUSIONS: CR, AR, and AS had a distinct composition of urine EVs. Urine EVs could be an indicator for assessing allergic airway diseases in children.


Assuntos
Bactérias/metabolismo , Bacteriúria/metabolismo , Bacteriúria/microbiologia , Vesículas Extracelulares/metabolismo , Hipersensibilidade Respiratória/etiologia , Hipersensibilidade Respiratória/metabolismo , Fatores Etários , Bactérias/classificação , Bactérias/genética , Criança , Pré-Escolar , Feminino , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Masculino , Filogenia , RNA Ribossômico 16S/genética , Hipersensibilidade Respiratória/diagnóstico
14.
Braz J Med Biol Res ; 51(12): e7558, 2018 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-30365724

RESUMO

The association between pet ownership and the development of allergic and respiratory diseases has been the aim of several studies, however, the effects of exposure in adults remain uncertain. The aims of the present study were to investigate the prevalence of asthma and lung function status among dog and cat owners. This cross-sectional study was performed at two universities with students and workers who were allocated into 3 groups according to pet ownership in the previous year: cat owners, dog owners, and no pets (control group). Subjects underwent spirometry, bronchial challenge test with mannitol, skin prick tests, and questionnaires about animal exposures and respiratory symptoms. Control group comprised 125 subjects; cat owner group, 51 subjects; and dog owner group, 140 subjects. Cat owners had increased asthma prevalence (defined by symptoms and positive bronchial challenge test), but no changes in lung function compared to the control group. The dog owner group had lower spirometry values (forced expiratory volume in one second and lower forced vital capacity), but similar asthma prevalence, compared to the control group. In the cat owner group, excess of asthma may have an immunological basis, since we found an association with atopy. Although we did not have endotoxin data from volunteers' households, we postulated that low values of lung function were associated to exposure to endotoxins present in environments exposed to dogs.


Assuntos
Asma/epidemiologia , Asma/etiologia , Gatos , Cães , Pulmão/fisiopatologia , Propriedade/estatística & dados numéricos , Animais de Estimação , Adolescente , Adulto , Alérgenos/efeitos adversos , Análise de Variância , Animais , Asma/fisiopatologia , Brasil/epidemiologia , Criança , Estudos Transversais , Exposição Ambiental/efeitos adversos , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Masculino , Prevalência , Valores de Referência , Hipersensibilidade Respiratória/epidemiologia , Hipersensibilidade Respiratória/etiologia , Medição de Risco , Fatores de Risco , Testes Cutâneos , Espirometria , Capacidade Vital/fisiologia , Adulto Jovem
15.
Am J Physiol Lung Cell Mol Physiol ; 315(5): L787-L798, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30188746

RESUMO

Allergic asthma is a major cause of morbidity in both pediatric and adult patients. Recent research has highlighted the role of hyaluronan (HA), an extracellular matrix glycosaminoglycan, in asthma pathogenesis. Experimental allergic airway inflammation and clinical asthma are associated with an increase of shorter fragments of HA (sHA), which complex with inter-α-inhibitor heavy chains (HCs) and induce inflammation and airway hyperresponsiveness (AHR). Importantly, the effects of sHA can be antagonized by the physiological counterpart high molecular weight HA (HMWHA). We used a mouse model of house dust mite-induced allergic airway inflammation and demonstrated that instilled HMWHA ameliorated allergic airway inflammation and AHR, even when given after the establishment of allergic sensitization and after challenge exposures. Furthermore, instilled HMWHA reduced the development of HA-HC complexes and the activation of Rho-associated, coiled-coil containing protein kinase 2. We conclude that airway application of HMWHA is a potential treatment for allergic airway inflammation.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Modelos Animais de Doenças , Ácido Hialurônico/administração & dosagem , Inflamação/prevenção & controle , Pyroglyphidae/patogenicidade , Hipersensibilidade Respiratória/prevenção & controle , Animais , Feminino , Inflamação/etiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Peso Molecular , Hipersensibilidade Respiratória/etiologia
16.
PLoS Pathog ; 14(9): e1007260, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30235351

RESUMO

The gastrointestinal microbiota influences immune function throughout the body. The gut-lung axis refers to the concept that alterations of gut commensal microorganisms can have a distant effect on immune function in the lung. Overgrowth of intestinal Candida albicans has been previously observed to exacerbate allergic airways disease in mice, but whether subtler changes in intestinal fungal microbiota can affect allergic airways disease is less clear. In this study we have investigated the effects of the population expansion of commensal fungus Wallemia mellicola without overgrowth of the total fungal community. Wallemia spp. are commonly found as a minor component of the commensal gastrointestinal mycobiota in both humans and mice. Mice with an unaltered gut microbiota community resist population expansion when gavaged with W. mellicola; however, transient antibiotic depletion of gut microbiota creates a window of opportunity for expansion of W. mellicola following delivery of live spores to the gastrointestinal tract. This phenomenon is not universal as other commensal fungi (Aspergillus amstelodami, Epicoccum nigrum) do not expand when delivered to mice with antibiotic-depleted microbiota. Mice with Wallemia-expanded gut mycobiota experienced altered pulmonary immune responses to inhaled aeroallergens. Specifically, after induction of allergic airways disease with intratracheal house dust mite (HDM) antigen, mice demonstrated enhanced eosinophilic airway infiltration, airway hyperresponsiveness (AHR) to methacholine challenge, goblet cell hyperplasia, elevated bronchoalveolar lavage IL-5, and enhanced serum HDM IgG1. This phenomenon occurred with no detectable Wallemia in the lung. Targeted amplicon sequencing analysis of the gastrointestinal mycobiota revealed that expansion of W. mellicola in the gut was associated with additional alterations of bacterial and fungal commensal communities. We therefore colonized fungus-free Altered Schaedler Flora (ASF) mice with W. mellicola. ASF mice colonized with W. mellicola experienced enhanced severity of allergic airways disease compared to fungus-free control ASF mice without changes in bacterial community composition.


Assuntos
Basidiomycota/imunologia , Basidiomycota/patogenicidade , Microbioma Gastrointestinal/imunologia , Micobioma/imunologia , Hipersensibilidade Respiratória/etiologia , Alérgenos/administração & dosagem , Animais , Antibacterianos/efeitos adversos , Antígenos de Dermatophagoides/administração & dosagem , Basidiomycota/crescimento & desenvolvimento , Modelos Animais de Doenças , Microbiologia Ambiental , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Vida Livre de Germes/imunologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Micobioma/genética , Hipersensibilidade Respiratória/imunologia , Hipersensibilidade Respiratória/microbiologia , Simbiose/imunologia
17.
Clin Exp Allergy ; 48(12): 1665-1675, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30159930

RESUMO

BACKGROUND: Clinical and experimental studies have identified a crucial role for IL-33 and its receptor ST2 in allergic asthma. Inhalation of traffic-related pollutants, such as diesel exhaust particles (DEP), facilitates the development of asthma and can cause exacerbations of asthma. However, it is unknown whether IL-33/ST2 signalling contributes to the enhancing effects of air pollutants on allergic airway responses. OBJECTIVE: We aim to investigate the functional role of IL-33/ST2 signalling in DEP-enhanced allergic airway responses, using an established murine model. METHODS: C57BL/6J mice were exposed to saline, DEP alone, house dust mite (HDM) alone or combined DEP+HDM. To inhibit IL-33 signalling, recombinant soluble ST2 (r-sST2) was given prophylactically (ie, during the whole experimental protocol) or therapeutically (ie, at the end of the experimental protocol). Airway hyperresponsiveness and the airway inflammatory responses were assessed in bronchoalveolar lavage fluid (BALF) and lung. RESULTS: Combined exposure to DEP+HDM increased IL-33 and ST2 expression in lung, elevated inflammatory responses and bronchial hyperresponsiveness compared to saline, sole DEP or sole HDM exposure. Prophylactic interference with the IL-33/ST2 signalling pathway impaired the DEP-enhanced allergic airway inflammation in the BALF, whereas effects on lung inflammation and airway hyperresponsiveness were minimal. Treatment with r-sST2 at the end of the experimental protocol did not modulate the DEP-enhanced allergic airway responses. CONCLUSION: Our data suggest that the IL-33/ST2 pathway contributes to the onset of DEP-enhanced allergic airway inflammation.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Interleucina-33/metabolismo , Hipersensibilidade Respiratória/etiologia , Hipersensibilidade Respiratória/metabolismo , Transdução de Sinais , Alérgenos/imunologia , Animais , Biomarcadores , Modelos Animais de Doenças , Feminino , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Leucócitos/imunologia , Leucócitos/metabolismo , Linfócitos/imunologia , Linfócitos/metabolismo , Camundongos , Material Particulado/efeitos adversos , Pyroglyphidae/imunologia , Proteínas Recombinantes/farmacologia , Hipersensibilidade Respiratória/tratamento farmacológico , Hipersensibilidade Respiratória/patologia , Mucosa Respiratória/imunologia , Mucosa Respiratória/metabolismo
18.
Am J Physiol Lung Cell Mol Physiol ; 315(5): L662-L672, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30091379

RESUMO

Electronic cigarettes (e-cigs) are advertised as a less harmful nicotine delivery system or as a new smoking cessation tool. We aimed to assess the in vivo effects of e-cig vapor in the lung and to compare them to those of cigarette smoke (CS). We exposed C57BL/6 mice for either 3 days or 4 wk to ambient air, CS, or e-cig vapor containing 1) propylene glycol/vegetable glycerol (PG:VG-Sol; 1:1), 2) PG:VG with nicotine (G:VG-N), or 3) PG:VG with nicotine and flavor (PG:VG-N+F) and determined oxidative stress, inflammation, and pulmonary mechanics. E-cig vapors, especially PG:VG-N+F, increased bronchoalveolar lavage fluid (BALF) cellularity, Muc5ac production, as well as BALF and lung oxidative stress markers at least comparably and in many cases more than CS. BALF protein content at both time points studied was only elevated in the PG:VG-N+F group. After 3 days, PG:VG-Sol altered tissue elasticity, static compliance, and airway resistance, whereas after 4 wk CS was the only treatment adversely affecting these parameters. Airway hyperresponsiveness in response to methacholine was increased similarly in the CS and PG:VG-N+F groups. Our findings suggest that exposure to e-cig vapor can trigger inflammatory responses and adversely affect respiratory system mechanics. In many cases, the added flavor in e-cigs exacerbated the detrimental effects of e-cig vapor. We conclude that both e-cig vaping and conventional cigarette smoking negatively impact lung biology.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina/métodos , Inflamação/etiologia , Estresse Oxidativo , Hipersensibilidade Respiratória/etiologia , Fumar/efeitos adversos , Vaping/efeitos adversos , Animais , Sistemas Eletrônicos de Liberação de Nicotina/estatística & dados numéricos , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hipersensibilidade Respiratória/patologia
19.
Dig Dis Sci ; 63(11): 2930-2939, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30022451

RESUMO

BACKGROUND: Patients with inflammatory bowel disease have higher incidence of airway hyperresponsiveness compared to the general population. Lung inflammation leading to airway hyperresponsiveness causes illnesses for more than ten percent of the population in USA. AIMS: We investigated the lung response to bacterial endotoxin in colitic mice. METHODS: Rag-1 mice were transplanted with negatively selected splenic T cells. Some mice groups were treated with NSAID to develop colitis. All mice were treated with bacterial endotoxin and necropsied 3 weeks later. RESULTS: Colitic mice developed intensified lung inflammation on day 21 of treatment with bacterial endotoxin. Pulmonary lymphocytes from colitic mice displayed a proinflammatory cytokine profile, expressed high ICAM1 and low FoxP3. CD11c+, CD8+ cells bound and responded to non-systemic antigens from gut-localized microbiota and had higher expression of TLR4. CONCLUSIONS: Colitic mice developed exacerbated lung inflammation in response to bacterial endotoxin compared to non-colitic mice. Proinflammatory cytokines from pulmonary lymphocytes induced high expression of ICAM1 and suppressed FoxP3 on CD4+ cells. CD11c+, CD8+ cells binding and responding to gut-localized antigens as well as high expression of TLR4 indicate innate and adaptive lung response to bacterial endotoxin. Inflammatory cells from colons of colitic mice homed in the lungs as well as the intestine suggesting recirculation of sensitized immunocompetent cells. These data support our hypothesis that colitis intensifies lung inflammation.


Assuntos
Colite/complicações , Pulmão/imunologia , Hipersensibilidade Respiratória/etiologia , Animais , Movimento Celular , Colite/imunologia , Citocinas/metabolismo , Endotoxinas , Feminino , Fatores de Transcrição Forkhead/metabolismo , Helmintos , Molécula 1 de Adesão Intercelular/metabolismo , Pulmão/patologia , Linfócitos/metabolismo , Camundongos Endogâmicos C57BL , Receptor 4 Toll-Like/metabolismo
20.
Expert Rev Respir Med ; 12(9): 755-767, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30056777

RESUMO

INTRODUCTION: There is a major epidemic of obesity, and many obese patients suffer with respiratory symptoms and disease. The overall impact of obesity on lung function is multifactorial, related to mechanical and inflammatory aspects of obesity. Areas covered: Obesity causes substantial changes to the mechanics of the lungs and chest wall, and these mechanical changes cause asthma and asthma-like symptoms such as dyspnea, wheeze, and airway hyperresponsiveness. Excess adiposity is also associated with increased production of inflammatory cytokines and immune cells that may also lead to disease. This article reviews the literature addressing the relationship between obesity and lung function, and studies addressing how the mechanical and inflammatory effects of obesity might lead to changes in lung mechanics and pulmonary function in obese adults and children. Expert commentary: Obesity has significant effects on respiratory function, which contribute significantly to the burden of respiratory disease. These mechanical effects are not readily quantified with conventional pulmonary function testing and measurement of body mass index. Changes in mediators produced by adipose tissue likely also contribute to altered lung function, though as of yet this is poorly understood.


Assuntos
Pulmão/fisiopatologia , Obesidade/complicações , Obesidade/fisiopatologia , Adulto , Asma/etiologia , Asma/fisiopatologia , Índice de Massa Corporal , Criança , Dispneia/etiologia , Dispneia/fisiopatologia , Humanos , Respiração , Testes de Função Respiratória , Hipersensibilidade Respiratória/etiologia , Hipersensibilidade Respiratória/fisiopatologia
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