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1.
Front Endocrinol (Lausanne) ; 13: 893863, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35600600

RESUMO

Perinatal exposure to smoking has been associated with childhood asthma, one of the most common pediatric conditions affecting millions of children globally. Of great interest, this disease phenotype appears heritable as it can persist across multiple generations even in the absence of persistent exposure to smoking in subsequent generations. Although the molecular mechanisms underlying childhood asthma induced by perinatal exposure to smoking or nicotine remain elusive, an epigenetic mechanism has been proposed, which is supported by the data from our earlier analyses on germline DNA methylation (5mC) and histone marks (H3 and H4 acetylation). To further investigate the potential epigenetic inheritance of childhood asthma induced by perinatal nicotine exposure, we profiled both large and small RNAs in the sperm of F1 male rats. Our data revealed that perinatal exposure to nicotine leads to alterations in the profiles of sperm-borne RNAs, including mRNAs and small RNAs, and that rosiglitazone, a PPARγ agonist, can attenuate the effect of nicotine and reverse the sperm-borne RNA profiles of F1 male rats to close to placebo control levels.


Assuntos
Asma , Nicotina , Animais , Asma/induzido quimicamente , Feminino , Humanos , Masculino , Nicotina/efeitos adversos , Gravidez , RNA , Ratos , Ratos Sprague-Dawley , Espermatozoides
2.
Environ Int ; 164: 107262, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35569389

RESUMO

The health effects of traffic-related air pollution (TRAP) continue to be of important public health interest. Following its well-cited 2010 critical review, the Health Effects Institute (HEI) appointed a new expert Panel to systematically evaluate the epidemiological evidence regarding the associations between long-term exposure to TRAP and selected adverse health outcomes. Health outcomes were selected based on evidence of causality for general air pollution (broader than TRAP) cited in authoritative reviews, relevance for public health and policy, and resources available. The Panel used a systematic approach to search the literature, select studies for inclusion in the review, assess study quality, summarize results, and reach conclusions about the confidence in the evidence. An extensive search was conducted of literature published between January 1980 and July 2019 on selected health outcomes. A new exposure framework was developed to determine whether a study was sufficiently specific to TRAP. In total, 353 studies were included in the review. Respiratory effects in children (118 studies) and birth outcomes (86 studies) were the most commonly studied outcomes. Fewer studies investigated cardiometabolic effects (57 studies), respiratory effects in adults (50 studies), and mortality (48 studies). The findings from the systematic review, meta-analyses, and evaluation of the quality of the studies and potential biases provided an overall high or moderate-to-high level of confidence in an association between long-term exposure to TRAP and the adverse health outcomes all-cause, circulatory, ischemic heart disease and lung cancer mortality, asthma onsetin chilldren and adults, and acute lower respiratory infections in children. The evidence was considered moderate, low or very low for the other selected outcomes. In light of the large number of people exposed to TRAP - both in and beyond the near-road environment - the Panel concluded that the overall high or moderate-to-high confidence in the evidence for an association between long-term exposure to TRAP and several adverse health outcomes indicates that exposures to TRAP remain an important public health concern and deserve greater attention from the public and from policymakers.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Asma , Poluição Relacionada com o Tráfego , Adulto , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Asma/induzido quimicamente , Viés , Criança , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Humanos , Poluição Relacionada com o Tráfego/análise
3.
J Toxicol Sci ; 47(4): 147-149, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35370242

RESUMO

A patient who survived acute paraquat (PQ) poisoning for more than 5 years was followed up in the emergency room. The patient had recurrent coughing and wheezing one month after discharge. Re-examination of chest CT showed increased dual lung texture. Spirometry suggested severe ventilatory dysfunction while bronchial dilation test was positive. The serum IgE level was significantly high. It is considered that patients with acute PQ poisoning may develop asthma in the long term.


Assuntos
Asma , Paraquat , Asma/induzido quimicamente , Humanos , Pulmão/diagnóstico por imagem , Tomografia Computadorizada por Raios X
4.
Sci Rep ; 12(1): 5949, 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35396495

RESUMO

The comparative effectiveness of different inhaler therapies in mild-to-moderate asthma remains unclear. To assess this, we performed a systematic review and network meta-analysis of randomized controlled trials on the use of inhalers for mild-to-moderate asthma by searching PubMed, Cochrane, and Embase. A total of 29 trials including 43,515 patients and 12 types of inhaler therapies were included. For the prevention of severe and moderate-to-severe exacerbations, inhaled corticosteroid (ICS)/long-acting ß2-agonist (LABA) as maintenance and reliever (SMART) showed the highest rank for effectiveness. As-needed ICS/LABA or short-acting ß2-agonist (SABA) was similar to low-dose ICS and superior to as-needed SABA or LABA for the prevention of severe and moderate-severe exacerbations. As for lung function (FEV1), low-dose ICS/LABA had the highest rank; as-needed ICS/LABA was inferior to regular low-dose ICS but superior to placebo. Higher-dose ICS had a superior effect on the Asthma Control Questionnaire (ACQ) scores, and as-needed ICS/LABA and as-needed SABA or LABA had lower ranks in p-rankogram than did the regular use of low-dose ICS. As-needed ICS with LABA or SABA was more effective than a similar dose of regular ICS for preventing exacerbation in mild-to-moderate asthma. As-needed ICS showed some weakness in improving lung function and controlling asthma symptoms.


Assuntos
Antiasmáticos , Asma , Administração por Inalação , Corticosteroides , Antiasmáticos/uso terapêutico , Asma/induzido quimicamente , Asma/tratamento farmacológico , Quimioterapia Combinada , Humanos , Nebulizadores e Vaporizadores , Metanálise em Rede , Testes de Função Respiratória
5.
Nan Fang Yi Ke Da Xue Xue Bao ; 42(2): 181-189, 2022 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-35365441

RESUMO

OBJECTIVE: To explore the effect of transforming growth factor-ß (TGF-ß)-activated kinase 1 (TAK1) on toluene diisocyanate (TDI)-induced allergic airway inflammation in mice. METHODS: Thirty-two mice were randomly divided into AOO group, AOO+5Z-7-Oxozeaenol group, TDI group, and TDI+5Z-7-Oxozeaenol group. Another 32 mice were randomly divided into AOO group, TDI group, TDI +5Z-7-Oxozeaenol group, and TDI +5Z-7-Oxozeaenol + Necrostatin-1 group. TAK1 inhibitor (5Z-7-Oxozeaenol, 5 mg/kg) and/or RIPK1 inhibitor (Necrostatin-1, 5 mg/kg) were used before each challenge. Airway responsiveness, airway inflammation and airway remodeling were assessed after the treatments. We also examined the effect of TDI-human serum albumin (TDI-HSA) conjugate combined with TAK1 inhibitor on the viability of mouse mononuclear macrophages (RAW264.7) using CCK8 assay. The expressions of TAK1, mitogen-activated protein kinase (MAPK) and receptor interacting serine/threonine protease 1 (RIPK1) signal pathway in the treated cells were detected with Western blotting. The effects of RIPK1 inhibitor on the viability of RAW264.7 cells and airway inflammation of the mouse models of TDI-induced asthma were evaluated. RESULTS: TAK1 inhibitor aggravated TDI-induced airway inflammation, airway hyper responsiveness and airway remodeling in the mouse models (P < 0.05). Treatment with TAK1 inhibitor significantly decreased the viability of RAW264.7 cells, which was further decreased by co-treatment with TDI-HSA (P < 0.05). TAK1 inhibitor significantly decreased the level of TAK1 phosphorylation and activation of MAPK signal pathway induced by TDI-HSA (P < 0.05). Co-treatment with TAK1 inhibitor and TDI-HSA obviously increased the level of RIPK1 phosphorylation and caused persistent activation of caspase 8 (P < 0.05). RIPK1 inhibitor significantly inhibited the reduction of cell viability caused by TAK1 inhibitor and TDI-HSA (P < 0.05) and alleviated the aggravation of airway inflammation induced by TAK1 inhibitors in TDI-induced mouse models (P < 0.05). CONCLUSION: Inhibition of TAK1 aggravates TDI-induced airway inflammation and hyperresponsiveness and may increase the death of macrophages by enhancing the activity of RIPK1 and causing persistent activation of caspase 8.


Assuntos
Asma , Tolueno 2,4-Di-Isocianato , Animais , Asma/induzido quimicamente , Inflamação , Macrófagos , Camundongos , Proteína Serina-Treonina Quinases de Interação com Receptores , Sistema Respiratório , Tolueno 2,4-Di-Isocianato/efeitos adversos
6.
Artigo em Inglês | MEDLINE | ID: mdl-35409980

RESUMO

Little is known about the cleaning products used by early care and education programs that contribute to childhood asthma, particularly in Oklahoma where rates of uncontrolled asthma are higher than national rates (60.0% vs. 50.3%, respectively). We conducted a cross-sectional study of cleaning products used by Oklahoma-licensed family child care homes (FCCHs) (n = 50) to characterize and identify potential respiratory-health risks associated with chemical contents. Overall, 386 chemicals were abstracted from the 132 reported products. Of these, 100 unique chemicals were identified. Four percent (4.2%) of providers used a product with a sensitizer that may cause allergy or asthma symptoms if inhaled and 35.4% used a product with an irritant that may cause irritation to the respiratory tract. Most (62.5%) reported using a product with a chemical that had a C=C double bond in its molecular structure that may make it highly reactive with other substances in the air and produce secondary air pollutants and 83.3% reported using a sodium hypochlorite containing product. Twenty-three percent reported products that contain carcinogens. Policy, educational, and technical assistance interventions are needed to promote the use of safer products and reduce respiratory and other health risks posed by chemicals in Oklahoma FCCHs.


Assuntos
Asma , Cuidado da Criança , Asma/induzido quimicamente , Asma/epidemiologia , Criança , Saúde da Criança , Estudos Transversais , Humanos , Oklahoma/epidemiologia , Sistema Respiratório
7.
Environ Int ; 162: 107170, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35272140

RESUMO

Domestic cleaners have an increased risk of asthma-like and other respiratory symptoms and conditions. Uncertainty exists about which products are most hazardous. We aimed to investigate, among professional domestic cleaners, the associations of ocular/respiratory outcomes with using specific types of products at work and with the ability to choose their own products. Among domestic cleaners employed by "service vouchers" companies in Belgium, we administered an online questionnaire on ocular/respiratory symptoms (frequency and time relation to workdays), frequency of use of 40 types of products, and ability to choose one's own products. Work-relatedness was defined as symptoms improving/disappearing on days off-work. We studied associations between frequency of product-use with work-related outcomes (eye irritation, rhinitis symptoms, sore throat, laryngeal symptoms, asthma symptoms, cough) and with chronic bronchitis, using multivariable logistic and elastic net regression. Adjusted odds ratios (OR) with 95%-confidence intervals were obtained per time a product was used per week. Among 1,586 domestic cleaners (99% women), the number of times sprays were used (median 13/week) was significantly associated with all outcomes (ORs between 1.012 and 1.024 per time sprays were used per week). Bleach/disinfectant-containing liquid products were associated with all outcomes, except for laryngeal symptoms (ORs 1.086 to 1.150); ammonia with work-related upper airway symptoms and chronic bronchitis. Cleaners able to choose their own products had fewer work-related eye symptoms (OR 0.728;0.556-0.954), rhinitis (OR 0.735;0.571-0.946) and cough (OR 0.671;0.520-0.865). Using elastic net regression, work-related rhinitis was most strongly associated with mould removal spray (OR 1.108;1.006-1.248), carpet/seat/curtain spray (OR 1.099;1.001-1.304) and ammonia (OR 1.081;1.002-1.372); work-related asthma with carpet/seat/curtain spray (OR 1.103;1.017-1.322), mould removal spray (OR 1.029;0.995-1.199) and drain cleaner (OR 1.023;0.979-1.302). In a large group of domestic cleaners, we documented that cleaning products have a range of adverse respiratory effects. Empowering cleaners to choose their products may reduce the burden of symptoms.


Assuntos
Asma , Bronquite Crônica , Doenças Profissionais , Exposição Ocupacional , Rinite , Amônia , Asma/induzido quimicamente , Asma/etiologia , Tosse/epidemiologia , Tosse/etiologia , Detergentes , Feminino , Humanos , Masculino , Doenças Profissionais/induzido quimicamente , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Rinite/epidemiologia , Rinite/etiologia , Recursos Humanos
8.
Environ Int ; 163: 107209, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35358787

RESUMO

Alkyl organophosphate flame retardants (OPFRs), tri-n-butyl phosphate (TnBP) and tris(2-butoxyethyl) phosphate (TBOEP), are ubiquitously detected in indoor and outdoor environments and their inhalation may result in lung damage. This study examined pulmonary toxicity after exposure to TnBP or TBOEP and investigated aggravation of inflammation and immunoreaction by TnBP in an ovalbumin (OVA)-induced mice model. Transcriptomics were used to further reveal the underlying mechanism. Exposure to TnBP or TBOEP resulted in pathological damage, including edema and thickened alveolar septum. In comparison with the control, enhanced levels of superoxide dismutase (SOD) (p < 0.01 in TnBP (High) group and p < 0.05 in TBOEP (High) group), glutathione peroxidase (GSH-px) (p < 0.05), malondialdehyde (MDA) (p < 0.01), and cytokines under a dose-dependent relationship were noted, and the expression of the Fkbp5/Nos3/MAPK/NF-кB signaling pathway (p < 0.01) was upregulated in the TnBP and TBOEP groups. Moreover, the combined exposure of TnBP and OVA exacerbated the allergic inflammatory response, including airway hyperresponsiveness, leukocytosis, cellular exudation and infiltration, secretion of inflammatory mediators, and higher expression of IgE (p < 0.01). Transcriptomics results demonstrated that the PI3K/Akt/NF-кB signal pathway was involved in TnBP-aggravated asthmatic mice. Exposure to TnBP or TBOEP resulted in oxidative damage and leukocyte-induced lung injury. TnBP can further facilitate OVA-induced asthma through an inflammatory response. This study is the first to reveal the pulmonary toxicity and potential mechanism induced by OPFRs through an in-vivo model.


Assuntos
Asma , Retardadores de Chama , Pneumonia , Animais , Asma/induzido quimicamente , Retardadores de Chama/toxicidade , Camundongos , NF-kappa B , Organofosfatos/toxicidade , Ovalbumina , Fosfatidilinositol 3-Quinases , Transdução de Sinais
9.
Mol Med Rep ; 25(4)2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35234263

RESUMO

Sirtuin (SIRT)3 is closely related to inflammation and apoptosis and studies have described this relationship, including in the lungs. However, the expression of SIRT3 and its effect on apoptosis and inflammation in bronchial tissue in asthma remains to be elucidated. The present study found that SIRT3 expression decreased in the bronchial tissues of asthmatic mice and its upregulation could not only reduce increased bronchial epithelial cells apoptosis in the asthmatic mice but also significantly decreased the elevated expression of cytokines (TNF­α, IL­4, IL­5 and IL­13) in bronchoalveolar lavage fluid. Further study found that SIRT3 overexpression significantly decreased apoptosis­related protein expression (Bax/Bcl2 ratio and caspase 3 activity) and oxidative injury. In vitro, SIRT3 regulated oxidative stress­induced bronchial epithelial cell (16HBE) apoptosis and cytokine expression. In conclusion, SIRT3 expression decreased in bronchial tissues of asthmatic mice and the upregulation of SIRT3 expression could reduce the apoptosis of bronchial epithelium and airway inflammation. It was concluded that SIRT3 might be a potential target in asthma treatment.


Assuntos
Asma , Sirtuína 3 , Animais , Apoptose/genética , Asma/induzido quimicamente , Asma/genética , Líquido da Lavagem Broncoalveolar , Epitélio , Inflamação/induzido quimicamente , Camundongos , Sirtuína 3/genética
10.
Chemosphere ; 298: 134277, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35278445

RESUMO

Chronic exposure to arsenic via drinking water is a serious public health issue in many countries. Arsenic causes not only cancers but also non-malignant diseases, including asthma. We have previously reported that arsenic exposure increases the risk of Th2-mediated allergic asthma. The serum level of periostin, an extracellular matrix protein activated by Th2 cytokines, is recognized as a biomarker for Th2-mediated eosinophilic asthma and contributes to enhanced airway inflammation and remodeling. However, the role of periostin in arsenic-related asthma is unknown. Therefore, this study was designed to explore the associations of serum periostin levels with arsenic exposure and the features of asthma in 442 individuals in Bangladesh who participated in our previous study. Exposure levels of the participants were determined by measuring the arsenic concentrations in drinking water, hair, and nails through inductively coupled plasma mass spectroscopy. Periostin levels in serum were assessed by immunoassay. In this study, we found that serum periostin levels of the participants were increased with increasing exposure to arsenic. Notably, even the participants with 10.1-50 µg/L arsenic in drinking water had significantly higher levels of periostin than participants with <10 µg/L of water arsenic. Elevated serum periostin levels were positively associated with serum levels of Th2 mediators, such as interleukin (IL)-4, IL-5, IL-13, and eotaxin. Each log increase in periostin levels was associated with approximately eight- and three-fold increases in the odds ratios (ORs) for reversible airway obstruction (RAO) and asthma symptoms, respectively. Additionally, causal mediation analyses revealed that arsenic exposure metrics had both direct and indirect (periostin-mediated) effects on the risk of RAO and asthma symptoms. Thus, the results suggested that periostin may be involved in the arsenic-related pathogenesis of Th2-mediated asthma. The elevated serum periostin levels may predict the greater risk of asthma among the people living in arsenic-endemic areas.


Assuntos
Intoxicação por Arsênico , Arsênio , Asma , Água Potável , Arsênio/análise , Asma/induzido quimicamente , Asma/epidemiologia , Biomarcadores/análise , Água Potável/análise , Humanos , Unhas/química
11.
Zhongguo Zhong Yao Za Zhi ; 47(4): 1009-1016, 2022 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-35285201

RESUMO

The present study investigated the effect of active components of Descurainia sophia on allergic asthma and explored the underlying mechanism. SD male rats were randomly divided into a normal group(NC), a model group(M), a D. sophia decoction group(DS), a D. sophia fatty oil group(FO), a D. sophia flavonoid glycoside group(FG), a D. sophia oligosaccharide group(Oli), and a positive drug dexamethasone group(Y). The allergic asthma model was induced in rats by intraperitoneal injection of ovalbumin(OVA) and aluminum hydroxide gel adjuvant(sensitization) and atomization of OVA solution(excitation). After modeling, asthma-related indicators, tracheal phenol red excretion, inflammatory cell levels in the peripheral blood, lung permeability index(LPI), and oxygenation index(OI) of rats were detected. The pathological changes of lung tissues were observed by HE staining. Enzyme-linked immunosorbent assay(ELISA) was used to detect the content of inflammatory factors immunoglobulin E(IgE), interleukin-4(IL-4), and interferon-γ(IFN-γ) in the bronchoalveolar lavage fluid(BALF) and the content of endothelin-1(ET-1) and angiotensin-converting enzyme(ACE) in lung tissue homogenate. The serum content of nitric oxide(NO) was detected by colorimetry. Western blot was employed to determine the protein expression of Toll-like receptor 4(TLR4), nuclear factor κB-p65(NF-κB-p65), phosphorylated NF-κB-p65(p-NF-κB-p65), myosin light chain kinase(MLCK), vascular endothelial cadherin(VE cadherin), connexin 43, and claudin 5, and the mechanism of active components of D. sophia on allergic asthma was explored. As revealed by the results, the M group showed extensive infiltration of inflammatory cells around the bronchus of the lung tissues of the allergic asthma rats, thickened bronchial wall, severely deformed alveolar structure, increased number of wheezes, the content of IgE, IL-4, ET-1, and ACE, inflammatory cells, and LPI, and reduced latency of asthma, tracheal phenol red excretion, IFN-γ, NO content, and OI. After the intervention of the active components of D. sophia, the DS, FO, FG, Oli, and Y groups showed improved asthma-related indicators, tracheal phenol red excretion, and lung tissue lesions in allergic asthma rats, and the effects in the FO and Oli groups were superior. The content of inflammatory factors in BALF was recovered in the DS, FO, and Y groups and the FG and Oli groups. The number of inflammatory cells in rats was reduced in the DS and FO groups, and the FG, Oli, and Y groups to varying degrees, and the effect in the FO group was superior. DS, FO, Oli, and Y reduced ET-1, ACE, and LPI and increased NO and OI. FG recovered NO, ET-1, ACE, LPI, and OI to improve lung epithelial damage and permeability. Further investigation of inflammation-related TLR4/NF-κB pathways, MLCK, and related skeleton protein levels showed that TLR4, NF-κB-p65, p-NF-κB-p65, and MLCK levels were increased, and VE cadherin, connexin 43, and claudin 5 were reduced in the M group. DS, FO, FG, Oli, and Y could reduce the protein expression related to the TLR4 pathway to varying degrees, and regulate the protein expression of MLCK, VE cadherin, connexin 43, and claudin 5. It is inferred that the active components of D. sophia improve lung permeability in rats with allergic asthma presumedly by regulating the TLR4/NF-κB signaling pathway to improve airway inflammation, mediating MLCK and connexin, and regulating epithelial damage.


Assuntos
Asma , Animais , Asma/induzido quimicamente , Asma/tratamento farmacológico , Líquido da Lavagem Broncoalveolar , Inflamação/metabolismo , Pulmão , Masculino , Permeabilidade , Ratos
12.
BMC Pregnancy Childbirth ; 22(1): 220, 2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35303823

RESUMO

BACKGROUND: Several studies found an association between periconceptional folic acid supplementation and the risk of childhood asthma. But the epidemiologic evidence is still inconsistent and the underlying biological mechanisms remain unclear. METHODS: We conducted a hospital-based case-control study on childhood asthma with 548 cases and 816 normal controls in Shanghai, China. Mothers of the asthma children were asked about folic acid supplementation before and during pregnancy. Unconditional logistic regression models were employed to control for potential confounders. RESULTS: Periconceptional folic acid supplementation was associated with an increased risk of childhood asthma after adjusting for potential confounders (adjusted OR = 1.28 [95% CI 1.14-1.43]). Moreover, the adjusted OR varied by the timing of starting folic acid supplementation: before gestation: 1.31 [95% CI 1.01-1.70]; in the 1st month of gestation: 1.09 [95% CI 0.96-1.23]; and after the 1st month of gestation: 1.90 [95% CI 1.56-2.30]. We further found that the adjusted OR was the highest when periconceptional folic acid supplementation lasted more than 6 months (< 4 months: 1.21 [95% CI 1.07-1.37]; 4-6 months: 1.06 [95% CI 0.88-1.27]; > 6 months: 1.75 [95% CI 1.35-2.27]). CONCLUSIONS: Periconceptional folic acid supplementation was associated with an increased risk of childhood asthma in offspring. Further research on this issue is warranted.


Assuntos
Asma/induzido quimicamente , Suplementos Nutricionais/efeitos adversos , Ácido Fólico/efeitos adversos , Cuidado Pré-Concepcional , Cuidado Pré-Natal , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Estudos de Casos e Controles , Criança , Pré-Escolar , China , Duração da Terapia , Feminino , Humanos , Gravidez , Fatores de Risco
13.
Pol Arch Intern Med ; 132(2)2022 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-35226440

RESUMO

The first modern description of respiratory syndrome of aspirin hypersensitivity was published over half of the century ago, but the pathogenesis of the disease is still elusive. Just a few years after discovery how aspirin works, Andrew Szczeklik and his co­workers described that asthmatics with aspirin hypersensitivity cross­react to the whole class of nonsteroidal anti­inflammatory drugs. It took rest of his life to seek for an answer on how this disease, nowadays referred to as N ­ERD, develops and how it can be treated. In the meantime, cysteinyl leukotrienes, leukotriene modifying drugs, and novel subpopulations of lymphocytes were discovered. This review on aspirin hypersensitivity documents a progress in our understanding of mechanisms of hypersensitivity to nonsteroidal anti­inflammatory drugs. Current concepts about origin of the disease integrate advances in the field of allergology and inflammatory mechanisms of asthma. However, pharmacological inhibition of prostaglandin biosynthesis by nonsteroidal anti­inflammatory drugs has a pivotal role in these investigations. Presented is a central role of prostaglandin E2 , a double­faced lipid immunoregulatory mediator whose deficiency is related to the administration of an anti­inflammatory drug. Discussed are cysteinyl leukotrienes, the most reliable biomarkers of aspirin hypersensitivity and cells of innate immunity capable of leukotrienes production. Involvement of blood platelets and recently described mucosal basophils are areas of ongoing studies in the disease. Aspirin hypersensitivity is an acquired condition; therefore, the search for genetic predisposition using classic association studies was inconclusive. There is a new hope to explain mechanisms of aspirin hypersensitivity by studies of innate lymphoid cells, which have a central role in the regulation of respiratory mucosa function in asthma.


Assuntos
Asma Induzida por Aspirina , Asma , Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Asma/induzido quimicamente , Asma/tratamento farmacológico , Asma Induzida por Aspirina/tratamento farmacológico , Humanos , Imunidade Inata , Leucotrienos/efeitos adversos , Linfócitos
14.
Clin Exp Allergy ; 52(5): 616-627, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35174566

RESUMO

BACKGROUND: Severe asthma is a major cause of morbidity. Some patients may benefit from biological therapies. Most evaluations of these treatments are derived from randomized controlled trials (RCTs), but few patients are eligible for these trials. Studies involving more diverse groups of participants exist, but there is a lack of precise pooled estimates. OBJECTIVE: This systematic review aims to evaluate the real-world efficacy of recently and nearly licensed biological therapies for severe asthma to assess the generalizability of the RCT data. METHODS: Clinical outcomes including exacerbation rate, oral corticosteroid usage, forced expiratory volume in 1 second (FEV1 ) and fractional exhaled nitric oxide (FeNO) were examined. Studies were assessed for risk of bias using the Critical Appraisal Skills Programme checklist tool. The certainty of evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE). RESULTS: A total of 21 studies examining biologicals in real-world settings were identified; they mostly focused on benralizumab and mepolizumab. The introduction of biologicals reduced the annualzsed exacerbation rate significantly by -3.79 (95% confidence interval [CI] -4.53, -3.04), -3.17 (95% CI -3.74, -2.59) and -6.72 (95% CI -8.47, -4.97) with benralizumab, mepolizumab and reslizumab, respectively. Likewise, improvements were observed in FEV1 (0.17 L 95% CI 0.11, 0.24) and FeNO (-14.23 ppb 95% CI -19.71, -8.75) following the treatment with mepolizumab. After treatment with benralizumab, there was an increase in FEV1 (0.21 L 95% CI 0.08, 0.34). CONCLUSIONS: These data demonstrate that anti-IL5 biologicals may improve the clinical outcomes of patients with severe asthma in a clinic environment with similar effect sizes to RCTs. The data were mainly retrospective and unadjusted, so estimated effect sizes may not be reliable. More data are needed to acquire accurate effect estimates in different subpopulations of patients.


Assuntos
Antiasmáticos , Asma , Produtos Biológicos , Antiasmáticos/uso terapêutico , Anticorpos Monoclonais Humanizados , Asma/induzido quimicamente , Asma/diagnóstico , Asma/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
Oxid Med Cell Longev ; 2022: 9657933, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35154576

RESUMO

Ferroptosis was reported to be involved in the occurrence and development of asthma. However, the potential mechanism underlying the role of ferroptosis in asthma remains unclear. In this study, we established the mouse asthma model following the ovalbumin (OVA) method in C57BL/6 mice and the cell model with IL-13 induction in bronchial epithelial cells (BEAS-2B cells). Treatment of ferrostatin-1 (Ferr-1) and 3-methyladenine (3-MA) decreased iron deposition in IL-13-induced BEAS-2B cells and lung tissues of asthma mice, opposite to that in bronchoalveolar lavage fluid (BALF). Meanwhile, excessive lipid peroxidation asthma model in vivo and in vitro was alleviated by Ferr-1 or 3-MA treatment. In addition, Ferr-1 and 3-MA inhibited the expression of LC-3 in these cells and lung tissues of mice. Moreover, Ferr-1 and 3-MA also suppressed the production of inflammatory cytokines (IL-1ß, IL-6, and TNF-α) and oxidative stress factors (ROS and MDA), while promoting the level of SOD, in vivo and in vitro. Furthermore, application of Ferr-1 exhibited a greater inhibitory effect on iron release and lipid peroxidation in IL-13-induced BEAS-2B cells and asthma mice than 3-MA, accompanied with a weaker effect on ferritinophagy than 3-MA. Collectively, Ferr-1 and 3-MA ameliorated asthma in vivo and in vitro through inhibiting ferroptosis, providing a new strategy for the clinical treatment of asthma.


Assuntos
Adenina/análogos & derivados , Asma/induzido quimicamente , Asma/tratamento farmacológico , Brônquios/citologia , Cicloexilaminas/administração & dosagem , Células Epiteliais/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Interleucina-13/farmacologia , Ovalbumina/efeitos adversos , Fenilenodiaminas/administração & dosagem , Adenina/administração & dosagem , Animais , Asma/metabolismo , Líquido da Lavagem Broncoalveolar/química , Linhagem Celular , Citocinas/metabolismo , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Humanos , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
16.
J Expo Sci Environ Epidemiol ; 32(2): 312-319, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35110684

RESUMO

BACKGROUND: One of the most common pollutants in residences due to gas appliances, NO2 has been shown to increase the risk of asthma attacks after small increases in short term exposure. However, standard environmental sampling methods taken at the regional level overlook chronic intermittent exposure due to lack of temporal and spatial granularity. Further, the EPA and WHO do not currently provide exposure recommendations to at-risk populations. AIMS: A pilot study with pediatric asthma patients was conducted to investigate potential deployment challenges as well as benefits of home-based NO2 sensors and, when combined with a subject's hospital records and self-reported symptoms, the richness of data available for larger-scale epidemiological studies. METHODS: We developed a compact personal NO2 sensor with one minute temporal resolution and sensitivity down to 15 ppb to monitor exposure levels in the home. Patient hospital records were collected along with self-reported symptom diaries, and two example hypotheses were created to further demonstrate how data of this detail may enable study of the impact of NO2 in this sensitive population. RESULTS: 17 patients (55%) had at least 1 h each day with average NO2 exposure >21 ppb. Frequency of acute NO2 exposure >21 ppb was higher in the group with gas stoves (U = 27, p ≤ 0.001), and showed a positive correlation (rs = 0.662, p = 0.037, 95% CI 0.36-0.84) with hospital admissions. SIGNIFICANCE: Similar studies are needed to evaluate the true impact of NO2 in the home environment on at-risk populations, and to provide further data to regulatory bodies when developing updated recommendations.


Assuntos
Poluentes Atmosféricos , Asma , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Asma/induzido quimicamente , Criança , Exposição Ambiental/análise , Estudos de Viabilidade , Habitação , Humanos , Dióxido de Nitrogênio/análise , Projetos Piloto
17.
Int J Mol Sci ; 23(3)2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-35163544

RESUMO

Understanding the interaction between nanoparticles and immune cells is essential for the evaluation of nanotoxicity and development of nanomedicines. However, to date, there is little data on the membrane microstructure and biochemical changes in nanoparticle-loaded immune cells. In this study, we observed the microstructure of nanoparticle-loaded macrophages and changes in lipid droplets using holotomography analysis. Quantitatively analyzing the refractive index distribution of nanoparticle-loaded macrophages, we identified the interactions between nanoparticles and macrophages. The results showed that, when nanoparticles were phagocytized by macrophages, the number of lipid droplets and cell volume increased. The volume and mass of the lipid droplets slightly increased, owing to the absorption of nanoparticles. Meanwhile, the number of lipid droplets increased more conspicuously than the other factors. Furthermore, alveolar macrophages are involved in the development and progression of asthma. Studies have shown that macrophages play an essential role in the maintenance of asthma-related inflammation and tissue damage, suggesting that macrophage cells may be applied to asthma target delivery strategies. Therefore, we investigated the target delivery efficiency of gold nanoparticle-loaded macrophages at the biodistribution level, using an ovalbumin-induced asthma mouse model. Normal and severe asthma models were selected to determine the difference in the level of inflammation in the lung. Consequently, macrophages had increased mobility in models of severe asthma, compared to those of normal asthma disease. In this regard, the detection of observable differences in nanoparticle-loaded macrophages may be of primary interest, as an essential endpoint analysis for investigating nanomedical applications and immunotheragnostic strategies.


Assuntos
Asma/diagnóstico por imagem , Ouro/farmacocinética , Lipopolissacarídeos/efeitos adversos , Pulmão/química , Macrófagos/transplante , Ovalbumina/efeitos adversos , Animais , Asma/induzido quimicamente , Asma/metabolismo , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Estudos de Viabilidade , Feminino , Pulmão/diagnóstico por imagem , Macrófagos/química , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Nanopartículas Metálicas , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7 , Distribuição Tecidual , Tomografia
18.
Int J Mol Sci ; 23(3)2022 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-35163503

RESUMO

To investigate the effect of eupatilin in asthma treatment, we evaluated its therapeutic effect and related signal transduction in OVA-induced asthmatic mice and LPS-stimulated RAW264.7 cells. The BALF was tested for changes in lung inflammatory cells. Th2 cytokines in the BALF and OVA-IgE in the serum were measured by ELISA. H&E and PAS staining were used to evaluate histopathological changes in mouse lungs. The key proteins NF-κB, MAPK, and Nrf2 in lung tissues were quantitatively analyzed by Western blotting. Finally, we evaluated the effect of eupatilin on cytokines and related protein expression in LPS-stimulated RAW 264.7 cells in vitro. In OVA-induced asthmatic mice, eupatilin reduced the numbers of inflammatory cells, especially neutrophils and eosinophils. Eupatilin also decreased the levels of IL-5, IL-13 in the BALF and OVA-IgE in the serum. Furthermore, eupatilin inhibited the activation of NF-κB and MAPK pathways and increased the expression of Nrf2 in OVA-induced asthmatic mice. In vitro, eupatilin significantly reduced LPS-stimulated NO, IL-6, and ROS production. Additionally, the NF-κB, MAPK, and Nrf2 protein expression in LPS-stimulated RAW264.7 cells was consistent with that in OVA-induced asthmatic lung tissues. In summary, eupatilin attenuated OVA-induced asthma by regulating NF-κB, MAPK, and Nrf2 signaling pathways. These results suggest the utility of eupatilin as an anti-inflammatory drug for asthma treatment.


Assuntos
Asma/tratamento farmacológico , Flavonoides/administração & dosagem , Lipopolissacarídeos/efeitos adversos , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Ovalbumina/efeitos adversos , Animais , Asma/induzido quimicamente , Asma/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Modelos Animais de Doenças , Eosinófilos/efeitos dos fármacos , Eosinófilos/metabolismo , Feminino , Flavonoides/química , Flavonoides/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Lipopolissacarídeos/imunologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Estrutura Molecular , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Ovalbumina/imunologia , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo
19.
BMC Pulm Med ; 22(1): 61, 2022 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-35148729

RESUMO

BACKGROUND: Exposure to toluene diisocyanate (TDI) is a significant pathogenic factor for asthma. We previously reported that the receptor for advanced glycation end products (RAGE) plays a key role in TDI-induced asthma. Histone deacetylase (HDAC) has been reported to be important in asthmatic pathogenesis. However, its effect on TDI-induced asthma is not known. The aim of this study was to determine the role of RAGE and HDAC in regulating airway inflammation using a TDI-induced murine asthma model. METHODS: BALB/c mice were sensitized and challenged with TDI to establish an asthma model. FPS-ZM1 (RAGE inhibitor), JNJ-26482585 and romidepsin (HDAC inhibitors) were administered intraperitoneally before each challenge. In vitro, the human bronchial epithelial cell line 16HBE was stimulated with TDI-human serum albumin (TDI-HSA). RAGE knockdown cells were constructed and evaluated, and MK2006 (AKT inhibitor) was also used in the experiments. RESULTS: In TDI-induced asthmatic mice, the expression of RAGE, HDAC1, and p-AKT/t-AKT was upregulated, and these expressions were attenuated by FPS-ZM1. Airway reactivity, Th2 cytokine levels in lymph supernatant, IgE, airway inflammation, and goblet cell metaplasia were significantly increased in the TDI-induced asthmatic mice. These increases were suppressed by JNJ-26482585 and romidepsin. In addition, JNJ-26482585 and romidepsin ameliorated the redistribution of E-cadherin and ß-catenin in TDI-induced asthma. In TDI-HSA-stimulated 16HBE cells, knockdown of RAGE attenuated the upregulation of HDAC1 and phospho-AKT (p-AKT). Treatment with the AKT inhibitor MK2006 suppressed TDI-induced HDAC1 expression. CONCLUSIONS: These findings indicate that RAGE modulates HDAC1 expression via the PI3K/AKT pathway, and that inhibition of HDAC prevents TDI-induced airway inflammation.


Assuntos
Asma/prevenção & controle , Histona Desacetilase 1/metabolismo , Inflamação/prevenção & controle , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Asma/induzido quimicamente , Benzamidas/farmacologia , Linhagem Celular , Citocinas/metabolismo , Depsipeptídeos/farmacologia , Modelos Animais de Doenças , Histona Desacetilase 1/antagonistas & inibidores , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fosfatidilinositol 3-Quinases/metabolismo , Receptor para Produtos Finais de Glicação Avançada/antagonistas & inibidores , Tolueno 2,4-Di-Isocianato/toxicidade
20.
Artigo em Inglês | MEDLINE | ID: mdl-35162850

RESUMO

Studies investigating the association between urinary Polycyclic Aromatic Hydrocarbons (PAHs) and asthma in children provided inhomogeneous results. We aimed to use Mediation Analysis to discover whether a link between urinary PAHs and lung function exists and if it might be ascribed to a direct or a symptom-mediated (indirect) effect in children with asthma. This single-center prospective study was conducted in Palermo, Italy, between March and July 2017 and involved 50 children with persistent mild-moderate asthma, aged 6-11 years. At each time visit (day 0, 30, 60, and 90), physical examination, spirometry, and urine collection for detection of urinary cotinine and PAHs were performed. A symptom score was computed. The sum of individually calculated molar mass of nine PAH metabolites (ΣPAH), naphthalene metabolites (ΣPAHn) and phenanthrene metabolites (ΣPAHp) were calculated. Three children withdrew from the study due to technical problems (n = 1) and adverse events (n = 2). PAHs indirect effects on FEV1 (ΣPAH: -0.011, p = 0.04; ΣPAHn: -0.011, p = 0.04; ΣPAHp: -0.012, p < 0.001) and FVC (ΣPAH: -0.012, p = 0.02; ΣPAHn: -0.0126, p = 0.02; ΣPAHp: -0.013, p < 0.001) were statistically significant. In conclusion, PAHs exposures have significant indirect (symptom-mediated) effects on lung function, emphasizing the role of PAHs-induced respiratory morbidity in decreasing lung function in children with asthma.


Assuntos
Asma , Hidrocarbonetos Policíclicos Aromáticos , Asma/induzido quimicamente , Criança , Humanos , Pulmão , Análise de Mediação , Hidrocarbonetos Policíclicos Aromáticos/análise , Estudos Prospectivos
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