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1.
Int J Mol Sci ; 22(9)2021 May 07.
Artigo em Inglês | MEDLINE | ID: covidwho-1231495

RESUMO

Extracellular vesicles (EVs) are membranous structures, which are secreted by almost every cell type analyzed so far. In addition to their importance for cell-cell communication under physiological conditions, EVs are also released during pathogenesis and mechanistically contribute to this process. Here we summarize their functional relevance in asthma, one of the most common chronic non-communicable diseases. Asthma is a complex persistent inflammatory disorder of the airways characterized by reversible airflow obstruction and, from a long-term perspective, airway remodeling. Overall, mechanistic studies summarized here indicate the importance of different subtypes of EVs and their variable cargoes in the functioning of the pathways underlying asthma, and show some interesting potential for the development of future therapeutic interventions. Association studies in turn demonstrate a good diagnostic potential of EVs in asthma.


Assuntos
Asma/metabolismo , Vesículas Extracelulares/metabolismo , Animais , Asma/genética , Asma/microbiologia , Asma/fisiopatologia , Biomarcadores/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Modelos Biológicos
2.
Int J Mol Sci ; 22(9)2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34067156

RESUMO

Extracellular vesicles (EVs) are membranous structures, which are secreted by almost every cell type analyzed so far. In addition to their importance for cell-cell communication under physiological conditions, EVs are also released during pathogenesis and mechanistically contribute to this process. Here we summarize their functional relevance in asthma, one of the most common chronic non-communicable diseases. Asthma is a complex persistent inflammatory disorder of the airways characterized by reversible airflow obstruction and, from a long-term perspective, airway remodeling. Overall, mechanistic studies summarized here indicate the importance of different subtypes of EVs and their variable cargoes in the functioning of the pathways underlying asthma, and show some interesting potential for the development of future therapeutic interventions. Association studies in turn demonstrate a good diagnostic potential of EVs in asthma.


Assuntos
Asma/metabolismo , Vesículas Extracelulares/metabolismo , Animais , Asma/genética , Asma/microbiologia , Asma/fisiopatologia , Biomarcadores/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Modelos Biológicos
3.
Molecules ; 26(11)2021 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-34071080

RESUMO

The main purpose of this study was to investigate whether the blockade of the interaction between the receptor activator of nuclear factor-κB (NF-ĸB) ligand (RANKL) and its receptor RANK as well as the blockade of NF-κB inhibitor kinase (IKK) and of NF-κB translocation have the potential to suppress the pathogenesis of allergic asthma by inhibition and/or enhancement of the production by CD4+ and CD8+ T cells of important cytokines promoting (i.e., IL-4 and IL-17) and/or inhibiting (i.e., IL-10 and TGF-ß), respectively, the development of allergic asthma. Studies using ovalbumin(OVA)-immunized mice have demonstrated that all the tested therapeutic strategies prevented the OVA-induced increase in the absolute number of IL-4- and IL-17-producing CD4+ T cells (i.e., Th2 and Th17 cells, respectively) indirectly, i.e., through the inhibition of the clonal expansion of these cells in the mediastinal lymph nodes. Additionally, the blockade of NF-κB translocation and RANKL/RANK interaction, but not IKK, prevented the OVA-induced increase in the percentage of IL-4-, IL-10- and IL-17-producing CD4+ T cells. These latter results strongly suggest that both therapeutic strategies can directly decrease IL-4 and IL-17 production by Th2 and Th17 cells, respectively. This action may constitute an important mechanism underlying the anti-asthmatic effect induced by the blockade of NF-κB translocation and of RANKL/RANK interaction. Thus, in this context, both these therapeutic strategies seem to have an advantage over the blockade of IKK. None of the tested therapeutic strategies increased both the absolute number and frequency of IL-10- and TGF-ß-producing Treg cells, and hence they lacked the potential to inhibit the development of the disease via this mechanism.


Assuntos
Asma/imunologia , Asma/metabolismo , Animais , Asma/fisiopatologia , Linfócitos T CD8-Positivos/imunologia , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Hipersensibilidade/fisiopatologia , Imunoglobulina E/imunologia , Interleucina-17/imunologia , Interleucina-4/imunologia , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Ligante RANK/metabolismo , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Células Th17/efeitos dos fármacos , Células Th2/efeitos dos fármacos
4.
Respirology ; 26(6): 552-565, 2021 06.
Artigo em Inglês | MEDLINE | ID: covidwho-1218177

RESUMO

Coronavirus disease 2019 (COVID-19) caused by infection with severe acute respiratory syndrome coronavirus 2 was first detected in Wuhan, China, in late 2019 and continues to spread worldwide. Persistent questions remain about the relationship between the severity of COVID-19 and comorbid diseases, as well as other chronic pulmonary conditions. In this systematic review and meta-analysis, we aimed to examine in detail whether the underlying chronic obstructive pulmonary diseases (COPD), asthma and chronic respiratory diseases (CRDs) were associated with an increased risk of more severe COVID-19. A comprehensive literature search was performed using five international search engines. In the initial search, 722 articles were identified. After eliminating duplicate records and further consideration of eligibility criteria, 53 studies with 658,073 patients were included in the final analysis. COPD was present in 5.2% (2191/42,373) of patients with severe COVID-19 and in 1.4% (4203/306,151) of patients with non-severe COVID-19 (random-effects model; OR = 2.58, 95% CI = 1.99-3.34, Z = 7.15, p < 0.001). CRD was present in 8.6% (3780/44,041) of patients with severe COVID-19 and in 5.7% (16,057/280,447) of patients with non-severe COVID-19 (random-effects model; OR = 2.14, 95% CI = 1.74-2.64, Z = 7.1, p < 0.001). Asthma was present in 2.3% (1873/81,319) of patients with severe COVID-19 and in 2.2% (11,796/538,737) of patients with non-severe COVID-19 (random-effects model; OR = 1.13, 95% CI = 0.79-1.60, Z = 0.66, p = 0.50). In conclusion, comorbid COPD and CRD were clearly associated with a higher severity of COVID-19; however, no association between asthma and severe COVID-19 was identified.


Assuntos
Asma/epidemiologia , COVID-19/epidemiologia , Gravidade do Paciente , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Asma/fisiopatologia , Doença Crônica/epidemiologia , Comorbidade , Humanos , SARS-CoV-2
5.
JAMA ; 325(24): 2466-2479, 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34009257

RESUMO

Importance: The benefits and harms of adding long-acting muscarinic antagonists (LAMAs) to inhaled corticosteroids (ICS) and long-acting ß2-agonists (LABAs) for moderate to severe asthma remain unclear. Objective: To systematically synthesize the outcomes and adverse events associated with triple therapy (ICS, LABA, and LAMA) vs dual therapy (ICS plus LABA) in children and adults with persistent uncontrolled asthma. Data Sources: MEDLINE, Embase, CENTRAL, ICTRP, FDA, and EMA databases from November 2017, to December 8, 2020, without language restriction. Study Selection: Two investigators independently selected randomized clinical trials (RCTs) comparing triple vs dual therapy in patients with moderate to severe asthma. Data Extraction and Synthesis: Two reviewers independently extracted data and assessed risk of bias. Random-effects meta-analyses, including individual patient-level exacerbation data, were used. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used to assess certainty (quality) of the evidence. Main Outcomes and Measures: Severe exacerbations, asthma control (measured using the Asthma Control Questionnaire [ACQ-7], a 7-item list with each item ranging from 0 [totally controlled] to 6 [severely uncontrolled]; minimal important difference, 0.5), quality of life (measured using the Asthma-related Quality of Life [AQLQ] tool; score range, 1 [severely impaired] to 7 [no impairment]; minimal important difference, 0.5), mortality, and adverse events. Results: Twenty RCTs using 3 LAMA types that enrolled 11 894 children and adults (mean age, 52 years [range, 9-71 years]; 57.7% female) were included. High-certainty evidence showed that triple therapy vs dual therapy was significantly associated with a reduction in severe exacerbation risk (9 trials [9932 patients]; 22.7% vs 27.4%; risk ratio, 0.83 [95% CI, 0.77 to 0.90]) and an improvement in asthma control (14 trials [11 230 patients]; standardized mean difference [SMD], -0.06 [95% CI, -0.10 to -0.02]; mean difference in ACQ-7 scale, -0.04 [95% CI, -0.07 to -0.01]). There were no significant differences in asthma-related quality of life (7 trials [5247 patients]; SMD, 0.05 [95% CI, -0.03 to 0.13]; mean difference in AQLQ score, 0.05 [95% CI, -0.03 to 0.13]; moderate-certainty evidence) or mortality (17 trials [11 595 patients]; 0.12% vs 0.12%; risk ratio, 0.96 [95% CI, 0.33 to 2.75]; high-certainty evidence) between dual and triple therapy. Triple therapy was significantly associated with increased dry mouth and dysphonia (10 trials [7395 patients]; 3.0% vs 1.8%; risk ratio, 1.65 [95% CI, 1.14 to 2.38]; high-certainty evidence), but treatment-related and serious adverse events were not significantly different between groups (moderate-certainty evidence). Conclusions and Relevance: Among children (aged 6 to 18 years) and adults with moderate to severe asthma, triple therapy, compared with dual therapy, was significantly associated with fewer severe asthma exacerbations and modest improvements in asthma control without significant differences in quality of life or mortality.


Assuntos
Corticosteroides/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Antiasmáticos/administração & dosagem , Asma/tratamento farmacológico , Antagonistas Muscarínicos/administração & dosagem , Administração por Inalação , Adulto , Antiasmáticos/efeitos adversos , Asma/mortalidade , Asma/fisiopatologia , Criança , Quimioterapia Combinada/efeitos adversos , Volume Expiratório Forçado , Humanos , Nebulizadores e Vaporizadores , Qualidade de Vida , Índice de Gravidade de Doença , Exacerbação dos Sintomas , Xerostomia/induzido quimicamente
6.
Respirology ; 26(6): 552-565, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33955623

RESUMO

Coronavirus disease 2019 (COVID-19) caused by infection with severe acute respiratory syndrome coronavirus 2 was first detected in Wuhan, China, in late 2019 and continues to spread worldwide. Persistent questions remain about the relationship between the severity of COVID-19 and comorbid diseases, as well as other chronic pulmonary conditions. In this systematic review and meta-analysis, we aimed to examine in detail whether the underlying chronic obstructive pulmonary diseases (COPD), asthma and chronic respiratory diseases (CRDs) were associated with an increased risk of more severe COVID-19. A comprehensive literature search was performed using five international search engines. In the initial search, 722 articles were identified. After eliminating duplicate records and further consideration of eligibility criteria, 53 studies with 658,073 patients were included in the final analysis. COPD was present in 5.2% (2191/42,373) of patients with severe COVID-19 and in 1.4% (4203/306,151) of patients with non-severe COVID-19 (random-effects model; OR = 2.58, 95% CI = 1.99-3.34, Z = 7.15, p < 0.001). CRD was present in 8.6% (3780/44,041) of patients with severe COVID-19 and in 5.7% (16,057/280,447) of patients with non-severe COVID-19 (random-effects model; OR = 2.14, 95% CI = 1.74-2.64, Z = 7.1, p < 0.001). Asthma was present in 2.3% (1873/81,319) of patients with severe COVID-19 and in 2.2% (11,796/538,737) of patients with non-severe COVID-19 (random-effects model; OR = 1.13, 95% CI = 0.79-1.60, Z = 0.66, p = 0.50). In conclusion, comorbid COPD and CRD were clearly associated with a higher severity of COVID-19; however, no association between asthma and severe COVID-19 was identified.


Assuntos
Asma/epidemiologia , COVID-19/epidemiologia , Gravidade do Paciente , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Asma/fisiopatologia , Doença Crônica/epidemiologia , Comorbidade , Humanos , SARS-CoV-2
7.
Pediatr Pulmonol ; 56(7): 1951-1956, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33848402

RESUMO

The Coronavirus disease 2019 (COVID-19) pandemic profoundly impacted health care utilization. We evaluated asthma-related emergency department (ED) and inpatient health care utilization by a county-specific Medicaid population, ages 2-18, during the COVID-19 pandemic and compared it to utilization from a 3-year average including 2017-2019. All-cause ED utilization and asthma medication fill rates were evaluated during the same timeframes. Relative to the 2017-2019 3-year average, cumulative asthma-related ED visits from January through June decreased by 45.8% (p = .03) and inpatient admission rates decreased by 50.5% (p = .03). The decline in asthma-related ED utilization was greater than the reduction of overall ED use during the same time period, suggesting that the decline involved factors specific to asthma and was not due solely to avoidance of health care facilities. Fill rates for asthma controller medications decreased during this time (p = .03) and quick relief medication fill rates had no significant change (p = .31). Multiple factors may have contributed to the decrease in acute asthma health care visits. Locally, decreased air pollution and viral exposures coincided with the "Stay-at-home" order in Ohio, and increased utilization of telehealth for assessment during exacerbations may have impacted outcomes. Identification of the cause of the decline in visit rates could spur new interventions to limit the need for ED and inpatient visits for asthma patients, leading to both economic and health-associated benefits.


Assuntos
Asma/fisiopatologia , COVID-19/epidemiologia , Pandemias , Adolescente , Poluição do Ar , Asma/complicações , Asma/tratamento farmacológico , COVID-19/complicações , COVID-19/virologia , Criança , Pré-Escolar , Serviço Hospitalar de Emergência , Feminino , Humanos , Pacientes Internados , Masculino , Medicaid , Morbidade , Ohio/epidemiologia , Aceitação pelo Paciente de Cuidados de Saúde , Admissão do Paciente/estatística & dados numéricos , SARS-CoV-2 , Telemedicina , Estados Unidos
8.
Pediatr Pulmonol ; 56(7): 1951-1956, 2021 07.
Artigo em Inglês | MEDLINE | ID: covidwho-1179015

RESUMO

The Coronavirus disease 2019 (COVID-19) pandemic profoundly impacted health care utilization. We evaluated asthma-related emergency department (ED) and inpatient health care utilization by a county-specific Medicaid population, ages 2-18, during the COVID-19 pandemic and compared it to utilization from a 3-year average including 2017-2019. All-cause ED utilization and asthma medication fill rates were evaluated during the same timeframes. Relative to the 2017-2019 3-year average, cumulative asthma-related ED visits from January through June decreased by 45.8% (p = .03) and inpatient admission rates decreased by 50.5% (p = .03). The decline in asthma-related ED utilization was greater than the reduction of overall ED use during the same time period, suggesting that the decline involved factors specific to asthma and was not due solely to avoidance of health care facilities. Fill rates for asthma controller medications decreased during this time (p = .03) and quick relief medication fill rates had no significant change (p = .31). Multiple factors may have contributed to the decrease in acute asthma health care visits. Locally, decreased air pollution and viral exposures coincided with the "Stay-at-home" order in Ohio, and increased utilization of telehealth for assessment during exacerbations may have impacted outcomes. Identification of the cause of the decline in visit rates could spur new interventions to limit the need for ED and inpatient visits for asthma patients, leading to both economic and health-associated benefits.


Assuntos
Asma/fisiopatologia , COVID-19/epidemiologia , Pandemias , Adolescente , Poluição do Ar , Asma/complicações , Asma/tratamento farmacológico , COVID-19/complicações , COVID-19/virologia , Criança , Pré-Escolar , Serviço Hospitalar de Emergência , Feminino , Humanos , Pacientes Internados , Masculino , Medicaid , Morbidade , Ohio/epidemiologia , Aceitação pelo Paciente de Cuidados de Saúde , Admissão do Paciente/estatística & dados numéricos , SARS-CoV-2 , Telemedicina , Estados Unidos
9.
Int J Mol Sci ; 22(9)2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33926084

RESUMO

Asthma is a major global health issue. Over 300 million people worldwide suffer from this chronic inflammatory airway disease. Typical clinical symptoms of asthma are characterized by a recurrent wheezy cough, chest tightness, and shortness of breath. The main goals of asthma management are to alleviate asthma symptoms, reduce the risk of asthma exacerbations, and minimize long-term medicinal adverse effects. However, currently available type 2 T helper cells (Th2)-directed treatments are often ineffective due to the heterogeneity of the asthma subgroups, which manifests clinically with variable and poor treatment responses. Personalized precision therapy of asthma according to individualized clinical characteristics (phenotype) and laboratory biomarkers (endotype) is the future prospect. This mini review discusses the molecular mechanisms underlying asthma pathogenesis, including the hot sought-after topic of microbiota, add-on therapies and the potential application of probiotics in the management of asthma.


Assuntos
Asma/tratamento farmacológico , Asma/fisiopatologia , Medicina de Precisão/métodos , Asma/metabolismo , Produtos Biológicos/uso terapêutico , Biomarcadores , Humanos , Microbiota/fisiologia , Fenótipo , Probióticos/uso terapêutico , Células Th2
10.
Tuberk Toraks ; 69(1): 1-8, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33853300

RESUMO

Introduction: Airway hyper-responsiveness (AHR) is a characteristic feature of asthma. The aim of this study was to compare the impulse oscillometry (IOS) and spirometry to methacholine for AHR detection among individuals with clinically hyper-reactive airway disease suggestive of bronchial asthma and baseline spirometry were normal. Materials and Methods: Adults with symptoms suggestive of AHR and normal baseline spirometry test were selected. The short protocol of methacholine challenge test (MCT) was performed for all subjects using IOS and spirometry simultaneously. The primary endpoint was to compare the methacholine dosage causing a 20% drop in forced expiratory volume in one second (FEV1), with methacholine dosage that causing 40% increasing the baseline respiratory resistance at 5 hertz (R5), as measured by IOS. Result: A total of 235 participants were analyzed, 184 (78.2%) had positive test results with R5, while 81 (34.4%) had positive MCT results with FEV1.The sensitivity and specificity of MCT with R5were 87.3%, 64.6%, and MCT with FEV1 were 39.1%, 85.4%, respectively. The area under the receiver operating characteristic (ROC) curve was greater at lower doses of MCT at R5, (AUROC: 0.653; p= 0.01). Conclusions: The results showed higher sensitivity, negative predictive value, and earlier response of the short protocol of MCT with IOS, compared to MCT with spirometry. Our study suggested the utility of IOS in addition to conventional spirometry as a method of choice in MCT for detection of AHR.


Assuntos
Asma/diagnóstico , Cloreto de Metacolina/administração & dosagem , Testes de Função Respiratória/métodos , Hipersensibilidade Respiratória/diagnóstico , Adulto , Obstrução das Vias Respiratórias/diagnóstico , Resistência das Vias Respiratórias , Asma/fisiopatologia , Testes de Provocação Brônquica/métodos , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Oscilometria/métodos , Curva ROC , Sensibilidade e Especificidade , Espirometria/métodos
11.
Nutrients ; 13(4)2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33918391

RESUMO

Per the Centers for Disease Control and Prevention, asthma prevalence has steadily risen since the 1980s. Using data from the National Health and Nutrition Examination Survey (NHANES), we investigated associations between milk consumption and pulmonary function (PF). Multivariable analyses were performed, adjusted for a priori potential confounders for lung function, within the eligible total adult population (n = 11,131) and those self-reporting asthma (n = 1,542), included the following variables: milk-consumption, asthma diagnosis, forced vital capacity (FVC), FVC%-predicted (%), forced expiratory volume in one-second (FEV1), FEV1% and FEV1/FVC. Within the total population, FEV1% and FVC% were significantly associated with regular (5+ days weekly) consumption of exclusively 1% milk in the prior 30-days (ß:1.81; 95% CI: [0.297, 3.325]; p = 0.020 and ß:1.27; [0.16, 3.22]; p = 0.046). Among participants with asthma, varied-regular milk consumption in a lifetime was significantly associated with FVC (ß:127.3; 95% CI: [13.1, 241.4]; p = 0.002) and FVC% (ß:2.62; 95% CI: [0.44, 4.80]; p = 0.006). No association between milk consumption and FEV1/FVC was found, while milk-type had variable influence and significance. Taken together, we found certain milk consumption tendencies were associated with pulmonary function values among normal and asthmatic populations. These findings propound future investigations into the potential role of dairy consumption in altering lung function and asthma outcomes, with potential impact on the protection and maintenance of pulmonary health.


Assuntos
Asma/fisiopatologia , Ingestão de Líquidos/fisiologia , Leite/estatística & dados numéricos , Adulto , Idoso , Animais , Asma/epidemiologia , Estudos Transversais , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Leite/efeitos adversos , Análise Multivariada , Inquéritos Nutricionais , Prevalência , Testes de Função Respiratória , Estados Unidos/epidemiologia , Capacidade Vital , Adulto Jovem
12.
Nutrients ; 13(4)2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33805960

RESUMO

Background: Asthma physiology affects respiratory function and inflammation, factors that may contribute to elevated resting energy expenditure (REE) and altered body composition. Objective: We hypothesized that asthma would present with elevated REE compared to weight-matched healthy controls. Methods: Adults with asthma (n = 41) and healthy controls (n = 20) underwent indirect calorimetry to measure REE, dual-energy X-ray absorptiometry (DEXA) to measure body composition, and 3-day diet records. Clinical assessments included spirometry, fractional exhaled nitric oxide (FENO), and a complete blood count. Results: Asthmatics had greater REE than controls amounting to an increase of ~100 kcals/day, even though body mass index (BMI) and body composition were similar between groups. Inclusion of asthma status and FENO in validated REE prediction equations led to improved estimates. Further, asthmatics had higher white blood cell (control vs. asthma (mean ± SD): 4.7 ± 1.1 vs. 5.9 ± 1.6, p < 0.01) and neutrophil (2.8 ± 0.9 vs. 3.6 ± 1.4, p = 0.02) counts that correlated with REE (both p < 0.01). Interestingly, despite higher REE, asthmatics reported consuming fewer calories (25.1 ± 7.5 vs. 20.3 ± 6.0 kcals/kg/day, p < 0.01) and carbohydrates than controls. Conclusion: REE is elevated in adults with mild asthma, suggesting there is an association between REE and the pathophysiology of asthma.


Assuntos
Asma/fisiopatologia , Metabolismo Basal/fisiologia , Absorciometria de Fóton , Adulto , Composição Corporal/fisiologia , Índice de Massa Corporal , Calorimetria Indireta , Estudos Transversais , Feminino , Humanos , Masculino
13.
J Environ Pathol Toxicol Oncol ; 40(2): 11-21, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33822513

RESUMO

Global industrialization not only improved the quality life of millions but also paved the way to solving many health problems. One among them is allergic asthma, which affects approximately 20% of the global population. Poor air quality is the major culprit in allergic asthma, which not only affects the individual's health, but also impairs his or her life quality and that of family members. Asthma is a chronic pulmonary inflammatory disease characterized by excess mucus production, airway hyperresponsiveness, and bronchoconstriction. Inhalation of corticosteroids, leukotriene modifiers, and ß-adrenergic agonists is one treatment prescribed to control the symptoms of asthma, but there is still no effective cure. Phytochemicals such as carotenoids, phenolics, alkaloids, and nitrogen and organosulfur compounds are proven to possess immense pharmacological properties. Betalain is one such phytochemical present in plants of the order Caryophyllales. It is a water-soluble nitrogen-based pigment proven to possess antimicrobial, antioxidant, anti-inflammatory, hepatoprotective, antilipidemic, antidiabetic, and anticancer properties. We examined the curative potential of betalain against allergic asthma in a mouse model. Betalain treatment effectively decreased lung weight and infiltration of inflammatory cells in BAL fluid, and lowered IgE, eotaxin, and cytokine levels in asthma-induced mice. It also improved pulmonary mechanics and decreased oxidative stress and nitric oxide levels. Betalain significantly decreased gene expression of TGF-ß and its downstream signaling Smad proteins. Lung histology confirmed that betalain protected the lung tissue of mice from ovalbumin-induced allergic asthma. Overall, our results show that betalain is a potent antiallergic drug that effectively protects mice from ovalbumin-induced allergic asthma. With further research, it can be prescribed as a treatment for asthma in humans.


Assuntos
Antiasmáticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Asma/tratamento farmacológico , Betalaínas/uso terapêutico , Proteínas Smad/imunologia , Fator de Crescimento Transformador beta1/imunologia , Alérgenos , Animais , Antiasmáticos/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Asma/imunologia , Asma/patologia , Asma/fisiopatologia , Betalaínas/farmacologia , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Imunoglobulina E/imunologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Pulmão/fisiopatologia , Camundongos Endogâmicos BALB C , Ovalbumina , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/genética , Fator de Crescimento Transformador beta1/genética
14.
Pan Afr Med J ; 38: 74, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33889240

RESUMO

Boerhaave's syndrome is an uncommon syndrome characterized by spontaneous rupture of the oesophagus with a high mortality rate. While excessive alcohol intake and binge-eating are the classic precipitants of this syndrome, medication-induced vomiting causing Booerhave's is quite uncommon. Traditionally managed operatively, conservative management is being increasingly reported in selected cases. We report the case of 21-year-old male with who developed sudden onset chest pain and dyspnoea after pentazocine induced vomiting. He was referred after lack of response to initial treatment for acute severe asthma. A chest CT scan showed pneumomediastinum, subcutaneous emphysema and oesophageal tear. He was managed conservatively with oxygen therapy, nil per mouth and antibiotics with improvement of symptoms and discharge after 8 days.


Assuntos
Perfuração Esofágica/diagnóstico por imagem , Doenças do Mediastino/diagnóstico por imagem , Pentazocina/efeitos adversos , Vômito/complicações , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Antibacterianos/administração & dosagem , Asma/fisiopatologia , Asma/terapia , Dor no Peito/etiologia , Dispneia/etiologia , Perfuração Esofágica/etiologia , Perfuração Esofágica/terapia , Humanos , Masculino , Doenças do Mediastino/etiologia , Doenças do Mediastino/terapia , Oxigenoterapia , Pentazocina/administração & dosagem , Tomografia Computadorizada por Raios X , Vômito/induzido quimicamente , Adulto Jovem
15.
Neurosci Lett ; 751: 135795, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33667601

RESUMO

Neural changes underly hyperresponsiveness in asthma and other airway diseases. Afferent sensory nerves, nerves within the brainstem, and efferent parasympathetic nerves all contribute to airway hyperresponsiveness. Inflammation plays a critical role in these nerve changes. Chronic inflammation and pre-natal exposures lead to increased airway innervation and structural changes. Acute inflammation leads to shifts in neurotransmitter expression of afferent nerves and dysfunction of M2 muscarinic receptors on efferent nerve endings. Eosinophils and macrophages drive these changes through release of inflammatory mediators. Novel tools, including optogenetics, two photon microscopy, and optical clearing and whole mount microscopy, allow for improved studies of the structure and function of airway nerves and airway hyperresponsiveness.


Assuntos
Asma/fisiopatologia , Neurônios Aferentes/metabolismo , Sistema Nervoso Parassimpático/fisiologia , Animais , Asma/metabolismo , Humanos , Neurônios Aferentes/fisiologia , Optogenética/métodos , Sistema Nervoso Parassimpático/metabolismo , Receptores Muscarínicos/genética , Receptores Muscarínicos/metabolismo , Transdução de Sinais
16.
Ann Allergy Asthma Immunol ; 127(1): 91-99, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33775900

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic period is experiencing better asthma control, fewer exacerbations, and health care utilization, with limited data on factors that could explain this phenomenon. OBJECTIVE: To confirm these improved asthma outcomes during COVID-19 and evaluate potential contributing factors. METHODS: In 18,912 pediatric patients with asthma treated in the Children's Hospital of Orange County network from 2017 to 2020, monthly asthma-related encounters and medication summaries were extracted from electronic health records, particulate matter 2.5 (PM2.5) air pollution from the California Air Resources Board, and influenza-like illness from Illness Surveillance Network for the first 6 months of each year. Changes in outcomes between January to March and April to June (post-COVID-19 shutdown in 2020) were compared with historical data using generalized estimating equations analyses for patient outcomes and generalized linear models for pollution exceedance, influenza-positive, and telehealth visit rates. RESULTS: During COVID-19, we found 78%, 90%, 68% reductions in hospitalization, emergency department visits, and exacerbations, respectively, compared with pre-COVID-19 2020, with significantly greater changes than the same time period of 2017 to 2019 and significant reductions in albuterol and inhaled corticosteroid use (P < .05). Emergency department visit reduction was not seen for African Americans. The PM2.5 and influenza rates were also significantly reduced during COVID-19 (P < .05). Increased rates in telehealth visits were greater in the publicly insured group when compared with commercially insured. CONCLUSION: Our data confirm reduced health care utilization and suggest better asthma control during COVID-19, except for African Americans. This was associated with a significant increase in telehealth visits and reductions in PM2.5 and influenza infections, but not better asthma controller adherence.


Assuntos
Asma/tratamento farmacológico , Asma/fisiopatologia , COVID-19/epidemiologia , Influenza Humana/epidemiologia , Adolescente , Corticosteroides/uso terapêutico , Albuterol/uso terapêutico , COVID-19/diagnóstico , COVID-19/prevenção & controle , California/epidemiologia , Criança , Pré-Escolar , Registros Eletrônicos de Saúde , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Hospitalização/estatística & dados numéricos , Hospitais Pediátricos , Humanos , Influenza Humana/diagnóstico , Modelos Lineares , Masculino , Material Particulado/análise , SARS-CoV-2 , Telemedicina/estatística & dados numéricos
17.
Am J Physiol Lung Cell Mol Physiol ; 320(5): L880-L891, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: covidwho-1232370

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic spreading at an alarming rate has taken a heavy toll on the public healthcare systems and economies worldwide. An abnormal and overactivated inflammatory response is occasionally elicited by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and this hyperinflammation is associated with worse prognosis of COVID-19. Theoretically, one would expect patients with asthma to be at a greater risk of SARS-CoV-2 infection considering their increased susceptibility to common respiratory virus-associated exacerbations. Surprisingly, current data do not consistently suggest an increased prevalence of asthma among patients with COVID-19. Considering the high global prevalence of asthma, the characteristics of the disease and/or their conventional therapy might play a role in their potential defense against COVID-19. This may be attributed to the T helper type 2 immune response predominantly seen in patients with asthma. Likewise, asthma therapeutics, including corticosteroids and biologics, may in fact benefit the patients with asthma by alleviating the development of hyperinflammation. On the other hand, elevated IL-17 levels are characteristically seen in a subset of asthma patients with severe disease as well as in patients with COVID-19. Targeting the IL-17 pathway as a treatment strategy could plausibly alleviate acute respiratory distress syndrome (ARDS) in patients with COVID-19 and asthma demonstrating a predominant T helper type 17 response. A clinical trial including a drug targeting this pathway may thus, constitute a logical addition to the global pursuit for effective therapeutics against COVID-19. The complex interplay between the asthma endotypes and COVID-19 is not very well understood and will be discussed in this mini-review.


Assuntos
Asma/fisiopatologia , COVID-19/patologia , SARS-CoV-2/isolamento & purificação , COVID-19/virologia , Humanos , Fatores de Risco
18.
BMJ Open Respir Res ; 8(1)2021 03.
Artigo em Inglês | MEDLINE | ID: covidwho-1150244

RESUMO

INTRODUCTION: SARS-CoV-2 has restricted access to face-to-face delivery of pulmonary rehabilitation (PR). Evidence suggests that telehealth-PR is non-inferior to outpatient PR. However, it is unknown whether patients who have been referred to face-to-face programmes can feasibly complete an online-PR programme. METHODS: This service evaluation used a mixed-methods approach to investigate a rapid PR service remodelling using the University of Gloucestershire eLearn Moodle platform. Quantitative baseline demographic and PR outcome data were collected from online-PR participants, and semistructured interviews were completed with PR staff and participants. RESULTS: Twenty-five individuals were eligible from a PR waiting list. Thirteen declined participation and 14 completed PR. Significant pre-post online PR improvements were achieved in 1 min sit-to-stand (CI 2.1 to 9 (p=0.004)), Generalised Anxiety Disorder (CI -0.3 to -2.6 (p=0.023)), Primary Health Questionnaire-9 (CI -0.3 to -5.1 (p=0.029)), Chronic Respiratory Questionnaire dyspnoea (CI 0.5 to 1.3 (p=0.001)), fatigue (CI 0.7 to 2 (p=0.0004)), emotion (CI 0.7 to 1.7 (p=0.0002)), mastery (CI 0.4 to 1.3 (p=0.001)). Interviews indicated that patient PR inclusion was made possible with digital support and a PR introduction session improved participant engagement and safety. Incremental progression of exercise was perceived as more successful online compared with face-to-face PR. However, perceptions were that education sessions were less successful. Online-PR required significant staff time resource. DISCUSSION: Online-PR improves patient outcomes and is feasible and acceptable for individuals referred for face-to-face PR in the context of a requirement for social distancing. Face-to-face programmes can be adapted in a rapid fashion with both staff and participants perceiving benefit. Future pragmatic trials are now warranted comparing online-PR including remote assessments to centre-based PR with suitably matched outcomes, and patient and staff perceptions sought regarding barriers and facilitators of online delivery.


Assuntos
Internet , Modalidades de Fisioterapia , Doença Pulmonar Obstrutiva Crônica/reabilitação , Telerreabilitação/métodos , Idoso , Idoso de 80 Anos ou mais , Ansiedade/psicologia , Asma/fisiopatologia , Asma/psicologia , Asma/reabilitação , COVID-19 , Depressão/psicologia , Tolerância ao Exercício , Estudos de Viabilidade , Feminino , Humanos , Doenças Pulmonares Intersticiais/fisiopatologia , Doenças Pulmonares Intersticiais/psicologia , Doenças Pulmonares Intersticiais/reabilitação , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/psicologia , Qualidade de Vida , SARS-CoV-2 , Resultado do Tratamento
19.
Ann Allergy Asthma Immunol ; 127(1): 91-99, 2021 07.
Artigo em Inglês | MEDLINE | ID: covidwho-1198608

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic period is experiencing better asthma control, fewer exacerbations, and health care utilization, with limited data on factors that could explain this phenomenon. OBJECTIVE: To confirm these improved asthma outcomes during COVID-19 and evaluate potential contributing factors. METHODS: In 18,912 pediatric patients with asthma treated in the Children's Hospital of Orange County network from 2017 to 2020, monthly asthma-related encounters and medication summaries were extracted from electronic health records, particulate matter 2.5 (PM2.5) air pollution from the California Air Resources Board, and influenza-like illness from Illness Surveillance Network for the first 6 months of each year. Changes in outcomes between January to March and April to June (post-COVID-19 shutdown in 2020) were compared with historical data using generalized estimating equations analyses for patient outcomes and generalized linear models for pollution exceedance, influenza-positive, and telehealth visit rates. RESULTS: During COVID-19, we found 78%, 90%, 68% reductions in hospitalization, emergency department visits, and exacerbations, respectively, compared with pre-COVID-19 2020, with significantly greater changes than the same time period of 2017 to 2019 and significant reductions in albuterol and inhaled corticosteroid use (P < .05). Emergency department visit reduction was not seen for African Americans. The PM2.5 and influenza rates were also significantly reduced during COVID-19 (P < .05). Increased rates in telehealth visits were greater in the publicly insured group when compared with commercially insured. CONCLUSION: Our data confirm reduced health care utilization and suggest better asthma control during COVID-19, except for African Americans. This was associated with a significant increase in telehealth visits and reductions in PM2.5 and influenza infections, but not better asthma controller adherence.


Assuntos
Asma/tratamento farmacológico , Asma/fisiopatologia , COVID-19/epidemiologia , Influenza Humana/epidemiologia , Adolescente , Corticosteroides/uso terapêutico , Albuterol/uso terapêutico , COVID-19/diagnóstico , COVID-19/prevenção & controle , California/epidemiologia , Criança , Pré-Escolar , Registros Eletrônicos de Saúde , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Hospitalização/estatística & dados numéricos , Hospitais Pediátricos , Humanos , Influenza Humana/diagnóstico , Modelos Lineares , Masculino , Material Particulado/análise , SARS-CoV-2 , Telemedicina/estatística & dados numéricos
20.
Int Immunopharmacol ; 95: 107342, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33684878

RESUMO

Autophagy plays an essential role in modulating asthma progression. MiR-20a-5p can regulate autophagy, but its effects on allergic asthma are still unclear. The aim of this study was to explore the potential of miR-20a-5p on autophagy-modulated airway remodeling and to reveal the underlying molecular mechanisms. We found that miR-20a-5p expression was markedly down-regulated in lung of ovalbumin (OVA)-induced mouse model with allergic asthma and in cells stimulated by OVA. Meanwhile, autophagy, apoptosis, fibrosis and inflammatory response were detected in pulmonary tissues from OVA-treated mice. Importantly, luciferase assays showed that ATG7 was a target of miR-20a-5p. We also found that miR-20a-5p over-expression markedly reduced ATG7, while its inhibition promoted ATG7 in cells. In addition, over-expressing miR-20a-5p in OVA-treated cells significantly decreased ATG7 expression levels, along with markedly reduced autophagy, apoptotic cell death, fibrosis and inflammatory response. These results were similar to the effects of autophagy inhibitor 3-Methyladenine (3-MA), indicating that miR-20a-5p was involved in autophagy-induced apoptosis, fibrosis and inflammation. In vivo experiments further demonstrated that miR-20a-5p over-expression was associated with ATG7 reduction in parallel with the alleviated airway remodeling in OVA-treated mice also through suppressing collagen accumulation, apoptosis and inflammation. Similarly, animal studies further confirmed that miR-20a-5p functioned as an autophagy inhibitor to mitigate allergic asthma development. Therefore, miR-20a-5p may be a promising biomarker and therapeutic target during asthma progression by regulating ATG7-modulated autophagy.


Assuntos
Asma/genética , Proteína 7 Relacionada à Autofagia/imunologia , MicroRNAs/imunologia , Alérgenos , Animais , Apoptose , Asma/imunologia , Asma/patologia , Asma/fisiopatologia , Biomarcadores , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Fibrose , Inflamação/genética , Inflamação/imunologia , Inflamação/patologia , Inflamação/fisiopatologia , Pulmão/imunologia , Pulmão/patologia , Camundongos Endogâmicos C57BL , Ovalbumina
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