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1.
Clin Exp Allergy ; 52(1): 115-126, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34431147

RESUMO

BACKGROUND: Genetic variants of dipeptidyl peptidase 10 (DPP10) have been suggested to contribute to the development of NSAID-exacerbated respiratory disease (NERD). However, the mechanisms of how DPP10 contributes to NERD phenotypes remain unclear. OBJECTIVE: To demonstrate the exact role of DPP10 in the pathogenesis of NERD. METHODS: Patients with NERD (n = 110), those with aspirin-tolerant asthma (ATA, n = 130) and healthy control subjects (HCs, n = 80) were enrolled. Clinical characteristics were analysed according to the serum DPP10 levels in both NERD and ATA groups. The function of DPP10 in airway inflammation and remodelling was investigated with in vitro, ex vivo and in vivo experiments. RESULTS: NERD patients had higher levels of serum DPP10 and TGF-ß1 with lower FEV1 than ATA patients or HCs (p < .05 for each). NERD patients with higher DPP10 levels had higher TGF-ß1, but lower FEV1 (p < .05 for all), whilst no differences were noted in ATA patients. Moreover, the seum DPP10 levels had a positive correlation with TGF-ß1 (r = 0.384, p < .001), but a negative correlation with FEV1 (r = -0.230, p = .016) in NERD patients. In in vitro studies, expression of DPP10 in airway epithelial cells was enhanced by TGF-ß1 treatments. Furthermore, DPP10 was found to be produced from immune cells and this molecule induced the ERK phosphorylation in airway epithelial cells, which was suppressed by anti-DPP10 treatment. In asthmatic mouse models, increased levels of DPP10 in the serum and TGF-ß1 in the bronchoalveolar lavage fluid were noted, which were suppressed by anti-DPP10 treatment. Moreover, anti-DPP10 treatment inhibited the ERK phosphorylation and extracellular matrix deposition in the lungs. CONCLUSIONS AND CLINICAL RELEVANCE: These findings suggest that increased production of DPP10 may contribute to TGF-ß1-mediated airway dysfunction in NERD patients, where blockade of DPP10 may have potential benefits.


Assuntos
Asma , Dipeptidil Peptidases e Tripeptidil Peptidases/metabolismo , Doenças Respiratórias , Animais , Anti-Inflamatórios não Esteroides , Asma/metabolismo , Dipeptidil Peptidases e Tripeptidil Peptidases/genética , Humanos , Pulmão/metabolismo , Camundongos , Doenças Respiratórias/patologia , Fator de Crescimento Transformador beta1
2.
Biomed Res Int ; 2022: 4168308, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35941975

RESUMO

Acupoint application has been used in China to treat various illnesses for ages. In cough variant asthma (CVA), the main clinical sign is episodic night cough. Acupoint application therapy of traditional Chinese medicine is an effective procedure to treat cough variant asthma. The current study is designed to systematically assess the effectiveness of acupoint application therapy in traditional medicine for patients with cough variant asthma. The comprehensive computer retrieval related to comparison between acupoint application and nonacupoint application therapy for cough variant asthma was carried out in various databases (n = 8) from database establishment until July 4, 2021. Both English and Chinese articles about original investigations in humans were searched. Two independent authors extracted the data, and disagreements were resolved by discussion. ReviewManager 5.3 software provided by Cochrane did a meta-analysis of selected randomized controlled trials (RCTs). Quality of experimentation and risk bias were analyzed by the Cochrane Handbook tool. A total of thirteen randomized controlled clinical articles along with 1237 patients were included in the study. Findings of meta-analysis showed that compared with nonacupoint application treatment, the total effective rate of acupoint application treatment is more effective (RD = 0.13, 95% CI (0.09, 0.17), Z = 6.70, P < 0.00001). Besides, acupoint application can improve patients' lung function, the lung function index FVC (mean difference = 0.55, 95% confidence interval (0.42, 0.68), Z = 8.40, P < 0.00001), FEV1 (MD = 0.35, 95% CI (0.23, 0.47), Z = 5.86, P < 0.00001), FEV1/FVC (%) (MD = 12.68, 95% CI (4.32, 21.03), Z = 2.97, P = 0.003), FEV1 (%) (MD = 8.63, 95% CI (8.01, 9.25), Z = 27.44, P < 0.00001), and PEF (day) (MD = 0.62, 95% CI (0.52, 0.71), Z = 12.40, P < 0.00001) of patients treated by acupoint application therapy were increased. Moreover, acupoint application might lower the level of immunoglobulin E (MD = -54.58, 95% CI (-63.54, -45.61), Z = 11.93, P < 0.00001) and EOS (MD = -0.21, 95% CI (-0.35, -0.06), Z = 2.77, P = 0.006). The LCQ (Leicester cough questionnaire) total score of CVA patients was also increased (MD = 2.30, 95% CI (1.55, 3.06), Z = 5.98, P < 0.00001). Acupoint application therapy is effective in controlling symptoms of CVA. It also has a positive effect in improving lung function and life quality of patients. It can reduce the eosinophil levels and peripheral blood IgE levels of patients as well.


Assuntos
Pontos de Acupuntura , Asma , Asma/tratamento farmacológico , Tosse/terapia , Humanos , Medicina Tradicional Chinesa , Ensaios Clínicos Controlados Aleatórios como Assunto , Testes de Função Respiratória
3.
Chron Respir Dis ; 19: 14799731221117297, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35938497

RESUMO

INTRODUCTION: Specialist management of asthma has been shown to associate with socioeconomic status (SES). However, little is known about the influence of SES on care burden in universal healthcare settings. METHODS: Patients aged 18-45 years using inhaled corticosteroids (ICS) were followed in national databases. Impact of asthma was investigated using negative binomial regression adjusted for age, sex, comorbidity, and GINA 2020 Step. Uncontrolled asthma was defined as >600 annual SABA puffs, ≥2 prednisolone courses and/or ≥1 hospitalization. RESULTS: A total of 60,534 (55% female, median age 33 (IQR 25-39)) patients were followed for 10.1 years (IQR 5.2-14.3)). Uncontrolled asthma resulted in 6.5 and 0.51 additional annual contacts to primary care and pulmonologists, respectively.Unscheduled and primary care burden was dependent on SES, increasing with rural residence, lower education, income and receiving welfare. Differences in planned respiratory care were slight, only seen among divorced, low income- or welfare recipients. Lower SES was consistently associated with an increased utilization of SABA and prednisolone. No dose-response relationship between ICS use and SES could be identified. CONCLUSION: Lower SES in asthma is a risk factor for a predominance of unscheduled care and adverse outcomes, warranting further attention to patients' background when assessing asthma care.


Assuntos
Antiasmáticos , Asma , Administração por Inalação , Corticosteroides/uso terapêutico , Adulto , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Asma/epidemiologia , Estudos de Coortes , Efeitos Psicossociais da Doença , Feminino , Humanos , Masculino , Aceitação pelo Paciente de Cuidados de Saúde , Prednisolona/uso terapêutico , Classe Social , Adulto Jovem
4.
Front Immunol ; 13: 930862, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35911708

RESUMO

T helper type 2 cells (Th2 cells) and group 2 innate lymphoid cells (ILC2s) play an important role in the pathophysiology of asthma, including airway eosinophilic inflammation. ILC2s are activated by epithelial-derived cytokines [interleukin-25 (IL-25), IL-33, and thymic stromal lymphopoietin (TSLP)] from airway epithelial cells, leading to the release of high amounts of type 2 cytokines, such as IL-5 and IL-13. ILC2s induce airway inflammation in an antigen-independent manner, and ILC2s are considered to be involved in the pathogenesis of asthma exacerbation. Furthermore, ILC2 activation might also confer steroid resistance. Many recent studies in humans and mice are increasingly demonstrating that the function of ILC2s is regulated not just by epithelial-derived cytokines but by a variety of cytokines and mediators derived from innate immune cells. Furthermore, the biologics targeting these cytokines and/or their receptors have been shown to reduce asthma exacerbations and improve lung function and quality of life in asthmatics. This article reviews the current treatment landscape for type 2 airway inflammation in asthma and discusses the therapeutic potential for targeting ILC2s.


Assuntos
Asma , Imunidade Inata , Animais , Citocinas , Humanos , Inflamação , Linfócitos , Camundongos , Qualidade de Vida
5.
Comput Math Methods Med ; 2022: 4586458, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35912149

RESUMO

Background: In clinical practise, it can be challenging to tell the difference between asthma and chronic obstructive pulmonary disease (COPD) and heart failure (HF), which share comparable dyspnea symptoms. We aimed to examine whether renal function indexes blood urea nitrogen (BUN), creatinine (Cr), and the ratio of BUN to Cr (BUN/Cr) can be used to distinguish HF from asthma and COPD. Methods: A total of 170 patients were admitted for dyspnea symptoms in this retrospective study. There are 69 patients with HF (HF group), 50 patients with asthma (asthma group), and 51 patients diagnosed with COPD (COPD group). The levels of BUN, Cr, and the ratio of BUN/Cr in the three groups were compared. Student's t-test or the one-way analysis of variance (ANOVA) test was used to compare means. Using the area under the receiver operating characteristic curve, model differentiation was evaluated (AUC). Z-test comparisons of AUC were carried out. Results: Compared with the asthma/COPD group (asthma group + COPD group) or the COPD group, the levels of BUN and Cr were raised in the HF group, while there was no significant difference of the BUN/Cr ratio. Compared with those in the asthma group, the levels of BUN, Cr, and BUN/Cr ratio were significantly increased in the HF group (all p < 0.05), whereas no significant differences of BUN, Cr, and BUN/Cr ratio were found between asthma and COPD. The AUC in distinguishing HF from asthma/COPD were 0.736 and 0.751 for BUN and Cr, respectively, and no significant difference was observed between BUN and Cr. The cutoff values (specificity, sensitivity, and Youden index) in distinguishing between HF and asthma/COPD were 20.45 mg/dL (79.21%, 56.52%, and 0.357) for BUN and 0.782 mg/dL (72.28%, 68.12%, and 0.404) for Cr, respectively. Conclusions: BUN and Cr showed accurate and reliable diagnostic values which could be potential biomarkers for differentiating HF from asthma and/or COPD.


Assuntos
Asma , Insuficiência Cardíaca , Doença Pulmonar Obstrutiva Crônica , Asma/diagnóstico , Nitrogênio da Ureia Sanguínea , Creatinina , Dispneia , Insuficiência Cardíaca/diagnóstico , Humanos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Estudos Retrospectivos
6.
South Med J ; 115(8): 611-615, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35922047

RESUMO

Of the patients with asthma, 20% to 25% progress to severe symptoms, resulting in poor quality of life and increased episodes of exacerbation. There is a broad range of drugs used for asthma; the most used medications for severe asthma are inhaled glucocorticoids with or without long-acting ß-agonists. Systemic glucocorticoids and other treatments as add-on therapies are also given as needed. Chronic glucocorticoid use is associated with numerous adverse effects, including diabetes mellitus, osteoporosis, anxiety, depression, and cataracts. The occurrence of these side effects has been reduced because of the emergence of new biological therapies. One such treatment is dupilumab, which helps in the reduction of type 2 inflammation involved in the pathophysiology of asthma. We conducted a literature review to assess the efficacy, adverse effects, and pharmacological benefits of dupilumab in glucocorticoid-dependent asthma. In most randomized controlled trials, dupilumab has shown significant efficacy and safety profile in patients with severe asthma with corticosteroid dependence. Associated adverse effects such as injection site reaction and transient eosinophilia have been reported. Our review of the literature indicates that dupilumab has proven to improve lung function, reduce the rate of asthma exacerbations, and reduce the use of corticosteroids.


Assuntos
Antiasmáticos , Asma , Corticosteroides/uso terapêutico , Antiasmáticos/efeitos adversos , Anticorpos Monoclonais Humanizados , Asma/tratamento farmacológico , Quimioterapia Combinada , Glucocorticoides/efeitos adversos , Humanos , Qualidade de Vida
7.
Front Immunol ; 13: 947724, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35924252

RESUMO

Background: Asthma patients potentially have impaired adaptive immunity to virus infection. The levels of SARS-CoV-2-specific adaptive immunity between COVID-19 survivors with and without asthma are presently unclear. Methods: COVID-19 survivors (patients with asthma n=11, with allergies n=8, and COVID-19 only n=17) and non-COVID-19 individuals (asthmatic patients n=10 and healthy controls n=9) were included. The COVID-19 patients were followed up at about 8 months and 16 months after discharge. The clinical characteristics, lymphocyte subsets, memory T cells, and humoral immunity including SARS-CoV-2 specific antibodies, SARS-CoV-2 pseudotyped virus neutralization assay, and memory B cells were analyzed in these subjects. Results: The strength of virus-specific T cell response in COVID-19 survivors was positively correlated with the percentage of blood eosinophils and Treg cells (r=0.4007, p=0.0188; and r=0.4435, p=0.0086 respectively) at 8-month follow-up. There were no statistical differences in the levels of SARS-CoV-2-specific T cell response between the COVID-19 survivors with, and without, asthma. Compared to those without asthma, the COVID-19 with asthma survivors had higher levels of SARS-CoV-2-specific neutralizing antibodies (NAbs) at the 8-month follow-up (p<0.05). Moreover, the level of NAbs in COVID-19 survivors was positively correlated with the percentage of Treg and cTfh2 cells (r=0.5037, p=0.002; and r=0.4846, p=0.0141), and negatively correlated with the percentage of Th1 and Th17 cells (r=-0.5701, p=0.0003; and r=-0.3656, p=0.0308), the ratio of Th1/Th2, Th17/Treg, and cTfh1/cTfh2 cell (r=-0.5356, r=-0.5947, r=-0.4485; all p<0.05). The decay rate of NAbs in the COVID-19 survivors with asthma was not significantly different from that of those without asthma at 16-month follow-up. Conclusion: The level of SARS-CoV-2-specific NAbs in COVID-19 survivors with asthma was higher than that of those without asthma at 8-month follow-up. The SARS-CoV-2-specific T cell immunity was associated with blood eosinophils and Treg percentages. The SARS-CoV-2-specific humoral immunity was closely associated with cTfh2/cTfh1 imbalance and Treg/Th17 ratio. According to the findings, asthmatic patients in COVID-19 convalescent period may benefit from an enhanced specific humoral immunity, which associates with skewed Th2/Th1 and Treg/Th17 immune.


Assuntos
Asma , COVID-19 , Imunidade Adaptativa , Anticorpos Neutralizantes , Anticorpos Antivirais , Humanos , SARS-CoV-2 , Sobreviventes
9.
Eur Rev Med Pharmacol Sci ; 26(14): 5081-5091, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35916804

RESUMO

OBJECTIVE: It has been shown that asthma is significantly associated with the risk of cardiovascular disease (CVD). Under this background, this study aimed to systematically classify and summarize the epidemiological evidence of asthma and the risk of 4 specific cardiovascular diseases (CVDs) and cardiovascular mortality (CVM). MATERIALS AND METHODS: PubMed and Embase databases were searched from inception to December 1st, 2021 in order to identify relevant studies. The random-model was used to assess the pooled results. All pooled results were expressed as risk ratios (RRs) and corresponding 95% confidence intervals (CIs). RESULTS: Finally, a total of 18 studies were included in the present meta-analysis. Compared with non-asthmatic group, patients with asthma had significantly increased risks of subsequent cardiovascular heart disease (CHD, RR 1.33; 1.19-1.50, I2=80.3%; p<0.001), and CVM (RR 1.35; 1.15-1.59, I2=0%; p<0.001). Similarly, the risks of heart failure (HF, RR 2.10; 1.98-2.22, I2=17.4%; p<0.001) and myocardial infraction (MI, RR 1.39; 1.16-1.66, I2=59.3%; p<0.001) were higher in the asthmatic population. However, the higher risk of atrial fibrillation (RR 1.70; 1.45-2.00, I2=0%; p<0.001) was observed only in the active asthmatic population. CONCLUSIONS: In general, asthma is associated with subsequent increased risks of CHD, MI, AF, HF, and CVM. In addition, among patients with asthma, females have a higher risk of CHD than males, while active asthmatic patients have a higher risk of CVM than non-active asthmatic patients.


Assuntos
Asma , Fibrilação Atrial , Doenças Cardiovasculares , Insuficiência Cardíaca , Asma/complicações , Asma/epidemiologia , Fibrilação Atrial/complicações , Estudos de Coortes , Feminino , Insuficiência Cardíaca/complicações , Humanos , Masculino
10.
FASEB J ; 36(9): e22452, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35916017

RESUMO

House dust mite (HDM) allergens cause inflammatory responses and chronic allergic diseases such as bronchial asthma and atopic dermatitis. Here, we investigate the mechanism by which HDM induces C-C chemokine ligand 20 (CCL20) expression to promote chronic inflammation and airway remodeling in an HDM-induced bronchial asthma mouse model. We showed that HDM increased CCL20 levels via the Akt-ERK1/2-C/EBPß pathway. To investigate the role of CCL20 in chronic airway inflammation and remodeling, we made a mouse model of CCL20-induced bronchial asthma. Treatment of anti-CCL20Ab in this mouse model showed the reduced airway hyper-responsiveness and inflammatory cell infiltration into peribronchial region by neutralizing CCL20. In addition, CCL20 induced the Nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation through NLRP3 deubiquitination and transcriptional upregulation in BEAS-2B cells. As expected, anti-CCL20Ab markedly suppressed NLRP3 activation induced by CCL20. Moreover, HDM-induced CCL20 leads to epithelial-mesenchymal transition in the lung epithelium which appears to be an important regulator of airway remodeling in allergic asthma. We also found that anti-CCL20Ab attenuates airway inflammation and remodeling in an HDM-induced mouse model of bronchial asthma. Taken together, our results suggest that HDM-induced CCL20 is required for chronic inflammation that contributes airway remodeling in a mouse model of asthma.


Assuntos
Asma , Pyroglyphidae , Remodelação das Vias Aéreas , Animais , Asma/metabolismo , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal , Inflamação/complicações , Ligantes , Pulmão/metabolismo , Sistema de Sinalização das MAP Quinases , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
11.
J Korean Med Sci ; 37(30): e236, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35916048

RESUMO

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are airway diseases with similar clinical manifestations, despite differences in pathophysiology. Asthma-COPD overlap (ACO) is a condition characterized by overlapping clinical features of both diseases. There have been few reports regarding the prevalence of ACO in COPD and severe asthma cohorts. ACO is heterogeneous; patients can be classified on the basis of phenotype differences. This study was performed to analyze the prevalence of ACO in COPD and severe asthma cohorts. In addition, this study compared baseline characteristics among ACO patients according to phenotype. METHODS: Patients with COPD were prospectively enrolled into the Korean COPD subgroup study (KOCOSS) cohort. Patients with severe asthma were prospectively enrolled into the Korean Severe Asthma Registry (KoSAR). ACO was defined in accordance with the updated Spanish criteria. In the COPD cohort, ACO was defined as bronchodilator response (BDR) ≥ 15% and ≥ 400 mL from baseline or blood eosinophil count (BEC) ≥ 300 cells/µL. In the severe asthma cohort, ACO was defined as age ≥ 35 years, smoking ≥ 10 pack-years, and post-bronchodilator forced expiratory volume in 1 s/forced vital capacity < 0.7. Patients with ACO were divided into four groups according to smoking history (threshold: 20 pack-years) and BEC (threshold: 300 cells/µL). RESULTS: The prevalence of ACO significantly differed between the COPD and severe asthma cohorts (19.8% [365/1,839] vs. 12.5% [104/832], respectively; P < 0.001). The percentage of patients in each group was as follows: group A (light smoker with high BEC) - 9.1%; group B (light smoker with low BEC) - 3.7%; group C (moderate to heavy smoker with high BEC) - 73.8%; and group D (moderate to heavy smoker with low BEC) - 13.4%. Moderate to heavy smoker with high BEC group was oldest, and showed weak BDR response. Age, sex, BDR, comorbidities, and medications significantly differed among the four groups. CONCLUSION: The prevalence of ACO differed between COPD and severe asthma cohorts. ACO patients can be classified into four phenotype groups, such that each phenotype exhibits distinct characteristics.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Asma/complicações , Asma/diagnóstico , Asma/epidemiologia , Broncodilatadores/uso terapêutico , Volume Expiratório Forçado , Humanos , Fenótipo , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia
12.
J Allergy Clin Immunol ; 150(2): 235-249, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35934678

RESUMO

Airway inflammation in asthma involves complex, interactive, and redundant cascades mediated by an array of proinflammatory cytokines, including a type 2 (T2) pattern of injury. T2 inflammation is characterized by elevations in absolute peripheral or sputum eosinophil counts and levels of IgE (total and allergen-specific) and fractional exhaled nitric oxide, which serve as biomarkers for the presence of this type of inflammation. T2 inflammation is mediated by key "downstream" cytokines, particularly IL-4, IL-5, and IL-13, which act at the effector cell level, as well as upstream cytokines, or "alarmins," such as thymic stromal lymphopoietin, IL-25, and IL-33 generated by epithelial cells. The relevance of these pathways has led to the development of biologic therapies targeting these T2 cytokines, which have not only resulted in modifying these biomarker signatures for inflammation but have also reduced the disease burden associated with asthma exacerbations, systemic corticosteroid use, and lung function compromises. This review will summarize experiences with anticytokine biologics to highlight which specific asthma outcomes they affect and how these effects reflect inflammatory pathways modified by biologics and may relate to pathophysiologic features of asthma.


Assuntos
Asma , Produtos Biológicos , Alérgenos , Asma/metabolismo , Produtos Biológicos/uso terapêutico , Citocinas/metabolismo , Humanos , Inflamação
13.
Zhonghua Jie He He Hu Xi Za Zhi ; 45(8): 803-808, 2022 Aug 12.
Artigo em Chinês | MEDLINE | ID: mdl-35927050

RESUMO

The atopic march reveals that infants with atopic dermatitis are prone to food allergy, allergic rhinitis and asthma later in life. The hygiene hypothesis holds that the cleaner the personal hygiene and environment, the higher the incidence rate of asthma and allergy. It is believed that Toll like receptors (TLRs) are the bridge between innate immunity and adaptive immunity, playing an important role in inflammatory and immune diseases. More and more evidence shows that TLRs, involved in the pathophysiology of atopic march, connect atopic march with hygiene hypothesis as a potential therapeutic target for asthma and allergy.


Assuntos
Asma , Dermatite Atópica , Rinite Alérgica , Asma/epidemiologia , Dermatite Atópica/complicações , Dermatite Atópica/epidemiologia , Humanos , Hipótese da Higiene , Lactente , Receptores Toll-Like
14.
Front Immunol ; 13: 921077, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35911691

RESUMO

Asthma encompasses a spectrum of heterogenous immune-mediated respiratory disorders sharing a similar clinical pattern characterized by cough, wheeze and exercise intolerance. In horses, equine asthma can be subdivided into severe or moderate asthma according to clinical symptoms and the extent of airway neutrophilic inflammation. While severe asthmatic horses are characterized by an elevated neutrophilic inflammation of the lower airways, cough, dyspnea at rest and high mucus secretion, horses with moderate asthma show a milder neutrophilic inflammation, exhibit intolerance to exercise but no labored breathing at rest. Yet, the physiopathology of different phenotypes of equine asthma remains poorly understood and there is a need to elucidate the underlying mechanisms tailoring those phenotypes in order to improve clinical management and elaborate novel therapeutic strategies. In this study, we sought to quantify the presence of neutrophil extracellular traps (NETs) in bronchoalveolar lavage fluids (BALF) of moderate or severe asthmatic horses and healthy controls, and assessed whether NETs correlated with disease severity. To this end, we evaluated the amounts of NETs by measuring cell-free DNA and MPO-DNA complexes in BALF supernatants or by quantifying NETs release by BALF cells by confocal microscopy. We were able to unequivocally identify elevated NETs levels in BALF of severe asthmatic horses as compared to healthy controls or moderate asthmatic horses. Moreover, we provided evidence that BALF NETs release was a specific feature seen in severe equine asthma, as opposed to moderate asthma, and correlated with disease severity. Finally, we showed that NETs could act as a predictive factor for severe equine asthma. Our study thus uniquely identifies NETs in BALF of severe asthmatic horses using three distinct methods and supports the idea that moderate and severe equine asthma do not rely on strictly similar pathophysiological mechanisms. Our data also suggest that NETs represent a relevant biomarker, a putative driver and a potential therapeutic target in severe asthma disease.


Assuntos
Asma , Armadilhas Extracelulares , Animais , Asma/patologia , Asma/veterinária , Líquido da Lavagem Broncoalveolar , Tosse/patologia , Tosse/veterinária , Cavalos , Inflamação/patologia , Inflamação/veterinária , Neutrófilos/patologia , Gravidade do Paciente
15.
West Afr J Med ; 39(7): 721-728, 2022 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-35925033

RESUMO

BACKGROUND: Asthma symptoms are often mediated by changes in immune responses to allergens measured by the levels of immunoglobulin E (IgE) and non-protein regulators such as 25-hydroxycholecalciferol (25 (OH) vitamin D3). The relationship between serum levels of IgE, 25 (OH) Vitamin D3, and asthma control in asthma patients remains unclear. OBJECTIVE: To measure the serum IgE and 25 (OH) vitamin D3 levels in asthma patients and determine their relationship with patient's asthma control. METHODS: This was a cross-sectional study of children and adults with asthma aged 5 to 60 years old; and their controls seen in a tertiary hospital in Enugu, south eastern Nigeria from October 2018 to January 2019. Serum levels of IgE, and 25 (OH) vitamin D3 were determined by sandwich enzyme-linked immunosorbent assay (ELISA); and compared between groups using the Student's t-tests. Association between IgE, 25 (OH) vitamin D3 levels, and asthma control were determined using the Chi-square. RESULTS: Sixty-five (65) asthma patients and thirty-three (36) non-asthma controls were studied. Mean serum level of IgE (411.32± 220.18 IU/ml) was significantly raised in asthma patients compared to controls (163.51 ± 186.36 lU/ml); p=0.001. There was no significant difference in mean 25 (OH) vitamin D3 levels in asthma (68.55 ± 25.91 ng/ml) compared to controls (77.25 ± 34.01 ng/ml); p=0.153. No significant association was found between patient's asthma control status, and serum IgE and 25 (OH) vitamin D3 levels. CONCLUSION: Asthma control status was not associated with Immunoglobulin E and 25 (OH) vitamin D3 levels in those studied. More robust study is required to evaluate the relationship between asthma control, IgE and vitamin D levels.


BACKGROUND: Les symptômes de l'asthme sont souvent médiés par des changements des réponses immunitaires aux allergènes, mesurées par les taux d'immunoglobuline E (IgE) et de régulateurs non protéiques tels que le 25- hydroxycholécalciférol (25 (OH) vitamine D3). La relation entre les niveaux sériques d'IgE, de 25 (OH) vitamine D3 et le contrôle de l'asthme chez les patients asthmatiques n'est pas claire. OBJECTIF: Mesurer les taux sériques d'IgE et de 25 (OH) vitamine D3 chez les patients asthmatiques et déterminer leur relation avec le contrôle de l'asthme chez les patients. MÉTHODES: Il s'agit d'une étude transversale d'enfants et d'adultes asthmatiques âgés de 5 à 60 ans; ainsi que de leurs témoins vus dans un hôpital tertiaire d'Enugu, dans le sud-est du Nigeria, d'octobre 2018 à janvier 2019. Les taux sériques d'IgE et de 25 (OH) vitamine D3 ont été déterminés par dosage immuno-enzymatique en sandwich (ELISA); et comparés entre les groupes à l'aide des tests t de Student. L'association entre les niveaux d'IgE, de 25 (OH) vitamine D3 et le contrôle de l'asthme a été déterminée à l'aide du chi carré. RÉSULTATS: Soixante-cinq (65) patients asthmatiques et trentetrois (36) témoins non asthmatiques ont été étudiés. Le taux sérique moyen d'IgE (411,32 ± 220,18 UI/ml) était significativement plus élevé chez les patients asthmatiques que chez les témoins (163,51 ± 186,5 UI/ml); p=0,001. Il n'y avait pas de différence significative dans les taux moyens de 25 (OH) vitamine D3 chez les asthmatiques (68,55 ± 25,91 ng/ml) par rapport aux témoins (77,25 ± 34,01 ng/ml); p=0.153. Aucune association significative n'a été trouvée entre le statut de contrôle de l'asthme du patient et les taux sériques d'IgE et de 25 (OH) vitamine D3. CONCLUSION: Le contrôle de l'asthme n'était pas associé aux taux d'immunoglobulines E et de 25 (OH) vitamine D3 chez les personnes étudiées. Une étude plus solide est nécessaire pour évaluer la relation entre le contrôle de l'asthme, les taux d'IgE et de vitamine D. Mots clés: 25 hydroxyl vitamine D3, Immunoglobuline E, Contrôle de l'asthme, Enfants, contrôle, Enfants.


Assuntos
Asma , Vitamina D , Adolescente , Adulto , Calcifediol , Criança , Pré-Escolar , Estudos Transversais , Humanos , Imunoglobulina E , Pessoa de Meia-Idade , Nigéria , Adulto Jovem
16.
PLoS One ; 17(8): e0271884, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35925922

RESUMO

OBJECTIVE: Asthma is a common chronic illness affecting 19 million US adults. Inhaled corticosteroids are a safe and effective treatment for asthma, yet, medication adherence among patients remains poor. Shared decision-making, a patient activation strategy, can improve patient adherence to inhaled corticosteroids. This study aimed to explore whether audio-recorded patient-primary care provider encounters can be used to: 1. Evaluate the level of patient-perceived shared decision-making during the encounter, and 2. Predict levels of patient's inhaled corticosteroid adherence. MATERIALS AND METHODS: Shared decision-making and inhaled corticosteroid adherence were assessed using the SDM Questionnaire-9 and the Medication Adherence Report Scale for Asthma (MARS-A). Speech-to-text algorithms were used to automatically transcribe 80 audio-recorded encounters between primary care providers and asthmatic patients. Machine learning algorithms (Naive Bayes, Support Vector Machines, Decision Tree) were applied to achieve the study's predictive goals. RESULTS: The accuracy of automated speech-to-text transcription was relatively high (ROUGE F-score = .9). Machine learning algorithms achieved good predictive performance for shared decision-making (the highest F-score = .88 for the Naive Bayes) and inhaled corticosteroid adherence (the highest F-score = .87 for the Support Vector Machines). DISCUSSION: This was the first study that trained machine learning algorithms on a dataset of audio-recorded patient-primary care provider encounters to successfully evaluate the quality of SDM and predict patient inhaled corticosteroid adherence. CONCLUSION: Machine learning approaches can help primary care providers identify patients at risk for poor medication adherence and evaluate the quality of care by measuring levels of shared decision-making. Further work should explore the replicability of our results in larger samples and additional health domains.


Assuntos
Asma , Percepção da Fala , Corticosteroides/uso terapêutico , Adulto , Asma/tratamento farmacológico , Teorema de Bayes , Tomada de Decisões , Tomada de Decisão Compartilhada , Humanos , Adesão à Medicação , Atenção Primária à Saúde , Fala , Inquéritos e Questionários
17.
Front Immunol ; 13: 964575, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935956

RESUMO

Rationale: Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, has been considered as an important regulator for immune diseases. We have previously shown that AhR protects against allergic airway inflammation. The underlying mechanism, however, remains undetermined. Objectives: We sought to determine whether AhR specifically in type II alveolar epithelial cells (AT2) modulates allergic airway inflammation and its underlying mechanisms. Methods: The role of AhR in AT2 cells in airway inflammation was investigated in a mouse model of asthma with AhR conditional knockout mice in AT2 cells (Sftpc-Cre;AhRf/f ). The effect of AhR on allergen-induced autophagy was examined by both in vivo and in vitro analyses. The involvement of autophagy in airway inflammation was analyzed by using autophagy inhibitor chloroquine. The AhR-regulated gene profiling in AT2 cells was also investigated by RNA sequencing (RNA-seq) analysis. Results: Sftpc-Cre;AhRf/f mice showed exacerbation of allergen-induced airway hyperresponsiveness and airway inflammation with elevated Th2 cytokines in bronchoalveolar lavage fluid (BALF). Notably, an increased allergen-induced autophagy was observed in the lung tissues of Sftpc-Cre;AhRf/f mice when compared with wild-type mice. Further analyses suggested a functional axis of AhR-TGF-ß1 that is critical in driving allergic airway inflammation through regulating allergen-induced cellular autophagy. Furthermore, inhibition of autophagy with autophagy inhibitor chloroquine significantly suppressed cockroach allergen-induced airway inflammation, Th2 cytokines in BALFs, and expression of autophagy-related genes LC3 and Atg5 in the lung tissues. In addition, RNA-seq analysis suggests that autophagy is one of the major pathways and that CALCOCO2/NDP52 and S1009 are major autophagy-associated genes in AT2 cells that may contribute to the AhR-mediated cockroach allergen-induced airway inflammation and, subsequently, allergic asthma. Conclusion: These results suggest that AhR in AT2 cells functions as a protective mechanism against allergic airway inflammation through controlling cell autophagy.


Assuntos
Asma , Receptores de Hidrocarboneto Arílico , Alérgenos , Células Epiteliais Alveolares/metabolismo , Animais , Autofagia , Cloroquina/farmacologia , Citocinas/metabolismo , Inflamação , Camundongos , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo
18.
Front Immunol ; 13: 951361, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35936001

RESUMO

Tissue-resident memory CD4 T cells (Trm) are thought to be a major contributor to asthma relapse, but the role of circulatory T cells in asthma exacerbations or to maintaining the population of lung Trm cells is not fully understood. Here, we used a house dust mite allergen-based murine model of asthma relapse, and monitored the development of lung effector/Trm phenotype CD44hiCD62LloCD69+ CD4 T cells. To determine the contribution of circulatory cells, mice were treated with FTY720, to block lymphocyte egress from lymph nodes. Inhibiting the primary migration of circulatory cells to the lungs mitigated the accumulation and expansion of allergen-driven Trm phenotype cells, but subsequent allergen challenges still resulted in strong lung inflammation and Trm cell accumulation. This was blocked if FTY720 was also given at the time of allergen re-exposure, showing that new circulatory cells contributed to this lung memory/effector T cell pool at times well after the initial sensitization. However, once lung-localized Trm cells developed at high frequency, circulatory cells were not required to maintain this population following allergen re-encounter, even though circulatory cells still were major contributors to the overall asthmatic lung inflammatory response. Our results suggest that strategies that target the response of circulatory memory T cells and Trm cells together might be required to strongly inhibit T cell reactivity to airborne allergens and to limit exacerbations of asthma and their reoccurrence, but the contribution of circulatory T cells might vary in long-term asthmatics possessing a large stable Trm cell population in the lungs.


Assuntos
Asma , Pneumonia , Alérgenos , Animais , Asma/patologia , Linfócitos T CD4-Positivos , Cloridrato de Fingolimode/farmacologia , Memória Imunológica , Pulmão , Camundongos , Pneumonia/patologia , Recidiva
19.
Front Immunol ; 13: 911300, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35936002

RESUMO

Background: Allergic respiratory diseases have increased dramatically due to air pollution over the past few decades. However, studies are limited on the effects of inorganic components and particulate matter with different particle sizes in smog on allergic diseases, and the possible molecular mechanism of inducing allergies has not been thoroughly studied. Methods: Four common mineral elements with different particle sizes in smog particles were selected, including Al2O3, TiO2, Fe2O3, and SiO2. We studied the relationship and molecular mechanism of smog particle composition, particle size, and allergic reactions using mast cells, immunoglobulin E (IgE)-mediated passive cutaneous anaphylaxis (PCA) model, and an ovalbumin (OVA)-induced asthmatic mouse model in vitro and in vivo, combined with transmission electron microscopy, scanning transmission X-ray microscopy analysis, and transcriptome sequencing. Results: Only 20 nm SiO2 particles significantly increased ß-hexosaminidase release, based on dinitrophenol (DNP)-human serum albumin (HSA) stimulation, from IgE-sensitized mast cells, while other particles did not. Meanwhile, the PCA model showed that Evan's blue extravasation in mice was increased after treatment with nano-SiO2 particles. Nano-SiO2 particles exposure in the asthmatic mouse model caused an enhancement of allergic airway inflammation as manifested by OVA-specific serum IgE, airway hyperresponsiveness, lung inflammation injury, mucous cell metaplasia, cytokine expression, mast cell activation, and histamine secretion, which were significantly increased. Nano-SiO2 particles exposure did not affect the expression of FcϵRI or the ability of mast cells to bind IgE but synergistically activated mast cells by enhancing the mitogen-activated protein kinase (MAPK) signaling pathway, especially the phosphorylation levels of the extracellular signal-regulated kinase (ERK)1/2. The ERK inhibitors showed a significant inhibitory effect in reducing ß-hexosaminidase release. Conclusion: Our results indicated that nano-SiO2 particles stimulation might synergistically activate IgE-sensitized mast cells by enhancing the MAPK signaling pathway and that nano-SiO2 particles exposure could exacerbate allergic inflammation. Our experimental results provide useful information for preventing and treating allergic diseases.


Assuntos
Asma , Hipersensibilidade , Lesão Pulmonar , Animais , Modelos Animais de Doenças , Humanos , Imunoglobulina E , Inflamação , Mastócitos , Camundongos , Proteínas Quinases Ativadas por Mitógeno , Dióxido de Silício/efeitos adversos , Smog , beta-N-Acetil-Hexosaminidases
20.
Am J Respir Cell Mol Biol ; 67(2): 155-163, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35914321

RESUMO

This report presents the proceedings from a workshop titled "Microbiome, Metabolism and Immunoregulation of Asthma" that was held virtually May 13 and 14, 2021. The workshop was jointly sponsored by the American Thoracic Society (Assembly on Allergy, Immunology, and Inflammation) and the National Institute of Allergy and Infectious Diseases. It convened an interdisciplinary group of experts with backgrounds in asthma immunology, microbiome science, metabolomics, computational biology, and translational pulmonary research. The main purpose was to identify key scientific gaps and needs to further advance research on microbial and metabolic mechanisms that may contribute to variable immune responses and disease heterogeneity in asthma. Discussions were structured around several topics, including 1) immune and microbial mechanisms of asthma pathogenesis in murine models, 2) the role of microbes in pediatric asthma exacerbations, 3) dysregulated metabolic pathways in asthma associated with obesity, 4) metabolism effects on macrophage function in adipose tissue and the lungs, 5) computational approaches to dissect microbiome-metabolite links, and 6) potential confounders of microbiome-disease associations in human studies. This report summarizes the major points of discussion, which included identification of specific knowledge gaps, challenges, and suggested directions for future research. These include questions surrounding mechanisms by which microbiota and metabolites shape host health versus an allergic or asthmatic state; direct and indirect influences of other biological factors, exposures, and comorbidities on these interactions; and ongoing technical and analytical gaps for clinical translation.


Assuntos
Asma , Hipersensibilidade , Microbiota , Animais , Asma/etiologia , Criança , Humanos , Hipersensibilidade/complicações , Imunidade , Camundongos , National Institute of Allergy and Infectious Diseases (U.S.) , Estados Unidos
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