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1.
Medicine (Baltimore) ; 98(44): e17845, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689875

RESUMO

BACKGROUND: Shegan Mahuang Decoction (SMD) was used widely for treatment of asthma in China; however, the clinical effect of SMD on asthma was not well concluded. METHODS: Seven electronic databases (Medline, Cochrane library, EMBASE database, Chinese National Knowledge Infrastructure, Wanfang database, Chongqing VIP database, and Chinese Biomedicine database) will be searched for randomized controlled trials which meet the eligible criteria. Two reviewers will select studies and extract data independently. Risk of bias will be evaluated using modified Jadad score. Data synthesis will be carried out using RevMan 5.3. Sensitivity analysis and publication bias will also be investigated. RESULTS: This systematic review and meta-analysis will review and synthesis current clinical evidence of SMD for the treatment of asthma. CONCLUSION: This systematic review and meta-analysis will provide high quality evidence of SMD for the treatment of asthma. REGISTRATION: PROSPERO CRD42019141810.


Assuntos
Asma/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Metanálise como Assunto , Preparações de Plantas/uso terapêutico , Revisão Sistemática como Assunto , Adolescente , Adulto , Idoso , Humanos
2.
Zhonghua Jie He He Hu Xi Za Zhi ; 42(11): 845-851, 2019 Nov 12.
Artigo em Chinês | MEDLINE | ID: mdl-31694095

RESUMO

Objective: To explore the role of S100A8, the receptor for advanced glycation endproducts (RAGE) and Caveolin-1 in neutrophilic asthmatic rats, and to further study the intervention of roxithromycin and the possible mechanisms. Methods: Male Brown Norway rats were randomly assigned to a control group, an asthma group and a Roxithromycin group. The asthmatic rat model was established by intraperitoneal injection of ovalbumin (OVA) and Freund's complete adjuvant (FCA) mixture, and aerosol inhalation of OVA. Rats in the Roxithromycin group were given roxithromycin injection 30 mg/kg 30 minutes before each challenge. Rats in the control and the asthma groups were replaced with equal volumes of saline, respectively. Bronchoalveolar lavage fluid (BALF) neutrophil percentage (Neu%) and pathological changes of pulmonary tissue (hematoxylin-eosin, HE staining) were measured to confirm the establishment of asthmatic models. The concentration of inflammatory cytokines and S100A8 were quantified by enzyme-linked immunosorbent assay (ELISA), and the expression of Caveolin-1 and RAGE at protein levels were detected by immunohistochemistry and Western blot. Results: Neu% in BALF of the asthma group was significantly higher than those of the control group, and Neu% in the Roxithromycin group was lower than the asthma group (all P<0.01). Pulmonary histology revealed that there were a large number of inflammatory cells infiltrated in the bronchial and perivascular, pulmonary interstitial and alveolar spaces, and the bronchial wall and smooth muscles were thickened obviously in the asthma group. Rats in the Roxithromycin group showed milder inflammation and airway remodeling change than the asthma group. There was no obvious pathological damage in the control group. The concentration of IL-6 and IL-17 in BALF and serum of rats in the asthma group were significantly higher than those in the control group (P<0.01), and Roxithromycin inhibited the high expression of these cytokines (P<0.05). The expression of S100A8 and RAGE in the asthma group were significantly higher than those in the control group [(20.6±4.4) vs (7.1±2.0) ng/L; (885±118) vs (462±102) ng/L; (14.2±1.7) vs (7.6±1.8) ng/L; (774±166) vs (406±69) ng/L, all P<0.05], and Roxithromycin inhibited the high expression of these proteins [(14.3±3.7) vs (20.6±4.4) ng/L; (650±53) vs (885±118) ng/L; (10.4±1.2) vs (14.2±1.7) ng/L; (560±64) vs (728±72) ng/L] (all P<0.05). Meanwhile, the expression of Caveolin-1 in the asthma group was significantly lower than that in the control group (P<0.01), and Roxithromycin up-regulated its expression (P<0.01). Correlation analysis showed that there was a significantly positive correlation between the expression of S100A8 and RAGE (r=0.706, P<0.01), while there was a significantly negative correlation between the expression of S100A8 and Caveolin-1 (r=-0.775, P<0.01), and between the expression of Caveolin-1 and RAGE (r=-0.919, P<0.01). Conclusion: S100A8 and Caveolin-1 may play an important role in neutrophilic asthma via RAGE, and Roxithromycin may exerts anti-inflammatory effects and inhibition of airway remodeling partly through this signaling pathway.


Assuntos
Antibacterianos/farmacologia , Asma/tratamento farmacológico , Calgranulina A/efeitos dos fármacos , Caveolina 1/efeitos dos fármacos , Roxitromicina/farmacologia , Remodelação das Vias Aéreas , Animais , Antibacterianos/administração & dosagem , Western Blotting , Líquido da Lavagem Broncoalveolar , Calgranulina A/metabolismo , Caveolina 1/metabolismo , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica , Pulmão/fisiopatologia , Masculino , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Ovalbumina , Ratos , Receptor para Produtos Finais de Glicação Avançada , Roxitromicina/administração & dosagem
3.
Rev Med Suisse ; 15(671): 2074-2079, 2019 Nov 13.
Artigo em Francês | MEDLINE | ID: mdl-31742937

RESUMO

The international recommendations of the management of asthma have been modified last years. Several therapies used since long time have no place in the management of moderate asthma today. The use of targeted immunotherapies against phenotypes of asthma are used more and more. Inhalant therapies are becoming more targeted towards the patient's wishes. This article specifies the novelties in management of asthma for de general practitioner, including the use of short acting beta2-agonists, which are no longer to be used without inhaled corticosteroid.


Assuntos
Asma/terapia , Atenção Primária à Saúde , Administração por Inalação , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Agonistas Adrenérgicos beta/administração & dosagem , Agonistas Adrenérgicos beta/uso terapêutico , Asma/tratamento farmacológico , Humanos , Imunoterapia
4.
Ther Umsch ; 76(6): 301-310, 2019 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-31762413

RESUMO

Development of inhaled therapies for COPD and asthma Abstract. Inhaled therapies still represent one of the most important pillars of the COPD and asthma treatments. In recent years, the importance of inhaled corticosteroids in the treatment of COPD changed again and again and currently it seems that they are gaining more importance again. In the future, inhaled therapies will increasingly focus on biomarkers. New to the market are the "triple therapies as a fixed combination", whose success will be evident in the next few years. Despite the great variety of new agents, new combinations and new inhalation systems, it is important to keep a good overview and to focus on the individual benefit of the patients. The goal is to find the products that are suitable for the individual patient in a dosage form that is ideal for him. A correct inhalation technique and a good medication adherence to the prescribed treatment plan is crucial for the success of an inhaled therapy.


Assuntos
Asma , Broncodilatadores/administração & dosagem , Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Corticosteroides , Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , Feminino , Humanos , Masculino , Adesão à Medicação , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
5.
Ther Umsch ; 76(6): 311-316, 2019 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-31762414

RESUMO

The data situation for the use of ICS in asthma is clear. In the case of COPD, on the other hand, where in recent years the pendulum has moved away from ICS towards a dual therapy based on LABA / LAMA, the discussion is open again thanks to new work. However, it would certainly be wrong to recommend ICS as a meaningful therapy for all COPD patients at this point in time, since therapy with ICS is associated with side effects, in particular an increase in the risk of developing pneumonia or osteoporosis. However, there is no doubt that patients with asthma COPD overlap require ICS therapy.


Assuntos
Corticosteroides/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2 , Asma , Broncodilatadores/uso terapêutico , Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Asma/tratamento farmacológico , Quimioterapia Combinada , Humanos , Antagonistas Muscarínicos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
6.
Ther Umsch ; 76(6): 317-321, 2019 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-31762416

RESUMO

Monoclonal antibodies for severe asthma (review) Abstract. Monoclonal antibodies against central steps in the inflammatory cascade of bronchial asthma offer welcome new treatment options for a selected group of patients with severe asthma. The main challenge for the clinician, however, lies in the selection and workup of potential patients. This review discusses the mechanisms of action and the clinical use of these new biologicals.


Assuntos
Antiasmáticos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Asma , Asma/tratamento farmacológico , Asma/imunologia , Humanos
7.
J Environ Pathol Toxicol Oncol ; 38(3): 229-238, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679310

RESUMO

Asthma has affected more than 300 million people worldwide and is considered one of the most debilitating global public health problems based on a recent statistical report from the Global Initiative for Asthma. Inflammation of the airways leads to the various interrelated mechanisms of innate and adaptive immunity acting mutually with the epithelium of the respiratory organ. Fucoxanthin is an orange or brown pigment which is naturally found in various seaweeds. To the best of our knowledge, there are no scientific claims or evidence of the curative effects of fucoxanthin against asthma. Hence, this present research was designed to investigate the curative activity of fucoxanthin against ovalbumin-induced asthma in a mouse model. Fucoxanthin (50 mg/kg) showed significant (P < 0.001) antiasthma activity. It effectively decreased intracellular secretion of reactive oxygen species and increased antioxidant enzyme activity. Fucoxanthin also decreased inflammatory cytokine markers in bronchoalveolar lavage fluid. Because fucoxanthin showed effective antiasthma activity against ovalbumin-induced asthma in experimental animals, further research on this natural antioxidant could lead to development of a novel drug for the treatment of asthma in humans.


Assuntos
Antiasmáticos/farmacologia , Antioxidantes/metabolismo , Asma/tratamento farmacológico , Citocinas/imunologia , Inflamação/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Xantofilas/farmacologia , Animais , Biomarcadores/metabolismo , Líquido da Lavagem Broncoalveolar/química , Citocinas/efeitos dos fármacos , Inflamação/induzido quimicamente , Masculino , Camundongos , Ovalbumina/toxicidade
8.
Life Sci ; 236: 116790, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31626791

RESUMO

AIMS: Although the bulk of research into the biology of serotonin 5-HT2A receptors has focused on its role in the CNS, selective activation of these receptors in peripheral tissues can produce profound anti-inflammatory effects. We previously demonstrated that the small molecule 5-HT2 receptor agonist (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI] inhibits TNF-α-mediated proinflammatory signaling cascades and inflammation via 5-HT2A receptor activation and prevents the development of, and inflammation associated with, acute allergic asthma in a mouse ovalbumin (OVA) model. Here, we investigated the ability of (R)-DOI to reverse inflammation and symptoms associated with established asthma in a newly developed model of chronic asthma. METHODS: An 18-week ovalbumin challenge period was performed to generate persistent, chronic asthma in BALB/c mice. Four once daily intranasal treatments of (R)-DOI were administered one week after allergen cessation, with respiratory parameters being measured by whole-body plethysmography (WBP). Cytokine and chemokine levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR) in homogenized lung tissue, bronchoalveolar (BALF) fluid was analyzed for chemokine modulation by multiplex assays, and Periodic Acid-Schiff and Masson's Trichrome staining was performed to determine goblet cell infiltration and overall changes to lung morphology. KEY FINDINGS: 5-HT2 activation via (R)-DOI attenuates elevated airway hyperresponsiveness to methacholine, reduces pulmonary inflammation and mucus production, and reduces airway structural remodeling and collagen deposition by nearly 70%. SIGNIFICANCE: Overall, these data provide support for the therapeutic potential of (R)-DOI and 5-HT2 receptor activation for the treatment of asthma, and identifies (R)-DOI as a novel therapeutic compound against pulmonary fibrosis.


Assuntos
Remodelação das Vias Aéreas/efeitos dos fármacos , Anfetaminas/farmacologia , Asma/tratamento farmacológico , Pneumonia/prevenção & controle , Receptores 5-HT2 de Serotonina/metabolismo , Agonistas do Receptor 5-HT2 de Serotonina/farmacologia , Remodelação das Vias Aéreas/imunologia , Animais , Asma/induzido quimicamente , Asma/imunologia , Asma/patologia , Doença Crônica , Feminino , Hipersensibilidade/imunologia , Hipersensibilidade/patologia , Hipersensibilidade/prevenção & controle , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/toxicidade , Pneumonia/imunologia , Pneumonia/patologia
9.
Medicine (Baltimore) ; 98(38): e17190, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567962

RESUMO

AIM: Effects of azithromycin on asthma reported in clinical trials are less consistent. We aimed to further clarify the efficacy and safety of azithromycin in treatment of asthma. METHODS: The protocol registration number was CRD42017074318 (http://www.crd.york.ac.uk/Prospero). We searched PubMed, EMBASE, Cochrane databases, China National Knowledge Internet (CNKI), and Wanfang databases for the randomized controlled trials (RCTs) with prolonged treatment of azithromycin for more than 3 weeks. Random-effects or fixed-effects model was applied to calculate risk ratio (RR) and mean difference (MD) for dichotomous and continuous data respectively. RESULTS: A total of eight studies were included for analysis. The pooled result of adjunctive azithromycin therapy in asthma showed a small, but statistically significant increase in forced expiratory volume in one second (FEV1) (MD = 0.06, 95% confidence interval [CI]: 0.01-0.12, P = .02), but no significant differences in exacerbation frequency (MD = -0.42, 95%CI: -1.13 to 0.30, P = .25) and peak expiratory flow (PEF) (MD = 0.20, 95% CI: -0.05 to 0.44, P = .12), fractional exhaled nitric oxide (FeNO) (MD = 4.12, 95% CI: -2.06 to 10.30, P = .19), asthma quality of life questionnaire (AQLQ) (MD: 0.05, 95% CI: -0.17 to 0.28, P = .65), asthma control questionnaire (ACQ) (MD: -0.03, 95% CI: -0.21 to 0.15, P = .75). The subgroup analysis revealed that azithromycin could decrease FeNO among Asian asthma (MD = 15.04, 95% CI: 6.18-23.90, P = .0009). CONCLUSIONS: Add-on therapy of azithromycin in asthma patients could improve the FEV1, but failed to improve asthma exacerbations, PEF, ACQ, AQLQ, and FeNO. Subgroup analysis indicated that azithromycin could improve FeNO in Asian group asthmatics.


Assuntos
Antibacterianos/uso terapêutico , Asma/tratamento farmacológico , Azitromicina/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Azitromicina/administração & dosagem , Azitromicina/efeitos adversos , Humanos , Resultado do Tratamento
10.
West Afr J Med ; 36(3): 267-273, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31622490

RESUMO

BACKGROUND: Asthma is known to constitute a huge economic burden to its sufferers and their carers. There is a dearth of studies documenting this burden among asthmatics in Nigeria. OBJECTIVE: This study assessed the relationship between economic cost and psychiatric morbidity among stable Nigerian patients with asthma. METHODS: 85 patients with asthma completed a socio-demographic and illness-related questionnaire, the modified Economic Cost Questionnaire and General Health Questionnaire 12 (GHQ 12). Associations between socio-demographic characteristics, illness related variables, psychiatric morbidity and the direct, indirect and total costs in relation to asthma were assessed. RESULTS: The average annual total, direct and indirect cost were $309, $190.65 and $118.34 respectively per patient for subjects with asthma. Direct cost constituted 62.7% while the indirect cost was 38.3% of the total cost for asthma. Drugs and hospitalisation were leading contributors to direct costs for asthma. Psychiatric morbidity was found to be present in 35% of subjects with asthma, those with psychiatric morbidity had a higher economic burden. CONCLUSION: The economic cost of asthma is high, psychiatric morbidity increases this cost. The cost is largely due to drugs and hospitalisations for exacerbation. There is an urgent need to optimize means of helping to minimize this cost and increase measures for detecting and treating psychiatric morbidity.


Assuntos
Antiasmáticos/economia , Asma/economia , Gastos em Saúde , Hospitalização/economia , Transtornos Mentais/epidemiologia , Antiasmáticos/administração & dosagem , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Asma/epidemiologia , Efeitos Psicossociais da Doença , Custos e Análise de Custo , Custos Diretos de Serviços/estatística & dados numéricos , Recursos em Saúde/estatística & dados numéricos , Humanos , Morbidade , Nigéria/epidemiologia , Qualidade de Vida
11.
Rev Assoc Med Bras (1992) ; 65(9): 1223-1228, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31618342

RESUMO

OBJECTIVE: The objective of this article was to conduct a systematic review of the treatment of moderate-to-severe asthma by administrating Dupilumab. METHODS: A search on the online databases EBSCO, Scielo, PubMed, Medline Bireme, Lilacs, and The New England Journal of Medicine was conducted, publications from 2010 to 2018 were selected. The inclusion criteria were articles which contained control groups, tested the validity of Dupilumab, and verified the response of patients through controlled tests. For the search of such articles, the following keywords were used: "Dupilumab", "asthma", "Bronchial Asthma" AND "Asthma, Bronchial" AND their correspondent in Portuguese "asma", "Asma brônquica" and "Asma brônquica". The exclusion criteria were literature reviews, news, articles without control groups, articles on different subjects, Dupilumab studies on other diseases, articles concerning asthma without the use of Dupilumab, and repeated articles on the databases were discarded. RESULTS: The literature considers that the medication shows a good response for the treatment of moderate-to-severe asthma and assists in the improvement of lung function, aside from resulting in few side effects. It presents good efficacy, safety, and tolerance by patients. CONCLUSIONS: Dupilumab is promising for the treatment of asthma, whereas conventional therapy is deemed to be insufficient. More additional studies are needed to confirm the long-term safety and effectiveness.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Asma/tratamento farmacológico , Ensaios Clínicos Controlados como Assunto , Volume Expiratório Forçado , Humanos , Resultado do Tratamento
12.
Cochrane Database Syst Rev ; 9: CD006924, 2019 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-31553802

RESUMO

BACKGROUND: Epidemiological evidence has suggested a link between beta2-agonists and increases in asthma mortality. There has been much debate about whether regular (daily) long-acting beta2-agonists (LABA) are safe when used in combination with inhaled corticosteroids (ICS). This updated Cochrane Review includes results from two large trials that recruited 23,422 adolescents and adults mandated by the US Food and Drug Administration (FDA). OBJECTIVES: To assess the risk of mortality and non-fatal serious adverse events (SAEs) in trials that randomly assign participants with chronic asthma to regular formoterol and inhaled corticosteroids versus the same dose of inhaled corticosteroid alone. SEARCH METHODS: We identified randomised trials using the Cochrane Airways Group Specialised Register of trials. We checked websites of clinical trial registers for unpublished trial data as well as FDA submissions in relation to formoterol. The date of the most recent search was February 2019. SELECTION CRITERIA: We included randomised clinical trials (RCTs) with a parallel design involving adults, children, or both with asthma of any severity who received regular formoterol and ICS (separate or combined) treatment versus the same dose of ICS for at least 12 weeks. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We obtained unpublished data on mortality and SAEs from the sponsors of the studies. We assessed our confidence in the evidence using GRADE recommendations. The primary outcomes were all-cause mortality and all-cause non-fatal serious adverse events. MAIN RESULTS: We found 42 studies eligible for inclusion and included 39 studies in the analyses: 29 studies included 35,751 adults, and 10 studies included 4035 children and adolescents. Inhaled corticosteroids included beclomethasone (daily metered dosage 200 to 800 µg), budesonide (200 to 1600 µg), fluticasone (200 to 250 µg), and mometasone (200 to 800 µg). Formoterol metered dosage ranged from 12 to 48 µg daily. Fixed combination ICS was used in most of the studies. We judged the risk of selection bias, performance bias, and attrition bias as low, however most studies did not report independent assessment of causation of SAEs.DeathsSeventeen of 18,645 adults taking formoterol and ICS and 13 of 17,106 adults taking regular ICS died of any cause. The pooled Peto odds ratio (OR) was 1.25 (95% confidence interval (CI) 0.61 to 2.56, moderate-certainty evidence), which equated to one death occurring for every 1000 adults treated with ICS alone for 26 weeks; the corresponding risk amongst adults taking formoterol and ICS was also one death (95% CI 0 to 2 deaths). No deaths were reported in the trials on children and adolescents (4035 participants) (low-certainty evidence).In terms of asthma-related deaths, no children and adolescents died from asthma, but three of 12,777 adults in the formoterol and ICS treatment group died of asthma (both low-certainty evidence).Non-fatal serious adverse eventsA total of 401 adults experienced a non-fatal SAE of any cause on formoterol with ICS, compared to 369 adults who received regular ICS. The pooled Peto OR was 1.00 (95% CI 0.87 to 1.16, high-certainty evidence, 29 studies, 35,751 adults). For every 1000 adults treated with ICS alone for 26 weeks, 22 adults had an SAE; the corresponding risk for those on formoterol and ICS was also 22 adults (95% CI 19 to 25).Thirty of 2491 children and adolescents experienced an SAE of any cause when receiving formoterol with ICS, compared to 13 of 1544 children and adolescents receiving ICS alone. The pooled Peto OR was 1.33 (95% CI 0.71 to 2.49, moderate-certainty evidence, 10 studies, 4035 children and adolescents). For every 1000 children and adolescents treated with ICS alone for 12.5 weeks, 8 had an non-fatal SAE; the corresponding risk amongst those on formoterol and ICS was 11 children and adolescents (95% CI 6 to 21).Asthma-related serious adverse eventsNinety adults experienced an asthma-related non-fatal SAE with formoterol and ICS, compared to 102 with ICS alone. The pooled Peto OR was 0.86 (95% CI 0.64 to 1.14, moderate-certainty evidence, 28 studies, 35,158 adults). For every 1000 adults treated with ICS alone for 26 weeks, 6 adults had an asthma-related non-fatal SAE; the corresponding risk for those on formoterol and ICS was 5 adults (95% CI 4 to 7).Amongst children and adolescents, 9 experienced an asthma-related non-fatal SAE with formoterol and ICS, compared to 5 on ICS alone. The pooled Peto OR was 1.18 (95% CI 0.40 to 3.51, very low-certainty evidence, 10 studies, 4035 children and adolescents). For every 1000 children and adolescents treated with ICS alone for 12.5 weeks, 3 had an asthma-related non-fatal SAE; the corresponding risk on formoterol and ICS was 4 (95% CI 1 to 11). AUTHORS' CONCLUSIONS: We did not find a difference in the risk of death (all-cause or asthma-related) in adults taking combined formoterol and ICS versus ICS alone (moderate- to low-certainty evidence). No deaths were reported in children and adolescents. The risk of dying when taking either treatment was very low, but we cannot be certain if there is a difference in mortality when taking additional formoterol to ICS (low-certainty evidence).We did not find a difference in the risk of non-fatal SAEs of any cause in adults (high-certainty evidence). A previous version of the review had shown a lower risk of asthma-related SAEs in adults taking combined formoterol and ICS; however, inclusion of new studies no longer shows a difference between treatments (moderate-certainty evidence).The reported number of children and adolescents with SAEs was small, so uncertainty remains in this age group.We included results from large studies mandated by the FDA. Clinical decisions and information provided to patients regarding regular use of formoterol and ICS need to take into account the balance between known symptomatic benefits of formoterol and ICS versus the remaining degree of uncertainty associated with its potential harmful effects.


Assuntos
Corticosteroides/efeitos adversos , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Antiasmáticos/efeitos adversos , Asma/tratamento farmacológico , Fumarato de Formoterol/efeitos adversos , Administração por Inalação , Corticosteroides/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Antiasmáticos/administração & dosagem , Antiasmáticos/uso terapêutico , Quimioterapia Combinada , Fumarato de Formoterol/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
N Engl J Med ; 381(13): 1227-1239, 2019 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-31553835

RESUMO

BACKGROUND: Morbidity from asthma is disproportionately higher among black patients than among white patients, and black patients constitute the minority of participants in trials informing treatment. Data indicate that patients with inadequately controlled asthma benefit more from addition of a long-acting beta-agonist (LABA) than from increased glucocorticoids; however, these data may not be informative for treatment in black patients. METHODS: We conducted two prospective, randomized, double-blind trials: one involving children and the other involving adolescents and adults. In both trials, the patients had at least one grandparent who identified as black and had asthma that was inadequately controlled with low-dose inhaled glucocorticoids. We compared combinations of therapy, which included the addition of a LABA (salmeterol) to an inhaled glucocorticoid (fluticasone propionate), a step-up to double to quintuple the dose of fluticasone, or both. The treatments were compared with the use of a composite measure that evaluated asthma exacerbations, asthma-control days, and lung function; data were stratified according to genotypic African ancestry. RESULTS: When quintupling the dose of fluticasone (to 250 µg twice a day) was compared with adding salmeterol (50 µg twice a day) and doubling the fluticasone (to 100 µg twice a day), a superior response occurred in 46% of the children with quintupling the fluticasone and in 46% of the children with doubling the fluticasone and adding salmeterol (P = 0.99). In contrast, more adolescents and adults had a superior response to added salmeterol than to an increase in fluticasone (salmeterol-low-dose fluticasone vs. medium-dose fluticasone, 49% vs. 28% [P = 0.003]; salmeterol-medium-dose fluticasone vs. high-dose fluticasone, 49% vs. 31% [P = 0.02]). Neither the degree of African ancestry nor baseline biomarkers predicted a superior response to specific treatments. The increased dose of inhaled glucocorticoids was associated with a decrease in the ratio of urinary cortisol to creatinine in children younger than 8 years of age. CONCLUSIONS: In contrast to black adolescents and adults, almost half the black children with poorly controlled asthma had a superior response to an increase in the dose of an inhaled glucocorticoid and almost half had a superior response to the addition of a LABA. (Funded by the National Heart, Lung, and Blood Institute; BARD ClinicalTrials.gov number, NCT01967173.).


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Afro-Americanos , Asma/tratamento farmacológico , Broncodilatadores/administração & dosagem , Fluticasona/administração & dosagem , Glucocorticoides/administração & dosagem , Xinafoato de Salmeterol/administração & dosagem , Administração por Inalação , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Masculino , Estudos Prospectivos
15.
Expert Opin Investig Drugs ; 28(11): 931-940, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31549891

RESUMO

Introduction: Thymic stromal lymphopoietin (TSLP) is overexpressed in the airways of severe asthmatics and is an upstream cytokine that orchestrates inflammatory responses in asthma. TSLP exerts its effects by binding to a high affinity heteromeric receptor complex composed of TSLPR and IL-7Rα. An association of polymorphisms in TSLP with airway hyperresponsiveness, IgE, eosinophilia and asthma has been documented. TSLP has been implicated in asthma pathophysiology. Tezepelumab is a first-in-class human monoclonal antibody that binds to TSLP, thus inhibiting its interaction with TSLP receptor complex. Tezepelumab given as an add-on-therapy to patients with severe uncontrolled asthma has shown safety, tolerability and efficacy. Several trials are evaluating the long-term safety and the efficacy of tezepelumab in adults and adolescents with severe uncontrolled asthma.Areas covered: We provide an overview of the monoclonal antibody therapeutics market for severe uncontrolled asthma, examine the underlying pathophysiology that drives TSLP and discuss the use of tezepelumab for the treatment of severe uncontrolled asthma,Expert opinion: TSLP is a promising target for T2-high and perhaps some patients with T2-low asthma. The results of preliminary clinical trials are encouraging. Several unanswered questions concerning basic pathophysiological aspects of TSLP variants, the long-term safety and efficacy of tezepelumab with different phenotypes/endotypes of asthma should be addressed.


Assuntos
Antiasmáticos/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Asma/tratamento farmacológico , Adolescente , Adulto , Animais , Antiasmáticos/efeitos adversos , Antiasmáticos/farmacologia , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacologia , Asma/imunologia , Asma/fisiopatologia , Citocinas/imunologia , Humanos , Índice de Gravidade de Doença
17.
Expert Opin Investig Drugs ; 28(10): 827-833, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31474120

RESUMO

Introduction: A compound that simultaneously inhibits PDE3 and PDE4 should increase airway caliber by relaxing the smooth muscle and, simultaneously, suppress airway inflammatory responses. Ensifentrine (RPL554) is considered a PDE3/4 inhibitor, although its affinity for PDE3 is 3,440 times higher than that for PDE4, that is under clinical development for the treatment of asthma and COPD and, potentially, cystic fibrosis. Areas covered: We analyze the development of this molecule from its basic pharmacology to the present clinical Phase II studies. Expert opinion: Ensifentrine is an interesting drug but there is a lack of solid studies that still does not allow us to correctly allocate this molecule in the current COPD and even asthma therapeutic armamentarium. Furthermore, apparently ensifentrine has not yet entered Phase III clinical development and, in any case, there is no reliable evidence of its ability to elicit an anti-inflammatory activity in patients with COPD or asthma. Therefore, the real anti-inflammatory profile of ensifentrine must be clarified with new studies of basic pharmacology and adequate clinical studies specifically designed. However, at present the most intriguing perspective is linked to its possible use in the treatment of cystic fibrosis, also considering the lack of valid therapeutic options for this disease.


Assuntos
Asma/tratamento farmacológico , Isoquinolinas/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Pirimidinonas/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Asma/fisiopatologia , Fibrose Cística/tratamento farmacológico , Fibrose Cística/fisiopatologia , Desenvolvimento de Medicamentos/métodos , Humanos , Isoquinolinas/farmacologia , Inibidores da Fosfodiesterase 3/farmacologia , Inibidores da Fosfodiesterase 3/uso terapêutico , Inibidores da Fosfodiesterase 4/farmacologia , Inibidores da Fosfodiesterase 4/uso terapêutico , Pirimidinonas/farmacologia
18.
Arerugi ; 68(7): 869-873, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31406083

RESUMO

The two biologic therapies, anti-IgE (omalizumab) and anti-IL-5 antibodies (mepolizumab), are used in the treatment of severe pediatric asthma. We present here a case study of a 13-year-old girl with severe asthma who switched from omalizumab to mepolizumab therapy and achieved good control over her asthma. The patient was diagnosed with asthma at one year of age and presented with poor disease control, even while taking high doses of inhaled corticosteroids (ICS). As such, she was considered to have severe persistent asthma. At 10 years old, she began omalizumab therapy which improved asthma control. However, after two years of this therapy, she manifested frequent acute exacerbations. At 12 years old, she switched to mepolizumab and has since maintained good control of asthma. Additionally, total serum IgE levels and peripheral eosinophil counts decreased. As the underlying mechanisms of omalizumab and mepolizumab therapy are distinct, it is recommended to use either one if the other proves ineffective.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Substituição de Medicamentos , Omalizumab/uso terapêutico , Adolescente , Corticosteroides , Criança , Feminino , Humanos
19.
Medicine (Baltimore) ; 98(34): e16958, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441897

RESUMO

BACKGROUND: Asthma is a complex disease associated with many factors such as immunologic, environmental, genetic, and other factors. Common medicines used to treat asthma include ß-agonist and glucocorticoid. However, in the long-term treatment, the effect of the above-mentioned drugs is not satisfactory, so many patients choose oral Chinese medicines instead of western medicines. The introduction of Chinese medicines therapies, a rapid proliferation of the literature on management of asthma in general, call for novel ways of evidence synthesis in this area. This systematic review is to systematically summarize and evaluate a large number of evidences for Chinese herbal interventions for asthma. Evaluate the efficacy and safety of Chinese medicines in the treatment of asthma and inform a decision aid for the clinical encounter between patients and clinicians. In addition, it helps to establish a future research agenda. METHODS: Five English databases (PubMed, Web of science, EBASE, Springer Cochrane Library, and WHO International Clinical Trials Registry Platform) and 4 Chinese databases (Wanfang Database, Chinese Scientific Journal Database, China National Knowledge Infrastructure Database, and Chinese Biomedical Literature Database) will be searched normatively according to the rule of each database from the inception to the present. The literature screening, data extraction, and quality assessment will be conducted by 2 researchers independently. Data will be synthesized by either the fixed-effects or random-effects model according to a heterogeneity test. Asthma control test symptom score will be assessed as the primary outcome. The curative effect of single symptom and sign; Withdrawal and reduction of western medicines in a course of treatment, including: time, type, and quantity; Maintenance of western medicines after the course of treatment, including: type, quantity; Asthma Quality of Life Questionnaire; laboratory efficacy indexes as the secondary outcome. General physical examination; routine examination of blood, urine, and stool; electrocardiogram; liver and kidney function examination; possible adverse reactions and related detection indicators as the security indexes. Meta-analysis will be performed using RevMan5.3.5 software provided by the Cochrane Collaboration. RESULTS: This study will provide high-quality synthesis based on current evidence of Chinese medicines treatment for asthma in several aspects, including asthma control score, side effects and laboratory examination such as lung-function test, serum total immunoglobulin, and so on. CONCLUSION: The results of this study will provide updated evidence for whether Chinese medicines is an effective and safe intervention for asthma. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019136074.


Assuntos
Asma/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Medicina Tradicional Chinesa , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisão Sistemática como Assunto , Resultado do Tratamento
20.
Medicine (Baltimore) ; 98(33): e16630, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415356

RESUMO

BACKGROUND: Asthma is a chronic inflammatory disease characterized by recurrent attacks of breathlessness and wheezing, which often worsen at night or in the early morning and vary from person to person in severity and frequency. Chuankezhi injection (CKZ), as a new Chinese medicine, was recently found to have a good clinical effect on asthma. Whereas neither systematic nor meta-analysis of randomized controlled trials (RCTs) explain the efficacy of CKZ in treating asthma. Therefore, we provide a protocol to evaluate the efficacy and safety of CKZ for asthma. METHODS: From inception until April 2019, a systematic and comprehensive literature search will be conducted in both 4 Chinese databases and 3 English databases. RCTs will be included related to CKZ for asthma. We will assess the quality of the included trials in accordance with the risk of bias tools in Cochrane manual 5.1.0. We will use the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method to assess the certainty of the estimated evidence. Data analysis will be performed using the STATA 15.0. RESULTS: This systematic review aims to assess the effectiveness and safety of CKZ for the treatment of asthma, in order to provide evidence for the clinical practice of Chinese medicine. This protocol will be conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement. The results of this meta-analysis will be submitted to a peer-reviewed journal once it is completed. CONCLUSION: The consequence of this study will furnish proof to evaluate if CKZ is effective in the treatment of asthma. PROSPERO REGISTRATION NUMBER: ROSPERO CRD42019134458.


Assuntos
Asma/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Adulto , Doença Crônica , Feminino , Humanos , Injeções , Masculino , Metanálise como Assunto , Projetos de Pesquisa , Revisão Sistemática como Assunto , Resultado do Tratamento
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