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1.
Lancet ; 395(10221): 371-383, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32007172

RESUMO

Asthma is a disease of reversible airflow obstruction characterised clinically by wheezing, shortness of breath, and coughing. Increases in airway type 2 cytokine activity, including interleukin-4 (IL-4), IL-5, and IL-13, are now established biological mechanisms in asthma. Inhaled corticosteroids have been the foundation for asthma treatment, in a large part because they decrease airway type 2 inflammation. However, inhaled or systemic corticosteroids are ineffective treatments in many patients with asthma and few treatment options exist for patients with steroid resistant asthma. Although mechanisms for corticosteroid refractory asthma are likely to be numerous, the development of a new class of biologic agents that target airway type 2 inflammation has provided a new model for treating some patients with corticosteroid refractory asthma. The objective of this Therapeutic paper is to summarise the new type 2 therapeutics, with an emphasis on the biological rationale and clinical efficacy of this new class of asthma therapeutics.


Assuntos
Antiasmáticos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Adulto , Biomarcadores/metabolismo , Ensaios Clínicos Fase III como Assunto , Citocinas/antagonistas & inibidores , Citocinas/fisiologia , Eosinófilos/fisiologia , Previsões , Humanos , Ácidos Indolacéticos/uso terapêutico , Interleucina-4/antagonistas & inibidores , Interleucina-5/antagonistas & inibidores , Omalizumab/uso terapêutico , Piridinas/uso terapêutico , Células Th2/fisiologia , Resultado do Tratamento
2.
Life Sci ; 242: 117222, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31881223

RESUMO

BACKGROUND: Asthma is a complex inflammatory disease which affects multiple individuals worldwide especially pediatric ages. AIMS: This study aimed to assess the possible protective effect of carvacrol, as natural antioxidant anti-inflammatory drug, against bronchial asthma induced experimentally in rats. MAIN METHODS: Rats were randomly allocated into 5 groups; a normal control group, control drug group received only carvacrol, an asthma control group, a standard treatment group receiving dexamethasone (DEXA) and carvacrol treatment group. Bronchial asthma was induced by sensitization with i.p dose followed by challenge with intranasal dose of ovalbumin (OVA). 24 h after the last challenge, absolute eosinophil count (AEC) were determined in bronchoalveolar lavage fluids (BALF). Immunoglobulin E (IgE) was determined in serum. Inflammatory biomarkers like Interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin 13 (IL-13), tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) were also measured in BALF. Nitrosative stress biomarker namely inducible nitric oxide synthase (iNOS) was determined in BALF as well as oxidative stress biomarkers namely superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) were determined in lung tissue. Additionally, histopathological study, immunohistochemical study of UCN and western blot analysis of SP-D were performed. KEY FINDINGS: Carvacrol administration significantly reduced the values of AEC, IgE, IL-4, IL-5, IL-13, TNF-α, IFN-γ, iNOS and MDA, while it significantly increased the values of SOD and GSH as compared to the asthmatic group. Histopathological, immunohistochemical and western blot study reinforced the biochemical results. SIGNIFICANCE: Carvacrol may be a promising protective agent against bronchial asthma induced experimentally in rats.


Assuntos
Antiasmáticos/farmacologia , Anti-Inflamatórios/farmacologia , Asma/tratamento farmacológico , Fatores Imunológicos/farmacologia , Animais , Antiasmáticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Asma/induzido quimicamente , Asma/patologia , Western Blotting , Modelos Animais de Doenças , Fatores Imunológicos/uso terapêutico , Interleucina-13/metabolismo , Interleucina-4/metabolismo , Interleucina-5/metabolismo , Masculino , Óxido Nítrico Sintase Tipo II/metabolismo , Ovalbumina/farmacologia , Proteína D Associada a Surfactante Pulmonar/metabolismo , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real
4.
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
5.
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
8.
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
9.
Lancet ; 394(10202): 919-928, 2019 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-31451207

RESUMO

BACKGROUND: In adults with mild asthma, a combination of an inhaled corticosteroid with a fast-onset long-acting ß-agonist (LABA) used as reliever monotherapy reduces severe exacerbations compared with short-acting ß-agonist (SABA) reliever therapy. We investigated the efficacy of combination budesonide-formoterol reliever therapy compared with maintenance budesonide plus as-needed terbutaline. METHODS: We did a 52-week, open-label, parallel-group, multicentre, superiority, randomised controlled trial at 15 primary care or hospital-based clinical trials units and primary care practices in New Zealand. Participants were adults aged 18-75 years with a self-reported doctor's diagnosis of asthma who were using SABA for symptom relief with or without maintenance low to moderate doses of inhaled corticosteroids in the previous 12 weeks. We randomly assigned participants (1:1) to either reliever therapy with budesonide 200 µg-formoterol 6 µg Turbuhaler (one inhalation as needed for relief of symptoms) or maintenance budesonide 200 µg Turbuhaler (one inhalation twice daily) plus terbutaline 250 µg Turbuhaler (two inhalations as needed). Participants and investigators were not masked to group assignment; the statistician was masked for analysis of the primary outcome. Six study visits were scheduled: randomisation, and weeks 4, 16, 28, 40, and 52. The primary outcome was the number of severe exacerbations per patient per year analysed by intention to treat (severe exacerbations defined as use of systemic corticosteroids for at least 3 days because of asthma, or admission to hospital or an emergency department visit because of asthma requiring systemic corticosteroids). Safety analyses included all participants who had received at least one dose of study treatment. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12616000377437. FINDINGS: Between May 4, 2016, and Dec 22, 2017, we assigned 890 participants to treatment and included 885 eligible participants in the analysis: 437 assigned to budesonide-formoterol as needed and 448 to budesonide maintenance plus terbutaline as needed. Severe exacerbations per patient per year were lower with as-needed budesonide-formoterol than with maintenance budesonide plus terbutaline as needed (absolute rate per patient per year 0·119 vs 0·172; relative rate 0·69, 95% CI 0·48-1·00; p=0·049). Nasopharyngitis was the most common adverse event in both groups, occurring in 154 (35%) of 440 patients receiving as-needed budesonide-formoterol and 144 (32%) of 448 receiving maintenance budesonide plus terbutaline as needed. INTERPRETATION: In adults with mild to moderate asthma, budesonide-formoterol used as needed for symptom relief was more effective at preventing severe exacerbations than maintenance low-dose budesonide plus as-needed terbutaline. The findings support the 2019 Global Initiative for Asthma recommendation that inhaled corticosteroid-formoterol reliever therapy is an alternative regimen to daily low-dose inhaled corticosteroid for patients with mild asthma. FUNDING: Health Research Council of New Zealand.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Combinação Budesonida e Fumarato de Formoterol/uso terapêutico , Adolescente , Adulto , Idoso , Antiasmáticos/administração & dosagem , Broncodilatadores/administração & dosagem , Broncodilatadores/uso terapêutico , Budesonida/administração & dosagem , Budesonida/uso terapêutico , Combinação Budesonida e Fumarato de Formoterol/administração & dosagem , Esquema de Medicação , Estudos de Equivalência como Asunto , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Nebulizadores e Vaporizadores , Índice de Gravidade de Doença , Terbutalina/administração & dosagem , Terbutalina/uso terapêutico , Resultado do Tratamento , Adulto Jovem
10.
Pediatr Clin North Am ; 66(5): 925-939, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31466682

RESUMO

Asthma is a complex, heterogeneous chronic airway disease with high prevalence of uncontrolled disease. New therapies, including biologics, are now available to treat T2 high asthma. Treatment of T2 low asthma remains a challenge. Asthma guidelines need be to updated to incorporate new therapeutics.


Assuntos
Antiasmáticos/uso terapêutico , Asma/terapia , Termoplastia Brônquica , Anticorpos Monoclonais/uso terapêutico , Asma/imunologia , Asma/fisiopatologia , Produtos Biológicos/uso terapêutico , Humanos , Guias de Prática Clínica como Assunto , Índice de Gravidade de Doença
11.
Pediatr Clin North Am ; 66(5): 967-979, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31466685

RESUMO

Inner-city children with asthma are known to have high disease mortality and morbidity. Frequently, asthma in this high-risk population is difficult to control and more severe in nature. Several factors, including socioeconomic hardship, ability to access to health care, adherence to medication, exposure to certain allergens, pollution, crowd environment, stress, and infections, play an important role in the pathophysiology of inner-city asthma. Comprehensive control of home allergens and exposure to tobacco smoke, the use of immune based therapies, and school-based asthma programs have shown promising results in asthma control in this population.


Assuntos
Asma/etiologia , Asma/prevenção & controle , População Urbana , Alérgenos/imunologia , Antiasmáticos/uso terapêutico , Criança , Exposição Ambiental/efeitos adversos , Exposição Ambiental/prevenção & controle , Poluentes Ambientais/efeitos adversos , Humanos , Imunoterapia , Fatores de Risco , Meio Social
12.
J Pak Med Assoc ; 69(Suppl 2)(6): S2-S9, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31369528

RESUMO

Objectives: To estimate the economic burden of asthma treatment by quantifying direct medical expenditures at one of Southern Vietnam's public hospitals base on the hospital perspective. Methods: A retrospective, prevalence-based, cost-of-illness analysis was developed using the hospital's electronic medical record data to calculate the economic burden of asthma (ICD-10 code J45, J46) through direct medical costs from January 2014 to December 2017. All costs were converted to US dollars and to the year 2018. Data were analyzed using descriptive statistics. The potential correlations between variables were evaluated using the chisquare test and bootstrap difference. Results: The average direct medical cost of asthma was estimated to range from $34.7 to $55.3 per - outpatient and $45.1 to $107.2 per - inpatient annually. The total economic burdens for 4 years from 2014 to 2017 were $110,387.4 from outpatients and $13,413.8 from inpatients. The most influential component was medication cost. Conclusions: Asthma places a high economic burden on individuals and the healthcare system in Vietnam. The findings of this study provide health administrators with important evidence to enhance surveillance of the disease and to allow suitable drafting of national health policy.


Assuntos
Assistência Ambulatorial/economia , Antiasmáticos/economia , Asma/economia , Efeitos Psicossociais da Doença , Gastos em Saúde , Hospitalização/economia , Adolescente , Adulto , Antiasmáticos/uso terapêutico , Asma/terapia , Criança , Custos de Medicamentos , Feminino , Custos Hospitalares , Hospitais Públicos , Humanos , Seguro Saúde , Masculino , Estudos Retrospectivos , Espirometria/economia , Vietnã , Adulto Jovem
13.
J Pak Med Assoc ; 69(Suppl 2)(6): S41-S48, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31369533

RESUMO

Objectives: Asthma is a disease that causes significant health and economic burdens worldwide. The prevalence and incidence of asthma have been rising around the world over recent decades. The current study is to capture the direct medical costs of inpatient and outpatient asthma treatment for the period from 2013 to 2017. Methods: This study was conducted at Military Hospital 175 in Vietnam. The study was performed from the patient and social insurance perspective, which means all types of costs were identified and measured based on patients' healthcare insurance. Cost analysis was measured using the medical records for estimating the economic burden of asthma. The study adopted descriptive statistics and bootstrap techniques to calculate asthma-related costs as well as analyze the background characteristics of asthma patients. Results: The average outpatient and inpatient costs were US$64.90 and US$141.20, respectively, over the period from 2013 to 2017, for which out-of-pocket payments accounted for 10-12%. Medications, specifically asthma controller drugs, were the key driver leading to the substantial burden of direct medical costs for treating asthma. The cost burden was also significantly higher for adult patients compared to children. Conclusions: Asthma continues to be a concerning problem in Vietnam. The economic impact of either preventive or promotive health interventions that can reduce the prevalence of asthma can be predicted from the statistics found in this research. Moreover, this data will help policymakers plan and allocate national expenditures for asthma treatment in a more rational way.


Assuntos
Assistência Ambulatorial/economia , Antiasmáticos/economia , Asma/economia , Hospitalização/economia , Hospitais Militares , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiasmáticos/uso terapêutico , Asma/terapia , Criança , Pré-Escolar , Feminino , Custos de Cuidados de Saúde , Gastos em Saúde , Humanos , Seguro Saúde , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Vietnã , Adulto Jovem
14.
Respir Res ; 20(1): 173, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375102

RESUMO

Despite the availability of treatment guidelines and inhaled medications for asthma and chronic obstructive pulmonary disease (COPD), much remains to be done to lessen the burden of these respiratory diseases for patients. The challenge of selecting effective and efficacious drugs for patients is a key focus area for healthcare professionals. Here we discuss the concept of "drivers of effectiveness"- features of a medicine which may increase or decrease its effectiveness in the presence of real-world factors - and highlight the importance of considering these drivers in the early stages of drug development, and exploring their impact in carefully designed pragmatic trials. Using the Salford Lung Studies (SLS) in asthma and COPD as an illustrative example, we discuss various features of the inhaled corticosteroid/long-acting ß2-agonist combination, fluticasone furoate/vilanterol (FF/VI), as potential drivers of effectiveness that may have contributed to the improved patient outcomes observed with initiation of FF/VI versus continuation of usual care in the UK primary care setting.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Gerenciamento Clínico , Desenvolvimento de Medicamentos/tendências , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Antiasmáticos/economia , Asma/diagnóstico , Asma/economia , Análise Custo-Benefício/métodos , Desenvolvimento de Medicamentos/economia , Humanos , Adesão à Medicação , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/economia , Resultado do Tratamento
15.
BMC Pulm Med ; 19(1): 129, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31315668

RESUMO

BACKGROUND: Tralokinumab is an anti-interleukin (IL)-13 monoclonal antibody investigated for the treatment of severe, uncontrolled asthma in two Phase III clinical trials, STRATOS 1 and 2. The STRATOS 1 biomarker analysis plan was developed to identify biomarker(s) indicative of IL-13 activation likely to predict tralokinumab efficacy and define a population in which there was an enhanced treatment effect; this defined population was then tested in STRATOS 2. METHODS: The biomarkers considered were blood eosinophil counts, fractional exhaled nitric oxide (FeNO), serum dipeptidyl peptidase-4, serum periostin and total serum immunoglobulin E. Tralokinumab efficacy was measured as the reduction in annualised asthma exacerbation rate (AAER) compared with placebo (primary endpoint measure of STRATOS 1 and 2). The biomarker analysis plan included negative binomial and generalised additive models, and the Subgroup Identification based on Differential Effect Search (SIDES) algorithm, supported by robustness and sensitivity checks. Effects on the key secondary endpoints of STRATOS 1 and 2, which included changes from baseline in standard measures of asthma outcomes, were also investigated. Prior to the STRATOS 1 read-out, numerous simulations of the methodology were performed with hypothetical data. RESULTS: FeNO and periostin were identified as the only biomarkers potentially predictive of treatment effect, with cut-offs chosen by the SIDES algorithm of > 32.3 ppb and > 27.4 ng/ml, respectively. The FeNO > 32.3 ppb subgroup was associated with greater AAER reductions and improvements in key secondary endpoints compared with the periostin > 27.4 ng/ml subgroup. Upon further evaluation of AAER reductions at different FeNO cut-offs, ≥37 ppb was chosen as the best cut-off for predicting tralokinumab efficacy. DISCUSSION: A rigorous statistical approach incorporating multiple methods was used to investigate the predictive properties of five potential biomarkers and to identify a participant subgroup that demonstrated an enhanced tralokinumab treatment effect. Using STRATOS 1 data, our analyses identified FeNO at a cut-off of ≥37 ppb as the best assessed biomarker for predicting enhanced treatment effect to be tested in STRATOS 2. Our findings were inconclusive, which reflects the complexity of subgroup identification in the severe asthma population. TRIAL REGISTRATION: STRATOS 1 and 2 are registered on ClinicalTrials.gov ( NCT02161757 registered on June 12, 2014, and NCT02194699 registered on July 18, 2014).


Assuntos
Antiasmáticos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Asma/tratamento farmacológico , Biomarcadores/análise , Adolescente , Adulto , Idoso , Moléculas de Adesão Celular/sangue , Criança , Progressão da Doença , Método Duplo-Cego , Eosinófilos/citologia , Expiração , Feminino , Humanos , Imunoglobulina E/sangue , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/análise , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
16.
Cells ; 8(7)2019 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-31284537

RESUMO

Asthma is a common respiratory disease worldwide. Cytokines play a crucial role in the immune system and the inflammatory response to asthma. Abnormal cytokine expression may lead to the development of asthma, which may contribute to pathologies of this disease. As cytokines exhibit pleiotropy and redundancy characteristics, we summarized them according to their biologic activity in asthma development. We classified cytokines in three stages as follows: Group 1 cytokines for the epithelial environment stage, Group 2 cytokines for the Th2 polarization stage, and Group 3 cytokines for the tissue damage stage. The recent cytokine-targeting therapy for clinical use (anti-cytokine antibody/anti-cytokine receptor antibody) and traditional medicinal herbs (pure compounds, single herb, or natural formula) have been discussed in this review. Studies of the Group 2 anti-cytokine/anti-cytokine receptor therapies are more prominent than the studies of the other two groups. Anti-cytokine antibodies/anti-cytokine receptor antibodies for clinical use can be applied for patients who did not respond to standard treatments. For traditional medicinal herbs, anti-asthmatic bioactive compounds derived from medicinal herbs can be divided into five classes: alkaloids, flavonoids, glycosides, polyphenols, and terpenoids. However, the exact pathways targeted by these natural compounds need to be clarified. Using relevant knowledge to develop more comprehensive strategies may provide appropriate treatment for patients with asthma in the future.


Assuntos
Antiasmáticos/farmacologia , Asma/tratamento farmacológico , Citocinas/antagonistas & inibidores , Mediadores da Inflamação/antagonistas & inibidores , Preparações de Plantas/farmacologia , Antiasmáticos/uso terapêutico , Asma/imunologia , Citocinas/imunologia , Citocinas/metabolismo , Humanos , Mediadores da Inflamação/imunologia , Preparações de Plantas/uso terapêutico , Plantas Medicinais/química , Receptores de Citocinas/antagonistas & inibidores , Receptores de Citocinas/metabolismo
17.
Immunol Allergy Clin North Am ; 39(3): 429-445, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31284931

RESUMO

Monoclonal antibodies block specific inflammatory pathways involved in the pathogenesis of asthma. These pathways are important in host defense against pathogens, and in particular, against parasites. Despite theoretical concerns about infection risk, biologics seem to have a favorable safety profile. Data from large clinical trials and postmarketing surveillance for these drugs have not shown increases in severe infections, including those from parasitic organisms. This may be due to redundancy of effector cells within the immune system. Certain drugs have special considerations and precautions, and therefore, the prescribing physician should be familiar with product recommendations and warnings.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Produtos Biológicos/uso terapêutico , /etiologia , Animais , Antiasmáticos/administração & dosagem , Antiasmáticos/efeitos adversos , Asma/complicações , Asma/diagnóstico , Asma/etiologia , Produtos Biológicos/administração & dosagem , Produtos Biológicos/efeitos adversos , Eosinófilos/imunologia , Eosinófilos/metabolismo , Humanos , Imunoglobulina E/imunologia , Medição de Risco , Fatores de Risco , Transdução de Sinais , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
18.
Eur Respir Rev ; 28(152)2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31285286

RESUMO

Asthma incidence and severity are increased in obese populations. Systematic reviews have shown benefit from weight-loss interventions on asthma outcomes, but the role of bariatric surgery is still unclear. In this review, cohorts of obese asthmatic patients undergoing bariatric surgery were examined regarding different asthma outcomes. The available data on patients who were followed up showed improvements in asthma control, exacerbation risk, asthma-related hospitalisation, medication use and airway hyperresponsiveness, with some patients not requiring further treatment for asthma. Follow-up duration was variable, being mostly of 1 year, with some studies reporting long-term outcomes after 5 years. The studies reviewed had many limitations, including small numbers of patients, lack of control arm in some studies and lack of standardisation of asthma diagnosis, classification and outcome measures, in addition to possible reporting bias. Data on small numbers of patients also show the possibility of benefit exclusively in nonallergic asthma. Larger, more stringent clinical trials are needed before recommending bariatric surgery for treatment of asthma.


Assuntos
Antiasmáticos/uso terapêutico , Asma/terapia , Cirurgia Bariátrica , Pulmão/efeitos dos fármacos , Obesidade/cirurgia , Asma/diagnóstico , Asma/epidemiologia , Asma/fisiopatologia , Humanos , Incidência , Pulmão/fisiopatologia , Obesidade/diagnóstico , Obesidade/epidemiologia , Obesidade/fisiopatologia , Prevalência , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Perda de Peso
19.
Eur Respir Rev ; 28(152)2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31285291

RESUMO

The European Respiratory Biologics Forum gathered participants from 21 countries in Madrid, Spain, to discuss the management and treatment of severe asthma in the era of biologics. The current insights on the pathophysiology of severe asthma were discussed, as well as the role of respiratory biologics in clinical practice and strategies for eliminating chronic use of oral corticosteroids. The participants also highlighted the key challenges in identifying patients with severe asthma based on phenotypes, biomarkers and treatable traits, and the existing problems in patient referral to specialist care. The monitoring of treatment was debated and the need for a change towards precision medicine and personalised care was emphasised throughout the meeting. This review provides a summary of the discussions and highlights important concerns identified by the participants regarding the current management of severe asthma.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Pulmão/efeitos dos fármacos , Antiasmáticos/efeitos adversos , Asma/imunologia , Asma/fisiopatologia , Produtos Biológicos/efeitos adversos , Consenso , Humanos , Pulmão/imunologia , Pulmão/fisiopatologia , Fenótipo , Índice de Gravidade de Doença , Resultado do Tratamento
20.
Int J Pediatr Otorhinolaryngol ; 125: 66-70, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31260810

RESUMO

OBJECTIVES: Research has shown improvement in apnea-hypopnea index in children with mild obstructive sleep apnea treated with anti-inflammatory medications. Data on quality of life outcomes in children receiving these medications is lacking. We aim to assess quality of life in children with mild obstructive sleep apnea treated with montelukast and fluticasone. METHODS: Children between 3 and 16 years old with mild sleep apnea (apnea-hypopnea index > 1 and ≤ 5) presenting to a pediatric otolaryngology clinic were recruited prospectively and treated with 4 months of montelukast and fluticasone. Subjects' caregivers completed the OSA-18, a validated quality of life survey, at baseline and 4 months. Children with ongoing obstruction at follow-up underwent adenotonsillectomy. RESULTS: Thirty-one patients were included. Mean (SD) age was 6.8 (3.9) years. Most subjects (54.8%) were black and 48% were obese. Mean (SD) apnea-hypopnea index of the subjects was 2.8 (1.0). The mean (SD) baseline OSA-18 score was 60.2 (18.5), indicating a moderate impact of sleep disturbance on quality of life. Following treatment, there was significant improvement (p < 0.005) in mean OSA-18 score. Four children discontinued montelukast due to behavioral side effects. Seven children (22%) underwent adenotonsillectomy after failing medical therapy. Demographic factors such as obesity [OR 0.63 (0.11, 3.49)] and apnea hypopnea index [OR 1.38 (0.59, 3.66)] failed to predict which children would respond to anti-inflammatory medications. CONCLUSIONS: Children with mild obstructive sleep apnea treated with montelukast and fluticasone experience significant improvements in quality of life. Further research is needed to determine optimal duration of therapy.


Assuntos
Acetatos/uso terapêutico , Fluticasona/uso terapêutico , Quinolinas/uso terapêutico , Síndromes da Apneia do Sono/tratamento farmacológico , Adenoidectomia , Adolescente , Antiasmáticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Obesidade Pediátrica/complicações , Estudos Prospectivos , Qualidade de Vida , Síndromes da Apneia do Sono/cirurgia , Tonsilectomia
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