Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 12 de 12
Filtrar
1.
Lancet ; 391(10122): 783-800, 2018 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-29273246

RESUMO

Asthma-one of the most common chronic, non-communicable diseases in children and adults-is characterised by variable respiratory symptoms and variable airflow limitation. Asthma is a consequence of complex gene-environment interactions, with heterogeneity in clinical presentation and the type and intensity of airway inflammation and remodelling. The goal of asthma treatment is to achieve good asthma control-ie, to minimise symptom burden and risk of exacerbations. Anti-inflammatory and bronchodilator treatments are the mainstay of asthma therapy and are used in a stepwise approach. Pharmacological treatment is based on a cycle of assessment and re-evaluation of symptom control, risk factors, comorbidities, side-effects, and patient satisfaction by means of shared decisions. Asthma is classed as severe when requiring high-intensity treatment to keep it under control, or if it remains uncontrolled despite treatment. New biological therapies for treatment of severe asthma, together with developments in biomarkers, present opportunities for phenotype-specific interventions and realisation of more personalised treatment. In this Seminar, we provide a clinically focused overview of asthma, including epidemiology, pathophysiology, clinical diagnosis, asthma phenotypes, severe asthma, acute exacerbations, and clinical management of disease in adults and children older than 5 years. Emerging therapies, controversies, and uncertainties in asthma management are also discussed.


Assuntos
Asma , Adulto , Antiasmáticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Asma/diagnóstico , Asma/etiologia , Asma/terapia , Criança , Humanos , Testes de Função Respiratória
2.
Ann Allergy Asthma Immunol ; 123(1): 57-63.e2, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31028894

RESUMO

BACKGROUND: In 2004, the landmark Gaining Optimal Asthma Control (GOAL) study demonstrated that most patients can achieve asthma control through sustained treatment and that adding a long-acting ß2-adrenoreceptor agonist to an inhaled corticosteroid (ICS) is more effective than ICS alone in this regard. Definitions of asthma control have since evolved, and the consequent implications for the GOAL study findings are unclear. OBJECTIVE: To evaluate the efficacy of fluticasone propionate and salmeterol and fluticasone propionate alone in achieving and maintaining asthma control, as derived from the Global Initiative for Asthma (GINA) 2016 report. METHODS: In total, 3416 patients were stratified by prior medication (ICS-naive [stratum 1], low-dose ICS [stratum 2], or medium-dose ICS [stratum 3]) and randomized to receive fluticasone propionate and salmeterol or fluticasone propionate. The primary end point was the proportion of patients achieving well-controlled or partly controlled asthma; secondary end points included the proportion of patients achieving well-controlled asthma. Control was evaluated during the last 4 weeks of each dose titration. RESULTS: In all strata, more patients achieved well-controlled or partly controlled asthma with fluticasone propionate and salmeterol vs fluticasone propionate alone (stratum 1: 91% vs 85%; P = .003; stratum 2: 86% vs 82%; P = .07; and stratum 3: 76% vs 66%; P < .001), as well as patients with well-controlled asthma (stratum 1: 64% vs 56%; P = .005; stratum 2: 59% vs 41%; P < .001; and stratum 3: 40% vs 22%; P < .001). CONCLUSION: A markedly higher proportion of patients with uncontrolled asthma in each stratum achieved control according to GINA 2016 criteria compared with the original study criteria. The proportion of patients achieving control remained greater with fluticasone propionate and salmeterol than with fluticasone propionate alone.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , Fluticasona/uso terapêutico , Xinafoato de Salmeterol/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada/métodos , Humanos
3.
J Pediatr ; 178: 246-253.e2, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27622699

RESUMO

OBJECTIVE: To evaluate the dose-response, efficacy, and safety of fluticasone furoate (FF; 25 µg, 50 µg, and 100 µg), administered once daily in the evening during a 12-week treatment period to children with inadequately controlled asthma. STUDY DESIGN: This was a Phase IIb, multicenter, stratified, randomized, double-blind, double-dummy, parallel-group, placebo- and active-controlled study in children aged 5-11 years with inadequately controlled asthma. The study comprised a 4-week run-in period, 12-week treatment period, and 1-week follow-up period. Children were randomized to receive either placebo once daily, fluticasone propionate (FP) 100 µg twice daily, FF 25 µg, FF 50 µg, or FF 100 µg each once daily in the evening. Primary endpoint was the mean change from baseline in daily morning peak expiratory flow (PEF) averaged over weeks 1-12. Adverse events (AEs) also were investigated. RESULTS: In total, 593 children were included in the intent-to-treat population. The difference vs placebo in change from baseline daily morning PEF averaged over weeks 1-12 was statistically significant for the FF 25, FF 50, FF 100, and FP 100 groups (18.6 L/min, 19.5 L/min, 12.5 L/min, and 14.0 L/min, respectively; P < .001 for all). The incidence of AEs was greater in the FF groups (32%-36%) than in the placebo group (29%); the most frequent AE was cough. CONCLUSION: FF and FP resulted in significant improvements in morning PEF compared with placebo, suggesting that they are effective treatments for children with inadequately controlled asthma. All treatments were well tolerated; no new safety concerns were identified. TRIAL REGISTRATION: ClinicalTrials.gov:NCT01563029.


Assuntos
Androstadienos/administração & dosagem , Asma/tratamento farmacológico , Broncodilatadores/administração & dosagem , Administração por Inalação , Androstadienos/efeitos adversos , Broncodilatadores/efeitos adversos , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Masculino , Resultado do Tratamento
4.
Respir Res ; 17: 37, 2016 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-27044326

RESUMO

BACKGROUND: Inhaled corticosteroids (ICS) are effective maintenance treatments for childhood asthma; however, many children remain uncontrolled. Vilanterol (VI) is an inhaled long-acting beta-2 agonist which, in combination with the ICS fluticasone furoate, is being explored as a once-daily treatment for asthma in children. We evaluated the dose-response, efficacy, and safety of once-daily VI (6.25 µg, 12.5 µg and 25 µg) administered in the evening over 4 weeks, on background fluticasone propionate (FP) in children with asthma inadequately controlled on ICS. METHODS: This was a Phase IIb, multicentre, randomised, double-blind, parallel-group, placebo-controlled study in children ages 5-11 years with persistent asthma on ICS and as-needed short-acting beta-agonist. The study comprised a 4-week run-in, 4-week treatment period, and 1-week follow-up. From study start, children replaced their current ICS with open-label FP 100 µg twice daily. Children were randomised to receive placebo, VI 6.25 µg, VI 12.5 µg or VI 25 µg once daily. Primary endpoint was treatment difference between VI 25 and placebo groups in mean change from baseline in evening peak expiratory flow averaged over the 4-week treatment. Secondary endpoints included change from baseline in trough forced expiratory volume in one second (FEV1) at Week 4 and change from baseline in percentage of rescue-free and symptom-free 24-h periods. Safety assessments included incidence of adverse events (AEs) and asthma exacerbations. RESULTS: In total, 456 children comprised the intention-to-treat population. The adjusted treatment difference between VI 25 and placebo groups for the primary endpoint was not statistically significant (p = 0.227) so no statistical inference was made for other VI dose comparisons or other endpoints. No difference in change from baseline in trough FEV1 was observed for any VI treatments versus placebo; however, VI 25 resulted in an additional 0.6 rescue-free days and 0.7 symptom-free days per week versus placebo. The incidence of AEs was slightly higher in the VI groups (28-33 %) versus placebo (22 %). Nine children experienced asthma exacerbations during the treatment period. CONCLUSION: VI plus FP did not result in significant improvements in lung function versus placebo plus FP, but was well tolerated at all doses assessed. TRIAL REGISTRATION: NCT01573767 (ClinicalTrials.gov).


Assuntos
Corticosteroides/administração & dosagem , Asma/diagnóstico , Asma/tratamento farmacológico , Álcoois Benzílicos/administração & dosagem , Clorobenzenos/administração & dosagem , Fluticasona/administração & dosagem , Administração por Inalação , Corticosteroides/efeitos adversos , Antiasmáticos/administração & dosagem , Álcoois Benzílicos/efeitos adversos , Broncodilatadores/administração & dosagem , Broncodilatadores/efeitos adversos , Criança , Pré-Escolar , Clorobenzenos/efeitos adversos , Terapia Combinada/métodos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Fluticasona/efeitos adversos , Humanos , Masculino , Efeito Placebo , Resultado do Tratamento
5.
Eur Respir J ; 46(3): 622-39, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26206872

RESUMO

Over the past 20 years, the Global Initiative for Asthma (GINA) has regularly published and annually updated a global strategy for asthma management and prevention that has formed the basis for many national guidelines. However, uptake of existing guidelines is poor. A major revision of the GINA report was published in 2014, and updated in 2015, reflecting an evolving understanding of heterogeneous airways disease, a broader evidence base, increasing interest in targeted treatment, and evidence about effective implementation approaches. During development of the report, the clinical utility of recommendations and strategies for their practical implementation were considered in parallel with the scientific evidence.This article provides a summary of key changes in the GINA report, and their rationale. The changes include a revised asthma definition; tools for assessing symptom control and risk factors for adverse outcomes; expanded indications for inhaled corticosteroid therapy; a framework for targeted treatment based on phenotype, modifiable risk factors, patient preference, and practical issues; optimisation of medication effectiveness by addressing inhaler technique and adherence; revised recommendations about written asthma action plans; diagnosis and initial treatment of the asthma-chronic obstructive pulmonary disease overlap syndrome; diagnosis in wheezing pre-school children; and updated strategies for adaptation and implementation of GINA recommendations.


Assuntos
Asma/tratamento farmacológico , Gerenciamento Clínico , Saúde Global , Guias de Prática Clínica como Assunto , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Corticosteroides/administração & dosagem , Antiasmáticos/administração & dosagem , Asma/diagnóstico , Asma/mortalidade , Feminino , Previsões , Humanos , Masculino , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/mortalidade , Índice de Gravidade de Doença
7.
J Allergy Clin Immunol Pract ; 10(7): 1813-1824.e1, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35364340

RESUMO

BACKGROUND: Inhaled medications are central to treating asthma and chronic obstructive pulmonary disease (COPD), yet critical inhaler technique errors are made by up to 90% of patients. In the clinical research setting, recruitment of subjects with poor inhaler technique may give a false impression of both the benefits and the necessity of add-on treatments such as biologic therapies. OBJECTIVE: To assess the frequency with which inhaler technique is assessed and reliably optimized before and during patient enrollment into randomized controlled trials (RCTs) addressing the efficacy of topical therapy, and the escalation of therapy for asthma and COPD. METHODS: Systematic searches were conducted of PubMed and Embase for RCTs published in the past 10 years involving patients with a diagnosis of asthma or COPD undergoing escalation of baseline inhaled therapy (stepping up, changing, adding, switching, increasing, etc) or the introduction of biologic agents. RESULTS: Searches highlighted 1,014 studies, 118 of which were eligible after the removal of duplicates as well as screening and full text review. Of these, only 14 (11.9%) included accessible information in the methods section or referred to such information in online supplements or protocols concerning assessment of participants' inhaler technique. We therefore developed the proposed Best Practice Inhaler Technique Assessment and Reporting Checklist. CONCLUSIONS: Our study identifies a concerning lack of checking and correcting inhaler technique, or at least reporting that this was undertaken, before enrollment in asthma and COPD RCTs, which may affect the conclusions drawn. Mandating the use of a standardized checklist in RCT protocols and ensuring all published RCTs report checking and correcting inhaler technique before enrollment are important next steps.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Asma/tratamento farmacológico , Lista de Checagem , Humanos , Nebulizadores e Vaporizadores , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
8.
J Allergy Clin Immunol Pract ; 8(6): 1815-1827, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32006721

RESUMO

Although nebulized corticosteroids (NebCSs) are a key treatment option for young children with asthma or viral-induced wheezing (VIW), there are no uniform recommendations on their best use. This systematic review aimed to clarify the role of NebCSs in children 5 years or younger for the management of acute asthma exacerbations, asthma maintenance therapy, and the treatment of VIW. Electronic databases were used to identify relevant English language articles with no date restrictions. Studies reporting efficacy data in children 5 years or younger, with a double-blind, placebo- or open-controlled, randomized design, and inclusion of 40 or more participants (no lower patient limit for VIW) were included. Ten articles on asthma exacerbation, 9 on asthma maintenance, and 7 on VIW were identified. Results showed NebCSs to be at least as efficacious as oral corticosteroids in the emergency room for the management of mild to moderate asthma exacerbations. In asthma maintenance, nebulized budesonide, the agent of focus in all trials analyzed, significantly reduced the risk of further asthma exacerbations compared with placebo, cromolyn sodium, and montelukast. Intermittent NebCS treatment of VIW was as effective as continuous daily treatment. In summary, NebCSs are effective and well tolerated in patients 5 years or younger for the management of acute and chronic asthma.


Assuntos
Antiasmáticos , Asma , Administração por Inalação , Corticosteroides/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Asma/epidemiologia , Budesonida/uso terapêutico , Criança , Pré-Escolar , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sons Respiratórios
9.
J Allergy Clin Immunol ; 120(5): 1036-42, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17935765

RESUMO

BACKGROUND: During the Gaining Optimal Asthma controL study, 3416 patients with uncontrolled asthma were randomized to receive salmeterol/fluticasone propionate combination (SFC) or fluticasone propionate (FP) for 1 year. Approximately two thirds of patients achieved well-controlled (WC) asthma, and one third continued to have asthma that was not well controlled (NWC). OBJECTIVE: This analysis aimed to (1) identify factors influencing treatment response and (2) assess the clinical benefits of SFC and FP in patients with NWC asthma. METHODS: Logistic regression analysis was used to investigate whether covariates influenced the achievement of at least WC asthma in the study population. In patients with NWC asthma, predefined criteria were used to assess improvements in 6 clinical outcomes. RESULTS: Factors affecting the probability of having NWC asthma included smoking status (current vs never: odds ratio [OR], 2.757; 95% CI, 2.061-3.689; P < .0001; former vs never: OR, 1.274; 95% CI, 1.031-1.574; P = 0.0273), sex (women vs men: OR, 0.652; 95% CI, 0.527-0.806; P < .0001), history of inhaled corticosteroid use (no history vs history: OR, 0.546; 95% CI, 0.437-0.683; P < .0001), and treatment (FP vs SFC: OR, 1.972; 95% CI, 1.686-2.308; P < .0001). Of patients with NWC asthma, 86% to 96% showed improvements in 1 or more clinical outcomes. CONCLUSION: It is imperative for good asthma control that patients stop smoking. Patients who did not have at least WC asthma demonstrated clinical improvements in individual asthma outcomes. CLINICAL IMPLICATIONS: Although not all patients can achieve guideline-defined control, long-term treatment with SFC or FP is associated with clinical improvements in nearly all patients, regardless of smoking history or inhaled corticosteroid use.


Assuntos
Agonistas Adrenérgicos beta/uso terapêutico , Albuterol/análogos & derivados , Androstadienos/uso terapêutico , Antialérgicos/uso terapêutico , Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , Adulto , Fatores Etários , Idoso , Albuterol/uso terapêutico , Estatura , Quimioterapia Combinada , Feminino , Fluticasona , Humanos , Masculino , Pessoa de Meia-Idade , Xinafoato de Salmeterol , Fatores Sexuais , Fumar
10.
J Asthma ; 44(8): 667-73, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17943579

RESUMO

BACKGROUND: Using a composite measure based on clinical outcomes, the GOAL study showed that achievement of Total Control of asthma was time dependent with the proportion of controlled patients continuing to rise through the year-long study. Taking data from this study, we compared time taken to achieve Total Control with time taken to achieve total control of each individual clinical criterion on treatment with salmeterol/fluticasone propionate (SFC) or fluticasone propionate (FP) alone. METHODS: Time to achieving total control of individual outcomes (day-time symptoms, night-time awakenings, rescue medication use, PEF > or =80% predicted every day) were analyzed by Kaplan Meier plots and compared with achievement of composite Total Control. RESULTS: Night-time awakenings responded most rapidly and daytime symptoms took longest to respond. After 12 weeks, the proportion of patients who achieved control of any individual clinical criterion was higher than the proportion who achieved control when using the composite outcome (no night-time awakenings achieved by 73% with SFC and 65% with FP; PEF > or =80% predicted every day, 55% and 45% respectively; no rescue usage 46% and 35% respectively; and no daytime symptoms, 35% and 24% respectively, compared with Total Control, 23% and 14% respectively). In every measure except night-time awakenings, more rapid responses were seen for SFC compared with FP alone. CONCLUSIONS: Speed of response of individual asthma measures varies and evaluation of control using any single measure overestimates total asthma control. Treatment should be continued until composite control is reached, rather than control of individual outcomes.


Assuntos
Albuterol/administração & dosagem , Androstadienos/administração & dosagem , Antiasmáticos/administração & dosagem , Asma/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Asma/prevenção & controle , Criança , Quimioterapia Combinada , Feminino , Fluticasona , Humanos , Individualidade , Masculino , Pessoa de Meia-Idade , Pico do Fluxo Expiratório/efeitos dos fármacos , Qualidade de Vida
11.
J Asthma Allergy ; 10: 35-46, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28331346

RESUMO

BACKGROUND: The inhaled corticoteroid (ICS) ciclesonide (Cic), controls asthma symptoms in the majority of patients at the recommended dose of 160 µg/day. However, the relationship between the level of asthma control and increasing doses of Cic is unknown. This study investigated whether long-term treatment with higher doses of Cic would further improve asthma symptoms in patients with uncontrolled asthma despite ICS use. PATIENTS AND METHODS: In a double-blind, randomized, parallel-group study, 367 patients were allocated to one of three treatment arms (Cic 160, 320 and 640 µg/day). After a single-blind, 3-week baseline period with Cic 160 µg/day, eligible patients were randomized to receive 52 weeks of treatment with Cic 160, 320 or 640 µg/day (double-blind period) during which forced expiratory volume in 1 second (FEV1), exacerbations and Asthma Control Questionnaire (ACQ) scores were measured. RESULTS: Treatment with all the three doses was associated with significant improvements in ACQ scores, FEV1 and asthma symptoms (P<0.01). There were no statistically significant differences between the three doses. The results of the primary end point analysis showed a numerical improvement in the ACQ score with Cic 640 µg/day compared with Cic 160 µg/day (least square [LS] mean: -0.122; two-sided P-value: 0.30). Post hoc subgroup analyses showed that the improvement in the ACQ score with Cic 640 µg/day compared with Cic 160 µg/day was statistically significant in subjects who experience at least one exacerbation per year (LS mean: -0.586; 95% confidence interval: -1.110, -0.062, P=0.0285). Adverse events were low and consistent with the known safety profile of Cic. CONCLUSION: In patients with persistent, uncontrolled asthma, increasing the Cic dose from 160 to 640 µg/day provided no clear additional effect. Patients who experience more than one exacerbation per year may benefit from higher doses; however, further studies are necessary to confirm this. All Cic doses were well tolerated.

12.
Am J Respir Crit Care Med ; 170(8): 836-44, 2004 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-15256389

RESUMO

For most patients, asthma is not controlled as defined by guidelines; whether this is achievable has not been prospectively studied. A 1-year, randomized, stratified, double-blind, parallel-group study of 3,421 patients with uncontrolled asthma compared fluticasone propionate and salmeterol/fluticasone in achieving two rigorous, composite, guideline-based measures of control: totally and well-controlled asthma. Treatment was stepped-up until total control was achieved (or maximum 500 microg corticosteroid twice a day). Significantly more patients in each stratum (previously corticosteroid-free, low- and moderate-dose corticosteroid users) achieved control with salmeterol/fluticasone than fluticasone. Total control was achieved across all strata: 520 (31%) versus 326 (19%) patients after dose escalation (p < 0.001) and 690 (41%) versus 468 (28%) at 1 year for salmeterol/fluticasone and fluticasone, respectively. Asthma became well controlled in 1,071 (63%) versus 846 (50%) after dose escalation (p < 0.001) and 1,204 (71%) versus 988 (59%) at 1 year. Control was achieved more rapidly and at a lower corticosteroid dose with salmeterol/fluticasone versus fluticasone. Across all strata, 68% and 76% of the patients receiving salmeterol/fluticasone and fluticasone, respectively, were on the highest dose at the end of treatment. Exacerbation rates (0.07-0.27 per patient per year) and improvement in health status were significantly better with salmeterol/fluticasone. This study confirms that the goal of guideline-derived asthma control was achieved in a majority of the patients.


Assuntos
Albuterol/análogos & derivados , Albuterol/uso terapêutico , Androstadienos/uso terapêutico , Asma/prevenção & controle , Broncodilatadores/uso terapêutico , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Adulto , Albuterol/administração & dosagem , Albuterol/efeitos adversos , Androstadienos/administração & dosagem , Androstadienos/efeitos adversos , Antiasmáticos/administração & dosagem , Antiasmáticos/efeitos adversos , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Broncodilatadores/administração & dosagem , Broncodilatadores/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Fluticasona , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Masculino , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Qualidade de Vida , Xinafoato de Salmeterol , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA