RESUMO
PURPOSE OF REVIEW: A modified Delphi process was undertaken to provide a US expert-led consensus to guide clinical action on short-acting beta2-agonist (SABA) use. This comprised an online survey (Phase 1), forum discussion and statement development (Phase 2), and statement adjudication (Phase 3). RECENT FINDINGS: In Phase 1 (n = 100 clinicians), 12% routinely provided patients with ≥4 SABA prescriptions/year, 73% solicited SABA use frequency at every patient visit, and 21% did not consult asthma guidelines/expert reports. Phase 3 experts (n = 8) reached consensus (median Likert score, interquartile range) that use of ≥3 SABA canisters/year is associated with increased risk of exacerbation and asthma-related death (5, 4.75-5); SABA use history should be solicited at every patient visit (5, 4.75-5); usage patterns over time, not absolute thresholds, should guide response to SABA overuse (5, 4.5-5). Future asthma guidelines should include clear recommendations regarding SABA usage, using expert-led thresholds for action.
Assuntos
Antiasmáticos , Asma , Humanos , Administração por Inalação , Antiasmáticos/administração & dosagem , Antiasmáticos/efeitos adversos , Asma/tratamento farmacológico , Tomada de Decisão Clínica , Consenso , Técnica Delphi , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Concurrent use of intranasal corticosteroids (INCSs) and inhaled corticosteroids (ICSs) is indicated for patients who are comorbid for asthma and allergic rhinitis. Clinicians need to know the data regarding INCS safety for their patients with asthma. OBJECTIVE: To discuss INCS safety data for the use of INCSs in patients with asthma and allergic rhinitis. METHODS: INCS safety studies were selected for their relevance to the discussion. RESULTS: To date, most studies regarding INCS safety are performed in patients with allergic rhinitis. These studies reveal no evidence of increased risk of nasal atrophy, and only isolated cases of septal perforation have been reported. Evidence of hypothalamic-pituitary-adrenal axis suppression is inconsistent and not clinically significant. Early growth studies indicated that beclomethasone dipropionate but not other INCSs have systemic effects on growth; however, newer, larger, and better designed studies are detecting small but significant growth effects in other INCSs. INCSs do not increase the risk of cataracts or glaucoma, although there are anecdotal data on transient elevated intraocular pressure. Data on concurrent use of INCSs and ICSs are limited, but these limited data reveal no evidence of systemic effects on the hypothalamic-pituitary-adrenal axis. CONCLUSION: More studies of concurrent therapy are needed because concurrent use of ICSs and INCSs is common in practice. Clinicians might want to consider monitoring whether there are risk factors, such as a family history of glaucoma.
Assuntos
Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Antialérgicos/administração & dosagem , Antialérgicos/efeitos adversos , Administração Intranasal , Adulto , Asma/complicações , Asma/tratamento farmacológico , Atrofia , Criança , Desenvolvimento Infantil/efeitos dos fármacos , Pré-Escolar , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/patologia , Perfuração do Septo Nasal/etiologia , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Rinite Alérgica/complicações , Rinite Alérgica/tratamento farmacológicoRESUMO
Intranasal corticosteroids (INSs) have been effectively used for >40 years for the treatment of seasonal allergic rhinitis (SAR) and perennial AR (PAR). Following the Montreal Protocol, the initial aerosol formulations using chlorofluorocarbon (CFC) propellants were phased out. For the past 20 years, aqueous solutions have been the only available option for INS treatment. In 2012, the U.S. Food and Drug Administration approved two new nonaqueous aerosol AR treatments that use a hydrofluoroalkane (HFA) propellant. In 2012, the first intranasal aqueous combination product was also approved. This article reviews the clinical profiles of HFA beclomethasone dipropionate (BDP) and HFA ciclesonide (CIC) and the aqueous combination intranasal antihistamine (INA)/INS formulation of azelastine hydrochloride/fluticasone propionate (AZE/FP). The medical literature was searched for clinical trials investigating the use of BDP, CIC, and AZE/FP in SAR and PAR. Clinical trials involving aqueous solutions and CFC propellant or HFA propellant delivery were included. Data from prescribing information and published efficacy and safety data were presented as part of the clinical profile for the reviewed agents. AZE/FP has shown efficacy and safety comparable or greater with the current AR treatment options. Although efficacy comparisons of new HFA formulations have not been investigated in head-to-head clinical trials with aqueous formulations, HFA formulations have shown similar efficacy rates. Furthermore, HFA formulations may have some additional benefits, including a preferable sensory profile for some patients. These new formulations will provide additional options for clinicians and patients to better individualize therapy for control of AR.
Assuntos
Antialérgicos/administração & dosagem , Rinite Alérgica/tratamento farmacológico , Administração Intranasal , Propelentes de Aerossol , Beclometasona/administração & dosagem , Química Farmacêutica , Combinação de Medicamentos , Humanos , Pregnenodionas/administração & dosagemRESUMO
Allergic rhinitis (AR) affects at least 60 million people in the United States each year, resulting in a major impact on patient quality of life, productivity, and direct and indirect costs. As new therapies, data, and literature emerge in the management of AR, there is a need to communicate and disseminate important information to health care professionals to advance the practice of medicine and lessen the disease burden from AR. Treatment recommendations for AR have not been updated since the 2012 Food and Drug Administration approval of nonaqueous intranasal aerosol agents using hydrofluoroalkane propellants and the first aqueous intranasal combination product. Here, we present an updated algorithm for the pharmacologic treatment of AR that includes these new treatment options. Treatment recommendations are categorized by disease severity (mild versus moderate/severe) and duration of symptoms (episodic versus nonepisodic, with episodic defined as <3 days/wk or for <3 weeks). Preferred treatments are suggested, as well as alternative options for consideration by clinicians in the context of individual patient needs. This recommendation article also outlines the importance of treatment monitoring, which can be conducted using the recently developed Rhinitis Control Assessment Test. Successful therapeutic outcomes depend on multiple factors, including use of the most effective pharmacologic agents as well as patient adherence to therapy. Therefore, it is imperative that rhinitis patients not only receive the most effective therapeutic options, but that they also understand and are able to adhere to the comprehensive treatment regimen. Successful treatment, with all of these considerations in mind, results in better disease outcomes, improved quality of life for patients, and greater economic productivity in the home and workplace.
Assuntos
Antialérgicos/uso terapêutico , Rinite Alérgica/tratamento farmacológico , Algoritmos , Antialérgicos/administração & dosagem , Efeitos Psicossociais da Doença , Humanos , Adesão à Medicação , Avaliação de Resultados em Cuidados de Saúde , Guias de Prática Clínica como Assunto , Qualidade de Vida , Rinite Alérgica/diagnóstico , Rinite Alérgica/economiaRESUMO
Cytokine antagonists are monoclonal antibodies that offer new treatment options for refractory asthma but will also increase complexity because they are effective only for patients with certain asthma subtypes that remain to be more clearly defined. The clinical and inflammatory heterogeneity within refractory asthma makes it difficult to manage the disease and to determine which, if any, biologic therapy is suitable for a specific patient. The purpose of this article is to provide a data-driven discussion to clarify the use of biologic therapies in patients with refractory asthma. We first discuss the epidemiology and pathophysiology of refractory asthma. We then interpret current evidence for biomarkers of eosinophilic or type 2-high asthma so that clinicians can determine potential treatments for patients based on knowledge of their effectiveness in specific asthma phenotypes. We then assess clinical data on the efficacy, safety, and mechanisms of action of approved and pipeline biologic therapies. We conclude by discussing the potential of phenotyping or endotyping refractory asthma and how biologic therapies can play a role in treating patients with refractory asthma.
Assuntos
Antiasmáticos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Asma/terapia , Terapia Biológica , Imunoterapia/métodos , Animais , Asma/diagnóstico , Asma/epidemiologia , Biomarcadores/metabolismo , Canadá/epidemiologia , Diagnóstico Diferencial , Eosinófilos/imunologia , Medicina Baseada em Evidências , Humanos , Fenótipo , Recidiva , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Previous studies of inflammation in allergic rhinitis using nasal irrication have been unsatisfactory because of 1) poor reproducibility; 2) the tendency of irrigation to overdilute mediators; and 3) the failure of this technique to evaluate interstitial concentrations of relevant mediators. For this study we used filter paper as a matrix to collect nasal secretions in patients undergoing nasal antigen challenge. OBJECTIVE: To evaluate inflammatory mediators of allergen-induced rhinitis during a clinical trial of fexofenadine. METHODS: Subjects evaluated at a referral medical center were placed on traditional dosing of fexofenadine at 60 mg, twice daily, or placebo in a double-blind, crossover fashion for 1 week before the nasal challenge. Nasal challenge was performed with nasal insufflation of either 1,000 AU timothy or 0.1 mL ragweed (1:100 wt/vol) extract outside the pollen season. Nasal secretions were collected at baseline and then at 2, 4, and 6 hours after nasal challenge. Secretions were evaluated for expression of the cellular adhesion molecule-1, tumor necrosis factor (TNF)-alpha, interleukin (IL)-4, IL-10, macrophage inflammatory protein (MIP)-1alpha, and granulocyte-macrophage colony-stimulating factor (GM-CSF) using commercially available enzyme-linked immunoadsorbent assay kits. Patients' symptom scores were evaluated during the nasal challenge. RESULTS: Significantly (P < 0.05) increased peak levels of TNF-alpha, IL-4, IL-10, and MIP-1alpha were detected after antigen challenge as compared with baseline levels. There was a nonsignificant trend toward an increase in GM-CSF after antigen challenge (P = 0.07). There was no difference in the peak levels of TNF-alpha, IL-4, IL-10, MIP-1alpha, or GM-CSF measured when patients were on fexofenadine versus placebo. Finally, there were no significant differences in patients' symptom scores during antigen challenge when subjects were on fexofenadine versus placebo. CONCLUSIONS: Collection of nasal secretions using a filter paper matrix provides a reproducible model for accurately detecting and evaluating changes in cytokine levels after nasal challenge. Cytokine levels tend to peak 3 to 4 hours after antigen challenge. Standard doses of fexofenadine do not seem to have a mitigating effect on the production of these cytokines. Symptoms of allergic rhinitis using this type of antigen challenge did not differ from treatment with fexofenadine versus placebo.