In this consensus document we summarize the current knowledge on major asthma, rhinitis, and atopic dermatitis endotypes under the auspices of the PRACTALL collaboration platform. PRACTALL is an ...initiative of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology aiming to harmonize the European and American approaches to best allergy practice and science. Precision medicine is of broad relevance for the management of asthma, rhinitis, and atopic dermatitis in the context of a better selection of treatment responders, risk prediction, and design of disease-modifying strategies. Progress has been made in profiling the type 2 immune response-driven asthma. The endotype driven approach for non-type 2 immune response asthma, rhinitis, and atopic dermatitis is lagging behind. Validation and qualification of biomarkers are needed to facilitate their translation into pathway-specific diagnostic tests. Wide consensus between academia, governmental regulators, and industry for further development and application of precision medicine in management of allergic diseases is of utmost importance. Improved knowledge of disease pathogenesis together with defining validated and qualified biomarkers are key approaches to precision medicine.
Allergy immunotherapy (AIT) is an effective treatment for allergic asthma and rhinitis, as well as venom-induced anaphylaxis. In addition to reducing symptoms, AIT can change the course of allergic ...disease and induce allergen-specific immune tolerance. In current clinical practice immunotherapy is delivered either subcutaneously or sublingually; some allergens, such as grass pollen, can be delivered through either route, whereas others, such as venoms, are only delivered subcutaneously. Both subcutaneous and sublingual immunotherapy appear to have a duration of efficacy of up to 12 years, and both can prevent the development of asthma and new allergen sensitivities. In spite of the advances with AIT, safer and more effective AIT strategies are needed, especially for patients with asthma, atopic dermatitis, or food allergy. Novel approaches to improve AIT include use of adjuvants or recombinant allergens and alternate routes of administration. As part of the PRACTALL initiatives, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology nominated an expert team to develop a comprehensive consensus report on the mechanisms of AIT and its use in clinical practice, as well as unmet needs and ongoing developments in AIT. This resulting report is endorsed by both academies.
Many patients with allergic disorders continue to have uncontrolled symptoms despite new and better pharmacologic options. Novel biologic agents that target specific and critical pathophysiologic ...pathways have been developed to better manage these patients. The utility of biologic agents for the management of allergic diseases has been facilitated by recent advances in better characterizing patients, including identification of relevant biomarkers that predict clinical responsiveness. This has led to the ability to phenotype and endotype patients, allowing for a more rational approach to picking a specific biologic agent for a specific patient. In this review I focus on point-of-care biomarkers that enhance the usefulness of biologics to manage uncontrolled asthma, urticaria, and nasal polyposis. I discuss biologic agents already approved for the management of allergic and respiratory disorders and biologics currently in development or recently abandoned because of a lack of efficacy or intolerable side effects. The successes and failures of biologics in clinical trials have facilitated our ability to better understand which molecules and pathways are most important in the pathogenesis of allergic diseases and in the development of symptoms and impairment in individual patients.
Background In North America and Europe, millions of patients experience symptoms of allergic rhinitis with or without conjunctivitis (AR/C) on exposure to ragweed pollen. The disease burden can be ...significant, with most patients relying on symptomatic medications without disease-modifying potential. However, novel sublingual immunomodulatory treatment options may potentially play an important role if efficacy and side effect profiles allow the convenience of self-administration. Objectives This study evaluated an allergy immunotherapy tablet (AIT; SCH 39641/MK-3641) for treatment of ragweed-induced AR/C in the first large randomized, double-blind multinational trial of this therapeutic modality for ragweed allergy. Methods Adults (n = 784) with short ragweed-induced AR/C were randomly assigned to approximately 52 weeks of daily self-administered ragweed AIT of 1.5, 6, or 12 units of Ambrosia artemisiifolia major allergen 1 (Amb a 1-U) or placebo. Subjects could use as-needed allergy rescue medication. Symptoms and medications were recorded daily. The primary efficacy end point was total combined daily symptom/medication score (TCS) during peak ragweed season. Safety was monitored through adverse event diaries maintained through study duration. Results During peak ragweed season, ragweed AIT of 1.5, 6, and 12 Amb a 1-U reduced TCS by 9% (−0.76; P = .22), 19% (−1.58; P = .01), and 24% (−2.04; P = .002) compared with placebo. During the entire season, ragweed AIT of 1.5, 6, and 12 Amb a 1-U reduced TCS by 12% (−0.88; P = .09), 18% (−1.28; P = .01), and 27% (−1.92; P < .001) compared with placebo. Treatment was well tolerated; no systemic allergic reactions occurred. Conclusions In this trial, ragweed AIT of 12 Amb a 1-U was effective and tolerable with a safety profile that permitted daily self-administration of ragweed allergen immunotherapy.
It is increasingly clear that asthma is a complex disease made up of number of disease variants with different underlying pathophysiologies. Limited knowledge of the mechanisms of these disease ...subgroups is possibly the greatest obstacle in understanding the causes of asthma and improving treatment and can explain the failure to identify consistent genetic and environmental correlations to asthma. Here we describe a hypothesis whereby the asthma syndrome is divided into distinct disease entities with specific mechanisms, which we have called “asthma endotypes.” An “endotype” is proposed to be a subtype of a condition defined by a distinct pathophysiological mechanism. Criteria for defining asthma endotypes on the basis of their phenotypes and putative pathophysiology are suggested. Using these criteria, we identify several proposed asthma endotypes and propose how these new definitions can be used in clinical study design and drug development to target existing and novel therapies to patients most likely to benefit. This PRACTALL (PRACtical ALLergy) consensus report was produced by experts from the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology.
Background Allergic rhinitis represents a global health problem affecting 10% to 20% of the population. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines have been widely used to treat ...the approximately 500 million affected patients globally. Objective To develop explicit, unambiguous, and transparent clinical recommendations systematically for treatment of allergic rhinitis on the basis of current best evidence. Methods The authors updated ARIA clinical recommendations in collaboration with Global Allergy and Asthma European Network following the approach suggested by the Grading of Recommendations Assessment, Development and Evaluation working group. Results This article presents recommendations about the prevention of allergic diseases, the use of oral and topical medications, allergen specific immunotherapy, and complementary treatments in patients with allergic rhinitis as well as patients with both allergic rhinitis and asthma. The guideline panel developed evidence profiles for each recommendation and considered health benefits and harms, burden, patient preferences, and resource use, when appropriate, to formulate recommendations for patients, clinicians, and other health care professionals. Conclusion These are the most recent and currently the most systematically and transparently developed recommendations about the treatment of allergic rhinitis in adults and children. Patients, clinicians, and policy makers are encouraged to use these recommendations in their daily practice and to support their decisions.
Background Chronic urticaria is a frequent and debilitating skin disease. Its symptoms commonly fluctuate considerably from day to day. As of yet, the only reliable tool to assess disease activity is ...the Urticaria Activity Score, which prospectively documents the signs and symptoms of urticaria for several days. Objective We sought to develop and validate a novel patient-reported outcome instrument to retrospectively assess urticaria control, the Urticaria Control Test (UCT). Methods Potential UCT items were developed by using established methods (literature research and expert and patient involvement). Subsequently, item reduction was performed by using a combined approach, applying impact and regression analysis. The resulting UCT instrument was then tested for its validity, reliability, and screening accuracy. Results A 4-item UCT with a recall period of 4 weeks was developed based on 25 potential UCT items tested in 508 patients with chronic urticaria. A subsequent validation study with the 4-item UCT in 120 patients with chronic urticaria demonstrated that this new tool exhibits good convergent and known-groups validity, as well as excellent test-retest reliability. In addition, the screening accuracy to identify patients with urticaria with insufficiently controlled disease was found to be high. Conclusions The UCT is the first valid and reliable tool to assess disease control in patients with chronic urticaria (spontaneous and inducible). Its retrospective approach and simple scoring system make it an ideal instrument for the management of patients with chronic urticaria in clinical practice.
Background According to meta-analyses and reviews, subcutaneous allergen immunotherapy (SCIT) and sublingual allergen immunotherapy (SLIT) are beneficial in patients with allergic rhinitis (AR) and ...allergic asthma (AA) induced by house dust mites (HDMs). However, the reported effect sizes have varied greatly from one study to another. Objective We sought to perform an evidence-based medicine assessment of commercially available SCIT and SLIT formulations in patients with HDM-induced AA and HDM-induced AR. Methods We searched for double-blind, placebo-controlled randomized clinical trials and analyzed study designs, doses, regimens, patient-reported outcomes, safety reporting, and compliance. Results Forty-four studies met our inclusion criteria. Some studies tested both SLIT and SCIT or scored both AA and AR outcomes; therefore we reviewed 35 treatment arms in patients with AA (20 for SCIT and 15 for SLIT) and 23 treatment arms in patients with AR (7 for SCIT and 16 for SLIT). The treatment duration ranged from 6 weeks to 3 years. For SCIT, the dose of Der p 1 major allergen (when reported) ranged from 7 to 30 μg for maintenance doses and 60 to 420 μg for cumulative doses. For SLIT, the doses of Der p 1 (when reported) were 0.8 to 70 μg for maintenance doses and 60 to 23,695 μg for cumulative doses. Safety data were often absent or poorly reported. A statistically significant active versus placebo symptom score was observed more frequently for SCIT than for SLIT. Conclusion There is no consensus on basic treatment parameters (eg, dose and duration) in HDM SCIT and SLIT. There is an urgent need for rigorous, long-term, double-blind, placebo-controlled randomized clinical trials with an efficacy criterion that reflects the particular features of HDM-induced allergic disease.
To describe the concept of precision medicine in treating severe asthma and the utility of relevant biomarkers.
PubMed was searched for published articles on human clinical trials using biologics for ...T-helper type 2 cell (TH2)-low and TH2-high asthma.
Studies were selected if they were double-masked, randomized, placebo-controlled trials published in peer-reviewed journals and relevant to the topic.
Multiple immune response modifiers have been evaluated in TH2-high asthma geared at blocking interleukin (IL)-5, IL-13, immunoglobulin E, prostaglandin D2, and other pathways. Currently, 3 immune response modifiers approved by the Food and Drug Administration are available for treating severe TH2-high asthma (1 anti-immunoglobulin E and 2 anti-IL-5 monoclonal antibodies) and other TH2-high therapies are in various stages of clinical development. Thus far, many of the TH2-high therapies have shown better efficacy when certain biomarkers are elevated, especially blood eosinophils. The TH2-low endotype does not have any readily available point-of-care biomarkers, so TH2-low asthma is often diagnosed based on a lack of TH2-high biomarkers. These patients tend to have greater resistance to steroids and the development of therapies has lagged behind that for TH2-high asthma.
Two major endotypes for asthma have been described, TH2-high, manifested by increased eosinophils in the sputum and airways of patients, and TH2-low, with increased neutrophils or a pauci-granulocytic profile. Using these classifications and specific biomarkers has led to promising new therapeutics, especially for TH2-high asthma.
Cardiovascular Care Facts Masoudi, Frederick A., MD, MSPH; Ponirakis, Angelo, PhD; Yeh, Robert W., MD ...
Journal of the American College of Cardiology,
11/2013, Letnik:
62, Številka:
21
Journal Article
Recenzirano
Odprti dostop
Objectives The aim of this report was to characterize the patients, participating centers, and measures of quality of care and outcomes for 5 NCDR (National Cardiovascular Data Registry) programs: 1) ...ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry–GWTG (Get With The Guidelines) for acute coronary syndromes; 2) CathPCI Registry for coronary angiography and percutaneous coronary intervention; 3) CARE (Carotid Artery Revascularization and Endarterectomy) Registry for carotid revascularization; 4) ICD Registry for implantable cardioverter defibrillators; and the 5) PINNACLE (Practice INNovation And CLinical Excellence) Registry for outpatients with cardiovascular disease (CVD). Background CVD is a leading cause of death and disability in the United States. The quality of care for patients with CVD is suboptimal. National registry programs, such as NCDR, permit assessments of the quality of care and outcomes for broad populations of patients with CVD. Methods For the year 2011, we assessed for each of the 5 NCDR programs: 1) demographic and clinical characteristics of enrolled patients; 2) key characteristics of participating centers; 3) measures of processes of care; and 4) patient outcomes. For selected variables, we assessed trends over time. Results In 2011 ACTION Registry–GWTG enrolled 119,967 patients in 567 hospitals; CathPCI enrolled 632,557 patients in 1,337 hospitals; CARE enrolled 4,934 patients in 130 hospitals; ICD enrolled 139,991 patients in 1,435 hospitals; and PINNACLE enrolled 249,198 patients (1,436,328 individual encounters) in 74 practices (1,222 individual providers). Data on performance metrics and outcomes, in some cases risk-adjusted with validated NCDR models, are presented. Conclusions The NCDR provides a unique opportunity to understand the characteristics of large populations of patients with CVD, the centers that provide their care, quality of care provided, and important patient outcomes.
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