Efficacy and safety of a first-in-class inhaled PDE3/4 inhibitor (ensifentrine) vs salbutamol in asthma

This study aimed to investigate the dose-response and pharmacology of a range of single doses of nebulised ensifentrine (RPL554), an inhaled dual phosphodiesterase (PDE) 3/4 inhibitor in patients with asthma.MethodsIn this randomised, placebo-controlled, double-blind crossover study, patients received single nebulised doses of ensifentrine 0.4, 1.5, 6 and 24 mg, salbutamol 2.5 and 7.5 mg, and placebo. Eligible patients were adults with asthma, pre-bronchodilator forced expiratory volume in 1 s (FEV1) 60–90% predicted and ≥1.5 L, with post-salbutamol FEV1 increase ≥15%. The co-primary objectives were peak and average FEV1 over 12 h for ensifentrine vs placebo and salbutamol. Secondary endpoints included: peak and average systolic and diastolic blood pressure, pulse rate and ECG heart rate; and safety and tolerability (adverse events [AEs], and serum potassium). ClinicalTrials.gov: NCT02427165.ResultsA total of 29 patients were randomised, with 25 (89%) completing the study. For the two co-primary endpoints there was a clear ensifentrine dose-response relationship, with all treatments superior to placebo (p 
Source: Pulmonary Pharmacology and Therapeutics - Category: Respiratory Medicine Source Type: research

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ConclusionPresent study suggest that, EJ effectively protects against allergic airway inflammation thus possessing potential therapeutic option for allergic asthma management.Graphical abstract
Source: Journal of Ethnopharmacology - Category: Drugs & Pharmacology Source Type: research
In this study, we aimed to investigate the protective effects and underlying antitussive mechanisms of Suhuang on pulmonary function in ovalbumin (OVA)-induced CVA rats. Administration (i.g.) of Suhuang significantly alleviated pulmonary damage and dysfunction. Suhuang improved ER stress and PKCε translocation via regulation of Ca2+ trafficking. Suhuang also inhibited NLRP3 inflammasome activation, as evidenced by disrupting the assembly of NLRP3 inflammasome and reducing the expression of cleaved caspase-1, and decreased IL-1β secretion. Besides, it’s identified that TXNIP induction and RIP1-RIP3-Drp1 p...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
Abstract The allergic airway diseases, including chronic rhinosinusitis (CRS), asthma, allergic bronchopulmonary mycosis (ABPM) and many others, comprise a heterogeneous collection of inflammatory disorders affecting the upper and lower airways and lung parenchyma that represent the most common chronic diseases of humanity. In addition to their shared tissue tropism, the allergic airway diseases are characterized by a distinct pattern of inflammation involving the accumulation of eosinophils, type 2 macrophages, innate lymphoid cells type 2 (ILC2), IgE-secreting B cells, and T helper type 2 (Th2) cells in airway t...
Source: Advances in Immunology - Category: Allergy & Immunology Authors: Tags: Adv Immunol Source Type: research
ry JC Abstract Men and women differ in their susceptibility to develop autoimmunity and allergy but also in their capacity to cope with infections. Mechanisms responsible for this sexual dimorphism are still poorly documented and probably multifactorial. This review discusses the recent development in our understanding of the cell-intrinsic actions of biological factors linked to sex, sex hormones and sex chromosome complement, on immune cells, which may account for the sex differences in the enhanced susceptibility of women to develop immunological disorders, such as allergic asthma or systemic lupus erythematosu...
Source: Advances in Immunology - Category: Allergy & Immunology Authors: Tags: Adv Immunol Source Type: research
Abstract Asthma is a genetically and phenotypically complex disease that has a major impact on global health. Signs and symptoms of asthma are caused by the obstruction of airflow through the airways. The epithelium that lines the airways plays a major role in maintaining airway patency and in host defense. The epithelium initiates responses to inhaled or aspirated substances, including allergens, viruses, and bacteria, and epithelial-derived cytokines are important in the recruitment and activation of immune cells in the airway. Changes in the structure and function of the airway epithelium are a prominent featur...
Source: Advances in Immunology - Category: Allergy & Immunology Authors: Tags: Adv Immunol Source Type: research
Authors: Kim H, Kwon GE, Kim YH, Callaway Z, Han YS, Seo JJ, Jiao F, Kim CK Abstract Objective: Eosinophil-derived neurotoxin (EDN) is associated with recurrent wheezing episodes after bronchiolitis, childhood asthma, and allergic rhinitis. We investigated if there is a measurable difference between serum EDN levels in children with wheezing and non-wheezing respiratory infections. Methods: 171 children who visited a university hospital with respiratory infections were enrolled in the study. Subjects were divided into two groups: wheezing (n = 46) and non-wheezing (n = 125). Serum EDN le...
Source: Journal of Asthma - Category: Respiratory Medicine Tags: J Asthma Source Type: research
Conclusion: Budesonide/formoterol in mild asthma instead of salbutamol produces better patient outcomes, decreases total costs with increases in drug cost offset by reductions in non-drug costs due to fewer exacerbations. Budesonide/formoterol is a budget saving option for guideline-directed treatment, from the economic perspective of the payer and the health perspective of the patient. PMID: 31298593 [PubMed - as supplied by publisher]
Source: Journal of Medical Economics - Category: Health Management Tags: J Med Econ Source Type: research
Authors: Machado JN, Costa JC, Ferreira C, Costa T, Arrobas A PMID: 31292032 [PubMed - in process]
Source: Acta Medica Portuguesa - Category: General Medicine Tags: Acta Med Port Source Type: research
Asthma, a common yet complex airway disorder affecting about 11% of Australians, is well-controlled in only 54% of people with asthma. Those with difficult-to-treat and severe asthma are more likely to experie...
Source: BMC Family Practice - Category: Primary Care Authors: Tags: Research article Source Type: research
AbstractThe use of biologic agents as therapies for atopic diseases such as asthma and atopic dermatitis has increased greatly in recent years. The biological agents used to treat atopic diseases are for the most part monoclonal antibodies that suppress the immune response and reduce inflammation by targeting particular cytokines or other molecules involved in Th1, Th2, or Th17 immune reactions. Various side effects and rare complications have been reported from these agents. In this review, we discuss mechanisms of various adverse effects for the biologic agents currently in use or in development for atopic and inflammato...
Source: Clinical Reviews in Allergy and Immunology - Category: Allergy & Immunology Source Type: research
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