Increased airway smooth muscle mass, a feature of airway remodeling in asthma, is the strongest predictor of airflow limitation and contributes to asthma-associated morbidity and mortality. No current drug therapy for asthma is known to affect airway smooth muscle mass. Although there is increasing evidence that prostaglandin D2 type 2 receptor (DP2) is expressed in airway structural and inflammatory cells, few studies have addressed the expression and function of DP2 in airway smooth muscle cells. We report that the DP2 antagonist fevipiprant reduced airway smooth muscle mass in bronchial biopsies from patients with asthma who had participated in a previous randomized placebo-controlled trial. We developed a computational model to capture airway remodeling. Our model predicted that a reduction in airway eosinophilia alone was insufficient to explain the clinically observed decrease in airway smooth muscle mass without a concomitant reduction in the recruitment of airway smooth muscle cells or their precursors to airway smooth muscle bundles that comprise the airway smooth muscle layer. We experimentally confirmed that airway smooth muscle migration could be inhibited in vitro using DP2-specific antagonists in an airway smooth muscle cell culture model. Our analyses suggest that fevipiprant, through antagonism of DP2, reduced airway smooth muscle mass in patients with asthma by decreasing airway eosinophilia in concert with reduced recruitment of myofibroblasts and fibrocytes to the airway smooth muscle bundle. Fevipiprant may thus represent a potential therapy to ameliorate airway remodeling in asthma.
This paper explores key issues in the development of open access to research data. The use of digital means for developing, storing and manipulating data is creating a focus on 'data-driven science'. One aspect of this focus is the development of 'open access' to research data. Open access to research data refers to the way in which various types of data are openly available to public and private stakeholders, user communities and citizens. Open access to research data, however, involves more than simply providing easier and wider access to data for potential user groups. The development of open access requires attention to the ways data are considered in different areas of research. We identify how open access is being unevenly developed across the research environment and the consequences this has in terms of generating data gaps. Data gaps refer to the way data becomes detached from published conclusions. To address these issues, we examine four main areas in developing open access to research data: stakeholder roles and values; technological requirements for managing and sharing data; legal and ethical regulations and procedures; institutional roles and policy frameworks. We conclude that problems of variability and consistency across the open access ecosystem need to be addressed within and between these areas to ensure that risks surrounding a data gap are managed in open access.
RECODE will leverage existing networks, communities and projects to address challenges within the open access and data dissemination and preservation sector, and produce policy recommendations for open access to research data based on existing good practice. The open access to research data sector includes several different networks, initiatives, projects and communities that are fragmented by discipline, geography, stakeholder category (publishers, academics, repositories, etc.) as well as other boundaries. Many of these organisations are already addressing key barriers to open access to research data, such as stakeholder fragmentation, technical and infrastructural issues, ethical and legal issues, and state and institutional policy fragmentation. However, these organisations are often working in isolation or with limited contact with one another. RECODE will provide a space for European stakeholders interested in open access to research data to work together to provide common solutions for these issues. RECODE will culminate in a series of over-arching policy recommendations for a policy framework to support open access to European research data targeted at different stakeholders and policy-makers (http://www.recodeproject.eu).
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