The European Sleep Apnoea Database (ESADA) ERS Clinical Research Collaboration: past, present and future

The start of the European Sleep Apnoea Database

The European Sleep Apnoea Database (ESADA) study began in 2007 as a joint project within the European Union (EU) Cooperation in Science and Technology (COST) Action B26 on obstructive sleep apnoea (OSA) and cardiovascular risk, as a network of nationally appointed sleep apnoea experts. At that time, there were few cohorts of OSA patients, mainly in the context of epidemiological studies in the general population [1–6]. The COST Action only provided funding for networking, and each participating centre entered data into the web-based database on a voluntary basis. Collected data included anthropometrics, results of blood tests, current medications, and sleep data derived from full polysomnography or cardiorespiratory nocturnal monitoring, according to the diagnostic procedure chosen by the physician. Importantly, quality controls of the dataset were performed at regular intervals since the start of the project.

During the first 2 years of the ESADA project, 5000 patients had been enrolled by 22 European sleep laboratories and stored at the coordinating centre in Gothenburg, Sweden [7]. The study continued after the end of the COST Action in 2010, thanks to financial support by the industry, and both the number of participating centres and the number of patients grew to reach the current figures of 33 and 25 000, respectively.

Before the approval of the ESADA project as a European Respiratory Society (ERS) Clinical Research Collaboration (CRC) in 2015, some important changes occurred. First, members of the ESADA group gathered each year in late winter or early spring in different European sleep centres for a 2–3-day meeting to discuss current and new projects and to work on manuscripts. Such meetings, as well as short-term exchanges of young researchers between ESADA laboratories, have strengthened the relationship between members and provided a creative, generous and friendly environment, while increasing the research productivity of the network. In 2014, four studies were published, reporting cross-sectional analyses on blood pressure [8], metabolic disorders [9, 10] and car accidents [11]. Secondly, a new generation of clinicians and scientists became involved in the ESADA study group and contributed enthusiastically to patient recruitment and new research projects, setting the premises for continuity of the project beyond the “founders”. Thirdly, it was recognised that it was important to set up a longitudinal cohort rather than continuing with recruitment of new patients at a high rate. Indeed, the aim of the first CRC in 2015 was to implement follow-up visits and longitudinal studies, and data on renal function [12] and body weight change [13] according to OSA treatment during follow-up have been recently published. Meanwhile, digging into the dataset in cross-sectional studies continued, with published research papers on methodological issues related to the diagnostic method [14], the association of OSA with chronic kidney disease [15], asthma [16] or dyslipidaemia [17], and the search for clinical phenotypes [18].

Where does ESADA currently stand?

The approval of the CRC by the ERS, and its recent renewal, greatly increased the visibility and prestige of ESADA worldwide, together with the cohesion and motivation of its members, in particular the commitment for further improvements, especially regarding OSA patient care and patient outcomes, which represent the ultimate goal of the ESADA project.

Current research projects include the association of OSA with cancer, definition of risk associated with mild OSA, and differences in OSA phenotypes between European countries. At the time of writing (in August 2018), there are more than 37 000 visits in the database, including first and follow-up visits. The monthly inclusion rate is ∼150–200 patients and the scientific activity is high (13 abstracts accepted in international conferences in 2018 and several manuscripts in preparation/submission). The ESADA serves as a reference database on European sleep apnoea patients and continues to provide a bridge for education and knowledge transfer between the various participating centres. Following early enabling grants, the ESADA has remained a low-budget study based on strong voluntary input from participating centres.

The future of the ESADA CRC

We would like to extend the network to include new sleep centres from countries not yet represented in the current CRC. Involvement of OSA patient organisations will be promoted with the help of the European Lung Foundation, in order to jointly address the problem of treatment acceptance and non-adherence, a highly hot topic nowadays. While collection of longitudinal data will continue, contacts were established with other clinical cohorts of OSA patients in Europe during a workshop held in Palermo, Italy, in early July 2018, when the possibility of joint projects on “big data” was discussed and awaits approval by the members of ESADA and other cohorts to proceed to formal agreements.

The current debate [19, 20] on randomised controlled trials (RCTs) to evaluate the effects of continuous positive airway pressure (CPAP) on cardiovascular risk suggests that new study designs, adopted to obtain clinically relevant results applicable to different subgroups of patients, should be introduced. Inclusion of OSA patients in long-term RCTs on the effects of OSA treatment has, for ethical reasons, been limited to non-sleepy patients who are poorly compliant to CPAP treatment. Negative results of RCTs could therefore be secondary to poor treatment adherence, rather than to inefficacy of treatment [19]. In this regard, the ESADA CRC could be a powerful instrument to collect a large amount of longitudinal data in OSA patients in the European context. Adoption of the specific methodology required in pragmatic trials will be the next challenge for ESADA and other investigators in the years to come.

There are some critical issues that determine the sustainability of the ESADA project in the long term. We need to develop strategies to maintain high data quality and enable new research activities related to the database. Funding may be provided by public and academic institutions or by collaborations with industry. We plan to submit EU research or public health projects, and cooperation with other cohorts will help to reach the critical mass necessary to cover the entire European area. Again, the CRC is a very good opportunity to pursue this goal, not only for the visibility provided by the endorsement of a leading society like the ERS, but also for the practical support in submission of big projects. With these prospects, we anticipate a bright future for the highly successful collaborative ESADA project.