DanFund Study - extended introduction

Functional disorders are frequent and can be defined as syndromes that, after appropriate medical assessment, cannot be explained in terms of conventional medical or surgical diseases. People affected by a functional disorder experience a number of physical symptoms in a degree that often makes it challenging to sustain a normal functional everyday life. Some examples of these conditions are irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, whiplash associated disorders and multiple chemical sensitivity. Collectively, no well-described and widely accepted medical explanations exist for these conditions, and how to best define functional disorders is a controversial topic among health professional and researcher. Some of the conditions included in DanFunD study does have a WHO's ICD-10 classification code (irritable bowel syndrome and fibromyalgia), however, that does not necessarily mean that the cause of these conditions is known, or that there exist a professional consensus on how to delimit them. We are also aware that the unifying label for these conditions has been interchanging, but we have chosen to use the term “functional disorders" because it is a terminology commonly used in the scientific literature. However, it is important to emphasise that we use the term functional disorders without any pre-assumption about the underlying medical causes. How best to define a disease, identification of the primary causes and uncovering the consequences of a disease for persons and the society are all classic research questions within public health science and likewise the primary motivation behind this epidemiological study.

One of the major challenges for the area of functional disorders is the general lack of consensus among researchers and health professionals regarding the nature of functional disorders. Combined with our limited understand of both the major risk factors and the pathogenesis of these conditions, this lack of consensus has made it impossible to optimize and implement rational prevention and treatment strategies for functional disorders. As a result, patients have a high risk of being misdiagnosed or being offered health care solutions with limited or no effect.

One of the main reasons why we still know so little about functional disorders is that these conditions are yet to be adequately investigated in larger and coordinated epidemiological population based surveys. These types of high impact studies have provided essential knowledge about other major chronic diseases and made it possible to develop highly efficient guidelines for prevention and treatment. A well know example of such a study is the Framingham study from the USA, a longitudinal population based survey initiated in the late 40ties focusing on cardiovascular diseases. In the years around the World War II, a dramatic increase in the incidence of heart attacks and high blood pressure had been observed, and cardiovascular diseases represented at that time the primary cause of dead in the USA. Motivated by the almost complete lack of knowledge about causes and risk factor for cardiovascular diseases, funding for the Framingham study was provided by the US government with the aim to unravel the prevalence, causes and risk factors for cardiovascular diseases. Together with the findings from later population based surveys from other countries, we can now explain the majority of heart disease in the population and thus prevent them.

Some of the current challenges:

  • Definitions of functional disorders are not consistent, neither nationally or international
  • Huge variation in estimated occurrences of functional disorders between different studies
  • Most studies of risk factors in functional disorders have been cross-sectional studies. However, cross-sectional studies have considerable methodologically limitations compared to longitudinal studies. In the cross-sectional studies, the participants are only examined ones compared to in the longitudinal studies, where the same people are being investigated periodically over a number of years.
  • The complex causal web of functional disorders has not been disentangled and in most studies of these conditions, the combined role of social factors, lifestyle, genetics, inflammation, mental parameters etc. are not being investigated in a combined causal model.
  • The impact of functional disorders for the individuals and society as a whole is poorly described

It is our ambition with the DanFunD study - in collaboration with national and international partners - to replicate the success story of cardiovascular diseases. We expected that findings from DanFunD will lead to a better delimitation of functional disorders, including whether they represents distinct but closely associated conditions or whether they are in fact all different manifestations of the same condition. We also expect the DanFunD study to provide more knowledge about the causes for functional disorders, why they are chronic for some people but fluctuate or disappear after a period for others and what the consequences of functional disorders are on an individual level and for the society as a whole.

This fairly ambitious plan involves collaboration between a number of relevant research institutions in Denmark with combined expertise within epidemiology and population based studies, functional disorders, basic research and the required statistical knowhow. The study material is based partly on already completed population based surveys of more than 100,000 people, who either have completed a comprehensive health examination and/or have answered a questionnaire, and partly on the data from nearly 10,000 people, which has been collected specific for the DanFunD study. The DanFunD survey includes a thorough description of the individual participant’s symptom profile, their lifestyle, pain sensation, disabilities and mental health. In addition, we have created a biobank with blood, urine, faeces, and DNA for future testing of various hypotheses about the causes of the diseases and have access to information from the Danish central health registry. The project is led by a scientific group with representatives from the involved research institutions and we intend to establish close cooperation to interested research institutions globally (please see "Publications and Presentation, DanFunD Study”)

 

To summarize, we intend to answers the following five superior questions about functional disorders:

1. How best to delimitate functional disorders

How frequent are these conditions? What type of symptoms and symptom complexes best represents these conditions? Should we completely reinvent the area of functional disorders and only look at the individual symptoms exclusively? We do not really know whether we are dealing with one or multiple conditions, though findings from epidemiological studies of other chronic diseases substantiate that we are likely to be dealing with several conditions with different causes. How best to delimitate functional disorders will be examined using advanced statistical tools supplemented by standardized diagnostic interviews with selected study participants. A better delimitation of functional disorders will likewise lead to more precise estimates of the true prevalence and incidence.

2. How common are functional disorders

An improved delimitation of functional disorders will also lead to more precise estimates of the true prevalence and incidence.

3. Mechanisms involved in the development of functional disorders

It is our intention to describe the causal web of functional disorders using a highly interdisciplinary approach. Our strategy is to examine various factors frequently suggested in the litterateur as being important in the development of functional disorders. Some of the factors of interest genetics, the microbiome, inflammation, fatty acids, autonomic nervous system functioning, central pain regulation, personality traits and psychological parameters.

4. Identify primary risk factor

What are the common risk factors for developing a functional disorder? We want to identify important risk factors for the development of functional disorders and determine if the same risk factors are important for all the different form of functional disorders in focus. Possible risk factors could be lifestyle and major life events, the role of social factors, being exposure to organic pollutants, genetic variants, infections etc. 

5. What is the prognosis for functional disorders? 

We want to assess the consequences of functional disorders, both on an individual level and for society as a whole. To obtain an exhaustive figure describing the total burden cause by functional disorders, our analyses will include information about the course of the conditions (remission, stability, and exacerbation), development of other diseases, and socio-economic consequences. This type of information can only be obtained using large longitudinal population based surveys like the DanFunD study.

Finding the answers to the five superior questions above represent the traditional approach used in the field of epidemiology to describe and understand diseases. Although we today have a very good understand of the causes for diseases such as type 2 diabetes and cardiovascular diseases, intensive research are still being carried out to identify new causes and risk factor for these diseases.


Current status on the DanFunD study

Data collection was complete in 2015 encompassing a cohort of 9,656 men and women aged 18-76 years, representing a random sample from the general population. Most of the quality control of the collected data was likewise completed by end of 2016. We expect the first results from the DanFunD study to be published late 2016/early 2017 and all publications base on DanFunD data will be presented on our homepage ("Publications and Presentation, DanFunD Study”). Nevertheless, as it is for all larger epidemiological studies we have to be patient before we can expect to see the major scientific breakthroughs and we expect this study to continue for the next 10-15 years. In the Framingham study, it took nearly 15 years of research and several re-examinations before the major risk factors for cardiovascular diseases were identified and a similar scenario is expectable when it comes to functional disorders

The vision behind the DanFunD study

  • Challenge the way we understand and describe pain and fatigue
  • Assess whether we should move away from the traditional delimitations of functional disorders
  • Create a platform for translational studies 
  • Create a room for interdisciplinary collaborations 
  • Generate the required knowledge about functional disorders to meet the growing demand for prevention and treatment
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