SRISM

Projects

Immunological and Molecular Fingerprinting of Elite Athletes, Amateur Athletes and Non-sportive Controls

Background:

Allergic diseases such as asthma, atopic dermatitis and allergic rhinitis currently affect more than one billion people worldwide and cause enormous health-care costs, as well as economic loss due to work absences. Professional athletes in particular suffer from impaired performance and have failure to succeed, especially as a result of upper respiratory symptoms. So far, there have not been any studies examining the burden of asthma and allergic diseases in athletes in regard to chronic exercise-induced changes and predisposition to develop respiratory infections.

Specific aims:

The project presented here will be the among the first of a series of studies on exercise immunology, molecular mechanisms of performance and susceptibility to infectious disease in amateur and professional athletes: Our aim is to establish Swiss Research Institute for Sports Medicine (SRISM) as a leading institute for front research in exercise medicine. The initiation of this project in 2020 allowed us to set up of the first Swiss Registry and biobank for athletes, and to perform first analyses on collected blood samples. Our goal is to build on this foundation and grow the registry while performing exciting research, focusing mainly on immune response, inflammation and metabolism on a molecular level.

We will focus on three major research aims:

Aim 1. Molecular mechanisms of infection susceptibility linked to exercise and sports 

This part of our research will focus on upper respiratory symptoms (being caused by infections, allergic rhinitis, chronic rhinosinusitis and asthma i.a.) – which represent the main reason athletes present to doctor’s offices, apart from injuries.

Aim 2. Molecular mechanisms of sports performance 

This part of our research will focus on selected professional performance indexes and questionnaire together with peripheral blood immunological and metabolism biomarkers. We have a technology to determine up to 1500 biomarkers in serum with small amounts of blood and will perform studies before and after intense training. In addition, longitudinal (monthly) analyses and follow-up throughout the whole season in a selected group of professional athletes will be performed.

Aim 3. Immunology and metabolism of asthmatic athletes

Asthma affects approximately 30 % of athletes in Europe and the US, and in-depth characterization of asthmatic athletes represents an important missing link in professional sports. In addition, sports activities of asthmatic children have been encouraged, however it was never approached by using the novel molecular techniques that are available at SIAF. According to preliminary data on asthma and allergic diseases, there are different disease endotypes (distinct functional and pathobiological mechanisms) that call for therapies with specific biologicals. The identification of such endotypes in athletes could optimize individual training programs and improve preventive and/or therapeutic strategies.

In summary, our research specifically aims at:

  • Identifying the reasons for the susceptibility to infections & allergies in athletes
  • Examining the role of metabolic changes linked to susceptibility of developing upper respiratory diseases
  • Identifying molecular targets and the metabolic pathways of infection susceptibility
  • Identifying effects of intense exercise on immune response and cellular metabolism
  • Demonstration of molecular and metabolic markers of sports performance 

 

Experiments to be performed, protocols, methods:

Most front technologies, such as multiple omics, targeted proteomics, single cell sequencing and microbiome sequencing will
be applied in this multicenter case-control observational study after a thorough clinical characterization of the subjects from three cohorts (elite athletes, amateur athletes, nonsportive controls), in the context of the project “Clinical, Immunological and Molecular Fingerprinting of Elite Athletes, Amateur Athletes and Non-sportive Controls” (ethical permission, Zurich Ethics Commission, ID 2019-02002).

Study Cohorts:

 A) A Multicenter case-control observational research involving human subjects will be performed. Three groups (each n = 50) will constitute: elite athletes, amateur athletes, non-sportive control group. Time frame for observation is 24 months. Sampling of blood and stool, as well as nasal and skin swabs will be performed.

B) One longitudinal cohort of professional athletes (n=10) will be analyzed for 10 months by collecting monthly samples. This group will also have single cell sequencing to investigate the immune and inflammatory status of all peripheral blood cells.

C) One cohort of physician-diagnosed asthmatic professional athletes (n= 40) will be analyzed for three time points throughout one year. The selected timepoints are August (mid-summer), December (mid-winter), April-May (mid-grass pollen season). The controls will be nonasthmatic athletes (n=40) and non-sportive subjects (n=30).

 Measurements:

Assessment of molecular differences regarding immune response, inflammatory markers, metabolism and cardiovascular markers, microbiome differences, single cell expressions between elite athletes, amateur athletes and non-sportive controls. Characterization of subsets (endotypes) of athletes with different underlying mechanisms for upper respiratory symptoms/allergies/asthma and suggestion of molecular targets for novel prevention or therapeutic measures

 Significance and novelty:

This study is likely to yield generalizable knowledge that enhances society’s understanding about the influence of physical activity on our immune system and cellular metabolism. By combining a very thorough characterization of study subjects with the most advanced methodology, we expect to shed light on the connection between chronic intense exercise and our immune system, which has so far, in the context of asthma and allergic diseases, only been studied vaguely. Our research aims to bring precision medicine to the athlete, representing a new approach to limit training interruption and loss of performance due to upper respiratory symptoms. The collection of data and biological material from athletes of different ages and disciplines signifies the establishment of the first Swiss Registry and biobank of sportsmen and -women.