LABORATORY EXPERIMENTS – essential to exposome research

The REMEDIA project studies the impact of the exposome on the course of lung diseases, with a particular focus on two chronic lung diseases: chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). Our research aims to determine how and to what extent the exposome affects the severity and morbidity of COPD and CF.

In this opinion piece, we focus on REMEDIA’s innovative laboratory-based experiments, and the essential role of such experiments in the design of prevention and care programs.

The exposome and the quest for understanding health and disease

Recent decades have seen a major evolution in the study of health and diseases, moving from a restricted “one exposure, one disease” approach to a broader concept, the exposome, which encompasses all the environmental exposures to which we are subjected throughout our lives and behaviors, via our diet, the air we breathe, our psycho-affective, socio-economic environment, among many others.

The challenge of unravelling the exposome’s role in health and disease

Deciphering the role of the exposome in complicated health trajectories is a major challenge. Firstly, the exposome refers to a broad spectrum of parameters whose individual effects on health are already highly complex. Second, these parameters need to be considered dynamically in both space and time. Finally, the characterization of real-life exposures is in itself a great challenge.

It is clear that the challenge of unravelling the role of the exposome in health and disease cannot be met by epidemiological studies alone. These studies need to be complemented by experimental ones, in which the impact of each exposome parameter can be addressed as a complex set of exposures, in a controlled environment.

The REMEDIA project tackles the question of the impact of exposome on health and diseases not only through epidemiological studies, but also through innovative experimental studies focused on air pollution.

Air pollution is a complex mixture

Air pollution is a complex mixture of pollutants present in a gas phase and a particulate phase. This mixture is made up of thousands of chemical compounds, most of which are present at trace levels.

The gas phase corresponds to all gaseous pollutants present in the atmosphere: nitrogen oxides (NOx), sulfur dioxide (SO₂), ozone (O₃), volatile organic compounds (VOCs), etc.

The particulate phase, also known as aerosols, corresponds to all liquid or solid particles suspended in air. Particulate matter, or PM, is categorized according to its size, which ranges from a few nanometers to several micrometers. PM₁₀ includes all particles with a mean aerodynamic diameter (see Note below) of less than 10 micrometers. PM_2.5 and PM_0.1, include only the smaller particles known as fine and ultrafine particles (UFP), that have aerodynamic diameters of less than 2.5 and 0.1 µm respectively. In addition to this size diversity, particles have variable morphologies, composition (inorganic, organic, mineral). Particle size and chemical composition are strongly influenced by the nature of the source emitting the particles but also change often dramatically in the atmosphere due to the corresponding chemical and physical processes.

Note: The aerodynamic diameter of a particle is defined as that of a sphere, whose density is 1 g.cm⁻³ (cf. density of water), which settles in still air at the same velocity as the particle in question.

The challenge of realistically simulating the atmospheric mixture

So far, experimental studies aiming to decipher the biological/health impact of air pollution on living organisms use a single pollutant or a mixture of a few compounds which are then put into contact with cells (in vitro tests) or with preclinical models (in vivo tests). However, these studies do not consider the complexity of the air pollution mixture, which reduces the overall relevance of such an experimental approach. To meet this challenge, atmospheric simulation chambers (a.k.a. smog chambers) have been developed over the past few decades, allowing the production of atmospheric mixtures that mimic real urban atmospheres. This enables researchers to replicate and study the effects of air pollution on health in a controlled laboratory environment.

View of the experimental simulation platform. (1): the LISA atmospheric simulation chamber which consists of a stainless-steel reactor (4.2 m³) (covered by a khaki tarpaulin obscuring the light emitted from the irradiation system). (2): the FORTH mobile atmospheric simulation chamber (FORTH-MSC) to add biomass burning to the simulation. (3): devices coupled to the chamber, allowing the exposure of preclinical models to the simulated mixture (isolators).

This experimental set-up allowed us to study the impact of air pollution on the course of cystic fibrosis, and emphasized the added value of considering air pollution with a multi-pollutant approach (Blayac et al. 2023).

Going beyond air pollution simulation for experimental exposome research 

The idea behind the “PolluRisk” platform is to reproduce the exposome in the laboratory, and monitor the impacts on the health of murine models. Simulation of air pollution can be considered as a first step in a more comprehensive experimental simulation of the exposome, while retaining the ability to control and reproduce the experimental conditions. Other components of the exposome, such as age, sex, tobacco consumption, noise, social stress, diet etc can be added to the experimental simulation.

Combining atmospheric simulation chamber(s) with exposure devices for living organisms enables trans-disciplinary research into the impact of the exposome on health and disease.

These studies using the PolluRisk platform illustrate the potential of this approach

Maternal exposure during pregnancy:

Modification of immunity and intestinal development (Guilloteau et al., 2022)

Altered lung development and susceptibility to develop COPD in adulthood (Lu et al., 2022)

Adult exposures:

Worsening/emergence of the pulmonary phenotype in mice with cystic fibrosis (Blayac et al., 2023)

Modification of lung regeneration capacities in naive mice (Belgacemi et al., 2023).

This experimental approach should be extended to all areas of exposome research, to assist policy makers in their decisions and allow the development of preventative measures.