Acute exposure to realistic simulated urban atmospheres exacerbates pulmonary phenotype in cystic fibrosis-like mice.

Cystic Fibrosis (CF) is a lethal genetic disorder caused by pathogenic mutations of the CFTR gene. CF patients show a high phenotypic variability of unknown origin. In this context, the present study was therefore dedicated to investigating the effects of acute exposure to air pollution on the pulmonary morbidity of a CF-like mice model. To achieve our aim, we developed a multidisciplinary approach and designed an innovative protocol using a simulation chamber reproducing multiphasic chemical processes at the laboratory. A particular attention was paid to modulate the composition of these simulated atmospheres, in terms of concentrations of gaseous and particulate pollutants. Exposure to simulated urban atmospheres induced mucus secretion and increased inflammatory biomarkers levels, oxidative stress as well as expression of lung remodeling actors in both WT and CF-like mice. The latter were more susceptible to develop such a response. Though we could not establish direct mechanistic link between biological responses and specific components, the type of immune response induced depended on the chemical composition of the atmospheres. Overall, we demonstrated that air pollution is an important determinant of CF-like lung phenotypic variability and emphasized the added value of considering air pollution with a multi-pollutant approach.

The Impact of Air Pollution on the Course of Cystic Fibrosis: A Review.

Cystic fibrosis (CF) is a lethal and widespread autosomal recessive disorder affecting over 80,000 people worldwide. It is caused by mutations of the CFTR gene, which encodes an epithelial anion channel. CF is characterized by a great phenotypic variability which is currently not fully understood. Although CF is genetically determined, the course of the disease might also depend on multiple other factors. Air pollution, whose effects on health and contribution to respiratory diseases are well established, is one environmental factor suspected to modulate the disease severity and influence the lung phenotype of CF patients. This is of particular interest as pulmonary failure is the primary cause of death in CF. The present review discusses current knowledge on the impact of air pollution on CF pathogenesis and aims to explore the underlying cellular and biological mechanisms involved in these effects.