Bridging human and in vitro evidence in occupational asthma: a translational approach

Asthma is a respiratory disease that affects approximately 300 million people worldwide. The most common form of asthma is allergic asthma, and when it is exacerbated in the workplace due to chemicals exposure, it is called occupational asthma. This condition is characterised by complex interactions between cells of the respiratory system, the immune system and immunological mediators. Recent evidence has reported alterations in the expression of microRNAs (miRNAs) in a variety of lung diseases, including allergic asthma. Although their role has not yet been clarified, it is known that many of them are associated with asthma and airway inflammation. The central hypothesis of this project, based entirely on human samples and cells, is that miRNAs play a key role in activating the immune system. The aim is to identify miRNAs associated with this pathology and inflammatory signatures in human samples and to compare them with responses observed in an in vitro model to assess its translational relevance. The project is based on a translational approach, integrating human serum and exhalate breath condensate samples from healthy subjects, asthmatic patients, and individuals exposed to a respiratory sensitizer (toluene diisocyanate, TDI) with an in vitro alveolar model, to allow a direct comparison between the two systems and the identification of differences across common immune and inflammatory endpoints. The experimental approach involves miRNA sequencing of serum samples, while exhaled breath is used to analyse cytokine patterns (IL-17A, TNF-α, IL-10, IL-6 and IL-8) and perform quantitative profiling of thousands of proteins using an omic approach. In vitro samples are used for comparison following exposure to the same respiratory sensitiser used for human samples, through analysis of the same cytokines and the most significant markers detected in the latter’s analysis. The results obtained from miRNA sequencing show statistical significance for the expression of miRNA between healthy and asthmatic patients, such as miR-107, 146b-5p and 203a-3p, notably involved in asthma pathogenesis, while miR-130a-3p, associated with modulation of the airway inflammatory response, was highlighted as statistical significant in the TDI exposed samples. Cytokines and omic analysis will be performed. This integrated strategy may enable the identification of novel molecular targets, supporting the development of mechanism based biomarkers to better understand the processes that underline occupational asthma.