Furthermore, patients with difficult to control severe asthma show an enlargement of airway smooth muscle associated with PAR2 overexpression, as well as high levels of PAR2-ligands recovered in BALF, PAR2-knockout mice show lower levels airway hyperresponsiveness and airway inflammation in comparison to wild type mice, and monoclonal anti-PAR2 treatment reduces airway inflammation in an asthma model in mice27. This evidence concerns the gene F2RL1 and airway hyperresponsiveness.