Mucus is a perfectly normal fluid that helps to keep our bodies running smoothly, but not all forms of the slimy substance are created equal. People with chronic respiratory diseases tend to produce thicker forms of mucus and scientists have now uncovered one of the key reasons why, raising new treatment possibilities for conditions like asthma, cystic fibrosis and chronic obstructive pulmonary disease (COPD). “A healthy amount of mucus is very important for capturing and clearing potential threats to the lung, such as dust particles, dead cells and bacteria, so we’re not looking to remove mucus altogether,” explains Associate Professor Ethan Goddard-Borger from the Walter and Eliza Hall Institute and lead author of the new study. “We are seeking to develop innovative approaches for reducing the viscosity of the mucus to aid in clearing excess mucus from the lungs of patients with chronic respiratory disease.” Goddard-Borger led a research team in investigating the makeup up of especially thick mucus in sufferers of chronic respiratory illnesses, with the work centering on long protein strands known as mucin glycoproteins. These, together with water, form the basis of mucus, but other proteins called trefoil factors also play a role in dictating the consistency of the fluid. “Trefoil factors have long been known to make mucus more viscous (thicker), and it has been postulated that this thickening occurs in respiratory diseases,” says Goddard-Borger. “However, until now we did not completely understand how the trefoil factor proteins achieved this.” The team’s work in the lab has uncovered the mechanisms by which these trefoil factors drive up viscosity levels in mucus spurred by chronic respiratory illness. The researchers were able to demonstrate that the proteins naturally adhere to the mucin glycoproteins via binding sites on their surface, which cross-link them together to make the fluid viscous. “Within mucus, trefoil factors essentially ‘staple’ the mucin strands into a mesh: the more staples, the denser the mesh and the thicker the mucus becomes,” says Goddard-Borger. The team says this finding is a significant step forward in our understanding of mucus and how it behaves in sufferers of chronic respiratory illnesses. It also raises the prospect of new technologies that could break down or prevent the bonds between the trefoil factors and the mucin glycoproteins, which could aid in the treatment of conditions like asthma, cystic fibrosis and COPD. “The next step is to work with commercial collaborators to progress our vision to develop new mucolytic drugs that can more effectively clear mucus from the airways,” says Professor Goddard-Borger. “Achieving this could make a significant impact on the quality of life and life expectancy of people struggling with debilitating respiratory conditions.” The research was published in the journal Nature Communications.