The design of treatments for lung surface pathologies such as chronic obstructive pulmonary disease (COPD), asthma and cystic fibrosis is based on the quantitative details of lung mucociliary flows, and transport within these, despite the fact that we have a very poor understanding of these phenomena. Our research in this area, in collaboration with colleagues from the University of Birmingham, has provided a biophysical basis for why the (rare) electrolyte metabolism disorder, pseudo-hypoaldosteron, does not induce lung failure despite excess airway surface liquid production. It has also predicted that mucolytic drugs are relatively ineffective in increasing muco-ciliary clearance in the lung, especially compared to enhancing the cilia beat cycle time with β-andrenergic agents such as salbutamol, this is in general agreement with clinical observation. Future work will investigate predictions on how one may attempt to enhance transport for lung epithelia with patches lacking cilia in the presence of mucus hypersecretion, a phenotype existing in COPD. This phenotype appears to be present after fatal asthma attacks. It would thus be instructive to understand if it has a severe deleterious effect on muco-ciliary clearance. This, in turn, would indicate whether such tethering could be a contributing factor to the build-up of airway blocking mucus plugs observed after fatal asthma attacks and thus whether it should be targeted therapeutically. This question is especially pertinent given the debate in the literature on the role of mucus plug in asthma deaths.
Please contact Dr Eamonn Gaffney for more details.
Key references in this area
- D. J. Smith, E. A. Gaffney and J. R. Blake (2009). Mathematical modelling of cilia-driven transport of biological fluids. Proc. Roy. Soc. A 465:2417-2439. (eprints)
- D. J. Smith, E. A. Gaffney and J. R. Blake (2008). Modelling mucociliary clearance. Resp. Physiol. Neurobi. 163:178-188. (eprints)
- D. J. Smith, E. A. Gaffney and J. R. Blake (2007). A viscoelastic traction layer model of mucociliary flow. Bull. Math. Biol. 69:289-327. (eprints)