Idiopathic pulmonary fibrosis is a relentlessly progressive disease that is responsible for
the deaths of over 5000 people in the UK each year. At present, despite a dramatic increase
in clinical trials in the last decade, there are no licensed treatments for IPF. The
pathogenesis of the condition remains incompletely understood, nonetheless there is good
evidence to suggests that the condition arises as the consequence of an aberrant wound
healing response in genetically susceptible individuals. Basic science research into IPF has
identified a wide range of potential treatment targets. However, in many cases developing
compounds to act against these targets, because of their role in normal wound healing, is
limited by the possibility of major systemic side effects.
The lung is highly amenable to topical therapy in the form of inhaled drug preparations and
this route is utilised in the treatment of the majority of respiratory disease. The inhaled
route offers a number of important potential advantages for administration of therapy to
patients with IPF. Firstly, by limiting systemic exposure to drugs, the inhaled route offers
the potential for achieving higher lung doses of drugs that might otherwise cause systemic
toxicity. Secondly, inhaled treatment may more effectively reach the areas of abnormality in
IPF, namely the hyperplastic epithelium and the underlying fibroblastic foci. Thirdly, the
inhaled route offers an alternative to parenteral administration of compounds that are poorly
absorbed through the gastro-intestinal tract e.g. monoclonal antibodies. It should be noted
however, that the fibrosis in IPF develops peripherally involving the alveolar interstitium
and the terminal bronchioles. Furthermore, the disease causes architectural destruction and
distortion of the lung that is liable to alter the normal laminar flow of air (and inhaled
particles) through the bronchial tree. It is therefore, by no means certain that it is
possible to deliver inhaled therapies directly to regions of fibrosis in IPF.
The feasibility of delivering inhaled drugs in IPF has not been previously studied. This
research by assessing the effect of particle size on inhaled particle deposition and by
relating to this the pharmacokinetic profile of salbutamol aims to validate the potential of
the inhaled route in IPF. This study is an important precursor to the development of specific
topical therapies for patients with IPF.