The interstitial lung diseases (ILDs) are a group of over 200 disease that may lead to
progressive fibrosis and respiratory failure. ILDs are heterogenous, with varying amounts of
inflammation and fibrosis, and differ in response to therapy and outcome. The most severe
fibrotic (f) ILD, idiopathic pulmonary fibrosis (IPF), has a median survival of just three years.
Progressive fILD may respond to antifibrotic treatments which slow down, but do not
reverse, fibrosis albeit often with significant side effects. Better treatments or delivery of
treatments are needed.
Diagnosis of ILD relies on clinical history, imaging and, in some cases lung biopsy, with
associated risks. Better diagnostic and prognostic biomarkers in ILD are urgently needed.
This thesis examines the approach to diagnosis, prognostication, and treatment in fILDs,
and, in particular IPF. It begins with the finding that Neutrophil Lymphocyte Ratio (NLR),
derived from a simple, widely available blood test, is a prognostic biomarker in IPF. The role
of lung biopsy in the diagnostic pathway is considered and the use of a relatively new
minimally invasive technique of transbronchial cryo lung biopsy (TBCB) as an alternative to
surgical lung biopsy (SLB) is described. The value of TBCB to obtain lung tissue for research
is demonstrated with evaluation of the distribution of inhaled ipratropium in fILD. Using
matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) on samples of
lung taken using TBCB, it was demonstrated that inhaled medication was able to reach the
fibrotic lung, presenting a new approach to drug delivery in fILD. Further discussion focusses
on the current role of SLB in the diagnostic pathway in ILD, the presentation of a systematic
literature review, and a discussion of future trials to assess the potential benefits of a wider
use of TBCB.