Transbronchial cryobiopsy and Neutrophil Lymphocyte Ratio - new precision medicine tools and markers in Interstitial Lung Disease

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

Noninterventional statistical comparison of BTS and CHEST guidelines for size and severity in primary pneumothorax.

Hilar rather than apical interpleural distance more accurately predicts need for intercostal chest drain insertion http://ow.ly/JvKFYThe study was funded by the East Anglian Thoracic Society. M.Z. Nikolić is a Wellcome Trust PhD Programme for Clinicians Fellow at the University of Cambridge. S.J. Marciniak is a Medical Research Council Senior Clinical Fellow. J. Wason is funded by the Cambridge Biomedical Research Centre. Funding information for this article has been deposited with FundRef.This is the final version of the article. It first appeared from the European Respiratory Society via http://dx.doi.org/10.1183/09031936.0011861

Multi-center evaluation of baseline neutrophil-to-lymphocyte (NLR) ratio as an independent predictor of mortality and clinical risk stratifier in idiopathic pulmonary fibrosisResearch in context

Summary: Background: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder with a variable disease trajectory. The aim of this study was to assess the potential of neutrophil-to-lymphocyte ratio (NLR) to predict outcomes in IPF. Methods: We adopted a two-stage discovery (n = 71) and validation (n = 134) design using patients from the UCL partners (UCLp) cohort. We then combined discovery and validation cohorts and included an additional 794 people with IPF, using real-life data from 5 other UK centers, to give a combined cohort of 999 patients. Data were collected from patients presenting over a 13-year period (2006–2019) with mean follow up of 3.7 years (censoring: 2018–2020). Findings: In the discovery analysis, we showed that high values of NLR (>/ = 2.9 vs < 2.9) were associated with increased risk of mortality in IPF (HR 2.04, 95% CI 1.09–3.81, n = 71, p = 0.025). This was confirmed in the validation (HR 1.91, 95% CI 1.15–3.18, n = 134, p = 0.0114) and combined cohorts (HR 1.65, n = 999, 95% CI 1.39–1.95; p < 0·0001). NLR correlated with GAP stage and GAP index (p < 0.0001). Stratifying patients by NLR category (low/high) showed significant differences in survival for GAP stage 2 (p < 0.0001), however not for GAP stage 1 or 3. In a multivariate analysis, a high NLR was an independent predictor of mortality/progression after adjustment for individual GAP components and steroid/anti-fibrotic use (p < 0·03). Furthermore, incorporation of baseline NLR in a modified GAP-stage/index, GAP–index/stage-plus, refined prognostic ability as measured by concordance (C)-index. Interpretation: We have identified NLR as a widely available test that significantly correlates with lung function, can predict outcomes in IPF and refines cohort staging with GAP. NLR may allow timely prioritisation of at-risk patients, even in the absence of lung function. Funding: Breathing Matters, GSK, CF Trust, BLF-Asthma, MRC, NIHR Alpha-1 Foundation