Poster Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

Proteome biomarkers for reflux aspiration in cystic fibrosis (#709)

Rosemary E Maher 1 , Robert W Lord 2 , Victoria M Harman 1 , Jaclyn A Smith 2 , Andrew M Jones 2 , Paul McNamara 3 , Robert J Beynon 1
  1. Centre for Proteome Research, University of Liverpool, Liverpool, Merseyside, United Kingdom
  2. Manchester Adult Cystic Fibrosis Centre, University Hospital of South Manchester, Manchester, United Kingdom
  3. Respiratory Unit, Alder Hey Children's Hospital NHS Foundation Trust, Liverpool, United Kingdom

The introduction of gastric contents into the respiratory tract, a process known as reflux aspiration, potentially contributes to lung damage in cystic fibrosis (CF). At present, there is no method to identify patients with reflux aspiration, presenting a major challenge for the management of patients presumed to be at risk. Here we describe a quantitative proteomics approach to assess differences in the sputum proteome between CF patients based on gastro-oesophageal reflux (GOR) measures to identify protein biomarkers for reflux aspiration.

Spontaneous sputum samples were collected from CF subjects (n=37), and sputum was induced from healthy volunteers (HV, n=33) for comparison. The sputum proteome was analysed by bottom-up shotgun proteomic analysis using liquid chromatography/mass spectrometry. All CF patients had GOR measured using 24-hour pH-impedance; sputum samples were compared from those with the highest (n=5) and lowest (n=5) risk for reflux aspiration, based on total, proximal and/or supine reflux episodes.

There were significant differences between the CF and HV sputum proteome with large increases in inflammatory proteins, predominantly neutrophil granulocyte proteins. There were also significant differences in the proteome between CF patients with highest and lowest reflux measures. These protein differences were not indicative of inflammation but other underlying cellular processes. No proteins of gastric origin were identified by shotgun proteomic analysis. 

These data suggest the sputum proteome of CF subjects may be influenced by gastro-oesophageal reflux. Although this appears to support a relationship between reflux and CF lung disease, it is not currently possible to conclude if this is a consequence of reflux aspiration. Gastric proteins, if present, will likely be at low abundance and more targeted approaches may be required for their detection. Using targeted analysis against a panel of gastric proteins, we aim to explore further the sputum proteome differences and identify specific biomarkers to diagnose reflux aspiration.