Sputum proteomics of CF, BE and COPD with or without NTM infections

Abstract

Non-tuberculous mycobacterial infections (NTM) affect patients with cystic fibrosis (CF), bronchiectasis (BE), and chronic obstructive pulmonary disease (COPD). Identification of biomarkers and diagnostic tools are complicated by the differences in underlying disease. The aim of this study was to investigate biomarkers of NTM infection across the spectrum of respiratory diseases. <b>Methods:</b> Patients with CF (n=15), BE (n=21) and COPD (n=19) with and without NTM infection (IDSA/ATS criteria) were enrolled from two centres (Ninewells Hospital, Dundee and Royal Brompton Hospital, London). NTM patients had monthly sputum samples from diagnosis until 6 months after enrolment. <b>Results:</b> Comparison of protein markers between CF, BE and COPD showed significant increases in 12 proteins including MPO, AZU1, CTSG, CAT and RNASE3 in CF compared to COPD, with the downregulation of 21 proteins including SCGB1A1, IGFBP2, SFTPB, GC and CFD. The only significant difference between COPD and BE was the increased KLK1 expression in BE. There were no significant changes in protein levels between BE and CF. Comparing patients with and without NTM infections across diseases revealed small but non-significant differences between groups. Protein expression in the NTM group during antibiotic treatment showed no consistent association with the NTM status. This is in contrast with the response associated with antibiotic clearance of other systemic pathogens. <b>Conclusion:</b> These results indicate a differential inflammatory response primarily dependent on the disease setting with minimal influence from NTM infection status.