Phenotyping and outcomes of hospitalized COPD patients using rapid molecular diagnostics on sputum samples

Abstract

Nawaf M Alotaibi,1,2 Virginia Chen,1,3,4 Zsuzsanna Hollander,1,3,4 Jonathon A Leipsic,5 Cameron J Hague,5 Darra T Murphy,5 Mari L DeMarco,1,6 JM FitzGerald,3,7,8 Bruce M McManus,1,3,4,6 Raymond T Ng,4,9 Don D Sin1,3,7 1Centre for Heart Lung Innovation, James Hogg Research Centre, St Paul’s Hospital, Vancouver, BC, Canada; 2Department of Medicine, Division of Pulmonary Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 3Institute for Heart and Lung Health, Vancouver, BC, Canada; 4PROOF Centre of Excellence, Vancouver, BC, Canada; 5Department of Radiology, St Paul’s Hospital, Vancouver, BC, Canada; 6Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada; 7Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, BC, Canada; 8The Lung Centre, Vancouver General Hospital, Vancouver, BC, Canada; 9Department of Computer Sciences, University of British Columbia, Vancouver, BC, Canada Background: Etiologies of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are heterogeneous. We phenotyped severe AECOPD based on molecular pathogen detection of sputum samples collected at hospitalization of COPD patients and determined their outcomes.Methods: We phenotyped 72 sputum samples of COPD patients who were hospitalized with a primary diagnosis of AECOPD using a molecular array that detected common bacterial and viral respiratory pathogens. Based on these results, the patients were classified into positive or negative pathogen groups. The pathogen-positive group was further divided into virus or bacteria subgroups. Admission day 1 blood samples were assayed for N-terminal prohormone brain natriuretic peptide, CRP, and complete blood counts.Results: A total of 52 patients had a positive result on the array, while 20 patients had no pathogens detected. The most common bacterial pathogen detected was Haemophilus influenzae and the most common virus was rhinovirus. The pathogen-negative group had the worse outcomes with longer hospital stays (median 6.5 vs 5 days for bacteria-positive group, P=0.02) and a trend toward increased 1-year mortality (P=0.052). The bacteria-positive group had the best prognosis, whereas the virus-positive group had outcomes somewhere in between the bacteria-positive and pathogen-negative groups.Conclusion: Molecular diagnostics on sputum can rapidly phenotype serious AECOPD into bacteria-, virus-, or pathogen-negative groups. The bacteria-positive group appears to have the best prognosis, while pathogen-negative group has the worst. These data suggest that AECOPD is a heterogeneous event and that accurate phenotyping of AECOPD may lead to novel management strategies that are personalized and more precise. Keywords: COPD, molecular pathogen detection, exacerbation phenotypes

Keywords

• Chronic Obstructive Pulmonary Disease
• Molecular Pathogen Detection
• Exacerbation Phenotypes