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

Abstract

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; exacerbation phenotypes; molecular pathogen detection.

Figure 1

AECOPD-phenotype pie charts. Notes: Bacteria: patients who had a positive result for bacterial organisms; Virus: patients who had a positive result for viral organisms either independently or with bacterial organisms. (A) Patients divided by having either a negative or a positive result; (B) positive group subdivided by viral detection. Abbreviation: AECOPD, acute exacerbations of chronic obstructive pulmonary disease.

Figure 2

Box plots depicting length of hospital stay in the three groups. Note: The pathogen-negative group had longer hospitalization than the bacteria group (P=0.02), and a significant linear trend was present demonstrating that length of hospital stay decreased from the pathogen-negative group to the bacteria group (P=0.017).

Figure 3

Box plots depicting the significantly different variables between groups. Notes: Significant differences were present in NT-proBNP (P=0.042), hemoglobin (P=0.031), and RDW (P=0.025) between the pathogen-negative and -positive groups. Abbreviations: NT-proBNP, N-terminal prohormone brain natriuretic peptide; RDW, red-blood-cell distribution width. *Represents an extreme outlier, >3× the IQR from a quartile. °Outliers with values between 1.5–3 box lengths from the upper or lower edge of the boxplot.

Figure 4

Kaplan–Meier survival-analysis curves for 1-year mortality according to panel groups. Notes: (A) According to negative or positive result; (B) positive group subdivided by viral detection.