Abstract
Background
Annual influenza epidemics cause significant morbidity and mortality. New, emerging strains threaten to cause catastrophic pandemics. Assay of exhaled breath for volatile organic compounds (VOCs) via gas chromatography-mass spectroscopy (GC-MS) is an emerging diagnostic modality ideally suited to fill the gap in influenza diagnostics.
Methods
Patients with influenza like illness (ILI) presenting to the Troop Medical Clinic on JBSA Fort Sam Houston, TX, from 3/2017 to 3/2019 submitted a 2-minute breath sample in addition to a nasopharyngeal swab collected for polymerase chain reaction (PCR) assay for influenza virus. ILI was defined as temperature > 100.40F AND respiratory symptoms like cough, sputum production, chest pain and/or sore throat. Breath VOCs were assayed with GC-MS and data were analyzed in order to identify the significant breath VOC biomarkers that discriminated between ILI patients with and without a PCR assay positive for influenza with greater than random accuracy.
Results
Demographic, clinical, PCR and breath data were available for 237 episodes of ILI. PCR was positive for influenza for 32 episodes (30 influenza A and 2 B). The median age of participants was 21 (IQR 19, 23) and 69% were male. There were no differences in age, gender, education, race, or smoking, between the influenza positive and negative groups. Likewise, there was no difference in days of limited activity or missed work, or symptoms at presentation between the groups. The algorithm achieved near maximal predictive accuracy of 78% with four biomarkers (74% sensitivity and 70% specificity). Based on their mass spectra, these biomarker VOCs were tentatively identified as 2-amino-1-propanol, 2-butanamine, n-nitro, 3-methyl-hexanal, and heptane, which are consistent with products of oxidative stress.
Figure. Accuracy, Sensitivity, and Specificity of Influenza Breath Test. Receiver operating characteristic (ROC) of the breath test (sensitivity versus 1-specificity). The accuracy of the breath test was 78%. With a cutoff point at the “shoulder” of the ROC curve, the test had 74% sensitivity and 70% specificity.
Conclusion
Our findings bolster available benchtop and clinical data suggesting that breath testing may be a useful diagnostic modality for influenza infection. The next step will be to study the predictive algorithm developed in this protocol in a blinded validation cohort. If the predictive algorithm performs well in a validation study, adaptation for its use in a portable, tabletop GC would be warranted to allow for a rapid, accurate, universal point-of-care influenza diagnostic test.
Disclosures
Michael Phillips, MD, Menssana Research, Inc (Grant/Research Support)
Predictive Accuracy and Densitometric Analysis of Point-of-Care Immunoassay for Adenoviral Conjunctivitis
