Non-invasive approach to diagnosis of pulmonary tuberculosis using microdroplets collected from exhaled air

Abstract

In this report we present a proof-of-principle study aimed at developing non-invasive diagnostics for pulmonary TB that are based on analyzing TB biomarkers in exhaled microdroplets of lung fluid (MLFs). Samples were collected on electrospun filters recently developed by the authors, and then tested for the presence of Mycobacterium tuberculosis (Mtb) cells, Mtb DNA, and protein biomarkers (secreted Mtb antigens and antigen-specific antibodies). The latter were detected using rapid ultra-sensitive immunochemistry methods developed in our laboratory. Neither Mtb cells (limit of detection, LOD = 1 cell) nor Mtb DNA (LOD ∼ 10 CFU) were found in the MLF samples exhaled by TB patients. However, immunoglobulin A (IgA) was found in over 90% of samples from TB patients and healthy volunteers. Antigen-specific IgA were detected at higher rates in the patient samples as compared to those from nominally healthy volunteers resulting in a modest discrimination level of 72% sensitivity and 58% specificity. As such, this novel, non-invasive and fast breath diagnostic method shows promise for further development.

Breath can discriminate tuberculosis from other lower respiratory illness in children

“…Consistently, approximately half of pediatric patients diagnosed with TB fall into the unconfirmed TB category in studies 4,5 . There is a clear need for improved diagnostics for children, particularly for those in the unconfirmed TB category 3,10 .Previously, we and others have demonstrated that exhaled breath can be collected, analyzed, and mined for putative biomarkers for TB in adults [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] . The APOPO non-profit organization have demonstrated that African…”

“…Previously, we and others have demonstrated that exhaled breath can be collected, analyzed, and mined for putative biomarkers for TB in adults [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] . The APOPO non-profit organization have demonstrated that African…”

Specificity and sensitivity of the new test for serological evaluation of tuberculosis using MPT83-MPT63 fusion antigen

“…Dozens of commercial serological tests for TB are being marketed in many parts of the world, despite previous systematic reviews having reported variable sensitivity and specificity of these tests [19,20]. However, despite this, the shortcomings of the current methods for controlling TB are obsolete and very inaccurate.…”

Breath analysis for respiratory infections

“… 4 Morozov and colleagues performed a proof-of-principle study aimed at developing noninvasive diagnostics for pulmonary TB based on potential TB biomarkers in microdroplets exhaled by TB patients and collected on electrospun fibers. 5 This study involved 42 TB patients (including recent and chronic TB cases) and 13 healthy volunteers. Samples were tested for the presence of Mtb cells, Mtb DNA, and protein biomarkers.…”