Table 1.
Study characteristics and sensitivity-specificity for TB diagnosis by breath test.
| Source | Number of patients included in analysis | Type of study subjects | Clinical setting and country | Type of study | Index test | Reference test | Collection of air samples | Type of sensors | Exclusion | Analysis | Funding sources | Rounded sensitivity, % (95% CI) | Rounded specificity, % (95% CI) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Bruins et al. [22] | PoP phase: 30 (15 PTB, 15 healthy); VS phase: 194 (34 TB, 114 non-TB, 46 healthy controls) | PTB patients, PTB suspects, and healthy controls; Children and adults (≥15 years) | Hospital and chest clinics, Bangladesh | PoP: case-control, retrospective; VS: cross-sectional, prospective. Consecutive enrolment: unclear. | Electronic nose | Culture | Separate bags | 12 metal-oxide sensors | Invalid measurement, outliers data | Artificial Neural Networks (ANN), participants for training and validation were overlap. Leave-one-out cross validation (LOO-CV) approach. | Partially funded by BD | 75 (59–89) | 87 (81–92) |
| Nakhleh et al. [19] | 198 (64 TB, 67 non-TB, 67 healthy controls) | PTB patients, control: 1) healthy volunteers, and 2) TB-negative subjects; Adults. | Three sites in Cape Town, South Africa | Case-control, prospective. Consecutive enrolment: unclear. | Electronic nose | Culture | Separate tubes | 12 nanomaterial-based sensors | Not mentioned | Principal Component Analysis (PCA); independent subjects in the validation phase. | Orgenics Ltd | 90 (68–99) | 93 (80–98) |
| Mohamed et al. [35] | 123 (67 PTB, 56 healthy controls) | Newly diagnosed, treatment-naive PTB patients vs healthy controls; Adults (≥18 years) | Chest hospitals, Egypt | Case-control, prospective Consecutive enrolment: yes. | Electronic nose | SSM and liquid culture on modified LJ medium | Separate bag/sacks | 10 metal-oxide sensors | Previous history of TB, coexisting medical or surgical illnesses, chronic bronchitis, bronchiectasis, lung abscess, default TB, relapse TB, latent TB | PCA and ANN, different participants for training (60%), testing (25%), and validation (15%). | Science and Technology Development Fund, Egyptian Ministry of Higher Education and Scientific Research, Cairo, Egypt | 100 (95–100) | 98 (90–100) |
| Zetola et al. [21] | 71 (51 PTB, 20 healthy controls) | Newly diagnosed PTB patients and healthy controls; Adults (≥21 years) | Hospital, Botswana | Case-control, prospective. Consecutive enrolment: yes. | Electronic nose | MGIT culture | Separate bag/sacks | 8 metallo-porphyrins coated quartz microbalance (QMB) gas sensors | Smokers | PCA and k-Nearest Neighbours, participants for training and validation were overlap. LOO-CV approach. | NIH/NIAID grants | 94 (84–99) | 90 (68–99) |
| Teixeira et al. [23] | 106 (41 TB, 19 non-TB, 46 healthy controls) | PTB suspects, asthma or COPD patients and healthy controls; Adults (>18 years) | National Reference Centre for pulmonary diseases, Paraguay | Case-control, prospective. Consecutive enrolment: unclear. | Electronic nose | Culture, or other strong supporting evidence when the culture result is negative | Inside the device | 3 metal-oxide sensors | TB suspects not able to expectorate sputum, with respiratory failure or having received TB treatment in the past 6 months. | ANN, participants for training and validation were overlap. | Sonnevanck Suppletie fonds, Harderwijk, The Netherlands | 88 (74–96) | 92 (83–97) |
| Poli et al. [39] | 84 (34 TPE/TB Pleural Effusion, 50 non-TPE) | TPE suspects, HIV-negative; Children and adults (≥15 years) | Venezuela | Cross-sectional, prospective. Consecutive enrolment: unclear. | Electronic nose | Histopathology of the pleural biopsy | Inside the device | 3 metal-oxide sensors | Poor general condition, difficulty to breath, no follow-up. | ANN, participants for training and validation were overlap. | Servicio Autónomo Instituto de Biomedicina “Dr. Jacinto Convit”, Venezuela | 88 (73–97) | 94 (83–99) |
| McNerney et al. [20] | 60 (31 PTB, 29 non-TB) | Patients with respiratory complaints; Adults (≥17 years) | Outpatient clinic of a hospital, Ethiopia | Cross-sectional, prospective. Consecutive enrolment: unclear. | RBS Breathalyzer (immunosensor and bio-optical technology) | Combination of clinical assessment, SSM, and CXR | Separate plastic tubes | Immunosensor (coated prism with TB antibodies labeled with a fluorescent dye) | Not mentioned | Evanescent wave fluorimetry | TARGETS Communicable Diseases Research Consortium funded by Department for International Development, UK | 74 (55–88) | 79 (60–92) |
| van Beek et al. [36] | 226 (90 TB, 136 healthy controls) | Culture-confirmed TB patients and healthy controls; Adults (≥ 18 years) | Lung Hospital and construction company, Vietnam | Case-control, prospective. Consecutive enrolment: yes. | eNO (Nitric Oxide) analyser | LJ Culture | Inside the device | N.A. | Negative culture, difficulty to breath, no CXR, HIV(+), current TB treatment. | The concentration of NO was noted in ppb. | Not mentioned | 78 (68–86) | 62 (47–75) |
| Phillips et al. [18] | 251 (130 PTB, 121 healthy controls) | PTB patients and healthy controls; Children and adults (≥13 years) | Hospitals and Health Sciences Institute in Phillipines, United Kingdom, and India | Case-control, prospective. Consecutive enrolment: unclear. | The BreathLink system (portable gas chromato-graph coupled to a surface acoustic wave detector) | Culture and/or SSM and/or CXR | Inside the device | N.A. | On anti-TB therapy, received anti-TB therapy in the last six months, technically unsatisfactory breath test samples | Multiple Monte Carlo simulations; Weighted Digital Analysis (WDA) multivariate predictive algorithm. | Menssana Research, Inc., United States Air Force | 72 (63–79) | 72 (63–80) |
| Kolk et al. [40] | Training: 100 (50 culture-proven TB, 50 culture-negative non-TB); Validation: 71 (21 PTB, 50 non-TB) | PTB suspects; Adults (> 18 years) | TB clinics, South Africa | Cross-sectional, prospective. Consecutive enrolment: yes. | GC-TOF-MS | MGIT Culture | Separate bags | N.A. | On anti-TB therapy | Support vector machine; LOO-CV approach; independent subjects in the validation phase. | UBS (Union Bank of Switzerland) Optimus Foundation and the Foundation for Innovative New Diagnostics (FIND) | 62 (38–82) | 84 (71–93) |
| Maiga et al. [37] | 56 (20 PTB, 36 healthy controls) | Newly diagnosed PTB patients and healthy controls; Adults (≥18 years) | Health centers and Hospital, Mali | Case-control, prospective.Consecutive enrolment: yes. | BreathTek™ urease breath test | MGIT and 7H11 culture | Inside the device | N.A. | Use of any antibiotic, proton pump inhibitors or bismuth containing preparations <15 days before study; HIV positivity; pregnancy | Measurement of the ratio of 13CO2 to 12CO2 in a breath sample. | NIH/NIAID grants, the Howard Hughes Medical Institute, the University of Sciences, Techniques, Bamako | 70 (46–88) | 11 (3–26) |
| Sahota et al. [24] | 40 (21 PTB/EPTB, 2 non-TB, 17 healthy controls) | Suspect PTB and EPTB, TB patients within 1 week of TB treatment; Adults (≥ 18 years) | TB clinics or in-patient admission in a teaching hospital, United Kingdom | Case-control, prospective. Consecutive: unclear. | FAIMS (Field Asymme-tric Ion Mobility Spectro-metry) | Culture, histology or radiology | Separate bags | N.A. | Not mentioned | Gaussian Process Classifier; LOO-CV method. | Medical Research Council, UK | 81 (58–95) | 79 (54–94) |
| Beccaria et al. [41] | 50 (32 PTB, 18 non-TB) | PTB suspects, including smokers and patients with HIV (+); Adults (≥18 years) | Wits Reproductive Health and HIV Institute, South Africa | Cross-sectional, prospective. Consecutive: unclear. | GC-TOF-MS | Gene Xpert and MGIT culture | Separate bags | N.A. | Not mentioned | Random Forest, linear Support Vector Machines, Partial Least-Squares Discriminant Analysis; Data was divided into training (60%) and validation (40%) phases; LOO-CV method. | Burroughs Wellcome Fund | 100 (89–100) | 61 (36–83) |
| Morozov et al. [58] | 55 (42 PTB, 13 healthy controls) | Recent and chronic TB; Adults (≥ 18 years) | Russia | Case-control, prospective. Consecutive: unclear. | Rapid ultrasensi-tive immuno-chemistry method | Clinical and CXR, culture and/or PCR or positive responses to anti-TB therapy | Separate bags | N.A. | Not mentioned | Immunoassay | Russian Science Foundation | 72 (53–86) | 58 (28–85) |
N.A.: Not Applicable.