Research Article: Sensitivity and specificity of an electronic nose in diagnosing pulmonary tuberculosis among patients with suspected tuberculosis

Date Published: June 13, 2019

Publisher: Public Library of Science

Author(s): Antonia M. I. Saktiawati, Ymkje Stienstra, Yanri W. Subronto, Ning Rintiswati, Jan-Willem Gerritsen, Henny Oord, Onno W. Akkerman, Tjip S. van der Werf, Katalin Andrea Wilkinson.


To investigate the potency of a hand-held point-of-care electronic-nose to diagnose pulmonary tuberculosis (PTB) among those suspected of PTB.

Setting: Lung clinics and Dr. Sardjito Hospital, Yogyakarta, Indonesia. Participants: patients with suspected PTB and healthy controls. Sampling: 5 minutes exhaled breath. Sputum-smear-microscopy, culture, chest-radiography, and follow-up for 1.5–2.5 years, were used to classify patients with suspected PTB as active PTB, probably active PTB, probably no PTB, and no PTB. After building a breath model based on active PTB, no PTB, and healthy controls (Calibration phase), we validated the model in all patients with suspected PTB (Validation phase). In each variable (sex, age, Body Mass Index, co-morbidities, smoking status, consumption of alcohol, use of antibiotics, flu symptoms, stress, food and drink intake), one stratum’s Receiver Operating Characteristic (ROC)-curve indicating sensitivity and specificity of the breath test was compared with another stratum’s ROC-curve. Differences between Area-under-the-Curve between strata (p<0.05) indicated an association between the variable and sensitivity—specificity of the breath test. Statistical analysis was performed using STATA/SE 15. Of 400 enrolled participants, 73 were excluded due to extra-pulmonary TB, incomplete data, previous TB, and cancer. Calibration phase involved 182 subjects, and the result was validated in 287 subjects. Sensitivity was 85% (95%CI: 75–92%) and 78% (95%CI: 70–85%), specificity was 55% (95%CI: 44–65%) and 42% (95%CI: 34–50%), in calibration and validation phases, respectively. Test sensitivity and specificity were lower in men. The electronic-nose showed modest sensitivity and low specificity among patients with suspected PTB. To improve the sensitivity, a larger calibration group needs to be involved. With its portable form, it could be used for TB screening in remote rural areas and health care settings.

Partial Text

On 26 September, 2018, the United Nations (UN) had a high-level meeting in the UN headquarters in New York on tuberculosis (TB). The discussion focused on accelerating actions to end TB by 2030 [1]. In 2017, the death toll was still huge–with 1.3 Million death, and an additional 300 000 among HIV-coinfected, TB leads the causes of death by an infectious disease; in 2017 alone, 10 Million people fell ill with TB [1]. Clearly, new diagnostic tools are needed to identify individuals in the community–and in health care facilities–that continue to spread this airborne disease. In many TB high-burden countries, pulmonary tuberculosis (PTB) is commonly diagnosed by sputum smear microscopic examination [1]. Sputum microscopy is labor-intensive, and the technique does not differentiate Mycobacterium tuberculosis (MTB) from non-tuberculosis mycobacteria [2]. Though sputum culture is considered gold standard, it is problematic in low-resource settings, because it is expensive, time-consuming, and vulnerable to technical failure [3]. Nucleic acid amplification techniques such as Xpert MTB/ RIF allows for fast identification of MTB [4], but costs remain challenging; it still requires sputum sampling and is neither portable nor fit for point-of-care in remote rural areas with unstable electricity supply. For all of the above-mentioned sputum-based tests, appropriate sputum specimens are required. Meanwhile, not all patients with suspected TB were able to collect an adequate and good quality sputum sample. Chest radiography (CXR), a non-sputum-based test that is usually used, lacks specificity [3].

We included 360 consecutive patients with suspected PTB and 40 healthy controls; 73 study participants were excluded for various reasons, resulting in a total of 327 study participants (Fig 2). Table 2 shows that median age of study participants in calibration and validation phase was 40 (range: 18–85) and 46 (range: 18–85) years old, respectively. Diagnoses for patients who turned out to have no PTB included asthma, pneumonia, bronchiectasis, chronic bronchitis, COPD, Obstructive Syndrome Post TB, lung fibrosis, lung abscess, empyema, and polycystic lung disease.

This is the first study testing the e-nose (Aeonose) to diagnose PTB among patients with suspected PTB. The study in Bangladesh used a prototype of the e-nose (participants exhaled into a bag, then the bag content was examined using a laboratory version of the e-nose), and with smaller sample size [11]. Other studies with e-nose devices did not diagnose PTB among patients with suspected PTB [12,24,25]. The sensitivity in our study was modest, while specificity was low.