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Person exhales—doctor diagnoses his case

7 Jun '18
Russian scientists have come up with a new method of noninvasive tuberculosis diagnostics at a very early stage. All they need to diagnose a case are a few samples of the air the person exhales.

The core of the problem

Two stages of pulmonary tuberculosis are known: latent (hidden) and active (acute). An estimated 30% of the Earth’s population have this disease in them, but most do not develop the acute stage and stay innocuous for other people. Even as tuberculosis develops into the active stage, its symptoms do not grow obvious immediately; already a person may be contagious but unaware of it.

It’s mycobacteria that trigger tuberculosis. Mycobacteria are intracellular parasites that live inside macrophages, the cells that protect our body by absorbing and destroying germ and virus cells. Some of the adverse microorganisms happen to be “smart” enough to “learn” ways of escaping death inside macrophages, inhabiting and multiplying inside those instead. As they multiply, the mycobacteria ooze special proteins that form a thin film to cover the entire surface of a lung. The presence of such proteins as markers in the pulmonary fluid is a sign of tuberculosis advancing rapidly.

However, unlike blood or urine, getting a sample of pulmonary fluid is not so easy and usually causes much discomfort to a patient. Scientists at the Institute of Theoretical and Experimental Biophysics in the town of Pushchino outside Moscow have proposed a way of avoiding such nuisance by catching and studying the part of the pulmonary fluid which is found as microdroplets in the air one exhales.

How it works

To catch pulmonary fluid droplets, the researchers suggest using an ordinary Petryanov filter known for more than half a century as a Soviet Union designed device to clean the ambient air from radioactive dust at nuclear energy sites. The filter has been remodeled as a very simple and inexpensive disposable device to collect microdroplets in exhaled air.

During tests at a specialized clinic 42% of patients who had been admitted but had not begun therapy yet were given the filter to breathe through for 10 minutes, and then doctors would study the cloth for possible tuberculosis biomarkers. They found that in the air samples there were no living mycobacteria, their DNA or antigens, but there were antibodies specific to antigens which a mycobacterium secretes.

These antibodies (in very small quantities of a few thousand molecules) are typically found in samples taken from most tuberculosis patients. To identify such an insignificant amount of adverse stuff an ultra-sensitive multicomponent chip based immunoanalysis technique was used, enabling the fast (5-10 minutes) identification of several antibodies or antigens simultaneously.

So, tests revealed for the first time that the exhaled air did contain specific markers, which are antibodies generated to counter fast-multiplying infectious matter.

With an eye to improvements

In addition to samples taken in the clinic, the scientists also looked into the air exhaled by 13 healthy volunteers. As it turned out, antibodies specific to mycobacterium pathogens could help diagnose tuberculosis in its acute form with a sensitivity and specificity of about 60-70%.

It’s difficult to do more precise diagnostics at this stage as some of healthy people who have long been in contact with tuberculosis patients have the same antibodies developing in their lungs as do their sick contacts. The researchers think that the problem can be addressed if antibody study is enhanced with checking for inflammation in the lungs, another sign of infection which can be detected by finding in the exhaled air special regulatory proteins called interleukins. Incorporating this test into their methodology is the next task for the Pushchino team—provided that their project gets further funding.

The scientists have published an article describing the effort in detail in the English-language Journal of Breath Research journal.