Asthma diagnosis via a drop of blood
A research team at the Fraunhofer Institute for Marine Biotechnology and Cell Technology EMB is working with high-tech companies to develop a rapid test that only requires a drop of blood to diagnose asthma. The partners use the machine learning method.
In the "KillAsthma" project funded by the state of Schleswig-Holstein, Fraunhofer EMB, together with the Pattern Recognition Company and Raytrix GmbH, is addressing the problem that many measurement methods are unsuitable for detection, for example for children. With a new quick test, the result should be available after 60 to 90 minutes. The highlight: All that is needed to diagnose asthma is a drop of blood and the immune cells in it.
"In asthma, the movement of immune cells is greatly slowed when they experience an inflammatory stimulus," explained Dr. Daniel Rapoport, head of the cell processing group at Fraunhofer EMB. The research group used this knowledge to develop the test set. The idea is to observe the immune cells from the drop of blood under a specially developed holographic microscope for about 90 minutes and, based on their movement patterns, to assess whether an asthma disease is present. The microscope, also known as a cell scanner, enables automatic, three-dimensional tracking of cells in real time. Artificial intelligence (AI) plays a decisive role, recognizing characteristic patterns in the complex movement patterns of thousands of cells.
But how does the technology work in detail? The blood and a substance that triggers the inflammatory stimulus are filled into a microfluidic cartridge and then pushed into the miniaturized microscope. This includes an LED and an optical CMOS PhotoSensor that is connected to the computer software. The image evaluation is carried out using specially developed algorithms. "We can observe 2,000 to 3,000 cells at the same time, which guarantees a high level of statistical accuracy," says Rapoport. The movement patterns determined are then transferred to a neural network. Self-learning algorithms analyze the blood cell movement patterns and calculate the diagnostic index. "With AI you can recognize deviations in the patterns. To record the differences, we use self-learning algorithms. Based on a lot of training data, the neural networks learn patterns and can differentiate the profiles of sick and healthy people."
This leads to the conclusion that AI is also able to learn other deviations from the norm. "Our method can also be used to analyze other diseases. This applies in particular to autoimmune and chronic inflammatory diseases such as Crohn's disease, ulcerative colitis and rheumatism. Here the diagnoses are lengthy and can be accelerated significantly with an adapted rapid test," said the Lübeck-born Researcher: "The first tests have been successfully completed. The image evaluation showed that our holographic microscope is superior to a high-performance microscope." Rapoport and its project partners are currently optimizing the hardware and the process. The long-term goal is to recognize the individual characteristics of asthma diseases in order to be able to develop a personalized treatment plan.
Ketogenic Diet Helpful For Asthmatics?
Can a special diet help against certain cases of asthma? A new study at the University of Bonn at least suggests this conclusion. Accordingly, mice that were switched to a so-called ketogenic diet showed significantly less inflammation of the airways.
Asthma patients react to even low concentrations of some allergens with severe inflammation of the bronchi. These are also accompanied by an increased production of mucus, which makes breathing even more difficult. Cells of the innate immune system, which were discovered only a few years ago and are called Innate Lymphoid Cells (ILC), play a central role in this. They take on an important protective function in the lungs by regenerating damaged mucous membranes. To do this, they produce inflammatory messengers from the group of cytokines, which stimulate the mucous membrane cells to divide and promote mucus production.
This mechanism is actually very useful: the body can quickly repair damage caused by pathogens or harmful substances. The mucus then transports the pathogens out of the bronchi and protects the airways against renewed infestation. "In asthma, however, the inflammatory reaction is far stronger and longer than normal," emphasized Prof. Dr. Christoph Wilhelm from the Institute for Clinical Chemistry and Pharmacology, who is a member of the ImmunoSensation Cluster of Excellence at the University of Bonn. The result is extreme breathing difficulties that can even be life-threatening.
The ILC multiply rapidly in this process and produce large amounts of pro-inflammatory cytokines. The scientists hope that if their division could be slowed down, the excessive reaction could presumably be brought under control. In fact, the results that have now appeared point exactly in this direction. "We have investigated which metabolic processes are active in the ILC when they switch to propagation mode," explained Wilhelm's colleague Dr. Fotios Karagiannis: "Then we tried to block these metabolic pathways and thus reduce the speed at which the cells divide."
In fact, in dividing ILCs, some metabolic pathways were significantly more active. Above all, they ensure that the cells are supplied with energy and with the building blocks they need for reproduction. The latter include, for example, fatty acids that are needed for the production of the cell membrane. "Activated ILC therefore absorb fatty acids from their environment and store them briefly inside in small droplets, an important intermediate step in order to be able to generate membranes from them," Karagiannis explained.
But what if the cells are forced to use these fatty acids elsewhere? To answer this question, the researchers put mice with asthma on a diet that consisted primarily of fats, but hardly any carbohydrates and proteins. With this diet, also known as the ketogenic diet, the metabolism of the cells changed: the energy they needed was now obtained from burning fat. However, they lacked fatty acids that they need for the formation of new membranes during cell division.
As a consequence, the dividing activity of the ILC decreased in the rodents fed accordingly - and drastically: "Normally, when there is contact with allergens, the number of ILCs in the bronchi increases fourfold," said Prof. Wilhelm: "In our test animals, however, it remained almost constant. Accordingly, both mucus production and other asthma symptoms decreased. "
This is not only due to the switch to fats as an alternative source of energy and the resulting shortage of fatty acids. Presumably, the glucose deficiency also contributes directly to the reduced activity of the ILC. "Asthma has increased in frequency over the past few decades. This may also have something to do with the increasingly high-sugar and fat-rich diet," speculated Wilhelm.
The scientists now want to investigate in patients whether a ketogenic diet can prevent asthma attacks. However, this is not entirely safe in the long term and should only be carried out after consulting a doctor. "We are trying to find out which components of the change in diet are responsible for the effect", Wilhelm explained the approach further: "Perhaps that opens up the way for the development of new drugs."
It is known that a ketogenic diet can be an effective therapy for some diseases. Patients with certain forms of epilepsy are treated with this method. And the change in diet should also help with some tumors - after all, the cells in them also multiply unusually strongly.
Asthma: Immature mast cells trigger the immune response
Mast cell progenitor cells not only cause an increase in mature mast cells during inflammation, but also play an active role in diseases such as asthma. This comes from a new study by immunology researchers published in the Journal of Allergy and Clinical Immunology. The study also underscores that progenitor cells can generally play an active role in inflammation and challenges the popular belief that only mature immune cells are involved in immune responses.
"We have shown that mast cell progenitor cells become immunologically activated when exposed to allergic stimulation. They can produce the cytokine IL-13, which is known to contribute to the development of asthma," says Erika Mendez-Enriquez, researcher for Immunology at Uppsala University.
Mast cells are rare immune cells found in tissues that come into contact with the outside world, such as the airways and skin. In contrast to other immune cells, mast cells develop from precursor cells that migrate into the tissue via the blood. Mast cells play a detrimental role in the development of asthma and allergies, primarily through their expression of the high-affinity receptor for IgE, the most important antibody in connection with allergic reactions. Mast cells are activated when the IgE bound to the IgE receptors binds to allergens and releases substances that trigger physiological reactions such as the narrowing of the airways in allergic asthma.
Mast cell precursors are extremely rare in healthy people, but their frequency increases during inflammation, which later leads to an increase in mature mast cells. It is well documented that mast cells increase in many types of inflammatory diseases.
"Our previous studies have shown that mast cell progenitor cells outnumber mature mast cells during acute inflammation. Mast cell progenitor cells in both mice and humans also have IgE receptors. This is why we wondered whether mast cell progenitor cells were also caused by allergic ones Stimulation can be activated, and in our new study we were able to confirm this. In the future, we will investigate whether and how different types of asthma treatments affect mast cell progenitor cells, "says Jenny Hallgren Martinsson, Senior Lecturer in Immunology at Uppsala University and Head of the Study.
Why asthma is often worse at night
Up to 75 percent of people with asthma have more severe symptoms at night. By significantly changing the daily rhythm of test subjects with asthma, they were able to demonstrate that the body's internal clock plays an important role in this.
In addition to physical activity and sleep, the internal clock makes a significant contribution to the worsening of asthma at night: although patients in the laboratory stayed awake at night under artificial light or kept a longer daily rhythm for a week, they used asthma spray up to four times more often during the normal nighttime, write the researchers in the journal "The Proceedings of the National Academy of Sciences".
"This is one of the first studies to carefully isolate the influence of circadian rhythms from other behavioral and environmental factors, including sleep," said Dr. Frank Scheer from Brigham and Women's Hospital in Boston. People with severe asthma suffered from the worsening particularly at night. Activities, such as sleeping, also had a greater effect on severity.
The internal clock, also known as the circadian system, consists of a central pacemaker in the brain and other “clocks” distributed throughout the body. They are important for the coordination of body functions and to react to changes in the environment during the day.
In order to decouple the influence of the circadian system from that of sleep and other behavioral and environmental factors, the researchers examined 17 people with asthma, who treated their symptoms with asthma spray as required, under changed daily rhythms in the laboratory: The patients either stayed with in weak light regular small meals were awake for 38 hours continuously or lived with a daily rhythm of 28 hours for a week.
Significantly more asthma diagnoses in adults
Between 2009 and 2016, the incidence of asthma in outpatient care increased by 35 percent, but only in adults. In children and adolescents, on the other hand, the proportion of patients receiving asthma remained largely constant over the observation period. This emerges from a new study in the supply atlas of the central institute for the Kassenärztliche supply in Germany (Zi).
The study also identifies differences between urban and rural regions. In large cities, the proportion of those insured for asthma was around 25 percent higher than in rural areas.
For the present evaluation, the researchers of the Supply Atlas have used nationwide contract medical billing data for the years 2009 to 2016. For the year 2016 alone, they have included more than 70 million billing data. Patients with asthma were identified according to the ICD-10 classification (code J45.- "bronchial asthma").
For the prevalence calculation, the scientists included those patients who had their asthma coded in at least two different quarters of a calendar year. The one-year diagnosis prevalence was determined as the proportion of asthma patients in all insured persons who had used contracted-care services at least once in each calendar year. According to this classification, the prevalence of asthma in 2016 was 5.9 percent in adults and 5.1 percent in children and adolescents.
In the observation period from 2009 (4.3 percent) to 2016 (5.9 percent), there was a significant increase in the prevalence of diagnoses in adults, while there was only a small increase in children and adolescents (4.9 percent in 2009 and 5.1 Percent 2016).