COPD

Respiratory distress as a permanent condition

<b>Unknown common illness</b> Many people who suffer from COPD are dependent around the clock on breathing apparatus. Image: pathdoc/shutterstock

Chronic lung diseases are rarely treatable. But research scientists in many disciplines are working to change this.

Just after getting up in the morning, he sat back down on the edge of his bed and blew into the measurement device. It indicated 51 percent. Karl-Heinz Peters hence is only able to make it to half of the target value. A healthy individual can pump, in the first seconds of exhalation, twice as much air out of his lungs to make space for the next breath of air.

Half speed ahead: all told, things are actually still going quite well for the 71-year-old Berliner despite his ailing lungs. Karl-Heinz Peters is mobile, he takes care of himself, drives through the city in his small Citroën and rides his bike for a few hours in the park. He always has his emergency-relief spray in the right-hand pocket of his jacket. Once or twice a week he has to pull it out when he can’t get any air and the panic has returned that he might lose control. At some point, that will no longer be enough.

Peters was diagnosed with COPD, an abbreviation for Chronic Obstructive Pulmonary Disease. This signifies an obstruction of the respiratory tracts. Symptoms of the disease are severe coughing, an increase in mucous production in the lungs, difficulty in breathing – at first primarily during physical exertion, but later on in an idle state as well. The risk of contracting this disease increases with age. Peters didn’t really understand what it meant after the diagnosis – he had never heard of the disease before. Then after he read up on the subject – he was shocked.   

COPD is an incurable widespread disease and has presented scientists with a mystery. Now 6.8M people in Germany suffer from it

Karl-Heinz Peters is not an exception. Every year more and more people are inflicted with chronic lung diseases: bronchitis, emphysema, fibroses, lung infection or asthma (see box at the end of the article). According to the “White Paper” published in 2014 by the German Respiratory Society, approximately every eighth person in Germany dies of diseases of the respiratory system. The major risk factor is smoking, and environmental and dust pollution are in second place.

Even if the medical name is more or less unknown, COPD is a widespread disease. Today 6.8 million individuals in Germany are afflicted, and by the year 2050, according to an extrapolation, it will be 8 million. This incurable disease has presented scientists with a mystery: Why doesn’t every smoker get it, instead of – according to the White Paper – only about every fourteenth smoker? Why do non-smokers also come down with it? Why does the disease have such a diverse progression? From Kiel to Munich – infection research scientists, molecular biologists, stem-cell physicians, geneticists and biotechnologists are working on finding the answers for these questions and methods for discovering how to stop the disease.

There is no grey fog of polluted air hanging over Berlin – the last smog alarm was removed in the early 90s. Karl-Heinz Peters did not work in a factory, not at a construction site, nor did he inhale poisonous dust working in an open-pit mine. He was an information engineer, working with computers until his retirement. The disease was presumably brought about by the perpetually joyful man himself – he began smoking at the age of 25, and eventually it was two packs a day. He tells his story in the self-help groups of the patient organisation “Lung Emphysema COPD Germany”, which he has been supervising for years.

Senior physician Simone Rosseau works in a renovated brick building at the Berliner Universitätsklinikum Charité. She is specialist for intensive and respiratory medicine in the Clinic for Pneumology. COPD therapy is oriented to the medical condition of the individual and the severity of the disease; she says: “But it always has to be the patient’s first step – to stop smoking.”

It is not possible to be completely cured of COPD, but the symptoms can be mitigated by means of drugs. Some remedies expand the bronchial tubes; others allow the mucous membranes to subside and alleviate the formation of mucous or inhibit the advance of the infection. If patients are suffering primarily from lung emphysema in which damaged air sacs in the lungs prevent complete exhalation of the spent air, a surgical procedure can relieve the breathing. Simone Rosseau explains: “Small valves or metal spirals are inserted into the bronchial tubes by physicians via endoscopy, through which excess air can slowly escape. This allows the volume of the over-expanded lungs to decrease, and there is more space to breath in new air.” If a patient with advanced COPD has problems inhaling, mechanical ventilation through a mask can ease the breathing and improve the quality of life. “We know in the mean time that it can also extend the life expectancy,” says Rosseau.

Oliver Eickelberg is working in Munich on therapies for lung diseases. He is one of the leading German research scientists in this field: Eickelberg is Director of the Institute of Lung Biology and Diseases at the Helmholtz Zentrum München, leads the Institute for Experimental Pneumology at the Ludwig-Maximilians-Universität and is currently setting up, under the auspices of the German Center for Lung Research and as Scientific Director of the Comprehensive Pneumology Center, a regional research network. “First of all, once the lung has become irreversibly diseased, a transplant is frequently nowadays the patient’s last chance,” he says. About 250 such operations have been carried out in Germany annually, but the risk is high and a compatible donor lung is frequently difficult to find.

In the future, Eickelberg is sure, it will be possible to have the diseased lung tissue regenerate itself. The lung could be induced, through messenger substances, to block pathogenic processes. This is already possible with mice – substances have been found for them that induce new development of their lung tissue. Advances have also been made in stem-cell research. “We are working on exogenous regeneration,” says the research scientist. This involves taking organ-supportive connective tissue matrices, i.e. meshes made of connective tissue cells, out of the lung and implanting healthy stem-cells upon them. This procedure as well has been carried out on mice. When these artificial, laboratory-produced lungs are implanted into the animals, they are accepted by their immune system.

Research is also being conducted on pig lungs in the Munich research network, but these experiments are still in the beginning stages, says Eickelberg. He says the initial objective is to remove the animals’ lungs and to construct a lung matrix made from respective components: fine connective tissue meshes, lung air sacs, very small blood vessels and lymphatic vessels. This matrix is then meant to be colonised with human stem-cells. In five years, says Oliver Eickelberg, such a lung structure could perhaps be individually adapted to each patient, with the application of 3D printers, and colonised with his/her own cells. Thus, rejection by the immune system could be prevented. It is conceivable that in five to ten years appropriate genetic therapy could be developed: a stem-cell is removed, the genetic defect is rectified, the new cell is multiplied and then used to colonise a lung matrix made of bio-compatible material – which is then implanted.

If new toxins are introduced again and again into the lungs, the immune cells soon overreact and begin to attack healthy cells as well

Change of location: a laboratory in the Helmholtz Centre for Infection Research in Braunschweig. Scientists are conducting experiments on mice here under the direction of Dunja Bruder, concerning the development of chronic lung infections that have not been caused by viruses or bacteria – such as with smokers, whose respiratory organs become chronically infected through inhaled toxins. The professor explains what happens here: “The damaged cells send out messenger substances in order to alert the immune system, which then sends out so-called scavenger cells to destroy the infected cells. They are thus able to prevent the infection from spreading. But if new toxins continuously make their way into the lungs, the immune cells soon overreact and start to attack healthy cells as well. A vicious circle has been triggered that leads to continued progress of the infection,” says Dunja Bruder.

The Braunschweig researchers have recently made two exciting discoveries with their experimental animals. First, they ascertained that the mice’s immune system suddenly switches to protection mode in an early stage of the infection, and that the immune cells no longer attack healthy cells: “If we could find out which substances stop the misdirected immune cells, then we could develop drugs from this substance that would prevent spreading of the infection, thus interrupting the vicious circle,” Bruder predicts.

The second discovery: Her team recognised that the animals’ immune system protects the lung against pneumococci in a certain stage of the disease more readily than in the rest of the disease progression. Pneumococci frequently cause severe infections in the diseased lung; if one could find out what it is that triggers this resistance, one would be able to contain such bacterial secondary diseases. But this could take a while. “Until we reach the point at which, based on the initial research with animals, applied medicine for human beings is utilised – years or decades will have gone by,” says Bruder.

Karl-Heinz Peters has not given up hope yet that research will soon find new approaches – “even for me”, he says. But he approaches the issue pragmatically: He recently began making plans regarding what has to be changed in his life if his air is cut off more and more frequently, and he is no longer able at some point to climb the small stairway in his maisonette apartment.

Bronchial Asthma

In the respiratory tract of human beings with asthma, there exists an on-going infection which leads to constriction of the upper airways. Typical symptoms are inhalation with a whistling sound, shortness of breath and breathlessness, a feeling of tightness in the chest, and coughing.

Bronchitis

There are three different kinds of bronchitis. Acute bronchitis is initiated by bacteria or viruses and leads to severe coughing and formation of mucous. Chronic bronchitis has the same symptoms: severe coughing and formation of mucous. It is caused by smoking or inhalation of pollutants that irritate the lung tissue again and again, until the self-cleansing mechanism in the bronchial tubes no longer functions. It is a pre-stage for chronic-obstructive bronchitis. With this infliction, the constant irritation due to pollutants leads to long-term narrowing of the airways. In addition to severe coughing and congested lungs, shortness of breath will also emerge.

COPD

This abbreviation stands for “Chronic Obstructive Pulmonary Disease“. This means narrowing of the airways. One distinguishes between COPD, chronic bronchitis and lung emphysema. The crossovers are fluid and frequently both forms appear. The first symptom is increasingly stubborn coughing. Added to this is the emission of mucous plus shortness of breath, which at first only occurs under stress, but later on during rest periods as well. The disease has a progressive development and worsens in stages. Smokers represent 80 to 90 percent of those affected. But the disease can also be attributed to pollutants in the environment, ozone and fine dust particles.

Lung emphysema  

With emphysema, the air sacs in the lung are destroyed step by step; these are responsible for releasing oxygen into the blood and carbon dioxide back into the air. Large air-filled bubbles form, which constrict the space for the gas exchange. The used air can no longer be completely conveyed to the outside, and sufficient oxygen can no longer be taken from the air.

Lung infection  

With lung infection, the lung tissue becomes infected; depending on the mode of infection, the air sacs in the lungs or the tissue between the air sacs and blood vessels are diseased. It is generally triggered by infections from bacteria, viruses or fungi, although it can also be caused by external factors such as inhalation of irritant gases.

Pulmonary fibrosis  

The term ‘scarred lung tissue’ is also used; between the pulmonary air sacs and the surrounding blood vessels, more and more connective tissue is formed. The tender lung structure becomes less elastic. This leads to scarring of the lung tissue, it can no longer stretch, and absorbs less oxygen. Typical symptoms are shortness of breath and dry cough. The fibrosis can be the consequence of a chronic infection, or result from recurrent inhalation of pollutants.

Lung cancer  

Various kinds of tumours rank among lung cancer, also referred to as lung carcinoma. They are typically malignant in that the altered cells multiply unchecked. They grow into surrounding tissue and destroy it. The largest risk factor for lung cancer is tobacco smoke. Pollution burden in the air or fine dust can also serve as triggers.

17.07.2016 , Marion Koch
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