The bronchial asthma (from ancient Greek ἆσθμα asthma , German , shortness of breath, heavy, short of breath, tightness' ), or bronchial asthma , often only asthma called, is a chronic , inflammatory disease of the airways with permanently existing hypersensitivity. In appropriately predisposed persons (with an overly sensitive bronchial system ), the inflammation leads to attacks of breathlessness as a result of acute narrowing of the airways - a so-called bronchial obstruction (definition of the International consensus report on diagnosis and treatment of asthma ). This airway constriction is increased secretion of mucus , spasm of the bronchial muscles and formation of edema caused the bronchial mucosa, it is by treatment regress (reversible). A large number of stimuli cause an increase in the sensitivity of the airways ( bronchial hyperreactivity or bronchial hyperreactivity ) and the associated inflammation. 5% of adults and 7 to 10% of children suffer from bronchial asthma.
Asthma is a borrowing from ancient Greek ἆσθμα āsthma , which has been proven in German since the 16th century , which in turn seems to be morphologically unclearly derived from an Indo-European word stem * hma with the meaning “breathe”.
The term asthma was first used in the Corpus Hippocraticum . In antiquity it was the name for the entire spectrum of diseases "caused by the catarrh condensing in the brain and flowing down the lungs , which clogged the airways , made them gradually purulent and rotten." The patients were treated with bloodletting , cupping , laxative - crushing - sneezing , urinary - and sweat-inducing agents. Even with Aulus Cornelius Celsus asthma v to 50th Mentioned. The pneumatist Aretaios of Cappadocia was the first to describe the symptoms and describe the sputum as moist and sticky. He also said that asthmatics can only breathe well when they are in an upright position. He particularly recommended dietary measures to these people. Galen , on the other hand, approached the therapy with food that thins juices, a vegetarian diet and drugs with a dividing effect such as sea onion vinegar, sea onion sour honey and horseradish as emetics . The therapeutic agents used in antiquity could not prevent an asthma attack, but only trigger an expectorant effect .
In Arabic medicine, only Moses Maimonides worked on bronchial asthma and he wrote the treatise Tractatus contra passionem asthmatis for the Emir of Damascus Ali al-Malik al-Afdal Nur in Cairo , in which he described the asthma attack in detail and suggested medication for treatment. He placed the greatest value on prophylaxis, in the form of dietetic and hygienic measures.
Paracelsus wrote in Von der Bergsucht und other mountain diseases that the disease is triggered by cold, heat, fog, acid or sweetness and is a chemical process in which tartar , which is otherwise excreted through the lungs, settles on the inner wall of the lungs , forms a sticky mucus that clogs the airways. He treated mountain addiction with a mixture of tartar, ferric oxide and opium . Gerolamo Cardano preferred asthma therapy in the form of allergen avoidance . In 1522, for example, he treated John Hamilton with cassia syrup, hyssop powder , trochisci made from violets , cardamoms , colocanthus and, from his point of view even more important, by replacing his feather bed and pillow with a straw- filled linen pillow and a throw made of unspun silk . The attribution of asthma to allergens was also recognized by Santorio Santorio , Thomas Bartholin and Georg Agricola .
In 1648 Johann Baptist van Helmont's Ortus medicinae appeared in Amsterdam , in which he first described the convulsive asthma attack. Then Thomas Willis realized that the pulmonary spasm was due to the nervous system . John Floyer (1649–1734) published the work A treatise of the asthma in 1698 and described here the symptoms of the asthma attack. Later, Samuel Auguste Tissot (1728–1797) and William Cullen reported on the influence of the nervous system on an asthma attack. In 1700, Bernardino Ramazzini described the occupational diseases caused by allergens in De morbis artificum diatriba . At that time, however, only tobacco , sassafras , radix chinae (from Smilax chinae ), antimony and ether were added as medicinal products .
Based on the assumption that coffee , or later caffeine , dries out the phlegm in the body, therapy with coffee increased over time. Jakob Pahl finally discovered the breath-maleptic and bronchodilatory effects of caffeine.
Johann Leopold Edlem von Auenbrugger developed the percussion procedure in 1761 and René Théophile Hyacinthe Laennec the auscultation procedure . At the beginning of the 19th century it was possible to differentiate between the various bronchial diseases. Laennec was also able to confirm Thomas Willis' thesis that an asthma attack is a convulsive event. Josef Berson (1812–1902) then made the distinction between bronchial and cardiac asthma and defined bronchial asthma as an independent disease.
Anton von Störck investigated the drugs Datura stramonium (thorn apple), Hyoscyamus niger (henbane) and Atropa Belladonna (deadly nightshade) and found all three useful for asthma therapy. So they were used individually or as mixtures. Even Georg August Richter (1778-1832) and (1771-1842) used Josef Frank Solanaceae for the treatment of asthma. Most of the time, the stems were dried and chopped up and then lit in the pipe . The so-called asthma cigarettes became obsolete over time and were replaced by metered dose inhalers . In 1974 Boehringer Ingelheim first launched one that contained ipratropium bromide and was named Atrovent . In 2002 Boehringer Ingelheim developed the long-acting tiotropium .
Samuel Samson (1769-1843) used lobelia for therapy , for which he received the first patent in 1813 , in 1808 the root of Lobelia Syphylitica , which was included in the Pharmacopoeia of Massachussett's Medical Society , and in 1820 the tincture of the leaves, which was sold in the US -Pharmacopoeia received. While this therapy was particularly popular in the USA, therapy with morphine , emetine , codeine , quinine , caffeine , atropine and cocaine was tried . Sigmund Freud dealt with the use of cocaine in asthma in his work Ueber Coca and also the laryngologist Oskar Herrmann Bischörner (1843-1904) and the internist Karl Friedrich Mosler (1831-1911) treated asthma with the subcutaneous injection of Cocainum salicylicum. This lasted until 1920 when cocaine fell under the Narcotics Act .
Ephedrine was synthesized early by August Eberhard (1887–1960) and Ernst Schmidt (1845–1921), but it was not until 1924 that Ko Kuei Chen (born 1898) and Carl Frederic Schmidt drew attention to the sympathomimetic properties, so that ephedrine then through the Work by Friedrich Otto Hess (1882–1952) became one of the most important anti-asthmatics of the 20th century.
In 1888 Albrecht Kossel isolated the substance theophylline from the leaves of Camellia sinensis , which was marketed by Byk Gulden under the name Theocin in 1902 . In 1908 Reinhold Grüter (born 1882) synthesized the easily soluble theophylline ethyl diamine, which came onto the market as euphylline. David Israel Macht (1882–1961) and Giu-Ching Ting were able to recommend theophylline for therapy and in 1922 Samson Raphael Hirsch (1890–1960) brought a mixture of 1,3-dimethylxanthine and theobromine sodium, called spasmopurine, onto the market. In 1936, Grüter described the use of theophylline-phenylethylbarbituric acid-ethylenediamine in acute asthma attacks.
In India , snakehead fish are also used for a dubious therapy against asthma and are eaten with a herbal paste. The Indian government supports the annual ceremony of the Bathini Goud family in Hyderabad , in which around 5000 people take part, with special trains.
Prevalence data on medically diagnosed asthma are often inhomogeneous. The analysis of one and the same data source, the World Health Survey 2003 of the World Health Organization (WHO), led in one case to a lifetime prevalence in adults of 4.3%, in another case to a value of 6.0%. The values fluctuate even more in relation to individual regions and countries. Teresa To's working group found prevalences from 1.0% in Vietnam to 21.5% in Australia. While the prevalence of asthma has increased in many countries over the past few decades, progression seems to have stalled in Western countries. The countries with the highest prevalence of asthma are Australia (21.5%), Sweden (20.2%), the United Kingdom (18.2%), the Netherlands (15.3%) and Brazil (13.0%). According to the KiGGS study, up to 10% of children and adolescents in Germany suffer from bronchial asthma. In the case of adults, around 7.5% of the population in this country are affected.
Causes of different forms
One differentiates the allergic ( extrinsic ) asthma from non-allergic ( intrinsic ) asthma . In their pure form, however, these occur in only about ten percent of patients; mixed forms are observed in the majority. While allergic asthma is more common in children, the non-allergic form occurs more frequently in old age. Cigarette smoke in the parental home promotes asthma. There is also evidence that cultural and civilizational circumstances, as well as certain drug uses, promote asthma in early childhood.
The allergic exogenous asthma , at appropriate genetic predisposition to atopy by external stimuli (allergy-causing substances in the environment, so-called allergens triggered). Type E ( IgE ) immunoglobulins are formed which, in interaction with specific allergens , cause allergenic messenger substances such as histamine , leukotrienes and bradykinins to be released from mast cells . These substances then trigger the narrowing of the airways. In addition to this type I immediate reaction after inhalation of the allergen, a delayed reaction can occur after 6 to 12 hours; this is triggered by immunoglobulins of type G ( IgG ). Often both reactions occur (English dual reaction ).
The observation that children of parents who both suffer from allergic asthma have a disease risk of 60–80% suggests a polygenic inheritance . On the island of Tristan da Cunha , half of the population suffer from asthma due to familial inheritance. Hay fever (seasonal allergic rhinitis ), which, like asthma, is an allergic inflammatory disease of the mucous membrane of the nasopharynx, can spread to the lower respiratory tract and lead to asthma there (" change of floor "). As a result, almost a quarter of these patients develop pollen asthma after more than 10 years. In addition, a certain allergen is usually the focus at the beginning; Over the years, however, the trigger spectrum often expands, so that allergen avoidance becomes more and more difficult or even impossible for the patient.
There is evidence that rural life protects unborn children from asthma: children of women who have had contact with animals, grain or hay during pregnancy are less likely to develop allergic respiratory and skin diseases later in life. For a certain protection against these complaints, however, continuous contact with farm animals or grain is necessary.
The non-allergic endogenous asthma may, however, be caused by other stimuli: infections , mostly respiratory medication intolerances - so-called. Analgesics-asthma (a pseudo-allergic reaction to painkillers , mostly non-steroidal anti-inflammatory drugs such as aspirin ) z, adverse drug reactions (eg beta blockers. and cholinesterase inhibitors), the effects of poisonous (toxic) or irritating substances ( solvents , cold air, additives and others), particular physical exertion ( stress asthma ) and reflux disease (reflux of gastric acid) are possible causes of this form. Some connections and other causes have not yet been clarified.
Animal experiments provide evidence that tobacco consumption can lead to asthma over generations. In a study carried out in 2014 with the aim of finding indications for this in humans too, this could not be proven.
Three pathophysiological processes are characteristic for the development of the disease ( pathogenesis ):
Inflammation of the bronchi
Allergens or other stimuli trigger an inflammatory reaction in the bronchial mucosa. This is of central importance in asthma. In addition to mast cells and their secreted messenger substances ( inflammation mediators , see above), eosinophilic granulocytes and T lymphocytes play an important role.
In most asthmatics, nonspecific bronchial hyperreactivity (general airway hypersensitivity to stimuli) can be demonstrated. The hyperreactivity (also hyperreactivity) can often be objectified by inhaling irritant substances, e.g. B. with the methacholine test , histamine test or with loads such as the race test (overexertion of the bronchi when running, especially in children) or by cold air provocation. The neuropeptide substance P detected in the respiratory tract is believed to be involved in the pathogenesis of bronchial hyperreactivity.
Insufficient bronchial cleaning (clearance)
The obstruction is the narrowing of the lumen of the airways (reduction of the available cross-section) as a result of mucosal edema (fluid retention in the mucous membrane), increased or impaired mucous secretion ( hypercrinia or dyscrinia ) and bronchospasm (cramping of the smooth muscles of the bronchi) . This reduces the self-cleaning effect of the lungs: the secretion cannot drain away and in turn increases the damage up to complete obstruction , the so-called bronchial discharge .
An asthma attack leads to acute shortness of breath ( dyspnoea ). Exhalation is particularly difficult and this is often accompanied by wheezing breath noises ( expiratory stridor ). Sometimes coughing occurs, also in the form of coughing fits. In children, cough is usually the leading symptom, so the diagnosis of “asthma” is often made late. Difficult breathing and shortness of breath can lead to feelings of anxiety with restlessness, speech difficulties and nausea. Asthma is characterized by the absence of symptoms in the symptom-free interval.
A lung function test ( spirometry ) helps with the diagnosis
- the total volume of air inhaled and exhaled ( vital capacity , VC) and
- the volume exhaled in one second with forced exhalation ( one-second capacity , FEV 1 ) can be determined.
The ratio of one-second capacity to forced vital capacity (FEV 1 / FVC) is called the relative one-second capacity , relative second capacity or Tiffeneau index and is used as a measure of the narrowing of the airways.
With the help of whole-body plethysmography (body plethysmography ) and spirometry, the airway resistance and the extent of pulmonary overinflation can be determined.
For diagnosis and therapy monitoring also serves PEF value ( p eak e xpiratory f low ). This is the maximum value of the air flow volume (flow rate) during exhalation. It serves as an indicator of the free cross section in the windpipe when exhaling. This value usually falls before an asthma attack. It is measured with a " peak flow meter ", which is available in various age-appropriate designs.
Typical X-ray findings for asthma can occur in an acute situation, such as increased radiation transparency of the lungs, narrow heart silhouette, low diaphragms.
Changes in the ECG during an acute asthma attack can be varied: P-pulmonary, rotation of the heart axis in the right direction (from the indifference type to the steep type), S I Q III type as a sign of a right heart strain, sinus tachycardia .
When diagnosing bronchial asthma, it is important to check whether an allergic sensitivity to an allergen or various allergens in the environment are responsible as the trigger. Various allergy tests are used for this purpose . Attempts at provocation, for example against working substances, may also be necessary. In allergic asthma, blood tests may reveal an increase in the specific IgE ( immunoglobulins ) typical for allergies and / or eosinophilia .
Supplementary test methods such as the so-called FeNO measurement (fractionated exhaled nitrogen monoxide) can be used to determine the extent of airway inflammation in allergic asthma. Nitric oxide (NO) is an important messenger substance in the organism that occurs naturally in different places in the body. For example, NO is increasingly formed in the lower airways by the mucous membrane cells (epithelial cells) lining the bronchi. The highest NO concentrations occur in the paranasal sinuses, the concentration is lower in the bronchi.
In order to be able to obtain a sample of the NO formed in the bronchi, the exhaled air must be fractionated. The measurement of the so-called fractional exhaled NO (FeNO) was standardized for clinical use , and can use special instruments to be determined. The concentration of exhaled NO is measured in the unit ppb (“parts per billion”). That is, a concentration of 10 ppb corresponds to 10 nitric oxide molecules per billion air particles.
Studies confirm the importance of FeNO measurement for confirming the diagnosis and prognosis of the response to inhalable steroids. , , Through regular FeNO measurement of the course of airway inflammation can be monitored better, it supports therapy management and can help reduce the incidence of asthma attacks. , Rising FeNO values indicate before the lung function test, a deterioration of the disease process and thus allow early therapeutic countermeasures.
An Australian study group was able to show that regular FeNO monitoring in pregnant asthmatics reduced the children's risk of developing early childhood asthma.
Division into degrees of severity
Asthma is divided into the following degrees of severity:
|designation||Symptoms||FEV 1 or PEF
(in% of the setpoint)
|1. intermittent||Day: ≤ 1 × per week
Night: ≤ 2 × per month
|2. persistent, light||Day: <1 × per day
Night:> 2 × per month
|3. persistent, moderate||Day: daily
night: once a week
|4. persistent, severe||Day: all the time
Furthermore, a distinction is made between difficult asthma and severe asthma :
The difficult asthma is characterized by the disease process aggravating factors such as poor compliance, psychosocial problems, repeated exposure to pollutants and allergens or other untreated disease.
Differential diagnoses (selection)
- Chronic obstructive pulmonary disease (COPD)
- Heart failure (" asthma cardiale ")
- Recurrent pulmonary embolism
- Obstruction of the airways (e.g. inflammation of the windpipe , pseudo croup )
- Vocal cord dysfunction (VCD)
- Hyperventilation syndrome
- Rheumatic diseases with lung involvement (e.g. eosinophilic granulomatosis with polyangiitis ( Churg-Strauss syndrome ), granulomatosis with polyangiitis )
The treatment of asthma is mainly done with inhalable drugs, which are delivered as metered dose aerosols or powder with the help of inhalers, respectively. Powder inhalers are administered, less often than inhalation solutions, which are nebulised with electrically operated inhalers. Own patient training courses are offered.
Therapy options outside of a crisis
In the case of a proven allergy, the triggering substance must first be avoided (examples: change of occupation in the case of baker's asthma, elimination of pets that have fur). For asthma that is caused by mites or pollen , desensitization , also known as “specific immunotherapy” (SIT) , is sometimes an option . For some allergens, a respirator can provide relief.
In 2013 the German Respiratory League recommended the following treatment concept, also known as asthma step therapy (which is no longer up to date):
Long-term medication ("controller")
- Stage 1 (intermittent asthma):
Long-term medication is not required.
- Stage 2 (mild asthma):
Inhalation of low-dose, locally active glucocorticoids ( budesonide , beclometasone , fluticasone , mometasone , ciclesonide ), possibly orally a leukotriene receptor antagonist ( montelukast ); The alternative mast cell stabilizers ( cromoglicic acid ) should only be considered in special cases in the therapy of children and adolescents.
- Step 3 (Mittelgradiges asthma):
Either inhalation of locally acting glucocorticoids intermediate dose or inhalation of locally active glucocorticoids in low doses together with long-acting β 2 - sympathomimetics inhalation ( salmeterol or formoterol ). Alternatively, a low dose of an inhaled glucocorticoid can be administered orally in addition to montelukast or theophylline
- Step 4 (Severe asthma):
A high dose inhaled corticosteroid together with a long-acting inhaled β 2 - sympathomimetic . In justified cases, the inhaled β 2 -sympathomimetic can be replaced by montelukast and / or theophylline.
- Level 5 (very severe asthma):
In addition to level 4, there are orally administered glucocorticoids (e.g. prednisolone ) or, in allergic asthma, omalizumab ( Xolair ), an anti-IgE antibody, for the treatment of adults and children from 12 years of age indicated with severe persistent asthma. The antibodies mepolizumab ( Nucala ), reslizumab ( Cinqaero ) and benralizumab ( Fasenra ), which are directed against interleukin-5 and thus inhibit eosinophilic inflammation, are currently available for patients with severe asthma with an increased number of eosinophilic granulocytes in the blood . Another therapy option for severe and very severe bronchial asthma is bronchial thermoplasty , an endoscopic procedure in which the thickened bronchial muscles are directly reduced using high-frequency electricity.
In all degrees of severity, short-acting β 2 sympathomimetics can be inhaled ("reliever") if necessary .
When allergic asthma in children resorted to some extent still sometimes to cromolyn, nedocromil or montelukast. A more effective therapy is an inhaled corticosteroid . All of the drugs mentioned are mainly used to prevent asthma attacks (“controllers”), so in order to achieve a sufficient anti-inflammatory effect, they must be used long-term, if not permanently.
Asthma therapy should be cause-oriented. Since there is occasionally a psychosomatic component, psychotherapy can sometimes also bring about an improvement in the symptoms. It is also important that asthma patients who smoke give up smoking . Doctors led by Neil Thomson from the University of Glasgow have found that lung function improves by 15 percent just six weeks after the last cigarette. According to this, asthmatics who smoke can reduce inflammation in their airways by quitting smoking.
Intermittent fasting could be a possible therapeutic approach for overweight patients . In a study with asthmatics, the patient's symptoms improved significantly as a result of this measure. The peak flow improved from an average of 335 l / min to 382 l / min within three weeks after the start of the fast and remained at this level over the course of the study. The ASUI ( Asthma Symptom Utility Index ) of the patients also rose in parallel. A number of biomarkers for inflammation, such as TNF-α and BNDF , and oxidative stress , such as nitrotyrosine , 8-isoprostane and carbonyl proteins (CP), were markedly reduced in the blood serum of the intermittent fasting patients. Further studies with more patients are still necessary for a final assessment of this approach.
A completely new approach, the stimulation of an immune response mediated by T H 1 lymphocytes , was successfully tested in a study with 63 patients. In this case were affected intravenous injections with a TLR9 - agonists administered.
For allergic asthma, eating a high-fiber diet can also help relieve symptoms. The altered intestinal flora caused by dietary fiber affects the bone marrow and the respiratory tract , which weakens allergic reactions. The starting point for the studies in this area was the observation that the number of allergies in society increases as the replacement of fiber with carbohydrates and fats increases.
Therapy for asthma attacks
The (acute) asthma attack can be dramatic. The maximum variant, the so-called status asthmaticus , represents an immediate threat to life. The following procedure is recommended:
- Oxygen supply through a tube or mask in order to maintain an oxygen saturation of more than 90%, in pregnant women and patients with heart disease more than 95%.
- Bronchodilation : short-acting β 2 agonists (e.g. salbutamol , fenoterol or terbutaline ) inhalatively, if necessary also subcutaneously or intravenously. Additionally ipratropium bromide (an anticholinergic ) or adrenaline help given by inhalation (with nebulizer or inhaler). Adrenaline or terbulatin can also be administered intramuscularly.
- Anti-inflammatory: corticosteroids ( methyl prednisolone or prednisolone ) intravenously or ( prednisone ) rectally.
- Further bronchodilation can be achieved with intravenous administration of magnesium sulfate .
- If the response to the above drugs is unsatisfactory, xanthines should also be given, such as: B. theophylline intravenously or possibly the narcotic ketamine .
From the early 1970s, the drug perphyllon intravenously and / or in tablet form (active ingredients atropine , etofylline and theophylline; injection solution additionally papaverine ) was used in general medicine in the Federal Republic of Germany for acute treatment.
Asthma and exercise
Asthma and sport are not mutually exclusive; on the contrary, sport even promotes recovery.
Drugs with a potential to exacerbate asthma
The drugs that can cause severe, sometimes life-threatening attacks ( exacerbations ) in patients with asthma include the following pain relievers : acetylsalicylic acid (aspirin), paracetamol (extremely rare), and nonsteroidal anti-inflammatory drugs . The use of beta blockers in particular is sometimes contraindicated in patients with asthma, as this can cause bronchial constriction. This is true even for β 1 -selective receptor blockers and for local application (such as eye drops for glaucoma ). Alternatives from other drug classes are available.
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