The role of chronic allergic inflammation in the pathogenesis of bronchial asthma

Bronchial asthma has been known since ancient times. Many scientists and thinkers, including Hippocrates, who asserted that “body inspection is a whole matter: it requires knowledge, hearing, smell, touch, language, reasoning,” thought about the causes, as well as features of the course and the possibilities of therapy, one could speak about such a millennium ago. And it was really necessary to reflect on this topic, since even then a huge number of children, adolescents, adults and old people periodically had asthma and coughing attacks with the separation of scanty transparent sputum.

It was Hippocrates who coined the term “asthma,” which in Greek means “suffocation.” In his writings in the section on internal suffering, there are indications that asthma is spastic, and one of the causes of suffocation is dampness and cold. The teaching of Hippocrates, who sought to explain the emergence of diseases, including bronchial asthma, by certain material factors, was subsequently continued in the works of many doctors.

So, in the III century BC. er the ancient healer Aretey made an attempt to divide asthma into two forms. One of them was close to the modern notion of “recurrent cardiac asthma” that occurs in a patient during a minor exercise. Another form of dyspnea, according to Aretea , was provoked by cold and humid air, and manifested by spastic breathing difficulties – it was she who was close to the idea of ​​true bronchial asthma.

Even then, it became clear that the ailment under study was rather serious, and the subsequent observation of patients made it possible to establish that the disease fundamentally changes their quality of life far from the best and is difficult to treat. By the way, the only method of treating asthma at that time was bloodletting and fresh air, and it took centuries to take several steps to conquer this disease.

However, the causes of the disease and its exacerbation for a long time remained unknown and unexplored.

In the II century BC. er Roman doctor Galen tried to experimentally substantiate the causes of difficulty in breathing, and although his experiments were not crowned with success, the very fact of investigating the mechanism of respiratory impairment in asthma was a single phenomenon and very progressive.

In the Renaissance, scientific research in various fields of medicine became very popular. Italian doctor Gerolamo Cardano (1501–1576), diagnosing bronchial asthma in the English bishop, prescribed him as a treatment for diet, exercise and the replacement of the feather bed on which the bishop slept, with a bed of ordinary tissue. The patient recovered. It was a brilliant guess from a doctor of that time in the field of treatment of bronchial asthma.

Confirming the participation of allergens in the development of asthma, the Belgian scientist van Helmont (1577–1644) was the first to describe a choking attack, arising in response to the inhalation of house dust and the consumption of fish. He suggested that the place where the painful process in asthma develops is the bronchi. The conjecture that asthma arises from the contraction of the muscles of the bronchi is almost a century later expressed by John Hunter in 1750. Today, it is well known and widely proven that hypersecretion of mucus, edema of the bronchial mucosa and bronchospasm play a role in the pathogenesis of bronchoobstruction , and for the level of science of the XVII century these were quite bold statements.

Thus, the role of allergies and chronic allergic inflammation in the pathogenesis of bronchial asthma was proven several centuries ago, and the first targeted steps in its treatment then became elimination measures and exclusion of allergens from food.

Later, in the 20s of the last century, scientists suggested calling a form of bronchial asthma atopic , thereby emphasizing its underlying allergic component.

However, it should be noted that not all bronchial asthma is dependent on allergen exposure. Thus, in most countries of Europe and America, since 1918, asthma has been divided into external factors ( asthma extrinsic ) and related to internal causes ( asthma intrinsic ).

According to modern concepts, the first corresponds to the concept of non-infectious- allergic, or atopic , bronchial asthma, and the second is infectious-dependent, including cases associated with acute and chronic infectious diseases of the respiratory apparatus, endocrine and psychogenic factors.

Also, as separate variants, so-called aspirin asthma and asthma of physical effort are distinguished .

“ A person with asthma who has just fallen asleep wakes up with a feeling of tightness in his chest. This condition is not pain, but it seems that some kind of gravity is laid on his chest, as if he is being crushed and stifled by external force . The man jumps out of bed, looking for fresh air. On his pale face is expressed melancholy and fear from strangling. These phenomena , then increasing, diminishing, continue until 3 or 4 am, after which the spasm subsides and the patient can take a deep breath. With relief, he clears his throat and tired to sleep … “. – tons ak doctors characterize the symptoms of asthma

Returning to today’s reality, it should be noted that in the USA bronchial asthma is diagnosed in 10% of children and in 5% of the adult population, and about 2/3 of the patients become ill with it in childhood . Bronchial asthma is registered in 1% of adult residents of the capital; however, with more thorough studies, this prospect may increase to 8% .

Mortality from asthma also continues to grow, and about 80% of all deaths are related to factors that could potentially be prevented. .

First of all, it is:

  • the inability of the doctor to correctly assess the patient’s condition and the severity of the developed exacerbation of bronchial asthma;
  • abnormal behavior of the patient, consisting in an incorrect assessment of his condition, and failure to comply with the recommendations of the doctor;
  • inadequate patient education (level of evidence A);
  • insufficient use in the treatment of bronchial asthma inhalation glucocorticosteroids (GCS).

Acute bronchial obstruction in the case of atopic asthma develops when exposed to the bronchial walls of mediators of an allergic reaction of type I (level of evidence A). A possible pathogenetic role in the reaction of immunoglobulins G ( subclass lgG 4). The genesis of the late reaction is explained by inflammation of the bronchial wall with the involvement of neutrophils and eosinophils by the chemotactic factors of an allergic reaction of type I. There is reason to believe that it is the late reaction to the allergen that significantly enhances bronchial hyperreactivity to nonspecific stimuli. In some cases, it is the basis for the development of asthmatic status .

There are also a number of risk factors for the development of bronchial asthma, divided into predisposing and causal, which sensitize the respiratory tract and provoke the onset of the disease, as well as aggravating and trigger, which contribute to the development of the next exacerbation of the disease.

  • The most important predisposing factor for the development of asthma is considered to be atopy , a genetic predisposition to allergic reactions.
  • Causal factors include inhalation (house dust mites, animal dander, plant pollen), occupational (levels of evidence B , C), medicinal (Aspirin) and food (preservatives, dyes) allergens.
  • In the role of aggravating factors can be smoking (levels of evidence B , C), air pollution, respiratory viral infection, parasitic infections.
  • Triggers, or substances that directly cause exacerbation, are allergens, respiratory viral infection, physical exertion, strong odors, cold air, changing weather, emotional stress.

As is known, the diagnosis of bronchial asthma is often mistakenly made to patients with chronic obstructive bronchitis. There are a number of signs that allow anamnestic , clinically and instrumental differentiation of these diseases.

It must be remembered that with bronchial asthma, the limitation of the air flow rate is often completely reversible (both spontaneously and under the influence of treatment), while with chronic obstructive pulmonary disease (COPD) there is no complete reversibility and the disease progresses, if the effects of pathogenic agents.

Help in the diagnosis has a clarification of the family history and atopic background. The diagnosis of bronchial asthma is almost certainly confirmed by repeated attacks of night cough in healthy children. In some children, asthma is provoked by exercise. To make a diagnosis, it is necessary to study the function of external respiration with a bronchodilator , a spirometric exercise test, as well as an allergy test with the determination of general and specific Ig E , the production of skin tests.

One of the groups of patients, where the doctor diagnoses asthma or does not diagnose or misses, is made up of elderly people. In old age, it is difficult not only to diagnose asthma, but also to assess the severity of its course.

As mentioned earlier, asthma is often incorrectly diagnosed and, as a result, inadequate therapy is prescribed. It is especially difficult to diagnose asthma in children, the elderly, as well as under the influence of occupational risk factors, seasonal asthma, and with the cough variant of asthma. Most often, the great difficulty is the diagnosis of asthma in children, as the episodes of wheezing and coughing are the most common symptoms in childhood diseases.

Pathognomonic signs of bronchial asthma, testifying in favor of the presence of an allergic component in inflammation, are blood eosinophilia (eosinophil count 500–1000 μl ), with a fluctuation in the number of eosinophils — an increase during the night and during contact with the allergen and a decrease during GCS treatment. The addition of the infection is accompanied by a decrease in the number of eosinophils and an increase in the number of neutrophils. ESR is usually normal, and its increase indicates the accession of the infection. For the diagnosis of asthma, the definition of leukocyte formula is not needed, it is shown only if a secondary infection is suspected.

The general analysis of sputum is also important, which allows to identify some elements specific to bronchial asthma, such as:

  • Kurshman spirals are whitish-transparent, corkscrew-shaped convoluted tubular formations, which are the “casts” of the bronchioles, which are found, as a rule, at the time of bronchospasm;
  • Charcot – Leiden crystals are smooth, colorless octahedron-shaped crystals that consist of protein released by the breakdown of eosinophils, present in large quantities during allergic inflammation;
  • a large number of eosinophils (up to 50–90% of all leukocytes).

To successfully help patients in the prehospital stage, it is necessary to remember that patients with asthma, in addition to the broncho-obstructive syndrome, have a huge range of comorbidities, consisting of a combination of three or more nosologies. This situation is combined in the concept of ” polypathy ”

Thus, in women, COPD in combination with postinfarction cardiosclerosis (PIX), gallstone disease (GIB) and uterine myoma occurs in 28% of cases, in combination with PIX and nodular goiter (US) – in 16%, and in combination with GCB and US – in 11% of cases .

Among male patients, COPD in combination with PICS and benign prostatic hyperplasia (BPH) occurs in 20% of cases, in combination with PICS and malignant neoplasms of various localization – in 12%, and in combination only with tumors – in 8% of cases

Therefore, the simultaneous appointment of several drugs using theophyllines, cromones , leukotriene receptor antagonists, etc., is unacceptable in these cases. In the current situation, new technologies of non-invasive , namely aerosol, methods of fast delivery of selective drugs to the respiratory tract acquire a special role , which results in high local activity of inhalation drugs, allowing not only to effectively reduce the manifestations of bronchospasm , but also to a large extent reduce the frequency systemic side effects.

The only group of drugs that reduce allergic inflammation in the bronchi is GCS, in particular inhaled GCS.

What should guide the doctor, prescribing drug therapy? What determines the indications for hospitalization of patients with bronchial asthma? The answer to these questions can only be an algorithm – a certain sequence of actions of a medical professional in order to diagnose and relieve bronchial obstruction syndrome , which should include:

  • making a diagnosis;
  • determining the severity of exacerbation of the disease;
  • the choice of the drug, its dose and form of administration;
  • evaluation of the effect of treatment;
  • definition of further tactics of the patient.

In the guidelines for the diagnosis and treatment of bronchial asthma, the main role in the treatment is given to the joint use of inhaled GCS and long – acting beta2-agonists. Inhaled corticosteroids as a means of basic therapy of asthma are recognized throughout the world. For good control of the course of the disease, they require prolonged use. Their doses are determined by the severity of asthma, the full clinical effect of steroid use appears after 2-3 weeks of planned use.

According to the criteria for the effectiveness of treatment, the response to therapy is considered:

  • “Good”, if the patient’s condition is stable, shortness of breath and the number of dry rales in the lungs decreased, the peak expiratory flow rate (PSV) increased by 60 l / min (in children – by 12–15% from the initial);
  • “Incomplete”, if the patient’s condition is unstable, the symptoms are pronounced as before, poor breathing conductivity persists and there is no increase in PSV
  • “Bad” if the symptoms are as pronounced or increasing, and the PSV is worsening.

The method of delivery of the drug to the bronchial receptors is also important. At present, nebulizer therapy is becoming more widely used . The word ” nebulizer ” comes from the Latin word ” nebula “, which means “fog.”

A nebulizer is a device for converting a liquid into an aerosol with particularly fine particles that can penetrate primarily into the peripheral bronchi. The goal of nebulizer therapy is to deliver a therapeutic dose of the drug in aerosol form directly to the patient’s bronchi and obtain a pharmacodynamic response in a short period of time (5–10 minutes). Nebulizer therapy, creating high concentrations of the medicinal substance in the lungs, does not require coordination of inhalation with the act of inhalation, which has a significant advantage over metered aerosol inhalers.

The effectiveness of inhalation depends on the dose of aerosol and is determined by several factors:

  • the amount of aerosol produced;
  • particle characteristics;
  • the ratio of inhalation and exhalation;
  • anatomy and geometry of the respiratory tract.

Experimental data suggest that aerosols with a particle diameter of 2–5 microns are optimal for entering the respiratory tract and, accordingly, recommended for use . Smaller particles (less than 0.8 microns) enter the alveoli, where they are quickly absorbed or exhaled, not lingering in the respiratory tract and not providing a therapeutic effect. Thus , a higher therapeutic index of medicinal substances is achieved, which determines the efficacy and safety of the treatment being carried out.

Nebulizer therapy has several advantages over metered aerosol inhalers (level of evidence A):

  • no need for coordination of respiration with aerosol intake;
  • the possibility of using high doses of the drug and obtaining a pharmacodynamic response in a short period of time;
  • continuous supply of medicinal aerosol with fine particles;
  • rapid and significant improvement due to the effective delivery of the drug substance to the bronchi;
  • light inhalation technique.

Preparations for nebulizer therapy are used in special containers, nebulas , as well as solutions produced in glass bottles. This makes it possible to dose the drug easily, correctly and accurately.

In addition, speaking of chronic allergic inflammation, it is impossible not to mention its prevention. The absolute exclusion or maximum limitation of contact with allergens today in the framework of modern ecology and the peculiarities of working conditions of people is often impossible. Therefore, the global initiative on asthma offers a new concept of the use of combination drugs (SMART – Symbicort Maintenance and Reliever Therapy ), based on the possibility of using a combination of adrenomimetic and corticosteroids in one inhaler as a means of basic therapy, so as to relieve symptoms of bronchial asthma in the “on demand” mode.

The total number of inhalations of the drug can be quite large, but should not exceed eight per day. The use of this combination of bronchodilators on demand, according to the concept of SMART, allows you to increase the amount of anti-inflammatory therapy by more than 4 times in response to the very first signs of exacerbation. According to the experts of GINA, SMART should be used in the case when it is not enough to use only inhaled GCS to achieve control of bronchial obstruction.

Currently, there is a rich evidence base for the use of inhaled GCS, which is widely covered in modern literature and therefore does not require repeated detailed analysis.
For the purpose of pharmacotherapy of bronchial asthma and the prevention of its next exacerbation, it is inhaled GCS that has proven to be effective and safe drugs should be first-line drugs, and nebulizer therapy should be the preferred method of drug delivery.



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