1 UDC 616.248.1–085–084.001.5 Y.I. Feshchenko, I.F. Illyinskaya, L.V. Arefieva, L.M. Kuryk SO «National Institute Phthysiology and pulmonology named after F. G. Yanovsky NAMS of Ukraine» Non-controlled bronchial asthma: the contemporary condition of the problem Key words: bronchial asthma. Among all allergic diseases the most common is bron- of asthma [10, 13]. Different authors, when allocat- chial asthma (BA). In the world there are already about ing certain of its phenotypes and subtypes, rely on clini- 300 million patients with this ailment and in the forecast cal and morphological characteristics, the most significant by 2025 their number will increase by another 100 mil- triggers, the presence of concomitant pathology, as well lion. Chronization and deepening of the pathological pro- as unique responses to treatment. Thus, in the materials cess in asthma leads to a significant deterioration in the of GINA [10, 13, 20], there are those phenotypes of asthma quality of life of patients, decrease their activity, and also that can be easily identified. Distinguish: allergic asthma, causes growth disability and mortality from this illness. non-allergic asthma, childhood asthma / recurrent obstruc- According to official statistics in Ukraine, almost 500 pa- tive bronchitis, late-on asthma, asthma with obstruction tients with asthma suffer from 100 thousand adults, and this and a fixed rate of airflow, obesity asthma, occupational disease is diagnosed annually for about 8 thousand peo- asthma, asthma, severe asthma, and BA-COPD over- ple. According to experts, this does not correspond to the lapped syndrome. At the same time, the European respi- actual situation due to existing shortcomings in the diag- ratory community and the American Thoracic Community nosis of this pathology, but in fact the number of patients tend to focus more on a combination of clinical and patho- is much higher [15]. physiological aspects (so-called eosinophilic / neutrophilic According to modern concepts, BA is a genetically de- asthma, severe allergic asthma, etc.). In relation to the du- termined disease that is heterogeneous in its clinical man- ration and severity of the disease, specialists are diagnosed ifestations, pathophysiological and immunopathological with early / childhood asthma, late-on asthma, asthma mechanisms, which is characterized by chronic inflamma- with frequent exacerbations, asthma with fixed bronchial tion of the respiratory tract. Common symptoms of asthma obstruction, asthma with severe course («refractory», «brit- include attacks of breathlessness (shortness of breath), tle or lumbar», «steroid-resistant»). [12] Identification wheezing, chest compression and coughing. In patients, of markers of the dominant subtype of inflammation, al- they may be of varying intensity and manifest in combi- lows to allocate its eosinophilic, neutrophilic, mixed and nation with variable airway obstruction (Global Initiative agranulocytic variants [10. 13. 20]. The presence of vari- for Asthma) [10, 20]. That is why it is now generally ac- ous triggers and some concomitant conditions determine cepted to isolate the phenotypes of asthma, which are de- certain features of the clinical picture and the course fined as clinical characteristics of the course of the disease, of asthma. It allows to separate into separate phenotypes: as well as the features of the systemic and local (in the air- virus-induced asthma, asthma physical activity, aspirin ways) inflammatory process [10, 20]. It allows to deter- asthma, smoker’s asthma, asthma associated with obe- mine the individual characteristics of the patient and assign sity, asthma with obstructive sleep apnea, asthma associ- him personified treatment [6, 10, 13, 16–18, 25–27, 30]. ated with gastroesophageal reflux disease, and BA-COPD- However, there is still no consensus on the phenotyping Overlap [13]. Modern classifications of asthma determine not only the phenotypes of asthma but also the endotypes © , Y.I. Feshchenko, I.F. Illyinskaya, L.V. Arefieva, L.M. Kuryk 2018 that they are responsible for. An endotype is a subtype www.search.crossref.org DOI: АСТМА ТА АЛЕРГІЯ, № 2 • 2018 ISSN 2307-3373 2 of a disease characterized by a unique or distinct patho- in different countries ranges from 40% to 67% [23]. physiological (pathogenetic) mechanism, which largely de- According to reports from the Russian Federation, in this termines the response of patients with therapy [16, 18, 19, country, complete control of asthma occurs in only 5% 25]. Yes, stand out: 20% of patients. Currently, uncontrolled asthma is a spe- – allergic asthma: eosinophilic, Th2-induced inflamma- cial medical and social problem, which is associated with tion, with sensitivity to steroids, with sensitivity to anti- high disability, often severe life-threatening exacerbations, IgE, with sensitivity to interleukin-5 (IL-5), with sensitiv- high risk of death of patients, as well as significant eco- ity to anti-IL-4 / IL-13, with sensitivity to allergen-specific nomic costs for health care (about 80% of all costs for treat- immunotherapy (ASIT); ment). bronchial asthma in general [9]. It is worth noting – endogenous BA: eosinophilic, neutrophilic, associated that among the experts there is a certain terminological with autoantibodies / superantigens, with steroid suscepti- anarchy, and often one concept is replaced by another. bility, with steroid resistance; Thus, the term «difficult» («hard», «hard», «difficult»), – neutrophilic BA: with the activation of congenital im- asthma, difficult («heavy», «severe»), uncontrollable («un- munity, with increased survival of neutrophils, with resis- controlled», «difficult-to-treat») is often used in the sci- tance to steroids, with anti-oxidant / macrolide suscepti- entific literature. «),» Resistant «(« resistant «,» therapy- bility, with anti-TNF-α sensitivity; resistant «),» refractory «asthma. Severe asthma is often – aspirin BA: eosinophilic, with a violation of the me- identified with severe, severe – uncontrolled, and uncon- tabolism of eicosanoids / sensitivity to leukotrienes C4, D4, trolled – with resistance or refractory. In fact, this is a com- E4, with sensitivity to glucocorticosteroids, with sensitivity pletely different concept: severe BA – an asthma that re- to anti-leukotriene drugs; quires 4–5 steps to maintain control, that is, the use of high – BA with respiratory remodeling: with diffuse remodel- doses of inhaled glucocorticosteroids / ²2-agonists of pro- ing, with activation of endothelial-mesenchymal transfor- longed duration, and uncontrolled – an asthma in which mation (EMT), etc. [13, 16–18]. the appointment of adequate therapy does not lead before The personification of therapy taking into account the the control of the disease [12, 13, 20]. In turn, the resis- phenotypes and BA endotypes consists in directing treat- tant or refractory is considered to be one of the components ment on the main immunopathological targets, which plays of uncontrolled bronchial asthma. «Labor» or «heavy» a leading role in the emergence and maintenance (persis- BA in general combines several phenomena and differ- tence) of the chronic inflammatory process in each individ- ent characteristics, and the general feature of them is that ual case – the so-called target therapy (from target – target, they are all threatening to life. Such terminological confu- English). The development of targeted therapy for asthma sion essentially complicates both the diagnosis of asthma was devoted to the numerous projects of the last 2 decades, and the choice of adequate therapeutic tactics [2]. In or- thanks to which the arsenal of drugs was supplemented with der to diagnose uncontrolled asthma by experts from the anti-leukotriene, anti-IgE monoclonal antibodies, anti- European Respiratory and American Thoracic Community cytokine monoclonal antibodies, and their appointment in 2014, the following criteria were proposed: to patients with asthma was regulated by international [15, 1. Insufficient symptom control: questionnaires ACQ-5> 17, 18, 22, 24, 27, 30] and national recommendations [7, 1.5, AST <20. 14]. Due to the fact that BA is a chronic inflammatory 2. Frequent severe exacerbations: 2 or more courses disease, the main purpose of modern treatment of patients of systemic glucocorticosteroids (GCS) for more than today is not to cure them (because it is now a long-term 3 days each year in the previous year. future), but to achieve and maintain full control over the 3. At least one hospitalization, treatment in the inten- disease, namely, achievement and support good control sive care unit, use of respiratory support during the pre- of clinical symptoms over a long period of time, minimiz- vious year. ing the risks of future exacerbations of asthma, fixed airway 4. The volume of forced exhalation for 1 second (FEV1) obstruction and unwanted side effects of treatment [7, 14, is less than 80% due to the administration of bronchodi- 20, 24]. According to the GINA (2014) criteria, achieving lators. full control of the asthma implies [10, 20, 22]: Reasons that can be explained by the lack of control – absence of daytime symptoms or attacks twice or less of asthma, are divided into endogenous and exogenous. once a week; Exogenous factors include: – no restriction of physical activity during the day, – inadequate basic therapy, which is often associated – absence of asthma symptoms, which makes you wake with inadequate qualifications of the doctor, or underesti- up at night; mation of the patient’s condition