• Asthma is usually defined clinically as a reversible restriction of airflow, but modern definitions also take into account the presence of airway hyperresponsiveness to bronchoconstrictor stimuli, such as histamine; and eosinophilic airway inflammation. • In the UK, asthma affects 2.5 million children and 3 million adults. In approximately 70% of asthmatics, asthma is atopic (i.e., they have an IgE response to common allergens such as pollen, dust and animal dander) and 30% are non-atopic. • Asthma triggers can be occupational hazards, drugs (including acetylsalicylic acid – 1%). Attacks or exacerbations of asthma cause viral infections, contact with an allergen, or non-specific irritants. • A genetic analysis of asthma identifies genes associated with atopy, airway hyperresponsiveness, or asthma symptoms: including IgE receptor genes and genes associated with impaired epithelial regeneration. Diagnosis of asthma Asthma is diagnosed based on the variable symptoms of cough, wheezing, chest tightness and shortness of breath and is confirmed by a demonstration of reversibility of narrowing of the airways, either spontaneously over time or in response to inhaled b2-agonists. This is documented as an improvement in peak expiratory flow rate or OOB1 by 15% or more. Radiography demonstrates hyperinflation, but does not help in the diagnosis, except for the exclusion of other diseases. A characteristic sign of asthma is a sharp narrowing of the airways in response to specific or nonspecific stimuli, referred to as GR. This is evaluated in the lung function laboratory by controlled inhalation of drugs such as histamine to determine the dose of histamine that causes a 20% decrease in FEV1 from baseline (PD20). Such a measurement is usually not required for diagnosis, but helps in doubtful cases. Allergies and asthma: • Most asthmatics have atopy and allergies and concomitant diseases of the nasal airways. • The treatment of rhinitis is important for controlling symptoms and actually helps control asthma, although there is insufficient direct evidence. • The determination of allergies in asthma using scarification skin tests and medical history plays an important role in resolving the issue of aHTH-IgE therapy. Allergen avoidance measures have proven ineffective in studies where they have been widely used in asthmatics sensitized to house dust mites. Further research is needed to determine whether specialized interventions for severe asthma will be effective with predominant monosensitization to house dust mites, along with contact in the home. • An asthmatic condition caused by anaphylactic shock forms “fragile asthma” type 1 and requires an examination for allergic sensitization. These rare patients need injectable epinephrine to administer it to relieve the attack. At a practical clinical level, patients find it useful to confirm sensitization to pets and pollen allergens. Aspergillus sensitization and screening for allergic bronchopulmonary aspergillosis are part of the study of all symptomatic asthmatics (skin tests or a specific allergy allergy-absorbent IgE test, the number of eosinophils in the blood (and / or sputum), aspergillus precipitates and CT are indicated for symptoms of chronic sputum production). Airway inflammation in asthma • An autopsy of patients who have died of asthma reveals extensive inflammatory airway infiltration, often with severe eosinophilia and mucous plugs. • The use of bronchial biopsy and induced sputum to take airway tissue samples shows that exfoliation of the epithelium and eosinophilia of the airways, along with mast cells and lymphocytic infiltration, is present even with mild and asymptomatic asthma. • How exactly inflammation affects the narrowing of the airways and GH remains controversial, although many of these signs correlate with the severity of the disease, determined bysymptoms, shortness of breath, or GR. • Currently, a bronchial biopsy is not used in the diagnosis of asthma, since usually the changes are nonspecific. However, a “normal” biopsy (no remodeling or inflammation) is useful for visible refractory asthma to concentrate on other causes of the symptoms. IgE and mast cells and basophils for asthma: • Some asthmatics have atopy and the formation of IgE for common allergens. • In these patients, contact with the allergen triggers an attack by cross-linking with high affinity IgE receptors on mast cells and basophils, causing the release of histamine, cytokines and growth factors from the accumulated granules and de novo synthesis of leukotrienes and cytokines. • Histamine and lipid mediators cause a sudden narrowing of the airways (in minutes) due to edema, stagnation of blood vessels and muscle contraction. This plays an important role in the asthmatic condition associated with anaphylactic shock, or in some cases of “fragile asthma.” • It is believed that cytokines and growth factors support further inflammation in the airways and their remodeling. These factors form the basis for the development of aHTH-IgE therapy for asthma (omalizumab): see key problems: antibody therapy for asthma, appendix): such antibodies interfere with the binding of IgE to receptors on mast cells and basophils. IgEs are also known to fall into “antigenic traps”, as dendritic cells have high affinity for IgE receptors and “capture” allergens for processing into peptides in the cell for subsequent presentation to T lymphocytes and for their activation: anti-IgEs also block this process. • It is known that asthmatics without atopy also increase the number of cells with IgE receptors in the respiratory tract, along with signs of local IgE synthesis and a minimal increase in serum IgE concentration. The mechanism is important, or the target for treatment remains unclear. Key problems: Antibody therapy for asthma Anti-IgE (Omalizumab) is currently the only licensed antibody therapy: according to the data, it reduces the frequency of exacerbations by 50% and reduces the need for steroids. Studies have not identified effects on lung function. It is used only with a total IgE of 30-700 IU / L. There are no clear recommendations on how to evaluate the response. Anti-IL-5: clinically studies are inconclusive, although they tend to reduce the frequency of exacerbations. Do not completely eliminate airway eosinophilia. Unlicensed. Anti-TNF: one positive but at least two other negative studies for severe / moderate asthma. Unlicensed. Others: antibodies to the receptor IL-4, IL-13, IL-5, antichemokines (eotaxin is either not approved or is currently not available, but the examination stimulates the use of subgroups).