In any person, bronchial reactivity increases after respiratory viral infections and under the influence of oxidizing agents present in the air, primarily ozone and nitrogen dioxide (but not sulfur dioxide). Viral infection causes a prolonged, up to several months, increased bronchial reactivity. On the contrary, oxidizing agents, in particular ozone , increase it by only a few days.
After contact with an allergen, bronchial reactivity rises very quickly, within a few minutes, and remains elevated up to several weeks. If the dose of the allergen was high, obstruction of the bronchi can occur daily for a long time without repeated contact with the allergen, under the influence of any non-specific irritants.
Still do not know why the increased reactivity of the bronchi in patients with bronchial asthma. Among the many possible causes, one is now universally recognized – inflammation of the respiratory tract mucosa. In the bronchial washings , patients find a large number of lowered epithelium , mast cells , neutrophils , eosinophils and lymphocytes , which are known to contain many biologically active substances. A biopsy in the bronchial mucosa often reveals edema, infiltration with eosinophils, neutrophils and lymphocytes, a thickening of the basement membrane of the epithelium, and hypertrophy of the mucous glands. The most permanent changes are cell infiltration and hyperemia due to vasodilation and opening of previously non-functioning capillaries. Less commonly, desquamation of the epithelium is detected. The meaning of the described histological changes is not completely clear. It is believed that the manifestations of bronchial asthma are due to the interaction of the own cells of the respiratory tract mucosa with the cells that infiltrate it.
The leading role in the pathogenesis of bronchial asthma is played by increased reactivity of the bronchi , which leads to their periodic reversible obstruction. It manifests itself:
– increased airway resistance;
– overstretching of the lungs;
– hypoxemia caused by focal hypoventilation and the mismatch between ventilation and perfusion of the lungs;
– hyperventilation.
The pathogenesis of bronchial asthma is based on a nonspecific increase in bronchial reactivity. The higher the reactivity of the bronchi , the harder the disease, the more difficult the treatment, and the higher the risk of night and morning attacks (due to significant daily fluctuations in lung function).
Mast cells , eosinophils , macrophages , neutrophils and lymphocytes play an important role . Released during degranulation of mast cells of mediators of inflammation – histamine , bradykinin , leukotriene C , leukotriene D and leukotriene E , platelet activating factor , and prostaglandin E2 , prostaglandin E2alfa and prostaglandin D2 – cause acute inflammatory reaction : spasm of smooth muscles of the bronchi, vasodilation , edema of the mucosa. Leukotrienes , in addition, are involved in other pathogenetic mechanisms – they cause secretion of mucus and impaired upward flow of mucus, which creates the conditions for the transition of acute into chronic inflammation.
Under the influence of chemotaxis factors ( leukotriene B4 , anaphylactic factor of chemotaxis of eosinophils and anaphylactic factor of chemotaxis of neutrophils ), migration of eosinophils , platelets and neutrophils to the focus of inflammation occurs . These cells, as well as alveolar macrophages and epithelium of the respiratory tract become an additional source of inflammatory mediators .
The leading role in the development of further events, apparently, belongs to eosinophils . Proteins contained in eosinophil granules – the main major protein of eosinophils and cationic protein of eosinophils – damage the epithelium of the respiratory tract. It sloughs into the lumen of the bronchi and is found in sputum in the form of clusters of epithelial cells. Damage to the epithelium leads to the loss of its barrier and secretory functions, as well as to the secretion of chemotaxis factors and a further increase in inflammation . In addition, irritation of the sensitive nerve endings is possible, as a result of which a generalized reflex reaction of the bronchi to local inflammation occurs.
An important role in the development of inflammation also belongs to T-lymphocytes . These cells, present in large numbers in patients in the bronchi , secrete cytokines and are involved in the regulation of cellular and humoral immunity . Type 1 T-helpers , secreting IL-2 and interferon gamma , stimulate the proliferation and differentiation of T-lymphocytes and activate macrophages . Type 2 T-helpers , secreting IL-4 and IL-5 , stimulate the proliferation of B-lymphocytes and the synthesis of immunoglobulins . IL-5 , in addition, stimulates the proliferation, differentiation and activation of eosinophils , and possibly degranulation of basophils .
The contribution of each of the above cellular and humoral factors to the formation of increased bronchial reactivity and the development of bronchial asthma is unknown. By itself, none of them can cause disease.
Firstly, substances released during mast cell degranulation are found in increased amounts in blood in patients with urticaria and other mast cell- mediated diseases, in bronchi – in people suffering from atopic diseases other than asthma . It is likely that these substances provoked an attack of bronchial asthma, some special conditions are necessary.
Secondly, inflammatory infiltration of the bronchial mucosa, which was considered pathognomonic for bronchial asthma, was also detected in patients suffering from other atopic diseases , and, therefore, should be attributed to non-specific signs of atopy .
And finally, the introduction of cytokines ( IL-2 preparations , mogramostim , sargramostim ) for cancer patients for therapeutic purposes causes them eosinophilia and activation of immunocompetent cells , but not bronchial asthma.
The factors provoking asthma attacks can be divided into seven groups: allergens, drugs and chemical compounds, air pollutants, occupational hazards, infections, physical exertion, emotional overload.