Bronchial asthma - from psychosomatic illness to proinflammatory cytokines and asthma phenotypes

Bronchial asthma is a chronic inflammatory heterogeneous disease of the airways that is clinically manifested in episodes of heavy breathing, especially at the phase of expirium, shortness of breath accompanied by wheezing, and cough and expectoration of a thick, tough and sticky secretions . Pathogenically, asthma is characterized by chronic inflammation of bronchial mucosa and bronchial hypersensitivity, which result in the appearance of the variable, predominantly obstructive disorder of pulmonary ventilation, or by reducing the air flow rate while breathing . Asthma was known in ancient times, in Egypt and in ancient Greece, as evidenced by the writings of Hippocrates (460–370 BC; άσθμα gasping). It is present in 1–18% of the population, depending on the countries and regions . During 2004, it was estimated that asthma affects about 300 million people worldwide of all age structure, and it is estimated that by 2025 some 100 million people more will have this disease 5, . Knowledge of the etiology and pathophysiology of events in asthma has evolved with the progress of medical science: from data of “hay fever” from the 19th century through the theories of “psychosomatic disease” from the first half of the 20th century 7, 8 to the present knowledge of inflammation and bronchial hypersensitivity and hyperreactivity. Risk factors for the onset, development and exacerbations of asthma are divided into host factors and environmental factors. Host factors are predisposing factors for the development of inflammation, which in conjunction with other factors can lead to the clinical manifestations of the disease. They are: genetic predisposition, atopic constitution, airway hyperreactivity, gender and race/ethnic factor. Environmental factors are usually responsible for the manifestation of the disease: allergens indoors and outdoors as well as in the workplace, smoking, air pollution, respiratory infections, parasitic infections, socio-economic status, drugs, food additives and obesity. Bronchoconstriction is responsible for both bronchospasm and increased mucosal secretion and mucosal edema of the airways for the occurrence of symptoms of asthma . The main underlying pathophysiological mechanism of asthma is the airway inflammation, and occasionally variable airway obstruction and bronchial hyperreactivity are its feature manifestations. Inflammation of the airways includes interaction of a large number of mechanisms: hyperresponsiveness, mucosal edema of the respiratory tract, bronchial gland hypersecretion and increased production of mucus, hypertrophy of the smooth muscle cells and airway remodeling which represents an irreversible process due to collagen deposition. In the development and maintenance of chronic inflammation in the airways following factors are participating: inflammatory and structural cells, neuroregulatory substances and mediators (histamine and chemotactic factors, leukotrienes and many cytokines [granulocyte macrophage stimulating factor, tumor necrosis factor, interleukins (IL) 1, 2, 3 , 4, 5, 6, 8, 11, 13, 17 and others] . For the inflammation in asthma, the most important cells are activated mast cells, activated T-lymphocytes as regulatory cells and eosinophils. In the early asthmatic reaction, in sensitized persons, upon exposure to the allergen and its binding to specific antibodies, activated mast cells secrete mediators of the acute phase (which include leukotrienes and inflammatory cytokines) which have a role to maintain the inflammatory phase . They also release IL-5, leading to a Th2 lymphocyte differentiation, chemotaxis and differentiation of eosinophil leukocytes, modification of basophil activity, and activation of the enzyme tryptase, which results in the further development of the inflammation in the airways 14, 15 . Mobilized and activated eosinophils play a central effector role in the development and