**2.1. Respiratory tract damages**

Influenza virus replicates in the respiratory tracts of humans, mainly in the lungs. Extrapulmonary multiplication of this virus has not been proven in people with influenza, nor in experimental conditions in influenza virus-infected laboratory animals. Influenza virus replicates throughout the whole respiratory tree. Tracheobronchitis is the common clinical picture of influenza. In the acute stage, multifocal destruction and desquamation of the columnar epithelium of the trachea and bronchi accompanied with edema and congestion of the submucosa are characteristic. In about 50% of cases, tracheitis and bronchitis have a hemorrhagic character. Cell necrosis is the final stage of desquamation of the affected epithelium with concomitant attainment of the mucus glands. Small- and medium-sized bronchioles are strongly affected by the processes seen in the larger airways, with an entirely necrotic bronchiolar wall associated with polymorphonuclear cell infiltrate. Influenza virus pneumonia very often proceeds to secondary bacterial pneumonias. Destruction of alveolar epithelium and endothelium can worsen the severity of lung injury [4, 15].

Lung disorders in influenza virus infection may be triggered by: (i) a massive infiltration of leukocytes, mainly polymorphonuclear leukocytes, into the alveolar space; (ii) a decrease in the partial pressure of oxygen, causing the development of hypoxia; (iii) an increase in the partial pressure of CO2 and development of metabolic acidosis; (iv) a "cytokine storm"—a release of cytokines, eicosanoids and prostaglandin E2 and an enhanced immune response; and (v) the development of oxidative stress [5, 7, 16, 17].

Our previous data and that of most of the literature showed that experimental influenza virus infection in susceptible laboratory animals (mice and ferrets) imitates the above influenza clinical picture: progressive damage of the alveolar cells, acute inflammatory reaction, and development of massive bronchitis and probably pneumonia, in parallel with a decrease in endogenous lipid- and water-soluble antioxidants levels, as well as the compensatory changes of antioxidant enzyme activities [18–21].
