The Role of Small Airways in Respiratory Failure Caused by Covid-19 Infection

Abstract

Small airways are the “silent zone” of lungs because there is a limited range of methods to assess their function. At the same time this lung zone plays an important role in local distribution between ventilation and perfusion, that in turn influences the effectiveness of gas exchange. Small airways are incorporated into the lung elastic network and their patency is strongly influenced by the pathological processes that occur in lung parenchyma. ACE2 receptors which are the bindng sites for SARS-Cov-2 virus most densly are located on the epihelium of upper airways, second type alveolocytes and club cells. Damage to mucosa of pharynx and proximal bronchi explains the symptoms of mild covid-19 disease, but affections to alveolar epthelium opens the access to pulmonary vessels which increase permeability inducing interstitial oedema, initiate infiltration of lung interstitium with inflammatory cells and release from endothelial cells vasodilatory mediators which in turn inactivate the mechanism of hypoxic pu;monary vasoconstriction. Ventilation/perfusion mismatch in favour of perfusion that develpops as the consequence of described events leads to intrapulmonary blood shunting, arterial hypoxaemia and severe dispnoea that poorely associates with mild changes in X-ray examination findings. Progressing of parenchymal inflammation further increases the pulmonary vascular permeability that recruits more alveoli, increases the lung weight and affects gas diffusion through alveolo-capillary membrane making hypoxemia more severe. During the acute period of covid-19 pneumonia small airways demonstrate more functional rather than organic obstruction. However, during the post-acute period proliferation of bronchiolar epitelial cells occurs, they transdifferentiate and ingrow into alveolar space and initiate lung and airways fibrosis. This review has summarized recent research findings that uncover the small airways role in different pathogenetic mechanisms involved in the course of covid-19 infection both in acute and recovery period.