Acute Respiratory Distress Syndrome: Focus on Viral Origin and Role of Pulmonary Lymphatics.

Acute respiratory distress syndrome (ARDS) is a serious affection of the lung caused by a variety of pathologies. Great interest is currently focused on ARDS induced by viruses (pandemic influenza and corona viruses). The review describes pulmonary changes in ARDS and specific effects of the pandemic viruses in ARDS, and summarizes treatment options. Because the known pathogenic mechanisms cannot explain all aspects of the syndrome, the contribution of pulmonary lymphatics to the pathology is discussed. Organization and function of lymphatics in a healthy lung and in resorption of pulmonary edema are described. A future clinical trial may provide more insight into the role of hyaluronan in ARDS but the development of promising pharmacological treatments is unlikely because drugs play no important role in lymphedema therapy.

Oral inhalation for delivery of proteins and peptides to the lungs.

Oral inhalation is the preferred route for delivery of small molecules to the lungs, because high tissue levels can be achieved shortly after application. Biologics are mainly administered by intravenous injection but inhalation might be beneficial for the treatment of lung diseases (e.g. asthma). This review discusses biological and pharmaceutical challenges for delivery of biologics and describes promising candidates. Insufficient stability of the proteins during aerosolization and the biological environment of the lung are the main obstacles for pulmonary delivery of biologics. Novel nebulizers will improve delivery by inducing less shear stress and administration as dry powder appears suitable for delivery of biologics. Other promising strategies include pegylation and development of antibody fragments, while carrier-encapsulated systems currently play no major role in pulmonary delivery of biologics for lung disease. While development of various biologics has been halted or has shown little effects, AIR DNase, alpha1-proteinase inhibitor, recombinant neuraminidase, and heparin are currently being evaluated in phase III trials. Several biologics are being tested for the treatment of coronavirus disease (COVID)-19, and it is expected that these trials will lead to improvements in pulmonary delivery of biologics.