Revisiting the role of pulmonary surfactant in chronic inflammatory lung diseases and environmental exposure

Abstract

Pulmonary surfactant is a crucial and dynamic lung structure whose primary functions are to reduce alveolar surface tension and facilitate breathing. Though disruptions in surfactant homeostasis are typically thought of in the context of respiratory distress and premature infants, many lung diseases have been noted to have significant surfactant abnormalities. Nevertheless, preclinical and clinical studies of pulmonary disease too often overlook the potential contribution of surfactant alterations – whether in quantity, quality or composition – to disease pathogenesis and symptoms. In inflammatory lung diseases, whether these changes are cause or consequence remains a subject of debate. This review will outline 1) the importance of pulmonary surfactant in the maintenance of respiratory health, 2) the diseases associated with primary surfactant dysregulation, 3) the surfactant abnormalities observed in inflammatory pulmonary diseases and, finally, 4) the available research on the interplay between surfactant homeostasis and smoking-associated lung disease. From these published studies, we posit that changes in surfactant integrity and composition contribute more considerably to chronic inflammatory pulmonary diseases and that more work is required to determine the mechanisms underlying these alterations and their potential treatability.

Development of severe colitis is associated with lung inflammation and pathology

“…Pulmonary surfactant is well recognized for its role in increasing lung compliance to facilitate breathing (39). Additionally, SP-A and SP-D play critical antimicrobial roles essential for host defense (39,55). These functions can be fully appreciated in either the absence of SP or when it is in excess, which result in changes in surface tension in the lung and thus altered lung function (55).…”

Anti-inflammatory and anti-viral actions of anionic pulmonary surfactant phospholipids

“…PG and PI facilitate the interactions between SP-B and surfactant lipids to stabilize surfactant films during dynamic compression of the lung [ 27 ]. PI binds to SP-D and contributes to regulate surfactant uptake by alveolar type 2 cells [ 23 , 28 ].…”

Response: Commentary: Pattern Recognition Proteins: First Line of Defense Against Coronaviruses

“…As noted, numerous studies highlighted the value of high serum SP-D levels upon development of severe COVID-19 disease ( 1 , 2 ). As correctly pointed out, deficient pulmonary SP-D levels have been reported in severe COVID-19 and have been associated with increased risk of acute respiratory distress syndrome ( 1 , 3 , 4 ) and were also found in several chronic pulmonary diseases ( 5 ). These findings support the idea of using recombinant human pulmonary surfactant protein-D (rhSP-D) for the treatment of SARS-CoV-2 infection in order to reduce COVID-19 disease severity ( 4 ).…”