Co-aerosolized Pulmonary Surfactant and Ambroxol for COVID-19 ARDS Intervention: What Are We Waiting for?

Abstract

After more than 225 days of the first reports of the novel coronavirus from China, COVID-19 pandemic is still on surge. The search for an effective and efficient therapeutic and pharmaceutical intervention is as important and urgent now as it was on Day 1. Majority of the efforts in this direction are toward finding small molecule interventions via repurposing or redirecting the therapeutic approaches. This hypothesis proposes a physical intervention approach directed toward rescuing the complex lung pathology observed in COVID-19 related acute respiratory distress syndrome (CARDS). The loss of content as well as the synthesis and turnover of the surfactant in ARDS has been termed as a "collateral damage." A synergistic, early stage, cost-effective, pharmaceutically viable, safe, and immediately available solution is hence required. The effectiveness of exogenous surfactant treatment in ARDS has been marred with several limitations as pointed out in various clinical trials and require revised protocols related to surfactant dose and mode of delivery. This hypothesis proposes aerosolized surfactant delivery taking the optimal dosing and coating costs into account along with co-delivery of ambroxol to provide synergistic benefits. Ambroxol is reported to have anti-inflammatory,-oxidant,-viral, and-bacterial activities and has a direct impact on the production and secretion of the surfactant from the alveolar Type 2 cells. If aerosolized, atomized, or nebulized in the form of ambroxol-loaded phospholipid nanovesicles at the early stages of ARDS, depleted surfactant levels may be reinstated and surfactant turnover can be initiated and maintained. The ability to deliver both the components in aerosolized-nebulized form may have a huge impact on alleviating the healthcare burden in low resource settings where the availability of ventilators is limited. In conclusion, the surfactant-ambroxol co-aerosolized intervention approach hypothesized here has implications reaching to clinical and pharmaceutical translation worldwide.

Use of exogenous pulmonary surfactant in acute respiratory distress syndrome (ARDS): Role in SARS-CoV-2-related lung injury

“…Kumar describe a novel and innovative physical therapeutic intervention for COVID-19 related ARDS ( Kumar, 2020 ): co-somministration of exogenous pulmonary surfactant and ambroxol may provide synergistic benefits. The prolonged presence of ambroxol in lungs can stimulate phospholipid synthesis and plays a role in generation and secretion of pulmonary surfactant ( Kumar, 2020 ). Moreover, ambroxol can increases the expression levels of SP-B and SP-C and hence may contribute to the interfacial turnover of the surfactant ( Kumar, 2020 ).…”

“…The prolonged presence of ambroxol in lungs can stimulate phospholipid synthesis and plays a role in generation and secretion of pulmonary surfactant ( Kumar, 2020 ). Moreover, ambroxol can increases the expression levels of SP-B and SP-C and hence may contribute to the interfacial turnover of the surfactant ( Kumar, 2020 ).…”

The Role of Pulmonary Surfactants in the Treatment of Acute Respiratory Distress Syndrome in COVID-19

“…A recent review article by Francesco et al ( Cattel et al, 2021 ) has highlighted the potential use of exogenous surfactants early in the treatment of COVID-19 ARDS. Kumar et al ( Kumar, 2020 ) has proposed an innovative hypothesis that co-aerosolized exogenous pulmonary surfactant and ambroxol can be a potential therapeutic option for the treatment of COVID-19 ARDS. The hypothesis was made based on reported evidences on beneficial effects of exogenous surfactants ( Davidson et al, 2006 ; Dushianthan et al, 2012 ; Zhang et al, 2013 ; Meng et al, 2019 ) and ambroxol ( Malerba and Ragnoli, 2008 ; Paleari et al, 2011 ; Kantar et al, 2020 ) in the treatment of ARDS.…”

The Role of Pulmonary Surfactant in COVID-19 Understanding

“…This includes either replacing the depleted lung surfactant or protecting type II alveolar cells to maintain the surfactant secreting function [112]. Among several efforts that were directed toward finding an effective treatment for COVID-19, Pradeep Kumar proposed a hypothesis about using surfactant-ambroxol co-aerosolized as a physical therapeutic intervention approach for COVID-19 related ARDS [113]. This hypothesis is based on the function of ambroxol (2-amino-3,5-dibromo-N-[trans-4hydroxycyclohexyl]benzylamine) as a potent stimulant of surfactant production and its assistance of surfactant lipid secretion by alveolar type 2 cells as well as its activities as an anti-inflammatory and antioxidant agent [114][115][116][117].…”