Meta‐analysis of high doses of ambroxol treatment for acute lung injury/acute respiratory distress syndrome based on randomized controlled trials

Abstract

This study seeks to evaluate the potential benefits of high doses of ambroxol treatment for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) by conducting a meta-analysis based on randomized controlled trials (RCTs). We searched the Pubmed, Embase, China National Knowledge Infrastructure, and Wanfang databases through December 2013. Only RCTs evaluating high doses of ambroxol (≥15 mg/kg or 1000 mg/day) treatment for patients with ALI/ARDS were selected. We included 10 RCTs involving 508 patients. Adjuvant treatment with high doses of ambroxol increased PaO(2)/FiO(2) (weight mean differences [WMD] = 69.18, 95% confidence intervals [CI]: 41.71-96.65), PO(2) (WMD = 11.74, 95% CI: 8.50-14.99), and SaO(2) (WMD = 2.15, 95% CI: 1.60-2.71) compared with usual treatment. Treatment with high doses of ambroxol appeared to reduce serum tumor necrosis factor-α level (WMD -7.92 µg/L; 95% CI, -10.94 to -4.9) and interleukin-6 level (WMD = -20.65 µg/L, 95% CI: -24.74 to -16.55) and to increase serum superoxide dismutase level (WMD = 19.07 NU/mL, 95% CI: 6.16-31.97). The findings suggest that treatment with high doses of ambroxol appears to improve PaO(2)/FiO(2), PO(2), and SaO(2), and the benefits might be related to ambroxol's anti-oxidant and anti-inflammatory properties.

Ambroxol and Ciprofloxacin Show Activity Against SARS-CoV2 in Vero E6 Cells at Clinically-Relevant Concentrations

“…This is especially so, as AMB is known to be safe at much higher doses than BHX, with these high doses also showing effects in ARDS that would be highly desirable in COVID-19 patients; increasing oxygenation (PaO 2 /FiO 2 ratio, PO 2 and SaO 2 ) while also reducing inflammatory markers (TNF-α and IL-6). 19 Mechanistically, BHX is a potent inhibitor of the protease TMPRSS2, 21 whose activity is necessary for SARS-CoV2 entry into many cell types, 22 including respiratory epithelia, and so its lack of effects here might be considered puzzling. However, recent work shows that Vero E6 cells do not express TMPRSS2, and instead viral entry is achieved through an alternative and CQ-inhibited pathway .…”

Ambroxol Hydrochloride Combined with Fluconazole Reverses the Resistance of Candida albicans to Fluconazole

“…In addition, this study demonstrated the utility of the G. mellonella larva model as an inexpensive, rapid in vivo model to prescreen potential novel antifungal therapies prior to more extensive mammalian animal models. Although, the concentration of ABH required to induced the in vivo effects may be higher than the usual doses that ABH achieves in humans, high doses of ABH are widely used in clinics, and a large number of clinical trials have proven that treatment with high doses of ABH (more than 15 mg/kg or 1,000 mg/day) appears to improve the condition of patients with acute or mild respiratory distress syndrome and acute lung injury (Wu et al, 2014). Therefore, the ABH concentration used in this study still has the potential to be used clinically.…”

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

“…For the purpose of current application; it is worth noting that high dose ambroxol (≥15 mg/kg or 1,000mg/day) has previously been employed for ARDS intervention and has been reported to improve PaO 2 /FiO 2 , PO 2 , and SaO 2 as well as an improvement in the phospholipid profile of tracheal effluent in ARDS patients (Wu et al, 2014). In addition, the meta-analysis concluded that high-dose ambroxol treatment has been reported to reduce SOD, TNF-α, and IL-6 levels in the serum as well as reduction in acute contusion of lung and the ICU stay (Wu et al, 2014). Furthermore, ambroxol has shown high affinity toward the lung tissue (16 times higher than that of the serum) and may stay for over 8 h at this level (Mezzetti et al, 1990).…”