Abstract
Background The population of uncontrolled asthma patients represents a large therapeutic burden. The PDE3-inhibitor enoximone is a strong and quick bronchodilator and is known to successfully treat life-threatening bronchial asthma (status asthmaticus). Translational mice models showed anti-inflammatory effects when PDE3 was targeted. Methods Here, we investigated the effectiveness of PDE3-inhibitor enoximone as oral treatment for chronic asthma in a real-life off-label setting. Investigational use of PDE3-inhibitor enoximone: 51 outpatients (age 18–77) with chronic asthma were followed using off-label personalized low doses of the PDE3-inhibitor enoximone. Duration of treatment was 2–8 years. Results Four groups could be distinguished as follows: The first group includes patients who use enoximone as an add-on, because it helps them in maintaining a better general wellbeing; they still use their traditional medication (n = 5). The second group consists of patients who use enoximone and were able to phase down their traditional medication without deterioration of their asthma symptoms (n = 11). The third group comprises patients who were able to discontinue their traditional medication and use only enoximone without deterioration of their asthma symptoms (n = 24). The last one has patients who, after having used enoximone for some time, saw their symptoms disappear and now use no medication at all, not even enoximone (n = 11). All patients reported improvement or at least alleviation of their asthma symptoms. All patients reported a better quality of life and greater drug compliance. Conclusion The evaluation shows that PDE3-inhibitor enoximone is a viable alternative for or addition to current asthma therapeutics, as both add-on and stand-alone, considerably reducing the use of LABAs/SABAs/ICS, with no or negligible side effects. Additional studies are advisable.
Highlights
Asthma is an inflammatory obstructive airway disease [1, 2]
In vascular wall smooth muscle cells, enoximone causes an increase in cyclic adenosine monophosphate (cAMP) and in cyclic guanosine monophosphate, resulting in relaxation and subsequent vasodilatation; the same applies to bronchial smooth muscle cells, causing bronchodilation [10, 11]
Based on the idea of bronchodilation, enoximone has been used successfully in 8 cases of status asthmaticus after all other treatments according to asthma guidelines had failed [5, 6]. is in turn led to preoperative treatment, in small doses, for asthma patients, who are known to face higher risk of pulmonary complications during and after surgery [14]
Summary
Asthma is an inflammatory obstructive airway disease [1, 2]. Causes for developing asthma are to be found in an interplay of environmental factors and the degree of exposure to those factors, combined with a multitude of genetic variations that become apparent in a wide range of immune cells and structural cells. PDE3-inhibition reduces granulocyte-macrophage colony-stimulating factor (GM–CSF)– production of the epithelial cell cultures, supports tight junction protein expression, and improves mucosal barrier function [21]. In vivo, it shows anti-inflammatory effects by reduced serum Tumor Necrosis Factor-alpha (TNF-α) levels [22, 23]. (iv) Single and/or multiple escalation dose finding studies that should be performed, showing correlation between pharmacokinetics and pharmacodynamics is paper reports the results of long-term real-life investigational use of orally administered enoximone, using a personalized dose, for maintenance treatment of (chronic) asthma, showing a decrease in asthma symptoms, an improvement in quality of life, a substantial reduction in ICS/ LABAs/SABAs, and a high patient compliance to the drug
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