Reduction of chronic lung inflammation by inhalation of the compatible solute ectoine: a population-based intervention study with elderly individuals
23 February 2017 (online)
Chronic lung inflammation induced by inhaled xenobiotics is the major cause for chronic obstructive pulmonary disease (COPD). In preliminary studies, we identified pro-inflammatory molecular mechanisms triggered by combustion-derived nanoparticles in lung cells in vitro and in vivo. Seeking for preventive strategies, we identified compatible solutes as group of substances which specifically reduce these molecular reactions. By stabilising the membrane compartment of cells they prevent pro-inflammatory signalling in response to particle exposure and life span extension of neutrophil in the inflammatory environment of the lung. As compatible solutes are very well tolerated by the human body, we aimed to test the therapeutic value of ectoine in a human system.
We therefore performed a placebo-controlled double blind crossover study to test for efficacy, safety, and feasibility of the inhalation of an ectoine-containing medical device (EFECT study). Individuals (33) suffering from mild COPD due to life long exposure to environmental air pollution which were earlier identified during epidemiological studies were included in the study. During two test periods of 28 days, flanked by examinations, daily inhalation of ectoine or placebo was performed. Besides analyses of the general health status, quality of life, and lung function, inflammatory parameters in the sputum were investigated.
Per protocol analyses revealed a significant reduction of nitrogen oxides as markers of oxidative and nitrosative inflammatory stress. Ancillary analyses considering period effects showed a significant sustained reduction of sputum neutrophils due to ectoine treatment. Considering these specific effects we suggest to treat patients suffering from severe forms of COPD. The feasibility documented by a very high compliance, and the safety of the treatment with almost no treatment-related adverse effects indicates that this strategy can be tested in clinical studies.