title: Reduction of neutrophilic lung inflammation by inhalation of the compatible solute ectoine: a randomized trial with elderly individuals.
abstract: BACKGROUND
  Compatible solutes are natural substances that are known to stabilize cellular functions. Preliminary ex vivo and in vivo studies demonstrated that the compatible solute ectoine restores natural apoptosis rates of lung neutrophils and contributes to the resolution of lung inflammation. Due to the low toxicity and known compatibility of the substance, an inhalative application as an intervention strategy for humans suffering from diseases caused by neutrophilic inflammation, like COPD, had been suggested. As a first approach to test the feasibility and efficacy of such a treatment, we performed a population-based randomized trial.
  
  
  OBJECTIVE
  The objective of the study was to test whether the daily inhalation of the registered ectoine-containing medical device (Ectoin®inhalation solution) leads to a reduction of neutrophilic cells and interleukin-8 (IL-8) levels in the sputum of persons with mild symptoms of airway disease due to lifelong exposure to environmental air pollution.
  
  
  METHODS
  A double-blinded placebo-controlled trial was performed to study the efficacy and safety of an ectoine-containing therapeutic. Prior to and after both inhalation periods, lung function, inflammatory parameters in sputum, serum markers, and quality-of-life parameters were determined.
  
  
  RESULTS
  While the other outcomes revealed no significant effects, sputum parameters were changed by the intervention. Nitrogen oxides (nitrate and nitrite) were significantly reduced after ectoine inhalation with a mean quotient of 0.65 (95% confidence interval 0.45-0.93). Extended analyses considering period effects revealed that the percentage of neutrophils in sputum was significantly lower after ectoine inhalation than in the placebo group (P=0.035) even after the washout phase.
  
  
  CONCLUSIONS
  The current study is the first human trial in which the effects of inhaled ectoine on neutrophilic lung inflammation were investigated. Besides demonstrating beneficial effects on inflammatory sputum parameters, the study proves the feasibility of the therapeutic approach in an aged study group.
authors: IUF Leibniz Research Institute of Environmental Medicine.
authors: Klaus
authors: K
authors: Unfried
authors: IUF Leibniz Research Institute of Environmental Medicine.
authors: Ursula
authors: U
authors: Krämer
authors: IUF Leibniz Research Institute of Environmental Medicine.
authors: Ulrich
authors: U
authors: Sydlik
authors: IUF Leibniz Research Institute of Environmental Medicine.
authors: Andrea
authors: A
authors: Autengruber
authors: bitop AG, Witten.
authors: Andreas
authors: A
authors: Bilstein
authors: IUF Leibniz Research Institute of Environmental Medicine.
authors: Sabine
authors: S
authors: Stolz
authors: IUF Leibniz Research Institute of Environmental Medicine.
authors: Alessandra
authors: A
authors: Marini
authors: IUF Leibniz Research Institute of Environmental Medicine.
authors: Tamara
authors: T
authors: Schikowski
authors: Department of Cardiology, Pneumology and Angiology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
authors: Stefanie
authors: S
authors: Keymel
authors: IUF Leibniz Research Institute of Environmental Medicine.
authors: Jean
authors: J
authors: Krutmann
mesh_terms: D000280:Administration, Inhalation; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000599:Amino Acids, Diamino / Q000008:administration & dosage* / Q000009:adverse effects; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects; D017209:Apoptosis / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005240:Feasibility Studies; D005260:Female; D005858:Germany; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D011014:Pneumonia / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D011788:Quality of Life; D012129:Respiratory Function Tests; D013183:Sputum / Q000276:immunology / Q000378:metabolism; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000599:Amino Acids, Diamino; D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D009566:Nitrates; D009573:Nitrites; C045628:ectoine
keywords: SALIA cohort; air pollution; extremolytes; molecular prevention; neutrophil apoptosis; osmolytes