title: Tolerability of inhaled N-chlorotaurine in an acute pig streptococcal lower airway inflammation model.
abstract: BACKGROUND
  Inhalation of N-chlorotaurine (NCT), an endogenous new broad spectrum non-antibiotic anti-infective, has been shown to be very well tolerated in the pig model recently. In the present study, inhaled NCT was tested for tolerability and efficacy in the infected bronchopulmonary system using the same model.
  
  
  METHODS
  Anesthetized pigs were inoculated with 20 ml of a solution containing approximately 108 CFU/ml Streptococcus pyogenes strain d68 via a duodenal tube placed through the tracheal tube down to the carina. Two hours later, 5 ml of 1% NCT aqueous solution (test group, n = 15) or 5 ml of 0.9% NaCl (control group, n = 16) was inhaled via the tracheal tube connected to a nebulizer. Inhalation was repeated every hour, four times in total. Lung function and haemodynamics were monitored. Bronchoalveolar lavage samples were removed for determination of colony forming units (CFU), and lung samples for histology.
  
  
  RESULTS
  Arterial pressure of oxygen (PaO2) decreased rapidly after instillation of the bacteria in all animals and showed only a slight further decrease at the end of the experiment without a difference between both groups. Pulmonary artery pressure increased to a peak 1-1.5 h after application of the bacteria, decreased in the following hour and remained constant during treatment, again similarly in both groups. Histology demonstrated granulocytic infiltration in the central parts of the lung, while this was absent in the periphery. Expression of TNF-alpha, IL-8, and haemoxygenase-1 in lung biopsies was similar in both groups. CFU counts in bronchoalveolar lavage came to 170 (10; 1388) CFU/ml (median and 25 and 75 percentiles) for the NCT treated pigs, and to 250 (10; 5.5 × 105) CFU/ml for NaCl treated pigs (p = 0.4159).
  
  
  CONCLUSIONS
  Inhaled NCT at a concentration of 1% proved to be very well tolerated also in the infected bronchopulmonary system. This study confirms the tolerability in this delicate body region, which has been proven in healthy pigs previously. Regarding efficacy, no conclusions can be drawn, mainly because of the limited test period of the model.
authors.affiliation: Department of Pediatrics, Division of Cardiology, Pulmology, Allergology and Cystic Fibrosis, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Schwienbacher
authors.forename: Benedikt
authors.initials: B
authors.lastname: Treml
authors.forename: Anna
authors.initials: A
authors.lastname: Pinna
authors.forename: Ralf
authors.initials: R
authors.lastname: Geiger
authors.forename: Hannes
authors.initials: H
authors.lastname: Reinstadler
authors.forename: Iris
authors.initials: I
authors.lastname: Pircher
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Schmidl
authors.forename: Christian
authors.initials: C
authors.lastname: Willomitzer
authors.forename: Johannes
authors.initials: J
authors.lastname: Neumeister
authors.forename: Michael
authors.initials: M
authors.lastname: Pilch
authors.forename: Maria
authors.initials: M
authors.lastname: Hauer
authors.forename: Thomas
authors.initials: T
authors.lastname: Hager
authors.forename: Consolato
authors.initials: C
authors.lastname: Sergi
authors.forename: Sabine
authors.initials: S
authors.lastname: Scholl-Bürgi
authors.forename: Thomas
authors.initials: T
authors.lastname: Giese
authors.forename: Alexander
authors.initials: A
authors.lastname: Löckinger
authors.forename: Markus
authors.initials: M
authors.lastname: Nagl
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D001996:Bronchopneumonia / Q000188:drug therapy* / Q000382:microbiology; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D013290:Streptococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000187:drug effects* / Q000302:isolation & purification; D013552:Swine; D013553:Swine Diseases / Q000188:drug therapy* / Q000382:microbiology; D013654:Taurine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D000890:Anti-Infective Agents; D013654:Taurine; C043410:N-chlorotaurine