title: Safety of an alkalinizing buffer designed for inhaled medications in humans.
abstract: BACKGROUND
  Airway acidification plays a role in disorders of the pulmonary tract. We hypothesized that the inhalation of alkalinized glycine buffer would measurably alkalinize the airways without compromising lung function or causing adverse events. We evaluated the safety of an inhaled alkaline glycine buffer in both healthy subjects and in subjects with stable obstructive airway disease.
  
  
  METHODS
  This work includes 2 open-label safety studies. The healthy controls were part of a phase 1 safety study of multiple inhalations of low-dose alkaline glycine buffer; nebulized saline was used as a comparator in 8 of the healthy controls. Subsequently, a phase 2 study in subjects with stable obstructive airway disease was completed using a single nebulized higher-dose strategy of the alkaline inhalation. We studied 20 non-smoking adults (10 healthy controls and 10 subjects with obstructive airway disease), both at baseline and after inhalation of alkaline buffer. We used spirometry and vital signs as markers of clinical safety. We used changes in fraction of exhaled nitric oxide (NO) and exhaled breath condensate (EBC) pH as surrogate markers of airway pH modification.
  
  
  RESULTS
  Alkaline glycine inhalation was tolerated by all subjects in both studies, with no adverse effects on spirometric parameters or vital signs. Airway alkalinization was confirmed by a median increase in EBC pH of 0.235 pH units (IQR 0.56-0.03, P = .03) in subjects after inhalation of the higher-dose alkaline buffer (2.5 mL of 100 mmol/L glycine).
  
  
  CONCLUSIONS
  Alkalinization of airway lining fluid is accomplished with inhalation of alkaline glycine buffer and causes no adverse effects on pulmonary function or vital signs.
authors.affiliation: Adult Health and Nursing System, Virginia Commonwealth University, Richmond, VA 23298, USA. mdavis35@vcu.edu
authors.forename: Michael D
authors.initials: MD
authors.lastname: Davis
authors.forename: Brian K
authors.initials: BK
authors.lastname: Walsh
authors.forename: Scott T
authors.initials: ST
authors.lastname: Dwyer
authors.forename: Casey
authors.initials: C
authors.lastname: Combs
authors.forename: Nico
authors.initials: N
authors.lastname: Vehse
authors.forename: Alix
authors.initials: A
authors.lastname: Paget-Brown
authors.forename: Thomas
authors.initials: T
authors.lastname: Pajewski
authors.forename: John F
authors.initials: JF
authors.lastname: Hunt
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D054316:Biomarkers, Pharmacological / Q000032:analysis; D001944:Breath Tests / Q000379:methods; D002021:Buffers; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D045853:Exhalation; D005260:Female; D005998:Glycine / Q000008:administration & dosage / Q000009:adverse effects; D018684:Glycine Agents / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008173:Lung Diseases, Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D009569:Nitric Oxide / Q000032:analysis; D012129:Respiratory Function Tests / Q000379:methods; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
chemical_list: D054316:Biomarkers, Pharmacological; D002021:Buffers; D018684:Glycine Agents; D009569:Nitric Oxide; D005998:Glycine