@article {Davisrespcare.01753, author = {Michael D Davis and Brian K Walsh and Scott T Dwyer and Casey Combs and Nico Vehse and Alix Paget-Brown and Thomas Pajewski and John F Hunt}, title = {Safety of an alkalinizing buffer designed for inhaled medications in humans}, elocation-id = {respcare.01753}, year = {2012}, doi = {10.4187/respcare.01753}, publisher = {Respiratory Care}, 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. OBJECTIVE: To evaluate the safety of an inhaled alkaline glycine buffer in both healthy subjects and in subjects with stable obstructive airway disease. METHODS: This work includes two 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 exhaled nitric oxide (eNO) and exhaled breath condensate pH (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 = 0.031) in subjects after inhalation of the higher-dose alkaline buffer (2.5 ml of 100 mmol/L glycine). CONCLUSIONS: Alkalinization of airway lining fluid (ALF) is accomplished with inhalation of alkaline glycine buffer and causes no adverse effects on pulmonary function or vital signs.}, issn = {0020-1324}, URL = {https://rc.rcjournal.com/content/early/2012/12/11/respcare.01753}, eprint = {https://rc.rcjournal.com/content/early/2012/12/11/respcare.01753.full.pdf}, journal = {Respiratory Care} }