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.

Keywords: COPD; NO; airway acidification; airway pH; buffer; exhaled breath condensate; exhaled nitric oxide; glycine.

Fig. 1.

Timeline of events for study 1.

Fig. 2.

Comparison of alkaline glycine to normal saline inhalation (study 1). Median percentage change in F_ENO from baseline at 5 time points during the study: saline compared to glycine. Time 0 is baseline, followed by an F_ENO measurement after each nebulization (alkaline glycine is represented by the white bars, normal saline is represented by the shaded bars). The final (recovery) measurement was taken 30 min later, prior to discharge from the clinical research unit. Each data bar shows the median (horizontal line inside the bar), upper and lower quartile (top and bottom of the bar), and minimum and maximum (whiskers).

Fig. 3.

Exhaled breath condensate (EBC) pH results from study 1 and study 2. Median EBC pH increased 0.235 pH units (P = .03) after inhalation of 120 mmol/L alkaline glycine, compared to no statistically significant change after low-dose alkaline glycine and normal saline.