Safety of Chronic Hypertonic Bicarbonate Inhalation in a Cigarette Smoke-Induced Airway Irritation Guinea Pig Model

Background Cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) are often associated with airway fluid acidification. Mutations in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene leads to impaired bicarbonate secretion contributing to CF airway pathology. Chronic cigarette smoke (CS) -the major cause of COPD- is reported to induce acquired CFTR dysfunction underlying airway acidification and inflammation. We hypothesize that bicarbonate-containing aerosols could be beneficial for patients with CFTR dysfunctions. Thus, we investigated the safety of hypertonic sodium bicarbonate (NaHCO 3 ) inhalation in CS-exposed guinea pigs. Methods Animals were divided into groups inhaling hypertonic NaCl (8.4%) or hypertonic NaHCO 3 (8.4%) aerosol for 8 weeks. Subgroups from each treatment groups were further exposed to CS. Respiratory functions were measured at 0 and after 2, 4, 6 and 8 weeks. After 8 weeks blood tests and pulmonary histopathological assessment were performed. Results Neither smoking nor NaHCO 3 -inhalation affected body weight, arterial and urine pH, or histopathology significantly. NaHCO 3 -inhalation did not worsen respiratory parameters. Moreover, it normalized the CS-induced transient alterations in frequency, peak inspiratory flow, inspiratory and expiratory times. Conclusion Long-term NaHCO 3 -inhalation is safe in chronic CS-exposed guinea pigs. Our data suggest that bicarbonate-containing aerosols might be carefully applied to CF patients.