The paper shows that adding sodium bicarbonate makes the lung‑killing peptide LL‑37 work better against Pseudomonas and helps immune cells destroy the bacteria more efficiently, also boosting the formation of NETs. This suggests that raising airway bicarbonate (e.g., with low‑dose nebulized or oral sodium bicarbonate) could be a simple way to improve lung defenses, especially for people with cystic fibrosis or chronic lung infections, though it’s not yet proven in large human trials.

The primary defect in cystic fibrosis (CF) is abnormal chloride and bicarbonate transport in the cystic fibrosis transmembrane conductance regulator (CFTR) epithelial ion channel. The apical surface of the respiratory tract is lined by an airway surface liquid layer (ASL) composed of mucin comprising mainly MUC5A and MUC5B glycoproteins. ASL homeostasis depends on sodium bicarbonate secretion into the airways and secretion deficits alter mucus properties leading to airway obstruction, inflammation, and infections. Downstream effects of abnormal ion transport in the lungs include altered intrinsic immune defenses. We observed that neutrophils killed <i>Pseudomonas aeruginosa</i> more efficiently when it had been exposed to sodium bicarbonate, and formation of neutrophil extracellular traps (NETs) by neutrophils was augmented in the presence of increasing bicarbonate concentrations. Physiological levels of bicarbonate sensitized <i>P. aeruginosa</i> to the antimicrobial peptide cathelicidin LL-37, which is present in both lung ASL and in NETs. Sodium bicarbonate has various uses in clinical medicine and in the care of CF patients, and could be further explored as a therapeutic adjunct against <i>Pseudomonas</i> infections.