Small-molecule ion channels increase host defences in cystic fibrosis airway epithelia.

Loss-of-function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) compromise epithelial HCO3- and Cl- secretion, reduce airway surface liquid pH, and impair respiratory host defences in people with cystic fibrosis1-3. Here we report that apical addition of amphotericin B, a small molecule that forms unselective ion channels, restored HCO3- secretion and increased airway surface liquid pH in cultured airway epithelia from people with cystic fibrosis. These effects required the basolateral Na+, K+-ATPase, indicating that apical amphotericin B channels functionally interfaced with this driver of anion secretion. Amphotericin B also restored airway surface liquid pH, viscosity, and antibacterial activity in primary cultures of airway epithelia from people with cystic fibrosis caused by different mutations, including ones that do not yield CFTR, and increased airway surface liquid pH in CFTR-null pigs in vivo. Thus, unselective small-molecule ion channels can restore host defences in cystic fibrosis airway epithelia via a mechanism that is independent of CFTR and is therefore independent of genotype.

Clinical predictors of the medical interventions provided to patients with low back pain in the emergency department.

BACKGROUND: Low back pain is a common complaint in emergency departments (ED), where deviations from standard of care have been noted. OBJECTIVE: To relate the ordering of advanced imaging and opioid prescriptions with the presentation of low back pain in ED. METHODS: Six hundred adults with low back pain from three centers were prospectively analyzed for history, examination, diagnosis, and the ordering of tests and treatments. RESULTS: Of 559 cases the onset of pain was less than one week in 79.2%; however, most had prior low back pain, 63.5% having warning signs of a potential serious condition, and 83.9% had psychosocial risk factors. Computer tomography (CT) or magnetic resonance imaging (MRI) were ordered in 16.6%, opioids were prescribed in 52.6%, and hospital admission in 4.5%. A one-year follow-up of 158 patients found 40.8% received subsequent spine care and 5.1% had a medically serious condition. Caucasian race, age 50 years or older, warning signs, and radicular findings were associated with advanced imaging. Severe pain and psychosocial factors were associated with opioid prescribing. CONCLUSIONS: Most patients present to the ED with acute exacerbations of chronic low back pain. Risk factors for a serious condition are common, but rarely do they develop. Racial disparities and psychosocial factors had concerning relationships with clinical decision-making.