In a laboratory discovery that upended their own expectations, Stanford Medicine researchers found that two existing medications—formoterol and methacholine—work together to dramatically improve mucus clearance in the lungs of animals with cystic fibrosis. The finding, published in the Journal of Clinical Investigation in June 2026, emerged almost by accident when scientists testing whether various drugs could enhance mucociliary clearance stumbled upon an unexpected synergy.
The discovery matters because it opens a treatment avenue for cystic fibrosis patients who fall through the cracks of current therapies. Cystic fibrosis affects one in every 3,000 to 4,000 babies born in the United States, and while CFTR modulators—drugs that restore chloride channel function—have transformed care for many patients, they simply don't work for 10 to 20 percent of CF sufferers whose genetic mutations are incompatible with these medications. For those patients, options remain limited and lung infections remain chronic.
Nam Soo Joo, Ph.D., the lead author and senior research scientist at Stanford Medicine, initially doubted the combination would help CF patients at all. Formoterol is a beta adrenergic agonist, and people with CF are known to have an abnormal response to drugs in this category. Methacholine is a cholinergic agonist, and when given alone, it causes airways to constrict in an asthma-like manner—a serious safety concern. "I really hope this discovery can help CF patients," Joo said. "If these drugs improve mucociliary clearance in people as much as they do in our animal models, we expect this to help remove pathogens from the lungs and reduce patients' airway infections."
The research team, led by senior author Carlos Milla, M.D., a professor of pediatrics at Stanford Medicine and pulmonologist at Stanford Medicine Children's Health, showed that the drug combination was safe and well-tolerated in a small study that included both CF patients and healthy volunteers. Both medications are already approved by the U.S. Food and Drug Administration for other uses, which accelerates the pathway toward clinical testing. The scientists are now planning a trial to test the combination's effectiveness directly in CF patients.
The mechanism at work involves mucociliary clearance—the coordinated beating of cilia, hairlike projections that line the passages into the lungs, to move mucus and bacteria out of the airways. In healthy people, this process keeps the lungs clear. In CF patients, thick, sticky mucus clogs the lungs and harbors bacteria that cause chronic infections. By synergizing, formoterol and methacholine appear to enhance this natural clearing mechanism.
The potential applications extend beyond cystic fibrosis. Joo noted that the combination may also help people with other respiratory conditions, including chronic obstructive pulmonary disease and bronchiectasis, a chronic lung disease characterized by severe airway scarring. For now, the focus remains on CF patients who have exhausted or cannot use existing therapies—a group that has waited too long for options that could meaningfully reduce the infections that define their disease.