College of Veterinary Medicine Research Brochure

Studying the Cough Mechanism“There are profoundregulatory differencesbetween coughand breathing.”Dr. Don BolserIIt’s a nagging, hacking,wheezing, gasping problem,and it’s the second most commonreason people in the United Statessee doctors, according to theCenters for Disease Controland Prevention.It’s the cough, a common problemthat is uncommonly complex, saysUniversity of Florida physiologistDonald Bolser.“It’s a difficult problem to deal withclinically,” said Bolser, a professorand researcher in UF’s College ofVeterinary Medicine. “Just because apatient is coughing doesn’t mean weknow why.“When I first started workingon this issue, I was amazed at howlittle information existed, howmuch fundamental informationis not known about cough andhow cough-suppressant drugswork,” Bolser said. “It seemsalmost any experiment I devisewill yield important andfundamental information.”Bolser is among the relatively fewscientists working on understandinghow and why we cough andwhether our treatments for coughdo what we think they do.“Codeine, for example, is one of themost widely prescribed drugs in theworld, yet we know relatively littleabout what it actually does,” Bolsersaid. “It doesn’t work on everyone,and when it does work, no oneknows exactly how it’s working.”The issue, Bolser said, is finding outwhich areas of the brain triggercough, then deciphering how theyfunction and react to drugs. He hasconducted research from both sidesof the issue, working inpharmaceutical testing anddevelopment at Schering-Ploughand moving to UF to study thescience and physiology of cough.Breathing is controlled in thebrainstem, and scientists long havethought that the mechanism thatcontrols cough originates there, too.However, drugs that suppress coughhave no effect on breathing, sosomething more is at work. Bolsercalls it a hidden regulatory elementin the control system for cough.“What is the nature of thatelement?” Bolser asks. “We have alot of knowledge about breathingand the brainstem, and we knowthat the neural elements that governcough are restricted to thebrainstem, but there are profoundregulatory differences betweencough and breathing.”In one model Bolser has proposed,he theorizes that there may bepreviously unidentified neuronsthat are active only during a cough.These neurons may have remainedunidentified because they arelocated in a region of the brain notthought to be related to breathing. Ifthat turns out to be true, it presentsresearchers with a challenge both inunderstanding cough and treating it.The challenge is magnified furtherbecause different coughs – forexample, a laryngeal cough asopposed to a cough from theairways farther into the lungs – maywell be controlled differently by thebrain.Cough suppressants like codeineand dextromethorphan act onthe brainstem, but how theysuppress cough – when they do– is not known.Bolser is designing an experiment toinject codeine into the brainstem oflaboratory animals to see where thecodeine goes to work. Making thelaboratory animals cough and thenfiguring out how to control thecough will yield new informationthat may eventually help in studyingcough in humans, Bolser said.Pharmaceutical companies recentlyhave turned their attention fromasthma medications to coughmedications, Bolser said.“Another medicine was not neededfor asthma,” Bolser said. “So theystarted looking at cough. Ourcurrent array of medicines isinadequate, even codeine, the onethought to be the gold standard.”Bolser collaborates with otherresearchers and UF’s own BrainInstitute. He said medical researchfunding organizations, such as theNational Institutes of Health, arereceptive to research proposals oncough, partly because they recognizehow unique the work is.“When you see someone cough,what are they actually doing?”Bolser asks. “We have to explore thefundamentals, how cough isproduced in humans and why drugs,while powerful, don’t always work.This is an emerging issue.”Photo left: Dr. Donald Bolser,shown with scientist Melanie Rose,is among the relatively few scientistsworking on understandinghow and why we cough.24Research • University of Florida College of Veterinary Medicine••Physiology • www.vetmed.ufl.edu25