The Cure for Chronic Cough?
FDA drug authorization to study new therapy a milestone for campus research
By Nathalie Wolfram
Patients who visit UM researcher Laurie Slovarp for treatment often have experienced years of uncontrolled coughing, leading them to feel desperate, socially isolated and depressed.
Slovarp hopes her clinical research will help more of these patients find relief. An associate professor in UM’s School of Speech, Language, Hearing and Occupational Sciences, she directs the Voice Outcomes and Inquiry of Cough and Essentials in Swallowing (VOICES) Lab, which conducts research on swallowing disorders and chronic cough.
In early 2019, she received Investigational New Drug authorization from the U.S. Food and Drug Administration to begin research on whether a molecule found in chili peppers can enhance behavioral therapy for people who experience chronic cough due to cough hypersensitivity.
She is one of the first UM faculty members ever to submit a full IND application to the FDA to administer an investigational drug as part of clinical research.
“I’ve been told that this FDA authorization is a milestone in UM research,” Slovarp says. “Unless a project qualifies for an exemption, FDA authorization is required for any research that involves administering an investigational drug to humans.”
Slovarp will study the effectiveness of administering the FDA-approved molecule during behavioral cough therapy sessions to assist patients in developing the ability to suppress coughing. She hypothesizes that administering the molecule will enhance the therapy and result in a reduction in cough sensitivity and cough frequency.
Behavioral therapy alone helps many patients alleviate chronic cough. But for patients who do not initially respond to the therapy, administering the molecule may create the conditions for it to succeed.
Many patients who visit Slovarp’s clinic have suffered for years with chronic cough, despite visiting multiple physicians, undergoing extensive medical tests and trying several different medications.
After a newspaper featured her research in March, Slovarp received several phone calls and emails from people desperate for effective treatment, including
a New Yorker who wrote she would be willing to travel to Montana for the promise of relief from chronic cough.
Her research has particular relevance in Montana, which is home to five of the 25 worst-ranking counties in the nation for short-term air particulate pollution, a leading cause of chronic cough. The malady is the top nonemergency reason people see a doctor, and up to 20% of chronic-cough patients do not respond to standard medical treatment. Compounding the public health problem is a shortage of trained speech-language pathologists and other medical providers equipped to treat the condition.
Slovarp first tested the treatment on a group of healthy individuals, all of whom experienced a significant change in cough sensitivity following the treatment. Her study was recently published in the Annals of Translational Medicine.
She hopes her research ultimately will generate a standardized therapy that all types of providers, including physicians and respiratory therapists, could be trained to implement.
“If this new therapy is found to be effective, it could become a noninvasive and inexpensive treatment option for many people who currently have limited options,” she says.
To that end, Slovarp also collaborates with Sarjubhai Patel, an associate research professor in UM’s College of Health Professions and Biomedical Sciences, trying to understand the underlying mechanism responsible for the success of behavioral cough therapy, which remains poorly understood despite its clinical success.
Slovarp and Patel believe the answer might have to do with neuroplasticity — the nervous system’s ability to adapt. They hypothesize that behavioral therapy actually changes sensory receptors in the airway that cause — the urge to cough.
In other words, behavioral therapy is “not just teaching people to become really good at controlling their cough — it’s causing a physiological change in sensitivity.”
With funding from two National Institutes of Health-sponsored programs, the Montana IDeA Network of Biomedical Research Excellence and the Mountain West IDeA Clinical and Translational Research-Infrastructure Network, Slovarp and Patel now are conducting a proof-of-concept study investigating whether change in cough sensitivity is due to change in expression of these receptors, which is found in the epithelial tissue in the nose and epiglottis, the flap in the throat behind the tongue.
To establish a baseline representing healthy individuals who do not experience chronic cough, Patel will measure the presence of the receptor in a healthy line of cells. Then, working with a surgeon at Rocky Mountain Ear, Nose and Throat, Slovarp will take biopsies — which invoves taking tiny amounts of tissue from the inside of the nose and the epiglottis of patients with chronic cough — both before and after they undergo behavioral cough therapy.
Patel, a microbiologist, will analyze the biopsy samples to identify whether the therapy results in actual physiological change, as measured by a change in the amount of receptors. If the researchers succeed in identifying a change in the receptors following behavioral therapy, they plan to repeat the study using the new therapy technique involving the FDA-approved molecule.
Their findings could have real implications for patients suffering from chronic cough. While these same receptors have been the focus of previous clinical trials of drugs that combat the receptor, the side effects of the drugs have been prohibitive.
At the heart of Slovarp and Patel’s study is the question, “Can we fix this behaviorally so that people don’t have to be on a medication?”
Ultimately, Slovarp, Patel and their collaborators at the University of Utah hope that the proof-of-concept study will position them to pursue further NIH funding for a larger-scale study.
Slovarp credits her mentors and colleagues for encouraging and helping shape her research. Originally from Whitehall, Montana, she launched her career in Arizona, where she had completed her master’s degree in speech and hearing science. She relocated to Missoula and was running her own speech therapy practice when she enrolled as a doctoral student at UM.
Because the communicative sciences and disorders department at that time did not offer a Ph.D., she pursued a degree in interdisciplinary studies, a track that allowed her to design her studies around her interests, including neuroscience. In a research paper assignment in one of her neuroscience courses, she delved into the question of how behavioral cough therapy works neurologically, seeding her eventual research.
The School of Speech, Language, Hearing and Occupational Sciences recently moved to the College of Health Professions and Biomedical Sciences. The department has added a speech-language pathology Ph.D. program and has grown significantly since Slovarp began teaching in 2010 while completing her doctorate. Her research now helps advance the department’s next phase of growth, which will build and deepen collaboration among the speech-language therapy, physical therapy, occupational therapy and related social work, pharmacy, biomedical and neuroscience fields.
“Our ultimate dream is to develop a regional rehabilitation, research and clinical center, where all rehabilitative therapy programs and related neuroscience fields are together doing interprofessional work, both clinical and research,” Slovarp says.
Toward that dream goal, the VOICES Lab serves as a training ground for interdisciplinary, collaborative research. Slovarp is quick to recognize the vital role that her undergraduate and graduate research assistants play in her research.
“I would not be able to do what I have done without my students,” she says.
One of these students is Sarah Popp, a senior undergraduate double majoring in neuroscience and speech, language and hearing sciences. Popp has worked as a research assistant in the VOICES Lab since her sophomore year. She says Slovarp’s research appeals to her because it focuses on “getting down to the bottom” of chronic cough and “helping people reduce their sensitivity instead of giving people medication and hoping it works.”
Popp recently presented her work on Slovarp’s biopsy study at the UM Conference on Undergraduate Research and continued working in the VOICES Lab with a summer research fellowship through UM’s Center for Structural and Functional Neuroscience.
Emma Bozarth, who also began working in Slovarp’s lab as a sophomore undergraduate, is now in her fourth year with the lab and is working on a master’s thesis based on the cough desensitization trial.
“Dr. Slovarp did a really good job of exposing me to every aspect of research — from writing [Institutional Review Board proposals] to day-to-day work in the lab like data collection,” she says, noting that she published on her undergraduate capstone research as a co-author with Slovarp.
Slovarp says her lab attracts students interested in the medical side of speech therapy.
“Even getting a bachelor’s degree in speech pathology doesn’t necessarily mean that students know that some speech therapists work with issues like chronic cough, because it’s such a wide field,” she says. “And when they see the impact that the therapy makes, it’s super motivating for them.”
Imagine if that tickle in your throat and resulting cough never ended. This UM research might provide relief. •