Gastroenterologists like Dhyanesh Patel, M.D., of Vanderbilt University Medical Center, regularly see patients with chronic cough or throat-clearing.
This can be a symptom of gastroesophageal reflux disease (GERD), which is one of the most common GI conditions in the United States, and such cases are commonly referred to a GI specialist for evaluation.
However, for a minority of these patients, diagnostic testing comes back negative for GERD and their symptoms do not resolve with acid-suppressing medications.
“These patients may have already tried several antacids with their primary care physician before turning to a gastroenterologist, who, when they find no evidence of GERD, may refer them to a pulmonologist,” Patel said. “When lung-related tests come back negative, they can be referred to an ENT, or allergist, and so on. They keep searching and find no answers.”
Like GERD, but in the Esophagus
Some of these patients are eventually diagnosed with laryngopharyngeal reflux, or LPR. Defined as a type of GERD occurring mainly in the esophagus, symptoms can be nonspecific but include chronic cough, hoarseness, dysphonia, recurrent throat clearing and globus pharyngeus, or the sensation of something caught in the throat.
A LPR diagnosis, however, does not establish a clear treatment path.
As Patel noted in a 2018 survey of the LPR literature published in Gastroenterology & Hepatology, diagnosis and treatment of the condition are challenging. Diagnostic symptoms are highly variable and subjective. Even with a diagnosis, patients do not typically respond well to proton-pump inhibitors, considered the best treatment for other acid-driven GI conditions.
“Current testing has high interrater variability, leading to overdiagnosis and inappropriate treatment with acid-suppressive medications, resulting in societal and patient burden of cost, frequent referrals to numerous providers, and delay in diagnosis and treatment,” Patel concluded at the time.
Cost of Lengthy Diagnosis
This cycle is not only bad for the patient – who continues to suffer from persistent, disruptive symptoms – it is costly to the health care system overall. Patel performed a comparative cost analysis on LPR patients in 2013.
Evaluation and treatment of patients with typical GERD cost about $9 billion annually in the United States. For patients with LPR or chronic cough with a presumed reflux cause, the cost burden was $50 billion, Patel found.
“That’s nearly the cost of treating cancer,” Patel said. “Half of the high cost is due to all the evaluations with different specialists and the other half of the cost can be attributed to all of the trials with different proton-pump inhibitors that turn out to be ineffective – all because we are presuming that the symptoms are related to reflux.”
Reframing the Issue
Patel is still looking for answers, which has led him to re-examine the basic assumption about the role of reflux in LPR.
“We have been jumping through all these hoops instead of considering: Maybe this is not reflux. Maybe we’re not treating the right disease,” Patel said.
“We have been jumping through all these hoops instead of considering: Maybe this is not reflux. Maybe we’re not treating the right disease.”
By examining laryngeal reflux patients with fresh eyes and taking detailed histories, Patel and his colleagues determined that the symptoms experienced by many patients may be nerve hypersensitization rather than reflux.
“They might have an insulting event, like severe flu or COVID, during which they had a cough, nausea, vomiting, muscle aches,” Patel said. “The other symptoms got better, but their cough never went away.”
Despite resolution of the acute disease, the hypersensitive laryngeal nerves continue to signal the urge to cough.
“We have found that if you actually target that nerve hypersensitivity, patients get better in terms of their quality of life,” Patel said. “Instead of throwing pills at the problem, we’re taking a closer, more individualized look that re-centers the patient, and asks, ‘How do we help this person feel better?’
“I think that’s the key, and it could represent a huge paradigm shift from how we treat these patients.”
Partnering with Functional Medicine
Patel is partnering with functional medicine specialists at VUMC as he explores this new approach. Functional medicine is a science-based approach that focuses on lifestyle and nutrition as contributing factors to disease. The focus is on quality of life, risk prevention, maintaining balance and giving patients the tools to personalize their treatment plan.
Patel acknowledges the discourse is not dissimilar to what is happening in other areas of medicine, such as chronic pain, where medications are becoming less of a focus. The mind-body connection has become a larger factor in the patient experience .
“Things like stress, anxiety, lack of sleep and suboptimal diet – these habits can have a huge impact on symptoms in our gut,” Patel said. “The key in any patient is you always want to look at the mind and the body together. The same thing applies for the gut.”
Patel is working with functional medicine and GI colleagues to develop better pathways for patients showing symptoms of laryngeal reflux. He wants to identify them and get them help more quickly. With this patient-centered approach, they will co-develop individualized approaches.
“It’s an incredibly interesting time to be working with these patients as we reframe everything we thought we knew.”
VUMC’s functional medicine staff includes clinicians, nutritionists, therapists, and experts in mind-body techniques like mindfulness meditation and mindful movement. The team already works with patients with other conditions, like Celiac disease, chronic fatigue syndrome, Crohn’s disease, fibromyalgia, irritable bowel syndrome, hypothyroidism and ulcerative colitis.
Such an approach is the first step toward better treatments for patients with chronic cough. Patel hopes research to establish new protocols will follow. “It’s an incredibly interesting time to be working with these patients as we reframe everything we thought we knew,” Patel said. “Ultimately, we want to get these patients the right kind of help and get them on the path to getting better.”
