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Laryngeal Hypersensitivity Eyed as a Reason Behind Refractory, Unexplained Cough


Laryngeal hypersensitivity may be a key factor in refractory and unexplained cough.

Defining the characteristics and better understanding laryngeal hypersensitivity may help in the treatment of refractory and unexplained cough, according to a new study.

Researchers reviewed data from questionnaires filled out by patients with refractory chronic cough (RCC) and unexplained chronic cough (UCC), which are common problems seen in primary care and subspecialty clinics.

The study, published in ERJ Open Research, found cough hypersensitivity was documented in all 60 patients analyzed, with multiple cough triggers occurring in 75%. The study also found that 95% complained of laryngeal sensations that triggered their coughs, 50% reported voice abnormalities, and 25% reported difficulty breathing in the upper airway.

Examination by nasoendoscopy documented laryngeal functional abnormalities in 44 of 60 patients, all of whom were examined within the University of Utah Health System. Data was collected in 2019.

In most patients, cough is believed to be caused by gastroesophageal reflux disease (GERD), rhinosinusitis, or cough variant asthma. However, those causes fail to account for many cases. Estimates place cases of UCC and RCC at 5% to 42% of chronic cough patients.

Cough hypersensitivity, characterized by decreased cough thresholds and nonnoxious stimuli, has been proposed as an explanation for refractory and unexplained cough.

In the study, nearly all patients (57 of 60) described a tickle, lump or sensation in the throat, irritation, dry throat, and presence of mucus in the throat. Women reported a higher prevalence of abnormal throat sensations, which were associated with increasing age. Nearly half of patients reported frequent throat clearing.

More than half of patients reported voice abnormalities, which included hoarseness, loss of voice with talking or singing, change in pitch, or raspy voice quality. One-quarter reported symptoms of upper airway dyspnea, such as throat constriction and difficulty getting in air.

Structural abnormalities were found in nearly half of patients, with a majority having reddening or irritation as well as edema. Only 5 patients had normal laryngeal appearance and function. Of the 60 patients, 24 had overlapping structural and functional abnormalities.

Treatment included behavioral speech therapy (BST; 56 of 60 patients), with 34 completing the course of treatment. Management of comorbid obstructive sleep apnea (OSA) was also recommended, with 43% of patients completing treatment and 22 new diagnoses of OSA given. Treatment for OSA patients included behavioral speech therapy, continuous positive airway pressure therapy, and management of other conditions such as GERD.

Cough hypersensitivity in RCC and UCC is attributed to changes in cough pathways within the central and peripheral limbs of cough reflex pathways. Peripheral sensitization and alteration in modulating influences of central descending pathways are believed related to cough, the authors said. However, much remains to be understood about mechanical causes in terms of neurostructure and neurofunctionality

However, they added, “there is increasing clinical recognition of the role of the larynx and surrounding structures in chronic cough.”

The effectiveness of BST points to a role for laryngeal hypersensitivity in diagnosing chronic cough, the authors said. Many such patients are treated for GERD or OSA without success in decreasing cough.

Nearly 75% of patients in the study were female, with 85% of all patients over age 40. Patients over age 70 comprised one-third of patients and had the longest duration of cough.


Sundar KM, Stark AC, Hu N, et al. Is laryngeal hypersensitivity the basis of unexplained or refractory chronic cough? ERJ Open Res. 2021;7(1):00793-2020. doi:10.1183/23120541.00793-2020

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