BackgroundRefractory chronic cough (RCC) and unexplained chronic cough (UCC) are common problems seen in primary care and subspecialty clinics. The role of cough hypersensitivity and laryngeal dysfunction in contributing to the persistence of cough in RCC/UCC is not well recognised.MethodsData of patients with RCC and UCC evaluated in 2019 by an interdisciplinary cough clinic led by a pulmonologist and speech-language pathology team was reviewed. Patients completed validated questionnaires including the Leicester cough questionnaire (LCQ), voice handicap index (VHI) and dyspnea index questionnaire (DI) at initial encounter. Presence of cough hypersensitivity was based upon a history of allotussia and hypertussia. Laryngeal dysfunction was diagnosed in those with a history of laryngeal paresthesias, throat clearing, voice abnormalities, upper airway dyspnoea and documentation of functional or anatomic laryngeal abnormalities on nasoendoscopy.FindingsOf the 60 UCC/RCC patients analysed, 75% of patients were female and 85% were over 40 years of age. Cough hypersensitivity was documented in all patients and multiple cough triggers occurred in 75% of patients. 95%, 50% and 25% of patients reported laryngeal paresthesias, voice abnormalities and upper airway dyspnoea, respectively. Significant associations between LCQ and VHI and DI scores occurred when adjusting for age, gender, ethnicity and body mass index. Laryngeal functional abnormalities were documented on 44/60 patients on nasoendoscopy.InterpretationHypertussia, allotussia and laryngeal dysfunction are common in patients with RCC and UCC. Evaluation of UCC and RCC can delineate laryngeal hypersensitivity and allows appropriate treatment to be directed at this phenotype.

Vocalization in mammals, birds, reptiles, and amphibians occurs with airways that have wide openings to free-space for efficient sound radiations, but sound is also produced with occluded or semi-occluded airways that have small openings to free-space. It is hypothesized that pressures produced inside the airway with semi-occluded vocalizations have an overall widening effect on the airway. This overall widening then provides more opportunity to produce wide-narrow contrasts along the airway for variation in sound quality and loudness. For human vocalization described here, special emphasis is placed on the epilaryngeal airway, which can be adjusted for optimal aerodynamic power transfer and for optimal acoustic source-airway interaction. The methodology is three-fold, (1) geometric measurement of airway dimensions from CT scans, (2) aerodynamic and acoustic impedance calculation of the airways, and (3) simulation of acoustic signals with a self-oscillating computational model of the sound source and wave propagation.

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Objectives: Injury to the recurrent laryngeal nerve (RLN), if severe enough, can result in vocal fold paralysis. Reinnervation surgery can improve patient outcomes, but previous studies have reported a negative correlation between time since onset of paralysis and surgical outcomes. The ability of the paralyzed nerve to serve as a conduit for donor nerve fibers may be a factor in the success of reinnervation; however, changes in RLN composition after paralysis have not been well studied. Therefore, we investigated the morphometric composition of explanted RLN sections from patients who had experienced vocal fold paralysis for varying length of times. Methods: Nine nerve sections from unilateral vocal fold paralysis (UVP) patients and seven control nerve sections were analyzed for morphometric parameters including fascicular area, fiber count, fiber density, fiber packing, mean g-ratio, and fiber diameter distribution. Nerves from UVP patients were also compared as a function of time since UVP onset. Results: In comparison to control nerves, paralyzed nerves were found to have significantly lower fiber densities and fiber packing, higher mean g-ratio values, and a shift in diameter distributions toward smaller diameter fibers. With respect to paralysis duration, no significant differences were observed except in fiber diameter distributions, where those with paralysis for >2 years had distributions that were significantly shifted toward smaller diameter fibers. Conclusions: The morphometric data presented here suggest that correlations between the time since onset of vocal fold paralysis and reinnervation outcomes may be due to fiber size changes in the paralyzed nerve over time.

A number of studies have shown that irritable larynx syndrome, vocal cord dysfunction or muscle tension dysphonia have overlapping features with refractory chronic cough (RCC). Identifying laryngeal hypersensitivity can assist speech pathologists in developing targeted behavioral speech therapy (BST). A novel scoring system was created to quantify the severity of laryngeal hypersensitivity in RCC patients. This study was conducted to determine if a correlation existed between a composite laryngeal hypersensitivity score (LHS) and validated measures of cough severity. Method: A composite laryngeal hypersensitivity scoring system was created based on features of cough hypersensitivity, presence of laryngeal paresthesia, frequent throat clearing, voice problems, and upper airway dyspnea (Table 1). Cough hypersensitivity was based upon findings of allotussia (coughing in response to stimuli that typically do not lead to cough such as talking, cold air, changes in position, exertion etc.) and/or hypertussia (an exaggerated response to cough in response to typical stimuli at lower doses). Data from patients with RCC seen at the University of Utah multidisciplinary cough clinic in 2019 was analyzed to evaluate relationships between chronic cough and laryngeal hypersensitivity using this scoring system. Results: Data from 60 patients with RCC was analyzed. Composite LHS score was increased in all subjects with an average value of 2.27±0.68 (maximum value of 4) without any significant difference between different age groups (18-40, 41-70, >70 years) or sexes. Correlation between LHS score and cough severity (visual analog scale-VAS) or quality of life scores (Leicester Cough Questionnaire-LCQ) showed no association between LHS and VAS scores (r=0.133, ) but a significant negative association between LHS and total LCQ scores (r=-0.369, p-value =0.005). When adjusting for age, sex, BMI and duration of cough, this relationship persisted (p-value=0.355 and 0.003, respectively). Amongst the major categories of treatment strategies offered, there was no difference in LHS score of those groups responding to BST only as compared to BST with treatment for comorbid sleep apnea (mean LHS = 2.18 and 2.28 respectively, p=.66). Due to few non-responders to BST, it was difficult to ascertain whether this LHS score could be utilized to predict response to BST in patient with RCC. Conclusion: A simple scoring system to assess for presence of laryngeal hypersensitivity shows a high correlation between cough intensity and cough-quality of life scores. Further studies to validate this score are required to assess its ability to diagnose laryngeal hypersensitivity in RCC and predict responsiveness to BST.