Characterization of Patients With Refractory or Unexplained Chronic Cough Participating in a Phase 2 Clinical Trial of the P2X3-Receptor Antagonist Gefapixant.

PURPOSE: This analysis assesses clinical characteristics of patients with refractory chronic cough (RCC) or unexplained chronic cough (UCC) enrolled in a phase 2 study to better understand this patient population. METHODS: Patients with RCC/UCC lasting for ≥ 1 year and cough severity visual analog scale (VAS) score of > 40 mm at screening were eligible. Demographics, clinical characteristics, and medical history were collected at baseline. Cough-related measures included cough severity VAS, Cough Severity Diary (CSD), Leicester Cough Questionnaire (LCQ), and a structured cough-trigger questionnaire. Medication history included all medications 30 days before screening and chronic cough treatments within 1 year before screening. Data were summarized using descriptive statistics. RESULTS: Patients (N = 253; female, 76%; mean age, 60 years) had severe (mean cough severity VAS, 57.5 mm) and long-lasting (median duration, 11 years) cough. The most burdensome self-reported aspects included psychological and social factors (LCQ) and cough frequency and intensity (CSD). Patient-reported triggers were consistent with cough hypersensitivity (e.g., 95% to 96% reported irritation or tickle in throat). Common reported comorbidities included gastroesophageal reflux disease (GERD; 56%), allergic rhinitis (47%), and asthma (30%); 12% of patients had been diagnosed with all 3 conditions. The most common prior medications included inhaled or oral steroids (21%), antihistamines (15%), and antacids (15%). CONCLUSION: Patients with RCC/UCC had severe, long-lasting, and burdensome cough with clinical features of cough hypersensitivity. Many patients had been diagnosed with GERD, allergic rhinitis, and asthma but had a persistent cough despite treatment of these conditions. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02612610; registered November 20, 2015.

Long-Term Treatment Outcomes after Behavioral Speech Therapy for Chronic Refractory Cough.

INTRODUCTION: Current literature reveals that up to 88% of individuals undergoing behavioral speech therapy (BST) for chronic refractory cough (CRC) demonstrate benefit at 4-8 weeks post-treatment. However, investigations of BST are confounded by overlapping use of neuromodulators, missing follow-up data, and an absence of long-term outcomes. This study investigated treatment outcomes beyond 6 months in individuals diagnosed with CRC, and whose treatment outcomes were clinically undocumented. METHODS: Participants with CRC 6 months or greater beyond treatment completion were recruited. Participants completed a post-treatment Leicester Cough Questionnaire (LCQ) and a telephone interview. Demographic data, cough characteristics, treatment adherence, BST outcomes, and pre- and post-treatment LCQ scores were evaluated. RESULTS: 80 individuals met inclusion criteria and 29 consented to participate. Of these, 27 were recommended BST. The majority were female (19/27) with average age of 58 years (SD = 12). Mean cough duration was 60 months (SD = 98) and mean post-BST duration was 20 months (SD = 9). A significant increase in pre- to post-treatment LCQ scores occurred [4.4 (SD = 4.2)] (p < 0.0001). CONCLUSION: This study addressed long-term BST benefit for CRC and demonstrated a significant improvement in long-term post-treatment LCQ total scores more than a year after BST for CRC. More than half of participants indicated improvement or elimination of their cough. These findings further support the benefit of BST for CRC. Future research should consider patient perspectives about treatment outcomes given that 44% of participants reported no benefit from BST.

Heterogeneity of cough hypersensitivity mediated by TRPV1 and TRPA1 in patients with chronic refractory cough.

BACKGROUND: The differential sensitivity of cough to antitussive therapies implies the existence of heterogeneity in cough hypersensitivity, but how such heterogeneity is expressed across individual patients is poorly understood. We investigated the phenotypes of cough hypersensitivity by examining transient receptor potential ankyrin 1 (TRPA1)- and transient receptor potential vanilloid 1 (TRPV1)-mediated cough sensitivity in patients with chronic refractory cough. METHODS: Using a selective TRPA1 agonist, allyl isothiocyanate (AITC), we established an AITC cough challenge as a measure of TRPA1-mediated cough sensitivity. The AITC cough challenge and the widely used capsaicin (a selective TRPV1 agonist) cough challenge were performed with 250 patients with chronic refractory cough and 56 healthy subjects. The concentration of AITC or capsaicin solution causing at least two (C2) and five coughs (C5) was recorded. Cough sensitivity was expressed as the mean (95% confidence interval) of log C5, and cough hypersensitivity was defined as a log C5 value lower than that of healthy subjects. RESULTS: A distinct concentration-response effect of inhaled AITC was identified both in patients with chronic refractory cough and in healthy subjects. Cough sensitivity to AITC and capsaicin was significantly higher in patients than in healthy subjects (AITC: 2.42 [2.37-2.48] vs 2.72 [2.66-2.78] mM, p = 0.001; capsaicin: 1.87 [1.75-1.98] vs 2.53 [2.36-2.70] µM, p = 0.001) and was higher in females than in males for both healthy subjects and patients (all p < 0.05). Among the 234 patients who completed both challenges, 25 (10.7%) exhibited hypersensitivity to both AITC and capsaicin, 44 (18.8%) showed hypersensitivity to AITC only, 28 (11.9%) showed hypersensitivity to capsaicin only, and 137 (58.6%) exhibited hypersensitivity to neither. Those with TRPA1- and/or TRPV1-mediated hypersensitivity were predominantly female, while those without TRPA1- and TRPV1-mediated hypersensitivity were mainly male. CONCLUSIONS: Four phenotypes of cough hypersensitivity were identified by the activation of TRPV1 and TRPA1 channels, which supports the existence of heterogeneity in cough pathways and provides a new direction for personalized management of chronic refractory cough. TRIAL REGISTRATION: ClinicalTrials.gov NCT02591550 .

Gabapentin for Chronic Refractory Cancer Cough.

Vagal sensory neuropathy or vagal hypersensitivity has been implicated in the pathophysiology of chronic cough. Earlier reports have shown gabapentin to be effective in sensory laryngeal neuropathy and symptom conditions that have a proven neural origin. We present a case report of a patient with chronic refractory cough due to a soft tissue mass in the lung that caused compression of the mediastinal structures. The patient was successfully treated with gabapentin with reduction in the cough intensity, duration, and frequency.

Evaluation of the surgical fat-filling procedure in the treatment of refractory cough after systematic mediastinal lymphadenectomy in patients with right lung cancer.

BACKGROUND: To evaluate the efficacy of the surgical fat-filling procedure (SFFP) in the treatment of refractory cough and quality of life (QOL) after systematic mediastinal lymphadenectomy in patients with right lung cancer. METHODS: This is a blinded, randomized, controlled clinical trial to evaluate refractory cough and QOL in patients after mediastinal lymphadenectomy for lung cancer. One hundred eligible lung cancer patients were randomly divided into two groups: the fat-filling group and non-filling group. In the fat-filling group, post-lymphadenectomy residual cavities (PLRCs) were filled with fatty tissue autografts after lymph node dissection. In the non-filling group, the PLRCs remained unfilled. Clinical endpoints were postoperative cough score and QOL. RESULTS: The SFFP did not increase intraoperative bleeding, extend operation time, or hospital stay. Further, night cough was significantly improved after 4 wk in the fat-filling group after the removal of a chest drainage tube. QOL issues, such as emotional condition, functional status, and additional concerns, demonstrated a remarkable improvement in the fat-filling group at postoperative 1 mo compared with the non-filling (control) group. CONCLUSIONS: This study demonstrates that filling PLRCs with fatty tissue autografts is a safe and partially effective treatment for refractory cough after major pulmonary resection and mediastinal lymphadenectomy. This novel procedure significantly improved patient QOL and may prove useful as a relatively safe preventive surgical adjunct operation for refractory cough.

The Impact of Medical Comorbidities on Cough Improvement Following Superior Laryngeal Block.

INTRODUCTION: Chronic refractory cough is defined as cough lasting greater than 8 weeks and with an unclear etiology. Blockade of the internal branch superior laryngeal nerve (iSLN) has been shown to be safe and effective in the treatment of chronic cough. It remains unknown, however, if underlying comorbidities impact patient response to iSLN blockade. METHODS: A total of 44 patients aged 18 years and older were seen at our institution's Laryngology clinics between 2019 and 2022 and treated with iSLN blockade. Patient demographics, comorbidities, and pre- and post-treatment cough severity index (CSI) scores were collected from electronic medical records. Two-tailed independent T tests were used to compare CSI scores between groups with and without 4 underlying comorbidities: GERD, pulmonary history, smoking history, and evidence of vocal fold paresis or asymmetry on stroboscopy. RESULTS: Patients with a history of GERD or smoking and those with evidence of glottic insufficiency had similar improvements in CSI compared to those who did not (22.5 ± 26.4 vs 45.0 ± 47.1, P = .36; 32.7 ± 27.8 vs 29.0 ± 38, P = .85; 41.3 ± 18.8 vs 27.2 ± 37.7, P = .195). Patients with underlying pulmonary conditions had a significantly reduced response to iSLN blockade than did patients without underlying disease (9.85 ± 15.0 vs 47.4 ± 38.1, P = .028). CONCLUSION: Underlying lung pathology may contribute to decreased iSLN blockade efficacy in the treatment of chronic refractory cough from laryngeal hypersensitivity and its treatment is likely necessary for optimal symptom reduction. Characterizing patient comorbidity profiles can help guide patient counseling on expected treatment efficacy.

Knowledge, attitude, and practice of healthcare providers on chronic refractory cough: A cross-sectional study.

Objective: Previous studies from outside China showed that the knowledge, attitudes, and practice (KAP) of chronic refractory cough (CRC) was moderate among physicians. This study examined the KAP toward CRC in Chinese healthcare providers. Methods: This single-center cross-sectional study was conducted at The Sixth Affiliated Hospital of Nantong University, Yancheng Third People's Hospital, from July 2022 to January 2023 and enrolled healthcare providers. The demographic characteristics and KAP scores were collected using a questionnaire (Cronbach's α = 0.934) developed based on CRC guidelines. Results: The study included 539 healthcare providers. The mean knowledge score was 8.27 ± 2.37 (maximum of 14, 59.07%), indicating poor knowledge. The highest rates of inaccuracies pertained to knowledge about the definition of chronic cough, empirical treatment methods, and potential risks of different treatments, suggesting a need for unified training in all aspects of CRC for medical staff. The mean attitude score was 49.74 ± 63.63 (maximum of 60, 82.90%), indicating favorable attitudes. Most healthcare providers believed that CRC affects normal work and life and that it would be necessary to provide more help to patients from the perspectives of drug treatment and psychological counseling. The mean practice score was 23.20 ± 6.28 (maximum of 35, 66.29%), indicating poor practice. Conclusion: This study suggests that healthcare providers in Yancheng have poor knowledge, favorable attitudes, and poor practice of CRC. This study provides points that should be targeted in future training and continuing education activities.

Gabapentin for chronic refractory cough: A system review and meta-analysis.

Objective: To evaluate the efficacy and safety of gabapentin in the treatment of chronic refractory cough by Meta-Analysis. Methods: Literatures were retrieved from PubMed, Embase (OvidIP), Cochrane Library, CNKI, VIP, Wanfang Database and China Biomedical Management System and eligible prospective studies were screened. Data were extracted and analyzed by using RevMan 5.4.1 software. Results: Six articles (2 RCTs and 4 prospective studies) with 536 participants were finally included. Meta-analysis showed that gabapentin was better than placebo in cough-specific quality of life (LCQ score, MD = 4.02, 95%CI [3.26,4,78], Z = 10.34, P < 0.00001), cough severity (VAS score, MD = -29.36, 95% CI (-39.46, -19.26), Z = 5.7, P < 0.00001), cough frequency (MD = -29.87, 95% CI [- 43.84, -15.91], Z = 4.19, P < 0.0001) and therapeutic efficacy (RR = 1.37,95%CI [1.13,1.65], Z = 3.27, P = 0.001), and equal in safety (RR = 1.32,95%CI [0.47,3.7], Z = 0.53, P = 0.59). Gabapentin was similar to other neuromodulators in therapeutic efficacy (RR = 1.07,95%CI [0.87,1.32], Z = 0.64, P = 0.52), but its safety was better. Conclusion: Gabapentin is effective in the treatment of chronic refractory cough in both subjective and objective evaluations, and its safety is better than other neuromodulators.

Management of non-pharmacologic therapy for chronic refractory cough: Mechanism, composition, applicable population, and assessment.

Chronic cough is common in the clinic and can seriously affect the quality of life of patients. Following the existing guidelines for treatment, refractory chronic cough is defined as a clinical condition in which the cause of the cough remains unclear after comprehensive examination and treatment, or the cause is clear but symptomatic treatment is ineffective. It has been found that non-pharmacologic therapy can effectively improve the quality of life and reduce the frequency of coughing for some patients with refractory chronic cough. Compared with pharmacological therapy, non-pharmacologic therapy has no obvious adverse effects; therefore, non-pharmacologic therapy has good application prospects in the diagnosis and treatment of refractory chronic cough. This paper summarizes the composition, indication, action and mechanism of non-pharmacologic therapy in the diagnosis and treatment of refractory chronic cough and prospects for research on non-pharmacologic therapy.

Chronic Refractory Cough: Long-Term Outcomes Following Cough Suppression Therapy.

OBJECTIVE: This study aimed to determine the long-term outcomes of patients with chronic refractory cough (CRC) following treatment for cough suppression therapy (CST). Currently, there is a lack of objective data regarding the long-term outcome of behavioral treatment for CRC. METHODS: From the charts of 106 adult patients diagnosed with CRC, 24 patients were identified as having long-term data at least 3 months post-CST in the form of otolaryngologic examination, Voice Handicap Index-10 (VHI-10), and Cough Severity Index (CSI) scores. Patients underwent otolaryngologic evaluation and completed the VHI-10 and CSI assessments during pretreatment, posttreatment, and long-term follow-up visits. Patients were also divided into two groups based on their number of comorbidities. RESULTS: Twenty of the 24 patients had significant reduction in cough severity after completing CST (P < 0.001). A significant difference was also found in CSI scores from pretherapy to the long-term follow-up visits (P = 0.001). No significant difference was found in CSI scores from posttherapy to long-term follow-up visits (P = 0.93). No significant difference was found in VHI-10 scores over time (P = 0.83). No correlation was found between changes in cough and voice severity and number of comorbidities at the tested level. CONCLUSIONS: Findings of no significant change in CRC over the long term compared to posttherapy measures suggest that patients were able to maintain improvement in cough over the long term despite various comorbidities. The current results suggest that CST represents a satisfactory approach to treating CRC and provides patients with an ongoing tool to maintain reduced cough severity. No significant correlations between number of comorbidities and mean CSI or VHI-10 scores were found over the long term.

Intrapulmonary IFN-γ instillation causes chronic lymphocytic inflammation in the spleen and lung through the CXCR3 pathway.

Some patients with chronic refractory cough have high levels of pulmonary IFN-γ and IFN-γ-producing T lymphocytes. Pulmonary IFN-γ administration causes acute airway lymphocytic inflammation and cough hypersensitivity by increasing the number of pulmonary IFN-γ-producing T lymphocytes, but these lymphocytes may be recruited from other organs. Intraperitoneal IFN-γ injection can increase the spleen weight of mice. It remains elusive whether pulmonary IFN-γ can induce chronic airway lymphocytic inflammation and cough hypersensitivity by stimulating the proliferation of IFN-γ -producing T lymphocytes in the spleen. Here, we found that pulmonary IFN-γ administration induced chronic airway inflammation and chronic cough hypersensitivity with an increased number of IFN-γ-producing T lymphocytes in the spleen, blood and lung. Pulmonary IFN-γ administration also increased 1) the proliferation of spleen lymphocytes in vivo and 2) the IP-10 level and CXCR3+ T lymphocyte numbers in the spleen and lung of mice. IP-10 could promote the proliferation of spleen lymphocytes in vitro but not blood lymphocytes or lung-resident lymphocytes. AMG487, a potent inhibitor of binding between IP-10 and CXCR3, could block pulmonary IFN-γ instillation-induced chronic airway lymphocytic inflammation and the proliferation of IFN-γ-producing T lymphocytes in mouse spleens. In conclusion, intrapulmonary IFN-γ instillation may induce the proliferation of splenic IFN-γ-producing T lymphocytes through IP-10 and the CXCR3 pathway. The IFN-γ-producing T lymphocytes in blood, partly released from the mouse spleen, may be partly attracted to the lung by pulmonary IP-10 through the CXCR3 pathway. IFN-γ-producing T lymphocytes and IFN-γ in the lung may cause chronic airway lymphocytic inflammation and chronic cough hypersensitivity.

The Diagnosis and Time of Onset of Voice Disorders in Patients with Chronic Cough.

OBJECTIVES: Chronic cough is a complaint of up to 46% of patients referred to specialist clinics. Patients with cough often report hoarseness at the time of the cough diagnosis. When the cough fails to resolve with standard medications, referrals to other specialists including otolaryngologists are made. This is the first study to report the specific diagnosis and length of time it took to obtain a specific voice disorder diagnosis in patients with chronic cough. STUDY DESIGN: Case Series METHODS: The charts of 105 patients referred to the Loma Linda Voice and Swallowing Center were reviewed. The first complaint of cough and/or hoarseness and the specific voice disorder diagnosis following otolaryngologic evaluation were identified. Voice disorders were divided into neurogenic or other/functional disorders and common comorbidities were identified. Statistical analysis between diagnostic groups, gender, and age were obtained. RESULTS: The specific voice disorders in the cohort were identified. There was a high prevalence of neurogenic voice disorders (n = 85, 81%). There were significant relationships between chronic cough and the two most common neurogenic voice disorders, vocal fold paresis and vocal fold atrophy. The average length of time between complaint of hoarseness and the specific voice disorder diagnosis was 32.3 months. Most patients (86%) complained of voice problems after diagnosis of chronic cough. A significant association was found in prevalence of asthma (OR = 4.52, P = 0.02) and dyspnea (OR = 4.24, P = 0.02) in the cohort who presented first with voice complaints and later developed chronic cough. CONCLUSIONS: There is a high incidence of neurogenic voice disorders accompanying patients with chronic cough. Understanding the relationship between chronic cough and hoarseness provides the clinician with specific diagnostic information in the treatment of both disorders.

The efficacy of gabapentin for the treatment of refractory cough associated with interstitial lung disease: study protocol for a randomized, double-blind and placebo-controlled clinical trial.

INTRODUCTION: Gabapentin, a neurotransmitter modulator, is thought to treat refractory cough associated with interstitial lung disease by improving cough hypersensitivity. METHODS/DESIGN: This is a single-center, prospective, randomized, double-blind, placebo-controlled trial. The trial will investigate the effect of a 10-week course of oral gabapentin 900 mg/day on refractory cough associated with interstitial lung disease (ILD) and explore the possible mechanisms involved in improving cough symptoms. A total of 84 individuals will be randomized in a 1:1 ratio to two treatment groups and will be followed for a total of 14 weeks from the first dose. The primary endpoint of the study will be the change in cough symptom scores at 14 weeks. The secondary endpoints include the change in Leicester Quality of Life Questionnaire (LCQ), Gastroesophageal Reflux Disease Questionnaire (Gerd Q), and Hull Airway Reflux Questionnaire (HARQ) scores; cough sensitivity (C2 and C5) values; and safety. DISCUSSION: This study will be the first randomized, controlled clinical trial to investigate gabapentin for the treatment of refractory cough associated with interstitial lung disease and provide data on efficacy, safety, and quality of life. If the study confirms that gabapentin is effective in improving refractory cough associated with interstitial lung disease, it will indicate that a deeper understanding of its mechanisms may reveal new therapeutic targets. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100045202 . Registered on 8 April 2021, www.chictr.org.cn.

Structural and Functional Correlates of Higher Cortical Brain Regions in Chronic Refractory Cough.

BACKGROUND: Chronic refractory cough significantly impairs the psychological and social aspects of quality of life. Loss of inhibitory control is suggested as a potential central neurobiological mechanism underlying chronic refractory cough. RESEARCH QUESTION: Do structural and functional changes related to chronic cough occur in higher cortical brain regions? STUDY DESIGN AND METHODS: The structural and resting-state functional alterations in the brains of 15 patients with chronic refractory cough and 15 age- and sex-matched healthy control participants were evaluated. Gray matter volumes of the whole brain were measured using voxel-based morphometry based on T1-weighted MRI. Intrinsic functional connectivity within large-scale brain networks was examined on resting-state functional MRI. Correlation analyses were performed to examine the relationships of these brain changes with duration, severity, and impact of cough. RESULTS: Compared with healthy control participants, patients with chronic refractory cough demonstrated a lower gray matter volume in the left frontal cluster and enhanced functional connectivity within the left frontoparietal network, which were associated with greater cough scores. Furthermore, enhanced functional connectivity within the left frontoparietal network was associated with a greater psychological and social impact of coughing. Lower left frontal gray matter volume was associated with longer cough duration. INTERPRETATION: Structural and functional alterations in the left frontal brain regions may be implicated in the psychological and social impact and disease duration of chronic refractory cough. Our findings provide new perspectives on developing interventional approaches targeting the cognitive modulation of chronic coughing.

Chronic Refractory Cough: Objective Improvement With Aerodynamic-Focused.

OBJECTIVE: Previous investigations have reported that a chronic cough that is refractory to medical therapies improves with behavioral therapies. However, the treatment parameters that may account for improvement in cough symptoms have not yet been objectively documented. The purpose of this study was to document changes in chronic refractory cough using a breath training protocol. METHODS: The charts of 27 patients with a long-term chronic cough (>6 months) refractory to various medical treatments were reviewed. These patients received 2-4 sessions of breath training therapy over a 6-month period. Treatment sessions consisted of breathing modification exercises such as those reported in the literature. Aerodynamic parameters including mean estimated subglottal air pressure, mean airflow rate, laryngeal airway resistance, and maximum phonation time were obtained before treatment and 6 months after therapy. Patients also completed the Cough Severity Index at the first visit and 6 months after treatment. RESULTS: Twenty four of the 27 patients (M:F = 6:21), with a mean age of 62.4 (range = 28-78, median = 66) had significant Cough Severity Index improvement from 16.74 to 10.04 (P< 0.001) after therapy. Maximum phonation time increased significantly from 12.00 to 16.38 seconds (P= 0.006); mean estimated subglottic air pressure decreased significantly from 7.58 to 6.36 cm H2O (P= 0.004); laryngeal airway resistance decreased significantly from 52.97 to 40.64 ppm (P= 0.013). CONCLUSION: This investigation provides evidence that patients who followed a protocol that focused on a breath training program reduced their chronic cough. Significant relationships between patient self-assessment of chronic cough and aerodynamic measures of subglottic pressure and glottal airway resistance were found in this group.

Pressure and length of the lower esophageal sphincter as predictive indicators of therapeutic efficacy of baclofen for refractory gastroesophageal reflux-induced chronic cough.

BACKGROUND: Therapeutic efficacy of baclofen is suboptimal in the treatment of refractory gastroesophageal reflux-induced chronic cough (GERC). The purpose of the study is to identify its therapeutic predictors in a prospective clinical study. METHODS: 138 patients with suspected refractory GERC were treated with baclofen. Before the therapy, all the patients underwent esophageal manometry and multichannel intraluminal impedance-pH monitoring to establish the diagnosis. After the efficacy of baclofen was evaluated, a stepwise logistic regression analysis was performed to identify the therapeutic predictors of baclofen and to establish a regression prediction model. RESULTS: The overall response rate of baclofen treatment was 52.2% (72/138). The lower esophageal sphincter pressure (LESP) (odds ratio (OR) = 0.592, P = 0.000) and lower esophageal sphincter length (LESL) (OR = 0.144, P = 0.008) were independent predictors of baclofen efficacy. The optimal cut-off point to predict baclofen efficacy for LESP was 11.00 mmHg, with a sensitivity of 83.7% and specificity of 79.1% while that for LESL was 2.35 cm, with a sensitivity of 81.6% and specificity of 72.1%. The highest predictive specificity (90.7%) was achieved when both LESP and LESL were jointly used. CONCLUSIONS: LESP and LESL may be used to screen the patients with refractory GERC suitable for baclofen therapy and help improve the therapeutic precision. CLINICAL TRIAL REGISTRATION: ChiCTR- ONC-13003123.

Effects of Cough Suppression Therapy on Voice Disorder Severity.

OBJECTIVES//HYPOTHESIS: To determine changes in voice severity when treating chronic cough refractory to medical treatment with cough suppression therapy (CST) in patients with chronic cough and voice complaints. Chronic cough has been reported to be refractory to medical treatment and frequently co-occurs with voice disorders. The possible effects of CST on self-assessed changes in chronic cough and voice disorders have not been demonstrated. STUDY DESIGN: Retrospective analysis of the effects of cough suppression therapy (CST) on self-assessed changes in chronic cough and voice disorder severity in patients with both chronic cough and voice disorders. METHODS: Forty-three adult patients with the primary complaint of chronic refractory cough underwent pre- and post-treatment diagnostic examinations, completed pre- and post-treatment Voice Handicap Index-10 (VHI-10) and Cough Severity Index assessments, and were treated by a licensed speech-language pathologist using CST. Twenty-seven subjects were assigned to the cough (C) group and 16 to the cough-voice (CV) group based on the severity of their VHI-10 scores. RESULTS: Post-test analysis showed significant improvement in cough severity for both groups and significant improvement in voice severity for the CV group. The VHI-10 scores for the C group did not change significantly. The median number of treatment sessions was 3, with a range of 1-13 sessions. Correlation between changes in severity and number of treatment sessions was not found to be significant at the tested level. CONCLUSIONS: CST represents a unifying approach for treatment of patients with CRC and comorbid voice disorders. CST offered cross-over effects to the voice when subjects were treated for their primary complaint of chronic cough. This treatment of the primary complaint improves function in systems that share a common pathway. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2747-2751, 2021.

A study on the esophageal dynamics in patients with gastroesophageal reflux disease and with refractory cough undergoing esophageal high-resolution manometry.

OBJECTIVE: To analyze the esophageal dynamics in patients with gastroesophageal reflux disease (GERD) and with refractory cough while undergoing esophageal high-resolution manometry (HRM). METHODS: A total of 32 patients with GERD and with refractory cough and 48 patients with GERD admitted to our hospital from February 2019 to July 2020 were assigned to the combined group and the GERD group, respectively, and 40 healthy volunteers were assigned to the healthy group. All the patients underwent HRM. The lower esophageal sphincter (LES) and the upper esophageal sphincter (UES) parameters, the types of peristalsis of the esophageal body, the esophageal body motility, the i relaxation of LES and UES incidence rates, and the esophageal body motility disorders were compared among the three groups. RESULTS: The combined group and the GERD group had lower esophageal sphincter pressure (LESP) levels and lower 4-s integrated relaxation pressure (4 s IRP) levels, shorter lower esophageal sphincter lengths (LESL), and higher frequencies and longer durations of transient lower esophageal sphincter relaxation (TLESR) compared with the healthy group (P < 0.05). The upper esophageal sphincter lengths (UESL) in the GERD group were longer than they were in the healthy group (P < 0.05). Compared with the healthy group and the GERD group, the combined group had longer distal latencies (DL), break distances, and peristaltic breaks (PB), longer large and small peristaltic breaks, a greater number of ineffective swallows, lower upper esophageal sphincter pressure (UESP) levels, distal contraction integrals (DCI), contractile front velocities (CFV), and a higher incidence rate of esophageal body motility disorders (P < 0.05). CONCLUSION: Patients with GERD and with refractory cough often also have esophageal body motility disorders, longer PB, elevated UESP levels, and lower DCI. HRM can be used to objectively evaluate the esophageal dynamics and to differentiate among diseases.

ACR Appropriateness Criteria® Chronic Cough.

Chronic cough is defined by a duration lasting at least 8 weeks. The most common causes of chronic cough include smoking-related lung disease, upper airway cough syndrome, asthma, gastroesophageal reflux disease, and nonasthmatic eosinophilic bronchitis. The etiology of chronic cough in some patients may be difficult to localize to an isolated source and is often multifactorial. The complex pathophysiology, clinical presentation, and variable manifestations of chronic cough underscore the challenges faced by clinicians in the evaluation and management of these patients. Imaging plays a role in the initial evaluation, although there is a lack of high-quality evidence guiding which modalities are useful and at what point in time the clinical evaluation should be performed. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.