2025 American Cough Conference

Background: There is a significant unmet medical need for a safe, effective and well-tolerated treatment of chronic cough in patients with idiopathic pulmonary fibrosis (IPF). Preclinical and preliminary clinical results suggest that ME-015 (suplatast tosilate), an oral immunomodulator with presumed effects on nicotinic Acetylcholine receptor currents at the paratracheal ganglion, could be effective in treating fibrotic cough in IPF.

Methods: COSMIC-IPF is a Phase 2a, placebo-controlled, randomized controlled trial conducted as a multi-centre study in about 40 patients with externally adjudicated diagnosis of IPF and objectively measured of cough frequency using the VitaloJak device. After a single-blinded placebo run-in phase, patients are randomized to one of two treatment arms with a sequential design of 2 weeks of blinded treatment with oral ME-015 followed by 2 weeks of blinded treatment with placebo or vice versa, interspersed by a 2-week blinded placebo wash-out period.

Results: The study has been fully recruited within the targeted timelines and the last patient last visit is expected in June 2025. Preliminary blinded safety and baseline cough results measured by VitaloJak are presented. The screen failure rate of 35% was mainly due to non-confirmation of IPF by external high-resolution CT (HRCT) review. To date, 4 out of 40 randomized patients have withdrawn from the study (none for safety or tolerability reasons). Adverse events were mostly mild and not related to treatment. One death occurred due to progression of the underlying disease and was judged unrelated to study treatment by Investigator and Sponsor. Baseline waking time cough counts are shown.

Conclusions: With topline results expected early in the third quarter of 2025, these preliminary blinded results suggest that ME-015 is safe and well tolerated in patients with idiopathic pulmonary fibrosis and chronic cough.

Keywords IPF cough, Suplatast tosilate, Melius Pharma, Phase 2

Disclosures CN, OP and MK are employees or consultants of Melius Pharma.

Background: Subacute cough remains a therapeutic challenge due to limited evidence-based treatment options. QR052107B is a novel P2X3 receptor antagonist that targets sensory pathways involved in cough reflex sensitization. This phase 2a trial evaluated the efficacy and safety of QR052107B in patients with subacute cough subsequent to respiratory infection.

Methods: In this multicenter, double-blind study, 270 adults with 3 to 8 weeks of postinfectious cough and inadequate response to standard antitussives were randomized (1:1:1) to QR052107B 400 mg once daily (QD), QR052107B 100 mg QD, or placebo for 9 days. The primary endpoint was the geometric mean ratio (GMR) of 24-h cough frequency on day 10 vs. baseline. Subgroup analyses were conducted in patients with ≥ 20 coughs/h at baseline.

Results: The mean age across all patients was 35 years; 54% of patients were female. All groups showed reductions in cough frequency by day 10. Based on the GMR, placebo-adjusted percentage changes in 24-h cough frequency were − 3.32% [95% confidence interval (CI) − 30.85%, 35.18%] for 400 mg and − 9.56% (95% CI − 35.12%, 26.08%) for 100 mg. Among patients with ≥ 20 coughs/h at baseline, the placebo-adjusted reductions were more pronounced at day 10: − 26.06% (95% CI − 54.72%, 20.73%) for 400 mg and − 23.16% (95% CI − 53.07%, 25.82%) for 100 mg. Both doses were generally well tolerated. Adverse events (AEs) were mild and similar across groups.

Conclusions: QR052107B was well tolerated, with minimal taste-related AEs. All groups showed evident improvements in objective cough frequency by day 10; numeric trends in reduced cough frequency for QR052107B vs. placebo were more pronounced among patients with higher baseline cough burdens. These findings support continued investigation of QR052107B as a nonopioid option for subacute cough.

Keywords Subacute cough, P2X3 antagonist, QR052107B, Cough frequency

Disclosures HZ, YC, JY, DL, and GR are employed by the study sponsor.

Background: Chronic bronchitis (CB) is a prevalent respiratory condition characterized by a persistent, mucus-producing cough lasting at least 3 months/year for two consecutive years. CB is most often a consequence of chronic airway irritation, typically due to smoking or prolonged exposure to environmental irritants. It can have a significant impact on quality of life (QoL). Extended-release guaifenesin is commonly used to manage respiratory symptoms and thin mucus. Its potential long-term benefits for stable chronic bronchitis (SCB) have not been well studied.

Methods: This study explored the real-world use of extended-release guaifenesin and its effectiveness in SCB. The study was an open-label, multicenter, single-cohort trial evaluating the effectiveness of extended-release guaifenesin in SCB patients over 12 weeks, following a 2-week run-in period during which time patients received only their maintenance therapy. During the treatment phase, patients took Mucinex® (1200 mg twice daily; 2400 mg/day), Reckitt Benckiser LLC, US and completed weekly surveys, including the Cough and Sputum Assessment Questionnaire (CASA-Q).

Results: The study analysis included 75 patients. A strong, consistent positive correlation was observed between COUI and SPUI scores across all 12 treatment weeks (r = 0.86–0.95, all p < 0.05), indicating a stable relationship over time. A moderate to strong positive correlation was also observed between COUS and SPUS scores (r = 0.49–0.76, all p < 0.05), suggesting a sustained association over time.

Conclusions: The strong correlation between COUI and SPUI over the 12 treatment weeks highlights the major impact of sputum-related symptoms on cough and overall QoL in SCB patients. Similarly, the moderate correlation between COUS and SPUS reinforces the interdependence of cough and sputum symptomology. These findings emphasize the importance of effectively managing mucus and sputum-related symptoms, as their relief may lead to significant improvements in cough burden and patient QoL.

Keywords Real-world, Chronic bronchitis, Mucinex

Disclosures This study was sponsored by Reckitt. The authors declare no competing interests.

Permissions: All data presented here is original and has not been previously published.

Background: Chronic cough (CC) is a highly prevalent disorder in the general population that is seen with increased frequency in middle-aged to elderly adults. Patients frequently report symptoms such as irritability, frustration, anger, pain, sleep disturbances, and are associated with deterioration of quality of life. Additionally, CC is associated with increased healthcare utilization, including frequent doctor visits and diagnostic testing [1, 2]. Many patients receive empirical treatments for CC, even when the presumed diagnosis may be incorrect [1, 3]. The most common treated causes of CC include gastroesophageal reflux disease (GERD), cough-variant asthma, and upper airway cough syndrome, with other causes including respiratory infections, smoking, angiotensin-converting enzyme inhibitors, and bronchitis [1–3]. Despite this, a substantial number of patients persist with highlight gaps in our knowledge of its diagnosis and management—these patients are characterized as refractory chronic cough (RCC).

Objective: To use a data-driven approach to characterize CC by identifying affected patients, by excluding comorbid chronic lung disease, smoking and other above listed etiologies of chronic cough.

Methods: We conducted a retrospective observational cohort study using data from TriNetX, a global health research network providing access to real-world clinical data with over 120 million patients from 95 healthcare organizations. Adults aged ≥ 18 were included if they had either:

Results: The chronic cough cohort was predominantly female (58%) and showed a higher prevalence among individuals aged 60–69 years. In terms of healthcare utilization, 26.98% (n = 3821) of patients had three visits, 21.28% (n = 3014) had four visits, and 51.74% (n = 7328) had five or more visits within the 56–120-day timeframe.

Conclusions: A substantial number of patients with RCC demonstrate repeated healthcare utilization, underscoring the clinical and economic burden of this condition. Our next step is to apply unsupervised machine learning techniques to identify distinct chronic cough phenotypes based on patient characteristics and comorbidities. A deeper understanding of the underlying mechanisms driving cough development may inform more targeted and effective management strategies.

Keywords Refractory chronic cough, Healthcare utilization, Phenotyping, Data-driven approach

Disclosures Sundar is Co-founder of Hypnosecure LLC—a software application for population management of sleep apnea through the University of Utah Technology Commercialization Office. Gouripeddi is funded by NIH/NCATS Award UM1TR004409. The authors declared no competing interests.

Introduction: Patients with refractory chronic cough (RCC) often report impact on social lives, an inability to work, suicidal ideation, and everyday life interruptions because of their cough. Higher anxiety levels have been reported in RCC patients compared to those without a cough and those with a cough of known etiology. The aim of this study is to identify the diagnostic prevalence of anxiety and its influence on cough behavior in those with RCC.

Methods: Participant groups are RCC-only, RCC + anxiety, anxiety-only, and healthy controls. The experimental protocol includes baseline, stress induction, and recovery, during which electrocardiogram (ECG), respiratory rate (RR), and electrodermal activity (EDA) are recorded. Our primary outcome variable is the high frequency heart rate variability (HF-HRV) measure, as it is commonly used to detect anxiety and reflects vagal activity. Cough frequency count and urge-to-cough and anxiety ratings are completed throughout. Additionally, demographic data, cough quality of life (i.e., Leicester Cough Questionnaire), anxiety and depression scales, and voice and dysphagia rating scales are collected.

Conclusions: This study addresses diagnostic prevalence of anxiety in RCC and its effect on cough behavior. Preliminary outcomes show a moderate effect of cough on our primary outcome variable, HF-HRV. Continuing data collection will be used to evaluate differences between those with RCC and anxiety. These findings will help elucidate clinical phenotypes of RCC and lend support to optimal methods for diagnosing anxiety and determining its impact on RCC.

Disclosures None.

Background: Vagus Associated Neurogenic Cough Occurring due to Unilateral Vascular Encroachment of its Root (VANCOUVER syndrome) was recently published by our team as a case report and proof of concept that compression of the intracranial portion of a vagus nerve could cause an intermittent tickling sensation deep in the larynx/tracheobronchial tree leading to a chronic dry cough [1]. We now describe the clinical presentations of three patients who were investigated for a chronic cough due to VANCOUVER syndrome and highlight the diagnostic protocol and treatment outcomes.

Methods: A case series of three patients with VANCOUVER syndrome is presented. Clinical information was reviewed from the patients’ charts highlighting their symptoms, physical examination, brain imaging studies and response to standard therapies. The technique of unilateral vagus nerve block is presented as part of a newly proposed diagnostic protocol.

Results: Patients presented with a 15-, 20- and 31-year history of chronic dry cough. Severe coughing with normal intervening episodes progressed in frequency and intensity over the years leading to disability from work. Coughing caused tussive headaches, pre-syncope and an abdominal hernia. Triggers included prolonged vocalization, singing, exercise, cold air and harsh fumes. Pulmonary, gastroenterology and otolaryngology examinations were normal. Treatment with anti-neuralgia medications improved the cough but produced sedative side-effects [2]. Brain imaging (MRI) demonstrated unilateral distortion of a vagus nerve at the brainstem by a blood vessel in each case. Ipsilateral cervical vagus nerve block (on the side of the vagus compression) stopped the cough for the duration of the local anesthetic. Contralateral vagus nerve block had no effect on the cough (but caused expected temporary hoarseness). The technique of ultrasound guided cervical vagus nerve block is presented. Neurosurgical decompression of the affected vagus nerve resolved the cough with 6- and 1-year follow-up (third patient is pre-op). There were no complications in this small cohort. Intraoperative imaging is presented with new insights into the functional anatomy of the intracranial vagus nerve (pure sensory rootlets can be found rostral to mixed motor/sensory rootlets).

Conclusions: Three patients with chronic neurogenic cough due to unilateral vascular compression of an intracranial vagus nerve are presented. The response to ipsilateral not contralateral vagus nerve block is a diagnostic feature that may predict resolution of cough following surgical decompression of the affected vagus nerve.

Keywords Neurogenic cough, Chronic cough, VANCOUVER syndrome, Vagal neuralgia

Disclosures None.

Background: Chronic cough without medical explanation and refractory to guideline treatment have been reported to include > 40% of adult patients presenting to specialty cough clinics [1, 2]. In contrast, most children with refractory chronic cough without medical explanation have the habit cough syndrome [3, 4]. Habit cough is a habit disorder [5] susceptible to treatment by suggestion [6, 7]. Treatment of habit cough by suggestion therapy has been described for children since 1966 [8, 9] and has become the standard of care at many pediatric referral centers [10]. We now report adults with refractory chronic cough who have the same clinical presentation as in children diagnosed with habit cough, i.e., a daily repetitive dry cough that is absent during sleep, also respond to suggestion therapy with cessation of their cough.

Results: From 2019 to 2025, more than 100 parents reported by email that their child, ages 4–17 years (median 10 years), stopped coughing during or shortly after watching the video. Forty-five adults, ages 21–70 years (median 41 years) with a prior duration of chronic cough, ranging from 1 to 300 months (median 24 months) reported sustained cessation of their chronic cough after watching the same video. All of those adults described the same clinical characteristics seen in children diagnosed with habit cough.

Conclusions: Cessation of previously undiagnosed refractory chronic cough in adults after viewing successful cessation of habit cough in a 12 y.o. girl receiving suggestion therapy is evidence that adults with refractory chronic cough may have habit cough as the cause of their chronic cough. This indicates that the differential diagnosis of adults with a dry daily repetitive chronic cough that is absent during sleep includes the habit cough syndrome that can be treated with a non-pharmacologic behavioral method.

Keywords: Chronic cough, Habit cough, Habit disorder, Suggestion therapy

Disclosures None.

Background: Refractory chronic cough (RCC) is a prevalent and debilitating condition with limited treatment options [1,2]. Behavioral cough suppression therapy (BCST) is highly efficacious [3,4]; however, access to treatment is limited due to geographic barriers and limited number of properly trained clinicians. The purpose of this pilot study was to assess efficacy of BCST in a group telehealth format.

Methods: BCST was delivered via telehealth in small-group sessions using a rolling enrollment model. Each group session consisted of 2–5 participants. Sessions lasted 60–90 min, and participants attended 4–6 sessions. A speech–language pathologist with expertise in BCST and a speech–language pathology graduate student clinician led each session following a structured format. Each session included: (1) education on cough hypersensitivity and rationale for cough suppression as the treatment to reduce hypersensitivity via neuroplasticity, (2) assessment of adherence to cough suppression (for those beyond session 1), (3) instruction and review of cough suppression techniques, (4) review of the “Three Rs” principle of BCST, and (5) discussion and troubleshooting of cough suppression challenges specific to participant concerns. The Leicester Cough Questionnaire (LCQ) and Patient Global Impression of Severity (PGIS) for cough were used as primary outcome measures. Cough frequency monitoring via the Hyfe, Inc. CoughPro smartphone application was included as an optional secondary outcome measure.

Conclusions: The outcomes of this BCST study, which focused primarily on consistent cough suppression in a group telehealth setting, were considerably greater than traditional one-on-one BCST outcomes, which typically results in a mean change in LCQ of approximately 4.5 points [4]. This not only provides strong evidence that BCST can effectively be delivered in a group telehealth format, but it may be more effective than individual treatment.

Keywords Chronic cough, Cough hypersensitivity, Behavioral cough suppression therapy, Group telehealth

Disclosures The first and second authors receive salary from University of Montana and are paid consultants of Hyfe, Inc. This study was not supported by grant funding.

Background: Ambulatory cough monitoring is important for measuring symptom severity in chronic cough and monitoring change following treatment. In clinical settings, ambulatory cough counting is still in its infancy and patient recall of cough timing and frequency is unreliable. Cough frequency monitoring has the potential to enhance behavioural treatments for cough by providing real time measurement between therapy sessions along with early signs that intervention needs to be modified. Further work is required to incorporate cough monitoring technologies in real-world settings along with addressing issues relating to feasibility and acceptability.

Methods: This is a prospective pilot study of patients referred for behavioural management of chronic cough in a tertiary outpatient service. Inclusion criteria is chronic cough for longer than 8 weeks, age 18 or above, and access to private Wi-Fi, smart phone and email address. Exclusion criteria is untreated lung disease, rhinitis, reflux or asthma and unable to engage with assessment or treatment.

Results: Participants include 18 patients with a mean age of 63 (SD = 11) years, and 11 (75%) were female. The median cough duration was 64 weeks (range 16 to 417). Five patients had unexplained chronic cough, 4 had asthma, 3 were had post-viral cough, and 1 had cough associated with treated lower airway disease. Three patients declined cough monitoring. This paper will present data on the correlation between Leicester Cough Questionnaire and cough frequency monitoring results as well as changes in cough frequency following speech pathology intervention. Data will also be presented on patient perspectives including the logistics of using the device and on the value of biofeedback between therapy sessions.

Conclusions: This proposal and preliminary data will demonstrate the patient perception of cough monitoring in terms of feasibility as well as the personal value of the information provided by the system.

Keywords Chronic cough, Cough suppression

Disclosures This study is funded by Carepath Technologies GmbH.

*Corresponding author: Laurie Slovarp, laurie@coughcoach.com

Background: Patients with refractory or unexplained chronic cough (RCC/UCC) experience persistent symptoms despite following standard treatment guidelines, highlighting a clear unmet need. Non-drug approaches such as behavioral cough suppression techniques can reduce cough frequency by interrupting the reflex mechanism, ultimately lowering the urge to cough itself. This study evaluates a novel digital therapeutic combining passive cough monitoring with targeted behavioral cough management techniques, delivered through the globally accessible smartphone wellness app, CoughPro.

Methods: Participants with refractory or unexplained chronic cough (RCC/UCC) voluntarily consent to continuously monitor their cough using the Hyfe’s dedicated CoughMonitor smartwatch connected to the CoughPro wellness application. Following a 7-day baseline monitoring period, participants complete the educational content on behavioral cough suppression techniques delivered digitally via the Cough Management (CM) feature within CoughPro, and continue practicing the techniques over the period of 4 weeks. Objective hourly cough rate and cough bouts are passively captured by Hyfe’s CoughMonitor smartwatch. Additionally, participants complete subjective cough assessments at baseline and after the intervention, followed by a qualitative feedback interview to evaluate usability and engagement.

Results: Preliminary data from 14 CoughPro users before this trial demonstrated a meaningful improvement, with an average baseline cough frequency of 12 coughs/hour and 23 bouts/day reduced by 28% and 31%, respectively, following the introduction of digital cough management interventions. No adverse events have been reported. Further data collection is ongoing for presentation at the 10th American Cough Conference.

Conclusions: Initial findings indicate that a digital therapeutic approach integrating behavioral cough suppression techniques with objective cough monitoring could improve adherence, enhance patient motivation, and effectively reduce cough symptoms in RCC. Validation of these early observations through additional participant data following a new protocol could justify a randomized, sham-controlled clinical trial.

Keywords Cough, Digital therapeutic, Cough management

Disclosures RM, MG and PMS are employees of Hyfe, Inc. LS and JRS are Scientific Advisors to Hyfe, Inc.

Background: Innovative means to obtain cough frequency measures from cough montoring systems such as VitaloJAK® are of interest for clinical applications. Currently, cough analysis of VitaloJAK data comprises manually annotating coughs after automatic removal of non-cough activity. However, fully automated approaches may improve efficiency. Here, we present a pilot study assessing the performance of our audio-based automated cough analysis system (ABACAS™) for analysis of real-world audio recordings collected using VitaloJAK.

Methods: A total of 380 24-h ambulatory audio recordings were obtained from 77 adult chronic cough subjects (60F/17M) participating in a clinical study*. Subjects were divided randomly into training (60%), development (20%) and testing (20%) datasets. Trained analysts annotated coughs in the recordings to provide ground truth totaling 236,738 coughs. ABACAS was trained and optimized to detect coughs before testing, where it annotated the time point of peak amplitude of each detected cough. Sensitivity, positive-predictive value (PPV) and median false positive coughs per hour (MFPH) were computed per recording. A true positive ABACAS annotation was defined as being within +/− 200 ms of a ground truth annotation. Agreement between 24-h cough frequency derived from ground truth versus ABACAS annotations was assessed using intra-class correlation, linear regression and Bland–Altman analyses.

Conclusions: These results highlight the potential for ABACAS to automatically annotate coughs and provide cough frequency measures from VitaloJAK recordings.

Keywords VitaloJAK, Cough frequency, Algorithm, ABACAS

Disclosures TT, HV, DD, ET, YZ and FK are employees of Vitalograph. JS consults for Vitalograph and her hospital receives royalties from Vitalograph for use of a cough compression algorithm. MK and OP are employees of Axalbion Therapeutics Limited.

Results: Recordings contained 222,103 total coughs with 71.8% contained in bouts. Recordings analyzed contained a total of 53,806 bouts with an average of 2.96 ± 1.8 coughs/bout (median 2.0). Mean cough amplitude was 9.4% higher in coughs contained in bouts than in isolated single coughs (p < 0.001). Moreover, peak cough amplitude in bouts was 47% higher than in single coughs (p < 0.001).

Keywords Cough bouts, Cough severity, Chronic cough, Subacute cough