Surinder Singh Birringer

Introduction: Refractory chronic cough (RCC; duration >8 weeks) persists despite treatment and is associated with psychological co-morbidities. Little is known about suicidal ideation prevalence in chronic cough. This observational study aimed to investigate the prevalence and associations of suicidal ideation and psychological distress in patients with RCC. Methods: Cough symptoms and impact were assessed in consecutive patients with RCC by cough severity visual analogue scale (VAS), Patient Global Impression of Severity (PGI-S) scale and cough-specific health status Leicester Cough Questionnaire (LCQ) at a specialist cough clinic. Treatable traits were identified by the clinician and recorded. Suicidal ideation was identified through the Patient Health Questionnaire (PHQ-9). Depression and anxiety symptoms were self-reported with PHQ-9 and Generalised Anxiety Disorder Assessment (GAD-7) respectively. Results: A total of 339 participants completed assessment; 73% female, median (IQR) age 57 (45–67) years and duration of cough 4 (2–10) years. 36 (11%) participants reported suicidal ideation, and 104 (31%) and 62 (20%) participants reported moderate or more severe depression (PHQ-9>10) and anxiety (GAD-7≥10) symptoms, respectively. Suicidal ideation in RCC was associated with cough severity VAS, cough-specific LCQ health status, and anxiety (GAD-7) and depression (PHQ) symptoms (all p≤0.02). In contrast, suicidal ideation was not associated with age, sex, duration of cough or presence of treatable traits. Conclusion: Suicidal ideation, depression and anxiety were common in patients with RCC, and the former was associated with cough severity, health-status and depressive symptoms. Thus, an assessment of suicidal ideation and psychological comorbidities should be integral to RCC management.

Chronic cough significantly impacts patients’ quality of life, yet validated Arabic-language tools for its assessment are lacking. This study aimed to translate, culturally adapt, and validate the Arabic version of the Leicester Cough Questionnaire (LCQ-A) among Arabic-speaking patients. This cross-sectional study involved the translation, cross-cultural adaptation, and psychometric validation of the LCQ among Arabic-speaking patients with chronic cough. Participants completed the LCQ-A and the COPD Assessment Test (CAT). Internal consistency was assessed using Cronbach’s α, test–retest reliability using intraclass correlation coefficients, and convergent validity via Spearman’s correlation with the CAT cough item. A total of 56 adult patients with chronic cough were recruited with a mean age of 28.5 ± 4.8 years. Clinical causes or conditions associated with chronic cough included postinfection cough (26.8%), sinusitis (17.9%), asthma (14.3%), and an unknown cause (41.1%). The mean LCQ-A total score was 16.9 ± 3.7, with subdomain scores of 5.3 ± 1.3 (physical), 5.9 ± 1.2 (psychological), and 5.8 ± 1.5 (social). Cronbach’s α demonstrated excellent internal consistency across domains (physical, 0.870; psychological, 0.882; social, 0.925; total, 0.952). Test–retest reliability of the LCQ-A in participants with no change in cough symptoms was excellent, with intraclass correlation coefficient values ranging from 0.859 to 0.944 for single measures and 0.924 to 0.971 for average measures (all P < .001). Strong interdomain correlations were observed (ρ = 0.877–0.957, P < .001), indicating high internal coherence. However, LCQ-A scores did not significantly correlate with the CAT cough item (ρ = −0.030 to 0.057, P > .05). The LCQ-A demonstrates excellent reliability and strong internal consistency, confirming its suitability for assessing cough-related quality of life in Arabic-speaking populations. While convergent validity with the CAT cough item was not observed, the LCQ-A provides a culturally adapted and psychometrically robust instrument for clinical and research use.

Background and Objective: Cardiovascular disease (CVD) is a prevalent comorbidity in asthma, yet its impact on clinical outcomes across disease states remains poorly characterised. Methods: We analysed data from two independent prospective cohorts. Cohort I comprised 1058 stable asthma patients (CVD: n = 107; non‐CVD: n = 951) followed for 12 months to assess asthma exacerbations. Cohort II comprised 825 patients hospitalised for an acute exacerbation (CVD: n = 233; non‐CVD: n = 592). Missing data were handled by multiple imputation, and the CVD and non‐CVD groups were balanced using propensity score overlap weighting. Associations were estimated using negative binomial, gamma, and logistic regression. Mediation and dominance analyses were performed as exploratory analyses. Results: Patients with CVD exhibited greater airflow obstruction and a predominantly non‐T2 inflammatory profile characterised by increased neutrophilic inflammation. White blood cells, neutrophils, and monocytes partially mediated the association between CVD and lower FEV ₁ /FVC ratio, while monocytes additionally mediated the association between CVD and severe exacerbations. In Cohort I, CVD was independently associated with severe exacerbations (adjusted IRR = 1.96, 95% CI (1.12, 3.44)), hospitalisations, and emergency visits. In Cohort II, CVD was associated with longer hospital stay (adjusted IRR = 1.14, 95% CI (1.01, 1.30)) and higher direct costs, with stroke and coronary heart disease as leading contributors to prolonged stay. Conclusion: CVD is independently associated with worse clinical outcomes across the asthma disease spectrum. These findings support recognition of CVD as an important treatable trait in asthma and highlight the need for integrated cardiopulmonary management.

Chronic cough is one of the most frequent and burdensome symptoms in patients with interstitial lung disease (ILD), substantially impairing quality of life and, in idiopathic pulmonary fibrosis (IPF), being associated with disease progression. Despite its clinical relevance, the mechanisms underlying cough in ILD remain incompletely understood, and effective therapeutic options are limited. This narrative review summarizes current evidence on the epidemiology, pathophysiology, clinical assessment, and management of cough across the spectrum of ILD. Current data support the concept that ILD-related cough results from a complex interplay between cough reflex hypersensitivity, mechanical distortion of the fibrotic lung, airway and parenchymal inflammation, neural remodeling, and common comorbidities such as gastroesophageal reflux disease and obstructive sleep apnea. Disease-specific mechanisms are also discussed in connective tissue disease-associated ILD, sarcoidosis, and hypersensitivity pneumonitis. We review currently available qualitative and quantitative methods for cough assessment, including patient-reported outcome measures and objective cough monitoring technologies, highlighting their strengths and limitations in clinical practice and research. Finally, we examine established and emerging therapeutic approaches. While antifibrotic therapies have shown limited and inconsistent effects on cough, recent randomized clinical trials provide encouraging evidence for low-dose morphine and extended-release nalbuphine in IPF-associated chronic cough. Nonpharmacological interventions, particularly physiotherapy and speech and language therapy, also demonstrate meaningful benefits. Several novel therapeutic strategies targeting neural and inflammatory pathways are currently under investigation. A better understanding of the mechanisms driving cough in ILD, together with standardized assessment tools and adequately powered clinical trials, will be essential to develop effective, disease-specific treatments for this disabling symptom.

Introduction: Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a genetic neurodegenerative condition associated with chronic cough and cough hypersensitivity. The neuropathic mechanisms underlying cough in CANVAS are unknown. In a father and son with CANVAS-associated cough, we investigated clinical and neuropathophysiological features including bronchial and skin biopsies. Methods: Patients completed assessments for cough severity (visual analogue scale, VAS), impact (Leicester Cough Questionnaire, LCQ), triggers (Cough Hypersensitivity Questionnaire), objective frequency with Leicester Cough Monitor, and reflex sensitivity with capsaicin cough challenge. Bronchoscopic airway biopsies were analysed for nerve morphology and compared to a healthy control. Neurological assessments included skin biopsies, nerve conduction studies, and microneurography. Results: The father (age 62) and son (age 37) had advanced and early CANVAS, with a refractory chronic cough of 37 and 9 years duration, respectively. The cough in the father and son was of moderate severity (VAS 58 and 54 mm) and impact (LCQ score 15.9 and 13.1), with raised objective cough frequencies of 6 and 16 coughs hr ⁻¹ , and heightened cough reflex sensitivity to capsaicin with concentrations to evoke five coughs (C5) of 14.9 and 3.3 μmol L ⁻¹ , respectively. Bronchoscopic airway biopsies demonstrated severely depleted sensory small nerve fibres in the father and son compared to a healthy control: median (IQR) total nerve length 0 (0–0) and 0 (0–125) μm vs 944 (461–1323) μm, respectively. Skin biopsies showed absent intraepidermal nerve fibres, with densities of 0.0 fibres.mm ⁻¹ in both patients. Functional microneurography revealed nociceptor fibre paucity and dysfunction. Conclusion: In CANVAS, despite the loss of bronchial and cutaneous nerve fibres, there was heightened cough reflex sensitivity. Further studies are needed to elucidate underlying neural mechanisms.

Chronic cough is a debilitating condition that affects quality of life and often signals underlying respiratory disease. Clinical studies currently rely on audio recordings reviewed by human analysists to objectively quantify cough frequency, but this process is time-consuming and limits long-term monitoring. Emerging automated cough measurement tools enable multi-day measurements and therefore offer a more accurate assessment of a patient’s actual cough burden. At the same time, they are expected to show varying performance across patients. The tradeoff between algorithmic accuracy and the number of measurement days required to obtain a valid estimate of an individual’s objective cough burden has not previously been explored. In this study, we aimed to validate the performance of our proprietary cough detection algorithm, part of an automated cough monitoring system, in patients with chronic cough. We also investigated how algorithm performance and daily variability in cough frequency affect the optimal number of monitoring days. The algorithm was evaluated under real-life conditions in 51 patients with chronic cough, achieving a median sensitivity of 0.93 and a median precision of 0.94. By using a confidence score to identify unreliable data and applying bootstrapping simulations to model variability, we found that the largest gains in measuring true cough burden were achieved with three days of monitoring, with diminishing returns beyond seven days. In conclusion, because cough frequency fluctuates daily, automated cough counting tools can enhance human-annotated data by enabling multi-day monitoring to more accurately capture true cough burden.

Background: There is increasing interest in the use of home-based monitoring in people with chronic lung diseases to improve access to care, support patient self-management, and facilitate the collection of information for clinical care and research. However, integration of home-based monitoring into clinical and research settings requires careful consideration of test performance and other attributes. There is no published guidance from professional respiratory societies to advance the science of home-based monitoring for chronic lung disease. Methods: An international multidisciplinary panel of 32 clinicians, researchers, patients, and caregivers developed a multidimensional framework for the evaluation of home-based monitoring in chronic lung disease developed through consensus using a modified Delphi survey. We also present an example of how the framework could be used to evaluate home-based monitoring using spirometry and pulse oximetry in adults with asthma, bronchiectasis/cystic fibrosis, chronic obstructive pulmonary disease, and interstitial lung disease. Results: The PANACEA framework includes seven domains (test Performance, disease mANAgement, Cost, patient Experience, clinician Experience, researcher Experience, and Access) to assess the degree to which home-based monitoring assessments meet the conditions for clinical and research use in chronic lung disease. Knowledge gaps and recommendations for future research of home spirometry and pulse oximetry in asthma, bronchiectasis/cystic fibrosis, chronic obstructive pulmonary disease, and interstitial lung disease were identified. Conclusions: The development of the PANACEA framework allows standardized evaluation of home-based monitoring in chronic lung diseases to support clinical application and future research.

Chronic cough is a complex disorder that affects up to 5–10% of the general population. It can be challenging to manage as there are few effective treatments, although several novel antitussives are in clinical development. The endpoints used to assess their efficacy in clinical trials should be optimal; most large clinical trials currently use objective measures as the primary outcome, especially cough frequency. There are strengths in this approach, although taking the view that other measures of chronic cough are less important, including patient-rated cough severity, psychosocial impact and other associated symptoms. Patient-reported outcome measures (PROMs) explore patients’ personal experiences of health and disease, and the effects of particular conditions on their lives. Numerous validated PROMs exist for chronic cough, from simple visual analogue scales, to those that focus on cough hypersensitivity and cough-specific quality of life. Medicine regulators in the European Union (EU) and United States of America (USA) encourage the use of PROMs in clinical trials but have voiced concerns over their content validity, clinically meaningful thresholds for change, and discordance with objective measures. There are recent and ongoing studies to address these limitations. This review discusses currently available PROMs used to assess chronic cough and discusses their potential role as primary outcome measures in clinical trials.

Background: In phase 3 trials of refractory or unexplained chronic cough, a higher percentage of participants (pts) receiving gefapixant 45 mg twice daily (BID) vs placebo (pbo) were Leicester Cough Questionnaire (LCQ) total score responders (≥1.3-point increase) after 52 weeks. Response to gefapixant across LCQ domains has not been reported. Aims and objectives: To evaluate improvement in LCQ domains with gefapixant treatment. Methods: Post hoc domain-level LCQ responder analyses were calculated for pts who received gefapixant 45 mg BID or pbo through Week 52 (COUGH-1, NCT03449134; COUGH-2, NCT03449147; pooled). Responders were defined by the following increases in domain scores from baseline: social, ≥0.8 points; psychological, ≥0.9 points; physical, ≥0.8 points (Martin Nguyen et al. Ther Adv Respir Dis. 2022;16:1-13). Results: Of 1299 pts (gefapixant, n=655; pbo, n=644), a greater percentage receiving gefapixant vs pbo were LCQ domain responders through Week 52 (social, 69.5% vs 59.3%; psychological, 65.6% vs 55.1%; physical, 62.1% vs 52.5%; Figure A). Odds of achieving a clinically meaningful response across domains were greater with gefapixant (Figure B). Conclusions: A higher percentage of pts receiving gefapixant reported clinically meaningful improvements in LCQ social, psychological, and physical domains vs pbo, supporting the broad benefit of gefapixant on cough-specific quality of life. erj;64/suppl_68/PA323/F1 F1 F1