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INTRODUCTION: Refractory or unexplained chronic cough (RUCC) is a common clinical problem with no effective diagnostic tools. The Sensations and Triggers Provoking Cough questionnaire (TOPIC) was developed to characterise cough in RUCC versus cough in other conditions. METHODS: Content analysis of participant interviews discussing the sensations and triggers of chronic cough informed TOPIC development. Participants with chronic cough completed the draft-TOPIC (a subset repeating 5-7 days later), St George's Respiratory Questionnaire (SGRQ), Cough Severity Diary (CSD) and Global Rating of Change Scale. The draft-TOPIC item list was reduced in hierarchical and Rasch analysis to refine the questionnaire to the TOPIC. RESULTS: 49 items describing the triggers and sensations of cough were generated from participant interviews (RUCC n=14, chronic obstructive pulmonary disease (COPD) n=11, interstitial lung disease (ILD) n=10, asthma n=11, bronchiectasis n=3, cystic fibrosis n=7). 140 participants (median age 60.0 (19.0-88.0), female 56.4%; RUCC n=39, ILD n=38, asthma n=45, COPD n=6, bronchiectasis n=12) completed draft-TOPIC, where items with poor 'fit' for RUCC were removed to create TOPIC (8 trigger items, 7 sensation items). Median TOPIC score was significantly higher in RUCC (37.0) vs ILD (24.5, p=0.009) and asthma (7.0, p<0.001), but not bronchiectasis (20.0, p=0.318) or COPD (18.5, p=0.238), likely due to small sample sizes. The Rasch model demonstrated excellent fit in RUCC (χ2=22.04, p=0.85; PSI=0.88); as expected. When all participant groups were included, fit was no longer demonstrated (χ2=66.43, p=0.0001, PSI=0.89) due to the increased heterogeneity (CI=0.077). TOPIC correlated positively with SGRQ (r=0.47, p<0.001) and CSD (r=0.63, p<0.001). The test-retest reliability of TOPIC (intraclass correlation coefficient) was excellent (r=0.90, p<0.001). CONCLUSIONS: High TOPIC scores in the RUCC patients suggest their cough is characterised by specific sensations and triggers. Validation of TOPIC in cough clinics may demonstrate value as an aid to identify features of RUCC versus cough in other conditions.
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Tos , Humanos , Tos/etiología , Tos/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Encuestas y Cuestionarios , Enfermedad Crónica , Adulto , Anciano de 80 o más Años , Adulto Joven , Sensación , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Bronquiectasia/diagnóstico , Bronquiectasia/fisiopatología , Asma/diagnóstico , Asma/complicaciones , Asma/fisiopatología , Índice de Severidad de la Enfermedad , Reproducibilidad de los Resultados , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/fisiopatología , Enfermedades Pulmonares Intersticiales/complicaciones , Fibrosis Quística/complicaciones , Fibrosis Quística/fisiopatología , Tos CrónicaRESUMEN
Blocking NMDA receptors with memantine in refractory chronic cough patients is poorly tolerated and demonstrates no improvement in cough https://bit.ly/3kgx2g1.
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Tos , Procesamiento de Señales Asistido por Computador , Algoritmos , Tos/diagnóstico , HumanosRESUMEN
BACKGROUND AND OBJECTIVES: Gefapixant has previously demonstrated efficacy in the treatment of refractory chronic cough at a high daily dose. The current investigations explore efficacy and tolerability of gefapixant, a P2X3 receptor antagonist, for the treatment of chronic cough using a dose-escalation approach. MATERIALS AND METHODS: Two randomised, double-blind, placebo-controlled, crossover, dose-escalation studies recruited participants with refractory chronic cough. Patients were assigned to receive ascending doses of gefapixant (study 1: 50-200â mg, study 2: 7.5-50â mg) or placebo for 16â days, then crossed-over after washout. The primary end-point was awake cough frequency assessed using a 24-h ambulatory cough monitor at baseline and on day 4 of each dose. Patient-reported outcomes included a cough severity visual analogue scale and the cough severity diary. RESULTS: In clinical studies, gefapixant doses ≥30â mg produced maximal improvements in cough frequency compared with placebo (p<0.05); reported cough severity measures improved at similar doses. Taste disturbance exhibited a different relationship with dose, apparently maximal at doses ≥150â mg. CONCLUSIONS: P2X3 antagonism with gefapixant demonstrates anti-tussive efficacy and improved tolerability at lower doses than previously investigated. Studies of longer duration are warranted.
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Tos , Pirimidinas , Enfermedad Crónica , Tos/tratamiento farmacológico , Método Doble Ciego , Humanos , Sulfonamidas , Resultado del TratamientoRESUMEN
BACKGROUND: Cough is a common, disabling symptom of idiopathic pulmonary fibrosis (IPF), which may be exacerbated by acid reflux. Inhibiting gastric acid secretion could potentially reduce cough. This study aimed to determine the feasibility of a larger, multicentre trial of omeprazole for cough in IPF, to assess safety and to quantify cough. METHODS: Single-centre, double-blind, randomised, placebo-controlled pilot trial of the proton pump inhibitor (PPI) omeprazole (20 mg twice daily for 3 months) in patients with IPF. Primary objectives were to assess feasibility and acceptability of trial procedures. The primary clinical outcome was cough frequency. RESULTS: Forty-five participants were randomised (23 to omeprazole, 22 to placebo), with 40 (20 in each group) having cough monitoring before and after treatment. 280 patients were screened to yield these numbers, with barriers to discontinuing antacids the single biggest reason for non-recruitment. Recruitment averaged 1.5 participants per month. Geometric mean cough frequency at the end of treatment, adjusted for baseline, was 39.1% lower (95% CI 66.0% lower to 9.3% higher) in the omeprazole group compared with placebo. Omeprazole was well tolerated and adverse event profiles were similar in both groups, although there was a small excess of lower respiratory tract infection and a small fall in forced expiratory volume and forced vital capacity associated with omeprazole. CONCLUSIONS: A large randomised controlled trial of PPIs for cough in IPF appears feasible and justified but should address barriers to randomisation and incorporate safety assessments in relation to respiratory infection and changes in lung function.
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Tos/tratamiento farmacológico , Tos/etiología , Fibrosis Pulmonar Idiopática/complicaciones , Omeprazol/uso terapéutico , Inhibidores de la Bomba de Protones/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Estudios de Factibilidad , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Reflujo Gastroesofágico/complicaciones , Reflujo Gastroesofágico/tratamiento farmacológico , Humanos , Fibrosis Pulmonar Idiopática/fisiopatología , Masculino , Persona de Mediana Edad , Omeprazol/efectos adversos , Omeprazol/farmacología , Proyectos Piloto , Inhibidores de la Bomba de Protones/efectos adversos , Inhibidores de la Bomba de Protones/farmacología , Resultado del Tratamiento , Capacidad Vital/efectos de los fármacosRESUMEN
BACKGROUND: Cough is a common and troublesome symptom in asthmatic patients, but little is known about the neuronal pathways that trigger cough. The mechanisms by which airway inflammation, airway hyperresponsiveness, and variable airflow obstruction cause cough are unclear. OBJECTIVE: We sought to investigate the effects of allergen exposure on cough reflex sensitivity. METHODS: We performed a 9-visit, randomized, single-blind, placebo-controlled, 2-way crossover study comparing cough responses to inhaled capsaicin in patients with mild atopic asthma after allergen challenge compared with diluent control. Full-dose capsaicin challenge was performed at screening to determine the capsaicin dose inducing a half-maximal response, which was subsequently administered at 30 minutes and 24 hours after inhaled allergen/diluent challenge. Spontaneous coughing was measured for 24 hours after allergen/diluent. Methacholine challenge and sputum induction were performed before and after allergen/diluent challenge. RESULTS: Twelve steroid-naive subjects completed the study (6 female subjects; mean age, 34.8 years). Allergen inhalation caused both an early (mean ± SD, 38.2% ± 13.0%) and late (mean ± SD, 23.7% ± 13.2%) decrease in FEV1 and an increase in sputum eosinophil counts 24 hours later (after diluent: median, 1.9% [interquartile range, 0.8% to 5.8%]; after allergen: median, 14.9% [interquartile range, 8.9% to 37.3%]; P = .005). There was also an increase in capsaicin-evoked coughs after allergen exposure compared with diluent at both 30 minutes (geometric mean coughs, 21.9 [95% CI, 16.5-29.20] vs 12.1 [95% CI, 8.3-17.7]; P < .001) and 24 hours (geometric mean coughs, 16.1 [95% CI, 11.3-23.0] vs 9.8 [95% CI, 6.1-15.8]; P = .001). Allergen exposure was also associated with an increase in spontaneous coughs over 24 hours. CONCLUSION: Allergen-induced bronchoconstriction and airway eosinophilia result in increased cough reflex sensitivity to capsaicin associated with an increase in 24-hour spontaneous coughing.