A review on the efficacy and safety of gabapentin in the treatment of chronic cough

Introduction: Effective antitussives available to control cough are limited. Consolidation among different afferent branches of the vagus nerve is needed to bring about cough. A general, widely accepted view is that the chronic increase in the sensitivity of the cough reflex is associated with inflammatory hypersensitivity such as from gastro-esophageal reflux disease. There is increasing evidence that an important mechanism is a sensory disorder of the laryngeal branches of the vagus nerve. Neuromodulating drugs are effectively used in the treatment of chronic pain and neuropathic disorders and may have a role in the treatment of refractory chronic cough (CC).

Areas covered: Current evidence on the efficacy and safety of gabapentin in the treatment of CC is reviewed. Relevant randomized controlled trials, case reports and reviews were identified through a PubMed search of English-language literature referring to cough, sensory neuropathy and gabapentin over the last 10 years.

Expert opinion: Gabapentin appears to be effective and well tolerated in the treatment of CC and in other sensory neuropathic disorders. Relevant clinical trials investigating its efficacy and safety profile in the treatment of cough are limited and further studies are needed. Gabapentin has been shown to cause minimal to no toxicity in overdose.     

Impacto de la vacunación de las embarazadas frente a la tosferina en las hospitalizaciones de menores de un año en un hospital de tercer nivel de Cataluña

IntroductionThe recommendation for pertussis vaccination in pregnancy was established in Catalonia in February 2014. The objective of this study was to compare the hospitalization rate for pertussis in children under one year of age before and after the implementation of the vaccination program.MethodsObservational and retrospective study of patients under one year of age admitted to hospital with a diagnosis of pertussis. The hospitalization rate of patients under one year of age of the period prior to the vaccination program (2008-2013) was compared with the period with vaccination program (2014-2019) in the total of children under one year of age and in 2 subgroups: children under 3 months and between 3-11 months.ResultsHospitalization rate was significantly lower in the period with vaccination program in children under one year of age and specifically in children under 3 months (2.43 vs. 4.72 per 1,000 person-years and 6.47 vs. 13.11 per 1,000 person-years, respectively). The rate ratios were: 0.51 (95% CI 0.36-0.73) for children under one year of age; 0.49 (95% CI 0.32-0.75) for those younger than 3 months and 0.56 (95% CI 0.30-1.03) for those with 3-11 months. No statistically significant differences were observed in the clinical severity between both periods.ConclusionThe introduction of the pertussis vaccination program in pregnancy was associated with a global lower hospitalization rate for pertussis in children under one year of age and specifically in those under 3 months of age.     

Reflux-related symptoms reflect poor asthma control and the presence of airway neuronal dysfunction

BackgroundGastroesophageal reflux may be associated with the worsening of asthma by increasing cough reflex sensitivity. Hull Airway Reflux Questionnaire (HARQ) consists of 14 prevalent reflux-related symptoms. It may be useful in predicting the presence of cough reflex hypersensitivity in asthma.MethodsFrom August 2018 to July 2020, 266 asthmatic patients completed the HARQ. They underwent blood analysis, spirometry, fraction of exhaled nitric oxide (FeNO) measurement, and the capsaicin cough challenge test. Patients were considered to have reflux-related symptoms if their HARQ scores were 13 points or higher. We evaluated the association between reflux-related symptoms and clinical asthma outcomes. Finally, we performed a multivariate analysis to determine the clinical significance of the HARQ for asthma. This study was registered in the University Hospital Medical Information Network (UMIN000040732).ResultsThe mean HARQ scores were 13.1 (standard deviation 12.0). Patients in the high HARQ scores group (HARQ ≥13, n = 105) showed a lower prevalence of atopic predisposition, lower levels of FeNO, heightened capsaicin cough reflex sensitivity, poorer asthma control, and more frequent admissions due to asthma than those in the low HARQ groups (all p values < 0.05). The HARQ was useful in selecting patients with poor controlled asthma and those with severe cough when the cut-off value was set at 13. Multivariate analysis revealed that heightened capsaicin cough reflex sensitivity affected reflux-related symptoms, as well as lower levels of FeNO and younger age.ConclusionsHigher HARQ scores (≥13) may be useful in predicting not only poor asthma condition but also the presence of airway neuronal dysfunction in patients with asthma to some extent.     

Development of a parent-proxy quality-of-life chronic cough-specific questionnaire: clinical impact vs psychometric evaluations

BACKGROUND: Chronic cough affects at least 7% of children, and the impact of this on families is significant. Although adult cough-specific quality-of-life (QOL) instruments have been shown to be a useful cough outcome measure, no suitable cough-specific QOL for parents of children with chronic cough exists. This article compares two methods of item reduction (clinical impact and psychometric) and reports on the statistical properties of both QOL instruments. METHOD: One hundred seventy children (97 boys and 73 girls; median age, 4 years; interquartile range, 3 to 7.25 years) and one of their parents participated. A preliminary 50-item parent cough-specific QOL (PC-QOL) questionnaire was developed from conversations with parents of children with chronic cough (ie, cough for > 3 weeks). Parents also completed generic QOL questionnaires (eg, Pediatric Quality of Life Inventory, version 4.0 [PedsQL4.0] and the 12-item Short Form Health Survey, version 2 [SF-12v2]). RESULTS: The clinical impact and psychometric method of item reduction resulted in 27-item and 26-item PC-QOL questionnaires, respectively, with approximately 50% of items overlapping. Internal consistency among the final items from both methods was excellent. Some evidence for concurrent and criterion validity of both methods was established as significant correlations were found between subscales of the PC-QOL questionnaire and the scales of the SF-12v2 and PedsQL4.0 scores. The PC-QOL questionnaire derived from both methods was sensitive to change following an intervention. CONCLUSION: Chronic cough significantly impacts on the QOL of both parents and children. Although the PC-QOL questionnaires derived from a clinical impact method and from a psychometric method contained different items, both versions were shown to be internally consistent and valid. Further testing is required to compare both final versions to objective and subjective cough measures.     

Chronic Idiopathic Cough: A Discrete Clinical Entity?

STUDY OBJECTIVES: Despite the success of specialist cough clinics, there is increasing recognition of a subgroup of chronic coughers in whom a diagnosis cannot be made even after thorough, systematic investigation. We call this condition chronic idiopathic cough (CIC). The aim of this study is to compare the clinical characteristics of CIC patients with those of coughers in whom a diagnosis has been established (non-CIC) to see if there is a recognizable clinical pattern that distinguishes CIC from non-CIC. DESIGN: Retrospective analysis of the medical records of chronic cough patients. SETTING: The Royal Brompton Hospital Chronic Cough Clinic, London. PATIENTS: One hundred patients with chronic cough referred to the Royal Brompton Hospital Cough Clinic between October 2000 and February 2004. RESULTS: Seventy-one percent of all patients were female. Median age was 57 years (range, 19 to 81 years), with a median duration of symptoms of 48 months (range, 2 to 384 months). The primary diagnoses were CIC (42%), postnasal drip syndromes (22%), gastroesophageal reflux disease (16%), asthma (7%), and others (13%). In CIC patients, the median age at referral, age at onset of cough, and proportion of females did not differ significantly from non-CIC patients. CIC patients had a longer median duration of cough (72 months vs 24 months, p = 0.002), were more likely to report an upper respiratory tract infection (URTI) as the initial trigger of their cough (48% vs 24%, p = 0.0014), and had a significantly lower cough threshold in response to capsaicin (log concentration of capsaicin required to induce five or more coughs, - 0.009 vs 0.592, p = 0.032) than non-CIC patients. CONCLUSIONS: Patients with CIC commonly describe a URTI that initiates their cough, which then lasts for many years, and they demonstrate an exquisitely sensitive cough reflex. We believe that CIC may be a distinct clinical entity with an as-yet unidentified underlying pathology.     

王会仍教授自拟“王氏止咳方”治疗慢性咳嗽的临床疗效观察

目的:观察"王氏止咳方"治疗慢性咳嗽的临床效果。方法:在呼吸内科门诊选择124例诊断为慢性咳嗽的患者,随机分为对照组和观察组,每组62例。对照组用西药常规治疗,观察组口服"王氏止咳方"加减治疗,观察两组的临床疗效。结果:经治疗后对照组总有效率为70.97%,观察组总有效率为91.94%,观察组总有效率明显优于对照组(P0.05)。结论:"王氏止咳方"加减治疗慢性咳嗽疗效明显,且无不良反应,值得临床推广应用。     

布地奈德治疗儿童感染后咳嗽的临床疗效观察

目的观察雾化吸入布地奈德治疗儿童感染后咳嗽的临床疗效。方法收集2012年1月至2013年12月在我院诊断为感染后咳嗽的患儿的临床资料,对其进行回顾性分析。40例符合诊断标准的患儿分为治疗组22例,对照组18例。对照组给予常规治疗,开瑞坦5~10 m L/次,1次/d+易坦静口服液,5~10 m L/次,2次/d,对症止咳祛痰;治疗组在上述治疗的基础上,吸入布地奈德1 m L,2次/d。两组疗程均为2周,对两组的临床疗效进行评价。结果两组患儿咳嗽症状积分均明显下降,治疗组的有效率高于对照组,两组比较差异有统计学意义(P<0.01)。结论雾化吸入布地奈德在儿童感染后咳嗽治疗中具有较好的疗效,明显优于常规治疗方法。     

Cough threshold in reflux oesophagitis: influence of acid and of laryngeal and oesophageal damage

BACKGROUND: Gastro-oesophageal reflux is often associated with cough. Patients with reflux show an enhanced tussive response to bronchial irritants, even in the absence of respiratory symptoms. AIM: To investigate the effect of mucosal damage (either oesophageal or laryngeal) and of oesophageal acid flooding on cough threshold in reflux patients. PATIENTS: We studied 21 patients with reflux oesophagitis and digestive symptoms. Respiratory diseases, smoking, and use of drugs influencing cough were considered exclusion criteria. METHODS: Patients underwent pH monitoring, manometry, digestive endoscopy, laryngoscopy, and methacholine challenge. We evaluated the cough response to inhaled capsaicin (expressed as PD5, the dose producing five coughs) before therapy, after five days of omeprazole therapy, and when oesophageal and laryngeal damage had healed. RESULTS: In all patients spirometry and methacholine challenge were normal. Thirteen patients had posterior laryngitis and eight complained of coughing. Twenty patients showed an enhanced cough response (basal PD5 0.92 (0.47) nM; mean (SEM)) which improved after five and 60 days (2.87 (0.82) and 5.88 (0.85) nM; p<0.0001). The severity of oesophagitis did not influence PD5 variation. On the contrary, the response to treatment was significantly different in patients with and without laryngitis (p = 0.038). In patients with no laryngitis, the cough threshold improved after five days with no further change thereafter. In patients with laryngitis, the cough threshold improved after five days and improved further after 60 days. Proximal and distal oesophageal acid exposure did not influence PD5. Heartburn disappeared during the first five days but the decrease in cough and throat clearing were slower. CONCLUSIONS: Patients with reflux oesophagitis have a decreased cough threshold. This is related to both laryngeal inflammation and acid flooding of the oesophagus but not to the severity of oesophagitis. Omeprazole improves not only respiratory and gastro-oesophageal symptoms but also the cough threshold.