Cough suppression therapy: Does it work?

Cough suppression therapy (CST), also known as cough suppression physiotherapy and speech pathology management is a promising non-pharmacological therapeutic option for patients with refractory chronic cough. CST may consist of education, improving laryngeal hygiene and hydration, cough suppression techniques, breathing exercises and counselling. It is an out-patient therapy delivered in 2-4 sessions. There is evidence to support the efficacy of CST: a randomised controlled trial reported a significant reduction in cough symptoms and other studies have reported improved cough related quality of life, reduced cough reflex hypersensitivity and cough frequency. The mechanism of action of CST is not clear, but it has been shown to reduce cough reflex sensitivity, paradoxical vocal fold movement (PVFM) and extrathoracic hyperresponsiveness. Further research is needed to determine the optimal components of CST, the characteristics of patients in whom it is most effective and to increase the understanding of its mechanisms of action. The effectiveness of CST in other respiratory conditions such as asthma, pulmonary fibrosis, chronic obstructive pulmonary disease and sarcoidosis should also be investigated.     

Cough induction by high-frequency chest percussion in healthy volunteers and patients with common cold

BACKGROUND: In patients with chronic obstructive pulmonary disease, chest percussion is often used to facilitate the drainage of respiratory secretions which may be removed from the airway by coughing. The cough reflex is believed to be mediated by mechanically sensitive rapidly adapting receptors (RARs). Chest percussion stimulation may stimulate RAR cough receptors, but there is no evidence that mechanical airway stimulation in man induces cough. The aim of this study was to determine if cough can be induced by high-frequency chest percussion in healthy subjects and in patients with acute upper respiratory tract infection (URTI). METHODS: Two groups were studied: 15 healthy subjects and 29 subjects with URTI, mean age 22 years. Percussion stimulation (70 Hz) was applied to the chest. Cough frequency and latency were recorded. All subjects were asked to complete a questionnaire about how they felt after the chest percussion by questionnaires. RESULTS: The results demonstrate that high-frequency chest percussion causes cough in human subjects with a recent history of URTI, but induces relatively little cough in healthy subjects. In URTI subjects there was a significant increase in the number of coughs after three periods of airway vibration, whereas in healthy subjects there was no change in cough. Furthermore, analysis of the questionnaires showed that more of the subjects with URTI felt an urge to cough compared to the healthy subjects in the subjective questionnaires. CONCLUSIONS: This study demonstrates that cough can be induced in subjects with URTI by chest percussion. This method of inducing cough in subjects with URTI may be useful for studies on the mechanism of cough and for studies on antitussive medicines.     

慢性咳嗽新概念：慢性咳嗽高反应综合征

慢性咳嗽的病因学分类在临床运用当中存在一定困难。新近提出慢性咳嗽高反应综合征的概念,它是一类具有咳嗽反射高反应性的不同临床情况的统一诊断。本文将对慢性咳嗽高反应综合征这一概念作一综述。     

Mechanisms of chronic cough

Chronic and uncontrollable cough is one of the most common and debilitating symptoms found in patients with chronic airway diseases. The physical trauma and stresses of chronic cough on the airway mucosa and respiratory muscles can further worsen the deteriorating process of the airway diseases. The articles presented in this section focus primarily on the effect of chronic cough on the cell structure and protective function of the airway mucosa, the mechanisms underlying the hypersensitivity of chronic cough, and new target areas for antitussive drug development. A major emphasis has been placed on the neuronal plasticity found at the peripheral and central sites of the neural pathway mediating the cough reflex, and its potential role in the development of chronic cough is discussed. A number of new and important questions concerning the physiological and pharmacological mechanisms underlying chronic cough have emerged in these presentations. Further studies are required to answer these questions, which should bring a better understanding of the pathogenic mechanisms of chronic cough and lead to the development of new therapeutic strategies.     

Severe chronic cough after Lap-Band gastric surgery

Respirologists are often consulted in cases of chronic cough. Most patients have diagnoses of asthma, upper airway cough or gastroe-sophageal reflux disease. The present case describes a newly recognized cause of a cough in a patient who had undergone laparoscopic adjustable gastric banding for weight loss. The cough was persistent and severe for several months, and did not respond to any therapeutic interventions. Imaging studies were not helpful in making the diagnosis, which was confirmed by deflating the Lap-Band, thereby eliminating the cough.As more patients undergo bariatric surgery, physicians must anticipate and be familiar with potential complications.     

Cough induced by airway vibration as a model of airway hyperreactivity in patients with acute upper respiratory tract infection

Patients with acute upper respiratory tract infection (URTI) have been shown to be hyperreactive to inhaled tussigens such as citric acid and capsaicin, and the authors propose that this may be due to an increased sensitivity of airway receptors that mediate cough. In recent studies we have demonstrated that cough may be induced by vibration of the airway at the level of the throat or chest in patients with URTI but that the same stimuli induce little or no cough in healthy subjects. The difference between the patients with URTI and healthy subjects in their response to airway vibration may be explained on the basis of hyperreactivity of airway sensory receptors. We propose that the model of cough induced by airway vibration may be useful for studies on the pathophysiology and pharmacology of airway hyperreactivity in acute cough. The airway vibration model of cough may have some advantages over inhaled tussigens as the stimulus is easily controlled and the method is safe for use in children.     

复方磷酸可待因溶液和美敏伪麻溶液治疗急性咳嗽的疗效和安全性比较

目的以美敏伪麻溶液（惠菲宁）为阳性对照,对复方磷酸可待因溶液（奥亭止咳露）治疗急性咳嗽的有效性和安全性进行评价。方法以由急性上呼吸道感染、急性气管/支气管炎、慢性支气管炎急性加重和上气道咳嗽综合征引起的咳嗽患者为研究对象,采用多中心、分层区段随机、拟双盲对照的临床试验方法,观察两组患者首次服药0、15、30、60和120min以及治疗前后咳嗽、痰黏度和排痰难易程度总积分（TSS）。结果符合方案集4个中心治疗结束时试验组症状总分较对照组低[（1.082±1.590）分vs（1.699±1.866）分],试验组症状总分下降较对照组明显[（6.412±1.978）分vs（4.313±2.347）分],治疗有效性（痊愈和显效）试验组优于对照组[（68.60%和13.95%）vs（44.58%和22.89%）]（P值均〈0.05）,4个中心试验组总有效率高于对照组（82.56%vs67.47%）。试验组15、30、60和120min时TSS均低于对照组（P值均〈0.05）。治疗后咳嗽程度改善试验组优于对照组（P〈0.05）,而两组痰黏度和排痰难易程度改善差异无统计学意义（P〉0.05）。全分析集与符合方案集结果一致。研究期间两组均无严重不良事件发生,两组不良事件发生率以及合并用药的比例差异均无统计学意义（P〉0.05）。结论复方磷酸可待因溶液对于控制咳嗽症状具有起效快的特点,并且在服药15min时其疗效已经显著优于美敏伪麻溶液。通过5～7d治疗,复方磷酸可待因溶液对于控制咳嗽症状的效果可能优于美敏伪麻溶液。     

Inhaled corticosteroid for persistent cough following upper respiratory tract infection

OBJECTIVE: The aim of this study was to determine the clinical effect of inhaled corticosteroid treatment for persistent cough, post upper respiratory tract infection (URTI) in previously healthy individuals, and on bronchial hyperresponsiveness (BHR). METHODOLOGY: This was a prospective, randomized, double-blinded, placebo-controlled study conducted at a university hospital. A total of 30 non-asthmatic, non-smoking patients who were >15 years old and who had persistent post-URTI cough for >3 weeks were assessed by a physical examination, CXR and spirometry, and were allocated to receive inhaled budesonide (400 microg/puff, twice daily) or placebo for 4 weeks. If a patient suffered from sinusitis, it was a requirement that it had been well treated. A symptom score (frequency of cough, frequency of coughing bouts, symptoms associated with cough, night-time cough, frequency of taking medications to relieve cough, and number of medications) was recorded at entry, and after 2 and 4 weeks of treatment. A methacholine challenge test was performed at entry and after 4 weeks of treatment. RESULTS: The mean symptom scores for the treatment group (9.4) and the placebo group (9.8) at baseline were not significantly different (P=0.79), and no differences were found between the groups after week 2 and week 4 of treatment (3.93 and 4.27 vs 2.26 and 2.66, P=0.29). The mean change in symptom scores from baseline to week 2 and to week 4 of treatment were also not different between groups (5.93 and 5.6 vs 7.00 and 7.58, P=0.23). No difference between groups was found in the mean changes in FEV(1), FVC, and FEF(25--75%) after 4 weeks of treatment. A positive bronchial provocation test occurred in three patients (10%) but these were borderline. CONCLUSION: Inhaled corticosteroid is ineffective in treating persistent post-URTI cough in previously healthy individuals.     

慢性咳嗽患者咳嗽激发试验的意义

目的 初步观察咳嗽激发试验在不同性别、病程、病因的慢性咳嗽患者中的差异,以期为进一步评价咳嗽激发试验的临床意义及对临床诊疗慢性咳嗽提供启迪和帮助.方法 选择进行了咳嗽激发试验并最终确诊为上气道咳嗽综合征(UACS)、咳嗽变异性哮喘(CVA)、胃食管反流性咳嗽(GERC)的慢性咳嗽患者108例,分析咳嗽激发试验在不同病因、病程、性别的慢性咳嗽患者间的差异.结果 108例慢性咳嗽患者中UACS 76例,CVA 19例,GERC 13例.咳嗽敏感性阈值的对数(lgC5)女性患者(1.80)显著低于男性(2.40,P<0.05);病程≥12个月患者lgC5(1.80)显著低于病程<12个月的患者(2.40,P<0.05);不同病因患者lgC5存在显著差异,其中GERC患者的lgC5(1.49)显著低于CVA(2.40,P<0.05)和UACS(2.40,P<0.05)患者.结论 不同病因、病程、性别的慢性咳嗽患者咳嗽敏感性均存在差异,咳嗽激发试验在慢性咳嗽病因诊断中具有重要价值.

Abstract：

Objective Preliminary study of the cough reflex sensitivity test in chronic cough patients with different gender,disease duration and causes to evaluate the clinical diagnostic significance of the test and further provide some information for the treatment of chronic cough.Methods Totally 108 chronic cough patients in our hospital were enrolled in the study with the final diagnosis of upper airway cough syndrome(UACS),cough variant asthma(CVA)and gastroesophageal reflux cough(GERC).They all went through the cough reflex sensitivity test and the retrospective analysis of the results was made.Results In 108 patients with chronic cough(76 UACS,19 CVA and 13 GERC),lgC5 was significantly slower in the female(1.80)than the male(2.40,P<0.05)and in the patients with cough duration over 12 months(1.80)than those with cough duration under 12 months(2.40,P<0.05).Cough sensitivity in patients with different causes was significantly different(P<0.05)with lower lgC5 in GERC patients(1.49)than CVA (2.40,P<0.05)and UACS(2.40,P<0.05)patients.Conclusion Cough sensitivity is different in chronic cough patients with different gender,disease duration and causes.Cough reflex sensitivity test is of great value in the etiology diagnosis of chronic cough.     

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.     

支气管激发试验在慢性咳嗽病因诊断中的运用价值

目的 探讨支气管激发试验(bronchial provocation test,BPT)在慢性咳嗽及咳嗽变异型哮喘(cough variant asthma,CVA)诊断中的应用价值.方法 对1 155例慢性咳嗽患者进行乙酰甲胆碱BPT,检测其气道高反应性.结果 1 155例慢性咳嗽患者中,各年龄组肺功能参数比较差异无统计学意义.BPT阳性584例,阴性571例,阳件率50.6%.确诊为CVA 547例;其余37例BPt阳性慢性咳嗽患者中25例为感染后咳嗽,12例为慢性支气管炎.BPT诊断CVA的特异度为93.6%.小于30岁年龄组CVA比例最高,占慢性咳嗽68.8%;≥60岁组CVA百分比最低,为23.5%.结论 CVA足慢性咳嗽的主要病因,对不明原因的慢性咳嗽患者应及时进行BPT,有助于早期明确诊断并施以正确治疗.     

112例误诊为支气管炎的老年慢性咳嗽病因分析

目的探讨老年患者慢性咳嗽的误诊及病因分布。方法基层医院误诊为支气管炎的112例老年慢性咳嗽患者,采用咳嗽诊治指南制定的诊断程序,判断病因并予针对性治疗。结果最终病因明确107例(95.54%),其中单一病因为89例(79.46%),复合病因为18例(16.07%)。老年患者病因诊断前三位为胃食管返流性咳嗽、咳嗽变异型哮喘、上气道咳嗽综合征,在女性患者和男性患者中分别占26.39%,20.83%,18.06%和29.31%,22.41%,18.97%。三者占慢性咳嗽病因的67.69%,其次是ACEI诱发的咳嗽。经特异性治疗后咳嗽明显减轻或消失为103例,有效率为91.96%,其余均为部分缓解。结论老年慢性咳嗽病因复杂常被误诊,规范慢性咳嗽病因诊断程序对提高老年慢性咳嗽诊治水平有重要意义。     

慢性咳嗽病因分布频率的季度差异

目的 探讨一年间各季度慢性咳嗽病因分布频率的改变.方法 收集2009年1月至2009年12月间连续在同济大学附属同济医院呼吸内科就诊并经逐步诊断流程探查病因的290例慢性咳嗽患者,以季度为单位分成4组,通过X2检验分析各季度病因分布频率的差异.结果 一年中慢性咳嗽病例数第2季度最多,第4季度最少.咳嗽变异性哮喘的分布频率因季节不同而变化,从第1季度63.8%降至第4季度35.4%(X2=11.334,P＝0.01).而其他病因无明显季节差异.结论 咳嗽变异性哮喘的分布频率随季度而变化.     

新疆地区150例不明原因咳嗽临床病因分析

目的 分析新疆地区不明原因咳嗽的病因及治疗效果.方法 采用Irwin慢性咳嗽解剖学诊断程序,并补充诱导痰细胞分类检查,对慢性咳嗽的病因进行分类,并针对病因进行特异性治疗.结果 应用该方法对150例慢性咳嗽患者进行分析发现,病因确诊率为96%（144/150）.患者中单一咳嗽者125例（86.8%）,复合咳嗽者19例（13.2%）,慢性咳嗽病因比例依次为：上气道咳嗽综合征58例（34.3%）,咳嗽变异型哮喘41例（24.3%）,嗜酸粒细胞性支气管炎为24例（14.2%）,胃食管反流为14例（8.3%）,支气管结核10例（5.9%）,其他病因16例（9.5%）,病因未明6例（3.6%）,经过针对病因特异性治疗,有93%（140/150）患者的咳嗽症状明显减轻或消失.结论 在本地区除上气道咳嗽综合征、咳嗽变异型哮喘、嗜酸粒细胞性支气管炎和胃食管反流等病因外,支气管结核亦是慢性不明原因咳嗽的重要病因,诊断性治疗有效是确诊病因的重要环节.     

新疆地区儿童慢性咳嗽病因构成分析

目的分析新疆地区儿童慢性咳嗽的病因特点。方法对收集的653例慢性咳嗽患儿的临床资料进行前瞻性研究,包括主要病因、年龄、民族、过敏原、家族史、环境因素、肺功能情况。结果新疆地区儿童慢性咳嗽病因多为呼吸道感染和感染后咳嗽192例(29.40%)、咳嗽变异性哮喘158例(24.20%)和上气道咳嗽综合征140例(21.44%)。另外,其他病因163例(24.96%),其中双重病因84例(12.87%),病因不明5例(0.77%);慢性咳嗽的主要病因在不同年龄、不同民族亦不同:婴幼儿(0~3岁)慢性咳嗽的主要病因为感染/感染后咳嗽,学龄前儿童(4~6岁)主要病因亦为感染/感染后咳嗽(PIC),学龄期儿童(6~14岁)主要病因为咳嗽变异性哮喘(CVA)和上气道咳嗽综合征(UACS);汉族和哈萨克族儿童慢性咳嗽主要病因以PIC最多,维吾尔族、回族和蒙古族儿童中则以CVA多见。结论新疆地区儿童慢性咳嗽的主要病因依次为呼吸道感染和感染后咳嗽、咳嗽变异性哮喘和上气道咳嗽综合征,不同年龄、不同民族慢性咳嗽的病因构成比不同。具有个人过敏史、家族过敏史、不良外界环境接触史及肺功能异常的患儿更易诊断为咳嗽变异性哮喘。     

A Preliminary Study of PEFR Monitoring in Patients with Chronic Cough

It is important to make a differential diagnosis of cough variant asthma in patients with chronic cough. To examine whether or not peak expiratory flow rate (PEFR) is useful for the differential diagnosis of cough variant asthma in such patients, diurnal variation rates of PEFR were calculated in 23 patients who presented with dry cough lasting four or more weeks and who showed no abnormalities on chest radiographs. None of the patients had wheezes, and pulmonary function testing at the time of visit to the hospital revealed no abnormalities. During the control period, the mean diurnal variation rate of PEFR in 23 patients was 16.3 ± 7.9%. Six, nine and eight patients had PEFR diurnal variations rates of <10% (Group 1), 10–19% (Group 2), and 20% (Group 3), respectively. At week 3 of treatment with bronchodilators, only Group 3 showed a significant decrease in PEFR diurnal variation rate from 25.7% to 10.1%. The cough score decreased significantly in Group 3 only. These patients had enhanced bronchial hyperresponsiveness and showed eosinophils in induced sputum, leading to the diagnosis of cough variant asthma (CVA). After making the diagnosis of CVA, an inhaled corticosteroid or a Th2 cytokine production inhibitor suplatast tosilate was administered to patients; consequently, they showed no recurrence of cough. PEFR monitoring allowed the detection of morning dip and was suggested to be potentially useful for the differential diagnosis of cough variant asthma in patients with chronic cough.     

Down-regulation of cough sensitivity after eucapnic dry air provocation in chronic idiopathic cough

Down-regulation of cough sensitivity in humans is rarely discussed in terms other than pharmacological treatment of cough or hypersensitive cough reflex. Chronic cough and increased cough sensitivity could be due to a number of airway and other diseases. When such conditions are excluded, there still remains a group of patients with no evident medical explanation for persistent coughing; such patients are often described as having “chronic idiopathic cough”.The aim of this study was to use a standardized eucapnic dry air provocation among patients with chronic idiopathic cough in order to study physiological parameters and measure their possible influence on capsaicin cough sensitivity. Fourteen female patients with chronic idiopathic cough and ten healthy controls underwent a capsaicin inhalation provocation on two occasions. In all patients, irritating environmental factors were known to induce cough and airway symptoms. One of the two capsaicin provocations was preceded by a eucapnic dry air provocation. Number of coughs, spirometry, respiratory rate, pulse rate, end-tidal CO₂, and oxygen saturation by pulse oximetry (PSaO₂) were registered and compared. The patients showed increased capsaicin sensitivity compared with the control subjects. This sensitivity was decreased when the capsaicin test was preceded by a eucapnic dry air provocation. Before the dry air provocation and after the capsaicin provocations, end-tidal CO₂ was decreased among the patients in comparison with the controls. After dry air provocation, spirometry values remained unchanged.The results suggest that in patients with chronic idiopathic cough, physiological down-regulation of the cough sensitivity is possible with a eucapnic dry air provocation.     

小儿慢性咳嗽的诊断体会

目的探讨小儿慢性咳嗽的诊断方法。方法对146例慢性咳嗽患儿临床资料按年龄分婴幼儿、学龄前、学龄儿童三组进行回顾性分析。结果咳嗽变异性哮喘、反复呼吸道感染、上气道咳嗽综合征是小儿慢性咳嗽主要病因,其次为结核感染、上感后慢性咳嗽、支原体感染。不同年龄慢性咳嗽病因不尽相同,年龄越小,反复呼吸道感染所占比率越高,年龄越大,咳嗽变异型哮喘比率越高。结论小儿慢性咳嗽的病因复杂多样,除病史、体检以外,患儿年龄、针对性的辅助检查及试验性治疗的反应都能提供诊断线索。     

Serum LDH in chronic cough: a potential marker of airway inflammation

Introduction and Objectives: Lactate dehydrogenase (LDH) is found in almost all tissues of the body and five different isoenzymes are known (LDH‐1 to LDH‐5). LDH can be elevated in many pathological conditions. We have observed serum LDH to be increased in patients with chronic cough. We wanted to confirm this finding, study the reproducibility and determine the origin of the LDH. Methods: Patients prospectively seen at the Hull Cough Clinic had total and specific LDH isoenzyme levels in serum determined. A subgroup of patients also had a serum creatine phosphokinase (CK) measured. Patients completed cough symptom scores and the Hull Airway Reflux Questionnaire (HARQ). Spirometry was performed. Results: Eighty‐three patients were included. Forty‐two percent had LDH values above the reference range and 78% had LDH values in the fourth quartile of the reference range or above. This increase in LDH was predominantly because of a rise in isoenzymes 4 and 5. The increase in LDH was found to be reproducible at 8 weeks. Ten percent had CK values above the normal range. There was no correlation observed between LDH values and the cough scores, HARQ scores or lung function. Conclusion: Serum LDH levels are elevated in a substantial proportion of patients with chronic cough. This rise is likely to be due to airway inflammation known to be associated with chronic cough. Please cite this paper as: Faruqi S, Wilmot R, Wright C and Morice AH. Serum LDH in chronic cough: a potential marker of airway inflammation. Clin Respir J 2012; 6: 81–87.     

病毒感染后咳嗽发病机制的研究进展

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