不明原因慢性咳嗽的诊断探讨

目的 探讨不明原因慢性咳嗽的病因诊断及其分布。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86例慢性咳嗽患进行分析发现，病因确诊率为89．5％(77／86)。其中咳嗽变异型哮喘(CVA)为27．9％(24／86)，鼻后滴漏综合征(PNDs)为25．6％(22／86)，嗜酸粒细胞性支气管炎(EB)为15．1％(13／86)，胃食管反流(GER)为14．0％(12／86)，双病因为7．0％(6／86)，病因未明为10．5％(9／86)。经过针对病因特异性治疗，有93．5％(72／77)患的咳嗽症状明显减轻或消失。结论 除了CVA、PNDs和GER等病因外，EB亦是慢性不明原因咳嗽的常见病因；试验性病因治疗有效是确诊病因的重要环节。     

胃食管反流性咳嗽的临床特征与诊断探讨

目的分析胃食管反流性咳嗽(GERC)的临床特征,为临床诊断GERC提供资料。方法收集我所2003年6月—2004年6月因慢性咳嗽而就诊的患者,对疑为GERC或诊断不明者行食管24hpH值监测,记录患者反流症状与呼吸道症状,包括监测期间出现的反胃、反酸、胸骨后烧灼感、胸闷和咳嗽等,记录食管上、下电极的Demeester总积分及24h食管pH<4的反流次数、反流时间>5min的次数、最长反流时间,计算总、立位、卧位pH<4的时间占监测时间的百分比,并与非GERC组患者(23例)进行比较。结果共评价250例慢性咳嗽,资料完整的192例,根据病情需要有50例行食管24hpH值监测,确诊GERC20例(GERC组),有13例存在进食相关性咳嗽,显著多于非GERC组(P<0.01),而伴反流相关症状、胃病史的发生率2组差异无统计学意义。进食相关性咳嗽对提示GERC诊断的特异性、阳性预计值和敏感性分别为91.3%、86.7%、65%。食管24hpH值监测结果显示:下电极立位pH<4的时间占监测时间的百分比显著大于卧位(P<0.05),餐后反流明显大于餐时反流(P<0.01)和立位反流(P<0.05)。结论进食相关性咳嗽对GERC的诊断有重要价值。食管24hpH值监测结果显示,GERC以餐后反流及立位反流为主,与临床表现相一致。     

慢性咳嗽病因分布的初步调查

目的 了解上海地区慢性咳嗽病因分布的特点.方法 以中华医学会制定的<咳嗽的诊断与治疗指南>(2009版)中慢性咳嗽诊断流程为指导,对98例咳嗽时间≥8周的患者进行病因分析、咳嗽症状积分、视觉模拟评分及Leicester咳嗽问卷调查.结果 98例患者中明确咳嗽病因诊断94例(95.92%),病因未明者4例(4.08%).94例患者中,单一病因82例(87.23%),双重病因12例(12.77%).咳嗽病因包括咳嗽变异性哮喘(CVA)44例(40.00%),上气道咳嗽综合征(UACS)28例(25.45%),嗜酸粒细胞性支气管炎(EB)21例(19.08%),变应性咳嗽5例(4.55%),胃食管反流性咳嗽4例(3.64%),感染后咳嗽3例(2.73%).治疗前后咳嗽积分、视觉模拟评分及Leicester咳嗽积分比较差异有统计学意义(P＜0.05).结论 CVA、UACS和EB是上海地区慢性咳嗽的常见原因.     

The Role of Speech Pathology in the Management of Patients with Chronic Refractory Cough

Cough remains refractory to medical treatment in approximately 20% of cases. Speech pathology intervention is a useful treatment option for patients with chronic cough that is refractory to treatment based on the anatomic diagnostic protocol. One of the reasons for this is that the larynx can be implicated in the pathogenesis of chronic refractory cough. There is an overlap in symptoms and clinical findings in patients with cough and those with laryngeal conditions such as paradoxical vocal fold movement. Furthermore, there is a high prevalence of voice symptoms in patients with chronic cough. Speech pathology intervention for cough comprises four components: (1) education, (2) strategies to control cough, (3) vocal hygiene training, and (4) psychoeducational counselling. The efficacy of speech pathology intervention has been examined in a single blind randomised control trial. In this trial 87% of patients in the treatment group improved, whereas 14% on the placebo group improved. Cough reflex sensitivity has also been shown to improve following speech pathology intervention for cough. This review outlines the potential mechanisms for improvement in cough, indicators for referral to speech pathology for cough, and exclusion criteria.     

Importance of atopic cough, cough variant asthma and sinobronchial syndrome as causes of chronic cough in the Hokuriku area of Japan

OBJECTIVE: A prospective multicentre study was conducted to elucidate the causes of chronic cough in Japan. METHODOLOGY: All consecutive and unselected patients complaining of cough lasting 8 weeks or more, who visited our clinics from 1 June to 31 December 2001, were registered. The causes of chronic cough were diagnosed based on the criteria for definite and probable causes of cough as recommended by the Japanese Cough Research Society. RESULTS: Of the 248 patients enrolled, 72 patients (29.0%) were unavailable for follow up before their diagnostic assessment had been finalized. Among the 176 patients who were adequately assessed, a diagnosis was made in 165 patients (93.7%) either as single cause or as one of two causes: atopic cough in 48 (29.1%) and 11 patients (6.7%); cough variant asthma in 46 (27.9%) and nine patients (5.5%); cough predominant asthma in 14 (8.5%) and three patients (1.8%); and sinobronchial syndrome (SBS) in 28 (17.7%) and 14 patients (8.5%), respectively. A diagnosis of gastro-oesophageal reflux-associated cough was made in a total of four patients (2.4%). CONCLUSION: Atopic cough, asthmatic cough consisting of cough variant asthma and cough predominant asthma, and SBS are major causes of chronic cough in Japan.     

Clinical benefit of sequential three-step empirical therapy in the management of chronic cough

Background and objective:   A prospective study was conducted to investigate the efficacy of empirical therapy in the management of chronic cough.
Methods:   A three-step empirical therapy protocol was used to treat patients who had a chronic cough and a normal CXR and normal lung function testing. In step one antihistamine decongestants plus bronchodilators were taken, corticosteroids in the second step, and a combination of a proton pump inhibitor and a prokinetic agent in the third step. Cough symptom scores were recorded before and after each step in the protocol.
Results:   There were 102 patients recruited; mean age 49 ± 16 years and with a history of cough of between 2 and 120 months at presentation. The cough resolved in 67.6% ( n  = 69) of the patients after the first-step therapy; in a further 12.7% (13) after the second-step therapy, and in another 7.8% (8) after the third-step of the treatment protocol. In three patients cough improved after the first-step of therapy but only achieved complete resolution when this treatment was combined with the third-step therapy. Overall, the three-step empirical therapy was successful in 88.2% ( n  = 90) of the patients. Cough symptom scores decreased from 3.30 ± 0.75 to 0.30 ± 0.97 ( P  < 0.001). The mean duration of treatment was 2.70 ± 1.52 weeks (range 1–12). Cough was controlled in <4 weeks in 79.4% ( n  = 81) of patients.
Conclusions:   Three-step empirical therapy seemed to be useful in most patients and has practical application in the management of chronic cough.     

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。     

Chronic cough as the sole presenting manifestation of gastroesophageal reflux

Nine patients complaining only of chronic cough of unknown cause were prospectively studied with prolonged esophageal pH monitoring (EPM) before and after cough had disappeared as a complaint in order to determine if and why gastroesophageal reflux (GER) was causing their coughs. Coughs disappeared as a complaint an average of 161 +/- 75 days after medical therapy for GER. Comparisons of pretreatment and post-treatment EPM data revealed the following: numbers of coughs (p = 0.029), total refluxes (p = 0.001), refluxes greater than or equal to 5 min (p = 0.019), and reflux-induced coughs (p = 0.005) had significantly decreased in the distal esophagus, and total refluxes (p = 0.05) had significantly decreased in the proximal esophagus. During the entire study period, the number of coughs were significantly correlated with the number of total refluxes (p = 0.039), longest reflux (p = 0.019), number of refluxes greater than or equal to 5 min (p = 0.006), and percent of total time that pH was less than 4 (p = 0.017) in the distal esophagus. On the basis of these results, we conclude that (1) cough can be the sole presenting manifestation of GER, and it gradually responds to standard GER therapy; (2) prolonged EPM is safe, well-tolerated, and extremely useful in diagnosing clinically silent GER; (3) the mechanism by which GER causes cough is related to a critical number and/or duration of reflux episodes in the distal and/or proximal esophagus.     

The Japanese respiratory society guidelines for the management of cough and sputum (digest edition)

Cough and sputum are common complaints at outpatient visits. In this digest version, we provide a general overview of these two symptoms and discuss the management of acute (up to three weeks) and prolonged/chronic cough (longer than three weeks). Flowcharts are provided, along with a step-by-step explanation of their diagnosis and management. Most cases of acute cough are due to an infection. In chronic respiratory illness, a cough could be a symptom of a respiratory infection such as pulmonary tuberculosis, malignancy such as a pulmonary tumor, asthma, chronic obstructive pulmonary disease, chronic bronchitis, bronchiectasis, drug-induced lung injury, heart failure, nasal sinus disease, sinobronchial syndrome, eosinophilic sinusitis, cough variant asthma (CVA), atopic cough, chronic laryngeal allergy, gastroesophageal reflux (GER), and post-infectious cough. Antibiotics should not be prescribed for over-peak cough but can be considered for atypical infections. The exploration of a single/major cause is recommended for persistent/chronic cough. When sputum is present, a sputum smear/culture (general bacteria, mycobacteria), cytology, cell differentiation, chest computed tomography (CT), and sinus X-ray or CT should be performed. There are two types of rhinosinusitis. Conventional sinusitis and eosinophilic rhinosinusitis present primarily with neutrophilic inflammation and eosinophilic inflammation, respectively. The most common causes of dry cough include CVA, atopic cough/laryngeal allergy (chronic), GER, and post-infectious cough. In the last chapter, future challenges and perspectives are discussed. We hope that the clarification of the pathology of cough hypersensitivity syndrome will lead to further development of “pathology-specific non-specific therapeutic drugs” and provide benefits to patients with chronic refractory cough.     

慢性咳嗽病因分布的初步调查

目的了解上海地区慢性咳嗽病因分布的特点。方法以中华医学会制定的《咳嗽的诊断与治疗指南》（2009版）中慢性咳嗽诊断流程为指导,对98例咳嗽时间≥8周的患者进行病因分析、咳嗽症状积分、视觉模拟评分及Leicester咳嗽问卷调查。结果 98例患者中明确咳嗽病因诊断94例（95.92%）,病因未明者4例（4.08%）。94例患者中,单一病因82例（87.23%）,双重病因12例（12.77%）。咳嗽病因包括咳嗽变异性哮喘（CVA）44例（40.00%）,上气道咳嗽综合征（UACS）28例（25.45%）,嗜酸粒细胞性支气管炎（EB）21例（19.08%）,变应性咳嗽5例（4.55%）,胃食管反流性咳嗽4例（3.64%）,感染后咳嗽3例（2.73%）。治疗前后咳嗽积分、视觉模拟评分及Leicester咳嗽积分比较差异有统计学意义（P〈0.05）。结论 CVA、UACS和EB是上海地区慢性咳嗽的常见原因。     

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.     

A pathogenic triad in chronic cough: asthma, postnasal drip syndrome, and gastroesophageal reflux disease.

BACKGROUND: Coughing may be produced by a number of different disorders in distinct anatomic sites. Chronic cough causes major functional limitation in a considerable patient population and requires careful evaluation. METHODS: Seventy-eight nonsmoking patients of both genders who complained of cough for > or =3 weeks and had normal findings on plain chest radiographs were studied prospectively. Their histories were obtained, and physical examinations were performed. The diagnostic workup included pulmonary function tests, CT of the paranasal sinuses and chest, carbachol provocation test, fiberoptic rhinoscopy, fiberoptic bronchoscopy, and 24-h esophageal pH monitoring. The final diagnosis depended on clinical, radiologic, and laboratory findings; a successful response to therapy was required for confirmation. RESULTS: The causes of chronic cough were determined in all patients. Coughing was due to a single cause in 30 patients (38.5%) and multiple causes in 48 patients (61.5%). The five most important causative factors were asthma (46 patients; 58.9%), postnasal drip syndrome (PNDS; 45 patients; 57.6%), gastroesophageal reflux disease (GERD; 32 patients; 41.1%), bronchiectasis (14 patients; 17.9%), and tracheobronchial collapse (11 patients; 14.1%). INTERPRETATION: Asthma, PNDS, and GERD, alone or in combination, were responsible for 93.6% of the cases of chronic cough. The presence of these three conditions was so frequent that the expression "pathogenic triad of chronic cough" should be acknowledged in specialized literature. It is essential to consider pulmonary and extrapulmonary causes in order to prescribe a successful specific therapy for chronic cough.     

Cough and Asthma

Cough is the most common complaint for which patients seek medical attention. Cough variant asthma (CVA) is a form of asthma, which presents solely with cough. CVA is one of the most common causes of chronic cough. More importantly, 30 to 40% of adult patients with CVA, unless adequately treated, may progress to classic asthma. CVA shares a number of pathophysiological features with classic asthma such as atopy, airway hyper-responsiveness, eosinophilic airway inflammation and various features of airway remodeling. Inhaled corticosteroids remain the most important form of treatment of CVA as they improve cough and reduce the risk of progression to classic asthma most likely through their prevention of airway remodeling and chronic airflow obstruction.     

Gastroesophageal reflux: pathogenesis, diagnosis, and treatment.

Gastroesophageal reflux (GER) is a common problem confronting physicians involved in the care of children and adults. With the association of GER with asthma and chronic cough, physicians specializing in allergy/immunology require information on the pathogenesis, diagnosis, and management of GER. Eosinophilic esophagitis or eosinophilic gastroenteritis are poorly understood entities that may also lead to symptoms mimicking GER and are associated in many cases with underlying hypersensitivity of unknown immunologic mechanism.     

Pathologic gastroesophageal reflux in patients with bronchial asthma

Gastrooesophageal reflux (GER) and asthma bronchiale are frequent diseases. Asthma affects some 3-10% of adults. Gastrooesophageal reflux is present in some 45-89% asthmatic patients. Symptoms of GER are not only gastrooesophageal, and recently increased attention is focused on extraoesophageal symptoms where in particular the relationship of GER and asthma or chronic cough is investigated. At our clinic we implemented a pilot study with the objective to monitor the presence of pathological GER in patients with asthma and to assess whether antireflux therapy will influence the respiratory complaints of the patients. The group was formed by 14 patients selected at random with different severity of asthma and different symptoms of GER. The patients had a baseline examination evaluating the presence of GER (24-hour pH metry) and pulmonary function (FEV1). In case of a pathological GER the patients were treated by antireflux therapy and then check-up examinations were made. It was found that after treatment of GER in patients with asthma in particular subjective symptoms improved such as cough and pyrosis which leads to a substantial improvement of the quality of life. On the other hand reflux treatment did not exert a basic effect on pulmonary functions and it was not possible to reduce the medication of asthma.     

不明原因慢性咳嗽的病因分布及诊断程序的建立

目的观察慢性咳嗽的病因分布,在此基础上建立慢性咳嗽的病因诊断程序。方法对于入选的慢性咳嗽患者,在询问病史和查体的基础上,进行诱导痰、肺通气功能+气道高反应性、X线胸片、鼻窦X线片或CT、24h食管pH值监测等检查,根据检查结果和治疗反应,最后确定病因诊断。结果共收集慢性咳嗽患者194例,平均年龄(41±12)岁(16～71岁),平均咳嗽时间(62±86)个月(2～487个月)。慢性咳嗽病因比例依次为:嗜酸粒细胞性支气管炎51例次(22.4%)、鼻炎/鼻窦炎39例次(17.1%)、咳嗽变异型哮喘31例次(13.6%)、变应性咳嗽28例次(12.3%)、胃食管反流性咳嗽27例次(11.8%)、其他病因43例次(18.8%),病因未明9例次(3.9%)。单一病因咳嗽者153例(82.7%),复合病因32例(17.3%)。结论慢性咳嗽的病因分布与国外相比有着较大的差别,嗜酸粒细胞性支气管炎和变应性咳嗽是慢性咳嗽的重要病因。根据上述慢性咳嗽病因分布和临床特征,提出了新的慢性咳嗽病因诊断程序。     

Cough and asthma

Cough variant asthma and the closely related corticosteroid responsive cough syndromes eosinophilic bronchitis and atopic cough are common causes of chronic cough. The diagnosis is often not overt but detailed investigation of airway responsiveness and airway inflammation can be helpful. Cough variant asthma, eosinophilic bronchitis and atopic cough are all associated with eosinophilic airway inflammation, which is similar to that seen in non-cough predominant asthma. However, evidence of activated mast cells and increased concentrations of mast cell products appears to be confined to the conditions associated with cough, suggesting a role for mast cell degranulation in the superficial airway structures in the pathogenesis of cough. Cough variant asthma is typically corticosteroid responsive; leukotriene antagonists and antihistamines also help. Further study of this interesting asthma variant may increase our understanding of the relationship between airway inflammation and airway dysfunction.     

Gastro-oesophageal reflux disease and respiratory disease

Abstract An epidemiological survey showed that respiratory symptoms with gastro-oesophageal reflux (GER) were twice as high as those without GER symptoms. In 46 cases of unknown chronic cough or asthma, 67% had positive oesophageal pH monitoring. Of 34 patients with snoring and reflux symptoms, 16 (47.1%) were confirmed as positive for obstructive sleep apnoea (OSA) and GER. Anti-reflux therapy significantly improved both GER and OSA.     

Cough variant asthma: a review of the clinical literature.

Cough variant asthma is an occult form of asthma of which the only sign or symptom is chronic cough. This review examines 15 clinically oriented research articles on cough variant asthma and summarizes what is known about its frequency of occurrence, clinical presentation, diagnosis, treatment, and natural history. Cough variant asthma is a common problem among all ages that frequently goes unrecognized. Pulmonary function, as measured by spirometry, is often within normal limits. Any patient with a nonproductive, nocturnal cough lasting more than two weeks, should receive an empiric trial of bronchodilators. The natural history of cough variant asthma is variable. A significant proportion of patients followed over time develop the classic signs and symptoms of asthma, whereas for many patients, cough resolves without need for further treatment.     

Current Status and Future Directions of Chronic Cough in China

Chronic cough is one of the most common complaints for which patients in China seek medical attention. However, there are no nationwide data on the prevalence and socioeconomic burden of chronic cough. Although approximately 50% of Chinese men smoke, the vast majority of patients presenting for evaluation of chronic cough are never smokers. An equal sex distribution and a middle-aged predominance have been observed in the Chinese chronic cough population, despite demonstration of a higher cough reflex sensitivity in females and older patients. The role of air pollution in the distinct age and sex distribution requires further study. In terms of the etiologies of chronic cough in China, cough-variant asthma, upper airway cough syndrome, nonasthmatic eosinophilic bronchitis, and atopic cough are the most common causes, comprising 75.2% to 87.6% of cases across different regions. Chinese Guidelines for Diagnosis and Treatment of Cough were initially published in 2005, and updated in 2009 and 2016. In addition, the China Cough Coalition was established in 2016. Great progress has been made in both cough-related clinical practice and research in recent years, however, there are still challenges ahead. To facilitate optimal management of chronic cough in China, efforts promoting the dissemination and application of published guidelines will be essential, especially in community-based healthcare and in rural regions. As chronic refractory cough has been identified as a huge challenge to clinicians worldwide, continued international cooperation will be essential in optimizing evaluation and management of chronic cough.