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。     

慢性咳嗽病因变迁的回顾性分析

目的 探讨慢性咳嗽病因变迁的临床意义.方法 收集2004年1月至2008年12月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940例慢性咳嗽患者,以年为单位分成5组,通过x2检验回顾性分析慢性咳嗽病因分布频率和构成的变化趋势.结果 慢性咳嗽的常见病因依次为咳嗽变异性哮喘(437/940,46%)、上气道咳嗽综合征/鼻后滴流综合征(304/940,32%)、嗜酸粒细胞性支气管炎(87/940,9%)、胃食管反流性咳嗽(83/940,9%)、感染后咳嗽(60/940,6%)和血管紧张素转换酶抑制剂相关咳嗽(46/940,5%).5年间慢性咳嗽病因分布频率存在明昆差异(x2=60.6,P=0.0001),咳嗽变异性哮喘从44%增至51%(x2=12.8,P=0.010),上气道咳嗽综合征/鼻后滴流综合征从49%降至29%(x2=20.1,P=0.001),胃食管反流性咳嗽从2%增至10%(x2=17.6,P=0.002),而嗜酸粒细胞性支气管炎、感染后咳嗽和血管紧张素转换酶抑制剂相关咳嗽分布频率保持不变.结论 慢性咳嗽主要病因随时间发生变迁,可影响相应的诊治策略.     

"不明原因"慢性咳嗽的病因构成和临床特征分析

目的 分析经遵循我国慢性咳嗽诊断流程明确的慢性咳嗽患者的病因构成和临床特征,为经验性诊治慢性咳嗽提供依据.方法 对"不明原因"慢性咳嗽患者,遵循我国咳嗽指南慢性咳嗽诊断流程,在询问病史和查体的基础上,进行常规肺通气功能测定和支气管激发试验、诱导痰细胞学检查、鼻窦X线片或CT、24 h食管pH值监测等检查,根据检查结果和治疗后反应,最后确定病因诊断.收集卫生部中日友好医院患者病因资料并与广州呼吸疾病研究所的研究结果进行比较,以x2检验比较构成比差异.结果 2005年10月至2009年2月共收集不明原因慢性咳嗽患者103例,明确诊断咳嗽病因123例次.慢性咳嗽病因分布依次为咳嗽变异性哮喘41例次(33.3%),鼻炎/鼻窦炎30例次(24.4%),胃食管反流性咳嗽25例次(20.3%),药物性咳嗽7例次(5.7%),嗜酸粒细胞性支气管炎6例次(4.9%),变应性咳嗽4例次(3.3%),肺间质纤维化2例次(1.6%),左心功能不全和支气管扩张各1例次(0.8%),病因未明6例次(4.9%).单一病因咳嗽者86例(83.5%),二重病因14例(13.6%)、三重病因3例(2.9%).咳嗽变异性哮喘患者夜间咳嗽发生率最高[80.9%(36/41),x2=19.81,P<0.01],63.4%(26/41)合并鼻炎,68.3%(28/41)有季节性加重,其中67.8%(19/28)于秋季加重;胃食管反流性咳嗽以日间咳嗽为主,56.0%(14/25)有进食相关性咳嗽,68.0%(17/25)伴有反流相关症状;鼻炎/鼻窦炎患者有痰咳嗽发生率最高[73.3%(22/30),x2=24.99,P<0.01].与广州资料相比,咳嗽变异性哮喘和胃食管反流性咳嗽比例高于广州(x2值分别为9.52和4.56,均P<0.01),而嗜酸粒细胞性支气管炎和变应性咳嗽比例低于广州(x2值分别为17.61和7.86,均P<0.01).结论 慢性咳嗽常见病因构成为咳嗽变异性哮喘、鼻炎/鼻窦炎、胃食管反流性咳嗽、药物性咳嗽、嗜酸粒细胞性支气管炎和变应性咳嗽,与广州资料比较具有一定的差异.各种病因的咳嗽具有一定的临床特征,慢性咳嗽的病因构成和临床特征可为经验性诊治慢性咳嗽提供依据.     

慢性咳嗽的病因分布及其治疗研究

目的探讨慢性咳嗽常见病因分布及治疗方法。方法介绍在我院呼吸内科及耳鼻喉科门诊或住院的157例慢性咳嗽患者的病史、体检、血常规、心电图、胸部X线、肺功能、副鼻窦X线及心脏彩超等进行检查,确定病因诊断及相应的治疗。结果慢性咳嗽病因分布的顺序依次为：上气道咳嗽综合征40例（25.5%）,咳嗽变异性哮喘33例（21.0%）,胃食管反流性咳嗽29例（18.5%）,感染后咳嗽27例（17.2%）,嗜酸粒细胞性支气管炎7例（4.5%）,血管紧张素转化酶抑制剂（ACEI）类药物诱导的药物性咳嗽7例（4.5%）,慢性心功能不全6例（3.8%）,原因未明8例（5%）。149例（94.9%）患者经病因治疗后咳嗽症状消失或明显减轻。结论慢性咳嗽常见的主要病因为：上气道咳嗽综合征、咳嗽变异性哮喘、胃食道反流性咳嗽等。慢性咳嗽病因复杂,误诊率高,应针对病因予以治疗,明确病因是治疗成功的关键。     

嗜酸粒细胞性气道炎症和慢性咳嗽

嗜酸粒细胞性气道炎症是以气管和支气管壁存在明显嗜酸粒细胞浸润为特征的一种病理状态.哮喘、咳嗽变异性哮喘及非哮喘性嗜酸粒细胞性支气管炎是慢性咳嗽的常见病因,嗜酸粒细胞性气道炎症是其共同病理过程,提示嗜酸粒细胞性气道炎症与慢性咳嗽的发生可能有密切联系,并呈现不同的临床表型.     

大理地区138例慢性咳嗽患者病因诊断

目的探讨大理地区慢性咳嗽患者的病因构成。方法分析138例慢性咳嗽患者的临床资料。结果胃食管反流27例(19.57%),慢性咽喉炎26例(18.84%),鼻后滴漏综合征25例(18.16%),咳嗽变异性哮喘21例(15.22%),感染后咳嗽15例(10.87%),嗜酸粒细胞性支气管炎9例(6.52%),支气管内膜结核5例(3.62%),心理源性咳嗽3例(2.17%),慢性心功能不全3例(2.17%),支气管异物1例(0.72%),原因未明3例(2.17%)。结论胃食管反流、慢性咽喉炎、鼻后滴漏综合征、咳嗽变异性哮喘、感染后咳嗽是大理地区慢性咳嗽的主要病因。     

成人慢性咳嗽病因诊断探讨-附120例报告

目的探讨成人慢性咳嗽的病因诊断方法。方法对120例慢性咳嗽通过询问病史,进行血常规、X线胸片、胸部CT检查、痰液检查、外周血嗜酸粒细胞测定、肺功能测试、最大呼气流量测定、纤维支气管镜、胃镜、鼻咽镜、CT等检查,若全部的检查结果均为阴性,给予试验性治疗。结果 120慢性咳嗽病因包括咳嗽变异性哮喘35例、鼻后滴漏综合征31例、胃食管反流性咳嗽24例、嗜酸细胞性支气管炎11例、心理源性咳嗽9例、支气管异物5例,病因未明5例。结论慢性咳嗽病因构成复杂,应对慢性咳嗽的病因有充分的认识,规范慢性咳嗽的诊断流程有助于提高慢性咳嗽病因正确诊断率。     

对慢性咳嗽的再认识

慢性咳嗽占呼吸科门诊1／3以上，很长时间对胸透正常，咳嗽症状迁延不愈者多诊断为“支气管炎”。近年来人们逐渐认识到这部分人中约50％并非支气管炎。“慢性咳嗽”是指患者连续咳嗽3周以上者。之所以定为3周，因为大部分呼吸道感染(多为病毒引起)一般多在3周内已治愈，其咳嗽症状随之消失。临床上应经过胸透等检查初步排除肺炎、     

慢性咳嗽的临床分析

目的探讨慢性咳嗽的病因及临床诊治方法。方法对2007年1月～2008年1月在我们就诊的慢性咳嗽患者60例,进行系统的诊治,分析其临床资料,明确其病因、症状、诊断、治疗、及预后。结果本组诊断明确者56例,其中鼻后滴漏综合征（PNDS）24例（40％）,咳嗽变异性哮喘（CVA）18例（30％）,胃食管反流（GER）11例（18％）,嗜酸细胞性支气管炎（EB）3例（5％）,原因不明4例（7％）,其中胃食管反流并发咳嗽变异性哮喘4例（7％）,鼻后滴漏综合征并发咳嗽变异性哮喘6例（10％）。2个月内患者咳嗽明显减轻或消失为有效,总有效率为94％。结论引起慢性咳嗽的病因较多,其中PNDS、CVA、GER为较常见病因,明确诊断,给予相应治疗,效果满意。     

嗜酸细胞性支气管炎是慢性咳嗽的一个重要原因

目的　调查门诊慢性咳嗽病人中嗜酸细胞性支气管炎的发病率。方法　对门诊慢性咳嗽 ,干咳和已用抗生素或支气管扩张剂治疗 2～ 3月的病人 ,以及查体无喘息无哮鸣音的病人 ,X胸片正常 ,肺功能正常。这些病人再进行诱导痰细胞学分析、肺功能峰流速变异率观察测定、支气管激发试验测定等 ,进行规范的程序诊断。结果　确诊嗜酸细胞性支气管炎 1 8例慢性咳嗽病人 ,肺功能 FEV1 =1 1 3± 8.2 % ;FEV1 / FEV81± 7.6 %。组织胺激发试验阴性 PC2 0 >=8mg/ ml。嗜酸细胞数占诱导痰涂片细胞总数的百分比是 2 2 .5± 1 8%。门诊嗜酸细胞性支气管炎发病率是 3.4 6 %。结论　嗜酸细胞性支气管炎是慢性咳嗽的一个重要原因     

胃食管反流与慢性咳嗽关系的临床观察

[目的]探讨胃食管反流(GER)与慢性咳嗽的关系,以及GER所致的慢性咳嗽——胃食管反流性咳嗽(GERC)的临床特征、诊断和治疗.[方法]50例GERC患者(病例组)和30例健康体检者(对照组)纳入研究,行24h食管pH监测来分析慢性咳嗽与GER的相关性.病例组患者随机分为2亚组,A亚组22例,给予雷尼替丁(150mg,2次/d);B亚组28例,给予奥美拉唑(20mg,2次/d)和莫沙比利(5mg,3次/d)口服;疗程均为8周.比较病例组与对照组24 h食管pH监测指标,病例组中A、B亚组疗效和治疗后24 h食管pH监测指标变化.[结果]病例组患者Demeester总积分均≥12.7,各项反流指标均显著高于对照组(P＜0.05).病例组患者治疗8周后24h食管pH监测各项反流指标均较治疗前降低(P＜0.05),B亚组疗效优于A亚组(z=2.332,P＜0.05);且B亚组24 h食管pH监测各项反流指标均较A亚组降低(P＜0.05).[结论]GER与慢性咳嗽密切相关,是导致GERC的一个重要原因,对GERC患者应给予抑酸和抗反流治疗.     

胃食管反流相关性慢性咳嗽并咽喉反流患者的反流特征

目的探讨胃食管反流相关性慢性咳嗽（GERC）并伴喉咽反流（LPR）患者的反流特征。 方法选取2019年1月至2019年6月间在新疆维吾尔自治区人民医院住院收治的60例慢性咳嗽患者。对所有患者进行反流症状指数（RSI）问卷调查，分析咳嗽症状评分以及高分辨率食管测压和24 h pH监测。 结果按照食管24 h pH监测反流次数、酸暴露时间百分比及DeMeester评分，对患者进一步分为非酸性GERC组（n=32）和酸性GERC组（n=28）。在非酸性GERC组中，RSI评分25.00（8.00）显著高于酸性GERC组16.00（6.50），且差异有统计学意义（Z=-3.105，P＜0.05）。此外，非酸性GERC患者的“持续清嗓”和“呼吸困难或窒息发作”比酸性GERC患者更明显。 结论LPR与GERC部分重叠，RSI评分较高的非酸性GERC患者可能表现出更多的非酸性反流和呼吸困难。     

Exhaled nitric oxide levels in patients with atopic cough and cough variant asthma

Background and objective:   Atopic cough (AC) is an established clinical entity in Japan, in which patients present with a chronic persistent non-productive cough. Exhaled nitric oxide (NO) is a biomarker of eosinophilic airway inflammation. The present study examined whether exhaled NO levels were increased in AC in comparison with cough variant asthma (CVA) and bronchial asthma (BA).
Methods:   Consecutive patients presenting with an isolated cough lasting at least 8 weeks were enrolled in the study. The aetiology of the chronic cough was determined according to the Japanese Respiratory Society guidelines for management of cough. Exhaled NO, capsaicin cough sensitivity (capsaicin concentration eliciting five or more coughs (C5)) and bronchial reversibility were measured at the patients' first visit. Bronchial responsiveness (PC20 to methacholine) was measured at their second visit following a 6-day course of bronchodilator therapy.
Results:   There were 58 patients recruited and fully investigated; of these 9 and 11 patients were diagnosed with AC and CVA, respectively, as single causes of chronic cough. Ten patients with BA who had not received corticosteroid therapy in the previous 4 weeks and who attended the same clinic in the same time period acted as controls. Exhaled NO levels in patients with AC were significantly lower than those in patients with CVA and BA. There was no significant difference in the exhaled NO levels between patients with CVA and BA.
Conclusions:   Exhaled NO may reflect eosinophilic inflammation of peripheral airways and its measurement may be useful in differentiating CVA from AC and other causes of chronic non-productive cough.     

Chronic cough and hoarseness in patients with severe gastroesophageal reflux disease

Gastroesophageal reflux may be responsible for atypical symptoms such as chronic cough and hoarseness. Our aim was to evaluate and treat patients with severe gastroesophageal reflux and chronic cough or hoarseness with intensive antireflux therapy. Twenty-seven patients with typical heartburn symptoms in addition to significant cough or hoarseness were treated with aggressive antireflux therapy. We recorded the response of each symptom to the antireflux therapy. Two patients were lost to follow-up. Twenty of the 25 (80%) patients showed some improvement in cough or hoarseness, nine (36%) had no atypical symptoms at follow-up. The response of heartburn to therapy was strongly predictive of successful therapy for the atypical symptoms. Cough and hoarseness improved in only two of the five patients with residual heartburn symptoms compared to 18 of 20 patients with no heartburn (P<0.04). Only patients with no heartburn symptoms at follow-up had complete resolution of atypical symptoms. There were no important differences on ambulatory pH monitoring between partial and complete responders. Improvement in atypical reflux symptoms, such as chronic cough and hoarseness, is common with aggressive antireflux therapy. There are no findings on ambulatory esophageal pH monitoring that uniquely identify patients who are likely to respond to antireflux therapy.     

咳嗽变异型哮喘与胃食管反流的关系

目的许多研究发现支气管哮喘与胃食管反流有关，通过本文研究明确咳嗽变异型哮喘与胃食管反流的关系，并指导其治疗。方法将咳嗽变异型哮喘患者200例进行筛选，伴有胃食管反流108例，根据治疗方法分为对照组52例，实验组56例。结果两组比较，实验组缓解率大于对照组，差异具有显著性（P〈0．05）。结论大约54％的咳嗽变异型哮喘伴有胃食管反流。抑酸及增加胃动力可以明显缩短缓解时间。     

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.     

Temporal correlation between chronic cough and gastroesophageal reflux disease

Reflux disease (GERD) and chronic cough often coexist, but a temporal correlation using the symptom association probability has not been reported. Our aim was to determine if a temporal correlation exists between cough and GERD. Sixty-one patients with chronic cough had esophageal pH monitoring with sensors 5 and 20 cm above the LES. The symptom (SI) and symptom sensitivity (SSI) indices and the symptom association probability (SAP) were used to test cough–reflux association. Pathological reflux was defined as the percentage of time pH <4 exceeded 4.2%. A significant temporal association between cough and distal reflux was made in 35% of patients by SAP compared with only 14.8% by SI and SSI alone (P < 0.002). Patients with pathologic reflux had a greater likelihood of a temporal symptom correlation (57.1%) when not on acid-blocking medications. In conclusion, a temporal association between cough and distal reflux exists in one third of patients, especially those with pathological reflux. The SAP is a more sensitive measure of temporal association than SI or SSI.     

Neurotrophins in chronic cough: association with asthma but not with cough severity

Background and Aims: Chronic cough is associated with an enhanced excitability of airway cough receptors, possibly due to action of neurotrophins. The present study aimed to compare the neurotrophin levels between healthy subjects and patients with chronic cough and to analyze the factors associated with these levels. Methods: Serum and sputum levels of nerve growth factor (NGF), serum levels of brain‐derived neurotrophic factor (BDNF), and neurotrophin‐3 (NT‐3) were analyzed by enzyme immunoassay in 19 healthy subjects and 47 patients with chronic cough. In addition, cough sensitivity to hypertonic saline was assessed, cough diary was kept, Leicester Cough Questionnaire was filled in, peak flow was monitored and spirometry, skin prick tests, exhaled nitric oxide measurement and histamine challenge were performed. Results: The NGF levels did not differ between the healthy subjects and the patients with chronic cough and were not associated with any index describing cough severity. However, these levels in both serum (P = 0.01) and sputum (P = 0.025) samples were associated with asthma. There was a statistically significant association between serum and sputum NGF levels (R = 0.45, P = 0.026). The serum BDNF levels did not differ between the groups and were not associated with any of the background characteristics. The serum NT‐3 levels were below the detection limit in most subjects and therefore these data were not analyzed. Conclusions: Neither chronic cough nor its severity is associated with abnormal neurotrophin levels. High NGF levels among some patients with chronic cough may indicate a presence of asthma. Please cite this paper as: Koskela HO, Purokivi MK and Romppanen J. Neurotrophins in chronic cough: association with asthma but not with cough severity. The Clinical Respiratory Journal 2009; DOI:10.1111/j.1752‐699X.2009.00143.x.