The Relationship Between Psychogenic Cough and the Diagnosis and Misdiagnosis of Asthma: A Review

The differential diagnoses of persistent nonproductive cough include numerous pulmonary and nonpulmonary organic disorders as well as functional illnesses. Many diseases can cause cough, and several studies have shown asthma among the most common etiologies associated with chronic cough in adult nonsmokers, as well as children. Psychogenic cough and its relationship to asthma and other asthma-like illnesses is complex since distinct maladies with similar features may coexist individually or in combination in any given patient. While chronic cough may occur as a sole presenting manifestation of bronchial asthma in all age groups, recent findings suggest that most children with persistent cough without other respiratory symptoms do not have asthma. Since several organic, as well as functional diseases, may present with persistent cough as their sole manifestation in either adults or children, cough should not be used as a single or major determinant to diagnose and treat asthma, especially when empirically focused therapy trials fail. Given the range of illnesses causing cough, no single management guideline can be expected to be universally effective.     

Chronic wet cough: Protracted bronchitis, chronic suppurative lung disease and bronchiectasis

The role of persistent and recurrent bacterial infection of the conducting airways (endobronchial infection) in the causation of chronic respiratory symptoms, particularly chronic wet cough, has received very little attention over recent decades other than in the context of cystic fibrosis (CF). This is probably related (at least in part) to the (a) reduction in non-CF bronchiectasis in affluent countries and, (b) intense focus on asthma. In addition failure to characterize endobronchial infections has led to under-recognition and lack of research. The following article describes our current perspective of inter-related endobronchial infections causing chronic wet cough; persistent bacterial bronchitis (PBB), chronic suppurative lung disease (CSLD) and bronchiectasis. In all three conditions, impaired muco-ciliary clearance seems to be the common risk factor that provides organisms the opportunity to colonize the lower airway. Respiratory infections in early childhood would appear to be the most common initiating event but other conditions (e.g., tracheobronchomalacia, neuromuscular disease) increases the risk of bacterial colonization. Clinically these conditions overlap and the eventual diagnosis is evident only with further investigations and long term follow up. However whether these conditions are different conditions or reflect severity as part of a spectrum is yet to be determined. Also misdiagnosis of asthma is common and the diagnostic process is further complicated by the fact that the co-existence of asthma is not uncommon. The principles of managing PBB, CSLD and bronchiectasis are the same. Further work is required to improve recognition, diagnosis and management of these causes of chronic wet cough in children.     

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.     

慢性咳嗽的相关疾病及其治疗现状

本文对慢性咳嗽干性或湿性的性质进行病因分类,并对咳嗽变异性哮喘、嗜酸粒细胞性支气管炎、胃食管反流性咳嗽、上呼吸道咳嗽综合征、感染后咳嗽、特应性咳嗽、血管紧张素转换酶抑制剂所致的咳嗽、心理性咳嗽、慢性阻塞性肺疾病及其他咳嗽发生率较少的器质性肺部疾病的病因病机、临床诊断和鉴别诊断及其治疗现状进行综述,以供临床参考.     

Methacholine and adenosine 5'-monophosphate challenges in preschool children with cough-variant and classic asthma

Bronchial challenge with different stimuli provides different information and may be used as an adjunct to understand the pathophysiology of cough variant asthma (CVA) in young children in whom the mechanism of disease is still unresolved. This study was designed to investigate the hypothesis that airway hyperresponsiveness (AHR) to methacholine and adenosine 5'-monophosphate (AMP) is similar in preschool children with CVA and classic asthma. We examined airway response to methacholine and AMP in well-defined 3-6-year-old children with CVA (n = 18), classic persistent asthma (n = 31), and healthy controls (n = 10) by transcutaneous oxygen monitorization. The number of AMP responsive children was significantly lower in the group with CVA (38.9%) than classic persistent asthma (67.7%) (P = 0.049). Mean provocative concentration of AMP causing a 15% fall in transcutaneous oxygen tension (PC15PtcO2 AMP) in children with CVA and classic persistent asthma were 234.58 and 36.35 mg/ml, respectively (P = 0.001). None of the healthy children in the control group responded to AMP. The severity of methacholine responsiveness was found similar in CVA and classic persistent asthma groups (P = 0.738). Although both asthma groups showed a similar pattern in methacholine responsiveness, preschool children with CVA were found to differ from children with classic persistent asthma with regard to response profiles to AMP challenge which may point to different pathophysiologic mechanisms of CVA in the young age group.     

Extrathoracic airway responsiveness in children with asthma-like symptoms,including chronic persistent cough

Asthma-like symptoms, including chronic persistent cough, are not always specific for classical asthma. In order to investigate whether assessment of extrathoracic airway hyperresponsiveness (EAHR) during methacholine bronchial challenge helped in the evaluation of pediatric patients with asthma-like symptoms such as chronic cough, we examined 133 consecutive, unselected patients (mean age, 10.06 +/- 2.16 years) who had neither established asthma nor bronchial obstruction previously. We recorded the forced mid-inspiratory flow (FIF(50)) as an index of extrathoracic airway narrowing. In addition, a 25% decrease in FIF(50) (PD(25)FIF(50)) below the cutoff concentration of < or = 8 mg/mL methacholine was assumed to indicate EAHR. According to the methacholine response, 81 patients had EAHR, and 41 of them had combined EAHR and bronchial hyperresponsiveness (BHR); 39 patients had only BHR. Airway hyperresponsiveness was not demonstrated in 13 patients and not in any of the control children. When patients with cough as the sole presenting symptom (60.9%) were compared with those with cough and wheeze (20.3%), those with cough alone had a significantly greater probability of having EAHR (OR, 4.16; 95% CI, 1.32-13.13) and a lower probability of having BHR (OR, 0.70; CI, 0.25-1.95) than those with cough and wheeze. Patients with cough, wheeze, and dyspnea (18.8%) had a significantly greater chance of having BHR than those with cough alone (OR, 5.08; CI, 1.55-16.64). Patients with cough and wheeze as compared with those with cough, wheeze, and dyspnea had significantly greater probability of having both EAHR and BHR (OR, 4.71; CI, 1.94-11.47).In order to ascertain the clinical relevance of EAHR, we assessed in the second part of the study whether the effects of treatment of the underlying disease would result in relief of airway hyperresponsiveness. Rhinosinusitis and perennial allergic rhinitis accounted for EAHR in 71 patients, and 34 of them also demonstrated BHR. They received specific therapy for their upper airway diseases for 4 weeks. Compared with values before treatment, FIF(50) and forced expiratory volume in 1 sec (FEV(1)) did not change significantly. The dose of methacholine causing a 20% fall in FEV(1) (PD(20)FEV(1)) and PD(25)FIF(50) values were significantly increased from 2.40 +/- 1.39 to 4.22 +/- 1.13 mg /mL (P < 0.001) and from 1.03 +/- 1.75 to 8.71 +/- 1.21 mg /mL (P < 0.0001), respectively.We conclude that measurements of EAHR and BHR are the most important ways to evaluate children with asthma-like symptoms, including chronic persistent cough when chest X-rays and pulmonary function tests remain within normal limits. Therefore, empirical treatment is not necessary when these investigations are available. Our results suggest that specific treatment of inflammation in the upper airways reversed persistant cough, and may play an important role in modulating lower airways responsiveness in patients with concomitant BHR.     

Comparison of atopic and nonatopic children with chronic cough: bronchoalveolar lavage cell profile

Chronic cough is a common complaint in children and its relationship with asthma is controversial. The aim of the present study was to determine the pattern of airway inflammation in atopic and nonatopic children with chronic cough, and to investigate whether atopy is a predictive factor for eosinophilic inflammation in cough. Bronchoalveolar lavage (BAL; three aliquots of 1 ml/kg saline) was performed in the right middle lobe of 24 (11 atopic and 13 nonatopic) children with persistent cough (8 females, 16 males), mean age 4.7 years (range: 1-11). Atopy was defined as an elevated total serum IgE or a positive RAST test. Both atopic and nonatopic children with persistent cough had an increase in total cells/ml in BAL (atopic: median 39 x 10(4), range: 20-123; nonatopic: median 22 x 10(4), range: 17-132) compared to nonatopic controls (median 11 x 10(4), range 9-30). The increases were mainly in neutrophils (atopic: median 17%, range 2.5-88.5%; nonatopic: median 6%, range 1.0-55.0%) compared to controls (median 1.55%, range 0.5-7.0%; atopics vs. controls, P < 0.005). There were no significant increases in eosinophils, lymphocytes, epithelial cells, or mast cells. Eosinophils were elevated in only 5/11 atopic and none of the nonatopic children. The increased percentage of neutrophils in the BAL fluid of atopic and nonatopic children with persistent cough could be due to an underlying inflammatory process driving the cough, or even conceivably, due to the effect of coughing itself. In this highly selected series, the absence of eosinophilic inflammation in the majority suggests that most would be predicted not to respond to inhaled corticosteroid therapy. This study underscores the need to be cautious about treating coughing children with inhaled corticosteroids, even in the context of a tertiary referral practice.     

Relationship between bronchial hyperresponsiveness and development of asthma in children with chronic cough

To evaluate the relationship between bronchial hyperresponsiveness (BHR) and the development of asthma in children with chronic cough, we performed methacholine inhalation challenges and transcutaneous oxygen pressure (tcPO2) measurements in 92 children with chronic cough aged from 1-13 years (55 boys and 37 girls; mean, 5.3 years) and followed them for > or = 10 years. Forty-four age-matched children with asthma (24 males and 20 females; mean, 6.5 years) and 44 age-matched children without cough or asthma served as controls (18 males and 26 females; mean, 4.6 years). Consecutive doubling doses of methacholine were inhaled until a 10% decrease in tcPO2 from baseline was observed. The cumulative dose of methacholine at the inflection point of the tcPO2 record (Dmin-PO2) was considered to represent hyperresponsiveness to inhaled methacholine. After 10 years or more of follow-up, 60 of the 92 subjects with cough answered our questionnaire, and 27/60 had been diagnosed with asthma. There was a statistical difference in Dmin-PO2 between the children who presented with chronic cough originally and who developed asthma (asthma-developed group) and those who did not develop asthma (asthma-free group). There was no difference in the value of Dmin-PO2 between the asthma-developed group and the asthma group, or between the asthma-free group and the age-matched control group. Among the children with chronic cough, there was no difference in Dmin-PO2 between girls and boys, either in the asthma-developed group or in the asthma-group. We conclude that 45% of the children with a chronic cough in early life developed asthma, and that BHR in children with chronic cough during the childhood period is a strong risk factor for the development of asthma.     

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.     

Chronic cough at a non‐teaching hospital: Are extrapulmonary causes overlooked?

OBJECTIVE: To estimate the prevalence, assess the diagnostic approach and to identify specific causes and treatment response of chronic persistent cough (CPC) in consecutive adult patients attending the chest clinic at a non-teaching hospital in Riyadh, Saudi Arabia. METHODOLOGY: Chronic persistent cough was defined as cough persisting for more than 3 weeks. Patients were assessed clinically and investigated according to the suspected diagnosis. The specific causes were confirmed by appropriate investigations, as well as response to specific therapy. Improvement in cough following therapy was assessed subjectively by patients on a scale from 0 to 100%. RESULTS: Of 1332 patients seen in the chest clinic, 136 (10.2%; 95% confidence interval 8.6-11.8%) presented with CPC as the main complaint. One hundred patients (55% males) were assessed, after excluding 36 patients who were lost to follow up. The common presenting diagnoses (for the 81 patients who had previously consulted a physician) were upper respiratory tract infection (17.1%), asthma (15.9%), bronchitis (9.8%) and unknown in 30.8% of patients. Final diagnoses (as a sole or contributory cause) were established in 96% of patients and included rhinosinusitis (RS; 60%), asthma (26%), gastro-oesophageal reflux (GERD; 9%), postinfectious cough (8%) and bronchiectasis (5%). The agreement between the presenting and final diagnoses was generally poor, especially for extrapulmonary causes, which was as low as 5.3%. All patients, except for one, had complete or substantial improvement in the severity of cough. CONCLUSIONS: In a non-teaching hospital setting, CPC is a common benign disorder that rarely requires specialized investigations and is easily treated once the causes are identified. The multiplicity of causes and extrapulmonary triggers of CPC, particularly RS, are often overlooked. The principal causes in our series remain the same as in studies elsewhere, namely RS, asthma and GERD.     

33例咳嗽变异性哮喘的诊断分析

目的探讨咳嗽变异性哮喘的诊断及治疗。方法对诊断为咳嗽变异性哮喘的33例患者进行回顾性分析。结论咳嗽变异性哮喘因缺乏典型哮喘的临床表现,常误诊为其它疾病,应重视其诊断与鉴别。     

Prevalence and clinical features of cough variant asthma in a general internal medicine outpatient clinic in Japan

OBJECTIVE: The aims of the present study were to examine the prevalence and clinical features of cough variant asthma (CVA) among patients with chronic and persistent cough at an outpatient clinic in Japan, and the efficacy of treatment with an inhaled corticosteroid. METHODOLOGY: This prospective study was conducted at a general internal medicine outpatient clinic in Japan over a 12-month period. CVA was diagnosed as chronic cough without wheezing or any apparent cause, that had persisted for more than 8 weeks, with a normal CXR and spirometry but with bronchial hyperresponsiveness to methacholine, and relief of cough after bronchodilator treatment. We also examined the effects of inhaled beclomethasone propionate on symptoms and differences in PEF between early morning and evening. RESULTS: Of 55 patients suffering from chronic cough, 23 satisfied the criteria for CVA. Their cough occurred more frequently at night and early in the morning. Early morning PEF was significantly lower than evening PEF with a mean variability of 11.5 +/- 4.1%. Treatment with beclomethasone propionate improved coughing and significantly increased early morning PEF, reducing variability to less than 10%. CONCLUSIONS: These findings suggest that CVA is most common among patients with chronic cough not due to any apparent cause. The efficacy of inhaled corticosteroid suggests that early intervention is effective in the treatment of CVA.     

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。     

Psychogenic Cough in an Asthmatic Child: Case Report with Unusual Findings

A 9-year-old girl with known mild intermittent asthma presented with a persistent cough. Her cough exhibited a four-beat staccato rhythm, was nonproductive, and persisted only while awake. On physical examination, she displayed several unique findings not previously described. An extensive yet non-diagnostic medical workup coupled with absence of aggressive medical treatment for the more usual causes of cough lead to psychologic investigation and intervention with subsequent cough resolution. The appropriate use of psychologic consultation, testing, and success with supportive reinforcement therapy confirmed a psychogenic etiology. Extended medical follow-up of the patient concerning cough reoccurrence remains uneventful.     

Psychogenic Cough in an Asthmatic Child: Case Report with Unusual Findings

A 9-year-old girl with known mild intermittent asthma presented with a persistent cough. Her cough exhibited a four-beat staccato rhythm, was nonproductive, and persisted only while awake. On physical examination, she displayed several unique findings not previously described. An extensive yet non-diagnostic medical workup coupled with absence of aggressive medical treatment for the more usual causes of cough lead to psychologic investigation and intervention with subsequent cough resolution. The appropriate use of psychologic consultation, testing, and success with supportive reinforcement therapy confirmed a psychogenic etiology. Extended medical follow-up of the patient concerning cough reoccurrence remains uneventful.     

茶碱控释片在治疗慢性咳嗽中的应用

目的：了解茶碱控释片在治疗哮喘的慢性咳嗽中的作用。方法：35例患者按随机原则分为治疗组和对照组，以咳嗽程度为观察指标，用Ridit分析。结果:茶碱控释片组治疗后咳嗽程度较治疗前显著改善．茶碱控释片组较对照组咳嗽程度显著改善。结论:哮喘的迁延性咳嗽，茶碱控释片治疗是有效的。     

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.     

Tracheopathia Osteoplastica Misdiagnosed as Asthma

Tracheopathia osteoplastica (TPO) is a rare disorder characterized by cartilaginous or bony mucosal nodules in the tracheobronchial tree. Due to most patients being asymptomatic, the majority are diagnosed post-mortem. If symptoms are present, they typically include chronic cough, dyspnea, hemoptysis, hoarseness, and wheezing, with some of these symptoms overlapping with asthma. This case report describes an adult female with chronic cough who was diagnosed with asthma that was refractory to therapy for 8 years. Computed tomography (CT) of the chest revealed several soft tissue masses in the trachea with bronchoscopy revealing TPO in the upper portion of the trachea. She was diagnosed with TPO and started on airway clearance and a nasal corticosteroid spray with resolution of the cough at follow-up 3 months later.     

Tracheopathia Osteoplastica Misdiagnosed as Asthma

Tracheopathia osteoplastica (TPO) is a rare disorder characterized by cartilaginous or bony mucosal nodules in the tracheobronchial tree. Due to most patients being asymptomatic, the majority are diagnosed post-mortem. If symptoms are present, they typically include chronic cough, dyspnea, hemoptysis, hoarseness, and wheezing, with some of these symptoms overlapping with asthma. This case report describes an adult female with chronic cough who was diagnosed with asthma that was refractory to therapy for 8 years. Computed tomography (CT) of the chest revealed several soft tissue masses in the trachea with bronchoscopy revealing TPO in the upper portion of the trachea. She was diagnosed with TPO and started on airway clearance and a nasal corticosteroid spray with resolution of the cough at follow-up 3 months later.     

Paediatric and adult bronchiectasis: Specific management with coexisting asthma,COPD, rheumatological disease and inflammatory bowel disease

Bronchiectasis, conventionally defined as irreversible dilatation of the bronchial tree, is generally suspected on a clinical basis and confirmed by means of chest high‐resolution computed tomography. Clinical manifestations, including chronic productive cough and endobronchial suppuration with persistent chest infection and inflammation, may deeply affect quality of life, both in children/adolescents and adults. Despite many cases being idiopathic or post‐infectious, a number of specific aetiologies have been traditionally associated with bronchiectasis, such as cystic fibrosis (CF), primary ciliary dyskinesia or immunodeficiencies. Nevertheless, bronchiectasis may also develop in patients with bronchial asthma; chronic obstructive pulmonary disease; and, less commonly, rheumatological disorders and inflammatory bowel diseases. Available literature on the development of bronchiectasis in these conditions and on its management is limited, particularly in children. However, bronchiectasis may complicate the clinical course of the underlying condition at any age, and appropriate management requires an integration of multiple skills in a team of complementary experts to provide the most appropriate care to affected children and adolescents. The present review aims at summarizing the current knowledge and available evidence on the management of bronchiectasis in the other conditions mentioned and focuses on the new therapeutic strategies that are emerging as promising tools for improving patients’ quality of life.