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PubMedDate not supplied

Etiology of chronic cough in a population of children referred to a pediatric pulmonologist.

BACKGROUND: Chronic cough is a common complaint encountered by physicians who care for children. It is also a common reason for referral to a pulmonologist. Determining the cause of chronic cough, however, rarely requires specialized diagnostic procedures that are unavailable to the primary care physician. METHODS: A computerized listing of new patients referred to a pediatric pulmonologist between July 1993 and June 1995 was reviewed. Of 299 patients examined as outpatients during this period, 95 were referred for chronic cough. The diagnosis and diagnostic procedures were examined to determine how frequently procedures available exclusively to subspecialists were necessary to determine the cause of chronic cough. RESULTS: Of the 95 patients who were examined for cough during the period studied, the diagnosis was made by history in 5, pulmonary function testing in 11, radiographic tests in 15, and a therapeutic trial in 58. In only 6 cases was the diagnosis made using tests unavailable to the primary care physician (5 bronchoscopy, 1 allergy skin testing). CONCLUSIONS: In 89 cases the cause of chronic cough was determined by procedures available to the referring physician. In most cases chronic cough in children can be diagnosed and managed by physicians who are aware of the spectrum of common disorders that lead to cough.

Asthma↗
PubMed1997

[Cough-variant asthma successfully treated with a peptide leukotriene receptor antagonist].

A 47-year-old woman complained of coughing for over 5 weeks. The coughing was not relieved by bronchodilators (theophylline, beta 2-adrenoceptor agonist; procaterol), anti-allergic agents (azelastine, ozagrel), an inhaled corticosteroid (beclomethasone dipropionate), a macrolide antibiotic (clarithromycin), or codeine phosphate. A peptide leukoriene receptor antagonist (pranlukast) completely abolished the coughing and increased the cough threshold to capsaicin. The patient was given a diagnosis of cough-variant asthma because her sputum contained many eosinophils and her airway responsiveness to methacholine was slightly higher than normal. Peptide leukotriene may have contributed to the coughing. The fact that coughing associated with cough-variant asthma was abolished by a peptide leukotriene receptor antagonist is clinically important.

Anti-Asthmatic Agents↗
PubMed1997

[Clinical features of postinfectious chronic cough].

Postinfectious cough has been drawing attention as a factor involved in the etiology of chronic cough in the United States. In Japan, clinical features of postinfectious chronic cough (PICC) have not been described in detail. We investigated 22 patients with PICC diagnosed by the established criteria (Jpn. J. Allergol. 1995; 44: 1418). All patients were nonsmokers and none received ACE inhibitors. None had a history of atopy or sinus diseases. There were four men and 18 women with a median age of 65 years. These 22 patients underwent clinical examinations including chest roentgenograms, respiratory function tests, eosinophil counts in venous blood, serum IgE titers, antibody titers to Mycoplasma pneumoniae, sputum cytologic findings taken from ten patients, and histological features of bronchial biopsy specimens obtained from two patients; all findings were within normal limits. Clinical course of cough in 20 of the patients with PICC was evaluated using a cough diary. One patient did not keep a cough diary. Ten patients improved with dextromethorphan hydrobromide (D) and oxatomide (O). Three of the remaining 9 patients improved with Bakumondo-to (B) only, 4 with D+O+B, and 2 with D+O+B+ozagrel hydrochloride. The duration of cough before treatment showed a significant correlation with the time from the start of treatment to recovery (r = 0.47, p < 0.05). These results indicate that PICC tends to occur in elderly women and to improve with treatment combining with D, O, and B. We hope to establish a standard therapy for postinfectious chronic cough.

Adult↗
PubMed1997

Chronic cough.

Chronic cough is defined as a cough that lasts for more than three weeks. More than 90 percent of cases of chronic cough result from five common causes: smoking, post-nasal drip, asthma, gastroesophageal reflux and chronic bronchitis. Although in most patients chronic cough has a single cause, in up to one fourth of patients, multiple disorders contribute to the cough. A stepwise evaluation in patients with chronic cough can minimize the invasiveness and expense of the work-up. Initial screening of patients with chronic cough should search for smoking, occupational exposure to an airway irritant, cough-inducing medications, airway hyperresponsiveness following upper respiratory infection, chronic bronchitis or any systemic symptoms suspicious for serious disease. Patients who are not diagnosed after an initial screening are evaluated or empirically treated in a stepwise fashion for postnasal drip, asthma and reflux. Bronchoscopy is reserved for use in the few patients still without a diagnosis after the previous steps have been completed.

Algorithms↗
PubMed1997

[Headaches due to cough, exertion and sexual intercourse].

The aim of this study was to review the advances in cough, exertional and sexual headaches. We perform a critical analysis of the literature and of our experience with 72 patients. About one-half of patients having cough headache will have benign cough headache. The remaining half suffer from Chiari type I malformation. Benign cough headache begins typically in men above age 50, while symptomatic cough headache begins under 50 and appears with the same frequency in both sexes. Indomethacin is the treatment of choice of benign cough headache, but has no effect in symptomatic cases, which respond to suboccipital craniectomy. Although also showing male predominance, exertional and sexual headaches begin under age 50. Subarachnoid bleeding due to aneurism is the most frequent etiology for exertional and sexual headaches. Cough headache and exertional headache are separate clinical entities, whereas exertional headache and sexual headache seem to be different expressions of the same clinical entity. These data allow, in addition, the clinical differentiation between benign and symptomatic cough headache.

Adult↗
PubMed1998

[Use of an accelerometer to measure coughing].

Coughing was detected by measuring body-surface acceleration. Twenty-seven patients with a chief complaint of coughing were studied. The sensor used is an apparatus for sound communication in aircraft, in which cranial vibrations that occur as the pilot speaks are converted into acceleration waves. An acceleration sensor was fixed to the body of each subject. The acceleration of the chest wall was recorded as a voltage change. Subjects rested in bed to exclude acceleration due to body movement. Acceleration waves of large amplitude were recognized during coughing. Conversation or laughter only caused very weak acceleration waves. Sound has often been used as an indicator of coughing, because coughing was thought to be one kind of human vocalization. However, distinguishing speaking from coughing was difficult, and complicated analysis was necessary. We regarded coughing as a movement causing acceleration of the body surface, and measured it without using sound. We plan to collect data on acceleration of the body surface in 3 dimensions simultaneously. After a continuous long-term recorder of coughing is developed the effects of antitussive drugs can be assessed.

Acceleration↗
PubMed1998

[Actions of drugs affecting the cough reflex].

BACKGROUND AND AIM: Authors evaluated the part of some receptor systems in the antitussive activity of drugs. METHOD: The cough was induced by mechanical stimulation of the airways. Unanesthetized cats were used in this study. RESULTS: They followed: 1. statistically highly significant decrease of cough parameters after administration the drugs influencing the different types of opiate receptors--tramadol, tilidine, pentazocine, codeine and butorphanol. Every of these drugs were administered in a dose 10 mg/kg b.w. intraperitoneally, 2. the antitussive activity of codeine was decreased by pretreatment with naloxone only in part, 3. selective antagonist 5-HT2 receptors ketanserine (1 mg/kg b.w.) decreased antitussive effect of codeine by 10% and effect of tramadol by 20%, 4. the ability of codeine to reduce the cough parameters was unchanged after pretreatment with haloperidol (0.1 mg/kg b.w.), 5. whereas the pretreatment with reserpine decreased the cough-suppressing effect of codeine, 6. the application of gabaergic agent gabalid leads to the highly significant decrease the cough parameters. Results of these experiments showed that gaba-ergic mechanism might be involved in the mechanism of action of narcotic antitussives agents, 7. we showed, that inhibition of glutaminergic synaptic transmissions afferent impulses from cough receptors with dextromethorphan leads to suppressing cough reflex in cats. CONCLUSIONS: Antitussive activity of agents is not only mediated by means of mí opiate receptors. The results suggest, that gabaergic, serotoninergic systems and activity of NMDA receptors play an important role in the mechanism of action of antitussive drugs. Decrease in levels of brain monoamines modifies the cough-depressant effect of codeine. (Fig. 7, Ref. 23.)

Animals↗
PubMed2004

A placebo-controlled trial of two intranasal vaccines to prevent tracheobronchitis (kennel cough) in dogs entering a humane shelter.

A placebo-controlled field trial was conducted to compare the effectiveness of intranasal (IN) vaccines containing Bordetella bronchiseptica and canine-parainfluenza virus, with (IN-BPA) or without (IN-BP) canine-adenovirus type 2, for prevention of kennel cough at a humane shelter. Dogs were examined on admission to the shelter and those without respiratory signs of disease were assigned daily, on a rotating basis, to receive one of three vaccines. We enrolled 972 healthy dogs. Dogs were monitored for up to 30 days post-vaccination for coughing and other clinical signs of respiratory disease. Thirty-three (10.7%; 95% confidence interval (CI): 7.2%, 14.2%) dogs in the IN-BP group, 36 (10.2%; CI: 7.0%, 13.4%) [corrected] dogs in the IN-BPA group, and 42 (13.5%; CI: 9.7%, 17.3%) [corrected] dogs in the IN-P group coughed spontaneously for > or = 1 day within 30 days of vaccination (P = 0.37). The IN-BP and IN-BPA vaccines were 20.7 and 24.4% effective, respectively, in reducing coughing compared with a placebo vaccine. The strongest prognostic factor for coughing (regardless of vaccine group) was the number of days spent at the shelter, with each additional day increasing the risk of coughing by 3% (95% CI: 1.01, 1.06) [corrected] The low incidence of coughing in the shelter during this study precluded observation of differences in vaccine effectiveness. No differences in vaccine-associated adverse events (coughing, sneezing, nasal or ocular discharge) were noted during the first 3 days post-administration or thereafter.

Adenoviridae↗
PubMed2005

Phosphodiesterase 3 inhibition and cough in elderly asthmatics.

AIMS: Cough is a common symptom of bronchial asthma, a chronic inflammatory airway disease. Recently, the therapeutic effects of selective phosphodiesterase (PDE) inhibitors have been focused on bronchial asthma. This study was designed to investigate the clinical effect of PDE 3 inhibition on cough reflex sensitivity in elderly patients with bronchial asthma. METHODS: Effects of cilostazol, a PDE 3 inhibitor, on cough response to inhaled capsaicin were examined in 11 patients over 70 years with stable asthma in a randomized, placebo-controlled cross over study. Capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of airway cough reflex sensitivity. RESULTS: The cough threshold was significantly (p < 0.05) increased after two-week treatment with cilostazol (100 mg twice a day orally) compared with placebo [48.8 (GSEM 1.4) vs. 29.2 (GSEM 1.3) muM]. CONCLUSION: These findings indicate that PDE 3 inhibition may be a novel therapeutic option for elderly patients with asthma, especially for their cough symptoms.

Journal Article↗
PubMed2005

An overview of the sensory receptors regulating cough.

The cough reflex represents a primary defensive mechanism for airway protection in a variety of mammalian species. However, excessive and inappropriate coughing can emerge as a primary presenting symptom of many airway diseases. Cough disorders are characterized by a reduction in the threshold for reflex initiation and, as a consequence, the occurrence of cough in response to stimuli that are normally innocuous in nature. The current therapeutic strategies for the treatment of cough disorders are only moderately effective. This undoubtedly relates in part to limitations in our understanding of the neural components comprising the cough reflex pathway. The aim of this review is to provide an overview of current concepts relating to the sensory innervation to the mammalian airways, focusing particularly on the sensory receptors that regulate cough. In addition, the review will highlight particular areas and issues relating to cough neurobiology that are creating controversy in the field.

Journal Article↗
PubMed2005

Comparison of cough reflex sensitivity after an inhaled antigen challenge between actively and passively sensitized guinea pigs.

BACKGROUND: Late asthmatic response is observed following antigen challenge in actively, but not passively, sensitized guinea pigs. Although cough reflex sensitivity is increased after antigen challenge in actively sensitized guinea pigs, it is unknown whether the antigen-induced increase in cough reflex sensitivity develops in passively sensitized animals. The aim of this study was to compare the cough reflex sensitivity to inhaled capsaicin after an inhaled antigen challenge between actively and passively sensitized guinea pigs. METHODS: Measurement of number of coughs elicited by increasing concentrations of capsaicin (10(-6) and 10(-4) M) and bronchial responsiveness to ascending concentrations of methacholine, and analysis of bronchoalveolar lavage fluid (BALF) were separately performed 24 h after an antigen challenge in actively and passively sensitized guinea pigs. RESULTS: Percentage of eosinophils in BALF and bronchial responsiveness to methacholine were increased 24 h after the antigen challenge in both actively and passively sensitized animals compared with saline-challenged actively and passively sensitized animals, respectively. Absolute number of eosinophils in BALF from actively sensitized and antigen-challenged guinea pigs was significantly greater than that from passively sensitized and antigen-challenged animals. Cough response to capsaicin and concentration of substance P in BALF were increased 24 h after the antigen challenge in actively sensitized guinea pigs, but not in passively sensitized guinea pigs. Bronchial responsiveness, cough reflex sensitivity and substance P concentration and total cells in BALF were increased in actively sensitized and saline challenged guinea pigs compared with passively sensitized and saline challenged animals. CONCLUSION: The results suggest that active sensitization per se increases cough reflex sensitivity accompanied by increased inflammatory cells and substance P level in BALF, and antigen challenge further increases them, while simple IgE- and/or IgG-mediated allergic reaction per se or the low intensity of eosinophil infiltration in the airway itself may not affect cough reflex sensitivity in guinea pigs.

Journal Article↗
PubMed2007

Prostaglandin I2 enhances cough reflex sensitivity to capsaicin in the asthmatic airway.

Inflammatory mediators are involved in the pathogenesis of airway inflammation, but the role of prostaglandin I2 (PGI2) remains obscure. This study was designed to investigate the role of PGI2 in cough reflex sensitivity of the asthmatic airway, which is characterized by chronic eosinophilic airway inflammation. The effect of beraprost, a chemically and biologically stable analogue of PGI2, on cough response to inhaled capsaicin was examined in 21 patients with stable asthma in a randomized, placebo-controlled cross over study. Capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of airway cough reflex sensitivity. The cough threshold was significantly (p < 0.05) decreased after two weeks of treatment with beraprost [17.8 (GSEM 1.20) microM] compared with placebo [30.3 (GSEM 1.21) microM]. PGI2 increases cough reflex sensitivity of the asthmatic airway, suggesting that inhibition of PGI2 may be a novel therapeutic option for patients with asthma, especially cough predominant asthma.

Journal Article↗
PubMed2001

[Chronic cough in children: signs of serious disease and investigations].

Only in some particular cases chronic cough requires special investigations. Respiratory diseases linked to environment are frequent in children. Cough is the most common symptom in child asthma and usually occurs during sleep or exercise. Environmental tobacco smoke exposure may concern up to 30% of families. Questioning should systematically check for parental smoking in children with chronic cough since avoidance is the only effective treatment. The incidence of whooping cough appears to be increasing and the diagnosis may be difficult among already immunized children in whom symptoms are often nonspecific. Nowadays Bordetella pertussis can easily be detected on nasal smears (ELISA, PCR, cultures). Swallowing dysfunction may cause productive cough in toddlers, most often related to functional dyspraxia, yet possibly due to aerodigestive tract malformation. Unrecognized bronchial foreign body is a well-known pitfall particularly between 9 and 36 months of age. Bronchiectasis and cystic fibrosis are responsible for chronic productive cough in toddlers and older children. In teenagers, psychogenic coughing is difficult to manage and usually requires psycho- and speech therapy.

Asthma↗
PubMed2006

Leukotriene receptor antagonist for prolonged non-specific cough in children.

BACKGROUND: Non-specific cough is defined as non-productive cough in the absence of identifiable respiratory disease or known aetiology. It is commonly seen in paediatric practice. These children are treated with a variety of therapies including a variety of asthma medications. The leukotriene pathway is reported to be involved in the sensory (neurogenic) pathway, which is a mechanism thought to be involved in the pathogenesis of chronic cough. OBJECTIVES: To evaluate the effectiveness of leukotriene receptor antagonist (LTRA) in treating children with prolonged non-specific cough. SEARCH STRATEGY: The Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register, MEDLINE and EMBASE databases were searched by the Cochrane Airways Group. The latest searches were carried out in September 2005. SELECTION CRITERIA: All randomised controlled trials comparing LTRA with a placebo medication in children with non-specific cough. DATA COLLECTION AND ANALYSIS: Results of searches were reviewed against pre-determined criteria for inclusion. One eligible trial was identified but no data was available for analysis. It was not possible to separate results from children with non-specific cough from those without. MAIN RESULTS: There was no significant difference in all study endpoints between the montelukast and placebo groups (total N=256). AUTHORS' CONCLUSIONS: With the lack of evidence, the routine use of LRTA in treating children with non-specific cough cannot be recommended.

Acetates↗
PubMed1997

Valsartan, a new angiotensin II receptor antagonist: a double-blind study comparing the incidence of cough with lisinopril and hydrochlorothiazide.

The present study compares the occurrence of a dry, persistent cough with doses of 80 mg of valsartan, 10 mg of lisinopril, or 25 mg of hydrochlorothiazide in patients with a history of angiotensin-converting enzyme inhibitor-induced cough. This was a randomized, double-blind, active-controlled, parallel group, multicenter trial involving 129 adult outpatients with essential hypertension. After confirmation of angiotensin-converting enzyme inhibitor-induced cough during a 2 to 4 week challenge with lisinopril (followed by a washout period of 2 weeks), patients were randomized to receive 6 weeks of double-blind treatment once daily with 80 mg valsartan, 10 mg lisinopril, or 25 mg hydrochlorothiazide. Assessments were made at baseline and after 3 and 6 weeks of treatment. Comparability of response to treatment was assessed by mean sitting diastolic and systolic blood pressure at the end of treatment. The occurrence of a dry, persistent cough was significantly less (P < 0.001) at 3 and 6 weeks with valsartan (19.5%) than with lisinopril (68.9%), with no significant difference between valsartan and hydrochlorothiazide (19.0%). There were no statistically significant differences in reduction of blood pressure among the three treatment groups. The overall incidence of adverse experiences, whether or not treatment-related, was highest for lisinopril (86.7%) compared with valsartan (57.1%), and hydrochlorothiazide (61.9%). A dry cough in the lisinopril group accounted for this difference. There were no clinically significant changes in physical signs or in results of clinical laboratory evaluations during double-blind treatment, except for from metabolic changes in 3 patients receiving hydrochlorothiazide. In hypertensive patients with a history of angiotensin-converting enzyme inhibitor-induced cough, a single daily dose of 80 mg of valsartan produced therapeutic efficacy comparable to lisinopril but with significantly less cough.

Angiotensin Receptor Antagonists↗
PubMed1998

Inhibition of capsaicin-induced cough by the gamma-aminobutyric acid agonist baclofen.

Gamma-aminobutyric acid (GABA) is a central inhibitory neurotransmitter that also exists in the lungs. The GABA-agonist baclofen has been shown to have antitussive activity via a central mechanism in animals. Recently it was demonstrated that a 14-day course of baclofen given three times daily significantly inhibits the cough reflex in healthy volunteers. Because of the prolonged antitussive effect of baclofen that has been previously observed, the present study was conducted to evaluate the antitussive effect of low-dose, oral baclofen given once daily. Forty-one healthy volunteers were randomly assigned in a double-blind manner to receive a 28-day course of baclofen, either 10 mg or 20 mg once daily, or placebo. Subjects underwent cough challenge testing with inhaled capsaicin to establish baseline cough reflex sensitivity, and subsequently after 14 and 28 days of therapy. Subjects receiving baclofen 20 mg daily demonstrated significant inhibition of cough sensitivity after 14 days and after 28 days of therapy compared with baseline. Neither placebo nor baclofen 10 mg daily had a significant effect on cough sensitivity. No serious side effects were experienced by any study participant. These results confirm the recent observation that baclofen has significant antitussive activity in humans. Further, once-daily administration of a relatively low dose of baclofen is sufficient to achieve significant cough inhibition, although at least 14 to 28 days of therapy may be required to attain maximal antitussive effect. These results support further investigation of baclofen or other GABA-agonists as potential therapeutic agents for chronic, nonproductive cough.

Administration, Oral↗
PubMedDate not supplied

Brainstem respiratory networks and cough.

The focus of this review is work that supports a model of the medullary neuronal network that is involved in producing the cough motor pattern of inspiratory and expiratory pump muscles. Evidence is presented that supports the following hypotheses: (1) Bulbospinal drive to respiratory motoneurons during cough arises, at least in part, from the same medullary neurons involved in providing drive during eupnoea. (2) Medullary Bötzinger/ rostral ventral respiratory group neurons implicated in generating and shaping the eupnoeic pattern of breathing are also involved in producing the central cough motor pattern. The results were not consistent with a "cough centre" separate from the BOT/VRG. Observed neurons (in cats) included most of all previously identified respiratory modulated "types". The results showed that there were alterations in discharge patterns of all respiratory neurons during fictive cough. Many "types" responded as predicted by cough model network simulations. Based on neuron behaviours in our studies and inferred synaptic actions among BOT/VRG neurons, we propose a preliminary model for cough generation by the BOT/rVRG network.

Animals↗
PubMed2002

Paediatric problems of cough.

All children cough, but most children are normal. In a child with isolated cough, a detailed history and examination, followed in a small number of cases by targeted investigations, should allow the child to be placed in one of five diagnostic categories. These are normal child; the child with a serious illness such as cystic fibrosis, tuberculosis etc. the child with non-serious, but treatable causes of cough and wheeze, for example gastro-oesophageal reflux or postnasal drip; the child with an asthma syndrome and an overestimation of symptoms for psychological or other reasons by either or both of child or family. Treatment is of the underlying condition if appropriate. Non-specific treatment with cough syrups are not useful. Attention to environmental factors such as active and passive smoking, and exposure to dust and pets is important. The diagnosis of cough variant asthma should only be made in older children after variable airflow obstruction and response to bronchodilator has been demonstrated physiologically. In younger children, rational diagnostic criteria are an abnormally increased cough, with no evidence of any non-asthma diagnosis, a clear-cut response to a therapeutic trial of asthma medication, usually moderate dose inhaled corticosteroids, and relapse on stopping medications with second response to recommencing them. Some such children go on to develop more typical asthma, with wheeze and bronchial hyper-reactivity. It is important however, not to over-diagnose asthma in children who in fact have a chronic non-specific cough. Such children require no treatment, get better with time, and have normal long-term lung function.

Asthma↗