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PubMed2006

Prevalence of depressive symptoms among patients with chronic cough.

STUDY OBJECTIVES: Cough is the most common complaint for which patients in the United States seek medical attention. Although the significant effect of cough on quality of life has been reported, the association of chronic cough with depressive symptomatology has not previously been investigated. DESIGN: Prospective, nonrandomized evaluation. SETTING: Outpatient department of academic medical center. PATIENTS: Representative sample of patients presenting to a specialty center seeking evaluation and treatment of chronic cough. INTERVENTIONS: Participants completed the Center for Epidemiologic Studies Depression Scale (CES-D), a 20-item self-report questionnaire designed to measure depressive symptomatology and risk for clinical depression, on initial evaluation and again after 3 months. Patients also provided subjective cough scores reflecting the severity of their cough. MEASUREMENTS AND RESULTS: Of 100 patients undergoing initial evaluation, 53% scored positive (>/= 16) on the CES-D. Mean CES-D score was 18.3 +/- 13.2 (+/- SD). Among 81 subjects followed up at 3 months, mean CES-D score fell to 7.4 +/- 10.4, and subjective cough score decreased from 10 to 4.9 +/- 3.1. There was a statistically significant improvement in both cough and depression scores after 3 months (p < 0.001). Improvement in cough score correlated significantly with improvement in depression score (p = 0.003; Spearman rho = 0.323). CONCLUSION: Depressive symptomatology is very common in patients with chronic cough. Physicians and other caregivers must be aware of the significant risk of clinical depression in this patient population.

Adult↗
PubMed1991

Cough in hot pepper workers.

STUDY OBJECTIVE: To determine whether there is an effect on the prevalence of respiratory symptoms, an alteration in lung function, or an increase in the cough threshold to capsaicin among workers chronically exposed to hot chili (Capsicum) peppers. DESIGN: Cross-sectional study of responses to a structured questionnaire, lung function assessed by spirometry and cough threshold to inhalation of capsaicin aerosol in a group of occupationally-exposed Capsicum workers as compared to non-exposed employees of the same work site. SETTING: Spice manufacturing facility. PARTICIPANTS: Twenty-two Capsicum-exposed and 19 nonexposed workers. MEASUREMENTS AND MAIN RESULTS: When evaluated by questionnaire, 13 (59 percent) of the Capsicum-exposed workers reported cough as compared to 4 (21 percent) of the nonexposed workers (p less than 0.05). Baseline FEV1 and FVC did not differ between the two groups. Cough threshold, as assessed by the lowest concentration of inhaled capsaicin eliciting cough, was related to workplace exposure (p = 0.05), displaying a bimodal pattern of higher and lower cough thresholds among the Capsicum workers as compared to a unimodal distribution among the nonexposed workers. Within the exposed group, a higher cough threshold was significantly related to male gender (p = 0.03) and was associated to a lesser extent with dietary preference for hot food (p = 0.09) and cumulative cigarette smoking (p = 0.07). CONCLUSION: Chronic occupational exposure to chili peppers is associated with complaints of cough but does not alone lead to decreased responsiveness of capsaicin-sensitive nerves when assessed by cough threshold. The cough response to capsaicin inhalation may be modified by the effects of multiple, potentially interactive factors.

Adult↗
PubMed2003

Interaction of noscapine with the bradykinin mediation of the cough response.

Angiotensin Converting Enzyme Inhibitors (ACEI) like captopril and enalapril, can induce persistant cough in man. Noscapine, an antitussive alkaloid, can be used to suppress ACEI-induced cough. Some workers have suggested a role for bradykinin in precipitation of ACE-induced cough. Work carried out in our laboratory has shown noscapine to be a non-competitive inhibitor of bradykinin in guinea pig ileum. It is therefore possible that noscapine suppresses cough by blocking the effect of bradykinin receptor activation in the airways. Guinea pigs were placed in a cough-chamber connected to an air pump and a pressure transducer. Capsaicin was sprayed into the chamber and cough was recorded as a distinctive change in air pressure inside the cough-chamber. Animals treated with 1 mg/kg captopril and enalapril for 7 days, showed increased cough response. Ten microgram/kg FR190997, a non-peptide agonist of the bradykinin B2 receptor, also increased the cough response. Noscapine at 0.5, 1 and 2 mg/kg was able to reverse the effects of ACEI and FR190997. Naloxone, a specific opioid receptor inhibitor, did not block the antitussive effects of noscapine in enalapril or FR190997 treated guinea pigs. This antitussive effect of noscapine is not mediated via the mu, kappa or delta opioid receptors. It is therefore possible that noscapine exerts its antitussive action by interfering with the bradykinin cough mediation.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Discrimination of productive and non-productive cough by sound analysis.

There are two types of coughs, productive and non-productive; the former is caused by excess airway secretions. The analysis of cough may provide important clues not only to aid diagnosis, but also for the selection of drugs for treatment. In this study, cough sounds recorded in a free acoustic field from patients with productive cough and non-productive cough due to chronic airway diseases were compared with those of voluntary cough of healthy subjects and were analyzed by sound spectrogram and time-expanded waveform. All cough sounds could be separated into two or three phases. The implementation of the novel technique to record cough sounds in the free acoustic field and to analyze the sounds of the high frequency range enable recognition of the characteristics of the cough sounds in phase 2 of the cough.

Acoustics↗
PubMed2001

Bordetella pertussis in the aetiology of chronic cough in adults. Diagnostic methods and clinic.

Cough is one of the most common complaints causing patients to seek medical attention, and chronic cough, defined as a cough period of at least three weeks, accounts for more than a third of referrals to a chest physician. Cough is an important factor in the spread and survival of microorganisms, but until recently little attention has been given to Bordetella pertussis (B. pertussis) in patients with chronic cough. This review summarizes the B. pertussis diagnostic methods--culture--polymerase chain reaction (PCR), and serology--and surveys the literature on B. pertussis and chronic cough in adults. There is growing evidence that B. pertussis is an important cause of persistent cough in adults; thus prevalence of pertusssis of 12.4-26% has been reported in studies from US, Australia and Germany. Recently we found evidence of pertussis as the cause of chronic cough in 16% of otherwise healthy adults in Denmark. Therefore, patients with chronic cough should be examined for B. pertussis infection. The demonstration of B. pertussis in an adult patient with chronic cough has two advantages: 1) the patient can be reassured that symptoms will disappear spontaneously, why more or less invasive examinations and empirical therapeutic trials can be omitted, 2) the source of infection can be eradicated, and contact persons, particularly non vaccinated infants in whom pertussis might be very severe, can be treated in order to avoid or attenuate clinical symptoms.

Adult↗
PubMed2005

The effect of chemical stimulation of esophageal mucosa on citric acid induced cough and specific airway resistance in guinea pig.

BACKGROUND: Gastroesophageal reflux disease is one of the most common causes of chronic cough. The mechanism of the cough initiation in these patients remains unresolved. OBJECTIVES: This study was designed to investigate the effect of intraesophageal (IE) administration of capsaicin on cough and specific airway resistance (Saw) in guinea pigs. METHODS: Male TRIK strain guinea pigs were used. In the first experiment 12 controls received IE saline, 9 animals (group 1) received IE capsaicin (400 microM, 0.2 ml) and 12 guinea pigs (group 2) received IE capsaicin (400 microM, 0.2 ml) 24 hours after IE administration of hydrochloric acid (3 M, 0.2 ml). Cough induced by inhalation of citric acid (CA) and Saw was determined after IE administration of saline in controls and capsaicin in groups 1 a 2. In the second experiment, CA induced cough was determined in guinea pigs (n=13) in the beginning of the study (control response), after NaOH (1 M, 0.2 ml) was administered IE. One week later in conditions of corrosive esophagitis CA induced cough was determined after IE administration of capsaicin (cough during esophageal stimulation). RESULTS: There was no difference in CA induced cough between controls, group 1 and 2 (p=0.98). Saw was hot affected by IE capsaicin stimulation and CA inhalation in group 1 and group 2. There was no difference found between control cough response and those induced after IE capsaicin in animals with corrosive esophagitis (p=0.75). CONCLUSION: Esophageal stimulation with capsaicin did not trigger and/or modulate CA induced cough and Saw in guinea pigs models. (Fig. 5, Ref. 22.)

Airway Resistance↗
PubMed1991

[Angiotensin converting enzyme (ACE) inhibitor-induced cough in non-smoking hypertensive patients].

The author studied the characteristics of ACE inhibitor-induced cough in 41 non-smoking hypertensive patients. For at least 6 months, 20 patients (10 males and 10 females) were treated with enalapril, and 21 (11 males and 10 females) with aracepril. The results were as follows. 1) ACE inhibitor-induced cough was induced in 7 cases (1 male and 6 females). The incident rate of cough was 17.1%. ACE inhibitor-induced cough was not significantly related to past allergic history or to the beta-adrenergic blocker therapy. The laboratory findings of the cough sufferers--such as eosinophil percent in venous blood, serum GOT and GPT, urea nitrogen, creatinine, renal function (PSP excretion test and creatinine clearance), and pulmonary function (%FVC, FEV1.0% and %V25)--were not significantly different from those of the non-coughers. 2) Inhibitory effects of ipratropium bromide inhalation of ACE inhibitor-induced cough were noted in 83.3% of the patients, but their coughs did not completely disappear. From these findings, the pathogenesis of this cough may be related to be as follows. The cough seems to be related to the release of acetylcholine from vagal nerve terminals or to the stimulation of irritant receptors and vagal reflex. 3) Chronic persistent cough or bronchial asthma did not occur after stopping the treatment with ACE inhibitors. The mean follow-up period was 15.6 months.

Acetylcholine↗
PubMed1987

Airway anaesthesia and the cough reflex.

Topically and intravenously administered local anaesthetic agents are widely used to inhibit cough, but little quantitative, pharmacological data seems to be available. Various aspects of local anaesthetic agents as inhibitors of cough and other airway reflexes are discussed. Nebulized lidocaine dose-dependently inhibited both mechanically (trachea, carina) and ammonia vapour-induced cough. Lidocaine had a similar potency on each type of cough but inhibited that caused by mechanical stimulation for a significantly longer period of time. This observation supports the hypothesis of a more peripheral location for receptors mediating chemical cough. Nebulized tetracaine appeared to be more potent and to have a significantly longer duration of action than lidocaine. The Hering-Breuer inflation reflex was attenuated by both agents and in doses larger than those needed to inhibit cough. This observation is compatible with the view that the cough receptors are located close to the airway lumen and those mediating the Hering-Breuer reflex within the smooth muscle. Airway anaesthesia is commonly used to block the cough reflex during endoscopic procedures. Nebulized lidocaine has been reported also to suppress severe chronic cough but further studies on airway anaesthesia and cough in acute and chronic lung disease are warranted.

Aerosols↗
PubMed1986

A search for subclinical infection during a small outbreak of whooping cough: implications for clinical diagnosis.

The transmission of whooping cough in a general practice community was followed after the identification of the first case for nearly three years. Intensive case-finding was undertaken to detect contacts of known cases of whooping cough and to take pernasal swabs from those with any cough; 102 swabs were taken. In three months 39 cases of whooping cough were clinically diagnosed, 17 (44%) of which were confirmed bacteriologically. All had a prolonged paroxysmal cough, one-third reported a catarrhal phase, 18 (46%) vomited with paroxysms and nine (23%) whooped. No isolations of Bordetella pertussis were obtained from the 84 contacts with non-paroxysmal coughs. There was no evidence that subclinical bordetella infection (showing none of the signs of whooping cough) is a common occurrence.It is probable that many recognizable cases of whooping cough are missed because it can be a milder illness than is often realized and commonly exhibits neither whooping, vomiting nor a catarrhal phase. Paroxysms may be infrequent. The diagnosis of whooping cough should be suspected from a prolonged paroxysmal cough alone.

Adolescent↗
PubMed1995

Modulation of the renin-angiotensin-aldosterone system and cough.

OBJECTIVES: To review the clinical features of the cough related to angiotensin-converting enzyme (ACE) inhibitor therapy, and to suggest from a prospective controlled study that angiotensin II (Ang II) receptor antagonists are not associated with this particular side effect to the same extent as observed with ACE inhibitors. DATA SOURCES: All pertinent data from reports published between 1972 and 1994 were identified through a comprehensive medical literature search. Additionally, results are presented from an international multicentre study examining the occurrence of cough in 135 patients with mild to moderate hypertension, with a history of ACE inhibitor-related cough, who were randomly given either losartan (a type I Ang II receptor antagonist), lisinopril (an ACE inhibitor), or hydrochlorothiazide (a thiazide diuretic). STUDY SELECTION: More than 500 articles were identified; those reporting frequency, characterization, mechanism and treatment of ACE inhibitor-induced cough were chosen. For the multicentre study, men and women with uncomplicated hypertension and a history of ACE inhibitor dry cough were eligible to enter, provided their cough had completely resolved. DATA EXTRACTION AND SYNTHESIS: Relevant information from published case reports, abstracts, postmarketing surveillance studies, hospital series and randomized controlled trials was examined and synthesized. In a recent multicentre study in which patients with a prior history of ACE inhibitor-related cough were randomized into three treatment groups, the percentage of patients with a dry cough was significantly higher in the lisinopril group (72%) than in the losartan (29%) or the hydrychlorothiazide (34%) groups. CONCLUSIONS: Ang II receptor antagonists are novel pharmacological agents that block the renin-angiotensin-aldosterone system at the level of tissue receptors, without affecting interdependant systems. Results from the prospective study reported in the present manuscript demonstrate that the higher specificity of the type I Ang II receptor antagonist losartan is associated with a significantly lower incidence of cough than seen with ACE inhibitors. Losartan thus represents a potential new treatment for hypertensive patients in whom ACE inhibition or Ang II receptor antagonists are indicated, but who develop cough with ACE inhibitors.

Angiotensin II↗
PubMed1994

Outcome of cough variant asthma treated with inhaled steroids.

BACKGROUND: Cough variant asthma is defined as a persistent nonproductive cough with minimal wheezing or dyspnea. The uncontrolled coughing may interfere with sleep, work, and social activities. Cough precipitating fecal or urinary incontinence can be extremely distressing. The diagnosis is established within 1 to 2 weeks by a trial of prednisone, 30 mg a day. The cough will be controlled within that time and subsequent management can consist of inhaled corticosteroids. OBJECTIVE: To evaluate the course of ten patients with cough variant asthma and their response to inhaled corticosteroids. METHODS: Retrospective analysis of the presentation, diagnosis, course, and response to oral and inhaled steroids in ten patients with cough variant asthma. RESULTS: Ten patients whose chief complaint was persistent debilitating cough for periods of 2 months to 20 years underwent a diagnostic and therapeutic trial of prednisone as previously described. At a mean follow-up period of 28 months all were free of debilitating cough. Eight of ten patients were still receiving inhaled steroids and two needed low dose alternate day oral steroid therapy. Two patients had complete remission of symptoms. None required daily inhaled or oral bronchodilators and there were no hospital admissions for respiratory symptoms. CONCLUSIONS: Inhaled corticosteroid therapy after a diagnostic trial of oral steroids is effective for long-term control of cough variant asthma.

Administration, Inhalation↗
PubMed1998

[A pilot phase II study of combination therapy with oxatomide, an antihistamine, plus dextromethoraphan and bakumondo-to, an herbal drug, in patients with postinfectious persistent cough].

Previously, we reported the effectiveness of treatment with oxatomide (O), an antihistamine, plus dextromethorphan (D), and that of Bakumondo-to (B), an herbal drug that inhibits the activation of C-fibers, in patients with persistent coughing after upper-airway infection. In this study, we evaluated the efficacy and side effects of combination therapy (O + D + B) in patients with postinfectious persistent cough. Patients who had been coughing for more than three weeks and had a history of upper-airway infection took part in the study. None had any history of nasal disease, gastroesophageal reflux, bronchial asthma, or other chronic pulmonary disease. All patients were non-smokers, and none used angiotensin converting enzyme (ACE) inhibitors. All had normal chest roentgenograms and normal pulmonary function. The following hematological data were obtained before treatment: peripheral eosinophil counts. CRP levels, serum IgE concentrations, and titers of cold agglutinins and antibodies to Mycoplasma pneumoniae. The effects of one week of treatment with O + D + B on the severity of coughing, as estimated with a cough diary, were examined. Thirty-six patients entered the study, but only 18 with normal hematological findings who satisfied the study criteria were eligible for efficacy and side-effect analyses. Cough scores decreased significantly from 5.1 +/- 2.4 (range, 2-9) to 1.2 +/- 1.9 (range, 0-6), and the rate of cough disappearance was 50%. Two patients reported slight drowsiness. Therapy with O + D + B reduced perception of coughing as estimated with a cough diary. These results suggest that this therapy (O + D + B) may be useful in patients with postinfectious persistent cough.

Adrenergic beta-Agonists↗
PubMed2026

The Genetic Architecture of Chronic Cough: From Sensory Hypersensitivity to Treatable Trait.

Chronic cough is a prevalent global clinical disorder with substantial quality-of-life impairment, and refractory cases remain a major unmet medical need. Cough hypersensitivity syndrome is the core pathological mechanism of chronic cough, and growing genetic evidence has confirmed that inherited susceptibility shapes cough hypersensitivity, clinical heterogeneity and therapeutic responsiveness, redefining chronic cough as a biologically mediated sensory-neural disorder rather than a non-specific secondary symptom of airway diseases. This review summarises genetic evidence for chronic cough from family-based studies, pharmacogenomics and genome-wide association studies (GWAS), revealing distinct genetic architectures of chronic dry cough and sputum production, with enrichment of sensory-neural pathway variants and key genetic loci such as replication factor C subunit 1 (RFC1) functional genomic analyses link genetic variation to vagal afferent excitability, and rare genetic neurological disorders further illuminate the neurogenic basis of cough hypersensitivity. Moreover, genetic insights identify tractable treatable traits and rationalise antitussive drug development, supporting genotype-guided patient stratification. We conclude that integrating genetic architecture into clinical phenotyping and translational research provides a critical framework for precision management of chronic cough, and future progress relies on harmonised deep phenotyping and multi-ancestry genetic studies.

RFC1 gene↗
PubMed2006

Chronic cough due to occupational factors.

Within the large variety of subtypes of chronic cough, either defined by their clinical or pathogenetic causes, occupational chronic cough may be regarded as one of the most preventable forms of the disease. Next to obstructive airway diseases such as asthma or chronic obstructive pulmonary disease, which are sometimes concomitant with chronic cough, this chronic airway disease gains importance in the field of occupational medicine since classic fiber-related occupational airway diseases will decrease in the future. Apart from acute accidents and incidental exposures which may lead to an acute form of cough, there are numerous sources for the development of chronic cough within the workplace. Over the last years, a large number of studies has focused on occupational causes of respiratory diseases and it has emerged that chronic cough is one of the most prevalent work-related airway diseases. Best-known examples of occupations related to the development of cough are coal miners, hard-rock miners, tunnel workers, or concrete manufacturing workers. As chronic cough is often based on a variety of non-occupational factors such as tobacco smoke, a distinct separation into either occupational or personally -evoked can be difficult. However, revealing the occupational contribution to chronic cough and to the symptom cough in general, which is the commonest cause for the consultation of a physician, can significantly lead to a reduction of the socioeconomic burden of the disease.

Journal Article↗
PubMed2005

No effect of omeprazole on pH of exhaled breath condensate in cough associated with gastro-oesophageal reflux.

BACKGROUND: Endogenous airway acidification evaluated as pH in exhaled breath condensate (EBC) has been described in patients with chronic cough. Proton pump inhibitors improve gastro-oesophageal reflux (GOR)-associated cough. METHODS: We examined pH levels in EBC and capsaicin cough response in 13 patients with chronic cough (mean age 41 years, SD 9) associated with GOR before and after omeprazole treatment (40 mg/day for 14 days) and its relationship with clinical response. RESULTS: Omeprazole abolished symptoms associated with GOR. Patients with chronic cough had an EBC pH of 8.28 (SD 0.13) prior to treatment but this did not change with omeprazole treatment. There was a significant improvement in the Leicester Cough Questionnaire symptom scores from 80.8 points (SD 13.2) to 95.1 (SD 17) (p = 0.02) and in a 6-point scale of cough scores, but there was no change in capsaicin cough response. CONCLUSION: An improvement in GOR-associated cough was not associated with changes in EBC pH or capsaicin cough response. These parameters are not useful markers of therapeutic response.

Journal Article↗
PubMed2006

Comparative efficacy and tolerability of pholcodine and dextromethorphan in the management of patients with acute, non-productive cough : a randomized, double-blind, multicenter study.

INTRODUCTION: The aim of this study was to compare the efficacy and tolerability of pholcodine with that of dextromethorphan, one of the most used cough sedative products, in patients with acute, non-productive cough. METHODS: 129 adults with a diagnosis of acute, frequent, non-productive cough participated in a randomized, double-blind, parallel-group, multicenter trial. Medications were in a syrup formulation and were taken orally three times daily for 3 days. The efficacy endpoints were the change from baseline in the daytime and night-time cough frequency on 5-point scales at day 3, and cough intensity. RESULTS: A reduction of 1.4 and 1.3 points in the mean daytime cough frequency at day 3 was seen in the pholcodine and dextromethorphan groups, respectively, in the per-protocol population. The reduction in mean night-time cough was 1.3 for both groups. Cough intensity reduction was 0.7 for pholcodine and 0.8 for dextromethorphan. CONCLUSIONS: These findings indicate that the efficacy of a 3-day course of pholcodine is similar to that of dextromethorphan in the treatment of adult patients with acute, non-productive cough. Both medications were well tolerated.

Cough↗
PubMed1977

Cough. A comprehensive review.

An understanding of the anatomic, physiologic, and pathophysiologic aspects of cough is necessary to appropriately diagnose and treat patients with cough. In the majority of persons, cough that is acute and self-limiting is usually secondary to a viral upper respiratory tract infection; cough that is chronic and persistent is usually due to chronic bronchitis or postnasal drip. In the remaining persons, to determine the cause of cough, it is necessary to systematically consider anatomic locations were receptors and afferent nervous pathways are located. Definitive treatment of cough depends on determining its precise cause and then initiating specific therapy for the underlying disorder. Only when the cause of cough remains unknown or when cough performs no useful function and its complications represent a potential hazard to the patient, should symptomatic treatment be considered. Combination cough preparations should not be prescribed.

Antitussive Agents↗
PubMed1998

Recurrent cough: natural history and significance in infancy and early childhood.

We investigated the outcome for a sample of children in whom recurrent cough was reported in the preschool years to determine 1) whether they shared the characteristics attributed to cough variant asthma, and 2) the proportion who developed classical wheezy asthma at follow-up during the early school years. A cohort of children identified as having recurrent cough in the preschool period was reassessed during the early school years. Previously identified asymptomatic preschool children who remained symptom-free provided a comparison group with respect to current respiratory symptoms, lung function, bronchial reactivity to inhaled methacholine, atopic status, peak flow variability, and recorded night cough. The response rate was modest, with 41% attending the follow-up study; information on current symptoms was available from a further 16%. Ascertainment of current symptoms showed that 70 of 125 (56.0% [95% CI 47.3-64.5%]) were symptom-free at follow-up, 46 (36.8% [28.7-45.5%]) continued to have recurrent cough in the absence of colds, and 9 (7.2% [3.6-12.8%]) reported recent attacks of wheeze. When comparing the 46 children whose recurrent cough persisted from the preschool period through to follow-up with subjects from the asymptomatic comparison group, the former had significantly more night cough (50.0% vs. 16.8%; P< 0.01), were more likely to be treated (10.9% vs. 1.7%; P=0.01), or were diagnosed (26.1% vs. 5.7%; P < 0.001) as asthmatic. They also showed greater bronchial reactivity than their asymptomatic counterparts (1.23 mg/ml vs. 3.35 mg/ml; P=0.002). Atopic status and other indices of lung function were similar between groups. We conclude that there are a group of children with long-term recurrent cough who display features consistent with a diagnosis of cough variant asthma, but at 2-4 years of follow-up, few progress to develop asthma characterized by wheeze.

Asthma↗