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At least 649 records · Page 36Linked to original sources
PubMed1989

Sensitivity of the human cough reflex: effect of inflammatory mediators prostaglandin E2, bradykinin, and histamine.

Prostaglandins may cause hyperresponsiveness to bronchoconstrictor agents in the lung and hyperalgesia in the skin. Increased airway concentration of both prostaglandins and bradykinin has been suggested as the possible cause of the increased cough sensitivity sometimes found in patients with cough associated with taking drugs that inhibit angiotensin-converting enzyme. We have therefore investigated the effect of prostaglandin E2 (PGE2), bradykinin (BK), histamine (H), and citric acid (C) on capsaicin-induced cough and increase in respiratory resistance (Rrs). Capsaicin-induced changes in Rrs and dose-cough response were measured before and after inhaling 0.76 mumol of PGE2, BK, H, and C. All the test substances caused cough, which was subject to tachyphylaxis, but no significant change in Rrs. Neither BK, H, nor C altered the capsaicin cough or Rrs response. However, PGE2 significantly increased both responses to capsaicin, the geometric mean (95% Cl) for the dose of capsaicin causing 5 or more coughs being 16.2 (14.3 to 18.3) nmol before and 4.4 (2.4 to 7.9) nmol after PGE2 (p less than 0.05). The percent increase (95% Cl) in Rrs after capsaicin was 20 (16.5 to 23.5)% before and 37.2 (32.2 to 43.2)% after PGE2 (p less than 0.05). The results suggest that the cough reflex will be increased in the presence of PGE2 in the airway.

Adult↗
PubMed1983

Mechanism of cough and bronchoconstriction induced by distilled water aerosol.

We studied the relationship between cough and bronchoconstriction caused by inhaled distilled water aerosol in 8 subjects with asthma by measuring specific airways resistance (SRaw) and recording cough while subjects breathed serially increasing volumes of distilled water or normal saline aerosol produced by an ultrasonic nebulizer. We performed the distilled water dose-response curves after no treatment and after treatment with cromolyn aerosol, lidocaine aerosol, or atropine aerosol in doses of 0.2 mg and 2.0 mg on separate days. Without prior treatment, distilled water aerosol caused cough in 7 of 8 subjects and a marked increase in SRaw in every subject, whereas saline aerosol did not cause cough or a greater than 50% increase in SRaw in any subject. The 2 doses of atropine caused an equivalent reduction in baseline SRaw, but 2.0 mg caused greater inhibition of water-induced bronchoconstriction than did 0.2 mg. Neither dose of atropine inhibited cough. These data suggest that water-induced bronchoconstriction involves cholinergic nerves and that water-induced cough is not dependent on bronchoconstriction. Lidocaine inhibited cough but not bronchoconstriction, whereas cromolyn inhibited bronchoconstriction but not cough, suggesting that cromolyn does not inhibit bronchoconstriction by a generalized inhibition of airway afferent nerves.

Adolescent↗
PubMed2003

A study of the cough reflex in idiopathic pulmonary fibrosis.

Little is known about the pathogenesis of cough in idiopathic pulmonary fibrosis (IPF). We hypothesized that abnormalities of respiratory tract tachykinin-containing sensory nerves may be implicated. We studied cough response to capsaicin, substance P (SP), and bradykinin in 10 healthy control subjects and 10 patients with IPF. Six patients were tested before and after steroid therapy. Induced sputum cell counts and neurotrophic factor levels were also measured in 13 patients and 13 control subjects. The results show that cough sensitivity to capsaicin was greater in patients (p < 0.01). Neither SP nor bradykinin induced cough in normal subjects. SP and bradykinin induced cough in 7/10 patients (p < 0.002) and 2/10 patients (not significant) with IPF, respectively. Prednisolone caused a reduction in cough sensitivity to capsaicin (p < 0.05) and SP (p < 0.05) in all six patients treated. There were significantly more neutrophils (p = 0.001) and higher levels of nerve growth factor (p < 0.01) and brain-derived neurotrophic factor (p < 0.01) in patient's sputa. These findings suggest functional upregulation of lung sensory neurones in IPF. The cough response to inhaled SP in most patients may reflect disrupted respiratory epithelium. The response to corticosteroids demonstrates that the cough is amenable to therapy.

Aged↗
PubMed2003

Cough-generated aerosols of Mycobacterium tuberculosis: a new method to study infectiousness.

The concentration and size distribution of infectious aerosols produced by patients with pulmonary tuberculosis (TB) has never been directly measured. We aimed to assess the feasibility of a method that we developed to collect and quantify culturable cough-generated aerosols of Mycobacterium tuberculosis. Subjects were recruited from a referral hospital and most had multidrug-resistant TB. They coughed into a chamber containing microbial air samplers while cough frequency was measured during two 5-minute sessions. Cough-generated aerosol cultures were positive in 4 of 16 subjects (25%) with smear-positive pulmonary TB. There was a rapid decrease in the cough-generated aerosol cultures within the first 3 weeks of effective treatment. Culture-positive cough aerosols were associated with lack of treatment during the previous week (p = 0.007), and there was a trend in the association with cough frequency (p = 0.08). The size distributions of these aerosols were variable, but most particle sizes were in the respirable range. Quantification of viable cough-generated aerosols is feasible and offers a new approach to study infectiousness and transmission of M. tuberculosis and other airborne pathogens.

Aerosols↗
PubMed2006

Respiratory retraining therapy and management of laryngopharyngeal reflux in the treatment of patients with cough and paradoxical vocal fold movement disorder.

OBJECTIVES: We describe the outcome of patients with cough and paradoxical vocal fold movement disorder (PVFMD) treated with respiratory retraining therapy and management of laryngopharyngeal reflux (LPR). METHODS: Twenty patients with the complaint of cough were given a diagnosis of PVFMD and treated with proton pump inhibitors for a minimum of 6 months followed by 3 to 5 sessions of respiratory retraining therapy. Pulmonary function testing (PFT) and subjective rating of cough and reflux (reflux symptom index; RSI) were performed. Also, PFT and rating of cough were performed on a group of 10 healthy volunteers with no complaint of cough. RESULTS: The study group comprised 13 women and 7 men. The baseline cough rating and ratio of forced inspiratory volume at 0.5 second to forced inspiratory vital capacity (FIV0.5/FIVC) on PFT were significantly worse in the treatment group than in the control group. After therapy, 20 patients (100%) experienced improvement in cough, 19 patients (95%) experienced improvement on PFT, and 17 patients (85%) experienced improvement in the RSI score. The differences were statistically significant. CONCLUSIONS: Respiratory retraining therapy combined with management of LPR is an effective treatment for patients with cough and PVFMD when a single-modality treatment is not sufficient.

Adolescent↗
PubMed1996

Capsaicin cough receptor sensitivity test in children.

Capsaicin has been used as a tussive agent in studies in adults to determine cough receptor sensitivity. The aim of this study was to determine the tolerance, repeatability and influence of inspiratory flow on the capsaicin cough receptor sensitivity test in children. Thirty children (mean age 11 yrs; range 6-16 yrs) were tested on two different days, to determine the lowest concentration of capsaicin required to stimulate two or more coughs (cough threshold (Cth)), 2-4 coughs (C2), and five or more coughs (C5). Capsaicin was nebulized through a dosimeter, with an arrangement that allowed the subjects to visualize and regulate their inspiratory flow. Using a constant inspiratory flow of 20 L x min(-1), tests were reproducible for C2, C5 and Cth (doubling dose changes of 1.13, 1.03 and 1.08, respectively). An increase in the inspiratory flow from 20 to 60 L x min(-1) significantly increased C2 (19.5 to 46.8 microM; p=0.016) and C5 (46.8 to 128.8 microM; p=0.008). We conclude that in children, the capsaicin cough challenge test: 1) is well-tolerated; 2) is highly repeatable; and that 3) the inspiratory flow significantly influences cough receptor sensitivity and repeatability of the test and should, thus, be regulated.

Adolescent↗
PubMed1998

Airway dynamics, oesophageal pressure and cough.

This study hypothesizes that: peak supramaximal airflow during cough reflects expiratory muscle effort, and that expiratory muscle function during cough might be assessed from the airflow signal alone. We monitored airflow and oesophageal pressure (Poes) in normal subjects during cough generated under two conditions: 1) voluntarily from functional residual capacity (FRC); and 2) involuntarily after inhalation of citric acid (CA). Maximal expiratory cough flow was quantified as the quotient of maximal flow during a given cough divided by maximal flow at the matched volume of thoracic gas (Vtg) as identified on the maximal expiratory flow-volume curve. We found: flow ratios correlated poorly with Poes; the variance of flow ratios associated with a series of voluntary coughs was poorly explained by Poes. During CA inhalation, when the Vtg compressed during cough could not be controlled, correlation of Poes with flow ratio remained poor. We conclude that to study the motor limb of the cough reflex, measurements of both airflow and oesophageal pressure are required.

Administration, Inhalation↗
PubMed1975

[Pharmacological studies on the cough reflex].

The artificially induced cough reflex in experimental animals should necessarily be similar to the cough which occurs naturally in humans. The curve demonstrated during a cough of each patient with respiratory disease was characteristic. Compared with the curve of a cough-like reflex (CLR) induced by DMPP, the curve of a cough induced by electrical stimulation of the tracheal mucosa was similar to that of a cough in humans. In dogs and cats anesthetized with alpha-chloralose (80 similar to 100 mg/kg i.p.), the number of CLR with DMPP was dose dependent. Tachphylaxis did not occur despite repeated administration of DMPP. DMPP (5 similar to 10 mug/kg i.v.) did not affect airway resistance. CLR with DMPP was depressed not only by morphine, codeine, oxymethebanol, picoperidamine, piclobetol and hexacol but also by hexamethonium. Thus, it appears that the mechanism of CLR with DMPP is different from that in the cough reflex. This CLR may be utilized for determining the physiology of cough reflex and the site of action of antitussives.

Airway Resistance↗
PubMed1978

Influence of tracheal muscular tone on the initiation of cough reflex.

We devised a canine blood-perfusion preparation which made feasible administration of drugs directly at the local tracheal site. The hypothesis of Salem and Aviado on cough mechanism that a local airway constriction induced by stimuli may be a trigger in stimulating cough receptors was investigated using this preparation. Close intraarterial injections of acetylcholine (ACh) and histamine did not elicit a cough although intense tracheal constrictions were evident. The cough reflex elicited by electrical stimulation of the mucosa of isolated upper trachea in situ was accompanied by a slight systemic hypotension, tracheal vasodilatation and tracheal muscular constriction. The latter two changes occurred after a time lag following coughs. Close intraarterial infusions of isoproterenol and papaverine caused a prominent tracheal dilatation, but did not suppress the coughs. Pretreatment with atropine sufficiently inhibited cholinergic tracheoconstriction but had no effect on the electrically induced coughs. Furthermore, an augmentation of the tracheal muscular tone produced by an infusion of ACh did not enhance the cough reflex. In light of our observations, the aforementioned hypothesis should be reconsidered.

Acetylcholine↗
PubMed1982

Analysis of efferent discharges of the phrenic nerve during the cough reflex.

The response of the phrenic nerve activities during the cough reflex was investigated in anesthetized dogs. The phrenic nerve activities were recorded from the central cut end of the nerve. Changes in phrenic nerve activities were evaluated by means of computer analysis using the programs for power spectrum, amplitude histogram, pulse density variation, and autocorrelation. The cough reflex was induced by mechanical stimulation of the tracheal mucosa. The cough reflex evoked was accompanied by an increase in the number of spike potentials and shortening of the respiratory burst period of the phrenic nerve activities. There was a significant correlation between the intensity of expiration and the multiplication product of the mean amplitude of spike potentials and spike numbers of the phrenic nerve activities during the cough reflex. Total activity of the discharge, amplitude of spike potentials, and pulse density of the phrenic nerve activities also increased during the cough reflex, while the autocorrelation coefficient decreased. These changes were inhibited by codeine. The responses of the phrenic nerve activity during the cough reflex were also observed under artificial respiration as well as under spontaneous respiration. These findings indicate that the phrenic nerve activity can be an indicator of the cough reflex, and it is useful for the indicator to investigate the central mechanisms of the cough reflex.

Animals↗
PubMed2005

Mechanisms of capsaicin- and citric-acid-induced cough reflexes in guinea pigs.

Previously, we developed a novel coughing model that evoked coughs via citric acid microinjection into the larynx of unanesthetized, unrestrained guinea pigs. Here, we compared the effects of capsaicin and citric acid administration into the larynx using this model. Inhalation of capsaicin (30 microM) or citric acid (0.4 M) for 5 min induced cough mimetic responses over a 10-min observation period (mean +/- S.E.M.: 8.85 +/- 1.60 and 10.40 +/- 1.17 coughs, respectively, n = 18). Microinjection of 0.4 M citric acid into the larynx (20 microl in total in 10 aliquots of 2 microl at 30-s intervals) induced 27.29 +/- 2.69 coughs over a 10-min observation period, whereas microinjection of 3 mM capsaicin evoked a maximum of 8.32 +/- 1.82 coughs (n = 18). Desensitization of C-fibers by capsaicin (100 mg/kg, s.c.) abolished the coughs evoked upon inhalation or microinjection of capsaicin and inhalation of citric acid, but had no significant effect on those induced by microinjection of citric acid. These results indicate that there were fewer non-myelinated C-fiber afferents in the larynx area than in other regions (bronchi or alveoli). Consequently, citric acid microinjected into the larynx may induce the cough reflex by stimulating other fibers (for example, Adelta-fibers), rather than C-fibers. In contrast, inhaled citric acid predominantly stimulated C-fibers, and hardly affected Adelta-fibers.

Animals↗
PubMed2005

Possible warfarin interaction with menthol cough drops.

OBJECTIVE: To report a case of possible interaction of menthol cough drops (Halls) with warfarin in a patient awaiting cardioversion. CASE SUMMARY: A 57-year-old white male awaiting cardioversion for atrial fibrillation was prescribed warfarin. His dosage was adjusted to 7 mg daily to provide stable international normalized ratio (INR) values of 2.28-2.68. Approximately one week later, his INR fell to 1.45. During a follow-up interview, the patient reported that he experienced a flu-like illness during the previous week and had been using menthol cough drops. No other potential causes for the decreased INR were found. Illness will most often elevate the INR; we therefore concluded that the cough drops were the likely cause of this reaction, and the warfarin dose was increased to 53 mg/wk. After discontinuing use of menthol cough drops, the warfarin dose was returned to the previous amount and the INR remained stabilized. DISCUSSION: An objective causality assessment suggests that the decreased INR was possibly related to the use of menthol cough drops during warfarin therapy. The active ingredient in these cough drops is menthol. Menthol has been shown to affect the pharmacokinetics of other drugs by inducing or inhibiting cytochrome P450 isoenzymes and slowing drug absorption. It is not clear whether these mechanisms played a role in this case. As of January 5, 2005 this is the first case report documenting an interaction between warfarin and cough drops containing menthol. CONCLUSIONS: This case documents a significant decrease in the INR following the use of menthol cough drops. Patients who are ill have several factors that can potentially affect their INR and should be monitored closely.

Cough↗
PubMed1999

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

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

Adolescent↗
PubMed2000

Is there an association between angiotensin-converting enzyme gene variants and chronic nonproductive cough?

BACKGROUND: It is unclear why some patients develop a chronic nonproductive cough. Angiotensin-converting enzyme (ACE) inactivates tussive peptides in the airways such as bradykinin and tachykinins. An insertion/deletion polymorphism in the ACE gene accounts for variation in ACE levels, and patients with the II genotype have lowest serum ACE levels compared with ID and DD genotypes. We hypothesized that the II genotype would be associated with increased risk of developing a chronic cough. MATERIALS AND METHODS: We recruited 47 patients (33 women), referred for evaluation of cough (median cough duration, 24 months; range, 2 to 240 months). Cough patients were evaluated using a comprehensive diagnostic protocol, and cough reflex sensitivity was measured using a capsaicin inhalation challenge. ACE genotyping was performed on DNA samples from patients using the polymerase chain reaction followed by agarose gel electrophoresis. ACE genotypes in patients with chronic cough were compared with those in 199 healthy control subjects. Serum ACE levels were determined using a colorimetric assay. RESULTS: Genotype frequencies for the ACE gene were similar between patients and control subjects. There was no correlation between capsaicin sensitivity and ACE genotypes or serum ACE levels. CONCLUSION: Susceptibility to develop chronic cough is not associated with ACE genotype.

Adolescent↗
PubMed2005

Noneosinophilic CD4 lymphocytic airway inflammation in menopausal women with chronic dry cough.

BACKGROUND: Chronic dry cough without dyspnea and wheezing is a well-known condition that is considered to be clinically overrepresented in women. The etiology and morphology remain unknown in many cases despite thorough investigations. DESIGN: To examine inflammatory cells and the lymphocyte profile in the lower airways and blood in women with chronic cough of unknown etiology. SETTING: University hospital department of respiratory medicine. PARTICIPANTS: Twenty-five otherwise healthy women with idiopathic cough and 11 age-matched healthy control women, all nonatopic nonsmokers. MEASUREMENTS: In order to characterize the cough, a careful standardized interview of the patients was made. Lung functions were tested. Cells were collected by BAL and analyzed for differential cell counts separate in the bronchial (first) wash and in the pooled peripheral washes (BAL fluid). The lymphocyte profile in BAL fluid and blood was characterized by dual-color flow cytometry. RESULTS: Eleven female patients formed a specific group with a history of a dry, nonproductive cough that always started in connection with an airway infection coinciding with menopause. Neither exercise, climate, nor seasonal change influenced the cough. BAL fluid contained an increased number of T (CD3+) lymphocytes: median. Seventy-three percent of T lymphocytes were T-helper lymphocytes (CD4+). A median of 57% of the BAL fluid T cells expressed HLA-DR activation marker compared with a median of 20% in the control subjects and in the other 14 included patients with chronic cough but with minor expectoration periodically (p < 0.001 and p < 0.0001, respectively). No differences between the groups were found in the blood. CONCLUSIONS: HLA-DR-activated CD4+ lymphocytic airway inflammation with a low number of eosinophils was identified in a group of nonsmoking, nonatopic otherwise healthy women patients with dry cough of life-long character. The disease appeared exclusively in connection to menopause.

Adult↗
PubMed2005

Bronchial sensitivity and bronchial reactivity in children with cough variant asthma.

BACKGROUND: Cough variant asthma (CVA) is diagnosed in some children with chronic cough who do not have wheezing. However, the precise mechanism of CVA in children is unclear. OBJECTIVE: To evaluate the physiologic differences in the airways of children with classic asthma and CVA, the methacholine dose-response curves of respiratory resistance (Rrs) were studied. PATIENTS AND METHODS: CVA was diagnosed in 31 children with chronic cough (age range, 5 to 14 years; 19 boys and 12 girls; mean age, 8.5 years) on the basis of methacholine inhalation challenge using an oscillation method. For comparison, the study included 86 age-matched children with classic asthma (age range, 5 to 15 years; 42 boys and 44 girls; mean age, 9.5 years), 25 age-matched children with cough (age range, 5 to 15 years; 17 boys and 8 girls; mean age, 8.8 years), and 23 age-matched control subjects (8 boys and 15 girls; mean age, 9.2 years). Consecutive doses of methacholine were doubled until a 200% increase in Rrs from baseline was reached. The cumulative dose of methacholine at the inflection point of Rrs was considered to represent the bronchial sensitivity to inhaled methacholine (minimum dose of methacholine [Dmin]). The slope of the methacholine dose-response curve (SRrs), which was considered to represent bronchial reactivity, was measured from the increasing Rrs curve. RESULTS: The values of Dmin in classic asthma patients and in CVA patients were significantly lower than those for cough patients and control subjects. There was no significant difference in the values of Dmin between the classic asthma and CVA patients. The value of SRrs in CVA patients was significantly lower than that in classic asthma patients, cough patients, and control subjects (p < 0.05, p < 0.01, and p < 0.01, respectively). There was no significant difference in the value of SRrs between classic asthma patients, cough patients, and control subjects. CONCLUSIONS: These data show that bronchial reactivity in the children with CVA was significantly lower than that in the children with classic asthma, and this specificity has an effect on prolonged cough without wheezing in children with CVA.

Administration, Inhalation↗
PubMed2006

Chronic cough due to tuberculosis and other infections: ACCP evidence-based clinical practice guidelines.

BACKGROUND: Although tuberculosis (TB) and other lung infections are common throughout the developing world, they are not among the most common causes of chronic cough. METHODS: Articles were selected from a MEDLINE search from 1966 through 2003 (using medical subject heading words "cough," "tuberculosis," and "lung infection"), and World Health Organization and Centers for Disease Control and Prevention web sites. RESULTS: Because of the contagious nature of TB and its potential for devastating morbidity and mortality for individual patients and society, TB should be considered early on in the workup of patients with chronic cough when the likelihood of active TB is high. On a worldwide basis, many cases of chronic cough are caused by infection including TB, and endemic fungi and parasites are important causes of cough in specific geographic regions. The convergence of the AIDS epidemic with the high prevalence of TB in the developing world has fueled the marked increase in cases of TB. Persons who live and work in facilities like prisons and nursing homes are also susceptible to tuberculous infection, and they spread it to others. Infection with endemic fungi and parasites should be considered in patients with chronic cough who live, or have lived, in these areas. CONCLUSION: Patients with unexplained chronic cough who have resided in areas having endemic infection with TB, fungi, or parasites should undergo diagnostic evaluation for these pathogens when more common causes of cough have been ruled out.

Chronic Disease↗
PubMed2006

Potential future therapies for the management of cough: ACCP evidence-based clinical practice guidelines.

BACKGROUND: When the etiology of a patient's chronic cough is established, specific antitussive therapy that is aimed at a particular cause of cough is highly effective. Nevertheless, in certain situations, therapy with cough suppressants, which previously were classified as nonspecific antitussive therapy, and which aim at suppressing the cough reflex regardless of the cause of cough, will be necessary. METHODOLOGY: The data for this review were obtained with the aid of a National Library of Medicine (PubMed) search, which was performed in June 2004, of literature published in the English language from 1966 to 2004, using the search terms "cough," "antitussive," "pharmacotherapy," "future therapies, " and "potential therapies." RESULTS/CONCLUSIONS: Currently available cough-suppressant therapy is severely limited by a dearth of effective agents and/or their unacceptable side effects. Several classes of pharmacologic agents are currently under investigation in an attempt to develop clinically useful cough suppressants.

Antitussive Agents↗