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PubMed1989

Objective assessment of cough suppressants under normal and pathological experimental conditions.

The influences of the antitussive activity of glaucine were studied in 56 non-anaesthetized cats under normal and pathological conditions. Cough was induced by mechanical stimulation of the airways with a nylon fibre. The authors found that if glaucine was administered at a dose of 5.0, 7.5 and 10.0 mg/kg b.w., i.p., it evoked statistically significant suppression on single cough components. After inflammation of the airways was induced with unsoluted croton oil, no decrease in antitussive activity of glaucine could be observed, according to the number of cough efforts, frequency, intensity of maximal cough effort, and intensity of cough attack during expiration. Glaucine used under such conditions was not found to be powerful enough to suppress either the intensity of maximal cough effort or the intensity of cough attack during inspiration. The antitussive effect of glaucine was stronger under pathological conditions (Staphylococcus-induced inflammation). The antitussive effect of glaucine was approximately the same as with codeine if administered in equal doses.

Animals↗
PubMed1987

[A secondary effect of converting enzyme inhibitors: cough].

Cough associated with angiotensin-converting enzyme (ACE) inhibitors has long been considered a rare side effect. We report 8 cases, 7 with enalapril (10 to 20 mg/day) 1 with quinapril (40 mg/day) in which cough occurred after a mean duration of treatment of 39 days. In all patients, cough disappeared with a mean delay of 2 days with no other treatment than withdrawal of the drug. In 6 patients, cough was reinduced within less than a day with the same drug; in 5 patients a second reinduction with another ACE inhibitor gave the same result. These data suggest that cough is probably more frequent than it would appear from the literature. In clinical practice, if cough occurs in a patient treated with an ACE inhibitor, the drug may be continued for a few days in order to exclude an acute viral infection; if cough lasts more than a week, specific diagnostic procedures for pulmonary disease should be initiated; if it stops, the patient may be treated either for hypertension or chronic heart failure with another ACE inhibitor.

Aged↗
PubMed1987

Afferent pathways for the cough reflex.

Cough is most often a reflex act elicited by the stimulation of nervous receptors in the respiratory tract. The most important tussigenic areas are at the level of the larynx and the more distal portion of the trachea with its bifurcation. Laryngeal rapidly adapting receptors with myelinated fibres are promptly activated by tussigenic stimuli, but it is unlikely that they are the only ones responsible for laryngeal coughing. In fact, some evidence supports the involvement of laryngeal C-fibre receptors. Cough in response to inhalation of aqueous aerosols containing low chloride concentrations may involve the same category of receptors with myelinated fibres that mediate apnoea in the newborn. Within the tracheobronchial tree, there are rapidly-adapting irritant receptors responsive to several tussigenic stimuli and concentrated at tussigenic sites. Animal species without this type of ending do not cough. However, some results for the tracheobronchial tree suggest a role for other types of receptors. Slowly adapting stretch receptors may play an indirect role through their stimulatory effect on expiratory muscles. A role for C-fibre receptors is proposed considering the activation of these endings by substances (capsaicin, lobeline, bradykinin, SO2) capable of inducing cough. Bronchial C-fibre receptors, present also in proximal airways, respond to light mechanical probing. Contrary to an involvement of pulmonary C-fibres is the observation that cough is not part of the lung chemoreflex, although during this reflex syndrome (apnoea followed by rapid and shallow breathing, bradycardia and hypotension) cough can be induced by mechanical irritation of the trachea.

Afferent Pathways↗
PubMed1988

Assessment of the antitussive effect of vadocaine hydrochloride using citric acid-induced cough in healthy volunteers.

Vadocaine hydrochloride (2',4'-dimethyl-6'-methoxy-3-(2-methylpiperidyl)propionanilide+ ++ hydrochloride, OR K-242-HCl; INN: vadocaine) is a novel compound with potent antitussive and local anaesthetic action. The antitussive profile of this compound was evaluated in 40 healthy volunteers in double-blind, placebo-controlled cross-over study design using inhaled citric acid a cough inducer. In Part I, vadocaine was compared in 20 healthy volunteers at two dose levels (10 and 30 mg) with codeine phosphate (50 mg) and a placebo. In part II, vadocaine (30 mg) and a placebo were compared in 20 healthy volunteers. In Part I, no statistically significant differences were found between the 3 compounds tested. However, statistically significant rises from the pre-dose value in the cough threshold stimulus level were observed following 10 and 30 mg doses of vadocaine. Neither codeine phosphate nor the placebo produced any statistically significant change in the cough threshold stimulus level. In Part II, vadocaine at a dose of 30 mg dose was found to be a potent antitussive with a statistically significant difference (p less than 0.0001) as compared with the placebo. The maximum cough threshold stimulus level was achieved 2 h after administration and was 72.6% higher than at pre-dose. With the placebo the cough threshold stimulus level also rose to some extent after 4 h, although the change was not statistically significant. The use of inhaled citric acid in graded concentrations for induction of the cough response was found to be a reliable method when the baseline cough threshold stimulus level is maintained within narrow limits throughout the entire study population.

Adult↗
PubMed1987

Cough and mucociliary clearance.

Cough is a host defence mechanism of the lungs. Theoretical considerations indicate that the efficacy of cough in clearing secretions is limited to the first few airway generations of the human lung. Studies utilizing radioaerosols as markers of mucus support the theoretical predictions and show that cough is effective in the proximal airways only in the presence of excess secretions. Limited studies on the efficacy of cough on regional clearance of secretions have been equivocal regarding its effect in the "peripheral" regions of the lungs. Persistent coughing can result in temporary slowing or even cessation of lung mucociliary clearance at the flow-limiting segments of the lung. The forced expiration technique, which is not accompanied by the compressive phase associated with cough, is more effective than coughing in clearing excess secretions from the lungs.

Aerosols↗
PubMed1987

The origin of cough sounds.

We have analyzed the origin of the first and second cough sounds recorded by tussiphonography. About 10,000 tussiphonograms were performed in about 1,000 healthy and diseased subjects. Changes in the first cough sound are due to pathological processes in the airways, for example, the presence of mucus or acute inflammatory disease. The first cough sound may then become divided. In bronchial asthma the first sound is also abnormal because of the narrowed airways. The origin of the second sound becomes clear by its absence in patients after laryngectomy or in those with paralysis of the vocal folds. The reappearance of the second cough sound may indicate rehabilitation of the vocal folds. With laryngotracheitis there is a pattern of multiple sounds. In patients with cough of psychogenic origin, the second sound is absent and cough sounds "bovine". Treatment of patients with bronchodilating drugs did not improve their pathological cough sounds in spite of improvement in airway obstruction.

Asthma↗
PubMed1979

Elimination of test particles from the human tracheobronchial tract by voluntary coughing.

The effect of coughing on the elimination of inhaled 6 micrometer radioactively tagged teflon particles in humans was studied by external measurements of the radioactivity retained in the lungs before and after 1--2 min of voluntary coughing. In six healthy subjects coughing produced no substantial elimination of the particles. Six out of eight patients with lung disease produced expectorate and also eliminated particles from the lungs by coughing. The other two patients had no phlegm, did not produce any expectorate and did not eliminate particles by coughing. An increased amount of tracheobronchial secretion thus seems to be necessary for coughing to be effective. In the patients, the elimination of particles by coughing was fairly reproducible, suggesting that the test model may be useful for investigation of the influence of physiological and pharmacological factors on the elimination process.

Adult↗
PubMed1983

Effects of psychotropics on the periodic fluctuation in EEG synchronized with respiratory rhythms during cough reflex.

It is known that the psychotropics reduce the cough reflex. To clarify the relation between the higher centers and cough reflex, we investigated the psychotropics property of the respiratory periodic fluctuation in EEG during cough reflex and after administration of psychotropics. Male mongrel dogs immobilized were maintained with artificial respiration. The efferent activities of phrenic nerve and scalp EEG were recorded, and on the basis of the resulting observations, crosscorrelation coefficients were computed using a digital computer. The cough reflex was accompanied by an increase in crosscorrelation coefficient (C. C.) between EEG and phrenic nerve activities. the C. C. between EEG and phrenic nerve activities decreased after iv administration of chlorpromazine ( mg/kg), while administration of imipramine (1-3 mg/kg) and diazepam (1-3 mg/kg) increased the C. C., respectively. The increase in the C. C. observed during cough reflex was inhibited by iv administration of these three drugs. The fact that the C. C. increased during cough reflex suggested that the ascending output from respiratory center to the higher center reinforced during this period. Furthermore, it is suggested that the psychotropics inhibited the neuronal mechanisms of the brain stem that plays an important role in cough reflex by acting upon the feedback loop located between the respiratory center and the higher centers.

Animals↗
PubMed1984

Acute airway changes induced by coughing.

The effects of voluntary coughs on specific conductance measurements were studied in normal, atopic and asthmatic subjects before and after bronchoconstriction with histamine. The responses were variable, the most frequent change being temporary bronchodilation in the 30 seconds after a voluntary cough in the presence of histamine-induced bronchoconstriction. The effects of the two components of coughing, namely a full inhalation and a cough without a preceding deep inhalation, were studied in a similar manner. After challenge with histamine had reduced specific conductance by approximately 50%, full inhalations produced a temporary increase in conductance. Modified coughs without deep inhalation after histamine most often resulted in a temporary small decrease in conductance. One atopic subject showed marked, prolonged airway narrowing after a single full inhalation before histamine. We conclude that the major effects on airway smooth muscle produced by coughs result from the deep inhalation. In challenge studies coughs may affect subsequent airways resistance measurements. Such brief changes are not clinically important but may affect the results of inhalation challenge studies. Occasionally individuals show more prolonged bronchoconstriction after such manoeuvres.

Airway Resistance↗
PubMed1984

The cough and the bedsheet.

Of 33 patients with psychogenic cough tic, 31 were successfully treated using an unusual reinforced suggestion technique. The cough usually follows an incidental upper respiratory tract infection and persists as a loud paroxysmal barking or honking sound for weeks to months. Paroxysms occur all day but cease with sleep. The diagnosis is often delayed for weeks to months while the patient is exposed to an increasing intensity of diagnostic procedures and therapy. Thirty percent of some 20 patients previously reported in the literature had been hospitalized. The reinforced suggestion technique depends upon the physician's convincing the patient that the persistent cough has weakened the chest muscles, which are now unable to contain the cough, and that a bedsheet tightly wrapped around the chest will provide the necessary support to stop the cough within 24 to 48 hours. The typical patient can produce the cough on command, has an ambivalent response to the prospect of care, is unconcerned about his symptoms, submits willingly to the examination and procedures, and is kept out of school for the duration of the cough. Findings on physical examination are normal except for abnormal gag and corneal reflexes. The gag reflex was depressed in six and absent in 20 of the 31 patients. The corneal reflex was depressed in 16 and absent in 5 of the 31 patients. These abnormal responses help to corroborate the psychogenic etiology. Early recognition of the nonorganic nature of this syndrome will reduce parental anxiety, loss of school time, risk of iatrogenic complications, and unnecessary medical and hospital expense.

Adaptation, Psychological↗
PubMed1980

[Effects of peripheral airway response on the cough reflex (author's transl)].

The modification of cough reflex by contraction and relaxation of the peripheral airway was investigated in anesthetized dogs. For administration of the drugs directly into the peripheral airway, an arterial cannula was chronically implanted in the right bronchial artery via the right intercostal artery. The cough reflex was induced by electrical stimulation of the upper tracheal mucosa by means of an electrode-cannula. Evaluation of the cough response was made by changes in frequency and amplitude of coughs. Drug solutions were infused for 5 min at a rate of 0.17 ml/min into the right bronchial artery. Intraarterial infusion of isoproterenol, 1-3 mu g/min, reduced the amplitude, but had no effect on the frequency of coughs, while that of histamine, 3-10 mu g/min, increased the frequency and amplitude of coughs. Atropine, 100 mu g/min, caused no significant changes in amplitude and frequency, respectively. Benzonatate, 0.85 mg/min, reduced the frequency, but had no effect on the amplitude. Thus, the tonus of the peripheral airway, in particular the airway contraction, may the increase the frequency of cough reflex by lowering the threshold of the airway receptors.

Airway Resistance↗
PubMed1995

Toxicodynamic analysis of cough and inflammatory reactions by angiotensin-converting enzyme inhibitors in guinea pig.

Angiotensin-converting enzyme (ACE) inhibitors are one of the first drugs of choice for the treatment of hypertension. However, there have been many reports of persistent chronic dry cough and inflammatory skin reactions (rash and/or angioedema, etc.) induced by ACE inhibitors. In this study, in order to evaluate the cough and inflammatory reaction, we measured the number of citric acid-induced coughs and the intradermal inflammation with ovalbumin in guinea pigs consecutively treated with ACE inhibitors (lisinopril, enalaprilat and imidapril) for 3 days. The number of citric acid-induced coughs and the inflammatory responses were significantly enhanced by treatment with lisinopril and enalaprilat, whereas imidapril produced no change in either response. These results correspond to the frequency of adverse effects in clinical practice, which suggests that imidapril has the least ability to induce the inflammatory skin response and cough. Furthermore, the enhancement produced by the ACE inhibitors in the number of coughs and the inflammatory responses were significantly reduced by pretreatment with indomethacin (prostaglandin synthesis inhibitor). This finding suggests that PGs at least participate in the mechanism for ACE inhibitor-induced cough and inflammatory skin response.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

The efficacy and safety of moguisteine in comparison with codeine phosphate in patients with chronic cough.

We conducted a multicentre, double-blind, parallel group study to compare the clinical efficacy of a new antitussive drug, moguisteine (100 mg t.i.d.), to that of a reference standard, codeine (15 and 30 mg, t.i.d.). Both drugs were given orally for a period of two days. A group of 119 patients (mean age 54 yrs; 61 females and 58 males) with chronic, dry or slightly productive cough, associated with various respiratory disorders (including chronic obstructive pulmonary disease, respiratory malignancies and pulmonary fibrosis) were enrolled at six participating centres. The percentage reduction in the number of morning coughs over a period of 6 h after the first administered dose compared to baseline assessment, was 21% with moguisteine (n = 39), 28% with codeine 15 mg (n = 38), and 29% with codeine 30 mg (n = 36). Differences between treatments were not significant. The percentage reduction in the number of nocturnal coughs per hour, after the last evening dose compared to baseline assessment, was 33, 46 and 52%, respectively. Subjective assessments (patients' visual analogue scale scores of cough frequency, cough intensity and sleep disturbance, and investigators' ranking of cough severity) indicated that there was a similar improvement in cough symptoms in all treatment groups. Adverse events were observed in two patients on moguisteine, three on codeine 15 mg, and five on codeine 30 mg. No event was serious, but discontinuation of treatment was required in two patients on codeine 30 mg. The results of our study suggest that moguisteine 100 mg t.i.d. is safe, and seems to have an antitussive activity similar to that of codeine 15-30 mg t.i.d.

Administration, Oral↗
PubMedDate not supplied

Psychogenic cough treated with biofeedback and psychotherapy. A review and case report.

Psychogenic cough is a barking or honking cough, which is persistent and disruptive to normal activity. The cough may be a debilitating condition that interferes with work and social relationships. Although the frequency of this condition is low, it is not rare. The majority of cases reported involve pediatric or adolescent patients. Surprisingly, there are scant data describing this condition in the adult population and no reports of biofeedback being used to treat this syndrome. We present a case report of an adult patient with psychogenic cough and review the available pediatric and adult literature. A 41-yr-old obese female presented with a complex 7-yr history of intractable, nonproductive, chronic cough. She had been avoiding social activities because of embarrassment by her repeated episodes of coughing. Extensive diagnostic work-up failed to find an organic etiology. Numerous medical and surgical treatments had failed. The patient was treated with a combination of biofeedback-assisted relaxation training, psychotherapy, and physical therapy. Review of the literature revealed only one report on adults, in which three of four patients were successfully treated with a combination of speech therapy, relaxation techniques, breathing exercises, and psychotherapy. Our success suggests a possible future use of this treatment protocol for cases of psychogenic cough.

Adult↗
PubMed1994

Cough with angiotensin converting enzyme inhibitors: how much of a problem?

PURPOSE: To review the occurrence of angiotensin converting enzyme (ACE) inhibitor-related cough, and to examine its impact on the quality of life. DATA SOURCES: Data from published reports, postmarketing surveillance studies, hospital case series and randomly allocated controlled trials were reviewed. Data are presented from a nested case-control study examining the effects of ACE inhibitor-related cough in 36 subjects compared with 69 controls on various measures of quality of life. RESULTS: Low rates of ACE inhibitor-related cough were found in postmarketing studies, ranging from 0.1% (early studies) to 3%. Much higher figures were reported from double-blind randomly allocated controlled trials using self-administered questionnaires; the net increase over baseline was between 13 and 25% compared to 2% with the comparator drug. The nested case-control study suggested that the ACE inhibitor-related cough is associated with some deterioration in well-being. During ACE inhibitor treatment the patients tended to be more fatigued (P = 0.1) and depressed (P < 0.05) than controls. Reports of a sore throat increased by 27% (P < 0.01). CONCLUSIONS: Cough is a common side effect of ACE inhibitor treatment, with conservative estimates suggesting that around one in 10 patients treated with an ACE inhibitor will develop a dry persistent cough. Half of these may be withdrawn from treatment. This cough is probably associated with some deterioration in well-being, but larger studies are required to confirm this.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Association between cough and angiotensin converting enzyme inhibitors versus angiotensin II antagonists: the design of a prospective, controlled study.

BACKGROUND: A common adverse experience in hypertensive patients treated with angiotensin converting enzyme (ACE) inhibitors is a tickling dry cough. OBJECTIVES: The aim of the present study was to review clinical observations and mechanisms of cough associated with ACE inhibitors. In addition, since the AT1-type angiotensin II antagonists (represented by losartan, MK954, DuP753) are not expected to influence other systems (kinins, prostaglandins) affected by ACE inhibitors, we explored the hypothesis that antihypertensive therapy with these agents will not be associated with cough at a similar frequency or quality to that seen with ACE inhibitors. DESIGN AND METHODS: Patients with a history of an ACE inhibitor-associated dry cough confirmed by a second challenge with lisinopril were enrolled into an international, multicenter, randomly allocated, double-blind, parallel-group, controlled trial, to be treated with losartan, lisinopril or hydrochlorothiazide. The presence and severity of cough were assessed by a self-administered questionnaire and a visual analog scale, respectively. CONCLUSIONS: It is expected that the new class of antihypertensive agents, angiotensin II antagonists, will not be associated with the high incidence of dry cough associated with the use of ACE inhibitors. It appears that this cough is not related to alterations in the renin-angiotensin system but to kininase II effects.

Adult↗
PubMed1995

High prevalence of persistent cough with angiotensin converting enzyme inhibitors in Chinese.

1. Angiotensin converting enzyme (ACE) inhibitors are in common use for the treatment of hypertension and heart failure. Whereas they are, in general, well tolerated, a dry cough can develop which, on occasion, requires termination of therapy. The reported prevalence of cough with ACE inhibitor therapy has varied from 0.2 to 25%, depending upon methods of data collection, analysis and symptom reporting. 2. To evaluate the prevalence of cough in Chinese patients receiving ACE inhibitors, interviews were carried out in 191 patients in Hong Kong who were taking therapy which included captopril or enalapril for hypertension or heart failure, and 382 patients matched for sex and age receiving alternative medications which excluded an ACE inhibitor (controls). Patients and controls were interviewed in a blinded manner by the same interviewer using a common adverse-effect questionnaire. 3. Persistent cough was reported in 44% of patients taking an ACE inhibitor (46% of those receiving captopril and 41.8% of patients taking enalapril), and in 11.1% of the controls (P < 0.001). The prevalence of other adverse reactions was similar, with no significant difference between the two treatment groups. The complication of cough was not related significantly to age, sex, underlying disease, drug dosage or smoking status. 4. This study indicates that cough is a common side effect of treatment with ACE inhibitors in Hong Kong Chinese, although in most patients cessation of therapy is not required. Whether Chinese are particularly susceptible to ACE-inhibitor cough requires a formal prospective study comparing Chinese and non-Chinese patients.

Adult↗
PubMed1994

Effects of doxycycline in patients with acute cough and purulent sputum: a double blind placebo controlled trial.

BACKGROUND: Acute cough with purulent sputum is a common complaint presented to general practitioners. AIM: A randomized, double blind, placebo controlled clinical trial was undertaken to determine the efficacy of doxycycline in persons aged 18 years and over presenting to 22 general practices in the Netherlands with acute cough and purulent sputum. METHOD: Patients were excluded if they were pregnant, had an allergy or intolerance to tetracyclines, had severe dyspnoea and fine crackles on auscultation, purulent rhinitis together with maxillary tenderness, chronic airways disease, or had taken antibiotics in the previous two weeks. Patients entered in to the study were given oral doxycycline for 10 days, 200 mg on the first day, followed by 100 mg on the next nine days, or placebo. RESULTS: Duration of frequent daytime cough after entry was a mean of 1.5 days shorter in the group of 71 patients receiving doxycycline than in the group of 69 patients on placebo (4.7 days versus 6.2 days, respectively). In patients aged 55 years and over the mean duration of frequent day-time cough after entry was 4.1 days shorter in the group taking doxycycline than in the placebo group. Patients with a very frequent cough and who also felt ill at entry regained their normal daily activities 2.1 days earlier when using doxycycline than the control group. CONCLUSION: Doxycycline has small beneficial effects in patients with acute cough and purulent sputum. These beneficial effects are more prominent, and probably clinically relevant, in patients aged 55 years and over and in patients who cough very frequently and who also feel ill.

Acute Disease↗