Persistent nocturnal cough: randomised controlled trial of high dose inhaled corticosteroid.
OBJECTIVE: To investigate the effect of a short course of inhaled corticosteroid in the treatment of isolated and persistent nocturnal cough in children. DESIGN: Randomised double blind placebo controlled study. SETTING: Subjects' homes in east London, England. SUBJECTS: Consecutively referred children, 1-10 years old, with persistent nocturnal cough. INTERVENTIONS: Placebo or fluticasone propionate 1 mg twice daily for three nights and 500 microg twice daily for 11 nights. Videotaping of children at night: two nights' baseline, nights 3 and 4 after three days of inhaled corticosteroid, and nights 15 and 16. MAIN OUTCOME MEASURE: A fall in 75% of coughs from baseline. RESULTS: 50 subjects were recruited. The median number of coughs in the baseline period for the inhaled corticosteroid group and placebo group were 92 and 71, respectively (p = 0.43) and, on nights 15 and 16, 8 and 36, respectively (p < 0. 01). Compared to baseline, both groups of subjects improved significantly by nights 15 and 16 (p < 0.01; p < 0.01). Comparing the inhaled corticosteroid and placebo groups, coughs fell to a median of 22% and 57% of baseline totals on nights 3 and 4, respectively (p = 0.38), and 8% and 35% on nights 15 and 16, respectively (p = 0.02). 17 of 24 subjects on inhaled corticosteroid who completed the study and 8 of 23 on placebo improved by 75% after two weeks (p = 0.03). CONCLUSIONS: Children with persistent nocturnal cough improve in two weeks after referral on placebo. There is a modest benefit from a two week course of high dose inhaled corticosteroid. (+info)
Repeatability of cough-related variables during fog challenges at threshold and suprathreshold stimulus intensity in humans.
Cough-related variables such as cough frequency, time to onset (i.e. the time until the first cough occurs) and the cough index (i.e. the ratio between the cough frequency and the time to onset) may be important when interpreting results of cough challenges for therapeutic interventions or for comparative research purposes. Nevertheless, repeatability (or reproducibility) for these widely used variables has been poorly studied. In thirty normal subjects, coughing was induced by inhalation of threshold (T) and suprathreshold (1.6 x T) concentrations of ultrasonically nebulized distilled water (fog). Cough threshold was taken as the lowest fog concentration that evoked at least one cough effort during two challenges separated by a 30-min interval. During challenges performed at both threshold and suprathreshold stimulus intensity, cough frequency, time to onset, and the cough index were assessed; within-subject repeatability for these variables was subsequently evaluated. Median +/- interquartile range cough threshold value was 0.9+/-0.5 mL x min(-1). During the two challenges performed to assess cough threshold, the mean +/-SD values of cough frequency, time to onset, and cough index were similar (5.0+/-2.7 and 5.3+/-3.1 coughs x min(-1), 32.4+/-13.3 and 32.9+/-13.6 s, and 0.2+/-0.2 and 0.2+/-0.2, respectively). However, none of these cough-related variables proved to be sufficiently repeatable. During the two challenges performed at suprathreshold stimulus intensity, mean values of cough frequency, time to onset, and cough index were also similar (20.0+/-9.0 and 18.2+/-10.2 coughs x min(-1), 13.5+/-5.8 and 12.0+/-4.62 s, and 1.7+/-1.0 and 1.8+/-1.2); furthermore, all considered variable of suprathreshold challenge turned out to be reproducible. In conclusion, during fog challenges at threshold stimulus intensity, cough frequency, time to onset and cough index cannot reliably be used for evaluating cough responses. However, these cough-related variables may represent useful and reliable research tools in the evaluation of suprathreshold cough responses. (+info)
Contrast transcranial Doppler ultrasound in the detection of right-to-left shunts: comparison of different procedures and different contrast agents.
BACKGROUND AND PURPOSE: Cardiac right-to-left shunts can be identified by transesophageal echocardiography (TEE) and by transcranial Doppler ultrasound (TCD) with the use of different contrast agents and different provocation procedures. Currently, data on an appropriate time window for the appearance of contrast bubbles in the TCD recording after the injection of the contrast medium and the comparison of different provocation maneuvers to increase right-to-left shunting are insufficient. METHODS: Forty-six patients were investigated by both TEE and bilateral TCD of the middle cerebral artery. The following protocol with 6 injection modes was applied in a randomized way: (1) injection of 10 mL of agitated saline without Valsalva maneuver, (2) injection of 10 mL of agitated saline with Valsalva maneuver, (3) injection of 10 mL of a commercial galactose-based contrast agent (Echovist) without Valsalva maneuver, (4) injection of 10 mL of Echovist with Valsalva maneuver, (5) injection of 10 mL of Echovist with standardized Valsalva maneuver, and (6) injection of 10 mL of Echovist with coughing. RESULTS: In 20 patients, a right-to-left shunt was demonstrated by TEE and contrast TCD (shunt-positive). Sixteen patients were negative in both investigations, no patient was positive on TEE and negative on TCD, and 10 patients were only positive on at least 1 TCD investigation but negative during TEE. The amount of microbubbles detected in the various tests decreased in the following order: Echovist and Valsalva maneuver, Echovist with coughing, Echovist and standardized Valsalva maneuver, saline with Valsalva maneuver, Echovist, and saline. With a time window of 20 to 25 seconds for the bubbles to appear in the TCD recording and with a sequence of first Echovist and Valsalva maneuver and then Echovist with coughing, all shunts were reliably identified with a specificity of 65% compared with TEE as the traditional gold standard. The time of first microbubble appearance was not helpful to distinguish between shunts detected on TEE and other shunts. CONCLUSIONS: TCD performed twice with 2 provocation maneuvers using Echovist is a sensitive method to identify cardiac right-to-left shunts also identified by TEE. (+info)
The antitussive effect of dextromethorphan in relation to CYP2D6 activity.
AIMS: To test the hypothesis that inhibition of cytochrome P450 2D6 (CYP2D6) by quinidine increases the antitussive effect of dextromethorphan (DEX) in an induced cough model. METHODS: Twenty-two healthy extensive metaboliser phenotypes for CYP2D6 were studied according to a double-blind, randomised cross-over design after administration of: (1) Placebo antitussive preceded at 1 h by placebo inhibitor; (2) 30 mg oral DEX preceded at 1 h by placebo inhibitor (DEX30); (3) 60 mg oral DEX preceded at 1 h by placebo inhibitor (DEX60); (4) 30 mg oral DEX preceded at 1 h by 50 mg oral quinidine sulphate (QDEX30). Cough frequency following inhalation of 10% citric acid was measured at baseline and at intervals up to 12 h. Plasma concentrations of DEX and its metabolites were measured up to 96 h by h.p.l.c. RESULTS: Inhibition of CYP2D6 by quinidine caused a significant increase in the mean ratio of DEX to dextrorphan (DEX:DOR) plasma AUC(96) (0.04 vs 1.81, P<0.001). The mean (+/-s.d.) decrements in cough frequency below baseline over 12 h (AUEC) were: 8% (11), 17% (14.5), 25% (16.2) and 25% (16.9) for placebo, DEX30, DEX60 and QDEX30 treatments, respectively. Statistically significant differences in antitussive effect were detected for the contrasts between DEX60/placebo (P<0.001; 95% CI of difference +80, +327) and QDEX30/placebo (P<0.001, +88, +336), but not for DEX30/placebo, DEX30/DEX60 or DEX30/QDEX30 (P=0.071, -7, +241; P=0.254, -37, +211; P=0.187, -29, +219, respectively). CONCLUSIONS: A significant antitussive effect was demonstrated after 60 mg dextromethorphan and 30 mg dextromethorphan preceded by 50 mg quinidine using an induced cough model. However, although the study was powered to detect a 10% difference in cough response, the observed differences for other contrasts were less than 10%, such that it was possible only to imply a dose effect (30 vs 60 mg) in the antitussive activity of DEX and enhancement of this effect by CYP2D6 inhibition. (+info)
Development of wheezing in patients with cough variant asthma during an increase in airway responsiveness.
Two theories explaining the mechanism for the manifestation of cough without wheeze in patients with cough variant asthma (CVA) are either a higher wheezing threshold or a milder degree of airway hyperresponsiveness. A significant proportion of patients diagnosed as having CVA eventually develop wheezing. The aim of this study was to investigate whether this change in the manifestation of asthma was associated with a decrease in wheezing threshold and/or an increase in airway hyperresponsiveness. Thirty-six children (7-15 yrs) with CVA were prospectively studied for 4 yrs. Bronchial provocation tests with methacholine using the stepwise increasing concentration technique were performed annually to measure the provocative cumulative dose producing a 20% fall in forced expiratory volume in one second (PD20). Wheezing thresholds were additionally determined at the initiation of and the end of the study (development of wheezing, or after 4 yrs). Sixteen (Group 1) of 29 patients available for the follow-up developed clinical wheezing during the period; 13 patients (Group 2) stayed as CVA or their cough resolved. There was no significant change in wheezing thresholds from the initiation to the end of the study (Group 1: 40.9+/-8.2% versus 40.2+/-8.3%; Group 2: 41.4+/-7.1% versus 40.1+/-7.3%). Methacholine PD20 (geometric mean, range of 1 SD), expressed as breath unit (BU), significantly decreased in Group 1 patients as they developed wheezing (initial versus wheezing year: 60.8 BU, 29.2-126.5 versus 32.8 BU, 11.5-93.3; p<0.01), whereas the value did not change in Group 2 patients (initial versus after 4 yrs: 85.3 BU, 45.2-161.1 versus 84.3 BU, 39.7-179.1; NS). The results suggest that an increase in airway hyperresponsiveness, but not a decrease in wheezing threshold, may have a pathogenetic role in the development of wheezing during the course of cough variant asthma in childhood. (+info)
Effects of drugs on mucus clearance.
Mucociliary clearance (MCC), the process in which airway mucus together with substances trapped within are moved out of the lungs, is an important defence mechanism of the human body. Drugs may alter this process, such that it is necessary to know the effect of the drugs on MCC. Indeed, agents stimulating MCC may be used therapeutically in respiratory medicine, especially in patients suspected of having an impairment of their mucociliary transport system. In contrast, caution should be taken with drugs depressing MCC as an undesired side-effect, independently of their therapeutic indication. Since cough clearance (CC) serves as a back-up system when MCC fails, the influence of drugs must be examined not only on MCC but also on CC. Ultimately, the clinical repercussions of alterations in mucus transport induced by drug administration must be studied. Tertiary ammonium compounds (anticholinergics), aspirin, anaesthetic agents and benzodiazepines have been shown to be capable of depressing the mucociliary transport system. Cholinergics, methylxanthines, sodium cromoglycate, hypertonic saline, saline as well as water aerosol have been shown to increase MCC. Adrenergic antagonists, guaifenesin, S-carboxymethylcysteine, sodium 2-mercapto-ethane sulphonate and frusemide have been reported not to alter the mucociliary transport significantly. Amiloride, uridine 5'-triphosphate (UTP), quaternary ammonium compounds (anticholinergics), adrenergic agonists, corticosteroids, recombinant human deoxyribonuclease (rhDNase), N-acetylcysteine, bromhexine and ambroxol have been reported either not to change or to augment MCC. Indirect data suggest that surfactant as well as antibiotics may improve the mucociliary transport system. As for the influence of drugs on CC, amiloride and rhDNase have been demonstrated to increase the effectiveness of cough. A trend towards an improved CC was noted after treatment with adrenergic agonists. The anticholinergic agent ipratropium bromide, which is a quaternary ammonium compound, has been suggested to decrease CC significantly. Bromhexine, ambroxol and neutral saline seemed not to alter CC, either positively or negatively. Finally, treatment with either amiloride, recombinant human deoxyribonuclease, bromhexine, ambroxol, N-acetylcysteine, S-carboxymethylcysteine or hypertonic saline has been suggested as a possible cause of clinical improvement in patients, such as the experience of dyspnoea, the case of expectoration or the frequency of infective exacerbations. Other agents did not show a clinical benefit. (+info)
Difference in the incidence of cough induced by angiotensin converting enzyme inhibitors: a comparative study using imidapril hydrochloride and enalapril maleate.
To compare the incidence of cough between two angiotensin converting enzyme (ACE) inhibitors, imidapril and enalapril, comparative crossover study was performed in 489 patients (228 men and 261 females) with essential or renal parenchymal hypertension. Patients were randomly assigned to one of two treatment groups, a group receiving imidapril for 12 wk (Period I) followed by enalapril for 12 wk (Period II), and a group in which the order of drugs was reversed. The occurrence of cough during treatment was monitored by questionnaire in all cases. There were no differences in background characteristics between the two groups. The incidence of cough during Period I was 15.2% (32/210) in the group initially treated with imidapril (Group IE) and 38.6% (85/220) in the group initially treated with enalapril (Group EI), the difference being statistically significant (p < 0.001). During Period I, decrease in blood pressure was observed in 63.9% (115/180) of Group IE and 64.6% (115/178) of Group EI patients. In approximately half of the patients in Group EI who developed cough during Period I and in whom the treatment was subsequently switched to imidapril, cough subsequently disappeared. It was concluded that the incidence of cough was significantly less under imidapril than under enalapril treatment, while there was no difference in the antihypertensive effects of the two ACE inhibitors. (+info)
Chronic cough due to bronchobiliary fistula.
Bronchobiliary fistula is a rare cause of chronic cough. Here we describe a 70-year-old woman complaining of chronic cough and copious dark-yellow watery sputum. The presence of air in the biliary tract in the lower cuts of a computerized tomography scan of the chest and positive bile in the sputum led to the suspicion of bronchobiliary fistula. The diagnosis was confirmed by percutaneous transhepatic cholangiography. Drainage of the intrahepatic biliary tract resulted in complete resolution of her symptoms. (+info)