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Cough after inhalation of corticosteroids delivered from spacer devices in children with asthma.

Children using a spacer device rather than another device for delivering inhaled corticosteroids (ICS) has been identified as a risk factor for cough immediately after inhalation. The aim of this study was to point out the different factors influencing the occurrence of such lateral side-effects. We studied this local side-effect in 402 asthmatic children (55.6 +/- 34.9 months; 65.6% boys) treated for at least 1 month with beclomethasone dipropionate (n = 331), budesonide (n = 47) or fluticasone propionate (n = 24) delivered from pressurized metered-dose inhalers and small (75.1%) or large volume (24.8%) spacer devices mainly used with face mask (90.7%). A total of 219 patients (54.5%), treated with either high doses of ICS or ICS and long-acting beta2-agonist, were considered as having severe asthma. Cough was reported after each inhalation of corticosteroids in 216 patients (53.7%). Among them, about 30% also complained of cough with beta2-agonists. Despite different propellants and dispersants, all corticosteroids induced cough similarly. Cough was not linked with asthma severity, but was significantly related to therapy duration and use of long-acting beta2-agonist. Type and volume of the spacer device, use of a face mask or mouthpiece were not influencing factors. Cough after inhalation of corticosteroids delivered from spacer devices is a frequent local side-effect in children with asthma. This side effect can greatly alter compliance. A practitioner must be sought at each visit.

Administration, Inhalation↗

Dietary vitamin C intake is inversely related to cough and wheeze in young smokers.

We aimed to investigate whether dietary vitamin C intake, an important antioxidant, is inversely related to self-reported respiratory symptoms in young adults of a community. A random sample of 4300 subjects, aged 20-44 years, living in Bergen, Norway, received a postal questionnaire on respiratory symptoms; 80% responded. Vitamin C intake (mg per week) was estimated from a food-frequency questionnaire asking how often the subject, during the last year, had consumed units of orange juice, oranges, potatoes, carrots and tomatoes. Significant differences in the intake of vitamin C were observed across smoking categories with current smokers having the lowest intake, while there was no variation by gender, age or occupational dust exposure. Dietary vitamin C intake was in univariate analyses inversely related to "morning cough", "chronic cough", "wheeze" and "wheeze ever". After adjusting for gender, age, body mass index, "occupational exposure" pack-years as well as having and stratified on smoking habits in multiple logistic regression analyses, the relationship between dietary vitamin C intake and "cough" and "wheeze" tended to be associated to smoking. The odds ratio (OR) for "morning cough" was 0.68 (95% CI: 0.35-0.95), "chronic cough" OR 0.69 (95% CI: 0.47-1.04) and "wheeze ever" OR 0.75 (95% CI: 0.56-1.01) in current-smokers with dietary vitamin C intake in the upper (> or =395 mg/ week) vs. the lower (<209 mg/week) tertile. The OR for "wheeze" was 0.56 (95% CI: 0.35-0.88) in ex-smokers. The magnitude ofthese effects remained after excluding subjects with supplementary vitamin C intake (n=199) from the statistical analyses. Among young Norwegian adults, having a low prevalence of asthma and high prevalences of smoking-related respiratory symptoms, dietary vitamin C intake may act as an antioxidant and thereby reduce cough and wheeze in smokers having high oxidant stress.

Adult↗

[Does the inhalation of a 1% L-menthol solution in the premedication of fiberoptic bronchoscopy affect coughing and the sensation of dyspnea?].

BACKGROUND: Inhalation of l-menthol inhibits cough and has been shown to reduce respiratory discomfort associated with loaded breathing. We investigated the effect of the inhalation of a 1% l-menthol solution in the premedication of fiberoptic bronchoscopy (FB) on the frequency of cough and the irritability of the tracheobronchial mucosa during FB in a blinded, randomized and placebo controlled study. METHODS: 64 pat. (30-78 yrs, 55 males) underwent routine FB. Premediction: atropine and hydrocodone s.c., inhalation of oxybuprocain by means of a jet nebulizer, sedation on demand. Verum-group: inhalation of 3 ml 1% l-menthol-solution. Placebo-group: 3 ml 0.05% l-menthol (to provide the typical smell). Before and after inhalation peak respiratory flow (PEF) was registered, during FB the frequency of cough was measured. The bronchoscopist scored the irritability of the tracheobronchial mucosa using a visual analog scale. The patients answered a questionnaire addressing their perception of dyspnea and cough on the day after FB compared to the day before. RESULTS: The cough counts didn't show a significant difference between the groups. The irritability of the mucosa was increased in the verum group (main bronchus verum 62.2 +/- 22, placebo 48.6 +/- 23 [mm vissual analog scale, p = 0.03]). Cough and dyspnea reported by the patients decreased on the day after FB significantly compared to the day before (no difference between the groups). The inhalation of 1% l-menthol induced a significant increase of the PEF (verum 307 +/- 103 pre, 329 +/- 84 post [l/min, p = 0.003]) compared to placebo. CONCLUSIONS: The inhalation of 1% l-menthol did not enhance the tolerability of the FB. However, l-menthol induced a significant increase of the PEF immediately after inhalation. Finally sensation of dyspnea was decreased in both groups at the day post FB.

Administration, Inhalation↗

Chronic cough in patients with HIV infection.

We retrospectively studied the clinical spectrum, course and outcome of 26 patients with HIV infection and chronic cough. All except 2 were homo-/bisexual males. 22 (85%) had AIDS. They had cough for a mean of 75 d with sputum production (88%) and dyspnoea (77%) being the commonest associated symptoms. Sputum examination and chest X-ray were useful initial investigations. CT scan of the chest and sinuses had a high rate of abnormal results for selected patients (89-100%). Cause of cough was found in 21 patients (81%): bronchopulmonary infections (17), Kaposi's sarcoma (5) and sinus infections (3). Patients with sinopulmonary infections tended to have longer duration of cough. Overall, 4 patients (15%) had significant improvement in the illness with cough during the study period. Four patients with bronchopulmonary infections died. We concluded that chronic cough is a heterogeneous clinical problem in advanced HIV-infected patients, most commonly caused by an infective process. Extrapulmonary disease, such as sinusitis, has to be considered and investigated. The clinical course and outcome is unfavourable for most of the patients.

Chronic Disease↗

Evidence of Bordetella pertussis infection in adults presenting with persistent cough in a french area with very high whole-cell vaccine coverage.

Although France has had a vaccination program for 40 years, since 1990, an increase in whooping cough cases with parent-infant transmission has been observed. This study prospectively assessed the frequency of Bordetella pertussis infection in adults who consulted general practitioners for a persistent cough without an evident diagnosis. Among 217 patients, 70 (32%) confirmed whooping cough cases were identified. One case was culture positive, 36 were polymerase chain reaction positive, and 40 had increases or decreases of > or =2-fold in anti-pertussis toxin IgG titer between serum samples collected during the acute and convalescent phases. The median duration of cough in confirmed cases was 49 days (range, 13-123 days). Of the patients, 60% reported vaccination, and 33% reported whooping cough in infancy. Pertussis should be considered for diagnosis of acute and chronic cough in adults. Future studies should evaluate the public health interest of booster doses of pertussis vaccine in adults.

Adolescent↗

Chronic cough in primary health care attendees, Harare, Zimbabwe: diagnosis and impact of HIV infection.

BACKGROUND: Cough lasting for > or = 3 weeks (i.e., chronic cough) indicates that a patient has suspected tuberculosis (TB). At the primary health care level, the spectrum of disease that causes chronic cough has not been previously investigated in a setting with a high prevalence of human immunodeficiency virus (HIV) infection. METHODS: A total of 544 adults with chronic cough were recruited systematically from 2 primary health care clinics, and they were evaluated using preset first- and second-line investigations and diagnostic case definitions. RESULTS: The overall prevalence of HIV infection among the study cohort was 83%. TB was the most common diagnosis, with 207 HIV-positive patients (46%) and 27 HIV-negative patients (30%) having confirmed or probable TB. Of these, 145 HIV-positive patients with TB (70%) and 20 HIV-negative patients with TB (74%) had smear-positive cases of TB. Only 17 HIV-positive and 2 HIV-negative patients had smear-negative but culture-positive cases of TB. Lower respiratory tract infections (n = 178; HIV prevalence, 79%) and pneumonia (n = 87; HIV prevalence, 89%) were the next most common diagnoses. Asthma (n = 26; HIV prevalence, 46%), posttuberculous disease and other fibrotic lung disease (n = 34; HIV prevalence, 88%), and cardiac disease (n = 15; HIV prevalence, 93%) were more common than were Pneumocystis jiroveci pneumonia and cryptococcosis (n = 8 and n = 5, respectively; HIV prevalence, 100%), and we found no cases of nocardiosis or histoplasmosis. CONCLUSIONS: TB was diagnosed for 43% of patients who presented with chronic cough to primary health care clinics in Harare, with 71% having smear-positive disease. The findings of TB culture added relatively little to the findings of fluorescent microscopy of concentrated sputum specimens. The prevalence of HIV infection was high across a range of diagnoses, suggesting that an HIV test should be recommended in the initial investigation of chronic cough.

Adolescent↗

Sensitivity of the cough reflex in young and elderly subjects.

OBJECTIVE: To compare the sensitivity of the cough reflex--which is said to be normal in elderly people--in elderly and young subjects. SUBJECTS: 20 elderly (14 female) subjects, mean (SEM) age 83 (1) years and 20 young (nine female) subjects, mean (SEM) age 27 (1) years, who were all non-smokers. None of the subjects was taking antitussive drugs and none suffered from clinically evident lung, cardiac or neurological disease. Five elderly subjects were unable to perform adequate spirometry and were excluded from analysis. DESIGN AND OUTCOME MEASURES: Each subject inhaled 10 ml of nebulized distilled water and isotonic saline (as placebo) for 30 s, 10 min apart in a randomized double-blind crossover fashion. The cough frequency induced with each treatment was recorded on a click counter. RESULTS: Cough frequency on inhaling distilled water was significantly lower in the elderly group than in the younger group, with a difference of 9.53 (95% confidence intervals: 3.63, 15.4; P < 0.001). None of the subjects coughed when inhaling placebo solution, resulting in significant differences in cough frequencies between distilled water and placebo of 5.87 (2.82, 8.92; P < 0.05) for the elderly group and 15.4 (11.0, 19.8; P < 0.0005) for the younger group. CONCLUSIONS: The sensitivity of the cough reflex appears to be significantly reduced in elderly subjects. This may increase the risk of aspiration and bronchopulmonary infection in old age, even in the absence of respiratory disease.

Adult↗

Symptoms of wheeze and persistent cough in the first year of life: associations with indoor allergens, air contaminants, and maternal history of asthma.

In a cohort of 849 infants with an asthmatic sibling, the authors examined the relations of exposure to allergens (dust mite, cockroach, cat, and dog), nitrogen dioxide, and mold with symptoms of wheeze and persistent cough in the first year of life (1998-2000). Among infants whose mothers had physician-diagnosed asthma, neither dust mite allergen nor dog allergen was associated with either symptom. Exposure to cockroach allergen (Bla g 1 at >or=2 U/g) modestly increased the risk for wheeze (odds ratio (OR) = 1.87, 95% confidence interval (CI): 0.94, 3.71), and exposure to cat allergen modestly decreased the risk (OR = 0.60, 95% CI: 0.35, 1.03). Among infants of mothers with no asthma history, exposure to gas stoves (OR = 1.50, 95% CI: 1.05, 2.15) and wood-burning stoves (OR = 2.09, 95% CI: 1.12, 3.91) increased the risk of persistent cough. Similarly, measured nitrogen dioxide concentration was associated with persistent cough (OR = 1.21, 95% CI: 1.05, 1.40). Persistent mold affected both infants of mothers with asthma (for wheeze, OR = 2.27, 95% CI: 1.27, 4.07; for cough, OR = 1.83, 95% CI: 1.04, 3.22) and infants of mothers without asthma (for cough, OR = 1.55, 95% CI: 1.04, 2.31). Reported exposure was confirmed by an association of measured fungi with wheeze (OR = 1.23, 95% CI: 1.01, 1.49). This appears to have been the first study to measure all of these home exposures (indoor allergens, nitrogen dioxide, fungi) and to prospectively measure the frequency of infant wheeze and persistent cough.

Adult↗

Comparative study of the effects of three angiotensin converting enzyme inhibitors on the cough reflex.

To compare the effects of three different angiotensin converting enzyme (ACE) inhibitors on the cough reflex, capsaicin and citric acid challenge tests were done in normal subjects and hypertensive patients before and after administration of delapril, captopril, or enalapril. Two groups of 7 normal subjects (single dose study: 15 mg delapril v 18.75 mg captopril or 2.5 mg enalapril) and a group of 6 mildly hypertensive patients (1 week study: cross-over administration of 30 mg/day delapril, 37.5 mg/day captopril, or 5 mg/day enalapril) were studied. Another group of 6 patients with essential hypertension was treated with three ACE inhibitors for 4 weeks in a randomized order, with a 2 week washout period between active therapies. Aerosols of 1 mumol/L and 3 mumol/L capsaicin and 0.68% citric acid in 0.9% NaCl were generated by an ultrasonic nebulizer, and the frequency of cough was counted during inhalation. Delapril treatment resulted in substantially fewer patients with a significant increase (greater than or equal to 4 coughs during treatment than during the control period) in the frequency of cough than did captopril treatment. In the 1 and 4 week studies, enalapril and captopril had substantially more occurrences of significantly increased capsaicin-induced cough than did delapril. These results indicate that delapril has the least cough stimulatory effect among these ACE inhibitors, which may be clinically beneficial.

Administration, Inhalation↗

Peak flow and peak cough flow in the evaluation of expiratory muscle weakness and bulbar impairment in patients with neuromuscular disease.

OBJECTIVE: To study the expiratory muscle force and the ability to cough estimated by the peak expiratory flow and peak cough flow in patients with Duchenne muscular dystrophy and amyotrophic lateral sclerosis. DESIGN: A total of 27 patients with amyotrophic lateral sclerosis and 52 patients with Duchenne muscular dystrophy were studied. From the group of 144 normal subjects of this laboratory, we selected 38 for comparison. RESULTS: The maximal inspiratory pressure in patients with Duchenne muscular dystrophy and amyotrophic lateral sclerosis was 64.5 +/- 24.7% and 37.8 +/- 21.8%, respectively, and maximal expiratory pressure was 64.2 +/- 32.5% and 37.7 +/- 21.6%, respectively. Patient groups showed a significant lower peak expiratory flow than normal subjects. Higher peak cough flow than peak expiratory flow was found in all groups. The peak cough flow-peak expiratory flow difference was 46 +/- 18% in normal subjects, 43 +/- 23% in patients with Duchenne muscular dystrophy, and 11 +/- 17% in patients with amyotrophic lateral sclerosis. The peak expiratory flow and peak cough flow were not different in bulbar onset amyotrophic lateral sclerosis. In patient groups, the dynamic and static behavior correlated positively. CONCLUSIONS: These results suggest that peak cough flow-peak expiratory flow is useful to monitor expiratory muscle weakness and bulbar involvement and to assess its evolution in these patients.

Adolescent↗

Angiotensin converting enzyme inhibitors and cough.

Angiotensin converting enzyme (ACE) inhibitors produce a dry, nonproductive cough in some patients. Retrospective surveys have suggested an incidence of cough of between 0.7 and 14%. Those patients who develop cough show a marked increase in the sensitivity of the cough reflex to inhalation of the extract of red pepper, capsaicin. They have a normal response before treatment, and the sensitivity of the cough reflex returns to normal when therapy is discontinued. The mechanism of this important side effect is not known. Further studies are required to clarify the mechanism of cough, both as a side effect of therapy and as a common symptom of respiratory disease.

Angiotensin-Converting Enzyme Inhibitors↗

The antitussive effect of placebo treatment on cough associated with acute upper respiratory infection.

OBJECTIVE: The objective of this study was to determine the effects of a placebo treatment on cough in patients with cough associated with acute upper respiratory tract infection (URTI). METHODS: Patients with dry or slightly productive cough associated with a history of URTI were recruited. Cough frequency (CF) over 15 minutes was recorded by means of a microphone connected to a pen recorder. Cough suppression time (CST) was recorded when patients were instructed by means of a red light to try not to cough. Patients received either a single dose of vitamin E (placebo treatment) or no treatment. CF and CST were recorded before and 15 minutes after treatment. RESULTS: Twenty-seven patients were randomized to placebo treatment and 27 to the no-treatment group (mean age 22.6 years). The median difference between post- and pretreatment CF was -3 in the no-treatment group and -18 in the placebo group (p = .0003). There was a significant increase in CST in the placebo group compared with no treatment (p = .027). CONCLUSIONS: The results demonstrate that placebo treatment has significant antitussive activity. This placebo effect may be related to generation of central neurotransmitters such as endogenous opioids.

Acute Disease↗

Reproducibility of angiotensin converting enzyme inhibitor induced cough: a double-blind randomised study.

1. The reproducibility of angiotensin converting enzyme inhibitor induced cough was examined in a double-blind cross over study in patients previously shown to have exhibited this side effect. 2. Ninety-seven patients who had experienced angiotensin converting enzyme inhibitor cough within the last 2 years were challenged with enalapril 20 mg daily for 4 weeks to establish eligibility. Eighty-eight of 97 (91%) patients experienced a repeat of their cough symptoms. Sixty-four patients entered the double-blind part of the study where they were treated with enalapril 20 mg and a renin inhibitor for up to 4 weeks in random order. These periods were separated by a minimum 4 week placebo wash out. 3. Of 59 evaluable patients who received enalapril a second time, 37 (62.7%) experienced cough again. Of 62 patients on the renin inhibitor 16 (25.8%) experienced cough, however as it was not equi-efficacious to enalapril no valid comparison could be made. 4. Angiotensin converting enzyme inhibitor cough is not reproducible within patients, as other factors are involved in the aetiology. Objective testing with blinded assessment together with symptom reporting, would give a more accurate measure of the incidence, and mechanism of this side effect.

Adult↗

Lack of effect of codeine in the treatment of cough associated with acute upper respiratory tract infection.

Codeine is often used as a standard antitussive against which new antitussives are compared. However there is little information available about the effects of codeine on cough associated with upper respiratory tract infection. The present study investigated the effects of codeine syrup B.P. (30 mg/10 ml, q.d.s.) or syrup vehicle on cough frequency and the subjective severity of cough during a 3-h laboratory phase and a 4-day home phase of treatment. Cough frequency and subjective scores of cough severity were significantly decreased during the 3-h laboratory phase but at no time point was there a significant difference between the codeine- and placebo-treated groups. The results of the 4-day home phase diary were similar to those of the laboratory phase as at no time point was there a significant difference between the mean scores for the codeine- and placebo-treated groups. The results indicate that codeine, either as a single 30-mg dose or in a total daily dose of 120 mg, is no more effective than the syrup vehicle in controlling cough associated with acute upper respiratory tract infection.

Acute Disease↗

Controlling the proliferation of Zygosaccharomyces bailii in ephedrine anti-phlegm cough mixture.

BACKGROUND AND OBJECTIVE: To explain a reported proliferation of Zygosaccharomyces bailii in a commercially available ephedrine anti-phlegm cough mixture preserved with 0.1% sodium benzoate, and to present a strategy for controlling its growth. METHODS: A yeast strain was isolated from the cough mixture and identified using biochemical tests, selective media and 18S rDNA sequencing. Preservative minimum inhibitory concentrations (MICs) were determined based on the broth microdilution technique. The cough mixture was reproduced using benzoate and a number of other candidate preservatives. Bottles were challenged with the yeast using the test for antimicrobial efficacy outlined in the monographs of the European Pharmacopoeia. RESULTS: The contaminating yeast was identified as Z. bailii. The yeast MIC value for benzoate was close to or above the concentration used in the commercially available cough mixture. Reintroduction of the strain into bottles preserved with benzoate or sorbate, gave an initial reduction in the inoculum concentration (>1 log) followed by growth to values close to those found in the contaminated product. Furthermore, yeast cells taken from bottles at the end of the challenge test, suffered no initial reduction in numbers and grew in fresh bottles of the product, possibly suggesting adaptation to weak-acid preservatives. Two paraben-based preservative systems passed the challenge test. CONCLUSION: Preservatives of the weak-acid type do not control the growth of Z. bailii in ephedrine cough mixture for reasons discussed in this article. If the raw juice used in production of the product cannot be treated to eliminate the yeast, other preservatives must be sought. We show that paraben-based systems are effective in this role, and these are discussed as possible replacements for benzoate in the cough mixture.

Adrenergic Agents↗

Medullary respiratory neurones and control of laryngeal motoneurones during fictive eupnoea and cough in the cat.

1. This study addressed the hypothesis that ventrolateral medullary respiratory neurones participate in the control of laryngeal motoneurones during both eupnoea and coughing. 2. Data were obtained from 28 mid-collicular decerebrated, artificially ventilated cats. Cough-like motor patterns (fictive cough) in phrenic, lumbar and recurrent laryngeal nerves were elicited by mechanical stimulation of the intrathoracic trachea. Microelectrode arrays were used to monitor simultaneously several neurones in the ventral respiratory group, including the Bötzinger and pre-Bötzinger complexes. Spike trains were evaluated for responses during fictive cough and evidence of functional connectivity with spike-triggered averages of efferent recurrent laryngeal nerve activity. 3. Primary features were observed in averages triggered by 94 of 332 (28 %) neurones. An offset biphasic wave with a positive time lag was present in the unrectified average for 10 inspiratory and 13 expiratory neurones. These trigger neurones were respectively identified as inspiratory laryngeal motoneurones with augmenting, decrementing, plateau and "other" discharge patterns, and expiratory laryngeal motoneurones with decrementing firing patterns. 4. Rectified averages triggered by inspiratory neurones included 37 offset peaks, 11 central peaks and one offset trough. Averages triggered by expiratory neurones had 12 offset peaks, six central peaks and four offset troughs. Relationships inferred from these features included premotor actions of inspiratory neurones with augmenting, decrementing, plateau and "other" patterns on inspiratory laryngeal motoneurones, and premotor actions of decrementing and "other" expiratory neurones on expiratory laryngeal motoneurones. Corresponding changes in neuronal firing patterns during fictive cough supported these inferences. 5. The data confirm and extend previous results on the control of laryngeal motoneurones during eupnoea and support the hypothesis that the same premotor neurones help to shape motoneurone firing patterns during both eupnoea and coughing.

Action Potentials↗

The effect of nedocromil sodium, sodium cromoglycate and codeine phosphate on citric acid-induced cough in dogs.

1. The effects of nedocromil sodium, sodium cromoglycate and codeine phosphate on citric acid-induced cough have been studied in conscious tracheostomised dogs. 2. Nedocromil sodium (approximately 15 mg given as an aerosol) and codeine phosphate (5 mg kg-1, i.v.) significantly increased the time to the first cough when dogs were challenged with citric acid aerosol. The mean number of coughs in the initial period of coughing fell after treatment of dogs with nedocromil sodium or with codeine phosphate, but this reduction in mean cough number was not statistically significant. 3. Neither sodium cromoglycate (approximately 15 mg given as an aerosol) nor saline had significant effect on a citric acid challenge. 4. It is concluded that nedocromil sodium, but not sodium cromoglycate, possesses an anti-tussive action that may result from inhibition of sensory nerve activity in the lung. Nedocromil sodium may prove useful in the treatment of unproductive cough in situations where the use of a centrally-acting antitussive is undesirable.

Animals↗

Ocular compression maneuver aborts benign cough-induced headache.

Benign cough-induced headache is a short-lasting cranial discomfort. The therapeutic role of lumbar puncture (LP) or indomethacin in benign patients with benign cough-induced headache patients is debatable. Transient ocular compression (OC) raises intraocular pressure (IOP) and can limit the impact of cough-induced choroidal venous congestion. A self-applied maneuver that instantaneously aborts cough-induced headache is described in two patients. The effect of this maneuver supports a recent hypothesis that cough-induced headache may be due to ocular choroidal venous congestion and mechanical antidromic trigeminal nerve activation. The OC maneuver has several potential complications and its self-application in benign cough-induced headache should be regarded as an experimental procedure until more data regarding its efficacy and safety become available.

Adult↗