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PubMed2005

Gastro-oesophageal reflux treatment for prolonged non-specific cough in children and adults.

BACKGROUND: Cough is a very common symptom presenting to medical practitioners. Gastroesophageal reflux disease (GORD) is said to be the causative factor in up to 41% of adults with chronic cough. However cough and GORD are common ailments and their co-existence by chance is high. Also cough can induce reflux episodes. Treatment for GORD includes conservative measures (diet manipulation), pharmaceutical therapy (motility or prokinetic agents, H(2) antagonist and proton pump inhibitors (PPI)) and fundoplication. OBJECTIVES: To evaluate the efficacy of GORD treatment on chronic cough in children and adults with GORD and prolonged cough that is not related to an underlying respiratory disease i.e. non-specific chronic cough. SEARCH STRATEGY: The Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register Collaboration and Cochrane Airways Group, MEDLINE and EMBASE databases, review articles and reference lists of relevant articles were searched. The date of last search was 4th April 2004. SELECTION CRITERIA: All randomised controlled trials on GORD treatment for cough in children and adults without primary lung disease. DATA COLLECTION AND ANALYSIS: Results of searches were reviewed against pre-determined criteria for inclusion. Two independent reviewers selected, extracted and assessed data for inclusion. Authors were contacted for further information. Data was analysed as "intention to treat" as well as "treatment received". Paediatric and adults data were considered separately. Sensitivity analyses were performed. MAIN RESULTS: 11 studies (3 paediatric, 8 adults; 383 participants) were included. None of the paediatric studies could be included in meta-analysis. In adults, analysis on use of H(2) antagonist, motility agents and conservative treatment for GORD were not possible (from lack of data) and there were no controlled studies on fundoplication as an intervention. Five adult studies comparing PPI (2-3 months) to placebo were analysed for various outcomes in the meta-analysis. Enrollment of subjects for two studies were primarily from medical clinics and another three studies were otolaryngeal clinic patients. Using "intention to treat", pooled data from three studies resulted in no significant difference between treatment and placebo in total resolution of cough. Pooled data revealed no significant improvement in cough outcomes (end of trial or change in cough scores). Significant differences were only found in sensitivity analysis. A significant improvement in change of cough scores was found in end of intervention (2-3 months) in those receiving PPI with a standardised mean difference of -0.41 (95%CI -0.75, -0.07) using GIV analysis on cross over trials. Two studies reported improvement in cough after 5 days to 2 weeks of treatment. Significant heterogeneity was found between studies using omeprazole and other PPIs. AUTHORS' CONCLUSIONS: There is insufficient evidence to definitely conclude that GORD treatment with PPI is beneficial for cough associated with GORD in adults. The beneficial effect was only seen in sub-analysis and its effect was small. The optimal duration of such a trial of therapy to evaluate response could not be ascertained in the meta-analysis although two RCTs reported significant change by two weeks of therapy. Clinicians should be cognisant of a period (natural resolution with time) and placebo effect in studies that utilise cough as an outcome measure. Data in children are inconclusive. Future paediatric and adult studies are needed whereby studies should be double blind, randomised controlled, parallel design, using treatments for at least two months, with validated subjective and objective cough outcomes and include ascertainment of time to respond as well as assessment of acid and/or non acid reflux whilst on therapy.

Adult↗
PubMed2006

Gastro-oesophageal reflux treatment for prolonged non-specific cough in children and adults.

BACKGROUND: Cough is a very common symptom presenting to medical practitioners. Gastroesophageal reflux disease (GORD) is said to be the causative factor in up to 41% of adults with chronic cough. However cough and GORD are common ailments and their co-existence by chance is high. Also cough can induce reflux episodes. Treatment for GORD includes conservative measures (diet manipulation), pharmaceutical therapy (motility or prokinetic agents, H(2) antagonist and proton pump inhibitors (PPI)) and fundoplication. OBJECTIVES: To evaluate the efficacy of GORD treatment on chronic cough in children and adults with GORD and prolonged cough that is not related to an underlying respiratory disease i.e. non-specific chronic cough. SEARCH STRATEGY: The Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register Collaboration and Cochrane Airways Group, MEDLINE and EMBASE databases, review articles and reference lists of relevant articles were searched. The date of last search was 7th April 2006. SELECTION CRITERIA: All randomised controlled trials on GORD treatment for cough in children and adults without primary lung disease. DATA COLLECTION AND ANALYSIS: Results of searches were reviewed against pre-determined criteria for inclusion. Two independent reviewers selected, extracted and assessed data for inclusion. Authors were contacted for further information. Data was analysed as "intention to treat" as well as "treatment received". Paediatric and adults data were considered separately. Sensitivity analyses were performed. MAIN RESULTS: Thirteen studies (3 paediatric, 10 adults) were included. Data from six were available for analysis. None of the paediatric studies could be included in meta-analysis. In adults, analysis on use of H(2) antagonist, motility agents and conservative treatment for GORD were not possible (from lack of data) and there were no controlled studies on fundoplication as an intervention. Six adult studies comparing PPI (2-3 months) to placebo were analysed for various outcomes in the meta-analysis. Enrolment of subjects for two studies were primarily from medical clinics and another 4 studies were otolaryngology clinic patients or patients with laryngitis. Using "intention to treat", pooled data from 4 studies resulted in no significant difference between treatment and placebo in total resolution of cough, Odds Ratio 0.46 (95% CI 0.19 to 1.15). Pooled data revealed no overall significant improvement in cough outcomes (end of trial or change in cough scores). Significant differences were only found in sensitivity analyses. A significant improvement in change of cough scores was found in end of intervention (2-3 months) in those receiving PPI with a standardised mean difference of -0.41 (95%CI -0.75, -0.07) using GIV analysis on cross over trials. Two studies reported improvement in cough after 5 days to 2 weeks of treatment. AUTHORS' CONCLUSIONS: There is insufficient evidence to definitely conclude that GORD treatment with PPI is universally beneficial for cough associated with GORD in adults. The beneficial effect was only seen in sub-analysis and its effect was small. The optimal duration of such a trial of therapy to evaluate response could not be ascertained in the meta-analysis although two RCTs reported significant change by 2 weeks of therapy. Clinicians should be cognisant of a period (natural resolution with time) and placebo effect in studies that utilise cough as an outcome measure. Data in children are inconclusive. Future paediatric and adult studies are needed whereby studies should be double blind, randomised controlled, parallel design, using treatments for at least two months, with validated subjective and objective cough outcomes and include ascertainment of time to respond as well as assessment of acid and/or non acid reflux whilst on therapy.

Adult↗
PubMed2003

Pilot study of objective cough monitoring in infants.

Cough is common in childhood, resulting in significant morbidity and frequent medical consultation. Despite this, little is known about the frequency or development of cough, particularly in infants and young children. Recent progress in monitoring has enabled cough to be measured objectively both day and night. However, to date, objective measurement has only been used in adults and older children. The aim of this study was to see whether such methods could be extended to allow objective cough monitoring in infants. Thirty infants were recruited: 13 with coughing illnesses (group 1), and 17 normal, healthy babies (group 2) born to nonatopic, nonsmoking parents. Group 2 infants were studied when well, several times in the first year of life. Coughs were recorded using an adapted commercial cough monitor (Logan Research LR100) and simultaneous infrared video and sound recording. Thirty-eight recordings with simultaneous cough monitor and video data were analyzed: 9 from group 1, and 29 from group 2. Overall, the sensitivity of the monitor when compared to video was 81%, with a positive predictive value of 0.8. There was good agreement between the two methods for infants with infrequent cough (<5 coughs per hour). Agreement in infants with more frequent cough was not as good, because more coughs were consistently identified by the cough monitor. The portability and small size of the cough monitor made it easy to use, although there were difficulties in keeping the leads attached in older, more mobile infants. In conclusion, objective assessment of cough is practical in infants, enabling the pattern of cough in illness and in health to be studied further.

Age Factors↗
PubMed1994

Combined ambulatory esophageal manometry and dual-probe pH-metry in evaluation of patients with chronic unexplained cough.

Fifteen consecutive patients referred because of suspicion that gastroesophageal reflux was the cause of their chronic, unexplained cough underwent combined ambulatory esophageal manometry and pH-metry in order to correlate cough episodes with gastroesophageal and gastrohypopharyngeal acid reflux. Cough episodes, which were recognized manometrically as phasic bursts of brief simultaneous elevations in all intraesophageal pressure leads, were markedly underreported by patients. If all cough events were considered, that is, single coughs plus "bursts" of coughing, patients reported on average 10% of the total manometrically recorded coughs, whereas if only cough bursts were considered, patients reported an average of 23%. Gastrohypopharyngeal acid reflux preceded 1% and 1.8%, whereas gastroesophageal reflux preceded 9% and 13%, of the total coughs and cough bursts, respectively. One percent and 1.6% of total coughs and cough bursts, respectively, appeared to precipitate reflux. Gastrohypopharyngeal reflux events were rare, with only 15 episodes recorded in nine of the 15 patients. In 13 asymptomatic volunteers, no episodes of gastrohypopharyngeal acid reflux were recorded. This study suggests that ambulatory esophageal manometry/pH-metry provides an objective measure of temporal relationships between cough episodes and acid reflux events that is superior to relying on the patients' reporting of cough episodes. In this study population, the incidence of a direct temporal correlation between reflux and cough episodes was relatively low. However, a high proportion of patients had gastrohypopharyngeal reflux, suggesting that acid reflux to the laryngeal inlet may indirectly play a role in chronic unexplained cough.

Adult↗
PubMed2004

A guinea pig model for cough variant asthma and role of tachykinins.

Cough variant asthma is known as a major cause of chronic cough. Fundamental features of cough variant asthma are prolonged nonproductive cough responding to bronchodilator therapy, no history of wheezing or dyspnea attack, normal cough sensitivity, and slightly increased bronchial responsiveness. Animal model of cough variant asthma has not been reported. The aim of this study was to establish an animal model for studying detailed pathophysiology of cough variant asthma. Bronchial responsiveness to methacholine and cough reflex sensitivity to capsaicin were measured 72 hours after antigen (ovalbumin, OA) inhalation in actively sensitized guinea pigs. Next, cough number and specific airway resistance (sRaw) were measured during 20 minutes following reinhalation of OA solution, which was carried out 72 hours after the first OA inhalation, and then total cell number and cell differentials in bronchoalveolar lavage fluid (BALE) were measured. Bronchial responsiveness to methacholine, but not cough reflex sensitivity to capsaicin, was significantly increased 72 hours after the first inhalation of OA solution. Number of coughs, sRaw and total cell number in BALF increased significantly by the OA reinhalation, and the cough number and the increase in sRaw were significantly suppressed by beta2 agonist, procaterol. FK224, a specific neurokinin (NK) receptor antagonist, did not significantly influence the OA reinhalation-induced cough and increase in sRaw and total cell number in BALF in this model In conclusion, pathophysiologic feature of this animal model is similar to that of clinical cough variant asthma. Tachykinins may not play an important part in antigen-induced cough associated with bronchoconstriction and airway inflammation in cough variant asthma.

Airway Resistance↗
PubMed2006

Differences in motor activation of voluntary and reflex cough in humans.

OBJECTIVES: To study motor activation patterns of voluntary and reflex cough adjusted for cough flow rates. METHODS: Surface electromyography (EMG) and cough flow rate were measured in 10 healthy volunteers. Voluntary cough was assessed for 20 efforts in each quintile of increasing cough flow rate. Reflex cough was assessed for 25 efforts produced by nebulised l-tartaric acid. EMG was recorded over the expiratory (rectus abdominis, obliques, lower intercostals) and accessory (trapezius, pectoralis major, deltoid, latissimus dorsi) muscles. EMG activity, burst duration and onset were compared for each quintile of voluntary cough, and between voluntary and reflex cough matched for cough flow rate. RESULTS: EMG activity and burst duration of expiratory and accessory muscles during voluntary cough increased in proportion to cough flow. Expiratory muscles had longer EMG burst duration (difference 68 ms (95% CI 34 to 102), p<0.01) and earlier onset of EMG activity (difference 44 ms (95% CI 20 to 68), p<0.0001) compared with accessory muscles. EMG activity in all muscles was increased (mean 110.2% v 56.1%, p<0.001) and burst duration (mean 206 ms v 280 ms, p = 0.013) decreased in reflex cough compared with voluntary cough of equal flow rate. There were no differences in EMG onset (difference 8 ms (95% CI 25 to -9) or burst duration (difference 27 ms (95% CI 58 to -4) between expiratory and accessory muscles. CONCLUSIONS: Functional organisation of motor activity differs between voluntary and reflex cough. Voluntary cough is characterised by sequential activation whereas reflex cough is associated with early and simultaneous activation of expiratory and accessory muscles.

Adult↗
PubMed2005

Cough quality in children: a comparison of subjective vs. bronchoscopic findings.

BACKGROUND: Cough is the most common symptom presenting to doctors. The quality of cough (productive or wet vs dry) is used clinically as well as in epidemiology and clinical research. There is however no data on the validity of cough quality descriptors. The study aims were to compare (1) cough quality (wet/dry and brassy/non-brassy) to bronchoscopic findings of secretions and tracheomalacia respectively and, (2) parent's vs clinician's evaluation of the cough quality (wet/dry). METHODS: Cough quality of children (without a known underlying respiratory disease) undergoing elective bronchoscopy was independently evaluated by clinicians and parents. A 'blinded' clinician scored the secretions seen at bronchoscopy on pre-determined criteria and graded (1 to 6). Kappa (K) statistics was used for agreement, and inter-rater and intra-rater agreement examined on digitally recorded cough. A receiver operating characteristic (ROC) curve was used to determine if cough quality related to amount of airway secretions present at bronchoscopy. RESULTS: Median age of the 106 children (62 boys, 44 girls) enrolled was 2.6 years (IQR 5.7). Parent's assessment of cough quality (wet/dry) agreed with clinicians' (K = 0.75, 95%CI 0.58-0.93). When compared to bronchoscopy (bronchoscopic secretion grade 4), clinicians' cough assessment had the highest sensitivity (0.75) and specificity (0.79) and were marginally better than parent(s). The area under the ROC curve was 0.85 (95%CI 0.77-0.92). Intra-observer (K = 1.0) and inter-clinician agreement for wet/dry cough (K = 0.88, 95%CI 0.82-0.94) was very good. Weighted K for inter-rater agreement for bronchoscopic secretion grades was 0.95 (95%CI 0.87-1). Sensitivity and specificity for brassy cough (for tracheomalacia) were 0.57 and 0.81 respectively. K for both intra and inter-observer clinician agreement for brassy cough was 0.79 (95%CI 0.73-0.86). CONCLUSIONS: Dry and wet cough in children, as determined by clinicians and parents has good clinical validity. Clinicians should however be cognisant that children with dry cough may have minimal to mild airway secretions. Brassy cough determined by respiratory physicians is highly specific for tracheomalacia.

Australia↗
PubMed1993

Chronic cough due to gastroesophageal reflux. Clinical, diagnostic, and pathogenetic aspects.

BACKGROUND: Gastroesophageal reflux (GER) is a common cause of chronic cough. Moreover, chronic cough can be the sole presenting manifestation of GER disease (GERD). It has been suggested recently that GER most often causes chronic cough by stimulating the distal esophagus. To gain further diagnostic and pathophysiologic knowledge, we prospectively evaluated a group of patients with chronic cough likely to be due to GER with extensive gastrointestinal and respiratory studies and then observed their response to antireflux therapy. METHODS: We prospectively characterized 12 subjects whose chronic cough was likely to be due to GER by chest radiographs, barium esophagography, 24-h esophageal pH monitoring (EPM) with probes in the distal and proximal esophagus, esophagoscopy, and bronchoscopy. Then, prior to instituting antireflux therapy, we objectively counted coughs during the distal esophageal infusion of 0.1 N HCl or 0.9 percent saline solution administered in a randomized, double-blind, standardized fashion (ie, Bernstein acid-perfusion test). RESULTS: Gastroesophageal reflux was determined to cause cough in all subjects based on disappearance of cough with antireflux therapy. It was clinically "silent" in 75 percent. The EPM was the test most frequently abnormal (sensitivity, 92 percent). Distal esophageal data revealed that 10 of 12 subjects had GER-induced coughs (12 +/- 12) while only 7 of 12 had an abnormal esophageal pH conventional parameter (eg, percent time pH < 4). Compared with the distal esophagus, GER to the proximal esophagus occurred (p = 0.017) and induced cough (p = 0.004) less often. Compared with baseline (9.3 +/- 17.6), there were no differences in coughs induced by the infusion of saline solution (9.2 +/- 15.9) or acid (15.1 +/- 26.7); the number of coughs induced by acid was negatively correlated with distal esophageal acid-GER events during EPM (r = -0.64, p = 0.01). Neither bronchoscopy nor chest radiographs were consistent with aspiration. CONCLUSIONS: There is a clinical profile that prospectively predicts which patients have chronic cough due to GER. The cough was most likely due to stimulation of the distal esophagus, not aspiration. Intraesophageal acid is unlikely to be the sole mediator in gastric juice causing the cough. While EPM is the single most helpful diagnostic test, conventionally utilized diagnostic indices of GERD can be misleadingly normal; observing GER-induced coughs is more frequently helpful.

Adult↗
PubMed2005

Pathophysiology and therapy of chronic cough.

Cough is an essential protective mechanism for the airways and lungs. Cough receptors are situated in the larynx and tracheobronchial tree, and are mediated by rapidly-adapting (irritant) Adelta fibers, although other receptors such as C-fiber receptors may contribute. Cough plasticity and interactions of cough pathways may occur centrally to enhance the cough reflex. The presence of an increased cough reflex as measured by a tussive response to capsaicin or citric acid in patients with a chronic cough indicate that there is sensitisation of the cough reflex. The most common cause of acute cough is that after a common cold, which usually lasts for less than 2 weeks. Cough that persists longer may be due to asthma and its variant forms (cough variant asthma and eosinophilic bronchitis), rhinosinusitis (postnasal drip), gastro-esophageal reflux, bronchiectasis, chronic bronchitis, and angiotensin-converting enzyme (ACE) inhibitor therapy. Chronic persistent cough can contribute to a significant worsening of quality of life measures. Bronchial tumors must be excluded with a chest radiograph. The management of chronic cough includes investigation and treatment of any associated causes, which sometimes leads to control of cough. In a proportion of patients, cough may be idiopathic and remain uncontrolled. Currently-available antitussives such as dextromethorphan or codeine are modestly successful in controlling cough. New antitussives may be developed that act on the sensory receptors or prevent their sensitisation.

Asthma↗
PubMed1997

Citric acid-induced cough thresholds in normal subjects, patients with bronchial asthma, and smokers.

Several challenge procedures have been developed to characterize the cough reflex in patients with airway diseases. This study was performed to compare the interindividual range of cough sensitivity in asthmatic and normal subjects as well as smokers using an identical method. Sixteen normal subjects, 20 patients with mild bronchial asthma, 6 patients with moderate to severe bronchial asthma, 9 current smokers, and 7 occasional smokers were included. In all subjects, methacholine challenges and standardized citric acid challenges were performed. Sensitivity of the cough reflex was expressed as cough threshold, i.e., as concentration at which coughing occurred. Reproducibility was assessed in 23 subjects. Within a concentration range of 0.625-320.0 mg/ml, inhaled citric acid caused cough in all subjects. Geometric mean (range) cough threshold was 13 (2.5-160) in normal subjects, 14 (5-40) in patients with mild, and 32 (20-40) mg/ml in patients with moderate to severe asthma, 40 (20-80) in current smokers, and 119 (80-160) in occasional smokers. Cough thresholds were reproducible within one doubling concentration. In normal subjects and patients with mild bronchial asthma, thresholds were not significantly different from each other but lower than those of the other groups (p<0.05 each). Cough thresholds in smokers and patients with moderate to severe asthma did also not differ significantly and were lower than in occasional smokers (p<0.05). There was no significant correlation between cough threshold, baseline FEV subset1 , and methacholine responsiveness. Our data indicate that (1) subjects with mild asthma showed on average similar cough thresholds as normal subjects, (2) there was a large variation in cough thresholds within groups, (3) the reproducibility of cough thresholds was within one doubling concentration, (4) cough thresholds did not correlate with methacholine responsiveness or baseline airway tone. In view of the prevalence of cough as a symptom of bronchial asthma, it appears that the determination of citric acid-induced cough thresholds does not yield additional diagnostic information in these subjects.

Administration, Inhalation↗
PubMed2006

Establishing a gold standard for manual cough counting: video versus digital audio recordings.

BACKGROUND: Manual cough counting is time-consuming and laborious; however it is the standard to which automated cough monitoring devices must be compared. We have compared manual cough counting from video recordings with manual cough counting from digital audio recordings. METHODS: We studied 8 patients with chronic cough, overnight in laboratory conditions (diagnoses were 5 asthma, 1 rhinitis, 1 gastro-oesophageal reflux disease and 1 idiopathic cough). Coughs were recorded simultaneously using a video camera with infrared lighting and digital sound recording. The numbers of coughs in each 8 hour recording were counted manually, by a trained observer, in real time from the video recordings and using audio-editing software from the digital sound recordings. RESULTS: The median cough frequency was 17.8 (IQR 5.9-28.7) cough sounds per hour in the video recordings and 17.7 (6.0-29.4) coughs per hour in the digital sound recordings. There was excellent agreement between the video and digital audio cough rates; mean difference of -0.3 coughs per hour (SD +/- 0.6), 95% limits of agreement -1.5 to +0.9 coughs per hour. Video recordings had poorer sound quality even in controlled conditions and can only be analysed in real time (8 hours per recording). Digital sound recordings required 2-4 hours of analysis per recording. CONCLUSION: Manual counting of cough sounds from digital audio recordings has excellent agreement with simultaneous video recordings in laboratory conditions. We suggest that ambulatory digital audio recording is therefore ideal for validating future cough monitoring devices, as this as this can be performed in the patients own environment.

Journal Article↗
PubMed2004

Effect of salbutamol on smoking related cough.

Smokers have an increased prevalence of chronic cough and may complain of exacerbation of cough when attempting smoking cessation. We investigated the use of smokers cough as a model for testing anti-tussive agents. The effect of salbutamol was compared with placebo in healthy adult smokers. In a randomised double blind crossover study the effect of 400 microg salbutamol via MDI plus spacer versus placebo was studied. Cough was assessed before and after the first cigarette of the day (received at 20 minutes) and throughout the day. Cough frequency, citric acid cough challenge, change in cough symptoms and peak flow were recorded. Salbutamol reduced the mean cough frequency between 0 and 20 min. A mean of 4.5 compared to 6 on placebo (p<0.05). A significant reduction in cough followed cigarette consumption in those on placebo. Mean pre-cigarette 6 compared to 3.9 post-cigarette (p<0.02). The citric acid concentration causing two coughs (C2) at 60 min increased on salbutamol. Geometric mean 278.8 compared to 190.4 mM on placebo (p<0.03). Cough frequency is reduced in smokers following a cigarette. The reduction in cough frequency and evoked cough after salbutamol suggests that beta agonists have modest activity in smoking related cough and that smokers cough represents a sensitive model to test anti-tussive activity.

Adult↗
PubMed1999

Test-retest reliability of the cough stress test in the evaluation of urinary incontinence.

OBJECTIVE: To determine the test-retest reliability of the cough stress test in women who present with complaints of urinary incontinence. METHODS: This prospective observational study involved 50 women between the ages of 28 and 78 years with primary complaints of urinary incontinence. All subjects underwent a pelvic examination, cystometrogram, and a cough stress test. The cough stress test was performed in the standing position at a bladder volume of 300 mL or at maximum cystometric capacity if it was less than 300 mL. The results of the cough stress test were recorded as positive if urine loss occurred with a cough or as negative if no urine loss was seen and the bladder volume was recorded. The women returned in 1-4 weeks for a second cough stress test performed at the same bladder volume as at the initial examination. RESULTS: Of the 50 women studied, 45 (90%) had similar results with both cough stress tests. Thirty-five had a positive cough stress test on the initial examination, and 32 of these patients (91%) also had a positive cough stress test at a repeat visit. Fifteen patients had a negative initial cough stress test, and 13 of these 15 (87%) had a negative cough stress test on repeat examination. All 20 patients diagnosed as having pure genuine stress incontinence had a positive cough stress test on initial and repeat examinations. Of the 15 patients diagnosed with detrusor instability or sensory urge incontinence, 13 (86%) had negative cough stress tests on initial and repeat examinations. Of the 15 patients diagnosed with mixed incontinence, 12 (80%) had positive cough stress tests on initial and repeat examinations. CONCLUSION: The cough stress test appears to be a reliable test. The reliability is more consistent in women with a diagnosis of pure genuine stress incontinence.

Adult↗
PubMed2001

[Eosinophilic bronchitis without asthma--an additional rare cause for chronic persistent cough (CPC)? A 30-year old patient with severe CPC due to eosinophilic bronchitis without asthma or hyperreactivity].

In non-smokers the underlying causes for chronic persistent cough (CPC) e.g. chronic cough without diagnostic chest X-ray or pulmonary function test--are usually as follows: several common upper airways diseases, bronchial (cough type) asthma, gastrooesophageal reflux or treatment with an ACE (angiotensin converting enzyme)--inhibitor. In 10% of CPC however the cause remains uncertain. We report a 30 year old non-smoker with severe coughing and repeated vomiting for two months. No laboratory or technical data could be collected suggestive of a common cause of CPC: Upper airways disease, bronchial flow limitation or hyperresponsiveness, ACE inhibitor medication, B. pertussis infection, gastrooesophageal reflux disease (by 24 hours pH-probe) were ruled out. Fiberbronchoscopic findings remained unremarkable, except for the bronchial biopsy specimen, which showed moderate eosinophilic inflammation of the mucosa and marked thickening of the subepithelial layer. Since the cough was non-productive, sputum induction with 3 ml nebulised 3% NaCl solution was performed. 28% of the granulocytes were eosinophil stained. A low quality morning sputum (< 1 ml) showed 21% eosinophilia. Thus, the diagnosis of eosinophilic bronchitis was established. 400 micrograms budesonide dry powder inhalations b.i.d. for one week resolved the cough, treatment was stopped after three weeks. No recurrence was seen two months later. Both the cough type asthma and the eosinophilic bronchitis could represent a form fruste of classical bronchial asthma beyond wheezing or dyspnoea, but with the common main symptom: cough. Since hyperresponsiveness and cough are phenotypic hallmarks of cough variant asthma, in eosinophilic bronchitis--beside cough--another two features of asthma are present: eosinophilic inflammation of the mucosa along with sputum eosinophilia and subepithelial layer thickening. Not surprisingly, eosinophilic bronchial inflammation could be shown in patients with cough variant asthma as well, who--up to 56% during a four year-period--develop classic asthma. The long-term outcome of eosinophilic bronchitis is not known, however. Thus, asthma, cough variant asthma and cough due to eosinophilic bronchitis can mirror different phenotypes or phases of the same entity. CPC due to either the cough type asthma or the eosinophilic bronchitis is like asthma fast responding to inhalative steroids. (Induced) sputum staining should be added to the diagnostic armamentarium of CPC.

Adult↗
PubMed2003

The duration of acute cough in pre-school children presenting to primary care: a prospective cohort study.

BACKGROUND: Professional and parental uncertainty about the natural history of cough in pre-school children may in part be responsible for the high consultation and reconsultation rates and widespread antibiotic use in primary care. A recent systematic review of the natural history of cough included studies of unrepresentative, selected patients with heterogeneous measures and definitions of cough duration. OBJECTIVES: The aim of the present study was to describe the post-consultation duration of cough, compare this with clinician and parental prediction of cough duration, and to determine the clinical factors associated with prolonged cough. METHODS: A prospective cohort study of children aged 0-4 years with cough < or =28 days without asthma presenting to eight general practices in Leicestershire, UK was carried out. Socio-demographic and clinical data were collected, and parents and clinicians were asked to predict the proportion recovering within 7, 14, 21 and 28 days. Parents used a symptom diary to record cough and five other symptoms. Survival analysis was used to describe cough duration, and multivariable Cox regression was used to identify the factors independently associated with prolonged cough. RESULTS: Fifty percent of the children had recovered at 10 days and 90% at 25 days. Cough was associated with fever, breathlessness, disrupted sleep and reduced activity in a high proportion of children. Longer post-consultation cough was associated with longer pre-consultation cough and use of day care facilities. Clinicians overestimated how quickly children recovered from acute cough. Parents' predictions were accurate within 2 weeks, but they underestimated the proportion recovering in weeks 3 and 4. CONCLUSIONS: Clinicians should be aware that from the parental perspective, acute cough is not a trivial illness and that some children remain unwell at 3-4 weeks. For health professionals negotiating the use of antibiotics, this information may enable parental self-care, reduce medicalization and displace the need to prescribe.

Child, Preschool↗
PubMed2004

Coughing during mannitol challenge is associated with asthma.

STUDY OBJECTIVES: To define whether coughing during mannitol challenge is a nonspecific side effect of this challenge or is associated with asthma. DESIGN: A prospective study. SETTING: University hospital. PARTICIPANTS: Thirty-seven steroid-naive, asthmatic subjects and 10 healthy subjects. MEASUREMENTS: The participants completed a symptom questionnaire, recorded peak expiratory flows (PEFs), and underwent spirometry, skin tests, and bronchial provocations with mannitol, histamine, and cold air. Seventeen of the asthmatic subjects were treated with budesonide, 800 micro g per day, and the measurements were repeated after 3 and 6 months of treatment. Coughs were recorded during the mannitol challenges, and the cough sensitivity was expressed as the cumulative number of coughs divided by the cumulative dose of mannitol. RESULTS: The asthmatic subjects coughed more during the mannitol challenge than the healthy subjects (8.3 coughs per 100 mg [95% confidence interval (CI), 6.2 to 11.0] vs 1.1 coughs per 100 mg [95% CI, 0.4 to 3.0]; p < 0.0001). Even those asthmatic subjects who did not develop bronchoconstriction after the maximal cumulative dose of mannitol (635 mg) coughed significantly more than the healthy subjects (53 coughs [95% CI, 34 to 72] vs 12 coughs [95% CI, 4 to 21]; p = 0.003). Budesonide treatment decreased the cough sensitivity (p = 0.023), which was significantly associated with improvements in overall symptom frequency, cough frequency, diurnal PEF variation, FEV(1), and bronchial hyperresponsiveness. CONCLUSIONS: Coughing during mannitol challenge is associated with asthma and occurs independently of bronchoconstriction. It can be used to study the mechanisms of asthmatic cough. Furthermore, the measurement of the mannitol-provoked coughing may be useful both in the diagnosis of asthma as well as in the assessment of the effects of an anti-inflammatory therapy on this common disorder.

Adult↗
PubMed2006

Future directions in the clinical management of cough: ACCP evidence-based clinical practice guidelines.

OBJECTIVES: To impart a call for further research into the identified domains of particular interest in the etiology, management, and treatment of cough. DESIGN/METHODOLOGY: A literature review was performed using the search term "cough" in PubMed between 1983 and 2004. The final draft of this guideline was reviewed, in addition to recent studies on cough, and suggestions provided by the authors were collated into a definitive inventory of specific areas in which the lack of quality evidence encumbered the development of clinically relevant evidence-based recommendations. RESULTS/CONCLUSIONS: Although our understanding of the causes and optimal management of chronic cough have significantly increased over the past 25 years, further research remains to be done on this common symptom. This is reflected by the generally low level of evidence for many of the recommendations in these guidelines. Research is particularly needed on the optimal treatment of postinfectious cough, how to distinguish acute bronchitis from other conditions, how to reliably diagnose and treat cough due to gastroesophageal reflux disease, clearly identifying a role for nonpharmacologic protussive treatment modalities in diseases associated with an increased production of bronchial secretions, determining how often cough in patients with interstitial lung disease is due to conditions other than these, establishing the spectrum and frequency of causes of chronic cough in the immunocompromised hosts, and better characterizing psychogenic cough. Further studies are also needed on methods for the assessment of cough, in particular, noninvasive measures of airway inflammation, and pharmacotherapy. It should be determined how often unexplained cough (previously referred to as idiopathic cough) is due to the use of non-evidence-based guidelines or to environmental causes, and assessed whether an empiric, integrative approach of diagnosing chronic cough leads to better outcomes, including cost-effectiveness, than routine testing. While much work has been done on chronic cough, we need studies on the spectrum and frequency of acute and subacute coughs.

Cough↗
PubMed2004

[A prospective study on the cough mechanism induced by angiotensin-converting enzyme inhibitors in patients with hypertension].

OBJECTIVE: To explore the possible mechanisms underlying cough induced by angiotensin-converting enzyme inhibitors (ACEI) in patients with hypertension. METHODS: 127 patients with hypertension were enrolled to receive ACEI (97 cases prescribed cilazapril and 30 cases prescribed benazepril hydrochloride) for 8 weeks. Patients who had coughed in the period were assigned to the cough group (48 cases) and patients who hadn't coughed were assigned to the non-cough group (79 cases). The serum ACE activity before and after administration of the drugs and the polymorphism of ACE gene (including homozygous-alleles II, DD, and heterozygous ID) were analyzed. Binary logistic regression was used as a statistical method to determine the factors associated with cough. RESULTS: The frequencies of the I alleles and II genotype of ACE gene in the cough group (0.70% and 56.3%) were significantly higher than those in the non-cough group (0.42% and 23.3%, P < 0.05). The mean serum ACE activity before and after administration of the ACEI in the cough group [(26 +/- 6) U/L, (4 +/- 4) U/L] was significantly lower than that in the non-cough group [(33 +/- 8) U/L, (8 +/- 8) U/L, all P < 0.01]. The difference in the range of decrease of serum ACE activity after ACEI between the cough group [(22 +/- 7) U/L] and the non-cough group [(25 +/- 9) U/L] was not significant (P = 0.077). Serum ACE activity before ACEI was highest in the homozygous-alleles DD group [(36 +/- 8) U/L], secondly in the heterozygous ID group [(29 +/- 6) U/L] and the lowest in homozygous-alleles II group [(26 +/- 7) U/L], differences being significant among three groups (P < 0.01). ACEI-related cough showed no relationship with sex, smoking habit and the ACEI used. CONCLUSIONS: The serum ACE activity was associated with polymorphism of ACE gene. Cough induced by ACEI was related to I allele and II genotype. There was a relationship between the serum ACE activity before administration of ACEI and cough induced by ACEI.

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