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Efficacy and tolerability of a fluid extract combination of thyme herb and ivy leaves and matched placebo in adults suffering from acute bronchitis with productive cough. A prospective, double-blind, placebo-controlled clinical trial.

STUDY OBJECTIVE: To assess the efficacy and tolerability of a fixed fluid extract combination of thyme and ivy leaves (thyme-ivy combination) and matched placebo in patients suffering from acute bronchitis with productive cough. METHODS: In a double-blind, placebo-controlled, multicentre Phase IV study 361 outpatients with acute bronchitis and > or =10 coughing fits during the day, onset of bronchial mucus production with impaired ability to cough up at a maximum of 2 days prior to recruitment, and a Bronchitis Severity Score (BSS) > or =5 score points were randomly assigned to an 11-day treatment (5.4 ml three times daily) with either thyme-ivy combination syrup (Bronchipret Saft; N=182) or placebo syrup (N=179). After the baseline examination (Visit 1 = Day 0), 2 control examinations were scheduled (Visit 2 = Day 4; Visit 3 = Day 10/end of treatment). The efficacy of study treatment on acute bronchitis was evaluated by the patient's daily counting of coughing fits during the daytime (manual counter), assessment of acute bronchitis related symptoms and by the investigator's assessment of the most important symptoms of acute bronchitis using the BSS. Evaluation of tolerability was based upon adverse event (AE) monitoring, measurement of vital signs as well as the Primary outcome was the change in frequency of coughing fits during daytime on days 7-9 according to patient's accurate daily recording with a manual counter and documentation in the diary. Treatment effects were analysed by analysis of variance (ANOVA) adjusted for centre effects. Due to significant deviation from the "preconditions" of the ANOVA, the Wilcoxon test (stratified by centre) was carried out additionally. RESULTS: The mean reduction in coughing fits on days 7 to 9 relative to baseline was 68.7% under thyme-ivy combination compared to 47.6 % under placebo (p < 0.0001). In the thyme-ivy combination group, a 50% reduction in coughing fits from baseline was reached 2 days earlier compared to the placebo group. The symptoms of acute bronchitis (BSS) improved rapidly in both groups, but regression of symptoms was faster and the responder rates (p < 0.0001) compared to placebo were higher at Visit 2 (83.0% vs 53.9%) and Visit 3 (96.2% vs. 74.7%) under the treatment of thyme-ivy combination. Treatment was well tolerated with no difference in the frequency or severity of AEs between thyme-ivy combination and placebo groups. Severe or serious AEs were not reported. CONCLUSION: Oral treatment of acute bronchitis with thyme-ivy combination for about 11 days was superior to pla-

Adult↗

Antitussive effects of the H1-receptor antagonist epinastine in patients with atopic cough (eosinophilic bronchitis).

Chronic cough is the only symptom of eosinophilic bronchitis (EB). There is considerable overlap between EB and atopic cough. To investigate the antitussive effects of a histamine H1-recetor antagonist, epinastine hydrochloride (epinastine, CAS 80012-43-7, Alesion; 20 mg/day, once daily), cough scores, pulmonary function, capsaicin cough threshold, and bronchial hyperresonsiveness (BHR) to methacholine (MCh) were evaluated before and after a 4-week treatment with epinastine in patients with EB. In the epinastine group, the cough scores were decreased significantly (18.3 +/- 6.1 in week 1, 17.4 +/- 6.7 in week 2, 15.1 +/- 6.2 in week 3, 14.0 +/- 4.8 in week 4) in comparison with the value of 35.3 +/- 8.7 in week -2). The cough threshold for capsaicin improved from 1.70 +/- 3.04 micromol/l to 12.7 +/- 17.6 micromol/l in the epinastine group (p < 0.05; baseline vs. week 4) The bronchial hyperresponsiveness to MCh (Dmin) did not change significantly either in the epinastine or the placebo groups. The morning and evening peak expiratory flow rate (PEFR, L/min) did not change from the baseline period in either the epinastine or the placebo groups. These results suggested that epinastine may be useful for treating patients with EB and that histamine H1-receptor is related to the pathophysiology of coughing in EB.

Adult↗

Th2 cytokine inhibition and cough in asthmatic and bronchitic patients.

BACKGROUND: Activated T helper lymphocytes are present in the airway and their production of cytokines is important in the pathogenesis of asthma, however, the relationship between T helper lymphocyte-derived cytokines and airway cough reflex sensitivity remains unknown. METHODS: The effect of the orally active Th2 cytokine inhibitor suplatast tosilate on cough response to inhaled capsaicin was examined in eleven patients with stable atopic asthma and compared with patients having non-atopic asthma and chronic bronchitis (the latter of which is not related to Th2 cytokines). Capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of airway cough reflex sensitivity. Concentration of serum total IgE level was also measured after treatment with suplatast tosilate. RESULTS: The cough threshold after two weeks treatment with suplatast tosilate was significantly greater than the value with placebo accompanied by decrease of serum IgE level in atopic asthmatics. This significance was not observed in patients with non-atopic asthma or chronic bronchitis. CONCLUSIONS: Th2 cytokines may be possible modulators augmenting airway cough reflex sensitivity in atopic asthmatic airways but not in non-atopic asthmatic or bronchitic airways.

Adult↗

The prevalence of potentially pathogenic bacteria in nasopharyngeal samples from individuals with a long-standing cough-clinical value of a nasopharyngeal sample.

BACKGROUND: A long-standing cough is a common cause for visits to a GP. If the patient also has a respiratory tract infection, one of the concerns of the doctor is to decide if the cough is caused by an underlying bacterial infection. OBJECTIVES: Our aim was to investigate whether a nasopharyngeal sample, obtained in routine medical practice, could yield information about the aetiology of a long-standing cough in patients with a respiratory tract infection. METHODS: The prevalence of potentially pathogenic bacteria (Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis) in nasopharyngeal swab samples from 618 healthy individuals was compared with that from 236 patients with a respiratory tract infection and long-standing cough (>9 days) of the same age in a defined geographical area. RESULTS: The proportion of cultures with potentially pathogenic bacteria decreased with age and was 44% among healthy individuals of pre-school age, 13% in schoolchildren and 6% in adults. The corresponding figures for patients with a long-standing cough were 83, 35 and 36%, respectively. All types of potentially pathogenic bacteria were found more frequently in pre-school children and in adults with a long-standing cough compared with healthy individuals of the same age. CONCLUSIONS: In patients with a respiratory tract infection and a long-standing cough, where a bacterial infection is suspected on clinical grounds, a nasopharyngeal culture could yield information about the aetiology. If M.catarrhalis is found in pre-school children, or if H.influenzae is found in adults, they are likely to be the aetiological agent.

Adolescent↗

An outbreak of whooping cough in a highly vaccinated urban community.

In 1950 a whole-cell pertussis vaccine was introduced in Cape Town and was followed by a marked decline in reported whooping cough mortality and morbidity. This resulted in reduced awareness of whooping cough as a clinical problem and, in recent years, no routine diagnostic tests for Bordetella pertussis have been performed. An outbreak of whooping cough occurred in Cape Town between 1 June 1988, and 31 May 1989, with 292 children admitted to hospital for whooping cough during this period (hospital admission rate in children under 5 years of age = 187 per 100,000). In an investigation of 239 children attending four pre-primary schools in the city, the whooping cough attack rate was 33 per cent, while pertussis vaccine coverage was 95 per cent. In the latter part of the outbreak nasopharyngeal swabs and serology were performed in patients presenting to a children's hospital with suspected whooping cough. Bordetella pertussis was isolated from 3 out of 34 (9 per cent) children tested and the first isolate was serotyped as type 1,2,4. Available clinical and laboratory evidence indicated that the organism responsible for the outbreak was Bordetella pertussis. Coverage studies for pertussis vaccine in Cape Town indicated that between 81 and 93 per cent of children were fully immunized by 13 months of age. These findings suggest that, since its introduction, the whole-cell pertussis vaccine produced in South Africa has been highly effective in controlling whooping cough. However, it was not able to prevent a moderate scale outbreak, even in the presence of high vaccination levels.

Child↗

Putative mechanisms of cough after treatment with angiotensin converting enzyme inhibitors.

BACKGROUND: A dry cough is the most common adverse effect of angiotensin converting enzyme (ACE) inhibitors, even if it is not particularly serious. Controlled studies have suggested that the incidence may eventually be as high as 20% and the problem seems to occur much more often in women. MECHANISM OF ACE INHIBITOR COUGH: The mechanism of the cough associated with ACE inhibitor treatment is unrelated to inhibition of the renin-angiotensin system because treatment with angiotensin receptor blockers and renin inhibitors has not caused similar problems. Other substrates of ACE have been implicated, and the side effect has been linked in particular to an accumulation of bradykinin or tachykinins in the airways with consequent stimulation of vagal afferents that subserve the cough reflex, particularly the non-myelinated or C fibres. Some of the effects of bradykinin in particular may be due to secondary activation of prostaglandins (PG), especially PGE2 and PGI2. Anecdotal evidence that cyclooxygenase inhibitors prevent the cough has not been sustained in well controlled clinical trials, but recent evidence suggests that inhaled cromoglycate may have a significant inhibitory effect. The mechanism of action of cromoglycate is not well understood but evidence of inhibition of local neural reflexes has been inferred, mostly from animal studies. The observation seems unlikely to have much practical benefit for it is difficult to envisage routine use of an inhaled agent to prevent a drug side effect. The question of whether ACE inhibitors are safe in patients with asthma is still open, and most rechallenge studies have shown little effect on lung function. Data from one large-scale surveillance study suggest that a few individuals may experience dyspnoea and wheezing but no causal relationship has been established. CONCLUSION: Delineation of the mechanism of the ACE inhibitor cough may lead to a better understanding of the mechanism of cough in inflammatory airways disease.

Angiotensin-Converting Enzyme Inhibitors↗

Respiratory retraining of refractory cough and laryngopharyngeal reflux in patients with paradoxical vocal fold movement disorder.

OBJECTIVES/HYPOTHESIS: The objective was to describe a case series of patients with refractory cough and paradoxical vocal fold movement disorder treated with respiratory retraining therapy. STUDY DESIGN: Retrospective review of a case series in a tertiary medical care center. METHODS: Five patients with laryngopharyngeal reflux were identified with refractory cough and paradoxical fold movement disorder on transnasal fiberoptic laryngoscopy by a greater than 50% reduction in airway during inspiration. The were four women and one man (age range, 42-67 y). All patients had normal forced vital capacity and forced expiratory flow but decreased ratio of forced inspiratory volume at 0.5 seconds (FIV(0.5)) to forced inspiratory vital capacity (FIVC) before starting therapy. All patients were treated with more than 6 months of twice-daily proton pump inhibitor therapy with improvement in reflux symptoms but persistent and severe daytime cough. They were subsequently treated with respiratory retraining therapy. Patients were asked to rate subjectively the severity of cough at the onset and conclusion of therapy. All patients underwent pulmonary function testing before and after therapy. Long-term follow-up ranged from 5 to 17 months. RESULTS: Patients received two to seven sessions of respiratory retraining therapy. The mean severity score changed from 9.2 before therapy to 1.3 after therapy. All patients subjectively described an improvement in the severity of their cough. Transnasal flexible laryngoscopy demonstrated improvement in paradoxical vocal fold movement, and pulmonary function testing showed improvement in the FIV(0.5)/FIVC ratio. CONCLUSION: Patients with laryngopharyngeal reflux and refractory cough in the absence of pulmonary disease should be evaluated for paradoxical vocal fold movement disorder. Respiratory retraining therapy may represent an effective therapy for cough in the absence of relief from standard management of laryngopharyngeal reflux.

Adult↗

Detection of cough signals in continuous audio recordings using hidden Markov models.

Cough is a common symptom of many respiratory diseases. The evaluation of its intensity and frequency of occurrence could provide valuable clinical information in the assessment of patients with chronic cough. In this paper we propose the use of hidden Markov models (HMMs) to automatically detect cough sounds from continuous ambulatory recordings. The recording system consists of a digital sound recorder and a microphone attached to the patient's chest. The recognition algorithm follows a keyword-spotting approach, with cough sounds representing the keywords. It was trained on 821 min selected from 10 ambulatory recordings, including 2473 manually labeled cough events, and tested on a database of nine recordings from separate patients with a total recording time of 3060 min and comprising 2155 cough events. The average detection rate was 82% at a false alarm rate of seven events/h, when considering only events above an energy threshold relative to each recording's average energy. These results suggest that HMMs can be applied to the detection of cough sounds from ambulatory patients. A postprocessing stage to perform a more detailed analysis on the detected events is under development, and could allow the rejection of some of the incorrectly detected events.

Algorithms↗

Effect of frusemide on the induction and potentiation of cough induced by prostaglandin F2 alpha.

We examined whether inhaled frusemide could reduce the potentiation of capsaicin-induced cough by prostaglandin (PG) F2 alpha. Eight non-smoking normal subjects, after a baseline capsaicin challenge were given inhaled frusemide or saline followed by capsaicin challenge, then PGF2 alpha and finally capsaicin challenge again. PGF2 alpha-induced coughs were reduced after frusemide to 3.6 +/- 1.0 compared with 5.7 +/- 1.2 after saline (P less than 0.05). PGF2 alpha increased capsaicin-induced coughs by 11.1 +/- 3.7 and 7.9 +/- 3.4 after placebo and frusemide, respectively (P less than 0.05). Frusemide had no effect on capsaicin-induced cough alone. Changes in local ionic concentrations by frusemide, particularly chloride ions within the vicinity of epithelial cough receptors, may determine the cough response to low chloride solutions and to PGF2 alpha, but not to capsaicin which acts directly on the cough receptors, and alter the sensitivity of the receptors to capsaicin.

Administration, Inhalation↗

The effect of inhaled and oral dextromethorphan on citric acid induced cough in man.

1. Dextromethorphan is a widely used antitussive agent which is a non-narcotic codeine analogue. We have investigated whether inhaled administration of dextromethorphan provides antitussive activity in a citric acid induced cough model. 2. Twenty normal subjects underwent repeated cough challenge with 5% citric acid. Subjects were studied on six occasions. Study medication consisted of oral dextromethorphan 30 mg or oral matched placebo or 1, 3 and 30 mg inhaled dextromethorphan or matched inhaled placebo. Cough challenge was administered 10 min after study medication and hourly thereafter up to 250 min. 3. No significant differences were seen between baseline cough responses. Oral dextromethorphan (30 mg) produced a mean percentage reduction in cough of 38% (P < 0.002), which remained significant at 250 min. Inhaled dextromethorphan had no clinically significant effect although activity at later time points was not excluded. The antitussive effect of oral dextromethorphan is confirmed with prolonged inhibition of induced cough. It is possible that dextromethorphan or its active metabolites act centrally to inhibit the cough reflex.

Administration, Inhalation↗

Cough variant asthma is associated with a higher wheezing threshold than classic asthma.

Cough variant asthma is an occult form of asthma in which the only sign or symptom is chronic cough. It is a common problem amongst all ages that frequently goes unrecognized, leading to underdiagnosis and undertreatment. To characterize the pathophysiological abnormalities in these patients, we performed bronchial provocation tests with methacholine using the stepwise doubling concentration technique, and measured the concentration of methacholine and the severity of airway obstruction when wheezing was first detected. Airway hyperresponsiveness, defined as PC20 in the cough variant asthma group was not significantly different from that of classic asthma. There was a good correlation between the PCW (the concentration of methacholine causing wheezing) and the PC20 with the PCW values higher than PC20 values in both groups. However, in the cough variant asthma group, the PCW:PC20 ratio was greater than that of the classic asthma group. Furthermore, the mean % fall in FEV1 at which wheezing was first detected in the former group was significantly larger than that of the latter group. The results indicated that the mechanism for the manifestation of cough without wheeze in the cough variant asthma may be a higher wheezing threshold, i.e. wheezing becomes audible at the greater degree of airway obstruction than classic asthma. They suggested that patients with cough variant asthma may represent a subset of asthmatic subjects whose airways are less able to produce a wheeze.

Adolescent↗

Nasal mask continuous positive airway pressure in the treatment of chronic nocturnal cough in a young child.

The objective of this case report was to define the effects of nasal mask continuous positive airway pressure (CPAP) on the respiratory and sleep characteristics of a 3 year-old boy with a 2 year history of snoring and 1 year history of chronic nocturnal cough. The method employed was all-night polysomnography before and during treatment with CPAP after the identification of partial upper airway obstruction in association with cough. The results indicated that the child had evidence of mild upper airways obstruction on initial all-night sleep study. Nasal mask CPAP was instituted. On a subsequent sleep study 4 weeks later, this was documented to prevent the upper airway obstruction at a pressure of 5.2 cm of water. In addition, nasal mask CPAP markedly reduced the nocturnal coughing, the total number of coughs decreasing from 92 to one. The rate of cough per h of study (cough disturbance index) decreased from 9.8-0.1. Sleep efficiency (total sleep time as a percentage of study duration) improved on CPAP from 87 to 99%. This study suggests that chronic nocturnal cough can result from upper airway obstruction in sleep in children and is an important initial observation.

Child, Preschool↗

Airway cough sensitivity to inhaled capsaicin and bronchial responsiveness to methacholine in asthmatic and bronchitic subjects.

The objective of this study was to evaluate the effect of chronic airway inflammation on airway cough sensitivity and non-specific bronchial responsiveness, and the relationship between them. The capsaicin cough threshold, defined as the lowest concentration of capsaicin causing five or more coughs, and non-specific bronchial responsiveness, defined as the methacholine concentration causing a 20% fall in forced expiratory volume in 1 s (FEV1) (PC20-FEV1), were measured in 18 asthmatic, 13 bronchitic (sinobronchial syndrome) and 28 healthy non-atopic subjects. All subjects were non-smoking men. The geometric mean values (mumol) of the cough threshold were 18.9 (GSEM 1.29), 8.69 (GSEM 1.29) and 27.6 (GSEM 1.31) in asthmatic, bronchitic and normal subjects, respectively. The value in bronchitic subjects was significantly lower (P << 0.02) than that in normal subjects. The geometric mean value of PC20-FEV1 in asthmatic subjects (0.48 mg/ml (GSEM 1.38)) was significantly lower than that in bronchitic subjects (18.5 mg/ml (GSEM 1.75)) (P << 0.001). There was no correlation between cough threshold and PC20-FEV1 values (correlation coefficient (r) = 0.155). These results indicate that cough sensitivity is potentiated by chronic airway inflammation in bronchitis but not in asthma, and suggest that cough sensitivity and bronchial responsiveness may be independently potentiated by different mechanisms resulting from chronic airway inflammation.

Administration, Inhalation↗

How much coughing is normal?

A new multiparametric device (RBC-7) was used for recording cough in ambulatory children over a 24 hour period. The number of coughs and the pattern of coughing can easily be studied with the aid of a personal computer and dedicated computer software. Forty one 'normal' children were recorded, identified from a primary school with the aid of a questionnaire. They were free from any respiratory infection for one month, and had a normal examination and spirometry immediately before recording. Cough frequency was 11.3, range 1 to 34, cough episodes per 24 hours. This was unaffected by passive smoking or the presence of furry pets in the home. Nocturnal and prolonged coughing was unusual in these children. The device was highly acceptable to the children, and no adverse effects were reported. Such objective data on cough outside the laboratory setting are unique, help to determine what is normal, and may help in the diagnosis and assessment of many respiratory diseases.

Child↗

Stability of respiratory symptoms in unlabelled wheezy illness and nocturnal cough.

OBJECTIVE: To assess the natural history of respiratory symptoms not labelled as asthma in primary schoolchildren. DESIGN: Repeat questionnaire survey of subgroups identified from a previous questionnaire survey after a two year delay. SUBJECTS: The original population of 5321 Sheffield children aged 8-9 years yielded 4406 completed questionnaires in 1991(82.8%). After excluding children with a label of asthma, there were 370 children with current wheeze, 129 children with frequent nocturnal cough, and a random sample of 222 children with minor cough symptoms and 124 asymptomatic children. RESULTS: Response rates in the four groups were 233 (63.0%), 77 (59.7%), 160 (72.1%), and 90 (72.6%) respectively. Of those who initially wheezed, 114 (48.9%) had stopped wheezing and 42 (18.0%) had been labelled as having asthma. Those with more frequent wheezing episodes (p < 0.02) and a personal history of hay fever (p < 0.01) in 1991 were more likely to retain their wheezy symptoms. In the children with frequent nocturnal cough in 1991, 20.1% had developed wheezing, 42.9% had a reduced frequency of nocturnal coughing, and 14.2% had stopped coughing altogether two years later. One sixth had been labelled as having asthma. Children with nocturnal cough were more likely to develop wheezing if they had a family history of atopy (p = 0.02). Only 3.8% and 3.3% of those with minimal cough and no symptoms respectively in 1991 had developed wheeze by 1993 (1.9% and 1.0% labelled as asthma). CONCLUSIONS: Most unlabelled recurrent respiratory symptoms in 8-10 year olds tend to improve. Unlabelled children who have persistent symptoms have other features such as frequent wheezing attacks and a family or personal history of atopy. If a screening questionnaire were to be used to identify such children, a combination of questions should be employed.

Asthma↗

Systematic review and meta-analysis of randomised controlled trials of gastro-oesophageal reflux interventions for chronic cough associated with gastro-oesophageal reflux.

OBJECTIVE: To evaluate the efficacy of treatment for gastro-oesophageal reflux disease (GORD) on chronic cough in children and adults without an underlying respiratory disease. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Cochrane, Medline, and Embase databases, references from review articles. INCLUDED STUDIES: Randomised controlled trials on GORD treatment for cough in children and adults without primary lung disease. Two reviewers independently selected studies and extracted paediatric and adult data on primary (clinical failure) and secondary outcomes. RESULTS: 11 studies were included. Meta-analysis was limited to five studies in adults that compared proton pump inhibitors with placebo. All outcomes favoured proton pump inhibitors: the odds ratio for clinical failure (primary outcome) was 0.24 (95% confidence interval 0.04 to 1.27); number needed to treat (NNT) was 5 (harm 50 to infinity to benefit 2.5). For secondary outcomes, the standardised mean difference between proton pump inhibitors and placebo was -0.51 (-1.02 to 0.01) for mean cough score at the end of the trial and -0.29 (-0.62 to 0.04) for change in cough score at the end of the trial. Subgroup analysis with generic inverse variance analysis showed a significant mean change in cough (-0.41 SD units, -0.75 to -0.07). CONCLUSION: Use of a proton pump inhibitor to treat cough associated with GORD has some effect in some adults. The effect, however, is less universal than suggested in consensus guidelines on chronic cough and its magnitude of effect is uncertain.

Adult↗

The anal reflex elicited by cough and sniff: validation of a neglected clinical sign.

BACKGROUND: It is unclear whether contraction of the external anal sphincter (EAS) following a voluntary cough is an integral component of the cough response itself, or a reflex response to the abdominal and pelvic floor dynamics induced by the cough. Clinical experience suggests a reflex origin for this response. OBJECTIVE: To compare motor latencies for intercostal, abdominal, and EAS muscle contraction after transcranial magnetic stimulation with those following voluntary coughing and sniffing. METHODS: A needle electrode inserted into the EAS measured responses, which were confirmed by tonic electromyographic recording. Direct motor latencies from the cerebral cortex to the intercostal, rectus abdominis and EAS muscles were obtained using transcranial magnetic stimulation. Sniff and cough induced responses were also recorded in these muscles. RESULTS: The results suggest that EAS responses following a voluntary cough or sniff represent a polysynaptic reflex. CONCLUSIONS: As the cough induced anal reflex response is consistent and easily elicited, its use in clinical neurological examination is appropriate.

Adult↗

Cough frequency in children with mild asthma correlates with sputum neutrophil count.

BACKGROUND: A study was undertaken to measure cough frequency in children with stable asthma using a validated monitoring device, and to assess the correlation between cough frequency and the degree and type of airway inflammation. METHODS: Thirty six children of median age 11.5 years (interquartile range (IQR) 9-14) with stable asthma were recruited. They underwent spirometric testing, exhaled nitric oxide (eNO) measurement, sputum induction for differential cell count, and ambulatory cough monitoring for 24 hours. Coughing episodes were counted both as individual spikes and as clusters. RESULTS: All children had mild intermittent asthma and their median forced expiratory volume in 1 second and eNO were 83.3% (IQR 81.1-97.6) and 56.1 ppb (IQR 37.4-105), respectively. The median number of cough episodes per day was 25.5 (IQR 16-42.8). Sputum induction was successful in 69% of the subjects and cough frequency was found to have a significant positive correlation with sputum neutrophil count (r = 0.833, p = 0.0001). CONCLUSIONS: Children with stable mild asthma have increased cough frequency that might be driven by a neutrophilic inflammatory pathway.

Asthma↗