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Effect of influenza A virus infection on acid-induced cough response in children with asthma.

Although it is well-known that some types of respiratory viral infections cause airway hyperresponsiveness in humans, the effect of viral infection on the cough threshold in asthmatics is not known. We, therefore, evaluated the effects of naturally-acquired influenza A virus infection on the cough threshold to inhaled acid in children with asthma. Twelve children with asthma (9 boys and 3 girls, mean +/- SEM age of 10.8 +/- 0.6 yrs), who had naturally-acquired influenza A virus infection in winter (January-February, 1992) during an epidemic of influenza A (H1N1), were enrolled in this prospective, uncontrolled study. All patients underwent acetic acid (AA) inhalation challenge 2, 4 and 6 weeks after the influenza infection. The cough threshold values (the lowest concentrations of AA eliciting coughs) after 2, 4 and 6 weeks of the illness were 3.7 +/- 0.9, 5.3 +/- 1.0 and 8.1 +/- 1.4% (mean +/- SEM), respectively. Cough threshold values 4 or 6 weeks after the illness improved significantly over that at 2 weeks (p < 0.05 and p < 0.01, respectively). In contrast, baseline forced expiratory volume in one second did not change throughout the study. These results indicate that influenza A virus infection attenuates the cough threshold independently of airway obstruction in children with asthma. The enhanced cough response following virus infection is probably mediated by damage to the airways epithelium.

Acetic Acid↗

Efficacy and safety of levodropropizine and dihydrocodeine on nonproductive cough in primary and metastatic lung cancer.

Nonproductive cough is a frequent and distressing symptom in patients with lung cancer, and it is not even relieved by palliative chemotherapy. A double-blind, randomized clinical trial regarding the treatment of nonproductive cough was performed in 140 adults with primary lung cancer or metastatic cancer of the lungs. The therapeutic efficacy and the tolerability of a 7-day treatment with levodropropizine drops (75 mg t.i.d.) were evaluated in comparison with dihydrocodeine drops (10 mg t.i.d.; 7 days). Efficacy was assessed on the basis of cough severity scores, number of night awakenings due to cough, and overall estimate of antitussive efficacy. Tolerability was evaluated by laboratory results, vital signs and any adverse event occurring during the clinical trial, including presence or absence of somnolence. Subjective cough severity was significantly reduced during treatment with either levodropropizine and dihydrocodeine, the antitussive effect and its time-profile being similar for both drugs. Also, according to the investigator's evaluation, both levodropropizine and dihydrocodeine produced a significant decrease in cough severity. Concurrently with the relief of cough, the number of night awakenings was decreased significantly by both drugs, with no difference between the two treatments. No change in laboratory test values was considered clinically relevant, and vital signs were not clinically affected. The number of patients reporting adverse events was similar in the levodropropizine (n=6) and dihydrocodeine (n=4) group. However, the percentage of patients experiencing somnolence in the group receiving levodropropizine (8%) was significantly lower as compared with that of the dihydrocodeine group (22%). These results confirm the antitussive effectiveness of levodropropizine and suggest a more favourable benefit/risk profile when compared to dihydrocodeine.

Administration, Oral↗

Cough and reflux esophagitis in children: their co-existence and airway cellularity.

BACKGROUND: There are no prospective studies that have examined for chronic cough in children without lung disease but with gastroesophageal reflux (GER). In otherwise healthy children undergoing flexible upper gastrointestinal endoscopy (esophago-gastroscopy), the aims of the study were to (1) define the frequency of cough in relation to symptoms of GER, (2) examine if children with cough and reflux esophagitis (RE) have different airway cellularity and microbiology in bronchoalveolar lavage (BAL) when compared to those without. METHODS: Data specific for chronic cough (> 4-weeks), symptoms of GER and cough severity were collected. Children aged < 16-years (n = 150) were defined as 'coughers' (C+) if a history of cough in association with their GER symptoms was elicited before BAL were obtained during elective esophago-gastroscopy. Presence of esophagitis on esophageal biopsies was considered reflux esophagitis positive (E+). RESULTS: C+ (n = 69) were just as likely as C- (n = 81) to have esophagitis, odds ratio 0.87 (95%CI 0.46, 1.7). Median neutrophil percentage in BAL was significantly different between groups; highest in C+E- (7, IQR 28) and lowest in C-E+ (5, IQR 6). BAL positive bacterial culture occurred in 20.7% and were more likely present in current coughers (OR 3.37, 95%CI 1.39, 8.08). Airway neutrophilia (median 20%, IQR 34) was significantly higher in those with BAL positive bacterial cultures than those without (5%, 4; p = 0.0001). CONCLUSION: In children without lung disease, the common co-existence of cough with symptoms of GER is independent of the occurrence of esophagitis. Airway neutrophilia when present in these children is more likely to be related to airway bacterial infection and not to esophagitis.

Adolescent↗

Assessment of aspiration risk in stroke patients with quantification of voluntary cough.

BACKGROUND: Dysphagia and subsequent aspiration are serious complications of acute stroke that may be related to an impaired cough reflex. It was hypothesized that aspirating stroke patients would have impaired objective measures of voluntary cough as compared with both nonstroke control subjects and nonaspirating stroke patients. METHODS: Swallowing was evaluated by standard radiologic or endoscopic methods, and stroke patients were grouped by aspiration severity (severe, n = 11; mild, n = 17; no aspiration, n = 15). Airflow patterns and sound pressure level (SPL) of voluntary cough were measured in stroke patients and in a group of normal control subjects (n = 18). Initial stroke severity was determined retrospectively with the Canadian Neurological Scale. RESULTS: All cough measures were altered in stroke patients as a group relative to nonstroke control subjects. Univariate analysis showed that peak flow of the inspiration phase (770.6 +/- 80.6 versus 1,120.1 +/- 148.4 mL/s), SPL (90.0 +/- 3.1 versus 100.2 +/- 1.6 dB), peak flow of the expulsive phase (875.1 +/- 122.7 versus 1,884.1 +/- 221.6 mL/s), expulsive phase rise time (0.34 +/- 0.1 versus 0.09 +/- 0.01 s), and cough volume acceleration (5.5 +/- 1.3 versus 27.8 +/- 3.9 mL/s/s) were significantly impaired in severe aspirators as compared with nonaspirators. Aspirating patients had more severe strokes than nonaspirators (mean Canadian Neurological Scale score 7.7 +/- 0.7 versus 9.8 +/- 0.3). Multivariate logistic regression found only expulsive phase rise time values during cough correlated with aspiration status. CONCLUSION: Objective analysis of cough may provide a noninvasive way to identify the aspiration risk of stroke patients.

Aged↗

[No relation between angiotensin-converting enzyme (ACE) inhibitor-induced cough and ACE gene polymorphism, plasma bradykinin, substance P and ACE inhibitor concentration in Japanese patients].

Persistent dry cough is well known as the most common side-effect of angiotensin-converting enzyme (ACE) inhibitors. We examined the relationship between a cough and ACE gene polymorphism, plasma bradykinin (BK), substance P (SP) and ACE inhibitor concentrations in patients with hypertension or chronic nephritis. First, ACE genotyping was carried out in 96 patients, 42 with coughs and 54 without coughs, which had been treated with various kinds of ACE inhibitors. However, no significant difference in the ACE genotypes was observed between the two groups. Second, the plasma concentrations of BK, SP and ACE inhibitor were measured in 12 patients, which were treated with trandolapril at a daily dose of 1 mg for 4-33 weeks. In 3 patients, the cough was induced during the trandolapril therapy, while it was induced not in 9 patients. The plasma levels of BK and SP did not significantly change after trandolapril administration in the patients with and without coughs. Between the two groups, there were no significant differences in the plasma levels of BK and SP either before or after the trandolapril therapy. Also the plasma concentrations of trandolapril and trandolaprilat, the active metabolite of trandolapril, did not significantly differ between the two groups. These results suggest that there is no significant relationship between the ACE inhibitor-induced cough and ACE gene polymorphism, plasma BK, SP and ACE inhibitor concentrations in patients with hypertension or chronic nephritis.

Aged↗

Effects of eppikahangeto, a Kampo formula, and Ephedrae herba against citric acid-induced laryngeal cough in guinea pigs.

To evaluate the efficacy of three common antitussive Kampo formulas, eppikahangeto (EPP), bakumondoto (BAK), and shoseiryutogomakyokansekito (SGM), a new cough model of guinea pig was used, which could specifically induce a laryngeal cough by microinjection of citric acid solution into the larynx. Kampo extract was dissolved in water and the animals were given access ad libitum for 3 days, and then the number of coughs during 10 min was counted. EPP extract decreased the number of coughs dose-dependently (0.3% extract, -22.9 +/- 6.6%, P<0.01; 1.0% extract, -32.4 +/- 5.5%, P<0.01). BAK extract and SGM extract had no significant effect. Intraperitoneal injection of codeine (60 mg/kg) also decreased the number of coughs (-36.1 +/- 9.1%, P<0.05). Furthermore, Ephedrae herba (EH) extract reduced the number of coughs (-18.3 +/- 6.0%, P<0.05), but the extract of EPP without EH did not. These results suggest that EPP has an antitussive effect against laryngeally-induced cough in guinea pigs, and the crucial herbal medicine is EH.

Animals↗

Measurement of gastric emptying in gastroesophageal reflux-related chronic cough.

STUDY OBJECTIVES: Gastroesophageal reflux (GER) is one of the most common causes of chronic cough, but the mechanisms of GER-related cough are not well-understood. We tested the hypothesis that gastric emptying is delayed in patients with GER-related chronic cough. DESIGN: We studied 12 patients (7 women; mean age, 53 years; age range, 37 to 68 years) with GER-related chronic cough and a control group of 27 asymptomatic healthy volunteers (16 women; mean age, 37 years; age range, 18 to 62 years). Gastric emptying scintigraphy was performed, and the time at which 50% of the radiolabeled material had left the stomach (T(1/2)) was calculated. RESULTS: There was no statistically significant difference in T(1/2) values between healthy volunteers and subjects with GER-related cough (99 +/- 26 min vs 86 +/- 20 min, respectively; difference between the means, 13 min [95% confidence interval, -4 to 30 min]; p = 0.13). CONCLUSIONS: Gastric emptying was not delayed in patients with GER-related chronic cough. The measurement of gastric emptying did not therefore provide further insights into the mechanisms of GER-related cough or clinically relevant information that would assist in patient management.

Adolescent↗

The clinical utility of flexible bronchoscopy in the evaluation of chronic cough.

STUDY OBJECTIVES: To assess the clinical utility of flexible bronchoscopy (FB) in the evaluation of patients with chronic cough and normal or nonlocalizing chest radiographic findings. DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: Forty-eight patients with chronic cough and no other clinical or radiographic indications for FB who underwent the procedure from 1996 to 2001. RESULTS: Before FB, 45 patients had a chest radiograph and 21 patients had a chest CT performed. On visual inspection, 37 of 48 of the FB findings (82%) were normal, 9 were consistent with "bronchitis," one patient had a "small tracheal plaque," and one patient had "minimal arytentoid redundancy." Three of the 27 patients who had a microbiologic assessment performed during their FB demonstrated potentially pathogenic organisms. Antibiotic treatment based on culture data did not result in improvement in cough. Cytologic examination was performed in specimens from 33 patients; 1 patient was noted to have reactive squamous atypia, and the remainder were normal. The patient noted to have minimal arytenoid redundancy and the patient with a tracheal plaque each had another etiology for their cough identified, the treatment of which resulted in cough improvement. CONCLUSIONS: FB adds little to the diagnosis of chronic cough in the context of normal or nonlocalizing chest radiographic or CT findings. FB did not result in successful treatment alteration, nor did it contribute to the identification of the cough etiology.

Adult↗

Cough: occupational and environmental considerations: ACCP evidence-based clinical practice guidelines.

OBJECTIVES: This section of the guideline aims to review the role of occupational and environmental factors in causing and contributing to cough. It also aims to indicate when such causes should be considered in a clinical setting, and a general approach to assessment and management. METHODS: A review was performed of published data between 1985 and 2004 using PubMed. The search terms used included "air pollution," "sick building syndrome," "occupational asthma," "occupational lung disease," "hypersensitivity pneumonitis" (HP), "cigarette smoke," and "asthma." Selected articles were chosen when meeting the objectives, but the extent of articles available and the limited space for this section does not permit a fully comprehensive review of all of these areas, for which the reader is referred to other sections of this clinical practice guideline, the published literature, textbooks of occupational lung disease, or more specific review articles. RESULTS/CONCLUSIONS: Almost any patient presenting with cough may have an occupational or environmental cause of or contribution to their cough. The importance of this is that recognition and intervention may result in full or partial improvement of the cough, may limit the need for medication/symptomatic treatment, and may improve the long-term prognosis. Nonoccupational environmental contributing factors for upper and lower airway causes of cough include indoor irritant and allergenic agents such as cigarette smoke, cooking fumes, animals, dust mites, fungi, and cockroaches. Causes of HP indoors include birds and fungal antigens. Outdoor pollutants and allergens also contribute to upper and lower airway causes of cough. Occupational exposures can cause hypersensitivity responses leading to rhinitis and upper airway cough syndrome, previously referred to as postnasal drip syndrome, as well as asthma, HP, chronic beryllium disease, and hard metal disease, as well as irritant or toxic responses. The diagnosis is only reached by initially considering possible occupational and environmental factors, and by obtaining an appropriate medical history to determine relevant exposures, followed by objective investigations. This may require referral to a center of expertise.

Air Pollutants↗

Overview of common causes of chronic cough: ACCP evidence-based clinical practice guidelines.

OBJECTIVE: To review the literature on the most common causes of chronic cough. METHODS: MEDLINE was searched (through May 2004) for studies published in the English language since 1980 on human subjects using the medical subject heading terms "cough," "causes of cough," and "etiology of cough." Case series and prospective descriptive clinical trials were selected for review. Also obtained were any references from these studies that were pertinent to the topic RESULTS: Upper airway cough syndrome (UACS) due to a variety of rhinosinus conditions, previously referred to as postnasal drip syndrome, asthma, nonasthmatic eosinophilic bronchitis (NAEB), and gastroesophageal reflux disease (GERD) are the most common causes of chronic cough. Each of these diagnoses may be present alone or in combination and may be clinically silent apart from the cough itself. CONCLUSION: In the absence of evidence for the presence of another disorder, an approach focused on detecting the presence of UACS, asthma, NAEB, or GERD, alone or in combination, is likely to have a far higher yield than routinely searching for relatively uncommon or obscure diagnoses.

Asthma↗

Parents on the web: risks for quality management of cough in children.

BACKGROUND: Health information on the Internet, with respect to common, self-limited childhood illnesses, has been found to be unreliable. Therefore, parents navigating on the Internet risk finding advice that is incomplete or, more importantly, not evidence-based. The importance that a resource such as the Internet as a source of quality health information for consumers should, however, be taken into consideration. For this reason, studies need to be performed regarding the quality of material provided. Various strategies have been proposed that would allow parents to distinguish trustworthy web documents from unreliable ones. One of these strategies is the use of a checklist for the appraisal of web pages based on their technical aspects. OBJECTIVE: The purpose of this study was to assess the quality of information present on the Internet regarding the home management of cough in children and to examine the applicability of a checklist strategy that would allow consumers to select more trustworthy web pages. METHODS: The Internet was searched for web pages regarding the home treatment of cough in children with the use of different search engines. Medline and the Cochrane database were searched for available evidence concerning the management of cough in children. Three checklists were created to assess different aspects of the web documents. The first checklist was designed to allow for a technical appraisal of the web pages and was based on components such as the name of the author and references used. The second was constructed to examine the completeness of the health information contained in the documents, such as causes and mechanism of cough, and pharmacological and nonpharmacological treatment. The third checklist assessed the quality of the information by measuring it against a gold standard document. This document was created by combining the policy statement issued by the American Academy of Pediatrics regarding the pharmacological treatment of cough in children with the guide of the World Health Organization on drugs for children. For each checklist, the web page contents were analyzed and quantitative measurements were assigned. RESULTS: Of the 19 web pages identified, 9 explained the purpose and/or mechanism of cough and 14 the causes. The most frequently mentioned pharmacological treatments were single-ingredient suppressant preparations, followed by single-ingredient expectorants. Dextromethorphan was the most commonly referred to suppressant and guaifenesin the most common expectorant. No documents discouraged the use of suppressants, although 4 of the 10 web documents that addressed expectorants discouraged their use. Sixteen web pages addressed nonpharmacological treatment, 14 of which suggested exposure to a humid environment and/or extra fluid. In most cases, the criteria in the technical appraisal checklist were not present in the web documents; moreover, 2 web pages did not provide any of the items. Regarding content completeness, 3 web pages satisfied all the requirements considered in the checklist and 2 documents did not meet any of the criteria. Of the 3 web pages that scored highest in technical aspect, 2 also supplied complete information. No relationship was found, however, between the technical aspect and the content completeness. Concerning the quality of the health information supplied, 10 pages received a negative score because they contained more incorrect than correct information, and 1 web page received a high score. This document was 1 of the 2 that also scored high in technical aspect and content completeness. No relationship was found, however, among quality of information, technical aspect, and content completeness. CONCLUSIONS: As the results of this study show, a parent navigating the Internet for information on the home management of cough in children will no doubt find incorrect advice among the search results. (ABSTRACT TRUNCATED)

Antitussive Agents↗

Inhibitory actions of procaterol, a beta-2 stimulant, on substance P-induced cough in normal subjects during upper respiratory tract infection.

We studied substance P (SP)-induced cough in normal subjects without and with colds, and the effects of orally administered procaterol on SP-induced cough in normal subjects with colds. SP aerosols caused cough at a concentration of approximately 10(-15) M in subjects with colds whereas it did not cause cough at a concentration of up to 10(-5) M in subjects without colds. Procaterol (50 micrograms) completely inhibited SP-induced cough in normal subjects with colds. These results suggest that cough response to SP remarkably increases during colds and that beta-2 stimulant may be a useful tool for treatment of cough during colds in normal subjects.

Adrenergic beta-Agonists↗

Cough variant asthma: a review of the clinical literature.

Cough variant asthma is an occult form of asthma of which the only sign or symptom is chronic cough. This review examines 15 clinically oriented research articles on cough variant asthma and summarizes what is known about its frequency of occurrence, clinical presentation, diagnosis, treatment, and natural history. Cough variant asthma is a common problem among all ages that frequently goes unrecognized. Pulmonary function, as measured by spirometry, is often within normal limits. Any patient with a nonproductive, nocturnal cough lasting more than two weeks, should receive an empiric trial of bronchodilators. The natural history of cough variant asthma is variable. A significant proportion of patients followed over time develop the classic signs and symptoms of asthma, whereas for many patients, cough resolves without need for further treatment.

Adrenergic beta-Agonists↗

Cough-induced rib fractures.

OBJECTIVES: To define the demographic, clinical, and radiological features of patients with cough-induced rib fractures and to assess potential risk factors. PATIENTS AND METHODS: For this retrospective, single-center study, we identified all cases of cough-induced rib fractures diagnosed at the Mayo Clinic in Rochester, Minn, over a 9-year period between January 1, 1996, and January 31, 2005. Bone densitometry data from patients' medical records were analyzed, and T scores were used to classify patients into bone density categories. RESULTS: The mean +/- SD age of the 54 study patients at presentation was 55+/-17 years, and 42 patients (78%) were female. Patients presented with chest wall pain after onset of cough. Rib fracture was associated with chronic cough (> or =3 weeks' duration) in 85% of patients. Rib fractures were documented by chest radiography, rib radiography, computed tomography, or bone scan. Chest radiography had been performed in 52 patients and revealed rib fracture in 30 (58%). There were 112 fractured ribs in 54 patients. One half of patients had more than one fractured rib. Right-sided rib fractures alone were present in 17 patients (26 fractured ribs), left-sided in 23 patients (35 fractured ribs), and bilateral in 14 patients (51 fractured ribs). The most commonly fractured rib on both sides was rib 6. The fractures were most common at the lateral aspect of the rib cage. Bone densitometry was done in 26 patients and revealed osteopenia or osteoporosis in 17 (65%). CONCLUSIONS: Cough-induced rib fractures occur primarily in women with chronic cough. Middle ribs along the lateral aspect of the rib cage are affected most commonly. Although reduced bone density is likely a risk factor, cough-induced rib fractures can occur in the presence of normal bone density.

Adult↗

Cough in tetraplegic subjects: an active process.

STUDY OBJECTIVE: To determine the role of the clavicular portion of the pectoralis major during cough in tetraplegic subjects. PATIENTS: Eight patients with longstanding traumatic transection of the lower cervical cord. METHODS: The electromyographic activity of the pectoralis major and abdominal external oblique muscles and the changes in the anteroposterior diameter of the lower rib cage, the upper rib cage, and the abdomen were measured during voluntary coughing efforts in the seated posture. RESULTS: When coughing, all subjects showed a large amount of electrical activity in the pectoralis major with no activity in the external oblique. Simultaneously, they had a clear-cut decrease in the anteroposterior diameter of the upper rib cage together with an increase in the anteroposterior diameter of the abdomen. In five subjects, the anteroposterior diameter of the lower rib cage also showed an initial increase. These changes were seen when cough was initiated at functional residual capacity or at a higher lung volume; they were also seen during a fit of coughing. CONCLUSIONS: In tetraplegic subjects the clavicular portion of the pectoralis major plays a major role during coughing. Its contraction causes a reduction in the size of the upper part of the rib cage and a rise in intrathoracic pressure; this pressure rise results secondarily in an outward (paradoxical) motion of the abdomen and the lower rib cage. Cough in tetraplegic subjects is thus an active, rather than a passive, process, and its effectiveness might be improved by a combination of specific muscle training and abdominal binding.

Abdomen↗

Advances in understanding and treatment of cough.

Many different conditions and diseases cause cough. The commonest acute causes are pollution, including cigarette smoke, and upper respiratory tract infection. The commonest chronic causes are postnasal drip, asthma, chronic bronchitis and gastro-oesophageal reflux. Epidemiological studies give widely different patterns of incidence. The different conditions that cause cough have in common the fact that the cough is mediated via the vagus nerves, with sensory receptors in and under the epithelium from the larynx down to the smaller bronchi. These receptors are polymodal, responding to a large variety of stimuli, including mechanical and chemical irritants, inflammatory mediators, intraluminal material and large volume changes of the lungs. With irritation and inflammation, C fibre receptors release neurokinins such as substance P, which in turn stimulate cough receptors. The central nervous pathways for the cough reflex are poorly understood. They can be activated or inhibited voluntarily. Studies on the pharmacology of the central nervous pathways of coughing are opening up new therapeutic possibilities. Other new therapies include drugs acting on the sensory receptors for cough, thereby avoiding adverse central nervous effects.

Animals↗

[Chronic cough caused by gastroesophageal reflux].

We reported a case of chronic cough due to gastroesophageal reflux (GER). The patient was a 29-year-old woman who had suffered from persistent chronic cough for more than 3 years. She had been treated with high doses of inhaled steroids, oral bronchodilators, and oral corticosteroids on a presumed diagnosis of asthma. However, her cough was not alleviated by these treatments, and the patient was referred to our hospital. She did not exhibit typical GER symptoms except for belch. Although esophagoscopy did not disclose reflux esophagitis, esophageal pH monitoring revealed acid reflux 7 to 8 times higher than the reference value. The patient was treated with a proton-pump inhibitor, which markedly alleviated her cough. Chronic cough due to GER was diagnosed. Although the incidence of chronic cough due to GER was thought to be rare in Japan, the findings in our case report underscored the importance of this association to the differential diagnosis of chronic cough.

Adult↗

Comparison between tidal breathing and dosimeter methods in assessing cough receptor sensitivity to capsaicin.

OBJECTIVE: Dosimeter method and tidal breathing method have been used to assess cough sensitivity to inhaled capsaicin, a C-fibre ending stimulator. The aim of the present study was to evaluate the repeatability of and the agreement between the two methods. METHODOLOGY: Cough threshold, the lowest concentration of capsaicin causing five or more coughs, was measured twice 1-3 weeks apart by each method in 26 normal subjects. Increasing concentrations of capsaicin were inhaled by a single breath in the dosimeter method or by 15 s tidal breathing in the tidal breathing method in 1 min intervals. RESULTS: Coefficients of repeatability of the cough threshold measurement were 1.89 and 2.71 doubling concentration in the tidal breathing method and the dosimeter method, respectively, suggesting good repeatability in the cough threshold measurement by both methods. The cough threshold was significantly (P < 0.0001) greater by 1.75 doubling concentration on the dosimeter method than the tidal breathing method. The coefficient of agreement between the two methods was 2.53 doubling concentration. Five subjects complained of burning sensation in the throat in the dosimeter method but no patient complained about the tidal breathing method (P < 0.05). CONCLUSIONS: Although the agreement between the two methods was considered to be good, higher concentrations of capsaicin solution were required to determine the cough threshold in the dosimeter method, resulting in an unpleasant sensation in the throat.

Administration, Inhalation↗