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The acoustic properties of capsaicin-induced cough in healthy subjects.

Acoustic analysis of cough both in the time and frequency domain has been reported using voluntary and spontaneous cough. The main aim of this study was to discover whether such analysis of capsaicin-induced cough enables differences between normal subjects to be recognized. We present data from 13 healthy subjects (with normal lung function and no history of respiratory disease) using a new method of acoustic analysis, which presents the data in three graphical forms: 1) spectrogram; 2) overall spectral energy, 3) root mean square (RMS) pressure plots. Using the RMS sound pressure traces, different subjects had either two peaks, a single peak or multiple peaks. The occurrence of single and multiple peaks has previously been associated with disease states but we found them in normal subjects. The number of peaks and the visual pattern of the spectrogram was reproducible within and specific to each individual over time. During a peal of coughs in a single expiration, the peak amplitude of successive coughs decreased as lung volume reduced. Despite similarities in the overall spectral energy between individuals, there were marked differences in the small visual details of the spectrograms. However, in an individual, these small details were remarkably constant both within and between days, and can be regarded as a "cough signature". This type of spectrographic analysis provides a new approach to the analysis both of normal and abnormal cough sounds, and has identified similarities and differences in capsaicin-induced cough in normal individuals. It has potential as a tool with which to study the pathophysiology of cough.

Acoustics↗

Effect of environmental tobacco smoke on cough in children with a history of tonsillectomy or adenoidectomy.

We examined the possible impact of tonsillectomy or adenoidectomy (T/A) on the relationship between environmental tobacco smoke (ETS) exposure and respiratory outcomes. This study was conducted in Humboldt, Saskatchewan, in 1993. The target population included all residents aged 6-17 yrs. Of the 1,019 eligible subjects, 892 participated (88%). Estimates of ETS exposure were based on the reported smoking habits of the children's household members. We defined current cough as a positive response to the question: "Does this child usually have a cough?". Information also included morning cough, night cough and a history of T/A. For children with no history of T/A, the prevalence of current cough was 8.9%, 12.2% and 14.5% for those living in families with 0, 1, and 2+ smokers respectively. The corresponding prevalence was 7.0%, 30.2% and 36.8% for children with history of T/A. Similar effects of ETS exposure were observed on morning cough and night cough. The results did not change significantly when we used various ETS measures and controlled for confounding factors. Compared to children living in nonsmoking families and without history of T/A, the adjusted odds ratio for children with a history of T/A was 7.19 (p<0.001) if they were living in families smoking >20 cigarettes x day(-1) at home. The corresponding odds ratio was only 1.64 (p=0.11) for children without a history of T/A. We concluded that children living in smoking family were more likely to cough than those living in nonsmoking families and tonsillectomy or adenoidectomy increased the apparent influence of environmental tobacco exposure on cough.

Adenoidectomy↗

Involvement of central serotonergic mechanisms in the cough reflex.

To determine the role of central serotonergic systems in modulating the cough reflex, the effects of serotonergic agonists on the respiration and the cough reflex were comparatively studied. Male and female cats were anesthetized with sodium pentobarbital. Respiration and cough reflex were measured using a pneumotachograph via a cannula inserted into the trachea. The cough reflex was elicited by electrical stimuli to the superior laryngeal nerve. Tranylcypromine, a MAO inhibitor, in a dose of 5 mg/kg, i.v., increased the respiration, but depressed the cough reflex. The serotonin precursor 5-hydroxytryptophan (5 mg/kg, i.v.) depressed the respiration and the cough reflex. Haloperidol (2 mg/kg, i.v.) abolished the tranylcypromine-stimulated respiratory responses, and it intensified the tranylcypromine induced cough depression. It is concluded that the increase in serotonin levels in the brain has a depressant influence on the central generating mechanisms of the cough reflex. Furthermore, central dopaminergic mechanisms seem to play a modulating role on the cough reflex.

5-Hydroxytryptophan↗

Regional mucus transport following unproductive cough and forced expiration technique in patients with airways obstruction.

It has previously been shown that unproductive coughing in both healthy subjects and patients with airways obstruction is not effective in clearing lung secretions. This study investigates the regional mucus transport in a group of subjects with airways obstruction who failed to expectorate following instructed cough and forced expiration technique. Fourteen patients (mean +/- SEM age: 68 +/- 2 years) with airways obstruction (mean +/- SEM percent predicted. FEV1: 54 +/- 5; daily wet weight sputum: 9.1 +/- 2.0 g) took part in the study which was a randomized, three-way crossover within-patient design. Each patient underwent three treatment maneuvers: control, cough (30 coughs over a 10-min period), and forced expiration (30 forced expirations over a 10-min period). An objective radioaerosol technique was used to monitor regional mucus movement within the lungs of the patients. The lungs were divided arbitrarily into four regions of interest: tracheal, inner, intermediate, and outer. Peak expiratory flow rate during cough and forced expiration was measured at the mouth. There was no correlation between the radioaerosol clearance from all regions and (1) mean peak flow during cough and forced expiration, and (2) mean 24-h sputum production prior to the study day. There were no differences in regional radioaerosol clearance between cough and forced expiration. However, both cough and forced expiration resulted in significant clearance compared with control for all regions with the exception of the forced expiration in the outer region. To our knowledge, this study is the first to demonstrate that unproductive cough and forced expiration result in movement of secretions proximally from all regions of the lung in patients with airways obstruction.

Cough↗

Diagnostics of spontaneous cough in childhood asthma: results of continuous tracheal sound recording in the homes of children.

Spontaneous cough is a symptom with diffuse diagnostic significance for childhood asthma. Information on the interrelations between presence/frequency of cough and other symptoms of asthma are not available to the physician. Tracheal sounds were continuously recorded in the homes of 60 children with and 30 without asthma, at 72 and 24 h, respectively. Presence and frequency of cough and presence of wheeze were scored by trained examiners. Wheeze was used to indicate airway obstruction during hours when peak expiratory flow (PEF) values were not available. PEF and self-reported dyspnea were assessed every 4 h. Results showed that asthmatics coughed significantly more often than control subjects during exacerbations, but not during remission. The highest diagnostic sensitivity percentages of cough were 72% for wheeze and 69% for a reduction in PEF > 20%. However, the diagnostic specificity was poor, 41% for wheeze and 34% for a reduction in PEF > 20%. Cough and dyspnea were independent. Three children did not cough during exacerbations. Persistent, isolated cough was observed in two children. It was concluded that spontaneous cough is modestly predictive of asthmatic exacerbations, but not of a diagnosis of asthma or severity of asthma.

Adolescent↗

Measuring persistent cough in children in epidemiological studies: development of a questionnaire and assessment of prevalence in two countries.

STUDY OBJECTIVE: Cough is a common symptom in children that is frequently encountered in general practice. However, most of the information on the prevalence of persistent cough has come from studies that use different, often ambiguous, definitions for persistent cough. It is therefore important that a validated questionnaire to accurately measure persistent cough is developed and is appropriate for use in different age groups of children and in different cultures. Such a questionnaire is essential for accurately measuring the prevalence of persistent cough and the factors associated with its occurrence. DESIGN: A parent-administered respiratory questionnaire was developed and administered twice during a 3-week interval pilot study to test repeatability. The questionnaire was then administered to a randomly selected cross-section of Australian children aged 5 to 7 years old and 8 to 11 years old (N = 511 and N = 654, respectively), and to 566 Nigerian children aged 8 to 11 years old. RESULTS: The new questionnaire was reliable, with most of the questions having a kappa value of above 0.6. The prevalence of persistent cough was similar in younger and older Australian children, but significantly less in Nigerian children (p < 0.001). Also, persistent cough was more prevalent in children of high rather than low socioeconomic status among older Australian children (p = 0.04). CONCLUSIONS: The newly developed questionnaire will be an important tool in epidemiological studies for measuring the prevalence, morbidity, and risk factors of persistent cough in childhood. Although our findings showed that persistent cough does not occur more frequently in younger than in older Australian children, it is more frequent in Australian than in Nigerian children.

Australia↗

The role of sinus imaging in the treatment of chronic cough in adults.

PRIMARY STUDY OBJECTIVE: To determine the appropriate role and timing of sinus imaging studies in the evaluation and treatment of chronic cough. DESIGN: Prospective study of chronic cough. All patients underwent sinus imaging, the results of which identified prospectively the following: (1) fluid in sinuses, with or without opacification, and (2) mucosal thickening. Patients then were treated using an algorithm that sequentially addresses the etiologies of chronic cough. Patients whose sinus imaging studies had demonstrated fluid were treated initially for sinusitis, but mucosal abnormalities alone were not considered an indication to change the algorithm. After workup, relationships between abnormalities on sinus imaging studies and diagnoses were determined. SETTING: University hospital pulmonary outpatient clinic. PATIENTS: Thirty-six patients (31 women, 5 men; mean age, 58.4 years). Cough duration averaged 5.2 years (range, 4 weeks to 30 years). RESULTS: Diagnoses were made in 100% of patients, and cough resolved in 86%. Mucosal thickening correlated with sinusitis as a cause of cough in only 29% of cases. CONCLUSIONS: Mucosal thickening is not diagnostic of sinusitis as a cause of chronic cough; in most patients, cough will resolve without treatment for sinusitis. Given this lack of specificity, it is reasonable to delay sinus imaging until after efforts at treating rhinitis have failed and, in the absence of complaint or findings of postnasal drip, until after completion of evaluation for asthma. The principles of diagnosis and treatment of chronic cough remain simple: go sequentially from the most common to the least common cause; use tools that begin with the most available and least expensive and invasive modality; then move as needed to tools that are more expensive and invasive.

Adult↗

Airway inflammation as an assessment of chronic nonproductive cough.

OBJECTIVES: The possibility that a bronchial inflammatory process could be involved with a chronic nonproductive cough without other potential causes such as postnasal drip syndrome, bronchial asthma, gastroesophageal reflux, chronic bronchitis, bronchiectasis, or the use of angiotensin-converting enzyme inhibitors has not been clearly described. We investigated the possibility that a chronic nonproductive cough without other potential causes is associated with airway inflammation, and if this is so, what the relationship might be between this inflammation and the possible etiology of the cough. SUBJECTS: Twenty-five adults with chronic nonproductive cough as an isolated symptom over a 3-week period, and 5 healthy control subjects were studied. MEASUREMENTS AND RESULTS: Clinical assessments, cough scores, methacholine challenges, allergy skin prick tests, and bronchoscopies for bronchial biopsies were performed. In the bronchial biopsies, the patients were divided into the following two subgroups: 21 patients who were infiltrated with eosinophils vs the healthy control group (median, 12.0 vs. 0.0 cells/mm(2), respectively; p < 0.01); and 4 patients who were infiltrated with lymphocytes vs the healthy control group (median, 84.5 vs. 22.0 cells/mm(2), respectively; p < 0.01). With the methacholine challenge test, 5 of the 21 eosinophil-infiltrated patients received diagnoses of cough-variant asthma, and the other 16 patients received diagnoses of eosinophilic bronchitis. In the lymphocyte-infiltrated group, all four patients received diagnoses of lymphocytic bronchitis. CONCLUSIONS: These results suggest that a chronic nonproductive cough as an isolated symptom is associated with airway inflammation due to eosinophil and lymphocyte infiltration. The causes of the chronic nonproductive cough were eosinophilic bronchitis, cough-variant asthma, and lymphocytic bronchitis.

Adult↗

Workplace-related chronic cough on a mushroom farm.

BACKGROUND: Mushroom spores have frequently been associated with respiratory allergy. The aims of this study were to elucidate the incidence and causes of chronic cough in a mushroom farm. METHODS: Participants were 69 mushroom workers who produce Hypsizigus marmoreus (Bunashimeji) and 35 control subjects. We excluded six workers because they had had asthma or allergic rhinitis before working. Participants completed a cross-sectional health survey 2 years after starting work at the mushroom farm. RESULTS: The mean airborne endotoxin levels in the harvesting and packing rooms were approximately 60-fold higher than those in the offices. Of 63 workers, 42 workers (67%) reported chronic cough after working on this farm, 19 workers had no cough, while 2 workers had hypersensitivity pneumonitis develop to the spore, which has been previously reported by us. Of the 42 workers with cough, 6 workers had organic dust toxic syndrome (ODTS), 18 workers had postnasal drip syndrome, 15 workers had cough variant asthma, and 3 workers had eosinophilic bronchitis. Seventy-one percent of the workers noticed the cough in the first 3 months, and the mean latent period in ODTS workers was the shortest. The cough had a trend to improve or disappear after weekend holidays. Bronchial hyperresponsiveness but not FEV(1)/FVC% in the 42 workers with cough was significantly (p < 0.001) increased as compared with the control subjects. CONCLUSIONS: Working on a mushroom farm carries a significant risk for chronic cough from inhalation of mushroom spores, and we suggest that elevated airborne endotoxin on this farm is the cause.

Adult↗

Cough reflex sensitivity in cigarette smokers.

STUDY OBJECTIVES: To evaluate cough reflex sensitivity in a population of young, healthy, male cigarette smokers. DESIGN: Cross-sectional comparison. SETTING: Academic medical center. PARTICIPANTS: Twenty healthy, male current-smokers (mean [+/- SEM] age, 32.2 +/- 1.2 years). MEASUREMENTS: Subjects underwent baseline spirometry followed by capsaicin cough challenge testing, which involved the inhalation of capsaicin in ascending, doubling concentrations until the concentrations inducing two or more coughs (C(2)) and those inducing five or more coughs (C(5)) were reached. The data were compared to those from a group of 50 healthy, male nonsmokers who had undergone identical cough challenge testing. RESULTS: The two groups did not differ in terms of age or baseline pulmonary function. Cough sensitivity was significantly diminished in the current-smokers compared to control subjects. The mean (+/- SEM) log C(2) values in smokers and nonsmokers were 1.26 +/- 0.13 and 0.81 +/- 0.08, respectively (p = 0.004). The mean log C(5) values in smokers and nonsmokers were 2.03 +/- 0.10 and 1.20 +/- 0.08, respectively (p < 0.000001). CONCLUSIONS: Cough reflex sensitivity is significantly diminished in young, healthy, male current-smokers compared to a similar population of nonsmokers. The mechanism of cough suppression in smokers remains speculative but may involve long-term tobacco smoke-induced desensitization of the cough receptors within the airway epithelium.

Adult↗

Differences in acoustic and dynamic characteristics of spontaneous cough in pulmonary diseases.

The aim of this study was to determine whether the flow dynamics and sound spectra of spontaneous cough show characteristic differences in asthma, acute and chronic bronchitis, TBCS and FPD. During the cough, the air flow from the mouth and the sound from the sternal manubrium were simultaneously recorded. The cough sounds were analyzed spectrographically. Peak expiratory flow during cough was significantly lower in asthma than in TBCS, acute bronchitis or FPD. Duration of the first cough sound was longer in asthma than in FPD, TBCS or chronic bronchitis. The number of additional cough sounds was smaller in asthma than in the other conditions. The highest frequency components of cough sound were lower in asthma than in chronic bronchitis or TBCS. The results indicate that pulmonary diseases differ with respect to acoustic and dynamic characteristics of spontaneous cough. This finding may prove useful in the diagnosis of cough.

Acoustics↗

Cough: potential pharmacological developments.

Cough is an important defensive reflex of the upper airway and is also a very common symptom of respiratory disease. Cough following an upper respiratory viral infection is transient, and persistent cough is associated with a whole range of conditions, such as asthma, rhino-sinusitis and gastro-oesophageal reflux. Treatment directed at these conditions may improve the associated cough. There is often a need, however, to control cough itself whatever the cause. The most effective drugs in this class are the opioids, such as morphine, codeine or pholcodeine, but at effective doses they have side effects including drowsiness, nausea, constipation and physical dependence. Investigations into the cough reflex and into the potential mechanisms of sensitised cough reflex have uncovered several potential targets for novel drugs. New opioids apart from mu-agonists such as kappa- and delta -receptor agonists, have been developed, in addition to non-opioids such as nociceptin. Neurokinin receptor antagonists, bradykinin receptor antagonists, vanniloid receptor VR-1 antagonists may be beneficial by blocking effects of tachykinins and sensory nerve activation. Local anaesthetics, blockers of sodium-dependent channels and maxi-K Ca2+-dependent channel activators of afferent nerves are inhibitors of the cough reflex. Some of these novel agents may act centrally or peripherally or at both sites as antitussives. Large scale trials of these novel compounds have not been carried out in cough in man but there is a serious need for more effective antitussives devoid of side effects.

Animals↗

Effects of bronchial intermittent constrictions on explosive flow during coughing in the dogs.

This study tested the hypothesis that intrathoracic bronchi intermittently constrict during coughing and attempted to elucidate the effect on explosive flow. The subjects were 21 dogs having undergone tracheostomy. In the first group A (n = 7), the diameter of the fifth-generation bronchus was measured with a balloon-tipped catheter and the change during coughing was analyzed. In the other group (n = 14), the dogs were vagotomized and coughing was simulated by sequential application of positive and negative airway pressures (sham cough). The effects of the bronchial constriction, elicited by the stimulation of vagus efferent fibers, on explosive flow and airway pressure of sham cough were analyzed. The bronchus was constricted in explosive phase of spontaneous coughing in all the dogs of the first group. When cough bouts were repetitively developed, bronchial constriction and phrenic burst developed simultaneously. The intermittent bronchial constrictions fused and virtually acted as tonic constriction. In the second group of dogs the explosive flow of sham cough consisted of two phases; a short bout followed by a near-constant flow. When the bronchus was constricted, the explosive flow was still biphasic in 12 dogs and an exponential decay pattern formed in 2 of them. In these 12 dogs, the peak explosive flow slightly but significantly decreased (mean +/- SD, 1.39 +/- 0.23 vs. 1.34 +/- 0.23 l/s) and airway pressure in the segmental bronchus became smaller (-1.18 +/- 0.53 vs. -0.15 +/- 0.94 cmH(2)O). We concluded that intermittent bronchial constrictions act as tonic one during coughing. Bronchial constriction slightly decreased the peak explosive flow and moved the choke point to the proximal airway.

Animals↗

Cough as the ambiguous indicator of airway obstruction in asthma.

This study tested the hypothesis that cough frequency during induced airway obstruction in children and adolescents with asthma relates significantly to other symptoms. The second hypothesis was that cough during remission may often be a conditioned or voluntary response. In experiment 1, tracheal sounds were recorded from 30 participants with asthma during a histamine challenge test. In experiment 2, tracheal sounds were recorded from 30 participants with and 30 without asthma during a standardized physical exercise task. Cough and respiratory wheeze were assessed from the sound records by two examiners independently. The results showed that cough during airway obstruction did not relate to other variables. Only the second hypothesis was supported. In both experiments the frequency of cough was independent of lung function (forced expiratory volume in 1 sec [FEV1]), wheezing, dyspnea, and severity of asthma. The percentage of participants with asthma who coughed in experiment 1 increased from 21% (baseline) to 71% after histamine inhalation. During experiment 2, the cough percentage increased from 52% to 69% in asthmatics, and from zero to 57% in controls. It was concluded that cough in asthma is not diagnostically useful for assessment of airway obstruction. Excessive baseline cough among asthmatics could be the result of acquired responses to anticipated exercise-induced symptoms.

Adolescent↗

Assisted cough and pulmonary compliance in patients with Duchenne muscular dystrophy.

The aim of this study was to investigate the factors affecting cough ability, and to compare the assisted cough methods in patients with Duchenne muscular dystrophy (DMD). A total seventy-one male patients with DMD were included in the study. The vital capacity (VC) and maximum insufflation capacity (MIC) were measured. The unassisted peak cough flow (UPCF) and three different techniques of assisted peak cough flow were evaluated. UPCF measurements were possible for all 71 subjects. But when performing the three different assisted cough techniques, peak cough flows (PCFs) could be obtained from only 51 subjects. The mean value of MICs (1801 +/- 780 cc) was higher than that of VCs (1502 +/- 765 cc) (p< 0.01). All three assisted cough methods showed a significantly higher value than the unassisted method (F=80.92, p< 0.01). The manual assisted PCF under MIC (MPCFmic) significantly exceeded those produced by manual assisted PCF (MPCF) or PCF under MIC (PCFmic). The positive correlation between the MIC, VC difference (MIC-VC), and the difference between PCFmic and UPCF (PCFmic-UPCF) was seen (r=0.572, p< 0.01). The preservation of pulmonary compliance is important for the development of an effective cough as well as assisting the compression and expulsive phases. Thus, the clinical importance of the inspiratory phase and pulmonary compliance in assisting a cough should be emphasized.

Adolescent↗

Early and late allergic phase related cough response in sensitized guinea pigs with experimental allergic rhinitis.

Cough is a common and important symptom of asthma and allergic rhinitis. Previous experimental evidence has shown enhanced cough sensitivity during early phase of experimental allergic rhinitis in guinea pigs. We hypothesized that airway inflammation during the late phase response after repeated nasal antigen challenge may affect the afferent sensory nerve endings in the larynx and tracheobronchial tree and may also modulate cough response. In the present study we evaluated the cough sensitivity during a period of early and late allergic response in sensitized guinea pigs after repeated nasal antigen challenges. Forty-five guinea pigs were sensitized with ovalbumin (OVA). Four weeks later 0.015 ml of 0.5 % OVA was intranasally instilled to develop a model of allergic rhinitis that was evaluated from the occurrence of typical clinical symptoms. Animals were repeatedly intranasally challenged either by OVA (experimental group) or by saline (controls) in 7-day intervals for nine weeks. Cough was elicited by inhalation of citric acid aerosols. Cough was evaluated at 1 or 3 h after the 6th nasal challenge and 17 or 24 h after the 9th nasal challenge. The cough reflex was significantly increased at 1 and 3 h after repeated nasal challenge in contrast to cough responses evoked at 17 and 24 h after repeated nasal challenge. In conclusion, enhanced cough sensitivity only corresponds to an early allergic response after repeated nasal challenges.

Allergens↗

Symptom research on chronic cough: a historical perspective.

This review provides a perspective on how research on the management of cough has evolved, looks at key methodologic lessons that have been learned from this research and how they may relate to the management of other symptoms, identifies important methodologic challenges that remain to be solved, and lists important questions that still need to be answered. Three important methodologic lessons have been learned. First, cough must be evaluated systematically and according to a neuroanatomic framework. Second, the response to specific therapy must be noted to determine the cause or causes of cough and to characterize the strengths and limitations of diagnostic testing. Third, multiple conditions can simultaneously cause cough. Among the three methodologic challenges that still need to be solved are 1) definitively determining the diagnostic accuracy and reliability of 24-hour esophageal pH monitoring and how best to interpret pH test results, 2) definitively determining the role of nonacid reflux in cough due to gastroesophageal reflux disease, and 3) developing reliable and reproducible subjective and objective methods with which to assess the efficacy of cough therapy. Numerous important clinical questions are still unanswered: What role do empirical therapeutic trials play in diagnosing the cause of chronic cough? What is the most cost-effective approach to the diagnosis and treatment of chronic cough: empirical therapeutic trials or laboratory testing-directed therapeutic trials? How often is environmental air pollution, unrelated to allergies or smoking, responsible for chronic cough?

Clinical Protocols↗

Cough threshold in people with spinal cord injuries.

BACKGROUND AND PURPOSE: The purpose of this study was to compare the cough threshold between people with and without spinal cord injury (SCI). The effect of smoking on cough threshold was also investigated. SUBJECTS: The participants were 26 people with SCI (15 smokers, 11 nonsmokers) and 18 people without SCI (9 smokers, 9 nonsmokers). METHODS: Aerosols of citric acid were delivered with incremental doubling concentration from 62.5 mmol to 2 mol. Cough threshold was defined as the first concentration of citric acid that induced at least 2 coughs, which is associated with large chest excursion and concurrently acoustic response. RESULTS: The mean cough thresholds of smokers and nonsmokers with SCI (209 and 417 mmol, respectively) were lower than those of smokers and nonsmokers without SCI (467 and 1,072 mmol, respectively). The mean citric acid cough thresholds decreased in smokers with and without SCI when compared with nonsmokers with and without SCI. CONCLUSION AND DISCUSSION: The cough sensitivity increased in subjects with SCI, and smoking could also increase the cough sensitivity. Training about the frequency and technique of cough in patients with SCI should be carefully monitored.

Adult↗