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PubMed1998

From a prospective study of chronic cough: diagnostic and therapeutic aspects in older adults.

BACKGROUND: Cough is the most common complaint for which adults see a physician in the ambulatory setting in the United States. An anatomical diagnostic protocol has been used since 1981 to evaluate patients with chronic cough. It has been shown to be effective in diagnosing the cause of cough and leading to specific treatment in a variety of adult populations but has never been evaluated specifically in a population of older adults. OBJECTIVES: To question whether the spectrum and frequency of causes of chronic cough and the response to therapy would be different in older adults. METHODS: Thirty patients at least 64 years of age with a history of cough lasting at least 3 weeks were prospectively evaluated with a protocol designed to detect diseases that stimulate the afferent limb of the cough reflex. The final diagnosis of the cause of chronic cough required fulfillment of pretreatment criteria and having cough disappear with specific therapy. When more than one disease fulfilled pretreatment diagnostic criteria, therapy was instituted in the order that these were fulfilled. Probability statistics were used to describe the testing characteristics of individual components of the diagnostic protocol in terms of sensitivity, specificity, positive predictive value, and negative predictive value as they applied to chronic cough. RESULTS: Forty causes of chronic cough were identified in all 30 patients. Postnasal drip syndrome, gastroesophageal reflux disease, and asthma were the most common causes of chronic cough, accounting for 85% of all causes found. Among patients with normal chest radiograph findings who were not cigarette smokers and not taking an angiotensin-converting enzyme inhibitor, postnasal drip syndrome, gastroesophageal reflux disease, and asthma accounted for 100% of all causes found. Specific therapy was successful in eliminating chronic cough in 100% of the patients studied. Except for barium esophagography, all laboratory tests for which information was available had sensitivities and negative predictive values of 100%. CONCLUSIONS: Postnasal drip syndrome, gastroesophageal reflux disease, and asthma accounted for 85% of all causes of chronic cough in older adults. Chronic cough caused substantial physical and emotional morbidity among older patients. The major value of performing objective testing in evaluating chronic cough is its ability to rule out specific diseases as a diagnostic possibility. The following clinical profile consistently predicts patients with cough attributable to gastroesophageal reflux disease: the patient has cough that has been persistently troublesome for at least 3 weeks; does not smoke cigarettes; does not take an angiotensin-converting enzyme inhibitor; does not have or has not responded to therapy for postnasal drip syndrome and asthma; and has normal or nearly normal findings and stable chest radiograph. The differences between what we observed regarding chronic cough in older adults and observations by ourselves and others regarding chronic cough in general are minor.

Aged↗
PubMed2006

Effective antitussives for the cough patient: an unmet need.

Chronic cough is a prevalent symptom in the community but it is likely that only a small fraction of chronic coughers seek medical attention. Chronic cough can be controlled by addressing the 'cause' of the cough, but not all cough is controlled using this approach; an 'idiopathic' cough or cough of unknown aetiology is becoming more well-recognized. In these patients and in those whose cough has not responded to treatment of the cause(s), there is a lack of efficacious antitussive therapies ('non-specific' antitussives). Even in those whose cough is controlled by treatment of the cause, an efficacious antitussive for symptomatic relief would be useful for breakthrough symptoms. It is necessary to address the mechanisms underlying chronic cough, particularly the process of sensitization, both peripherally and centrally, that is the basis of chronic cough; such a process may persist even in the absence of the initiating event that first induced the cough. Currently-available antitussives in both acute and chronic cough are not very effective. Novel targets that may result in effective antitussives have been identified and with the development of clinical tools to measure cough accurately and reliably (e.g. cough counts and cough-specific quality-of-life questionnaires) and the evoked cough response (e.g. citric acid or capsaicin challenges), clinical trials should be performed. The chronic cough population is clinically heterogeneous but is characterized by an enhanced cough reflex; this should be the target population for study. Patients with chronic cough are in desperate need of effective antitussives that can be used either on demand or on a long-term basis.

Acute Disease↗
PubMed2001

Characterization of increased cough sensitivity after antigen challenge in guinea pigs.

Increased sensitivity of cough reflex is a fundamental feature of bronchodilator resistant non-productive cough associated with eosinophilic tracheobronchitis. Our hypothesis is that cough sensitivity is increased by airway allergic reaction characterized by airway eosinophilic inflammation. The aim of this study was to elucidate the hypothesis and clarify the characteristics of the increased cough sensitivity. Number of coughs elicited by inhalation of increasing concentrations of capsaicin (10-8, 10-6 and 10-4 M) was counted 24 h after an aerosolized antigen or saline in actively sensitized or non-sensitized (naive) conscious guinea pigs and then bronchoalveolar lavage was performed. The cough response was also measured 1 day before and 1, 2, 3, 5 and 7 days after an aerosolized antigen challenge in sensitized or naive animals. In addition, effect of procaterol (0.1 mg/kg), atropine (1 or 10 mg/kg), phosphoramidon (2.5 mg/kg) given intraperitoneally 30 min before the capsaicin challenge or capsaicin desensitization on the cough response was examined. Furthermore, the thromboxane A2 (TXA2) receptor antagonist S-1452 in a dose of 0.01 or 0.1 mg/kg or vehicle (saline) was given intraperitoneally at 24 and 1 h before the measurement of cough response. Number of coughs caused by capsaicin was extremely increased 24 h after an antigen challenge in sensitized guinea pigs compared with a saline or an antigen challenge in naive animals or a saline challenge in sensitized animals. The increased cough response disappeared at 3-7 days after the antigen challenge. Eosinophils in bronchoalveolar lavage fluid obtained after the measurement of capsaicin-induced coughs, which was performed 24 h after the antigen challenge, were significantly increased in sensitized guinea pigs. The eosinophil count was significantly correlated to the number of capsaicin-induced coughs. Procaterol or atropine did not alter the antigen-induced increase of cough sensitivity, whereas atropine did reduce the cough response in naive animals. Phosphoramidon increased the number of capsaicin-induced coughs in naive guinea pigs but not in sensitized and antigen-challenged animals. Capsaicin desensitization decreased the cough response in both antigen-challenged sensitized guinea pigs and naive animals. S-1452 reduced the antigen-induced increase of cough response in sensitized guinea pigs, but not in naive animals. Airway allergy accompanied with airway eosinophilia induces transient increase in cough sensitivity, which is not mediated by bronchoconstriction. The increased cough sensitivity may result in part from inactivation of neutral endopeptidase and TXA2, one of the inflammatory mediators.

Allergens↗
PubMed2005

Cough and glottic-stop reflex sensitivity in health and disease.

STUDY OBJECTIVES: Little is known about the normal ranges and repeatability of cough reflex sensitivity measurements, or the relationship of cough reflex sensitivity to other upper airway reflexes in subjects with chronic dry cough. We set out to define the normal range of cough reflex sensitivity and its repeatability in health and disease, and to assess its relationship to the glottic-stop reflex. DESIGN: Prospective, cross-sectional study. SUBJECTS AND METHODS: We measured capsaicin cough reflex sensitivity in 134 healthy subjects and 88 patients with respiratory disease, and assessed the repeatability over 2 weeks in a subgroup of individuals (healthy subjects, 15; chronic cough patients, 15). In another subgroup (healthy patients, 16; chronic cough patients, 14), we measured the sensitivity of the glottic-stop reflex (using inhaled ammonia). RESULTS: Capsaicin cough sensitivity varied widely in the population of healthy subjects, and there was considerable overlap of cough reflex sensitivity between healthy control subjects and patients with cough. The intraclass correlation coefficients for repeatability of cough sensitivity (concentration of capsaicin that causes two coughs, and concentration of capsaicin that causes five coughs) were 0.89 and 0.88, respectively. Patients with chronic cough had a significantly more sensitive glottic-stop reflex than healthy subjects (glottic-stop sensitivity threshold, 483 ppm vs 1,029 ppm, respectively; p = 0.01), and there was a significant positive correlation between glottic-stop and cough reflex sensitivity (r = 0.5; p < 0.01). CONCLUSIONS: We have shown a wide variation of cough reflex sensitivity in healthy subjects, although the measurement does have good 2-week repeatability. There was a reasonably close relationship between cough sensitivity and glottic-stop reflex sensitivity, indicating either that the cough reflex and the glottic-stop reflex share a common pathway or that subjects who have a chronic cough have a global abnormality of upper airway reflexes.

Ammonia↗
PubMed1996

Predictive values of the character, timing, and complications of chronic cough in diagnosing its cause.

BACKGROUND: It is not clear whether careful history taking with detailed questioning of the characteristics of cough is diagnostically useful. OBJECTIVE: To determine if the character, timing, or complications of chronic cough were helpful in determining its cause. METHODS: A prospective, descriptive study of consecutive, unselected, immunocompetent patients referred to our university outpatient clinic because of chronic cough. All patients were evaluated by a previously published and validated systematic diagnostic protocol, a self-administered questionnaire, and by observing the character of involuntary and voluntary coughs. The final diagnosis of the cause of cough required fulfillment of pretreatment criteria plus having cough disappear or substantially improve as a complaint with specific therapy. RESULTS: Eighty-eight patients met inclusion criteria and were fully evaluated. The mean +/- SD age was 53.1 +/- 16 years (range, 15-83 years) and 24 were males and 64 were females with a mean +/- SD history of cough for 6.6 +/- 9.8 years (range, 1 month-44 years). The cause of chronic cough was established in 86 (98%) of 88 patients. Eighty-one (92%) of 88 had cough disappear as a complaint. Cough was as a result of a single cause in 39% and multiple causes in 59%. Gastroesophageal reflux disease, postnasal drip syndrome, and asthma were the 3 most common causes of chronic cough and accounted for 90% of diagnoses. Gastroesophageal reflux disease, postnasal drip syndrome, and asthma were again found to be the 3 most common causes of chronic cough irrespective of patient estimated quantity of daily sputum production. These 3 conditions caused chronic cough in 99.4% of patients with the following characteristics: (1) nonsmoker; (2) not receiving an angiotensin-converting enzyme inhibitor drug; and (3) normal or nearly normal and stable chest radiograph. With respect to the spectrum and frequency of diagnoses and their interrelationships with the character, timing, and complications of cough, multiple stepwise linear regression analysis showed that none of the variability of the character, timing, or complications of cough could be explained by any specific diagnosis. CONCLUSIONS: A carefully taken history with detailed questioning of the character, timing, and complications of chronic cough is not likely to be useful in diagnosing the cause of cough. The cause can be determined and successfully treated with specific therapy in the greatest majority of cases. Chronic cough is often caused by multiple, simultaneously contributing causes. Postnasal drip syndrome, asthma, and gastroesophageal reflux disease remain the 3 most common causes of chronic cough and there is a clinical profile that nearly always predicts their presence in immunocompetent patients.

Adolescent↗
PubMed2004

Over-the-counter medications for acute cough in children and adults in ambulatory settings.

BACKGROUND: Acute cough due to upper respiratory tract infection (URTI) is a common symptom. Many health practitioners recommend non-prescription over-the-counter (OTC) medicines as a first-line treatment for cough, but there is little evidence as to whether these drugs are effective. OBJECTIVES: To assess the effects of oral over-the-counter cough preparations for acute cough. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2004); MEDLINE (January 1966 to June Week 3, 2004); EMBASE (January 1990 to March 2004); and the UK Department of Health National Research Register (December 2003, http://www.update-software.com/National/nrr-frame.html). We also searched personal collections of references and reference lists of articles. We wrote to study investigators and pharmaceutical companies for information on further published or unpublished studies. There were no constraints based on language or publication status. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing oral OTC cough preparations with placebo in children and adults suffering from acute cough in ambulatory settings. We considered all cough outcomes (such as frequency and severity, continuous and categorical data, using different ways of measurement). The second outcomes of interest were adverse effects. DATA COLLECTION AND ANALYSIS: Two investigators screened potentially relevant citations independently. Any differences at any stage of the review were resolved by discussion. We also extracted data and assessed the quality of studies independently. We contacted investigators for additional information and performed quantitative analysis when appropriate data were available. MAIN RESULTS: Twenty four trials (17 in adults, seven in children) involving 3,392 people (2,876 adults and 516 children) were included. RESULTS OF STUDIES IN ADULTS: 1. Antitussives: Six trials compared antitussives with placebo. Codeine was no more effective than placebo in reducing cough symptoms. Two studies favoured dextromethorphan over placebo, whereas a third did not show an effect. Moguisteine was no more effective than placebo apart from a reduction of cough in a subgroup of participants with more severe night cough. 2. Expectorants: Two trials compared guaifenesin with placebo. In the larger study, 75 per cent of participants taking guaifenesin stated that the medicine was helpful compared to 31 per cent in the control group. In the second study, both groups showed improvement with respect to cough frequency and severity, with no statistically significant differences between groups. 3. Mucolytics: One trial compared a mucolytic with placebo. Active treatment reduced cough frequency and symptom scores on day four and eight. 4. Antihistamine-decongestant combinations: Two studies compared antihistamine-decongestant combinations with placebo. Antihistamine-decongestants were significantly more effective than placebo in one of the studies, whereas the other did not show any difference between the study groups. 5. Other drug combinations: Three studies compared combinations of drugs other than antihistamine-decongestant with placebo. Two studies were effective in reducing cough symptoms, and one study showed relief at night but not during the day. 6. Antihistamines: Three trials compared antihistamines with placebo. Antihistamines were no more effective than placebo in relieving cough symptoms. RESULTS OF STUDIES IN CHILDREN: 1. Antitussives: Antitussives were no more effective than placebo (one study) 2. Expectorants: No studies using expectorants met our inclusion criteria. 3. Mucolytics: The results of one trial favoured active treatment over placebo from day four until day 10. 4. Antihistamine-decongestant combinations: Two studies showed no difference between antihistamine-decongestant combinations and placebo. 5. Other drug combinations: One trial tested two paediatric cough syrups. Compared to placebo, both preparations showed a 'satisfactory response' in 46 per cent and 56 per cent of children compared to 21 per cent of children in the placebo group. One study compared an antitussive/bronchodilator combination in children, which showed no difference between the treatment groups. 6. Antihistamines: In one trial that tested antihistamines active treatment was no more effective than placebo. REVIEWERS' CONCLUSIONS: There is no good evidence for or against the effectiveness of OTC medicines in acute cough. The results of this review have to be interpreted with caution due to differences in study designs, populations, interventions and outcomes between studies. The numbers of studies in each group were small, and studies often showed conflicting results. Effect sizes in many studies were unclear and it is questionable as to whether all of the positive results are clinically relevant. More evidence about the effectiveness of OTC cough preparations would be helpful, as identification of effective self-care treatments may help reduce the burden of days lost at work due to acute cough as well as the number of consultations in primary care. Identification of ineffective preparations could avoid costs for consumers and health care providers.

Acute Disease↗
PubMed2005

Nature of airway inflammation and remodeling in chronic cough.

BACKGROUND: Chronic cough may be a result of asthma and non-asthma causes, but it is unclear whether there are specific inflammatory or remodeling changes. OBJECTIVE: We determined airway mucosal changes in patients presenting with asthmatic cough and cough associated with non-asthmatic causes. METHODS: Patients with chronic cough of non-asthmatic (n=33; postnasal drip/rhinitis in 6, gastroesophageal reflux in 5, bronchiectasis in 3, and idiopathic in 19) and asthmatic (n=14) causes and 15 healthy controls underwent fiberoptic bronchoscopy. Morphometry of bronchial biopsies and capsaicin cough sensitivity were assessed. RESULTS: Compared with controls, submucosal eosinophils and neutrophils were increased in patients with asthmatic cough (P<.005) and submucosal mast cells in patients with non-asthmatic cough (P=.01). Sub-basement membrane thickness, goblet cell area, vascularity, and vessel size were also increased in both groups. Smooth muscle area was higher only in patients with non-asthmatic cough (P=.0007 vs control and P=.019 vs asthmatic cough). None of the pathologic changes were related to the duration of coughing. Cough sensitivity was heightened in patients with non-asthmatic cough compared with controls and patients with asthmatic cough. The degree of goblet cell hyperplasia and epithelial shedding positively correlated with cough sensitivity in patients with non-asthmatic cough (r=0.43; P=.01; and r=0.40; P=.02, respectively). CONCLUSION: Features of airway wall remodeling are prominent in the airways with non-asthmatic as well as asthmatic cough. These are linked to chronic cough rather than to asthma. Mast cell hyperplasia rather than eosinophilia is distinctive for non-asthmatic cough.

Adult↗
PubMed2006

Effect of codeine on objective measurement of cough in chronic obstructive pulmonary disease.

BACKGROUND: Codeine is the standard antitussive treatment to which novel agents are compared. Little is known about the objective effect of any treatments on cough in chronic obstructive pulmonary disease (COPD). OBJECTIVE: To quantify the effect of codeine on objective cough frequency (quantified as time spent coughing: cough seconds, cs/h), citric acid cough threshold, and subjective measures in a double-blind, placebo-controlled crossover study in COPD. METHODS: We studied 21 patients with physician-diagnosed, stable disease who complained of cough (76.9% male; mean age, 67.7 years; mean predicted FEV(1), 53.4%; median smoking history, 43.5 pack-years). Each subject performed a cough challenge (single breath, citric acid), 10-hour daytime ambulatory and overnight cough recordings, subjective cough scores, and visual analog scales at baseline and on 2 study days, 1 week apart. Codeine phosphate 60 mg or matched placebo were given, in random order, at the start of each cough recording (0 and 12 hours). RESULTS: Median time spent coughing at baseline was 8.27 cs/h (interquartile range [IQR], 5.94-11.67); after placebo treatment, 7.22 cs/h (IQR 4.42-10.40); and after codeine treatment, 6.41 cs/h (IQR 3.86-9.10). Codeine treatment had a significant effect on time spent coughing compared with baseline (P = .02) but not compared with placebo (P = .52). There were no significant differences in cough challenge thresholds (log concentration of tussive agent causing 2 coughs or log concentration of tussive agent causing 5 coughs) or subjective cough measures for codeine compared with placebo. CONCLUSION: In this study, codeine was no more effective than placebo in patients with COPD complaining of cough. CLINICAL IMPLICATIONS: Codeine is the antitussive agent to which we compare new treatments; however, in a group of stable patients with COPD, it had no effect on cough frequency over placebo.

Aged↗
PubMed1997

Assessment of the antitussive efficacy of codeine in cough associated with common cold.

Codeine is generally accepted as the standard antitussive against which new antitussive medications are compared. This presents a problem because the support for codeine's antitussive activity comes from studies on cough in animals, and chronic and induced cough models in man, whereas antitussives are almost exclusively used for the treatment of cough associated with acute upper respiratory tract infection (URTI). The aims of this study were twofold. Firstly, to study the antitussive efficacy of codeine in cough associated with URTI and, secondly, to validate a sound meter as tool for quantifying cough. The efficacy of codeine was assessed in a double-blind, stratified, placebo-controlled, parallel-group, clinical trial using three different measures of cough: cough sound-pressure levels (CSPLs) measured on a sound meter; subjective scores of cough severity; and cough frequency recorded by means of a microphone connected to an ink-pen recorder. A group of 82 subjects (51 females and 31 males; mean age 23.5 years, range 18-46 years) with cough owing to acute URTI were included in the study. The study took place on two separate study days. On study day 1 cough measurements were made before and 90 min after treatment with a single dose of either 50 mg codeine or matched placebo in capsule form. The same three measures of cough were repeated 2-5 days later (study day 2). On study day 1 a highly significant (P < 0.0001) decrease in all three measures of cough was found after treatment with both placebo and codeine yet there was no significant difference between the treatment groups. A highly significant (P < 0.0001) decrease in the three measures of cough was also found between days 1 and 2. The results demonstrate that codeine is no more effective than placebo in reducing cough associated with acute URTI, as measured by CSPLs, cough frequency or subjective symptom scores. This result might be explained on the basis of two central pathways for cough; a reflex pathway via the brain-stem which is sensitive to codeine and a voluntary pathway via the cortex which is unaffected by codeine. The results also demonstrate that the sound-level meter appears to be a potentially useful investigative tool for the assessment of cough and antitussive efficacy.

Adolescent↗
PubMed1997

[A new portable monitor for long-term cough recording].

Cough is a common symptom of pulmonary diseases. For a number of reasons it would be of interest to have information about the frequency of coughs over a given period of time. So far, the cough recorders which are available are either too expensive or unwieldy. Hence, we developed a cough recorder linked to a portable, commercially available actigraph (about the size of a pack of cigarettes) that records coughing as an acoustic signal and ventral thorax movement. The signals are filtered via a band pass and sampled by a peak detektor with different time constants to separate the impulse character of the cough signal from the background noise level. The cough recorder registers coughing cumulatively over a period of one minute and has a storage time of one week. Since the acoustic signals are essential for the interpretation of the recordings, the analogue circuit was subjected to a separate validation programme. For this purpose, the distinction between active coughs of 10 volunteers (total number of coughs 550) and background noises (male and female voices and other defined noises, total number of noises 336) was tested. The complete assembly was then tested over night on 7 hospitalised patients with chronic cough. An infrared video camera system was used to make a reference recording of the overnight coughing. The results show that nearly every cough of the 10 volunteers was recorded (r = 0.99). 97.1% of the background noise was correctly interpreted. The complete recorder assembly correctly recorded 98.9% of the coughs (total 870) in the 7 patients. 4.8% of the background noise was erroneously registered as coughing. Summing up, it can be said that the portable cough recorder affords accurate recording of coughing over a period of one week, correctly distinguishing coughing from background noise.

Adult↗
PubMed2004

Cough induced by mechanical stimulation of the upper airway in humans.

OBJECTIVES: Cough has previously been induced in animals by means of mechanical stimulation of the upper airway but this method has not previously been applied to humans. The aims of this study were to determine if cough could be induced in humans on mechanical stimulation of the upper airway and to see if this mechanically induced cough was reproducible. We also wished to investigate if there was any difference in cough sensitivity between healthy subjects and those with acute upper respiratory tract infection (URTI). MATERIAL AND METHODS: In the first investigation, 2 groups were studied: 15 healthy subjects and 30 subjects with URTI with a mean age of 20 years. Cough was induced by vibration of the airway at the level of the trachea using a modified men's shaver. In the second investigation to determine the reproducibility of this mechanically induced cough, two groups from a different population were studied: 15 healthy subjects and 29 subjects with URTI with a mean age of 20.3 years. Cough was induced by airway vibration before and after a 90-min rest period. RESULTS: In the first investigation it was demonstrated that cough can be induced within 2 s of vibration; subjects with URTI are more sensitive to cough induction and cough approximately five times more than healthy subjects; cough increases with repeated stimulation and reaches a maximum after three periods of vibration; the cough response may be mediated by rapidly adapting airway sensory receptors. In the second investigation there was no significant difference in mean cough counts before and after a 90-min rest period in both groups, which demonstrates that the mechanically induced cough is reproducible. CONCLUSION: This is the first study to elicit cough in humans by mechanical stimulation of the upper airway. This new method of inducing cough in subjects with URTI may be useful for studying both the mechanism of cough and the effects of antitussive medicines.

Adolescent↗
PubMed2006

Objective measurement of cough during pulmonary exacerbations in adults with cystic fibrosis.

BACKGROUND: Little is known about cough frequency in adults with cystic fibrosis (CF). This study aimed to determine (1) daytime and overnight cough rates in patients with CF at the beginning and end of a course of antibiotics for treatment of an exacerbation; (2) the relationship between cough frequencies and standard clinical measures of disease; and (3) the relationship between objective cough rates and the subjective assessment of cough. METHODS: Nineteen adult patients admitted with a pulmonary exacerbation performed daytime and overnight sound recordings on admission; 13 had repeat recordings prior to discharge. Coughs were manually quantified in cough seconds (time spent coughing). Patients subjectively scored their cough using a visual analogue scale (VAS) and numerical score. Lung function, C-reactive protein (CRP) levels, and sputum weights were recorded. RESULTS: Cough rates fell substantially with treatment; median fall in cough rate was 51.3% (IQR 32.3-77.5) (p<0.001) for daytime and 72.2% (28.6-90.1) (p = 0.049) for overnight. Multivariate regression analyses showed that forced expiratory volume in 1 second and CRP levels predicted overnight cough rates on admission. On discharge, sputum volume predicted daytime cough rates. Only the change in overnight VAS correlated with the change in objective cough rates. CONCLUSIONS: The cough rate significantly decreases with treatment of a pulmonary exacerbation in adults with CF. Lung function, sputum volume, and CRP influences the cough rate, with the effects differing from day to night and between admission and discharge. Subjective reporting of a nocturnal cough may indicate a pulmonary exacerbation of CF in adults.

Adult↗
PubMed1998

Subjective scoring of cough in children: parent-completed vs child-completed diary cards vs an objective method.

Cough is often used as an outcome measure, although the reporting of cough is unreliable. Using a 24 h ambulatory cough meter to measure cough frequency, the aim of this study was to compare: 1) the correlation of child-completed diary cards to the objective measurement, with that of parent-completed diary cards; and 2) the visual analogue scale (VAS) to the verbal category descriptive (VCD) score. The cough meter consisted of a previously validated Holter monitor and a cough processor. Eighty four children (39 with recurrent cough and 45 controls, aged 6-17 yrs) used a cough meter at least once. Thirty three subjects used the cough meter twice. Parents and children completed separate diary cards using the VAS and VCD scores. The strength of the relationship between the subjective scores and the objective recordings was analysed by spearman's rank correlation coefficient. For daytime cough, child-completed diary cards and the VCD correlated better to the objective measurement than parent-completed diary cards and the VAS, respectively. In subjects that used the cough meter twice, the difference between the cough frequency correlated to the difference in the subjective scores. The confidence intervals for the correlation coefficients were wide. The agreement between the objective and subjective presence of daytime cough was good but that for night-time cough was poor. We conclude that the severity of cough defined on diary cards may not represent cough frequency. Objective readings are first choice but currently not yet practical. The verbal category descriptive diary card completed by children and assisted by parents has the highest correlation to cough frequency measured objectively.

Adolescent↗
PubMed2006

Assessing cough severity and efficacy of therapy in clinical research: ACCP evidence-based clinical practice guidelines.

OBJECTIVES: To review the literature on identifying cough and to make evidence-based recommendations for assessing the efficacy of cough-modifying agents in clinical research. DESIGN/METHODOLOGY: Ovid MEDLINE literature review (through March 2004) for all studies published in the English language since 1953 using the medical subject heading terms "assessing the impact of cough," "assessing the efficacy of cough treatments," "tussigenic challenges," "cough counting," "character and timing of cough," "visual analog scales," "cough scoring systems," "health related quality of life instruments," "cough-specific health-related quality of life instruments," "citric acid challenge," "capsaicin challenge," "flow-volume loops," "assessing airway inflammation," "lipid laden macrophages in sputum," and "exhaled nitric oxide." RESULTS/CONCLUSIONS: To optimally evaluate the efficacy of cough-modifying agents, investigators should use both subjective and objective methods, because they have the potential to measure different things. A patient's subjective response is likely the only one that measures the impact of the intensity of cough. With respect to subjective methods, it is recommended that a cough-specific health-related quality-of-life instrument be utilized because valid and reliable instruments exist. Even though visual analog scales have not been psychometrically tested, they are recommended because they are commonly used and valid, and they are likely to yield different but complementary results. Because there are cough-specific health-related quality-of-life instruments that have been fully psychometrically tested, and the same cannot be said for visual analog scales, this is a reason to use cough-specific health-related quality-of-life instruments as the primary, subjective outcome measure of choice. With respect to objective methods, tussigenic challenges can be used before and after the intervention to assess the effect of therapy on cough sensitivity. They are most likely to be helpful in disease states in which cough reflex sensitivity is known to be heightened. Because the act of coughing has the potential to traumatize the upper airway (eg, vocal cords), assessing the presence of upper airway edema before and after therapy with flow-volume loops may be useful. Investigators must be cautious and not assume that observing changes suggestive of inflammation and edema of upper airway structures is specific for any particular disease. Cough counting is recommended with a computerized methodology that is reliable and accurate, noninvasive and portable, and easy to use in unattended, ambulatory real-life settings within a subject's home environment when it can be done over a 24-h period of time.

Clinical Trials as Topic↗
PubMed2006

Chronic upper airway cough syndrome secondary to rhinosinus diseases (previously referred to as postnasal drip syndrome): ACCP evidence-based clinical practice guidelines.

OBJECTIVE: To review the literature on postnasal drip syndrome (PNDS)-induced cough and the various causes of PNDS. Hereafter, PNDS will be referred to as upper airway cough syndrome (UACS). METHODS: MEDLINE search (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," "etiology of cough," "postnasal drip," "allergic rhinitis," "vasomotor rhinitis," and "chronic sinusitis." Case series and prospective descriptive clinical trials were selected for review. Also, any references from these studies that were pertinent to the topic were obtained. RESULTS: In multiple prospective, descriptive studies of adults, PNDS due to a variety of upper respiratory conditions has been shown either singly or in combination with other conditions, to be the most common cause of chronic cough. The symptoms and signs of PNDS are nonspecific, and a definitive diagnosis of PND-induced cough cannot be made from the medical history and physical examination findings alone. Furthermore, the absence of any of the usual clinical findings does not rule out a response to treatment that is usually effective for PND-induced cough. The differential diagnosis of PNDS-induced cough includes allergic rhinitis, perennial nonallergic rhinitis, postinfectious rhinitis, bacterial sinusitis, allergic fungal sinusitis, rhinitis due to anatomic abnormalities, rhinitis due to physical or chemical irritants, occupational rhinitis, rhinitis medicamentosa, and rhinitis of pregnancy. Because of a high prevalence of upper respiratory symptoms associated with gastroesophageal reflux disease (GERD), GERD may occasionally mimic PNDS. A crucial unanswered question is whether the conditions listed above actually produce cough through a final common pathway of PND or whether, in fact, in some circumstances they cause irritation or inflammation of upper airway structures that directly stimulate cough receptors and produce cough independently of or in addition to any associated PND. CONCLUSION: PNDS (ie, UACS) secondary to a variety of rhinosinus conditions is the most common cause of chronic cough. Because it is unclear whether the mechanisms of cough are the PND itself or the direct irritation or inflammation of the cough receptors located in the upper airway, the guideline committee has decided that, pending further data that address this difficult question, the committee unanimously recommends that the term upper airway cough syndrome be used in preference to postnasal drip syndrome when discussing cough associated with upper airway conditions.

Chronic Disease↗
PubMed2006

Interpreting the histopathology of chronic cough: a prospective, controlled, comparative study.

HYPOTHESIS: Trauma from chronic coughing produces airway inflammation similar to diseases causing cough. DESIGN: Prospective, cross-sectional, controlled, clinicopathologic correlation study in four groups: group 1, cough from intrapulmonary diseases; group 2, cough from extrapulmonary diseases; group 3, cough that was unexplained; and group 4, nonsmoking, asymptomatic control subjects. METHODS: Patients with chronic cough underwent a standardized workup including endobronchial biopsies before treatment. Causes were determined by a favorable response to therapy. Bronchial biopsy samples from control subjects were obtained from surgical specimens. RESULTS: There were 24 adult subjects (13 women and 11 men) with mean cough duration of 8.6 +/- 7.4 years (+/- SD). Thirteen patients had cough due to a specific disease: intrapulmonary diseases in 5 patients, and extrapulmonary diseases in 8 patients. Eleven patients had unexplained cough. Compared to control subjects, there was minimal-to-moderate chronic inflammation in all coughers (p < or = 0.0004), in group 1 (p < or = 0.039), group 2 (p = 0.061), and group 3 (p < or = 0.025) diseases that were not correlated with cough duration. There was no difference in type of inflammation, cough duration, or smoking history between groups, nor were there histologic differences between subjects with explained causes of cough compared with unexplained cough. CONCLUSIONS: Our findings suggest that airway inflammation associated with chronic cough, assessed on morphologic appearance and inflammatory cell counting in hematoxylin-eosin-prepared samples, may be due to the trauma of coughing, and the inflammation may be similar to that seen with diseases putatively thought to cause chronic cough. Investigators must be cautious when attributing pathogenic importance to observed inflammatory changes in airways of coughing subjects.

Asthma↗
PubMed1993

Voluntary cough suppression as an indication of symptom severity in upper respiratory tract infections.

The aim of the present study was to determine whether the ability to suppress cough voluntarily is an index of cough severity in upper respiratory tract infection. Cough was measured by means of a microphone linked to a pen recorder and subjects were instructed to voluntarily suppress cough in order to determine cough suppression time. Subjective scores of symptom severity, mood and psychological parameters were made prior to cough measurements. The baseline frequency of cough showed a distribution towards the higher frequencies, with a median of 2.1 (lower quartile 1.2, upper quartile 3.2) coughs.min-1. The results for cough suppression fell into two distinct groups, one group reaching a breaking point within 12.6 min; and another group which did not cough during the 20 min cough suppression period. In the group of subjects which broke from the cough suppression, there was an inverse relationship between the cough suppression time and the baseline frequency of cough. The median frequency of cough following cough suppression was significantly greater than the baseline median frequency of cough. The subjects who reached a breaking point had a greater baseline frequency of cough and a greater symptom severity score, and they also felt more feeble, clumsy, sad and antagonistic than the group which did not reach a breaking point. The subjects who reached a breaking point had significantly greater scores for the psychology parameter of obsessional symptoms than the group which did not reach a breaking point.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2001

Over-the-counter medications for acute cough in children and adults in ambulatory settings.

BACKGROUND: Acute cough due to upper respiratory tract infection (URTI) is a common symptom. Many health practitioners recommend non-prescription over-the-counter (OTC) medicines as a first-line treatment for cough, but there is little evidence as to whether these drugs are effective. OBJECTIVES: To assess the effects of oral over-the-counter cough preparations for acute cough. SEARCH STRATEGY: We searched the Cochrane Acute Respiratory Infections Group specialised register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE and the UK Department of Health National Research Register and reference lists of articles. We wrote to study investigators and pharmaceutical companies for information on further published or unpublished studies. There were no constraints based on language or publication status. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing oral OTC cough preparations with placebo in children and adults suffering from acute cough in ambulatory settings. We considered all cough outcomes (such as frequency and severity, continuous and categorical data, using different ways of measurement). The second outcomes of interest were adverse effects. DATA COLLECTION AND ANALYSIS: Two investigators screened potentially relevant citations independently. Any differences at any stage of the review were resolved by discussion. We also extracted data and assessed the quality of studies independently. We contacted investigators for additional information and performed quantitative analysis when appropriate data were available. MAIN RESULTS: Twenty two trials (16 on adults, eight in children) involving 4199 people (3716 adults and 483 children) were included. RESULTS OF STUDIES IN ADULTS 1. Antitussives Five trials compared antitussives with placebo. Codeine was no more effective than placebo in reducing cough symptoms. One study favoured dextromethorphan over placebo, whereas a second did not show an effect. Moguisteine was no more effective than placebo apart from a reduction of cough in a subgroup of participants with more severe night cough. 2. Expectorants Two trials compared guaifenesin with placebo. In the larger study, 75 per cent of participants taking guaifenesin stated that the medicine was helpful compared to 31 per cent in the control group (p less than 0.01). In the second study, both groups showed improvement with respect to cough frequency and severity, with no statistically significant differences between groups. 3. Mucolytics One trial compared a mucolytic with placebo. Active treatment reduced cough frequency and symptom scores on day four and eight. 4. Antihistamine-decongestant combinations Two studies compared antihistamine-decongestant combinations with placebo. Antihistamine-decongestant were significantly more effective than placebo (p less than 0.01). 5. Other drug combinations Three studies compared combinations of drugs other than antihistamine-decongestant with placebo. Two studies were effective in reducing cough symptoms, and one study showed relief at night but not during the day. 6. Antihistamines Three trials compared antihistamines with placebo. Antihistamines were no more effective than placebo in relieving cough symptoms. RESULTS OF STUDIES IN CHILDREN 1. Antitussives Antitussives were no more effective than placebo (one study) 2. Expectorants No studies using expectorants met our inclusion criteria. 3. Mucolytics The results of one trial favoured active treatment over placebo from day four until day 10 (p<0.01) 4. Antihistamine-decongestant combinations Two studies showed no difference between anthistamine-decongestant combinations and placebo. 5. Other drug combinations One trial tested two paediatric cough syrups. Compared to placebo, both preparations showed a 'satisfactory response' in 46 per cent and 56 per cent of children compared to 21 per cent of children in the placebo group. 6. Antihistamines In one trial that tested antihistamines active treatment was no more effective than placebo. REVIEWER'S CONCLUSIONS: There is no good evidence for or against the effectiveness of OTC medicines in acute cough. The results of this review have to be interpreted with caution due to differences in study designs, populations, interventions and outcomes between studies. The numbers of studies in each group were small, and studies often showed conflicting results. Effect sizes in many studies were unclear and it is questionable as to whether all of the positive results are clinically relevant.

Administration, Oral↗