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Unexplained (idiopathic) cough: ACCP evidence-based clinical practice guidelines.

OBJECTIVE: To review the literature on unexplained cough, previously referred to as idiopathic cough. METHODS: Search of MEDLINE (through May 2004) for studies published in the English language since 1980 on human subjects using the medical subject heading terms "cough," "unexplained cough," and "idiopathic cough." We selected case series and prospective descriptive clinical trials. We also obtained any references from these studies that were pertinent to the topic. RESULTS: The diagnosis of unexplained (idiopathic) cough should only be considered after a thorough diagnostic and treatment approach for the most common causes of cough has been completed and uncommon causes have been adequately evaluated Unless this is done, it is likely that many patients with a definable cause of cough will be misdiagnosed as having "unexplained cough." CONCLUSION: The diagnosis of unexplained cough is probably made too often based on an inadequate diagnostic workup or treatment course to determine the specific cause of cough. Nevertheless, there may be a group of patients in whom none of the usual explanations for cough may be present. For this group, the committee unanimously recommends using the diagnostic term unexplained cough, rather than idiopathic cough.

Biopsy↗

Pathophysiology and clinical presentations of cough.

The human cough reflex is still poorly understood, although it is known to occur independently of bronchoconstriction. Sensitization of the cough reflex is a unifying hypothesis for chronic dry cough in several conditions, including gastroesophageal acid reflux, angiotensin-converting enzyme inhibitor cough, and cough-variant asthma. The most common cause of chronic dry cough is a group of related conditions of chronic rhinitis, sinusitis, and postnasal drip. In these cases the cough reflex may be sensitized through an action of inflammatory mediators from the nasal mucosa on the airways or a reflex sensitization of airway sensory nerves. The association of cough with gastroesophageal reflux may occur through a local esophageal-tracheobronchial reflex. Angiotensin-converting enzyme inhibitor cough is a side effect of treatment in about 10% of patients; it probably results from inhibition of the degradation of kinins, particularly bradykinin, in the airway. Why some patients with asthma have cough as the principal feature of their disease is unclear. Tachykinins are probably involved in the mechanism of sensitization of the cough reflex, and the development of neuropeptide antagonists may open new research opportunities. A study that used ambulatory recording of cough in a group of subjects with asthma confirmed the presence of significant cough, the frequency of which did not correlate with lung function or diurnal variation in peak flow. This finding highlights the problem of cough in patients with asthma, a problem that probably has been underestimated in the past.

Angiotensin-Converting Enzyme Inhibitors↗

Increased sensitivity of the cough reflex in progressive systemic sclerosis patients with interstitial lung disease.

Cough is a common presenting symptom of interstitial lung disease (ILD). The aim of this study was to examine the cough reflex in patients with progressive systemic sclerosis (PSS), with and without associated ILD. The cough reflex to inhalation of chloride deficient solutions and capsaicin was determined in patients with PSS with associated ILD (n=12), compared to patients with PSS without ILD (n=12). In addition, patients with a chronic dry cough (n=12) and healthy subjects (n=10) without cough were studied. Cough responses to inhalation of isotonic solutions containing 150, 75, 37.5 and 0 mM Cl- ions and of capsaicin (0.9-500 mM) were measured. PSS patients with ILD reported a significantly higher cough score than PSS patients without ILD (p<0.03). ILD patients coughed more than those without ILD to Cl- of 37.5 and 0 mM (19.1+/-5.0 vs 6.2+/-1.9 coughs x min(-1) (p<0.03), and 29.2+/-5.0 vs 14.1/-4.1 coughs x min(-1) (p<0.04), respectively). The log concentration of capsaicin causing two or five coughs was lower in PSS with ILD compared to PSS without ILD (0.74+/-0.15 mM vs 2.12+/-0.26 mM; p<0.002). Patients with chronic dry cough had a similar degree of response to low-chloride and capsaicin solutions as patients with PSS and ILD, whilst healthy controls had a similar degrees of response to PSS patients. There is an increased cough reflex in patients with interstitial lung disease, which may represent sensitization of airway sensory nerves. This may be the basis for the chronic dry cough in patients with interstitial lung disease.

Bronchial Provocation Tests↗

Identification of acid reflux cough using serial assays of exhaled breath condensate pH.

BACKGROUND: Chronic cough is a common problem, frequently caused or exacerbated by acid reflux. Diagnosis of acid reflux cough is haphazard currently, often relying on long therapeutic trials of expensive medications. We tested the hypothesis that the most relevant mechanistic component of acid reflux in chronic cough is when it rises to the level of the airway where acid can potentially be aspirated. We further wished to determine if multi-sample exhaled breath condensate (EBC) pH profiles can identify chronic cough patients likely to respond to proton pump inhibitor therapy. METHODS: 59 subjects were recruited for this study. Initially we examined EBC pH (gas-standardized with Argon) in the setting of 15 experimental pharyngeal acid challenges to determine duration of EBC acidification. Subsequently, we enrolled 22 healthy subjects to determine a normal multi-sample exhaled breath condensate pH profile over 1-3 days. We additionally obtained multi-sample EBC pH profiles in 22 patients with chronic cough. These samples were timed to occur after coughing episodes. Exhaled breath condensate pH was measured after gas standardization. RESULTS: We found that exhaled breath condensate pH is substantially reduced for approximately 15 minutes after pharyngeal acid load. Healthy subjects rarely have any low EBC pH values (defined as < 7.4 based on a normative reference range from 404 healthy subjects). Patients with chronic cough who subsequently responded well to proton pump inhibition (n = 8) invariably had one or more cough episodes associated with EBC acidification. No patient who had normal EBC pH with each of their cough episodes reported a clinically relevant response to proton-pump inhibition. CONCLUSION: Patients whose cough responds to proton pump inhibition have transient exhaled breath condensate acidification with coughing episodes, supporting the role of airway acidification in reflux-triggered cough. Multi-sample EBC pH profiles, involving samples collected immediately subsequent to a coughing episode, may be useful appropriately to direct therapy to those patients with cough who have relevant acid reflux.

Journal Article↗

The automatic recognition and counting of cough.

BACKGROUND: Cough recordings have been undertaken for many years but the analysis of cough frequency and the temporal relation to trigger factors have proven problematic. Because cough is episodic, data collection over many hours is required, along with real-time aural analysis which is equally time-consuming. A method has been developed for the automatic recognition and counting of coughs in sound recordings. METHODS: The Hull Automatic Cough Counter (HACC) is a program developed for the analysis of digital audio recordings. HACC uses digital signal processing (DSP) to calculate characteristic spectral coefficients of sound events, which are then classified into cough and non-cough events by the use of a probabilistic neural network (PNN). Parameters such as the total number of coughs and cough frequency as a function of time can be calculated from the results of the audio processing. Thirty three smoking subjects, 20 male and 13 female aged between 20 and 54 with a chronic troublesome cough were studied in the hour after rising using audio recordings. RESULTS: Using the graphical user interface (GUI), counting the number of coughs identified by HACC in an hour long recording, took an average of 1 minute 35 seconds, a 97.5% reduction in counting time. HACC achieved a sensitivity of 80% and a specificity of 96%. Reproducibility of repeated HACC analysis is 100%. CONCLUSION: An automated system for the analysis of sound files containing coughs and other non-cough events has been developed, with a high robustness and good degree of accuracy towards the number of actual coughs in the audio recording.

Journal Article↗

Cough flow-volume relationships in normal and asthmatic children.

The flow-volume profile of a maximum voluntary cough resembles that of a maximum expiratory flow-volume (MEFV) curve with superimposed transient peak flows at the onset of each cough effort and portions of zero flow corresponding to periods of glottis closure. A straight line (the cough slope) can be drawn through the transient peak flows, and the ratio of MEFV-equivalent flow to the cough peak flow can be calculated. This cough ratio has been shown to fall during adult life and may be related to changes in airway compliance and cross-sectional area with age. The present study investigated the cough ratio, cough slope, and maximum flows measured from the cough flow-volume curve in a group of normal children aged 7 to 16 years. Maximum flows and the cough slope increased with height, but the cough ratio did not change with growth or age. In a similar group of asthmatic children, baseline measurements of cough showed a reduction in cough peak flow rates, MEFV-equivalent flow, and the cough ratio. These changes are related to alterations in airway compliance and cross-sectional area and are partly reversed following inhalation of a bronchodilator.

Adolescent↗

The placebo response to citric acid-induced cough: pharmacodynamics and gender differences.

Characteristics of the response to placebo in a citric acid-induced cough challenge were investigated as part of a randomized, double-blind crossover trial to assess the antitussive effect of dextromethorphan. Baseline cough responses were established on two occasions in 22 healthy subjects. They received 60 ml placebo antitussive syrup and cough frequency following five inhalations of 10% citric acid over 5 min was measured at regular intervals up to 12 h. Response-time models of varying complexity were used to describe the placebo cough suppression data. The cough response to placebo was also compared to that of the untreated state. The placebo cough response was best characterized by a non-linear increase in cough suppression up to a maximum reduction of 1.6 coughs from baseline at 4-4.5 h, followed by a non-linear return to baseline. The cough response in the untreated state was not different from that of placebo (P=0.99). Females coughed more frequently than males (median number of coughs=10.5 vs. 9.0, respectively P<0.001; Mann-Whitney U test), and adaptation to the cough stimulus was significantly more rapid in females (P<0.025). Accordingly, in trials that use citric acid-induced cough, gender should be considered in study design, particularly in relation to the timing of measurements.

Administration, Inhalation↗

Cough reflex in allergic dogs.

This study investigated the effects of antigen challenge on the cough reflex in dogs that were neonatally sensitized to ragweed. Tidal volume (V(T)), respiratory rate (f), pulmonary resistance (R(L)), dynamic lung compliance (C(Dyn)) and the number and amplitude (increase in mean peak expiratory pressure) of coughs induced by mechanical stimulation of the intrathoracic trachea were measured in propofol-anesthetized dogs. Aerosolized ragweed challenge had no effect to induce spontaneous cough but increased f and R(L) and reduced V(T) and C(Dyn). Mechanical stimulation of the intrathoracic trachea at this time produced 19+/-5 coughs with an average increase in cough amplitude of 11+/-1 cm H(2)O which differed significantly from the number (9+/-2 coughs) and amplitude (30+/-5.5 cm H(2)O) of mechanically induced coughs after treatment with aerosolized saline. Both the number and amplitude of mechanically induced coughs returned to baseline values by 24-48 h after the ragweed challenge. Similar results were obtained after challenge with aerosolized histamine (0.3-1% histamine) that did not induce spontaneous coughs but increased f, reduced V(T) and decreased C(Dyn) and increased the number but reduced the amplitude of the mechanically induced coughs. In conclusion, both antigen and histamine bronchoprovocation changed the characteristics of the mechanically induced cough in dogs to a response of increased cough number but reduced mean expiratory cough amplitude.

Aerosols↗

Measurement of cough.

Cough is one of the most common symptoms encountered by clinicians particularly when it is persistent. Assessment of cough is essential for determining treatment outcomes, testing new therapies and for study of pathophysiology and mechanisms. There are new tools for measuring different aspects of cough. Apart from the patient's subjective assessment of cough severity using clinical scores, the impact of cough on quality of life can be measured. Direct measurement of cough counts is now possible by using portable devices, but how the counts relate to severity is unclear. A measure of cough intensity is required. Cough reflex measured by response to inhaling citric acid or capsaicin provides a measure of cough sensitivity that may be related to cough severity. In many intervention studies of cough, the response has usually been measured in terms of physician assessment of cough and its changes in cough reflex. How the information obtained between these different measurements interrelate needs to be determined.

Animals↗

Assessing the laryngeal cough reflex and the risk of developing pneumonia after stroke.

OBJECTIVE: To determine the effectiveness of a new reflex cough test, using nebulized tartaric acid, in the evaluation of the laryngeal cough reflex and the development of aspiration pneumonia. STUDY DESIGN: In this two-phase study, the cough test assessed the cough reflex in 161 stroke subjects. Phase 1 was a double-blinded prospective study of 40 subjects scheduled to have both modified barium swallow and the reflex cough test. Phase 1 subjects with an abnormal cough test showed an increased pneumonia incidence, and therefore, phase 2 was not blinded. In phase 2, 121 subjects were evaluated using the cough test; 38 received a modified barium swallow. Test results were compared using the Fisher exact test. RESULTS: A total of 131 subjects from both phases had a normal reflex cough test; none developed pneumonia (p < .01). Thirty subjects from both phases had abnormal reflex cough test results; 5 developed pneumonia. Modified barium swallow findings did not reliably indicate the risk for developing pneumonia. Specificity of a normal reflex cough test was 100%. CONCLUSION: The reflex cough test reliably evaluated the laryngeal cough reflex and the associated risk of developing aspiration pneumonia in stroke patients. Testing the laryngeal cough reflex may significantly reduce morbidity, mortality, and costs in stroke patients.

Aged↗

Chronic cough resembles asthma with IL-5 and granulocyte-macrophage colony-stimulating factor gene expression in bronchoalveolar cells.

BACKGROUND: Chronic cough is a multifactorial condition, which, like asthma, can be associated with eosinophilic airway inflammation. In asthma, airway eosinophilia is believed to be mediated by cytokines such as interleukin-5 and granulocyte-macrophage colony stimulating factor (GM-CSF). The role of these cytokines in chronic cough is unclear. OBJECTIVE: The aim of this study was to examine gene expression for IL-5 and GM-CSF in chronic cough and compare the results with those found in asthma. METHODS: We studied adults with asthma (n = 12), chronic cough responsive to inhaled corticosteroid (ICS-responsive cough) (n = 9), and chronic cough not responsive to inhaled corticosteroid (non-ICS-responsive cough) (n = 4). Bronchoalveolar lavage (BAL) was performed, and cytokine gene expression was assessed by using a semiquantitative reverse transcriptase polymerase chain reaction. RESULTS: IL-5 mRNA was expressed by BAL cells from nine of 12 asthmatic subjects and six of nine subjects with ICS-responsive chronic cough. IL-5 mRNA was not detected in subjects with non-ICS-responsive chronic cough (zero of four subjects, p < 0.05). GM-CSF mRNA was expressed in BAL cells from seven of 12 asthmatic subjects and six of nine subjects with ICS-responsive cough. GM-CSF mRNA was not detected in non-ICS responsive cough subjects (zero of four subjects, p < 0.05). GM-CSF gene expression was related to the degree of methacholine airway responsiveness in asthmatic subjects (r = -0.59). CONCLUSION: We conclude that chronic cough, like asthma, is associated with airway inflammation and gene expression for IL-5 and GM-CSF. Ongoing expression of these cytokines is likely to be related to the persistence of airway inflammation and chronic cough.

Administration, Inhalation↗

Cough during emergence from isoflurane anesthesia.

UNLABELLED: We evaluated the effects of smoking history and albuterol treatment on the amplitude and frequency of cough during emergence from anesthesia. Before induction of anesthesia, 68 patients were randomized to receive two puffs of a placebo or two puffs of albuterol via a metered dose inhaler. Anesthesia was then induced with thiopental, fentanyl, and succinylcholine. The patients' tracheas were intubated with an 8.0 mm-endotracheal tube, and isoflurane administration was initiated. At the end of surgery, isoflurane was discontinued, and the pressure in the endotracheal tube cuff was monitored via the pilot balloon while the end-tidal isoflurane concentration was recorded. Of the 68 patients, 52 coughed before responding to command, but the incidence did not differ between smokers and nonsmokers (33 of 43 vs 19 of 25), nor did it differ between albuterol-treated and untreated patients. There was no difference in the frequency or amplitude of coughs between smokers and nonsmokers, nor did albuterol affect either variable. The mean end-tidal concentration at which cough first occurred was 0.30%+/-0.02%, and only 5% of patients coughed at values >0.6%. We conclude that 1) cough is frequent during emergence; 2) smoking does not affect emergence cough; 3) albuterol treatment does not affect emergence cough; and 4) patients are unlikely to cough at end-tidal values of isoflurane >0.6%. IMPLICATIONS: Most patients cough as they awaken from general anesthesia given via an endotracheal tube. In our study population, cough was frequent but generally did not occur until the end-tidal concentration of isoflurane was <0.6%. Smokers were no more likely to cough than nonsmokers, and the beta-adrenergic agonist albuterol did not prevent cough.

Albuterol↗

A review of voice and upper airway function in chronic cough and paradoxical vocal cord movement.

PURPOSE OF THE REVIEW: Chronic cough and paradoxical vocal fold movement (PVFM) are perplexing conditions. This paper reviews the recent literature in relation to the nature of PVFM and chronic cough and the management of symptoms associated with these disorders. RECENT FINDINGS: There are similarities in the voice and upper airway symptoms in chronic cough and PVFM. Clinically significant voice symptoms are present in approximately 40% of individuals with chronic cough and PVFM and are similar to those occurring in voice disorders such as muscle tension dysphonia. Chronic cough can be associated with PVFM in a large proportion of cases. Extrathoracic airway hyperresponsiveness is a common underlying mechanism in PVFM and chronic cough. Speech pathology intervention can be effective in controlling symptoms in chronic cough, which suggests that the anatomic diagnostic protocol could be expanded to incorporate this intervention. Chronic cough that fails to respond to medical management should be conceptualized as either due to PVFM or idiopathic. PVFM and chronic cough are not necessarily the result of underlying psychopathology. SUMMARY: Chronic cough and PVFM manifest in a range of clinically significant voice and upper airway symptoms. The anatomic diagnostic protocol used in the management of chronic cough could be expanded to include PVFM as a potential cause of cough, and speech pathology intervention as treatment for chronic cough.

Chronic Disease↗

Studies on the magnitude and the mechanism of cough potentiation by angiotensin-converting enzyme inhibitors in guinea-pigs: involvement of bradykinin in the potentiation.

One adverse effect of the angiotensin-converting enzyme (ACE) inhibitors used for treatment of hypertension and congestive heart failure is the production of dry coughs. Imidapril is a new type of ACE inhibitor with a very low incidence of coughs. The magnitude and the mechanism of cough potentiation of imidapril and other ACE inhibitors has been studied in guinea-pigs. In normal guinea-pigs single and repeated dosing of imidapril at 0.1 to 100 mg kg-1 had no effect on capasaicin- or citric acid-induced coughs. Single and repeated dosing of enalapril and captopril at 10 to 30 mg kg-1, respectively, significantly increased the number of capsaicin-induced coughs. Repeated dosing of 1 mg kg-1 enalapril also significantly augmented the capsaicin cough. In bronchitic guinea-pigs imidapril also had no effect on the coughs induced by the two stimulants. Enalapril and captopril significantly increased the number of coughs induced not only by capsaicin but also by citric acid. Lower doses of enalapril were enough to augment the capsaicin-induced coughs, whereas medium to large doses failed to augment the cough irrespective of the protocol of administration. Bradykinin-induced discharges of the vegal afferents from the lower airway were significantly increased by enalaprilat but not by imidaprilat. Capsaicin-induced discharges of the afferents were, on the other hand, significantly depressed by enalaprilat, but not by imidaprilat. Interestingly, enalaprilat depression of the discharges was significantly reversed by Hoe-140, a bradykinin B2 receptor blocker. In guinea-pigs pretreated with a low dose of enalapril, arterial infusion of bradykinin significantly potentiated the coughs induced by capsaicin. The results indicated that imidapril was less potent than enalapril and captopril in potentiating cough responses induced by capsaicin and citric acid in guinea-pigs, and further suggest that bradykinin might be a key substance in the mechanism of the potentiation of coughs associated with ACE inhibitors.

Angiotensin-Converting Enzyme Inhibitors↗

Clinical significance of cough and wheeze in the diagnosis of asthma.

OBJECTIVES: (1) To determine the prevalence of cough, wheeze, and breathlessness, both as single symptoms and in combination, in primary schoolchildren and their relation to doctor diagnosed asthma. (2) To identify in areas with different levels of dust pollution whether questionnaire reported 'cough alone' (without wheeze or breathlessness) had similar risk factors to the questionnaire reported triad of 'cough, wheeze, and breathlessness'. SUBJECTS AND METHODS: Two cross sectional community surveys of primary schoolchildren (5-11 years) were performed in 1991 and 1993. Parent completed questionnaires related to socioeconomic and respiratory factors were distributed through 15 schools in three areas of Merseyside, one of which had a relatively high level of dust pollution. Data were analysed to determine the prevalence of different respiratory symptom patterns. Univariate and multiple logistic regressions were used to investigate the associations between respiratory symptom profiles and potential risk factors. RESULTS: The proportions of completed questionnaires that were returned were similarly high in both surveys, 92% in 1991 (1872 of 2035) and 87% in 1993 (3746 of 4288). The proportions of children with different respiratory symptom patterns were similar in the two surveys: in 1991, asymptomatic children 70.1% (1109 of 1583), those with cough alone 8.9% (141 of 1583), and children with the symptom triad of cough, wheeze, and breathlessness 8.3% (132 of 1583); the figures for 1993 were 69.5% (2144 of 3083), 9.2% (284 of 3083), and 7.3% (224 of 3083) respectively. The prevalence of doctor diagnosed asthma increased from 17.4% in 1991 to 22.1% in 1993. The symptom of cough alone was associated with going to school in an area of increased air pollution. The symptom triad of cough, wheeze, and breathlessness was associated with reported allergies, familial history of atopy and preterm birth. In 1991, of children with the symptom of cough alone one in eight were diagnosed asthmatic; twice as many doctors made the diagnosis on this basis in 1993. CONCLUSION: The respiratory symptom of cough alone and cough, wheeze, and breathlessness represent clinical responses to different specific risk factors. Cough alone was associated with the environmental factors of school in the dust exposed zone and dampness in the home, whereas cough, wheeze, and breathlessness related to allergic history and preterm birth, and may be the best surrogate of asthma. Diagnosis of asthma on the basis of cough alone partly explains the increased prevalence of doctor diagnosed asthma, especially in dust polluted areas.

Analysis of Variance↗

Idiopathic chronic cough: association with organ specific autoimmune disease and bronchoalveolar lymphocytosis.

BACKGROUND: We have recently reported a strong association between organ specific autoimmune disease and idiopathic chronic cough and have suggested that cough may be caused by airway inflammation secondary to aberrant homing of activated lymphocytes to the lung. An immunopathological study was undertaken to test the hypothesis that idiopathic chronic cough is associated with lymphocytic airway inflammation. METHODS: Bronchoscopy, bronchial biopsies, bronchoalveolar lavage (BAL), and peripheral blood and BAL flow cytometry were performed in 19 patients with idiopathic chronic cough, 14 with explained chronic cough, and 11 normal subjects. RESULTS: Organ specific autoimmune disease or positive autoantibodies were present in eight of the 19 patients with idiopathic cough, in one of the 14 patients with explained cough, and in one of the 11 normal subjects. Median BAL fluid differential lymphyocyte counts were significantly higher in patients with idiopathic cough (10.0%) than in normal subjects (6.3%, 95% confidence interval of difference 1.5 to 11.9, p = 0.01) or patients with explained cough (5.2%, 95% CI of difference 2.0 to 10.4, p = 0.001). There were no differences in bronchial biopsy T lymphocyte counts between the groups. The mean (SE) proportion of CD3+ peripheral blood mononuclear cells expressing CD4 was significantly higher in normal subjects than in patients with idiopathic cough (69 (3)% v 58 (3)%, mean difference 11%, 95% CI of difference 2 to 20, p<0.02) but not than those with explained chronic cough (63 (2)%). There were no differences in BAL T lymphocyte phenotype between groups. CONCLUSION: BAL fluid lymphocytosis occurs in some patients with idiopathic chronic cough. The association of idiopathic chronic cough with organ specific autoimmune disease raises the possibility that this might be caused by lymphocyte homing from the primary site of autoimmune inflammation or the result of an autoimmune process in the lung.

Autoantibodies↗

Utility of signs and symptoms of chronic cough in predicting specific cause in children.

BACKGROUND: Paediatricians rely on cough descriptors to direct them to the level of investigations needed for a child presenting with chronic cough, yet there is a lack of published data to support this approach. A study was undertaken to evaluate (1) whether historical cough pointers can predict which children have a specific cause for their cough and (2) the usefulness of chest radiography and spirometry as standard investigations in children with chronic cough. METHODS: This was a prospective cohort study of children referred to a tertiary hospital with a cough lasting >3 weeks between June 2002 and July 2004. All included children completed a detailed history and examination using a standardised data collection sheet and followed a pathway of investigation until a diagnosis was made. RESULTS: In 100 consecutively recruited children of median age 2.8 years, the best predictor of specific cough observed was a moist cough at the time of consultation with an odds ratio (OR) of 9.34 (95% CI 3.49 to 25.03). Chest examination or chest radiographic abnormalities were also predictive with OR 3.60 (95% CI 1.31 to 9.90) and 3.16 (95% CI 1.32 to 7.62), respectively. The most significant historical pointer for predicting a specific cause of the cough was a parental history of moist cough (sensitivity 96%, specificity 26%, positive predictive value 74%). CONCLUSIONS: The most useful clinical marker in predicting specific cough is the presence of a daily moist cough. Both chest examination and chest radiographic abnormalities are also useful in predicting whether children have a specific cause of their cough.

Child↗

Prostaglandin F2 alpha enhancement of capsaicin induced cough in man: modulation by beta 2 adrenergic and anticholinergic drugs.

The effect of inhaled prostaglandin (PG) F2 alpha on the response to the inhaled tussive agent capsaicin was investigated in normal subjects. Seven subjects inhaled three breaths of four doses of capsaicin (0.3, 0.6, 1.2, and 2.4 nmol) before and immediately after inhaling PGF2 alpha (0.1 mumol) or placebo (0.15M NaCl) on separate days. The numbers of capsaicin induced coughs were greater after PGF2 alpha (mean 42.3 coughs) than after 0.15M sodium chloride (30.1). Visual analogue scores (0-10 on a 10 cm continuous scale) showed that capsaicin was more irritant after PGF2 alpha than after saline. Total respiratory resistance (Rrs), measured by the forced oscillation technique, was unaltered throughout the study. A double blind, placebo controlled study of the effects of inhaled salbutamol (200 micrograms, 0.6 mumol) and ipratropium bromide (40 micrograms, 0.1 mumol) on cough induced by capsaicin (2.4 nmol) and by PGF2 alpha (0.1 mumol) and on PGF2 alpha augmented, capsaicin induced coughing was performed in seven subjects. Neither drug had any effect on capsaicin induced coughing. Salbutamol reduced coughing due to PGF2 alpha (mean 7.7 coughs after salbutamol, 9.3 after placebo) but ipratropium bromide did not (mean 6.9 coughs after ipratropium bromide, 6.6 after placebo). Salbutamol also inhibited the augmentation of the capsaicin induced cough that followed inhalation of PGF2 alpha (mean augmentation 1.9 coughs after salbutamol, 4.1 after placebo), whereas ipratropium bromide did not (augmentation 1.7 coughs after ipratropium bromide, 2.7 after placebo). No changes in Rrs were seen after PGF2 alpha or either drug. Thus salbutamol reduces PGF2 alpha induced cough and the augmentation of capsaicin induced cough that follows PGF2 alpha.

Administration, Inhalation↗