1.
MMW Fortschr Med. 2020 Mar;162(Suppl 1):35-42. doi: 10.1007/s15006-020-0007-9.
[Cough following airway infections].
[Article in German]
KEYWORDS:
Acute cough; airway infection; antitussive agents; bronchial hyperreactivity; chronic cough
2.
Respirology. 2016 May;21(4):683-8. doi: 10.1111/resp.12748. Epub 2016 Mar 10.
Eosinophilic airway inflammation is common in subacute cough following acute upper respiratory tract infection.
Abstract
BACKGROUND AND OBJECTIVE:
Patients presenting with refractory postinfectious cough may respond to glucocorticosteroids but it is unclear whether airway eosinophilic inflammation exists in those patients. We aimed to determine the airway inflammation and causes of subacute cough following acute upper respiratory tract infection (AURTI).
METHODS:
One hundred and sixteen patients with persistent cough lasting 3-8 weeks after upper respiratory tract infection were evaluated with differential cell count in induced sputum, spirometry and methacholine bronchial challenge testing.
RESULTS:
In patients with subacute cough, sputum eosinophilia (median 8.5%,3.0-73.0%) was identified in 35 (33.6%) patients, 22 (18.5%) without bronchial hyperresponsiveness (BHR) were diagnosed as non-asthmatic eosinophilic bronchitis (NAEB), 13 (14.3%) of whom with BHR were diagnosed as cough variant asthma (CVA). Cough in patients with sputum eosinophilia improved after treatment with corticosteroids. Compared with postinfectious cough (PIC) and NAEB, CVA had significantly higher median eosinophil count in induced sputum (0.5% vs 7.5% vs 20.0%, P < 0.01). MMEF in CVA was significantly lower than PIC and NAEB (P < 0.05). The common causes of subacute cough following acute upper respiratory tract infection (AURTI) were PIC (37.8%), NAEB (18.5%), CVA (14.3%) and upper airway cough syndrome (UACS) (10.1%). Atopic cough (AC) (5.2%) and gastroesophageal reflux-related cough (GERC) (3.4%) were less common in subacute cough following AURTI, while 9 (7.8%) patients had unexplained cough.
CONCLUSION:
Subacute cough following AURTI can be attributed to different entities, eosinophilic airway inflammation is common. Induced sputum should be considered when evaluating patients with subacute cough following acute upper respiratory tract infection.
© 2016 Asian Pacific Society of Respirology.
KEYWORDS:
Cough; Eosinophilic inflammation; Etiology; Postinfectious cough; Upper airway infection
3.
Eur Respir J. 1996 Mar;9(3):478-85.
Effects of moguisteine, a peripheral nonnarcotic antitussive agent, on airway inflammation in guinea-pigs in vivo.
Abstract
Cough is a common symptom of respiratory diseases associated with irritation or inflammation of the airways, and symptomatic antitussive drugs are frequently prescribed to control an abnormal cough reflex. Our aim was to evaluate the effects of moguisteine, a novel, peripheral, nonnarcotic antitussive agent, on airway inflammation induced in guinea-pigs with a variety of stimuli. These stimuli included exposure to tobacco smoke for 10 min, to elicit airway hyperreactivity, eosinophil recruitment in bronchoalveolar lavage (BAL), airway epithelial damage and plasma exudation; graded platelet-activating factor (PAF) infusion (600 ng.kg-1 over one h), to induce airway hyperreactivity; 2% ovalbumin (OA) aerosol challenge in 1% OA-sensitized animals, to induce late-phase (17 and 72 h) airway leucocyte accumulation. We also assessed the activity of moguisteine on plasma leakage induced by capsaicin, on bronchoconstriction induced by acetylcholine (ACh), histamine (H) and PAF, and on leukotriene mediated allergic bronchospasm in OA-sensitized guinea-pig. Moguisteine (p.o. and i.m.) and dexamethasone (p.o. and i.m.) dose-dependently reduced tobacco smoke-induced bronchial hyperreactivity. Moguisteine and dexamethasone abolished eosinophil recruitment in BAL, prevented the sloughing of the epithelium and significantly reduced airway microvascular leakage. Both agents were also highly effective in reducing bronchial hyperreactivity elicited by PAF infusion. In addition, moguisteine was active in inhibiting airway neutrophil and eosinophil accumulation in BAL observed 17 and 72 h after OA challenge in sensitized guinea-pigs. In contrast to dexamethasone, moguisteine did not prevent capsaicin-induced plasma leakage. It was also ineffective against bronchoconstriction as induced by ACh, H, and PAF and failed to inhibit leukotriene-dependent bronchospasm. Our data suggest that moguisteine represents an antitussive compound endowed with interesting airway anti-inflammatory properties in guinea-pigs in vivo. Its mechanism of action remains to be elucidated.
4.
Pulm Pharmacol Ther. 2004;17(6):337-42.
Cough induced by airway vibration as a model of airway hyperreactivity in patients with acute upper respiratory tract infection.
Abstract
Patients with acute upper respiratory tract infection (URTI) have been shown to be hyperreactive to inhaled tussigens such as citric acid and capsaicin, and the authors propose that this may be due to an increased sensitivity of airway receptors that mediate cough. In recent studies we have demonstrated that cough may be induced by vibration of the airway at the level of the throat or chest in patients with URTI but that the same stimuli induce little or no cough in healthy subjects. The difference between the patients with URTI and healthy subjects in their response to airway vibration may be explained on the basis of hyperreactivity of airway sensory receptors. We propose that the model of cough induced by airway vibration may be useful for studies on the pathophysiology and pharmacology of airway hyperreactivity in acute cough. The airway vibration model of cough may have some advantages over inhaled tussigens as the stimulus is easily controlled and the method is safe for use in children.
5.
Int Immunopharmacol. 2012 Jul;13(3):301-7. doi: 10.1016/j.intimp.2012.04.019. Epub 2012 May 7.
Naringin attenuates enhanced cough, airway hyperresponsiveness and airway inflammation in a guinea pig model of chronic bronchitis induced by cigarette smoke.
Abstract
Naringin is a flavanone with various bioactivities including expectorant effect, antitussive effect and inhibitory effects on asthma and acute lung injury. In present study we examined the effects of naringin on enhanced cough, airway hyperresponsiveness (AHR) and airway inflammation in chronic cigarette smoke (CS) exposure-induced chronic bronchitis in guinea pigs. To achieve this, guinea pigs were exposed to CS for 8weeks (10cigarettes/day, 6days/week). Oral administration of naringin (9.2, 18.4 and 36.8mg/kg) significantly attenuated the enhanced cough and AHR in smoke-exposed guinea pigs, reduced the concentrations of interleukin-8 (IL-8), leukotriene B4 (LTB4) and tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid (BALF) and decreased the myeloperoxidase (MPO) activity in both BALF and lung tissue, but did not significantly decrease the leukocytes in BALF. Naringin also improved superoxidase dismutase (SOD) activity in lung tissue and increased the content of lipoxin A4 (LXA4) in BALF in this guinea pig model of chronic bronchitis. These results suggested that naringin exhibited antitussive, anti-AHR and anti-inflammation effects on chronic CS exposure-induced chronic bronchitis in guinea pigs, and may possess novel therapeutic potential in the treatment of chronic bronchitis.
Copyright © 2012 Elsevier B.V. All rights reserved.
6.
J Physiol Pharmacol. 2008 Dec;59 Suppl 6:473-82.
Influence of selective inhibitors of phosphodiesterase 3 and 4 on cough and airway reactivity.
Abstract
As the administration of many antitussive drugs is often associated with adverse effects, new alternatives are evaluated in experimental and clinical conditions. The aim of this study was to assess the influence of selective inhibitors of PDE3 (cilostazol) and PDE4 (citalopram) on cough and airway reactivity. The number of cough efforts, specific airway resistance, in vitro airway reactivity, and differential blood cells count were measured in healthy and in ovalbumin-sensitized guinea pigs before and after administration of cilostazol or citalopram (1 mg/kg). Cilostazol significantly suppressed citric acid induced cough only in healthy guinea pigs, whereas citalopram in both healthy and ovalbumin-sensitized animals. Both PDE inhibitors decreased in vivo and in vitro airway reactivity to histamine and the count of monocytes and neutrophils, confirming their anti-inflammatory potential. Administration of selective PDE3 and PDE4 inhibitors may influence cough and airway reactivity in the model of ovalbumin-sensitized guinea pigs.
7.
Lung. 2008;186 Suppl 1:S59-65. Epub 2007 Oct 10.
TRPV1 antagonists as potential antitussive agents.
Abstract
Cough is an important defensive pulmonary reflex that removes irritants, fluids, or foreign materials from the airways. However, when cough is exceptionally intense or when it is chronic and/or nonproductive it may require pharmacologic suppression. For many patients, antitussive therapies consist of OTC products with inconsequential efficacies. On the other hand, the prescription antitussive market is dominated by older opioid drugs such as codeine. Unfortunately, "codeine-like" drugs suppress cough at equivalent doses that also often produce significant ancillary liabilities such as GI constipation, sedation, and respiratory depression. Thus, the discovery of a novel and effective antitussive drug with an improved side effect profile relative to codeine would fulfill an unmet clinical need in the treatment of cough. Afferent pulmonary nerves are endowed with a multitude of potential receptor targets, including TRPV1, that could act to attenuate cough. The evidence linking TRPV1 to cough is convincing. TRPV1 receptors are found on sensory respiratory nerves that are important in the generation of the cough reflex. Isolated pulmonary vagal afferent nerves are responsive to TRPV1 stimulation. In vivo, TRPV1 agonists such as capsaicin elicit cough when aerosolized and delivered to the lungs. Pertinent to the debate on the potential use of TRPV1 antagonist as antitussive agents are the observations that airway afferent nerves become hypersensitive in diseased and inflamed lungs. For example, the sensitivity of capsaicin-induced cough responses following upper respiratory tract infection and in airway inflammatory diseases such as asthma and COPD is increased relative to that of control responses. Indeed, we have demonstrated that TRPV1 antagonism can attenuate antigen-induced cough in the allergic guinea pig. However, it remains to be determined if the emerging pharmacologic profile of TRPV1 antagonists will translate into a novel human antitussive drug. Current efforts in clinical validation of TRPV1 antagonists revolve around various pain indications; therefore, clinical evaluation of TRPV1 antagonists as antitussive agents will have to await those outcomes.
8.
Bratisl Lek Listy. 2011;112(12):670-5.
Antitussive activity of Althaea officinalis L. polysaccharide rhamnogalacturonan and its changes in guinea pigs with ovalbumine-induced airways inflammation.
Abstract
AIM:
The presented studies were aimed on experimental confirmation of Althaea officinalis polysaccharide rhamnogalacturonan antitussive effect and its changes in conditions of allergic inflammation.
METHODS:
We have tested whether rhamnogalacturonan inhibits cough reflex and modulates airways reactivity of guinea pigs in vivo. The cough in guinea pigs was induced by 0.3 M citric acid (CA) aerosol for 3 min interval, in which total number of cough efforts (sudden enhancement of expiratory flow accompanied by cough movement and sound) was counted. Specific airway resistance and its changes induced by citric acid aerosol were considered as an indicator of the in vivo reactivity changes.
RESULTS:
1) Althaea officinalis polysaccharide rhamnogalacturonan dose- dependently inhibits cough reflex in unsensitized guinea pigs. Simultaneously, plant polysaccharide shortened the duration of antitussive effect when it was been tested in inflammatory conditions. 2) Rhamnogalacturonan did not influence airways reactivity in vivo conditions expressed as specific resistance values neither sensitized nor unsensitized groups of animals. 3) The antitussive activity of codeine (dose 10 mg.kg(-1) b.w. orally) tested under the same condition was comparable to higher dose of rhamnogalacturonan in unsensitized animals. 4) The characteristic cellular pattern of allergic airways inflammation was confirmed by histopathological investigations.
CONCLUSION:
Rhamnogalacturonan isolated from Althaea officinalis mucilage possesses very high cough suppressive effect in guinea pigs test system, which is shortened in conditions of experimentally induced airways allergic inflammation (Tab. 1, Fig. 4, Ref. 25). Full Text in free PDF www.bmj.sk.
9.
Heart. 1996 Aug;76(2):144-9.
Airway and cough responsiveness and exhaled nitric oxide in non-smoking patients with stable chronic heart failure.
Abstract
OBJECTIVE:
To investigate the airway and cough responsiveness in non-smoking patients with stable chronic heart failure. Cough and wheeze, features associated with hyper-responsive airways, are not uncommon especially in decompensated chronic heart failure. Bronchial hyperresponsiveness has previously been demonstrated in chronic heart failure but this may have been confounded by smoking and acute decompensation.
DESIGN:
Case-control study.
SETTING:
Tertiary specialist hospital.
PATIENTS AND INTERVENTIONS:
Airway responsiveness to methacholine (a direct stimulant of smooth muscle in the airways), sodium metabisulphite (a putative stimulant of airway sensory nerves), and exercise was examined in 10 non-smoking patients with stable chronic heart failure (age 56.5 (3.2) (SEM) years; 7 men; radionuclide left ventricular ejection fraction 20.8 (2.9)%; radiographic cardiothoracic ratio 0.56 (0.02)). Exhaled nitric oxide, a product of the action of proinflammatory cytokines, was also measured to assess the contribution of local inflammation to airway responsiveness. The cough responses to low-concentration chloride solutions and to capsaicin were studied. Because all patients were receiving angiotensin-converting enzyme inhibitors, which may influence airway responsiveness and cough, 8 asymptomatic non-smoking controls taking angiotensin-converting enzyme inhibitors for essential hypertension were also studied (age 54.3 (2.8) years; 6 men; radiographic cardiothoracic ratio 0.46 (0.01)).
RESULTS:
The mean provocative concentration that induced a 20% decrease in forced expiratory volume in 1 second (FEV1) was 67.6 v 79.8 mg/ml (P = 0.71) for methacholine and 276.7 v 290.4 mg/ml (P = 0.79) for sodium metabisulphite in chronic heart failure patients and controls respectively. The change in FEV1 after maximal cardiopulmonary exercise testing was +1.44% in patients and +2.53% in controls (P = 0.47), indicating that there was no exercise-induced bronchospasm in either group (peak oxygen consumption was 16.9 (1.3) v 26.5 (2.3) ml/kg/min respectively, P < 0.01). Exhaled nitric oxide concentration was not increased in chronic heart failure (12.3 (1.7) v 16.2 (3.3) ppb, P = 0.32). The median cough counts after nebulised 0 mM and 37.5 mM chloride solutions were 2.5 v 1.0 (P = 0.6) and 5.5 v 5.5 (P = 0.5) respectively and the capsaicin concentration causing two or more coughs was 13.5 v 6.5 microM (P = 0.5).
CONCLUSION:
Airway hyper-responsiveness is not a predominant feature in non-smoking patients with stable chronic heart failure treated with, and tolerant to, angiotensin-converting enzyme inhibitors. It is unlikely to contribute to the exertional dyspnoea seen in these patients.
10.
J Ethnopharmacol. 2016 Dec 24;194:378-385. doi: 10.1016/j.jep.2016.08.008. Epub 2016 Aug 3.
Antitussive activity of the Schisandra chinensis fruit polysaccharide (SCFP-1) in guinea pigs models.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE:
Schisandra chinensis (Turcz.) Baill. (S. chinensis), locally known as "Wuweizi", has been used in the treatment of chronic cough as prescription medications of Traditional Chinese Medicine for thousands of years. However, the components of antitussive activity of S. chinensis and the mechanism are poorly understood.
AIM OF THE STUDY:
This study aims to investigate the antitussive activity of polysaccharides extracted from S. chinensis.
MATERIALS AND METHODS:
S. chinensis fruit polysaccharide-1 (SCFP-1) was extracted by 95% ethanol and distilled water successively, and then the water extraction was isolated with chromatographic columns. The preliminary characterization of SCFP-1 was analyzed by gel permeation chromatography (GPC), gas chromatography-mass spectrometry (GC-MS) and some other recognized chemical methods. Antitussive potential of SCFP-1 was estimated at dose of 250, 500, and 1000mg/kg respectively by peroral administration in a guinea pigs model with cough hypersensitivity induced by cigarette smoke (Chronic cough model) or acute cough guinea model induced by citric acid (Acute cough model). Also, the time-dependent antitussive effect of SCFP-1 were evaluated with acute cough model, and compared with codeine.
RESULTS:
The molecular of SCFP-1 was 3.18×104Da, mainly being composed of glucose and arabinose (66.5% and 29.4%, respectively). Peroral administration of SCFP-1 at 250, 500, and 1000mg/kg showed remarkable suppressive effects respectively on cough in both of chronic cough model and acute cough model. Meanwhile, inflammatory cell in BALF and some typical characteristics of nonspecific airway inflammation in animals exposed to CS was significantly attenuated after pretreatment with SCFP-1. The cough suppression of SCFP-1 (500 mg/kg) stablly lasted during the whole 5 h of time-dependent experiment, while no positive effect was observed after 300 min of oral administration of codeine.
CONCLUSIONS:
SCFP-1 is one of the antitussive components of S. chinensis.
Copyright © 2016. Published by Elsevier Ireland Ltd.
KEYWORDS:
Anti-inflammation; Antitussive activity; Cough; Polysaccharide; Schisandra chinensis
11.
Respirology. 1998 Dec;3(4):267-72.
Airway cough sensitivity to inhaled capsaicin and bronchial responsiveness to methacholine in asthmatic and bronchitic subjects.
Abstract
The objective of this study was to evaluate the effect of chronic airway inflammation on airway cough sensitivity and non-specific bronchial responsiveness, and the relationship between them. The capsaicin cough threshold, defined as the lowest concentration of capsaicin causing five or more coughs, and non-specific bronchial responsiveness, defined as the methacholine concentration causing a 20% fall in forced expiratory volume in 1 s (FEV1) (PC20-FEV1), were measured in 18 asthmatic, 13 bronchitic (sinobronchial syndrome) and 28 healthy non-atopic subjects. All subjects were non-smoking men. The geometric mean values (mumol) of the cough threshold were 18.9 (GSEM 1.29), 8.69 (GSEM 1.29) and 27.6 (GSEM 1.31) in asthmatic, bronchitic and normal subjects, respectively. The value in bronchitic subjects was significantly lower (P << 0.02) than that in normal subjects. The geometric mean value of PC20-FEV1 in asthmatic subjects (0.48 mg/ml (GSEM 1.38)) was significantly lower than that in bronchitic subjects (18.5 mg/ml (GSEM 1.75)) (P << 0.001). There was no correlation between cough threshold and PC20-FEV1 values (correlation coefficient (r) = 0.155). These results indicate that cough sensitivity is potentiated by chronic airway inflammation in bronchitis but not in asthma, and suggest that cough sensitivity and bronchial responsiveness may be independently potentiated by different mechanisms resulting from chronic airway inflammation.
12.
Jpn J Pharmacol. 1975 Dec;25(6):621-9.
The role of bronchoconstriction in cough reflex.
Abstract
To investigate the role of bronchoconstriction in the cough reflex, we compared antitussive effects of several drugs with their ability to effect the respiratory tract (i.e. bronchodilation vs. bronchoconstriction). Antitussive activities of five drugs administered either intravenously or orally on electrically-induced cough were evaluated in the non-anesthetized dog. The antitussive activities were as follows: morphine, 0.1 mg/kg (i.v.) and 0.5 mg/kg (p.o.); codeine, 1.0, 4.0; picoperidamine, 2.0, 9.8; piclobetol, 7.6, 9.0; HH-197, 12.5, 143.0, respectively. Morphine, codeine and HH-197 caused bronchoconstriction, but picoperidamine and picrobetol caused bronchodilation. The antitussive and bronchodilatation effects of isoproterenol were abolished by propranolol. Each bronchoconstricting drug (i.e. morphine, codeine and HH-197) was administered concurrently with isoproterenol (10 mug/kg, i.v., and non-antitussive activity), and the cough reflex was observed. Compared with the single administration of each drug, respiratory resistance was decreased and the antitussive effect was increased. These results indicate a strong correlation between bronchodilatation and increased antitussive activity.
13.
Bratisl Lek Listy. 2011;112(3):131-5.
The influence of the PDE inhibitors on cough reflex in guinea pigs.
Abstract
In this study the effects of non-selective PDE inhibitors (theophylline and theobromine) and selective inhibitors of PDE 1, 3, 4 and 5 on cough, induced by citric acid, were evaluated. Inhalation of citric acid aerosol was used for cough provocation in healthy and ovalbumin-sensitized guinea pigs and the number of cough efforts was registered after visual and acoustic control by a skilled observer, with subsequent evaluation of airflow changes in a double chamber whole body plethysmograph. The pre-treatment with theophylline and theobromine (10 mg/kg b.w. intraperitoneally) decreased the number of cough efforts evoked by inhalation of citric acid aerosol (0.6 mol/l) in both healthy and ovalbumin-sensitized animals. The selective inhibitors (all 1 mg/kg b.w. intraperitoneally) of PDE1 (vinpocetin), PDE3 (cilostazol), and PDE4 (citalopram) showed antitussive effects in healthy guinea pigs. Conversely, the antitussive potential of PDE1 (vinpocetin), PDE4 (citalopram), and PDE5 (zaprinast) was observed in ovalbumin-sensitized animals. We conclude that the administration of non-selective PDE inhibitors influenced the citric acid-induced cough both in healthy and ovalbumin-sensitized guinea pigs, indicating the participation of a bronchodilating action and suppression of airway hyperreactivity in the cough suppression. With selective inhibitors, PDE4 inhibition seems to be the most effective in cough suppression, confirming its positive effects tested in chronic airway inflammatory diseases associated with bronchoconstriction and cough (Fig. 6, Ref. 27).
14.
Clin Chest Med. 2004 Jun;25(2):321-30.
Airway function in women: bronchial hyperresponsiveness, cough, and vocal cord dysfunction.
Abstract
Bronchial hyperreactivity and cough are common medical problems that occur more frequently in women. Differences in size, hormonal effects, density, and sensitivity to receptors and psychologic factors may all play a role, which results in increased expression of upper and lower airway disease. The reason that VCD occurs more commonly in women is not clear but many of the same explanations regarding bronchial hyperreactivity and cough may apply.
15.
Pulm Pharmacol Ther. 2011 Jun;24(3):263-6. doi: 10.1016/j.pupt.2010.10.001. Epub 2010 Oct 13.
The airway sensory hyperreactivity syndrome.
Abstract
After exclusion of diverse pulmonary illnesses, the remaining explanations for chronic cough include medication with angiotensin-converting enzyme (ACE) inhibitor, gastroesophageal reflux disease (GERD), and post-nasal drip. Different clinics report shifting frequencies for both the causes of chronic cough and the success of treatment. However, after all evaluations, differential diagnosis still leaves a group of patients with unexplained cough. This unexplained cough is also known as chronic idiopathic cough (CIC), though there are widely varying opinions as to its existence. Among patients previously diagnosed with CIC, a subgroup has been identified with both upper and lower airway symptoms, including cough induced by odours and chemicals, and with increased cough sensitivity to inhaled capsaicin, which is known to stimulate the airway sensory nerves. A suggested explanation for this condition is a hyperreactivity of the sensory nerves of the entire airways, and hence the condition is known as sensory hyperreactivity (SHR). SHR affects more than 6% of the adult population in Sweden. It is a longstanding condition, and is clearly associated with significant social and psychological impacts.
Copyright © 2010 Elsevier Ltd. All rights reserved.
16.
J Laryngol Otol. 1989 Jul;103(7):680-2.
Cough as the sole manifestation of airway hyperreactivity.
Abstract
The authors report 18 patients who presented to the ENT department with isolated cough, which had begun one month to 14 years previously. As the ENT examination was negative, the patients were referred to the Department of General Medicine where a bronchial reactivity test with acetylcholine was found to be positive, leading to a diagnosis of airway hyperreactivity. The group was predominantly female (15/18) and atopy was rare; indeed, only one patient, who had a history of allergic rhinitis, was found to be atopic. Bronchodilators and inhaled steroids cured or helped the cough in 16/18 patients. When a patient presents with chronic cough without other respiratory symptoms it is important to consider a diagnosis of airway hyperreactivity and to confirm this with a challenge test of bronchoconstriction.
17.
Pulm Pharmacol. 1996 Oct-Dec;9(5-6):293-7.
Codeine, cough and upper respiratory infection.
Eccles R1.
Abstract
Codeine is generally accepted as a standard or reference antitussive against which new antitussive medications can be compared. However there are very few studies which have investigated the antitussive efficacy of codeine using cough associated with upper respiratory tract infection (URTI) and there is little if any evidence to support the antitussive efficacy of codeine in this model. This paper discusses the mechanism of cough in man and describes some clinical investigations on the effects of codeine on cough associated with URTI. The recent clinical investigations do not provide any evidence to support an antitussive action of codeine in the treatment of cough associated with URTI yet there is evidence in the literature which indicates that codeine inhibits fictive cough in animal models and also has antitussive activity against both induced and chronic cough models in man. In order to explain these different effects of codeine on the different models of cough, a hypothesis is put forward that there are two cough pathways in man. A voluntary pathway associated with cough related to URTI which is not affected by codeine, and a reflex pathway associated with induced and chronic cough which is inhibited by codeine.
18.
Lancet. 1995 Sep 23;346(8978):791-5.
Are asthma-like symptoms due to bronchial or extrathoracic airway dysfunction?
Abstract
Patients with asthma-like symptoms may not have asthma but obstruction of the extrathoracic airway (EA). To evaluate if dysfunction of the EA causes asthma-like symptoms, we assessed bronchial and EA responsiveness to inhaled histamine in 441 patients who presented with at least one of three key symptoms--cough, wheeze, dyspnoea--but had neither documented asthma nor bronchial obstruction. The histamine concentrations causing a 20% fall in forced expiratory volume in 1 s (PC20FEV1) and a 25% fall in maximal mid-inspiratory flow (PC25MIF50) were used as respective thresholds of bronchial and EA responsiveness. Values 8 mg/mL or less indicated bronchial (B-HR) or EA hyper-responsiveness (EA-HR). The influence of concurrent upper respiratory tract diseases, such as post-nasal drip (PND), pharyngitis, laryngitis and sinusitis, was also assessed. We found four response patterns to the histamine challenge: EA-HR in 26.5% of the patients, B-HR in 11.1%, combined EA-HR and B-HR in 40.6%, and no-HR in 21.8%. Cough was reported by 79% of the patients, wheeze by 53%, and dyspnoea by 40%. Patients with cough as the sole presenting symptom (34.2%), as compared with those with wheeze and/or dyspnoea (20%), had significantly greater probability of having EA-HR (OR 5.35, 95% CI 3.25-8.82) and lower probability of having B-HR (OR 0.45, CI 0.28-0.70); patients with cough plus wheeze and/or dyspnoea (45.8%) had significantly greater probability of having both EA-HR and B-HR than either those with cough alone (OR 2.48, CI 1.49-4.13), or those with wheeze and/or dyspnoea but not cough (OR 1.74, CI 1.36-2.22). EA-HR alone or combined with B-HR was strongly associated with EA diseases, particularly pharyngitis and PND. Cough was significantly associated with PND, either when it was the sole symptom (OR 2.16, CI 1.14-4.09) or when it was combined with wheeze and/or dyspnoea (OR 3.53, CI 1.97-6.33). Our results suggest that extrathoracic airway dysfunction may account for asthma-like symptoms, particularly chronic cough. This abnormality seems to be sustained by chronic diseases of the upper respiratory tract.
Comment in
- Extrathoracic airway dysfunction. [Lancet. 1995]
19.
Arzneimittelforschung. 1998 Feb;48(2):149-53.
Antitussive effect of azelastine hydrochloride in patients with bronchial asthma.
Abstract
To investigate the efficacy of azelastine hydrochloride (azelastine, CAS 79307-93-0, Azeptin) in suppressing cough, 22 bronchial asthma patients complaining mainly of cough were given the drug for four weeks. Peak flow rates (PEFR), pulmonary function tests, capsaicin cough threshold, and bronchial hyperresponsiveness were compared pre- and post-administration. After four-week's administration of azelastine (2 mg twice daily), cough decreased as demonstrated in a significant progressive improvement of cough points. The morning PEFR (1/min) was improved significantly at one week and two weeks post-administration. Changes were from 434 +/- 26.4 pre-administration to 461 +/- 25.8 at Week 1 (p < 0.05), 462 +/- 26.7 at Week 2 (p < 0.05), 452 +/- 22.5 at Week 3, and 462 +/- 20.8 at Week 4. The evening PEFR (1/min) showed 439 +/- 22.2 pre-administration, 454 +/- 21.4 at Week 1, 464 +/- 22.4 at Week 2, 457 +/- 19.3 at Week 3 and 467 +/- 17.8 at Week 4, improvement being significant at Week 1 (p < 0.05). Regarding pulmonary function tests no significant changes were observed. FVC (liter), FEV1 (liter), and FEV1/FVC (%) were 3.45 +/- 0.86, 2.68 +/- 0.52, and 83.6 +/- 5.93 pre-administration; and 3.48 +/- 0.21, 2.72 +/- 0.65, and 84.1 +/- 6.21 post-administration, respectively. The capsaicin cough threshold [Ccap (mumol/l)] showed significant improvement, changing from 5.95 (0.016-50.0) pre-administration to 19.7 (0.08-50.0) post-administration (p < 0.05). Conversely, an index of bronchial hyperresponsiveness, Dmin (mg/dl;U), showed no significant changes (14.9 +/- 5.2 vs. 19.7 +/- 5.3). These results suggest that azelastine inhibits cough in patients with bronchial asthma by increasing the level of the cough threshold without changing bronchial hyperresponsiveness.
20.
Drugs Exp Clin Res. 2004;30(4):133-41.
Levocloperastine in the treatment of chronic nonproductive cough: comparative efficacy versus standard antitussive agents.
Abstract
The medical and social impact of cough is substantial. Current antitussive agents at effective doses have adverse events such as drowsiness, nausea and constipation that limit their use. There is also recent evidence that standard antitussive agents, such as codeine, may not reduce cough during upper respiratory infections. Therefore, there is a need for more effective and better-tolerated agents. The efficacy of levocloperastine, a novel antitussive, which acts both centrally on the cough center and on peripheral receptors in the tracheobronchial tree in treating chronic cough, was compared with that of other standard antitussive agents (codeine, levodropropizine and DL-cloperastine) in six open clinical trials. The studies enrolled patients of all ages with cough associated with various respiratory disorders including bronchitis, asthma, pneumonia and chronic obstructive pulmonary disease. Levocloperastine significantly improved cough symptoms (intensity and frequency of cough) in all trials, and improvements were observed after the first day of treatment. In children, levocloperastine reduced nighttime awakenings and irritability, and in adults it was effective in treating cough induced by angiotensin-converting enzyme inhibitors. When compared with other antitussive agents, levocloperastine had improved or comparable efficacy, with a more rapid onset of action. Importantly, no evidence of central adverse events was recorded with levocloperastine, whereas drowsiness was reported by a significant number of patients receiving codeine. Levocloperastine is an effective antitussive agent for the treatment of cough in patients of all ages. It has a more rapid onset of action than standard agents with an improved tolerability profile.
21.
Phytomedicine. 2015 Apr 15;22(4):504-9. doi: 10.1016/j.phymed.2015.03.004. Epub 2015 Mar 20.
Evaluation of pharmacodynamic activities of EPs® 7630, a special extract from roots of Pelargonium sidoides, in animals models of cough, secretolytic activity and acute bronchitis.
Abstract
BACKGROUND:
EPs(®) 7630 is a proprietary aqueous-ethanolic extract from roots of Pelargonium sidoides DC and has been demonstrated to dispose among others of antibacterial, antiviral, immunomodulatory, antioxidant, and tissue-protective activity. It is an approved medicinal product in more than 50 countries for the treatment of airway infections such as acute bronchitis, common cold, and sinusitis.
PURPOSE:
While the pharmacological effects of EPs(®) 7630 have extensively been evaluated in diverse in vitro test systems, the number of publications reporting results from in vivo models is limited.
STUDY DESIGN:
In the present study antitussive, secretolytic, and anti-inflammatory effects of EPs(®) 7630 were assessed in animal experiments following oral administration at human equivalent doses.
METHODS:
Antitussive effects were evaluated using ammonia- and citric acid-induced models of cough in mice (20, 40, 120 mg/kg) and guinea pigs (10, 20, 45 mg/kg), respectively. For the determination of secretolytic activity tracheobronchial secretion of intraperitoneally injected phenol red was determined in mice, while antiinflammatory action was assessed in an acute bacterial bronchitis model in rats.
RESULTS:
A significant and dose-dependent reduction of cough frequency was observed in both cough models, which was accompanied by a prolongation of cough latency time. Similarly, the extract exerted a marked secretolytic activity in mice. Induction of acute bacterial bronchitis caused characteristic histopathological changes in lung tissue adjacent to trachea and bronchi. The degree of these lesions was significantly reduced in rats treated with EPs(®) 7630 at doses of 30 and 60 mg/kg. This protective effect at least partially seems to be mediated by an up-regulation of superoxide dismutase and a subsequent protective effect against oxidative stress as indicated by a reduced serum level of malondialdehyde.
CONCLUSION:
The present data further support the therapeutic use of EPs(®) 7630 in respiratory tract infections and provide a basis for detailed studies on its bioactive constituents as well as their in vivo mode of action.
Copyright © 2015 Elsevier GmbH. All rights reserved.
KEYWORDS:
Acute bronchitis; Airway infection; Antitussive; Herbal medicinal product; Pelargonium sidoides; Secretolytic
22.
Schweiz Med Wochenschr. 1985 Mar 2;115(9):307-11.
[Objectivation of the effect of antitussive agents using tussometry in patients with chronic cough].
[Article in German]
Abstract
The antitussive effect of several antitussive agents has been objectively evaluated in patients with chronic stable cough due to bronchial carcinoma, pulmonary tuberculosis or chronic obstructive lung disease. The patients received the active antitussive drugs or placebo in a double-blind, randomized crossover design. The preparations were administered at 10 p.m. and 2 a.m. on 7 consecutive nights and no antitussive was given for the following 20 hours. Cough frequency and intensity were recorded from 10 p.m. until 6 a.m. The active medications were noscapine (30 mg), dextromethorphan (20 mg), dihydrocodeine (30 mg) and codeine (20, 30 and 60 mg) at 10 p.m. and 2 a.m. Cough frequency and intensity were objectively assessed with a pressure transducer placed over the trachea and recorded on a chartrecorder. Statistical analysis was performed with analysis of variance and multiple range testing. Noscapine, dextromethorphan, dihydrocodeine and codeine (60 mg) significantly (p less than 0.001) reduced the cough frequency compared to placebo. They also produced a greater reduction of cough intensity than placebo, codeine (20 mg) and codeine (30 mg) (p less than 0.001). The duration of action of low-dose codeine (6 hours) was unsatisfactory. Subjective preference for dextromethorphan indicates a psychotropic central nervous action of this drug not assessed by the measuring device. Noscapine was equally well tolerated but more neutral psychologically.
23.
Respirology. 2003 Jun;8(2):168-74.
Sputum eosinophilia and bronchial responsiveness in patients with chronic non-productive cough responsive to anti-asthma therapy.
Abstract
OBJECTIVE:
We aimed to examine airway inflammation and bronchial responsiveness in patients with chronic non-productive cough responsive to anti-asthma therapy.
METHODOLOGY:
Bronchial responsiveness to methacholine as well as the number of inflammatory cells and concentration of eosinophil cationic protein (ECP) in induced sputum were measured in 42 patients with chronic non-productive cough of unknown origin. Their response to bronchodilator, antiallergic and inhaled or oral glucocorticoid therapy was subsequently assessed.
RESULTS:
Complete remission of coughing was attained with anti-asthma therapies in 34 patients (responder group), while eight patients did not respond (non-responder group). Twenty patients in the responder group and three in the non-responder group showed bronchial hyperresponsiveness (BHR). The number of eosinophils and ECP levels in the sputum from responders with BHR were significantly increased when compared with those from non-responders and healthy subjects. These sputum measures were also significantly increased in responders without BHR when compared with healthy subjects. However, there were no significant differences in these inflammatory markers between the responders with and without BHR. The neutrophil numbers in the sputum from non-responders and responders both with and without BHR were also significantly higher than in control subjects, but there were no significant differences.
CONCLUSIONS:
These findings suggest that patients with chronic non-productive cough responsive to anti-asthma therapy characteristically have eosinophilic airway inflammation, which may play an important role in the development of chronic cough. Furthermore, the evaluation of not only bronchial responsiveness but also airway inflammation by examination of induced sputum may be useful for diagnosis and deciding on therapeutic strategies.
24.
Handb Exp Pharmacol. 2009;(187):155-86. doi: 10.1007/978-3-540-79842-2_8.
Peripheral mechanisms II: the pharmacology of peripherally active antitussive drugs.
Abstract
Cough is an indispensable defensive reflex. Although generally beneficial, it is also a common symptom of diseases such as asthma, chronic obstructive pulmonary disease, upper respiratory tract infections, idiopathic pulmonary fibrosis and lung cancer. Cough remains a major unmet medical need and although the centrally acting opioids have remained the antitussive of choice for decades, they have many unwanted side effects. However, new research into the behaviour of airway sensory nerves has provided greater insight into the mechanisms of cough and new avenues for the discovery of novel non-opioid antitussive drugs. In this review, the pathophysiological mechanisms of cough and the development of novel antitussive drugs are reviewed.
25.
J Korean Med Sci. 2002 Oct;17(5):616-20.
Cough sensitivity and extrathoracic airway responsiveness to inhaled capsaicin in chronic cough patients.
Abstract
Enhanced cough response has been frequently observed in chronic cough. Recently, extrathoracic airway constriction to inhaled histamine was demonstrated in some chronic cough patients. However, relation between extrathoracic airway hyperresponsiveness (EAHR) and cough sensitivity determined by capsaicin inhalation is unclear in each etiological entity of chronic cough. Seventy-seven patients, with dry cough persisting for 3 or more weeks, normal spirometry and chest radiography, and 15 controls, underwent methacholine bronchial provocation test and capsaicin cough provocation test. Elicited cough number and flow-volume curve was examined after inhalation of capsaicin to evaluate cough sensitivity and EAHR. Thirty-three patients, with postnasal drip, showed normal extrathoracic airway responsiveness, and 27 of them showed normal cough sensitivity to capsaicin. Cough sensitivity was enhanced in 14 patients with cough variant asthma (CVA) who showed bronchial hyperresponsiveness; EAHR to inhaled capsaicin was present in 12 of them. The remaining 30 patients were tentatively diagnosed as idiopathic chronic cough (ICC). Eleven ICC patients showed enhanced cough sensitivity and EAHR to inhaled capsaicin while 19 patients showed normal values. These results indicate that cough sensitivity is closely related with extrathoracic airway responsiveness during capsaicin provocation in some chronic cough patients. EAHR and enhanced cough sensitivity to inhaled capsaicin may be a part of mechanism developing chronic cough.
- PMID:
- 12378011
- PMCID:
- PMC3054948
- DOI:
- 10.3346/jkms.2002.17.5.616
- [Indexed for MEDLINE]
26.
Respiration. 2012;83(4):308-15. doi: 10.1159/000332835. Epub 2011 Nov 17.
Clinical, physiological and anti-inflammatory effect of montelukast in patients with cough variant asthma.
Abstract
BACKGROUND:
Cough variant asthma (CVA) is a phenotype of asthma presenting solely with coughing, characterized by airway hyperresponsiveness, eosinophilic inflammation and a cough response to bronchodilators. Leukotriene receptor antagonists (LTRAs) are antiasthma medications with anti-inflammatory and bronchodilatory properties. Although LTRAs exert antitussive effects in CVA, the mechanisms involved are unknown.
OBJECTIVES:
This study aimed to clarify the antitussive mechanisms of LTRAs in CVA patients.
METHODS:
We prospectively observed the effect of montelukast (10 mg) daily for 4 weeks in 23 consecutive nonsmoking adults with anti-inflammatory treatment-naive CVA. We evaluated, before and after treatment, the cough visual analogue scale (VAS), pulmonary function (spirometry and impulse oscillation), methacholine airway responsiveness, cough receptor sensitivity, expressed by the concentration of capsaicin inducing 2 or more (C2) and 5 or more (C5) coughs, sputum eosinophil counts and levels of inflammatory mediators, including cysteinyl leukotrienes, leukotriene B(4), prostaglandin (PG) D(2), PGE(2), PGF(2)(α) and thromboxane B(2). We compared the baseline characteristics of the patients based on the symptomatic response to montelukast, defined as a decrease in the cough VAS of >25% (n = 15) or ≤25% (n = 8).
RESULTS:
Montelukast significantly decreased the cough VAS (p = 0.0008), sputum eosinophil count (p = 0.013) and cough sensitivity (C2: p = 0.007; C5: p = 0.039), whereas pulmonary function, airway responsiveness and sputum mediator levels remained unchanged. Multivariate analysis showed that a better response to montelukast was associated solely with younger age (p = 0.032).
CONCLUSION:
The antitussive effect of montelukast in CVA may be attributed to the attenuation of eosinophilic inflammation rather than its bronchodilatory properties.
Copyright © 2011 S. Karger AG, Basel.
27.
J Allergy Clin Immunol Pract. 2018 Jul - Aug;6(4):1313-1320. doi: 10.1016/j.jaip.2017.09.026. Epub 2017 Nov 8.
The Value of Fractional Exhaled Nitric Oxide and Forced Mid-Expiratory Flow as Predictive Markers of Bronchial Hyperresponsiveness in Adults with Chronic Cough.
Abstract
BACKGROUND:
Bronchial provocation tests are standard for diagnosing the etiology of chronic cough, but they are time consuming and can induce severe bronchospasm. A safer and faster clinical examination to predict bronchial hyperresponsiveness (BHR) is needed.
OBJECTIVE:
The objective of this study was to investigate whether small-airway function tests can predict BHR in adult patients with chronic cough.
METHODS:
A retrospective, cross-sectional study of diagnoses made using spirometry and bronchial provocation test results was performed in 290 patients with chronic nonproductive cough. BHR-predictive values were analyzed via the area under receiver operating characteristic curves (AUCs). Optimal cutoff values were determined by maximizing the sum of sensitivity and specificity.
RESULTS:
Patients with chronic cough with BHR showed lower forced expiratory flow between 25% and 75% (FEF25%-75%), higher fractional exhaled nitric oxide (FENO), and a higher percentage of eosinophils in blood than patients without BHR (P < .0001 for all). The AUCs of FENO and FEF25%-75% for a BHR diagnosis were 0.788 (95% CI, 0.725-0.851) and 0.702 (95% CI, 0.641-0.763), respectively. Optimal cutoff values were 43 ppb for FENO and 78.5% for FEF25%-75%, with negative predictive values of 85.38% and 81.34%, respectively. The combined use of FENO and FEF25%-75% increased the AUC to 0.843 (95% CI, 0.794-0.892), significantly higher than either FENO (P = .012) or FEF25%-75% (P < .0001) alone.
CONCLUSIONS:
Small-airway dysfunction is present in patients with chronic cough and BHR. FEF25%-75% has value as a negative predictive parameter for BHR, especially when combined with FENO. FENO > 43 ppb and FEF25%-75% < 78.5% strongly predicted a positive bronchial provocation test.
Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
KEYWORDS:
Asthma diagnosis; Bronchial provocation; Cough; Fractional exhaled nitric oxide; Small-airway function
28.
Chest. 2017 Jun;151(6):1288-1294. doi: 10.1016/j.chest.2017.02.001. Epub 2017 Feb 10.
A Randomized Clinical Trial Comparing the Effects of Antitussive Agents on Respiratory Center Output in Patients With Chronic Cough.
Abstract
BACKGROUND:
Cough is produced by the same neuronal pool implicated in respiratory rhythm generation, and antitussive drugs acting at the central level, such as opioids, may depress ventilation. Levodropropizine is classified as a nonopioid peripherally acting antitussive drug that acts at the level of airway sensory nerves. However, the lack of a central action by levodropropizine remains to be fully established. We set out to compare the effects of levodropropizine and the opioid antitussive agent dihydrocodeine on the respiratory responses to a conventional CO2 rebreathing test in patients with chronic cough of any origin.
METHODS:
Twenty-four outpatients (aged 39-70 years) with chronic cough were studied. On separate runs, each patient was randomly administered 60 mg levodropropizine, 15 mg dihydrocodeine, or a matching placebo. Subsequently, patients breathed a mixture of 93% oxygen and 7% CO2 for 5 min. Fractional end-tidal CO2 (Fetco2) and inspiratory minute ventilation (V˙i) were continuously monitored. Changes in breathing pattern variables were also assessed.
RESULTS:
At variance with dihydrocodeine, levodropropizine and placebo did not affect respiratory responses to hypercapnia (P < .01). The ventilatory increases by hypercapnia were mainly accounted for by a rise in the volume components of the breathing pattern.
CONCLUSIONS:
The results are consistent with a peripheral action by levodropropizine; the assessment of ventilatory responses to CO2 may represent a useful tool to investigate the central respiratory effects of antitussive agents.
TRIAL REGISTRY:
European Union Clinical Trials Register (EudraCT No.: 2013-004735-68); URL: https://www.clinicaltrialsregister.eu/.
Copyright © 2017. Published by Elsevier Inc.
KEYWORDS:
CO(2) rebreathing; breathing pattern; chronic cough; dihydrocodeine; levodropropizine
29.
Respiration. 1975;32(1):32-45.
Respiratory and cough mechanics in antitussive trials. Responsivity of objective indices to the treatment of acute upper respiratory tract infections.
Abstract
The relative responsitivy of nine expirographic and airway indices to antitussive therapy was studied in a randomized double-blind trial in which 60 adults without bronchopulmonary disorders, but suffering from common colds, were given oral doses of five drug formulations or placebo during their initial 48 h of symptoms. Thoracic gas volume (Vtg), nasal (Rn), lower (Ra), total t[Rn + Ra]) and specific (sRa) airway resistances were determined plethysmographically; forced vital capacity (FVC), forced expiratory volume for the first second (FEV1.0) and maximal mid-expiratory flow rate (MMEFR) were recorded spirometrically. Cough pressure at peak flow furnished an index of cough (CI). The measurements were made at baseline and for 4 h after drug; medication was continued for two additional doses and the indices determined again the following morning. Abnormal control means were noted for Rn and [Rn + Ra] (90.8%), cough resistance (83.3%), MMEFR (58.3%), Ra and sRa (30.0%), but less ofter for FEV1.0, Vtg and FVC (6.6, 5.1 and 0.0%, respectively). Nasal and total airways flow resistance means were as sensitive to active therapy and in discriminating the relative worth of medication as direct CI values, Ra and sRa were less reliable, and the three spirometric functions were the lease responsive. This ranking was consistent with the common central airways location of subepithelial receptors responsible for cough and the associated reflex bronchoconstriction. The greatest changes in cough resistance followed treatment with the most significant activity in the nasal, as well as the lower tract, component of total airway resistance.
30.
Zhonghua Jie He He Hu Xi Za Zhi. 2015 Jan;38(1):55-8.
[Characteristics of airway hyperresponsiveness in children with chronic cough of different causes].
[Article in Chinese]
Abstract
OBJECTIVE:
To study the characteristics of airway hyperresponsiveness in children with different causes of chronic cough.
METHODS:
A prospective study was conducted in children suffering from chronic cough caused by a single reason at the department of respirology of Children's Hospital of Soochow University from April 2012 to December 2013. Bronchial provocation test, induced sputum eosinophil count, and exhale nitric oxide were detected at beginning and 4 weeks later. The severity of the CVA was classified according to the integral dose of histamine which resulted in a 20% (PD20) fall in forced expiratory volume in 1 s (FEV1). All patients received treatment according to the recommended guidelines for chronic cough in children of China. According to the responses to the treatment and the results of physical examinations and laboratory findings, a final diagnosis was confirmed.
RESULTS:
A total of 66 children were enrolled in this study, including cough variant asthma (CVA)in 17, upper airway cough syndrome (UACS) in 37, and post infection cough (PIC) in 12 cases. Positive AHR in CVA, UACS, and PIC groups was found in 17, 13, and 9 cases respectively at the first visit, and after 4 weeks, it was found in 17, 5, and 2 cases respectively. The severity of AHR in CVA, UACS and PIC at beginning and after 4 weeks were moderate to severe in 5, 0, 0 cases and 1, 0, 0 case; Mild to very mild in 12, 13, 9 cases and 16, 5, 2 cases.Negative response was found in 0, 24, 3 cases and 0, 32, 10 cases, respectively. The values of PD20 in CVA group (0.47 ± 0.28) mg were statistically lower those in UACS group (1.8 ± 0.64) mg and PIC group (1.2 ± 0.80) mg (P < 0.01) . The sputum eosinophil count was > 3% in all cases of CVA but all <3% in UACS and PIC.FeNO and sputum eosinophil counts were positively correlated (r = 0.687, P = 0.000) .
CONCLUSION:
The characteristics of airway responsiveness of chronic cough caused by different causes were varied in different AHR severity and course. Bronchial provocation test combined with induced sputum showed certain values for confirming the cause of chronic cough in children.
31.
J Formos Med Assoc. 1993 Mar;92(3):231-6.
Bronchoprovocation test by forced oscillation technique: airway hyperresponsiveness in chronic cough and psychogenic dyspnea subjects.
Abstract
By measuring the respiratory resistance (Rrs) with the forced oscillation technique, we evaluated the airway responsiveness to methacholine in four groups of subjects (30 normal, 21 asthmatic, 60 chronic cough, and 30 psychogenic dyspnea subjects). After evaluating the airway responsiveness of normal and asthmatic subjects, four patterns of dose-response curves were found. All of the asthmatic subjects were responders (types III and IV), whereas all but two of the normal subjects were nonresponders (types I and II). The responders had more bronchoconstriction than the nonresponders who presented with a significant decrease in FEV1 after the test. If airway hyperresponsiveness to methacholine was defined as Cmin < or = 12.5 mg/mL, then this test showed 100% sensitivity, 97% specificity, a positive predictive value of 95.5%, and a negative predictive value of 100%. According to these criteria, 18 of 60 (30%) chronic cough subjects and six of 30 (20%) psychogenic dyspnea subjects had airway hyperresponsiveness. We conclude that bronchoprovocation test by the forced oscillation technique is a simple, safe and time-saving tool for measuring airway hyperresponsiveness. We also found that airway hyperresponsiveness is a common finding in subjects with chronic cough, and is also present in some subjects with psychogenic dyspnea.
32.
Pulm Pharmacol Ther. 2008 Oct;21(5):794-7. doi: 10.1016/j.pupt.2008.06.002. Epub 2008 Jun 22.
Inhaled ethanol potentiates the cough response to capsaicin in patients with airway sensory hyperreactivity.
Abstract
A suggested explanation for airway symptoms induced by chemicals and scents is sensory hyperreactivity (SHR) of airway mucosal nerves. Patients with SHR have increased cough sensitivity to inhaled capsaicin, mediated by transient receptor potential (TRP) ion channels. In animal experiments, some TRP receptors are potentiated by ethanol, which is why in this study, the aim was to evaluate whether a pre-inhalation of ethanol could influence the capsaicin cough response in patients with SHR. Fifteen patients with SHR and 15 healthy controls were provoked on three occasions with two concentrations of inhaled capsaicin. Before each capsaicin provocation, a pre-inhalation of saline or one of two concentrations of ethanol was given in a double-blind, randomized fashion. The participants reacted in a dose-dependent way with cough on the capsaicin inhalations. Among the patients, but not in the control group, pre-inhalation of ethanol increased the cough response dose-dependently. The results suggest that the pathophysiology of SHR is related to airway mucosal TRP receptors in the sensory nerves. In scented products, the combination of ethanol as a solvent and perfume may augment an airway reaction in sensitive individuals.
33.
Pulm Pharmacol Ther. 2015 Aug;33:59-65. doi: 10.1016/j.pupt.2015.07.002. Epub 2015 Jul 10.
Therapeutic effects of naringin in a guinea pig model of ovalbumin-induced cough-variant asthma.
Abstract
Naringin, a well known component isolated from Exocarpium Citri Grandis, has significant antitussive effects. Recently, Naringin exhibited novel anti-inflammatory effect in chronic inflammatory diseases. In this work, we firstly evaluated the effects of naringin on enhanced cough, airway hyper-responsiveness (AHR), and airway inflammation in an ovalbumin-induced experimental cough-variant asthma (CVA) model in guinea pigs. We investigated the effect of naringin (18.4 mg/kg, per os, single dose or consecutively) on cough to inhaled capsaicin after challenge with an aerosolized antigen in actively sensitized guinea pigs. The effect of naringin on AHR to inhaled methacholine was evaluated 24 h after cough determination. Airway inflammation was assessed via bronchoalveolar lavage fluid (BALF) cytology and lung histopathology. Naringin, given consecutively, significantly reduced ovalbumin-induced enhanced cough and AHR, inhibited the increases in the leukocytes, interleukin-4 (IL-4), IL-5, and IL-13 in BALF compared with the model group. Moreover, the pathologic changes in lung tissues were clearly ameliorated by naringin treatment. These results suggest that naringin may be a beneficial agent for CVA treatment.
Copyright © 2015 Elsevier Ltd. All rights reserved.
KEYWORDS:
Airway hyper-responsiveness (AHR); Anti-inflammation; CVA; Cough; Naringin; Naringin (PubChem CID: 442428)
34.
Arzneimittelforschung. 2004;54(4):207-12.
Antitussive effects of the H1-receptor antagonist epinastine in patients with atopic cough (eosinophilic bronchitis).
Abstract
Chronic cough is the only symptom of eosinophilic bronchitis (EB). There is considerable overlap between EB and atopic cough. To investigate the antitussive effects of a histamine H1-recetor antagonist, epinastine hydrochloride (epinastine, CAS 80012-43-7, Alesion; 20 mg/day, once daily), cough scores, pulmonary function, capsaicin cough threshold, and bronchial hyperresonsiveness (BHR) to methacholine (MCh) were evaluated before and after a 4-week treatment with epinastine in patients with EB. In the epinastine group, the cough scores were decreased significantly (18.3 +/- 6.1 in week 1, 17.4 +/- 6.7 in week 2, 15.1 +/- 6.2 in week 3, 14.0 +/- 4.8 in week 4) in comparison with the value of 35.3 +/- 8.7 in week -2). The cough threshold for capsaicin improved from 1.70 +/- 3.04 micromol/l to 12.7 +/- 17.6 micromol/l in the epinastine group (p < 0.05; baseline vs. week 4) The bronchial hyperresponsiveness to MCh (Dmin) did not change significantly either in the epinastine or the placebo groups. The morning and evening peak expiratory flow rate (PEFR, L/min) did not change from the baseline period in either the epinastine or the placebo groups. These results suggested that epinastine may be useful for treating patients with EB and that histamine H1-receptor is related to the pathophysiology of coughing in EB.
35.
Chest. 1989 Mar;95(3):544-8.
Bronchial hyperreactivity and cough due to angiotensin-converting enzyme inhibitors.
Abstract
Seventeen patients using angiotensin-converting enzyme (ACE) inhibitors for hypertension were evaluated with baseline spirometry followed by determination of bronchial reactivity by challenge with methacholine. There were nine coughers and eight noncoughers in the study. Among the nine coughers, eight demonstrated bronchial hyperreactivity. Conversely, none of the noncoughers disclosed bronchial hyperreactivity. Eight of the nine coughers were rechallenged two to six months following cessation of ACE inhibitor therapy. Six of these eight showed persistent bronchial hyperreactivity. We conclude that cough is associated with the use of ACE inhibitors in patients with underlying bronchial hyperreactivity. The findings indicate caution in administration of ACE inhibitors in asthmatic patients and those with known bronchial hyperreactivity.
36.
J Asthma. 2003 Sep;40(6):653-9.
Exhaled nitric oxide as a simple assessment of airway hyperresponsiveness in bronchial asthma and chronic cough patients.
Abstract
Exhaled nitric oxide (NO) has been suggested to be a marker of airway inflammation. The aim of this study was to evaluate the role of exhaled NO in bronchial asthma and chronic cough patients to predict bronchial hyperresponsiveness (BHR). We measured the exhaled NO concentration using the chemiluminescence method in 52 asthma patients (group I consisting of 24 without prior inhaled corticosteroid (ICS) use, and group II consisting of 28 previously on ICS and 16 chronic cough patients in group III). In addition to regular examinations, spirometry and methacholine inhalation tests using the Astograph were done. In group I, a significantly negative correlation was observed regarding the exhaled NO concentration with FEV1/FVC%, V50, and BHR that was assessed as Dmin and PD35-Grs, and a positive correlation with peripheral blood eosinophils. In group III, a significantly negative correlation was seen regarding the exhaled NO concentration with BHR. We thus concluded that measuring exhaled NO concentration appears to be a useful noninvasive method to predict the BHR, airway obstruction, and inflammation in asthma and chronic cough patients.
37.
J Hum Hypertens. 1992 Oct;6(5):387-92.
Airway responsiveness and cough induced by angiotensin converting enzyme inhibition.
Abstract
Dry cough is one of the most common side-effects of angiotensin converting enzyme inhibitors. The mechanism of cough induced by ACE inhibitors is not completely understood and may be related to bronchial hyperreactivity and/or an accumulation of kinins. In a placebo-controlled, double-blind randomised study, the effect of captopril on lung function and bronchial reactivity to histamine and bradykinin was investigated in eight asthmatic and 12 hypertensive patients (six with and six without cough during previous ACE inhibition). Lung function did not change in any patient after a single (25 mg) or short-term (2 x 25 mg for two weeks) administration of captopril. Bronchial reactivity to histamine and bradykinin remained unaltered in all groups. In hypertensive patients with cough, reactivity to histamine tended to be more pronounced and bronchial hyperreactivity to be more frequent than in those without cough. In conclusion, the present results do not support a major role for kinins in cough induced by ACE inhibition. On the other hand, bronchial hyperreactivity may be important in some patients. Additionally, these results demonstrate that treatment with ACE inhibitors is safe in most patients with bronchial asthma.
38.
Eur Respir J. 2000 Apr;15(4):682-6.
Airway inflammation, airway responsiveness and cough before and after inhaled budesonide in patients with eosinophilic bronchitis.
Abstract
Eosinophilic bronchitis is a common cause of chronic cough, characterized by sputum eosinophilia similar to that seen in asthma, but unlike asthma the patients have no objective evidence of variable airflow obstruction or airway hyperresponsiveness. The reason for the different functional associations is unclear. The authors have tested the hypothesis that in eosinophilic bronchitis the inflammation is mainly localized in the upper airway. In an open study the authors measured the lower (provocative concentration causing a 20% fall in forced expiratory volume in one second (PC20)) and upper (PC25 MIF50) airway responsiveness to histamine, lower and upper airway inflammation using induced sputum and nasal lavage, in II patients with eosinophilic bronchitis. The authors assessed changes in these measures and in cough reflex sensitivity to capsaicin and cough severity after 400 microg of inhaled budesonide for 4 weeks. A nasal eosinophilia was present in only three patients with one having upper airway hyperresponsiveness. Following treatment with inhaled corticosteroids the geometric mean sputum eosinophil count decreased from 12.8% to 2.9% (mean difference 4.4-fold, 95% confidence interval (CI) 2.14-10.02), the mean +/- sem cough visual analogue score on a 100 mm scale decreased from 27.2 +/- 6.6 mm to 12.6 +/- 5.7 mm (mean difference 14.6, 95% CI 9.1-20.1) and the cough sensitivity assessed as the capsaicin concentration required to cause two coughs (C2) and five coughs (C5) improved (C2 mean difference 0.75 doubling concentrations, 95% CI 0.36-1.1; C5 mean difference 1.3 doubling concentration, 95% CI 0.6-2.1). There was a significant positive correlation between the fold change in sputum eosinophil count and doubling dose change in C5 after inhaled budesonide (r=0.61). It is concluded that upper airway inflammation is not prominent in eosinophilic bronchitis and that inhaled budesonide improves the sputum eosinophilia, cough severity and sensitivity suggesting a causal link between the inflammation and cough.
39.
Adv Exp Med Biol. 2016;935:43-52. doi: 10.1007/5584_2016_30.
Cough and Arabinogalactan Polysaccharide from the Bark of Terminalia Arjuna.
Abstract
In this work we investigated the antitussive activity of the medicinal tree Terminalia arjuna. We used the stem bark for extraction and preparation of water extracted isolate and its two fractions: acetone-soluble (TA-S) and acetone precipitated (TA-P) fraction. The presence of a pectic arabinogalactan was confirmed in TA-P fraction by chromatographic and spectroscopic analysis. The antitussive activity of samples was assessed after oral administration in a dose of 50 mg.kg(-1) in healthy guinea pigs, in which cough was elicited by inhalation of citric acid (0.3 mol/L) in body plethysmograph. The water extracted isolate showed a significant ability to decrease the number of cough efforts by 64.2 %; the antitussive activity on par with that of codeine phosphate. The TA-P fraction showed the antitussive activity of 54.8 %. In contrast, TA-S fraction had only a mild antitussive activity. No changes in in vivo airway resistance were noted. We conclude that arabinogalactan is an essential component of Terminalia arjuna that underlies its antitussive action.
KEYWORDS:
Antitussive activity; Arabinogalactan; Codeine phosphate; Cough; Plethysmography
40.
Pol Merkur Lekarski. 1999 May;6(35):281-5.
[Cough, bronchoconstriction and bronchial hyperreactivity in relation to treatment with angiotensin-converting enzyme].
[Article in Polish]
Abstract
In the paper available information concerning the influence of treatment with angiotensin converting enzyme inhibitors (ACE-I) on cough, bronchial hyperreactivity and bronchoconstriction are reviewed. Cough occurs in 0.7% to 19% of patients treated with angiotensin converting enzyme inhibitors according to various reports. In the mechanism of angiotensin converting enzyme inhibitor-induced cough accumulation of bradykinin and substance P due to decreased degradation of this mediators caused by ACE-I may be involved. Part of tussive effect may be mediated via prostaglandins and histamine. In a few studies symptoms of airway obstruction and asthma worsening in relation to treatment with this drugs was reported. However, majority of reports suggest safety in taking ACE-I by patients with asthma. The only effective method to relieve angiotensin converting enzyme-induced cough is a drug withdrawal. The change of drugs within the whole class of ACE-I does not bring effect.
41.
Arerugi. 1998 Jan;47(1):48-53.
[Effects of oxatomide, H1-antagonist, on postinfectious chronic cough; a comparison of oxatomide combined with dextromethorphan versus dextromethorphan alone].
[Article in Japanese]
Abstract
H1 antihistamines have been shown to have antitussive effects in patients with asthma and postnasal drip. In Japan, no study has been performed to determine whether orally administered oxatomide, H1 antihistamine, can reduce the chronic cough seen in patients with post-upper-airway infection (postinfection). Patients who had chronic cough of more than three weeks' duration and a history of post-upper-airway infection took part in the study. None had any history of nasal disease, gastroesophageal reflux, bronchial asthma, or other chronic pulmonary disease. All patients were non-smokers, and none used ACE inhibitors. They had normal CRP concentrations, peripheral white blood cell and eosinophil counts, serum IgE concentrations, titers of cold agglutinins and antibodies to Mycoplasma pneumoniae, chest roentgenograms, and respiratory function tests. A prospective randomized, open design was used. The effect of one week of treatment with dextromethorphan (D) or with D plus oxatomide (D + O) on the severity of cough, as estimated by cough diary, were examined. Twenty-two patients entered the study, and 20 were eligible for efficacy and side-effect analyses. Nine patients receiving D and 11 receiving D + O completed the protocol. Patients' characteristics before the start of the study, such as severity and duration of cough, and laboratory data, were not significantly different between the two groups. From trial day 5 to 7, improved rates of cough were significantly higher with D + O than with D alone (p < 0.05). Combination therapy with oxatomide and dextromethorphan reduces subjective perception of cough as estimated by cough diary. These results suggest that oxatomide, H1 antihistamine may improve chronic cough in patients with post-upper-airway infection.
42.
Clin Respir J. 2017 Nov;11(6):733-738. doi: 10.1111/crj.12409. Epub 2015 Dec 7.
The duration of cough in patients with H1N1 influenza.
Abstract
BACKGROUND:
Cough is one of common symptoms of influenza, the cough duration and prevalence of postinfectious cough (PIC) after viral upper respiratory tract infection has not been well described.
OBJECTIVES:
We aim to investigate the duration of cough and prevalence of PIC and its relation with acute symptoms, airway inflammation and cough sensitivity in patients with H1N1 influenza.
METHODS:
Patients with acute symptoms of H1N1 influenza were enrolled and followed up until cough relived. Spirometry, induced sputum test, capsaicin challenge test were conducted in patients with PIC. Cough sensitivity was presented as logarithm of provocative concentration inducing five or more coughs (logC5).
RESULTS:
A total of 141 cases with H1N1 influenza were enrolled. In patients with H1N1 influenza, 97.2% of them complained cough. The duration of cough was as following: <1 week (73.0%); 1-2 weeks (7.8%); 2-3 weeks (7.8%); ≥3 weeks (8.5%). Twelve (8.5%) patients had cough lasting more than 3 weeks (PIC), 4 (2.8%) patients developed chronic cough (>8 weeks). Acute symptoms, spirometry, bronchial responsiveness and sputum differential cell count were similar between patients with PIC and those without PIC, however, there was a higher prevalence of previous PIC (58.3% vs 14.7%, P < 0.05) and elevated cough sensitivity (lgC5: 1.18 ± 0.58 vs 2.73 ± 0.33, P < 0.01) in patients with PIC as compared with the patients without PIC.
CONCLUSIONS:
Acute cough is common in patients with H1N1 PIC, only a few of patients develop chronic cough. Acute symptoms cannot predict PIC which is related with previous PIC and increased cough sensitivity.
© 2015 John Wiley & Sons Ltd.
KEYWORDS:
cough - cough sensitivity - influenza - postinfectious cough
43.
Pulm Pharmacol Ther. 2009 Apr;22(2):114-20. doi: 10.1016/j.pupt.2008.12.001. Epub 2008 Dec 16.
Eosinophilic airway disorders associated with chronic cough.
Abstract
Chronic cough is a major clinical problem. The causes of chronic cough can be categorized into eosinophilic and noneosinophilic disorders, the former being comprised of asthma, cough variant asthma (CVA), atopic cough (AC) and non-asthmatic eosinophilic bronchitis (NAEB). Cough is one of the major symptoms of asthma. Cough in asthma can be classified into three categories; 1) CVA: asthma presenting solely with coughing, 2) cough-predominant asthma: asthma predominantly presenting with coughing but also with dyspnea and/or wheezing, and 3) cough remaining after treatment with inhaled corticosteroid (ICS) and beta2-agonists in patients with classical asthma, despite control of other symptoms. There may be two subtypes in the last category; one is cough responsive to anti-mediator drugs such as leukotriene receptor antagonists and histamine H1 receptor antagonists, and the other is cough due to co-morbid conditions such as gastroesophageal reflux. CVA is one of the commonest causes of chronic isolated cough. It shares a number of pathophysiological features with classical asthma with wheezing such as atopy, airway hyperresponsiveness (AHR), eosinophilic airway inflammation and various features of airway remodeling. One third of adult patients may develop wheezing and progress to classical asthma. As established in classical asthma, ICS is considered the first-line treatment, which improves cough and may also reduce the risk of progression to classical asthma. AC proposed by Fujimura et al. presents with bronchodilator-resistant dry cough associated with an atopic constitution. It involves eosinophilic tracheobronchitis and cough hypersensitivity and responds to ICS treatment, while lacking in AHR and variable airflow obstruction. These features are shared by non-asthmatic eosinophilic bronchitis (NAEB). However, atopic cough does not involve bronchoalveolar eosinophilia, has no evidence of airway remodeling, and rarely progresses to classical asthma, unlike CVA and NAEB. Histamine H1 antagonists are effective in atopic cough, but their efficacy in NAEB is unknown. AHR of NAEB may improve with ICS within the normal range. Taken together, NAEB significantly overlaps with atopic cough, but might also include milder cases of CVA with very modest AHR. The similarity and difference of these related entities presenting with chronic cough and characterized by airway eosinophilia will be discussed.
44.
Eur Respir J. 1991 Oct;4(9):1078-9.
The effect of altering airway tone on the sensitivity of the cough reflex in normal volunteers.
Abstract
Cough is frequently the presenting symptom of bronchial asthma, although cough can result from a wide variety of other respiratory disease. Treatment of chronic cough has proved extremely difficult. It has been suggested that treatment with bronchodilators may reduce the symptom of cough. In this study the effect of altering airway tone on the sensitivity of the cough reflex was determined. Twelve normal, healthy volunteers took part. The number of coughs following inhalations of single breaths of doubling concentrations of capsaicin (1.95-500 microM) was recorded before and after doses of salbutamol, methacholine and saline which altered forced expiratory volume in one second (FEV1) by 6.2 +/- 2.6%, -8.8 +/- 3.2% and -0.18 +/- 1.38%, respectively. In a further study the cough response was recorded before and after doses of salbutamol and ipratropium bromide, both of which reduced baseline respiratory resistance and resistance measured after capsaicin. Ipratropium bromide, salbutamol and methacholine, despite having significant effects on airway tone, did not change the sensitivity of capsaicin-induced cough. Thus, if bronchodilator drugs are antitussive in non-asthmatic patients, then this is unlikely to be due to an effect on the sensitivity of the cough reflex.
45.
Pulm Pharmacol. 1992 Sep;5(3):191-8.
Relationship of airway responsiveness to agents causing bronchoconstriction and cough in sensitized guinea-pigs.
Abstract
The relationship between airway responsiveness to bronchoconstrictor- and cough-inducing stimuli has been examined in Ascaris suum-sensitized conscious guinea-pigs. Guinea-pigs were sensitized to Ascaris suum [4000 PNU and 100 mg Al(OH)3 i.p. on days 1 and 7] and then challenged with aerosolized antigen on days 21, 28 and 35. At day 35, antigen-exposure produced an early bronchoconstrictor response (EBR) and in about 50% of the animals also a late bronchoconstrictor response (LBR) commencing 4-8 h later. The bronchial responsiveness to inhaled histamine was increased in sensitized guinea-pigs and increased further 20-24 h after acute antigen challenge. Guinea-pigs developing only EBR were equally sensitive to histamine as those having both EBR and LBR. In contrast, the cough and reflex bronchoconstriction produced by inhaled citric acid (0.40 M, acting on capsaicin-sensitive sensory neurons) and cigarette smoke (3 min exposure; exciting both capsaicin-sensitive neurons and rapidly adapting stretch receptors) were not altered by sensitization. Furthermore, acute antigen challenge did not alter the effect of citric acid as measured 24 h later. The antigen-induced airway hyperresponsiveness to histamine was not accompanied by an altered sensitivity of airway sensory nerves mediating cough (and reflex bronchoconstriction), demonstrating that bronchial- (airway obstruction) and sensory- (cough) hyperresponsiveness involve separate and independent mechanisms.
46.
Pulm Pharmacol Ther. 2004;17(6):463-4.
Mechanisms of chronic cough.
Abstract
Chronic and uncontrollable cough is one of the most common and debilitating symptoms found in patients with chronic airway diseases. The physical trauma and stresses of chronic cough on the airway mucosa and respiratory muscles can further worsen the deteriorating process of the airway diseases. The articles presented in this section focus primarily on the effect of chronic cough on the cell structure and protective function of the airway mucosa, the mechanisms underlying the hypersensitivity of chronic cough, and new target areas for antitussive drug development. A major emphasis has been placed on the neuronal plasticity found at the peripheral and central sites of the neural pathway mediating the cough reflex, and its potential role in the development of chronic cough is discussed. A number of new and important questions concerning the physiological and pharmacological mechanisms underlying chronic cough have emerged in these presentations. Further studies are required to answer these questions, which should bring a better understanding of the pathogenic mechanisms of chronic cough and lead to the development of new therapeutic strategies.
47.
Pulm Pharmacol Ther. 2018 Apr;49:112-118. doi: 10.1016/j.pupt.2018.02.001. Epub 2018 Feb 10.
Small and large airway reactions to osmotic stimuli in asthma and chronic idiopathic cough.
Abstract
BACKGROUND:
Chronic cough is a common symptom and related to several pulmonary, airway and heart diseases. When all likely medical explanations for the coughing are excluded, there remains a large group of patients with chronic coughing, which is mostly a cough reflex easily triggered by environmental irritants and noxious stimuli. The main aim of this study was to improve the diagnostic ability to differentiate chronic idiopathic cough (CIC) from asthma.
METHODS:
Twenty-three patients with CIC, 16 patients with mild asthma and 21 control participants were included. The study consisted of three randomised bronchial provocations with osmotic stimuli: mannitol, eucapnic dry air and hypertonic saline. At each provocation lung function was assessed by spirometry and impulse oscillometry (IOS).
RESULTS:
In a comparison of the groups, while the FEV1 measurements did not differ, the CIC group had increased airway resistance and reactance after provocation with hypertonic saline compared to the control subjects. After mannitol provocation the patients with asthma had significantly increased airway resistance compared to the controls and from eucapnic dry air provocations these patients had a significant reduction in spirometry values and increased airway resistance compared to both the patients with CIC and the controls.
CONCLUSION:
The asthma group reacted in a predictable way with impaired lung function from osmotic provocations, whereas the patients with CIC demonstrated peripheral airway changes from hypertonic saline, also known to be a noxious stimulus. The IOS method uncovers differences between patients with CIC and control participants that contribute to our ability to provide a correct diagnosis.
Copyright © 2018. Published by Elsevier Ltd.
KEYWORDS:
Asthma; Chronic idiopathic cough; Impulse oscillometry; Osmotic stimuli; Sensory hyperreactivity; Small airways
48.
J Pharm Pharmacol. 1997 Oct;49(10):1045-9.
Assessment of the antitussive efficacy of codeine in cough associated with common cold.
Abstract
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.
49.
J Asthma. 1994;31(6):463-72.
Cough receptor sensitivity and bronchial responsiveness in patients with only chronic nonproductive cough: in view of effect of bronchodilator therapy.
Abstract
Twenty-two patients with only chronic nonproductive cough lasting for more than 2 months were prospectively examined to determine whether airway cough receptor sensitivity and bronchial responsiveness relate to the efficacy of bronchodilator therapy on the cough. Clenbuterol (10 micrograms, 4 times a day for 1 week) was effective on the cough in 10 patients (group 2) but not in the other 12 patients (group 1). Cough threshold to inhaled capsaicin was significantly less in group 1 than in group 2 at the first visit but not after the therapy when the cough stopped. Bronchial responsiveness to methacholine (PC20-FEV1) was not heightened in group 1, while that in group 2 was hyperreactive. These findings suggest that nonproductive cough is elicited based on two different mechanisms: (1) heightened airway cough receptor sensitivity in bronchodilator-resistant cough and (2) bronchoconstriction in bronchodilator-responsive cough such as cough-variant asthma.
50.
Med Pregl. 2010 Mar-Apr;63(3-4):170-4.
[The impact of inhaled corticosteroids on cough and bronchial hyperreactivity in cough variant asthma].
[Article in Serbian]
Abstract
INTRODUCTION:
Classic asthma is characterized by cough, wheezing and dyspnea. Cough, however, may be the sole presenting symptom of asthma and this type of asthma is known as cough-variant asthma. The therapeutic approach to cough variant asthma is similar to that of the typical form of asthma. A diagnosis of cough-variant asthma is made when a chronic cough is associated with airway hyperresponsiveness and a favorable response to asthma therapy in the absence of other discernible cause. The aims of this study were to analyse the influence of inhaled corticosteroids on cough and bronchial hyperresponsiveness.
MATERIAL AND METHODS:
The study included 55 patients with cough as the sole presenting symptom. 40 patients (Group A) were treated with inhaled corticosteroids and beta2 agonists for eight weeks while 15 patients (Group B) were treated only with oral beta2 agonists. The nonspecific bronchoprovocative test with histamine was performed on all the patients before the treatment and after the examination and there was established the provocative dose of histamine causing the 20% fall in FEVI (PD20).
RESULTS:
At the end of the study in Group A we found a statistically significant decrease of PD20 0.98 +/- 0.86 vs. 1.58 +/- 1.06 (p < 0.005), while in Group B there were no significant changes. In 90% of the patients treated with inhaled corticosteroids the cough was completely relieved while in 80% of the patients treated with only beta2 agonists the cough has remained unchanged.
CONCLUSION:
Inhaled corticosteroids are choice drugs for the treatment of cough-variant asthma because they relieve cough and decrease bronchial hyperresponsiveness, thus ultimately reducing the risk of classic asthma.
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