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Cough from a pharmacological point of view Abstract. Drugs with various protussive or antitussive mechanisms of action are used to alleviate cough symptoms. Phytopharmaceuticals also play an important role. When determining the etiology of persistent cough, long-term medication should be critically assessed and on suspicion of an adverse drug reaction adjusted as necessary.

Cough is the number one symptom for patients to visit a physician worldwide. It is an important neuronal reflex which serves to protect the airways from inhaled exogenous microorganisms, thermal and chemical irritants. Moreover, it prevents the airways from mucus retention.The cough reflex is initiated by activation of different cough receptors. These cough receptors can be divided into three groups according to their electrophysiological properties: into the two Aδ-fiber types "rapid-adapting mechanoreceptor" (RAR) and "slow-adapting mechanoreceptor" (SAR), and the C-fiber receptor.The stimulus is detected by cough receptors which conduct the signal to the cerebral cough centre via vagal-sensory neurons. The cough itself is mediated by efferent motoneurons. Hence the cough reflex consists of 5 functionally sequential parts 1: the cough receptors 2, the primary afferent fibres of the N. vagus 345, N. trigeminus and N. glossopharyngeus 1, the cough centre in the medulla oblongata (N. tractus solitarius) 678, the afferent fibres of the N. phrenicus, spinal nerve and N. laryngeus recurrens, as well as the diaphragm and the abdominal, intercostal and laryngeal muscles. The cough receptors are mainly located in the larynx, trachea and main bronchi 2.The event of coughing can be divided into four subsequent parts: After the first phase of fast inspiration with an opened glottis, there is compression with a closed glottis and increasing tracheal pressure, acceleration and ultimately maximum expiration with an opened glottis 9. According to its characteristics, cough can be split into two distinct types, "aspiration cough", which is loud and involuntary, and "urge-to-cough sensation", which describes an irritant, scratchy, and controlled cough of slowly increasing intensity 10.Acute cough mostly develops because of infection of the respiratory system 111213 and ends spontaneously after 4 weeks. In contrast to this, bacterial infection with pathogens like Adenovirus, Bordetella pertussis and Mycoplasms can last up to 8 weeks 121314. In additional to the division of cough according to its cause, it can also be differentiated according to its manner: dry and mucus-producing cough.With this review we want to give an overview of neuronal processes and mechanisms, as well as diagnostics of and therapy for chronic cough. Thereby the focus is also placed on the efficiency of already established and potential future antitussive agents., (© Georg Thieme Verlag KG Stuttgart · New York.)

There is a long list of differential diagnoses for chronic cough lasting longer than 4 weeks in children. Diagnostic work up starts with a detailed history taking and a clinical investigation followed by a chest X-ray (in one plane) and a spirometry. For the latter reliable results can be achieved by children older then 5 years. If the diagnostic work up is still inconclusive and if the child is in good clinical condition, a 4 weeks' course of inhalation therapy with steroids and betamimetics together with a 2 weeks' course of antibiotics with a macrolide is warranted. In case coughing persists a thorough diagnostic work up is indicated to rule out conditions like cystic fibrosis, relevant humoral immuno-deficiencies, primary ciliary dyskinesia, anatomic malformation or chronic pulmonary aspiration, preferably done by a pediatric pulmonologist. Chronic cough has to be considered abnormal in any child under the age of 1 year. For this age group a final diagnosis is of special importance.

Objective: For the investigation of the benefits and tolerability of a syrup made of extracts from thyme and ivy (Bronchipret Saft) in children and adolescents (ages: 2-17 years) with acute bronchitis and productive cough, a non-interventional postmarketing surveillance study was carried out., Methods: Prerequisites for participation in the surveillance study were productive cough for a maximum of two days, at least ten coughing fits per day prior to the initiation of treatment (estimation of the parents or adolescent) and a Bronchitis Severity Score (BSS) of at least five points. The primary outcome measure was the change in the clinical symptoms based on the BSS. Treatment was carried out using age-appropriate dosages prescribed by the doctor on a case-by-case basis in accordance with the summary of product characteristics. Documentation of the course of treatment for the surveillance study was to be taken on treatment days 0, 4 and 10., Results: For the descriptive, statistical evaluation of the surveillance study, the data from 1234 children and adolescents (623 boys and 611 girls) in the age groups < 2 years (N = 12), 2-5 years (N = 372), 6-11 years (N = 438) and 12-17 years (N = 412) were available. The correspondence of the dosages to the age-specific recommendations of the valid summary of product characteristics varied from 81.7% to 93.9% in the different age groups. The average BSS value decreased from 8.8 points to 4.8 on treatment day 4 and to 1.3 points after about ten days of treatment. Compared to that of the initial examination, the number of documented coughing fits had decreased on the average by 18.7 (81.3%) on day 10. The responder rates of the various age groups were 92.0% to 96.5%. The tolerability was rated as very good to good by the physicians in 96.5% of the cases. Two female patients had temporary, not serious adverse drug reactions (stomache ache, mild nausea)., Conclusion: Acute bronchitis with productive cough in (young) children and adolescents can be treated safely and effectively with the thyme and ivy syrup. A ten-day treatment using age-appropriate dosages led to a clear improvement in the symptoms or cure with very good tolerability.

Background: Inhalation of l-menthol inhibits cough and has been shown to reduce respiratory discomfort associated with loaded breathing. We investigated the effect of the inhalation of a 1% l-menthol solution in the premedication of fiberoptic bronchoscopy (FB) on the frequency of cough and the irritability of the tracheobronchial mucosa during FB in a blinded, randomized and placebo controlled study., Methods: 64 pat. (30-78 yrs, 55 males) underwent routine FB. Premediction: atropine and hydrocodone s.c., inhalation of oxybuprocain by means of a jet nebulizer, sedation on demand. Verum-group: inhalation of 3 ml 1% l-menthol-solution. Placebo-group: 3 ml 0.05% l-menthol (to provide the typical smell). Before and after inhalation peak respiratory flow (PEF) was registered, during FB the frequency of cough was measured. The bronchoscopist scored the irritability of the tracheobronchial mucosa using a visual analog scale. The patients answered a questionnaire addressing their perception of dyspnea and cough on the day after FB compared to the day before., Results: The cough counts didn't show a significant difference between the groups. The irritability of the mucosa was increased in the verum group (main bronchus verum 62.2 +/- 22, placebo 48.6 +/- 23 [mm vissual analog scale, p = 0.03]). Cough and dyspnea reported by the patients decreased on the day after FB significantly compared to the day before (no difference between the groups). The inhalation of 1% l-menthol induced a significant increase of the PEF (verum 307 +/- 103 pre, 329 +/- 84 post [l/min, p = 0.003]) compared to placebo., Conclusions: The inhalation of 1% l-menthol did not enhance the tolerability of the FB. However, l-menthol induced a significant increase of the PEF immediately after inhalation. Finally sensation of dyspnea was decreased in both groups at the day post FB.

History and Clinical Findings: A 58-year-old man was admitted after he was found to have a huge aneurysm of the thoracic aorta. 38 months previously he had first experienced subacute pain in the right thorax. After this the aneurysm gradually increased in size. On admission a pulsating mass, 20 cm in diameter, was obvious, having broken through the right ventral thoracic wall. It was causing venous inflow congestion in the upper part of the body. The patient's general condition was poor: he had marked orthopnoea., Investigations: Serological tests for syphilis gave the following results: VDRL test, 1:32; FTA-ABS test reactive; TPHA test, 1:8000; treponema-specific IgM negative. Computed tomography with contrast-medium injection exactly defined site and extent of the aneurysm. It started at the aortic root and extended to the aortic arch. Third-degree aortic valvar regurgitation was demonstrated on echocardiography. Pulmonary function tests indicated severe restrictive ventilatory abnormality with clearly reduced respiratory reserve., Treatment and Course: The symptoms improved after 2 weeks on oral medication of captopril (25 mg/d), furosemide (80 mg/d), spironolactone (100 mg/d), codeine phosphate (90 mg/d) and thick paraffin (20 mg/d as needed). The patient declined further treatment. He died 8 weeks later at home.

Cough is a powerful physiological reflex mechanism that causes central airways to be cleared of foreign material and excess secretions. Chronic cough is a very common presenting symptom in general practice with a prevalence in the population of about 5%. As a general rule, persistent cough represents organic disease of the upper and lower airways, the lung parenchyma, the pulmonary circulation, the pleural space, the mediastinum and the upper gastro-intestinal tract. The most common cause is cigarette smoking, but virtually any chronic lung disease may be occasionally associated with cough. Complications of coughing are tussive syncopes, rib fractures, rupture of respiratory muscles and eventually hernias. Based on a detailed clinical history and physical examination, the investigation includes a chest radiograph, spirometry, and sputum smears. Radiography of the sinuses, bronchoscopy and upper gastro-intestinal endoscopy may be added. If the treatment of an underlying disease is successful, chronic cough may disappear. There are few 'antitussive' drugs with proven suppression of the cough reflex.

Half of the patients with advanced cancer suffer from shortness of breath. This may be due to the cancer itself, result from its treatment or arise from concurrent conditions. Careful assessment should precede any intervention. Treatment should be directed toward altering the underlying pathological process as far as possible (e.g. tumour reduction or pleural puncture). The relieve of symptoms by reassuring presence and morphine application are the mainstay, when it is not possible to reverse the cause of dyspnea, and can also successfully complement specific therapy.

There is much divergence of opinion as to how spontaneous pneumothorax should be treated or even whether it should be treated at all. Nowadays this benign pulmonary disease is primarily treated surgically, although conservative management of spontaneous pneumothorax seems to provide equally good results, as already indicated in 1932 by KJAERGAARD. Histories and clinical findings for 87 patients who were initially treated for spontaneous pneumothorax were reviewed and the factors responsible for the choice of treatment established. The mean age of the patients was 34 years, and 60% of the patients were below 30. Males predominated over females by 8:1. No coexisting pulmonary diseases were found in 80% of the patients. 54 patients were treated conservatively (no treatment except antitussives or analgesics). 46 conservatively treated patients had pneumothorax for the first time; 4 patients each had pneumothorax for the second or third time or more. 46 of 66 patients with idiopathic pneumothorax received no treatment, whereas 12 of 20 patients who had coexisting pulmonary diseases were treated surgically. The pneumothorax did not recur in 30 of 37 patients treated conservatively and observed for 1--15 years. These data suggest that conservative management is as effective as surgical treatment in uncomplicated spontaneous pneumothorax.

In 183 cases of chronic obstructive pulmonary disease (COB, COPD) grades I to IV horses were treated with bronchospasmolytic and secretolytic drugs, corticosteroids, mass infusions of physiological saline solution and with combinations of these treatments. The long-term effects of the above described methods of treatment based on questionnaire with the owners will be discussed. The results are to be considered successful if there is no evidence of irreversible alterations of the lungs, and if the horse is kept away from dust as much as possible.

The prerequisite for an effective therapy of bronchial asthma is a sufficiently precise characterization of the disease. Based on the demonstration of allergy or not asthma can roughly be subdivided into an extrinsic (allergy present) and an intrinsic type (allergy not demonstrable). If exposition to allergens cannot be avoided, specific hyposensibilization has to be considered in the treatment of extrinsic asthma. Several drugs are available for the management of reversible airway obstruction in both types of asthma mentioned above. Basic pharmacological mechanisms, side effects and indications for systemic and inhalation therapy of beta-sympathicomimetics, methylxanthines, anticholinergic drugs, glucocorticoids, sodium cromoglycate and ketotifen are critically discussed. Great importance was attached to an adequate selection of one of these drugs or a combination of them with respect to the individual severity of the disease. For typical clinical situations a strategy of long-term treatment is recommended.