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  In this Article
 »  Abstract
 »  Introduction
 »  Normal Function ...
 »  Causes
 »  Treatment
 »  Cough suppressants
 »  Summary
 »  References
 »  Article Tables

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REVIEW ARTICLE
Year : 2006  |  Volume : 12  |  Issue : 2  |  Page : 51-55

Cough


1 Specialist Registrar Palliative Medicine, St. Luke’s Hospice, Little Common Lane, Sheffield S11 9NE, United Kingdom
2 Sheffield Palliative Care Studies Group, Sheffield, United Kingdom

Correspondence Address:
Georgina Keenleyside
Specialist Registrar Palliative Medicine, St. Luke’s Hospice, Little Common Lane, Sheffield S11 9NE
United Kingdom
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1075.30245

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 » Abstract 

Cough is a common symptom in palliative medicine and the causes may be multifactorial. When problematic it invariably affects quality of life. Evaluation must begin with a detailed history and examination with consideration given to further tests and imaging. Treatment must begin with the identification and correction of any reversible causes in addition to emperic treatment. A logical approach and regular monitoring is advised.



How to cite this article:
Keenleyside G, Vora V. Cough. Indian J Palliat Care 2006;12:51-5

How to cite this URL:
Keenleyside G, Vora V. Cough. Indian J Palliat Care [serial online] 2006 [cited 2019 Aug 23];12:51-5. Available from: http://www.jpalliativecare.com/text.asp?2006/12/2/51/30245



 » Introduction Top


Cough is a normal mechanism in the respiratory system designed to protect the individual from potential harm. Coughing helps to clear the central airways of foreign bodies and secretions and hence acts to maintain the patency of the airways. When cough becomes problematic, as when it is mediated by disease, it can cause distress, affect sleep, rest, eating, social activity and hence interfere significantly with quality of life.[1],[2],[3],[19],[26]

Cough is a common ailment in patients with cancer and prolonged coughing can lead to vomiting, muscle strain, rib fracture or syncope.[4],[27]


 » Normal Function and Cough Reflex Top


Cough helps the ciliated airways to bring mucus, fluid and inhaled foreign bodies up to the larynx. An effective cough involves a complex reflex arc initiated by stimulation of afferent structures innervated by the vagus nerve and its branches. The main anatomical areas stimulating the cough reflex are located in the larynx and upper airways which are richly supplied with sensory nerves. Cough sensitivity diminishes as the airways divide.[5],[25] Rapidly adapting myelinated pulmonary stretch receptors (and pulmonary and bronchial c fibre receptors) can be stimulated by mechanical (particles of inhaled matter/foreign body/dust/mucus), chemical (gas, cigarette smoke) and inflammatory/ immunological (acetylcholine, histamine, prostaglandins, substance P, bradykinin) stimuli.[6],[7],[24]

The vagal afferents terminate in the nucleus tractus solitarus within the brain stem and central processing occurs mainly in the medulla. Understanding of this central processing remains far from complete.[5],[25] Studies suggest a number of central neurotransmitters are involved in modulating the cough reflex. Input from higher centres allows cough to be voluntarily induced or suppressed. Cough can be precipitated at sites other than the respiratory tract, for example, instrumentation of the ear (in 2-16% population).[5],[25] These sites are all supplied by the vagus nerve.

The efferent arm of the cough reflex is a complex interaction involving the upper airways, facial muscles and a coordinated contraction of the respiratory musculature against a closed glottis.[3],[5],[26] The glottis then opens and the alveolar gas is expelled removing material from within the airways out through the mouth. The motor output acts via phrenic, spinal, motor and vagi nerves to vocal cords, diaphragm, abdominal, intercostal and accessory muscles. The cough reflex can be sensitised under inflammatory or disease conditions. Thus a slight irritant can cause significant response. Pathological changes occur around and within sensory nerve fibres leading to increased excitability within the neurones and phenotypic changes in receptors and neurotransmitter expression.[6]

Prevalence

In advanced cancer cough is reported by 37%[1],[19] of patients and in more than 60% of those with lung cancer.[1],[2] At the end of life cough can affect 48-80% of patients.[2]

Evaluation

The evaluation of any symptom should begin with a detailed history and physical examination to establish the cause.[2] The history should include questioning of the cough duration and characteristics, sputum production, smoking history, occupational history, drug history and associated symptoms. How the cough affects the patients daily living and activities should be established. Specific tests may include a sputum culture if infection is suspected and a chest X-ray. A swallowing assessment would be appropriate if aspiration was a possibility. Consideration could be given to referral for bronchoscopy or computed tomography scan for further evaluation. The search for a specific cause may be limited by the burden of multiple investigations.


 » Causes Top


May be multifactorial.

Cardiopulmonary

Postnasal drip

Irritant -smoking, FB

Infection

Acute

-URTI, pneumonia chronic

-Cardiac failure

-Bronchiectasis

Pulmonary oedema

Airways disease -asthma/COAD

Malignancy - 1o or 2o

Airway obstruction

Endobronchial tumour

Pleural effusion

Mesothelioma

Interstitial disease

Lymphangitis

Multiple lung metasteses

Vocal cord paralysis

Hilar tumour

Lymphadenopathy

SVCO

Tracheo-oesophageal fistula

Cardiac failure

Pericardial effusion

Oesophageal

Gastro oesophageal reflux disease

Aspiration

Gastro oesophageal reflux disease

Bulbar muscle weakness

Neuromuscular incoordination

Treatment

ACE inhibitors

B-blockers

Radiotherapy - fibrosis, pneumonitis

Chemotherapy -pulmonary toxicity

Pleural disease


 » Treatment Top
[Table - 1]

Treatment is determined by the type and cause of the cough and the patient's general condition and prognosis.[10] When possible, treatment begins with treatment of the underlying cause.[2],[7] An antibiotic should be considered if evidence of infection, a bronchodilator if evidence of airway constriction. In lung cancer radiotherapy or chemotherapy may be appropriate. Pleural effusions can be managed by drainage and pleurodesis.[9],[11] If the tumour is blocking an airway then consideration should be given to an endobronchial stent or laser treatment.[21]

Consideration should always be given to the positioning of the patient, for example to sit the patient up or advice to lie on the side of a pleural effusion. The need for a cough suppressant or mucolytic agent should then be determined.


 » Cough suppressants Top


Current antitussive drugs are divided broadly according to their site of action as either central or peripheral, although many antitussives act to some extent at both locations.[6]

1) Simple linctus (5 ml tds-qds)

Contains substances that stimulate the production of saliva and soothes the oropharynx when swallowed.[4]

2) Centrally acting cough suppressants

a) Opioids

The antitussive effect of opioids is reported to be mediated centrally by suppressing activity in the brain stem. The effect is mediated predominantly by mu receptors with a possible role of kappa receptors.[1],[6] Doses for cough are generally lower than those for analgesia. Starting with a low dose and titrating to the most effective dose with side effect monitoring is a standard practice when using opioids.

Codeine (15-30 mg qds) is probably the widest used opioid for cough. It has been shown to be an effective antitussive in pathological cough and has been used as such for over 150 years.[2] Studies have evaluated codeine for acute and chronic cough and the majority found codeine (10-120 mg/day) to be effective in relieving the frequency and intensity of cough and superior to placebo.[1] Alternatives include dihydrocodeine (10-30 mg qds)[2],[12] morphine,[1] hydrocodone (2.5-10 mg qds),[1],[13] hydromorphone[1] and methadone[1] (2.5 mg qds reduced to bd if prolonged use).[14],[27]

There is no evidence to suggest which opioid is the most potent antitussive. The most common side effects of opioids are lightheadedness, dizziness, sedation, nausea, vomiting and constipation.

b) Dextromethorphan hydrobromide (10-30 mg qds)

The most widely used antitussive worldwide and is present in proprietary cough mixtures. It is structurally related to opioids and lacks the analgesic or sedative side effects of these drugs. It is thought to act on sigma receptors (centrally and peripherally) rather than at the classic opioid receptors and have an action at NMDA receptors also.[6] It has been found to be effective in the management of acute and chronic cough.[1]

c) Baclofen

GABA is an inhibitory neurotransmitter that is present both centrally and in the periphery. Baclofen is a GABAB agonist which has found to have antitussive mechanisms in animal and human studies.[6],[20]

3) Peripherally acting cough suppressants

a) Benzonatate[15] (100-200 mg tds swallow whole)

A polyglycol derivative which is related to local anaesthetics. It acts to reduce activity within stretch receptors. Adverse effects include sedation, headache, dizziness, confusion, visual hallucinations, nasal congestion and nausea are uncommon.[1],[19]

b) Other local anaethetics - lidocaine

Found to be effective antitussives but the effects are transient and side effects problematic.[2],[6],[20] Their mechanism of action is believed to be through use-dependent inhibition of voltage-gated Na+ channels, thereby reducing action potential generation and transmission in afferent nerves.[20]

c) Levodropropizine (60-75 mg tds)

Acts by the modulation of sensory neuropeptides within the respiratory tract. Has been found to be safe and effective in non productive cough in primary and metastatic lung cancer.[12] Side effects include sleepiness, tiredness and nausea.[1],[19]

Others

Successful cough suppression has been reported with sodium cromoglycate (2p bd), nebulized morphine and paroxetine.[16] There are no trials involving steroids in lung cancer but they may be considered in certain indications.[17]

Expectorants and mucolytics

There is little data to demonstrate the efficacy of such drugs. Their aim is to promote mucus clearance. Care should be taken with a potential risk of the retrograde flow of secretions if the patient has respiratory muscle weakness or reduced expiratory flow. Examples include cysteine derivatives (N-acetylcysteine, carbocysteine) which liquefy the lung secretions, hypertonic saline which encourages liquid into the mucus from the epithelium and guaifenesin (200-400 mg 4 hrly) which enhances the output of secretions by reducing surface tension of the mucus. Consideration can be given to steam inhalation and physical therapy to clear sputum.

Future therapies

Investigations into the cough reflex have uncovered potential targets for new drugs. New opioids, non opioids and sodium channel blockers may act as antitussives and further investigation is required.[23]


 » Summary Top


Cough is a common symptom in palliative medicine and causes may be multifactorial. When problematic it invariably affects quality of life. Evaluation must start with a detailed history and examination with consideration given to further tests and imaging. Treatment must begin with the identification and correction of any reversible causes in addition to empiric treatment. A logical approach and regular monitoring is advised.

Example Pathway to treat dry cough in Palliative Medicine

Investigate cause as appropriate and patient's condition allows

Treat any reversible causes

If irreversible cause consider -

Nebulised saline 5 ml qds

Simple linctus 5-10 ml qds

Cough Suppression

Pholocodine 5 mg qds or codeine linctus 15-30 mg qds

Morphine Solution 2.5 mg qds

Consider methadone linctus (use with care due to long half life)

Consider trial dexamethasone

Example Pathway to treat productive cough in Palliative Medicine

Investigate cause as appropriate and patient's condition allows

Treat any reversible causes

If irreversible cause:

If loose secretions not being effectively cleared then consider physiotherapy

If tenacious secretions difficult to clear try N Saline nebuliser. If not effective consider mucolytic.

 
 » References Top

1.Homsi J, Walsh D, Nelson KA. Important drugs for cough in advanced cancer. Support Care Cancer 2001;9:565-74.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Estfan B, LeGrand S. Management of cough in advanced cancer. J Support Oncol 2004;2:523-7.  Back to cited text no. 2  [PUBMED]  
3.Available from: http://www.bnf.org.  Back to cited text no. 3    
4.Twycross R, Wilcock A. Symptom Management in Advanced Cancer. 3rd ed. Radcliffe Medical Press: 2001.  Back to cited text no. 4    
5.Doyle D, Hanks GW, MacDonald N, editors. Oxford textbook of palliative medicine. 3rd ed. Oxford University Press: Oxford; 2004.  Back to cited text no. 5    
6.Reynolds SM, Mackenzie AJ, Spina D, Page CP. The pharmacology of cough. Trends Pharmacol Sci 2004;25:569-76.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]
7.Twycross R, Wilcock A, Charlesworth S, Dickman A. Palliative care formulary. 2nd ed. Radcliffe Medical Press: 2002. Available from: http://www.palliativedrugs.com.  Back to cited text no. 7    
8.Escobar SJ, Granda OJ, Gutiιrrez JT, Delgado JM, Rodero BA, Saez VR. Endobronchial brachytherapy in the treatment of malignant lung tumours. Eur Respir J 2004;2493:348-52.  Back to cited text no. 8    
9.Ahmedzai SH, Davis C. Nebulised drugs in palliative care. Thorax 1997;52:S75-7.  Back to cited text no. 9    
10.Davis CL. ABC of palliative care. Breathlessness, cough and other respiratory problems. BMJ 1997;315:931-4.  Back to cited text no. 10    
11.Erasmus JJ, Patz EF. Treatment of malignant pleural effusions. Curr Opin Pulm Med 1999;5:250-5.  Back to cited text no. 11    
12.Luporini G, Barni S, Marchi E, Daffonchio L. Efficacy and safety of levodropropizine and dihydrocodeine on non-productive cough in primary and metastatic lung cancer. Eur Respir J 1998;12:97-101.  Back to cited text no. 12  [PUBMED]  [FULLTEXT]
13.Homsi J, Walsh D, Nelson KA, Sarhill Nl, Rybicki L, Legrand SB, et al . A phase II study of hydrocodone for cough in advanced cancer. Am J Hosp Palliat Care 2002;19:49-56.  Back to cited text no. 13    
14.Chung KF. Current and future prospects for drugs to suppress cough. Drugs 2003;6:781-6.  Back to cited text no. 14  [PUBMED]  
15.Doona M, Walsh D. Benzonatate for opioid-resistant cough in advanced cancer. Palliat Med 1998;12:55-8.  Back to cited text no. 15  [PUBMED]  [FULLTEXT]
16.Zylicz Z, Krajnik M. What has dry cough in common with pruritus? Treatment of dry cough with paroxetine. J Pain Symptom Manage 2004;27:180-4.  Back to cited text no. 16    
17.Kvale PA, Simoff M, Prakash UB. Lung cancer. Palliative care. Chest 2003;123:284S-311S.  Back to cited text no. 17    
18.Shaw P, Agarwal R. Pleurodesis for malignant pleural effusions. The Cochrane Database of Systemic Reviews 2004.  Back to cited text no. 18    
19.Dudgeon DJ. Managing dyspnea and cough. Hematol Oncol Clin North Am 2002;16:557-77.  Back to cited text no. 19  [PUBMED]  
20.Asimakopoulos G, Beeson J, Evans J, Maiwand M. Cryosurgery for malignant endobronchial tumors: Analysis of outcome. Chest 2005;127:2007-14.  Back to cited text no. 20    
21.Mohan A, Guleria R, Mohan C, Sharma R. Laser bronchoscopy-Current status. J Assoc Physics India 2004;52:915-20.  Back to cited text no. 21  [PUBMED]  
22.Ahmedzai SH. Cough in cancer patients. Pulm Pharmacol Ther 2004;17:415-23.  Back to cited text no. 22  [PUBMED]  
23.Chung KF, Chang AB. Therapy for cough: Active agents. Pulm Pharmacol Ther 2002;15:335-8.  Back to cited text no. 23  [PUBMED]  [FULLTEXT]
24.Fuller RW, Jackson DM. Physiology and treatment of cough. Thorax 1990;45:425-30.  Back to cited text no. 24  [PUBMED]  
25.Ahmedzai SH, Muers MF, editors. Supportive Care in Respiratory Disease. Oxford University Press: Oxford; 2005. p. 341-60.  Back to cited text no. 25    
26.Cough. Causes, Mechanisms and Therapy. Widdicombe and Boushey Blackwell Publishing: Chung; 2003.  Back to cited text no. 26    
27.www.bnf.org.  Back to cited text no. 27    


    Tables

[Table - 1]

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