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Evaluation of chronic cough
Mini-symposium
Respiratory
Evaluation of chronic cough
A. W. Boon The cough receptors may be stimulated by chemicals, physical irritants such as smoke or cold air and mechanical stimuli such as mucus in the airway. There is evidence that the sensitivity of cough receptors may be increased by viruses which strip away the mucosal epithelium. Sensitivity is also increased by inflammatory mediators such as prostaglandins, bradykinin and histamine.
A chronic cough is generally defined as having persisted for at least 3 weeks. It is a common symptom, affecting up to 22% of 7-S-year old children but becoming less common in older children. A cough can be a non-specific symptom of many disorders ranging from trivial to life-threatening. It is therefore important to evaluate a child with a chronic cough to determine the underlying aetiology.
A&rent
nerves: AlIerent impulses are carried in the vagus and laryngeal nerves.
Physiology of cough Coughing is partly under voluntary control but it is generally a reflex mechanism. The cough reflex consists of the following components: Cough
The central cough centre: This is believed to be in the
brain stem. EfSerent nerves: These carry impulses to the larynx,
receptors:
These are situated in large to medium-sized airways especially at the carina and the bifurcation of airways. However, cough receptors are also situated in the external auditory canal, pharynx and stomach. There appear to be four types of cough receptors:
expiratory muscles and smooth muscle in the respiratory tree. The musculature involved in coughing
The cough mechanism A cough consists of an inspiratory gasp followed by forceful contraction of the chest wall, diaphragm and abdominal muscles against a closed glottis. This causes a rapid rise in pleural, alveolar and subglottic pressure. The glottis then suddenly opens resulting in a rush of turbulent air out of the respiratory tract. Up to six coughs may occur during a single expiration.
Slowly adapting receptors responding to tactile stimulation. Rapidly adapting tactile receptors. These types of receptors are particularly found at the carina and in the larger bronchi. C-fibre endings. These are situated throughout the respiratory tree from the larynx to the alveoli and respond to chemical and mechanical stimulation. Pulmonary stretch receptors. These are found in the smooth muscle of the respiratory tree and respond to mechanical forces in the airway.
Andrew Boon MD, FRCP Consultant Paediatrician, Berkshire Hospital, London Road, Reading RG15AN. Correspondence and requests for offprints to AB. Current Paedinrrics 0 1994 Longman
Aetiology
The commonest cause of chronic cough is repeated viral upper respiratory tract infections. The mechanism of such a cough is probably via increased sensitivity of the cough receptors. A chronic cough is certainly a symptom of asthma. However, controversy persists about the existence of cough variant asthma. There is certainly a risk of
Royal
(1994) 4, 133-135
GroupLtd
133
134
CURRENT
PAEDIATRICS
greatly overdiagnosing asthma by labelling all children with a chronic cough as having asthma with resultant inappropriate treatment. Although sinusitis and rhinitis causing post-nasal drip may be an aetiological factor in up to 30% of chronic cough in adults, it is less clear whether postnasal drip results in chronic cough in childhood. Irritants such as tobacco smoke, dust, atmospheric pollutants and solvents may all stimulate cough receptors and result in a chronic cough. Some infections are particularly likely to result in a chronic cough. In early infancy, chlamydial pneumonitis typically produces a persistent cough and tachypnoea. Pertussis begins with upper respiratory symptoms followed by severe coughing paroxysms. Although inspiratory stridor, the ‘whoop’, classically follows the coughing paroxysms, this is often lacking, particularly in early infancy. The paroxysms of pertussis may also be followed by apnoea, cyanosis or vomiting. Cytomegalovirus infection and pneumocystis carinii may also produce a paroxysmal cough. Tuberculosis in childhood usually produces a dry non-productive cough from large airway compression by enlarged peri-hilar or paratracheal lymph nodes. Psychogenic cough is often initiated by a viral infection and has a typical brassy, honking character. It becomes more marked when attention is drawn to it or the child is anxious. The cough disappears during sleep. Foreign body aspiration is nearly always associated with a cough although there may be a time lag between the episode of aspiration and the onset of a cough. Large oesophageal foreign bodies may comTable 1
Causes of chronic cough
Viral upper respiratory tract infections Asthma Sinusitis Rhinitis Irritants
infections
Psychogenic Foreign Body
Recurrent aspiration Cystic fibrosis Bronchiectasis lmmotile cilia syndrome Immune deficiency Congenital abnormalities Drugs
Repeated infections especially adenovirus and influenza virus ?post-nasal
drip
Passive smoking Cigarette smoking Solvent abuse Chemicals-smoke -ammonia Pertussis Chlamydia Mycoplasma Tuberculosis Bronchus Oesophagus Stomach External auditory canal Gastro-oesophageal reflux Dysfunctional swallowing
press the trachea producing cough and stridor. Impacted wax in the external auditory canal has also been reported as a cause of chronic cough. Impaired mucus clearance is typically associated with a chronic cough as in cystic fibrosis, the immotile cilia syndrome and bronchiectasis. Immuno-deficiency - either congenital or acquired - may predispose to respiratory infections and chronic cough. Compression of airways by vascular rings or bronchogenic cysts may also produce a chronic cough. ACE inhibitors and beta blockers may increase bronchial hyper-reactivity with a resultant cough.
Evaluation Clinical history The age of the child is often a helpful diagnostic pointer. Congenital abnormalities such as laryngotracheomalacia usually produce symptoms in early infancy. The parents may notice a change in the symptoms on hyper-extending the child’s neck. It is important to take a careful history of the cough. A nocturnal or exercise-induced cough suggests asthma. A staccato cough in early infancy especially following a persisting conjunctivitis suggests chlamydial pneumonitis. A paroxysmal cough points towards pertussis particularly if associated with a whoop, apnoea or vomiting. However, cystic fibrosis may sometimes produce a cough which may sound very similar. A productive cough suggests bronchiectasis usually secondary to cystic fibrosis or the immotile cilia syndrome. In asthma the child produces clear sputum. A history of purulent sputum is against the diagnosis of uncomplicated asthma. A brassy honking cough which disappears at night suggests a psychogenic cough. The history should include enquiry about associated symptoms. Snoring, persistent sniffing, halitosis or mouth breathing suggest sinusitis or rhinitis. Recurrent vomiting or regurgitation in an infant with a chronic cough suggests recurrent aspiration secondary to gastro-oesophageal reflux. Failure to thrive and steatorrhoea raise the possibility of cystic fibrosis. One should also enquire about exposure to infection. Nursery attendance or older school-age siblings greatly increase exposure to infection. A family history of tuberculosis or tuberculosis contact may point towards the diagnosis of TB. A family history of atopy supports the diagnosis of asthma. It is also important to enquire about cigarette smokers and pets at home and in older children, to ask whether they smoke.
Examination Congenital and HIV Trachea-oesophageal fistula Laryngo-tracheomalacia Vascular ring ACE inhibitors Beta blockers
The child’s general condition should be assessed and the height and weight plotted on centile charts. Poor growth and weight gain suggest a more serious cause of the chronic cough. Clubbing suggests cystic fibrosis or suppurative lung disease as the cause of the cough.
EVALUATION Table 2
Investigations
OF CHRONIC
COUGH
which may be helpful in the child with chronic cough Diagnosis
Investigation
Abnormal
Chest x-ray
Over-inflated. Bronchial wall thickening Upper lobe consolidation Inflammatory changes Situs inversus Air-trapping
Asthma Gastro-oesophageal reflux Cystic fibrosis Kartagener’s syndrome Inhaled foreign body
Lymphocytosis Eosinophilia Neutropenia
Pertussis Atopy, parasitic infestation lmmunodeficiency Infection or active inflammation Congenital or acquired (HIV)
lnspiratory and expiratory films Full blood count
ESR lmmunoglobulins Sputum
finding
Raised lmmunodeficiency Raised IgE Of little value - does not usually reflect lower respiratory tract flora Positive culture Positive Air trapping
culture
Pernasal swab Mantoux skin test Pulmonary function testing Other investigations: Sinus X-rays Oesophageal pH studies - gastro-oesophageal reflux Barium swallow - trachea-oesophageal fistula, aspiration, Bronchoscopy Methacholine challenge
Table 3
Causes of cough and appropriate
Infection: Viral infections Chlamydia Pertussis
treatments
Treatment ineffective Erythromycin Erythromycin prevents spreads to others Anti-tuberculous therapy
TB Asthma: Bronchodilators Short course of Prednisolone Nebulised budesonide
135
Ideally by inhalation May be diagnostic 1
Sinusitis: Nasal steroid Anti-histamine ? Decongestant Reflwdaspiration: Thickened feeds Infant Gaviscon Cisapride ? Surgery
Examination of the head and neck may reveal features of atopy with dark rings under the eyes ‘allergic shiners’, a transverse nasal crease, conjunctivitis or rhinorrhoea. The child may also have atopic eczema. Mouth-breathing and halitosis suggest sinusitis. The respiratory rate should be noted as tachypnoea is an important indicator of lung disease especially in early childhood. A hyper-inflated chest suggests obstructive airways disease. The presence of expiratory wheeze is typical of asthma but sometimes the only clue to this diagnosis is prolongation of expiration. Crackles are associated with alveolar disease such as pneumonia, cystic fibrosis or bronchiectasis. Unilateral signs may suggest an inhaled foreign body. The cough may be heard during the consultation. The child with psychogenic cough will usually obligingly cough to order.
vascular
Atopy
Bordetella TB Asthma
pertussis
ring
J The remainder of the normal, but the presence of in childhood and indicate such as cystic fibrosis or the
examination is usually nasal polyps are unusual more serious pathology immotile cilia syndrome.
Investigations (Table 2) The majority of children with chronic cough should not be subjected to a battery of investigations, The investigations should be guided by the history and examination. It is often reasonable to postpone investigations in an otherwise well child with a chronic cough and to move straight onto a therapeutic trial - particularly if the working diagnosis is asthma.
Treatment (Table 3) Recurrent viral infections are unresponsive to treatment. Parents should be given reassurance and explanation that no treatment is required. In general the use of cough suppressants is of limited value and their use is not indicated in children.
Conclusion Chronic cough is quite a common problem. Viral infections and asthma are the main causes but it is important not to assume that every child who coughs has asthma.
References 1. Reisman JJ, Canny GJ, Levison MD. The approach to chronic cough in childhood. Anna1 Allerg. 1988,61: 163-169. 2. Kamei RK. Chronic cough in Children. Pediatr Clin North Am 1991,38: 593-605. 3. Hatch RT, Carpenter GB, Smith LJ. Treatment options in the child with a chronic cough. Drugs 1993; 45: 367-373. 4. McKenzie S. Cough - but is it asthma? Arch Dis Child 1994; 70: 1-2.
Respiratory
Evaluation of chronic cough
A. W. Boon The cough receptors may be stimulated by chemicals, physical irritants such as smoke or cold air and mechanical stimuli such as mucus in the airway. There is evidence that the sensitivity of cough receptors may be increased by viruses which strip away the mucosal epithelium. Sensitivity is also increased by inflammatory mediators such as prostaglandins, bradykinin and histamine.
A chronic cough is generally defined as having persisted for at least 3 weeks. It is a common symptom, affecting up to 22% of 7-S-year old children but becoming less common in older children. A cough can be a non-specific symptom of many disorders ranging from trivial to life-threatening. It is therefore important to evaluate a child with a chronic cough to determine the underlying aetiology.
A&rent
nerves: AlIerent impulses are carried in the vagus and laryngeal nerves.
Physiology of cough Coughing is partly under voluntary control but it is generally a reflex mechanism. The cough reflex consists of the following components: Cough
The central cough centre: This is believed to be in the
brain stem. EfSerent nerves: These carry impulses to the larynx,
receptors:
These are situated in large to medium-sized airways especially at the carina and the bifurcation of airways. However, cough receptors are also situated in the external auditory canal, pharynx and stomach. There appear to be four types of cough receptors:
expiratory muscles and smooth muscle in the respiratory tree. The musculature involved in coughing
The cough mechanism A cough consists of an inspiratory gasp followed by forceful contraction of the chest wall, diaphragm and abdominal muscles against a closed glottis. This causes a rapid rise in pleural, alveolar and subglottic pressure. The glottis then suddenly opens resulting in a rush of turbulent air out of the respiratory tract. Up to six coughs may occur during a single expiration.
Slowly adapting receptors responding to tactile stimulation. Rapidly adapting tactile receptors. These types of receptors are particularly found at the carina and in the larger bronchi. C-fibre endings. These are situated throughout the respiratory tree from the larynx to the alveoli and respond to chemical and mechanical stimulation. Pulmonary stretch receptors. These are found in the smooth muscle of the respiratory tree and respond to mechanical forces in the airway.
Andrew Boon MD, FRCP Consultant Paediatrician, Berkshire Hospital, London Road, Reading RG15AN. Correspondence and requests for offprints to AB. Current Paedinrrics 0 1994 Longman
Aetiology
The commonest cause of chronic cough is repeated viral upper respiratory tract infections. The mechanism of such a cough is probably via increased sensitivity of the cough receptors. A chronic cough is certainly a symptom of asthma. However, controversy persists about the existence of cough variant asthma. There is certainly a risk of
Royal
(1994) 4, 133-135
GroupLtd
133
134
CURRENT
PAEDIATRICS
greatly overdiagnosing asthma by labelling all children with a chronic cough as having asthma with resultant inappropriate treatment. Although sinusitis and rhinitis causing post-nasal drip may be an aetiological factor in up to 30% of chronic cough in adults, it is less clear whether postnasal drip results in chronic cough in childhood. Irritants such as tobacco smoke, dust, atmospheric pollutants and solvents may all stimulate cough receptors and result in a chronic cough. Some infections are particularly likely to result in a chronic cough. In early infancy, chlamydial pneumonitis typically produces a persistent cough and tachypnoea. Pertussis begins with upper respiratory symptoms followed by severe coughing paroxysms. Although inspiratory stridor, the ‘whoop’, classically follows the coughing paroxysms, this is often lacking, particularly in early infancy. The paroxysms of pertussis may also be followed by apnoea, cyanosis or vomiting. Cytomegalovirus infection and pneumocystis carinii may also produce a paroxysmal cough. Tuberculosis in childhood usually produces a dry non-productive cough from large airway compression by enlarged peri-hilar or paratracheal lymph nodes. Psychogenic cough is often initiated by a viral infection and has a typical brassy, honking character. It becomes more marked when attention is drawn to it or the child is anxious. The cough disappears during sleep. Foreign body aspiration is nearly always associated with a cough although there may be a time lag between the episode of aspiration and the onset of a cough. Large oesophageal foreign bodies may comTable 1
Causes of chronic cough
Viral upper respiratory tract infections Asthma Sinusitis Rhinitis Irritants
infections
Psychogenic Foreign Body
Recurrent aspiration Cystic fibrosis Bronchiectasis lmmotile cilia syndrome Immune deficiency Congenital abnormalities Drugs
Repeated infections especially adenovirus and influenza virus ?post-nasal
drip
Passive smoking Cigarette smoking Solvent abuse Chemicals-smoke -ammonia Pertussis Chlamydia Mycoplasma Tuberculosis Bronchus Oesophagus Stomach External auditory canal Gastro-oesophageal reflux Dysfunctional swallowing
press the trachea producing cough and stridor. Impacted wax in the external auditory canal has also been reported as a cause of chronic cough. Impaired mucus clearance is typically associated with a chronic cough as in cystic fibrosis, the immotile cilia syndrome and bronchiectasis. Immuno-deficiency - either congenital or acquired - may predispose to respiratory infections and chronic cough. Compression of airways by vascular rings or bronchogenic cysts may also produce a chronic cough. ACE inhibitors and beta blockers may increase bronchial hyper-reactivity with a resultant cough.
Evaluation Clinical history The age of the child is often a helpful diagnostic pointer. Congenital abnormalities such as laryngotracheomalacia usually produce symptoms in early infancy. The parents may notice a change in the symptoms on hyper-extending the child’s neck. It is important to take a careful history of the cough. A nocturnal or exercise-induced cough suggests asthma. A staccato cough in early infancy especially following a persisting conjunctivitis suggests chlamydial pneumonitis. A paroxysmal cough points towards pertussis particularly if associated with a whoop, apnoea or vomiting. However, cystic fibrosis may sometimes produce a cough which may sound very similar. A productive cough suggests bronchiectasis usually secondary to cystic fibrosis or the immotile cilia syndrome. In asthma the child produces clear sputum. A history of purulent sputum is against the diagnosis of uncomplicated asthma. A brassy honking cough which disappears at night suggests a psychogenic cough. The history should include enquiry about associated symptoms. Snoring, persistent sniffing, halitosis or mouth breathing suggest sinusitis or rhinitis. Recurrent vomiting or regurgitation in an infant with a chronic cough suggests recurrent aspiration secondary to gastro-oesophageal reflux. Failure to thrive and steatorrhoea raise the possibility of cystic fibrosis. One should also enquire about exposure to infection. Nursery attendance or older school-age siblings greatly increase exposure to infection. A family history of tuberculosis or tuberculosis contact may point towards the diagnosis of TB. A family history of atopy supports the diagnosis of asthma. It is also important to enquire about cigarette smokers and pets at home and in older children, to ask whether they smoke.
Examination Congenital and HIV Trachea-oesophageal fistula Laryngo-tracheomalacia Vascular ring ACE inhibitors Beta blockers
The child’s general condition should be assessed and the height and weight plotted on centile charts. Poor growth and weight gain suggest a more serious cause of the chronic cough. Clubbing suggests cystic fibrosis or suppurative lung disease as the cause of the cough.
EVALUATION Table 2
Investigations
OF CHRONIC
COUGH
which may be helpful in the child with chronic cough Diagnosis
Investigation
Abnormal
Chest x-ray
Over-inflated. Bronchial wall thickening Upper lobe consolidation Inflammatory changes Situs inversus Air-trapping
Asthma Gastro-oesophageal reflux Cystic fibrosis Kartagener’s syndrome Inhaled foreign body
Lymphocytosis Eosinophilia Neutropenia
Pertussis Atopy, parasitic infestation lmmunodeficiency Infection or active inflammation Congenital or acquired (HIV)
lnspiratory and expiratory films Full blood count
ESR lmmunoglobulins Sputum
finding
Raised lmmunodeficiency Raised IgE Of little value - does not usually reflect lower respiratory tract flora Positive culture Positive Air trapping
culture
Pernasal swab Mantoux skin test Pulmonary function testing Other investigations: Sinus X-rays Oesophageal pH studies - gastro-oesophageal reflux Barium swallow - trachea-oesophageal fistula, aspiration, Bronchoscopy Methacholine challenge
Table 3
Causes of cough and appropriate
Infection: Viral infections Chlamydia Pertussis
treatments
Treatment ineffective Erythromycin Erythromycin prevents spreads to others Anti-tuberculous therapy
TB Asthma: Bronchodilators Short course of Prednisolone Nebulised budesonide
135
Ideally by inhalation May be diagnostic 1
Sinusitis: Nasal steroid Anti-histamine ? Decongestant Reflwdaspiration: Thickened feeds Infant Gaviscon Cisapride ? Surgery
Examination of the head and neck may reveal features of atopy with dark rings under the eyes ‘allergic shiners’, a transverse nasal crease, conjunctivitis or rhinorrhoea. The child may also have atopic eczema. Mouth-breathing and halitosis suggest sinusitis. The respiratory rate should be noted as tachypnoea is an important indicator of lung disease especially in early childhood. A hyper-inflated chest suggests obstructive airways disease. The presence of expiratory wheeze is typical of asthma but sometimes the only clue to this diagnosis is prolongation of expiration. Crackles are associated with alveolar disease such as pneumonia, cystic fibrosis or bronchiectasis. Unilateral signs may suggest an inhaled foreign body. The cough may be heard during the consultation. The child with psychogenic cough will usually obligingly cough to order.
vascular
Atopy
Bordetella TB Asthma
pertussis
ring
J The remainder of the normal, but the presence of in childhood and indicate such as cystic fibrosis or the
examination is usually nasal polyps are unusual more serious pathology immotile cilia syndrome.
Investigations (Table 2) The majority of children with chronic cough should not be subjected to a battery of investigations, The investigations should be guided by the history and examination. It is often reasonable to postpone investigations in an otherwise well child with a chronic cough and to move straight onto a therapeutic trial - particularly if the working diagnosis is asthma.
Treatment (Table 3) Recurrent viral infections are unresponsive to treatment. Parents should be given reassurance and explanation that no treatment is required. In general the use of cough suppressants is of limited value and their use is not indicated in children.
Conclusion Chronic cough is quite a common problem. Viral infections and asthma are the main causes but it is important not to assume that every child who coughs has asthma.
References 1. Reisman JJ, Canny GJ, Levison MD. The approach to chronic cough in childhood. Anna1 Allerg. 1988,61: 163-169. 2. Kamei RK. Chronic cough in Children. Pediatr Clin North Am 1991,38: 593-605. 3. Hatch RT, Carpenter GB, Smith LJ. Treatment options in the child with a chronic cough. Drugs 1993; 45: 367-373. 4. McKenzie S. Cough - but is it asthma? Arch Dis Child 1994; 70: 1-2.