DR. SHERMAN is a pediatric pulmonologist in Roanoke, Va. The author has nothing to disclose in regard to affiliations with,
or financial interests in, any organization that may have an interest in any part of this article.
Cough is triggered by the presence of chemical receptors (circles) in the larynx and larger airways, and
by mechanical receptors (squares) in the lungs responding to mucus or a foreign body. Once triggered, the afferent impulse
(small arrows) travels to the brain, eliciting the efferent limb (large arrows) of the cough reflex.
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Cough is associated with many common childhood illnesses, and is thereby a common symptom in children. At any given time,
however, as many as 10% of preschool or young school-age children have been coughing longer than four weeks—what can be classified
as a chronic cough.1 Most coughs are caused by a self-limited respiratory tract infection, although viral infection can cause chronic cough long
after the viral illness resolves. How do you approach the workup of a cough in a child who has been coughing for weeks? The
history and physical examination—including diagnostic characteristics of the cough—often provide clues sufficient to begin
a therapeutic trial.2What makes a child cough?
A cough episode is triggered by the presence of chemical receptors in the larynx and in airways larger than bronchioles. Common
chemical triggers include serotonin, adenosine triphosphate (ATP), acetylcholine, acid, and bradykinin.3 One of these receptors, vanilloid receptor-1 (TRPV1), is stimulated by capsaicin, which is used in challenge tests for assessing
receptor sensitivity in much the same way as methacholine or histamine challenges are used in evaluating asthma. The endpoint
of a capsaicin challenge—production of two coughs or five following exposure to doubling doses of capsaicin—depends on the
protocol used. Many adults and children with chronic, nonspecific cough who undergo capsaicin challenge have increased cough
receptor sensitivity, which may be caused by a viral infection.4 Whether this increased sensitivity is transient or lasts years is unknown, but it is also associated with chronic cough
of both gastroesophageal reflux disease (GERD) and asthma.5,6
Major causes of chronic cough
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Cough is also triggered by mechanical receptors in the lungs as they respond to the presence of mucus or foreign bodies (see
the illustration). These receptors rapidly adapt to stimulation, however, so that a cough initiated by the presence of a foreign
body may resolve until the foreign body moves or until secretions caused by its presence shift in the airways. This adaptive
property explains why a child with a hypersecretory disorder, such as cystic fibrosis (CF), has an accentuated morning cough:
While asleep, the child's cough reflex is blunted, and any accumulating mucus is generally static. When the child awakens
and moves about, the pooled mucus shifts in the airways, causing the child to cough until the mucus is cleared.
Once the afferent impulse is triggered by a chemical or mechanical receptor, the impulse travels to a cough center in the
brain, eliciting the efferent limb of the cough reflex. Note that the utility of centrally-acting opioids, the most effective
cough suppressant medications, is limited by adverse effects of drowsiness, nausea, constipation, and physical dependence.
Research into receptor antagonists that act peripherally to decrease the afferent limb of the cough reflex is underway.7
The table lists the major causes of chronic cough among infants, preschool-age children, and school-age children and adolescents.
Nailing down the cause (the clues are in the cough!)
A child whose parent complains that he has been coughing for months may be experiencing a series of coughs that correspond to a series of viral infections—cough is common in viral infections, and children often have multiple
contacts. Thus established, such a series cough following viral illnesses does not meet the criterion of chronicity—a cough
that lasts longer than four weeks. This distinction between chronic cough and a series of coughs associated with a series
of viral illness is important, and should be considered before you proceed further with the diagnostic evaluation.
Findings in the history can generally narrow the diagnostic possibilities (see the algorithm). I ask about the timing of the
cough; one that is severe upon awakening suggests a hypersecretory state seen in CF, a lower respiratory infection, or bronchiectasis.
Exacerbation of the cough with the patient supine suggests postnasal drip or GERD. A cough that occurs primarily during the
very early morning hours is strongly suggestive of asthma, because pulmonary function is lowest at approximately 2 am or 3
am, often causing symptoms that are otherwise absent. A cough that is aggravated with exercise suggests asthma or a hypersecretory
state; one that worsens in the evening, disrupts the family, and disappears with sleep suggests a habit cough.
The characteristics of the cough are often useful information. Does the cough sound productive (most children do not produce
sputum, but parents usually can distinguish a dry cough from one that "makes them want to spit out something")? A cough that
sounds productive suggests mucus in the airway, as in post-nasal drip and bronchitis. A brassy, musical cough is usually caused
by vibration of the large airway structures and suggests tracheomalacia. A habit cough is often described as a honk. Tourette's
syndrome can produce a phonic tic that sounds like a vocalization or throat clearing, but that a parent may describe as a
cough.8 A child with these phonic tics will usually produce them in your office.
A paroxysmal cough is seen with CF, bronchiectasis, presence of a foreign body, and also pertussis. The cough of pertussis
is particularly distinctive—a vigorous inspiration and "whoop" punctuating a series of coughs with no intermittent inspiration.
Following such a coughing episode the child is red, breathless, apneic, and distressed, with mucus dripping from the mouth
and nose. The child appears fine between episodes. The cough is so characteristic as to be diagnostic, but parents may need
you to demonstrate the cough to confirm it. (Note, however, that adolescents and young adults with waning immunity from childhood
vaccines may not exhibit the typical pertussis-like cough when they have pertussis.) A video of a pertussis cough to show
parents is available at www.pertussis.com.
Other findings in the history will help you narrow the differential. A personal or family history of atopy or asthma supports
asthma or allergic rhinitis with postnasal drip. Growth failure, evidence of steatorrhea, digital clubbing, and nasal polyps
all suggest CF. A child with a history of ear infections, repeated pressure-equalizing tube placement, and chronic sinusitis
may have an immune deficiency or ciliary dyskinesia—50% of children with ciliary dyskinesia have situs inversus, lateral transposition
of the abdominal and thoracic viscera. A history of easy vomiting, chest pain, and sour taste suggests GERD. Chronic cough
in a patient contact merits consideration of tuberculosis, pertussis, or a mycoplasmal infection. A child with severe obstructive
sleep apnea may have recurrent microaspiration during sleep, causing a chronic low-grade infection that presents with cough.
Narrowing the differential, taking action
A therapeutic trial is often warranted when a single probable cause stands out following a thorough history and physical examination.
Allergic rhinitis and asthma both typically respond to a five-day course of a systemic corticosteroid (prednisolone, 2 mg/kg/day
in two divided doses). Postnasal drip associated with allergic rhinitis is often relieved with an oral antihistamine and nasal
steroid. Suspected GERD warrants an empiric trial of acid suppression therapy with a proton-pump inhibitor, which is generally
more effective than an antihistamine. Chronic sinusitis that does not respond to antibiotic therapy may be caused by a resistant
pathogen.
Nebulized lidocaine is beneficial for a chronic dry cough in both adults and children, and may also be an effective treatment
for habit cough.9,10 It is thought that the agent anesthetizes airway receptors—perhaps those capsaicin-sensitive receptors discussed earlier.
Note that lidocaine is well absorbed from the airway, requiring cautious dosing to avoid toxicity.
Breaking habit cough
The root cause of a habit cough may be elusive, and finding the right approach to the child's problem may require some effort.
If you suspect psychogenic cough in a child with concomitant somatic complaints, consider a psychiatric referral.11
Or, a child with habit cough may describe an itch in the throat that she scratches by coughing. You can help the child understand
that, although the cough does scratch the itch, doing so perpetuates the irritation-cough-irritation cycle, and that the solution
is to quit coughing until the itch goes away. I have found that four or five treatments of nebulized lidocaine for several
days, together with a full explanation and parental understanding, often helps the child to break the habit cough.9,10
Other approaches to treatment of habit cough are described in the literature; one that has proven particularly ineffective
in my practice is aversive therapy, involving a treatment that is so noxious to the child that he decides to no longer cough.
One such approach involves sending the child to school wrapped in a bedsheet!11,12
Minimal role for lab testing
Laboratory results may be used to support a diagnosis suggested by the history, but a random battery of tests is seldom useful.
A complete blood cell count demonstrating extreme lymphocytosis supports a diagnosis of pertussis; the presence of eosinophils
in sputum cytology or CBC suggests asthma or other allergic condition. Polymorphonuclear neutrophil leukocytes in sputum suggests
inflammation, leading to suspicion of CF, infection, GERD, or presence of a foreign body. Pertussis can be difficult to confirm
in the laboratory because the cough often persists well after bacteria are cleared. A recently available polymerase chain
reaction analysis promises both high specificity and sensitivity for pertussis. Chest imaging studies can help differentiate
foreign body, CF, heart disease, and tuberculosis, and may demonstrate the air trapping and peribronchial swelling seen with
asthma, GERD, aspiration syndromes, and in mild infection. Pulmonary function testing is useful for identifying asthma, CF,
and other chronic inflammatory conditions, whereas challenge tests with histamine, methacholine, and exercise can help confirm
the diagnosis of asthma, but are usually not necessary.
A caution about controlling a cough
A parent may ask your advice on quieting their child's vexing chronic cough. The American Academy of Pediatrics recommends
against the use of medications that contain codeine or dextromethorphan.13 Antihistamines also have no role in chronic cough in children, in whom over-the-counter antihistamine-containing drugs
are associated with significant morbidity, and are often unintentionally ingested by children. Systematic reviews of antihistamine
monotherapy or combinations of antihistamines with decongestants have shown no benefit over placebo, especially in younger
children. 14
You should underscore for parents the lack of benefit and potential for harm from using these OTC medications, and help parents
understand that the decision not to prescribe a cough suppressant is based on thoughtful consideration of available data.
Parents who nevertheless opt to use an OTC medication should understand the risk of overdose and should be advised to use
the drug as seldom as possible.
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