1-MINUTE CONSULT

brief answers
to specific
clinical
questions
Q: How should one investigate a chronic cough?
RYU P.H. TOFTS, MBChB
Department of Internal Medicine, Cleveland Clinic Florida, Weston ■■ COMMON CAUSES OF CHRONIC COUGH
GUSTAVO FERRER, MD
Department of Pulmonary, Allergy, and Critical Care Medicine, Cleveland The most common causes of chronic cough,
Clinic Florida, Weston accounting for 95% of cases, are chronic bron-
EDUARDO OLIVEIRA, MD chitis due to environmental irritants, upper
Department of Pulmonary, Allergy, and Critical Care Medicine, Cleveland
Clinic Florida, Weston
airway cough syndrome, GERD, asthma, non-
asthmatic eosinophilic bronchitis, and bron-

A: A chronic cough (ie, a cough lasting

more than 8 weeks1) has many pos-
sible causes. Physicians should use a structured
chiectasis (TABLE 1).1–8

Chronic bronchitis
diagnostic approach based on observing the As noted above, a history of exposure to an
clinical picture, trying therapy for the likely irritant suggests this diagnosis.
cause, obtaining targeted investigations, and
referring to a specialist when needed (FIGURE 1). Upper airway cough syndrome
To begin, obtain a clinical history, perform Upper airway cough syndrome (formerly
a physical examination, and order a chest ra- known as postnasal drip) is due to chronic up-
diograph. per respiratory tract irritation and hypersensi-
Look for In the history, look for exposure to envi- tivity of cough receptors.3,4 Sources of irrita-
a history ronmental irritants such as tobacco smoke, tion vary and include sinusitis and any form
allergens, or dust, or medications such as an- of rhinitis: allergic and nonallergic, postinfec-
of exposure giotensin-converting enzyme (ACE) inhibi- tious, environmental irritant-induced, vaso-
to irritants tors or oxymetazoline (Afrin). If a potential motor, and drug-induced.
irritant is present, it should be avoided or Patients complain of postnasal drip or
stopped immediately.1–3 If the cough improves frequent clearing of the throat. On physical
partially or fully when exposure to the irritant examination one can see mucus in the oro-
is stopped, this supports a diagnosis of chronic pharnyx or a cobblestone appearance. How-
bronchitis or, in the case of ACE inhibitors, ever, these symptoms and signs are not specific
ACE-inhibitor-induced cough. The character and may be absent.
of the cough (eg, paroxysmal, loose, dry, or A therapeutic trial is warranted, but be
productive1) has not been shown to be diag- aware that different rhinitides respond to spe-
nostically useful or specific. cific treatments:
If the chest radiograph is abnormal, then • Histamine-mediated or allergic rhinitis
the diagnostic inquiry should be guided by the will respond to allergen avoidance, new-
abnormality. Abnormalities that cause cough generation antihistamines such as lorata-
include bronchogenic carcinoma, sarcoidosis, dine (Claritin), mast cell stabilizers such as
and bronchiectasis. If the radiograph is nor- cromolyn (Intal), and intranasal glucocor-
mal, then upper airway cough syndrome, asth- ticoids such as fluticasone (Flovent).4,5
ma, gastroesophageal reflux disease (GERD), • Nonhistamine-mediated rhinitides (the
chronic bronchitis, or nonasthmatic eosino- common cold and perennial nonallergic rhi-
philic bronchitis is more likely. nitis) respond to older-generation antihista-
mines such as diphenhydramine (Benadryl)
doi:10.3949/ccjm.77a.10033

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 TOFTS AND COLLEAGUES

How to investigate a chronic cough

Review the history:
Current or former smoker
Use of an angiotensin-converting enzyme (ACE) inhibitor
Symptoms of gastroesophageal reflux disease (GERD)
Upper airway cough syndrome or sinus symptoms
Asthma-type symptoms

Obtain a chest radiograph

Abnormal Unremarkable

Consider Smoker or taking GERD symptoms Sinus symptoms Asthma symptoms

Sputum testing an ACE inhibitor Therapeutic trial Therapeutic trial Spirometry and bron-
Stop the ACE inhibitor of pH suppression, chodilator challenge
High-resolution CT If persistent or
promotility agents
Spirometry refractory, sinus
Bronchoscopy and Sputum analysis
If refractory, refer to radiograph
biopsy Smoking cessation (eosinophils)
specialist
Allergen testing
Video-assisted lung Therapeutic trial Therapeutic trial
biopsy of bronchodilators, of bronchodilators,
inhaled steroids steroids

Reassess for resolution or partial resolution

If cough has partially resolved

Do not discontinue partially successful therapies
Choose the next most likely cause and begin investigation and therapeutic trials until successful

FIGURE 1
and decongestant combinations. If these and the most difficult to exclude.5 Look for a
cannot be used, intranasal glucocorticoids history of reflux or heartburn and positional
and ipratropium (Atrovent) are alternatives. coughing, and have a low threshold for begin-
• Vasomotor rhinitis will respond to intrana- ning empiric therapy. Indeed, according to
sal ipratropium 0.3% for 3 weeks and then the 2006 American College of Chest Physi-
as required. cians Cough Guideline Committee,5,6 should
• Postinfective rhinitis, ie, a cough that be- a patient arrive in your clinic with a chronic
gan as severe bronchitis, would warrant an cough and a normal chest radiograph who does
antihistamine-decongestant combination. not smoke and is not on an ACE inhibitor,
With adequate treatment, the cough then you should start empiric reflux therapy.
should improve after 1 to 2 weeks; if rhinosi- Begin with lifestyle changes, acid suppression,
nus symptoms persist, consider bacterial sinus- and prokinetics. The cough may take 1 to 2
itis and obtain radiographs of the sinuses. If months before it begins to improve, and even
imaging shows mucosal thickening (> 5 mm) longer to resolve.
or an air-fluid level, treat with decongestants The gold standard for diagnosis is 24-hour
and antibiotics for 3 weeks.1,4,5 pH and impedance monitoring with patient
self-reporting of symptoms. However, this test
Gastroesophageal reflux disease is not available everywhere, and there is no
GERD is another common cause of cough, consensus on how to interpret the results.1,5,6 If
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 TOFTS AND COLLEAGUES

you strongly suspect the patient has GERD-re-

TABLE 1
lated cough but it fails to improve with intense
medical management, then refer to a special- Causes of chronic cough
ist, as antireflux surgery may be required. Common causes
Cough-variant asthma Chronic bronchitis1
Cough is the only symptom of asthma in Upper airway cough syndrome1–4
cough-variant asthma, in which the usual Gastroesophageal reflux disease5,6
features of dyspnea and wheezing are absent.7 Cough-variant asthma7,8
A methacholine challenge shows bronchial Nonasthmatic eosinophilic bronchitis7,8
hyperresponsiveness, and asthma therapy re- Bronchiectasis
solves the cough.
Uncommon causes
Nonasthmatic eosinophilic bronchitis Angiotensin-converting enzyme inhibitor use
It is important to distinguish asthma from Bronchogenic carcinoma
nonasthmatic eosinophilic bronchitis,7,8 an Interstitial pulmonary disease
underdiagnosed condition. Both conditions
respond equally well to treatment with in- Psychogenic causes
haled or oral steroids. However, patients who
have nonasthmatic eosinophilic bronchitis
have normal results on spirometry and the • Therapeutic trials are part of the workup.
methacholine challenge test. The diagnosis of • Do not stop therapy if it is only partially
nonasthmatic eosinophilic bronchitis is made successful: add to existing therapies
if more than 3% of the nonsquamous cells in • Start the investigation with the most like-
an induced sputum sample are eosinophils. ly cause.
• Treatment is 84% to 98% successful. ■
■■ UnCOMMON CAUSES OF COUGH
■■ REFERENCES Start empiric
The remaining 5% of cases of cough are caused 1. Irwin RS, Madison JM. The diagnosis and treatment of
GERD therapy if
cough. N Engl J Med 2000; 343:1715–1721.
by conditions that include bronchogenic car-
cinoma, chronic interstitial pneumonia, sar-
2. Vegter S, de Jong-van den Berg LT. Misdiagnosis and
mistreatment of a common side-effect—angiotensin-
the patient has
coidosis, left ventricular dysfunction, use of converting enzyme inhibitor-induced cough. Br J Clin
Pharmacol 2010; 69:200–203.
a chronic cough
ACE inhibitors, neurosensory cough, dynam-
ic airway collapse, aspiration due to pharyn-
3. Irwin RS, Baumann MH, Bolser DC, et al; American
College of Chest Physicians (ACCP). Diagnosis and
and a normal
geal dysfunction, and psychogenic causes.1 management of cough executive summary: ACCP chest x-ray,
evidence-based clinical practice guidelines. Chest
2006; 129(suppl):1S–23S. does not
■■ MULTIPLE CAUSES 4. Pratter MR. Chronic upper airway cough syndrome
secondary to rhinosinus diseases (previously referred smoke,
to as postnasal drip syndrome): ACCP evidence-
Therapeutic trials will support the diagnosis. based clinical practice guidelines. Chest 2006; and is not on
If more than one cause is suggested, start treat- 129(suppl):63S–71S.
ment in the order in which the abnormalities 5. Irwin RS. Chronic cough due to gastroesophageal reflux an ACE inhibitor
disease: ACCP evidence-based clinical practice guide-
are discovered. If treatment is only partially lines. Chest 2006; 129(suppl):80S–94S.
successful, then pursue further causes and add 6. Kahrilas PJ. Clinical practice. Gastroesophageal reflux
to the existing treatment without stopping it. disease. N Engl J Med 2008; 359:1700–1707.
7. Dicpinigaitis PV. Chronic cough due to asthma: ACCP
Cough may have more than one cause, evidence-based clinical practice guidelines. Chest
but in up to 98% of patients it can be success- 2006; 129(suppl):75S–79S.
fully treated. 8. Brightling CE. Chronic cough due to nonasthmatic
eosinophilic bronchitis: ACCP evidence-based clinical
practice guidelines. Chest 2006; 129(suppl):116S–
■■ Important points 121S.

ADDRESS: Ryu P.H. Tofts, MBChB, Department of Internal

• Multiple causes of chronic cough can co- Medicine, Cleveland Clinic Florida, 2950 Cleveland Clinic Bou-
exist. levard, Weston, FL 33331; e-mail: [email protected].

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