Cough

David Picker and Praveen R. Chenna

GENERAL PRINCIPLES

• Cough is a common symptom and a substantial driver of outpatient care visits.

• Cough accounts for nearly 30 million physician visits per year. Estimated costs for treatment may reach $1 billion annually, not including the cost of diagnostic testing and complications such as headache, hoarseness, urinary incontinence, musculoskeletal pain, and exhaustion.

• Due to the adverse effects on the quality of patients’ lives, a systematic approach is necessary for the diagnosis and management of cough in the adult patient.

CLASSIFICATION

Cough is classified based on the duration of symptoms, which can help provide a framework for diagnosis.¹

• Acute cough is defined as <3 weeks.

• Subacute cough is defined as >3 weeks, and <8 weeks.

• Chronic cough is defined as >8 weeks.

Acute Cough

Acute cough can be divided into three main categories; infectious, exacerbation of underlying disease process, and exposure-related.

• Infectious

Viral infections of the upper respiratory tract are the most common cause of acute cough. Rhinovirus, coronavirus, and respiratory syncytial virus are the pathogens most frequently associated with common cold symptoms. Less frequent causes include influenza, parainfluenza, and adenovirus.

Clinical features of the common cold include rhinorrhea, sneezing, irritation of the throat, lacrimation, and nasal obstruction. Fever may or may not be a presenting symptom. Coughing usually presents on day 4 or 5 after infection.

Chest radiograph is usually negative and therefore of low yield in the general population. However, certain exceptions should be considered in the elderly and immunocompromised to rule out potential pneumonia, or other insidious infection.

Viral or bacterial rhinosinusitis can also result in postnasal drainage and acute cough.

Viral rhinosinusitis may be difficult to distinguish from bacterial sinusitis.

Viral rhinosinusitis can be symptomatically managed with antihistamines and nasal decongestants.

Bordetella pertussis infection is common cause of acute cough in adults. Symptoms may include a barking cough and post-tussive emesis. Diagnosis may be confirmed by sputum culture or B. pertussis PCR testing.

• Exacerbation of underlying disease process

Allergic rhinitis is an IgE-mediated syndrome characterized by paroxysms of sneezing, nasal congestion, and irritation of the eyes and nose.

Postnasal drainage is probably the mechanism leading to acute exacerbation and may be a prominent symptom when cough is severe.

Symptoms are often improved by using nonsedating antihistamines and avoiding offending allergens.

COPD exacerbation may result from smoking, air pollutants, allergens, and infections.

Streptococcus pneumoniae, Haemophilus influenza, and Moraxella catarrhalis are among the most common bacterial pathogens isolated in COPD exacerbations.

Antibiotics may be prescribed if the acute cough is accompanied by worsening shortness of breath, increased oxygen requirements, increased sputum production, or change in the character of sputum.

• Exposure

Occupation or environmental exposures may also be contributors to cough. A thorough history, including workplace exposures, household exposures (including pets or new carpeting), and change in medications will help to pinpoint the diagnosis.

Chronic Cough

Cough >3 weeks is often attributable to one of a handful of diagnoses in nonsmokers. These include upper airway cough syndrome (UACS) which was previously referred to as postnasal drip syndrome, asthma, and gastroesophageal reflux disease (GERD).²

• Upper airway cough syndrome

The most common cause of persistent cough in nonsmokers.

Symptoms may include nasal discharge, frequent throat clearing, and a sensation of nasal discharge dripping into the back of the throat.

Physical examination may show secretions in the nasopharynx, and presence of cobblestoning.

However, postnasal drip may be silent, leaving the practitioner with nonspecific symptoms to help guide treatment.

Therefore, when there is a lack of alternative cause of a patient’s cough, empiric therapy for postnasal drip should be attempted before other extensive workups for alternate cough etiologies.

• Asthma

The leading cause of chronic cough in children and second most common cause of chronic cough in the adult population.

The clinical spectrum of symptoms includes recurrent episodic wheezing, chest tightness, breathlessness, and cough, particularly at nighttime and/or in the early morning.

Cough-variant asthma will often present with cough and may progress to encompass other common asthma symptoms.

• Gastroesophageal reflux

GERD is the third most common cause of chronic cough.

Symptoms include heartburn or a sour taste in the mouth, but some patients may also lack these symptoms.

Prolonged esophageal pH monitoring is generally considered the gold standard for confirmation of GERD.

• Chronic bronchitis

The most common cause of chronic cough in smokers.

Defined as cough productive of sputum ≥3 month’s duration in at least 2 consecutive years in the absence of other lung diseases that may cause cough.

Usually found with extensive smoking history, often >1 pack per day for more than 20 years.

An acute change of cough, or caliber of sputum is what may lead to initial presentation. It is important to remember these patients are at higher risk of developing neoplasm secondary to underlying smoking history.

• Angiotensin-converting enzyme inhibitors

Angiotensin-converting enzyme (ACE) inhibitors have been associated with cough in up to 15% of patients taking this class of medication.

Usually begins within 1 week of starting treatment but can be seen up to 6 months later.

Patients often report a “tickling” or “scratching” sensation in their throat, and the symptoms usually resolve within 1 week of discontinuing therapy (although it may take longer in some patients).

Mechanism is not entirely clear, but it is believed that accumulation of bradykinin may stimulate afferent nerve fibers in the airway. This is supported by data in patients who take angiotensin II receptor blockers (this class of medication does not affect kinin levels) and are not at increased risk of cough.

• Bronchiectasis

Bronchiectasis occurs less frequently.

Some studies show bronchiectasis is responsible for chronic cough in ∼4% of patients in the United States.

Bronchiectasis is the result of repeated damage from chronic infections and airway inflammation in the bronchial tree that leads to irreversible dilatation of the affected airways. This anatomical alteration can lead to easily collapsible airways, poor mucus excretion, and chronic infection.

Most patients will produce chronic mucopurulent sputum at baseline that becomes more purulent during acute infectious processes.

• Other etiologies of chronic cough

Eosinophilic bronchitis is increasingly being recognized as a cause of chronic cough.

Patients often have atopic sensitivities, elevated sputum eosinophils, and airway inflammation.

Although similar characteristics can be seen in patients with cough-variant asthma, patients with eosinophilic bronchitis do not demonstrate airway hyperresponsiveness.

Other causes include interstitial lung diseases, lung cancers, and lesions that compromise the upper airway, including arteriovenous malformations, retrotracheal masses, and broncholiths.

Although practitioners are frequently concerned about missing lung cancer as a cause of chronic cough, cough is an infrequent presentation of occult bronchogenic carcinoma.

Rare causes include tracheobronchomalacia, TB, tracheal diverticuli, occult cystic fibrosis, recurrent aspiration, hyperthyroidism, carcinoid syndrome, and psychogenic cough.

Psychogenic cough is always a diagnosis of exclusion, and occurs less frequently in adults than in children.

Many patients with this condition do not cough during sleep, are not awakened by cough, and do not cough when otherwise occupied (working or playing).

PATHOPHYSIOLOGY

• Cough receptors exist in the epithelium of the upper and lower respiratory tracts, pericardium, stomach, esophagus, and diaphragm.

Afferent receptors are located within the sensory distribution of the trigeminal, glossopharyngeal, superior laryngeal, and vagus nerves.

Efferent receptors located in the recurrent laryngeal and spinal nerves respond to signals from a cough center in the medulla.

• Irritation of the cough receptors by smoke, dust, or fumes leads to stimulation of a complex reflex arc.

Once stimulated, an impulse is sent to the cough center.

After a series of muscle contractions, an increase in intrathoracic pressure develops, leading to increased airflow through the trachea.

These shearing forces help to eliminate mucus and foreign materials.

DIAGNOSIS

The diagnosis can be narrowed down by a careful review of the patient’s history and physical examination. Focusing on the three most common causes of chronic cough—UACS, GERD, and asthma—is helpful in limiting the need for extensive evaluation.

Clinical Presentation

History

• Important clues include the onset, frequency, severity of the cough, as well as coexisting symptoms (fever, weight loss, dyspnea, night sweats).

• Patients should be questioned about medications, especially β-blockers and ACE inhibitors, environmental exposures, and recent respiratory tract infections within the past 3 months.

• Sputum production is an important consideration.

For patients with chronic bronchitis, sputum production is usually insidious.

It is often worse in the morning, and the appearance is whitish to gray.

During exacerbations, the sputum may become more profuse and more purulent.

Cigarette smokers are often used to their baseline productive cough, and are less likely to present to their physician unless there is a change in their respiratory status or the character of their sputum.

• It is also important to establish TB risk factors, and when appropriate, to determine when the last PPD skin test was completed.

• The medical history should focus on any underlying conditions that may predispose a patient to aspiration, congestive heart failure, and interstitial lung disease.

• Social history should include a detailed history of tobacco and alcohol use. A detailed occupational history should be obtained, including past and present exposure to asbestos, silica, coal dust, and fumes.

• Family history should include information regarding asthma and cystic fibrosis.

Physical Examination

• The patient should be observed for any signs of labored breathing.

• Frontal and maxillary sinuses should be palpated for tenderness.

• It is also important to evaluate the auditory canal and tympanic membranes, as irritation of the external canal by impacted foreign bodies or cerumen can lead to a chronic dry cough.

• The nose should be examined with attention to boggy turbinates, mucopurulent secretions, and polyps.

• Cobblestone appearance of the oropharynx suggests postnasal drip.

• Lung auscultation is a key component of the examination, and one must pay special attention to breath sounds, wheezes, and crackles.

• Remember to inspect the extremities for clubbing and peripheral edema. Clubbing may occur with interstitial lung disease, cystic fibrosis, and lung cancer.

Differential Diagnosis

• Upper airway cough syndrome

Absence of symptoms does not exclude the diagnosis of postnasal drip.

Patients may have silent postnasal drip and still have a favorable response to combination therapy with an antihistamine, nasal decongestant, and/or nasal steroids.

• Gastroesophageal reflux disease

The patient may complain of heartburn, regurgitation, or dysphagia.

Although these symptoms are seen in the majority of patients, they may be absent in up to 75% of cases.

• Asthma

The classic triad of cough, shortness of breath, and wheezing does not occur in every patient.

Chronic cough may be the sole presenting symptom in up to nearly 25% of all cases.

Diagnostic Testing

• CXR

CXR can be helpful in establishing an initial diagnosis in chronic cough cases for which there is low clinical suspicion of postnasal drip, asthma, or GERD.

A normal radiograph in an immunocompetent host makes a diagnosis such as sarcoidosis, TB, or bronchiectasis less likely.

Recent data suggest that a normal CXR is not the best way to screen for malignancy in the lung. If suspicion is high, CT scan is the preferred method.³

• Sinus CT scan

Limited sinus CT is the usual test of choice in selected cases with suspected sinus disease.

Plain films of the sinuses are not generally recommended.

A CT scan should be obtained if a patient has not responded to one or two courses of appropriate antibiotic therapy for sinusitis, which occurs in ∼10% of treated patients.

Nasal endoscopy is generally not indicated except in cases in which resistant or unusual organisms are suspected.

• Pulmonary function tests

Methacholine challenge testing should be performed in patients with a history and physical examination suggestive of asthma.

A negative test result essentially eliminates cough-variant asthma as the cause of chronic cough.

In patients with a positive response to methacholine challenge, a lack of improvement with bronchodilators may indicate a false positive test, and further workup should be initiated.

• Gastrointestinal evaluation

Diagnostic testing for suspected gastroesophageal disease is not routinely recommended.

An abnormal barium swallow may demonstrate cough induced by gastroesophageal reflux. However, this study is negative in the majority of patients.

Twenty-four–hour esophageal pH monitoring is the single most sensitive and specific test for reflux disease, but it is inconvenient and may not be readily available in some practices.

When postnasal drip and asthma have been ruled out, a 4-week trial of antireflux therapy can be initiated.

In the face of an inadequate response to a proton pump inhibitor, pH monitoring may be performed. The study should be performed while the patient is on the antireflux therapy to document the efficacy of the medication.

• Additional testing

If the history, physical examination, laboratory tests, and x-ray data do not provide a diagnosis, referral to a specialist should be considered.

A high-resolution chest CT can be performed to rule out rare causes of chronic cough such as bronchiectasis or interstitial lung disease. If the high-resolution CT scan is negative, then more invasive studies can be considered.

A bronchoscopy with or without biopsy may be indicated.

Echocardiography can be performed to rule out left ventricular dysfunction.

Other tests that may be performed include a sweat chloride test for cystic fibrosis and quantitative immunoglobulin’s to evaluate for rare immunodeficiences.

TREATMENT

The first step is establishing the underlying etiology. A systematic approach to the evaluation of persistent cough and treatment aimed at the underlying disorder is successful in >95% of cases.

• Chronic bronchitis

Chronic bronchitis is managed with smoking cessation and bronchodilator therapy (see Chapter 10).

Cough will improve in ∼95% of patients with cessation of smoking.

In patients who continue to smoke, medical therapy may still be helpful.

• Postnasal drip

Postnasal drip may be due to allergic, perennial nonallergic, or vasomotor rhinitis.

Removal of the offending environmental precipitant (if possible) is the treatment of choice.

Nasal steroids (i.e., fluticasone nasal spray, 2 sprays per nostril daily) can also be helpful.

Nonspecific therapy for any form of rhinitis includes antihistamines and topical decongestants in combination, and ipratropium nasal spray (0.03% nasal solution, 2 sprays each nostril 2–3 times daily).

First-generation antihistamines have been shown to be more effective in the treatment of cough than the newer, nonsedating agents.

Improvement can be expected within 7 days.

• Asthma

The treatment of cough-variant asthma is identical to that of atopic asthma.

Inhaled bronchodilators and/or inhaled corticosteroids (see Chapter 9) are the mainstays of therapy.

Short-course oral prednisone (0.5 mg/kg/d for 1–2 weeks) may be used with the initiation of inhaled therapy to decrease airway hyperreactivity.

• Gastroesophageal reflux disease

GERD is treated with both behavioral modification and medication.

Patients should avoid eating for 3 hours before bedtime, and specifically, avoid reflux-inducing foods (i.e., fatty foods, chocolate, and alcohol).

Patients should elevate the head of their bed with foam wedges or use a mechanized bed.

Treatment with a proton pump inhibitor should be instituted, especially in patients who do not respond to behavioral therapy, or in those patients with severe symptoms.

• Sinusitis

Most mild cases of mild sinusitis respond to topical or oral decongestants.

In more severe cases, or in recurrent infections, an antihistamine in combination with a decongestant may be more effective.

Bacterial sinusitis can be treated with an appropriate antibiotic (amoxicillin–clavulanate, 500 mg by mouth tid, or clarithromycin, 500 mg by mouth bid) for a 10–14-day course.

• Medication-induced cough

Discontinuation of the offending ACE inhibitors of β-blockers often results in relief of symptoms within 1–4 days, but may take up to 4 weeks.

Substitutions of alternate drugs within the same class are unlikely to be effective, although alternatives such as angiotensin II receptor blockers may be useful substitutes.

When a patient’s condition necessitates an ACE inhibitor, oral sulindac, indomethacin, or inhaled cromolyn sodium may provide relief.

• Eosinophilic bronchitis

Eosinophilic bronchitis is most often treated with a trial of inhaled corticosteroids.

In one study, inhaled budesonide, 400 µg bid for 4 weeks, markedly improved airway inflammation and cough sensitivity in patients with eosinophilic bronchitis.⁴

Optimal duration of therapy is not clear.

• Bronchiectasis

Antibiotics directed against the most frequently encountered pathogens (H. influenza, Pseudomonas aeruginosa, and S. pneumonia) help to reduce cough and sputum production.

Patients generally require a minimum of 7 days of therapy.

• Interstitial lung disease

Treatment is directed at the underlying lung disease.

• Lung cancer

For non–small-cell lung cancer, resection, if possible, is the treatment of choice.

Treatment for nonresectable malignancy involves chemotherapy and/or radiation therapy.

• Congestive heart failure

Treatment is directed at the underlying disorder.

• Psychogenic cough

Removal of psychological stressors and behavioral modification therapy are probably the best treatment modalities for psychogenic cough.

Antitussives have little or no proven role in the therapy of psychogenic cough.

• Cough of unknown etiology

Nonspecific therapy may be useful in those circumstances in which no cause of cough can be found.

Several therapies are believed to suppress cough through action on the central medullary cough center.

Codeine (codeine sulfate, 10–20 mg PO q4–6h) is the traditional narcotic agent used for cough suppression.

Dextromethorphan is the most common nonnarcotic agent used for treating cough.

Studies comparing these two agents have been limited and have yielded variable results with respect to efficacy.

REFERENCES

1. Irwin RS, Baumann MH, Bolser DC, et al. Diagnosis and management of cough executive summary: ACCP evidence based clinical practice guidelines. Chest. 2006;129:1S–23S.

2. Pratter MR. Overview of common causes of chronic cough: ACCP evidence-based clinical practice guidelines. Chest. 2006;129:59S–62S.

3. The National Lung Screening Trial Research Team; Aberle DR, Adams AM, Berg CD, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365:395–409.

4. Brightling CE, Ward R, Wardlaw AJ, et al. Airway inflammation, airway responsiveness and cough before and after inhaled budesonide in patients with eosinophilic bronchitis. Eur Respir J. 2000;15:682–6.

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