Cough

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[edit] Cough

J. Mark Madison

Richard S. Irwin

Cough is a reflex that serves as a clearance mechanism when tracheobronchial mucociliary clearance is inadequate. Airflow generated during cough is normally sufficient to expel secretions or foreign bodies from the respiratory tract. Even in their absence, however, cough still can be precipitated by disease processes that directly or indirectly stimulate the sensory nerve fibers of the vagus nerve that serve as cough receptors.

Normal people without an illness rarely cough. Cough is a very common clinical problem. In a national ambulatory medical care survey in the United States in 1991, cough was the most common complaint for which patients sought medical attention and the second most frequent reason for a general medical examination.^[1] The common cold is almost always associated with cough and accounts for many of these patient evaluations.

Cough can be a debilitating symptom. It is inappropriate to minimize a complaint of cough and advise the patient to “live with it.” Referrals of patients with persistently troublesome cough of unknown etiology account for up to 38% of a pulmonologist's outpatient practice.^[2] Relatively few conditions, however, account for most cases of persistently troublesome cough.^[3][4][2] In prospective studies that included smokers, chronic cough is caused by postnasal drip syndrome (PNDS), asthma, gastroesophageal reflux disease (GERD), chronic bronchitis, or bronchiectasis in 91% to 94% of cases. Among nonsmokers who are not taking an angiotensin-converting enzyme inhibitor (ACEI) drug and who have a normal chest radiograph, persistently troublesome cough is almost always caused by PNDS, asthma, or GERD. Multiple causes may contribute simultaneously to the cough in at least 25% of these patients.^[2]

[edit] History And Physical Examination.

The character and timing of cough are not helpful diagnostically.^[5] A comprehensive history should be taken seeking evidence for uncommon but potentially life-threatening causes of cough, such as congestive heart failure and pulmonary thromboembolism. The history should also specifically identify symptoms suggestive of asthma or GERD.

Examination of the nasopharynges and oropharynges may reveal mucopurulent secretions or a cobblestoned mucosa when PNDS occurs from rhinosinus conditions. A cobblestoned mucosa may also be caused by GERD with reflux of gastric contents into the posterior oropharynx. Wheezing heard on auscultation of the chest suggests but is not diagnostic of asthma.

[edit] Duration.

The differential diagnosis of cough depends on the duration of symptoms.^[4][2] Cough of less than 3 weeks' duration is defined as acute, whereas chronic cough is present for longer than 3 weeks and is persistently troublesome.

[edit] ACUTE COUGH

[edit] Common Cold.

The common cold is the most common cause of acute cough (see Chapter 33 ). The diagnosis is usually certain when an acute upper respiratory illness predominantly affects the nasal passages (rhinorrhea, sneezing, nasal obstruction, postnasal drip). Patients may also have fever, lacrimation, and irritation of the throat, with a normal chest examination. Since cough from the common cold is mainly caused by postnasal drip, its treatment relieves the cough (see L).^[6][4]

[edit] Immunocompromise.

For the patient who may be immunocompromised, acute cough should be evaluated further when the common cold seems unlikely clinically. An abnormal chest radiograph or a normal chest radiograph with a CD4 count less than 200 cells/mm³, a CD4 count of 200 to 499 cells/mm³ when the patient is clinically ill, and oxygen desaturation on exercise are indications for additional diagnostic studies to exclude intrathoracic opportunistic infection^[7] (see Chapter 32 ).

[edit] Other Causes.

Other common causes of acute cough are acute bacterial sinusitis, acute lower respiratory tract infections, exacerbation of chronic bronchitis, allergic rhinitis, environmental irritant rhinitis, and pertussis.^[3][4] When acute bronchitis causes cough in patients without underlying lung disease, it is most often caused by a virus, and antibiotics should not be given.

Pertussis needs to be considered in the evaluations of both acute and chronic cough.^[4] Adult patients may not have the characteristic inspiratory whoop at the end of a coughing paroxysm, but they often vomit and usually have a catarrhal stage followed by paroxysmal and convalescent stages. The physician should consider diagnostic testing and treatment for pertussis infection in patients with cough-vomit syndrome, characteristic whoop, recent close contacts, or particularly severe cough in a high endemic area. If taken early in the course of the illness, a nasopharyngeal smear for culture, direct fluorescent antibody (DFA), or more recently polymerase chain reaction (PCR) for Bordetella pertussis will confirm the diagnosis. Beginning treatment with a macrolide antibiotic within 8 days of infection is effective in decreasing the severity of infection and transmission. Because pertussis is contagious, prophylaxis for exposed persons is important.

[edit] Life-threatening Conditions.

Acute cough can also be the presenting symptom of serious illnesses such as pneumonia, asthma, congestive heart failure, pulmonary thromboembolism, tuberculosis, lung cancer, and aspiration.^[3] About 50% of patients with pulmonary embolism have cough, which may be the only respiratory complaint. Further workup (e.g., chest radiograph ventilation-perfusion scan) may be appropriate at this stage in patients at high risk for or with compelling clinical reasons to suggest a serious illness.

[edit] CHRONIC COUGH

[edit] Chest Radiograph.

After the history and physical examination, a chest radiograph is the first step in the evaluation of almost all patients with chronic cough.^[3][4][2] The chest radiograph is extremely useful in initially ranking diagnostic possibilities. A normal or near-normal radiograph makes PNDS, asthma, and GERD likely but makes bronchogenic carcinoma, interstitial disease of the lung parenchyma, and bronchiectasis unlikely. For a young nonsmoker without underlying cardiopulmonary disease who is taking an ACEI, the physician should consider stopping the ACEI before proceeding with radiographic evaluation.

[edit] HIV Disease.

If the patient is or may be immunocompromised by HIV disease and the chest radiograph is normal, a CD4 count and oximetry during exercise should be ordered (see D).

[edit] Diagnostic Studies.

For the immunocompetent host, chest radiograph abnormalities should be pursued with sputum analysis, bronchoscopy, high-resolution computed tomography (HRCT), and noninvasive cardiac studies according to the most likely diagnostic possibility.^[3] For the immunocompromised host, sputum analysis and bronchoscopy are used to identify opportunistic lung infections.

[edit] Pertussis.

Since the cough caused by pertussis infection can last more than 4 to 6 weeks, pertussis needs to be considered in the evaluations of both acute and chronic cough (see E).

[edit] Other Causes.

Diagnostic studies in current smokers or patients taking ACEIs should not be done until the response to smoking cessation or ACEI discontinuation for 4 weeks can be assessed.^[3][4] ACEI-induced cough has been reported to appear within a few hours of taking a first dose in many patients but may not become apparent for months. In general, cough from ACEIs should improve significantly within 4 weeks of stopping the medication. Cough appears to be a class effect of these drugs and is not dose related. Losartan, an angiotensin II receptor antagonist, is a different class of drug that has not been associated with cough and can be substituted for an ACEI.^[8]

Chronic bronchitis typically causes chronic cough, but smokers do not usually seek medical attention for cough. When evaluating a smoker with chronic cough, it is important to eliminate smoking for at least 4 weeks to see if this alone resolves the cough. A careful environmental and work history also should be taken to identify and eliminate other environmental irritants that could be triggering the cough (see Chapter 11 ).

[edit] Postnasal Drip Syndrome.

PNDS secondary to rhinosinus diseases refers to symptoms such as cough, dyspnea, and wheeze arising from the drainage of excessive secretions into the hypopharynx and larynx. Patients with PNDS often describe a dripping sensation in their throats, nasal discharge, and the frequent need to clear the throat. PNDS is the most common cause of chronic cough in adults.^[2] For adults with chronic cough from PNDS, sinusitis is the cause of the PNDS in 30% to 60% of patients.

The other major cause of PNDS is rhinitis of any cause. Rhinitis (e.g., allergic, perennial nonallergic, postinfectious, environmental irritant, vasomotor) leading to PNDS is treated with an antihistamine-decongestant combination and, when feasible, avoidance of environmental precipitating factors. For the initial therapy of rhinitis, our preference is to prescribe combination therapy that includes dexbrompheniramine as a first-generation H₁ antagonist plus pseudoephedrine as a decongestant, or equivalent drug. All forms of rhinitis generally respond to therapy that includes first-generation antihistamines. For patients with allergic rhinitis who do not tolerate the sedating effects, the newer nonsedating H₁ antagonists also are effective. Nonallergic rhinitis, which is not histamine mediated, does not respond to these H₁ antagonists because they lack significant anticholinergic activity. When antihistamine-decongestant combination therapy cannot be tolerated, rhinitis may respond to intranasal corticosteroids or intranasal ipratropium. These nasal medications should be used rather than older-generation antihistamine-decongestant combination therapy when the patient has glaucoma, benign prostatic hypertrophy, or poorly controlled hypertension.

If PNDS does not improve after 1 week of treatment for rhinitis, sinusitis may be the cause of the PNDS. Sinus radiographs should be ordered to confirm the diagnosis rather than prescribing antibiotics empirically. Treatment of cough caused by chronic sinusitis includes antibiotics, antihistamines, and decongestants that facilitate sinus drainage.^[4] Antibiotics should cover Haemophilus influenzae, Streptococcus pneumoniae, and upper respiratory tract anaerobes. The physician may also prescribe a first-generation antihistamine-decongestant oral medication for 3 weeks and a decongestant nasal spray for a maximum of 5 days.

[edit] Asthma.

Asthma is the second most common cause of chronic cough in adults.^[2] Patients with asthma complain of episodic wheezing, shortness of breath, and cough and may wheeze on examination. The examiner should recognize, however, that cough may be the only manifestation of asthma (i.e., cough-variant asthma). Nonspecific pharmacologic bronchoprovocation challenge testing with methacholine or histamine is extremely helpful in ruling out asthma as a cause of cough.^[9]

Uncomplicated cough-variant asthma responds to standard asthma medications.^[4] Cough begins to improve within 1 week of beginning inhaled β₂-adrenergic agonists and resolves within 6 to 8 weeks of beginning inhaled corticosteroids. Combination therapy with inhaled β₂-adrenergic agonists plus inhaled corticosteroids or inhaled nedocromil is recommended. If these agents themselves provoke cough, different proprietary formulations, spacer devices, and oral therapy are helpful.

A related, newly described cause of chronic cough is eosinophilic bronchitis.^[4] The prevalence of this disease as a cause of chronic cough is not yet established. Patients have sputum eosinophilia, negative bronchoprovocation challenge testing, and rapid improvement with corticosteroids.

[edit] Gastroesophageal Reflux Disease.

GERD is the third most common cause of chronic cough.^[6][10] GERD should be suspected as a cause of cough when patients complain of frequent heartburn, regurgitation, or sour taste. These symptoms are sufficient to make a diagnosis of GERD without resorting to barium esophagography or 24-hour esophageal pH monitoring. In the evaluation of cough, these diagnostic techniques are reserved for identifying “silent” GERD, or GERD producing cough without other symptoms.

Prolonged, 24-hour esophageal pH monitoring is helpful in linking silent GERD and cough in a cause-and-effect relationship. Cough and reflux events can be correlated when patients keep a symptom diary during the monitoring session. The session can be considered consistent with GERD as a cause of chronic cough when reflux events (acid or alkaline) are temporally correlated with cough and when any reflux parameter slips from the normal range (e.g., percentage of time that pH is less than 4.0). Although a less sensitive and less specific test for diagnosing GERD, barium esophagography may reveal reflux to the midesophagus or higher, even when not detected by pH probe testing.

For cough, maximal medical therapy for GERD is recommended initially: a high-protein, low-fat antireflux diet; acid suppression with H₂ antagonists or proton pump inhibitors; a prokinetic agent; treatment of obstructive sleep apnea; and when possible, elimination of medications for comorbid diseases that worsen GERD (see Chapter 24 ). If cough is not at least partially improved in 3 months, 24-hour esophageal pH monitoring can determine whether GERD is still the likely cause of cough but has failed to respond to therapy. In that case, surgery may be considered^[4] (see Chapter 101 ).

[edit] Aspiration Syndrome.

In the appropriate clinical context (e.g., patient with cerebrovascular accident) an aspiration syndrome should also be considered in the differential diagnosis of chronic cough. A modified barium swallow study is useful in evaluating this possibility.

[edit] Diagnoses and Therapies.

Diagnostic studies only suggest the cause(s) of chronic cough.^[3] The definitive diagnosis always depends on observing a favorable response to a specific treatment of the suspected cause. The general aproach to treating chronic cough is to begin specific therapy and observe for a clinical response. If at least partial resolution of cough occurs with the treatment regimen, the specific diagnosis is confirmed. After additional evaluation, other potential causes of cough may be identified, and then specific treatments are added to the existing regimen. This sequential addition of specific therapy is highly effective.^[3][2] Nonspecific antitussive therapy is indicated when specific therapy cannot be given, either because the cause of cough is not known or because specific therapy has not had a chance to work or will not work (e.g., inoperable lung cancer). Nonspecific therapies shown to be clinically effective are codeine, dextromethorphan, and ipratropium in chronic bronchitis.^[4]

[edit] Additional Studies.

Less common causes of chronic cough are bronchiectasis, bronchogenic carcinoma, chronic interstitial pneumonia (e.g., idiopathic pulmonary fibrosis), metastatic carcinoma, left ventricular failure, and psychogenic cough. The latter is a diagnosis of exclusion and, in our experience, rare.

The following additional testing may be useful if cough persists after evaluation and treatment for PNDS, asthma, and GERD^[3][4]: (1) ear, nose, and throat (ENT) consultation when sinusitis fails to respond to medical therapy; (2) allergy consultation when PNDS fails to respond to therapy but suspicion of allergic disease remains high; (3) bronchoscopy to check for endobronchial abnormalities; (4) HRCT scan to assess for interstitial lung disease and bronchiectasis; and (5) noninvasive cardiac studies.

[edit] Management Pitfalls.

The most common management pitfalls are (1) failure to consider common causes of cough when one diagnosis seems obvious on clinical or radiographic grounds; (2) failure to consider that cough may have more than one cause; (3) failure to consider ACEI as a cause of cough; (4) use of newer nonsedating H₁ antagonists to treat nonallergic inflammatory disease; (5) assumption that a positive methacholine challenge test is diagnostic of asthma as the cause of cough; (6) failure to recognize that inhaled asthma medications may cause cough; (7) failure to use prolonged esophageal pH monitoring and to assess the response to medical therapy; (8) failure to consider that treatment for GERD may require 2 to 3 months before being even partially effective; and (9) failure to consider that maximal medical treatment for GERD may fail.

[edit] REFERENCES