Combatting the cough that won’t quit

CASE Margaret’s physical exam was unremarkable. Her vital signs were stable, she had no cervical lymphadenopathy, and her chest was clear on auscultation. She had a dry cough that occurred twice during the exam, but not on inspiration.

The patient’s work-up included office spirometry, which was normal; a nasopharyngeal culture for Bordetella pertussis was negative. We prescribed a 2-week course of therapy with brompheniramine/sustained-release pseudoephedrine and scheduled a return visit shortly after it was completed.

There is no gold standard diagnostic test to confirm or rule out postnasal drip as the cause of cough. CT scanning of sinuses has a poor positive predictive value and is no longer recommended as part of an initial work-up,⁹ but may be useful for patients whose symptoms persist longer than 3 weeks.

Consider bronchodilator Tx when asthma is suspected

Cough-variant asthma is the second most common cause of persistent cough, and is responsible for an estimated 28% of cases.⁶ Asthma is the easiest of the conditions included in the differential diagnosis for persistent cough to establish in an office setting. The challenge is to remember to consider it in patients who present with cough but no sign of the classic expiratory wheezing. When you suspect that a patient has asthma, consider empiric bronchodilator therapy—or conduct spirometry testing.

Spirometric values of forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) <70% and a positive bronchodilator response (≥12%) are consistent with an asthma diagnosis. Management of asthma depends on severity, and patients should be evaluated based on the National Heart, Lung, and Blood Institute’s National Asthma Education and Prevention Program Guidelines for the Diagnosis and Management of Asthma.¹⁰

It is crucial to ask patients with asthma (and, indeed, to ask all patients with a persistent cough) about exposure to secondhand smoke, and to stress the importance of avoiding smoking and secondary exposure. Individuals who are regularly exposed to secondhand smoke report more nasal symptoms and greater use of nasal decongestants compared with people with no exposure to smoke;¹¹ they also have poor control of asthma.^12-14

Cough unresolved? Add therapy for GERD

Although GERD is primarily associated with heartburn and gastrointestinal distress, it is not unusual for cough to be its only sign or symptom.¹⁵ In fact, GERD is the third most common cause of subacute cough—affecting about 21% of patients who seek help for cough at primary care practices.³

CASE Margaret returned to the clinic shortly after completion of a 2-week course of brompheniramine/sustained-release pseudoephedrine, and reported that she was still coughing frequently—and that the medication had brought little improvement. Because of her history of heartburn, we added a 2-week trial with a proton pump inhibitor (PPI)—omeprazole 20 mg/d.

While there are diagnostic tests for GERD, including a pH probe of the esophagus, a barium esophagogram, and manometry testing, empiric therapy with a PPI—starting with a trial of at least 2 weeks—often eliminates the troublesome cough.¹⁶ If the patient responds to treatment, the medication can be continued. Risks associated with long-term PPI therapy include osteoporosis and interference with calcium and magnesium absorption,¹⁷ so it is important to monitor patients taking them and to discontinue treatment as soon as the cough symptoms resolve.

Have you ruled out postinfectious cough?

If a patient has a cough that has lingered for 3 to 8 weeks after his or her recovery from an acute upper respiratory infection (URI), postinfectious cough may be the reason.^18,19 Such a cough is subacute and self-limiting. (If the cough lasts >8 weeks after an acute illness, other diagnoses, such as chronic infection, are more likely.)

The pathogenesis for postinfectious cough may be related to postviral airway inflammation or bronchial hyperresponsiveness, and antibiotics are not indicated.⁴ Patients may be treated with a bronchodilator such as ipratropium rather than a beta-agonist or inhaled corticosteroids; oral tapered prednisone can be prescribed, if needed, for severe paroxysms, although there is limited evidence of its efficacy.²⁰ Central antitussive agents such as codeine and dextromethorphan can be used when other measures fail to bring relief.

Nonasthmatic eosinophilic bronchitis does not impede airflow

NAEB is less well known than the conditions discussed thus far, but it is a relatively common cause of persistent cough.^21-23 In some studies, up to 13% of patients with subacute cough were diagnosed with NAEB.⁶

Unlike asthma, NAEB is not associated with abnormalities in airway function; patients have no dyspnea and no wheezing, and no obstruction of airflow.²⁴ Patients will have FEV1 >80% and FEV1/FVC >75% on spirometric examination, a negative response to bronchoprovocation, and, typically, an elevated sputum eosinophil count of >3%. Because induced sputum or bronchoscopic washings are difficult, exhaled nitric oxide testing is another option. If these tests are not available, a trial of inhaled steroids is indicated, even if neither spirometry nor bronchoprovocation testing was abnormal.⁹