Pearls of Wisdom: Undifferentiated Cough

Bill, a 36-year-old hospital unit clerk, has had a nonproductive cough for 1 year. He has no associated symptoms. Results of chest radiography, sputum culture tests, tuberculosis tests, chest computed tomography, laryngoscopy, pulmonary function tests, and esophageal manometry were all within normal limits. Therapeutic trials of a short-acting β-agonist (SABA) (albuterol), a proton-pump inhibitor (PPI) (esomeprazole), and a nasal corticosteroid (fluticasone) have failed.

Which of these therapeutic options might be best for him to try?

A. Gabapentin
B. Tiotropium inhaler
C. Cimetidine
D. Azelastine nasal spray

What is the correct answer?
(Answer and discussion on next page)

Louis Kuritzky, MD, has been involved in medical education since the 1970s. Drawing upon years of clinical experience, he has crafted each year for almost 3 decades a collection of items that are often underappreciated by clinicians, yet important for patients. These “Pearls of Wisdom” often highlight studies that may not have gotten traction within the clinical community and/or may have been overlooked since their time of publishing, but warrant a second look.

Answer: Gabapentin

If you had pneumonia, I would expect you to have a cough. If you had accidentally inhaled a jelly bean, and it was in your lung, you would have a cough. If you had asthma, postnasal drip, or allergies, you would have a cough. Undifferentiated cough refers to individuals whose coughing has no discernible cause.

Read More...
The Case of the Coughing Obstetrician
Treatment of Acute and Subacute Cough: What Works, What Doesn't

Traditionally, the evaluation pathway for individuals with undifferentiated cough begins with thoracic pathology (eg, tuberculosis, cancer, inflammation), then to gastrointestinal tract pathology or ear, nose, and throat pathology, then to possible pharmacologic causes (eg, angiotensin-converting enzyme inhibitors), then to psychogenic causes (eg, anxiety).

The patient in this case has undifferentiated cough—he has no sign of any pathology that would explain why he is coughing. Trials of a SABA, a PPI, and a nasal corticosteroid were appropriate, since not all patients are aware of their allergic, asthmatic, or gastroesophageal reflux disease (GERD) status, and short trials of these medications can help to rule out various causes of cough. But all of these treatments have failed. So, what do we try next?

The Research

A randomized, double-blind, placebo-controlled trial evaluated the effects of the neuromodulator gabapentin in patients with undifferentiated cough. Sixty-two participants who had failed treatment for asthma, GERD, and rhinitis were randomly assigned to receive either gabapentin or placebo for 10 weeks. Those taking gabapentin were allowed to take up to 1800 mg/d.

The Results

The researchers measured success in their trial using the Leicester Cough Questionnaire, and they observed higher improvement scores in patients taking gabapentin than in those taking placebo. There was also reduced cough severity and cough frequency in those taking gabapentin.

What’s the “Take-Home”?

If you are without any obvious evidence leading to suspicion of a particular organ system as the culprit in chronic undifferentiated cough, the easiest way to evaluate the potential causes is to do short clinical trials of a SABA, an antihistamine, or a corticosteroid for allergies and a PPI for GERD. Should these trials fail, then gabapentin may be worth a try.

Reference:
Ryan NM, Birring SS, Gibson PG. Gabapentin for refractory chronic cough: a randomised, double-blind, placebo-controlled trial. Lancet. 2012;380(9853):1583-1589.