A 62-year-old woman comes to the office due to a nonproductive cough that is "quite disturbing." The cough has been present for 2 months and is accompanied by a tickling or scratching sensation in the throat. The patient cannot identify a provoking factor for the cough, which occurs mostly during the day. She has no fever, rhinorrhea, or chest pain. The patient has had no changes in appetite or weight, and her lifestyle is mostly sedentary. She has difficult-to-control hypertension. Her medications, which were last readjusted 3 months ago, include chlorthalidone, ramipril, and amlodipine. The patient, who emigrated from China 30 years ago, does not use tobacco, alcohol, or illicit drugs. Her temperature is 36.8 C (98.2 F), blood pressure is 130/90 mm Hg, pulse is 80/min, and respirations are 16/min. The patient's conjunctivae are normal, oropharynx is clear without erythema or cobblestoning, lungs are clear without wheezes or crackles, and heart sounds are normal. She has no peripheral edema. Complete blood count and chest x-ray are normal. Which of the following is the most likely cause of this patient's current symptoms?

Question

A 62-year-old woman comes to the office due to a nonproductive cough that is "quite disturbing."  The cough has been present for 2 months and is accompanied by a tickling or scratching sensation in the throat.  The patient cannot identify a provoking factor for the cough, which occurs mostly during the day.  She has no fever, rhinorrhea, or chest pain.  The patient has had no changes in appetite or weight, and her lifestyle is mostly sedentary.  She has difficult-to-control hypertension.  Her medications, which were last readjusted 3 months ago, include chlorthalidone, ramipril, and amlodipine.  The patient, who emigrated from China 30 years ago, does not use tobacco, alcohol, or illicit drugs.  Her temperature is 36.8 C (98.2 F), blood pressure is 130/90 mm Hg, pulse is 80/min, and respirations are 16/min.  The patient's conjunctivae are normal, oropharynx is clear without erythema or cobblestoning, lungs are clear without wheezes or crackles, and heart sounds are normal.  She has no peripheral edema.  Complete blood count and chest x-ray are normal.  Which of the following is the most likely cause of this patient's current symptoms?

Quizplus · Accepted Answer

This patient's chronic nonproductive cough is most likely an adverse effect of ACE inhibitor (eg, ramipril) therapy, which occurs in 5%-20% of patients. The cough typically begins within a week of drug initiation or dosage increase but can be delayed for months. The pathophysiologic mechanism of the cough is not completely understood. ACE is usually involved in the metabolism of kinins and substance P, so ACE inhibitor therapy leads to accumulation of these molecules. Kinin accumulation is thought to cause bronchial irritation through increased production of prostaglandins. ACE inhibition also activates the arachidonic acid pathway, which may contribute to cough through increased levels of thromboxane, leading to bronchoconstriction. Women and individuals of Chinese descent have a higher chance of developing cough due to ACE inhibitor therapy, and a tickling or scratching sensation in the throat (as reported by this patient) is a common feature. If the cough is significantly bothersome, discontinuing the drug typically results in resolution of the cough within days. (Choice A) Airway inflammation and reversible obstruction occur in asthma, which is a common cause of chronic cough. Ramipril use and the absence of wheezing make ACE inhibitor-induced cough more likely. (Choice B) Destruction and permanent damage of the conducting airways occur in bronchiectasis, which is characterized by a cough productive of large amounts of sputum. Nonproductive cough makes bronchiectasis very unlikely. (Choice D) Laryngeal stimulation by regurgitated foods and liquids occurs in patients with laryngopharyngeal reflux, which is a common cause of chronic cough. Laryngopharyngeal reflux is unlikely in the absence of other suggestive signs and symptoms (eg, oropharyngeal erythema, heartburn, hoarseness). (Choice E) Pulmonary venous hypertension occurs in congestive heart failure and often presents with cough due to pulmonary edema. The absence of peripheral edema and crackles on lung auscultation makes heart failure less likely. Additionally, cough due to heart failure is typically productive rather than nonproductive. (Choice F) The stimulation of cough receptors by nasal secretions occurs in upper airway cough syndrome (postnasal drip), which is a common cause of chronic cough. The absence of oropharyngeal cobblestoning on physical examination and lack of rhinorrhea make this condition less likely. Educational objective: Chronic nonproductive cough is a common side effect of ACE inhibitors that is likely due to increased circulating levels of kinins, substance P, prostaglandins, and thromboxane. References: A prospective study of frequency and characteristics of cough during ACE inhibitor treatment. (http://www.ncbi.nlm.nih.gov/pubmed/25992489)

A 62-Year-Old Woman Comes to the Office Due to a Nonproductive