Cough, cough, cough ... for 6 months!

Clinical pearls for frontline PCPs

A 35-year-old high school teacher presents with a chronic cough of 6 months’ duration. The cough is described as dry, irritating and persistent. He has tried every over-the-counter cough medicine that he could find to no avail.

The cough keeps him up at night, and his wife now has to sleep in another part of the house. The cough has been so severe that he has had to take half and even full days off from his job as a teacher. He has used up all his allotted sick days for the semester and is worried that he will lose his job. He has often had to excuse himself from teaching and staff meetings because of the cough.

Philip A. Bain

The patient has a past medical history of hypertension and GERD. He has no history of asthma. His current medications include 50 mg losartan daily and 40 mg omeprazole daily.

He drinks three to four glasses of wine per week. He also smokes about three to four cigarettes per day, down from half a pack per day 6 months ago.

The medical assistant (MA) checks him in and notes that he coughs throughout the visit. At one point, it looked as though he was going to vomit because he was coughing so hard.

The MA presents the patient to the physician:

“Doc, this 35-year-old teacher is here to sort out a 6-month history of a terrible cough. He doesn’t bring up any significant phlegm or blood. The cough is noted every single day, many times a day. He has had to miss a significant amount of school and is worried that he may be fired for exceeding his allotted sick days. He looks worn out from coughing. His meds are losartan and omeprazole. He smokes a few cigarettes per day.”

Source: Satia I, et al. Clin Respir J. 2021;doi:10.1080/24745332.2021.1979904.

The physician reviews the chart and enters the room. The patient describes the cough in detail and is noted to cough, at times, violently throughout the visit. On physical examination, his head and neck assessments were normal. The tympanic membrane and external auditory canals were both normal. No wheezing was noted, even on forced expiration. Chest X-ray was normal.

The physician made the following initial recommendations:

1. Completely stop smoking.
2. Get spirometry, including a methacholine challenge.
3. Start an empiric trial of a first-generation antihistamine diphenhydramine 25 mg twice daily.

At his follow-up visit 2 to 3 weeks later, the cough was essentially the same. The patient noted significant fatigue from the diphenhydramine, so he stopped it about 1 week ago. Spirometry, including methacholine challenge testing, was normal. He was able to stop all tobacco use.

At this visit, the physician recommended the following:

1. A pH probe study while continuing his high-dose omeprazole.
2. An empiric trial of inhaled corticosteroid was considered but not recommended because of his entirely normal spirometry, with and without provocation.
3. ENT referral for evaluation of possible chronic sinusitis and upper airway hyperreactivity syndrome.

At the next follow-up visit, the ear, nose and throat (ENT) notes were reviewed and indicated that the evaluation was negative for any ENT-related etiology. The pH probe study was normal for someone on high-dose omeprazole.

The patient was diagnosed with refractory unexplained chronic cough. He was started on gabapentin 100 mg at bedtime and this was increased to 300 mg at bedtime in 2 weeks. He was also referred to speech therapy.

At the follow-up visit, the patient reported approximately 50% improvement. He had not had to miss any school since last visit.

The patient said he found the speech therapist’s tips to be particularly helpful. He was still coughing at night, enough to keep him from sleeping well. He was tried on low-dose, long-acting morphine 5 mg at bedtime.

At his next visit 4 weeks later, the patient’s cough had essentially resolved. He had stopped the morphine about 1 week before the visit as he felt that he did not need it any longer. The physician tapered him off his gabapentin over 6 to 8 weeks, and he remained cough free.

Lessons learned

1. Chronic cough is very common. In one study, it was the third most common reason for an ambulatory primary care visit.
2. Acute cough is defined as a cough of less than 3 weeks. Subacute cough is a cough of 3 to 8 weeks. Chronic cough is a cough lasting longer than 8 weeks.
3. Many times, an underlying cause of the chronic cough can be identified.
4. Refractory cough is defined as a persistent cough despite optimal therapy of known underlying etiology.
5. A persistent cough for which no underlying etiology is identified is called an unexplained chronic cough.
6. The top five diagnoses for chronic cough include asthma, GERD, upper airway cough syndromes, postnasal drip due to allergic or nonallergic rhinitis and vocal cord dysfunction.
7. Red flags suggestive of a more ominous etiology include fever, hemoptysis, lymphadenopathy and unexplained weight loss.
8. One very rare, easily remediable etiology is a foreign body such as wax or a hair touching the tympanic membrane. Do not forget to conduct a simple ear exam.
9. Previously, it was common to recommend sequential 2- to 4-week empiric trials with a first-generation antihistamine, then an inhaled corticosteroid, followed by a potent gastric acid blocking agent such as a high-dose proton pump inhibitor. A more current approach seeks to rule out these conditions with ENT evaluation, spirometry and pH probe rather than medication trials.
10. A chest X-ray should be done if the cough persists longer than 8 weeks. Checking sputum for eosinophils and/or complete blood count with differential looking for eosinophils can help to diagnose eosinophilic bronchitis, a very treatable disorder.
11. Medications like angiotensin-converting enzyme (ACE) inhibitors (not angiotensin receptor blockers) are a common cause of cough. It can take up to 2 to 8 weeks for the ACE inhibitor-related cough to resolve after discontinuation.
12. Speech therapy can be very helpful to reduce the chronic cough.
13. For chronic undiagnosed refractory cough with negative evaluation for asthma, GERD and postnasal drip, an empiric trial of gabapentin or pregabalin can be tried. If not helpful, a trial of low-dose, long-acting morphine can be helpful. Ongoing trials of a new medication, PCSX inhibitor, look promising for some cases of chronic cough.
14. Referral to speech therapy, pulmonary, allergy, ENT and/or gastroenterology can be helpful depending on the predominant symptoms.

References:

• Michaudet CHARLIE, Malaty J. Am Fam Physician. 2017;96(9):575-580.
• Parker SM, et al. Thorax. 2023;doi:10.1136/thorax-2023-220592.
• Satia I, et al. Clin Respir J. 2021;doi:10.1080/24745332.2021.1979904.
• Slinger C, et al. Cochrane Database Syst Rev. 2019;doi:10.1002/14651858.CD013067.
• Solving mysterious chronic cough cases. https://acpinternist.org/archives/2018/07/solving-mysterious-chronic-cough-cases.htm. Published July 2018. Accessed Dec. 4, 2023.