Chronic persistent refractory cough — diagnosis by exclusion

Patient case: A 62-yr-old longstanding female patient presents to the pharmacy for an OTC consult for a chronic cough. Whenever my patients ask for an OTC recommendation, and it appears they have a chronic issue, I bring them in the office, search their file and have a quick glance at their med list. I think of OTC recommendations as acute episodic care concerns. Chronic issues require more investigation. For this particular patient, I scan her chart at the pharmacy and see:(No known drug allergies)Med conditions/Rx meds: breast cancer—post-bilateral mastectomy, not requiring chemo nor radiation; on letrozole 2.5mg/day (r/a in 5 yrs, Dec. 2024)asthma—on trelegy 100mcg, 1 inhalation daily and ventolin MDI 1 to 2 puffs four times daily as neededGERD—on esomeprazole 40mg/dayallergic rhinitis—on desloratadine 5mg/day OTC, dymista 1 spray IEN BIDIn my head, I quickly recall the top three causes of chronic cough: reactive airway, postnasal drip, acid reflux. Patient has all 3 conditions, and is being treated for all 3. I ask more about symptoms. Patient reports frequent periodic uncontrollable coughing fits with sneezing that is worse at night time, causing difficulty sleeping. This results in next day hangover and somnolence, affecting mood and quality of life. No feeling of acid reflux or burping or regurgitation that is unrelated to meal time. So at least in my head I have ruled out any cause of worsening GERD. During our few minutes of conversing, I witness the cough. I advise patient she can trial OTC dextromethorphan 30mg at bedtime as needed to see if that’ll help. In the interim, I will fax her family doc for step up treatment for asthma which will also help with allergy symptoms, to see if that may be the cause. She agrees.I fax a recommendation to step patient up to montelukast 10mg/day, GP accepts. 1 month later. Patient presents again reporting symptoms still there. Sneezing has improved with addition of montelukast, but otherwise the cough lingers. At this point, I wonder if it may be an oncologic cause. I look at Clinical Connect and see all patient CXR and CT scans and full body scans were fine immediately post-mastectomy but nothing since. I phone patient’s oncologist (no referral needed as patient is already followed by onco) and explain situation and request if we can do an CXR and CT chest to rule out any malignancy. She agrees and sets patient up for both. Results are both negative (thank God), and oncologist rules out oncology causes but asks patient and me to follow up with GP for other causes.The negative CXR and CT chest also rules out infective causes. Now acid reflux, infective, oncologic, and allergic causes are ruled out in my mind. I am still pondering asthma and postnasal drip. I fax GP again to suggest adding atrovent 20mcg MDI to regimen to see if that may help. GP sees my fax, doesn’t respond, but books patient in for appt (I know because patient told me and I received a prescription for a neti pot to use prior to Dymista). As I am counselling the patient on this, she reports that her GP thinks it is sinus-related given the style of cough with nasal symptoms, and nocturnal symptoms. 1 month later. Still no relief of symptoms with neti pot plus Dymista. Patient is frustrated. I fax GP requesting respirology referral. GP declines, states he thinks it is still sinus related, so refers to ENT. ENT assessment and endoscopy negative. At this point, I fax ENT suggesting a CT of sinuses and switch from OTC desloratadine 5mg/day to rupall 10mg/day as it is stronger, and going along the post nasal drip/ sinus- induced cough theory per GP speculation. ENT agrees, given patient has been struggling for months now. ENT goes one step further and also refers to allergist to rule out any other potential allergens. CT sinus is clear.Patient goes to allergist who rules out all allergens. So now we’ve ruled out acid reflux, infective, oncologic, allergic and post-nasal drip causes. Still pending is asthma-related. I fax GP again for respiratory referral, he agrees. Patient goes in for PFT testing, and respiratory referral appt is in 4 months. Patient presents exhausted and pleading for help, not wanting to wait 4 months! I am stumped. I tell her I will read more over the weekend and get back to her. After doing my research, I call her the following week, asking if she’s recently had COVID-19, and when the cough started. She reports testing positive for COVID-19 about nine months ago, which may vaguely be the start of her symptoms, as far as she recalls. A lightbulb turns on in my head. I tell her I will fax her GP for a suggestion, and read my letter to her GP that I just faxed:“Dr. X:Patient is still having chronic cough query neurogenic cough post-COVID-19 infection + approximately 9 months ago. She has since had many CXRs and CT scans (both chest and sinuses/head); all clear. She has had an oncology assessment + PFT testing done + ENT testing + allergist testing, all of which are negative, pending respirology appt.As such, I suspect it is a post-COVID neurogenic cough. Despite max dose triple therapy inhalers + Dymista + antihistamines + Singulair + neti pot, cough persists. Sub optimal benefit with dextromethorphan or codeine cough syrups OTCs, alluding to hyper sensitive cough reflex from vagal tone dysfunction from COVID infection. From what I’ve researched, COVID leads to vagal tone dysfunction through inflammation and immune modulation. How? The COVID virus enters the body via the ACE-2 enzyme, which is present in the brain and respiratory tract. The virus binds to the receptors, making the cough reflex more sensitive in the nervous system, resulting in inflammation of vagal tone and dysfunction, specifically in the parasympathetic nervous system WHICH IS NOT under conscious control (which explains why they can’t control the cough). What works to treat it are:- neuromodulatory agents like gabapentin and pregabalin (gabapentin is mentioned in the American chest guidelines but not pregabalin because studies occurred after guideline was published), and- centrally-acting cough meds like DM or codeine.This is because they act centrally to de-sensitize the abnormal cough reflex receptors, hence neurogenic cough.I suggest a trial of: a) Lyrica 25mg, 1 cap BID x 1 week then 50mg BID x 1 week then 75mg BID x 2 weeksb) Atrovent 20mcg MDI, 2 puffs QID x 2 to 4 weeks —> anticholinergic but also has centrally acting effects.”Of course, GP accepts the above immediately. I phone patient to counsel. 1 month later —> cough is virtually gone! (Patient still has 3 months left before her respirology appointment.)Lessons to learn from this case: be an inquisitive clinician —> remember that you entered this profession with an implied oath to continue lifelong learning—this is a prime example of why that is crucialwhen patients present with a chronic cough, you should always ask about history of COVID infections, as you would about any other chronic health conditionthere will always be patient cases that challenge you to the max. Go back to the basics, and it is important to have a structured approach and a chronological game plan in mind to make things clear and provide a systematic thought process to followinformation is knowledge and knowledge is power. Clinicians listen to one another initially based on titles and specialties, but we will always lean on those with the most information and knowledge. Pharmacists, family docs, specialists, we are all in this for the patient, who should always be the centre of our focus. If at any point during this case you thought “stay in your lane” or “you’re not a doctor” or “you just got lucky” or any other negative thought, then re-check your own intentions in your practice, and see if you put your patients above your own insecurities and inferiority complexespart of being a clinician is being humbled by your patients and other colleagues and constantly learning from them. We are a teamOntario (where I practice) has significant and critical healthcare system-wide issues that are absolutely appalling and concerning for patient care, be it extensive wait times for specialists and diagnostic imaging, lack of primary care access or lack of optimization of scope of exceptionally qualified practitioners like pharmacistsfor a case like this, where is my consult fee? What do I bill and how? the Ontario government must view us in a critically different light, one in which puts the patient at the forefront, and our education and expertise into practice

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Chronic persistent refractory cough — diagnosis by exclusion

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Samier Kamar

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