The Unsolved Mystery of The Chronic Cough

1. The Unsolved Mystery of The Chronic Cough Rhonda Hoyer, RN, MS, APRN-BC Nurse Practitioner Internal Medicine, University Station

3. Case Objectives Recognize extra-esophageal manifestations of GERD and the potential complications Identify differential diagnoses associated with chronic cough Identify the most appropriate course of treatment

4. Case CC: Severe cough for 6 days HPI: 42 yo female severe non-productive cough, so bad she almost vomits, keeping up at night, clear rhinitis and laryngitis. Fever 1st night of illness, nothing now. Appetite and energy good. Denies SOB, chest pain.

5. Past Medical History Asthma. Mild-intermittent, PRN albuterol. No maintenance inhalers ever. Hx of 1 exacerbation requiring prednisone and Advair. Abd pain thought to be related to gallbladder vs. uterine fibroids. Resolved s/p cholecystectomy and TAH in 2006 Hiatal hernia Depression/Anxiety. Seeing psychiatrist/counselor regularly.

6. History (continued) Surgical History TAH Cholecystectomy Tonsillectomy Appendectomy Social History: Single, apt living with her cats. NS, no alcohol or drug use. Warehouse worker.

7. Family History Negative for autoimmune disease Positive for CAD in her father No other significant FHx

8. Medications NKDA Albuterol PRN Cymbalta 60 mg, 2 capsules qAM Lamictal 200 mg QD Lorazepam 1-2 mg qHS PRN Prilosec 20 mg QD Seroquel 150 mg qHS Lexapro 10 mg QD

9. Objective Gen: pleasant, dry, harsh cough throughout visit, voice nearly absent VS: WT 248. BP, HR normal. T 98.7, RR 18, pox 95% HEENT: all normal Chest: Dim expiratory phase, cough with forced expiration; no wheeze, crackles or consolidation CV: RRR, no MRG Ext: normal, no edema, cyanosis

10. Objective (cont) Chest x-ray normal Spirometry: FVC 3.31, 90% FEV1 2.24, 71% FEV1/FVC 78 % PEF 4.67, 66%

11. Assessment/Plan Viral URI with asthma exacerbation Neb tx in clinic with sig improvement in cough. Repeat chest exam improved exp phase Prednisone burst Advair 250/50 BID, PRN albuterol � corrected technique F/U appt in 3-4 days

12. And it continues . . . 5 days later Cont SOB, occasional wheeze Coughing at night; coughing yellow phlegm Tired Denies fevers, chills, chest pain New: works in dusty warehouse, house dirty with dust Spiro today: FEV1 94% pred, PEF 81% pred

13. New A/P Asthma exacerbation, improving. ?Atypical infection. Zpac Cont pred, Advair ?Dust allergy given flare of asthma since return to work at warehouse add Loratadine daily

14. 3 days later . . . Fever, diaphoretic SOB, cont coughing Fatigue, poor energy Mild ST, very hoarse Denies abd pain, n/v/d, chest pain. Hx of abn EKG at Meriter with normal stress test

15. Objective Pale, diaphoretic, HR 101, BP stable, LS clr CXR peribronchial inflammation, and elevation of right hemidiaphragm, no pneumo or pleural effusion EKG: NSR, tachy 98. Inf Q waves II, III, aVF with diffuse non-specific T wave abnormalities; Troponin 0

16. A/P Admit to Inpatient IM services for 3d stay Change to moxifloxacin Given IV steroids while in house, then Advair on d/c Add Flonase for post nasal drip Optimize GERD therapy although symptomatically stable with Prilosec BID

17. Follow-up Hospital Reports sig improvement after hospitalization Though, continues to cough during visit Cont on prednisone taper Dehydrated � given IVF Cont Flonase and loratadine Check CT sinus to evaluate for underlying disease as a result of her symptoms which did show acute on chronic sinusitis of the maxillary sinuses, R>L

18. Additional Workup / Treatment Chest CT to characterize right hemidiaphragm elevation with subtle ground glass opacification in her bilateral lung zones. Increase GERD therapy with pantoprazole 40mg BID ENT evaluation for vocal cord dysfunction � normal; ? laryngeal sensitivity treated with gabapentin 300 mg TID

19. And the mystery continues . . . While off of antibiotics, within 3 days, patient again develops fever, coughing, diaphoresis New labs show elevated ESR of 44, CBC, chem- 7 normal. Spiro FEV1 2.32, 73% predicted: FEV1/FVC 110% predicted; PEF 5.33, 75% predicted; FEF25-75 3.94, 109% predicted; an FVC 2.45, 67% predicted

20. Pulmonary Consult RF, ANA, ANCA negative pH study ordered Nebulized lidocaine to interrupt cough cycle Thoughts: recurrent aspiration

21. Impedance Study Acid exposure data Total of 136 minutes of acid in the esophagus. This is significantly abnormal. Similarly, the percent times were abnormal in both positions. There was 16.7% of acid in the esophagus in the upright position and 3.6% in the supine. The total is 9.9% with normal for an individual on acid suppression is usually less than 1.3%. She had 52 acid reflux events despite the medication. The longest reflux event lasted 20 minutes. There were 8 of these such longer lasting reflux events of over 5 minutes in duration.

22. For the impedance data 57 minutes of acid in the esophagus, which corroborates with that of the pH probe. 88 minutes of non or mild acid liquid in the esophagus. 298 reflux events, which is significantly high. These were predominantly nonacid in character, but as well, there were still acid reflux events occurring. 113 of the 298 were acidic in nature, and 185 of the 298 were nonacid in nature. These occurred equally in the upright as well as the supine position. 194 of these reflux events reached the proximal esophagus, which is greater than 50%. There were 17 coughing episodes of which 11 were correlated to reflux events. There were 18 episodes of sensing food in her throat of which all 18 were correlated to reflux. Therefore, the reflux symptom index was 82% with coughing and 100% for regurgitation.

25. pH Impedance Testing Discriminates acid, nonacid reflux, gas Acid: classical GERD, responds to PPI Nonacid: i.e. pancreaticobiliary secretions Best used with atypical symptoms Usually endoscopy is normal 24 hour pH testing may not reveal significant acid reflux

26. Advantages/Disadvantages of MII-pH Highest sensitivity for detecting all reflux episodes Assess location, distribution and composition Example: Mainie, et al showed that 37% of patients on PPI therapy had nonacid reflux and would have originally tested negative on conventional pH testing Disadvantage: considerable training for interpretation; not widely available

27. Long story short . . . CXR in f/u showed new lung opacities which were corroborated on CT Bronchoscopy with BAL was normal Cardiac ECHO to evaluate for endocarditis was negative Further ENT evaluation with LandmarX protocol negative for sinus disease

28. And she lived happily ever after Dr. Gould referral for Nissen with persistent reflux, aspiration pneumonia, chronic cough Surgery felt ideal option would be Nissen given paraesophageal hernia and GERD with significantly positive pH impedance study Surgery successful � no preoperative symptoms remained, voice normal

29. Extraesophageal SymptomsPulmonary Asthma � nonseasonal, nonallergenic Chronic bronchitis Aspiration pneumonia Bronchiectasis Pulmonary fibrosis COPD Pneumonia

30. Extraesophageal SymptomsENT Chronic cough Laryngitis Hoarseness Globus Pharyngitis Sinusitis Vocal cord granuloma Laryngeal carcinoma (possible)

31. Extraesophageal SymptomsOthers Noncardiac chest pain Dental erosion Sleep apnea

32. GERD and Sinonasal Symptom Association 1878 adults, community dwelling Sinonasal sx in 71% of subjects Reflux in 59% Co-occurrence of symptoms in 45% Those with both GERD and sinus sx scored significantly worse on disease-specific and general physical and mental QOL questionnaires than those with either symptom alone CONCLUSION: Dual diagnoses sx are common and co-occur to a greater degree than chance alone

33. How do you know it�s not just plain asthma? Asthma manifesting in adulthood No FH of asthma Dx of GERD predates asthma dx Asthma worsened with exercise, eating or supine posture Nocturnal resp sx Pharmacologic agents such as B2 agonists no effect or worsen sx Difficult-to-control symptoms requiring steroids Absence of allergic component to asthma symptoms

34. Management of Atypical GERD Require longer therapy AND/OR increased dosages However nonacid reflux usually persists despite PPI therapy

35. GERD and Asthma management May require double the standard dose of treatment Requires 2-3 months minimally This study by Kiljander was prior to the use of MII-pH testingThis study by Kiljander was prior to the use of MII-pH testing

36. Controversy with Management Controversial thoughts on best management: Surgery with fundoplication � may not reliably improve laryngeal sx Referral to taste/swallow center, speech or diet counseling Psychoactive medications Promotility agents seemed to provide partial sx improvement in 25% of patients

37. References Nord, H. J. (2004). Extraesophageal symptoms: What role for the proton pump inhibitors? The American Journal of Medicine, 117 (5), 56S. Malhotra, A., Freston, J. & Aziz, K. (2008). Use of pH- Impedance testing to evaluate patients with suspected estraesophageal manifestations of gastroesophageal reflux disease. Journal of Clinical Gastroenterology, 42(3), 271. Kiljander, T. (2003). The role of proton pump inhibitors in the management of GERD-related asthma and chronic cough. The American Journal of Medicine, 115 (3A).

38. References, cont Pasic, T., et al. (2007). Association of extraesophageal reflux disease and sinonasal symptoms: Prevalence and impact on quality of life. Laryngoscope, 117, 2218. Tutuian, R., et al. (2006). Nonacid reflux in patients with chronic cough on acid-suppressive therapy. Chest, 130 (2).