The Unsolved The Unsolved Mystery of The Mystery of The Chronic CoughChronic Cough

Rhonda Hoyer, RN, MS, APRN-BCRhonda Hoyer, RN, MS, APRN-BC

Nurse Practitioner Nurse Practitioner

Internal Medicine, University StationInternal Medicine, University Station

Case ObjectivesCase Objectives

Recognize extra-esophageal Recognize extra-esophageal manifestations of GERD and the manifestations of GERD and the potential complicationspotential complications

Identify differential diagnoses Identify differential diagnoses associated with chronic coughassociated with chronic cough

Identify the most appropriate course Identify the most appropriate course of treatment of treatment

CaseCase

CC: Severe cough for 6 daysCC: Severe cough for 6 days

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

Past Medical HistoryPast Medical History

AsthmaAsthma. Mild-intermittent, PRN . Mild-intermittent, PRN albuterol. No maintenance inhalers ever. albuterol. No maintenance inhalers ever. Hx of 1 exacerbation requiring prednisone Hx of 1 exacerbation requiring prednisone and Advair.and Advair.

Abd painAbd pain thought to be related to thought to be related to gallbladder vs. uterine fibroids. Resolved gallbladder vs. uterine fibroids. Resolved s/p cholecystectomy and TAH in 2006s/p cholecystectomy and TAH in 2006

Hiatal herniaHiatal hernia Depression/AnxietyDepression/Anxiety. Seeing . Seeing

psychiatrist/counselor regularly.psychiatrist/counselor regularly.

History (continued)History (continued)

Surgical HistorySurgical History TAHTAH CholecystectomyCholecystectomy TonsillectomyTonsillectomy AppendectomyAppendectomy

Social HistorySocial History: : Single, apt living with her cats. NS, no Single, apt living with her cats. NS, no

alcohol or drug use. Warehouse worker.alcohol or drug use. Warehouse worker.

Family HistoryFamily History

Negative for autoimmune diseaseNegative for autoimmune disease Positive for CAD in her fatherPositive for CAD in her father No other significant FHxNo other significant FHx

MedicationsMedications

NKDANKDA Albuterol PRNAlbuterol PRN Cymbalta 60 mg, 2 capsules qAMCymbalta 60 mg, 2 capsules qAM Lamictal 200 mg QDLamictal 200 mg QD Lorazepam 1-2 mg qHS PRNLorazepam 1-2 mg qHS PRN Prilosec 20 mg QDPrilosec 20 mg QD Seroquel 150 mg qHSSeroquel 150 mg qHS Lexapro 10 mg QDLexapro 10 mg QD

ObjectiveObjective Gen: pleasant, dry, harsh cough Gen: pleasant, dry, harsh cough

throughout visit, voice nearly absentthroughout visit, voice nearly absent VS: WT 248. BP, HR normal. T 98.7, RR VS: WT 248. BP, HR normal. T 98.7, RR

18, pox 95%18, pox 95% HEENT: all normalHEENT: all normal Chest: Dim expiratory phase, cough Chest: Dim expiratory phase, cough

with forced expiration; no wheeze, with forced expiration; no wheeze, crackles or consolidationcrackles or consolidation

CV: RRR, no MRGCV: RRR, no MRG Ext: normal, no edema, cyanosisExt: normal, no edema, cyanosis

Objective (cont)Objective (cont)

Chest x-ray normalChest x-ray normal Spirometry: Spirometry:

FVC 3.31, 90%FVC 3.31, 90% FEV1 2.24, 71%FEV1 2.24, 71% FEV1/FVC 78 % FEV1/FVC 78 % PEF 4.67, 66%PEF 4.67, 66%

Assessment/PlanAssessment/Plan

Viral URI with asthma exacerbationViral URI with asthma exacerbation Neb tx in clinic with sig improvement in Neb tx in clinic with sig improvement in

cough. Repeat chest exam improved exp cough. Repeat chest exam improved exp phasephase

Prednisone burstPrednisone burst Advair 250/50 BID, PRN albuterol – Advair 250/50 BID, PRN albuterol –

corrected techniquecorrected technique F/U appt in 3-4 daysF/U appt in 3-4 days

And it continues . . . 5 And it continues . . . 5 days later days later

Cont SOB, occasional wheezeCont SOB, occasional wheeze Coughing at night; coughing yellow Coughing at night; coughing yellow

phlegmphlegm TiredTired Denies fevers, chills, chest painDenies fevers, chills, chest pain New: works in dusty warehouse, house New: works in dusty warehouse, house

dirty with dustdirty with dust Spiro today: FEV1 94% pred, PEF 81% Spiro today: FEV1 94% pred, PEF 81%

predpred

New A/PNew A/P

Asthma exacerbation, improving. ?Asthma exacerbation, improving. ?Atypical infection.Atypical infection. ZpacZpac Cont pred, AdvairCont pred, Advair

?Dust allergy given flare of asthma ?Dust allergy given flare of asthma since return to work at warehousesince return to work at warehouse add Loratadine dailyadd Loratadine daily

3 days later . . . 3 days later . . .

Fever, diaphoreticFever, diaphoretic SOB, cont coughingSOB, cont coughing Fatigue, poor energyFatigue, poor energy Mild ST, very hoarseMild ST, very hoarse Denies abd pain, n/v/d, chest pain. Denies abd pain, n/v/d, chest pain.

Hx of abn EKG at Meriter with Hx of abn EKG at Meriter with normal stress testnormal stress test

ObjectiveObjective

Pale, diaphoretic, HR 101, BP stable, Pale, diaphoretic, HR 101, BP stable, LS clrLS clr

CXR peribronchial inflammation, and CXR peribronchial inflammation, and elevation of right hemidiaphragm, no elevation of right hemidiaphragm, no pneumo or pleural effusionpneumo or pleural effusion

EKG: NSR, tachy 98. Inf Q waves II, EKG: NSR, tachy 98. Inf Q waves II, III, aVF with diffuse non-specific T III, aVF with diffuse non-specific T wave abnormalities; Troponin 0wave abnormalities; Troponin 0

A/PA/P

Admit to Inpatient IM services for 3d Admit to Inpatient IM services for 3d staystay Change to moxifloxacinChange to moxifloxacin Given IV steroids while in house, then Given IV steroids while in house, then

Advair on d/cAdvair on d/c Add Flonase for post nasal dripAdd Flonase for post nasal drip Optimize GERD therapy although Optimize GERD therapy although

symptomatically stable with Prilosec symptomatically stable with Prilosec BIDBID

Follow-up Hospital Follow-up Hospital

Reports sig improvement after Reports sig improvement after hospitalizationhospitalization Though, continues to cough during visitThough, continues to cough during visit Cont on prednisone taperCont on prednisone taper Dehydrated – given IVFDehydrated – given IVF Cont Flonase and loratadineCont Flonase and loratadine Check CT sinus to evaluate for underlying Check CT sinus to evaluate for underlying

disease as a result of her symptoms which disease as a result of her symptoms which did show acute on chronic sinusitis of the did show acute on chronic sinusitis of the maxillary sinuses, R>Lmaxillary sinuses, R>L

Additional Workup / Additional Workup / TreatmentTreatment

Chest CT to characterize right Chest CT to characterize right hemidiaphragm elevation with subtle hemidiaphragm elevation with subtle ground glass opacification in her ground glass opacification in her bilateral lung zones. bilateral lung zones.

Increase GERD therapy with Increase GERD therapy with pantoprazole 40mg BIDpantoprazole 40mg BID

ENT evaluation for vocal cord ENT evaluation for vocal cord dysfunction – normal; ? laryngeal dysfunction – normal; ? laryngeal sensitivity treated with gabapentin 300 sensitivity treated with gabapentin 300 mg TIDmg TID

And the mystery And the mystery continues . . .continues . . .

While off of antibiotics, within 3 days, While off of antibiotics, within 3 days, patient again develops fever, patient again develops fever, coughing, diaphoresiscoughing, diaphoresis

New labs show elevated ESR of 44, New labs show elevated ESR of 44, CBC, chem- 7 normal.CBC, chem- 7 normal.

Spiro FEV1 2.32, 73% predicted: Spiro FEV1 2.32, 73% predicted: FEV1/FVC 110% predicted; PEF 5.33, FEV1/FVC 110% predicted; PEF 5.33, 75% predicted; FEF25-75 3.94, 109% 75% predicted; FEF25-75 3.94, 109% predicted; an FVC 2.45, 67% predicted predicted; an FVC 2.45, 67% predicted

Pulmonary Consult Pulmonary Consult RF, ANA, ANCA negativeRF, ANA, ANCA negative pH study orderedpH study ordered Nebulized lidocaine to interrupt cough Nebulized lidocaine to interrupt cough

cyclecycle

Thoughts: recurrent aspirationThoughts: recurrent aspiration

Impedance StudyImpedance Study Acid exposure dataAcid exposure data Total of 136 minutes of acid in the esophagus. Total of 136 minutes of acid in the esophagus.

This is significantly abnormal. Similarly, the This is significantly abnormal. Similarly, the percent times were abnormal in both percent times were abnormal in both positions. positions.

There was 16.7% of acid in the esophagus in There was 16.7% of acid in the esophagus in the upright position and 3.6% in the supine. the upright position and 3.6% in the supine. The total is 9.9% with normal for an individual The total is 9.9% with normal for an individual on acid suppression is usually less than 1.3%.on acid suppression is usually less than 1.3%.

She had 52 acid reflux events despite the She had 52 acid reflux events despite the medication. The longest reflux event lasted 20 medication. The longest reflux event lasted 20 minutes. There were 8 of these such longer minutes. There were 8 of these such longer lasting reflux events of over 5 minutes in lasting reflux events of over 5 minutes in duration. duration.

For the For the impedance dataimpedance data 57 minutes of acid in the esophagus, which corroborates 57 minutes of acid in the esophagus, which corroborates

with that of the pH probe. with that of the pH probe. 88 minutes of non or mild acid liquid in the esophagus. 88 minutes of non or mild acid liquid in the esophagus. 298 reflux events, which is significantly high. These were 298 reflux events, which is significantly high. These were

predominantly nonacid in character, but as well, there predominantly nonacid in character, but as well, there were still acid reflux events occurring. were still acid reflux events occurring.

113 of the 298 were acidic in nature, and 185 of the 298 113 of the 298 were acidic in nature, and 185 of the 298 were nonacid in nature. These occurred equally in the were nonacid in nature. These occurred equally in the upright as well as the supine position. 194 of these reflux upright as well as the supine position. 194 of these reflux events reached the proximal esophagus, which is greater events reached the proximal esophagus, which is greater than 50%. than 50%.

There were 17 coughing episodes of which 11 were There were 17 coughing episodes of which 11 were correlated to reflux events. There were 18 episodes of correlated to reflux events. There were 18 episodes of sensing food in her throat of which all 18 were correlated sensing food in her throat of which all 18 were correlated to reflux. Therefore, the reflux symptom index was 82% to reflux. Therefore, the reflux symptom index was 82% with coughing and 100% for regurgitation. with coughing and 100% for regurgitation.

GI Motility online (May 2006) | doi:10.1038/gimo31

Figure 8 Combined multichannel intraluminal impedance and pH catheter.

GI Motility online (May 2006) | doi:10.1038/gimo31

Figure 9 Gastroesophageal reflux detected by combined multichannel intraluminal impedance and pH (MII-pH) monitoring.

pH Impedance TestingpH Impedance Testing

Discriminates acid, nonacid reflux, Discriminates acid, nonacid reflux, gasgas Acid: classical GERD, responds to PPIAcid: classical GERD, responds to PPI Nonacid: i.e. pancreaticobiliary Nonacid: i.e. pancreaticobiliary

secretions secretions Best used with atypical symptomsBest used with atypical symptoms

Usually endoscopy is normalUsually endoscopy is normal 24 hour pH testing may not reveal 24 hour pH testing may not reveal

significant acid refluxsignificant acid reflux

Advantages/DisadvantagesAdvantages/Disadvantages of MII-pH of MII-pH

Highest sensitivity for detecting all Highest sensitivity for detecting all reflux episodesreflux episodes

Assess location, distribution and Assess location, distribution and compositioncompositionExample: Mainie, et al showed that 37% Example: Mainie, et al showed that 37% of patients on PPI therapy had nonacid of patients on PPI therapy had nonacid reflux and would have originally tested reflux and would have originally tested negative on conventional pH testing negative on conventional pH testing

Disadvantage: considerable training for Disadvantage: considerable training for interpretation; not widely availableinterpretation; not widely available

Long story short . . .Long story short . . .

CXR in f/u showed new lung opacities CXR in f/u showed new lung opacities which were corroborated on CT which were corroborated on CT Bronchoscopy with BAL was normalBronchoscopy with BAL was normal

Cardiac ECHO to evaluate for Cardiac ECHO to evaluate for endocarditis was negativeendocarditis was negative

Further ENT evaluation with Further ENT evaluation with LandmarX protocol negative for sinus LandmarX protocol negative for sinus diseasedisease

And she lived happily And she lived happily ever afterever after

Dr. Gould referral for Nissen with Dr. Gould referral for Nissen with persistent reflux, aspiration persistent reflux, aspiration pneumonia, chronic cough pneumonia, chronic cough

Surgery felt ideal option would be Surgery felt ideal option would be Nissen given paraesophageal hernia Nissen given paraesophageal hernia and GERD with significantly positive and GERD with significantly positive pH impedance studypH impedance study

Surgery successful – no preoperative Surgery successful – no preoperative symptoms remained, voice normalsymptoms remained, voice normal

Extraesophageal SymptomsExtraesophageal SymptomsPulmonaryPulmonary

Asthma – nonseasonal, nonallergenicAsthma – nonseasonal, nonallergenic Chronic bronchitisChronic bronchitis Aspiration pneumoniaAspiration pneumonia BronchiectasisBronchiectasis Pulmonary fibrosisPulmonary fibrosis COPDCOPD PneumoniaPneumonia

Nord, 2004.

Extraesophageal SymptomsExtraesophageal SymptomsENTENT

Chronic coughChronic cough LaryngitisLaryngitis HoarsenessHoarseness GlobusGlobus PharyngitisPharyngitis SinusitisSinusitis Vocal cord granulomaVocal cord granuloma Laryngeal carcinoma (possible)Laryngeal carcinoma (possible)

Extraesophageal SymptomsExtraesophageal SymptomsOthersOthers

Noncardiac chest painNoncardiac chest pain Dental erosionDental erosion Sleep apneaSleep apnea

GERD and Sinonasal GERD and Sinonasal Symptom AssociationSymptom Association

1878 adults, community dwelling1878 adults, community dwelling Sinonasal sx in 71% of subjectsSinonasal sx in 71% of subjects Reflux in 59% Reflux in 59% Co-occurrence of symptoms in 45% Co-occurrence of symptoms in 45% Those with both GERD and sinus sx scored Those with both GERD and sinus sx scored

significantly worse on disease-specific and significantly worse on disease-specific and general physical and mental QOL general physical and mental QOL questionnaires than those with either questionnaires than those with either symptom alonesymptom alone

CONCLUSIONCONCLUSION: Dual diagnoses sx are : Dual diagnoses sx are common and co-occur to a greater degree common and co-occur to a greater degree than chance alonethan chance alone

Pasic, T., et al. 2007

How do you know it’s not just plain How do you know it’s not just plain asthma?asthma?

Asthma manifesting in adulthoodAsthma manifesting in adulthood No FH of asthmaNo FH of asthma Dx of GERD predates asthma dxDx of GERD predates asthma dx Asthma worsened with exercise, eating or Asthma worsened with exercise, eating or

supine posturesupine posture Nocturnal resp sxNocturnal resp sx Pharmacologic agents such as B2 agonists Pharmacologic agents such as B2 agonists

no effect or worsen sxno effect or worsen sx Difficult-to-control symptoms requiring Difficult-to-control symptoms requiring

steroidssteroids Absence of allergic component to asthma Absence of allergic component to asthma

symptomssymptoms Nord, 2004.

Management of Atypical Management of Atypical GERDGERD

Require longer therapy AND/OR Require longer therapy AND/OR increased dosagesincreased dosages

However nonacid reflux usually However nonacid reflux usually persists despite PPI therapypersists despite PPI therapy

GERD and Asthma GERD and Asthma managementmanagement

May require double the standard May require double the standard dose of treatmentdose of treatment

Requires 2-3 months minimallyRequires 2-3 months minimally

Kiljander, T, 2003

Controversy with Controversy with ManagementManagement

Controversial thoughts on best Controversial thoughts on best management:management: Surgery with fundoplication – may not Surgery with fundoplication – may not

reliably improve laryngeal sxreliably improve laryngeal sx Referral to taste/swallow center, speech Referral to taste/swallow center, speech

or diet counselingor diet counseling Psychoactive medicationsPsychoactive medications Promotility agents seemed to provide Promotility agents seemed to provide

partial sx improvement in 25% of patientspartial sx improvement in 25% of patientsPasic. T., et al, 2007

ReferencesReferences Nord, H. J. (2004). Extraesophageal symptoms:Nord, H. J. (2004). Extraesophageal symptoms:

What role for the proton pump inhibitors? What role for the proton pump inhibitors? The The American Journal of Medicine, 117 American Journal of Medicine, 117 (5), 56S.(5), 56S.

Malhotra, A., Freston, J. & Aziz, K. (2008). Use of Malhotra, A., Freston, J. & Aziz, K. (2008). Use of pH-pH- Impedance testing to evaluate patients with Impedance testing to evaluate patients with suspected estraesophageal manifestations of suspected estraesophageal manifestations of gastroesophageal reflux disease. gastroesophageal reflux disease. Journal of Clinical Journal of Clinical

Gastroenterology, 42Gastroenterology, 42(3), 271.(3), 271. Kiljander, T. (2003). The role of proton pump Kiljander, T. (2003). The role of proton pump

inhibitors in the management of GERD-related inhibitors in the management of GERD-related asthma and chronic cough. asthma and chronic cough. The American Journal of The American Journal of

Medicine, 115Medicine, 115 (3A). (3A).

References, contReferences, cont

Pasic, T., et al. (2007). Association of Pasic, T., et al. (2007). Association of extraesophageal extraesophageal reflux disease and reflux disease and sinonasal symptoms: Prevalence sinonasal symptoms: Prevalence and and impact on quality of life. impact on quality of life. LaryngoscopeLaryngoscope, , 117, 117, 2218.2218.

Tutuian, R., et al. (2006). Nonacid reflux Tutuian, R., et al. (2006). Nonacid reflux in patients in patients with chronic cough on with chronic cough on acid-suppressive therapy. acid-suppressive therapy. Chest, 130Chest, 130 (2).(2).