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©2014 MFMER | slide-1 The Evaluation of Chronic Cough Katrina M. Hynes, BAS, RRT, CPFT Assistant Supervisor, Mayo Clinic Pulmonary Function Lab Focus May 15-17, 2014
©2014 MFMER | slide-2 Background Chronic Cough Definition: A cough that persists beyond 8 weeks Symptom-based problem Requires further diagnostic evaluation Social impact Anxiety Physical discomfort Social and personal embarrassment Reduction in quality of life Iyer VN, Lim KG. Mayo Clin Proc. 88 (10) 1115-1126, 2013
©2014 MFMER | slide-3 Lancet 317 1364-74, 2008
©2014 MFMER | slide-4 Background Prevalence of cough? Cross-sectional survey of 36 general practices. 4003 Subjects Prevalence of chronic cough was 12% Severe 7% Thorax 2006;61:975–979.
©2014 MFMER | slide-5 Background Causes of Chronic Cough Infectious Airways disorders Lung parenchymal disease Tumors Irritation of the external auditory meatus Upper airway cough syndrome (UACS) Esophageal causes (GERD) Drugs (ACE inhibitors and β-blockers) Airway irritants
©2014 MFMER | slide-6 Clinical Practice Guidelines January 2006; 129(1_suppl) Diagnosis and Management of Cough: ACCP Evidence-Based Clinical Practice Guidelines 70-90% of cases seen in clinical practice Upper airway cough syndrome (UACS) GERD Asthma
©2014 MFMER | slide-7 Evaluation of Chronic Cough in the Pulmonary Function Lab 43 staff 24 procedure rooms 150-250 patients/day
©2014 MFMER | slide-8 Evaluation of Chronic Cough Spirometry Spirometry (meaning the measuring of breath) is the most common pulmonary function test (PFTs)
©2014 MFMER | slide-9 Spirometry and the Obstructive pattern Asthma Chronic Bronchitis Emphysema
©2014 MFMER | slide-10 Spirometry and the Restrictive pattern Intrinsic lung disease IPF, sarcoidosis, etc. Extra-pulmonary Pneumothorax, pleural effusion, etc. Neuromuscular ALS, myasthenia gravis etc. Chest wall: obesity, scoliosis, kyphosis
©2014 MFMER | slide-11 Bronchial Provocation - Guidelines Evaluation of Chronic Cough Bronchial Provocation - Guidelines American Thoracic Society (ATS)American Thoracic Society (ATS) Guidelines for Methacholine and Exercise Challenge Testing ( Am J Respir Crit Care Med Vol 161. pp 309-329, 2000)Guidelines for Methacholine and Exercise Challenge Testing ( Am J Respir Crit Care Med Vol 161. pp 309-329, 2000) ATS-ERS are in the process of revising – possible release late 2014ATS-ERS are in the process of revising – possible release late 2014 Pulmonary Function Laboratory Management and Procedure ManualPulmonary Function Laboratory Management and Procedure Manual In revisionIn revision www.thoracic.orgwww.thoracic.org
©2014 MFMER | slide-12 Challenge Testing Direct stimulus – Methacholine Challenge Effector cells Airway smooth muscle cells Airway smooth muscle cells Bronchial endothelial cells Bronchial endothelial cells Mucus producing cells Mucus producing cells Airflow limitation Indirect stimulus – Mannitol/Exercise Intermediary cells Inflammatory cells Inflammatory cells
©2014 MFMER | slide-13 Methacholine Challenge Test Methacholine chloride is a parasympathomimetic (cholinergic) bronchoconstrictor agent Methacholine is derived from acetylcholine, a naturally occurring substance in the body, and can cause the airways to tighten and swell, in sensitive people. FDA-approved methacholine Provocholine ®
©2014 MFMER | slide-14 Methacholine Test Methodology Protocols Five-breath dosimeter protocol Two-minute tidal breathing dosing protocol
©2014 MFMER | slide-15 Methacholine Dosing Protocols 1999 ATS – “Dose-Doubling” Protocol Diluent (optional) 0.031 mg/ml 1 mg/ml* 0.0625 mg/ml* 2 mg/ml 0.125 mg/ml 4 mg/ml* 0.25 mg/ml* 8 mg/ml 0.5 mg/ml 16 mg/ml* *”Dose quadrupling”
©2014 MFMER | slide-16 Methacholine Challenge Test Example: Baseline FEV1 4.0L Control (diluent) 3.75L 3.75*.8 = 3.0L 3.75*.9 = 3.38L PC 20 = 3.00L Mottram CD Ruppel’s Manual of Pulmonary Function Testing 10 th ed 2012
©2014 MFMER | slide-17 Methacholine Challenge Test CATEGORIZATION of BRONCHIAL RESPONSIVENESS PC 20 Interpretation (mg/ml) > 16 Normal bronchial 4.0 to 16Borderline BHR 1.0 to 4.0Mild BHR (positive test) < 1.0Moderate to severe BHR ATS AJRCCM Vol 161. pp 309-329, 2000
©2014 MFMER | slide-18 Mannitol Challenge Test Indirect and osmotic stimulant Increases osmolarity of airway surface liquid Release of inflammatory mediators from mast cells and basophils (e.g leukotriene) Sugar alcohol, dry powder (stored below 25°C) Utilizes a special dry-powder inhaler (DPI) No diluent or nebulization required Aridol™
©2014 MFMER | slide-19 Mannitol Challenge Test Aridol Kit Aridol capsules (mannitol) 1 empty capsule Osmohaler inhaler device (DPI)
©2014 MFMER | slide-20 Mannitol Challenge Procedure Dosing scheme Total maximum dose = 635 mg
©2014 MFMER | slide-21 Mannitol Challenge Test Procedure Pre-challenge spirometry FEV 1 at least 60% of predicted Administer mannitol using Osmohaler At 60 seconds perform spirometry
©2014 MFMER | slide-22 Mannitol Challenge Test Procedure Perform 2 acceptable FVC maneuvers (according to ATS/ERS Guidelines). Use the higher of these two values to calculate the change in FEV 1 If Baseline FEV 1 is >10% lower than pre- challenge FEV 1 - stop challenge Calculate target FEV 1 highest Baseline value * 0.85 Continue with subsequent dosages
©2014 MFMER | slide-23 Mannitol Challenge Test Reporting results Percent decrease in FEV 1 from post 0 mg dose (Baseline) value PD 15 - 2 decimal places in mg/mL (eg, 33.85 mg) 15% decline in FEV1 is a positive test If no 15% fall in FEV 1 after highest dose, PD 15 reported as greater than 635 mg (negative test)
©2014 MFMER | slide-24 Evaluation of Chronic Cough Exhaled Nitric Oxide Numerous biomarkers of inflammation that have been detected in exhaled breath Therapeutic Advances in Resp Disease 2007 1;5
©2014 MFMER | slide-25 Exhaled Nitric Oxide Guidelines 2005 ATS+ERS (www.thoracic.org)www.thoracic.org 2011 ATS Interpretation Am J Respir Crit Care Med Vol 184. pp 602–615, 2011
©2014 MFMER | slide-26 Exhaled Nitric Oxide eNO = F E NO * eNO is an index of eosinophilic (allergic) airway inflammation. eNO is not increased with bronchospasm. * The abbreviation for fraction of exhaled nitric oxide at a flow of 50mL/sec
©2014 MFMER | slide-27 Exhaled Nitric Oxide Prolonged Cough 71 pts c/o prolonged cough Bronchial asthma (30) Cough variant asthma (18) Bronchitis (8) Others (15) Conclusion: FeNO could be used as a diagnostic marker of prolonged cough, especially for the differential diagnosis BA and CVA from EB and others. Respiratory Medicine (2008) 102, 1452e1459
©2014 MFMER | slide-28 Exhaled Nitric Oxide ICS responders “Exhaled NO, A Predictor of Steriod Response” Smith AD, AJRCCM 2005. 52 patients presenting with undiagnosed respiratory symptoms in a single-blind, fixed- sequence, placebo controlled trial of inhaled fluticasone for 4 weeks.
©2014 MFMER | slide-29 Exhaled Nitric Oxide Instrumentation - Aerocrine Niox Flex Chemiluminescence analyzer FDA approved Expensive (>$35,000) Oral and nasal Niox Mino Electrochemical Hand-held, no vacuum pump Oral only Less expensive (~$3,000) Consumables per test (~$10.00) Niox Flex Niox Mino
©2014 MFMER | slide-30 Exhaled Nitric Oxide Normal or Abnormal? Low FENO: < 25 ppb, (< 20 ppb in children): implies no airway inflammation High FENO: >50 ppb (> 35 ppb in children) OR rising FENO (> 40% change from previously stable level): implies uncontrolled or deteriorating eosinophilic airway inflammation
©2014 MFMER | slide-31 Evaluation of Chronic Cough Rhinoscopy Flexible rhinoscopy is a quick, office-based procedure used to examine the entire nasal cavity Can be used in the evaluation Upper airway cough syndrome (UACS)
©2014 MFMER | slide-32 Evaluation of Chronic Cough 24 Hour Laryngopharyngeal pH monitoring
©2014 MFMER | slide-33 Evaluation of Chronic Cough 24 Hour Laryngopharyngeal pH monitoring Gastroesophageal Reflux Disease (GERD). Classic symptom: burning sensation in your lower chest (heartburn). Major cause of chronic cough GERD may lead to Barrett’s esophagus, a type of intestinal metaplasia ] which is a precursor for carcinoma ] Laryngopharyngeal reflux (LPR) is similar to GERD Does not have the classic symptoms of GERD
©2014 MFMER | slide-34 Evaluation of Chronic Cough 24 Hour Laryngopharyngeal pH monitoring Laryngopharyngeal reflux (LPR) is sometimes termed “Silent reflux” Common symptoms: Excessive throat clearing, sore throat Persistent cough Hoarseness A "lump" in the throat that doesn't go away with repeated swallowing
©2014 MFMER | slide-35 Evaluation of Chronic Cough 24 Hour Laryngopharyngeal pH monitoring New Diagnostic/Monitoring Technology pH measurement system revolutionizes pH testing. Technology uniquely capable of sensing and recording both aerosolized and liquid pH levels allows for less invasive placement
©2014 MFMER | slide-36 Evaluation of Chronic Cough 24 Hour Laryngopharyngeal pH monitoring Off PPI or H2blocker for 10 days prior to study System uses small catheter introduced via the naris and placed just behind/beside the uvula for the study Data collected via a transmitter that transfers to a recorder
©2014 MFMER | slide-37 Journal of Voice, Vol. 23, No. 4, 2009
©2014 MFMER | slide-38 The Journal of Family Practice | August 2011 | Vol 60, No 8
©2014 MFMER | slide-39 Pediatric cough is a common complaint in 35% of preschool children and 9% of 7–11-year-olds. Current Opinion in Otolaryngology & Head and Neck Surgery 2011, 19:204–209
©2014 MFMER | slide-40 Case 1 26 yo female referred for multiple pulmonary nodules and chronic cough #1 Multiple pulmonary nodules r/o histoplasmosis. PPD negative. Pet exposure (kitty litter boxes, toxocara as well as toxoplasma). #2 Increasing cough The possibility of reflux is very strong. #3 Suspect obstructive sleep apnea
©2014 MFMER | slide-41 Case 1 Histoplasmosis – negative Toxocara Antibody - POSITIVE This indicates exposure to the and does not necessarily mean those nodules are active Toxocara infection. Toxocariasis is a human illness caused by immature parasite worms of either the dog roundworm (Toxocara canis) or the cat roundworm (Toxocara cati). Chronic cough and dental erosion 24 Hour Laryngopharyngeal pH monitoring
©2014 MFMER | slide-42 Case 1 24 Hour Laryngopharyngeal pH monitoring
©2014 MFMER | slide-43 Evaluation of Chronic Cough Iyer VN, Lim KG. Mayo Clin Proc. 88 (10) 1115-1126, 2013 Mayo Clinic’s Clinical Flowchart
©2014 MFMER | slide-44 Questions & Discussion
The Use of Fraction of Exhaled Nitric Oxide in Pulmonary Practice Kaiser G. Lim, MD, FCCP; and Carl Mottram, RRT, RPFT CHEST 2008; 133:1232–124 Jeung Eun.
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