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Asthma, GERD and LaryngealPharyngeal Reflux (LPR)Richard F. Lockey, M.D.Division of Allergy and ImmunologyDepartment of Internal MedicineUniversity of South FloridaCollege of MedicineandJames A. Haley Veterans’ Medical CenterTampa, Florida

Outline1.Definition and Description2.Symptoms3.Prevalence and RD and Upper Airway Disorders8.GERD and Asthma9.Management

Outline1.Definition and Description2.Symptoms3.Prevalence and RD and Upper Airway Disorders8.GERD and Asthma9.Management

Definitions GER: backflow of stomach contents into theesophagus, usually acidic GERD: abnormal GER– DeMeester score with pH probe– Dobhan criteria for proximal GERD– May result in inflammation of esophagus LPR: laryngopharyngeal reflux

Definition of GERD –Genval Workshop “The term GERD should be used to include allindividuals who are exposed to the risk ofphysical complications from gastroesophagealreflux, or who experience clinically significantimpairment of health-related well-being (qualityof life) due to reflux-related symptoms, afteradequate reassurance of the benign nature oftheir symptoms”Dent et al. Gut 1998

Heartburn Heartburn is the most common manifestation ofGERD The word ‘heartburn’ is often misinterpreted bypatients1 Description of heartburn as “a burning feeling risingfrom the stomach or lower chest up towards theneck” can help patients to recognize this symptom1 When heartburn is the main or only symptomexperienced by a patient, it is strongly suggestive ofthe presence of GERD21Carlssonet al. Scand J Gastroenterol 19982Klauser et al. Lancet 1990

Typical symptoms of GERD otherthan heartburn Regurgitation (GER) an effortless returnof gastric contents into the esophagus andfrequently into the mouth; often confused withvomiting Dysphagia difficulty swallowingYounes and Johnson. Gastroenterol Clin North Am 1999

Definition Laryngopharyngeal Reflux: a form ofgastroesophageal reflux disease thatproduces prominent symptoms and signs inthe pharynx and larynx characterized byacute, chronic, and intermittent laryngitisand ionary.phpDecember 1, 2010

Outline1.Definition and Description2.Symptoms3.Prevalence and RD and Upper Airway Disorders8.GERD and Asthma9.Management

Atypical symptoms of GERD Throat clearingGlobusLaryngospasmDental erosion1Mujica Chest painHoarsenessChronic coughSore throatWheezinget al. Postgrad Med 19992DeVault et al. Am J Gastroenterol 1999

Symptom patterns in GERD Reflux-related symptoms occur predominantlyafter meals Reflux-related symptoms are often triggered by––––unusually large mealsfatty, spicy, or acidic foodsbending, stooping, or lying downlifting, straining, or other strenuous activities The frequency of reflux-related symptoms varieswidelyJohnsson et al. Gullet 1992

Distribution of GERD symptomsover 24 hoursLunchDinner45n 1053015Time of dayJohnsson et al. Gullet 1992am6am3ightmidn129pmpm6pm3noon12am9am06Number of episodes ofreflux symptoms/hour(mean x 102)Breakfast

Outline1.Definition and Description2.Symptoms3.Prevalence and RD and Upper Airway Disorders8.GERD and Asthma9.Management

Prevalence of GERD worldwideHeartburnRegurgitation3-month prevalence (%)2522201415108101011104501817Italyn 999Japann 500Scandinavian 1010Canadan 1036Stanghellini. Scand J Gastroenterol 1999United Statesn 1020

Age-adjusted prevalence of GERD symptoms:the DIGEST studyThe proportion of respondents experiencingsymptoms increased significantly withage (P 0.001).3-month prevalence (%)20151050 2121-3536-50Age in years51-65 65N 5581Includes all respondents from US, Canada, European countries, and Japan.Stanghellini. Scand J Gastroenterol 1999

Frequency of heartburn% 050Daily1/week 1/ week 1/month 1/month 1/monthFrequency of heartburnOliveria et al. Arch Intern Med 1999

Patients with heartburn (%)Severity of GERD symptoms does notcorrelate with severity of disease60No heartburnMild heartburnModerate heartburnSevere heartburn50403020100Grade A(n 1466)Grade B(n 1634)Grade C(n 869)N 4283Levine et al. Am J Gastroenterol 1999Grade D(n 314)

Approximately half of all patients withreflux symptoms have erosiveesophagitisPatients presentingwith reflux symptoms (n 97)Barrett’sesophagusErosive esophagitis46%12%42%No erosive esophagitisWinters et al. Gastroenterology 1987

Symptoms are not reliably predictive ofmucosal damage Patients with and without erosive esophagitisare similar with respect to symptom severity1 Patients with and without erosive esophagitisare similar with respect to symptom frequency1 Patients with different grades of erosiveesophagitis are similar with respect to symptomseverity21Smout.Aliment Pharmacol Ther 19972Lundell et al. Gut 1999

Outline1.Definition and Description2.Symptoms3.Prevalence and RD and Upper Airway Disorders8.GERD and Asthma9.Management

Pathogenesis of GERD –overview GERD results from exposure of the esophagealmucosa to refluxed gastric contents In most patients with GERD, exposure of theesophagus to refluxate is greater than normal In a minority of patients, exposure is withinnormal limits; in these patients, GERD may bedue to decreased mucosal resistance torefluxate1DeVaultet al. Am J Gastroenterol 19992Dent et al. Gut 19983Shi et al. Gut 1995

Defective esophageal clearance Ineffective peristalsis Reduced salivarysecretion Reduced secretion fromesophageal submucosalglands

LES ‘dysfunction’ Inappropriate andprolonged transientrelaxations Reduction in basalLES pressure/tone

Hiatal hernia May trap a reservoir ofgastric contents abovethe diaphragm,increasing reflux May compromise LESfunction

Increased intra-abdominal pressure PregnancyObesityBendingStrainingCoughingTight clothes

Delayed gastric emptying May result in anincrease in thevolume of gastriccontents availablefor reflux into theesophagus Exact role in GERDremains to beclarified

Causes of increased exposure of theesophagus to gastric refluxate

Medications that may aggravate GERDsymptoms by damaging the esophagealmucosa TetracyclineQuinidinePotassium chloride tabletsIron saltsAspirin and other NSAIDsBisphosphonates

Medications that may aggravate GERDsymptoms by impairing LES function β-adrenergic epressants Progesterone α-adrenergicantagonists Diazepam Calcium channelblockers

Outline1.Definition and Description2.Symptoms3.Prevalence and RD and Upper Airway Disorders8.GERD and Asthma9.Management

Complications of GERD Esophageal– Barrett’sesophagus– adenocarcinoma– stricture– ulceration– bleeding Extra-esophageal– asthma– reflux laryngitis– vocal cord ulcers– subglottic stenosis– tracheal stenosis

Outline1.Definition and Description2.Symptoms3.Prevalence and RD and Upper Airway Disorders8.GERD and Asthma9.Management

Diagnostic methods in GERD HistoryRhinoscopyEndoscopyEmpiric therapypH monitoringRadiology

History History-taking is the primary diagnostic tool forGERD Typical GERD can usually be diagnosed on thebasis of history alone

Outline1.Definition and Description2.Symptoms3.Prevalence and RD and Upper Airway Disorders8.GERD and Asthma9.Management

GERD and Chronic Rhinosinusitis Upper respiratory symptoms frequent amongsubjects with symptomatic GERD Dx’d byesophageal study GERD associated with chronic rhinosinusitisin children and adultsTheodoropoulos DS et al. Am J Resp Crit Care Med 2001;164:72-6Barbero GJ. Otolaryngol Clin North Am 1996;29:27-38Phipps CD et al. Arch Otolaryngol Head Neck Surg 2000;126:831-6Ulualp SO et al. Am J Rhinol 199;13:197-202DiBaise et al. Ann Int Med 1998;1291078-83

GERD and Upper Airway DisordersFactors Associated with GERD Lifestyle issues– EtOH, cigarette smoking Obesity Medications– Beta agonists, theophylline, first generationantihistamines Food– High fat diet

GERD and Upper Airway DisordersTheodoropoulos DS, Ledford DK, Lockey RF et al. Am J Respir Crit Care Med 2001;164:72-76

GERD and Upper Airway DisordersPathophysiology Direct irritation by acidNeurogenic reflex (increased vagal tone)Neurogenic inflammationVisceral sensitivity

GERD and Upper Airway DisordersPathophysiology

GERD and Upper Airway DisordersPathophysiologyTheodoropoulos DS, Ledford DK, Lockey RF et al. Am J Respir Crit Care Med 2001;164:72-76

GERD and Upper Airway DisordersPathophysiologyOdds Ratio of GERDURS Score 4URS Score 8URS Score 111.53.86.8Theodoropoulos DS, Ledford DK, Lockey RF et al. Am J Respir Crit Care Med 2001;164:72-76

GERD and Upper Airway DisordersPathophysiologyUpper Airway Symptoms Related toGER or GERD Throat clearing Voice change Hoarseness Cough Post nasal drip Nasal congestionTheodoropoulos DS, Ledford DK, Lockey RF et al. Am J Respir Crit Care Med 2001;164:72-76

GERD and Upper Airway DisordersPathophysiologyUpper Airway Symptoms Possibly Related to GER orGERD Rhinorrhea Ear ache/fullness Sneezing Otitis media with effusion Sinusitis Serous otitis media Sinus Headache Upper airway itchingTheodoropoulos DS, Ledford DK, Lockey RF et al. Am J Respir Crit Care Med 2001;164:72-76

GERD and Upper Airway DisordersPathophysiologyTheodoropoulos DS, Ledford DK, Lockey RF et al. Am J Respir Crit Care Med 2001;164:72-76

GERD and Upper Airway DisordersNormalFrom www.voiceproblem.orgLarynx with GERD

GERD and Upper Airway DisordersBelafsky Score for Diagnosis of LPR(0-4 score for each component)7 or more is diagnostic of LPR Diffuse edemaSubglottic edemaVentricular obliteration GranulomaVocal fold edemaPosterior commissure hypertrophy

Outline1.Definition and Description2.Symptoms3.Prevalence and RD and Upper Airway Disorders8.GERD and Asthma9.Management

GERD and Asthma William Osler noted “ attacks may be due todirect irritation of the bronchial mucosa or indirectly, too, by reflex influences from thestomach ”. Up to 80% of patients with asthma have GERD.Smith LJ, Winslow C. Asthma and Surgery. In Asthma & Rhinitis 2.Bussee W and Holgate S (eds). Blackwell Science 2000, pp 1834-5.

Risk factors for exacerbation ofdifficult-to-treat asthma39 had 3 severe exacerbations/yr136 subjects29 had 1 severe exacerbation/yrBrinke , et al. Eur Respir J 2005; 26: 812.

Conclusions1) Odds ratio (OR) associated with 3 exacerbationsa) severe sinus disease, OR 3.7b) GERD, OR 4.9c) URIs, OR 6.9d) Psychological dysfunction, OR 10.8e) Obstructive sleep apnea, OR 3.42) All patients with frequent exacerbations had 1/5 while52% had 3/5Brinke , et al. Eur Respir J 2005; 26: 812.

Effects of 24 weeks of lansoprazole onasthma in patients with GERD symptomsMulticenter, DB, randomized, placebocontrolled trial of 206 subjects with moderateto-severe asthma with reflux symptoms givenlansoprazole, 30 mg bid vs. placebo.Littner MR, et al: Chest 2005; 128: 1128.

ConclusionDid not improve symptoms by:a) Assessment by:1) participant2) investigatorb) Pulmonary function studiesc) Decrease in albuterol useBut did:a) Decrease asthma exacerbationb) Improve quality of life.Littner MR, et al: Chest 2005; 128: 1128.

Randomized DBPC Study of 770Subjects with GERD and Asthma Randomized to receive esomeprazole 40 mg or P2x QD for 16 wk No statistical difference in morning PEF overall Patients with nocturnal symptoms (NOC) improvedAM PEF 8.7-L/min ( p 0.03) and PM 10.2-L/min(p 0.012) over placebo 304 subjects on LABA improved both AM (12.2L/min, p 0.017) and PM (11.1-L/min, p 0.024)PEF, if they had GERD and NOC Conclusion: esomeprazole improves PEF inpatients with asthma and GERD and NOC Kiljander TO et al. Am J Respir Crit Care Med 2006;173:1091

Cochrane Data Base Review ofGERD Treatment for Asthma in Adults andChildren (2006) 12 randomized controlled trials of Rx for GERD in adultsand children 2 independent reviewers Interventions included proton pump inhibitors (6), H2receptor antagonists (5), surgery and conservativemanagement (1) Temporal relationship in 4 trials found between asthmaand GERD Anti-reflux Rx did not consistently improve lung function,asthma symptoms, nocturnal asthma and medication use Conclusion: No overall improvement but subgroups maygain benefit

Outline1.Definition and Description2.Symptoms3.Prevalence and RD and Upper Airway Disorders8.GERD and Asthma9.Management