Extraesophageal Manifestations of GERD in Children Jose Luis Martinez, M.D. Associate Professor University of California San Francisco Director Endoscopy Unit Children s Hospital Central California
Overview of GERD A common condition, affecting up to 10% of the adult population in the U.S. GERD appears to increase with age Most consequences of GERD affect the esophagus (i.e. strictures, Barrett s) 4-10% of chronic, non-specific laryngeal disease in adults is associated with GERD (Shaker A J Med 1997)
Pediatric GERD GER affects children in either a infantile form or as an affliction in older children GER is common & usually resolves between 1-2 yrs of age ( physiologic GER ) GER in older children is considered pathologic, or gastroesophageal reflux disease (GERD) Symptoms of GERD occur in an estimated 2-8 % of U.S. children aged 3-17 yrs
Pathogenic Factors in GERD Pharynx UES Mechanisms of GER Transient LES relaxation Intra-abdominal pressure Reduced esophageal capacitance Gastric compliance Delayed gastric emptying Esophagus Crural diaphragm Pylorus LES Angle of His Mechanisms of Esophageal Complications Impaired esophageal clearance Defective tissue resistance Noxious composition of refluxate Mechanisms of Airway Complications Vagal reflexes Impaired airway protection Stomach
El-Serag H, Gilger M et al. Gastroenterology 2001;121:1294-9 Tasker A et al. Laryngoscope 2002;112:1930-4 Extraesophageal Symptoms of GERD in Children Hoarseness Dental erosions Otitis / sinusitis Wheezing / asthma Extra- esophageal manifestations of GERD Apnea / bradycardia Chronic sore throat Chronic cough
Respiratory Symptoms of GER Apnea/ALTE Stridor and hoarseness Chronic cough Asthma/wheezing Recurrent pneumonia
ALTE Definition Frightening episode in infant that is characterized by: - apnea - change in color - change in muscle tone - choking or gagging and requires intervention by caretaker Potential causes - Cardiac disorder - Upper airway obstruction - CNS disorder - Infection - GER - Intentional suffocation
GER and ALTE Recurrent regurgitation in 60% to 70% of infants with ALTE Abnormal esophageal ph studies in 40% to 80% Relationship between GER and obstructive or mixed apnea most convincing when infant was: awake supine fed within past hour Rudolph et al, J Pediatr Gastroenterol Nutr 2001;32:S1
Relationship between Apnea and GERD 91% of children with GERD (ph-metry) showed no correlation with respiratory events Poly-Somnoencephalo-Gram with ph probe may be the best method of choice for studying the relationship between GERD and Apnea Harris P, et al. Child Care Health Dev. 2004 Jul;30(4):337-44
Association of GER with Apnea Chest Wall Movement Nasal Air Flow Esophageal ph Herbst et al, J Pediatr 1979;95:763 Time (sec)
Management of GER-Associated ALTE Esophageal ph monitoring is useful only if performed simultaneously with measurement of respiration and chest wall movement Infant is more likely to respond to antireflux therapy if: emesis or regurgitation is present at time of ALTE infant is awake obstructive apnea is present Therapeutic options include: thickened feedings acid suppression Antireflux surgery is considered only in severe cases Rudolph et al, J Pediatr Gastroenterol Nutr 2001;32:S1
Does GER Cause Asthma? GER GER GER GER Asthma Asthma Asthma Asthma
Asthma/GERD Association 36 children with bronchial asthma ages:13 months to 15 years GERD diagnosis via ph monitoring GERD found in 75% of patients Conclusion: GERD may be involved in the pathogenesis of asthma Ay M, et al. J Chin Med Assoc. 2004 Feb; 67(2):63-6
Relationship Between Asthma and GERD Indirect cause (reflex theory) Direct cause (reflux theory) Asthma leads to decrease in presusre of the LES Coughing increases de intra-abdominal pressure Certain anti-asthmatic medications may increase the risk of reflux (theophyline, cafeine) Harding, Cur Op in Pulmonary Medicine 2003;9:42
Prevalence of Gastroesophageal Reflux in Children With Pulmonary Disease 70 60 59 61 63 64 50 47 48 49 % of Patients 40 30 20 10 0 Shapiro et al, 1979 Friedland et al, 1973 Berquist et al, 1981 Danus et al, 1976 Buts et al, 1986 Euler et al, 1979 Martin et al, 1982
Prevalence of GER in Infants and Children with Asthma GER (abnormal esophageal ph studies) in 61% of infants and children with asthma 61% GER symptoms absent or mild in about 50% of those with persistent asthma and abnormal esophageal ph studies N=668 pts in 13 case series Rudolph et al, J Pediatr Gastroenterol Nutr 2001;32:S1
Nocturnal GER and Asthma Adults Children A correlation? Controversial Controversial Evidence? - Some treatment Acid infusion at night trials associated with - Significantly more bronchoconstriction and acid reflux during wheezing [2] sleep in asthmatics [1] Antireflux Effective in some but Modest improvement treatment not all studies with with H2RA effective? PPI or H2RA 1 Sontag et al, Dig Dis Sci 1990;35:849; 2 Davis et al, J Allergy Clin Immunol 1983;72:393
Effect of Antireflux Pharmacotherapy in Children with Asthma 63% N=168 pts in 4 case series Clinical improvement or reduced dosages of antiasthmatic therapy in 63% of asthma patients with GER treated with: Conservative management Prokinetic monotherapy H2RA monotherapy Duration of therapy (>3 months) important (adult studies) Rudolph et al, J Pediatr Gastroenterol Nutr 2001;32:S1
Effect of Antireflux Surgery in Children With Asthma Clinical improvement or reduced dosages of antiasthmatic therapy in 85% of children 85% Persistent asthma requiring intensive steroid therapy before surgery GER most often confirmed by ph studies N=258 pts in 6 case series Failure of antireflux medical therapy did not preclude response to antireflux surgery Rudolph et al, J Pediatr Gastroenterol Nutr 2001;32:S1
Asthma: When to Treat for GERD Persistent asthma and GER symptoms Persistent asthma and no GER symptoms Vigorous acid-suppressive therapy for 3 months, monitoring outcome variables Consider esophageal ph monitoring or empiric treatment trial in children with recurrent pneumonia nocturnal asthma > 1X weekly corticosteroid dependence If ph studies positive 3-month trial of antireflux medical therapy, monitoring outcome variables Rudolph et al, J Pediatr Gastroenterol Nutr 2001;32:S1
Causes of Recurrent Pneumonia in Children Causes Frequency Aspiration 48 % Immune disorder 10 Congenital heart disease 9 Asthma 8 Respiratory tract anomaly 8 GER 5 Other/unknown 12 N = 238 children hospitalized with pneumonia Owayed et al, Arch Pediatr Adolesc Med 2000;154:190
Recurrent Pneumonia and GER GER can cause recurrent pneumonia in absence of esophagitis Normal esophageal ph studies do not exclude GER as a cause Before considering GER, rule out other causes neuromuscular disease or esophageal or laryngeal anatomic abnormalities Incidence of GER-related recurrent aspiration in otherwise healthy infants and children is rare Rudolph et al, J Pediatr Gastroenterol Nutr 2001;32:S1 Berquist et al. Pediatrics 1981; 68.
Management of Recurrent Pneumonia and GER Combination of tests may aid in diagnosis flexible bronchoscopy with pulmonary lavage nuclear scintigraphy Video swallow test (liquid, thin barium) Severely impaired lung function consider antireflux surgery balance potential benefits with potential complications Minimal pulmonary disease consider medical therapy
Aspiration From Swallowing or GER? Lipid-Laden Macrophages
Aspiration From Swallowing or GER? Barium Swallow Technetium-99m Salivagram
ENT Findings of GERD Hoarseness Laryngitis, laryngomalacia, stridor Otitis Media,otalgia Sinusitis,chronic rhinitis Subglottic stenosis Globus pharyngeus Laryngeal Nodules Laryngeal Granuloma Ahmad et al. J Laryngol Otol. 2004;118(1):25
Possible Supraesophageal Complications of GER Dental erosion? Recurrent sinus disease? Otitis media? Present in 20/37 children Prevalence not increased in 53 with abnormal esophageal ph Improvement with antireflux treatment in 15/19 Prevalence similar in infants with and without GER Otalgia improved with GER therapy Prevalence not increased in children with GER Dahshan et al, J Pediatr 2002; El-Serag et al, Gastroenterology 2001; Gibson et al, Int J Pediatr Otorhinolaryngol 1994; Nelson et al, Pediatrics 1998; O Sullivan et al, Eur J Oral Sci 1998; Phipps et al, Arch Otolaryngol Head Neck Surg 2000
Otolaryngologic Manifestations of GERD Often occur in the absence of heartburn, thus referred to as silent GERD Accounted for only 3.5% of indications in 3000 ph studies in children (Brouchard et al, J Ped Surg 1999) However, abnormal ph studies were more common in children with stridor, laryngomalacia and laryngitis
Association of Otitis Media with Effusion and GERD in Children Analysis of middle ear effusions 54 childrens ages 2-8 years old undergoing myringotomy 45/54 effusions(83%) had presence of pepsin and/or pepsinogen concentration in levels were 1000 times greater than serum Especulation: Gastric reflux into the middle ear could explain those levels Tasker et al. Lancet 2002;359-493
GER and otitis media 6 children referred for chronic OM, all had either esophagitis or abnormal ph study, & all improved on medical rx (Gibson & Cochran, Int J Ped Oto 1994) 15/27 infants with chronic OM had abnormal ph studies (Rozmanic et al JPGN 2002) 83% of children with chronic OM undergoing myringotomy had pepsin or pepsinogen in middle ear fluid, suggesting GER was involved (Tasker et al, Lancet 2002)
GER & chronic rhinitis, sinusitis Higher nasopharyngeal ph< 6 in children with chronic rhinitis (Contencin and Narcy (Int J Oto 1991) No norms for pharyngeal ph Sinusitis, laryngitis & laryngomalacia are the most common manifestations of GERD (Brouchard et al J Ped Surg 1999, El-Serag & Gilger, Gastro 2001) Decreased sinus surgery after medical treatment of GERD (Bothwell et al Oto head neck Surg 1999)
Dental Erosions Relationship postulated between GERD and dental erosion Definition: Irreversible loss of dental enamel hard tissue by a chemical process in the absence of bacteria.
Pathophysiology of Dental Erosions The critical ph for dental enamel erosions is <5.5 At lower ph, substances have the potential to disolve hydroxyapatite crystals in enamel In vitro tooth erosion ph <2.0 Estimated ph of gastric reflux <2.0 Protective mechanism-saliva flow, buffering capacity of saliva» Lazarchik et al. Am J Gastroenterol, 2000;95 :S33
Interventions for Dental Erosions Evaluation for GERD Periodic dental assessment Preventive Measures Trial of PPI» Dahshan et al J Pediatr 2002; 140: 474
Evaluation and Management of GER-Related Laryngeal Symptoms Laryngoscopy generally indicated to rule out anatomic abnormalities of airway protection No randomized controlled trials of antireflux therapy in adults or children with laryngeal symptoms Adult studies suggest that therapeutic trial must last >3 months to adequately assess efficacy Clinical improvement followed by recurrence off treatment association with GER Rudolph et al, J Pediatr Gastroenterol Nutr 2001;32:S1
Normal Reflux laryngitis
Diagnostic testing Esophageal ph /dual channel ph No proof that esophageal reflux is causative Barium swallow/ugi useful for anatomy only Scintigraphy/Milk scan No correlation with ph monitoring, no norms Useful if positive Esophagoscopy Controversial whether biopsy correlates with ENT problems Laryngoscopy Logical but no biopsy data on healthy children Sermon et al.dig Liver Dis. 2004;36:102
Summary Asthma is the most common pulmonary manifestation of GERD Otolaryngologic manifestations are well known, but hard to prove Successful response to medical treatment remains the best diagnostic test (PPI) Randomized, prospective controlled trials are needed to determine the value of: Esophageal ph testing Esophageal intraluminal impedence measurement Laryngeal biopsy for the diagnosis of GERD