Respiratory Symptoms in Gastroeso phageal Reflux Disease (GERD) in Children

1. Respiratory Symptoms in Gastroesophageal Reflux Disease(GERD) in Children

2. Gastroesophageal Reflux Disease (GERD) The gastroesophageal reflux disease is the intermittent or permanent passing of the stomach content into the esophagus, which triggers a whole set of digestive, respiratory and/or neurobehavioral symptoms in the absence of any pains.

3. Physiology Role: - carrier of the food bolus - GER and EFRpreventionby the LES and UES Function: • carrier – due to the joint action of the muscles of the mouth, pharynx, esophagus and, indirectly, of the larynx • secretion– roleof esophagus mucous membrane lubrication thus enhancing food bolus progress - vagal mediation - the mucus is secreted by acinous glands found in the submucous membrane

4. Natural History • It is physiological during the first 3 months of life • Regurgitation usually disappears before the age of 12-24 months • Categories at risk: • Prematureand dysmature babies • Newbornsthat experienced perinatalhypoxiaor asphyxia • Infants that had an “a demeure” gastric probe • Infants suffering from lazy “gastric emptying” • Newborns that underwent surgery for esophageal atresia • Infants suffering from encephalopathy, etc.

5. Etiopathogenesis 3 pathogenic links: • LES dysfunction • Esophagus dysfunction • Stomach dysfunction LES dysfunction Transient LES relaxation – major mechanism triggering the GER

6. loweredby: - anticholinergics - theophylline - caffeine - nicotine - alcohol - dopaminergics - epinephrine - prostaglandins E1 and E2 -some hormones: glucagon secretin cholecystokinin - progesterone, estrogen increased by: - cholinergics - dopamine receptor agonists - serotonin - histamine - norepinephrine -phenylephrine - gastrin The Resting Pressure in the LESMay BeAltered by Drugs:

7. Esophagus Dysfunction • Esophageal clearance failure • 4 mechanisms are responsible for its efficiency: • Esophageal motor activity (peristaltic waves), motility disorders determine GER • Gravitational force – in its absence, the clearance is delayed • Saliva secretion – given its bicarbonate content it is a buffer for the acid coming from the stomach - decrease: tobacco, anticholinergic medication, radiotherapy, xerostomia • Esophageal gland secretion(mucous or non-mucous)

8. Stomach Dysfunction • Increased stomach volume – overfeeding • Gastric distention – air swallowing, prolonged overfeeding • Increased abdomen pressure: obesity, cough effort, sneezing, defecation • Delayed gastric evacuation – abnormal antral motility, duodenogastric reflux • Duodenogastric reflux • Gastric hypersecretion– determines esophageal peristaltic action disorders • The gastric H. pyloriinfection would decrease GER occurrence by decreasing gastric acidity

9. Digestive Manifestations • Regurgitation – physiological – first weeks of life, it disappears at the age of 12-18 months – pathological – abnormal asduration, number/24h, increased by posture changes or other situations responsible for higher abdomen pressure – requiresdifferential diagnosis from congenital (esophagus stenosis, atresia, hiatal hernia) or acquired (esophagitis, diverticuli, foreign bodies, retroesophageal abscess) esophageal obstruction • Vomitting – worsened by crying, horizontal position • Rumination (merycism) – rare, the food returns in the mouth, is chewed and swallowed again

10. Respiratory Manifestations • chronic cough, • episodes of obstructive apnea, • wheezing, • chronic or recurrent pneumonia, • simple chronic hoarseness, • episodes of cyanosis accompanied by stridor, hiccups, dysphonia, • Aspiration pneumonia,obstructive recurrent bronchitis • episodes of bronchial asthma, • recurrent otitis media,

11. Respiratory Manifestations The prevalence of respiratory manifestations associated with GERD is variable. Thus, in a study, (Navarro 2000) it was established a quantification of respiratory symptoms associated with GERD as follows: - chronic or recurrent respiratory symptoms - 31%; - paroxystic respiratory symptoms - 10%, expressed by: - episods of cyanosis - 5% - apnea - 3% - sudden death - 2% and concludes that it does not always exist a causal relationship between reflux and respiratory manifestations.

12. Respiratory Manifestations • Explanations on the connection of GERD and respiratory manifestations: • particle microaspiration – particles of acid refluate aspired in the respiratory system, suggested by the anatomic relation between the digestive and respiratory tracts (Mendelson, 1946); • common embryonic origin of the nervous esophagus and lung fibers – bronchospasm induced by vagal stimulation; • pulmonary manifestations may cause reflux – reversed relation. • well proven GERD – bronchial asthma relationship

13. Respiratory Manifestations • Association of GERD with asthma is well documented both in children and adults, so removing a possible reflux in a child with repeated pneumopathies, chronic coughing, wheezing, recurrent, repeated attacks of asthma has become a common practice. • Besides, even the amelioration of respiratory symptoms by medical therapy or anti-reflux surgery is an additional argument that certifies interrelation GERD - respiratory symptoms, especially asthmatic.

14. Neurobehavioral Manifestations • sleep disorders, • episodes of agitation and crying, • arching and rigidity, neck hyperextension, • general irritability, • sometimes convulsions or well-proven pseudopsychiatricbehavior In particular, in older children, Sandifer syndrome: head extension, torticollis, neck ricking, opisthotonus postures, sometimes facial asymmetry. It is associated with hiatal hernia, and in 50%of the cases it also accompanied by esophagitislessions.

15. Nutritional Consequences • weight and height gain disorders,“deficient growth” • signs ofchronic dehydration,even chronic ketosis • hypochromic microcytic anemia Associated symptoms • Simple or recurrent bradicardia, • Other heart rate disorders

16. PARACLINICAL GERDDIAGNOSIS • estabishes GER presence: - barium swallow procedure for esophagus examination, - esophageal pH-metry, - scintigraphy; • revealsGERD-induced lesions: - esophagoscopy, - histologic examination; • determinesGERDetiopathogenesis: - LES pressure measuring, - esophageal clearance determination, - intraesophagealpressure determination; • proves the causal symptom – GERD relation: - acid perfusion test (Bernstein test).

17. I. GERD THERAPY FOR CHILDREN OBJECTIVES: -treating digestive and extradigestive manifestations, - healing lesions, if present, - preventing disease recurrence and complications. PERFORMANCE: 1. General measures, 2. Pharmacological therapy, 3. Surgical therapy.

18. I.1 GENERAL MEASURES - compulsory for all patients; 1. Parent education: - they must be explained the physiological and benign nature of GER in infants; - a distinction must be made between physiological and pathological GER; 2. Posture recommendations (correct positions): - Proclive position at 30-40 degrees

19. 3. DIET MEASURES – infants - use food that thickens the meals or thick formulas (Gelopectose 3-5%, Gumilk 2%) or anti-reflux milk; - thicker food diminishes the number and severity of the regurgitation and vomiting episodes; - give the baby small and frequent meals.

20. DIET MEASURES – children and adolescents - small and frequent meals, at regular hours; - last meal - 2-3 hours before going to bed; - avoid sleeping immediately after a meal; - avoidcarbonated soft drinks, citrus fruit, tomatoes, chocolate, coffee, cocoa, black tea; - no active or passive smoking; - be careful – there are drugs decreasing LES pressure.

21. I.2DRUG THERAPY THREEFOLD - prokinetic - antacid - and antisecretion drugs.

22. a)PROKINETIC DRUGS 1.DOMPERIDOM (MOTILIUM): - increases LES pressure, inhibits gastric fundus relaxation; - dose: 0.75 - 1 mg/kg body wt/day, 2 times per day; - less side effects than Metoclopramid. 2.CISAPRIDE (PREPULSIDE, COORDINAX): - increases LES pressure, increases the esophageal motility index; - dose: 0.3mg/kg body wt 3 times per day; - adverse effects: slows down cardiac repolarization - QT interval prolongation - forbidden in many countries.

23. b)PROTON PUMP INHIBITORS (PPI) - the most efficient medication determining HCl suppression, cause covalent binding and deactivates proton pumps (H+, K+ - ATP-asis); - preferred drugs for GERD therapy, with over 90% efficiency ; - OMEPRAZOL, PANTOPRAZOL, LANSOPRAZOL, ESOMEPEAZOL... 1mg/kgc

24. I.3SURGICAL THERAPY - preferred surgical procedure – NISSEN FUNDOPLICATION: - very efficient in vomiting control, - is carried out using classical means or upper laparoscopic procedures; - postoperative complications: - immediate: dysphagia, early satiety or nausea, gas-bloat syndrome; - delayed: dumping syndrome, gastric stasis, cover hernia, intestine adherence or obstruction.

25. I.4ENDOLUMINAL GER THERAPY - modern means of solving reflux symptoms – highly specialized centers; - consists of a series of anti-reflux barriers achieved endoscopically: - Stretta procedure (radiofrequency energy), - Endocinch (Esophagus-Endoluminal Gastroplication), - NDO plicator throughout the thickness of the esophagus wall injecting etynil-vynil-alcohol non-absorbing substances (Enicryx) or plexiglas (PMMA) micro spheres suspended in gelatin, - implant in the submucous membrane of a temporary hydrogel prosthesis (Gatekeeper system).

26. II.GERD EVOLUTION - physiological GER – benign evolution, complete healing, normal growth; - pathological GER - consequences: - digestive, - respiratory, - neurological, - nutritional.

27. III.COMPLICATIONS (I) 1.PEPTIC ESOPHAGITIS - the most dreadful GERD complication, with clinical and endoscopic manifestations starting from the prenatal period and up to adolescence; - differentiated therapy depending on the severity of the lesions: - RH2 antagonists – light and moderate esophagitis, - IPP – severe refractory esophagitis.

28. COMPLICATIONS (II) Fig. 1 – 1st degree reflux Fig. 2 – 2nd degree reflux esophagitis esophagitis

29. COMPLICATIONS (III) Fig. 3 – 3rd degree reflux Fig. 4 – 4th degree reflux esophagistisesophagitis

30. COMPLICATIONS (IV) 2.PEPTIC STENOSIS - benign, located on the distal esophagus # congenital esophagitis # post-caustic esophagistis; - importance of dilating therapy. Fig. 5 – Peptic stenosis

31. COMPLICATIONS (V) 3. ESOPHAGEAL ULCER - rare complication - steady IPP therapy for 3-4 moths; 4. UPPER DIGESTIVE HEMORRHAGE - possible from neonatal period - hematemesis and/or melena - hypochromic anemie. 5. BARRETT ESOPHAGUS - squamous esophageal epithelium replaced by columnar cylindrical epithelium (metaplasia); - steady IPP therapy or surgical therapy; - close follow-up - dysplasia - adenocarcinoma (exceptional).

32. IV.GERD PROGNOSIS - GER is a condition with good prognosis, the only problem being the complicated reflux; - here are the unfavorableprognosis factors: - severe esophagitis, esophageal stenosis or Barrett esophagus; - encephalopathic children or children suffering from other neurological conditions or behavioral disorders; - other associated diseases (ex.sclerodermia, cystic fibrosis); - incorrect treatment, where the type of lession does not match the type of treatment used; - lack of compliance from the patients or the parents; - resistance to therapy (PPI non-responsive patients).

33. CONCLUSIONS 1. GERD – frequententity inpediatrics, whichisstillunder-diagnosed 2. Clinical symptoms, ratherpolymorphic, isdominated bypost-mealvomiting (sometimes in flush), sometimesresemblinghematemesis; theymaybeaccompanied by weight stagnation or loss and respiratory symptoms (from night cough to apneaepisodes, recurrentwheezing, aspiratonpneumoniaand evensuddendeath syndrome). 3. GERD therapy is threefold: general measures, pharmacological therapy, surgical therapy. 4. The initial drugs (prokinetic agents) have been lately replaced by proton-pump inhibitors, as they are considered the preferred medication able to determine reflux symptom disappearance in most of the cases. 5. The evolution is favorable for the physiological GER, while the pathological GER may be complicated by peptic esophagitis, stenosis, upper digestive hemorrhage or Barrett esophagus. 6. GERD is a good prognosis condition, with complete and sometimes spontaneous healing.