Respiratory Symptoms in Respiratory Symptoms in GastroesoGastroesophageal Reflux phageal Reflux

DiseaseDisease (GERD) in (GERD) in ChildrenChildren

Gastroesophageal Gastroesophageal Reflux Disease Reflux Disease ((GERDGERD))

The gastroesophageal reflux The gastroesophageal reflux diseasedisease is the intermittent or is the intermittent or permanent passing of the permanent passing of the stomach content into the stomach content into the esophagus, which triggers a esophagus, which triggers a whole set of digestive, respiratory whole set of digestive, respiratory and/or neurobehavioral symptoms and/or neurobehavioral symptoms in the absence of any pains.in the absence of any pains.

PhysiologyPhysiology

RolRolee: - : - carrier carrier of the food bolusof the food bolus

- - GER and GER and EFEFRR preventionprevention by the LES and by the LES and UESUES

FuncFunctiontion::• carriercarrier – – due to the joint action of the muscles of due to the joint action of the muscles of

the mouththe mouth, , pharynxpharynx, eso, esophagus and, indirectly, of phagus and, indirectly, of the larynxthe larynx

• ssecreecretion tion – rol– rolee of esophagus mucous membrane of esophagus mucous membrane lubrication thus enhancing food bolus progresslubrication thus enhancing food bolus progress

- vagal- vagal mediation mediation

- - the mucus is secreted by acinous the mucus is secreted by acinous glands found in the glands found in the submucosubmucous membraneus membrane

Natural HistoryNatural History

It is It is physiological physiological during the first during the first 3 3 months months of lifeof life RegurgitaRegurgitation usually tion usually disappears disappears bbeefore the age fore the age

of of 12-24 12-24 monthsmonths CategoriCategories at es at risriskk::

PPrematurrematuree and and ddyysmatursmature babiese babies NewbornsNewborns that experienced perinatal that experienced perinatal hhyypoxipoxiaa or or

asasphyxiaphyxia Infants that had an Infants that had an “a demeure”“a demeure” gastric probe gastric probe Infants suffering from lazy “gastric emptying”Infants suffering from lazy “gastric emptying” Newborns that underwent surgery for esophageal Newborns that underwent surgery for esophageal

atreatresiasia Infants suffering from encephalopathyInfants suffering from encephalopathy, etc., etc.

EtiopatEtiopathhogenogenesisesis

3 pathogenic links:3 pathogenic links: LES dysfunctionLES dysfunction Esophagus dysfunctionEsophagus dysfunction Stomach dysfunctionStomach dysfunction

LESLES dysfunction dysfunction

Transient LES relaxation – Transient LES relaxation – major major mechanism triggering the GER mechanism triggering the GER

The Resting Pressure in the LESThe Resting Pressure in the LES May May BeBe

Altered by DrugsAltered by Drugs::loweredlowered byby::- anticholinergic- anticholinergicss- theophylline- theophylline- c- caffeineaffeine- nicotin- nicotinee- alco- alcohholol- dopaminergic- dopaminergicss- epine- epinephphrinrinee- prostaglandin- prostaglandinss E1 E1 and and

E2E2--some some hormonhormoneses::

glucagonglucagonsecretinsecretincchholecolecyystostokininkinin

- progesteron- progesteronee, , estrogenestrogen

increased increased byby::- c- chholinergicolinergicss-- dopamine receptor dopamine receptor

agonistsagonists- serotonin- serotonin- histamin- histaminee- norepine- norepinephphrinrinee-- phenylephrine phenylephrine- gastrin- gastrin

Esophagus DysfunctionEsophagus Dysfunction

Esophageal clearance failureEsophageal clearance failure 44 mec mechanisms are responsible for its efficiencyhanisms are responsible for its efficiency:: Esophageal motor activity Esophageal motor activity (peristaltic(peristaltic waves waves), ),

motility disorders determine GERmotility disorders determine GER Gravitational force Gravitational force – – in its absence, the clearance is in its absence, the clearance is

delayeddelayed SSaliva secretion aliva secretion – – given its bicarbonate content it is a given its bicarbonate content it is a

buffer for the acid coming from the stomachbuffer for the acid coming from the stomach

- - decreasedecrease: : tobaccotobacco, antic, antichholinergicolinergic medicationmedication, radiot, radiotherapyherapy, xerostomi, xerostomiaa

Esophageal gland secretionEsophageal gland secretion (muco(mucous or us or nnon-mucouson-mucous))

Stomach DysfunctionStomach Dysfunction

Increased stomach volume Increased stomach volume – – overfeedingoverfeeding Gastric distention Gastric distention – a– air swallowingir swallowing, , prolonged prolonged

overfeedingoverfeeding Increased abdomen pressureIncreased abdomen pressure: obe: obesitysity, , cough cough

efforteffort, , sneezingsneezing, defeca, defecationtion Delayed gastric evacuation Delayed gastric evacuation – – abnormal antral abnormal antral

motilitymotility, duodenogastric reflux, duodenogastric reflux DDuodenogastricuodenogastric reflux reflux Gastric hypersecretion Gastric hypersecretion – determin– determines esophageal es esophageal

peristaltic peristaltic action disordersaction disorders The gastric The gastric H. pyloriH. pylori infection would decrease infection would decrease

GER occurrence by decreasing gastric acidityGER occurrence by decreasing gastric acidity

Digestive ManifestationsDigestive Manifestations RegurgitaRegurgitationtion

– – physiologicalphysiological – – first weeks of lifefirst weeks of life, , it disappears at it disappears at the age of the age of 12-18 12-18 monthsmonths

– – patpathhologicologicalal – a – abbnormal normal asas durationduration, num, numberber/24h, /24h, increased by posture changes or other situations increased by posture changes or other situations responsible for higher abdomen pressureresponsible for higher abdomen pressure

– – requiresrequires differential diagnosis from differential diagnosis from congenital (congenital (esophagus esophagus stenostenosissis, atre, atresiasia, hiatal, hiatal herniahernia) ) or acquired or acquired (eso(esophagitisphagitis, diverticuli, , diverticuli, foreign foreign bodiesbodies, retroeso, retroesophageal abscessphageal abscess)) esophageal esophageal obstruction obstruction

VVomitting omitting –– worsened by crying worsened by crying, , horizontal positionhorizontal position RuminaRuminationtion (mer (meryycism) cism) – rar– raree, , the food returns in the food returns in

the mothe mouuthth, , is chewed and swallowed againis chewed and swallowed again

Respiratory Respiratory ManifestationsManifestations

chronic coughchronic cough,, episodes of obstructive episodes of obstructive apneaapnea,, wheezingwheezing,, chronic or recurrent chronic or recurrent pneumoniapneumonia,, simple chronic simple chronic hoarsenesshoarseness,, episodes of episodes of cyanosiscyanosis accompanied by accompanied by stridorstridor, ,

hiccupshiccups, , dysphoniadysphonia,, Aspiration Aspiration pneumonia,pneumonia, obstructive recurrent obstructive recurrent

bronchitisbronchitis episodes of episodes of bronchial asthmabronchial asthma,, recurrent recurrent otitisotitis media, media,

Respiratory Respiratory ManifestationsManifestations

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.

Respiratory Respiratory ManifestationsManifestations

ExplExplanations on the connection of GERD and anations on the connection of GERD and respiratorrespiratory manifestationsy manifestations::

particle microaspirationparticle microaspiration – particles of acid refluate – particles of acid refluate aspired in the respiratory system, suggested by aspired in the respiratory system, suggested by the anatomic relation between the digestive and the anatomic relation between the digestive and respiratory tracts (Mendelson, 1946);respiratory tracts (Mendelson, 1946);

common embryonic origincommon embryonic origin of the nervous of the nervous esophagus and lung fibers – bronchospasm esophagus and lung fibers – bronchospasm induced by vagal stimulationinduced by vagal stimulation;;

pulmonary manifestationspulmonary manifestations may cause reflux – may cause reflux – reversed relation.reversed relation.

well proven GERD – bronchial asthma relationwell proven GERD – bronchial asthma relationshipship

Respiratory Respiratory ManifestationsManifestations

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.

Neurobehavioral Neurobehavioral ManifestationsManifestations

sleep sleep disordersdisorders,, episodes of episodes of agitation and cryingagitation and crying,, archingarching and and rigidityrigidity, neck , neck hyperextensionhyperextension,, general general irritabilityirritability,, sometimes sometimes convulsionsconvulsions or well-proven or well-proven

pseudopsychiatricpseudopsychiatric bbehaviorehavior

In particularIn particular, , in older childrenin older children,, Sandifer Sandifer syndromesyndrome: : head extensionhead extension, , torticoltorticolllisis, , neck rickingneck ricking, , opistopisthhotonusotonus postures postures, , sometimes sometimes facialfacial asymmetryasymmetry. . It is associated with It is associated with hiatalhiatal hernia hernia, , and and in in 50%50% of the cases it also accompanied by of the cases it also accompanied by esoesophagitis phagitis leslesssionsions..

Nutritional ConsequencesNutritional Consequences

weight and height gainweight and height gain disorders disorders,, ““deficient growthdeficient growth””

ssigns ofigns of chronic chronic dehdehydrationydration,, even chronic even chronic ketosisketosis

hypochromic microcytic anemiahypochromic microcytic anemia

Associated symptomsAssociated symptoms Simple or recurrent Simple or recurrent bbradicardiradicardiaa,, Other Other heart rate disordersheart rate disorders

PARACLINICAL GERPARACLINICAL GERDD DIAGNOSDIAGNOSISIS

eestabistabishes GER presenceshes GER presence:: - - barium swallow procedure for esophagus barium swallow procedure for esophagus

examinationexamination,, - - esophageal esophageal pH-metrpH-metryy,, - scintigra- scintigraphyphy;; rrevevealseals GERGERDD-induced -induced lelesionssions:: - eso- esophphagoscopagoscopyy,, - histologic- histologic examination examination;; determindetermineses GERGERDD etiopatetiopathogenesishogenesis:: - - LES LES prespressure measuringsure measuring,, - - esophageal esophageal clearanceclearance determination determination,, - - intraesophageal intraesophageal prespressure determinationsure determination;; proves the causal symptom – GERproves the causal symptom – GERDD relation relation:: - - acid perfusion testacid perfusion test (Bernstein (Bernstein test test).).

I.I. GER GERDD THERAPY FOR THERAPY FOR CHILDRENCHILDREN

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.

I.1I.1 GENERAL MEASURES 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

3.3. DIET MEASURES – infant DIET MEASURES – infantss

- 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.

DIET MEASURES – DIET MEASURES – children and adolescentschildren and adolescents

- small and frequent meals, at regular hours;

- last meal - 2-3 hours before going to bed;

- avoid sleeping immediately after a meal;

- avoid carbonated soft drinks, citrus fruit, tomatoes, chocolate, coffee, cocoa, black tea;

- no active or passive smoking;

- be careful – there are drugs decreasing LES pressure.

I.2I.2 DRUG THERAPYDRUG THERAPY

THREEFOLD - prokinetic

- antacid

- and antisecretion drugs.

a)a) PROKINETIC DRUGSPROKINETIC 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.

b)b) PROTON PROTON PUMP PUMP INHIBITORS (PPI)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

I.3I.3 SURGICAL THERAPYSURGICAL 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.

I.4I.4 ENDOLUMINAL GER ENDOLUMINAL GER THERAPYTHERAPY

- 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).

II.II. GERGERDD EVOLUTION EVOLUTION

- physiological GER – benign evolution, complete healing, normal growth;

- pathological GER - consequences:

- digestive,

- respiratory,

- neurological,

- nutritional.

III.III. COMPLICATIONS (I)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.

COMPLICATIONS (ICOMPLICATIONS (III))

Fig. 1 – 1st degree reflux Fig. 2 – 2nd degree reflux esophagitis esophagitis

COMPLICATIONS (ICOMPLICATIONS (IIIII))

Fig. 3 – 3rd degree reflux Fig. 4 – 4th degree reflux esophagistis esophagitis

COMPLICATIONS (ICOMPLICATIONS (IVV))

2. PEPTIC STENOSIS- benign, located on the distal esophagus # congenital

esophagitis # post-caustic esophagistis;- importance of dilating therapy.

Fig. 5 – Peptic stenosis

COMPLICATIONS (COMPLICATIONS (VV))

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).

IV.IV. GERGERDD PROGNOSIS PROGNOSIS

- GER is a condition with good prognosis, the only problem being the complicated reflux;

- here are the unfavorable prognosis 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).

CONCLUSIONSCONCLUSIONS1. GEGERRD – D – frequent entity infrequent entity in pediatricspediatrics, , which is still under-diagnosedwhich is still under-diagnosed

2. Clinical symptoms, , rather rather polpolymorphicymorphic, , is is dominatdominated byed by post-meal post-meal vomitingvomiting ( (sometimes in flushsometimes in flush), ), sometimes resembling sometimes resembling hematemehematemesissis; ; they may be accompanied by weight stagnation or loss and they may be accompanied by weight stagnation or loss and respiratorrespiratory symptomsy symptoms ( (from night cough to apnea episodesfrom night cough to apnea episodes, , recurrent recurrent wheezing, wheezing, aspiraton aspiraton pneumonipneumoniaa and even sudden death syndromeand even sudden death 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.