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Respiratory Diseases Cause Gastroesophageal Reflux

Respiratory Diseases Cause Gastroesophageal Reflux. Dr. Deniz Doğru Hacettepe Üniversitesi Tıp Fakültesi Çocuk Göğüs Hastalıkları Ünitesi. Gastroesophageal reflux (GER) B ackflow of stomach contents into the esophagus U p to 50 times a day, usually during meals and the

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Respiratory Diseases Cause Gastroesophageal Reflux

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  1. Respiratory Diseases Cause Gastroesophageal Reflux Dr. Deniz Doğru Hacettepe Üniversitesi Tıp Fakültesi Çocuk Göğüs Hastalıkları Ünitesi

  2. Gastroesophageal reflux (GER) • Backflow of stomachcontents into the esophagus • Up to 50 times a day, usuallyduring mealsand the postprandial state in healthy individuals, • No any symptoms • Physiologic in nature Gastroesophageal reflux disease (GERD) • A disease that is caused by GER • manifested by either symptoms and/or tissue damage

  3. The spectrum of GERD non-acid reflux in associationwith appropriate symptoms Reflux esophagitis

  4. Diagnosis of GERD • Radiography • Nuclear scintigraphy • 24 hour esophageal pH probe monitoring • Histological examination of esophageal biopsies • Esophageal manometry • Intraluminal impedancemonitoring Each modality has its strengths andweaknesses !

  5. GER is common • Adults More than 1/3 of the total adult US population have intermittent symptoms of GERD • Children Babies younger than 3 months 50% 4. month 67% 1. Year 5% The chance of having GER in any disease is high !

  6. Respiratory Disease GER Do not imply causation!

  7. pH monitorization Nmb of symptoms associated with GER Symptom index = X 100 Number of symptoms Nmb of GER associated with symptoms Sx sensitivity index = X 100 Number of GER SI > % 50 SSI > %10

  8. Respiratory Symptoms and GER • Childrenat 6 to 12 months of age • 63 case subjects whoregurgitate • 92 controlsubjects matched control subjects • One-year follow-up survey of parents • The Infant Gastroesophageal Reflux Questionnaire–Shortened and Revised Form • Children’s Eating Behavior Inventory • Several additional questions regarding the child’s health history and milkconsumption Nelson SP, et al. One-Year Follow-up of Symptoms of Gastroesophageal Reflux DuringInfancy. Pediatrics 1998;102(6): e67

  9. The mean frequenciesin the past 6 months of • ear infections Casesubjects: 1.8 control subject: 1.7 • sinus infections case subjects 1.3 control subjects 1.2 • wheezing case subjects1.2 Controlsubjects: 1.2 • The proportion of parents reporting frequent upperrespiratory infectionsin the past year case subjects 16% control subjects 9% (P>0.05) Nelson SP, et al. One-Year Follow-up of Symptoms of Gastroesophageal Reflux DuringInfancy. Pediatrics 1998;102(6): e67

  10. Respiratory Symptoms and GER • 116 infants 54 infants :only gastrointestinal symptoms, (vomiting,regurgitation) (aged 1–10 months) 62 infants: only respiratorysymptoms, but were suspected ofhaving GER 16: apnea 20: history of choking 14: history ofALTE 4: stridor 8:recurrent wheezing (aged 1–12 months). • prospectively studied by dual-level prolonged intraesophageal pH monitoring V. Vijayaratnam, et al. Lack of Significant Proximal Esophageal Acid Reflux inInfants Presenting With Respiratory Symptoms. Pediatric Pulmonology 27:231–235 (1999).

  11. abnormal distal esophageal acid reflux indices 17 of 54 infants with GI symptoms 16 of 63 infants with respiratory symptoms • The proximal acidreflux index and other parameters within normalrange in all 116 infants irrespective of whether they had normal or abnormal distal esophageal pH indices • no episodes of anyrespiratory symptoms(choking, ALTE, apnea, wheezing, and stridor) occurred during the duration of pHmonitoring V. Vijayaratnam, et al. Lack of Significant Proximal Esophageal Acid Reflux inInfants Presenting With Respiratory Symptoms. Pediatric Pulmonology 27:231–235 (1999).

  12. Respiratory Diseases and GER • Chronic cough • Asthma • Cystic fibrosis • Obstructive sleep apnea • COPD

  13. Cough and GER • Cough is a very common symptom presenting to medical practitioners • Gastroesophageal reflux disease is said to be the causative factor in up to 41% of adults with chronic cough

  14. Cough and GER • However cough and GORD are common ailments and their co-existence by chance is high • The coexistence of symptoms do not imply causation • Cough can induce reflux episodes

  15. Increased respiratory effort and cough • Changes in lung volume, affects relationship between diaphragm and LOS • Intraabdominal pressure is increased and this causes the retrograde flow of the gastric content

  16. Cough causes GER ! • 28 patients with chronic cough (daily cough of unclear aetiology for at least eight weeks) • 11 men; median age 56 years (range 42–81) • 24 hour ambulatory pressure-pH-impedancemonitoring Cough by gastro-oesophageal manometry GER by oesophageal pH-impedance acid(pH <4) weakly acidic (pH 7–4) weakly alkaline (impedance drops, pH >7) • A standardisedquestionnaire regarding typical and atypical symptoms of GORD “Symptomassociation probability (SAP) analysis” Sifrim D. Weakly acidic reflux in patients with chronic unexplainedcough during 24 hour pressure, pH, and impedance monitoring. Gut 2005;54:449–454.

  17. Cough bursts • 449/647 (69.4%): ‘‘independent’’ of reflux • 198/647 (30.6%): occurredwithin the two minute timewindow around a reflux episode. • 49% episodes were preceded by GER (refluxcough) • 51 % followed by reflux (coughreflux) • 45% had a positive SAP betweenreflux and cough: 5: acid 2: acid and weakly acidic 3: only with weakly acidic reflux Sifrim D. Weakly acidic reflux in patients with chronic unexplainedcough during 24 hour pressure, pH, and impedance monitoring. Gut 2005;54:449–454.

  18. In the cough-reflux episodes, the median time between cough andreflux was 40 seconds Sifrim D. Weakly acidic reflux in patients with chronic unexplainedcough during 24 hour pressure, pH, and impedance monitoring. Gut 2005;54:449–454.

  19. Cough causes GER ! • Retrospective case review • 10 patients had prolonged pH monitoring • 182 of 221 (80.9 +/- 4.6%) of cough episodes had no correlation with GER(p = 0.0001) • Of those cough episodes that appeared to be related to GER, 27 of 39 (69.2 %) occurred before GE reflux 12 of 39 (30.8 %) occurred after GE reflux (p = 0.06) Laukka MA, Cameron AJ, Schei AJ. Gastroesophageal reflux and chronic cough: which comes first? J Clin Gastroenterol. 1994;19:100-4.

  20. Cough causes GER ! • Cough and reflux were not related in the majority of episodes • Where there was a relationship, coughpreceded GER twice asoften as GER preceded cough • GER does not appear to be a frequent cause of chronic cough Laukka MA, Cameron AJ, Schei AJ. Gastroesophageal reflux and chronic cough: which comes first? J Clin Gastroenterol. 1994;19:100-4.

  21. GER and cough Aims In healthy children • Define the frequency of cough in relation to symptomsof GER • Examine if childrenwith cough and reflux esophagitis(RE) have differentairway cellularity and microbiology inbronchoalveolar lavage (BAL) Anne B Chang, et al. Cough and reflux esophagitis in children: their co-existence andairway cellularity. BMC Pediatrics2006, 6:4

  22. 150 children (91 boys, 56 girls) median age: 8.2 years • Suspicion of clinical GERD based upon a typicalhistory • Questions relating cough to GERD • Coughvisual analog scale • Electiveesophago-gastroscopy and oesophageal biopsy • Bronchoalveolar lavage • coughers (C+) and noncoughers (C-), • reflux esophagitis (E+) andwithout(E-) • GERD was considered present if histology ofoesophageal biopsy showed reflux esophagitis Anne B Chang, et al. Cough and reflux esophagitis in children: their co-existence andairway cellularity. BMC Pediatrics2006, 6:4

  23. 46% had chronic cough (C+) • No difference in cough score between E+and E- groups (p = 0.88) • C+ and C- were equally likely tohave RE (odds ratio 0.87) Anne B Chang, et al. Cough and reflux esophagitis in children: their co-existence andairway cellularity. BMC Pediatrics2006, 6:4

  24. Of the questionsrelating cough to GERD symptoms, none were associatedwith the presence of RE (p range from 0.13 to 0.77). Anne B Chang, et al. Cough and reflux esophagitis in children: their co-existence andairway cellularity. BMC Pediatrics2006, 6:4

  25. Median neutrophil percentage in BAL was significantly different between groups; Highestin C+E- Lowest in C-E+ • BAL positive bacterial culture occurred in 20.7% and more likely present in current coughers • Airway neutrophiliawas significantly higher in those with BAL positive bacterial cultures thanthose without Anne B Chang, et al. Cough and reflux esophagitis in children: their co-existence andairway cellularity. BMC Pediatrics2006, 6:4

  26. In children without lung disease • Cough was commonly present in association with gastro-intestinal symptoms suggestive of GERD • However cough was just as likely to be present in children with and without RE • none of the common symptoms of GERD with cough was associated with the presence of RE • the common co-existence of cough with symptomsof GER is independent of the occurrence of esophagitis • Airway neutrophilia when present in thesechildren is more likely to be relatedto airway bacterial infection and not to esophagitis Anne B Chang, et al. Cough and reflux esophagitis in children: their co-existence andairway cellularity. BMC Pediatrics2006, 6:4

  27. GER treatment for prolonged nonspecific cough in children and adults The Cochrane Database of Systematic Reviews 2005, Issue 1. Art. No.: CD004823.pub2. DOI:10.1002/14651858.CD004823.pub2.

  28. GER Treatment for Cough To evaluate the efficacy of GER treatment on chronic cough in children and adults with GER and prolonged cough that is not related to an underlying respiratory disease “non-specic chronic cough” The Cochrane Database of Systematic Reviews 2005, Issue 1. Art. No.: CD004823.pub2. DOI:10.1002/14651858.CD004823.pub2.

  29. GER Treatment for Cough All randomised controlled trials on GER treatment for cough in children and adults without primary lung disease The Cochrane Database of Systematic Reviews 2005, Issue 1. Art. No.: CD004823.pub2. DOI:10.1002/14651858.CD004823.pub2.

  30. GER Treatment for Cough • 12 studies (3 paediatric, 9 adults) Adults • Analysis on use of H2 antagonist, motility agents and conservative treatment for GORD and fundoplication were not possible (from lack of data) • 5 adult studies • Comparing proton pump inhibitor (2-3 months) to placebo were analysed The Cochrane Database of Systematic Reviews 2005, Issue 1. Art. No.: CD004823.pub2. DOI:10.1002/14651858.CD004823.pub2.

  31. GER Treatment for Cough Adults • Pooled data from 3 studies resulted in no signicant difference in cough outcomes • 2 studies reported improvement in cough after 5 days to 2 weeks of treatment The Cochrane Database of Systematic Reviews 2005, Issue 1. Art. No.: CD004823.pub2. DOI:10.1002/14651858.CD004823.pub2.

  32. GER Treatment for Cough Conclusion • Insufficient evidence to definitely conclude that GER treatment with PPI is benecial for cough associated with GORD in adults • The benecial effect was only seen in sub-analysis and its effect was small The Cochrane Database of Systematic Reviews 2005, Issue 1. Art. No.: CD004823.pub2. DOI:10.1002/14651858.CD004823.pub2.

  33. GER Treatment for Cough Children No metaanalysis for children 3 studies (2 in infants) • Infants did not have non-specic cough [Orenstein 1992]. • 2 studies reported on the use of specic anti-regurgitation formula milk that included cough as an outcome measure. *cough was reported as part of a symptom complex (with gag or choke) [Vanderhoof 2003] *open nonrandomised (but controlled) trial [Xinias 2003] • Children with asthma; and unclear if the study was a randomised study. [Dordal 1994] • No controlled trials on the use of PPIs or surgery in infants or children. The Cochrane Database of Systematic Reviews 2005, Issue 1. Art. No.: CD004823.pub2. DOI:10.1002/14651858.CD004823.pub2.

  34. GER Treatment for Cough In children • Absence of data on the utility of PPI for cough associated with GER • Data on milk modication for infants and cough with GER is insufficient to make specic recommendations The Cochrane Database of Systematic Reviews 2005, Issue 1. Art. No.: CD004823.pub2. DOI:10.1002/14651858.CD004823.pub2.

  35. GER Treatment for Cough In children Until more evidence is available in the form of well designed RCTs, other causes of cough should be considered in children with cough and GER prior to any consideration of empiric treatment with a prolonged course of GER medications/interventions !!! The Cochrane Database of Systematic Reviews 2005, Issue 1. Art. No.: CD004823.pub2. DOI:10.1002/14651858.CD004823.pub2.

  36. Respiratory Diseases and GER • Chronic cough • Asthma • Cystic fibrosis • Obstructive sleep apnea • COPD

  37. Asthma and GER • GER occurs both in children and in adults with theoverall incidence of 8% • In asthmatics, this incidenceis higher than in the general population • GER is estimatedto occur in 60–80% of asthmatic adults 50–60% of children • It is estimated that 50% ofchildren with chronic respiratory disorders 25–30% of adults have silent GER Inturn, 30–75% of these patients suffer from esophagitis

  38. Asthma and GER • Asthma and GER are common diseases • The coexistence of symptoms do not imply causation!

  39. Asthma and GER • About 200 studies concerned with the concurrence ofasthma and GER • Only 18 of them can provide the basis for assessmentof the frequency of this concurrence • Most studieswere aimed at elucidation of the mechanism of asthmaprovocation by GER • The estimation of actual frequencyof asthma and GER concurrence is difficult because, definitions of GER differ considerably, the methods of its confirmation were different. studies werecarried out in selected groups of patients, so it was difficultto estimate the actual incidence of GER in the generalpopulation of asthmaticpatients

  40. Asthma causes GER • 15 mild asthma • 15 control • 1 hour of baseline measurements • 1 hour of methacholine inhalation • 1 hour after the inhalation of 200 micrograms of salbutamol • Continuous monitoring of lower esophageal sphincter pressure and pH Moote DW, Lloyd DA, McCourtie DR, Wells GA. Increase in gastroesophageal reflux during methacholine-induced bronchospasm. J Allergy Clin Immunol 1986;78:619-23.

  41. During bronchospasm GER episodepH Asthma 3.9 +/- 1.5 2.23 +/- 0.3 Control0.8 +/- 0.3 3.22 +/- 0.3 (p< 0.05) Moote DW, Lloyd DA, McCourtie DR, Wells GA. Increase in gastroesophageal reflux during methacholine-induced bronchospasm. J Allergy Clin Immunol 1986;78:619-23.

  42. In patients with mild asthma methacholine-induced bronchospasm produced GER episodes of greater frequency and severity Moote DW, Lloyd DA, McCourtie DR, Wells GA. Increase in gastroesophageal reflux during methacholine-induced bronchospasm. J Allergy Clin Immunol 1986;78:619-23

  43. Asthma and GER Effects of Bronchial Obstruction on Lower EsophagealSphincter Motility and GER in Patients with Asthma • 8 patients suffering from intermittent asthma (five males; mean age, 23 years) • 8 healthy volunteers (six males; mean age, 22 years) Frank Zerbib, et al. Effects of bronchial obstruction on lower esophageal sphincter motility and gastroesophageal reflux in patients with asthma. Am J Respir Crit Care Med 2002; 166: 1206–1211

  44. Each subject fasted for at least 8 hours before the study • Subjects with asthma didn’t use inhaled bronchodilators during the previous 6 hours. LES motility and esophageal pH were monitored by an esophagealmotility catheter and a pH electrode • for a 30-minutebaseline period • After inhalation of methacholinefor a second 30-minute period • After inhalation of salbutamol for athird 30-minute Period Frank Zerbib, et al. Effects of bronchial obstruction on lower esophageal Sphincter motility and gastroesophageal reflux in patients with asthma. Am J Respir Crit CareMed 2002; 166: 1206–1211

  45. Resting LES pressure Frank Zerbib, et al. Effects of bronchial obstruction on lower esophageal Sphincter motility and gastroesophageal reflux in patients with asthma. Am J Respir Crit CareMed 2002; 166: 1206–1211

  46. Transient LES Relaxations Frank Zerbib, et al. Effects of bronchial obstruction on lower esophageal Sphincter motility and gastroesophageal reflux in patients with asthma. Am J Respir Crit CareMed 2002; 166: 1206–1211

  47. Time at pH below 4 and duration of acid reflux episodes and transient LES relaxations

  48. Number of acid reflux episodes Frank Zerbib, et al. Effects of bronchial obstruction on lower esophageal Sphincter motility and gastroesophageal reflux in patients with asthma. Am J Respir Crit CareMed 2002; 166: 1206–1211

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