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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 - PowerPoint PPT Presentation
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Respiratory Diseases Cause Gastroesophageal Reflux
Dr. Deniz Doğru Hacettepe Üniversitesi Tıp Fakültesi Çocuk Göğüs Hastalıkları Ünitesi
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Gastroesophageal reflux (GER)
Backflow of stomach contents into the esophagus Up to 50 times a day, usually during meals and thepostprandial 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
4
The spectrum of GERD
Reflux esophagitisnon-acid reflux
in association with appropriate symptoms
5
Diagnosis of GERD
Radiography Nuclear scintigraphy 24 hour esophageal pH probe monitoring Histological examination of esophageal biopsies Esophageal manometry Intraluminal impedance monitoring
Each modality has its strengths and weaknesses !
6
GER is common
AdultsMore than 1/3 of the total adult US population have intermittent symptoms of GERD
ChildrenBabies younger than 3 months 50%4. month 67%1. Year 5%
The chance of having GER in any disease is high !
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Respiratory Disease GER
Do not imply causation!
8
pH monitorization
Nmb of symptoms associated with GERSymptom index = X 100
Number of symptoms
Nmb of GER associated with symptomsSx sensitivity index = X
100 Number of GER
SI > % 50SSI > %10
9
Children at 6 to 12 months of age
63 case subjects who regurgitate 92 control subjects 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 During Infancy. Pediatrics 1998;102(6): e67
Respiratory Symptoms and GER
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The mean frequencies in the past 6 months of ear infections
Case subjects: 1.8control subject: 1.7
sinus infectionscase subjects 1.3 control subjects 1.2
wheezing case subjects 1.2 Control subjects: 1.2
The proportion of parents reporting frequent upper respiratory
infections in 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 During Infancy. Pediatrics 1998;102(6): e67
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116 infants 54 infants :only gastrointestinal symptoms, (vomiting,regurgitation)
(aged 1–10 months) 62 infants: only respiratory symptoms, but were suspected of having
GER 16: apnea20: history of choking14: history of ALTE4: stridor8: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 in Infants Presenting With Respiratory Symptoms. Pediatric Pulmonology 27:231–235 (1999).
Respiratory Symptoms and GER
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abnormal distal esophageal acid reflux indices 17 of 54 infants with GI symptoms 16 of 63 infants with respiratory symptoms
The proximal acid reflux index and other parameters within normal range in all 116 infants irrespective of whether they had normal or abnormal
distal esophageal pH indices
no episodes of any respiratory symptoms (choking, ALTE, apnea,wheezing, and stridor) occurred during the duration of pH monitoring
V. Vijayaratnam, et al. Lack of Significant Proximal Esophageal Acid Reflux in Infants Presenting With Respiratory Symptoms. Pediatric Pulmonology 27:231–235 (1999).
13
Respiratory Diseases and GER
Chronic cough Asthma Cystic fibrosis Obstructive sleep apnea COPD
14
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
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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
16
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
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Cough causes GER ! 28 patients with chronic cough (daily cough of unclear
aetiologyfor at least eight weeks) 11 men; median age 56 years (range 42–81) 24 hour ambulatory pressure-pH-impedance monitoring
Cough by gastro-oesophageal manometryGER by oesophageal pH-impedance
acid (pH <4)weakly acidic (pH 7–4)weakly alkaline (impedance drops, pH >7)
A standardised questionnaire regarding typical and atypical symptoms of GORD“Symptom association probability (SAP) analysis”
Sifrim D. Weakly acidic reflux in patients with chronic unexplained cough during 24 hour pressure, pH, and impedance monitoring. Gut 2005;54:449–454.
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Cough bursts 449/647 (69.4%): ‘‘independent’’ of reflux 198/647 (30.6%): occurred within the two minute time window
around a reflux episode.
49% episodes were preceded by GER (reflux cough) 51 % followed by reflux (cough reflux)
45% had a positive SAP between reflux and cough: 5: acid2: acid and weakly acidic3: only with weakly acidic reflux
Sifrim D. Weakly acidic reflux in patients with chronic unexplained cough during 24 hour pressure, pH, and impedance monitoring. Gut 2005;54:449–454.
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Sifrim D. Weakly acidic reflux in patients with chronic unexplained cough during 24 hour pressure, pH, and impedance monitoring. Gut 2005;54:449–454.
In the cough-reflux episodes, the median time between cough and reflux was 40 seconds
21
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.
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Cough and reflux were not related in the majority of episodes
Where there was a relationship, cough preceded GER twice as often as GER
preceded cough
GER does not appear to be a frequent cause of chroniccough
Laukka MA, Cameron AJ, Schei AJ. Gastroesophageal reflux and chronic cough: which comes first? J Clin Gastroenterol. 1994; 19: 100-4.
Cough causes GER !
23
Aims In healthy children Define the frequency of cough in relation tosymptoms of GER Examine if
children with cough and reflux esophagitis (RE) have different airway cellularity and microbiology
in bronchoalveolar lavage (BAL)
GER and cough
Anne B Chang, et al. Cough and reflux esophagitis in children: their co-existence and airway cellularity. BMC Pediatrics 2006, 6:4
24
150 children (91 boys, 56 girls) median age: 8.2 years Suspicion of clinical GERD based upon a typical history
Questions relating cough to GERD Cough visual analog scale Elective esophago-gastroscopy and oesophageal biopsy Bronchoalveolar lavage
coughers (C+) and non coughers (C-), reflux esophagitis (E+) and without (E-) GERD was considered present if histology of oesophageal
biopsy showed reflux esophagitis
Anne B Chang, et al. Cough and reflux esophagitis in children: their co-existence and airway cellularity. BMC Pediatrics 2006, 6:4
25
46% had chronic cough (C+)
No difference in cough score between E+ and E- groups (p = 0.88)
C+ and C- were equally likely to have RE (odds ratio 0.87)
Anne B Chang, et al. Cough and reflux esophagitis in children: their co-existence and airway cellularity. BMC Pediatrics 2006, 6:4
26
Of the questions relating cough to GERD symptoms, none were
associated with 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 and airway cellularity. BMC Pediatrics 2006, 6:4
27
Median neutrophil percentage in BAL was significantly different
between groups; Highest in C+E- Lowest in C-E+
BAL positive bacterial culture occurred in 20.7%and more likely present in current coughers
Airway neutrophilia was significantly higher in those with BAL
positive bacterial cultures than those withoutAnne B Chang, et al. Cough and reflux esophagitis in children: their co-existence and airway cellularity. BMC Pediatrics 2006, 6:4
28
In children without lung disease
Cough was commonly present in association with gastro-intestinalsymptoms suggestive of GERD However cough was just as likely to be present in children withand without RE none of the common symptoms of GERD with cough wasassociated with the presence of RE
the common co-existence of cough with symptoms of GER isindependent of the occurrence of esophagitis Airway neutrophilia when present in these children is more likelyto be related to airway bacterial infection and not to esophagitis
Anne B Chang, et al. Cough and reflux esophagitis in children: their co-existence and airway cellularity. BMC Pediatrics 2006, 6:4
29
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.
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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.
31
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.
GER Treatment for Cough
32
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.
GER Treatment for Cough
33
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.
GER Treatment for Cough
34
Conclusion
Insufficient evidence to definitely conclude thatGER treatment with PPI is benecial for coughassociated 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.
GER Treatment for Cough
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ChildrenNo 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
gagor 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.
GER Treatment for Cough
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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.
GER Treatment for Cough
37
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 GERprior 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.
GER Treatment for Cough
38
Respiratory Diseases and GER
Chronic cough Asthma Cystic fibrosis Obstructive sleep apnea COPD
39
Asthma and GER GER occurs both in children and in adults with the
overall incidence of 8% In asthmatics, this incidence is higher than in the
general population
GER is estimated to occur in 60–80% of asthmatic adults 50–60% of children
It is estimated that 50% of children with chronic respiratory disorders 25–30% of adults have silent GER
In turn, 30–75% of these patients suffer from esophagitis
40
Asthma and GER
Asthma and GER are common diseases
The coexistence of symptoms do not imply causation!
41
Asthma and GER
About 200 studies concerned with the concurrence ofasthma and GER
Only 18 of them can provide the basis for assessment of the frequency of this concurrence
Most studies were aimed at elucidation of the mechanism of asthma provocation by GER
The estimation of actual frequency of asthma and GER concurrence is difficult because,
definitions of GER differ considerably, the methods of its confirmation were different. studies were carried out in selected groups of patients, so
it was difficult to estimate the actual incidence of GER in the general population of asthmatic patients
42
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 refluxduring methacholine-induced bronchospasm. J Allergy Clin Immunol 1986;78: 619-23.
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During bronchospasm
GER episode pH Asthma 3.9 +/- 1.5 2.23 +/- 0.3
Control 0.8 +/- 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.
44
In patients with mild asthmamethacholine-induced bronchospasm
produced GER episodes of greater frequency and severity
Moote DW, Lloyd DA, McCourtie DR, Wells GA. Increase in gastroesophageal refluxduring methacholine-induced bronchospasm. J Allergy Clin Immunol 1986;78: 619-
23
45
Asthma and GER
Effects of Bronchial Obstruction on Lower Esophageal Sphincter 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 CareMed 2002; 166: 1206–1211
46
Each subject fasted for at least 8 hours before the study Subjects with asthma didn’t use inhaled bronchodilatorsduring the previous 6 hours.
LES motility and esophageal pH were monitored by anesophageal motility catheter and a pH electrode for a 30-minute baseline period After inhalation of methacholine for a second 30-minuteperiod After inhalation of salbutamol for a third 30-minutePeriod
Frank Zerbib, et al. Effects of bronchial obstruction on lower esophagealSphincter motility and gastroesophageal reflux in patients with asthma. Am J
RespirCrit Care Med 2002; 166: 1206–1211
47
Resting LES pressure
Frank Zerbib, et al. Effects of bronchial obstruction on lower esophagealSphincter motility and gastroesophageal reflux in patients with asthma. Am J RespirCrit Care Med 2002; 166: 1206–1211
48
Transient LES Relaxations
Frank Zerbib, et al. Effects of bronchial obstruction on lower esophagealSphincter motility and gastroesophageal reflux in patients with asthma. Am J RespirCrit Care Med 2002; 166: 1206–1211
49
Time at pH below 4 and duration of acid reflux episodes and transient LES relaxations
50
Number of acid reflux episodes
Frank Zerbib, et al. Effects of bronchial obstruction on lower esophagealSphincter motility and gastroesophageal reflux in patients with asthma. Am J RespirCrit Care Med 2002; 166: 1206–1211
51
In asthma, bronchial obstruction elicits an increase in
the rate of TLESRs, an effect that is reversed by thebeta 2-agonist salbutamol Number of reflux episodes also increased aftermethacholine inhalation, this effect was notreversed by salbutamol.
Frank Zerbib, et al. Effects of bronchial obstruction on lower esophagealSphincter motility and gastroesophageal reflux in patients with asthma. Am J RespirCrit Care Med 2002; 166: 1206–1211
52
In patients with asthma, meth acholine-inducedbronchospasm increases the rate of TLESR andthe number of reflux episodes
These results support the belief that,in asthma, bronchial obstruction may be
responsible forreflux or may aggravate reflux
53
FACTORS THAT MAY PROMOTE GASTROESOPHAGEAL REFLUX
IN PATIENTS WITH ASTHMA
Autonomic dysregulation Increased thoracoabdominal pressure gradient
duringan asthma exacerbation High prevalence of hiatal hernia Altered crural diaphragm function Bronchodilator medications Horizontal position Overeating
54
Autonomic dysregulation
Lower esophageal sphincter (LES) tone is mediatedthrough the dorsal nucleus of the vagus nerve
Transient LES relaxations (the major mechanism ofGER that accounts for 63% to 74% of reflux episodes)are vagally mediated
Patients with asthma have widespread cholinergichyperresponsiveness, so that autonomic dysregulation
maypredispose to GER
55
15 asthmatics with GER (6 men, 9 women; average age, 36 years)
Subjects were connected to an ECG monitor BP was measured by sphygmomanometer
After a resting period, each subject had heart rate and BPMonitored during an 80° passive tilt, Valsalva maneuver, quiet anddeep breathing Each autonomic function test was analyzed and defined as
normal,hypervagal, hyperadrenergic, or mixed (a combination of hypervagalAnd hyperadrenergic responses) as compared with 23 age-matchednormal control subjects
Lodi U, Harding SM, Coghlan HC, et al. Autonomic regulation in asthmatics with gastroesophageal reflux. Chest 1997;111:65–70.
56
All asthmatics with reflux had at least one autonomic function
test display a hypervagal response Overall response scores show that 8 of 15 asthmatics withGER had an overall hypervagal response, and seven had a
mixedresponse Of the 7 asthmatics with GER who had a mixed responsescore, 2 had a hypervagal predominant response
Lodi U, Harding SM, Coghlan HC, et al. Autonomic regulation in asthmatics with gastroesophageal reflux. Chest 1997;111:65–70.
57
Asthmatics with GER have evidence of autonomicdysfunction
Autonomic dysregulation could result in decreased LESpressure and allow transient LES relaxation
Lodi U, Harding SM, Coghlan HC, et al. Autonomic regulation in asthmatics with
gastroesophageal reflux. Chest 1997;111:65–70.
Autonomic dysregulation
58
Pressure in the lower esophageal sphincter (LES) in asthmatics is lower than in healthy subjects
Sontag SJ, O’Connel S, Khandelwal S: Most asthmatics have GER with or without
bronchodilator therapy, Gastroenterol, 1990; 99: 613-20Harper PC, Bergner A, Kaye MD: Antireflux treatment for asthma: improvement
inpatients with associated gastroesophageal reflux. Arch Intern Med, 1987; 147: 56-60
Positive correlation is observed between low LES tone and asthma attacks in asthmatic children
Mitsuhashi M, Tomomasa T, TokuyamaK et al: The evaluation of gastroesophageal
reflux symptoms in patients with bronchial asthma. Ann Allergy, 1985; 54: 317-20
59
Upper esophageal sphincter
consists mainly of thecricopharyngeal muscle pharyngoesophageal junction serves as the main barrier inpreventing laryngopharyngeal
reflux Ensures swallowing Prevents the aspiration Prevents swallowing of air
60
Role of upper esophageal sphincter (UES)
Patients with GER and chronic lung diseases have significantly
lower pressure in UES, LES and
reduced peristaltic amplitude both in LES and in UESwhich may favor aspiration
Patti MG, Debas HT, Pellegrini CA: Esophageal manometry and 24-hour
pH monitoring in the diagnosis of pulmonary aspiration secondary togastroesophageal reflux. Am J Surg, 1992; 163: 401-406
61
FACTORS THAT MAY PROMOTE GASTROESOPHAGEAL REFLUX
IN PATIENTS WITH ASTHMA
Autonomic dysregulation Increased thoracoabdominal pressure gradient
duringan asthma exacerbation High prevalence of hiatal hernia Altered crural diaphragm function Bronchodilator medications Horizontal position Overeating
62
Thoracoabdominal Pressure Gradient
At the end of expiration, the pressure gradient betweenthe stomach and the esophagus is approximately 4 to 6 mmHg
A normal LES pressure of 10 to 35 mm Hg is sufficient tocounteract this pressure gradient
In acute asthma exacerbations, wide pressure swings with
a more negative intrathoracic pressure occur with inspiration, and a more positive abdominal pressure results
63
FACTORS THAT MAY PROMOTE GASTROESOPHAGEAL REFLUX
IN PATIENTS WITH ASTHMA
Autonomic dysregulation Increased thoracoabdominal pressure gradient
duringan asthma exacerbation High prevalence of hiatal hernia Altered crural diaphragm function Bronchodilator medications Horizontal position Overeating
64
Hiatus hernia
65
Sliding hiatus hernia
Gastro-oesophagealjunction is located morethan 2– 3 cm proximal tothe impression of thecrural diaphragm
66
Sliding hiatus hernia
Loss of elasticity of phreno-oesophageal
ligaments excessive contraction of thelongitudinal oesophageal muscles, increased abdominal pressure, genetic predisposition age-related degeneration. acid exposition to the oesophagusinduces oesophageal shortening. So,
acidGOR itself might induce, maintainor even increase a sliding hiatus hernia
67
GER - Hiatus hernia
Hiatus hernia and oesophagitis are more common in
patients with symptoms of GER
A hiatus hernia is associated with more severeoesophagitis and higher oesophageal acid exposure
68
GER - Hiatus hernia
Reflux mechanisms responsible for the increased oesophageal acid
exposureassociated with
the presence of a hiatus hernia
low LOS pressure straining and swallow- induced LOS relaxations
69
Patients with asthma have a high prevalence of hiatal herniaPope CE II. Acid-reflux disorders. N Engl J Med 1994;331: 656–660.
64% of patients with asthma had a hiatal hernia as comparedwith 19% of normal control subjects
Mays EE. Intrinsic asthma in adults: association with gastroesophageal reflux.JAMA 1976;236:2626–2628.
58% prevalence of hiatal hernia in patients with asthmaSontag SJ, Schnell TG, Miller TQ, et al. Prevalence of oesophagitis in
asthmatics. Gut 1992;33:872–876.
Asthma - Hiatus hernia
70
FACTORS THAT MAY PROMOTE GASTROESOPHAGEAL REFLUX
IN PATIENTS WITH ASTHMA
Autonomic dysregulation Increased thoracoabdominal pressure gradient
duringan asthma exacerbation High prevalence of hiatal hernia Altered crural diaphragm function Bronchodilator medications Horizontal position Overeating
71
Crural Diaphragm Function
The crural diaphragm is important in LES pressure generation
Unlike the costal part of the diaphragm, the crural partof the diaphragm originates embryologically from theesophageal mesentery
Patients with asthma may have alterations in cruraldiaphragm function; chronic hyperinflation and air trappingcan cause the diaphragm to flatten and stretch
72
FACTORS THAT MAY PROMOTE GASTROESOPHAGEAL REFLUX
IN PATIENTS WITH ASTHMA
Autonomic dysregulation Increased thoracoabdominal pressure gradient
duringan asthma exacerbation High prevalence of hiatal hernia Altered crural diaphragm function Bronchodilator medications Horizontal position Overeating
73
Bronchodilators
Systemic administration of theophylline and beta-2-
mimetics decrease the LES tone and stimulatehydrochloric acid secretion
Inhalant beta-2-mimetics, as well as inhalant andsystemic GCS do not alter the LES tone
74
Horizontal position
Frequency of nocturnal wheezing episodes or cough is
higher in asthmatic patients with GER than in thosewithout GER
Independently of bronchodilator therapy, nightreflux is more pronounced in patients with asthma
thanin nonasthmatic patients
75
Diet
After abundant meals, when the stomach is full, horizontal position increases the risk of GER and obstruction, probably due to aspiration
Composition of diet significantly influences the LES function (decreasing its tone after products rich in fat, protein)
76
GER treatment for asthma in adults and children
The Cochrane Database of Systematic Reviews 2003, Issue 1. Art. No.: CD001496. DOI: 10.1002/14651858.CD001496.
77
Asthma and GER
Randomised controlled trials of treatment for GER in adults and children with a diagnosis of both asthma and GER
The Cochrane Database of Systematic Reviews 2003, Issue 1. Art. No.: CD001496. DOI: 10.1002/14651858.CD001496.
78
Asthma and GER
12 trials
TreatmentsProton pump inhibitors (n=6)Histamine antagonists (n=5) Surgery (n=1) Conservative treatment (n=1)
Treatment duration: 1 week – 6 months
The Cochrane Database of Systematic Reviews 2003, Issue 1. Art. No.: CD001496. DOI: 10.1002/14651858.CD001496.
79
Asthma and GERAntireflux treatment
did not consistently improve
lung function asthma symptoms nocturnal asthma use of asthma medications
The Cochrane Database of Systematic Reviews 2003, Issue 1. Art. No.: CD001496. DOI: 10.1002/14651858.CD001496.
80
Asthma and GER
Conclusion
No overall improvement in asthma following treatment for GER
The Cochrane Database of Systematic Reviews 2003, Issue 1. Art. No.: CD001496. DOI: 10.1002/14651858.CD001496.
81
A Critical Review of the Studies of the Effects of Simulated or Real Gastroesophageal Reflux on Pulmonary Function in Asthmatic Adults
Using the 1966 to 1997 MEDLINE database, asthma and lung disease were combined with GER
to identify studies of the effects of GER and acid perfusion of the
esophaguson pulmonary function
Field SK. A Critical Review of the Studies of the Effects of Simulated or Real Gastroesophageal Reflux on Pulmonary Function in Asthmatic Adults. Chest 1999; 115:848–856
82
A total of 254 citations
180 published in English
17 studies of GER and AP in asthmatic adults
Field SK. A Critical Review of the Studies of the Effects of Simulated or Real Gastroesophageal Reflux on Pulmonary Function in Asthmatic Adults. Chest 1999; 115:848–856
83
Field SK. A Critical Review of the Studies of the Effects of Simulated or Real Gastroesophageal Reflux on Pulmonary Function in Asthmatic Adults. Chest 1999; 115:848–856
Effects of AP in Asthmatics without Symptomatic GER
84
Field SK. A Critical Review of the Studies of the Effects of Simulated or Real Gastroesophageal Reflux on Pulmonary Function in Asthmatic Adults. Chest 1999; 115:848–856
Effects of AP in Asthmatics with Symptomatic GER
85
Field SK. A Critical Review of the Studies of the Effects of Simulated or Real Gastroesophageal Reflux on Pulmonary Function in Asthmatic Adults. Chest 1999; 115:848–856
86
There is little evidence to support the hypothesis that eitherspontaneous GER or AP has an effect on lung function inasthmatics Small changes have been reported in a minority ofasthmatics with symptomatic GER Although statistically significant in some cases, thechanges were small and unlikely to be clinically important The data on asthmatics without GER suggest that AP does
notaffect pulmonary function
Field SK. A Critical Review of the Studies of the Effects of Simulated or Real Gastroesophageal Reflux on Pulmonary Function in Asthmatic Adults. Chest 1999; 115:848–856
87
Cystic Fibrosis and GER
88
CF and GER
Incidence of GER is higher among patients with cystic
fibrosis (CF) than in the general population The frequency of GER among children with CF
rangefrom 25% to 81%
89
Factors favoring GER in CF
Agents reducing muscle tone of the lower esophageal sphincter (methylxanthines, betamimetics)
Persistent cough
Postural drainage and forced expiration
Diet with high fat content
90
CF and GER
Abnormalities of pancreatic and duodenal function increaseenteroglucagon levels, resulting in delayed gastric emptying
Gastric acid secretion may be excessive
increase of trans-diaphragmatic pressure by the forcedexpiration of coughing and wheezing
alteration of the shape of the chest wall and flattening ofthe diaphragm
91
CF and GER
40 CF aged 1.3 to 20 years Based on pH-metry results, the diagnosis of GER in 22 children (55%)
Mild GER : 12 children (54.5%)Moderate GER : 7 (31.8%) Severe GER : 3 (13.6%)
GER-related esophagitis in 8 severe cases No statistical difference of GER frequency and degree according to:age, sex, growth status, presence of type ∆F508 mutation
Jacek Brodzicki, et al. Frequency, consequences and pharmacological treatmentof gastroesophageal reflux in children with cystic fibrosis. Med Sci Monit 2002; 8:529-537.
92
In CF, a high probability of GER recurrence because of the fact that the factors predisposing for this disorder are very difficult, and sometimes impossible, to eliminate
In a study of children below 5 years of age examined one year after the completion of treatment observed the recurrence of GER in 50% of cases
Malfroot A, Dab I. New insights on gastro-oesophageal reflux in cystic fibrosis by longitudinal follow up. Arch Dis Child 1991; 66: 1339-45
93
Weinberger M. Gastroesophageal reflux disease is not a significantcause of lung disease in children. Pediatr Pulmonol Suppl. 2004;26:197
200.
Cough and fall in pH in 2 CF patients
94
Obstructive Sleep Apnea (OSA) and GER
95
Sleep itself can contribute to GER Decrease in the LES tone
Prolongation of acid clearance
Impaired swallowing
Episodes of upper airway obstruction during sleep are associated with large intrathoracic/esophageal negativepressures swings
increased a transdiaphragmatic pressure gradient
96
Obstructive Sleep Apnea (OSA)
Upper airway narrows or closes intermittently during sleep
resulting in increased airway resistance with a decrease in
airflow or complete cessation of airflow Reduction in airflow or the increase in airway
resistancecan arouse the patient and fragment sleep Muscle effort increases and leads toincreasingly negative intrathoracic pressures
97
OSA causes GER
negative intrathoracic pressure
OSA
transdiaphragmatic gradient of pressure
facilitate the migration of the gastric contents toward the esophagus
GER
Irreversible destructuring of phrenoesophageal ligament
LES insufficiency
depressed muscle control of the respiratory drive during sleep
muscle tone relaxation in the pharyngeal region
98
Chronic Obstructive Pulmonary Disease
and
GER
99
COPD and GER
5 prospective studies on GERD and COPD
Increased prevalence in 4 David P, et al. Fonction respiratoire et reflux gastro-cesophagien aucours de la bronchite chronique. [Respiratory function and gastroesophageal reflux during chronic bronchitis]. Bull Eur Physiopathol Respir1982; 18: 81–86. Duculone´ A, et al. Gastroesophageal reflux in patients with asthma andchronic bronchitis. Am Rev Respir Dis 1987; 135: 327–332. Mokhlesi B, et al. Increased prevalence of gastroesophageal refluxsymptoms in patients with COPD. Chest 2001; 119:1043–1048. Casanova C, et al. Increased gastro-oesophageal reflux disease inPatients with severe COPD. Eur Respir J 2004; 23: 841–845
100
COPD causes GER
Severe hyperinflation, vigorous cough, bronchospasm mayincrease intra-abdominal pressure change the relationship between the diaphragm and loweresophageal sphincter possibly decreasing diaphragmatic contribution to sphincter
tone Medications such as b2-agonists, anticholinergics,andtheophylline may increase GER by lowering esophageal
sphincter pressure
101
Mild-to-severe COPD (n:100)
Control group (n:51) without respiratory complaints
Modified version of the Mayo Clinic GER questionnaire
Mokhlesi B, et al. Increased Prevalence of Gastroesophageal Reflux Symptoms in Patients With COPD. Chest 2001;119;1043-1048
102
A greater proportion of COPD patients had significant GER than control subjects
heartburn and/or regurgitation (19% vs 0%, p<0.001)chronic cough (32% vs 16%; p:0.03)dysphagia (17% vs 4%; p:0.02)
Significant GER symptoms COPD patients with FEV1 <50%: 23% COPD patients with FEV1 >50%: 9%,
(p:0.08)
Mokhlesi B, et al. Increased Prevalence of Gastroesophageal Reflux Symptoms in Patients With COPD. Chest 2001;119;1043-1048
103
PFT results were similar
among COPD patients
with and without GER symptoms
Mokhlesi B, et al. Increased Prevalence of Gastroesophageal Reflux Symptoms in Patients With COPD. Chest 2001;119;1043-1048
104
Higher prevalence of weekly GER symptoms in COPD higher prevalence of GER symptoms in patients with severe
COPD (not statistically significant) PFT results were similar in COPD patients with and without
GERsymptoms
The data suggest that COPD may increase GER symptoms
Mokhlesi B, et al. Increased Prevalence of Gastroesophageal Reflux Symptoms in Patients With COPD. Chest 2001;119;1043-1048
105
12 patients with COPD
Mean age of 55.6
standard esophageal manometry, 24-h ambulatory pH testing, esophageal acid clearance evaluation during sleep,
and an assessment of pulmonary resistance with and without esophageal acid perfusion
Orr WC, et al. Esophageal function and gastroesophageal reflux during sleep and waking in patients with chronic obstructive pulmonary disease. Chest. 1992; 101: 1521-5.
106
Neither airway resistance nor conductance was altered by the esophageal acid infusion
LES pressures were normal acid clearance during waking appeared to be somewhat prolonged in the COPD patients
Patients with COPD do not have a bronchoconstrictive reflex to distal esophageal acidification
Orr WC, et al. Esophageal function and gastroesophageal reflux during sleep and waking in patients with chronic obstructive pulmonary disease. Chest. 1992; 101: 1521-5.
107
Summary
Respiratory diseases and GER are common disorders
Their coexistance does not always mean a relation
If there is a relation, respiratory diseases cause GER
Efective treatment of the underlying disease will prevent or improve GER