respiratory diseases cause gastroesophageal reflux

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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

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The spectrum of GERD

Reflux esophagitisnon-acid reflux

in association with appropriate symptoms

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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 !

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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!

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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

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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).

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Respiratory Diseases and GER

Chronic cough Asthma Cystic fibrosis Obstructive sleep apnea COPD

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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

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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


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In the cough-reflux episodes, the median time between cough and reflux was 40 seconds

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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 !

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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

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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


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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)


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Of the questions relating cough to GERD symptoms, none were

associated with the presence of RE (p range from 0.13 to 0.77).


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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

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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


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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”


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All randomised controlled trials on GER treatment for cough in children and adults

without primary lung disease



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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



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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



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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



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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.


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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



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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 !!!



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Respiratory Diseases and GER

Chronic cough Asthma Cystic fibrosis Obstructive sleep apnea COPD

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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

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Asthma and GER

Asthma and GER are common diseases

The coexistence of symptoms do not imply causation!

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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

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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.

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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-

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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

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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

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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

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Transient LES Relaxations


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

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Number of acid reflux episodes


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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.


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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

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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

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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

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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.

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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.

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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

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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

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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

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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

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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

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Hiatus hernia

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Sliding hiatus hernia

Gastro-oesophagealjunction is located morethan 2– 3 cm proximal tothe impression of thecrural diaphragm

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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

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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

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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

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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

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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

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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

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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

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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)

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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.

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Asthma and GER

Randomised controlled trials of treatment for GER in adults and children with a diagnosis of both asthma and GER


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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


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Asthma and GERAntireflux treatment

did not consistently improve

lung function asthma symptoms nocturnal asthma use of asthma medications


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Asthma and GER

Conclusion

No overall improvement in asthma following treatment for GER


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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

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A total of 254 citations

180 published in English

17 studies of GER and AP in asthmatic adults


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Effects of AP in Asthmatics without Symptomatic GER

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Effects of AP in Asthmatics with Symptomatic GER

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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


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Cystic Fibrosis and GER

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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%

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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

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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

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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.

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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

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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

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Obstructive Sleep Apnea (OSA) and GER

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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

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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

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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

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Chronic Obstructive Pulmonary Disease

and

GER

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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

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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

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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

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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)


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PFT results were similar

among COPD patients

with and without GER symptoms


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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


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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.

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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.

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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

respiratory diseases cause gastroesophageal reflux

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