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CHRONIC COUGH. due to. GASTROESOPHAGEAL REFLUX DISEASES. MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine. A cute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks. Chronic Cough. Lasting more than 8 weeks.

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GASTROESOPHAGEAL REFLUX DISEASES

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Gastroesophageal reflux diseases

CHRONIC COUGH

due to

GASTROESOPHAGEAL

REFLUX DISEASES

MÜNEVVER ERDİNÇ

Department of Chest Diseases

Ege University Faculty of Medicine


Gastroesophageal reflux diseases

Acute Cough

lasting less than 3 weeks

Subacute Cough

lasting 3 to 8 weeks

Chronic Cough

Lasting more than 8 weeks

Morice AH.Eur Respir J 2004 :24:481-492

Fontana GA.Thorax 2003;58:1092-1095

Irwin RS.NEJM 343(23): 1715-1721,2000

Irwin RS. Chest 1998; 114(suppl1) :133S-181S


Gastroesophageal reflux diseases

PNDS

12

ASTHMA

16

13

12

6

4

10

GERD

1.Gastroesophageal reflux disease(21-41%)

2. Cough variant asthma (24-59%)

3.Postnasal drip syndrome(41-58%)

Chest 1999;116:279-284


Gastroesophageal reflux diseases

Percentage of Cases Presenting 1,2,3, and 4 Causative Factors

Chest 1999;116:279-281


Gastroesophageal reflux diseases

Asthma and/or GERD, PNDS

responsible for 93.6% of the cases

of chronic cough

  • İmmunocompetent patients

  • Not exposed to enviromental irritants

  • Chest radiograph is normal

  • Not taking an ACE inhibitor

  • Nonsmoker

Harding SM .Chest 2003;123:659-660


Gastroesophageal reflux diseases

Cough

the most common complaint for seeking medical care

In the USA  Ist (1993)

GERD

the most common chronic disease

ın the USA!

R. C. Orlando


Gastroesophageal reflux diseases

Journal of the best Sabah. January 2004: 7


Gastroesophageal reflux diseases

GASTROESOPHAGEAL REFLUX

The backflow of stomach contentsinto the esophagus

(gastric acid, pepsin, bile, pancreatic enzymes)

Heartburn (pyrosis) and regurgitation

At least weekly symptoms

manifested by either by

extraesophageal reflux symptoms

and/or esophageal mucosal damage

GASTROESOPHAGEAL REFLUX DISEASE (GERD)

Irwin SR. Chest 2006:129:80S-94S


Gastroesophageal reflux diseases

What happens during nonpathologic reflux?

Kahrilas PJ.CCJM 70(5):S4-19,2003


Gastroesophageal reflux diseases

ANTIREFLUX BARRIERS

Diaphragma

Intrathoracic

-5 mmHg

Intraabdominal

+5 mmHg

LES +25mmHg

Expiration

Inspiration


Gastroesophageal reflux diseases

GERD ?

Decreased saliva

Impaired esophageal clearance

Functional defect in LES syphincter

Hiatal hernia

Delayed gastric emptying

İncreased intra-abdominal pressure

Katzka & DiMarino 1995


Gastroesophageal reflux diseases

Causative Factors in GERD

1.Gastroesophageal barrier function impairment

Hiatal hernia

İmpaired diyaphragmatic crus

Transient LES relaxations

2.Delayed esophageal clearance

Low amplitude or simultaneous contractions

Reduced salivation

3.Exogen factors

Alcohol, smoking, drugs, hot drinks , hypertonic foods, aging

4.Gastric factors

Acid hypersecretion ?

Delayed gastric emptying

Abnormal antropyloroduodenal motility (Alkalen reflux)

5.Impaired mucosal resistance


Gastroesophageal reflux diseases

Izmir, Türkiye (630) S.Bor et al. DDW 2000

Olmsted, USA (2073) Locke et al. Gastroenterology,1997

Gastroesophageal Reflux Diseasesİzmir - Olmsted Prevalance

20

18

16

14

12

15.6

10

20

17.8

19.8

Weekly symptoms %

8

10

6

4

6.3

2

0

Heartburn

Regurgitation

Pyrozis/

Regurgitation


Gastroesophageal reflux diseases

Menderes (Ege ÜTF)

Olmsted (Mayo)

Symptom

GERD (+)%

GERD (-) %

GERD (+) %

GERD (-) %

Dysphagia

35,7

7,9 *

29,4

13,5 *

NCCP

44,4

18,7 *

37

23,1 *

Odynophagia

10,3

2,4 *

Globus

23,8

8,1 *

14,2

10,6 *

Regurgitation

24,6

13,8 *

Hiccup

9,5

2,4 *

Cough

19,8

10,3 *

Hoarseness

28,6

13,1 *

Asthma

0,8

2,2

11,6

9,3

GERD Related Symptoms


Gastroesophageal reflux diseases

GERD SPECTRUM

Physiologic

Typical

Extraesophageal

NERD

Atypical

Complications

Chronic cough

Hoarseness

Asthma

Laryngitis

Aspiration pneumonia

Dental erosions

Snoring

Noncardiac chest pain

Chest pain

Hiccup

Dyspepsia

Night sweats

Globus

Sleep

disturbances

Stricture

Bleeding

Barrett

Adenocarcinoma

Esophagitis


Gastroesophageal reflux diseases

  • Edema and hyperemia of larynx

  • Vocal cord erythema, polyps, granulomas, ulcers

  • Hyperemia and lymphoid hyperplasia

  • of posterior pharynx

  • Interarytenoid changes

  • Subglottic stenosis

FLR

Signs


Gastroesophageal reflux diseases

GERD-related cough incidence

5 - 41%

ARRD 1981;123:413-417

Arch Intern Med 1996;156:997

Chest 1993;104:1511-1517

Irwin RS. Chest 2006;129:80S-94S

May be the sole presenting symptom

Association between cough andreflux is important

  • Esophageal-tracheal-bronchial reflex

  • Microaspiration

Pathogenesis

Nonacid factors?

Esophageal dysmotility?

Thorax 2003:58;1092-1095)

Chest 1997; 111: 1389-1402

Irwin RS. Chest 2006;129:80S-94S


Gastroesophageal reflux diseases

Central

Nervous

System

Esophagus

Tracheobronchial Tree

Airway

REFLUX

Microaspiration

.Mediator

Release

. Inflammation

. Edema

.Mucus

. Smooth

Muscle

Airway Vagal

Afferents

Esophageal

Vagal

Afferents

CNS

Airway Vagal

Efferents

Bronchial Hyperreactivity

Stein MR.Am J Med 2003

Chest 1997;111: 1389-1402


Diagnostic tests in gerd

Diagnostic TestsinGERD

History

PPI test

Impedans

Endoscopy

Bernstein test

Bilier scintigraphy

Esophagography

Aspiration methods

Bilier scintigraphy

Reflux scintigraphy

Esophageal biopsy

Esophageal manometry

Standardized acid reflux test

High magnificated endoscopy

24-h intraesophageal impedance and pH

Telemetric esophageal pH monitorization

24-h intraesophageal pH monitoring


Gastroesophageal reflux diseases

Oesophagus

Stomach


Gastroesophageal reflux diseases

The most sensitive and specific test for GERD is

24-h esophageal pH monitoring

DeMeester score

Distal

DeMeester score >14.7

-Total time below pH 4

- Fractional of total time 4.2% 

- Fractional time of upright position 6.3% 

- Fractional time of supine position 1.2% 

-Total reflux events 50 

- Length of time 9.2 min. 

-Total time below pH 4

- Fractional of total time 1.1% 

- Fractional time of upright position 1.7% 

- Fractional time of supine position 0.6% 

-Total reflux events 5

- Length of time 3 min. 

Proximal

Richter JE, DeMeester TR.Gastroenterology 1990;98:122


Gastroesophageal reflux diseases

Causes of chronic cough

Ayık SÖ, Başoğlu ÖK, Erdinç M.

Respir Med Vol. 97 (2003) 695-701


Gastroesophageal reflux diseases

Reflux symptoms in chronic cough patients are associated with pathologic reflux in proximal esophagus

Ayık SÖ,Erdinç M,Bor S


Gastroesophageal reflux diseases

Esophageal-pulmonary Reflux

  • Lipid-laden macrophages in BAL

  • Adding indicators to feedings

  • Glucose oksidase test

  • Scintigraphic monitoring

  • Exhaled breath condensate (EBC)

  • Esophageal pH monitoring

  • Symptoms

  • Empiric PPI therapy

Effros RM.Am J Med 2003;115:137S-143S


Gastroesophageal reflux diseases

90

30

28

DLCO ml/min/mmHg

85

FEV1/FVC %

26

80

24

22

75

20

70

18

GER (-)

Grade 1

İntermittent

GER Grade 2

Severei GER

Grade 3

GER (-)

Grade 1

İntermittent

GER Grade 2

Severei GER

Grade 3

GER severity

GER severity

DLCO decrease in severe GER

Schachter LM.Chest 2003;123:1932-38


Gastroesophageal reflux diseases

The empiric trial of medical therapy

is appropiate when pHmonitoring cannot

be done or is not available

American College of Chest Physicians

Chest 1998; 114(suppl1) :133S-181S

The empiric trial of medical therapy

should be considered even in cases pHmonitoring can be done

Thorax 2003 ;58:901-907

Poe RH.Chest 2003;123:679-684

Chest 2003 ;123:650-660


Gastroesophageal reflux diseases

24 hour pHmetry

Empiric PPI therapy

  • GERD the most common cause of chronic cough

  • Empiric PPI therapy is not only practical

  • but is also ‘cost-effective’

  • 3. Consensus should be reconsidered

  • 4. pHmetry should be done in nonresponsive

  • to empiric therapy

Harding SM. Chest 2003 ;123:650-660


Gastroesophageal reflux diseases

pHmetry,

High sensitive in typical symptoms

however diagnostic value

in extraesophageal symptoms

50 - 80%

Symptom / reflux association

is more important in atypical symptoms

Empiric PPI therapy sensitivity  62.5 - 81%

-Patients presented with laryngeal symptoms and cough-


Gastroesophageal reflux diseases

Respiratory symptoms

prevalance

with GERD symptoms

Roka R.Digest.2005:92-96


Gastroesophageal reflux diseases

17 cm

15 cm

9 cm

7 cm

pH - 5 cm

5 cm

6 impedance channels

3 cm

+

1 pH electrode

Multichannel intraluminal

impedance-pH catheter

Adult Standard

Model ZAN-S61C01E


Gastroesophageal reflux diseases

Symptoms

No symptoms

50

40

Percentage of subjects

30

Oesophageal

dysmotility ?

20

10

0

Abnormal

Manometry

alone

Abnormal

manometry

and 24-h pH

Abnormal

24-h pH

alone

Normal

investigations

Results of oesophageal manometry and 24 hour ambulatory pH monitoring

in patients with chronic cough with (n=34)

and without (n=9) symptoms of gastro-oesophageal reflux

Kastelik JA. Thorax 2003;58:699-702


Gastroesophageal reflux diseases

Weakly acidic reflux with chronic cough

Sifrim D.Gut 2005;54:449-54


Gastroesophageal reflux diseases

In patients with chronic cough who had failed

to respond very intensive medical therapy,

the improvement or elimination of cough in

all subjects 12 months following surgery

Irwin RS.Chest 2002;121:1132-1140

The term acid reflux disease when applied

to chronic cough due to GERD, can be misnomer

Irwin RS. Chest 2006;129:80S-94S


Gastroesophageal reflux diseases

Therapetic Options

Antacids/

alginates

Life-styles

PPIs

H2RB

GERD

Prokinetic agents

Fundoplication

Endoscopic

Hatlebakk & Berstad, Clin Pharmacokinet 1996; 31: 386–406.


Gastroesophageal reflux diseases

Pharmacological Therapy in GERD

  • 1) Acid inhibition / neutralization

  • Antascides

  • H2 receptor blockers

    • Ranitidin

    • Famotidin

    • Nizatidin

  • Proton pump inhibitors

    • Omeprazol

    • Lansoprazol

    • Pantoprazol

    • Rabeprazol

    • Esomeprazol

  • 2) Barrier

    Alginic acid

    3) Cytoprotectives

    Sucralfat

    Mizoprostol

    4) Prokinetics

    Cisapride

    Domperidon?

    Metoclopramid?


    Gastroesophageal reflux diseases

    Comparison of H2B with PPI

    Metaanalysis

    Study

    Risk ratio (95% CI)

    % Weight

    Bardhan 1995

    0.26 (0.15,0.46)

    5.0

    Klinkenberg-Knol 1987

    0.33 (0.16,0.69)

    3.3

    Havelund 1988*

    0.42 (0.28,0.62)

    7.1

    Sandmark 1988

    0.48 (0.33,0.69)

    7.8

    Bate 1990

    0.59 (0.48,0.73)

    11.1

    Dehn 1990*

    0.60 (0.37,0.98)

    5.9

    Bianchi Porro 1992

    0.63 (0.42,0.94)

    7.1

    Koop 1995

    0.72 (0.54,0.95)

    9.5

    IROSG 1991

    0.61 (0.38,0.99)

    5.9

    Robinson 1995

    0.37 (0.24,0.57)

    6.6

    Vantrappen 1988*

    0.26 (0.10,0.67)

    2.2

    Farley 2000

    0.64 (0.52,0.79)

    11.0

    Jansen 1999

    0.35 (0.21,0.59)

    5.5

    Armbrecht 1997

    0.59 (0.29,1.20)

    3.5

    Van Zyl 2000

    0.52 (0.36,0.76)

    7.6

    Soga 1999

    0.09 (0.01,0.62)

    0.6

    Overall (95% CI)

    0.50 (0.43,0.58)

    .012003

    1

    83.3135

    Risk ratio

    PPIH2RA

    Moayyedi. Health Care Needs Assessment, 2002


    Gastroesophageal reflux diseases

    Therapy in Esophageal-pulmonary reflux

    • Conservative and lifestyle measures

    • Pharmacological therapy: Proton pump inhibitors

      PPI x 2 / 3 months

    • Therapy failure  24 hour intraesophageal pHmetry

      ( pharyngeal pHmetry)

      GERD (+)

      High dose PPI

      Surgery, + H2 blocker agent

      Pulmonary and Crit Care Update 1994;Vol 9

      Morice AH. ERJ 2004;24:481-492


    Gastroesophageal reflux diseases

    J. A.Koufman. ENT-Ear, Nose & Throat Journal, Sep 2002 Supp

    Morice AH.ERJ 24:481-492,2004


    Gastroesophageal reflux diseases

    Esophagus

    PPI

    PPI

    Stomach


    Gastroesophageal reflux diseases

    Specific therapy

    for diagnosis and treatment

    Results of therapy

    in treating cough

    due to GERD

    Poe RH.Chest 2003;123:679-684


    Gastroesophageal reflux diseases

    Cumulative Response to GERD Therapy

    Weeks of antireflux therapy Patients responded

    No No (%)

    2 16 (41)

    4 38 (86)

    6 42 (95)

    8 43 (99)

    12 44 (100)

    Poe RH.Chest 2003;123:679-684


    Gastroesophageal reflux diseases

    Effect of the GABAB agonist baclofen

    on symptoms in patients with GERD

    Ciccaglione AF.Gut 2003;52:464-470


    Gastroesophageal reflux diseases

    Anti-Reflux Surgery

    Restore Intraabdominal esophagus

    Reduce Hiatal Hernia

    Approximate Diaphragmatic crurae

    Perform Fundoplication


    Gastroesophageal reflux diseases

    Preop

    pH <4: %23.6

    De Meester: 85

    Postop

    pH <4: %2.4

    De Meester: 9.9


    Gastroesophageal reflux diseases

    Preop

    pH <4: %14.5

    De Meester: 52.9

    Postop

    pH <4: %3.8

    De Meester: 14.2


    Gastroesophageal reflux diseases

    Clinical Profile That Chronic

    Cough İs Likely Due To‘Silent GERD’

    1.Chronic cough for at least 2 months

    2. Immunocompetent patients

    3. Chest radiograph is normal

    4. Not exposed to enviromental irritants nor a present smoker

    5. Not taking an ACE inhibitor

    6. Symptomatic asthma has been ruled out

    7. Rhinosinus diseases has been ruled out:

    8. ‘Silent sinusitis’ has been ruled out

    9. Nonasthmatic eosinophilic bronchitis

    has been ruled out:

    BPT is negative

    Cough has not improved

    with asthma therapy

    1st generation H1

    antagonists has been used

    Eo 3%

    in induced sputum

    Cough has not improved

    with steroids

    Irwin RS. Chest 2006;129:80S-94S

    İrwin RS. AJRCCM Vol 165; 1469-1474, 2002


    Gastroesophageal reflux diseases

    Chronic Cough

    History and

    Physical

    Avoid irritants

    Discontinue ACE ihibitors

    Smoking cessation

    normal

    abnormal

    Chest radiograph

    Sputum cytology,

    HRCT scan

    Bronchoscopy

    Esophagography

    Cardiac evaluation

    GERD symptoms

    (-) (+)

    Ampiric PPI

    Three months b.i.d.

    Asthma, PNDS

    Spirometry (BPT)

    ENTevaluation

    Spesific diagnosis

    and treatment

    Spesific diagnosis

    and treatment

    Cough persists

    pHmetry ( surgery?)

    Psychogenic cough(?)

    Cough persists

    Cough persists


    Gastroesophageal reflux diseases

    Pharyngeal pHmetry

    -

    +

    Increase dose PPI

    + alginate

    Not GERD

    Clinical GERD symptoms ?

    Nonacid, weakly acid reflux?

    Not improved

    İmproved

    Consider

    Simultaneously

    dual probes

    24 hours pHmonitoring

    and

    intraesophageal impedance

    pHmetry

    under treatment

    Continue

    Irwin RS.AJRCCM 165:1469-74,2002

    McGarvey LPA.Thorax 59:342-346,2004


    Gastroesophageal reflux diseases

    EGE REFLUX WORKING GROUP

    KBB

    Faringolaringeal

    reflü

    Gastroenteroloji

    Erişkin-Çocuk

    Göğüs,

    Pulmoner reflü

    Kardiyoloji

    NCCP

    Psikiyatri, Halk sağlığı

    Patoloji

    Diş Hek.

    Cerrahi

    Erişkin, Çocuk

    www.gerd-turkey.org


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