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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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CHRONIC COUGH

due to

GASTROESOPHAGEAL

REFLUX DISEASES

MÜNEVVER ERDİNÇ

Department of Chest Diseases

Ege University Faculty of Medicine


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


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



Ast Factorshma 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


Cough Factors

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 Factors

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


What happens during nonpathologic reflux? Factors

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


ANTIREFLUX BARRIERS Factors

Diaphragma

Intrathoracic

-5 mmHg

Intraabdominal

+5 mmHg

LES +25mmHg

Expiration

Inspiration


GERD ? Factors

Decreased saliva

Impaired esophageal clearance

Functional defect in LES syphincter

Hiatal hernia

Delayed gastric emptying

İncreased intra-abdominal pressure

Katzka & DiMarino 1995


Causative Factors in GERD Factors

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


Izmir, Türkiye (630) FactorsS.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


Menderes (Ege ÜTF) Factors

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


GERD SPECTRUM Factors

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


  • Edema and hyperemia of larynx Factors

  • Vocal cord erythema, polyps, granulomas, ulcers

  • Hyperemia and lymphoid hyperplasia

  • of posterior pharynx

  • Interarytenoid changes

  • Subglottic stenosis

FLR

Signs


GERD-related cough incidence Factors

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


Central Factors

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 Tests FactorsinGERD

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


Oesophagus Factors

Stomach


The most sensitive and specific test for GERD is Factors

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


Causes of chronic cough Factors

Ayık SÖ, Başoğlu ÖK, Erdinç M.

Respir Med Vol. 97 (2003) 695-701


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

Ayık SÖ,Erdinç M,Bor S


Esophageal-pulmonary Reflux with pathologic reflux in proximal esophagus

  • 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


90 with pathologic reflux in proximal esophagus

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


The empiric trial of medical therapy with pathologic reflux in proximal esophagus

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


24 hour pHmetry with pathologic reflux in proximal esophagus

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


pHmetry, with pathologic reflux in proximal esophagus

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-


Respiratory symptoms with pathologic reflux in proximal esophagus

prevalance

with GERD symptoms

Roka R.Digest.2005:92-96


17 cm with pathologic reflux in proximal esophagus

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


Symptoms with pathologic reflux in proximal esophagus

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


Weakly acidic reflux with chronic cough with pathologic reflux in proximal esophagus

Sifrim D.Gut 2005;54:449-54


In patients with chronic cough who had failed with pathologic reflux in proximal esophagus

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


Therapetic Options with pathologic reflux in proximal esophagus

Antacids/

alginates

Life-styles

PPIs

H2RB

GERD

Prokinetic agents

Fundoplication

Endoscopic

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


Pharmacological Therapy in GERD with pathologic reflux in proximal esophagus

  • 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?


    Comparison of H with pathologic reflux in proximal esophagus2B 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

    PPI H2RA

    Moayyedi. Health Care Needs Assessment, 2002


    Therapy in Esophageal-pulmonary reflux with pathologic reflux in proximal esophagus

    • 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


    J. A.Koufman. ENT-Ear, Nose & Throat Journal, Sep 2002 Supp with pathologic reflux in proximal esophagus

    Morice AH.ERJ 24:481-492,2004


    Esophagus with pathologic reflux in proximal esophagus

    PPI

    PPI

    Stomach


    Specific therapy with pathologic reflux in proximal esophagus

    for diagnosis and treatment

    Results of therapy

    in treating cough

    due to GERD

    Poe RH.Chest 2003;123:679-684


    Cumulative Response to GERD Therapy with pathologic reflux in proximal esophagus

    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


    Effect of the GABA with pathologic reflux in proximal esophagusB agonist baclofen

    on symptoms in patients with GERD

    Ciccaglione AF.Gut 2003;52:464-470


    Anti-Reflux Surgery with pathologic reflux in proximal esophagus

    Restore Intraabdominal esophagus

    Reduce Hiatal Hernia

    Approximate Diaphragmatic crurae

    Perform Fundoplication


    Preop with pathologic reflux in proximal esophagus

    pH <4: %23.6

    De Meester: 85

    Postop

    pH <4: %2.4

    De Meester: 9.9


    Preop with pathologic reflux in proximal esophagus

    pH <4: %14.5

    De Meester: 52.9

    Postop

    pH <4: %3.8

    De Meester: 14.2


    Clinical Profile That Chronic with pathologic reflux in proximal esophagus

    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


    Chronic Cough with pathologic reflux in proximal esophagus

    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


    Pharyngeal pHmetry with pathologic reflux in proximal esophagus

    -

    +

    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


    EGE REFLUX WORKING GROUP with pathologic reflux in proximal esophagus

    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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