GER or LPR reflux: What is important for lung (asthma) disease?

Richard J. Martin, M.D.Chairman Department of Medicine

National Jewish HealthEdelstein Chair in Pulmonary Medicine

Professor of MedicineNational Jewish Health

University of Colorado DenverProp

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Disclosures

• Consultant:– AstraZeneca– PMD Healthcare

• Investigator:– Chiesi Farmaceutici SpA– MedImmune– NHLBI Prop

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GERPrevalence

• U.S. Population – 10% have daily heartburn– 20% - heartburn 3X per month– 45% - heartburn at least 1X per month

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Gastroesophageal reflux

• Proximal & distal esophagus reflux is “Normal”• Pathologic Reflux

– Dysfunction of anti-reflux mechanisms• Caustic Material

– Acid, Non-acid pepsin, bile, pancreatic enzymes

• Duration of contact– Esophagus - more resistant– Extra-esophageal tissues – less resistant

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Measurement of GER

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Acid and non-acid reflux

• Acid reflux• Non-acid, non-erosive reflux

–Troublesome reflux-related symptoms without esophageal mucosal erosions with conventional endoscopy

–Potential explanations for sx• Microscopic inflammation

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Evaluation of GER/D

• Endoscopy• Bravo 48 hour esophageal pH probe - acid

– Done off PPI’s x 7 days, H2 blockers x 2 days

• pH with impedance monitoring – acid and non-acid as well as distal and proximal reflux measurementsProp

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Impedance pH probeMeasures distal and proximal acid and

non-acid reflux

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ESOPHAGEAL ANATOMY

STRIATED

SMOOTH

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If HCI is infused into the esophagus of an asthmatic patient overnight,

will lung function worsen?

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GER AND SLEEPING ASTHMATICS

Sleep study time (mins.)Tan ARRD 141:1990

Rla (cm H2O/

l/sec)

20

10

00 100 200 300 400

HCl infused

Saline infused

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Is it GER or LPR that is important?

• Can have acid or non-acid gastric reflux which can worsen or not worsen asthma–The upper esophageal sphincter is

key• Thus, LPR is overall what is important

for lung disease• How to determine importance?

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Normal Anatomy Upper AirwayEpiglottis

True Cords

Piriform Recess

Posterior Commissure

Arytenoids

False Cords

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Different Degrees of Upper Airway PathologyAll 4 patients have refractory asthma

Normal SGI = 2

Moderate SGI = 16

Mild SGI = 6

Severe SGI = 22

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Supraglottic Index: Upper Airway Evaluation

Edema Erythema/HyperemiaEpiglottis 0-3 0-3False Cords 0-3 0-3Arytenoid Cartilage 0-3 0-3

0-9 0-9 0-18Secretions/Mucosal ThickeningPiriform Recess 0 or 2 0 or 2Posterior Commissure 0 or 2 0 or 2

Possible Score 0-22

0 = Normal 1 = Mild 2 = Mod 3 = Severe

Normal 0-4Mild 5-9Mod 10-16Severe 17-22

Good, Martin. CHEST 2012;141:599-606

Total SGI Score

www.nationaljewish.org/sgiProp

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LaryngopharyngealReflux

• Laryngopharynx – lacks stripping motion to clear refluxate– Prolonged tissue exposure

• Laryngeal epithelium – Thin compared to esophagus– Less adapted to deal with acid (tight

junctions, etc.) and non-acid material

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PEFR & ASPIRATION

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GER AND SLEEPING ASTHMATICS

Sleep study time (mins.)Tan ARRD 141:1990

Rla (cm H2O/

l/sec)

20

10

00 100 200 300 400

HCl infused

Saline infused

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Brugman. Am Rev Respir Dis. 1993; 147:314-320.

Pre PrePost Post

Sinusitis AHR - Aspiration needed (Rabbit model)

Pre Post

Saline C5a des arg (chemotactic complement fragment)

Histamine (mg/ml)

Maxillary sinusinjection. Head up.

Maxillary sinusinjection. Head up.Intubated with ballooninflated.

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Phenotypes of refractory (severe) asthma

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LPR phenotype in 58 refractory asthmatics Comparison of SGI and impedance pH

• 44 (79%) SGI ≥ 10╺ 43 had GER testing with 34 documented

reflux• 14 (24%) SGI < 10╺ 9 had GER testing with 8 being negative

• SGI = 15.8 ± 3.6 in GER + test= 8.9 ± 5.5 in GER − testp < 0.0001

Good, Kolakowski, Groshong, Murphy, Martin. Chest 2012; 141:599-606

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*

5

10

15

20

25

GER (33)

SBI (13)

TissueEos (4)

Combo (13)

Non-specific (6)

Pre-BronchoscopyPost-Bronchoscopy 6 mo

ACTScore * *

ns

Asthma Control Test n = 58

*

(12fundoplications)

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**

100

80

60

40

0

20

FEV1 %Pred

FEV1% Predicted n = 58

* *ns

Pre-BronchoscopyPost-Bronchoscopy

GER (22)

SBI (13)

Tissue Eos (4)

Combo (13)

Non-specific (6)(12

fundoplications)

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12 months of aggressive anti-reflux therapy and taper improves SGI

Pre Rx Post Rx

SGI =15 SGI = 2

Impedance pH study: “negative” “normal amount of distal and proximal reflux”

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Refractory asthmatic patient

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Curschmann spiral

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Refractory asthmatic patient

Pre Tx Post anti-reflux TxProp

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The role of reflux in asthma: Is it GER or LPR that is important?

• GER is important with regard to esophageal symptoms and pathology, but in-of-itself does not participate in respiratory disease as long as the upper esophageal sphincter is competent.

• The SGI is a key to phenotyping asthma for those patients with the LPR. Asthma control and severity improve on fewer asthma medications with control of LPR.

• Treatment involves both pharmacologic and non-pharmacologic intervention.

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