Do You Believe in Reflux: Idiopathic Pulmonary Fibrosis

Patricia Raymond MD FACGGastroenterology Consultants, Virginia Beach

It’s funny, but you really never think much about breathing. Until its all you ever think about.

Tim Wilson

What is Idiopathic Pulmonary Fibrosis?

Chronic, progressive fibrotic disorder of the lower respiratory tract.

Affects about 128,100 people in the United States

48,000 new cases diagnosed annually

40,000 people die each year due to IPF, the same as from breast cancer

(this statistic is pre-new drugs)

Up to 80% of folks with IPF have GERD

What is GERD?Gastroesophageal Reflux Disease

Increased acid, bile, gastric contents moving up the esophagus

Typical symptom: burning in chest

May cause spasm in lungs (asthma)

May lead to microaspiration and fibrosis

Possible cause of, or worsening of, IPF

You may not know you have GERD

Typical symptoms: heartburn, chest pain, ‘acid brash’

Classic symptoms of GER (heartburn, acid regurgitation) were poor predictors of increased esophageal acid exposure among patients with moderate to severe IPF.

IPF & GERD RxN=4 newly dx IPF and GERD, who chose to be treated solely with anti-acid therapy were followed up regularly with pulmonary function tests (PFTs) over a period of 2 to 6 years.

Anti-acid GER therapy was administered using proton-pump inhibitors and/or fundoplication. Adequate suppression of acid GER was ascertained by 24-h esophageal pH monitoring.

PFTs stabilized or improved while their conditions were maintained with adequate treatment for acid GER. All patients were alive at the last follow-up, and none manifested an acute exacerbation of IPF or needed treatment for respiratory problems during this period. Sole treatment of acid gastroesophageal reflux in idiopathic pulmonary fibrosis: a case series. Raghu G, Yang ST, Spada C, et al.Chest. 2006;129(3):794.

IPF & GERD RxOne patient, after 4 years stable, deteriorated coincident with poor daily PPI use in 5th year. Stabilized again year 6.

Another patient initially deteriorated until taking PPIs as directed.

Conclusion: More clinical studies are needed to determine whether adequate treatment for increased acid GER in part improves the outcome of patients with IPF.Sole treatment of acid gastroesophageal reflux in idiopathic pulmonary fibrosis: a case series. Raghu G, Yang ST, Spada C, et al.Chest. 2006;129(3):794.

Maybe GERD doesn’t cause IPF, but…Reviewed published reports linking IPF and GERD 1980-2010.319 publications, 22 of them met the entry criteria

Relationship between GERD and idiopathic pulmonary fibrosis (IPF) 14 articles; systemic sclerosis (SSc) in 6 articles; mixed connective tissue disease (MCTD) in 2 articles

Prevalence of GERD and/or esophageal dysmotility to be higher in patients with different types of ILD as compared with those without ILD [Evidence B].

Among patients with IPF, 67-76% demonstrated abnormal esophageal acid exposure off PPI treatment.

Systematic review: the relationship between interstitial lung diseases and gastro-oesophageal reflux disease. Hershcovici T, Jha LK, Johnson T, et al. Aliment Pharmacol Ther. 2011 Dec;34(11-12):1295-305. Epub 2011 Oct 17.

Maybe GERD doesn’t cause IPF, but…No relationship was demonstrated between severity of GERD and severity of IPF [Evidence B].

Correlation between the severity of ILD and the degree of esophageal motor impairment in patients with SSc and MCTD [Evidence B].

Causal relationship between GERD and idiopathic pulmonary fibrosis cannot be established.

There is scant evidence about antireflux therapy in idiopathic pulmonary fibrosis patients.

.

Systematic review: the relationship between interstitial lung diseases and gastro-oesophageal reflux disease. Hershcovici T, Jha LK, Johnson T, et al. Aliment Pharmacol Ther. 2011 Dec;34(11-12):1295-305. Epub 2011 Oct 17.

Say hello to your

esophagus

GERD: It’s not only the acidN=30 IPF patients, 1999-2006 UCSF Esophageal manometry, and 24-hour dual sensor ambulatory pH monitoring

20 of 30 (67%) patients had abnormal esophageal reflux.

Typical reflux symptoms, although more common in those with reflux, were not reliable as a screening test (sensitivity 65%, specificity 71%).

65% low LES pressure50% abnormal peristalsis (vs 10% without GERD)

In 9 (30%) patients, acid refluxed into the proximal esophagus for over 1% of the study time. Gastroesophageal reflux in patients with idiopathic pulmonary fibrosis

referred for lung transplantation. Sweet MP, Patti MG, Leard LE, et al. J Thorac Cardiovasc Surg. 2007;133(4):1078.

GERD: It’s not the acidMost patients with idiopathic pulmonary fibrosis have pathologic reflux.

Symptoms do not distinguish between those with and without reflux.

In these patients, reflux is associated with a hypotensive lower esophageal sphincter and abnormal esophageal peristalsis, and often extends into the proximal esophagus. Gastroesophageal reflux in patients with idiopathic pulmonary fibrosis

referred for lung transplantation. Sweet MP, Patti MG, Leard LE, et al. J Thorac Cardiovasc Surg. 2007;133(4):1078.

Why does GERD matter?

IPFs with treated GERD

live longer.

N=204 34% with GERD symptoms45% with history of diagnosis of GERD47% used GERD medications5% has surgery for GERD (Nissan fundiplication)

The use of GERD medications was an independent predictor of longer survival time.

The use of GERD medications was associated with a lower radiologic fibrosis score.

These findings further support the hypothesis that GER and chronic microaspiration may play important roles in the pathobiology of IPF.

Gastroesophageal reflux therapy is associated with longer survival in patients with idiopathic pulmonary fibrosis. Lee JS, Ryu JH, Elicker BM, et al. Am J Respir Crit Care Med. 2011;184(12):1390.

GERD Rx in Placebo Patients in IPF Trials: An Unintentional Study

Looked at three studies of IPF, at the patients who received placebo N=242 patients

124 (51 percent) were taking a proton-pump inhibitor (PPI) or H2 blocker at enrollment.

Patients taking a PPI or H2 blocker at baseline had a smaller decrease in FVC at 30 weeks (-0.06 L, 95% CI -0.11 to -0.01) than those not taking anti-acid treatment (-0.12 L, -0.17 to -0.08; difference 0·07 L, 95% CI 0-0.14).

These data suggest that GERD treatment could be beneficial in patients with IPF and support the previous reports suggesting that abnormal acid gastroesophageal reflux contributes to disease progression. However, controlled clinical trials of acid reflux treatments in IPF are needed.Anti-acid treatment and disease progression in idiopathic pulmonary fibrosis: an analysis of data from three randomised controlled trials. Lee JS, Collard HR, Anstrom KJ, et al. , IPFnet Investigators Lancet Respir Med. 2013;1(5):369.

“However, controlled clinical trials

of acid reflux treatments in IPF are needed.”

Heck No.

What to do?GET DIAGNOSED:

Ask your GI, Internist (GP or FP) or Pulmonary doc to order a 24 hour pH test

ON MEDS if you are taking a PPI (Prilosec, Protonix, Aciphex, Nexium , Dexilant…) to see if fully suppressing the acid

On no acid reduction meds if we have not established you to have GERD

(if your test is ordered at SPAH, I will be assigned to read the test)

What to do (2)?Take your meds, EVERY DAY, even if you don’t feel heartburn.

Lifestyle modifications:

Elevate HOB

Avoid late meals, large meals, fatty meals

Sugar free candies or gum (increased saliva flow)

Antireflux diet (no acidic foods, no foods that relax the LES)

Whenever I feel blue, I start breathing again.

L. Frank Baum

"Do You Believe In Reflux" Do You Believe in Magic

The Lovin’ Spoonful1965

Do you believe in reflux, in lung fib-ro-sis How the acid can worsen your longterm

prognosis And it's reflux, if any acid is risin'

Even without symptoms, there's no compromisin'

Even mild reflux cannot be dismissed If 'Keep on Breathing's first on your bucket list

If you believe in reflux, start on PPIs Add a 24 hour pH probe if you're really

wise Just listen, you may have mild heartburn But it'll progress to a point of no return.

Although you wish I'd run away to Timbuktu

IFP and reflux can make you feel so 'blue'

Do you believe in reflux? Do you believe like I believe? Do you believe like I believe?

Do you believe in reflux?

Patricia Raymond MD FACG Gastroenterology Consultants, Virginia Beach

757-523-9755 x 2320 Nurse: Ms Debbie Miller LPN

1925 Glenn Mitchell Drive, Suite 102, Virginia Beach

(Sentara Princess Anne Hospital Campus)

References IPF & GERD1. Tobin RW, Pope CE 2nd, Pellegrini CA, et al. Increased prevalence of gastroesophageal reflux in patients

with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 1998; 158:1804. 2. Raghu G, Freudenberger TD, Yang S, et al. High prevalence of abnormal acid gastro-oesophageal reflux in

idiopathic pulmonary fibrosis. Eur Respir J 2006; 27:136. 3. Sweet MP, Hoopes C, Golden J, et al. Prevalence of delayed gastric emptying and gastroesophageal reflux

in patients with end-stage lung disease. Ann Thorac Surg 2006; 82:1570; author reply 1570. 4. Schachter LM, Dixon J, Pierce RJ, O'Brien P. Severe gastroesophageal reflux is associated with reduced

carbon monoxide diffusing capacity. Chest 2003; 123:1932. 5. Lee JS, Collard HR, Raghu G, et al. Does chronic microaspiration cause idiopathic pulmonary fibrosis? Am

J Med 2010; 123:304. 6. Pashinsky YY, Jaffin BW, Litle VR. Gastroesophageal reflux disease and idiopathic pulmonary fibrosis. Mt

Sinai J Med 2009; 76:24. 7. Bandeira CD, Rubin AS, Cardoso PF, et al. Prevalence of gastroesophageal reflux disease in patients with

idiopathic pulmonary fibrosis. J Bras Pneumol 2009; 35:1182. 8. Raghu G, Yang ST, Spada C, et al. Sole treatment of acid gastroesophageal reflux in idiopathic pulmonary

fibrosis: a case series. Chest 2006; 129:794. 9. Hershcovici T, Jha LK, Johnson T, et al. Systematic review: the relationship between interstitial lung

diseases and gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2011; 34:1295. 10. Sweet MP, Patti MG, Leard LE, et al. Gastroesophageal reflux in patients with idiopathic pulmonary fibrosis

referred for lung transplantation. J Thorac Cardiovasc Surg 2007; 133:1078. 11. Lee JS, Ryu JH, Elicker BM, et al. Gastroesophageal reflux therapy is associated with longer survival in

patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2011; 184:1390. 12. Lee JS, Collard HR, Anstrom KJ, et al. Anti-acid treatment and disease progression in idiopathic pulmonary

fibrosis: an analysis of data from three randomised controlled trials. Lancet Respir Med 2013; 1:369.