Clinical Case Conference
November 30th, 2011
Allen Hwang, MD
HPI
• 30 y/o M with h/o cystic fibrosis c/b multiple
pneumonias, chronic sinusitis, pancreatic
insufficiency, failure to thrive, chronic O2
requirement s/p bilateral lung transplant June,
2010 (CMV D-/R-).
HPI
• Post-operative course relatively uneventful,
extubated on POD #1. However, did develop:
– prednisone induced glucose intolerance
– gastric dysmotility and ileus requiring NGT
decompression
– self-limited atrial fibrillation
– sinus tachycardia
HPI
• One month post-operatively, developed:
– wound infection and PNA requiring admission and
intravenous antibiotics
– chronic MDR pseudomonas pneumonia
– multiple courses of outpatient antibiotics
– acute cellular rejection noted on serial
bronchoscopies
HPI
• Patient endorsed some reflux-type symptoms.
Given multiple episodes of rejection and
chronic pneumonia, concern for GERD as
underlying cause. Patient referred to GI for
further evaluation.
HPI
• In clinic, the patient reported intermittent
nausea, early satiety, and rare emesis
containing undigested food. He has not
gained any weight since his transplant surgery.
Mild dyspepsia controlled with PPI.
• Of note, he denies odynophagia, abdominal
pain, dysphagia, hematemesis, diarrhea, or
other changes in his bowel movements.
PMH
• As mentioned, CF c/b PNA, sinusitis, panc
insuff, s/p B lung transplant c/b Pseudomonal
infection and rejection
• Corticosteroid induced diabetes
• Sinus tachycardia
PMH
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FH: non-contributory
SH: works in office
Tob: none
Alc: none
IVDU: none
Medications
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Alendronate
ASA
Atovaquone
Calcium/VitD
Ferrous sulfate
Magnesium oxide
Metoprolol
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Mometasone
Omeprazole
Pancrelipase
Miralax
Prednisone
Tacrolimus
Valacyclovir
Allergy to Zosyn, Bactrim
Exam
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BP 110/70 P 100 T 98.1 RR 18
NAD
Trachea midline
Bibasilar rhonchi
RRR no m/r/g
soft, NT, ND, NABS, no succussion splash
Surgical scars present
Thin
Labs
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WBC 5.5, Hb 10.8, MCV 94.2, Plt 275
Albumin 4.5, Total Protein 7.6
TB 0.4, AST 17, ALT 15, AP 54
Na 140, K 4.4, Cl 106, CO2 20, BUN 44, Cr 1.42
PTT 36, INR 1.25
Labs
• Bronchoscopy/pathology
– Lung, right middle and lower lobes, transbronchial
biopsy: Fragments of alveolated lung parenchyma
with minimal acute cellular rejection, OISHLT
Grade A1
Labs
Many Pseudomonas aeruginosa, Mucoid Strain
Source: Bronch Wash
11-301-03081
F
F
F
F
F
F
F
F
Piperacillin-tazobactam
Ceftazidime
Cefepime
Meropenem
Amikacin
Gentamicin
Tobramycin
Levofloxacin
ORGANISM
R
R
R
R
R
R
R
R
What do you think?
• What is causing his nausea, vomiting, and
early satiety?
• Do you believe that his GERD is contributing to
his rejection and infections?
• Are there studies that you would like to
perform before deciding?
Gastric emptying study
• The residual activity within the stomach is
95% at one hour, 94% at two hours, 87% at 3
hours, and 80% at 4 hours.
Barium swallow test
• Normal swallowing function and normal
esophageal motility
• Patulous gastroesophageal junction with mild
to moderate gastroesophageal reflux
• Retained food debris in the stomach raising
possibility of gastroparesis
24-hr pH probe
24-hr pH probe
Esophageal manometry
Esophageal manometry
What to do next?
• Given this newly acquired information, do you
feel that this patient’s reflux is the cause of his
rejection and pneumonias?
• What do you believe is the next best course of
action?
GERD and acute lung rejection
• 1,200 lung transplant in US annually
• Significant improvement in 1 year survival
since 1963: >80%
• Five-year survival remains significantly lower
compared to other solid organ transplants:
Lung: 43% - 49%
Kidney 66-78%
Heart 64-74%
Liver 55%-72%
Bronchiolitis Obliterans Syndrome
• Long term morbidity and mortality after lung
transplantation are largely attributable to
bronchiolitis obliterans syndrome (BOS), a
form of chronic rejection
– CMV
– PNA
– HLA mismatch
– GERD?!!!!
GERD and BOS
• GERD has been proposed as a possible
mechanism for this to happen (all theoretical):
– Impaired cough reflex
– Impaired mucociliary clearance (15% after transplant)
– Esophageal and gastric dysmotility after transplant
(limited data; no prospective study)
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Vagal nerve injury
Ischemia
Scarring
Immunosuppressive drug
Does GERD cause BOS?
Observational studies
• Case series from Western Ontario with 11
heart/lung transplant patients
• 5 with BOS
• All had chronic cough, delayed gastric
emptying, esophageal dysmotility
Lancet. 1990 Jul 28;336(8709):206-8.
Does GERD cause BOS?
Observational studies
• Case report from Duke University
• Lung transplant recipient developed acute
decline in pulmonary function testing
• Biopsy showed acute inflammation, no
rejection
• Further testing showed severe reflux
• Underwent Nissen with full recovery
Chest. 2000 Oct;118(4):1214-7.
Does GERD cause BOS?
Rat studies
• WKY-to-F344 rat orthotopic lung transplant model
used
• Compared controls vs. 8 weekly gastric fluid aspirations
• 6/9 allografts with aspiration demonstrated
bronchioles with surrounding monocytic infiltrates,
fibrosis and loss of normal lumen anatomy
• None of the allografts without aspiration (n = 10)
demonstrated these findings (p = 0.002)
• Aspiration was associated with increased levels of IL-1
alpha, IL-1 beta, IL-6, IL-10, TNF-alpha and TGF-beta in
BAL and of IL-1 alpha, IL-4 and GM-CSF in serum
Am J Transplant. 2008 Aug;8(8):1614-21. Epub
2008 Jun 28.
Does GERD cause BOS?
Retrospective studies
• At Harefield Hospital in Middlesex, UK, 59 pts with LTP
underwent esophageal manometry
• Compared BOS-free survival between abnormal refluxers (37)
vs. control (HR 3.6, p=0.022) and abnormal acid control (16)
vs. control (NS)
J Heart Lung Transplant. 2009 Sep;28(9):870-5.
Does GERD cause BOS?
Retrospective studies
• Institutional observational study from Emory
• 60 LT subjects, 33 with GERD versus 27
without GERD.
• Observed 51 episodes of rejection.
• The rate of rejection was highest among
patients with GERD: 8.49 versus 2.58, an
incidence density ratio (IDR) of 3.29 (P =
.00016)
Transplant Proc. 2010 Sep;42(7):2702-6.
Does antireflux surgery prevent BOS?
Observational studies
• Case series from Western Ontario with 11
heart/lung transplant patients
• 5 with BOS
• All had chronic cough, delayed gastric
emptying, esophageal dysmotility
• Three patients improved with antireflux
precautions
• One patient improved with pyloroplasty
Lancet. 1990 Jul 28;336(8709):206-8.
Does antireflux surgery prevent BOS?
Retrospective studies
• Duke University, 18/298 lung transplant patients with
documented reflux
• Performed 13 laparoscopic Nissen fundoplications, four
laparoscopic Toupets, and one open Nissen
• Two of the 18 patients reported recurrence of
symptoms (11%), and two others reported minor GI
complaints postoperatively (nausea, bloating).
• There were no deaths from the antireflux surgery.
• After fundoplication surgery, 12 of the 18 patients
showed measured improvement in pulmonary function
(67%).
Surg Endosc. 2002 Dec;16(12):1674-8. Epub 2002 Jul 29.
Does antireflux surgery prevent BOS?
Retrospective studies
• Duke University,
retrospective cohort
survival analysis in no
reflux, reflux no
surgery, reflux early
surgery, reflux late
surgery
• Significantly reduced
incidence of BOS
Ann Thorac Surg. 2004 Oct;78(4):1142-51;
discussion 1142-51.
Does antireflux surgery prevent BOS?
Retrospective studies
• Duke University study of 222 patients that
underwent LTP.
• Divided into three groups: No GERD (pre/post
XP pH normal), GERD no fundo, GERD with
fundo
Ann Thorac Surg. 2011 Aug;92(2):462-8;
discussion; 468-9.
• Among GERD patient (no fundo):
Ann Thorac Surg. 2011 Aug;92(2):462-8;
discussion; 468-9.
• Between no GERD, GERD, and FUNDO groups:
Ann Thorac Surg. 2011 Aug;92(2):462-8;
discussion; 468-9.
Does antireflux surgery prevent BOS?
Retrospective studies
• At University of Pittsburgh, study done on the effect of antireflux surgery on pre-TP and post-TP patients
• Forty-three patients with ESLD and documented GERD (preLTx, 19; post-LTx, 24).
Arch Surg. 2011 Sep;146(9):1041-7.
How to perform Nissen fundoplication
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Step 1: Open patient
Step 2: Do a Nissen
Step 3: Close patient
Step 4: Celebratory beer
How to perform a Nissen
• Laparoscopic fundoplication with or without
pyloroplasty in patients with
gastroesophageal reflux disease
after lung transplantation: how I do it.
Christopher S. Davis, et al. J Gastrointest
Surg.;14(9):1434-1441.
Patient Course
• Patient underwent Nissen fundiplication with
pyloroplasty
• Post-operatively, continues to have difficulty
eating with peri-umbilical pain post-prandially,
with early satiety
• GES now normal
• However, less frequent cough, and resolution
of acute cellular rejection on subsequent BAL