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110
a barium swallow. The incidence of paraesophageal hernia may be increased if the
coronal suture is not used and the closure of the crura is not performed or if it is too
loose [ 13 , 16 ]. This step not only is essential for reducing the risk of paraesophageal
hernia [ 16 , 18 , 19 ], but also it is important from a physiologic point of view, as it
helps to strengthen the LES preventing refl ux.
Confl ict of Interest The authors have no confl icts of interest to declare.
References
1. Campos GM, Peters JH, DeMeester TR, Oberg S, Crookes PF, Tan S, DeMeester SR, Hagen
JA, Bremner CG. Multivariate analysis of factors predicting outcome after laparoscopic
Nissen fundoplication. J Gastrointest Surg. 1999;3:292–300.
2. Mainie I, Tutuian R, Agrawal A, Adams D, Castell DO. Combined multichannel intraluminal
impedance-pH monitoring to select patients with persistent gastro-esophageal refl ux for lapa-
roscopic Nissen fundoplication. Br J Surg. 2006;93:1483–7.
3. Patti MG, Robinson T, Galvani C, Gorodner MV, Fisichella PM, Way LW. Total fundoplication
is superior to partial fundoplication even when esophageal peristalsis is weak. J Am Coll Surg.
2004;198:863–9.
4. Herbella FA, Tedesco P, Nipomnick I, Fisichella PM, Patti MG. Effect of partial and total lapa-
roscopic fundoplication on esophageal body motility. Surg Endosc. 2007;21:285–8.
5. Tedesco P, Lobo E, Fisichella PM, Way LW, Patti MG. Laparoscopic fundoplication in elderly
patients with gastroesophageal refl ux disease. Arch Surg. 2006;141:289–92.
6. Meneghetti AT, Tedesco P, Galvani C, Gorodner MV, Patti MG. Outcomes after laparoscopic
Nissen fundoplication are not infl uenced by the pattern of refl ux. Dis Esophagus. 2008;21:
165–9.
7. Dallemagne B, Weerts J, Markiewicz S, Dewandre JM, Wahlen C, Monami B, Jehaes C.
Clinical results of laparoscopic fundoplication at ten years after surgery. Surg Endosc. 2006;20:
159–65.
8. Broeders JA, Rijnhart-de Jong HG, Draaisma WA, Bredenoord AJ, Smout AJ, Gooszen HG.
Ten-year outcome of laparoscopic and conventional nissen fundoplication: randomized clini-
cal trial. Ann Surg. 2009;250:698–706.
9. Morgenthal CB, Shane MD, Stival A, Gletsu N, Milam G, Swafford V, Hunter JG, Smith CD.
The durability of laparoscopic Nissen fundoplication: 11-year outcomes. J Gastrointest Surg.
2007;11:693–700.
10. Broeders JAJL, Mauritz FA, Ahmed Ali U, Draaisma WA, Ruurda JP, Gooszen HG, Smout AJ,
Broeders IA, Hazebroek EJ. Systematic review and meta-analysis of laparoscopic Nissen (pos-
terior total) versus Toupet (posterior partial) fundoplication for gastro-oesophageal refl ux dis-
ease. Br J Surg. 2010;97:1318–30.
11. Horvath KD, Jobe BA, Herron DM, Swanstrom LL. Laparoscopic Toupet fundoplication is an
inadequate procedure for patients with severe refl ux disease. J Gastrointest Surg. 1999;3:
583–91.
12. Oleynikov D, Eubanks TR, Oelschlager BK, Pellegrini CA. Total fundoplication is the operation
of choice for patients with gastroesophageal refl ux and defective peristalsis. Surg Endosc.
2002;16:909–13.
13. Patti MG, Arcerito M, Feo CV, De Pinto M, Tong J, Gantert W, Tyrrell D, Way LW. An analysis
of operations for gastroesophageal refl ux disease. Identifying the important technical elements.
Arch Surg. 1998;133:600–6.
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14. Patterson EJ, Herron DM, Hansen PD, Ramzi N, Standage BA, Swanström LL. Effect of an
esophageal bougie on the incidence of dysphagia following Nissen fundoplication: a prospec-
tive, blinded, randomized clinical trial. Arch Surg. 2000;135:1055–61.
15. Makris KI, Cassera MA, Kastenmeier AS, Dunst CM, Swanström LL. Postoperative dysphagia
is not predictive of long-term failure after laparoscopic antirefl ux surgery. Surg Endosc.
2012;26:451–7.
16. Horgan S, Pohl D, Bogetti D, Eubanks T, Pellegrini CA. Failed antirefl ux surgery. What have
we learned from reoperations? Arch Surg. 1999;134:809–17.
17. Patti MG, Gasper WJ, Fisichella PM, Nipomnick I, Palazzo F. Gastroesophageal refl ux disease
and connective tissue disorders: pathophysiology and implications for treatment. J Gastrointest
Surg. 2008;12:1900–6.
18. Watson DI, Jamieson GG, Devitt PG, Matthew G, Britten-Jones RE, Game PA, Williams RS.
Changing strategies in the performance of laparoscopic Nissen fundoplication as a result of
experience with 230 operations. Surg Endosc. 1995;9:961–6.
19. Wu JS, Dunnegan DL, Luttmann DR, Soper NJ. The infl uence of surgical technique on clinical
outcome of laparoscopic Nissen fundoplication. Surg Endosc. 1996;10:1164–70.
8 Minimally Invasive Treatment of GERD
113
P.M. Fisichella et al. (eds.), Surgical Management of Benign Esophageal Disorders,
DOI 10.1007/978-1-4471-5484-6_9, © Springer-Verlag London 2014
Abstract Research progress over the past few decades has helped us understand
the association between gastroesophageal refl ux disease (GERD), various pul-
monary diseases, and obesity. Even though the pathophysiology and mecha-
nisms behind the association have yet to be fully elucidated, treatment for GERD
in these special populations has dramatically changed over this period. While
lifestyle and dietary changes remain important for the management of GERD,
the results can be highly variable since they depend mostly on the compliance of
the patients. Pharmacologic agents such as proton pump inhibitors (PPIs) and
histamine-2 receptor antagonists are effective in reducing gastric acid and
thereby improving symptoms secondary to acidic refl ux; however, they do not
prevent nonacidic refl ux episodes and chronic microaspiration, which may con-
tribute to poorly controlled asthma, progression to end-stage lung disease, and
bronchiolitis obliterans syndrome (BOS) in lung transplant recipients. Therefore,
surgical intervention may be necessary in selected patients. Today, with the
advancement of laparoscopic techniques since their introduction in the 1990s,
morbidity and mortality of anti-refl ux and bariatric procedures have progres-
sively improved, making them the treatment of choice for GERD in this special
patient population.
Keywords Laryngopharyngeal refl ux (LPR) • Microaspiration • Bronchiolitis
obliterans syndrome (BOS) • Bariatric procedures • Asthma
Chapter 9
Minimally Invasive Treatment
of GERD: Special Situations
Yee M. Wong and P. Marco Fisichella
Y. M. Wong , MD • P. M. Fisichella , MD, MBA, FACS (*)
Department of Surgery, Stritch School of Medicine , Loyola University Medical Center ,
2160 South 1st Avenue , Maywood , IL 60153 , USA
e-mail: yewong@lumc.edu; pfi sichella@lumc.edu
114
Introduction
Gastroesophageal refl ux disease (GERD) is present in 10–20 % of the general popu-
lation in the United States, and classic or “typical” refl ux symptoms include heart-
burn and regurgitation. However, over the past few decades, increasing evidence has
shown a strong association between GERD and various pulmonary disorders.
Whether acid refl ux predisposes patients to some of these pulmonary disorders or
vice versa is still unclear, the diagnosis and treatment for these patients have posed
an immense challenge for clinicians, since many of these patients do not present
with the classic refl ux symptoms or may be entirely asymptomatic and response to
therapy is often variable. Lastly, as obesity is becoming an epidemic in the United
States, the incidence of GERD may also be on the rise since obesity is a known
contributing factor to the development of acid refl ux disease. The goal of surgical
intervention in this subset of patient addresses both the issues of obesity and refl ux
symptoms. In this chapter, the association between GERD, asthma, laryngopharyn-
geal refl ux, (LPR) end-stage lung disease, and obesity will be discussed, as well as
their challenges on diagnosis and treatment.
Asthma
Prevalence and Pathophysiology
The association between asthma and GERD has been well documented for years.
It has been reported that GERD on pH monitoring is present in up to 80 % of
patients with asthma [ 1 ]. A more recent systematic review looking at the preva-
lence of the two diseases showed that 59 % of patients with asthma also have a
diagnosis of GERD compared with only 38 % of controls. Patients with asthma are
also 1.8 times more likely to develop GERD compared to those without asthma. In
addition, the prevalence of asthma in patients with GERD is 1.2 times higher than
controls [ 2 ]. Even though the association seems clear, its pathophysiologic mecha-
nism is not completely understood. One hypothesis suggests that aspiration of
esophageal acid into upper airway leads to bronchospasm and increases airway
reactivity through a vagal refl ex [ 3 ]. On the other hand, bronchoconstriction in
asthmatics can also trigger refl ux symptoms. Further, lung hyperinfl ation in asthma
may cause an increase in the pressure gradient between the abdomen and chest,
which may lead to the herniation of the lower esophageal sphincter (LES) into the
chest. As a result, the pressure of the LES is decreased and acid is refl uxed into the
esophagus [ 4 ]. These fi ndings have since shaped the notion that surgical treatment
of GERD in patients with asthma may improve symptoms and outcomes of both
diseases.
Y.M. Wong and P.M. Fisichella
115
Symptoms and Diagnosis
Although the association between the GERD and asthma diseases has been well
established, GERD can be diffi cult to diagnose in asthmatic patients. About
40 % of patients with asthma do not present with typical refl ux symptoms, such
as regurgitation or heartburn, but have positive pH monitoring and are referred
to as having “silent GERD” [ 5 ]. These patients often fail standard therapy for
asthma control and may complain of frequent episodes of nocturnal respiratory
symptoms. Infl ammation of the esophageal mucosa from GERD can also cause
chronic cough and bronchospasm through neurogenic mechanisms [ 6 ].
Diagnosing GERD in this patient population can often be challenging and is
primarily a diagnosis of exclusion. A detailed clinical history should be obtained
with focus on the “atypical” refl ux symptoms, including substernal chest pain,
dysphagia, hoarseness, or worsening of asthma symptoms when recumbent.
A 24-h pH monitoring is commonly used to evaluate for acid refl ux in proximal
and distal esophagus. However, in patients with poorly controlled asthma, a
positive pH test is not associated with increased asthma symptoms, worse out-
come, decreased lung function, or increased airway hyperresponsiveness, if no
typical refl ux symptoms are present [ 7 ]. In addition, the result of a positive pH
monitoring does not predict response to acid suppression treatment; therefore,
the routine use of pH monitoring for poorly controlled asthmatics remains con-
troversial [ 8 ].
A diagnostic modality for GERD that has been gaining widespread popularity
since its introduction in 1991 is the multichannel intraluminal impedance test. It
allows for measurements of acidic and nonacidic events, which some suggest
may be the cause for poorly controlled asthma in some patients despite PPI ther-
apy. The probe contains multiple impedance sensors and a pH sensor and is
placed with its most distal impedance sensor within 2 cm of the lower esopha-
geal sphincter (LES). When a more distal impedance sensor detects substance in
the esophagus before the proximal sensors, it denotes a refl ux episode. A non-
acidic refl ux event can be distinguished from an acidic episode when the imped-
ance sensors are activated, but not the pH sensor. Another advantage of this
technique is that the sensors can detect the characteristics of the esophageal
refl uxate, such as gas, liquid, or a mixture of both. One study suggests that the
presence of gas in the refl uxate may be associated with worse perception of
symptoms by the patients [
9 ]. Weakly acidic or nonacidic refl ux episodes are
also associated with chronic cough in some studies [ 10 , 11 ]. In children with
persistent respiratory symptoms, pH-impedance testing has been shown to be
more useful in detecting nonacid refl ux events that are often associated with
respiratory symptoms than pH monitoring alone [
12 ], making it a more preferred
option in diagnosing GERD in asthmatic patients especially when they are
refractory to medical therapy.
9 Minimally Invasive Treatment of GERD: Special Situations
116
Treatment
Currently, the recommendations for conservative treatment of GERD are lifestyle
modifi cations and initiation of medical therapy. Compared to histamine-2 receptor
blockers, PPIs are superior in improving refl ux symptoms and healing esophagitis
[ 13 ]. However, in patients with moderate to severe asthma and symptoms of GERD,
treatment with PPIs fails to improve asthma symptoms and pulmonary function,
although patients usually report better quality of life and reduction in asthma exac-
erbation [ 14 , 15 ]. In a randomized controlled trial studying the effi cacy of PPIs in
poorly controlled asthmatics with mild or no refl ux symptoms, no benefi t was
shown with twice daily esomeprazole compared to placebo [ 5 ]. The results of these
studies may support the notion that nonacidic gastric content can also exacerbate
asthma. When comparing medical treatment with surgical intervention, multiple
studies have shown that anti-refl ux surgery is comparable, if not more effective, in
improving asthma symptoms in patients with GERD. In a randomized study by
Sontag et al., 62 patients were assigned to receiving Nissen fundoplication, raniti-
dine three times daily, or antacid as needed. The patients were followed for up to 19
years, and outcomes such as pulmonary medication requirement, asthma symptom
score, overall clinical status, peak expiratory fl ow, and pulmonary function were
collected. By 2 years, 74.9 % of patients in the surgical group had signifi cant
improvement in overall asthma status compared to 9.1 % of the medical group and
4.2 % of the control group. However, there was no signifi cant difference in medica-
tion requirement, pulmonary function, or peak expiratory fl ow in the three treatment
groups [ 16 ]. In a more recent study evaluating the effect of laparoscopic Nissen
fundoplication in the pediatric population with steroid-dependent asthma, 89 % of
patients reported signifi cant improvement in overall symptoms, 90 % had reduction
in nocturnal asthma, and 78 % of patients were weaned off oral steroids postopera-
tively [ 17 ]. Therefore, for patients with proven GERD and diffi cult to control
asthma, anti-refl ux surgery may provide symptomatic relief even if it may not
improve pulmonary function or overall survival.
Laryngopharyngeal Refl ux
Prevalence and Pathophysiology
Laryngopharyngeal refl ux (LPR) is defi ned as the retrograde fl ow of gastric con-
tent up to the level of the upper esophageal sphincter. About 24 % of patients with
GERD are also diagnosed with LPR [ 18 ]. LPR is associated with chronic laryngitis
and diffi cult-to-treat sore throat in up to 60 % of patients [ 19 ]. Unlike patients with
the “typical” GERD symptoms, only a small percentage of those diagnosed with
LPR have evidence of esophagitis on endoscopy [ 20 ]. The reason for this fi nding
is still poorly understood, but studies have shown that the presence of pepsin, in
Y.M. Wong and P.M. Fisichella
117
addition to a low pH, from gastric content, leads to tissue injury and altered epithe-
lial repair that is not readily seen in the esophagus [ 21 ]. Therefore, as few as three
proximal refl ux episodes per week can lead to LPR compared with up to 50 episodes
for GERD [ 22 ]. While the relationship between GERD and esophageal adenocarci-
noma is well established, the association between LPR and laryngeal squamous cell
carcinoma remains unproven. However, recent evidence suggests that pepsin pro-
motes epithelial proliferation in larynx and pharynx, which may imply a role in the
development of laryngeal cancer [ 23 ]. As a result of these studies, early diagnosis
of LPR may be important in preventing progression to malignancy.
Symptoms and Diagnosis
Since most patients with LPR often do not have the fi nding of esophagitis on EGD,
they may not complain of the typical GERD symptoms. More commonly, they may
report hoarseness (95 %), globus pharyngeus (95 %), persistent cough (97 %), and
throat clearing (98 %) [ 24 ]. A scoring system developed by Belafsky et al. can be
used to aid with diagnosis and to assess treatment response. The Refl ux Symptom
Index uses a scale of 0–5 to grade the following symptoms: hoarseness or voice
problem, throat clearing, excess throat mucus or postnasal drip, diffi culty swallow-
ing, coughing after eating or lying down, breathing diffi culties or choking spells,
persistent cough, sensation of something sticking or a lump in the throat, and heart-
burn, chest pain, indigestion, or regurgitation [ 25 ]. A score of 13 and above is con-
sidered abnormal and further diagnostic modalities are warranted.
Once LPR is suspected, laryngoscopy should be performed. Laryngeal infl am-
mation is a nonspecifi c fi nding, but posterior laryngitis, with thickening, erythema,
and edema concentrated in the posterior larynx, is a common fi nding in those with
LPR. Contact granuloma is highly suggestive of LPR, as it is present in 65–74 % of
patients with GERD on pH monitoring [ 26 ]. Another common fi nding at laryngos-
copy is pseudosulcus, where diffuse infraglottic edema causes linear indentation to
the medial edges of the vocal cords that resembles sulcus vocalis [ 27 ]. Other less
specifi c fi ndings include subglottic edema, diffuse laryngeal edema, ventricular
obliteration, and posterior commissure hypertrophy. Although these fi ndings are all
suggestive of LPR, to confi rm the diagnosis of refl ux, pharyngeal pH monitoring
and an ambulatory multichannel intraluminal impedance study are most commonly
performed. LPR is diagnosed when total acid exposure time, defi ned as percentage
of time when the sensor detects pH levels less than four during a 24-h monitoring,
is more than 1 % [ 28 ]. However, some studies found the false-positive rate of pha-
ryngeal pH monitoring ranging from 7 to 17 % [ 29 , 30 ], and a positive test result
does not necessarily correlate with response to PPI therapy [ 31 ]. More recently,
impedance testing has been recommended in patients who are refractory to medical
treatment since it offers more clinical information including nonacidic refl ux epi-
sodes that may contribute to the development of LPR [
32 ]. Lately, the Restech
Dx-pH probe, introduced to improve the diagnosis of LPR, allows measurements of
9 Minimally Invasive Treatment of GERD: Special Situations
118
pH in a nonliquid environment, such as the pharynx, and may be able to detect
refl ux in areas not otherwise evident during conventional pH monitoring or imped-
ance testing. One prospective study reported a sensitivity of 69 % and a specifi city
of 100 % with this diagnostic modality [ 33 ], although larger randomized studies are
still needed to compare its effi cacy with more traditional techniques.
Finally, although some clinicians may initiate a 3-month trial of high-dose PPIs
to confi rm the diagnosis of LPR before any invasive testing, it should be noted that
the response to medical treatment can be variable and similar to that achieved in the
asthmatic population with GERD. For these reasons, there is controversy today
regarding the effi cacy of PPIs in the treatment of LPR [ 19 ].
Treatment
Like those diagnosed with GERD, patients with LPR are counseled on dietary
changes, as well as behavioral modifi cations, such as weight loss, decreased alcohol
intake, and smoking cessation. One randomized controlled trial showed that life-
style changes for 2 months, with or without PPIs, signifi cantly improved symptoms
of LPR [ 34 ]. Despite controversy about the effi cacy of PPIs, the current recommen-
dation in a suspected case of LPR is to initiate a high dose of PPIs twice daily for
3 months. However, symptoms may take up to 6 months to resolve in some patients.
Therefore, unlike GERD, LPR should be treated more aggressively and conse-
quently may require a more prolonged course of treatment [ 35 , 36 ]. For patients
with GERD who are refractory to conservative therapy, laparoscopic anti-refl ux
surgery is generally recommended. Pharyngeal refl ux is reduced from 7.9 to 1.6
episodes per 24 h and esophageal acid exposure is reduced from 7.5 to 2.1 % after
surgical intervention in a study by Oelschlager et al. [ 37 ]. A recent systematic
review of literature that evaluated the effectiveness of laparoscopic fundoplication
on the treatment of LPR showed an improvement of symptoms after surgery across
the board [ 38 ]. However, because of the variability of the studies in terms of preop-
erative assessment, evaluation of outcomes, and inclusion criteria, clear recommen-
dations could not be made. Nevertheless, for patients with LPR unresponsive to
acid suppression treatment, laparoscopic fundoplication may successfully treat
laryngeal symptoms secondary to GERD in those with positive pH monitoring.
End-Stage Lung Diseases Before and After Lung
Transplantation
Since the fi rst lung transplantation performed by Dr. James Hardy in 1963, over
32,000 transplants have since been performed [ 39 ]. From 1995 to 2009, over one
third of the transplantations were for chronic obstructive pulmonary disease
(COPD). Idiopathic pulmonary fi brosis (IPF) is the second leading cause of
Y.M. Wong and P.M. Fisichella
119
transplant with 22 %, cystic fi brosis (CF) accounts for 16 %, and α
1
-antitrypsin
defi ciency (AATD) emphysema composes 7 % of the procedures. Other indications
include idiopathic pulmonary arterial hypertension, sarcoidosis, bronchiectasis,
congenital heart disease, connective tissue disease, cancer, and obliterative bronchi-
olitis [ 39 ].
Emerging studies over the past decade have shed light on the association between
some of these end-stage lung diseases, most notably IPF, and GERD. An early
study by Mokhlesi et al. evaluated the prevalence of GERD in patients with COPD
based on symptoms alone and found that a higher percentage of patients with mild
to severe COPD have one or more refl ux symptoms compared to those without
COPD or asthma [ 40 ]. A more recent study utilized esophageal pH monitoring to
confi rm refl ux events in patients with advanced COPD. The results of this study
showed an overall prevalence of GERD of 57 % compared to that of 10–20 % in the
general population and that only one third of these patients complained of symp-
toms of GERD [ 41 ]. The reasons for this increased prevalence are not entirely
understood. However, some suggest that hyperinfl ation, chronic cough, and bron-
chospasm may increase the intra-abdominal pressure and reduce the tone of the
LES by altering its relationship with the diaphragm. Some medications for the
symptomatic treatment of COPD, such as beta-agonists, anticholinergics, and the-
ophylline, have also been postulated to increase GERD by reducing the LES pres-
sure, but studies evaluating the association between GERD and these medications
have not been conclusive [ 42 , 43 ].
Similarly, there is an increased prevalence of GERD in patients with IPF with
Raghu et al. reporting it as high as 87 % [ 44 ]. A study by Sweet et al. also confi rmed
these fi ndings and showed a 67 % prevalence of GERD in IPF patients [ 45 ]. IPF
carries a high mortality rate with median survival between 3 and 5 years from diag-
nosis [ 46 ]. The traditional understanding of the pathogenesis of IPF has been
chronic interstitial infl ammation leading to fi brosis. Until recently, focus on the
treatment of IPF has been on immune modulators and anti-infl ammatory agents to
halt the progression of disease; however, results have not been very promising, and
mortality rate has not improved over the years, which has prompted a change in
direction in identifying the pathophysiologic mechanisms of this disease. With
increasing evidence of a strong association between GERD and IPF, many now
hypothesize that chronic microaspiration may be the etiological factor in the devel-
opment of pulmonary fi brosis [ 47 ]. Although the causal relationship remains
unclear, examination of surgical lung biopsies of some patients with chronic hyper-
sensitivity pneumonitis caused by aspiration also has shown the usual interstitial
pneumonia pattern typical of IPF [ 48 ]. In addition, esophageal dysmotility has been
proposed as a contributing factor to microaspiration leading to lung fi brosis. Patti
et al. evaluated patients with end-stage IPF awaiting lung transplantation for GERD
with esophageal manometry and pH monitoring. The authors found that refl ux epi-
sodes were associated with a hypotensive LES and abnormal esophageal peristalsis
in those with positive pH monitoring [ 49 ]. An additional fi nding that supports the
microaspiration hypothesis is the positive effect of anti-refl ux surgery on exercise
capacity and oxygen requirement in IPF patients awaiting lung transplantation [
50 ].
9 Minimally Invasive Treatment of GERD: Special Situations
120
The use of anti-refl ux medications has also been found to be an independent predic-
tor of longer survival time and lowers the radiologic fi brosis score in patients with
IPF [ 51 ]. New insight into the pathogenesis of idiopathic pulmonary fi brosis has
thus led to the focus of targeting the underlying cause of the aspiration with the hope
of improving mortality and quality of life.
In contrast to IPF, the pathogenesis of cystic fi brosis has been well established.
Like other indications for lung transplantation, there is also a higher prevalence of
GERD in the CF population. Mendez et al. from Loyola reported the prevalence of
refl ux disease in CF patients after transplantation to be as high as 90 % compared to
lung transplant patients with other pulmonary disorders. Interestingly, these patients
are also more prone to proximal refl ux, which has a profound implication for the
treatment of GERD in this population to prevent chronic allograft rejection [ 52 ]. In
addition, patients with CF are six to eight times more likely than controls to experi-
ence GERD symptoms [ 53 ]. A recent study by Blondeau et al. utilized impedance
pH monitoring to evaluate the prevalence of refl ux in 24 children with CF and found
67 % of them have increased esophageal acid exposure. One third of the patients
also tested positive for bile acid in their saliva, which may increase their risk for
aspiration [ 54 ]. However, the mechanism of association between GERD and CF is
still under debate and several theories have been proposed. Some contributing fac-
tors include increased frequency of transient LES relaxations, prolonged gastric
emptying, reduced pulmonary function from chronic obstruction of the airways,
chronic cough and wheezing with increased intra-abdominal pressure, high-fat diet,
and alpha-adrenergic medications [ 53 , 55 ]. Microaspiration from refl ux may also
contribute to poor control of CF and progression to end-stage lung disease necessi-
tating lung transplantation. Therefore, the treatment of GERD is again crucial in the
overall management of patients with end-stage CF.
Bronchiolitis Obliterans Syndrome
Chronic allograft rejection, also known as bronchiolitis obliterans syndrome (BOS),
contributes to the lower survival rate of lung transplant patients compared to recipi-
ents of other solid organs. It usually develops 6 months to 2 years after transplant
and affects 50–60 % of patients 5 years after transplantation. BOS is also respon-
sible for about 30 % of deaths after 3 years of transplantation [ 56 – 58 ]. The disease
is defi ned as a decreased of forced expiratory volume in 1 s (FEV
1
) from the best
postoperative value without any other cause, such as infection or anastomotic stric-
tures. Pathologically, BOS is characterized by progressive fi brosis of small airways,
sclerosis, intimal thickening, and damage to pulmonary vasculature [ 57 , 58 ]. Since
GERD is highly associated with other pulmonary disorders, chronic aspiration sec-
ondary to refl ux has also been suggested as a contributing factor to the development
of BOS after transplant, and the prevalence of GERD in posttransplant patients is
as high as 75 % [
57 ]. A study from Duke found an increased incidence of GERD
after transplant compared to before, as well as an increased acid exposure time from
Y.M. Wong and P.M. Fisichella