Download Pulmonary manifestations of gastro-oesophageal

AD_HTT_027_034___OCT29_04
22/10/04
2:24 PM
Page 27
How to Treat
pull-out section
read online @ www.australiandoctor.com.au
You can now earn CPD points with How to Treat by completing quizzes online (www.australiandoctor.com.au/cpd) or in every issue.
See page 34 for details and this week’s quiz.
INSIDE
Cough
Asthma
Interstitial lung
disease and
bronchiectasis
Obstructive sleep
apnoea
Lung
transplantation
Diagnosis of
pulmonary GORD
symptoms
Managing
pulmonary GORD
symptoms
The authors
Pulmonary manifestations
of gastro-oesophageal
Dr David Joffe, senior staff
physician, department of
respiratory and sleep
medicine, Royal North Shore
Hospital, Sydney, NSW.
reflux disease
Dr Garrett Smith, department
of surgery, Royal North Shore
Hospital, Sydney, NSW.
Background
GASTRO-oesophageal reflux disease (GORD) is a
common disorder. Studies from the US have estimated 20% of the population have at least weekly
GORD symptoms and more than 50% have experienced GORD symptoms at some time. Among adults
the prevalence of symptoms appears fairly constant
between 25 and 70 years and there is little gender
difference.
GORD thus represents one of the most common,
chronic medical conditions presenting to GPs, with
the most classic symptoms being heartburn and
regurgitation. With the ready availability of protonpump inhibitors and appropriate attention to lifestyle
factors, these symptoms are generally well managed
in general practice and do not require investigation
or specialist referral.
Evidence is emerging of the poor correlation
between endoscopic evidence of oesophagitis and
GORD severity, measured either by symptoms or
complications. This has led to the concept of nonerosive reflux disease, which may account for 50%
of all GORD patients.
There is also increasing reporting in the literature
of atypical and extra-oesophageal presentations of
GORD, ranging from dental to laryngeal and respiratory symptoms. The relationship of these symptoms with GORD may be difficult to assess, and
standard GORD therapies may not be as effective as
in the more traditional reflux patient.
This article seeks to highlight some of the putative
respiratory manifestations of GORD. The main conditions believed to be either a direct end product of
GORD or to have pulmonary disease manifestations
exacerbated by GORD include cough, asthma, interstitial lung disease, bronchiectasis, obstructive sleep
apnoea and lung transplantation.
www.australiandoctor.com.au
Dr Daniel Stiel, department of
gastroenterology, Royal North
Shore Hospital, Sydney, NSW.
29 October 2004 | Australian Doctor |
27
AD_HTT_027_034___OCT29_04
22/10/04
2:24 PM
Page 29
Cough
THE earliest reports of an association between reflux and cough
were published by Ing, et al in the early 1990s.1,2
Twenty-four-hour ambulatory pH monitoring was performed
in 13 patients with chronic persistent cough (defined as lasting
more than two months) in whom all other diagnostic tests were
negative. To assess the level of symptoms, cough diaries were
kept for eight weeks.
There was a significant difference in the number of reflux
episodes and the length of the episodes between the study group
and matched controls. Also, the amount of time when the pH
was less than four was considerably longer in the patient group.
Furthermore, gastro-oesophageal reflux occurred simultaneously with 78% of cough episodes, while cough occurred with
13% of reflux episodes, confirming an association between
asymptomatic reflux and chronic persistent cough.
Subsequent work by the same authors demonstrated impaired
acid clearance in a group of patients with persistent cough compared with a group of matched controls. These findings not
only supported the hypothesised relationship but also determined a likely pathological mechanism.
To further explore the possible aetiological mechanisms, Ing,
et al performed a double-blind placebo-controlled study in a
small group of patients and matched controls, in which either
saline or acid was instilled via a catheter to the lower
oesophageal sphincter.3
Although the cough frequency and amplitude were greater in
the patient group, the duration of the cough was not significantly
different.
The authors concluded that cough could be induced in normal
subjects with acid instillation, although the characteristics of
the cough in the symptomatic patient group were different.
Instillation of lignocaine to the lower oesophageal sphincter
impaired the cough reflex, suggesting local factors at the level of
the lower oesophageal sphincter were part of the mechanism of
cough genesis.
More recent work by Benini, et al4 demonstrated that patients
with reflux oesophagitis have a decreased cough threshold,
which appears to relate to both laryngeal inflammation and
acid flooding of the oesophagus.
A great deal of further research has added evidence to the original hypotheses of Ing and colleagues, to support the relationship
between cough and reflux.
A 2001 study by Theodoropoulos, et al5 used an inverse paradigm of investigation. Seventy-four subjects referred specifically to a gastroenterology service for investigation of symptomatic reflux were concomitantly administered a questionnaire
about upper respiratory symptoms.
After a 24-hour probe study it was found that 75% of
stressed some key points:
Reflux may be asymptomatic in patients with
chronic cough.
■ When aspiration predominates, gastroenterological
symptoms are prominent.
■ Extra-thoracic reflux may
lead to dysphonia, hoarseness, sore throat and gum
disease.
■ Treatment should only be
considered as failing if
double the standard doses of
a PPI have been used for at
least eight weeks.
Several recent publications
have demonstrated a diminution of cough with therapy for
gastroenterological symptoms,
whether medical or surgical.
In eight patients with
GORD-related but medically
resistant chronic cough, Irwin,
et al described a significant
decrease in the measures of
cough, after anti-reflux
surgery.7
The authors emphasised
that, while there is a clinical
profile that can predict
GORD as a cause of cough
(eg, cough related to meals,
speech or at night), GORD
cannot be excluded on clinical grounds alone. It is important to remember that if a
patient has a cough but no
reflux symptoms, it does not
mean the cough is unrelated
to reflux.
Papers published by Lindstrom, et al8 and Allen, et al9
have also demonstrated a
similar response of extraoesophageal manifestations
of GORD after fundoplication.
■
Reflux may be
asymptomatic in
patients with
chronic cough.
patients with proven upper
oesophageal reflux, and 68%
of patients with demonstrated
lower oesophageal reflux,
complained of laryngeal
symptoms for at least five
days each month. In comparison, only 36% of those with
normal pH studies and 9%
of normal volunteers reported
similar symptom scores.
This study suggested a
relationship between ‘symptomatic’ reflux and the likelihood of respiratory symptoms, and that those with a
primarily gastroenterological
presentation may have
unrecognised respiratory
complications. This is in contrast to Ing’s group, who had
a respiratory presentation
with a demonstrable gastroenterological disorder.
Evidence for abnormal
oesophageal motility in the
genesis of cough has been proposed more recently. Kastelik,
et al6 demonstrated manometric abnormalities in 32% of a
group of 43 patients complaining of chronic cough,
abnormal 24-hour pH monitoring in 15%, and combined
abnormalities in 53%. Only
one patient in the control
group had manometric abnormalities.
This later work provides
some substance to the argument that acid is not the sole
cause of cough but that dysmotility and so-called
‘volume-reflux’ (see Intraluminal oesophageal impedance
testing, page 31) may also be
crucial in the genesis of cough
and pulmonary manifestations
of reflux.
Several review articles have
further delineated the coughreflux hypothesis and have
Asthma
SEVERAL recent papers have taken
up the cudgel of reflux and its possible role in pre-existing pulmonary
disease, particularly asthma. We
know that gastro-oesophageal reflux
may trigger asthma. Data suggest
about 77% of people with asthma
experience reflux symptoms,
although GORD may be clinically
silent in some.
Oesophagitis is found in 43% of
patients with asthma, and 82% have
abnormal oesophageal acid contact
10
times on oesophageal pH testing.
In the first of many articles on this
subject, Harding, et al demonstrated
that the presence of “regurgitation
or excessive proximal oesophageal
reflux, predicted asthma response
with 100% sensitivity, 100% negative predictive value, specificity of
44% and a positive predictive value
of 79%” in a group of 30 non-smok11
ers with asthma.
The authors concluded that suppressive therapy with omeprazole
improved asthma symptoms and/or
peak flows by more than 20% and
improved pulmonary function in
73% of subjects with asthma and
GORD.
The study demonstrated persistent
effects beyond three months of acidsuppressive therapy. Notably, almost
30% of subjects with asthma
GORD is a
prominent feature of
patients with asthma
despite the absence of
symptoms.
required more than 20mg/day of
omeprazole to adequately suppress
acid.
A subsequent prevalence paper by
Harding demonstrated abnormal
24-hour pH testing in 62% of subjects with asthma, none of who had
reflux symptoms. Indeed, those with
higher amounts of proximal
oesophageal acid exposure had fewer
symptoms of GORD than those with
12
predominantly distal disease.
Thus the authors rightly assert that
GORD is a prominent feature of
patients with asthma despite the
absence of symptoms. This has clear
and practical implications for the
management of asthma, particularly
in difficult-to control and severe disease.
One of the prominent and wellrecognised features of severe asthma
www.australiandoctor.com.au
is nocturnal symptoms. In a review
article, Harding described evidence
from one study in a paediatric population showing that oesophageal
acid infusions caused more airway
responses at 4am than at midnight.
In addition, children with asthma
and nocturnal asthma symptoms
had higher reflux scores, with a positive correlation between reflux score
and night-time-associated wheez13
ing.
Although the evidence for a similar
response in adults has been less convincing, more recent work by Liou,
et al, using an analysis of patients in
a specialised asthma clinic, determined that symptomatic GORD and
chronic sinusitis are comorbid conditions associated with more severe
14
asthma. The work of Kiljander, et
al in two separate studies has demonstrated a reduction in cough and subsequently in nocturnal asthma symp15,16
toms when GORD is treated.
Both studies were performed in a
randomised, double-blind, placebo
crossover fashion, conferring a strong
correlation between treatment and
response while simultaneously defining a strong supportive evidence base
(level 1) for the role of GORD in
asthma. The authors again emphasise the “often silent” nature of
GORD in people with asthma.
29 October 2004 | Australian Doctor |
29
AD_HTT_027_034___OCT29_04
22/10/04
2:24 PM
Page 30
how to treat - pulmonary manifestations of gastro-oesophageal reflux disease
Interstitial lung disease and bronchiectasis
PERHAPS the most intriguing and recent advances of GORD
and lung disease have been the postulate that GORD may play
an aetiological role in the development of interstitial pulmonary
fibrosis and other parenchymal lung disease such as bronchiectasis.
Tobin, et al17 demonstrated that 16 of 17 patients with biopsyproven interstitial pulmonary fibrosis had distal and/or proximal
abnormalities on pH testing. In comparison, only four of eight
controls with other types of interstitial lung disease were found to
have abnormal pH readings.
Also, only 25% of the fibrosis patients with increased acidity
actually had symptoms typical of GORD and in this group the
acidity was predominantly nocturnal and occurred in the more
proximal oesophagus.
The authors speculated that GORD may well have a role in
the pathogenesis of interstitial pulmonary fibrosis.
Further to this hypothesis, Hope-Gill, et al showed that, in
comparison with a control group, patients with pulmonary
fibrosis had an increased cough sensitivity to capsaicin, which
was sensitive to corticosteroids.18 They hypothesised that there
was something intrinsic to the mechanism of disease in interstitial
pulmonary fibrosis that promotes the cough reflex.
In a study looking at diffusing capacity in patients with
GORD, Schachter, et al demonstrated that in patients with
severe GORD there was an appreciable fall in diffusing lung
capacity for carbon monoxide compared with patients with
mild GORD.19
This elegant study was the first to demonstrate a correlation
between a physiological variable known to be associated with
interstitial pulmonary fibrosis (and, indeed, with its prognosis)
and the measured severity of reflux.
These tantalising data hint at the possible relationship between
the development of interstitial lung disease and gastrooesophageal reflux, considering all other variables were
accounted for in the multiple regression analysis.
In response to these findings Raghu wrote: “Compelling clinical data suggest that a high percentage of patients with idiopathic pulmonary fibrosis also experience abnormal oesophageal
acid exposure, without necessarily experiencing the typical symptoms of gastro-oesophageal reflux disease (GORD). Aggressive,
long-term therapeutic trials of patients with GORD and evaluation of the therapeutic effects on pulmonary disease will allow
determination of the real influences of abnormal esophageal
acid exposure in the development of idiopathic pulmonary fibrosis.”20
Reports of the association between GORD and bronchiectasis
were described as early as 1978 when, in a case series of 1000
consecutive patients with reflux, 279 aspirated either by coughing and choking during swallowing, or as a result of night
reflux. Of these, 159 had associated respiratory symptoms,
GORD may well
have a role in the
pathogenesis of
interstitial
pulmonary
fibrosis.
which included cough, voice
change, recurrent respiratory
infection, bronchiectasis and
asthma.21
In a retrospective study of
more than 100,000 patients
with erosive eosophagitis and
stricture, pulmonary fibrosis
(odds ratio 1.36), bronchiectasis (OR 1.26), and pulmonary collapse (OR 1.31),
occurred more often in the
patient group, suggesting
patients with severe reflux
may harbour a large variety
of sino-pulmonary diseases.22
This work was confirmed
in a large population study of
nearly 70,000 participants.23
The relationship between hospitalisation for hiatus hernia,
and reflux oesophagitis, and
a subsequent hospitalisation
for a respiratory condition
was measured in persons free
of respiratory disease at baseline and at their first hospitalisation.
The relative risk of developing bronchiectasis in this
group was found to be 6.2.
The risk of pneumonia (RR
1.3), and asthma (RR 2.1),
while more traditionally associated with reflux, were not
as great as for bronchiectasis.
While the causal link
appears to be evident from
analysis of these papers,
Tsang, et al published a fascinating study in 1998 supporting a causal link between
reflux and bronchiectasis.24
In 100 consecutive patients
with bronchiectasis, of who
87 had active tuberculosis,
76% were found to be
seropositive for Helicobacter
pylori. However, only 54.3%
of controls and 52.9% of
matched patients with tuberculosis but no bronchiectasis
were H pylori seropositive.
There were significant associations between H pylori
serology and sputum volume
and age in the patients with
bronchiectasis, but not with
lung function indices or causes
of bronchiectasis. The H
pylori seroprevalence in
bronchiectasis was significantly higher in patients who
were excessively productive of
sputum (>5mL sputum/24
hours).
This was the first report of
a high H pylori seroprevalence
in bronchiectasis and suggests
there may be a common link
between these conditions and
that H pylori may have a
pathogenic role in the development of bronchiectasis once
deposited in the mucosa of the
airway.
While a thorough investigation of all possible causes in
cases of bronchiectasis has
been encouraged, assessment
of possible gastro-oesophageal
reflux, whether acid or
volume, often remains overlooked in clinical practice,
especially given the implications for treatment and prognosis.
Clearly reflux may cause
cough, a frequent symptom of
bronchiectasis. It may also
play a role in recurrent pneumonia — another frequent
consequence of abnormal
airway structure and function.
Indeed, the literature would
seem to support the hypothesis that reflux plays a role in
the genesis of bronchiectasis
and in the level of cough,
sputum and recurrent infection.
Thus, the finding of
bronchiectasis should alert the
physician to consider the
investigation and management
of reflux.
Obstructive sleep apnoea
THE earliest indications of a possible
interaction between obstructive sleep
apnoea (OSA) and reflux were predominantly case studies in which
small groups of patients with GORD
or aperistaltic disorders of
oesophageal motility were noted to
improve when treated with continuous positive airways pressure,
whether or not they had concomitant OSA.
The explanation appeared to be
that OSA predisposed to nocturnal
gastro-oesophageal reflux by lowering intrathoracic pressure and that
this added to the severity of sleep
fragmentation by increasing arousability and movements in sleep.
Whether the reflux contributed to
the OSA or vice versa remained
unclear.
In a study to help clarify the interaction between the two conditions,
25
Ing, et al studied the effect of antireflux therapy (nizatidine [Tazac])
on OSA parameters.
Patients with OSA were found to
have significantly more gastrooesophageal events than controls,
and the percentage of time spent at
pH <4.0 was also greater in the OSA
group.
Furthermore, in patients with
proven OSA, just over half of all
30
| Australian Doctor | 29 October 2004
Patients with
obstructive sleep
apnoea were
found to have
significantly more
gastro-oesophageal
events than controls.
gastro-oesophageal reflux episodes
were temporally related to apnoeas
or hypopnoeas. Less than half
(46.8%) of all apnoeas were temporally related to acid reflux, and only
43.8% of arousals were related to
reflux events.
Treatment reduced the frequency
of arousals but had no impact on the
apnoea-hypopnoea index. The
researchers concluded that patients
with OSA appeared to have a higher
prevalence of reflux than matched
controls, and that CPAP appeared to
ameliorate gastro-oesophageal reflux
parameters in a “non-specific” way.
They were unable to conclude a
causal link between GORD and the
development of OSA.
In the first prevalence study,
26
Valipour, et al studied patients
referred for overnight sleep studies
who were investigated for a breathing sleep disorder, occurrence of
symptomatic gastro-oesophageal
reflux, potential risk factors for both
conditions, and comorbidity.
Overall, nearly three-quarters of
the respondents reported refluxrelated symptoms, with heartburn
and/or acid regurgitation the leading
symptoms. No difference was
observed in the occurrence of symptomatic reflux between subjects who
www.australiandoctor.com.au
snored and those with OSA, and the
occurrence of reflux symptoms was
not influenced by the severity of
OSA.
The authors concluded the incidence of both conditions was high in
this patient group but there was no
discernable difference between snorers
and those with demonstrable OSA.
While this seems to suggest that
the two disorders are merely associated by way of common factors such
as body habitus and posture, it does
not exclude a separate association,
because even those with snoring only
may generate significant negative
intrathoracic pressures.
Despite the patient group being
derived from those presenting with
suspected sleep-disordered breathing (selection bias) it did confirm
the findings of Ing in concluding the
lack of evidence for reflux as an
aetiological factor in the genesis of
OSA.
Having determined that reflux was
not causally related to OSA, but that
OSA was likely to contribute to
reflux, investigators returned to the
possible effect of treating OSA on
reflux-associated outcomes.
27
Green, et al graded patients diagnosed with OSA on their frequency
of nocturnal reflux symptoms, with
all patients then prescribed CPAP for
their OSA and follow-up obtained
in almost 90%. Those who continued to use CPAP had a statistically
greater improvement in reflux symptoms than those who had abandoned
therapy.
An unexpected finding was the
strong correlation between CPAP
pressure and improvement in nocturnal reflux symptom scores. Contrary to the commonly held belief
that higher pressures would be more
problematic, patients with higher
CPAP pressures demonstrated a
greater improvement in their nocturnal reflux scores. Indeed, CPAP
improved nocturnal reflux by 48%
overall and higher pressures were
more beneficial.
This important paper puts pay to
the long-held argument that higher
pressures cause increased aerophagia
and discomfort; indeed, the response
to symptoms of GORD should lead
to consideration of a CPAP pressure
increase.
It also confirms the role of OSA
in the genesis of reflux and suggests
that a thorough history of snoring
and witnessed apnoeas should be
sought in all patients presenting for
investigation of dyspepsia and other
symptoms of GORD.
AD_HTT_027_034___OCT29_04
22/10/04
2:25 PM
Page 31
Lung transplantation
THE earliest observations of an
association between lung transplantation and GORD were small,
largely descriptive studies suggesting an increase in chronic cough,
slower-than-normal gastric emptying and/or oesophageal dysmotility in heart-lung recipients
with documented bronchiolitis
obliterans, long described as the
predominant feature of chronic
rejection.
The possibility of vagally mediated disorders of gastric emptying
was suggested because vagotomy
is an inevitable consequence of
transplant and was long purported
to be a surgical approach to hyperacidity before the age of inhibitors
and H pylori.
Given the increased risk of recurrent pulmonary sepsis and accelerated rejection in lung transplanta28
tion, Au, et al undertook a study
using oesophageal manometry,
24-hour pH monitoring, and
radioisotopic gastric emptying in
10 patients who had undergone
heart-lung transplantation.
They found three patients had
grossly delayed liquid and solid
emptying that was compatible with
complete vagotomy. Six other
Vagal injury during lung transplantation did not increase the risk of reflux.
patients had delayed liquid but
normal solid emptying, which is
the opposite of what would be
expected with vagal injury and
could not be explained by the
authors.
One patient demonstrated fasterthan-normal gastric emptying for
both solids and liquids, and two of
the remaining nine patients had
esophageal dysmotility but no
demonstrated gastro-oesophageal
reflux.
The authors of this small study
concluded that, while vagal injury
commonly occurred, the gastric
sequelae were not always predictable and did not appear to
increase the risk of reflux.
A more recent paper by Davis,
29
et al differed in its view of the
role of GORD and its implications
for transplantation. In this study
of 400 lung transplant patients,
128 underwent ambulatory
oesophageal pH monitoring. Of
these, 93 (almost 75%) had abnormal results consistent with GORD,
and 43 (about 33%) went on to
surgical fundoplication.
After fundoplication, 16
patients had improved bronchiolitis obliterans syndrome scores, 13
of these no longer meeting the criteria for the syndrome. In patients
at least six months post lung
transplantation and six months
after fundoplication, the FEV 1
improved by an average of 24%.
Overall survival was significantly
better in patients who had either
normal pH studies or fundoplication.
On balance it is difficult to
understate the importance of
GORD in the rate of progression of
bronchiolitis and indeed the likely
longer-term success of transplanted
lungs.
The authors stressed the need to
look for reflux early and to treat it
while the bronchiolitis obliterans
is in its early histological forms and
may possibly be reversed with
aggressive medical therapy or fun-
doplication. While the exact mechanism and the possible role of
vagotomy in the genesis of GORD
remain unclear, there is little doubt
about its consequences.
Alternative theories on the cause
of bronchiolitis obliterans, including the side effects of anti-rejection
drugs such as prednisone and
cyclosporine, and the mechanical
effects of surgery on the function of
the lower eosophageal sphincter,
may all be relevant and the aetiology is most likely to be multifactorial.
It is clear from the literature
that reflux and respiratory sequelae are strongly superimposed and
that unexplained respiratory
symptoms and/or disease should
always raise the possibility of
reflux in the mind of the attending
physician.
Furthermore, the inverse paradigm
is pertinent to those with symptoms
of reflux: a thorough history of
symptoms of cough, OSA, recurrent
chest infection or progressive pulmonary disease should be sought in
all patients with symptoms of reflux,
as it may well improve outcome and
dictate the need for surgical fundoplication.
Diagnosis of pulmonary GORD symptoms
SEVERAL investigations can be used in assessing patients
with suspected extra-oesophageal manifestations of GORD.
The exclusion of aetiology other than GORD in patients
with ENT or pulmonary symptoms often requires specialist
consultation and investigation.
Therapeutic trial of proton-pump inhibition
Provided there are no ‘alarm symptoms’ (dysphagia,
odynophagia, haematemesis, nocturnal choking attacks,
weight loss), a trial of antisecretory therapy may be carried
out before any investigation.
Investigation is indicated when any of these symptoms
are present, if the diagnosis is unclear, if symptoms persist or
are refractory to treatment, or if complications are suspected.
The trial of medication usually involves 2-8 weeks of
high-dose proton-pump inhibition. A good symptomatic
response, especially if followed by relapse on withdrawal of
treatment, is almost diagnostic of GORD.
Contrast radiology studies
Contrast barium radiological studies have a limited role in
assessing patients with GORD because the usual physiological disturbances seen in GORD (exaggerated transient lower
oesophageal sphincter relaxations) do not occur during swallowing.
Although free reflux may be observed during a barium
swallow in severe GORD cases, normal barium studies do
not exclude GORD. Associated hiatus hernia may be demonstrated radiologically, but this is not a prerequisite for
GORD.
Endoscopy is more appropriate for mucosal examination
of the oesophagus, and oesophageal physiological testing
provides a more accurate indicator of oesophageal function.
Endoscopy
The endoscopic demonstration of reflux oesophagitis
clinches the diagnosis of GORD.
However, as with many patients with heartburn who have
so-called non-erosive reflux disease, patients with pulmonary
manifestations of GORD often have a normal endoscopy,
that is, oesophagitis is usually absent, even if the patient
has not been using antisecretory medications.
As with radiology, the presence of a sliding hiatus hernia
may indicate that reflux disease is more likely, but this is not
diagnostic. Moreover, patients with long-term symptomatic
reflux are at greater risk than the general population of
developing Barrett’s oesophageal metaplasia, a condition
diagnosed only by endoscopy and biopsy.
Although acid
reflux has been
regarded as the
primary pathogenic
mechanism of most
GORD symptoms
... a small but
significant
proportion of the
reflux population
may have
pulmonary
symptoms.
Laryngoscopy
Direct laryngoscopy enables
direct visualisation of the
posterior larynx, where
supra-oesophageal signs due
to reflux may be seen. Early
changes indicating reflux
include reddening of the
posterior wall of the larynx,
which in more severe cases
may progress to fibrosis
with associated vocal cord
hyperaemia and nodules.
Oesophageal
physiological testing
Ambulatory oesophageal
pH monitoring
Ambulatory pH monitoring
www.australiandoctor.com.au
enables continuous measurement of acid exposure
in the distal oesophagus by
placement of an intraluminal probe via a soft
transnasal catheter. Additional sensors may be placed
more proximally to enable
measurement of acid in the
upper oesophagus and, by
inference, the larynx and
airways.
Ambulatory pH monitoring provides the current
gold standard for diagnosing GORD because, unlike
endoscopy, it does not
require the manifestation of
oesophagitis to provide a
diagnosis.
Moreover, its duration
over several hours permits
observation of the effects of
postprandial, interprandial
and nocturnal reflux
episodes.
It can also be used to correlate reflux events with
symptoms, which is particularly useful in patients who
complain predominantly of
cough or wheeze. It can also
be used as a reproducible
comparative and objective
measurement before and
after treatment (medical or
surgical).
Although acid reflux has
been regarded as the primary pathogenic mechanism
of most GORD symptoms
and complications, a small
but significant proportion of
the reflux population may
have pulmonary symptoms
due to so-called non-acid, or
‘volume’, reflux. These
patients are ideally investigated by intra-oesophageal
impedance testing.
Intraluminal oesophageal
impedance testing
Oesophageal impedance
testing uses a soft transnasal
catheter connected to an
ambulatory recording device
to measure the character,
quantity and direction of
bolus movement within the
oesophagus, independent of
pH. This enables the diagnosis of volume (ie, acid and
non-acid) reflux to be made.
Electrical current impedance between several small
electrodes along the catheter
is used to characterise intraoesophageal content at any
given time. In this way gas,
liquid and food bolus movement may be recorded.
Oesophageal impedance
testing may be combined
with pH and oesophageal
manometry testing, but is
not yet widely available in
Australia.
Oesophageal manometry
Oesophageal manometry
measures the muscular contractile activity of the
oesophagus, allowing assessment of both the lower
oesophageal sphincter and
the musculature of the
oesophageal body.
Primary oesophageal motility disorders such as achalasia
may need to be excluded by
manometry in patients with
airways-related symptoms, in
whom classical symptoms
such as dysphagia may not
be prominent.
A non-specific pattern of
ineffective oesophageal
motility may also be seen in
patients with pulmonary
manifestations of GORD.
29 October 2004 | Australian Doctor |
31
AD_HTT_027_034___OCT29_04
22/10/04
2:25 PM
Page 32
how to treat - pulmonary manifestations of gastro-oesophageal reflux disease
Managing pulmonary GORD symptoms
DETAILED discussion of the
conventional approaches to
GORD therapy is beyond the
scope of this article (see
Gastro-oesophageal Reflux
Disease in Adults: Guidelines
for Clinicians published by the
Digestive Health Foundation,
Gastroenterological Society of
Australia).30
The principles of therapy
for patients with pulmonary
symptoms due to GORD are
relief of symptoms and prevention of complications. The
important issue is to recognise
that the entity of pulmonary
GORD exists, even in the
absence of classic GORD
symptoms such as heartburn.
Lifestyle modification
As with standard GORD
management, the first
approach to treatment
involves lifestyle modification
when relevant, including
weight reduction, cessation of
smoking, moderation of alcohol and caffeine intake and,
possibly, elevation of the bedhead for nocturnal symptoms.
Medical management
This does not differ from the
standard therapy of GORD,
namely, potent acid suppression, usually with a PPI,
adopting a step-down
approach to find the lowest
effective maintenance dose.
PPIs available in Australia
include lansoprazole (Zoton),
esomeprazole (Nexium),
omeprazole (Acimax, Losec,
Probitor), pantoprazole
(Somac) and rabeprazole
(Pariet).
When volume symptoms
predominate (eg, regurgitation or pulmonary symp-
Authors’ case study
The fundus is wrapped around
the distal oesophagus.
Nissen fundoplication for control of gastroesophageal reflux.
toms), a prokinetic agent
such as domperidone may be
added, although this is a
short-acting drug and the
effectiveness of combined
therapy is uncertain. Nizatidine (Tazac), an H2-receptor
antagonist, has been reported
to have prokinetic effects.
Surgical management
Anti-reflux surgery by fundoplication re-establishes the
competence of the lower
oesophageal sphincter mechanism and prevents excessive
reflux of acid as well as nonacid material and digestive
enzymes into the proximal
oesophagus and respiratory
tract.
In this respect its aim is to
address the principal pathophysiology of GORD rather
than simply to control its consequences. It is an attractive
option for those with suspected volume or pulmonary
GORD symptoms.
Fundoplication, nowadays
almost exclusively performed
laparoscopically, is indicated
in patients with reflux whose
symptoms are not adequately
relieved by acid suppression
(as stated, this is especially
prevalent in those with nonacid volume-reflux symptoms
such as regurgitation or respiratory manifestations) or in
patients who have expressed
a preference for surgery rather
than lifelong medication.
About
70-80%
of
patients undergoing surgery
for GORD-related extraoesophageal symptoms
such as asthma will report
prolonged improvement.
Of these, those more likely
to be successfully treated by
fundoplication include those
with typical reflux symptoms
of heartburn and regurgitation
associated with their pulmonary symptoms, and those
who have previously reported
some degree of improvement
in symptoms while on antisecretory medication.
Unlike anti-secretory treatment of GORD, improvement
of pulmonary and other extraoesophageal symptoms may
not manifest for 6-12 months
after surgery.
Improved pulmonary
symptoms with
treatment of GORD
MRS RG, 52, presented in
June 2002 after repeated
hospital admissions for
infective exacerbations of
bronchiectasis, requiring IV
antibiotics and intensive
chest physiotherapy. There
was a background of four
years of severe steroiddependent asthma. She had
developed prednisoneinduced osteoporosis, with
fractures, requiring bisphosphonates.
She also gave a four-year
history of heartburn and
regurgitation, with endoscopy
in 1998 revealing grade B
reflux oesophagitis. Her
heartburn had responded well
initially to omeprazole 20mg
daily, but regurgitation persisted and was interfering
with attempts at postural
drainage. Subsequent therapy
with esomeprazole 40mg bd
and domperidone 10mg nocte
failed to control regurgitant
symptoms, steroid use or
infective episodes.
Following yet another
admission, this time with left
lower-lobe pneumonia, Mrs
RG underwent laparascopic
Nissen fundoplication in July
2002. Since then her requirement for steroids and antibiotics has reduced dramatically and she has had only
two hospitalisations for
chest infections, compared
with 10 in the preceding two
years.
References
1. Ing AJ, et al. Chronic persistent cough and gastro-oesophageal
reflux. Thorax 1991; 46(7):479-83.
2. Ing AJ, et al. Chronic persistent cough and clearance of
oesophageal acid. Chest 1992; 102(6):1668-71.
3. Ing AJ, et al. Pathogenesis of chronic persistent cough associated with gastroesophageal reflux. American Journal of Respiratory and Critical Care Medicine 1994; 149(1):160-67.
4. Benini L, et al. Cough threshold in reflux oesophagitis: influence of acid and of laryngeal and oesophageal damage. Gut 2000;
46(6):762-67.
5. Theodoropoulos DS, et al. Prevalence of upper respiratory
symptoms in patients with symptomatic gastroesophageal reflux
disease. American Journal of Respiratory and Critical Care Medicine 2001; 164(1):72-76.
6. Kastelik JA, et al. Abnormal oesophageal motility in patients
with chronic cough. Thorax 2003; 58(8):699-702.
7. Irwin RS, et al. Chronic cough due to gastroesophageal reflux
disease: failure to resolve despite total/near-total elimination of
esophageal acid. Chest 2002; 121(4):1132-40.
8. Lindstrom DR, et al. Nissen fundoplication surgery for extraesophageal manifestations of gastroesophageal reflux (EER).
Laryngoscope 2002; 112(10):1762-65.
9. Allen CJ, Anvari M. Gastro-oesophageal reflux related cough
and its response to laparoscopic fundoplication. Thorax 1998;
53(11):963-68.
10. Patterson PE, Harding SM. Gastroesophageal reflux disorders
and asthma. Current Opinion in Pulmonary Medicine 1999;
5(1):63-67.
11. Harding SM, et al. Asthma and gastroesophageal reflux: acid
suppressive therapy improves asthma outcome. American Journal
of Medicine 1996; 100(4):395-405.
12. Harding SM, et al. The prevalence of gastroesophageal reflux
in asthma patients without reflux symptoms. American Journal of
Respiratory and Critical Care Medicine 2000; 162(1):34-39.
32
| Australian Doctor | 29 October 2004
13. Harding SM. Nocturnal asthma: role of nocturnal gastroesophageal reflux. Chronobiology International 1999; 16(5):64162.
14. Liou A, et al. Causative and contributive factors to asthma
severity and patterns of medication use in patients seeking specialized asthma care. Chest 2003; 124(5):1781-88.
15. Kiljander TO, et al. Chronic cough and gastro-oesophageal
reflux: a double-blind placebo-controlled study with omeprazole.
European Respiratory Journal 2000; 16(4):633-38.
16. Kiljander TO, et al. Gastroesophageal reflux in asthmatics: a
double-blind, placebo-controlled crossover study with omeprazole. Chest 1999; 116(5):1257-64. [see comment — erratum
appears in Chest 2001; 120(2):691].
17. Tobin RW, et al. Increased prevalence of gastroesophageal
reflux in patients with idiopathic pulmonary fibrosis. American
Journal of Respiratory and Critical Care Medicine 1998;
158(6):1804-08.
18. Hope-Gill, BD, et al. A study of the cough reflex in idiopathic
pulmonary fibrosis. American Journal of Respiratory and Critical
Care Medicine 2003; 168(8):995-1002.
19. Schachter LM, et al. Severe gastroesophageal reflux is associated with reduced carbon monoxide diffusing capacity. Chest
2003; 123(6):1932-8.
20. Raghu G. The role of gastroesophageal reflux in idiopathic
pulmonary fibrosis. American Journal of Medicine 2003; 115
[Suppl. 3A]:60S-64S.
21. Henderson RD, Woolfe CR. Aspiration and gastroesophageal
reflux. Canadian Journal of Surgery 1978; 21(4):352-54.
22. el-Serag HB, Sonnenberg A. Comorbid occurrence of laryngeal or pulmonary disease with esophagitis in United States military veterans. Gastroenterology 1997; 113(3):755-60.
23. Ruhl CE, et al. Hospitalization with respiratory disease following hiatal hernia and reflux esophagitis in a prospective, population-based study. Annals of Epidemiology 2001; 11(7):477-83.
www.australiandoctor.com.au
24. Tsang KW, et al. High seroprevalence of Helicobacter pylori
in active bronchiectasis. American Journal of Respiratory and
Critical Care Medicine 1998; 158(4):1047-1051.
25. Ing AJ, et al. Obstructive sleep apnoea and gastroesophageal
reflux. American Journal of Medicine 2000; 108 [Suppl.
4a]:120S-125S.
26. Valipour A, et al. Symptomatic gastroesophageal reflux in
subjects with a breathing sleep disorder. Chest 2002;
121(6):1748-53.
27. Green BT, et al. Marked improvement in nocturnal gastroesophageal reflux in a large cohort of patients with obstructive
sleep apnea treated with continuous positive airway pressure.
Archives of Internal Medicine 2003; 163(1):41-45.
28. Au J, et al. Upper gastrointestinal dysmotility in heart-lung
transplant recipients. Annals of Thoracic Surgery 1993; 55(1):9497.
29. Davis RD Jr, et al. Improved lung allograft function after fundoplication in patients with gastroesophageal reflux disease
undergoing lung transplantation. Journal of Thoracic and Cardiovascular Surgery 2003; 125(3):533-42.
30. Digestive Health Foundation, Gastroenterological Society of
Australia: Gastro-oesophageal Reflux Disease in Adults: Guidelines for Clinicians. www.medeserv.com.au/gesa/members_guidelines/goreflux
Online resources
The Thoracic Society of Australia and New Zealand
(information about the society and its activities and links to
related scientific societies and groups): www.thoracic.org.au
Digestive Health Foundation, Gastroenterological Society of
Australia: Gastro-oesophageal Reflux Disease in Adults:
Guidelines for Clinicians. www.medeserv.com.au/gesa/
members_guidelines/goreflux
AD_HTT_027_034___OCT29_04
22/10/04
2:25 PM
Page 34
how to treat - pulmonary manifestations of gastro-oesophageal reflux disease
GP’s contribution
Case study
DR DIANNE CHAMBERS
Leichhardt, NSW
MRS MC, 62, had what was
always thought to be adultonset asthma. She had been
well controlled with inhaled
steroids and prn bronchodilators but recently
complained of worsening
cough with dyspnoea and
wheeze.
She was seen by a respiratory physician and a methacholine challenge test was
performed, which was negative. Her puffers were withdrawn but quickly re-instituted when she had
worsening of her wheeze
and cough.
Mrs MC’s other problems
include GORD, chronic rhinorrhoea and cholecystectomy. Previous investigation
included a gastroscopy,
which showed minor erosion
at the gastro-oesophageal
junction, with normal stomach and duodenum. A
urease test for H pylori was
positive both for her and her
husband.
A high-resolution CT of
the chest was negative for
bronchiectasis and other
chest pathology, while CT of
the sinuses showed significant pathology, with
mucoperiosteal thickening.
Mrs MC has had H pylori
eradication treatment on
two occasions and earlier
this year had sinus surgery.
However, her debilitating
cough persists. Current medications include Seretide
50/250 tds, Bricanyl tds,
Losec, Beconase and Zocor.
She is due to have a bladder repair and is very keen
to reduce her chronic cough.
there is no guarantee surgery
will cure her cough, even if it
resolves her GORD symptoms.
With these significant
caveats, laparoscopic fundoplication has a role in this
clinical setting.
Questions for the authors
Do you have additional
advice for management of
chronic cough?
Mrs MC should increase
her inhaled corticosteroid
dose perioperatively. Her
gynaecologist should arrange
nebulised sabutamol both
pre and postoperatively as
well as early postoperative
chest physiotherapy (with
incentive spirometry and/or
flutter valve) to reduce the
risk of atelectasis and worsening cough after the
surgery.
Could you comment on
H pylori eradication protocols
and their varying success
rates? Is it necessary to treat
other household members
concurrently? What should be
done about recurrent H pylori
infection? Should we document eradication by posttreatment assessment?
H pylori and its therapy
do not play major roles in
GORD or its respiratory
complications. However, if
the decision is made to treat
H pylori infection, an initial
one-week course of triple
therapy should be given,
comprising a PPI (double
standard dose), combined
with amoxicillin and clarithromycin.
A success rate of 80-90%
should be expected. Addition of bismuth subcitrate
may increase the eradication
rate slightly, but probably
not sufficiently to justify its
routine use.
Ideally, eradication should
be checked by urea breath
testing four weeks or more
after completion of triple
therapy (and at least one
week off PPIs). Routine testing and treatment of household members is controversial but not generally
necessary (unless, of course,
they have relevant symptoms).
Is reflux surgery likely to
help this woman?
A trial of double-dose PPI
therapy for two months
should first be given. Antireflux surgery should be
offered if there is no beneficial response to full medical
therapy and if the cough is
sufficiently disabling.
However, the patient
needs to be aware that it is
not certain her GORD,
cough and wheeze are
causally related, that her
symptoms do not reflect serious morbidity, and that
General questions
for the authors
Given the study results
implicating H pylori infection in bronchiectasis, do
you now consider that GPs
should routinely test all
patients with bronchiectasis
and, if so, which eradication
therapy would be recommended?
As there is only one study
showing an association (not
yet proven to be causal) it
is difficult to advise routine
H pylori testing in this
clinical situation. More data
are needed. However, a
diagnosis of GORD should
at least be considered if no
other causes of bronchiectasis are evident.
Fundoplication is now routinely done laparascopically.
What should patients be told
about this procedure? What
is the recovery time?
This is a keyhole version
of an operation that has
been in use for several
decades and which has stood
the test of time. Its great
advantage over the older
open operation is the shortened hospitalisation (generally 2-3 days) and recovery
time (about one week). In
experienced surgical hands,
the need to convert to open
operation is very infrequent.
More than 90% of
patients regard the operative
results as satisfactory and
are able to stop all antireflux medications. A small
number may notice inability
to belch, ‘gas bloat’ or mild
dysphagia. These adverse
effects need to be borne in
mind when considering the
indications for the operation
— that is, they may only be
acceptable when the initial
GORD symptoms or complications are severe and
refractory to maximal medical therapy.
Australian Doctor
How To Treat CPD
Instructions
Earn 2 CPD points by completing this quiz online or on the attached card. Mark your
answers on the card and drop in the post (no stamp required) or fax to (02) 9422 2844.
For immediate feedback click the ‘Earn CPD pts’ link at www.australiandoctor.com.au
Note that some questions have more than one correct answer. The mark required for CPD
points is 80%. Your CPD activity will be updated on your RACGP records every January,
April, July and October.
1. Which ONE condition is not thought to be
potentially caused or exacerbated by GORD?
a) Asthma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❏
b) Bronchiectasis . . . . . . . . . . . . . . . . . . . . . . . .❏
c) Hypersensitivity pneumonitis . . . . . . . . . . . . .❏
d) Interstitial lung disease . . . . . . . . . . . . . . . . . .❏
2. For more than two months Pam, 44, has
had a cough. She never smoked and has no
history of asthma, postnasal drip or
symptoms suggestive of GORD. Pam is
otherwise well. Examination is normal. Which
ONE of the following statements is correct
regarding initial management?
a) In the absence of symptoms of GORD,
no treatment for GORD should be
considered . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❏
b) A trial of high doses of proton-pump inhibitor
for 2-8 weeks may be diagnostic . . . . . . . . . . . .❏
c) Referral for endoscopy is required . . . . . . . . .❏
d) Regular bronchodilators should be
trialled . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❏
HOW TO TREAT
3. Which tests would assist with the diagnosis
of GORD (choose TWO)?
a) Barium swallow . . . . . . . . . . . . . . . . . . . . . . .❏
b) Ambulatory oesophageal pH
monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❏
c) Endoscopy . . . . . . . . . . . . . . . . . . . . . . . . . . .❏
d) CXR demonstrating a hiatus hernia . . . . . . . .❏
4. Pam has a good response to PPIs but
relapses when these are stopped. Which
statements concerning fundoplication are
correct (choose TWO)?
a) Fundoplication re-establishes the competence
of the lower oesophageal sphincter mechanism❏
b) After fundoplication the improvement of
pulmonary symptoms will be
immediate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❏
c) Fundoplication will only benefit symptoms
caused by increased acid reflux . . . . . . . . . . . .❏
d) Fundoplication can be offered as an option if
Pam prefers to avoid lifelong medication . . . . .❏
5. The diagnosis of volume reflux can be
made by which ONE investigation?
a) Oesophageal manometry . . . . . . . . . . . . . . . .❏
b) Direct laryngoscopy . . . . . . . . . . . . . . . . . . . .❏
c) Intraluminal oesophageal impedance
testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❏
d) Endoscopy . . . . . . . . . . . . . . . . . . . . . . . . . . .❏
6. Paul, 55, presents with dyspepsia and
daytime sleepiness. Questioning concerning
which symptom is least likely to be helpful
(choose ONE)?
a) Snoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❏
b) Weight loss . . . . . . . . . . . . . . . . . . . . . . . . . . .❏
c) Abdominal bloating . . . . . . . . . . . . . . . . . . . .❏
d) Dysphagia . . . . . . . . . . . . . . . . . . . . . . . . . . .❏
7. Investigations confirm oesophagitis (without
malignancy) and obstructive sleep apnoea.
Which ONE treatment option is least likely to
be beneficial in managing Paul’s dyspepsia?
a) Regular use of antacids . . . . . . . . . . . . . . . .❏
b) CPAP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❏
c) Regular use of PPIs . . . . . . . . . . . . . . . . . . . .❏
d) Lifestyle changes . . . . . . . . . . . . . . . . . . . . . .❏
8. Joan, 55, has some mild symptoms of
GORD, and extra-thoracic reflux is suspected.
Which symptoms may be relevant (choose
THREE)?
a) Gingivitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❏
b) Rhinorrhoea . . . . . . . . . . . . . . . . . . . . . . . . . .❏
c) Pharyngitis . . . . . . . . . . . . . . . . . . . . . . . . . . .❏
d) Dysphonia . . . . . . . . . . . . . . . . . . . . . . . . . . .❏
9. Norma has bronchiectasis. Current
literature appears to support the hypothesis
that GORD is associated with bronchiectasis.
Which ONE statement is incorrect?
a) In the investigation of bronchiectasis, reflux
should be considered . . . . . . . . . . . . . . . . . . . . .❏
b) Reflux possibly plays a role in recurrent
infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❏
c) Helicobacter pylori seroprevalence has not
been associated with bronchiectasis . . . . . . . . .❏
d) Reflux may play a role in the level of
cough . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❏
10. Norma has symptoms of GORD and starts
omeprazole 40mg/day with a plan to use the
step-down approach. Which statements about
the step-down approach are correct (choose
THREE)?
a) After six months an attempt should be made
to decrease Norma’s dose of omeprazole if there
has been symptomatic relief . . . . . . . . . . . . . . .❏
b) Lifestyle changes should complement the
step-down approach . . . . . . . . . . . . . . . . . . . . .❏
c) The step-down approach involves gaining
symptom relief quickly and then stepping down
the medication . . . . . . . . . . . . . . . . . . . . . . . . . .❏
d) The aim of step-down therapy is to maintain
the patient on the lowest possible dose that
provides effective relief . . . . . . . . . . . . . . . . . .❏
NEXT WEEK
Editor: Dr Lynn Buglar
The next How to Treat presents the benefits of rehabilitation in neurodegenerative and chronic neurological disorders The author, Dr Fary Khan, is lecturer
Co-ordinator: Julian McAllan
in rehabilitation medicine, department of medicine, University of Melbourne; neuro-rehabilitation physician at the Melbourne Extended Care Centre and Royal
Quiz compiled by Dr Marg Tait MBBS Melbourne Hospital, Melbourne Health; and head of the orthopaedic and musculoskeletal unit, Caulfield General Medical Centre, Bayside Health, Melbourne.
34
| Australian Doctor | 29 October 2004
www.australiandoctor.com.au