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Signature: Med Sci Monit, 2002; 8(3): RA64-71 WWW.MEDSCI MONIT.

COM
PMID: 11887043 Review Article

Received: 2001.06.11
Accepted: 2002.01.04 Asthma and gastroesophageal reflux in children
Published: 2002.03.11

Krystyna Wąsowska-Królikowska, Ewa Toporowska-Kowalska, Aneta Krogulska


Clinic of Pediatric Gastroenterology and Allergology, Institute of Pediatrics, Medical University of Łódź, Poland

Summary
Gastroesophageal reflux (GER) is a factor often neglected in the etiopathogenesis of asthma.
The estimated incidence of GER in asthmatic children reaches 50–60% and is higher than in
the general population. GER may accompany typical symptoms: hoarsness, sore throat, tho-
racic pain, cough or wheezing. GER may not only aggravate the course of bronchial obstruc-
tion, but may also cause it, or trigger obstruction due to other factors. Asthma and GER coin-
cidence has been acknowledged for many years. The paper presents a current review of stud-
ies concerning the relations between asthma and GER and attempts to establish, which is the
cause and which is the result. The hypotheses how GER can lead to bronchial obstruction,
and how obstruction can aggravate GER, are also presented. GER is believed to be a factor
causing obstruction by: 1. an indirect mechanism – reflex theory, 2. a direct mechanism –
reflux theory, and 3. a neuropeptide-mediated mechanism. The paper also presents diagnos-
tic methods allowing to detect GER in asthmatics. A review of recent studies concerning the
treatment of GER in asthmatics, both with pharmacological and surgical methods, is also
included. Beneficial effect of antireflux therapy on the course of asthma has been emphasized.
Therefore, antireflux therapy is recommended in all patients with concurrent asthma and
GER, irrespective of severity of clinical GER symptoms, even in those with silent GER. The
essential drugs used in the treatment of GER are proton pump inhibitors. Appropriately high
dose level and appropriately long duration of the therapy should be taken into consideration.

key words: asthma • gastroesophageal reflux • child

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Author’s address: Aneta Krogulska, Clinic of Pediatric Gastroenterology and Allergology, Institute of Pediatrics,
Medical University of Łódź, ul. Sporna 36/50, Łódź, Poland

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Med Sci Monit, 2002; 8(3): RA64-71 Wąsowska-Królikowska K et al – Asthma and gastroesophageal reflux in children

BACKGROUND 50–60% of children [2,3,6–9]. According to Tucci, reflux


is observed in 60–80% children with asthma, including
Gradual increase of the incidence of asthma, as well as 75% of asthmatic children with inappropriately con-
aggravation of the course of the disease, was observed trolled disease [10]. According to Andze, 75% children
during the last century. Intensive research aimed at elu- with asthma have GER [11]. It is estimated that 50% of
cidation of the reasons of this phenomenon are under children with chronic respiratory disorders [12] and
way. Asthma is known to be a multifactor disease char- 25–30% of adults have so-called silent GER [1,13]. In
acterized by bronchial hyperreactivity, mucosal constric- turn, 30–75% of these patients suffer from esophagitis.
tion, increased mucus production and development of Sontag reports that 40% of asthmatics have erosive
an inflammation as a result of released inflammatory esophagitis, 58% hiatus hernia, and over 80% pathologic
mediators. GER [9,14]. GER is regarded as the third most frequent
cause of chronic cough after asthma and sinobronchial
Gastroesophageal reflux (GER) is a factor often neglected syndrome. GER is diagnosed in 10–20% of patients
in the etiopathogenesis of asthma. GER may not only
aggravate the course of bronchial obstruction, but may also
seeking doctor's advice because of chronic cough. To
sum up, mean incidence of GER in asthmatic children
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cause it, or trigger obstruction due to other factors [1]. reaches ca. 56% and is similar to that observed in adults
[2]. If the incidence of GER concurrent with asthma is
On the other hand, sthma and its treatment may aggra- similar to general incidence of GER among children,
vate, and even induce GER. The relations between asth- the question can be asked what the size of morbidity is.
ma and GER have been extensively investigated. How- Two hypothetical answers are possible – all children
ever, it is still difficult to determine, which of them is the with asthma and GER carry on their disorders into
result, and which is the cause [2–4]. adult age (GER morbidity = 0), or some children with
asthma and GER ‘grow out’ of their diseases and GER
Asthma and GER coincidence has been acknowledged develops in some asthmatic adults, or conversely, some
for a long time. As early as the 12th century, Moses Mai- adults with GER develop asthma. It is possible that
monides wrote in his treatise that horizontal position some children apparently cured of asthma will become
was dangerous during dyspnea. Then, Nicholas Rosen adults with asthma and GER in future [2].
von Rosenstein was the first to use the term ‘stomachic
cough’ in the 18th century. In 1802, William Heberden According to the current views, diagnosis of gastroe-
wrote that ‘In many people respiration becomes more sophageal reflux disease (GERD) may be based both on
rapid and forced after meals’. In 1892, Sir William the basis of symptoms traditionally associated with the
Osler emphasized the necessity to avoid excessive eat- presence of gastroesophageal reflux and on so-called
ing, and Bray in 1934 – the tendency to develop ‘atypical’ ones. The typical symptoms include heart-
bronchial obstruction in subjects who had eaten a meal burn, eructation nausea and vomiting, acid taste in the
immediately after going to bed. In turn, Kennedy sug- pharynx, dysphagia. The atypical symptoms include
gested in 1962 the possibility of influence of silent reflux hoarseness, pharyngeal dryness sensation, excessive sali-
on respiratory disorders. Bronchial obstruction as a vation, pains in the neck, otalgia, sore throat, loss of
cause of GER was first observed by Barr in 1970 [2,5]. voice, sinusitis, choking, breathlessness. The possibility
of asymptomatic, so-called ‘silent’ reflux should be also
About 200 studies concerned with the concurrence of taken into consideration.
asthma and GER have been published to date. Howev-
er, only 18 of them can provide the basis for assessment Generally, two types of reflux has been distinguished:
of the frequency of this concurrence [2]. Most studies primary reflux due to disturbances of the so-called
were aimed at elucidation of the mechanism of asthma reflux barrier and secondary reflux, caused by the fac-
provocation by GER. The estimation of actual frequency tors associated both with gastrointestinal (inflammatory
of asthma and GER concurrence is difficult because, conditions, gastroparesis, impatency) and systemic
although there is a well-established definition of asthma, pathology (infections, metabolic disturbances, activation
the applied definitions of GER differ considerably, and, of the vomitus center in the CNS by various impulses –
what is more, the methods of its confirmetion in the visual, auditory and vagal stimuli, as well as those origi-
reviewed studies were different. According to many nating from the pharynx, gastrointestinal tract, urinary
publications, It was enough to observe characteristic tract or testes) [12].
clinical symptoms to diagnose GER, in others the diag-
nosis was based on abnormal pH values in pHmetry, A characteristic feature of reflux i8s aggravation of the
inflammation of esophageal mucosa, or presence of complaints after meals, alcohol consumption, in
esophageal hiatus hernia. Moreover, the studies were horisontal position, on exertion and at night (due to
carried out in selected groups of patients, so it was diffi- lower esophageal clearance than during the day).
cult to estimate the actual incidence of GER in the gen-
eral population of asthmatic patients. Cough, dyspnea, wheezing belong to the respiratory
symptoms associated with gastroesophageal reflux
GER occurs both in children and in adults with the (RARS – reflux-associated respiratory syndrome)
overall incidence of ca. 8%. In asthmatics, this incidence [1–3,5,15]. They may occur in asthma concurrent with
is higher than in the general population [4]. GER is esti- gastroesophageal reflux, or as pulmonary manifesta-
mated to occur in 60–80% of asthmatic adults and tions of gastroesophageal reflux disease.

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Review Article Med Sci Monit, 2002; 8(3): RA64-71

GER should be suspected in asthmatic patients in the GER has been extensively considered. GER is currently
following cases: regarded as a potential factor inducing bronchial
1. aggravating course of asthma or resistance to treat- smooth muscle contraction by the following mechanisms
ment [1–3,5,7,19–23]:
2. presence of typical or atypical GER symptoms
3. aggravation of asthma during sleep, after large meals, 1. indirect – a reflex mechanism induced by the effect
in horizontal position of acid gastric content getting to the esophagus on
4. onset of endogenous asthma in adult age vagal nerve terminals in the mucous membrane
5. aggravation of respratory symptoms after administra- (vago-vagal reflex). Reflex theory.
tion of bronchodilators
2. direct – epithelial damage due to aspiration of gastric
Does reflux cause asthma? Does asthma cause reflux? content getting to the esophagus ‘Reflux’ theory.
Do they aggravate the course of each other? Or do both
processes coincide but are not connected with each 3. changes in bronchial reactivity due to the effect of
other? We are trying to review the opinions on these neuropeptides.
issues below.
Ad. 1. The esophagus and the bronchial tree are known
REFLUX AS A CAUSAL FACTORS FOR ASTHMA ATTACKS to have common origin from the primary alimentary
tract and common innervation by the vagal nerve.
Under physiologic conditions, the respiratory tract does Bronchial contraction is believed to occur in response to
not come in direct contact with the gastrointestinal con- a vagal reflex initiated by the stimulation of receptors
tent owing to the efficient function of protective mecha- located in the esophagus by a decrease of pH and dilata-
nisms, including [5]: tion of its lumen. Lodi demonstrated some hyperreac-
1. swallowing reflex tivity of the vagal nerve in subjects with asthma and
2. reflexive closing of the larynx at the moment of sud- GER [6].
den esophageal dilatation
3. cough reflex Administration of acid into the esophagus in dogs
4. efficient function of the ‘antireflux barrier’ proved to induce an increase of bronchial resistance.
This response could be abolished by vagotomy [22].
In case of GER, the above mechanisms are impaired, Esophageal acid provocation (Bernstein test) in patients
which, consequently may induce bronchial obstruction. with asthma also causes a decrease of MEF 25 and MEF
50 values (MEF-maximal expiratory flow, MEF 25 and
Indirect evidence of the effect of reflux on asthma is MEF 50 stand for mean air flow velocity in the middle
provided by its remission after pharmacological or sur- phase of expiration). No reactions of this type were
gical cure of reflux [10]. Another piece of evidence for observed in healthy subjects and in patients with chron-
the association of asthma with GER is remission of ic bronchitis [1]. After acidification of the esophagus in
chronic wheezing as a result of pharmacological or sur- asthmatic, bronchial hyperreactivity after metacholin
gical treatment of GER in infants, observed by Eid [16]. was also noted. Metacholin-induced bronchial hyperre-
It cannot be, however, unequivocally assumed on the activity is more pronounced in patients with than in
basis of the cited studies that the respiratory symptoms those without GER symptoms. According to Wilson,
observed in the patients allowed the diagnosis of asth- intraesophageal administration of acid in children with
ma, although antireflux therapy led to improvement of atopic asthma did not cause PEF (peak expiratory flow)
the patients' complaints associated with the respiratory changes, but increased bronchial hyperreactivity to hist-
tract. amine and metacholin was observed [24]. Mansfield
suggests, that induction of vagal reflex by intrae-
Ineffective esophageal motility (IEM) belongs to the sophageal pH changes or increased pressure in its
most common GERD-related esophageal function dis- lumen may cause bronchospasm in patients with GER
turbances. This abnormality, manifested by chronic and asthma [22]. According to Schan, intraesophageal
cough, is reported in 41% of patients with GERD and administration of hydrochloric acid causes a decrease of
53% of patients with concurrent GER and asthma PEF and increased airway resistance in healthy subjects,
[5,15]. Coincidence of IEM and GER increases the risk asthmatics with and without GER and in isolated GER,
of respiratory disturbances because of prolonged which suggests the presence of vagal reflex [7].
esophageal clearance time observed in such motility
impairment [15]. Gustafsson, investigating esophageal Using 24h-pHmetry, Herbst demonstrated in infants
motility in 55 children with mild and severe forms of that GER was the cause of apnea, which was eliminated
asthma, observed in 60% of them disturbances involving by antireflux surgery and pharmacological treatment
decreased amplitude of peristaltic waves [17]. Another [25].
study reported abnormal peristaltic wave propagation
with so-called secondary peristalsis present in asthmatic The role of vagal reflex was confirmed by Harding, who
patients [18]. demonstrated that administration of atropine b oth to
healthy subjects and to asthmatics with GER prevented
The problem of the mechanisms leading to bronchitis, bronchospasm [26}.
pneumonia, pulmonary fibrosis or asthma as a result of

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Med Sci Monit, 2002; 8(3): RA64-71 Wąsowska-Królikowska K et al – Asthma and gastroesophageal reflux in children

Harding investigated PEF and pH using a two-channel of the bronchial tree than acidification of the distal
probe during intraesophageal administration of esophagus.
hydrochloric acid and did not observe the expected cor-
relation between the decrease of pH in the upper seg- Although numerous studies indicate the probability of
ment of the esophagus and the decrease of PEF, which both reflux and reflex theory, it is currently believed
may confirm the ‘reflex theory’ [26]. that the role of reflexive bronchospasm is more impor-
tant with respect to microaspiration [7,19,26].
The study by Gastal also seems to confirm the above
hypothesis [19]. On investigation of intraesophageal pH Ad. 3. A stimulus damaging esophageal mucosa acti-
with a two-channel probe, he observed, firstly, frequent vates the sensory fibers leading to the CNS, but may
occurrence of reflux in the distal portion of the esopha- also activate an antidromic efferent conduction path-
gus in patients with asthma (44%), chronic cough (50%) way. Such an impulse may induce the release of neu-
and thoracic pains (54%), and, secondly, significantly ropeptides from peripheral sensory nerve terminals.
more frequent frequent proximal reflux occurring in
patients with thoracic pains withough respiratory disor-
Numerous neuropeptides are distributed within the
autonomic nervous system at the same sites as classic
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ders (44%), than in those with asthma (24%) or chronic neurotransmitters [6]. Neuropeptides are produced also
cough (11%). outside the nervous system. They play different and
opposite roles in the respiratory tract – some of them
Davis reports that GER-induced bronchial obstruction cause contraction and other ones relaxation of the
requires a coincidence of various factors, such as [23]: bronchial muscles. They also regulate vascular tone and
1. presence of gastroespohageal reflux permeability, as well as the activity of immune cells. The
2. ‘acid-sensitive’ esophagus (positive Bernstein test) neuropeptide active withing the respiratory system is
3. low-threshold nocturnal sensitivity to bronchocon- substance P, which:
stricting stimuli. – decreases the tone and increases the permeability of
blood vessels.
According to Schan, bronchial obstruction due to esoph- – modulates the activity of immunocompetent cells,
agus acidification does not depend on esophagitis (inde- – increases bronchial smooth muscle tone,
pendently of Bernstein test) [7]. Therefore, esophago- – stimulates the release of mediators by mast cells, hista-
pulmonary reflex associated with the vagal nerve is min, leukotriens, and chemotactic factors.
believed to be present in everyone and may serve as a – enhances T lymphocyte proliferation and cytokine
physiological protective reflex, limiting airway exposure receptor (IL 1, IL 2, IL 6) expression as well as that of
to acid. On the other hand, in case of pathologic reflux, inflammatory mediators.
it may be induced too frequently.
As a result, the reactivity of bronchial smooth muscles is
Ad. 2. By simultaneous pH monitoring in the trachea altered.
and esophagus, Jack demonstrated in asthmatic falling
pH in those with GER – which was considered to pro- ASTHMA AS A REFLUX-INDUCING FACTOR
vide evidence for microaspirations [27]. Aspiration of
the gastric content leads to inflammatory conditions Asthma and its treatment may aggravate reflux by
within the airways, which may result in bronchial hyper- decreasing the tone of lower esophageal sphincter and
reactivity. increasing intraabdominal pressure due to the cough
reflex.
Food allergens present in the aspirated content sensitize
T cells of the peribronchial lymphoid tissue and induce Sontag and Harper demonstrated that the pressure in
specific IgE production. Another exposure to the same the lower esophageal sphincter (LES) in asthmatics is
allergens may cause IgE-dependent mediator release lower than in healthy subjects [9,20]. Then, Mitsuhashi
from mast cells and activation of T lymphocytes and sobserved in asthmatic children a positive correlation
eosinophils, leading to the development of an inflamma- between low LES tone and asthma attacks [30]. Reflux is
tion in the respiratory tract. Meer points to frequent known to be aggravated by:
occurrence of food allergy in patients with bronchopul- – decrease of LES tone due to the descent of the
monary dysplasia, asthma, and GER [28]. In his opin- diaphragm associated with the trapping of air as a
ion, a patient with asthma and GER should be evaluated result of bronchospasm.
for food allergy. – gradient increase due to more negative intrathoracic
pressure as opposed to more positive intraabdominal
Additionally, it has been observed that the more fre- pressure.
quent the aspirations are, the more pronounced
bronchial hyperreactivity to different stimuli becomes. The literature contains contradictory views concerning
Finally, hyperreactivity develops, which does not the role of UES (upper esophageal sphincter) in the
require the decrease of intraesophageal [2]. Other evi- pathogenesis of pulmonary symptoms accompanying
dence for the important role of microaspiration in gastroesophageal reflux disease. According to Patti,
bronchial obstruction are the studies carried out by patients with GER and chronic lung diseases have sig-
Tuchman [29]. He demonstrated that acidification of nificantly lower pressure in UES, LES and reduced
the airways in cats caused more pronounced obstruction

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peristaltic amplitude both in LES and in UES, which mimetics and ipratropium bromide 8 hours before,
may favor aspiration [31]. antireflux agents 72 h, and omeprazole 7 days [6].

Recent studies indicate that GER may be the cause ra- In patients with sthma and GER, the reflux symptoms
ther than the result of obstruction. were observed more frequently and were characterized
by longer duration of reflux episodes than in GERD
According to Sontag, the neverending debate whether patients [1].
asthma is the result of reflux or vice versa leads to the
conclusion that it is not important to establish whether Horizontal position
GER occurs in asthmatics, or whether pulmonary symp-
toms are observed in subjects with GER. Instead, find- Frequency of nocturnal wheezing episodes or cough is
ing the methods of management allowing to curb these higher in asthmatic patients with GER than in those
disorders is important [2]. The author also suggests that without GER. Additionally it has been observed that,
the asthma – GER relation is based on feedback, where independently of bronchodilator therapy, night reflux is
reflux aggravates the course of asthma and asthma, in more pronounced in patients with asthma than in non-
turn, enhances reflux. asthmatic patients [9].

POTENTIAL GER PROMOTERS Diet

Provocation of a GER-related asthma episode is favored After abundant meals, when the stomach is full, hori-
by many coincident factors, previously described by zontal position increases the risk of GER and obstruc-
Davis [23]. In turn, all the factors favoring GER will also tion, probably due to aspiration [30]. Similarly, the com-
favor the above relation [23,30]. Such factors include: position of diet significantly influences the LES function
– bronchodilators (decreasing its tone after products rich in fat, protein,
– horizontal position beverages).
– overeating
– hiatus hernia. Hiatus hernia

Bronchodilators Hiatus hernia seems to be the most important factor


inducing esophagitis. It is observed with 7-fold higher
Earlier studies, including those carried out by Mitsuha- frequency in patients with asthma and esophagitis than
shi, indicated decreasing the LES tone by bronchodila- in those without esophagitis [14]. It still remains unclear
tors [30]. Then, Sontag observed that reflux parameters whether the presence of hiatus hernia and esophagitis
were identical in the groups of asthmatic patients treat- are the indicators of asthma induced by, or coincident
ed and not treated with bronchodilators [9]. Thus, these with reflux.
studies clearly indicate that GER is an important, intrin-
sic abnormality in asthma rather than the result of LES DIAGNOSTICS OF GER IN ASTHMATIC PATIENTS
tone decrease by drugs [2,9].
GERD should be suspected as the cause for asthmatic
According to current views, administration of such symptoms in patients with:
preparations does not contribute significantly to the • asthma and typical or atypical symptoms of GERD;
development of pathologic GER [1]. Assuming that the • asthma and negative family history, no signs of atopy,
reflux symptoms are favored by transient LES relax- normal IgE and eosinophil level, signs of treatment-
ation and not its low baseline tone, there are no impor- resistant asthma, aggravation of symptoms after theo-
tant gastrological contraindications for the use of these phylline.
drugs [2,18].
In order to establish the correlation of the respiratory
Systemic administration of theophylline and beta-2- disorder with the presence of pathologic reflux, various
mimetics decrease the LES tone and stimulate research methods of different clinical value are used,
hydrochloric acid secretion [5,30]. Inhalant beta-2- including [1,2,21]:
mimetics, as well as inhalant and systemic GCS do not
alter the LES tone [1]. According to Hubert, theo- 1. methods documenting the presence of pathologic
phylline does not enhance GER [32], whereas other GER
investigators observed a 24% increase of GER after
theophylline and over 100% increase of GER-related • 24-hour pHmetry [9,21,33]. Many investigators employ
symptoms. pHmetry both to confirm and to exclude the relation-
ship between GER and asthma. z astmà. Confirmation
Because of the possible effect of drugs, despite some of of reflux by pHmetry can only suggest its role as a
the findings to the contrary, they were usually discon- causal factor for wheezing. It is not, however, direct
tinued before the investigations of the relationship evidence for the correlation between intraesophageal
between asthma and reflux: theophylline and oral beta- pH decrease and clinical manifestation in the form of
2-mimetics 72 h before the tests, short-acting beta-2- respiratory disorders [2]. Documenting such correla-
tion would require a technique involving simultane-

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Med Sci Monit, 2002; 8(3): RA64-71 Wąsowska-Królikowska K et al – Asthma and gastroesophageal reflux in children

ous evaluation of the respiratory function and reflux It is known that GER can cause dyspnea in healthy sub-
recording. Therefore, Wiener proposed an index for jects, which disappears after antireflux therapy.
assessment whether the respiratory symptoms are relat-
ed to GER; if respiratory symptoms coincide with GER The treatment of asthmatic patients with reflux utilizes
in less than 25% or more than 75% of time, the causal standard drugs such as neutralizing agents, H2 block-
relationship seems to be low or high, respectively. The ers, proton pump inhibitors, prokinetic drugs or
index, however, does not account for the total number surgery [39]. It should be remembered that in GERD
of respiratory episodes. Consequently, a significant H2 blocker doses should be 2-4-fold higher than the
causal relationship may be demonstrated both in a child standard ones, and the treatment should be continued
who had one respiratory episode coincident with one for 3 months [1].
episode of GER and in a child who had 50 respiratory
episodes coincident with GER [34]. Many studies indicate that neutralizing agents and H2
blockers, even used at standard doses, may cause in
RARS occurring during GER or within 10 min after it
seem to point to GER as a factor provoking asthmatic
asthmatics with GERD either improvement of both
reflux and pulmonary symptoms, or improvement of
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symptoms [35]. According to Sontag, RARS symptoms reflux symptoms only, or no improvement [20,32,40].
are observed during GER in 15.5% of patients, after Godall demonstrated by DBPCS (Double Blind Placebo
GER in 9.9% before GER in 20.4% and are unrelated to Control Study) method a clinical improvement in asth-
GER in 54.2% of cases [35]. matic patients treated with cimethidine. Such an effect
was not observed after placebo treatment [41]. Harper
• endoscopy with collection of bioptate for histopatho- observed statistically significant improvement of FEV1
logic investigation; (forced expiratory volume in one sec) after ranitidine
treatment [20].
• scintigraphy with isotope-labeled test meal;
It currently seems that prokinetics and proton pump
• radiological imaging in order to exclude hiatus hernia. inhibitors (PPI) are more effective. Harding demon-
strated alleviation of asthmatic symptoms in 62% of the
2. methods confirming the role of gastric content examined patients with parallel PEF increase and
microaspiration into the lungs reduction of drug consumption among patients treated
with Omeprazole [8].
• sputum analysis for lipid-laden alveolar macrophages
– lipids present in the lungs due to aspiration. Low In view of chronic character of the disease, considering
practical value because of very low specificity of the the use of prokinetics one should always take into
test [36] account the potential benefits and risk associated with
their long-term administration. Tucci demonstrated a
• lung scintigraphy after technetium-labeled meal – beneficial effect of such treatment in children with poor-
aspiration of gastric content into the lungs – low sensi- ly controlled asthma [10].
tivity [33].
The possibility of surgical treatment (classic or laparo-
The diagnostic methods used include also acidification scopic fundoplication) should be taken into considera-
of the esophagus to confirm the role of the vagal nerve tion in patients demonstrating improvement after phar-
in the development of bronchial obstruction [24] and macological treatment [1]. Four independent studies of
patient questionnaire assessing GER correlation with children with GER and pulmonary symptoms who
pulmonary symptoms. underwent surgery, although involving no comparison
with controls, demonstrated evident improvement mea-
None of these methods allows to establish which sured by disappearance of respiratory symptoms in
patients have GER-induced asthma, and in whom asth- 70–100% of cases [2,16]. However, it is difficult to estab-
ma is accompanied by GER. lish the diagnosis of asthma in infants if recurrent aspi-
rations and pneumonias are primary symptoms, but
Yellon reports that esophageal biopsy is a quick and safe surgical elimination of GER evidently leads to marked
method of GER diagnostics in children with reflux improvement in most children.
symptoms [37]. On endoscopy, Harding observed
esophagitis in 60–72% of asthmatic children [38] and Sontag demonstrated in 5-year follow-up a significant
Sontag in 42% of asthmatic adults [9]. improvement of pulmonary function, reduction of drug
consumption and disappearance of asthmatic symptoms
EFFECTS OF GER TREATMENT IN ASTHMATIC PATIENTS only in patients who had undergone surgery in compar-
ison with pharmacologically treated patients [42]. It is
Although the causal relationship between asthma and worth emphasizing that marked improvement due to
GER often remains unclear, the fact of marked the surgery results not only from the prevention of acid
improvement after surgical or pharmacological treat- reflux, but also of any other reflux, e. g. biliary [2].
ment of GER is evident [2,10]. Unfortunately, most of
these studies were not controlled and did not assess the In contrast, Field reports that the effectiveness of long-
pulmonary function before and after the surgery [2]. term pharmacotherapy is comparable with that of surgi-

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cal treatment. He observed reduction of GERD symp- CONCLUSIONS


toms in 90% of patients after surgery, alleviation of asth-
matic symptoms in 79%, reduction of antiasthmatic 1. Most of asthmatic patients have GER and it is a well-
drug consumption in 88%, and in 22% improvement of documented fact that GER plays an important role in
spirometric parameters [3]. patients with asthma.

After antireflux surgery, Harding observed remission of 2. Despite sophisticated methods and advanced diag-
asthmatic symptoms in 34% of patients, clinical nostic techniques, no tests allowing the differentia-
improvement in 42% and no improvement in 24% [38]. tion of patients with GER-induced asthma or vice
Then, Sontag demonstrated, after 5-year follow-up, versa or the identifications of patients likely to
improvement of clinical asthmatic symptoms in 74.9% of respond well to antireflux therapy are available.
patients subjected to antireflux surgery, 9% of those
treated with Ranitidine, 4% receiving placebo, and 3. It is difficult to establish the cause-and-effect relation-
aggravation in 47.8% of patients receiving placebo, ship between asthma and GER.
36.2% of those using H2 blockers and only in 6.2% of
patients after the surgery. Inprovement of PEF and pos- 4. Even positive results of diagnostic tests such as sputum
sibility of GCS discontinuation was observed in 33% of analysis or scintigraphy do not allow to establish the
operated patients, only in 11% of patients treated with cause or result and predict the course of the disease.
Ranitidine, leczonych Ranitydynà and none of the con-
trol group [42]. Contrary to Field's findings, Sontag 5. Ambulatory pHmetry can suggest, but not confirm,
demonstrates much better effects of antireflux surgery the presence of GER-induced asthma and clinical
as compared with pharmacotherapy [42]. Bittner decision cannot rely on findings concerning the
emphasizes that laparoscopic fundoplication may prove esoophageal content ph only.
not only to be a very effective, but also a cheap method
of treatment [43]. As a result of longitudinal studies car- 6. Provocations during PPI medication are recom-
ried out in a group of 243 children, Snajdauf observed mended to assess subjective or objective improve-
remission of GER symptoms in 83% and recommended ment, the doses must be sufficiently high and the
Nissen fundoplication as the most effective surgical duration of treatment sufficiently long (3 months) to
method [44]. observe even slight improvement, both objective and
subjective.
Although the correlation between asthma and reflux has
been clearly confirmed, the background of this correla- 7. Antireflux surgery should be taken into considera-
tion still remains controversial. GER symptoms occur in tion if GER is regarded as the cause of asthma exa-
asthmatic patients 4-5-fold more frequently than in cerbations.
other subjects. Many asthmatics experiencing RARS
(reflux-associated respiratory symptoms) use beta-ago- 8. Positive response to PPI treatment does not necessar-
nists during symptomatic GER. ily predict good response to antireflux surgery, and,
conversely, poor response to PPI does not predict
Antireflux therapy, although it alleviates the symptoms poor response to surgical treatment.
of asthma and reduces drug consumption, paradoxically
does not improve pulmonary function in objective 9. The ultimate antireflux therapy, which has proved
assessment [3,7,45]. There are attempts to explain this effective over time, involves:
by the positive effect of antireflux therapy attainable • avoiding eating later than 3 hours before going to
only in some patients with asthma and GER, despite the bed;
lack of data concerning the factors predisposing for • avoiding abundant and fatty meals, which delay
cure. The situation is compared to another aspect asso- gastric clearance;
ciated with asthma, i. e. that not all asthmatics react to • raising the head of the bed;
exertion, tobacco smoke or cold air [3]. • H2 blockers, e.g. Ranitidine 300 mg b.i.d.;
• PPI;
The elucidation of this paradox is a challenge for future • antireflux surgery.
research, similarly as selection of patients likely to Positive results of GER treatment in asthmatic pa-
respond positively to treatment. tients lead to:
• reduced frequency of hospitalizations;
If antireflux therapy allows to control asthma better, it • reduced pulmonary morbidity and mortality;
should be instituted in all patients, irrespective of the • reduced demand for pulmonary drugs;
severity of GER symptoms, and even in those with silent • lower absenteeism due to diseases;
reflux. It should be remembered that esophagitis devel- • reduced frequency of visits at the doctor's;
oped in the course of GER may result from reflux of • lower incidence of GCS-related complications.
bile acids and trypsin. Then the patients will not
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