The child with chronic cough: when does double-channel pH monitoring rule out gastroesophageal reflux

doi:10.4236/ojped.2011.13006

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Open Journal of Pediatrics, 2011, 1, 21-26

doi:10.4236/ojped.2011.13006 Published Online September 2011 (http://www.SciRP.org/journal/ojped/ OJPed

Published Online September 2011 in SciR es. http://www.scirp.org/journal/OJPed

The child with chronic cough: when does double-channel pH

monitoring rule out gastroesophageal reflux?

Richard Kitz1*, Peter Ahrens2, Olaf Eickmeier1, Hansjosef Boehles1, Markus A. Rose1

1Children’s Hospital, Goethe University, Frankfurt, Germany;

2Prinzessin Margaret Children’s Hospital, Darmstadt, Germany.

Email: *[email protected]

Received 13 May 2011; revised 3 July 2011; accepted 19 July 2011.

ABSTRACT

Background: gastroesophageal reflux (GER) plays a

major role in the pathogenesis of pediatric chronic

airway disease. Esophageal pH-monitoring (epHM) is

the diagnostic gold standard for acid GER. To date,

there are no cut-off values for chronically coughing

children ruling out relevant GER. Methods: 24-hour,

double-channel epHM was performed in 549 children

(3 months to 16 years old) with chronic pulmonary

disease. We stratified according to age as follows: ≤

1.5 years, > 1.5 - 4 years, > 4 - 8 years, > 8 < 12 years

and > 12 - 16 years. Following parameters were cal-

culated for both channels: total number of reflux epi-

sodes, number of reflux episodes > 5 minutes, dura-

tion of the longest reflux episode, and reflux index.

Results: according to the above given age classifica-

tion, the median number of reflux episodes in the

lower esophagus was 31, 27, 32, 34, and 42 and for

the upper esophagus 20, 13, 15, 14, and 11 respec-

tively. The median reflux index at the distal esopha-

gus was 2.55, 2.1, 2.3, 2.15, and 1.9; at the upper

esophagus it was 1.4, 1.0, 1.1, 0.9, and 0.6 respectively.

Conclusions: our data contribute useful support to

the evaluation of pediatric airway disease. We pro-

vide reference values for decisions in the exploration

of children with airway disorders and suspected

GER.

Keywords: Gastroesophageal Reflux; Pediatric Airway

Diseases; pH-Moni t o ri n g; C hronic Aspiration

1. INTRODUCTION

Numerous studies in chronic airway disease emphasize

the etiological role of gastroesophageal reflux (GER),

some of them also proving a significant epidemiological

correlation. The prevalence of respiratory symptoms

among patients with GER is high. Monitoring of eso-

phageal pH (epHM) is considered to be the gold stan-

dard in detecting classic GER. The North American So-

ciety for Pediatric Gastroenterology and Nutrition rec-

ommends performing epHM in patients with persistent

asthma, even in the absence of symptoms of GER, and

recommends medical treatment if epHM demonstrates

an increased frequency or duration of esophageal acid

exposure [1]. In asthmatic children with GER, antacid

treatment resulted in a significant reduction in asthma

medication [2].

Astonishingly, data upon normal values of acid expo-

sure of the esophagus in children with unspecific pul-

monary symptoms, measured by pH-monitoring, are

scarce. There are only three studies providing data on

multiple sites measuring in the esophagu s: Bagucka et al.

provided double-channel pH monitoring normal ranges

of gastroesophageal reflux parameters in the upper

esophagus in 200 infants aged 0.5 - 17 months, referred

with suspected GER disease [3]. Sondheimer [4] meas-

ured pH at three levels in the esophagus in only 11 chil-

dren without pathological GER and in 14 with patho-

logical GER. In an older study [5] on 27 healthy children

and adolescents (9.3 - 17.3 years old, mean 13.1) by

Gustafsson in 1988, values for the upper probe, 15 cm

above the cardia, were given as follows: RI 0.6%, num-

ber of reflux episodes in 19/24 h; the duration of longest

reflux episode being 3.3 minutes.

To date, there are no reference values available for the

upper esophagus in children with unspecific pulmonary

symptoms, but without typical gastrointestinal symptoms

of GER (e.g., vomiting). This is the first study to vali-

date the standard method in detecting GER in these chil-

dren from infancy to adolescence.

2. MATERIALS AND METHODS

Patients. At our institution, children undergo epHM in

search of evidence of GER when presenting chronic

cough throughout the year, recurrent wheezing, or re-

current bronchitis/pneumonia. Among those and over a

period of six years, 549 children (aged 3 months to 16

R. Kitz et al. / Open Journal of Pediatrics, 2011, 1, 21-26

years) had a normal epHM according to ESPGHAN-

protocol criteria (reflux index at the distal esophagus <

5%; see below) and were included into this study [6].

Exclusion criteria were other serious chronic diseases

(e.g., cystic fibrosis, perennial allergic disease, or food

allergy), neurological disorders with the risk of dys-

phagia, immunodeficiency, malformations of the tra-

cheobronchial tree, or chronic foreign body aspiration.

At the time of the study, none of the patients was on acid

suppression therapy or on theophylline antiasthmatic

treatment.

Examinations were performed on a walk-in basis. In-

formed consent was obtained from the patients or the

patients’ guardians ahead of the examination. Guardians

were asked to withhold their children’s normal diet and

allow customary sleeping positions throughout the 24-

hours period. Ethical approval was not obtained because

of the study’s retrospective design. For ethical reasons,

we renounced examining a heal t hy control group.

Continuous epHM was performed according to the

ESPGHAN standardized protocol. A monocrystalline

antimony double-channel pH probe (Medtronic Synec-

tics Medical, Sweden) was calibrated in buffers of pH

7.01 and pH 1.07 and then placed transnasaly into the

esophagus. The distance of the two pH sensors on the

probe was adjusted according to the body height of the

patient, using our previously published formula [7]. Af-

ter adjusting the probe for an optimal position within the

esophagu s, with th e use of a control chest x-ray, with the

upper probe position of the sensors between the clavicles.

The lower probe position was set in the distal esophagus.

Therefore we used three different distances between the

sensors: 5 cm in patients with a body height of  80 cm,

10 cm in patients with a body height of  120 cm, and 15

cm in patients with a body height of > 120 cm. This fa-

cilitates interindividual comparability for epHM. The

probes were then connected to a portable dig ital reco rder

(Digitrapper MK III, Synectics Medical AB, Sweden).

Patients and their guardians were then asked to keep a

diary for the next 24 hours. This diary included data on

the time and kind of consumed meals, beverages and

drugs as well as posture. After 24 hours, data were ana-

lyzed by the software “Esophogram®” (Synectics Medi-

cal AB, Sweden). Reflux episodes were defined as a

decrease of esophageal ph below 4 for longer than five

seconds followed by an increase of pH for minimum of

pH 4.5, thus avoiding oscillating phenomena. This en-

abled us to detect the number of reflux episodes at each

sensor in the past 24 hours, the longest reflux episode

and the number of long lasting reflux episodes (> 5 min-

utes). The summarized time of all reflux episodes di-

vided by the total recording time (in general over a pe-

riod of 24 hours) is the “reflux index” (RI).

Statistical analysis:

Statistical analysis was done with the software pack-

age SPSS for Windows® version 11.0 (SPSS Inc., Chi-

cago, Illinois/USA). Data of the study population were

tested for Gaussian distribution, however, Kolmogorov-

Smirnoff´s delta showed no normal distribution. Thus,

we decided to choose nonparametrical statistic testing.

Medians and interquartile ranges (IQR) between the

25% and 75% percentile, provide relevant descriptive

parameters. A Kruskal-Wallis analysis was performed to

compare epHM parameters of all age groups. In order to

facilitate a comparison with literature data, we addition-

ally provide mean values as well as standard deviations.

3. RESULTS

Among 549 patients with normal lower reflux index (RI)

values (< 5%), 126 were younger than 18 months, 148

were 18 months to 4 year s old, 195 were 4 to 8 year s old,

47 were 8 to 12 years old, and 33 were 12 to 16 years of

age.

Results for our four epHM parameters, studied in pa-

tients with distal RI < 5%, are listed in Table 1. Overall,

there was less reflux in the upper esophagus than in the

lower esophagus. Infants between 3 to 18 months of age

had the highest reflux activity of all examined age gr-

oups. As expected, physiological reflux diminishes as

maturation of the cardia proceeds. In all age groups, re-

flux episodes lasting longer than five minutes are scarce

and longer reflux episodes tended to occur in older chil-

dren, while the total number of reflux episodes was

higher in younger childr e n.

When comparing data of the age groups older th an 18

months, we only found a trend toward slight reflux ac-

tivity depending on age. No statistical significant differ-

ences for the epHM parameters could be found in the

Kruskal-Wallis analysis. Therefore, we decided to pool

children between the ages of 18 months to 16 years as

one group (Table 2). This was also true for children with

higher lower esophageal RIs (data not shown).

In infants younger than 18 months of age and normal

RIs in the lower esophagus, the median number of reflux

episodes in the upper esophagus was 21 (IQR 10 - 31)

over a 24-hour period. While the longest reflux episode

lasted 4 min. (IQR 2.0 - 8.2 minutes), the median num-

ber of episodes lasting more than 5 minutes was 0 (IQR

0 - 1) over a 24-hour period. The resulting reflux index

(RI) in the upper esophagus was 1.4 (IQR 0.5 - 2.5).

Children between the ages of 18 months to 16 years had

a total number of 14 (IQR 7 - 24) reflux episodes in the

upper esophagus. Their longest episode lasted 4 minutes

(IQR 2 - 8 min). The median number of reflux episodes

longer than 5 minutes was 0 (IQR 0 - 1). The resulting

reflux index RI was 1.0 (IQR 0.4 - 2) in this age group.

R. Kitz et al. / Open Journal of Pediatrics, 2011, 1, 21-26 23

Table 1. Upper and lower esophageal pH monitoring parameters in patients with normal di stal reflux index (RI) values (< 5%) strati-

fied for patient age.

Age (years) 3 - <18 months

n = 126

1.5 - <4 years

n = 148

4 - <8 years

n = 195

8 - <12 years

n = 47

12 - 16 years

n = 33

Mean 0.87 2.60 5.51 9.46 13.91

SD 0.34 0.74 1.10 1.10 1.14

25% quartile 0.59 1.86 4.55 8.59 13.04

Median 0.85 2.46 5.33 9.16 13.70

SEM 0.03 0.06 0.08 0.16 0.20

75% quartile 1.22 3.28 6.36 10.28 14.75

No. of reflux episodes

upper lower upper lower upper lower upper lower upper upper

Mean 21.80 31.96 17.20 29.75 16.93 35.50 19.53 47.48 15.30 44.82

SD 14.90 18.04 13.56 19.31 12.75 26.27 19.78 64.88 14.03 24.65

25% quartile 10.00 21.00 7.00 17.25 7.00 18.00 8.00 16.00 6.00 27.50

Median 20.50 31.00 13.00 27.00 15.00 32.00 14.00 34.00 11.00 42.00

SEM 1.33 1.61 1.11 1.59 0.91 1.88 2.89 9.36 2.44 4.29

75% quartile 31.00 40.25 26.75 39.00 23.00 47.00 26.00 53.75 23.50 55.50

p (dist./prox.) < 0.01 < 0.01 < 0.01 0.01 < 0.01

No. reflux-episodes ≥ 5 minutes

Mean 0.70 0.85 0.95 1.00 0.76 0.99 0.55 0.77 0.81 1.15

SD 1.20 1.07 1.49 1.18 1.07 1.02 1.33 0.90 1.65 1.32

25% quartile 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00

Median 0.00 0.00 0.00 1.00 0.00 1.00 0.00 0.50 0.00 1.00

SEM 0.10 0.09 0.12 0.10 0.08 0.07 0.19 0.13 0.29 0.23

75% quartile 1.00 1.00 1.00 1.75 1.00 2.00 1.00 1.00 1.00 2.00

p (dist./prox.) < 0.01 < 0.01 < 0.01 0.01 < 0.01

Longest reflux episode

Mean 6.20 7.18 6.88 7.43 8.10 8.18 6.42 7.37 12.39 8.76

SD 6.50 5.99 7.80 6.35 11.21 7.10 9.67 6.78 23.41 8.42

25% quartile 2.00 3.00 2.00 3.00 2.00 3.00 1.00 3.00 1.00 2.50

Median 4.00 5.00 5.00 6.00 5.00 6.00 3.00 4.50 3.00 6.00

SEM 0.58 0.54 0.64 0.52 0.80 0.51 1.41 0.98 4.08 1.47

75% quartile 8.20 11.00 8.00 10.00 9.00 11.00 7.00 10.50 13.50 11.00

p (dist./prox.) < 0.01 < 0.01 < 0.01 0.01 < 0.01

Reflux-Index (%)

Mean 1.70 2.43 1.64 2.20 1.51 2.31 1.37 2.19 1.96 2.44

SD 1.60 1.43 1.97 1.37 1.59 1.33 1.93 1.41 3.46 1.50

25% quartile 0.50 1.20 0.40 1.00 0.50 1.20 0.30 1.12 0.20 1.15

Median 1.40 2.55 1.00 2.10 1.10 2.30 0.90 2.15 0.60 1.90

SEM 0.14 0.13 0.16 0.11 0.11 0.09 0.28 0.20 0.60 0.26

75% quartile 2.50 3.52 2.17 3.30 2.00 3.30 1.60 3.40 2.45 4.00

p (dist./prox.) < 0.01 < 0.01 < 0.01 0.01 < 0.01

SEM = standard error of means; SD = standard deviation.

R. Kitz et al. / Open Journal of Pediatrics, 2011, 1, 21-26

OJPed

Table 2. Upper and lower esophageal pH monitoring parameters in patients with normal distal reflux index (RI) values (< 5%). Com-

parison of infants and children up to 16 years of age.

Age (years) Infants (3 - <18 months)

n = 126

Children (18 months - 16 years)

n = 423

Mean 0.87 5.62

SD 0.34 3.37

25% quartile 0.59 3.19

Median 0.85 4.89

SEM 0.03 0.16

75% quartile 1.22 7.18

No. of reflux episodes

upper lower upper lower

Mean 21.80 31.96 17.19 35.57

SD 14.90 18.04 14.05 31.53

25% quartile 10.00 21.00 7.00 18.00

Median 20.50 31.00 14.00 31.00

SEM 1.33 1.61 0.68 1.53

75% quartile 31.00 40.25 24.00 45.00

No. of reflux episodes lasting longer than 5 minutes

mean 0.70 0.85 0.81 0.98

SD 1.20 1.07 1.31 1.09

25% quartile 0.00 0.00 0.00 0.00

median 0.00 0.00 0.00 1.00

SEM 0.10 0.09 0.06 0.05

75% quartile 1.00 1.00 1.00 2.00

Longest reflux episode (minutes)

mean 6.20 7.18 7.82 7.87

SD 6.50 5.99 11.53 6.91

25% quartile 2.00 3.00 2.00 3.00

median 4.00 5.00 4.00 6.00

SEM 0.58 0.54 0.56 0.34

75% quartile 8.20 11.00 8.00 11.00

Reflux-Index

mean 1.70 2.43 1.57 2.27

SD 1.60 1.43 1.96 1.37

25% quartile 0.50 1.20 0.40 1.10

median 1.40 2.55 1.00 2.20

SEM 0.14 0.13 0.10 0.07

75% quartile 2.50 3.52 2.00 3.37

SEM = standard error of means; SD = standard deviation.

Statistical significant differences for epHM parame-

ters were found for the total number of reflux episodes

(p < 0.01) and the RI (p < 0.01), but not for the longest

episode and the number of episod es lasting longer than 5

minutes.

4. DISCUSSION

When GER is considered as a cause of chronic airway

disease, 2-channel epHM is the diagnostic tool of choice

to confirm diagnosis. In clinical practice, GER as the

cause of coughing may no t be readily appa rent, or cough

may be the sole presen ting symptom of GER. Each level

of the airways can be affected by GER [8]. Cough can

result from laryngeal irritation, from esophageal vagal

induced bronchoconstriction, or from pulmonary micro-

aspiration. Similar mechanisms have been postulated to

explain chronic GER-related respiratory disease. None-

theless, most of these children do not present gastroin-

testinal complaints [9]. It is therefore obvious that re-

cording of esophageal pH may detect acid- induced bron-

choconstriction (asthma) and measuring the proximal es-

ophageal acid exposure may help to better detect mi-

croaspiration.

In adults, Harding identified 18% of 1983 patients

with pathologic pH-recordings with self-reported asthma

according to ATS criteria [10]. The absence of clinical

reflux symptoms in these asthmatics with GER (known

as “silent reflux”) was frequent (18%). The German

ProGERD study in 6215 adult patients with GER found

prevalences for chronic extraoesophageal disorders in

chronic cough of 32.8%, in laryngeal disorders of 4.8%,

and in asthma of 13% [11]. An American case-control

study compared 1980 children aged 2 - 18 years with

GERD and 7920 controls without GER, showing a sev-

R. Kitz et al. / Open Journal of Pediatrics, 2011, 1, 21-26 25

eral-fold increased risk for sinusitis, asthma, pneumonia,

and bronchiectasis [12]. Others found a high incidence

of GER in asthmatic pediatric populations [13,14]. Val-

ues of esophageal pH (epH) are the highest in a sub-

group of infants with chronic respiratory disorders un-

dergoing 24-hour pH-monitoring [15]. Studies dealing

with the impact of epHM on respiratory diseases should

reflect these theories and normal values of acid exposure

are of great importance. This is even more important,

since overestimation of GER as a cause of asthma

symptoms may lead to nonjustified therapy of GER as

asthma treatment [16].

Reference values are mandatory to distinguish be-

tween physiological and pathologic reflux activity. De-

tecting the reflux in the upper esop hagus may be of spe-

cial interest in children with extraesophageal disorders.

While older studies propose the 95th percentile as the

cut-off value [17], more recent publications favor the

SEM as range of normal values [3]. Our study provides

both limits in order to give a solid base for data interpre-

tation. In order to avoid an over-treatment, we recom-

mend the conserv ative approach of taking valu es beyond

the 75th interquartile range as an indication for an anti-

acid treatment.

Bagucka et al. [3] published normal data for the upper

esophagus in children initially referred for exclusion of

suspected GER. According to ESPGHAN-recommenda-

tions, they stratified their study group depending on the

RI in the lower esophagus. While their values encom-

passed infants younger than 17 months of age, we now

extended the age range up to 16 year-old adolescents.

When comparing the data, we found consistencies in the

total number of reflux episodes and the absence of epi-

sodes lasting longer than five minutes. Discrepancies

were found for the RI (0.5% vs 1.2%) in the present

study. These findings could be explained by the different

mean ages of the groups < 1.5 years. Bagucka et al.

studied infants as young as 0.5 months old, whereas in

our study no child was younger than 3 months. Their

median age was 3.0 months, whereas our children had a

median age of 10.2 months. Taking into account the

more buffered stomach content of milk-fed children, less

amount of reflux can be detected by measuring only

pH-condition [18]. In other words: the longer the pH in

the stomach is below 4, the more reflux episodes can be

detected in the esophagus. More precisely, simultane-

ously performed intraluminal impedance measurement

of the esophagus can detect bolus movements, thus

broadening our diagnostic spectrum as to detect nonacid

reflux activity in the future [19,20].

Problems in the application of reference values may

occur due to the type of recording device and electrodes.

At present, mostly antimony electrodes are used. They

are less accurate than glass electrodes, however, they

provide multi-channel recording on different levels in

the esophagus and are easier to handle as well as to place

into the esophagus.

5. CONCLUSIONS

The present study prov ides reference values of proximal

esophageal pH-monitoring from infancy to adolescence.

The inter-quartile ranges appear as suitable threshold

levels when anti-acid treatment for the control of re-

flux-associated airway disease is considered.

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