Acta Neurol Belg
DOI 10.1007/s13760-016-0643-0
ORIGINAL ARTICLE
The interaction between breathing and swallowing in amyotrophic
lateral sclerosis
Nazan Simsek Erdem1 • Kamil Karaali2 • Ali Ünal1 • Ferah Kızılay1
Candan Öğüş 3 • Hilmi Uysal1,4
Received: 10 March 2016 / Accepted: 16 April 2016
Ó Belgian Neurological Society 2016
Abstract The aim of the study is to determine the asso-
ciation between respiratory swallow patterns in amy-
otrophic lateral sclerosis (ALS) patients. Furthermore, it
aims to clarify the role of the dysphagia limit in defining
the relationship between swallowing disorders and respi-
ratory disorders. Functional rating scales were used to
describe swallowing and respiratory function. Swallowing
was observed using the dysphagia limit. Dysphagia limit is
the volume at which a second or more swallows are
required to swallow the whole bolus. Laryngeal and chest
movement sensors, pulmonary function tests, submental,
and diaphragm electromyography activity were used to
evaluate the relationship between swallowing and respira-
tory phase. Of the 27 patients included in the study, 14
were dysphagic and 13 were non-dysphagic. Tests showed
normal respiratory function in 11 of the non-dysphagic
patients and 3 of the dysphagic patients. There was a high
correlation between the dysphagia limit and Amyotrophic
Lateral Sclerosis Functional Rating Scale swallowing
parameters. Non-dysphagic patients were able to swallow
during inspiration but only six patients in the dysphagic
group were able to swallow during inspiration. The
occurrence of dysphagia in ALS is related to piecemeal
& Hilmi Uysal
uysalh@akdeniz.edu.tr
1
Department of Neurology, Akdeniz University Faculty of
Medicine, 07070 Antalya, Turkey
2
Department of Radiology, Akdeniz University Faculty of
Medicine, 07070 Antalya, Turkey
3
Department of Pulmonary Diseases, Akdeniz University
Faculty of Medicine, 07070 Antalya, Turkey
4
Department of Clinical Neurophysiology, Akdeniz University
Faculty of Medicine, B Blok Level 2, 07070 Antalya, Turkey
•
deglutition and respiration consistency during swallowing.
Detecting the timing of disturbances in the relationship
between swallowing and respiration may be a way of
identifying dysphagia. Dysphagia limit may be a useful,
complementary test for assessing swallowing disturbances
in amyotrophic lateral sclerosis.
Keywords Dysphagia
Dysphagia limit
Respiration

Amyotrophic lateral sclerosis
Introduction
Amyotrophic lateral sclerosis (ALS) is a degenerative
motor neuron disease that affects breathing, feeding, and
locomotion functions [1]. These vital functions are closely
related to each other but how they are controlled by the
central nervous system is poorly understood [2]. It is well
known that breathing and feeding dysfunction determines
the prognosis of ALS [3–5]. Furthermore, some problems
such as the timing of percutaneous endoscopic gastrostomy
(PEG), non-invasive ventilation, and tracheostomy are still
important in patient follow-up. As mentioned in evidence-
based reports that are being used as a guide in these issues,
‘‘more studies are needed to examine the best tests of
respiratory function in ALS, as well as the optimal time for
starting PEG, the impact of PEG on quality of life and
survival’’ [4, 6–8].
In this prospective study, our objective is to understand
how the relationship between respiration and swallowing
function is affected in ALS patients who have dysphagia.
In the literature, there are a number of studies that inves-
tigate swallowing and respiration functions separately [8–
14]. However, there is no systematic study that investigates
the mutual relationship between both functions.
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Materials and methods
Twenty-seven consecutive patients were admitted to the
Neuromuscular Polyclinic between 2011 and 2013. They
were evaluated clinically and electrophysiologically and
diagnosed with ALS according to the revised ‘El Escorial’
Diagnostic Criteria [15]. These patients were followed up
for 2 years after enrollment in the study.
The Declaration of Helsinki, which describes ethics in
clinical trials, was taken into consideration in this study. The
methods were approved by the local ethics committee. All
patients were asked to sign a written informed consent form.
Patients with PEG and those receiving ventilator supports
were excluded. The total muscle strength of ALS patients
was measured manually using the Medical Research Council
Scale for clinical evaluation [16]. The ALS Functional
Rating Scale (ALSFRS) was used for all patients [17].
Assessment of respiratory function
Pulmonary function tests were performed using a spirom-
eter and the percentages of the estimated values of their
forced vital capacities (FVC) were evaluated. Patients were
also evaluated using the sniff nasal inspiratory pressure
(SNIP) test.
Evaluation of the swallowing function
Swallowing functions were evaluated via clinical bedside
examinations and the DL. Healthy adults swallow amounts
of 20 mL or more at a time [8, 18]. On the other hand,
dysphagic patients swallow smaller amounts according to
the degree of dysphagia [8, 19]. Increasing amounts of water
(3, 10, 15, and 20 mL) were placed in the patient’s mouth by
the researcher with a syringe. The patient was asked to hold
the water in his or her mouth and swallow on command. The
first swallow was observed during the 8-s period after the
swallow command. A second swallow in that period was
identified as pathologic. The patient’s DL was the smallest
volume of a second swallow. A patient with a DL of less
than 20 cc is considered to be dyphagic [8].
Electrophysiological studies on swallowing
and breathing
The patient’s head was inclined 45° during the study. The
part of the method relating to swallowing was defined by
Ertekin et al. [18], modified by including the pulmonary
function proposed by Uysal et al. [11]. It was based on the
recording of swallowing and respiratory variables by the
EMG device through various sensors. Records were made
with five channels. The first channel recorded diaphragmatic
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Acta Neurol Belg
EMG activity. The diaphragm was entered by passing
internal and external costal muscles with a needle electrode
in 7th–8th intercostal space on the midclavicular line. A fixed
position was given to the needle where muscle activity was
observed during inspiration, and diaphragmatic EMG
activity was recorded. In the second channel, swallowing
sensor activity was recorded via a laryngeal sensor. During
swallowing, the vertical motion of the larynx was measured
using a piezoelectric sensor, which was placed into the space
between the thyroid and cricoid cartilage in the midline. The
sensor and rubber receiver at the tip were held in place on the
neck with an elastic band, and a record was made in the
0.1–100 Hz frequency range. In the third channel, superficial
submental EMG activity was recorded. Bipolar surface
electrodes were placed on either side of the midline in the
submental area at approximately 2 cm intervals. During
swallowing, activity of the submental muscle complex,
which is composed of mylohyoid, anterior digastric, and
geniohyoid muscles, was recorded using the electrodes.
EMG activity obtained with this method was termed ‘sub-
mental electromyography’ (SM-EMG) and records were
made in the 5 Hz to 5 kHz frequency range with a sweep
duration of 10 s. In the fourth channel, expiratory and
inspiratory periods of breathing were recorded by means of a
pressure transducer air flow sensor, which was placed in the
nostrils (Pro-techÒ). Records were made in the 0.1–10 Hz
frequency range. Negative deflections according to the iso-
electric line were interpreted as inspiration and positive
deflections as expiration. In the fifth channel, expiratory and
inspiratory periods of breathing were recorded by the elastic
movement sensor (VelcroÒ Strap) that surrounds the entire
chest wall at nipple level. Records were made in the
0.1–10 Hz frequency range. These five channels were
recorded simultaneously. The trigger system and two divi-
sion delay were used for SM-EMG. Hence, muscular and
respiratory activity during before and after triggering of
swallowing was recorded (Fig. 1a–c). The respiratory
rhythm was listened to by the speaker and the ‘‘swallowing
stimulus’’ was given vocally by the EMG controller. The
swallowing stimulus was given during expiration and
inspiration, respectively. The study was completed after at
least two successful swallows during both inspiration and
expiration. The inspiratory and expiratory times as well as
the swallowing and deglutition apnea times were calculated.
At least two repetitions were made for each successful
swallow. While ALS patients were drinking 3 ml water at a
time, laryngeal sensor signals and SM-EMG records were
evaluated and A–0, A–C, O–2 parameters were measured,
which are defined below.
A–0 interval The time between point A, which is the
beginning of the SM-EMG, and point 0, which is the start
of the first laryngeal deflection.
Acta Neurol Belg
Fig. 1 Respiration and swallowing relationship of a non-dysphagic
ALS patient. a Respiration without swallowing, b Swallowing during
expiration, c Swallowing during inspiration. Arrows indicate
0–2 interval Two deflections are obtained by the
laryngeal sensor during swallowing. The first deflection
occurs during elevation of the larynx and the second at its
depression. This interval is the time between point 0, which
is the beginning of the first deflection, and point 2, which is
the beginning of the second deflection.
A–C interval The time period between start (point A)
and end (point C) of the SM-EMG.
Statistics
Data were analyzed using SPSS 18.0 (Chicago), which
provided descriptive statistics such as frequency distribu-
tion, mean, and standard deviation. A Student’s t test or
Mann–Whitney U test was used to analyze the continuous
distribution of the two groups. The Paired Sample t test or
Wilcoxon test was used to compare before and after values
of continuous variables. The Chi-squared test was used in
the analysis of categorical data according to the groups.
A Spearman or Pearson correlation was used in correlation
analysis of variables. All tests were carried out, respecting
their respective assumptions. The significance level was
95 % (a = 0.05).
Results
Twenty-seven cases were followed up between 2011 and
2013. Twenty-two of them were definite and five were
possible ALS patients according to the revised El Escorial
criteria. The group consisted of 20 male and 7 female
patients with a mean age of 53 ± 12 years (30–75).
respiratory apnea. The respiratory apnea of swallowing took place
during inspiration without transition to the expiration phase in panel
(c)
Patient’s mean age at onset was 51 ± 21 (range 28–73).
The mean interval from onset of symptoms to diagnosis
was 8.8 ± 5.6 months, the mean disease duration was
23.7 ± 26 months from the diagnosis. Onset region was
cervical in 10, lumbosacral in 12 patients, and bulbar in 5
patients. Patient’s mean FVC % was 65 % ± 22 of pre-
dicted, and mean SNIP was 52 ± 23 cm H2O. Seven
patients had an FVC lower than 50 % and 8 patients had an
FVC lower than 70 %.
The group was divided into subgroups according to DL,
which was evaluated following Ertekin et al. [18, 20, 21].
The average of all cases’ DL was 14.1 ± 7.3 cc. and
median of DL was 20 cc (3–20 min–max). In 14 cases, DL
was greater than 20 cc; 13 cases it was less than 20 cc. In
eight cases DL was B5 cc. The DL of five patients with
bulbar onset was 6.2 ± 6.6 cc, while it was 16.2 ± 5 cc
for the 22 patients with spinal onset. Bulbar involvement
was observed in the whole dysphagic group and in three
patients from the non-dysphagic group. Thirteen patients
(nine male, four female) had dysphagia and 14 did not (11
male, three female), according to DL. There was no sta-
tistically significant difference between the ALSFRS scores
for patients with and without dysphagia (Table 1). The DL
correlates with ALSFRS when a distinction is made
between dysphagic and non-dysphagic patients, as defined
by DL. The distribution defined as dysphagic by the
ALSFRS was evaluated (Table 2).
Findings related to pulmonary function tests
There was a correlation between pathology seen in pul-
monary function tests and dysphagia. Nine of 13 patients
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Table 1 The values of the

Scale Dysphagic Non-dysphagic Total p
ALSFRS, swallowing and
respiration sub-scales ALSFRS total 22.7 ± 11 26.5 ± 7.8 24.8 ± 9.2 0.553
ALSFRS- 2.67 ± 0.9 3.87 ± 7.8 3.33 ± 1.1 0.001
swallowing
ALSFRS- 3,7 ± 0.5 3,2 ± 0.8 3.5 ± 0.7 0.074
respiratory

Table 2 Correlation of dysphagia occurence according to swallowing scales and dysphagia limit
Scale According to the scale According to dysphagia limit Total (for scales) Pearson correlation
r/p
Dysphagic Non-dysphagic
13 14

ALSFRS Dysphagic 11 1 12 0.700

Swallowing Non dysphagic 2 13 15 0.000

who had dysphagia had normal respiratory tests, p = 0.013
(Chi square). The functional relationship between swal-
lowing and breathing was investigated using intervals A–C,
A–0, 0–2, swallowing apnea times during swallowing of
3 cc fluid, and number of inspirations and expirations with
or without swallowing (Table 3). Statistically, the swal-
lowing apnea time was significantly longer in the dys-
phagic group than in the non-dysphagic group. A
statistically significant negative correlation was seen in the
prolongation of inspiration times, dependent on swallowing
and FVC. Nine patients with breathing and swallowing
dysfunction and 11 patients without swallowing and res-
piratory dysfunction were compared; no statistically sig-
nificant difference was seen in terms of swallowing and
respiratory parameters. However, the combination of
breathing and swallowing function showed a significant
difference: whether or not the patient could swallow during
inspiration. All patients were able to swallow during
expiration (Fig. 1b) but the rate of successfully swallowing
during inspiration was significantly lower in the dysphagic
group (Fig. 2b) than in the non-dysphagic group (Fig. 1c).
(p = 0.002 Chi square).
Seven patients who could not swallow during inspiration
had a DL limit lower than 5 cc. The patients whose DL was
below 5 cc had a FVC lower than 50 %, SNIP lower than
60 %; the lowest FVC and SNIP were observed in these
patients (Fig. 3). Six patients who could swallow during
inspiration had a DL equal to or grater than 5 cc. Addi-
tionally, there was a statistically significant relationship
between the decrease in DL and being able to swallow
during inspiration (p = 0.0001).
Patient follow-up
During the 36-month follow-up, nine of the 27 patients
died. The 3-year overall survival rate was 74 %. Seven of
the 20 patients had a tracheostomy and were receiving
respiratory support (Fig. 3). Four of these seven patients
were being fed with PEG. Two patients who did not need
respiratory support were being fed with PEG.
Five of the 13 patients in the dysphagic group died. An
average of 25 months after, four of 13 in the dysphagic
group included in the study had a PEG. One of these four
patients had a PEG only, while the others had both PEG
and tracheostomy. One patient with dysphagia was living
with a tracheostomy only. The remaining three patients did
not have PEG or tracheostomy,
Three of the 14 patients in the non-dysphagic group
needed a tracheostomy an average of 14 months after being
included in the study. Four patients in this group died and
two patients were living with both PEG and tracheostomy,
while one patient had a PEG only.
End of the follow-up, the dysphagia limit was 20 cc in
the three patients of the non-dysphasic group without a
PEG and tracheostomy, and it was less than 20 cc in the
other three.
Discussion
Breathing and swallowing disorders are the main problems
for ALS prognosis. Dysphagia is an early symptom of the
disease in 10–30 % of cases. In almost all of the patients at
the advanced stages of the disease, dysphagia develops
[22–24].
In this study, we showed that the DL, which can be
checked during examination, has the potential to identify
swallowing dysfunction. The DL may be a complementary
test for the swallowing part of ALSFRS, as indicated in
Ruoppolo et al. [25]. In our study, there were no significant
differences in the total ALSFRS scores of dysphagic and
non-dysphagic groups. But the only difference between the

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Table 3 Swallowing parameters in dysphagic and non dysphagic groups

Swallowing and respiration functional interactions Dysphagic Non-dysphagic Total p

A–C duration (ms) 1601 ± 1021 1188 ± 149 1372 ± 704 0.18
A–0 duration (ms) 495 ± 277 326 ± 136 401 ± 223 0.60
0–2 duration (ms) 701 ± 202 659 ± 150 678 ± 173 0.15
Swallowing apnea (ms) 1465 ± 683 984 ± 257 1279 ± 597 0.005
Insprium duration (ms) 1214 ± 311 1408 ± 469 1389 ± 421 0.23
Exprium duration (ms) 1561 ± 515 1626 ± 390 1669 ± 467 0.70
Exprium duration with swallowing (ms) 3270 ± 992 3008 ± 914 3124 ± 865 0.48
Insprium duration with swallowing (ms) 3217 ± 1543 2615 ± 965 2802 ± 1140 0.31
Prolongation of inspiration due to deglulition (ms) 1923 ± 1534 1207 ± 969 1413 ± 1159 0.23
Prolongation of expiration due to deglulition (ms) 1708 ± 984 1381 ± 805 1451 ± 753 0.35

Fig. 2 Respiration and swallowing relationship of a dysphagic ALS was asked to swallow during inspiration (b), even if a swallow was
patient. a Swallowing during expiration, b Swallowing during achieved (there was some submental muscle activity), swallowing
inspiration. The patient could swallow during expiration and swal- was difficult during expiration
lowing apnea could be seen clearly (a). However, when the patient

groups was the ALSFRS swallowing component according
to the DL.
Ertekin et al. found that the relationship between swal-
lowing parameters, such as submental muscle activity, A–0
onset, and the time of laryngeal movement are significantly
longer in patients with ALS than in healthy patients [19, 21].
Normal swallowing became reflex swallowing in advanced
stages. Similar observations were made in our study.
Increasing A–0, 0–2, and A–C values are important indi-
cators of weakness in the motor component of swallowing.
Swallowing duration (A–C) is significantly longer in our
patients with ALS as compared to healthy individuals [11].
In this study, average deglutition apnea duration was
1279 ± 597 ms, which is similarity significant with A–C
duration (1372 ± 704 ms). Deglutition apnea durations
were significantly longer in the dysphagic group (Table 3).
Similarly, A–C durations were longer in the dysphagic
group than in the non-dysphagic group, although, statisti-
cally, these differences were insignificant. Swallowing and
respiration should be evaluated together to explain the
relationship between dysphagia and deglutition apnea
durations and prolongation of A–C. Dozier et al. [26]
studied the coordination of swallowing and breathing, and
showed that 80 % of normal swallowing occurs during

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Fig. 3 Dysphagic patients’
prognosis in the 3-year follow-
up. There were five exitus and
five patients with PEG and/or
invasive ventilation support in
the dysphagic group but four
exitus and three patients with
PEG and/or ventilation support
in the non-dysphagic group.
Only three of these patients had
SNIP values greater than 60 %.
The dysphagia limit was 20 cc
only in the three patients of the
non-dysphasic group
expiration. Paydarfar et al. [27] showed that most sponta-
neous swallowing occurs during expiration but it can also
occur during inspiration and that swallowing apnea is
linked to the bolus amount, not the respiratory phase. They
reported that swallowing during inspiration was associated
with increased aspiration, especially in patients with
swallowing and respiratory dysfunction. All of our patients,
including those with dysphagia, were able to swallow 3 cc
of fluids during the expiration stage. On the other hand,
seven of 13 patients with dysphagia could not swallow
during inspiration. Conversely, all patients without dys-
phagia could swallow during inspiration. Significantly, it
has been shown that normal people can successfully
swallow during inspiration [11]. This appears to be one of
the most important differences between those with and
those without dysphagia.
In our study, swallowing time during inspiration prolonged
as FVC decreases. Patients with an FVC of less than 40–50 %
cannot swallow during inspiration. It seems almost certain that
the inability to swallow during inspiration is an indicator of the
deterioration of the connection between swallowing and res-
piration. Pulmonary function tests revealed abnormalities in 9
of the 11 patients with dysphagia. On the other hand, 11 of the
14 patients without dysphagia had normal pulmonary func-
tion, which supports the idea that dysphagia is not only a
deglutition problem but also a deterioration in the relationship
between swallowing and breathing.
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In all patients, a respiratory rhythm can be generated,
which indicates that normal inspiration and expiration pat-
terns exist in all cases. Furthermore, all patients can swallow
during expiration despite dysphagia. Therefore, the pattern
needed for both respiration and swallowing works in its
normal rhythm. Nevertheless, patients have symptoms of
dysphagia. Hence, it may be that the problem occurs either
because of a deteriorating connection or coordination
between swallowing and respiration. Coordination of these
systems enables successful swallowing under normal con-
ditions. Swallowing and respiratory centers can generate
rhythmicity but swallowing with successful respiration
apnea cannot be achieved, especially during inspiration.
Swallowing function requires advanced coordination in
conjunction with respiration. Determining when incoordi-
nation begins and directing patients accordingly will enable
us to be more helpful in the clinical follow-up.
As anticipated, when patients were evaluated prognosti-
cally, mortality was higher in the dysphagic group and half
of these patients need invasive respiratory and nutritional
support. An evaluation of the DL would appear to be a
potential predictive parameter in patient prognosis (Fig. 3).
During the transition to PEG feeding in ALS patients,
one of the most critical steps is FVC value [8, 12, 28, 29]. It
should be emphasized that PEG implementation with non-
invasive ventilator support is possible in patients whose
FVC is less than 50 % and have respiratory failure. This
Acta Neurol Belg
shows that it is impossible to assess dysphagia separately
from respiratory dysfunction [7].
Consequently, the DL may be used in conjunction with
other diagnostic methods to define dysphagia in ALS
patients. The development of dysphagia can be objectively
checked and tracked with the DL during follow-up. These
diagnostic methods allow us to manage our patients’ health
better. Dysphagia problems that we observed in ALS
patients indicate that a new pathological mechanism should
be defined as being outside the safety boundaries of the
relationship between breathing and swallowing.
Acknowledgments We wish to thank Mrs.Barbara Kılıç who
reviewed the English for text. This study was supported by the
Akdeniz University Scientific Research Grant (grant number:
2011.04.0101.037). Some parts of this study were presented as a
poster at the World Neurology Congress 2013 and Joint Congress of
European Neurology 2014. The abstract is entitled ‘‘Swallowing and
Respiration Relationship in Amyotrophic Lateral Sclerosis.’’ in the
Journal of Neurological Sciences 2013, 333, e427–428.
Compliance with ethical standards
Conflict of interest The authors declare that they have no competing
interests.
Ethical standards The methods were approved by Clinical Research
Ethics Committee of Akdeniz University Faculty of Medicine
(B.30.2.AKD.0.20.05.05).
Informed consent The methods were approved by the local ethics
committee. All patients were asked to sign a written informed consent
form.
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