Breathing-Swallowing Interaction in Neuromuscular Patients:

a Physiological Evaluation

1Nicolas TERZI, 1David ORLIKOWSKI , 2Philippe AEGERTER,

1Michèle LEJAILLE,1Maria RUQUET, 4Gérard ZALCMAN ,

2Christophe FERMANIAN,1Jean-Claude RAPHAEL and 1,3Frédéric LOFASO.

1 Services de Réanimation Médicale, Physiologie - Explorations Fonctionnelles, et Centre

d’Innovations Technologiques, Hôpital Raymond Poincaré, AP-HP, 92380 Garches, France

2Unité de Recherche Clinique de l’Hôpital Ambroise Paré, AP-HP, 92100 Boulogne, France

3Inserm U 651, 94000 Créteil, France

4Service de Pneumologie, CHU de CAEN, 14000 Caen, France

Correspondence: Prof. F. LOFASO, Service de Physiologie-Explorations Fonctionnelles,

Hôpital Raymond Poincaré, 92380 GARCHES, FRANCE

Tel: (33-1) 47 10 79 41; Fax: (33-1) 47 10 79 43; E-mail: f.lofaso@rpc.ap-hop-paris.fr

Nicolas TERZI received a grant from the ANTADIR. The study was supported by the

Association d’Entraide des Polios et Handicapés (ADEP).

Running title: Swallowing in Neuromuscular Disease

Subject Category: 7

Word count (body of manuscript): 3357

This article has an online data supplement, which is accessible from this issue's table of

content online at www.atsjournals.org"

AJRCCM Articles in Press. Published on November 16, 2006 as doi:10.1164/rccm.200608-1067OC

Copyright (C) 2006 by the American Thoracic Society.

1

ABSTRACT

Rationale: Malnutrition and aspiration are major problems in patients with neuromuscular

disease for both. Because impaired swallowing contributes to malnutrition, means of

improving swallowing are needed.

Objectives: To investigate interactions between breathing and swallowing in neuromuscular

disorders and to evaluate the impact of mechanical ventilation on swallowing in

tracheostomized patients.

Methods: We studied 10 healthy individuals and 29 patients with neuromuscular disease and

chronic respiratory failure (including 19 with tracheostomy). The tracheostomized patients

who could breathe spontaneously were recorded during spontaneous breathing (SB) and with

mechanical ventilation (MV), in random order.

Measurements and Main Results: Breathing-swallowing interactions were investigated by

chin electromyography and inductive respiratory plethysmography, using three water-bolus

sizes (5, 10, and 15 ml) in random order. In contrast to healthy individuals, neuromuscular

patients showed piecemeal deglutition with several swallows over several breathing cycles for

each bolus. The percentage of swallows followed by expiration was about 50% in the patients

compared to nearly 100% in the controls. The number of swallows and total swallowing time

per bolus correlated significantly to maximal inspiratory pressure. In the 10 tracheostomized

patients who were recorded both in SB and MV, the number of swallows and total swallowing

time per bolus were significantly reduced during mechanical ventilation compared to

spontaneous breathing.

Conclusion: Neuromuscular patients showed abnormal breathing-swallowing interactions,

which correlated to maximal inspiratory pressure. Moreover, mechanical ventilation improved

the swallowing parameters in tracheostomized patients who were able to breathe

spontaneously.

2

Abstract word count: 236

Keywords: Neuromuscular disorder, swallowing, mechanical ventilation, control of

breathing, tracheostomy.

3

INTRODUCTION

Survival in patients with neuromuscular disease has improved considerably in recent

years as a result of changes in the management of respiratory failure (1). For example, the

introduction in 1990 of mechanical ventilation (MV) has improved survival in patients with

Duchenne muscular dystrophy (DMD) from about 15 years in the 1960s to more than 30 years

now. Quality of life, however, declines over time as the disease progresses. Malnutrition is

common: in a study of DMD, for instance, 44% of patients had malnutrition (1, 2). The main

causes of malnutrition are prolonged swallowing, respiratory failure, and dysphagia, which

jeopardize the patient's ability to meet intake needs. Feeding difficulties often develop

insidiously, being frequently missed by family members and healthcare professionals (3).

Aspiration is another important consequence of impaired swallowing that becomes

increasingly common as the disease progresses (1).

Little is known about interactions between swallowing and breathing in patients with

neuromuscular disorders (4). Swallowing-breathing interactions must be evaluated in each of

the breathing conditions encountered in patients with neuromuscular disease: spontaneous

breathing (SB), (5), noninvasive mechanical ventilation (NIV) (6-9), tracheostomy with SB

(10, 11), and tracheostomy with MV (10, 12, 13). Few data are available on swallowing in

neuromuscular patients who breathe spontaneously or use NIV. NIV is generally used only

during sleep, so that patients in this group usually eat without ventilatory assistance (1).

Whether tracheostomized patients should use the ventilator during meals remains

controversial. Patients who are not completely dependent on MV may prefer to be off their

machine during meals, for social reasons or to continue their pre-tracheostomy habits.

Tracheostomized patients on an assist-control mode of MV cannot prolong their expiratory

period, and during meals the ventilator determines whether expiration or inspiration occurs

4

after swallowing. Swallowing in normal individuals is nearly always followed by expiration

(14-16), a pattern that may contribute to prevention of aspiration.

The main objective of our study was to evaluate swallowing-breathing interactions in a

population of neuromuscular patients who exhibited different degrees of disability. Our

secondary objective was to assess the influence of MV during swallowing in tracheostomized

patients who were incompletely dependent on MV.

METHODS

Details are available in the online repository.

Study population

We studied 10 healthy volunteers and 29 consecutive patients who had neuromuscular

disorders responsible for respiratory muscle weakness with a vital capacity (VC) less than

60% but no episodes of acute respiratory failure within the last 2 months. Patients were

recruited during routine follow-up visits at the Raymond Poincaré teaching hospital, whereas

healthy volunteers were recruited among hospital staff members. The healthy volunteers had

no history of dysphagia or pulmonary disease. All study participants provided informed

consent. The study was approved by the relevant ethics committee (Hôpital A. Paré, Paris,

France).

Study procedures

Dysphagia was graded into three clinical grades (17). Locomotor function was

evaluated using the Hauser Ambulatory Index (18). Spirometry was performed in the sitting

position in all study participants and in the supine position in a subset of the patients (19).

Maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP) (20), and arterial

blood gas levels were measured in all study participants. Several clinical and laboratory

5

parameters reflecting nutritional status were collected. An otolaryngologist examined all the

study participants.

Experimental set-up

For respiratory parameter measurements, thoracic and abdominal movements were

monitored using respiratory inductive plethysmography (Respitrace; Ambulatory Monitoring,

Ardsley, NY), as described in detail in the online repository. Swallowing was monitored

noninvasively, using electromyography (EMG) to detect submental muscle activity via skin-

surface electrodes on the chin and a piezoelectric sensor placed between the cricoid and

thyroid cartilages on the midline to detect laryngeal motion (21). All signals were digitized

and recorded directly on a personal computer equipped with the MP 100 data-acquisition

system (Biopac System, Santa Barbara, CA). The system software (AcqKnowledge) was

configured so that EMG signals, laryngeal movements, and thoracic and abdominal

movements were displayed simultaneously on separate channels.

Experimental protocol

The study participant was seated comfortably, and the experiment was started after a

period of quiet breathing. The head was maintained in the neutral position to avoid bias due to

effects of position on swallowing (22). Water boluses were placed in the mouth using a

syringe. Three bolus sizes were used, (5, 10, and 15 ml), in random order. Four sets of three

boluses were studied, taking care not to use the same bolus size twice consecutively. The

study participants were blinded to bolus size. They were instructed to swallow normally while

trying to be as efficient as possible. In the 10 tracheostomized patients who could breathe

spontaneously, swallowing was tested during SB and MV, in random order. SB was tested

with the patient’s usual uncuffed tube (see Table E1 of the online repository) and a one-way

valve (Rusch 506500, Willy Rusch AG, Kermen, Germany). In this subgroup of patients, the

6

Borg Scale score (23) was determined at the end of each condition in order to evaluate the

influence of the breathing condition on dyspnea.

Data analysis

Swallowing onset was defined as the onset of phasic submental EMG activity and

swallowing termination as the beginning of the downward laryngeal movement detected by

the piezoelectric sensor (21). For each bolus size, we recorded the duration of swallowing,

number of swallows, and number of ventilatory cycles. Respiratory movement direction

(inspiration or expiration) immediately before and immediately after each swallow was

recorded, and for each patient the percentages of swallows preceded by expiration and of

swallows followed by expiration were computed.

Statistical analysis

For each subject and each bolus size the mean value of the four trials was calculated.

All results are reported as means±standard deviation in the tables and as means±standard error

of the mean in the figures. Statistical tests were run using the Stat View 5 package (SAS

Institute, Grenoble, France).

Group comparisons were based on data obtained during SB (the most physiological

condition), except in the 8 tracheostomized patients who were completely dependent on the

ventilator. Two-way (group effect and bolus-size effect) analysis of variance (ANOVA) with

repeated measures on volume was used.

To determine the influence in the patients of each disability parameter (Ambulatory

Index, MEP, MIP, VC, PaCO2, and dysphagia) and of tracheostomy on swallowing

performance, least-squares linear regression analysis was performed between the disability

parameters and the swallowing parameters with the largest bolus that all the patients were

able to swallow (24). Univariate analysis was used to evaluate the independent contribution of

7

each variable. Full-model, stepwise, multiple, linear regression analysis was then performed

to determine the influence of each variable (24).

In the tracheostomized patients who were recorded during both SB and MV, these two

conditions were compared using two-way (ventilatory-condition effect and bolus-size effect)

ANOVA with repeated measures (24). P values less than 0.05 were considered statistically

significant.

RESULTS

Study populations

Tables 1 and 2 report the characteristics of the 10 healthy volunteers and 29

neuromuscular patients included in the study (see also Table E1). No abnormal anatomical

obstruction of the upper airway or severe maxillofacial deformity was observed. MV was

consistently used in assist-control mode. All 19 tracheostomized patients used an uncuffed

tracheostomy tube (see Table E1). At the beginning of MV, the tidal volume was set between

10 and 12 ml/kg and the backup respiratory rate was set two to three breaths per minute below

the awake respiratory rate during SB, according to published recommendations (9, 25).

Subsequently, tidal volume was adjusted to obtain normocapnia during MV.

Of the 19 tracheostomized patients, 11 were able to breathe spontaneously for at least

2 hours per day. One patient who was able to breathe spontaneously refused to use MV during

the trial. Therefore, 10 patients were investigated during both SB and MV. During meals, 4 of

these 10 patients used MV, 4 breathed spontaneously, and 2 used MV or SB.

One tracheostomized patient who could breathe spontaneously and 2 tracheostomized

patients who were completely dependent on the ventilator were unable to swallow the largest

bolus (15 ml). Therefore, they could not be included in the ANOVAs.

8

Comparison between neuromuscular patients and healthy volunteers

Swallowing variables

The healthy volunteers usually required a single swallow per bolus (example in Figure

1A). In contrast, piecemeal deglutition occurred in the patients, with each bolus often

requiring several swallows over several breathing cycles (example in Figure 1B). The total

bolus swallowing time was significantly shorter and the numbers of swallows and breathing

cycles per bolus were significantly smaller in the healthy volunteers than in the patients

(P<0.0001, P=0.0004, and P=0.0007 respectively; ANOVA; Figures 2A, 2B and 2C).

Increasing the size of the bolus significantly increased the duration of swallowing and the

number of swallows but not the number of breathing cycles (P<0.0001; P< 0.0001, and

P=0.98, respectively; ANOVA).

Coordination between swallowing and respiration

The percentage of swallows preceded by expiration was not different between the

healthy controls and the patients (P= 0.18; ANOVA). The percentage of swallows followed

by expiration differed between the healthy controls and patients (P<0.0001; ANOVA) but

was not significantly influenced by bolus size (P=0.21; ANOVA) (Figure 2D). Expiration

occurred after nearly all swallows in the healthy controls, compared to only about 50% of

swallows in the patients.

Influence of the degree of disability and tracheostomy on swallowing

The percentage of swallows followed by expiration was not correlated with any of the

variables reflecting disability severity (all P values >0.15). Correlations between other

swallowing parameters and the disability variables are shown in Table 3. MIP and MEP

9

correlated with the swallowing variables but the dysphagia index and ambulatory index did

not.

The influence of tracheostomy on swallowing variables is reported in Table 4.

Tracheostomy significantly affected the number of swallows per bolus (P=0.022), the number

of breathing cycles per bolus (P=0.019), and the duration of swallowing (P=0.048).

In a stepwise regression analysis using the variables that correlated significantly with

the swallowing parameters, only MIP contributed to swallowing parameter variances (number

of swallows: R2=0.309, P=0.002; number of breathing cycles: R2=0.306, P=0.002; and

duration of swallowing: R2=0.223, P=0.01).

Impact of mechanical ventilation in the tracheostomized patients

In the 10 tracheostomized patients for whom recordings were obtained in both

conditions, MV was consistently associated with shorter swallowing times per bolus and

fewer swallows per bolus, compared to SB. Individual results with the largest bolus (15 ml)

are shown in Figure 3. Interestingly, the patient who could not swallow the largest bolus

while breathing spontaneously accomplished this task successfully while on MV (Figure 3).

Figure 4A further illustrates the decrease in the number of swallows per bolus seen with MV

compared to SB (P=0.0007; ANOVA). This smaller number of swallows translated into a

shorter swallowing time per bolus with MV than with SB (P=0.0001; ANOVA) (Figure 4B).

PaCO2 was lower with MV than with SB (P=0.0079; ANOVA). The Borg scale score was

significantly lower during MV than during SB (P=0.0144; ANOVA) (Figure 3C).

10

DISCUSSION

Our physiological study showed differences in swallowing-breathing interactions

between healthy volunteers and neuromuscular patients with chronic respiratory failure. In the

patients, several swallows spread over several breathing cycles were needed for each water

bolus. In addition, nearly half the swallows in the patients were followed by inspiration, a

pattern that was extremely rare in the healthy volunteers. In the tracheostomized patients

capable of breathing spontaneously, MV reduced both the swallowing time per bolus and the

number of swallows per bolus. Before discussing these physiological results and their

potential implications, we will address a number of methodological issues.

Methodological issues

We used a noninvasive method to explore swallowing. We did not use nasofibroscopy

or needle-EMG of the cricopharyngeal muscle. A previous study established that the period

between the two deflections of the laryngeal sensor corresponded to glottis closure as

documented by invasive EMG of the thyroarytenoid muscle (26). In addition, the first

deflection of the laryngeal sensor coincided with opening of the upper esophageal sphincter as

detected by cricopharyngeal EMG relaxation, and this coordination was lost only in patients

who had corticobulbar involvement (21, 27). None of our patients had corticobulbar disease.

Moreover, our method did not require direct connection of measurement devices to the

airway. Thus, the noninvasive method used in our study did not interfere with swallowing or

with the swallowing-breathing interaction.

Because our objective was to obtain data relevant to meals, we evaluated volitional

swallowing as opposed to spontaneous/automatic swallowing. Accordingly, the study

participants chose when to initiate swallowing once the bolus of water was placed in the

11

mouth. However, because in our physiological study the participants were investigated in the

neutral position, we were unable to evaluate potential compensatory positions that might

influence swallowing parameters.

Water was used in our study to investigate swallowing. This may explain why no

correlation was found between the swallowing parameters and the dysphagia grade, as our

patients tolerated water better than semi-solid or solid foods. However, water was used in

most of the previous studies (4, 14, 28, 29), which allowed us to compare our results to earlier

data. Chewing, which influences nutrition in neuromuscular patients, did not occur in our

study. Finally, our method did not ensure detection of aspiration. However, we used a

previously described method for which normal values were available (30, 31). None of our

patients had values within the normal range.

At our hospital, uncuffed tracheostomy is used in neuromuscular patients, to improve

comfort and speech (32). Our finding that tracheostomy influenced swallowing performance

suggests an effect of the material conditions of tracheostomy on swallowing. We continued to

use uncuffed tubes, as studies showed no effect of cuff status on aspiration (33, 34).

Moreover, because Suiter et al. (34), observed that cuff deflation using a one-way valve

improved swallowing and reduced aspiration frequency, we added a one-way valve when

patients were studied in SB.

Although DMD and Becker's muscular dystrophy predominated in our population (15

of 29 patients), a wide range of neuromuscular disorders was represented. However, none of

our patients had cerebral or bulbar involvement and/or rapidly progressive diseases such as

myotonic dystrophy or amyotrophic lateral sclerosis.

12

Interpretation of the results

Evaluation of swallowing

Several studies focused on swallowing neurophysiology in normal individuals and in

patients with neuromuscular disorders. Ertekin et al. (21, 27) showed that noninvasive

evaluation of swallowing using submental EMG activity and laryngeal motion detection by a

piezoelectric sensor was specific and sensitive for evaluating oropharyngeal dysphagia. With

this method, Ertekin et al. (27) found that water boluses of 20 ml or less were never associated

with piecemeal deglutition in normal individuals. In studies of the oropharyngeal phase of

swallowing in 18 patients with myotonic dystrophy (31) and in 25 patients with myasthenia

gravis (35), Ertekin et al. noted that impaired laryngeal elevation and bolus propulsion to the

esophagus was often the main abnormality. In these patients, the pharyngeal phase was often

prolonged. Similarly to Ertekin et al.(21), we noted piecemeal deglutition in our

neuromuscular patients. In addition, swallowing was spread over several breathing cycles and

nearly half the swallows were followed by inspiration, a pattern that was virtually nonexistent

among healthy individuals (15, 29, 36-38).

Swallowing-breathing interaction

The interaction between swallowing and breathing was evaluated by Paydarfar et al. in

30 healthy subjects (16) and Nishino et al. in 8 healthy subjects (14). The results showed that

most swallows started during expiration and were followed by expiration, a pattern believed

to contribute to airway protection during swallowing (4, 28). The mechanism involved in

swallowing-breathing coordination is not fully understood. Nishino et al. showed that this

coordination was partly maintained in unconscious patients, indicating a role for neural

mechanisms in addition to behavioral factors (36). Furthermore, both the respiratory center

13

and the central pattern of deglutition are located in the brainstem, where they share the same

structures.

Our results are in agreement with a previous study (4) showing that swallows were

more often followed by inspiration in patients with brain, spinal cord, and peripheral

neurological disorders. In healthy individuals, the occurrence of inspiration after swallows

was increased by hypercapnia (39) or application of an inspiratory elastic load (28). In

addition, laryngeal irritation was significantly more common with elastic loading compared to

baseline, suggesting that inspiration after swallowing was associated with aspiration (28).

Our patients with neuromuscular disorders had hypercapnia and probably an increased elastic

load (40, 41), and about half their swallows were followed by inspiration. Conceivably, this

abnormal swallowing-breathing pattern may be related to a respiratory drive increase in these

patients with chronic respiratory failure, compared to healthy individuals.

In keeping with previous studies (14, 15, 37), we found that our healthy volunteers

needed a single breathing cycle (and usually a single swallow) for water boluses smaller than

20 ml, whereas the patients needed several cycles. Although a larger number of respiratory

cycles per bolus would be expected to increase the risk of aspiration, as the patient must take

in air while holding material in the oropharyngeal cavity, we did not observe any correlation

between the swallowing parameters and the dysphagia grade. In fact, most of our patients

(n=18) had no signs or symptoms of dysphagia. However, clinical evaluation of dysphagia

may underestimate the frequency of aspiration as detected by an objective method (42). In

addition, we investigated swallowing of water boluses, which are not as effective as solids for

detecting dysphagia. The abnormalities detected in this physiological study probably explain

the prolonged swallowing during meals described by neuromuscular patients, which is known

to increase the risk of malnutrition (1, 2). Swallowing parameters correlated to respiratory

muscle performance, suggesting that the swallowing abnormalities originated in upper airway

14

muscle weakness. Weakness of the upper airway muscles may be similar to weakness of the

respiratory muscles, as the main muscles involved in the oropharyngeal phase of swallowing

share many physiological features with the inspiratory muscles (43). The other hypothesis is

that the abnormal swallowing behavior described in this study is merely a direct consequence

of respiratory failure and therefore could be improved by symptomatic treatment such as

mechanical ventilation.

Impact of mechanical ventilation on swallowing in tracheostomized patients

In the 10 tracheostomized patients who were studied during both SB and MV, MV

decreased both the swallowing time per bolus and the number of swallows per bolus,

compared to SB. These differences occurred regardless of the usual eating pattern (with MV,

with SB, or with either MV or SB). Several hypotheses can be put forward to explain the

improvements seen with MV. First, swallowing probably increased the work of the

respiratory muscles, whereas MV had the opposite effect, allowing the upper airway muscles

to serve only for swallowing. Second, some patients experience anxiety during SB.

Alleviation of anxiety related to the use of MV may improve swallowing. Third, patients do

not have to control their breathing while using MV and can therefore concentrate on

swallowing, which may improve swallowing performance. Fourth, MV maintains a positive

subglottic pressure throughout the breathing cycle, which reduces the risk of aspiration and

may improve swallowing (44). Finally, hypercapnia may alter swallowing performance (39)

and is corrected by MV.

Vitacca et al. (45) reported that tracheostomized patients who had severe obstructive

pulmonary disease and MV weaning difficulties experienced dyspnea during SB and should

therefore use MV during meals. Our patients were routinely asked about dyspnea during

meals. None reported severe dyspnea, in keeping with the reported decrease in the perception

of inspiratory difficulties by neuromuscular patients (46). However, the patients who were

15

investigated both with SB and with MV had significantly lower Borg scale values during MV

than during SB (Figure 3C). Finally, we agree with Vitacca et al. (45) that MV may be in

order during swallowing in tracheostomized patients. SB could be used during more passive

daytime periods.

In summary, patients with neuromuscular disorders exhibited piecemeal deglutition

leading to an increase in the time needed to swallow a water bolus, as well as occurrence of

inspiration after nearly half the swallows. These abnormalities, which correlated with the

reduction in respiratory muscle performance, may explain feeding difficulties. In

tracheostomized patients who could breathe spontaneously, piecemeal deglutition and

swallowing time per bolus were diminished by the use of MV. Further clinical studies are

needed to evaluate the impact of MV during an entire meal and to confirm the suggestion that

MV should be recommended during meals.

17

Acknowledgments: We thank Line Falaize and Alain Louis for their skillful technical

assistance.

18

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tracheostomy speaking valve placement on swallow physiology. Dysphagia 2003;18:284-292.

35. Ertekin C, Yuceyar N,Aydogdu I. Clinical and electrophysiological evaluation of

dysphagia in myasthenia gravis. J Neurol Neurosurg Psychiatry 1998;65:848-856.

36. Nishino T,Hiraga K. Coordination of swallowing and respiration in unconscious

subjects. J Appl Physiol 1991;70:988-993.

37. Preiksaitis HG, Mayrand S, Robins K,Diamant NE. Coordination of respiration and

swallowing: effect of bolus volume in normal adults. Am J Physiol 1992;263:R624-630.

38. Selley WG, Flack FC, Ellis RE,Brooks WA. Respiratory patterns associated with

swallowing: Part 1. The normal adult pattern and changes with age. Age Ageing 1989;18:168-

172.

22

39. Nishino T, Hasegawa R, Ide T,Isono S. Hypercapnia enhances the development of

coughing during continuous infusion of water into the pharynx. Am J Respir Crit Care Med

1998;157:815-821.

40. Gibson GJ, Pride NB, Davis JN,Loh LC. Pulmonary mechanics in patients with

respiratory muscle weakness. Am Rev Respir Dis 1977;115:389-395.

41. Estenne M, Heilporn A, Delhez L, Yernault JC,De Troyer A. Chest wall stiffness in

patients with chronic respiratory muscle weakness. Am Rev Respir Dis 1983;128:1002-1007.

42. Splaingard ML, Hutchins B, Sulton LD,Chaudhuri G. Aspiration in rehabilitation

patients: videofluoroscopy vs bedside clinical assessment. Arch Phys Med Rehabil

1988;69:637-640.

43. Onal E, Lopata M,O'Connor TD. Diaphragmatic and genioglossal electromyogram

responses to CO2 rebreathing in humans. J Appl Physiol 1981;50:1052-1055.

44. Eibling DE,Gross RD. Subglottic air pressure: a key component of swallowing

efficiency. Ann Otol Rhinol Laryngol 1996;105:253-258.

45. Vitacca M, Callegari G, Sarva M, Bianchi L, Barbano L, Balbi B,Ambrosino N.

Physiological effects of meals in difficult-to-wean tracheostomised patients with chronic

obstructive pulmonary disease. Intensive Care Med 2005;31:236-242.

46. Hours S, Lejaille M, Pozzi D, Falaize L, Zerah-Lancner F, Raphael JC,Lofaso F.

Perceived inspiratory difficulty in neuromuscular patients with primary muscle disorders.

Neuromuscul Disord 2004;14:289-296.

23

Figure legends Figure 1.

1A: Breathing-swallowing interaction in a healthy volunteer.

1B: Breathing-swallowing interaction in a tracheostomized patient who was breathing

spontaneously.

Figure 2.

Comparison of healthy controls and neuromuscular patients regarding duration of swallowing

per bolus (panel A), number of swallows per bolus (panel B), number of breathing cycles per

bolus (panel C), and percentage of swallows followed by expiration (panel D). Closed bars

represent neuromuscular patients and open bars represent healthy subjects.

Figure 3. Individual comparison of the duration of swallowing of the 15-ml bolus (panel A),

the number of swallows needed for the 15-ml bolus (panel B), and the Borg Scale score

during the swallowing trials (panel C) with spontaneous breathing (SB) and mechanical

ventilation (MV) in the 10 tracheostomized patients who were able to breathe spontaneously

and who accepted to test both conditions.

: Patients who used mechanical ventilation during meals

: Patients who used spontaneous breathing during meals

: Patients who used either mechanical ventilation or spontaneous breathing during meals

One patient (arrow) was unable to swallow 15 ml while breathing spontaneously.

Figure 4. Comparison of the swallowing time per bolus (panel A) and number of swallows

per bolus (panel B) according to bolus size (5, 10, and 15 ml) and ventilation condition

24

(spontaneous breathing ( ) or mechanical ventilation ( )) in the 9 tracheostomized patients

who were able to breathe spontaneously and who completed all the tests.

25

Table 1. Characteristics of the 10 healthy volunteers

Sex Age Height (cm)

Weight (Kg)

1 M 25 170 69.0 2 M 25 191 88.0 3 F 23 158 53.0 4 M 22 181 71.0 5 F 29 163 54.0 6 M 22 185 72.0 7 F 23 175 65.0 8 F 22 164 60.0 9 M 26 179 80.0 10 M 28 174 71.0

Abbreviations: F, female; M, male.

26

Table 2. Characteristics of the 29 patients with neuromuscular disorders and chronic

respiratory failure

Sex/Age Diagnosis Vent ConditionDuration of mechanical ventilation

VC (Sitting) Dysphagia AI

(yrs) (hours/day) (% ) Grade ( /9) 1 F/47 Glyc. SB N 60 2 3 2 F/24 UM SB N 59 1 1 3 M/45 Ac.Malt SB 10h/24 43 1 4 4 M/43 LGMD SB 8h/24 41 1 8 5 M/34 Cong.D SB 8h/24 37 2 9 6 M/36 Mito.m TSB+ 20h/24 25 3 7 7 M/49 SA TSB+ 12h/24 24 1 7 8 M/19 DMD SB 10h/24 24 2 9 9 F/49 Ac.Malt TSB+ 22h/24 20 1 9 10 M/29 G.glyc SB 8h/24 20 1 9 11 M/20 DMD SB 8h/24 17 2 9 12 M/38 BD TSB+ 12h/24 17 1 9 13 M/25 DMD TSB+ 22h/24 13 1 9 14 F/25 Cong.D TSB+ 12h/24 13 1 9 15 M/25 DMD TSB+ 22h/24 13 2 9 16 M/25 DMD TSB+ 7h/24 13 3 9 17 M/34 G.glyc SB 18h/24 12 3 9 18 M/21 DMD TSB+ 20h/24 12 1 9 19 M/19 DMD SB 8h/24 11 3 9 20 M/42 LGMD TSB+ 20h/24 10 3 9 21 M/18 Multi.m TSB- 24h/24 10 1 9 22 M/30 DMD TSB- 24h/24 10 1 9 23 M/42 BD TSB+ 21h/24 9 1 9 24 M/33 DMD TSB- 24h/24 9 1 9 25 M/26 DMD TSB- 24h/24 8 1 9 26 M/28 DMD TSB- 24h/24 8 1 9 27 M/22 DMD TSB- 24h/24 8 1 9 28 M/33 DMD TSB- 24h/24 7 2 9 29 F/70 Poliomyelitis TSB- 24h/24 0 1 9

27

Abbreviations: F, female; H, male; VC, vital capacity; AI, ambulatory index (details in the

online repository); Ac. Malt., acid maltase deficiency; DMD, Duchenne’s muscular

dystrophy; Mito.m., mitochondrial myopathy; G.glyc, gamma-sarcoglycanopathy; Cong. D.,

congenital muscular dystrophy; BD: Becker's muscular dystrophy; UM, unidentified

myopathy; SA, Spinal amyotrophy; Multi.m, multicore myopathy; Glyc., glycogenosis;

LGMD, limb girdle muscular dystrophy; ND, not done.

Vent. Condition; ventilation condition: SB, spontaneous breathing; TSB-: tracheostomized patients

unable to breathe spontaneously; TSB+: tracheostomized patients able to breathe spontaneously.

Dysphagia was graded like previously described by Ertekin et al.(17) (details are in the online

repository).

Patients # 6,7,9,12,13,14,15,16,18,20,23 were tracheostomized and able to breathe

spontaneously; they were to be tested both with spontaneous breathing and with mechanical

ventilation. However, patient #7 declined testing with mechanical ventilation because his

disease was not progressive and he was not accustomed to eating while using mechanical

ventilation. The 10 remaining patients (#) were tested under both conditions. Among them, 4

usually had their ventilator connected during meals (#13, 15, 18 and 23) and 4 the ventilator

disconnected (#9, 12,14 and 16 ); the remaining two patients (# 6 and 20) had no preference.

28

Table 3. Univariate regression analysis of swallowing variables on indices of level of

disability.

Abbreviations: VC, vital capacity; MIP, maximal inspiratory pressure; MEP, maximal

expiratory pressure; PaCO2, partial pressure of CO2 in arterial blood; AI, ambulatory index

(details are in the online repository).

Duration of swallowing

Number of swallows

Number of breathing cycles

Coefficient R2 P Coefficient R2 P Coefficient R2 P

VC -0.23 0.05 0.22 -0.22 0.05 0.24 -0.39 0.15 0.03

MIP -0.47 0.22 0.01 -0.56 0.30 0.002 -0.55 0.30 0.002

MEP -0.43 0.19 0.02 -0.43 0.18 0.02 -0.53 0.28 0.004

PaCO2 0.22 0.048 0.29 0.181 0.03 0.39 0.24 0.05 0.25

AI 0.26 0.068 0.17 0.241 0.05 0.20 0.35 0.12 0.06

Dysphagia 0.20 0.04 0.30 0.13 0.018 0.48 0.11 0.012 0.56

29

Table 4. Influence of tracheostomy on the swallowing parameters obtained with the 10-ml

bolus.

No Tracheostomy Tracheostomy n =10 n =19

Duration of swallowing (sec.) 3.1 ± 1.9 4.7 ± 2.0 *

Number of swallows 1.7 ± 1.0 2.7 ± 1.0 *

Number of breathing cycles 1.3 ± 0.4 2.0 ± 0.9 * *: Statistically significant difference between the groups with and without tracheostomy

30

Figure 1

A

B

Rib Cage

Laryngeal Sensor

Submental EMG

Rib Cage

Laryngeal Sensor

Submental EMG

A

B

Rib Cage

Laryngeal Sensor

Submental EMG

Rib Cage

Laryngeal Sensor

Submental EMG

Rib Cage

Laryngeal Sensor

Submental EMG

Rib Cage

Laryngeal Sensor

Submental EMG

Inspiration

Expiration

A

B

Rib Cage

Laryngeal Sensor

Submental EMG

Rib Cage

Laryngeal Sensor

Submental EMG

A

B

Rib Cage

Laryngeal Sensor

Submental EMG

Rib Cage

Laryngeal Sensor

Submental EMG

Rib Cage

Laryngeal Sensor

Submental EMG

Rib Cage

Laryngeal Sensor

Submental EMG

Inspiration

Expiration

31

Figure 2:

0

1

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ec.)

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32

Figure 3

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33

Figure 4:

A

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5 10 150

1

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4

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of sw

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lus

Volume (ml)

AN

OV

A: P

= 0.

0007

ANOVA : P = 0.0009

2

4

6

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0001

ANOVA : P = 0.0029

Tot

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(sec

)

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Tot

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)

34

Breathing-Swallowing Interaction in Neuromuscular Patients:

a Physiological Evaluation

Nicolas TERZI, David ORLIKOWSKI , Philippe AEGERTER,

Michèle LEJAILLE, Maria RUQUET, Gérard ZALCMAN ,

Christophe FERMANIAN, Jean-Claude RAPHAEL and Frédéric LOFASO.

Online data supplement

35

METHODS

Study population

We studied 10 healthy volunteers and 29 consecutive patients with neuromuscular

disorders responsible for respiratory muscle weakness with a vital capacity (VC) less than

60% but no episodes of acute respiratory failure within the last 2 months. Patients were

recruited between November 2005 and June 2006 during routine follow-up visits at the

Raymond Poincaré teaching hospital, whereas healthy volunteers were recruited among

hospital staff members. The healthy volunteers had no history of dysphagia or pulmonary

disease. All study participants provided informed consent. The study was approved by the

relevant ethics committee (Hôpital A. Paré, Paris, France). Values of the nutritional and

respiratory variables measured in the patients during the study are reported in Table E1.

Study procedures

Clinical evaluation

Dysphagia was graded as previously described by Ertekin et al.(1): Grade 1, no

clinical signs or symptoms of dysphagia; Grade 2, very mild dysphagia suspected by clinical

examination with no complaint of dysphagia from the patient; and Grade 3, the patient

complains of dysphagia, and this is supported by other clinical signs, but non-oral feeding is

not necessary at the time of investigation. Grade 4 dysphagia requires non-oral feeding and

therefore was a noninclusion criterion in our study.

The Hauser Ambulation Index (Table E2) was used to evaluate disability (2). All

patients were examined by an otolaryngologist, who confirmed the absence of abnormal

anatomical obstruction of the upper airway and of severe maxillofacial deformity.

36

Pulmonary function tests

All tests were conducted in a single session. All patients were investigated in the seated

position, and some of the patients were also investigated in the supine position. Spirometry

variables and lung volumes were measured using a Vmax 229 Sensormedics System

(Sensormedics, Inc., Anaheim, CA) according to standard guidelines (3).

Maximal static inspiratory and expiratory mouth pressures were measured using a

flanged mouthpiece at FRC and total lung capacity (TLC), respectively. The patient sat in

front of the computer screen. Each effort was accompanied with strong verbal encouragement

and visual feedback.

All signals were measured using a differential pressure transducer (Validyne, MP45,

Northridge, CA), amplified by a carrier amplifier (Validyne), and passed via an analogue-

digital board to a computer running AcqKnowledge software (Biopac System, Goleta, CA).

We used the highest recorded value of maximal static expiratory mouth pressure (MEP) and

maximal inspiratory mouth pressure (MIP).

Laboratory tests

Arterial blood gas levels were measured in capillary samples taken from the radial

artery after local anesthesia (lidocaine prilocaine, Emla®, Astra) and analyzed immediately

(Radiometer ABL 330, Tacussel, Copenhagen, Denmark).

The serum concentrations of albumin, pre-albumin, and C-reactive protein were

measured from venous blood samples.

Experimental set-up

Respiratory inductive plethysmography ((RIP) Respitrace Plus-Non Invasive

Monitoring-Systems, Ardsley, NY) was used to determine the thoracic and abdominal

contributions to tidal volume (VT). RIP coils were positioned around the chest above the

37

nipple line and around the abdomen at the umbilical level. As previously described for

neuromuscular patients (4), RIP was calibrated using the semi-quantitative single-position

method during natural breathing (Qualitative Diagnostic Method (5)), as well as using the

integrated flow signal of a Fleisch # 1 pneumotachometer (Lausanne, Switzerland) connected

to the mouth or the tracheostomy tube. The patient wore a noseclip and was examined for

leaks around the mouth and around the tracheostomy tube. This calibration was confirmed by

isovolumic maneuvers (6) if possible. We assumed a two-degrees-of-freedom model of the

chest wall and abdomen in which these two compartments defined lung expansion.

Swallowing was monitored noninvasively, using electromyography (EMG) to detect

submental muscle complex (mylohyoid, geniohyoid, and anterior digastric muscle) activity

via skin-surface electrodes on the chin, as well as a piezoelectric sensor placed between the

cricoid and thyroid cartilages on the midline, as determined by palpation, to detect laryngeal

motion (7-10) (see Figure 1). This piezoelectric sensor was originally a leg-movement-

detection device intended for sleep studies (Limb Movement Sensor System, Sleepmate

Technologies, Midlothian, VA) and was stripped of all its components except the sensor.

All signals were digitized at 1000 Hz and recorded directly on a personal computer

equipped with the MP 100 data-acquisition system (Biopac Systems, Santa Barbara, CA).

Signals were filtered (bandpass 45 to 55 Hz) and amplified. The system software

(AcqKnowledge) was configured so that the EMG signal, laryngeal movement signal, and

thoracic and abdominal movement signals were displayed simultaneously on separate

channels.

Experimental protocol

The study participants were seated comfortably in their usual breathing condition for

meals, i.e., in a chair for the healthy volunteers, in bed for 14 patients, in their usual

wheelchair for 12 patients, and in an armchair for the 3 remaining patients. The experiment

38

was started after a period of quiet breathing. The head was maintained in the neutral position

to avoid bias due to effects of position on swallowing (11) and to ensure homogeneity of the

recordings. Water boluses were placed in the mouth using a syringe, allowing us to be sure of

the bolus volume and to reduce the influence of fatigue caused by sipping. Three bolus sizes

were used (5, 10, and 15 ml), in random order. Four sets of three boluses were studied, taking

care not to use the same bolus size twice consecutively. The study participants were blinded

to bolus size. They were instructed to swallow normally while trying to be as efficient as

possible. The tracheostomized patients who could breathe spontaneously were tested during

both SB and MV, in random order.

In tracheostomized patients who were recorded in both conditions (MV,SB), we

evaluated dyspnea using the Borg scale (12) at the end of the tests in each condition. The

Borg scale is a vertical line that has gradations from 0 to 10, with each value corresponding to

a verbal descriptor of respiratory sensation. Care was taken to minimize the influence of

investigator bias on the subjects’ perceived dyspnea.

Data analysis

When tracings were evaluated, the observer was blinded to the randomization results

and therefore to bolus size. Unfortunately, the observer could easily differentiate patients

from healthy subjects and detect the use of mechanical ventilation. Therefore, the assessment

was not fully blinded.

Swallowing onset was defined as the onset of phasic submental EMG activity and

swallowing termination as the beginning of the downward laryngeal movement detected by

the piezoelectric sensor (7). For each bolus size, we recorded the duration of swallowing,

number of swallows, and number of breathing cycles. Respiratory movement direction

(inspiration or expiration) immediately before and immediately after each swallow was

39

recorded, and for each patient the percentages of swallows preceded by expiration and of

swallows followed by expiration were computed.

40

REFERENCES

E1. Ertekin C, Aydogdu I, Yuceyar N, Kiylioglu N, Tarlaci S,Uludag B.

Pathophysiological mechanisms of oropharyngeal dysphagia in amyotrophic lateral sclerosis.

Brain 2000;123 ( Pt 1):125-140.

E2. Hauser SL, Dawson DM, Lehrich JR, Beal MF, Kevy SV, Propper RD, Mills

JA,Weiner HL. Intensive immunosuppression in progressive multiple sclerosis. A

randomized, three-arm study of high-dose intravenous cyclophosphamide, plasma exchange,

and ACTH. N Engl J Med 1983;308:173-180.

E3. Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R,Yernault JC. Lung

volumes and forced ventilatory flows. Report Working Party Standardization of Lung

Function Tests, European Community for Steel and Coal. Official Statement of the European

Respiratory Society. Eur Respir J Suppl 1993;16:5-40.

E4. Perez A, Mulot R, Vardon G, Barois A,Gallego J. Thoracoabdominal pattern of

breathing in neuromuscular disorders. Chest 1996;110:454-461.

E5. Sackner MA, Watson H, Belsito AS, Feinerman D, Suarez M, Gonzalez G, Bizousky

F,Krieger B. Calibration of respiratory inductive plethysmograph during natural breathing. J

Appl Physiol 1989;66:410-420.

E6. Konno K,Mead J. Measurement of the separate volume changes of rib cage and

abdomen during breathing. J Appl Physiol 1967;22:407-422.

E7. Ertekin C, Pehlivan M, Aydogdu I, Ertas M, Uludag B, Celebi G, Colakoglu Z,

Sagduyu A,Yuceyar N. An electrophysiological investigation of deglutition in man. Muscle

Nerve 1995;18:1177-1186.

E8. Ertekin C, Aydogdu I,Yuceyar N. Piecemeal deglutition and dysphagia limit in normal

subjects and in patients with swallowing disorders. J Neurol Neurosurg Psychiatry

1996;61:491-496.

41

E9. Ertekin C, Aydogdu I, Yuceyar N, Tarlaci S, Kiylioglu N, Pehlivan M,Celebi G.

Electrodiagnostic methods for neurogenic dysphagia. Electroencephalogr Clin Neurophysiol

1998;109:331-340.

E10. Ertekin C, Yuceyar N,Aydogdu I. Clinical and electrophysiological evaluation of

dysphagia in myasthenia gravis. J Neurol Neurosurg Psychiatry 1998;65:848-856.

E11. Ertekin C, Keskin A, Kiylioglu N, Kirazli Y, On AY, Tarlaci S,Aydogdu I. The effect

of head and neck positions on oropharyngeal swallowing: a clinical and electrophysiologic

study. Arch Phys Med Rehabil 2001;82:1255-1260.

E12. Borg GA. Psychophysical bases of perceived exertion. Med Sci Sports Exerc

1982;14:377-381.

42

Figure legends Figure E1: Experimental condition in one of the study patients. The patient gave permission

to publish her photograph.

43

Table E1. Nutritional and respiratory variables in the 29 patients with neuromuscular

disorders and chronic respiratory failure.

# Vent. Condition

Duration of mechanical ventilation

Type of tracheostomy

tube

VC (seated)

VC (supine) MEP/MIP PaCO2

SB/MV BMI prealb/alb

(hours/day) Type/n° (% ) (% ) (cm H2O) (mm Hg) Kg/m2 (g/L)

1 SB N No 60 58 36/46 39/ND 24.3 0.16/38 2 SB N No 59 ND 19/38 37/ND 20.7 0.29/40 3 SB 10/24 h No 43 18 41/28 46/35 25.4 0.32/44 4 SB 8/24 h No 41 36 33/34 42/38 24.4 0.27/41 5 SB 8/24 h No 37 ND 30/15 ND/52 16.0 0.4/41 6 TSB+ 20/24 h Bivona/n°8 25 ND 50/40 44/35 14.3 0.22/31 7 TSB+ 12/24 h Tracoe/n°10 24 13 42/20 43/ND 13.4 0.21/35 8 SB 10/24 h No 24 23 30/33 40/30 21.3 0.23/40 9 TSB+ 22/24 h Tracoe/n°8 20 14 17/15 ND/26 24.1 NA/43 10 SB 8/24 h No 20 16 46/29 48/34 27.8 0.32/40 11 SB 8/24 h No 17 ND 30/35 46/32 19.0 0.25/42 12 TSB+ 12/24 h Tracoe/n°8 17 ND 25/20 52/28 25.7 0.25/41 13 TSB+ 22/24 h Tracoe/n°8 13 ND 5/10 ND/39 13.4 0.18/38 14 TSB+ 12/24 h Cliny/n°6 13 ND 10/10 40/35 14.8 0.23/34 15 TSB+ 22/24 h Cliny/n°6 13 ND 8/3 ND/35 16.2 0.22/43 16 TSB+ 7/24 h Tracoe/n°8 13 ND 15/13 56/27 21.2 0.26/44 17 SB 18/24 h No 12 ND 75/50 40/34 12.6 0.2/39 18 TSB+ 20/24 h Tracoe/n°8 12 ND 20/25 46/42 17.1 0.27/43 19 SB 8/24 h No 11 ND 10/12 48/ND 10.8 0.23/44 20 TSB+ 20/24 h Tracoe/n°10 10 ND 18/20 65/30 27.3 0.31/45 21 TSB- 24/24 h Cliny/n°5.5 10 ND ND/ND ND/19 28.4 0.25/41 22 TSB- 24/24 h Tracoe/n°7 10 ND 10/20 ND/26 14.5 0.36/41 23 TSB+ 21/24 h Tracoe/n°8 9 ND 10/10 53/34 18.2 0.36/47 24 TSB- 24/24 h Tracoe/n°8 9 ND <5/<5 ND/38 17.9 0.14/24 25 TSB- 24/24 h Tracoe/n°8 8 ND 10/15 ND/36 17.1 0.36/39 26 TSB- 24/24 h Tracoe/n°8 8 ND 8/5 ND/27 22.0 0.27/42 27 TSB- 24/24 h ND 8 ND 10/15 ND/47 9.0 0.22/47 28 TSB- 24/24 h Rusch/n°8 7 ND 10/5 ND/39 18.0 0.36/39 29 TSB- 24/24 h Tracoe/n°8 0 ND 0/0 ND/28 31.3 0.18/37

44

Abbreviations: VC, vital capacity; MIP, maximal inspiratory pressure; MEP, maximal expiratory

pressure; PaCO2, partial pressure of CO2 in arterial blood; ND, not done.

Vent. Condition, ventilation condition. Ventilation conditions were SB, spontaneous breathing;

TSB+, tracheostomized patients able to breathe spontaneously; and TSB-, tracheostomized patients

unable to breathe spontaneously.

Type of tracheostomy tubes: Bivona, Collin ORL, Cachan, France Tracoe, Pouret Medical, Clichy, France Rusch, Teleflex Medical, Le Faget, France Cliny, Ansell, Cergy-Pontoise, France

45

Table E2: Hauser Ambulation Index ((2))

*The use of a wheelchair may be determined by lifestyle and motivation. It is expected that patients in Grade 7 will use a wheelchair more frequently than those in Grade 5 or 6. Assignment in the range of 5 to 7, however, is determined by the patient’s ability to walk a given distance, and not by the extent to which by the patient uses a wheelchair.

0 Asymptomatic; fully active.

1 Walks normally, but reports fatigue that interferes with athletic or other demanding activities.

2 Abnormal gait or episodic imbalance; gait disorder is noticed by family and friends; able to walk 25 feet (8 meters) in 10 seconds or less.

3 Walks independently; able to walk 25 feet in 20 seconds or less.

4 Requires unilateral support (cane or single crutch) to walk; walks 25 feet in 20 seconds or less.

5 Requires bilateral support (canes, crutches, or walker) and walks 25 feet in 25 seconds or less; or requires unilateral support but needs more than 20 seconds to walk 25 feet.

6 Requires bilateral support and more than 20 seconds to walk 25 feet; may use wheelchair* on occasion.

7 Walking limited to several steps with bilateral support; unable to walk 25 feet; may use wheelchair * for most activities.

8 Restricted to wheelchair; able to transfer self independently. 9 Restricted to wheelchair; unable to transfer self independently.

46

Figure E1