Respiratory Muscle

A s s e s s m e n t i n Cl i n i c a l
Practice
Michael I. Polkey, MB ChB, PhD, FRCP

KEYWORDS
 Diaphragm  Sniff nasal inspiratory pressure  Magnetic phrenic nerve stimulation
 Expiratory muscle strength

KEY POINTS
 Inspiratory muscle weakness should always be considered in unexplained breathlessness, respira-
tory failure, or an inability to wean from mechanical ventilation.
 Inspiratory muscle weakness can often be excluded by simple tests.
 Inspiratory muscle strength is a continuous variable. Even where proven neuromuscular disease ex-
ists, values may be normal.
 Expiratory muscle weakness is prevalent in neurologic disease and increases susceptibility to chest
infections.

INTRODUCTION identical at a molecular level to, for example, the

Respiratory muscle weakness is relatively rare in
clinical practice and, therefore, it is seldom a clini-
cian’s first thought. However, it should always
be considered where a patient has unexplained
breathlessness see, for instance, cases # 5
and #6 Unraveling the Causes of Unexplained
Dyspnea: The Value of Exercise Testing, respira-
tory failure, or experiences difficulty weaning from
mechanical ventilation (see also in The Control of
Breathing during Mechanical Ventilation). Partic-
ular vigilance must be exercised when managing
patients with known neuromuscular disease. The
aim of this article was to explain normal physiology
and suggest a hierarchical approach whereby res-
piratory muscle weakness may be excluded or
included in the differential diagnosis.
Normal Physiology
Unlike cardiac muscle, which has an inherent
rhythmicity, respiratory muscle is histologically
and functionally composed of skeletal muscle,
quadriceps. The inspiratory muscles contract
only in response to signals received via motor
nerves, of which the most important are the 2
phrenic nerves, which innervate each hemidiaph-
ragm. Automatic control of the respiratory muscles
occurs at the brainstem, which is sensitive in
particular to increasing levels of carbon dioxide,
but can be overridden by the cortex to permit
speech and other functions. Importantly, all voli-
tional tests of respiratory muscle function require
intact cortical function and subnormal values are
obtained where cortical disease is present or
where the patient is unable (or indeed unwilling)
to make a fully maximal effort.
All volitional tests of respiratory muscle func-
tion require intact cortical function and sub-
normal values are obtained where cortical
disease is present or where the patient is unable
(or indeed unwilling) to make a maximal effort.
chestmed.theclinics.com

Disclosure Statement: Dr M.I. Polkey discloses personal and or institutional financial support for advice or
research, lecture fees from the following companies: Novartis, Biomarin, Amicus, Orion, GSK, and Genzyme-
Sanofi.
Department of Respiratory Medicine, Royal Brompton & Harefield NHS Foundation Trust, Fulham Road, Lon-
don SW3 6NP, UK
E-mail address: m.polkey@rbht.nhs.uk

Clin Chest Med 40 (2019) 307–315

https://doi.org/10.1016/j.ccm.2019.02.015
0272-5231/19/Ó 2019 Elsevier Inc. All rights reserved.
308
Fig. 1. Overview of normal physiology (blue); measurement opportunities indicated by red arrows. EMG, electro-
myogram; USS, ultrasound scan.
Anatomically, the inspiratory muscles are
composed of the 2 hemidiaphragms and the extra-
diaphragmatic muscles (scalenes, sternomastoid,
and intercostals). Traditionally, the diaphragm is
thought to account for 60% to 70% of lung volume
change,1 but there is sufficient capacity in the non-
diaphragmatic muscles that patients with bilateral
diaphragm paralysis can manage without ventila-
tory support.2 During inspiratory muscle contrac-
tion, the dome of the diaphragm is pulled caudally,
which increases lung volume both through its own
craniocaudal movement, but also through outward
movement of the rib cage mediated by transmission
of the rising intrabdominal pressure through the
zone of apposition.3 The increased volume within
the thorax leads to a subatmospheric pressure,
which in turn results in inward airflow. Expiration is
passive at rest in normal humans, but may be
increased, in the absence of flow limitation,4 by
expiratory muscle contraction. Expiratory muscles
are also necessary to generate the supraatmo-
spheric intrathoracic pressures associated with an
effective cough.5 Understanding physiology in turn
leads to identification of the ways in which respira-
tory muscle strength may be measured (Fig. 1).
During inspiratory muscle contraction, the dome
of the diaphragm is pulled caudally, which in-
creases lung volume (60%–70% of total change
at rest) through (a) its own craniocaudal move-
ment and (b) outward movement of the rib cage
mediated by transmission of the rising intrabdo-
minal pressure through the zone of apposition.
Because the respiratory muscles are striated
skeletal muscle, they are influenced by factors
known to influence other skeletal muscles. Of
these factors, the most important is length; in
isolated skeletal muscle, there is an optimal
length at which tension is generated and lower
tensions are elicited at lengths shorter, and to
some extent, longer than this6; in practice, in
human respiratory muscle the greatest pressures
are elicited close to the residual volume and
the lowest at total lung capacity,7 so reduced
tension generation owing to lengthening is
not an issue. Shortening of the diaphragm is
a consequence of hyperinflation that accom-
panies chronic obstructive pulmonary disease.
Hyperinflation also decreases the effective trans-
mission of tension to reduce intrathoracic pres-
sure and reduces the size of the zone of
apposition.
Clinical Causes of Respiratory Muscle
Weakness
The causes of respiratory muscle weakness are
summarized in Table 1. Broadly speaking from
a clinician’s perspective, respiratory muscle
weakness may either be a known and anticipated
feature of an existing diagnosis (eg, as in
muscular dystrophy) or may be a cause of a
new presentation with breathlessness or respira-
tory failure.
Clinical features suggesting respiratory muscle
weakness include breathlessness characteristi-
cally worse when bending forward (eg, when tying
shoelaces or getting out of a car) or lying flat,
 Respiratory Muscle Assessment in Clinical Practice 309

Table 1
Causes of respiratory muscle weakness

Pathology Nerve Neuromuscular Junction Muscle

Amyotrophic lateral sclerosis Myasthenic syndromes Muscular dystrophies
Guillain Barre Botulism ICUAW
ICUAW Lambert Eaton syndrome Pompes (Acid Maltase def.)
Enevnomation Poisoning (nerve agents) Hypokalemia/other biochemical
Polio
by speed of onset Rapid Onset (h/d) Slow Onset (mo/y)
Evenomation Past polio syndrome
Guillin Barrre Muscular dystrophies
Myasthenic decompensation Amyotrophic lateral sclerosis
Hypokalemia/other biochemical Pompes
Acute polio
Poisoning (nerve agents)
Organophosphates
ICUAW

Abbreviation: ICUAW, intensive care unit–acquired weakness.

although the latter can be feature of other cardio-
respiratory conditions. Classically, patients with
diaphragm weakness are more breathless in wa-
ter,8 although many patients referred for assess-
ment do not swim for other reasons. An
examination may yield signs consistent with
more generalized neurologic disease, but the car-
dinal feature of isolated diaphragm weakness—
paradoxic abdominal motion—is only present
where intact extradiaphragmatic muscles remain.
J. Alberto Neder and colleagues’ article,
“Incorporating Lung Diffusing Capacity for
Carbon Monoxide in Clinical Decision Making in
Chest Medicine,” in this issue).10
Chest radiography may show elevation of one or
both hemidiaphragms, although the latter is diffi-
cult to distinguish from a submaximal inspiration.
Chest radiography is only moderately predictive
of hemidiaphragm function when judged against
the gold standard of phrenic nerve stimulation.11

Clinical features suggesting respiratory muscle
weakness include breathlessness characteristi-
cally worse when bending forward (eg, when
tying shoelaces or getting out of a car) or lying
flat although the latter can be feature of other
cardiorespiratory conditions.
Standard Clinical Investigations
Respiratory muscle weakness is associated with a
reduced vital capacity, which occurs because
inspiratory muscle weakness decreases total
lung capacity and expiratory muscle weakness in-
creases residual volume. Clinician should be
aware that substantial inspiratory muscle weak-
ness may be present with a near normal vital ca-
pacity.9 The normal change in vital capacity on
adopting the supine position (<20%) may be
increased in respiratory muscle weakness and an
unequivocally normal supine vital capacity ex-
cludes important respiratory muscle weakness.
The lung transfer factor for carbon monoxide is
typically reduced but its coefficient adjusted for
lung volume is classically supernormal (see also
Bedside Tests
Bedside measurement of respiratory muscle
strength can be obtained by measuring pressure.
Classically, pressure is measured during a
maximal inspiratory effort against a closed shutter
(maximum inspiratory pressure) undertaken near
the residual volume and during an expiratory effort
(maximum expiratory pressure) undertaken at total
lung capacity. The American Thoracic Society
guidelines stipulate that the highest 1-second
average be recorded, as opposed to the highest
individual pressure12 (Fig. 2). An alternative test
of inspiratory muscle function is the sniff nasal
inspiratory pressure, which intuitively one might
imagine is easier for patients to do; unlike the
static maneuver, the highest single value observed
is recorded. Limits of agreement between the sniff
nasal inspiratory pressure and maximum inspira-
tory pressure are wide13,14 and thus both tests
can be used together on the basis that it is impos-
sible to get a falsely high result. Several reference
equations are available to define normality but
Rodrigues and colleagues15 showed recently that
3 of the equations available provided the best
310 Polkey
Fig. 2. Measurement of maximum inspiratory (A) and expiratory (B) mouth pressures. (From American Thoracic
Society/European Respiratory Society. ATS/ERS Statement on respiratory muscle testing. Am J Respir Crit Care
Med 2002;166(4):518–624.)
correspondence to patients with a phenotype of
inspiratory muscle weakness.
Advanced Tests
Pressures
Greater insight into the performance of the respira-
tory muscles can be obtained by measurement of
intrathoracic pressure by measurement of pres-
sure in the esophagus (Poes). This is often com-
bined with measurement of pressure in the
stomach (Pgas) and the arithmetical difference
Pgas–Poes is the transdiaphragmatic pressure
(Pdi). Although Poes and Pdi can be measured dur-
ing both static and sniff maneuvers, for the assess-
ment of strength they seldom offer an advantage
over noninvasive measurements (indeed this is
the basis for validating noninvasive measures).
Occasionally, however, nasal obstruction (owing
to polyps) or glottic dysfunction (common in
some neurologic diseases) can result in significant
underestimation of intrathoracic pressure by nasal
or mouth pressure measurements.
Continuous monitoring of pressures during a
stress (eg, exercise) can provide insights into respi-
ratory mechanics. The work done by the respiratory
muscles, if expressed as a product of pressure and
time (pressure–time product) can then be used to
measure the impact of therapeutic interventions,
such as noninvasive ventilation (Fig. 3).
Greater insight into the performance of the res-
piratory muscles can be obtained by measure-
ment of intrathoracic pressure: Poes, in the
stomach (Pgas) and the arithmetical difference
(Pgas–Poes) representing Pdi.
Phrenic nerve stimulation (PNS) can test the
function of the nerve–diaphragm unit. PNS was
originally undertaken with electrical stimulation,
but reproducible values are hard to achieve even
in experienced hands16 and, except where the pa-
tient has implanted ferrous metal, has been super-
seded by magnetic nerve stimulation. A detailed
discussion of this technique is beyond the scope
of this review (fuller details may be found in Man
and colleagues17), but briefly a strong magnetic
field is created over the phrenic nerve that induces
a nerve impulse that travels to the diaphragm. The
operator may then measure either the pressure
change termed twitch Pdi (Tw Pdi) or the action po-
tential elicited by diaphragm contraction (dis-
cussed elsewhere in this article). Stimulation may
be given to one or the other phrenic nerve in isola-
tion or to both nerves together. The indications for
PNS are shown in Box 1. The unpotentiated the
Tw Pdi in healthy adults, depending to some extent
on the technique used should be greater than 18 to
20 cm H2O and for unilateral stimulation
values greater than 7 cm H2O may be considered
normal; the effect of age is modest,18 but normal
values in the very elderly remain unknown. Where
the technique is used to follow sequential change
(with disease or treatment) or to detect fatigue it
is important to rigorously control for the other fac-
tors that affect Tw Pdi, principally prior contractile
activity19 (a phenomenon termed potentiation)
and lung volume.20 Fig. 4 shows an example of
pressures elicited by bilateral PNS in a patient
with chronic obstructive pulmonary disease.
As is the case with the sniff the esophageal
pressure elicited by PNS may be measured in
the upper airways as twitch mouth pressure,21 or
in intubated patients as endotracheal or tracheot-
omy pressure.22 One problem with this approach
 Respiratory Muscle Assessment in Clinical Practice
Fig. 3. The areas subtended by Poes (broad dashed
line). Pgas (dots), and Pdi (short dashed line) can be
measured to calculate the pressure–time product.
Flow is shown with the solid line and is necessary
to separate inspiratory and expiratory phases. (A) A
patients with chronic obstructive pulmonary disease
at rest. (B) The same patient at the end of exercise.
(C) The same patient at the end of a similar exercise
task where breathing was supported by noninvasive
ventilation, with a demonstrable decrease in res-
piratory muscle work. (Reproduced with permission
of the Ó ERS 2019. From Kyroussis D, Polkey MI,
Hamnegard CH, et al. Respiratory muscle activity in
patients with COPD walking to exhaustion with
and without pressure support. Eur Respir J. 2000
Apr;15(4):649–55.)
is that, as noted, the esophageal component of Tw
Pdi is disproportionately influenced by lung volume
change so this variable must be carefully
controlled.
Box 1
Indications for phrenic nerve stimulation
studies
 Measurement of phrenic nerve conduction
time (in demyelinating neuropathies)
 Evaluation of hemidiaphragm function
 Evaluation of bilateral diaphragm function
where
 Submaximal patient effort is suspected
 Patient cooperation is impossible (eg,
intensive care unit, cognitive difficulties)
311
Magnetic phrenic nerve stimulation can be used
to follow sequential change (with disease or
treatment) or to detect fatigue. However, it is
important to rigorously control for factors
such as prior contractile activity (potentiation)
and lung volume, which can interfere with the
pressure change induced by muscle activation
(twitch Pdi)
Electromyogram
Like pressure, the electrical activity of the dia-
phragm may be measured continuously or in
response to stimulation. Electrodes may be
placed on the skin surface,23 in the diaphragm
as a needle, or recorded from the crural dia-
phragm using an esophageal electrode. Needle
electrodes are favored by some neurophysiolo-
gists, but are not widely used in patients with res-
piratory disease because of the fear of
pneumothorax; surface electrodes can be
contaminated by extradiaphragmatic muscles
even where great care is exercised. Conse-
quently, recent studies have favored esophageal
electromyography, which has been reviewed in
detail elsewhere.24 Normal phrenic nerve con-
duction times depend on the stimulation modality
used,25 so it is important to observe local normal
ranges.
When used for continuous monitoring,
diaphragm electromyogram has been used
to demonstrate the relationship between res-
piratory muscle activity and breathlessness in
lung disease and obesity and to show, in
the case of dynamic hyperinflation, that
neural drive, rather than minute ventilation, best
tracks dyspnea,26 leading to the concept of
neuromechanical dissociation (Fig. 5) (further
discussion on the topic is provided in also
discussed in The Pathophysiology of Dyspnea
and Exercise Intolerance in COPD). The tech-
nique has also been used to evaluate upper
airway resistance27 and to adjudicate whether
apneas or central or obstructive in nature during
sleep.28
When used for continuous monitoring, dia-
phragm electromyogram has been used to
demonstrate that, in the case of dynamic hyper-
inflation, inspiratory neural drive, rather than
minute ventilation best tracks intensity of dys-
pnea.
312 Polkey

Fig. 4. Twitch pressures from a patient with severe chronic obstructive pulmonary disease. Note even at func-
tional residual capacity (FRC), the end-expiratory Poes is positive owing to air trapping. Twitches recorded at
increasing lung volumes shows no impact on Tw Pgas but a decrease in Tw Poes and consequently Tw Pdi. (Image
from the author’s own thesis.)

Imaging thickness32 and the shortening during inspiration

can be quantified.33 Ultrasound examination has
As noted, an elevated hemidiaphragm has only a
several features that make it an attractive method
modest relationship with hemidiaphragm function
for assessing respiratory muscle strength; specif-
assessed using phrenic nerve stimulation.11 Ultra-
ically, it is radiation free and suitable for use at
sound examination (and previously fluoroscopy)
the bedside. It has been particularly studied for
can be used to track diaphragm movement, but
the purpose of predicting weaning success; in
this approach is not quantitative and a 6% false-
2014 DiNino and associates34 reported the out-
positive rate for the detection of abnormal move-
comes of 63 patients undergoing mechanical
ment has been reported.29
ventilation. They measured diaphragm thickening
The first identification of the diaphragm using ul-
during a trial of either spontaneous breathing or
trasound was reported in 197930 and was soon fol-
pressure support ventilation and showed that
lowed by the observation that its movement
those able to mount a greater increase (>30%) in
following phrenic nerve stimulation could be
diaphragm thickening with inspiration were more
detected by ultrasound examination.31 Diaphragm
likely to successfully wean. Both diaphragm thin-
thickness, when measured by experienced opera-
ning and decreased excursion occur soon after
tors, has a good relationship with measured
the initiation of mechanical ventilation35 and are
associated with a poor prognosis and a prolonged
stay in the intensive care unit.36 One study has
compared diaphragm ultrasound data with the
endotracheal tube pressure elicited by phrenic
nerve stimulation in critically ill patients; Dubé
and colleagues37 found that the best correlates
of Tw Ptr were thickening and excursion rather
than thickness. Of note, and as might be ex-
pected, data recorded during assist control venti-
lation did not convey prognostic information. Their
cutoff value for diaphragm thickening which indi-
cated a good prognosis was very similar to that
of DiNino and coworkers.
Fig. 5. Data relate breathlessness to the electromyo-
gram (EMG) signal (solid line) and minute ventilation
in a group of patients with chronic obstructive pulmo-
nary disease during an exercise protocol. Because min- Ultrasound examination (and previously fluo-
ute ventilation cannot increase (owing to ventilatory roscopy) can be used to track diaphragm move-
constraints), the relationship with dyspnea is poor, ment. The method can also be used to assess
but well-captured by an EMG. (Data from Jolley CJ, diaphragm thickness and to quantify short-
Luo YM, Steier J, et al. Neural respiratory drive and ening during inspiration.
breathlessness in COPD. E Respir J 2015;45(2):355–64.)
 Respiratory Muscle Assessment in Clinical Practice
Assessment of Respiratory Muscle Function in
Children
Experienced operators can pass esophageal and
gastric balloons in older children to measure respi-
ratory muscle function and mechanics,38 but few
centers globally possess this ability. Therefore,
except for intubated and sedated children in
whom phrenic nerve stimulation is possible,39
minimally invasive tests are preferred. Children
over the age of approximately 6 years are usually
able to undertake the sniff maneuver and normal
values for this age range are available.40,41
Expiratory Muscle Function
Although the expiratory muscles are not used for
quiet respiration in healthy adults, they are acti-
vated during exercise42 and are necessary for
coughing, which serves as a useful protection
against foreign body intrusion into the airway and
for expectoration of secretions. The most wide-
spread method of measuring expiratory muscle
function is as maximum expiratory pressure (dis-
cussed elsewhere in this article), but many units
prefer to measure the peak cough expiratory
flow; reduced values (<270 L/min is used by
many units) are considered to be associated with
an increased risk of chest infection and, conse-
quently, in patients with neuromuscular disease,
an indication for the use of mechanical insuffla-
tion–exsufflation (MI-E), although the threshold
for MI-E is typically <160 L/min.43 However, phys-
iologically speaking, the peak cough expiratory
flow is a slightly unsatisfactory measure because
it is determined also by lung volume and, thus,
inspiratory muscle strength. Alternatives are
cough gastric pressure44 or the whistle mouth
pressure45; although the latter may be attractive
especially for children, users should be aware
that diaphragm tonicity sometimes results in the
imperfect transmission of gastric pressure to the
thorax.5,44 The thoracic nerve roots that innervate
the abdominal muscles can also be stimulated
by magnetic nerve stimulation,5,46 but it would be
unfair to describe this test as routine in clinical
practice. An effective cough is thought to be asso-
ciated with transient supramaximal flow, which
creates shear forces propelling mucus cranially.
Data from patients with amyotrophic lateral scle-
rosis suggest a critical level of strength necessary
to achieve this is a cough Pgas of greater than
50 cm H2O.47
Assessment for Diaphragm Pacing
Although few centers offer diaphragm pacing, it is
of reported value where the connection between
313
the brain and spinal motor neurons is irreversibly
interrupted, but the path of the phrenic nerve itself
is intact; a classical example is a high spinal lesion
as a result of trauma. A demonstration of the integ-
rity of the peripheral nerve is straightforward using
the techniques as described, but assessing the
integrity of the corticospinal pathway was more
problematic. Historically, although electrical stim-
ulation of the cortex was possible,48 the small
size of the diaphragm motor area made the tech-
nique unsuitable for clinical use. However, it has
been reported that magnetic stimulation of the
cortex can reliably detect a corticospinal pathway
that, in some patients, will eventually recover,
rendering a diaphragm pacemaker unnecessary.49
SUMMARY
In general clinical practice, diaphragm weakness
can often be ruled out by careful application of his-
tory, examination, and noninvasive bedside tests.
However, more quantitative tests also exist that
can be of value in the research environment and
for patients requiring sequential assessment. In
conditions where the predominant problem is res-
piratory muscle weakness these tests convey use-
ful prognostic information,36,37,50 which can be
used both for the management of an individual pa-
tient but also to enrich study populations allowing
reduced sample size in clinical trials.
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