©

or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access COPYRIGHT 2022 EDIZIONI MINERVA MEDICA
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© 2022 EDIZIONI MINERVA MEDICA Minerva Medica 2022 June;113(3):460-70

Online version at https://www.minervamedica.it DOI: 10.23736/S0026-4806.22.07974-5

REVIEW
CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Mechanical ventilation and COPD:

from pathophysiology to ventilatory management
Gaetano SCARAMUZZO, Irene OTTAVIANI, Carlo A. VOLTA *, Savino SPADARO

Department of Translational Medicine and for Romagna, University of Ferrara, Ferrara, Italy
*Corresponding author: Carlo A. Volta, Department of Translational Medicine and for Romagna, University of Ferrara, Via Aldo
Moro 8, 44100 Ferrara, Italy. E-mail: vlc@unife.it

A B S T RAC T
In the chronic obstructive pulmonary disease (COPD), lung and chest-wall morphological alterations determine impor-
tant and peculiar approaches to mechanical ventilation. Lung emphysema and reduced elastic recoil increase expiratory
time, thus worsening dynamic hyperinflation, while airways chronic inflammation rises resistances and can determine
distal air-trapping. Muscle wasting and fast fibers prevalence can result in weakness and in an earlier onset of muscle fa-
tigue, prolonging the weaning process. In this narrative review, we explored the connection between altered pathophysi-
ology and necessity for respiratory assistance in COPD, focusing on non-invasive and invasive respiratory management,
lung monitoring and weaning difficulties.
(Cite this article as: Scaramuzzo G, Ottaviani I, Volta CA, Spadaro S. Mechanical ventilation and COPD: from pathophysiol-
ogy to ventilatory management. Minerva Med 2022;113:460-70. DOI: 10.23736/S0026-4806.22.07974-5)
Key words: Pulmonary disease, chronic obstructive; Respiration, artificial; Positive-pressure respiration, intrinsic.

T he chronic obstructive pulmonary disease

(COPD) is a persistent respiratory disease
characterized by respiratory symptoms (i.e., dys-
pnea, cough, and sputum production) and air-
flow obstruction.1 The anatomical modifications
evolve at different rates and chronic respiratory
symptoms may precede the development of air-
flow limitation. Increased airway resistance, air-
flow limitation and impaired elastic recoil can
determine differences in the lung mechanical
properties of these patients as compared to the
non-COPD ones. In the exacerbation of COPD
(COPD), the sudden worsening of these symp-
toms can determine severe airflow limitation,
gas trapping, dynamic hyperinflation, the devel-
opment of intrinsic positive end-expiratory pres-
sure (PEEPi) and acute respiratory failure requir-
ing hospital admission and respiratory support.
Respiratory mechanics in COPD
Airway resistance and airflow obstruction
Airflow obstruction is a key characteristic of
COPD patients. Increased airway resistance of
both central and small airways occurs due to
bronchoconstriction, damage of the elastic tis-
sue in the airways, and mucus hypersecretion
caused by irritation of the epithelium.2 Despite
airflow obstruction is usually diagnosed during
a forced expiratory maneuver from total lung
capacity (FEV1/FVC ratio below 0.7), it can go
undetected when occurring in the small airways,
and patients with normal spirometry may have
an increase in the small airways’ resistance.3
During mechanical ventilation, the increased air-
way resistance can affect both the inspiratory and
expiratory part of the breathing. On one hand,

460 Minerva Medica June 2022

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MECHANICAL VENTILATION IN COPD SCARAMUZZO
during inspiration, narrowed airways produce a
high resistance to flow that can result in higher
peak airway pressures (Ppeak). Despite much of
this pressure is dissipated in providing gas flow
through obstructed airways and therefore does
not directly over-distend distal alveoli, the het-
erogeneous distribution of airflow obstruction,
seen in most airway diseases, can transiently ex-
pose the less obstructed alveolar regions to high-
er pressures and thus to the risk of injury.4 On
the other hand, increased airway resistance may
impair expiration and determine the phenome-
non of expiratory flow limitation (EFL).5 EFL is
characterized by the presence of a reduced expi-
ratory flow which is insensitive to the increase of
expiratory driving pressure.6 Applying an appro-
priate level of positive end-expiratory pressure
(PEEP) may reduce both inspiratory and expira-
tory resistances by stabilizing the small airways.
EFL and airway closure
EFL is a dynamic condition in which an increase
in expiratory driving pressure and / or expiratory
muscle activity does not increase the expiratory
flow, that has already reached its maximum value
(and therefore is “limited”). This condition can
worsen dynamic pulmonary hyperinflation, in-
crease muscular load, and impair hemodynamic
stability.7 In mechanically ventilated COPD pa-
tients, EFL is common for both the increase of
expiratory airway resistance and the reduction
of the lung elastic recoil. The reduction of expi-
ratory time, due for example to tachypnea, will
amplify this phenomenon, and increase dynamic
hyperinflation. Therefore, the end-expiratory
lung volume can increase proportionally to re-
spiratory rate and tidal volume and inversely to
expiratory time.8 The main mechanism causing
EFL is the increase of airway resistance which
can be furtherly enhanced by the dynamic airway
narrowing during expiration. When intrathoracic
pressure equals intrabronchial pressure (equal
pressure point, EPP or “chock point”) airways
downstream could be compressed if they lost
their rigidity. In this situation, when the pressure
outside the airways is higher that the pressure in-
side, the airways collapses, leading to airway clo-
sure9 and determining distal air-trapping.10 EFL
can occur also in during postoperative respiratory
Vol. 113 - No. 3 Minerva Medica 461
failure or in critically ill patients under mechani-
cal ventilation,6 postoperative respiratory failure
and in the acute respiratory distress syndrome
(ARDS).9 In these cases, EFL is mostly related to
increased airways resistance due to physiological
changes with age, body position11 but also to oe-
dema, fluid overload, use of muscle relaxant and
sedatives.12 Cumulative fluid balance seems to
contribute to flow limitation occurrence in criti-
cally ill patients, probably due to small airways
damage edema, and 17% of patients not affected
by EFL becomes flow-limited during the first 72
h of intensive care unit (ICU) stay.6 Several tools
exist to assess the presence of EFL. In sponta-
neously breathing patients, the application of a
negative expiratory pressure to the mouth (NEP)
could predict dyspnea and the risk of exacerba-
tion13 and worsening of dynamic hyperinfla-
tion.14, 15 In patients undergoing mechanical ven-
tilation, EFL can be assessed performing a PEEP
test, by increasing the expiratory driving pressure
through a sudden reduction of PEEP.16 The PEEP
withdrawal determines an increase of expiratory
driving pressure, since in the first expiration af-
ter PEEP reduction an extra amount of volume
must be exhaled (corresponding to the cmH2O of
pressure reduction). Hypothetically, if the patient
does not have EFL, the expiratory flow in the
first act after PEEP reduction should increase. On
the contrary, when EFL is present, the expiratory
curves of the two acts (before and after PEEP re-
duction) overlap on the flow-volume loop.17
Lung compliance, emphysema, and hyperinfla-
tion
For the elastic fibers disruption and the conse-
quent emphysema, lung compliance in COPD is
usually higher than expected and the increased
lung compliance leads to a re-setting of the respi-
ratory system’s relaxation volume to a higher lev-
el than in age-matched healthy individuals.18 This
phenomenon has been called “static” hyperinfla-
tion. Furthermore, a decrease of the elastic recoil
determined by the alveolar walls’ destruction will
reduce also expiratory flow and increase the time
needed to complete expiration. When expiration
is not complete, the end-expiratory lung volume
can increase (“dynamic” hyperinflation)19 until
the increased elastic recoil determined by an in-
 ©
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cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary information of the Publisher.
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically
to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove,
SCARAMUZZO MECHANICAL VENTILATION IN COPD
creased lung volume will allow a complete ex-
piration. The increase of expiratory lung volume
determined by dynamic hyperinflation will deter-
mine the presence of an intrinsic positive end-ex-
piratory pressure, called intrinsic PEEP or auto-
PEEP.7 This means that, while in healthy subjects
the alveolar pressure at the end of expiration is
zero, in patients with dynamic hyperinflation the
alveolar pressure remains positive throughout the
entire expiration. This will determine important
consequences in both passively ventilated and
assisted patients. In passive patients, dynamic
hyperinflation leads to an increase of static strain
and therefore to an increased risk of barotrauma
and hemodynamic instability while in assisted
patients, it will increase the force needed to trig-
ger the ventilator and therefore the occurrence of
patient-ventilator dyssyncrony.20
Oxygen support
and ventilatory strategies
High flow nasal oxygen
High flow nasal oxygen (HFNO) provides high
flow, humidified and heated oxygen mixture
through nasal cannula (HFNC)21 or tracheostomy
(HFTO)22 with a flowrate that generally goes from
30 L/min to more than 60 L/min. HFNC can be
used to support patients affected by exacerbation
of COPD (COPD) not requiring immediate ven-
tilatory support. HFNC therapy at 30 L/min has
shown to improve oxygenation, reduce respira-
tory rate and inspiratory effort.23 Lee et al.24 ran-
domized 88 patients with moderate hypercapnic
respiratory failure due to COPD to receive either
non-invasive ventilation (NIV) (N.=44) or HFNC
35L/min (N.=44) and found no differences in in-
tubation rate, respiratory failure and 30 days mor-
tality and the same result was confirmed by other
retrospective analysis.25 HFNC benefit effect can
be determined by an increased secretions clear-
ance,26 carbon dioxide (CO2) washout27 and may
have a small effect on end-expiratory lung vol-
ume.28, 29 Nevertheless, the advantages of HFNO
are still debated when used through a tracheos-
tomy. In a recent trial on tracheostomized patients
at high risk of weaning failure, HFTO did not
improve neuro-ventilatory drive, work of breath,
respiratory rate and gas exchange compared with
462 Minerva Medica June 2022
conventional O2.22 This can be explained by the
“braking effect” of HFNC, which is removed
when bypassing the upper airways. This mecha-
nism is confirmed by the restore of the benefic ef-
fects of HFTO when an expiratory resistance was
added to the device.30
Non-invasive ventilation
NIV can be considered the first line treatment in
patients with COPD requiring ventilatory sup-
port. NIV can be delivered through nasal-mouth
interface, total face mask or helmet and is use-
ful in reducing respiratory muscle load, fatigue
and improving gas exchanges.31 Indeed, NIV can
unload the respiratory muscle and relieve breath-
lessness, thus reducing CO2 production and dy-
namic hyperinflation. The improvement in alveo-
lar ventilation and gas exchanges results in a pro-
gressive improvement of neurological and respi-
ratory function without the detrimental effects of
endotracheal intubation. The noninvasive treat-
ment of hypercapnic respiratory failure patients
started in the late 1980s32 and quickly demon-
strated its superiority to endotracheal intubation
in supporting these patients.33 Indeed, several
RTCs demonstrated its usefulness in decreasing
mortality, need for invasive mechanical ventila-
tion, hospital stay, and pulmonary complications
compared to standard therapy.33-35 Furthermore,
the failure of NIV and the subsequent intubation
does not increase the mortality risk as compared
to patients in which intubation as the first line of
treatment.36 Usually, noninvasive ventilation is
used as a first step in COPD needing ventilatory
support, but it can be supplied also after extuba-
tion. When used immediately after the patient’s
extubation,37 NIV has been shown to reduce
the re-intubation rate and increase the weaning
success. Despite NIV has changed the outcome
of COPD patients in the last decades, there is a
considerable variation among different centers,
due to different ventilatory strategies and inter-
faces.38 Education strategies are fundamental to
improve the uptake of noninvasive ventilation
and may homogenize outcomes among differ-
ent centers. An ongoing trial (NCT04206735) is
evaluating if online education can be comparable
to interprofessional education in NIV training.39
Finally, NIV can be used to relieve dyspnea and
 ©
or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access COPYRIGHT 2022 EDIZIONI MINERVA MEDICA
cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary information of the Publisher.
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically
to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove,
MECHANICAL VENTILATION IN COPD SCARAMUZZO
to manage breathlessness in patients with ad-
vanced COPD in the palliative care setting.40
Invasive mechanical ventilation
Endotracheal intubation and invasive mechanical
ventilation (IMV) is indicated when NIV ven-
tilation is not feasible (e.g. unconscious patient)
or as a secondary step when NIV fails (e.g., for
severe respiratory acidosis, severe dyspnea with
tachypnea, muscular fatigue, compromised neu-
rological status, hemodynamic instability). The
early aim of IMV is not to normalize blood gases
but to prevent the complications related to dy-
namic hyperinflation and maintain an acceptable
pH.41 Endotracheal intubation requires the use of
muscle relaxant, and therefore a variable time of
controlled (passive) mechanical ventilation is in-
evitable. Since controlled mechanical ventilation
(CMV) requires the continuous administration of
muscle relaxant and/or high dosages of sedatives,
which can contribute to muscle atrophy42 and pro-
long the weaning process, it must be as short as
possible. In CMV, tidal volume (VT), respiratory
rate (RR), I:E ratio (i.e., inspiration to expiration
time) and PEEP must be chosen cautiously; each
of these variables has impact, indeed, on dynamic
hyperinflation, expiratory flow limitation and
overdistension and can therefore determine and/
or increase lung damage (ventilator induced lung
injury [VILI]).43-45 Ventilation with a tidal volume
of 6 mL/kg of ideal body weight has shown to de-
crease VILI.46 However, the acceptable tidal vol-
ume depends on the underlying disease. In severe
ARDS with low lung compliance, tidal volume
should probably be lower than 6 mL/kg while in
less severe conditions and in higher compliance,
VT can be set between 6 and 8 mL/kg.47 The com-
pensation of low tidal volume with respiratory rate
must be pursued carefully, since the increase in
RR can increase mechanical power and therefore
the risk of VILI itself. Moreover, by increasing
the respiratory rate, it becomes difficult to allow
enough time to expiration and keep Ppeak low,
therefore leading to an increased risk of ventila-
tion inhomogeneity and dynamic hyperinflation.
For the reduced elastic recoil and the increased ex-
piratory resistance that characterize COPD, expi-
ratory time tends to be prolonged. This time can-
not be set directly, since expiration is passive, but
Vol. 113 - No. 3 Minerva Medica 463
the physician can set the ratio between inspiratory
and expiratory time (I:E) and therefore the time
available for expiration before a new respiratory
act starts. The expiratory flow curve can be used to
assess an incomplete expiration and therefore the
need for expiratory time adjustments. In mechani-
cally ventilated COPD patients with PEEPi due to
flow limitation, PEEP levels exceeding the 85% of
PEEPi (Pcrit) can cause further hyperinflation and
compromise hemodynamics and gas exchange.48
Therefore, an assessment of PEEPi is fundamental
to set PEEP. Indeed, PEEP can increase static elas-
tance in both the respiratory system and the chest
wall, reduce cardiac index and affect hemody-
namics and gas exchange. Therefore, while titrat-
ing PEEP it is fundamental to evaluate Pplat and
stop increasing PEEP if Pplat increases, since this
could be an initial sign of overdistension. Finally,
PEEP can interact with the occurrence of EFL,
and this phenomenon must be evaluated as well
(see “PEEP test”). Since the presence of EFL has
been associate to the occurrence of complications
in patients admitted to the ICU, selecting PEEP to
reduce EFL may improve the ventilatory strategy,
despite final evidence is still missing.6
Assisted mechanical ventilation
When COPD patients restore spontaneous inspi-
ratory activity and thus trigger each mechanical
breath, the expiratory time is not constant. This
implies that VT can change and induce a differ-
ent degree of dynamic hyperinflation. During
assisted mechanical ventilation, the presence of
auto-PEEP can increase the work of breathing.
When starting the inspiration, the patient needs
to generate an appropriate negative pressure to
counterbalance the effects of auto-PEEP and to
generate a detectable trigger. In particular, the
amount of set PEEP should compensate the au-
to-PEEP due to flow limitation, thus decreasing
the inspiratory effort needed to start the assisted
breath and reducing the total work of breathing.
Pressure support ventilation
Pressure Support Ventilation (PSV) is the most
popular assisted mode used in the process of
weaning patients from mechanical ventilation,
whose goal is to provide an unload of the pa-
 ©
or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access COPYRIGHT 2022 EDIZIONI MINERVA MEDICA
cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary information of the Publisher.
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically
to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove,
SCARAMUZZO MECHANICAL VENTILATION IN COPD
tient’s respiratory muscles. During PSV, once
the patient triggers the ventilator, airway pres-
sure rises to a preset level, regardless of patient
effort. Thus, PSV provides a fixed level of in-
spiratory muscle unloading. An increase of level
of pressure support induces a decrease in trans-
diaphragmatic pressure, while tidal volume in-
creases and respiratory rate decrease. Generally,
the pressure support level is adjusted, at bedside,
to the lowest level providing comfortable breath-
ing. More evidence in literature suggests that the
most appropriate pressure support level results in
a respiratory rate of 25-30 breaths/minute. This
goal is achieved with large inter-individual vari-
ation of pressure support. The breathing pattern
can be influenced by the mechanical properties
of the respiratory system, the characteristics of
a single breath and the function of the ventila-
tor. Indeed, different levels of PSV may induce
different respiratory patterns and gas exchange,
since a support levels that improves blood gases
may result in asynchronies (ineffective efforts)
if external PEEP is not applied. A level of PEEP
not higher than auto-PEEP, can reduce the dia-
phragmatic work with no detrimental effects of
gas exchange.49 Moreover, the patient-ventilator
interaction can be improved by adjusting the
inspiratory trigger sensitivity, the expiratory cy-
cling,50 the pressure support level (avoiding high
VT and hyperinflation),51 reducing the inspira-
tory pressure rise time and decreasing resistance
to airflow. During PSV, the evaluation of auto-
PEEP is cumbersome and required an invasive
simultaneous recording of esophageal pressure
and airflow, visualizing the changes in esopha-
geal pressure before the start of inspiratory flow.
This method is valid only if the expiratory mus-
cles are relaxed but COPD patients frequently
exhibit an expiratory muscle recruitment.52 The
airway occlusion pressure (P 0.1), measured
from the airway pressure during the triggering
phase of assisted mode of ventilation, seems to
be able to evaluate the effects of external PEEP
in patients with auto-PEEP.53
Neurally adjusted ventilator assist
Patients with COPD showed an increased risk
of patient ventilator asynchrony54 and it can
result in NIV failure, increased work of breath-
464 Minerva Medica June 2022
ing, patient discomfort and thus endotracheal
intubation. For this reason, some authors sug-
gested that a reduction of rate of patient ventila-
tor asynchronies should improve the rate of NIV
success. The neurally adjusted ventilator assist
(NAVA) and non-invasive NAVA (NIV-NAVA),
guided by electrical activity of the diaphragm,
are a mode of assisted ventilation that improve
patient-ventilator interaction, both in terms of
timing and responding to increased demand, re-
gardless of leaks.55, 56 Using a dedicated nasogas-
tric tube, the signal of electrical activity of the
diaphragm (EAdi) that activates the diaphragm
is proportional to the output signal from the re-
spiratory center and it is not influenced by flow
limitation or intrinsic PEEP.57 The NAVA can be
used as initial mode of NIV for management of
acute hypercapnic respiratory failure in patients
with COPD. NIV-NAVA can synchronize the as-
sistance to inspiratory effort in COPD patients,
whereas PSV does not ensure an appropriate
patient-ventilator interaction.58 A recent study
demonstrated that NIV-NAVA may determine
patient-ventilator interactions and a reduction in
the severity of asynchrony in aeCOPD.59 These
results have been confirmed in a study that use
the NAVA through a helmet compared with pres-
sure support through a face mask, improving the
comfort, the triggering performance, and patient-
ventilator synchrony.60 The patients with COPD
exhibit an increasing dead space and decreasing
ventilation efficiency. To overcome these prob-
lems, the NAVA mode offers, by downregulation
of the EAdi signal, a reduced risk over-assis-
tance, showed a better heterogeneous ventilation
distribution and decreasing dead space compared
to PSV in in patients with COPD.61 Further larg-
er studies should clarify the use of NIV-NAVA
to evaluate its beneficial effects on clinical out-
comes regarding the rate of NIV failure, the
length of ICU or hospital stay and mortality.
Proportional assist ventilation
Proportional assist ventilation (PAV) mode
represents an alternative approach to respira-
tory muscle unloading, designed on physiologi-
cal basis. With PAV, there is no target of flow,
volume, or pressure. Rather, the physician sets
a pressure gain applied by the machine on the
 ©
or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access COPYRIGHT 2022 EDIZIONI MINERVA MEDICA
cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary information of the Publisher.
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically
to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove,
MECHANICAL VENTILATION IN COPD SCARAMUZZO
patient’s measured or estimated compliance
and resistance. This allows for a compensation
by the ventilator of an increase in either one or
both components. It has been demonstrated that
PAV could improve arterial blood gas and alveo-
lar ventilation as well as unload the respiratory
muscles in both acute62 and chronic patients.63
In intubated COPD patients, PAV improved min-
ute ventilation, decreased dyspnea, and reduced
work of breathing, while preserving the physi-
ological breath-by-breath VT variability better
than PSV. Despite these favorable effects, PAV
can be difficult to be used in the clinical setting.
Indeed, knowledge of the patients’ elastance and
resistance, a prerequisite for the correct titration
of their compensation by PAV, is most often un-
available to the clinician. Therefore, arbitrary
levels of compensation are often used, which, if
inappropriately chosen, can increase inspiratory
effort in some patients. Although physiological
advantages of PAV, a potential role for PAV could
be further explored.
Monitoring in mechanically
ventilated COPD patients
Inspiratory/expiratory hold maneuvers
During controlled mechanical ventilation, it can
be possible to estimate the different components
of the respiratory system by performing an end-
expiratory and an end-inspiratory hold maneu-
ver. Modern ventilators allow to perform this
maneuver easily. To obtain reliable measures,
the maneuver must be long enough to allow air
redistribution within the lungs but not too long,
since stress relaxation of the chest-wall and dis-
tal air reabsorption would reduce pressures pro-
gressively. In general, 0.5–2 seconds can provide
a good compromise64 but a higher time could be
necessary when the lungs are very heterogeneous.
When the patient is ventilated in controlled mode
with a constant flow (square flow waveform), an
inspiratory hold will provide 3 important pres-
sures called, in the order of appearance:
•  peak pressure (Ppeak), which is the maxi-
mal pressure reached during inspiration and is
determined by both intrinsic resistances and ad-
ditional resistances;
Vol. 113 - No. 3 Minerva Medica 465
•  end-inspiratory airway pressure at zero flow
(P1), which the fist value of pressure recorded
after the end of inspiratory flow;
•  plateau pressure (Pplat), which is the pressure
recorded at the end of the inspiratory pause and
therefore after air redistribution within the lungs.
The difference between these pressures can
provide important information about the resis-
tances and the compliance of the respiratory sys-
tem. Specifically, the resistances of the respira-
tory system (Rmax,rs) can be divided into intrin-
sic resistance (Rmin,rs) and additional resistance
(ØR,rs) being the latter as the result of viscoelas-
tic pressure dissipations within the pulmonary
and chest wall tissues. These 2 components can
be calculated as follows:
•  Rmin,rs = (Ppeak-1) / inspiratory flow;
•  ØR,rs = (P1-Pplat) / inspiratory flow;
•  Rmax,rs = Rmin,rs + ØR,rs.
COPD patients are usually characterized by
high levels of both intrinsic and additional re-
sistance, which results in high total resistances.
Rmin,rs are high for the occurrence of broncho-
constriction and airway collapse while and ØR,rs
are increased for the presence of heterogeneity in
inspiratory time constants and for the pendelluft
phenomenon.65 Furthermore, the expiratory hold
maneuver, which is usually performed before the
inspiratory hold one, allows to detect the pres-
ence of PEEPi. The pressure measured after the
4-seconds expiratory maneuver is the total PEEP
and the difference between the total PEEP and
the extrinsic PEEP (i.e., the one set on the ven-
tilator) is defined intrinsic PEEP, or auto-PEEP.
Finally, the difference between Pplat and PEEPt
is called driving pressure (DP)66 and gives infor-
mation about the dynamic strain of the lung tis-
sue. By diving the tidal volume for the DP, it is
possible to calculate the compliance of the respi-
ratory system (Crs=VT/[Pplat-PEEPt]), which is
usually higher in COPD patients for the presence
of lung emphysema.
Electrical impedance tomography
Electrical impedance tomography is a non-
invasive monitoring technique that allows the
continuous and bedside evaluation of regional
ventilation distribution without exposing the pa-
tient to radiations.67, 68 Moreover, using EIT it is
 ©
or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access COPYRIGHT 2022 EDIZIONI MINERVA MEDICA
cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary information of the Publisher.
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically
to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove,
SCARAMUZZO MECHANICAL VENTILATION IN COPD
possible to calculate the differences in lung me-
chanical properties (regional compliance) and in
the distribution of lung ventilation and perfusion
in different areas of the lung.69 In heterogeneous
lung diseases, like ARDS or COPD, by showing
the regional differences in the lung mechanical
properties,70 EIT could potentially help setting
PEEP, tidal volume71 and provide an appropriate
estimation of transpulmonary driving pressure.72
The expiratory time constant (τ) corresponds to
the time needed to exhale 2/3 of the tidal volume
and can be calculated by multiplying compli-
ance (Crs) and resistance (Rs) of the respiratory
system. When its value increases, the occurrence
of dynamic hyperinflation increases as well. In
COPD patients, EIT has been used to describe
the heterogeneous distribution of expiratory time
constant73 and regional ventilation delay (RVD),
which can be related to the phenomenon of air-
way closure.74 The advantage of EIT monitoring
is feasibility at the bedside, the possibility of lon-
gitudinal assessment of the patient – and there-
fore to evaluate the response to treatment75, 76
– and the real time evaluation of the interaction
ventilator-patient.
Lung and muscle ultrasound
Point of care ultrasound can be used at the bed-
side to assess both lung patterns77 and muscular
function.78 Lung ultrasound can evaluate both
artifactual images of normal/pathologic lung (re-
spectively A-lines and B-lines) and real images
of pathologic conditions (e.g., lung consolida-
tions, pleural effusion).79 The Lung Ultrasound
Score (LUS) have a good correlation with lung
aeration measured at CT scan, but a poor one
when assessing quantitative lung recruitment.80
The LUS can be used to assess the entity of pa-
renchymal involvement and the evolution of the
disease, but the assessment of the inner part of
the lung, which can have distinctive clinical and
pathophysiological characteristics,81 can be lim-
ited. In COPD, the respiratory muscles, and espe-
cially the diaphragm, are subjected to high load
and maximal activation during tidal breathing.
The composition of the muscular fibers can also
change as adaptation to fatigue, with an increase
in in the slow-twitch characteristics of the mus-
cle fibers increase.82 Monitoring the diaphrag-
466 Minerva Medica June 2022
matic activity can be useful to assess diaphrag-
matic disfunction and therefore the probability
of NIV or weaning failure.83, 84 The two indexes
more commonly used are the diaphragmatic dis-
placement (DD), which expresses the movement
of the diaphragm and is considered normal if >10
mm, and the thickening fraction (TF), which is
the difference in thickness between inspiration
and expiration and is expressed in percentage.
A thickening fraction >30% is considered nor-
mal and associated to an increase probability of
weaning success.85 Another interesting index is
the diaphragmatic rapid shallow breathing index
(D-RSBI), which is the ratio between respiratory
rate and the ultrasonographic evaluation of dia-
phragmatic displacement has been found to be
superior to the classical rapid shallow breathing
(RR/VT) in predicting weaning failure, also in
COPD patients.86, 87 Finally, the evaluation of
extra-diaphragmatic muscles (e.g., intercostal
muscles, parasternal muscles) is feasible and can
provide additional information on the capacity
load in patients affected by acute respiratory fail-
ure.88 The ultrasound evaluation of the abdomi-
nal muscles started to also get attention since an
abnormal activity of them has been associated to
a high risk of reintubation, with higher predic-
tive performance as compared to the isolated dia-
phragmatic assessment.89
Weaning from mechanical ventilation
Most mechanically ventilated patients are easily
weaned from the ventilators; however, for the
others, the time needed to wean can be consider-
able. One of the factors that explain a prolonged
duration of the weaning process is the presence
of COPD. Indeed, an occurrence of dynamic hy-
perinflation can play a pivotal role to determine a
weaning failure in COPD patients with respirato-
ry failure90 and more that 50% of COPD patients
can be defined difficult-to-wean.91 Decreasing
the breathing load by reducing airway resistance
and intrinsic PEEP can provide an improving of
respiratory muscle strength and endurance and
contribute to successful weaning. The occurrence
of respiratory muscles dysfunction due to weak-
ness, atrophy determined by drug induce myopa-
thy (corticosteroids and neuromuscular blocking)
may further worsen the respiratory pump perfor-
 ©
or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access COPYRIGHT 2022 EDIZIONI MINERVA MEDICA
cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary information of the Publisher.
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically
to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove,
MECHANICAL VENTILATION IN COPD SCARAMUZZO
mance in COPD patients. In addition, gas ex-
change abnormalities, physiological dependence
on the ventilator and congestive heart failure
may explain weaning failure.92 Furthermore, the
weaning phase is a “stress” test for these patients
that they do not maintain a preserved cardiovas-
cular functionality. Lemaire et al. described the
left ventricular dysfunction occurred during dis-
continuation of mechanical ventilation in COPD
patients93 and a decreased mixed venous oxygen
saturation and oxygen transport were observed
in unsuccessfully weaned patients.94 Finally, in
COPD patients, prophylactic NIV and high-flow
nasal oxygen can significantly decrease the risk
of reintubation compared with high-flow nasal
oxygen alone.95 The most reasonable approach
would be to evaluate which category of patients
might respond favorably to NIV after extubation.
Conclusions
In conclusion, mechanical ventilation in COPD
offers peculiar challenges to the treating physi-
cian; the main aim of respiratory support is to
limit hyperinflation by reducing minute venti-
lation, tidal volumes and therefore increase the
time available for expiration. The introduction
of non-invasive ventilatory support devices, like
HFNO and NIV, changed the outcome of this
category of patients, while monitoring tools, like
EIT and ultrasound, improved our understanding
in the pathophysiology of the disease. Finally, a
particular attention must be drawn on the wean-
ing from ventilation, since it could be more dif-
ficult for the higher risk of failure.
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Conflicts of interest.—The authors certify that there is no conflict of interest with any financial organization regarding the material
discussed in the manuscript.
Authors’ contributions.—All authors equally contributed to the manuscript, read and approved the final version of the manuscript.
History.—Manuscript accepted: February 14, 2022. - Manuscript revised: February 9, 2022. - Manuscript received: December 22,
2021.

470 Minerva Medica June 2022