[ ARDS and Acute Respiratory Failure CHEST Critical Care Reviews ]

ICU Management of the Patient

With Fibrotic Interstitial Lung Disease
Amita Krishnan, MD; David R. Janz, MD; and Matthew R. Lammi, MD

With the advent of new therapies and improvements in supportive care, survivorship in patients
with interstitial lung disease (ILD) is increasing. However, this increase in number of patients
living with ILD has resulted in an increase in the number of patients admitted to hospitals with
acute exacerbations of ILD, most commonly manifested as advanced hypoxemic respiratory
failure. In addition, patients with ILD may be admitted to the hospital as their first manifestation
of ILD or progression of an ILD of yet to be diagnosed cause. All of these presentations carry
significant risk of severe respiratory failure requiring admission to an ICU. It is therefore neces-
sary for the critical care practitioner to have an approach to the patient with ILD being admitted to
the ICU. This review summarizes an approach to the evaluation and management of patients
presenting to the ICU through a discussion of: (1) diagnosis of acute exacerbation in patients with
previously diagnosed ILD; (2) diagnosis of patients presenting with ILD of unknown cause; (3)
treatment of both acute exacerbations and underlying causes of ILD; (4) supportive ICU care for
advanced respiratory failure due to ILD; and (5) outcomes of patients with ILD and severe res-
piratory failure in the ICU. In addition, we offer suggested approaches to determining the cause of
respiratory deterioration in patients with ILD and deciding which advanced respiratory support
devices are reasonable in managing ILD patients who have progressive respiratory failure.
CHEST Critical Care 2023; 1(3):100020

KEY WORDS: acute exacerbation; acute respiratory failure; fibrotic lung disease; idiopathic
pulmonary fibrosis; interstitial lung disease

CLINICAL QUESTION
A 59-year-old man with idiopathic pulmonary fibrosis taking nintedanib and 2 L/min of oxygen is admitted to the ICU
for acute chronic hypoxemic respiratory failure. Three days prior to presentation, the patient developed increased
dyspnea, fevers, and myalgias after spending time with his grandchild who had been experiencing symptoms of a
respiratory tract infection. Currently, he is afebrile, normotensive, and has an oxygen saturation of 92% on high-flow
nasal cannula (50 L of flow, FIO2 0.7).
Which of the following is the most appropriate diagnostic test?
A: Bronchoscopy with transbronchial lung biopsy B: CT scan of the chest C: Thoracic ultrasound
D: Open lung biopsy E: Serum C-reactive protein
(See Answer/Rationale at the end of the article)

ABBREVIATIONS: AE-ILD = acute exacerbation of interstitial lung
disease; AE-IPF = acute exacerbation of idiopathic pulmonary fibrosis;
BTT = bridge-to-transplant; CTD = connective tissue disease; CTD-
ILD = connective tissue disease-associated interstitial lung disease;
CYC = cyclophosphamide; DAH = diffuse alveolar hemorrhage;
ECMO = extracorporeal membrane oxygenation; fHP = fibrotic hy-
persensitivity pneumonitis; HFNC = high-flow nasal cannula; ILD =
interstitial lung disease; IMV = invasive mechanical ventilation; IPF =
idiopathic pulmonary fibrosis; LTx = lung transplantation; MDA5 =
melanoma differentiation-associated gene 5; NIV = noninvasive
ventilation; PC = palliative care; PEEP = positive end-expiratory
pressure; RP-ILD = rapidly progressive interstitial lung disease;
UIP = usual interstitial pneumonia
AFFILIATIONS: From the LSU School of Medicine New Orleans,
Section of Pulmonary/Critical Care & Allergy/Immunology (A. K., D.
R. J., and M. R. L.), New Orleans, LA; Comprehensive Pulmonary
Hypertension Center, University Medical Center New Orleans (A. K.
and M. R. L.), New Orleans, LA; and the University Medical Center
New Orleans (D. R. J.), New Orleans, LA.
CORRESPONDENCE TO: Amita Krishnan, MD; email: akris1@lsuhsc.edu
Copyright Ó 2023 The Authors. Published by Elsevier Inc under li-
cense from the American College of Chest Physicians. This is an open
access article under the CC BY license (http://creativecommons.org/
licenses/by/4.0/).
DOI: https://doi.org/10.1016/j.chstcc.2023.100020

chestcc.org 1

Key Points

CT scan imaging of the chest is the first-line test in
the diagnosis of an acute exacerbation of idio-
pathic pulmonary fibrosis.

The diagnostic approach to ICU patients without a
previous diagnosis of interstitial lung disease
should proceed with caution, specifically for the
performance of bronchoscopy or open lung biopsy
during critical illness given the risk of worsening
respiratory failure with these procedures.

Rapidly progressive interstitial lung disease should
be considered in the differential diagnosis of crit-
ically ill adults with ARDS.

High-flow nasal cannula use is associated with
fewer discontinuations and increased oral intake
and ability to communicate compared with
noninvasive ventilation in critically ill adults with
interstitial lung disease.

Short- and long-term mortality is high (30-day
mortality, 78%; 6-month mortality, 96%) in pa-
tients with interstitial lung disease receiving inva-
sive mechanical ventilation.
Interstitial lung disease (ILD) is a broad group of diffuse
parenchymal lung injury patterns characterized by
varying degrees of inflammation and fibrosis. ILDs with
a fibrotic phenotype are characterized by features on
chest CT scan imaging such as reticulation, traction
bronchiectasis, and honeycombing.1 A fibrotic
phenotype can be found in several distinct ILDs,
including idiopathic pulmonary fibrosis (IPF), idiopathic
interstitial pneumonias, connective tissue disease-
associated ILD (CTD-ILD), fibrotic hypersensitivity
pneumonitis (fHP), pneumoconioses, medication- or
drug-induced ILDs, sarcoidosis, postinfectious ILD,
radiation-induced ILD, smoking-related ILD, and
unclassifiable ILDs.2,3
Acute exacerbation of ILD (AE-ILD) may occur at any
time during the course of disease, resulting in acute
hypoxemic respiratory failure that may warrant
admission to the ICU with significant morbidity and
mortality.4 This entity is best described in IPF and is
termed acute exacerbation of IPF (AE-IPF), although it
can occur in other types of fibrotic ILDs as well.5
Although there is no consensus definition for AE-ILD,
the criteria used to define AE-IPF are often applied: an
acute clinical worsening of dyspnea within the last
2 CHEST Critical Care Reviews
30 days characterized by new bilateral ground-glass
opacities/consolidation without an alternative etiology
(Fig 1).6-8 Results of surgical lung biopsy, although
recommended agains, may reveal diffuse alveolar
damage and/or organizing pneumonia superimposed on
the underlying fibrotic pattern.9
IPF is the most common form of idiopathic interstitial
pneumonia and carries the worst prognosis. Respiratory
failure is the most frequent cause of death in patients
with IPF and is seen more commonly in patients with
advanced disease.6,10 AE-IPF has an annual incidence of
4% to 20%,11 and approximately one-half of patients
hospitalized with AE-IPF will not survive, with those
admitted to the ICU having a mortality rate approaching
90%.12 Survivors of AE-IPF have a median survival
between 15.5 months13 and 36 months,14 which is
significantly shorter than patients with IPF who did not
have an acute exacerbation.13
AE-ILD in patients without IPF (AE-non-IPF ILD) is less
well described in the literature. Studies indicate that
patients with non-IPF ILD are at lower risk for
developing an acute exacerbation compared with patients
with IPF.8 In patients with fHP, an ILD most often
characterized by a fibrotic nonspecific interstitial
pneumonia or an usual interstitial pneumonia (UIP)
pattern, the 1-year incidence of an acute exacerbation was
6%.15 Within CTD-ILD, the estimated 1-year incidence
of acute exacerbation ranges from 1% to 3%. However,
the incidence increases to 5.6% in CTD-ILD with a UIP
pattern,8 including rheumatoid arthritis-associated ILD,
which has an annual acute exacerbation incidence of
11%.16 Patients with AE-non-IPF ILD seem to have lower
in-hospital (19%)17 and 90-day (33%)18 mortality than
those with AE-IPF (43%12-50%13 and 57%19-69%18,
respectively). Prognosis differs within CTD-ILD, with
patients having anti-melanoma differentiation-associated
gene 5 (MDA5) dermatomyositis and rheumatoid
arthritis-associated ILD (particularly with a UIP
pattern20) having the worst outcomes.16
As expected, those with worse lung function,
particularly FVC13,21-23 and diffusing capacity of the
lung for carbon monoxide,13,21-23 are at increased risk
for AE-ILD. Older age21,24 is also a risk factor for the
development of an acute exacerbation of CTD-ILD.
One study described a predictive model for AE-IPF
that incorporated radiographic honeycombing, age,
and lactate dehydrogenase with moderate accuracy.25
Prognostic factors for death from AE-ILD have also
been identified, with most studies reporting that
[ 1#3 CHEST Critical Care DECEMBER 2023 ]
worsened oxygenation is associated with poor
survival.21,24,26,27 Other negative prognostic factors
include elevated D-dimer,21 C-reactive protein,13 and
age.27 This article aims to summarize the existing
data and guideline recommendations regarding caring
for a critically ill adult with interstitial lung disease.
Diagnosis
Patients who are admitted to the ICU may have a known
diagnosis of ILD or a newly discovered undiagnosed
ILD. The international consensus guidelines for AE-IPF
can be applied to all patients with ILD to determine if
the patient’s respiratory deterioration is due to AE-ILD
or an alternative etiology (Fig 1).6,7 When acute
respiratory deterioration occurs in ILD, the first step is
to rule out extraparenchymal causes (eg, pneumothorax,
pleural effusion, pulmonary embolism), followed by
obtaining a chest CT scan to look for new bilateral
ground-glass opacities/consolidation (Fig 2). If these
acute findings are present and not fully explained by
fluid overload, the diagnosis of AE-ILD is then made.6
Known ILD
Acute exacerbations can be either idiopathic or
triggered by acute infection, aspiration, air pollution,
transfusions, drug toxicity, or recent procedures.
Obtaining a thorough history, respiratory cultures,
and viral panel, as well as reviewing medications,
help to determine cause and potential reversible
triggers.4,6,28
In an observational retrospective single-center study
of 182 patients, 50 cases of AE-ILD were triggered
by infection, which was bacterial in 23% of IPF
cases and 15% of non-IPF cases. The second most
common trigger in the IPF group was viral, whereas
it was fungal (including Pneumocystis jirovecii) in
the non-IPF ILD group.4 In contrast, patients with
ILD who present with acute hypoxemic respiratory
failure and lobar consolidation do not meet the
definition for AE-ILD and should be evaluated for
pneumonia.
If unable to obtain a sputum sample, BAL can then be
considered.7 Although BAL seems to be safe in stable
outpatients with IPF,29 there are limited data
examining the safety and utility of BAL in AE-ILD. One
study of 106 patients with AE-ILD reported significant
worsening of respiratory failure following BAL, with a
diagnostic yield of only 13%, which did not lead to
treatment changes that improved outcomes.30

Acute respiratory deterioration

(< 1 month duration)

Extraparenchymal causes ruled out

(PTX, PE, pleural effusion)

New, bilateral GGO/consolidations

(not explained by cardiac failure/fluid overload)

Acute ILD exacerbation

Known chronic ILD Newly diagnosed ILD

Special consideration
Work-up:
• Autoimmune panel
• Rheumatologic history
Potential causes: CTD-ILD • Drug history
• Infection • Medication history Figure 1 – Proposed approach for the evalu-
• Aspiration Potential causes: • Occupational history ation of acute exacerbation of ILD. CTD ¼
• Drug toxicity • Opportunistic infection • Environmental history connective tissue disease; GGO ¼ ground-
• Air pollution • Anti-MDA5 ARDS • Smoking history glass opacities; ILD ¼ interstitial lung disease;
• Recent surgery/ • Rheumatologic • Family history MDA5 ¼ melanoma differentiation-
procedure medications associated gene 5; PE ¼ pulmonary embolism;
• History of radiation therapy
PTX ¼ pneumothorax.

chestcc.org 3
Figure 2 – A-F, CT chest scan imaging showing acute exacerbation of interstitial lung disease in a patient with usual interstitial pneumonia related to
rheumatoid arthritis. Baseline outpatient scans (A-C) and scans during an exacerbation (D-F) show that new ground-glass opacities can be seen
bilaterally, indicative of acute exacerbation of interstitial lung disease.
In the setting of IPF, it may be prudent to
empirically treat infection if noninvasive culture data
cannot be obtained. However, many patients with
non-IPF ILD are receiving chronic
immunosuppression therapy and are predisposed to
opportunistic infections. If noninvasive culture data
cannot be obtained, BAL should be cautiously
considered in the diagnostic approach to AE-ILD
along with blood cultures, Legionella and
pneumococcal urinary antigen testing, serum
galactomannan levels, cryptococcus antigen testing,
and evaluation for endemic fungi.1,31
In patients with known CTD-ILD, there are other
causes of acute respiratory failure besides infection that
must be considered, including medication toxicity and
diffuse alveolar hemorrhage (DAH). Drug-induced
pneumonitis can be caused by numerous drugs used to
treat CTD such as methotrexate, leflunomide,
sulfasalazine, tumor necrosis factor-alpha inhibitors,
and cyclophosphamide (CYC).32 Small vessel
inflammation can lead to the development of DAH,
particularly in patients with lupus but also less
commonly in patients with rheumatoid arthritis, mixed
connective tissue disease, systemic sclerosis, and
dermatomyositis. DAH can be diagnosed with
sequential BAL samples revealing an increasing RBC
count. Patients with anti-MDA5 dermatomyositis have
a high risk of developing rapidly progressive ILD
leading to ARDS.33
4 CHEST Critical Care Reviews
Unknown ILD
In patients with newly discovered undiagnosed ILD who
have developed respiratory failure requiring ICU
admission, further investigation must ensue to determine
the underlying etiology. Reviewing a thorough history,
including occupational/environmental exposures,
medications, drug use, smoking, rheumatologic
symptoms, recent infections, family history, and radiation
therapy, is key. Obtaining a full CTD panel that includes
antinuclear antibody, rheumatoid factor, anti-cyclic
citrullinated peptide antibody, myositis autoantibodies,
and other extractable nuclear antigen autoantibodies
based on clinical history is imperative as ILD can be the
first and only feature of a CTD.34,35
One specific condition that should be considered in
anyone with ILD of unknown cause presenting to the
ICU is anti-MDA5 dermatomyositis. Although not seen
in all cases, many patients with anti-MDA5
dermatomyositis will have proximal muscle weakness
and/or cutaneous manifestations (periorbital heliotrope
rash, erythematous rash on the anterior chest or back
and shoulders, violaceous papules on the dorsal surface
of the finger joints, cracked palmar fingertips, or palmar
papules).36 A comprehensive myositis panel should
include anti-MDA5 antibody but may take days to
obtain results.
Bronchoscopy with BAL could help rule out acute
eosinophilic pneumonia, DAH, infection, and
[ 1#3 CHEST Critical Care DECEMBER 2023 ]
lymphocytic-predominant processes such as organizing
pneumonia and fHP but should be cautiously considered
in AE-ILD. Performing transbronchial biopsies can help
rule out granulomatous disease; however, this procedure
can worsen the patient’s already tenuous respiratory
condition in AE-ILD.7 Surgical biopsies are commonly
performed for the diagnosis of ILD, but nonelective
biopsies should be avoided in the inpatient setting,
especially in patients with AE-ILD due to the exceedingly
high postoperative mortality risk of 16%11,37 to 20%.38
Treatment
Because of the paucity of robust evidence supporting
treatment options, there is no standardized approach to
AE-ILD treatment. Treatment often focuses on the
administration of high-dose steroids in combination
with cytotoxic agents and broad-spectrum antibiotics.8
Treatment of AE-IPF
The management of AE-IPF is driven mainly by
supportive care, including supplemental oxygen and
palliation of symptoms, along with treatment of reversible
triggers.6 Observational cohort studies investigated
various treatments such as tacrolimus plus pulse-dose
steroids,39 cyclosporine plus corticosteroids,40,41
recombinant human thrombomodulin,42 rituximab plus
plasma exchange/IV immunoglobulin,43 and polymyxin
B-immobilized fiber column perfusion.44,45 Although
these treatments did show an association with improved
survival in the setting of acute exacerbation, efficacy
remains uncertain due to confounding.6 There is no
recommendation for initiating antifibrotic therapy during
an acute exacerbation,46 although one retrospective
study47 did show an association between starting
nintedanib and a lower mortality in AE-ILD.
The international consensus guidelines offer a weak
recommendation for corticosteroid use in AE-IPF.48
This recommendation places high value on anecdotal
reports of benefit4,6,28 and the poor prognosis associated
with AE-IPF. Most of these studies used doses between
0.5 and 1.0 mg/kg per day or less. One retrospective
study investigated 82 patients with AE-IPF, 37 of whom
received corticosteroids.49 There was no statistically
significant association between corticosteroid treatment
and in-hospital mortality, although overall survival was
reduced in patients with AE-IPF who received
corticosteroids (hazard ratio, 6.2; 95% CI, 1.4-28.1;
P ¼ .02), possibly due to residual confounding. With no
clear evidence of improved outcomes with
chestcc.org
corticosteroids in AE-IPF, caution should be taken in the
context of possible infection.50
The Exacerbation de Fibrose Pulmonaire Idiopathique
(EXAFIP) study was a double-anonymized, placebo-
controlled trial designed to evaluate the efficacy of CYC
pulses in addition to high-dose methylprednisolone for
AE-IPF. The findings showed a trend toward an increase
in all-cause mortality at 3 months (14.5%; 95% CI, 3.1
to 31.6; P ¼ .10) providing evidence against CYC use in
this population.51
Treatment of AE-Non-IPF ILD
All patients who are admitted for AE-ILD should be
started on antibiotic therapy while working to rule out
infection. Unlike in IPF, corticosteroids are widely used
in the treatment of AE-ILD related to other conditions
such as CTD, nonspecific interstitial pneumonia,
organizing pneumonia, sarcoidosis, hypersensitivity
pneumonitis, and drug-induced ILD. In an observational
retrospective single-center study of patients with AE-
ILD, high doses of corticosteroids seemed beneficial in
AE-non-IPF ILD. In addition, prednisolone doses >
1 mg/kg were associated with higher survival.4 A larger
prospective study of patients with AE-non-IPF is
necessary to address further clarification of
corticosteroid dosing. Steroid pulse dosing is typically
reserved for cases of vasculitis or anti-MDA5
dermatomyositis-associated rapidly progressive ILD.
Because of the risk for renal crisis, it is also important to
note that doses of prednisone > 15 mg/d should be used
with caution in patients with scleroderma who have AE-
ILD.
In the CTD patient population, four retrospective studies
have evaluated the use of CYC in the setting of AE-ILD,
with mixed outcomes.52-55 An association between CYC
and improved prognosis was found in AE-ILD patients
with rheumatoid arthritis54 and systemic sclerosis,55
although a negative association was found in other
patient groups.52,53,55 CYC also has a more toxic side
effect profile than other immunosuppressants. Further
randomized controlled trials are needed to elucidate the
benefit of CYC in acute exacerbation of CTD-ILD.56
For acute exacerbations in the setting of CTD-ILD, the
evidence is sparse regarding the use of alternate
immunosuppression. Clinical practice may include the
initiation of mycophenolate as a steroid-sparing agent as
it is relatively safe and well tolerated. In a small case
series, there was suggestion of benefit with rituximab as
rescue therapy in patients with severe CTD-ILD,
5
although this may have been confounded by
concomitant CYC use.57 In fHP, one retrospective study
reported no significant difference in treatment regimens
between survivors and nonsurvivors, including the use
of cytotoxic agents such as azathioprine, cyclosporine,
and CYC.15 It is important to note that the clinical
benefit derived from steroid-sparing agents may not be
seen for months. When DAH occurs in the setting of
systemic lupus erythematosus, initiation of
plasmapheresis to remove autoantibodies can be
considered in refractory cases in addition to intensive
immunosuppressive treatments to treat the underlying
disease.58 There is some evidence for improved short-
term renal outcomes but no mortality benefit associated
with plasmapheresis, and a meta-analysis of five studies
found that plasmapheresis use was associated with
increased mortality.59
Fulminant disease related to anti-MDA5
dermatomyositis needs to be treated aggressively with
combination therapy in addition to standard ARDS care.
Recommended options include pulse-dose
corticosteroids plus either a combination of calcineurin
inhibitor (tacrolimus) with CYC33 or a combination of
an antimetabolite (azathioprine and mycophenolate)
with tacrolimus or rituximab.60 Additional treatment
options for refractory disease include IV
immunoglobulin or plasmapheresis,60 both of which
have been associated with improved survival.61,62
High-Flow Nasal Cannula
Physiological Considerations
High-flow nasal cannula (HFNC) is an oxygen delivery
system that can achieve high flow rates of humidified
oxygen, titratable up to 100% FIO2. In patients with acute
hypoxemic respiratory failure, HFNC seems to reduce
mortality.63 There are numerous physiologic advantages
of HFNC compared with standard oxygen therapy,
including reducing dead space, providing small amounts
of positive end-expiratory pressure (PEEP), reducing
respiratory secretions, and lowering respiratory rate and
work of breathing.64 HFNC therefore has advantages
over standard oxygen therapy with improvements in
hypoxemia and lowered dead space, physiologic
hallmarks of AE-ILD.65 These advantages, combined
with improved patient comfort compared with
noninvasive or invasive ventilation, make HFNC
potentially the ideal form of respiratory support for
patients with ILD and decompensated hypoxemic
respiratory failure.
6 CHEST Critical Care Reviews
Clinical Data in Patients With ILD
There is a paucity of high-level data regarding HFNC in
patients with AE-ILD. In a single-center observational
study of patients with ILD in the ICU with a do-not-
resuscitate order, those who received HFNC had a lower
respiratory rate but no difference in dyspnea scores
compared with those receiving noninvasive ventilation
(NIV).66 HFNC was associated with fewer adverse events
and device interruptions/discontinuations compared with
NIV. Another small retrospective cohort study found that
patients with AE-ILD who were treated with HFNC were
less likely to be intubated than if NIV was used.67 Thirty-
day mortality was lower in those supported with HFNC
(23%) than with NIV (63%), with HFNC emerging as the
only significant independent factor associated with 30-day
survival (hazard ratio, 0.15; 95% CI, 0.03-0.88). Because
choice of respiratory support device was determined by the
treating clinician, it is possible that unmeasured
confounders may account for these differences.
Noninvasive Ventilation
Physiologic Considerations
NIV refers to the application of positive pressure through
a nasal/oral interface. The benefit of NIV in supporting
patients with acute hypoxemic respiratory failure is
strengthened by a meta-analysis of randomized trials
showing that NIV reduced intubation rates and improved
in-hospital mortality.68 The main physiologic benefit of
PEEP is increased oxygenation related to improved
alveolar recruitment, whereas bilevel NIV has the
additional benefits of reduced work of breathing and
improved CO2 levels. Although hypercapnia is not a
usual feature of patients with stable ILD, elevated CO2
levels may develop when respiratory muscles fail in the
face of reduced lung compliance that result in increased
mechanical load.65 Therefore, there are physiologic
reasons for why AE-ILD patients may benefit from NIV,
although concerns about high levels of PEEP may limit its
use in this clinical scenario.
Clinical Data in Patients With ILD
Three studies have described the use of NIV in the
setting of AE-ILD.69-71 Approximately 50% of patients
who received NIV avoided intubation and were
discharged from the ICU. NIV failure was predicted by a
higher respiratory rate70,71 but not by age, FVC, or
radiographic extent of ILD.71 However, it should be
emphasized that the median survival in the patients who
had “NIV success” was only 90 days, highlighting the
overall poor outcomes of AE-ILD, even in those who
[ 1#3 CHEST Critical Care DECEMBER 2023 ]
survive the index hospitalization. One multicenter
retrospective study described NIV use in AE-ILD.70 The
median use of NIV was 72 h, with 18% of patients
developing intolerance to the mask interface or pressure.
After 6 h of NIV, the PaO2/FIO2 ratio significantly
improved, although this improvement was noted only in
those with a clinical diagnosis of pneumonia.70 Thus, it
may be important to consider the cause of acute
exacerbation or worsened hypoxemia when selecting
supportive modalities.
Invasive Mechanical Ventilation
Physiological Considerations
There are numerous physiologic changes that occur in
patients with chronic ILD that affect the ability to use
invasive mechanical ventilation (IMV) in patients
experiencing an acute exacerbation. Lung compliance is
reduced in patients with IPF due to alterations in the
lung extracellular matrix and surfactant.65,72 It is
unknown whether cyclic opening and closing of alveolar
units occurs during tidal breathing in patients with
pulmonary fibrosis,72 which has significant implications
for recruitability with PEEP. Therefore, patients with
ILD (especially IPF) are challenging to ventilate due to
low lung compliance and a relative lack of alveolar
recruitability, along with an elevated risk for ventilator-
induced lung injury.
Clinical Data in Patients With ILD
Historically, outcomes for patients with AE-ILD
receiving IMV, particularly if lung transplantation (LTx)
is not an option, have been dismal. Single-center and
small multicenter retrospective studies have described
in-hospital mortality rates between 53%73 and 100%.74 A
more recent multicenter study found that, without LTx,
the 30-day and 6-month mortality rates after receiving
IMV for AE-ILD were 78% and 96%, respectively.75 In
another retrospective study, only 5% of patients with IPF
and 14% of patients with CTD-ILD left the hospital alive
following an AE-ILD that required IMV.76 Two large
studies were conducted by using the US National
(Nationwide) Inpatient Sample to describe outcomes of
patients with IPF undergoing IMV.77,78 Overall, 11% of
patients with IPF received IMV, with a 49% to
56% inpatient mortality; only 10% of patients with IPF
undergoing IMV were discharged home, although it is
unknown whether patients were mechanically ventilated
due to AE-ILD or other causes. Predictors of death in
patients with AE-ILD undergoing IMV include a low
PaO2/FIO2 ratio,73,76 elevated CO2, high levels of PEEP79
chestcc.org
and plateau pressure,79 and disease progression as their
underlying reason for ventilation.76 Due to very high
mortality of AE-ILD requiring IMV, it is important to
emphasize that end-of-life discussions are a critical
component of the ICU care of patients with ILD and
acute respiratory failure. Because most patients with AE-
ILD will not benefit from IMV, conducting a shared
decision-making conversation regarding do-not-
resuscitate status is imperative.
Although there is no strong evidence for best ventilator
strategies for AE-ILD, there are small studies that provide
some limited guidance. Because patients with ILD have
low lung compliance and generally poorly recruitable
alveoli, PEEP may not be as effective as in other forms of
acute hypoxemic respiratory failure. One study showed
that PEEP levels > 10 cm H2O did not improve the PaO2/
FIO2 ratio but did worsen plateau pressure, lung
compliance, and driving pressure.80 One prospective
study of five patients (four with CTD-ILD, one with IPF)
found that prone positioning was not associated with an
increase in PaO2/FIO2 ratio but was associated with
worsened plateau pressure and compliance.81
Extracorporeal Membrane Oxygenation and
LTx
LTx is a viable treatment option for patients with ILD
fulfilling guideline-based criteria. Although most LTx for
patients with ILD occurs as an outpatient for those with
stable but progressive disease, a subset of patients have
undergone LTx in the context of an AE-IPF. One single-
center description reported 89 patients with IPF
undergoing LTx, of whom 37 had an AE-ILD prior to
transplant listing.82 Of the 37 patients, 28 survived to
LTx with a 93% 30-day posttransplant survival
(compared with 100% for patients with stable IPF
undergoing transplant). However, 1- and 2-year survival
was significantly lower for those with AE-ILD compared
with those with stable IPF. One-third of the patients
with AE-ILD were placed on extracorporeal membrane
oxygenation (ECMO) support, with only 33% of them
surviving to LTx.82
ECMO is increasingly being used as a bridge to
transplant (BTT), and ILD is the main indication for this
support strategy. According to data from the United
Network for Organ Sharing, 74% of patients undergoing
ECMO as a BTT had ILD, with 62% of patients receiving
LTx, 16% dying prior to LTx, and 15% being removed
from the transplant waitlist due to worsening disease.83
An early single-center description of using ECMO as a
7
BTT in patients with ILD reported a low (27%) 1-year
survival rate.84 More contemporary cohorts have
described higher 1-year survival rates of 56%85 and
74%86 with ECMO as a BTT.
ECMO has been described in patients with anti-MDA5
dermatomyositis. Of 15 patients with anti-MDA5 and
rapidly progressive ILD who underwent ECMO, five
patients, none of whom was listed for transplant prior to
their hospitalization, underwent LTx; the remaining 10
patients died following a median of 30 days on ECMO.87
This highlights an important point, which is that ECMO
as a “bridge to recovery” in patients deemed not to be
candidates for LTx is almost universally unsuccessful in
patients with AE-ILD, whether it is specifically in anti-
MDA5 dermatomyositis88 or in other forms of ILD.84,85
Only 1% of patients from the United Network for Organ
Sharing database study survived an ECMO
hospitalization without undergoing LTx.83 Patients with
ILD who may not be adequate candidates for LTx may
have relative contraindications such as age > 65 years,
BMI > 35 or < 16 kg/m2, severe coronary artery disease,
unreliable social support, severe esophageal motility
disease, or significant psychiatric disease. Absolute
contraindications to LTx include active malignancy,
recent myocardial infarction or stroke, multi-organ
failure or septic shock, cirrhosis or acute liver failure, or a
glomerular filtration rate < 40 mL/min/1.73m2.89
Therefore, patients with these characteristics should not
be offered ECMO as a BTT. Due to the poor survival of
patients with AE-ILD who are provided ECMO and who
do not undergo LTx, we do not advocate using ECMO as
a bridge to decision (ie, using ECMO to “buy time” to
decide on LTx) if the patient does not seem to be an
acceptable transplant candidate.
Palliative Care
Many ILDs, particularly IPF, are incurable and may be
fatal; palliative care (PC) is thus a critical component of the
treatment of these patients. The majority of patients with
IPF die in the hospital, and most PC consultations occur
within the last month of life.90 Therefore, most patients do
not have an advance directive prior to admission for AE-
ILD. In a survey of centers caring for patients with ILD,
67% reported considering PC for the care of their patients
with AE-ILD,46 although actual rates of PC consultation
seem to be much lower at 15%90 to 25%.91
Compared with NIV or IMV, HFNC seems to be the
preferred oxygen support modality in patients with AE-
ILD at the end of their life. HFNC use led to a greater
8 CHEST Critical Care Reviews
ability to eat and converse shortly before death66 and
was associated with the highest Quality of Dying and
Death questionnaire score as rated by their family
members.92 Opioids are an effective treatment for
dyspnea in end-stage diseases and should be considered
an important treatment consideration in AE-ILD. In a
large survey of Japanese pulmonologists, 67% reported
using opioids in patients with AE-ILD, primarily at the
very end of the patient’s life.93 In one retrospective
study, 77% of patients were rated as having “good” or
“moderate” relief of dyspnea without a negative safety
profile,94 although another study suggested no benefit to
opioids in patients using NIV for respiratory support.95
Randomized studies are needed to understand the
benefit of opioids in relieving dyspnea in patients with
AE-ILD.96
Suggested Approach for Respiratory Support in
AE-ILD
The 2011 IPF guidelines48 provided a weak
recommendation (low-quality evidence) against IMV in
patients with IPF, stating that it may be a “reasonable
choice in the minority” of these patients, with the 2022
guidelines3 reiterating the recommendation against IMV
in the majority of patients with IPF and respiratory
failure. A suggested approach to oxygenation and
ventilatory support based on the data presented is
displayed in Figure 3. For patients who are receiving IMV
AE-ILD with severe hypoxemia
(may consider if n CO2 ) (preferred)
Palliative care
consultation
NIV HFNC
Consider
opioids for
Refractory dyspnea
severe dyspnea
or respiratory failure
Transplant
No candidate? Yes
Consider Consider IMV
palliative r ECMO as
focused a bridge to
approach transplant
Figure 3 – Suggested approach to oxygenation and ventilatory support in
patients with AE-ILD. AE-ILD ¼ acute exacerbation of interstitial lung
disease; ECMO ¼ extracorporeal membrane oxygenation; HFNC ¼
high-flow nasal cannula; IMV ¼ invasive mechanical ventilation;
NIV ¼ noninvasive ventilation.
[ 1#3 CHEST Critical Care DECEMBER 2023 ]
for AE-ILD, PEEP should be set at the minimum level to
maintain oxygenation and generally should not exceed
10 cm H2O.80 Higher levels of PEEP and/or prone
positioning could be considered if evidence (eg, imaging)
suggests that there is recruitable lung present, with careful
attention to signs of overdistension. When attempting to
liberate a patient with AE-ILD from the ventilator, the
clinician should consider the patient’s baseline breathing
pattern (ie, rapid and shallow) and baseline oxygen need
when judging appropriateness for extubation.
Conclusion
Survivorship in patients with ILD is thankfully
increasing over the past two decades. This increase in
survivorship also contributes to an increased number of
patients with ILD admitted to ICUs with AE-ILD and
respiratory failure. An approach to the evaluation and
treatment of this population of critically ill adults is
increasingly necessary to improve outcomes. The
approach outlined in this review represents our current
understanding of best practices; however will likely be
refined as more evidence is generated on how best to
care for this specific patient population.
Financial/Nonfinancial Disclosures
The authors have reported to CHEST Critical Care the
following: D. R. J. reports receiving consulting fees
from CytoVale, Inc.; and honoraria from the American
College of Chest Physicians. None declared (A. K., M.
R. L.).
Acknowledgments
Author contributions: A. K. and D. R. J. developed the topic and
structure of the manuscript. All authors conducted the literature
review, drafted the manuscript, and revised the manuscript. All authors
approved the final manuscript.

CLINICAL QUESTION
A 59-year-old man with idiopathic pulmonary fibrosis taking nintedanib and 2 L/min of oxygen is admitted to the
ICU for acute chronic hypoxemic respiratory failure. Three days prior to presentation, the patient developed
increased dyspnea, fevers, and myalgias after spending time with his grandchild who had been experiencing
symptoms of a respiratory tract infection. Currently, he is afebrile, normotensive, and has an oxygen saturation
of 92% on high-flow nasal cannula (50 L of flow, FIO2 0.7).
Which of the following is the most appropriate diagnostic test?
A: Bronchoscopy with transbronchial lung biopsy B: CT scan of the chest C: Thoracic ultrasound
D: Open lung biopsy E: Serum C-reactive protein

Correct answer: B: CT scan of the chest

Rationale: Published in 2016, an international working group developed criteria required to diagnose an acute
exacerbation of idiopathic pulmonary fibrosis. These four criteria include: (1) previous or concurrent diagnosis of
idiopathic pulmonary fibrosis; (2) acute worsening or development of dyspnea < 1 month duration; (3) CT imaging of
the chest with new bilateral ground-glass opacities or consolidation superimposed on a background pattern consistent
with usual interstitial pneumonia; and (4) deterioration not fully explained by cardiac failure or fluid overload.
Importantly, invasive testing and histopathologic analysis is not needed to make the diagnosis of acute
exacerbation of idiopathic pulmonary fibrosis, and procedures such as bronchoscopy are associated with worsening
exacerbations. Once the diagnosis of acute exacerbation of idiopathic pulmonary fibrosis is made, an assessment of
potential triggers is usually undertaken with an evaluation for infection, drug toxicity, aspiration, or postprocedural
deterioration in respiratory failure.

Bibliography:
1. Collard HR, Ryerson CJ, Corte TJ, et al. Acute exacerbation of idiopathic pulmonary fibrosis. An International Working Group Report. Am J
Respir Crit Care Med. 2016;194(3):265-275.

References 3. Raghu G, Remy-Jardin M, Richeldi L, et al. Idiopathic

1. Solomon JJ, Fischer A. Connective tissue disease-associated
interstitial lung disease: a focused review. J Intensive Care Med.
2015;30(7):392-400.
2. Spagnolo P, Distler O, Ryerson CJ, et al. Mechanisms of progressive
fibrosis in connective tissue disease (CTD)-associated interstitial
lung diseases (ILDs). Ann Rheum Dis. 2021;80(2):143-150.
pulmonary fibrosis (an update) and progressive pulmonary
fibrosis in adults: an official ATS/ERS/JRS/ALAT Clinical
Practice Guideline. Am J Respir Crit Care Med. 2022;205(9):
e18-e47.
4. Jang HJ, Yong SH, Leem AY, et al. Corticosteroid responsiveness in
patients with acute exacerbation of interstitial lung disease admitted
to the emergency department. Sci Rep. 2021;11(1):5762.

chestcc.org 9
 5. Charokopos A, Moua T, Ryu JH, Smischney NJ. Acute exacerbation
of interstitial lung disease in the intensive care unit. World J Crit
Care Med. 2022;11(1):22-32.
6. Collard HR, Ryerson CJ, Corte TJ, et al. Acute exacerbation of
idiopathic pulmonary fibrosis. An International Working Group
Report. Am J Respir Crit Care Med. 2016;194(3):265-275.
7. Amundson WH, Racila E, Allen T, et al. Acute exacerbation of
interstitial lung disease after procedures. Respir Med. 2019;150:
30-37.
8. Leuschner G, Behr J. Acute exacerbation in interstitial lung disease.
Front Med (Lausanne). 2017;4:176.
9. Churg A, Wright JL, Tazelaar HD. Acute exacerbations of
fibrotic interstitial lung disease. Histopathology. 2011;58(4):
525-530.
10. Ley B, Collard HR, King TE Jr. Clinical course and prediction of
survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med.
2011;183(4):431-440.
11. Ryerson CJ, Cottin V, Brown KK, Collard HR. Acute exacerbation of
idiopathic pulmonary fibrosis: shifting the paradigm. Eur Respir J.
2015;46(2):512-520.
12. Faverio P, De Giacomi F, Sardella L, et al. Management of acute
respiratory failure in interstitial lung diseases: overview and clinical
insights. BMC Pulm Med. 2018;18(1):70.
13. Song JW, Hong SB, Lim CM, Koh Y, Kim DS. Acute exacerbation of
idiopathic pulmonary fibrosis: incidence, risk factors and outcome.
Eur Respir J. 2011;37(2):356-363.
14. Yamazaki R, Nishiyama O, Yoshikawa K, et al. Clinical course and
prognosis in survivors of acute exacerbations of idiopathic
pulmonary fibrosis. Respir Investig. 2021;59(4):408-413.
15. Kang J, Kim YJ, Choe J, Chae EJ, Song JW. Acute exacerbation of
fibrotic hypersensitivity pneumonitis: incidence and outcomes.
Respir Res. 2021;22(1):152.
16. Toyoda Y, Hanibuchi M, Kishi J, et al. Clinical features and
outcome of acute exacerbation of interstitial pneumonia
associated with connective tissue disease. J Med Invest.
2016;63(3-4):294-299.
17. Faverio P, Stainer A, Conti S, et al. Differences between acute
exacerbations of idiopathic pulmonary fibrosis and other interstitial
lung diseases. Diagnostics (Basel). 2021;11(9).
18. Tachikawa R, Tomii K, Ueda H, et al. Clinical features and
outcome of acute exacerbation of interstitial pneumonia: collagen
vascular diseases-related versus idiopathic. Respiration. 2012;83(1):
20-27.
19. Miyashita K, Kono M, Saito G, et al. Prognosis after acute
exacerbation in patients with interstitial lung disease other than
idiopathic pulmonary fibrosis. Clin Respir J. 2021;15(3):336-344.
20. Izuka S, Yamashita H, Iba A, Takahashi Y, Kaneko H. Acute
exacerbation of rheumatoid arthritis-associated interstitial lung
disease: clinical features and prognosis. Rheumatology (Oxford).
2021;60(5):2348-2354.
21. Suzuki A, Kondoh Y, Brown KK, et al. Acute exacerbations of
fibrotic interstitial lung diseases. Respirology. 2020;25(5):525-534.
22. Alhamad EH, Cal JG, Alrajhi NN, AlBoukai AA. Acute
exacerbation in interstitial lung disease. Ann Thorac Med.
2021;16(2):178-187.
23. Xie M, Zhu C, Ye Y. Incidence, risk factors, and prognosis of acute
exacerbation of rheumatoid arthritis-associated interstitial lung
disease: a systematic review and meta-analysis. BMC Pulm Med.
2023;23(1):255.
24. Kamiya H, Panlaqui OM. A systematic review of the incidence, risk
factors and prognosis of acute exacerbation of systemic autoimmune
disease-associated interstitial lung disease. BMC Pulm Med.
2021;21(1):150.
25. Karayama M, Aoshima Y, Suzuki T, et al. A predictive model for
acute exacerbation of idiopathic interstitial pneumonias. Eur Respir
J. 2023;61(5):2201634.
26. Hozumi H, Kono M, Hasegawa H, et al. Acute exacerbation of
rheumatoid arthritis-associated interstitial lung disease: mortality
and its prediction model. Respir Res. 2022;23(1):57.
10 CHEST Critical Care Reviews
27. Schrader M, Sathananthan M, Jeganathan N. Patients with
idiopathic pulmonary fibrosis admitted to the ICU with acute
respiratory failure—a reevaluation of the risk factors and outcomes.
J Intensive Care Med. 2022;37(3):342-351.
28. Brereton CJ, Jo HE. Acute exacerbations of idiopathic pulmonary
fibrosis and the role of corticosteroids. Breathe (Sheff). 2020;16(3):
200086.
29. Molyneaux PL, Smith JJ, Saunders P, et al. BAL is safe and well
tolerated in individuals with idiopathic pulmonary fibrosis: an
analysis of the PROFILE study. Am J Respir Crit Care Med.
2021;203(1):136-139.
30. Arcadu A, Moua T. Bronchoscopy assessment of acute respiratory
failure in interstitial lung disease. Respirology. 2017;22(2):352-359.
31. Kadura S, Raghu G. Rheumatoid arthritis-interstitial lung disease:
manifestations and current concepts in pathogenesis and
management. Eur Respir Rev. 2021;30(160):210011.
32. Schwaiblmair M, Behr W, Haeckel T, Märkl B, Foerg W, Berghaus T.
Drug induced interstitial lung disease. Open Respir Med J. 2012;6:
63-74.
33. Jablonski R, Bhorade S, Strek ME, Dematte J. Recognition and
management of myositis-associated rapidly progressive interstitial
lung disease. Chest. 2020;158(1):252-263.
34. Raghu G, Remy-Jardin M, Myers JL, et al. Diagnosis of idiopathic
pulmonary fibrosis. An official ATS/ERS/JRS/ALAT Clinical
Practice Guideline. Am J Respir Crit Care Med. 2018;198(5):
e44-e68.
35. Zafrani L, Lemiale V, Lapidus N, Lorillon G, Schlemmer B,
Azoulay E. Acute respiratory failure in critically ill patients with
interstitial lung disease. PLoS One. 2014;9(8):e104897.
36. Nombel A, Fabien N, Coutant F. Dermatomyositis with anti-MDA5
antibodies: bioclinical features, pathogenesis and emerging therapies.
Front Immunol. 2021;12:773352.
37. Rotolo N, Imperatori A, Dominioni L, et al. Efficacy and safety of
surgical lung biopsy for interstitial disease. Experience of 161
consecutive patients from a single institution in Italy. Sarcoidosis
Vasc Diffuse Lung Dis. 2015;32(3):251-258.
38. Fisher JH, Shapera S, To T, Marras TK, Gershon A, Dell S.
Procedure volume and mortality after surgical lung biopsy in
interstitial lung disease. Eur Respir J. 2019;53(2):1801164.
39. Horita N, Akahane M, Okada Y, et al. Tacrolimus and steroid
treatment for acute exacerbation of idiopathic pulmonary fibrosis.
Intern Med. 2011;50(3):189-195.
40. Inase N, Sawada M, Ohtani Y, et al. Cyclosporin A followed by the
treatment of acute exacerbation of idiopathic pulmonary fibrosis
with corticosteroid. Intern Med. 2003;42(7):565-570.
41. Sakamoto S, Homma S, Miyamoto A, Kurosaki A, Fujii T,
Yoshimura K. Cyclosporin A in the treatment of acute
exacerbation of idiopathic pulmonary fibrosis. Intern Med.
2010;49(2):109-115.
42. Kataoka K, Taniguchi H, Kondoh Y, et al. Recombinant human
thrombomodulin in acute exacerbation of idiopathic pulmonary
fibrosis. Chest. 2015;148(2):436-443.
43. Donahoe M, Valentine VG, Chien N, et al. Autoantibody-targeted
treatments for acute exacerbations of idiopathic pulmonary fibrosis.
PLoS One. 2015;10(6):e0127771.
44. Abe S, Azuma A, Mukae H, et al. Polymyxin B-immobilized fiber
column (PMX) treatment for idiopathic pulmonary fibrosis with
acute exacerbation: a multicenter retrospective analysis. Intern Med.
2012;51(12):1487-1491.
45. Oishi K, Aoe K, Mimura Y, et al. Survival from an acute
exacerbation of idiopathic pulmonary fibrosis with or without
direct hemoperfusion with a polymyxin B-immobilized fiber
column: a retrospective analysis. Intern Med. 2016;55(24):
3551-3559.
46. Kreuter M, Polke M, Walsh SLF, et al. Acute exacerbation of
idiopathic pulmonary fibrosis: international survey and call for
harmonisation. Eur Respir J. 2020;55(4):1901760.
47. Urushiyama H, Jo T, Hasegawa W, et al. Effect of nintedanib on
acute exacerbations of fibrosing interstitial lung diseases: a national
[ 1#3 CHEST Critical Care DECEMBER 2023 ]
 database study in Japan. ERJ Open Res. 2022;8(4). 00209-2022-
02022.
48. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT
statement: idiopathic pulmonary fibrosis: evidence-based guidelines
for diagnosis and management. Am J Respir Crit Care Med.
2011;183(6):788-824.
49. Farrand E, Vittinghoff E, Ley B, Butte AJ, Collard HR. Corticosteroid
use is not associated with improved outcomes in acute exacerbation
of IPF. Respirology. 2020;25(6):629-635.
50. Papiris SA, Kagouridis K, Kolilekas L, et al. Survival in idiopathic
pulmonary fibrosis acute exacerbations: the non-steroid approach.
BMC Pulm Med. 2015;15:162.
51. Naccache JM, Jouneau S, Didier M, et al. Cyclophosphamide added
to glucocorticoids in acute exacerbation of idiopathic pulmonary
fibrosis (EXAFIP): a randomised, double-blind, placebo-controlled,
phase 3 trial. Lancet Respir Med. 2022;10(1):26-34.
52. Suda T, Kaida Y, Nakamura Y, et al. Acute exacerbation of
interstitial pneumonia associated with collagen vascular diseases.
Respir Med. 2009;103(6):846-853.
53. Tomiyama F, Watanabe R, Ishii T, et al. High prevalence of acute
exacerbation of interstitial lung disease in Japanese patients with
systemic sclerosis. Tohoku J Exp Med. 2016;239(4):297-305.
54. Ota M, Iwasaki Y, Harada H, et al. Efficacy of intensive
immunosuppression in exacerbated rheumatoid arthritis-
associated interstitial lung disease. Mod Rheumatol. 2017;27(1):
22-28.
55. Schulze AB, Evers G, Kümmel A, et al. Cyclophosphamide pulse
therapy as treatment for severe interstitial lung diseases. Sarcoidosis
Vasc Diffuse Lung Dis. 2019;36(2):157-166.
56. Innabi A, Gomez-Manjarres D, Alzghoul BN, Chizinga M,
Mehrad B, Patel DC. Cyclophosphamide for the treatment of acute
exacerbation of interstitial lung disease: a review of the literature.
Sarcoidosis Vasc Diffuse Lung Dis. 2021;38(1):e2021002.
57. Keir GJ, Maher TM, Hansell DM, et al. Severe interstitial lung
disease in connective tissue disease: rituximab as rescue therapy. Eur
Respir J. 2012;40(3):641-648.
58. Park JA. Treatment of diffuse alveolar hemorrhage: controlling
inflammation and obtaining rapid and effective hemostasis. Int J Mol
Sci. 2021;22(2):793.
59. Jiang M, Chen R, Zhao L, Zhang X. Risk factors for mortality of
diffuse alveolar hemorrhage in systemic lupus erythematosus: a
systematic review and meta-analysis. Arthritis Res Ther.
2021;23(1):57.
60. Romero-Bueno F, Diaz Del Campo P, Trallero-Araguás E, et al.
Recommendations for the treatment of anti-melanoma
differentiation-associated gene 5-positive dermatomyositis-
associated rapidly progressive interstitial lung disease. Semin
Arthritis Rheum. 2020;50(4):776-790.
61. Shirakashi M, Nakashima R, Tsuji H, et al. Efficacy of plasma
exchange in anti-MDA5-positive dermatomyositis with interstitial
lung disease under combined immunosuppressive treatment.
Rheumatology (Oxford). 2020;59(11):3284-3292.
62. Wang LM, Yang QH, Zhang L, et al. Intravenous immunoglobulin
for interstitial lung diseases of anti-melanoma differentiation-
associated gene 5-positive dermatomyositis. Rheumatology (Oxford).
2022;61(9):3704-3710.
63. Frat JP, Thille AW, Mercat A, et al. High-flow oxygen through nasal
cannula in acute hypoxemic respiratory failure. N Engl J Med.
2015;372(23):2185-2196.
64. Mauri T, Turrini C, Eronia N, et al. Physiologic effects of high-flow
nasal cannula in acute hypoxemic respiratory failure. Am J Respir
Crit Care Med. 2017;195(9):1207-1215.
65. Plantier L, Cazes A, Dinh-Xuan AT, Bancal C, Marchand-Adam S,
Crestani B. Physiology of the lung in idiopathic pulmonary fibrosis.
Eur Respir Rev. 2018;27(147):170062.
66. Koyauchi T, Hasegawa H, Kanata K, et al. Efficacy and tolerability of
high-flow nasal cannula oxygen therapy for hypoxemic respiratory
failure in patients with interstitial lung disease with do-not-intubate
chestcc.org
orders: a retrospective single-center study. Respiration. 2018;96(4):
323-329.
67. Omote N, Matsuda N, Hashimoto N, et al. High-flow nasal cannula
therapy for acute respiratory failure in patients with interstitial
pneumonia: a retrospective observational study. Nagoya J Med Sci.
2020;82(2):301-313.
68. Xu XP, Zhang XC, Hu SL, et al. Noninvasive ventilation in
acute hypoxemic nonhypercapnic respiratory failure: a
systematic review and meta-analysis. Crit Care Med. 2017;45(7):
e727-e733.
69. Yokoyama T, Kondoh Y, Taniguchi H, et al. Noninvasive ventilation
in acute exacerbation of idiopathic pulmonary fibrosis. Intern Med.
2010;49(15):1509-1514.
70. Aliberti S, Messinesi G, Gamberini S, et al. Non-invasive mechanical
ventilation in patients with diffuse interstitial lung diseases. BMC
Pulm Med. 2014;14:194.
71. Vianello A, Arcaro G, Battistella L, et al. Noninvasive
ventilation in the event of acute respiratory failure in patients
with idiopathic pulmonary fibrosis. J Crit Care. 2014;29(4):
562-567.
72. Marchioni A, Tonelli R, Rossi G, et al. Ventilatory support and
mechanical properties of the fibrotic lung acting as a "squishy ball."
Ann Intensive Care. 2020;10(1):13.
73. Fernández-Pérez ER, Yilmaz M, Jenad H, et al. Ventilator settings
and outcome of respiratory failure in chronic interstitial lung
disease. Chest. 2008;133(5):1113-1119.
74. Mollica C, Paone G, Conti V, et al. Mechanical ventilation in
patients with end-stage idiopathic pulmonary fibrosis. Respiration.
2010;79(3):209-215.
75. Gaudry S, Vincent F, Rabbat A, et al. Invasive mechanical ventilation
in patients with fibrosing interstitial pneumonia. J Thorac Cardiovasc
Surg. 2014;147(1):47-53.
76. Luo Z, Yang L, Liu S, et al. Mechanical ventilation for acute
respiratory failure due to idiopathic pulmonary fibrosis versus
connective tissue disease-associated interstitial lung disease:
effectiveness and risk factors for death. Clin Respir J. 2020;14(10):
918-932.
77. Rush B, Wiskar K, Berger L, Griesdale D. The use of mechanical
ventilation in patients with idiopathic pulmonary fibrosis in the
United States: A nationwide retrospective cohort analysis. Respir
Med. 2016;111:72-76.78.
78. Mooney JJ, Raimundo K, Chang E, Broder MS. Mechanical
ventilation in idiopathic pulmonary fibrosis: a nationwide analysis of
ventilator use, outcomes, and resource burden. BMC Pulm Med.
2017;17(1):84.
79. Bermejo J, Yotti R, Garcia-Orta R, et al. Sildenafil for improving
outcomes in patients with corrected valvular heart disease
and persistent pulmonary hypertension: a multicenter,
double-blind, randomized clinical trial. Eur Heart J. 2018;39(15):
1255-1264.
80. Marchioni A, Tonelli R, Ball L, et al. Acute exacerbation of
idiopathic pulmonary fibrosis: lessons learned from acute respiratory
distress syndrome? Crit Care. 2018;22(1):80.
81. Nakos G, Tsangaris I, Kostanti E, et al. Effect of the prone
position on patients with hydrostatic pulmonary edema
compared with patients with acute respiratory distress syndrome
and pulmonary fibrosis. Am J Respir Crit Care Med. 2000;161(2
pt 1):360-368.
82. Dotan Y, Vaidy A, Shapiro WB, et al. Effect of acute exacerbation of
idiopathic pulmonary fibrosis on lung transplantation outcome.
Chest. 2018;154(4):818-826.
83. Furfaro D, Rosenzweig EB, Shah L, et al. Lung transplantation
disparities based on diagnosis for patients bridging to transplant on
extracorporeal membrane oxygenation. J Heart Lung Transplant.
2021;40(12):1641-1648.
84. Lafarge M, Mordant P, Thabut G, et al. Experience of
extracorporeal membrane oxygenation as a bridge to lung
transplantation in France. J Heart Lung Transplant. 2013;32(9):
905-913.
11
85. Banga A, Batchelor E, Mohanka M, et al. Predictors of outcome
among patients on extracorporeal membrane oxygenation as a
bridge to lung transplantation. Clin Transplant. 2017;31(7).
86. Hakim AH, Ahmad U, McCurry KR, et al. Contemporary outcomes
of extracorporeal membrane oxygenation used as bridge to lung
transplantation. Ann Thorac Surg. 2018;106(1):192-198.
87. Bay P, de Chambrun MP, Roux A, et al. Extracorporeal life
support allows lung transplant in anti-MDA5þ rapidly
progressive interstitial lung disease. Eur Respir J. 2022;59(5):
2102968.
88. Rubin J, Black KE, Hallowell RW, et al. Veno-venous extracorporeal
membrane oxygenation for myositis-associated rapidly progressive
interstitial lung disease. Chest. 2021;160(6):2163-2167.
89. Leard LE, Holm AM, Valapour M, et al. Consensus document for
the selection of lung transplant candidates: an update from the
International Society for Heart and Lung Transplantation. J Heart
Lung Transplant. 2021;40(11):1349-1379.
90. Lindell KO, Liang Z, Hoffman LA, et al. Palliative care and location
of death in decedents with idiopathic pulmonary fibrosis. Chest.
2015;147(2):423-429.
91. Liang Z, Hoffman LA, Nouraie M, et al. Referral to palliative care
infrequent in patients with idiopathic pulmonary fibrosis
12 CHEST Critical Care Reviews
admitted to an intensive care unit. J Palliat Med. 2017;20(2):
134-140.
92. Koyauchi T, Suzuki Y, Sato K, et al. Impact of end-of-life
respiratory modalities on quality of dying and death and
symptom relief in patients with interstitial lung disease: a
multicenter descriptive cross-sectional study. Respir Res.
2022;23(1):79.
93. Akiyama N, Fujisawa T, Morita T, et al. End-of-life care for
idiopathic pulmonary fibrosis patients with acute exacerbation.
Respir Res. 2022;23(1):294.
94. Takeyasu M, Miyamoto A, Kato D, et al. Continuous
intravenous morphine infusion for severe dyspnea in terminally
ill interstitial pneumonia patients. Intern Med. 2016;55(7):
725-729.
95. Matsuda Y, Maeda I, Tachibana K, et al. Low-dose morphine for
dyspnea in terminally ill patients with idiopathic interstitial
pneumonias. J Palliat Med. 2017;20(8):879-883.
96. Matsuda Y, Morita T, Oyamada S, Ariyoshi K, Yamaguchi T,
Iwase S. Study protocol for a randomised, placebo-controlled, single-
blind phase II study of the efficacy of morphine for dyspnoea in
patients with interstitial lung disease (JORTC-PAL 15). BMJ Open.
2021;11(5):e043156.
[ 1#3 CHEST Critical Care DECEMBER 2023 ]