Cryobiopsy in ARDS

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Role of lung biopsy

in acute respiratory
distress syndrome
with unknown
etiology

張志豪醫師
林口長庚醫院/土城醫院
胸腔內科
2020-06-20
Outline

1. Heterogeneity of ARDS

2. Pathological findings in ARDS by open lung


biopsies or autopsies

3. Case sharing: Bronchoscopic cryobiopsies in


diffuse lung disease and ARDS
(CGMH experience)
Heterogeneity of ARDS
ICU book Chapter 22
acute respiratory distress syndrome

Physicians think they do a lot for a


patient when they give his disease
a name.
Gattinoni et al. Critical Care (2020) 24:154
Type 1: Near normal Type 2: Decreased
pulmonary compliance pulmonary compliance

Gattinoni et al. Critical Care (2020) 24:154


NIV (15%) in ARDS ?

Am J Respir Crit Care Med Vol 195, Iss 1, pp


67–77, Jan 1, 2017
Heterogeneity of ARDS

ARDS

我的ARDS
Lancet Respir Med 2020;8: 420–22
Pathology in COVID-19 ARDS

Histological examination showed bilateral diffuse


alveolar damage with cellular fibromyxoid exudates
(figure 2A, B).

Lancet Respir Med 2020;8: 420–22


Pathology in COVID-19 ARDS

The right lung showed evident desquamation of


pneumocytes and hyaline membrane formation,
indicating acute respiratory distress syndrome
(figure 2A).

The left lung tissue displayed pulmonary oedema with


hyaline membrane formation, suggestive of early-
phase ARDS

Lancet Respir Med 2020;8: 420–22


The Berlin definition of ARDS

Acute respiratory distress syndrome is a


heterogeneous syndrome with complex pathology
and mechanisms.
The proposed definition does not resolve this
problem.

JAMA. 2012;307(23):2526-2533
“Imitators” of the ARDS

Diffuse, noninfectious parenchymal lung diseases,


and fulfill all of the clinical, physiologic, and
radiographic criteria for ALI/ARDS.
• Acute interstitial pneumonia (AIP)
• Acute eosinophilicpneumonia (AEP)
• Cryptogenic organizing pneumonia (COP)
• Diffuse alveolar hemorrhage (DAH)
• Acute hypersensitivity pneumonitis (HP)

have different therapeutic implications and outcomes.

CHEST 2004; 125:1530–1535


Role of BAL

CHEST 2004; 125:1530–1535


Ten diseases that look like ARDS

Congestive heart failure, pulmonary edema,


Idiopathic pulmonary fibrosis, Cryptogenic
organizing pneumonia, Nonspecific interstitial
pneumonitis, Granulomatosis with polyangiitis
(Wegener’s granulomatosis), Diffuse alveolar
hemorrhage, Goodpasture’s syndrome, Acute
hypersensitivity pneumonitis, Acute eosinophilic,
pneumonia, Drug-induced lung disease

Intensive Care Med (2015) 41:1099–1102


ARDS mimickers

Curr Opin Crit Care 2017, 23:24–29


Acute eosinophilic pneumonia
contain numerous eosinophils on closer inspection

Arch Pathol Lab Med—Vol 134, May 2010


osinophilic pneumonia
abundant eosinophils are supportive of the diagnosis

Arch Pathol Lab Med—Vol 134, May 2010


Neutrophilic capillaritis
prominent neutrophils within the alveolar septa

Arch Pathol Lab Med—Vol 134, May 2010


ARDS mimickers are caused by specific diseases
requiring specific and urgent treatments

Curr Opin Crit Care 2017, 23:24–29


ARDS lacking common risk factor (ARDS crf-)

The prevalence of
ARDSCRF- was
7.5 %
immune(36 %),
drug-induced (26 %),
malignant (14 %),
idiopathic (24 %).

Intensive Care Med (2016) 42:164–172


ARDS risk factor (N=3022)

JAMA. 2016;315(8):788-800.
ARDS without common risk factors

Curr Opin Crit Care 2019, 25:29–36


Summary

1. ARDS is a heterogeneous syndrome

2. Many disease could mimic ARDS, about 7.5% to


10% are ARDS without common risk factors

3. Different disease require different therapeutic


implications and outcomes.
Pathological findings in ARDS by
open lung biopsies or autopsies
Diffuse alveolar damage (typical findings in ARDS)

Nature Reviews Disease Primers volume 5,


Article number: 18 (2019)
Diffuse alveolar damage

Acute ‘exudative’ phase (~7 days) of ARDS: hyaline


membranes are also defining features of DAD, the
classic histopathological hallmark of ARDS. The
other findings include alveolar haemorrhage,
accumulation of white blood cells, fibrin deposition
and some areas of alveolar atelectasis (collapse)

A ‘proliferative’ phase that can last >3 weeks in


survivors; interstitial fibrosis can also occur in this
phase

Nature Reviews Disease Primers volume 5,


Article number: 18 (2019)
DAD was found in 45% patients with clinical criteria for
ARDS (Autopsy)

Am J Respir Crit Care Med Vol 187, Iss. 7, pp 761–767, Apr 1, 2013
. The proportion of DAD significantly increased with the
severity of ARDS
Pathologic Criteria for DAD

Criteria for the diagnosis of DAD included the


presence of hyaline membranes plus at least one of
the following: intra-alveolar edema, alveolar type I
cell necrosis, alveolar type II cell (cuboidal cells)
proliferation progressively covering the denuded
alveolar-capillary membrane, interstitial proliferation
of fibroblasts and myofibroblasts, or organizing
interstitial fibrosis

Am J Respir Crit Care Med Vol 187, Iss. 7, pp 761–767, Apr 1, 2013
Open lung biopsy in ARDS (meta-analysis)

Ann Am Thorac Soc Vol 12, No 8, pp 1226–1230, Aug 2015


Histopathological diagnoses of open lung biopsies

Ann Am Thorac Soc Vol 12, No 8, pp 1226–1230, Aug 2015


Histopathological diagnoses of open lung biopsies

Ann Am Thorac Soc Vol 12, No 8, pp 1226–1230, Aug 2015


Tell the patient and his family the prognosis and make
more informed decisions about end-of-life care
Open lung biopsies in ARDS

CHEST 2016; 149(5):1155-1164


Intensive Care Med (2015) 41:222–230
Open lung biopsies in CGMH

Kao et al. Critical Care (2015) 19:228


Open lung biopsies in CGMH

Kao et al. Critical Care (2015) 19:228


Small biopsy specime

Arch Pathol Lab Med. 2010;134:719–727


Case sharing:
Bronchoscopic cryobiopsies in
diffuse lung disease and ARDS
Cryobiopsy advantage: larger specimen than TBLB

Cryobiopsy

Observation Surgical
TBLB
biopsy
Case 1
66 y/o M 2018/12 CXR
BiPAP at ICU
Case 2
62 M 2018/8 CXR
The patient was transferred from 桃分

2.出院診斷(Diagnosis on Discharge):
────────────────
1. Hypoxemia respiratory failure s/p intubation with
ventilator support on 8/13, bilateral pneumonia
related
2. Acute respiratory distress syndrome
3. Bilateral pneumonia, suspect necrotizing
pneumonitis
4. Septic shock
5. Right lung mass
Case 3
Case presentationˊ

This 63-year-old woman with


1.Type II diabetes mellitus, HbA1C:7.6 on 11/16
2.Hypertension
3.Asthma history
She had dyspnea for one week. The other associated
symptoms were sore throat, chest tightness,
productive cough and yellowish sputum. There was
no fever, no nausea or vomiting.
2 days ago before admission
CXR at admission: bilateral infiltration
Intubation due to ARDS (day 6)
CT scan
Treatment course

Chest CT report at the other hospital: multiple nodular


lesions and patchy pneumonitis.

After admission, antibiotic with Teicoplanin, Tienam,


Tamiflu, and Anidulafungin were given
No response to empiric antibiotics treatment
Pathology report

DX: Lung, LLL, biopsy----herpes virus infection


GROSS D:
The specimen submitted consists of 6 pieces of
tissue measuring 0.1 x 0.1 x 0.1 cm to 1.1 x 0.4 x
0.2 cm. All are submitted.
MICRO D:
Sections show bronchial tissue with necrosis, acute
and chronic inflammation, and focal chromatin
margination and nuclear molding of the epithelial
cells.
Pathology report

DX: Lung, RMB, biopsy----herpes virus infection


GROSS D:
The specimen submitted consists of 9 pieces of
tissue measuring 0.1 x 0.1 x 0.1 cm to 0.4 x 0.2 x
0.2 cm. All are submitted.
MICRO D:
Sections show bronchial tissue with extensive
necrosis, inflammatory exudates, and a few
epithelial cells with chromatin margination, nuclear
molding, and focal multinucleation.
Pathology report

Immunohistochemical study (IHC2019-9594):


The viable squamous epithelial cells are diffusely
positive for HSV-1 and HSV-2.
Microbiology report

Fungus culture
1 Aspergillus fumigatus Rare -
2 Aspergillus flavus Rare -

Virus culture
Virus HSV-1
Final diagnosis

1. ARDS
2. Pneumonia due to aspergillus and herpes virus
infection
Thank you for
Thanks for your attention
your attention

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