Pulmonary Disorders Part I: Developmental Diseases - PowerPoint Presentation

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Pulmonary Disorders Part I: Developmental Diseases

Nicole Cacho Do, MPH

August 16, 2018

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Objectives

Discuss Following Developmental Diseases of Neonatal Lung:

Pulmonary Dysplasia

Congenital Diaphragmatic Hernia

Capillary Alveolar Dysplasia

Congenital Pulmonary

Lymphangiectasia

Chylothorax

Congenital Cystic Pulmonary Malformations

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Pulmonary Dysgenesis

Agenesis-total absence of pulmonary parenchyma, its supporting vasculature and bronchi after the bifurcation

Aplasia-subset of agenesis

Hypoplasia-underdeveloped lungs

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Pulmonary Agenesis

Complete

agenesis is usually unilateral, although in some cases there has been dysgenesis of the second lung as

well

Rare

Likely vascular origin (dorsal aortic arch)

Associated with other congenital malformations, considered a subset of VACTERL sequence or

Goldenhar

syndrome

Malformations are ipsilateral to the pulmonary defect

Slide5

Pulmonary agenesis: Diagnosis

Antenatal ultrasound: mediastinal shift (to affected side) in the absence of diaphragmatic hernia

Antenatal echo: absence of pulmonary artery or one of the branches

MRI: confirm diagnosis, evaluate size of remaining lungs and look for other malformations

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Pulmonary Agenesis: CXR

Radiopaque

hemithorax and medial shift to

affected side

Jentzsch 2014

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Pulmonary Aplasia

Presence of blind-ending, rudimentary bronchus without associated lung parenchyma or pulmonary vasculature

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Pulmonary hypoplasia

Incomplete development of lung parenchyma leading to decreased number of distal airways, alveoli and associated pulmonary vessels.

Primary is intrinsic failure of normal lung development

Secondary can be from oligohydramnios, space occupying lesions, or absence or abnormal diaphragmatic activity from neuromuscular disorders

1/3 of patients with oligohydramnios have pulmonary hypoplasia

High mortality rate

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Pulmonary hypoplasia: Diagnosis

Measuring lung-to-body ratio

Only captures babies with lethal hypoplasia

Pathologic specimens

show low ratio of lung to body weight

low DNA content

decreased radial alveolar count

peripheral bronchioles and pulmonary arterioles are decreased in number

a

rterioles hypertrophied medial smooth muscle which predisposes to PPHN

Slide10

Pulmonary hypoplasia: Treatment

Inhaled nitric oxide

Gentle ventilation

Retrospective

cohort

of 151

matched-pairs

of 22-29

weekers

with

hypoplasia

.

iNO

did

not

improve

survival

prior

to

NICU

discharge

or transfer

JAMA

Pediatr

.

2018

Jul

2;172(7):

e180761

Slide11

Congenital Diaphragmatic Hernia: Epidemiology

Developmental defect during formation of diaphragm and abdominal contents herniate into thoracic cavityClassified by anatomic region affectedPosterior lateral (Bochdalek) 70%Anterior (Morgagni) 25%Central 5%Incidence 1/2000 to 1/3000Left sided is most common (85%)

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Congenital Diaphragmatic Hernia: Anomalies

Isolated or associated with other congenital anomalies (40-60%)

CDH Study Group reported a 28% incidence of severe malformations (major cardiac, syndromal, and chromosomal)

Importance of evaluation of associated malformations of these patients

Donnai

-Barrow (hearing, vision, brain,

omphalocele

)

Fryns

(abnormal facies, fingers/toes, cleft) and Pallister-Killian mosaic (

hypotonia

, course facies, severe develop delay) mosaic

Slide13

Congenital Diaphragmatic Hernia: Syndromes

Holder et al. 2007, Genetic

Factors in Congenital Diaphragmatic Hernia

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Congenital Diaphragmatic Hernia: Pathophysiology

Pulmonary insufficiency and PPHN (secondary to pulmonary hypoplasia, low # alveoli, and airway and vascular muscular hypertrophy associated with compression by abdominal contents)

Severity related to degree of lung hypoplasia

Size of defect

presence of liver in chest

how early in gestation abdominal contents were displaced

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Congenital Diaphragmatic Hernia: Outcomes

2007

Systematic

R

eview

by Logan et al found that ~60% cases diagnosed antenatal

Antenatal diagnosis is associate with poor prognosis

Infants with a prenatal diagnosis have better outcomes if born at a tertiary center

Predictors based on assessment of the contralateral lung

Lung area to head circumference ratio (LHR) between 22 and 28 weeks gestation

Liver in chest (most predictive)

Estimated fetal lung volume by MRI

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Congenital Diaphragmatic Hernia: OUtcomes

Corrected gestational age LHR=observed LHR/expected ratio

Fetal Corrected LHR (%)Survival (%)<15015-252026-35, or 36-45 liver up30-60>45, or 36-45 liver down>75

CDH registry n=184 with Left CDH 22-28 weeks

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Congenital Diaphragmatic Hernia: Index of Suspicion

Baby with severe respiratory distress, cyanosis, scaphoid abdomen and failure to improve with ventilation

Auscultation can reveal: no breath sounds on affected side or bowel sounds, displacement of heart sounds to contralateral side

Order CXR!!!!!

While waiting intubate, and OG tube to decompress stomach

Late presentation of

Bochdalek

hernia occurs in less than 3% of cases

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Congenital Diaphragmatic Hernia: CXR

Radiopaedia.org

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Congenital Diaphragmatic Hernia: Consistent approach

Multidisciplinary management plans have improved survival

Predetermined ECMO criteria

“Protect the lung” strategy

Low PIP, PaCO2 levels <65, HFOV, ?

iNO

, ECMO rescue therapy, delay repair until stable and PPHN improves

Heliox

as Adjunct Therapy?

Retrospective cohort of 45 infants (28 with

heliox

) facilitated

improvement in gas exchange, which allowed a decrease in ventilator settings and oxygen

exposure

Respir

Care.

2018 May

22

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Congenital Diaphragmatic Hernia: Follow up

GERD

FTT

Neurodevelopmental delay

Sensorineural hearing loss

Scoliosis

AAP recommended follow up schedule (2008)

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Capillary Alveolar dysplasia

AKA Misalignment of the pulmonary veins

Rare, often fatal

P

resents within 48

hrs

with severe hypoxemia and unresponsive PPHN

Term babies with good

A

pgars

Unknown incidence due to diagnosis made by pathology but not all babies have lung biopsy or autopsy

Autosomal recessive mutation in FOXF1 gene on 16q24.1 which may help prenatal diagnosis in high risk families

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Capillary Alveolar dysplasia

Minimal capillaries close to immature alveoli, anomalous misplaced distended pulmonary veins, medial thickening of small pulmonary arteries and

muscularization

of arterioles.

Pathology is diffuse in 85% of these patients and patchy in remaining

Pathophysiology

Failure of fetal lung vascularization with capillary hypoplasia and discontinuity of these capillaries and pulmonary veins impairing pulmonary blood flow as well as reactive pulmonary vasoconstriction

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Capillary Alveolar dysplasia

Bishop et al. 2011

Medial thickening of pulmonary arteries

Malpositioned

congested pulmonary veins

Dilated Bronchiole

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ChildHood interstitial lung disease

Group of rare lung diseases that can affect neonates, children and

adolesents

Neonatal types: capillary alveolar dysplasia, surfactant dysfunction mutations, pulmonary interstitial glycogenosis (PIG)

Diagnsosis

: CXR, CT chest, BAL, genetic panel

Treatment: Oxygen, bronchodilators, corticosteroids, other anti-inflammatory and immune modulators

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Congenital pulmonary lymphangiectasia: Epidemiology

Rare

Males more affected

Sporadic but family clusters suggest autosomal recessive pattern

Classification

Primary: Localized

or

diffuse. Patients

with generalized lymph disorder have less severe pulmonary involvement

Secondary: Associated

with cardiac malformations (TAPVR, HLHS

) and possibly non-immune

hydrops and congenital

chylothorax

Diagnosis made by lung biopsy as in CAD

Prognosis is better with later presentation

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Congenital pulmonary lymphangiectasia

CXR: Hyperinflation with

B/L interstitial infiltrates

Hagmann

and Berger 2003, N Engl J Med

Artery

Subpleural

and septal cystic lymphangiectasia

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chylothorax

Lymph fluid in the pleural cavity

Rare (1:10,000 births), more common in males and on right side

Classification

Primary:

lymph disorders (

Noonans

, trisomy 21), congenital heart disease, mediastinal malignancies

Secondary

:

thoracic surgery trauma, increased SVC pressure (thrombus)

A

nalysis of pleural fluid:

transudative

, pH>7.4, cell count<1000/mm3 with >80%

lymphs

, TG>110

Most cases resolve in less than 2 months

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Chylothorax: management

Nutritional: formulas

with high medium chained triglycerides (

Enfaport

-since lymphatic vessels are not required for absorption of

MCT), fat skimmed

breast

milk, may need increased protein supplementation

Pharmacological:

octreotide (somatostatin analogue,

more effective in primary than secondary, not significant

(P

=

0.10)

J

Paediatr

Child Health.

2018 Mar

30

)

Surgery if severe: chest tube,

pleurodesis

,

l

ymphovenous

anastomosis (

Plast

Reconstr

Surg.

2018 Aug;142(2):

581)

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Chylothorax: CXR

Ning-Hui Foo et al. 2011

B/L

chylothoracies

and ascites in late preterm infant

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Congenital cystic pulmonary Malformations

Congenital Cystic

A

denomatoid

Malformation (CCAM) or Congenital Pulmonary

A

irway

M

alformation (CPAM)

Bronchopulmonary Sequestration

Bronchogenic Cyst

Congenital Lobar Emphysema

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Congenital Pulmonary AIRWAY Malformation (CPAM)

Multiple

hamartomatous

lesions arising from the abnormal branching of the immature bronchial tree

Most common out of the 4 diseases, incidence 1:11,000-13,000, affecting more males

Unilobar

and usually lower lung predominance

Connected with tracheobronchial tree

and has a

pulmonary blood supply

Classification prenatally (

Adzick

et al. 1985)

Microcystic

(<5mm)

Macrocystic

(>5mm)



Better prognosis

Hydrops due to CCAM has ~100% mortality rate

High CCAM volume ratio (CVR) can predict risk of hydrops and help stratify which patients may benefit from fetal surgery

Antenatal steroids may be able to shrink CCAM and help resolve hydrops (

Puligandla

et al. 2012)

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Congenital Pulmonary AIRWAY Malformation: Stocker Classification

TypeOccurrence Cyst sizeHighlights0RareMultiple smallUsually lethal160-70%Large and smallMany regress prenatally215%Multiple smallOther anomalies35-10%Multiple smallAppear as solid mass410%LargeLate presentation

Stocker et al. 1977, 2002, 2009

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Bronchopulmonary sequestration

Microscopic cystic masses arising from foregut

Not connected to airway

and has

systemic

blood supply

Classification

Intralobar

: accessory bed arises before pleura is established

Extralobar

: accessory lung bud arises after pleura is established; can be under diaphragm; higher association with congenital anomalies

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Bronchopulmonary sequestration

Most significantly decrease in size as gestation continues, therefore most asymptomatic during first month of life

On CXR appear as posterior chest mass mostly on the left

High output cardiac failure is a unique feature

Surgery is encouraged for asymptomatic patient to prevent future infection or malignancy

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Bronchogenic Cyst

Single cyst lined by respiratory epithelium and lined by cartilage and smooth muscle

Arise from abnormal budding of foregut early in first trimester

Mostly found in mediastinum

Treatment is complete resection and has an excellent prognosis thereafter

Slide36

Bronchogenic Cyst: CXR

Case courtesy of Dr Ian Bickle, Radiopaedia.org, rID: 19947

Most found in mediastinal area

Slide37

Congenital lobar emphysema

Postnatal over distention of one or more lobes

Pathophysiology includes intrinsic or extrinsic obstruction causing air trapping, over distention and finally emphysema

dysplastic cartilage,

inspisated

mucus, abnormal vasculature, infection

Left upper lobe is most frequently involved

Presents in neonatal period with a similar clinical picture to a tension pneumothorax but without hemodynamic instability

 distinction is critical to avoid attempting aspiration and creating a pneumothorax

Surgical lobectomy has excellent prognosis

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Congenital lobar emphysema: CXR

Case courtesy of

Dr Jeremy Jones, Radiopaedia.org, rID: 27202

Left upper lobe

lucency

could be mistaken for a pneumothorax

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Summary

Many require surgical intervention

Better prognosis with later presentation

Many have male predominance

Predilection for distinct areas of thorax (focus on right or left)

Possible associated congenital anomalies may necessitate further workup

Knowing which are lethal may help avoid futile interventions

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Question 1:

Term male 3.2kg born with

A

pgars

of 8 and 8. Meconium aspiration with persistent cyanosis and oxygenation index of 40. Decision to go to ECMO. After prolonged ECMO, multiple pump failures, 2 codes, severe IVH parents decide to withdraw care. Parents refuse autopsy. Which genetics work up may have been helpful in this case?

A. VACTERL sequence

B.

Goldenhar

syndrome

C. FOX F1 gene testing

D. Karyotype

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Answer I: C

FOXF1 gene has been found in a cohort of ~40% of patients with CAD

Lung biopsy viewed by pathologist is the definitive diagnosis and can be done while patient is still alive to help redirect care

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Question 2:

You get a call on the fellow phone from the

Peds

ED requesting your presence for intubation of a 2 day old female who is

tachypneic

,

tachycardic

with poor perfusion and enlarged liver. The ED attending quickly mentions there appears to be a left sided chest mass and baby was born at home with limited prenatal care. What is your first imaging study of choice?

A. CT scan of chest

B. CT scan of brain

C. MRI of chest

D. Echocardiogram

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Answer 2: D

Echocardiogram since you are thinking that bronchopulmonary

seqestration

is your diagnosis. You will also call surgery to bedside and consider which imaging study will be faster (CT scan or MRI) and preferred by surgery to determine systemic blood supply of the mass

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Question 3

Which of the following are more commonly found on the left side?

A. Capillary alveolar dysplasia

B. Bronchopulmonary sequestration

C. CDH

D.

Chylothorax

E. Both B and C

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Answer 3: E

Capillary alveolar dysplasia is diffuse

Chylothorax

is usually right sided

Both Bronchopulmonary sequestration and Congenital diaphragmatic hernia are more commonly left sided

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Brodsky and Martin question review book

Try these questions on your own

Pulmonary questions: 10, 28, 45, 49