Transcript Infectious Disorders of the Lung Parenchyma

Infectious Disorders of
the Lung Parenchyma
Matthew L. Paden, MD
Pediatric Critical Care Fellow
Emory University
Children’s Healthcare of Atlanta at Egleston
Objectives



Worldwide epidemiology of the problem
Review common etiologies
Discuss empirical and disease specific treatment
Epidemiology

World wide

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Leading cause of death in
children
More than AIDS, malaria,
and measles combined
Most deaths in < 5 yo
United states
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
3rd leading cause of
hospitalization for kids
2% of deaths (5%
including neonates)
http://www.who.int/child-adolescenthealth/publications/CHILD_HEALTH/ISBN_92_806_4048_8.htm
Worldwide Epidemiology

Cases
 150 million

Hospitalizations
 11-20 million

Deaths
 2 million
Barriers to care

Recognizing there is a
problem

Seek appropriate care

Treatment with
antibiotics
Prevention

Adequate nutrition

Exclusive breastfeeding


Less than 1 yo, get any formula – 5 X increased risk of
death from pneumonia
Zinc supplementation
Prevention

Immunization

Measles –
Pneumonia is what they die of – often super-infection
 World-wide coverage rate – 76% in 2004
 Still having 30-40 million cases a year


HIB –
2-3 million cases of severe disease a year
 In 2003, developed world coverage – 92%
 Developing world – 42%
 Least developed countries – 8%

Prevention

Immunization

Strep pneumo –
7 –valent vaccine (Prevnar) in the US
 9, 11, or 13 valent vaccine for the rest of the world
 Gambia – 17,000 children
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
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37% reduction in pneumonia
15% reduction in hospitalization
16% reduction in mortality
Costs involved


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More than 1 million deaths a year can be prevented
with treatment and prevention
600,000 lives saved by just treatment alone
Cost analysis

Antibiotic treatment course

$ 0.27
$ 600 million total cost including :


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Cost of antibiotics
Cost of hospital stays
Increasing training of health care staff
Increasing physical plants to take care of these patients
Costs involved

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Those costs inflated by Mexico and Brazil
85% of deaths are in sub-Saharan Africa and
southeast Asia

$200 million dollars will expand coverage to those
regions only and potentially fix 85% of the problem
Potential solutions


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One F-22 fighter - $183 million
1997-2003, Defense Department purchased and then left unused
approximately 270,000 fully refundable commercial airline tickets at a total
cost of $100 million.
$4,000,000 for the Northern Line Extension

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A direct 82 mile train route from North Pole (pop. 1,778 in 2005) to Delta
Junction (pop. 840 in 2000)
$9,500,000 for the Extended Cold Weather Clothing System
$8,000,000 added by the Senate for special assistance DOD Dependents
Education.
$5,500,000 for The Ernest Gallo Clinic and Research Center at (USCF) to
study basic neuroscience and the effects of alcohol and drug abuse on the
brain.”
$1,650,000 to improve the shelf life of vegetables “This project will help our
troops in the field get fresh tomatoes…”
Diagnosis

Tachypnea
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Sensitive but not specific
Higher specificity
Decreased breath sounds
 Inspiratory rales
 Chest wall retractions
 Nasal flaring
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Absence of fever has high negative predictive
value for bacterial pneumonia
Etiologies
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Streptococcus pneumoniae
Most common cause outside of neonatal period
 Nasopharyngeal colonization – 50% of kids
 >90 serotypes – majority of invasive disease caused
by 10 serotypes
 Bacteremia in 25-30% of kids
 Gram stain – gram positive lancet shaped diplococci
(“gram positive cocci in pairs”)
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Age differences
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Adults – lobar
pneumonia
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Kids – lobar or
bronchopneumonia
Treatment - Streptococcus
pneumoniae
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2002 CDC Surveillance
data
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20% PCN resistant
4% Cefotaxime resistant
0% Vancomycin resistant
2003-2004 FAST
Surveillance data
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56% PCN resistant
Geographically-based evaluation of multi-drug resistance trends among
Streptococcus pneumoniae in the USA: findings of the FAST surveillance
initiative (2003-2004). Int J Antimicrob Agents. 2006 Dec;28(6):525-31.
2006 CHOA Data
Percent of organisms tested that have intermediate or resistant
sensitivity patterns
Organism Vanc CTX I
ECH
Strep
pneumo
CTX R PCN I
PCN R
0% 21/14% 20/6 %
14 %
46 %
SRH Strep 0 % 26/9 % 7/8 %
pneumo
34 %
31 %
Treatment – Strep pneumo
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Mechanism of resistance –
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PCN and Cephalosporins – change in penicillin
binding proteins (NOT beta lactamase)
Empiric : 3rd generation cephalosporin +
vancomycin until sensitivities are confirmed
Etiologies
 Staphylococcus
aureus
 Common
cause of ventilator associated and
nosocomial pneumonia
 Community acquired disease usually
coincident with viral infection (influenza)
 Viral
hemagglutinins – inhibit neutrophil and
monocyte activation
 Gram
stain – gram positive cocci in grape like
clusters
Diagnosis – Staphylococcal
pneumonia
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Classically a lobar
consolidation on CXR
Raise suspicion of staph
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Pneumatoceles
Pleural effusion
Air fluid levels
Necrosis
Treatment – Staphylococcus aureus
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Treatment has changed over the past 5 years with
emergence of caMRSA
Empiric therapy with Vancomycin
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VISA (1996, Japan, 1997 US)
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VRSA (2002, US)
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Mechanism – thickening of cell membrane – decreased penetration
of vancomycin – unclear mechanism
Mechanism – VanA from enterococcus – changes d-alanine, d-alanine
terminus to d-alanine, d-lactate – reduces affinity by 1,000 fold
VDSA
2006 CHOA Data
• ECH total % MRSA 53%
Organism
SRH total % MRSA 51%
Vanc Clinda* Bactrim Rifampin Gent
ECH
MRSA
0%
14%
1%
1%
1%
SRH
MRSA
0%
13 %
1%
1%
3%
* Not adjusted for inducible resistance
Staph Aureus treatment
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Get off Vancomycin if MSSA
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MSSA much more susceptible to Nafcillin
Use of Vancomycin or first-generation Cephalosporins for
the treatment of hemodialysis-dependent patients with
methicillin-susceptible Staphylococcus aureus bacteremia.
Clin Infect Dis. 2007 Jan 15;44(2):190-6.
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Treatment failure - Vancomycin 31.2% vs. Ancef 13% ; p=.02
Multivariable analysis - factors independently associated with
treatment failure included Vancomycin use (odds ratio, 3.53; 95%
confidence interval, 1.15-13.45)
Staph aureus treatment

Get off Vancomycin if MSSA
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Staphylococcus aureus bacteremia and endocarditis: the Grady Memorial
Hospital experience with methicillin-sensitive S aureus and methicillinresistant S aureus bacteremia. Am Heart J. 2004 Mar;147(3):536-9.
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MSSA bacteremia is associated with higher rates of endocarditis than MRSA.
Comparative activity of cloxacillin and vancomycin against methicillinsusceptible Staphylococcus aureus experimental endocarditis.
J Antimicrob Chemother. 2006 Nov;58(5):1066-9.
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Cloxacillin produced a greater decrease in the number of staphylococci than
vancomycin
41% of rabbits had sterile vegetations in comparison with 0% with
vancomycin (p=0.035)
New horizons
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Anti-MRSA beta-lactams in development, with a focus
on ceftobiprole: the first anti-MRSA beta-lactam to
demonstrate clinical efficacy. Expert Opin Investig
Drugs. 2007 Apr;16(4):419-29.
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Investigational beta-lactam antibiotic against methicillinresistant staphylococci, enterococcus faecalis, penicillinresistant streptococci and many Gram-negative pathogens.
Completed Phase III therapeutic trials
PPI0903 - injectable pro-drug of a broad-spectrum
cephalosporin with anti-MRSA activity
RO4908643 - a carbapenem with anti-MRSA activity
Etiologies

Pseudomonas aeruginosa
Common cause of bacterial nosocomial pneumonia
 More common in CF, tracheostomy dependant, or
immunocompromised
 Oxidase positive gram negative rod

Pseudomonas treatment
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Antibiotic resistance common
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Mechanism – extended spectrum beta-lactamase
Implication – serious or life-threatening infections should not
be treated with an anti-pseudomonal synthetic
penicillin/cephalosporin/carbapenem alone
Empiric therapy – anti-pseudomonal PCN + an
aminoglycoside
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Role of monotherapy has not been well defined.
Pseudomonas treatment
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Antibiotic choices
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Anti-pseudomonal synthetic penicillin
Ticarcillin +/- clavulanate
 Piperacillin +/- tazobactam

Pseudomonas treatment

Antibiotic choices
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Anti-pseudomonal synthetic penicillin
Ticarcillin +/- clavulanate
 Piperacillin +/- tazobactam
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Mechanism of Action
Inhibits bacterial cell wall synthesis by binding to one or
more of the penicillin-binding proteins
 Inhibits the final transpeptidation step of peptidoglycan
synthesis in bacterial cell walls
 Clavulanate and tazobactam prevents degradation of the
PCN by binding to beta-lactamases

Pseudomonas treatment

Antibiotic choices
Anti-pseudomonal synthetic penicillin
 4th generation cephalosporin – cefepime
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Ceftazidime – 2nd generation with pseudomonas activity
Pseudomonas treatment

Antibiotic choices
4th generation cephalosporin – cefepime
 Mechanism of Action

Inhibits bacterial cell wall synthesis by binding to one or
more of the penicillin-binding proteins
 Inhibits the final transpeptidation step of peptidoglycan
synthesis in bacterial cell walls

Pseudomonas treatment

Antibiotic choices
Anti-pseudomonal synthetic penicillin
 4th generation cephalosporin – cefepime
 Carbapenems – imipenem-cilastatin or meropenem

Pseudomonas treatment

Antibiotic choices
Carbapenems – imipenem-cilastatin or meropenem
 Mechanism of Action

Inhibits cell wall synthesis by binding to penicillin-binding
proteins (PBPs) with its strongest affinities for PBPs 2, 3
and 4 of E. coli and P. aeruginosa and PBPs 1, 2 and 4 of S.
aureus
 Meropenem reduces valproate levels by ~40%
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Pseudomonas treatment
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Antibiotic choices
Anti-pseudomonal synthetic penicillin
 4th generation cephalosporin – cefepime
 Carbapenems – imipenem-cilastatin or meropenem
 Aztreonam
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Pseudomonas treatment
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Antibiotic choices
Aztreonam
 Mechanism of Action

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Binds to penicillin-binding protein 3 which produces
filamentation of the bacterium inhibiting bacterial cell
wall synthesis and causing cell wall destruction
Pseudomonas treatment

Antibiotic choices
Anti-pseudomonal synthetic penicillin
 4th generation cephalosporin – cefepime
 Carbapenems – imipenem-cilastatin or meropenem
 Aztreonam
 Fluroquinolones – ciprofloxacin, levofloxacin, etc.
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Pseudomonas treatment
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Antibiotic choices
Fluroquinolones – ciprofloxacin, levofloxacin, etc.
 Mechanism of Action
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Inhibits DNA-gyrase and topoisomerase IV in susceptible
organisms; inhibits relaxation of supercoiled DNA and
promotes breakage of double-stranded DNA
Pseudomonas treatment

Antibiotic choices
Anti-pseudomonal synthetic penicillin
 4th generation cephalosporin – cefepime
 Carbapenems – imipenem-cilastatin or meropenem
 Aztreonam
 Fluroquinolones – ciprofloxacin, levofloxacin, etc.
 Aminoglycosides – amikacin, gentamicin,
tobramycin
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Pseudomonas treatment

Antibiotic choices
Aminoglycosides – amikacin, gentamicin,
tobramycin
 Mechanism of Action
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Inhibits cellular initiation of bacterial protein synthesis by
binding to 30S and 50S ribosomal subunits resulting in a
defective bacterial cell membrane
Pseudomonas treatment

Antibiotic choices
Anti-pseudomonal synthetic penicillin
 4th generation cephalosporin – cefepime
 Carbapenems – imipenem-cilastatin or meropenem
 Aztreonam
 Fluroquinolones – ciprofloxacin, levofloxacin, etc.
 Aminoglycosides – amikacin, gentamicin,
tobramycin

So which to choose?
2006 CHOA Data - Pseudomonas
Site
Time Zosyn Fortaz Cefep Merrem Aztre Cipro
ntin
ime
onam
Amik
acin
Gent
Tobra
ECH
12 %
6%
13 %
16 %
12 %
24 %
8%
12 %
20 %
13 %
SRH
6%
2%
4%
11 %
8%
n/a
14 %
10 %
29 %
16 %
* No CF patients included
2006 CHOA Data - Pseudomonas
Site
Time Zosyn Fortaz Cefep Merrem Aztre Cipro
ntin
ime
onam
Amik
acin
Gent
Tobra
ECH
12 %
6%
13 %
16 %
12 %
24 %
8%
12 %
20 %
13 %
SRH
6%
2%
4%
11 %
8%
n/a
14 %
10 %
29 %
16 %
* No CF patients included
Etiologies

“Atypical” Pneumonias
Mycoplasma pneumoniae
 Chlamydia pneumoniae
 Legionella pneumophilia
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Common cause of pneumonia in school age
children
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Persistent cough (for weeks after infection has
cleared)
“Atypical” Pneumonia diagnosis

Mycoplasma – clinical picture + serologic testing
Cold agglutinins are not specific
 Complications – arthritis, hemolysis, pericardial
effusions, myocarditis, encephalitis, Stevens-Johnson
syndrome
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Antibiotic therapy has not been conclusively shown to
help non-pulmonary manifestations
“Atypical” Pneumonia diagnosis
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Legionella pneumophilia
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Severe disease in immunocompromised
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Respiratory failure, pericarditis
Classic history triggers – exposure to travel, hot tubs,
or hospitalization
 DFA, culture, and serology available
 Urinary antigen – good sensitivity and specificity
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“Atypical” Pneumonia treatment
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Macrolide antibiotics
Erythromycin
 Azithromycin
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Mechanism of Action

Inhibits bacterial RNA-dependent protein synthesis
by binding to the 50S ribosomal subunit which
results in the blockage of transpeptidation
Etiologies

Viral
Respiratory syncytial virus
 Parainfluenza
 Influenza
 Adenovirus
 Human metapneumovirus
 Hantavirus

Respiratory syncytial virus

Enveloped, single
stranded, negative
polarity RNA
paramyxovirus

Seasonality – November
through May
Respiratory syncytial virus diagnosis

Viral culture is gold standard
DFA and PCR available
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PICU presentation
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Upper airway obstruction
 Lower airway obstruction
 Pneumonia
 Apnea
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Respiratory syncytial virus diagnosis
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Upper airway obstruction
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Laryngotracheobronchitis
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If fails traditional management (steroids, oxygen,
epinephrine, heliox, etc.) and is intubated get endotracheal
aspirate for bacterial superinfection
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Often staph or strep
Respiratory syncytial virus diagnosis
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Lower airway obstruction
Clinically bronchiolitis
 Increasing airway edema and mucous secretion
worsen the obstruction
 CXR confirms hyperinflation and patchy infiltrates
 Intubated patients commonly co-infected with
moraxella
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Respiratory syncytial virus treatment

Lower airway obstruction

Treatment –
Oxygen
 +/- nebulized B-agonists or epinephrine
 +/- nasal suctioning
 +/- vasoconstrictive nasal drops
 +/- NIPPV
 Mechanical ventilation based on reduction of obstruction


Lower rates and maximizing expiratory time
Respiratory syncytial virus treatment

Lower airway obstruction

Treatment –
Steroids – RSV alone, no efficacy in reducing stay
 Ribivirin – only FDA approved drug for RSV

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Many complications and expensive
May have a role in the immunocompromised
Respiratory syncytial virus diagnosis

RSV Pneumonia
Similar presentation as bronchiolitis
 Different pathophysiology – alveolar filling and
consolidation
 CXR


Discrete infiltrate and lack of hyperinflation
Greater degree of hypoxia
 More likely to progress to ARDS
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Respiratory syncytial virus diagnosis
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RSV Apnea
Not well described
 More common with increasing prematurity
 Polysomnography implies it is central apnea
 Pathophysiology – signaling from pulmonary nerves
through the GABA and substance P pathways
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
Pediatr Res. 2005 Jun;57(6):819-25.
Etiologies

Viral
Respiratory syncytial virus
 Parainfluenza
 Influenza
 Adenovirus
 Human metapneumovirus
 Hantavirus
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Parainfluenza diagnosis


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Enveloped, single stranded, negative polarity
RNA paramyxovirus
Similar presentations to RSV
Viral culture is gold standard
DFA or PCR available
4 different virus types
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Type 1 epidemic every other year
Parainfluenza seasonality
Parainfluenza treatment

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Similar supportive care to RSV
May be a role for both inhaled and intravenous
ribivirin in immunosuppressed patients
Etiologies

Viral
Respiratory syncytial virus
 Parainfluenza
 Influenza
 Adenovirus
 Human metapneumovirus
 Hantavirus
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Influenza diagnosis

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Negative sense, single stranded RNA viruses
Type A and B responsible for majority of
illnesses
Hemagglutinin – viral binding to respiratory
epithelial cells vial sialic acid
Neuroaminidase – cleaves sialic acid residues
once virus has multiplied in the cell allowing
viral spread
Influenza Viral Life Cycle
Influenza diagnosis
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
Clinical markers
Other manifestations
Laryngotracheobronchitis
 Myocarditis
 Rhabdomyolysis
 Reye’s syndrome
 Encephalitis
 Staph superinfection

Influenza diagnosis


Viral culture is gold standard
DFA, PCR, and rapid immunoassays available
Influenza treatment

Amantidine or rimantidine
Inhibits influenza M2 proteins and prevent viral
uncoating
 Need to give early or no benefit
 Resistance is documented

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Oseltamivir and zanamivir

Neuroaminidase inhibitors
Etiologies

Viral
Respiratory syncytial virus
 Parainfluenza
 Influenza
 Adenovirus
 Human metapneumovirus
 Hantavirus
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Adenovirus diagnosis
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Specifically types 3 and 7
Rapidly evolving life threatening pneumonia with
necrosis, pulmonary hemorrhage and bronchiolitis
obliterans
Survival dependant on degree of injury
Viral culture is gold standard
DFA, PCR, rapid ELISA are available
ECLS an option

Extracorporeal life support for the treatment of viral
pneumonia: collective experience from the ELSO registry.
Extracorporeal Life Support Organization. J Pediatr Surg.
1997 Feb;32(2):232-6.
Etiologies

Viral
Respiratory syncytial virus
 Parainfluenza
 Influenza
 Adenovirus
 Human metapneumovirus
 Hantavirus

Human metapneumovirus diagnosis


Also a paramyxovirus
In children and infants notable cause of lower respiratory tract
infections




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Bronchiolitis (59%)
Croup (18%)
Asthma exacerbations (14%)
Pneumonia (8%).
Symptoms very similar to RSV (cough 90%;
dyspnea 83%; coryza 88%; fever 52-92%)
Can cause severe disease in BMT patients
PCR based diagnosis at this point
Supportive treatment
Etiologies

Viral
Respiratory syncytial virus
 Parainfluenza
 Influenza
 Adenovirus
 Human metapneumovirus
 Hantavirus

Hantavirus diagnosis




A negative sense, single stranded RNA virus of the
bunyaviridae family
Multiple different viruses worldwide
Four corners region - Sin Nombre virus
All other bunyaviridae have arthropod vectors


Hantavirus – vector is the deer mouse
8% of hantavirus infections in US are children

33% mortality (similar to adults)
Hantavirus infection


Exposure/Travel history
Clinical syndrome
Fever
 Fulminant bilateral pulmonary disease
 Cardiogenic shock
 Pulmonary edema

Hantavirus diagnosis

Laboratory syndrome
Hemoconcentration
 Thrombocytopenia
 Leukocytosis
 Absence of granules in neutrophils
 Immunoblasts on smear

Hantavirus diagnosis

Laboratory syndrome
Testing via serologies, immunohistochemistry, and
rapid RNA PCR
 All via New Mexico/CDC


Treatment –
Study with IV Ribavirin via UNM/CDC
 Supportive

Hantavirus treatment


Above all – Consultation with experts at
University of New Mexico and CDC
From CDC Website :

Take-home Message for Care Providers
Rapid transfer to ICU
Careful monitoring
Fluid balance
Electrolyte balance
Blood pressure
Hantavirus treatment

Management with Swan-Ganz catheter essential
In contrast to septic shock, HPS patients have a low
cardiac output with a raised systemic vascular
resistance.
 Titrate fluid to keep wedge pressure to <12
 Poor prognostic indicators include a plasma lactate
of greater than 4.0 mmol/L or a cardiac index of
less than 2.2 L/min/m2
 Whilst pulmonary edema and pleural effusions are
common, multiorgan dysfunction syndrome is rarely
seen.

Hantavirus treatment




Prior to the use of extracorporeal membrane
oxygenation (ECMO) as a rescue therapy, a
cardiac index of less than 2.5 L/min/m2
predicted 100% mortality rate.
eMedicine – 15 patients, 9 intact survivors
Dramatic improvement usually seen in the first
day
Runs are usually 4-5 days
Etiologies

Fungal Pneumonias
Candida
 Aspergillus

Candida pneumonia diagnosis


Essentially a disease of immuno-compromised
Common upper airway and oral flora


Colonization vs. infection
Translocation across the gut -> hematogenous
spread to the lungs is another source in
neutropenic patients
Candida pneumonia diagnosis

ECH Procedure
Sensitivity done automatically on all sterile site
specimens
 Can be done request on others (ETT is NOT sterile)
 Done at SRH –

48 hour test – must be done on a 48 hour old sample
 Must be set up in the morning
 Don’t set it up on the weekend

Candida pneumonia diagnosis

Multiple species

C. albicans
Most common
 Quickest of the yeast to be identified – candida chrome
agar (green color change)

Candida Chrome Agar

Produces species
specific colorful
colonies of Candida
species.

Green: C. albicans
Blue: C. tropicalis
Pink: C. krusei
Candida pneumonia diagnosis

Multiple species

C. albicans
Most common
 Quickest of the yeast to be identified – candida chrome
agar (green color change)


C. parapsilosis


Second most common at ECH
C. glabrata, krusei, lusitaniea

More rare, but the ones to worry about
Antifungal Therapy


Not a lot of good, large number trials in
pediatric immuno-suppressed patients
Even less in treating pneumonia

Assume systemic spread in neutropenic patients
Antifungal Therapy


Mostly C. albicans fungemia in non-neutropenics
Flu (400/d) vs. AmB (0.5-0.6 mg/kg/d). %Success:





Randomized, N=206, Flu 70%, AmB 79%, P = 0.22
Randomized, N=103, Flu 56%, AmB 60%, P = 0.80
Observational, N=294, Flu 73%, AmB 69%, P = 0.58
Observational, N=479, Flu 71%, AmB 73%, P > 0.38
ABLC (5 mg/kg/d) vs. AmB (0.6-1 mg/kg/d)

Randomized, N=194, ABLC 65%, AmB 61%, P = 0.64
Rex, 1994; Phillips 1997; Nguyen, 1995; Anaissie, 1998
Candida sensitivities
Flucon Itra
AmB
C. albicans
S
S
S
C. parapsilosis S
S
S
C. tropicalis
S
S
S
C. glabrata
SDD-R SDD-R I
C. krusei
R
SDD-R I-r
C. lusitaniae
S
S-SDD R
5-FC
S
S
S
S
I-R
R
Aspergillus pneumonia



Organism – Aspergillus fumigatus
Increasing incidence in immuno-compromised
patients
Solid organ or BMT patients

Mortality approaches 75%
Aspergillus pneumonia diagnosis

Large areas of pulmonary necrosis


Can look like staph
Necrosis is because of direct blood vessel
invasion by the organism and subsequent
thrombosis
SAME PHYSIOLOGY AS A PULMONARY
EMBOLUS
 Wedge shaped emboli seen on CXR
 Right heart strain less often

Aspergillus pneumonia diagnosis

Fungal culture from BAL
sample is gold standard
Aspergillus pneumonia treatment

Empiric therapy with amphoteracin-B or
itraconazole

Lobectomy used if caught early and confined
Mortality remains high despite all treatment

Etiologies

Mycobacterium tuberculosis
TB diagnosis



Aerobic acid-fast bacilli
High index of suspicion
Exposure/risk factor history is key







Known TB cases
Incarceration (jail/prison)
Health care workers
Homeless/Community shelter
Immuno-compromised
Travel to/visitation from endemic areas (Grady)
Ask about BCG in immigrants
TB diagnosis

Recovery from culture is gold standard


AFB stain and culture
PCR available
TB Treatment


Get ID involved for recs and follow-up
Isolation in negative pressure room
Patient with surgical mask for any transport
 Parents to get CXR (surgical mask)

“When determining TB status on adult family members
of inpatients with diagnosed or strongly suspected TB,
external diagnostic resources (private physician, health
department) are considered first.”
 “When circumstances do not allow for this, Children’s will
provide diagnostic services only and refer, if needed, for
treatment of disease.”
 Write an order – parents register – pay or SW - get CXR –
Emory radiologists read it
