RSV Bronchiolitis

Mark A. Brown, M.D.

Professor of Clinical Pediatrics
Pediatric Pulmonary Section
University of Arizona
Bronchiolitis: Definition
Viral infection of the lower respiratory tract characterized by
acute inflammation, edema, and necrosis of epithelial cells
lining small airways, increased mucus production, and
bronchospasm

AHRQ Evidence Report
Epidemiology
Bronchiolitis statistics
90% of children 0-2 yrs. are infected with RSV
20% have lower respiratory infection
3% hospitalized
0.002% mortality
Age at presentation
Peak age 2-5 months
Rare in 1
st
month of life


Viral causes of bronchiolitis
Respiratory syncytial virus (RSV): 70%
Metapneumovirus 10-20%
Newly identified paramyxovirus
Similar seasonality and course to RSV
Parainfluenza
Influenza 10-20%
Adenovirus
Bocavirus ?

}
Seasonality
Bronchiolitis




RSV Isolates
Year
Hall, NEJM 2001
RSV Prime Cause of LRTI in Young Child
Hospitalization for RSV Bronchiolitis:
38% of all LRTI in first year of life
22% of all LRTI in 5 years of age
31 / 1,000 children < 12 mos each year
Economic Burden
Costs for LRTI hospitalizations:
$2.25 billion for infants, 14 to 26% from RSV
$3.73 billion for first 5 years of life,
1016% from RSV
Shay 99
Stang 01
Clinical course of bronchiolitis
Incubation period: 2-8 days
Upper respiratory infection: 1-3 days
Worsening lower airway disease: 3-5 days
Full recovery: 2-8 weeks

P
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Days of symptoms
0
20
40
60
80
100
0 5 10 15 20 25 30 35
Swingler et al. 2000
Clinical course
0 5 10 15 20 25 30 35
S
e
v
e
r
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t
y

Days
0 5 10 15 20 25
0
10
20
30
40
50
60
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80
Risk Factors for Hospitalization with RSV
1708 Hospitalized Infants in Rochester, NY
Prematurity
Chronic
Disease
Age < 6 wks
1 or more
Risk Factors
Percent with:
RSV Roentgenographic Findings
Diffuse interstitial pneumonitis most common in all
lobes
Hyperaeration > 50%
Lobar or segmental consolidation 2050%;
RUL, RML most common
Peribronchial thickening
Therapy for RSV
Oxygen, administered by means of a small
tent, gives these patients with cyanosis
definite relief, and is the treatment upon which
we have to rely for the most severely
ill infants.
J. Adams, Lancet 1945
Therapies
Supportive care
Airway clearance
Hydration
Oxygen
Bronchodilators
Supportive Care
Administer humidified oxygen
Nasal suctioning to clear upper airway
Monitor for apnea, hypoxemia, and impending respiratory
failure
Normalize body temperature
Rehydrate with oral or intravenous fluids
Monitor hydration status
Supportive Care
Quittell LM, et al. Am Rev Respir Dis. 1988;137:406A;
Chest Physiotherapy (CPT)
Little evidence to confirm
enhancement of mucociliary
clearance
QuickTime and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
Bronchodilators
Multiple studies of bronchodilators
Albuterol
Beta
2
adrenergic effects
Racemic epinephrine
Beta
2
adrenergic effects
Alpha adrenergic effects - ? vasoconstriction
Anticholinergics
No evidence for benefit in bronchiolitis
Effect on clinical score: Cochrane meta-analysis
Hartling et al. Cochrane Review 2004
Odds of improvement
Hartling et al. Cochrane Review 2004
Effect on hospitalization
Hartling et al. Cochrane Review 2004
Bronchodilators
Evidence for modest short-term improvement
Overall, 57% improved vs. 43% for placebo
1 infant will benefit for every 7 treated
Mild side effects common: tachycardia, hypoxemia
No impact on overall course of disease in inpatients
Albuterol Dobson et al. Pediatrics. 1998; 101:361-368.
Epinephrine Wainwright et al, N Eng J Med 2003; 49:27-35.
Studies comparing epinephrine vs. albuterol mixed


Hartling et al. Cochrane Review 2004
Bronchodilators and bronchiolitis
Bronchodilators have variable effects on infants with
bronchiolitis
Some improvesome get worseand the rest stay the same



Unknown
Therapies
Supportive Care
Suctioning/Airway Clearance
Upper airway congestion can contribute to symptoms
No evidence for role of deep suctioning
One RCT suggests benefit for using 3% saline with nebs
Sarrell, et al. Chest 2002; 122:2015-2020.
Chest physiotherapy
One small RCT found no benefit of routine Chest PT
Webb et al. Arch Dis Child 1985; 60:1078-
1079.
Hydration
Assess and follow I/Os (potential for SIADH)

Oxygen
Pulse oximetry detects hypoxemia not apparent on PE
Significance of mild hypoxemia (> 90%) unclear
Variability in saturation due to plugging / mismatch
Indication for starting oxygen unclear
Oxygen requirement associated with worse outcomes
Increased risk of need for ventilation
Wang et al. J Peds 1995; 126:212-219.
4 x increased inpatient LOS
Wainwright et al. 2003
? Continuous pulse oximetry vs. spot checking

Protection against lower respiratory infection
Natural immunity to RSV
Antibody to F and G surface proteins protect against LRI
Humoral immunity controls and terminates infection
Reinfections with RSV
Usually limited to URI
Healthcare workers at risk
Significant cause of illness in elderly

Prevention
Non-Specific Measures
Avoidance
Hygiene
Nutrition
Passive Immunization
Palivizumab (Synagis

)

RSV immunoprophylaxis
Attempts to provide immunity to RSV
Vaccine in 1960s worsened course of infection
New intra-nasal vaccine undergoing trials
Passive immunity via hyperimmune globulin
Monoclonal antibody to F protein (palivizumab)
55% hospitalizations for preterm/chronic lung disease
45% hospitalizations for congenital heart disease

The IMpact-RSV Study Group. Pediatrics. 1998;102(3):531-7; Palivizumab Outcomes Study Group. Pediatric Pulm.
2003;35:484-9; Hudak et al. J Perinatol. 2002;22:619, abstract P32; Data on file, MedImmune Inc.
Reduction in RSV Hospitalization Rate
IMpact-RSV study based on active collection of hospital data; Outcomes Registry based on passive reporting
8.1
11
9.8
12.8
4.8
1.8
5.8
2
7.9
2.9
2.1
4.5
1.6
5.8
1.5
1.2
1.7
1.3
2.2
1.1 1.2
1.6
1.9
10.6
0.7
0
2
4
6
8
10
12
14
All Patients Premature
w/o CLD
All <32 weeks
GA
All 32-35
weeks
Patients with
CLD
R
S
V

H
o
s
p

R
a
t
e

1996-1997 IMpact-RSV Trial-Placebo 1996-1997 IMpact-RSV Trial-Synagis
2000-2001 Synagis Outcomes Registry 2001-2002 Synagis Outcomes Registry
2002-2003 Synagis Outcomes Registry
*Receiving medical therapy for CLD within 6 months
Guidelines for RSV Prophylaxis
Premature, no CLD, no CHD
29-32 wks GA
Palivizumab if 6 months
at start of RSV season
28 wks GA
Palivizumab

if 12 months
at start of RSV season
32-35 wks GA
Palivizumab

if 6 months
at start of RSV season with two
risk factors present
Chronic Lung Disease* (CLD)
Hemodynamically Significant CHD
Palivizumab

if 2 years old at
start of RSV season
Apnea and RSV
Apnea reported in 20% of hospitalized infants with RSV
Risk factors for apnea
Age < 2-3 months
Prematurity
May be presenting symptom but usually follows URI/LRI
Recurrence rate 50%
Mortality < 2%

Levine et al. 2004
RSV and asthma link
40-50% of hospitalized bronchiolitics will wheeze again
Increased risk if > 12 months, atopy, eosinophilia

Martinez FD, Godfrey S, 2003
Reijonen 1997
Ehlenfield 2000
Otitis media
Otitis media a common complication
Cohort study of 42 infants with bronchiolitis
62% acute OM (tympanocentesis confirmed)
24% otitis media with effusion
14% normal throughout course
Andrade et al. 1998
Usual guidelines for AOM and OME apply

May there never develop in me the notion
that my education is complete, but give me
the strength and leisure and zeal continually
to enlarge my knowledge.

Moses Maimonides