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 1st month of life
Viral causes of bronchiolitis
• Respiratory syncytial virus (RSV):
• Metapneumovirus
– Newly identified paramyxovirus
– Similar seasonality and course to RSV
• Parainfluenza
• Influenza
• Adenovirus
• Bocavirus
}
70%
10-20%
10-20%
?
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
Shay ’99
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,
1016% from RSV
Stang ’01
Clinical course of bronchiolitis
Incubation period:
Upper respiratory infection:
Worsening lower airway disease:
Full recovery:
Percent
•
•
•
•
2-8 days
1-3 days
3-5 days
2-8 weeks
100
80
60
40
20
0
0
5
10
15 20
25
Days of symptoms
30 35
Swingler et al. 2000
Severity
Clinical course
0
0
5
10
15
5
20
25
10
15
Days
20
25
30
35
Risk Factors for Hospitalization with RSV
1708 Hospitalized Infants in Rochester, NY
80
70
1 or more
Risk Factors
Percent with:
60
50
40
30
20
10
0
Prematurity
Chronic
Disease
Age < 6 wks
RSV Roentgenographic Findings
• Diffuse interstitial pneumonitis most common in all
lobes
• Hyperaeration > 50%
• Peribronchial thickening
• Lobar or segmental consolidation 2050%;
RUL, RML most common
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
• Chest Physiotherapy (CPT)
– Little evidence to confirm
enhancement of mucociliary
clearance
Quittell LM, et al. Am Rev Respir Dis. 1988;137:406A;
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
Bronchodilators
• Multiple studies of bronchodilators
– Albuterol
• Beta2 adrenergic effects
– Racemic epinephrine
• Beta2 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 improve…some get worse…and 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; 60:10781079.
•
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
Reduction in RSV Hospitalization Rate
1996-1997 IMpact-RSV Trial-Placebo
2000-2001 Synagis Outcomes Registry
2002-2003 Synagis Outcomes Registry
14
RSV Hosp Rate
12
1996-1997 IMpact-RSV Trial-Synagis
2001-2002 Synagis Outcomes Registry
12.8
11
10.6
9.8
10
8.1
7.9
8
6
4
2
5.8
4.8
5.8
4.5
2.9
1.8 2.1
1.5
1.1
1.7 1.6
1.2 1.2
2
2.2
1.6
1.3
1.9
0.7
0
All Patients
Premature
All <32 weeks
All 32-35
Patients with
w/o CLD
GA
weeks
CLD
IMpact-RSV study based on active collection of hospital data; Outcomes Registry based on passive reporting
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.
Guidelines for RSV Prophylaxis
Premature, no CLD, no CHD
≤28 wks GA
Palivizumab if ≤12 months
at start of RSV season
29-32 wks GA
Palivizumab if ≤6 months
at start of RSV season
32-35 wks GA
Palivizumab if ≤6 months
at start of RSV season with two
risk factors present
Hemodynamically Significant CHD
Palivizumab if ≤2 years old at
start of RSV season
Chronic Lung Disease* (CLD)
*Receiving medical therapy for CLD within 6 months
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
Reijonen 1997
Ehlenfield 2000
Martinez FD, Godfrey S, 2003
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