rsv bronchiolitis mark a. brown, m.d. professor of clinical pediatrics pediatric pulmonary section...
TRANSCRIPT
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): 70%• Metapneumovirus 10-20%
– Newly identified paramyxovirus– Similar seasonality and course to RSV
• Parainfluenza• Influenza 10-20%• Adenovirus• Bocavirus ?
}
Seasonality
Bronchiolitis
RSV Isolates
YearHall, 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 BurdenCosts 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
Pe
rce
nt
Days of symptoms
020406080
100
0 5 10 15 20 25 30 35
Swingler et al. 2000
Clinical course
0 5 10 15 20 25 30 35
Se
veri
ty
Days
0 5 10 15 20 25
0
10
20
30
40
50
60
70
80
Risk Factors for Hospitalization with RSV 1708 Hospitalized Infants in Rochester, NY
Prematurity ChronicDisease
Age < 6 wks
1 or more Risk FactorsPercent 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 severelyill 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 aTIFF (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 inpatientsAlbuterol 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
TherapiesSupportive 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 ventilationWang et al. J Peds 1995; 126:212-
219.
• 4 x increased inpatient LOSWainwright 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
2.92.1
4.5
1.6
5.8
1.51.2
1.71.3
2.2
1.1 1.21.6 1.9
10.6
0.7
0
2
4
6
8
10
12
14
All Patients Prematurew/o CLD
All <32 weeksGA
All 32-35weeks
Patients withCLD
RS
V H
os
p R
ate
1996-1997 IMpact-RSV Trial-Placebo 1996-1997 IMpact-RSV Trial-Synagis2000-2001 Synagis Outcomes Registry 2001-2002 Synagis Outcomes Registry2002-2003 Synagis Outcomes Registry
*Receiving medical therapy for CLD within 6 months
Guidelines for RSV Prophylaxis
Premature, no CLD, no CHD
29-32 wks GAPalivizumab 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 CHDPalivizumab 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 1997Ehlenfield 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