rsv bronchiolitis mark a. brown, m.d. professor of clinical pediatrics pediatric pulmonary section...

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 ?

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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

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Swingler et al. 2000

Clinical course

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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

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All Patients Prematurew/o CLD

All <32 weeksGA

All 32-35weeks

Patients withCLD

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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