Sneeze or Wheeze? The Role of Infections in Pediatric Asthma

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Sneeze or Wheeze?The Role of Infections in
Pediatric Asthma

• E. Kathryn Miller, M.D., M.P.H.
• Pediatric Allergy and Immunology
• Vanderbilt Childrens Hospital

2
DisclosuresE. Kathryn Miller

• Financial no conflicts of interest to disclose
• Research funded by NIH K23, NIH R03, March of
  Dimes Basil OConner, and VCTRS K12 awards
• Organizational AAAAI, AAP

• Gifts nothing to disclose
• Legal Consult/Expert Witness nothing to disclose
• Other nothing to disclose
• Employment Vanderbilt University

3
Case She cant breathe!

• 2 y/o asthmatic with wheezing in September
• 2 day h/o rhinorrhea and cough
• 1 day h/o wheezing and increased work of
  breathing
• Social/Family History
• daycare, smoking, maternal asthma
• Physical Exam
• Tachypnea, hypoxia
• Expiratory wheezes bilaterally, subcostal
  retractions

4
Chest X-Ray
5
Hospital Course

• In Emergency Room
• Continuous albuterol, oral steroids, O2, Mg
• No improvement in 4hrs, increased respiratory
  distress
• In Pediatric ICU
• Terbutaline drip, Solu-Medrol q6h, Atrovent q6h
• Weaned over 5 days
• Home
• Pulmicort bid, prn albuterol, prednisone taper,
  smoking education

6
What is the most likely infectious trigger?

1. RSV (respiratory syncytial virus)
2. Streptococcus pneumonia
3. Influenza
4. HRV (human rhinovirus)

7
RT-PCR of Nasal Swabs

• RSV A and B negative
• Influenza A and B negative
• Human Rhinovirus (HRV) positive
• VP4/VP2 sequencing HRVC

8
What infection during infancy is most associated
with the subsequent development of childhood
asthma?

• RSV (respiratory syncytial virus)
• Streptococcus pneumonia
• Influenza
• HRV (human rhinovirus)

9
Which of the following appears to be associated
with asthma?

• A) Influenza
• B) HRV (human rhinovirus)
• C) hMPV (human metapneumovirus)
• D) Chlamydia pneumonia
• E) All of the above

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Overview Infections and Asthma in Pediatrics

• Viral Infections Ontogeny of Asthma
• Viral Infections Exacerbation of Asthma
• Infant and Toddler Wheezing Phenotypes
• Treatment of Recurrent Wheezing

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Ontogeny of Asthma Viral infections are
important in the development of asthma.
12
Ontogeny of Asthma Infections Helpful?
Hygiene Hypothesis

• Changes in Society
• ( family size, improved sanitation, etc)
• Decreased Childhood Infections
• Cytokine Imbalance
• Th1gtgtgtTh2 phenotype
• (favors atopic disease, asthma)

Strachan 1989
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Ontogeny of Asthma Infections Harmful?
Bronchiolitis-to-Asthma

• RSV bronchiolitis in infancy is an important risk
  factor for asthma and allergy at age 7.1
• HRV hospitalizations during infancy are an early
  predictor of subsequent asthma development. 2
• 1st year wheezing with HRV is the strongest viral
  predictor of wheezing at 3 yrs age (OR 6.6). 3

1. Sigurs AJRCCM 2000 2. Kotaneimi-Syrjanen
JACI 2003 3. Lemanske JACI 2005
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Early HRV Wheezing Is Most Associated With
Childhood Asthma
Jackson AJRCCM 2008
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Early HRV Wheezing Is Most Associated With
Childhood Asthma

• In Year 3
• HRV (OR 25.6) gtgt AE sensitization (OR 3.4)
• as risk factor for asthma at age 6
• 90 of children who wheezed with HRV in Yr 3
• had asthma at age 6

Jackson AJRCCM 2008
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Differential Effect of Infant RSV vs. HRV
Bronchiolitis on Early Childhood Asthma
Tennessee Asthma and Bronchiolitis Study
Carroll JACI 2009
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Does Bronchiolitis Severity Predict Risk of
Asthma?
Severity score high score by age 2 years may
predict asthma at age 10 yrs
Devulapalli Thorax 2008
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Exacerbation of Asthma Many viruses are
important in asthma exacerbations.
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Exacerbation of Asthma

• 85 of children with asthma flare have virus.
  1,2
• Among children hospitalized for wheezing,
  respiratory syncytial virus (RSV), influenza
  virus, and human rhinovirus (HRV) are most common
  in those lt3 years HRV in older. 3
• Bacterial causes Atypical bacteria and sinusitis

• Johnston BMJ 1995 2. Nicholson BMJ 1993
• 3. Heymann JACI 2004

20
Emerging Knowledge Viruses

• Human Metapneumovirus (hMPV)
• Human Coronaviruses (hCoV)
• Human Rhinovirus C (HRVC)

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The New Vaccine Surveillance Network (NVSN)
Prospective, population-based surveillance
2000-2006
Children lt5 yrs hospitalized with acute
respiratory illness (ARI) or fever Sites Roche
ster, NY Nashville, TN Cincinnati, OH (2001)
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NVSN Year 1 Viruses Identified in 70 of
Hospitalized Children With ARI or Fever
Iwane Pediatrics 2004 Mullins EID 2004 Miller
JID 2007 Dare, unpublished data
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HMPV Causes Fever/ARI in Young Children
26/668 (4) hMPV
Mullins EID 2004
In various studies, 14-67 of children with hMPV
have been diagnosed with asthma exacerbation, vs.
0-15 with other viruses.
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Coronaviruses (HCoV) in 2-5 of Hospitalized
Children in NVSN Study

• Years 2-3 23/1048 (2.2)
• Primarily NL63

• Year 1 27/551 (4.9)
• Primarily OC43 and 229E

Dare et al
Talbot et al
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HRV Associated With Significant Burden in
Hospitalized Children
(18)
(6)
(2)
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HRV Species Have Different Clinical Phenotypes
Seasonality of HRV Clades

• HRVC (new)
• More cough
• More wheezing
• More discharge diagnoses
• of asthma

• HRVA (classic)
• More dual infections
• Fever

plt0.05
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Mechanisms of Viral Wheeze

• Airway epithelial cells1
• Normal apoptosis
• Asthma viral replication
• Immune dysregulation1-5
• Altered innate immune responses
• Type 1-3 interferons (?, ?, ?, ?)
• Genetic polymorphisms6, 7
• CD14_159 and Toll 3 receptors

1. Contoli M et al. Nat Med 121023, 2006 2. Wark
PA et al. J Exp Med 201937, 2005 3. Copenhaver
CC et al. AJRCCM 170175, 2004 4. Parry DE et al.
JACI 105692, 2000
5. Miller EK et al. AJRCCM, 2011 6. Hewson CA et
al. J Virol 7912273 7. Martin AC et al. AJRCCM
173617, 2006
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Viral Wheezing lt2 Years Age

• Viral etiologies
• RSV gt HRV gt influenza, HMPV, coronavirus, PIV
• Risk factors
• Environmental tobacco smoke exposure
• Reduced lung function
• (Lack of breastfeeding)

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Viral Wheezing in Older Children

• HRV gtgtgtgt others
• September asthma epidemic
• Often have
• elevated IgE
• inhalant allergen sensitization
• maternal asthma

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Infection and Susceptibility

• Patients with asthma do not appear to be more
  susceptible to infection with HRV
• They are more likely to have lower respiratory
  symptoms with more protracted and severe course

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Infant and Toddler Wheezing Phenotypes
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Childhood Wheezing

• 50 of kids reported to have wheezing in 1st year
  of life
• 15 outpatient visits, 3 hospitalizations for
  wheezing
• 20 continue to later childhood

Martinez NEJM 1995
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Wheezing Phenotypes

• 51 never wheeze
• Of those who wheeze
• Early, transient wheeze (60) - began by 3,
  resolved by 6
• Non-atopic persistent wheeze (20) - began by 1,
  persisted to 6, fade by adolescence
• Atopic (IgE-associated) persistent wheeze (20)
  often begin after age 1, persist to late
  adolescence

Tuscon Classification (n1246)
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Risk Factors for Persistent Wheezers

• Non-atopic
• Lower lung function, enhanced airway reactivity,
  low socioeconomic status
• Atopic
• Parental asthma, male sex, atopic dermatitis,
  eosinophilia at 9 months, h/o wheeze with LRI,
  early sensitization to food, aeroallergens,
  symptoms between exacerbations

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Asthma Risk Factors

• Atopy
• Food/inhalant sensitization associated with
  persistent wheezing age 6
• Alternaria allergy associated with chronic asthma
  age 22
• Reduced lung function (age uncertain)
• Tuscon study normal function as infant, reduced
  by age 6 in asthmatics at age 22
• Norway/Australia studies reduced function in
  infancy in persistent wheezers age 10-11
• Viral Infections HRV synergistic

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Will My Child Get Asthma?
Modified Asthma Predictive Index
History of 4 wheezing episodes with at least one diagnosed by MD
Child must meet at least 1 major or 2 minor criteria
Major
Parental history of asthma
Physician-diagnosed atopic dermatitis
Allergic sensitization to 1 aeroallergen
Minor
Allergic sensitization to milk, egg, or peanut
Wheezing unrelated to viral illness
Serum eosinophils gt4
(PPV 47.5-51.5, NPV 91.6 for asthma age 6-13)
Adapted from Guilbert et al JACI 2004
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Approach to the Infant/Toddler with Persistent
Wheezing
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Medical History

• Timing, pattern of wheezing
• Cough or limitation outside of exacerbations
• Association with feeding, failure to thrive,
  unresponsive to B2-adrenergics other diagnosis?
• Comorbidities GER, rhinitis, sinusitis

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Therapy for Infant/Toddler Recurrent Wheeze

• Based on 2007 NAEPP asthma guidelines for 0-4
  years old if asthma-like
• Sxs lt2d/wk prn short acting B agonist
• Persistent sxs gt2d/wk low dose ICS
• Consider RISK for step-up therapy
• 2 oral steroids in 6 months?
• 4 episodes/yr gt1 day wheeze and risk factors for
  persistent asthma?

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Classifying Severity in Patients 0-4 Years of Age
Not Currently Taking Long-Term Controllers
Components of Severity Components of Severity Intermittent Intermittent Intermittent Persistent Persistent Persistent Persistent Persistent
Components of Severity Components of Severity Intermittent Intermittent Intermittent Mild Mild Moderate Moderate Severe
Impairment Symptoms Symptoms lt2 days/week lt2 days/week gt2 days/week but not daily gt2 days/week but not daily Daily Throughout the day Throughout the day
Impairment Nighttime awakenings Nighttime awakenings 0 0 1-2x/month 1-2x/month 3-4x/month gt1x/week gt1x/week
Impairment SABA use for symptom control (not EIB prevention) SABA use for symptom control (not EIB prevention) lt 2 days/week lt 2 days/week gt2 days/week but not daily gt2 days/week but not daily Daily Several times per day Several times per day
Impairment Interference with normal activity Interference with normal activity None None Minor limitation Minor limitation Some limitation Extremely limited Extremely limited
Risk Exacerbations requiring oral systemic corticosteroids Exacerbations requiring oral systemic corticosteroids 0-1/ year 0-1/ year gt2 exacerbations in 6 months requiring oral systemic corticosteroids, or gt4 wheezing episodes/1 year lasting gt1 day AND risk factors for persistent asthma gt2 exacerbations in 6 months requiring oral systemic corticosteroids, or gt4 wheezing episodes/1 year lasting gt1 day AND risk factors for persistent asthma gt2 exacerbations in 6 months requiring oral systemic corticosteroids, or gt4 wheezing episodes/1 year lasting gt1 day AND risk factors for persistent asthma gt2 exacerbations in 6 months requiring oral systemic corticosteroids, or gt4 wheezing episodes/1 year lasting gt1 day AND risk factors for persistent asthma gt2 exacerbations in 6 months requiring oral systemic corticosteroids, or gt4 wheezing episodes/1 year lasting gt1 day AND risk factors for persistent asthma
Risk Exacerbations requiring oral systemic corticosteroids Exacerbations requiring oral systemic corticosteroids Consider severity and interval since last exacerbation. Frequency and severity may fluctuate over time. Exacerbations of any severity may occur in patients in any severity. Consider severity and interval since last exacerbation. Frequency and severity may fluctuate over time. Exacerbations of any severity may occur in patients in any severity. Consider severity and interval since last exacerbation. Frequency and severity may fluctuate over time. Exacerbations of any severity may occur in patients in any severity. Consider severity and interval since last exacerbation. Frequency and severity may fluctuate over time. Exacerbations of any severity may occur in patients in any severity. Consider severity and interval since last exacerbation. Frequency and severity may fluctuate over time. Exacerbations of any severity may occur in patients in any severity. Consider severity and interval since last exacerbation. Frequency and severity may fluctuate over time. Exacerbations of any severity may occur in patients in any severity. Consider severity and interval since last exacerbation. Frequency and severity may fluctuate over time. Exacerbations of any severity may occur in patients in any severity.
Recommended Step for Initiating Treatment Recommended Step for Initiating Treatment Recommended Step for Initiating Treatment Step 1 Step 2 Step 2 Step 3 and consider short course of oral systemic corticosteroids Step 3 and consider short course of oral systemic corticosteroids Step 3 and consider short course of oral systemic corticosteroids Step 3 and consider short course of oral systemic corticosteroids
Recommended Step for Initiating Treatment Recommended Step for Initiating Treatment Recommended Step for Initiating Treatment In 2 to 6 weeks, depending on severity, evaluate level of asthma control that is achieved. If no clear benefit is observed in 4-6 weeks, consider adjusting therapy or alternative diagnoses. In 2 to 6 weeks, depending on severity, evaluate level of asthma control that is achieved. If no clear benefit is observed in 4-6 weeks, consider adjusting therapy or alternative diagnoses. In 2 to 6 weeks, depending on severity, evaluate level of asthma control that is achieved. If no clear benefit is observed in 4-6 weeks, consider adjusting therapy or alternative diagnoses. In 2 to 6 weeks, depending on severity, evaluate level of asthma control that is achieved. If no clear benefit is observed in 4-6 weeks, consider adjusting therapy or alternative diagnoses. In 2 to 6 weeks, depending on severity, evaluate level of asthma control that is achieved. If no clear benefit is observed in 4-6 weeks, consider adjusting therapy or alternative diagnoses. In 2 to 6 weeks, depending on severity, evaluate level of asthma control that is achieved. If no clear benefit is observed in 4-6 weeks, consider adjusting therapy or alternative diagnoses. In 2 to 6 weeks, depending on severity, evaluate level of asthma control that is achieved. If no clear benefit is observed in 4-6 weeks, consider adjusting therapy or alternative diagnoses.
EIB- exercise-induced bronchospasm SABA
short-acting beta agonist National Asthma
Education and Prevention Program. Expert Panel
Repot 3 Guidelines for the Diagnosis and
Management of Asthma (EPR 3-2007). U.S.
Department of Health and Human Services.
Available at http//www.nhlbi.nih.gov/guidelines/a
sthma/asthgdln.pdf. Accessed August 29, 2007.
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Assessing Asthma Control in Patients 0-4 Years of
Age
Components of Control Components of Control Well Controlled Not Well Controlled Very Poorly Controlled
Impairment Symptoms lt2 days/week gt2 days/week Throughout the day
Impairment Nighttime awakenings lt1x/month gt1x/month gt1x/week
Impairment SABA use for symptom control (not EIB prevention) lt 2 days/week gt2 days/week Several times per day
Impairment Interference with normal activity None Some limitation Extremely limited
Risk Exacerbations requiring oral systemic corticosteroids 0-1 / year 2-3 / year gt3 / year
Treatment-related adverse events Medication side effects can vary in intensity from none to very troublesome and worrisome. The level of intensity does not correlate to specific levels of control but should be considered in overall risk assessment. Medication side effects can vary in intensity from none to very troublesome and worrisome. The level of intensity does not correlate to specific levels of control but should be considered in overall risk assessment. Medication side effects can vary in intensity from none to very troublesome and worrisome. The level of intensity does not correlate to specific levels of control but should be considered in overall risk assessment.
Recommended Action for Treatment Recommended Action for Treatment Maintain current treatment Regular f/u every 1-6 months Consider step-down if well controlled for at least 3 months Step up (1 step) and Reevaluate in 2-6 weeks If no clear benefit in 4-6wks, consider alternative diagnoses or adjusting therapy For side effects, consider alternative treatment options Consider short course of oral systemic corticosteroids Step up (1-2 steps) and Reevaluate in 2 weeks If no clear benefit in 4-6 wks, consider alternative diagnoses of adjusting therapy For side effects, consider alternative treatment options
National Asthma Education and Prevention Program.
Expert Panel Report 3 Guidelines for the
Diagnosis and Management of Asthma (EPR 3-2007).
U.S. Department of Health and Human Services.
Available at L http//www.nhlbi.nih.gov/guidelines
/asthma/asthgdln.pdf. Accessed August 29, 2007.
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Stepwise Approach for Managing Asthma in Children
0-4 Years of Age
http//www.nhlbi.nih.gov/guidelines/asthma/asthgdl
n.htm
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Treatment for Recurrent Viral Wheeze in Young
Children

• Important ICS may control symptoms, do not alter
  lung function or subsequent symptoms1,2
• In subset with recurrent wheeze, daily low dose
  ICS not superior to intermittent high-dose ICS in
  reducing exacerbations3

1. Guilbert NEJM 2006 2. CAMP NEJM 2000 3.
Zeiger NEJM 2011
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Intermittent Medications for Viral-Induced Wheeze
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Inhaled Short-Acting Beta-Agonists

• First-line therapy
• Effective rescue from symptoms, especially if
  established asthma
• Not shown to improve clinical outcomes, decrease
  hospitalization, or decrease duration of
  hospitalization in children with bronchiolitis

Gadomski Cochrane Database 2006
47
? Inhaled Hypertonic Saline Plus B-Agonist ?

• Hypothesis viral infection (HRV) leads to
  dehydration of airway surface liquid and impaired
  mucous clearance1-3
• Small trial 41 aged 1-6 with wheeze in ER
  randomly assigned albuterol plus 5 vs 0.9
  saline. LOS, hospitalization lower in HS. 4

1. Daviskas J Aerosol Med 2006 2. Randell AJRCMB
2006 3. Mandelberg Pediatr Pulmonol 2010 4.
Ater Pediatrics 2012
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Intermittent HIGH Dose Inhaled Corticosteroids
(ICS)

• Started at onset of URI and continued up to 10
  days may decrease symptoms and need for oral
  steroids (fluticasone 750mcg bid1, budesonide 1mg
  bid2 studied, and others3-5)
• Maybe slight growth deficits?
• Unsure if effective if started after wheezing
  begins?
• Perhaps good in patient with asthma risk

1. Ducharme NEJM 2009 2. Zeiger NEJM 2011 3.
Connett Arch Dis Child 1993 4. McKean Cochrane
Review 2000 5. Papi Allergy 2009
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Intermittent STANDARD (low-medium) Dose ICS

• Intermittent dosing NOT effective in this
  population
• Particularly not if started after wheezing begins
• Daily use effective to prevent episodes
  (discussed later)

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Intermittent Systemic Corticosteroids

• Mixed data for treating virus-induced wheeze in
  preschoolers, but overall NOT EFFECTIVE
• Alternatively, initiating systemic CS at earliest
  signs of viral URI MAY prevent wheeze
• Response may differ by virus
• Unsure if response differs by atopy status?

Jarrti PAI 2007
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Intermittent Leukotriene Antagonists

• Mixed data
• One study with reduced severity on LTRA or ICS
  compared with placebo1
• One study with reduced visits, symptoms in LTRA
  vs placebo, but no difference in rescue
  medication or hospitalization2
• One study with no difference in asthma episode
  frequency3

1. Bacharier JACI 2008 2. Robertson AJRCCM 2007
3. Valovirta Ann Allergy Asthma Immunol 2011
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Daily Therapy for Viral-Induced Wheeze
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Daily Inhaled Glucocorticoids (ICS)

• Standard doses of daily ICS are effective in
  preventing episodic virus-induced wheezing in
  young children. 1-3
• Data from 16 RCTs patients on daily ICS had
  fewer wheezing exacerbations compared with
  placebo (18 vs 32, RR0.059, CI 0.52-0.67) 1
• Independent of atopy and age

1. Castro-Rodriguez Pediatrics 20092. Guilbert
JACI 2011 3. Papi Allergy 2009
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Daily Leukotriene Antagonists

• In 550 children 2-5 years age, monteleukast
  reduced rate of exacerbations by 32 and time to
  first exacerbations by 2 months c/w placebo1
• Need for oral steroids not different
• Other study with comparable time to first episode
  among monteleukast vs budesonide, but
  exacerbation rates lower with budesonide2

1. Bisgaard AJRCCM 2005 2. Szefler JACI 2007
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Punchline Treatment of Viral Wheeze

• Short-acting B-agonist (albuterol) in NS
• NOT inhaled steroid
• NOT oral steroid, unless severe symptoms and risk
  factors for persistent asthma or already on
  controller ICS

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Punchline Prevention of Viral Wheeze

• Intermittent high-dose steroids begun at onset of
  URI, up to 10 days
• NOT oral steroid at onset of URI, unless h/o
  hospitalization, high risk,
• Daily standard dose ICS if continued episodes
  despite intermittent high dose ICS or prior if
  h/o frequent oral steroids
• Intermittent or daily monteleukast is an
  alternative

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Key Points

• Ontogeny of Asthma Viral infections appear to be
  important in the development of asthma.
  Gene-environment interaction most likely.
• Exacerbation of Asthma Several new viruses
  appear to be important in asthma exacerbations.
• Wheezing Phenotypes may help predict risk and
  guide treatment
• Treatment of Episodic Viral Wheeze is under
  investigation but generally follows asthma
  guidelines

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Acknowledgements

• Vanderbilt Collaborators
• Fernando Polack, MD
• John Williams, MD
• Kathy Edwards, MD
• Tina Hartert, MD, MPH
• Marie Griffin, MD, MPH
• Stokes Peebles, MD
• Lab Group
• Jodell Jackson, PhD
• Yassir Mohammed
• Johanna Hernandez-Zea
• Amy Podsiad
• Laura-Lee Morin
• Sharon Tollefson
• Luke Heil
• David Kraft

• Vanderbilt Department of Pediatrics, Division of
  Pulmonary, Allergy and Immunology
• Donna Hummell, MD
• Paul Moore, MD
• NVSN Group
• Centers for Disease Control
• University of Rochester
• University of Cincinnati
• Funding
• NIH K12 VCTRS, NIH T32, NIH K23, NIH R03, NIH LRP
• March of Dimes Basil OConnor Award
• MedImmune Award
• Thrasher Research Fund
• Research Nurses
• Ann Clay, RN

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Ontogeny of Asthma Non-viral Infections?

• Hypopharyngeal bacterial colonization in
  asymptomatic infants is associated with
  wheezing/asthma by age 5.
• S. pneumoniae, H. influenza, M. catarrhalis
• (not S. Aureus)

Bisgaard et al. NEJM 2007 357 1487
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Bacterial Infections and Exacerbation of Asthma

• Generally unusual for bacterial respiratory
  infections to trigger asthma, even in setting of
  pneumonia.
• However, the following may precipitate worsening
  of asthma
• Chronic sinusitis (often bacterial)
• Respiratory infections with Mycoplasma or
  Chlamydia pneumoniae

Virant Ped Ann 200029434 Tsao Chest
2003123757 Biscardi Clin Infect Dis 2004
381341 Emre Arch Ped Adol Med 1994 148
727 Webley Am J Rep Crit Care Med 20051711083
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Ontogeny of Asthma When does airway inflammation
begin?

• BAL in wheezing children lt 3 yrs old
• ? inflammatory cells
• ? inflammatory mediators (leukotrienes)
• Krawiec AJRCCM 2001 1631338
• Bronchial biopsies in wheezing infants and
  toddlers with reversible airflow obstruction
• No ? thickness of laminar reticularis
• No ? in inflammatory cells
• Saglani AJRCCM 2005 171722
• Reticular BM thickening from 3mo-5yrs age
• Saglani S et al. AJRCCM 176858, 2007

65
September Asthma Epidemic

• Asthma hospitalizations in school-aged children
  in Canada
• After return to school from summer/other breaks
• "September asthma epidemic"
• 18 days after Labor Day
• Lesser increase in attacks
• 2 days later in preschoolers
• 6 days later in adults
• Viral infections were presumed cause

Johnston et al. JACI 2006 117557
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Etiology of Wheezing in First 6 Years of Life
Jackson AJRCCM 2008
67
Asthma and Invasive Pneumococcal Disease

• Asthma is a risk factor for invasive pneumococcal
  disease.
• Advisory Committee on Immunization Practices
  recently voted 14/0 to recommend vaccination in
  all asthmatics.
• Talbot et al. NEJM 2005 352 2082.

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Birth 4 Months Before Winter Virus Peak gtgt 29
Increased Odds of Asthma
Wu AJRCCM 20081781123-9
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Human Bocavirus

• Novel parvovirus identified in Swedish children
  with respiratory disease
• 17/540 (3) children
• Related to bovine and canine parvoviruses
• Bocavirus prevalence 4-11

Allander CID 2005
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Rhinovirus 16 with ICAM-1 Receptor Binding Sites
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Genome of HRV

• Single-stranded positive sense RNA

72
Respiratory Virus Identified in 88 of 728
Jordanian Children
73
Vanderbilt Vaccine Clinic Lower Respiratory
Illness (LRI) Study

• 2,009 healthy children over 25 years
• 687 LRI visits with nasal wash samples
• RSV (15 of all LRI)
• Total 41 previous viral diagnosis
• 49/248 (20) virus-negative samples MPV
• 12 of total LRI in this cohort
• Mostly bronchiolitis
• Not found in asymptomatic children

Williams NEJM 2004
74
Human Rhinoviruses (HRV)

• Member of the Picornaviridae family identified in
  1956
• Over 100 serotypes identified
• HRVA, HRVB groups until recently
• Seasonality
• Major cause of common cold
• Recent studies demonstrate role in
  LRI/asthma

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HRVC forms a distinct and diverse group
76
HRVC in Hospitalized Children lt5 Yrs in Amman,
Jordan

• 467/728 (64) RSV
• 266/728 (37) HRV
• 133 (66) HRVA
• 7 (4) HRVB
• 61 (30) HRVC
• HRVC more associated with wheezing and
  supplemental oxygen than HRVA

Halasa et al