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COCA Conference Call National Grand Rounds
2009 H1N1 Influenza and Asthma
CAPT David Callahan, MD National Center for
Environmental Health Centers for Disease Control
and Prevention Alkis Togias, MD National
Institute of Allergy and Infectious
Diseases National Institutes of Health Gail
Weinmann, MD National Heart, Lung, and Blood
Institute National Institutes of Health November
10, 2009
The findings and conclusions in this report are
those of the author and do not necessarily
represent the official position of the Centers
for Disease Control and Prevention.
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What is Asthma?

• Chronic inflammation of the airways
• Cytokine-mediated over short term
• Airway remodeling over long term
• Reversible bronchospasm
• Wheezing, breathlessness, coughing

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Overview

• Public health significance of asthma
• Inflammation and immune response in asthma
• Clinical management of asthma
• 2009 H1N1 Influenza and asthma
• Data from 2009 H1N1 influenza surveillance
• Clinical guidelines prevention and treatment
• COPD A high-risk group
• Conclusions
• Questions and Answers

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Asthma Public Health Significance

• Asthma prevalence 7.9
• 23 million people
• 7 million children
• Health care utilization in 2006
• 10.6 million office-based visits
• 1.8 million ED visits
• 444,000 hospitalizations
• Mortality 3,613 deaths in 2006

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Child and Adult Asthma Prevalence United
States,1980-2007

• Child
• Adult

Lifetime
Current
12-Month
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Current Asthma Prevalence for Youth by
Race/Ethnicity, Ages 5-17, 2005-2007
10.1 Overall
Centers for Disease Control and Prevention.
National Center for Health Statistics. Health
Data Interactive. www.cdc.gov/nchs/hdi.htm. July
15, 2009.
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Asthma Disparities Among U.S. Children

• More ED visits, hospitalizations, deaths
• Low-income
• Minorities
• Non-Hispanic black
• American Indian/Alaskan Native
• Some Hispanics (e.g., Puerto Ricans)
• Inner cities (although overall urbanrural)

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Population Disparities in Asthma

• Current asthma prevalence is higher among
• children than adults
• boys than girls
• women than men
• Asthma morbidity and mortality is higher among
• African Americans than Caucasians
• Low SES, both urban and rural
• Less access to health care

Source MMWR 200756(No. SS-8)1-54
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2009 H1N1 Influenza Virus and Asthma

• Alkis Togias, MD
• Asthma, Allergy and Inflammation Branch
• National Institute of Allergy and Infectious
  Diseases (NIAID), NIH

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Asthma and Viral Respiratory Infections

• Viral respiratory infections associated with most
  exacerbations in children and adults
• Explains peaks in fall, midwinter
• Aeroallergens and respiratory viral infection
  play a synergistic role in exacerbations
• Correct asthma management reduces the risk of
  asthma exacerbations
• N W Johnston and M R Sears. Asthma exacerbations
  1 Epidemiology. Thorax 200661722-728

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Airway inflammation and hyperreactivity
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Asthma and Viral Respiratory Infections

• No good evidence that people with asthma are more
  likely to get infected by respiratory viruses,
  including influenza
• Controversy whether viral replication is enhanced
  in the airway of people with asthma

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Asthma and Viral Respiratory Infections

• Most asthma virus-induced exacerbations are
  secondary to rhinovirus infections
• All guidelines recommend seasonal influenza
  vaccination for patients with asthma
• Yet, the impact of influenza on asthma was not
  fully appreciated prior to the 2009 H1N1 pandemic

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Clinical Management of Asthma

• Expert Panel Report 3
• National Asthma Education and Prevention Program
• National Heart, Lung and Blood Institute, 2007

http//www.nhlbi.nih.gov/guidelines/asthma/
Source http//www.nhlbi.nih.gov/guidelines/asthma
/asthgdln.pdf
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Stepwise Approach for Managing Asthma in Children
5-11 Years of Age
Persistent Asthma daily medication Consult
with asthma specialist if step 4 or higher
required consider consult for Step 3!
Intermittent Asthma
STEP 6 Preferred High-dose ICS LABA oral
systemic steroids Alternative High-dose ICS
either LTRA or Theophylline oral systemic
steroids
STEP 5 Preferred High-dose ICS
LABA Alternative High-dose ICS either LTRA or
Theophylline
STEP 4 Preferred Medium-dose ICS
LABA Alternative Medium-dose ICS either LTRA
or Theophylline
STEP 3 Preferred EITHER Low-dose ICS either
LABA, LTRA or Thoephylline OR Medium-dose ICS
STEP 2 Preferred Low-dose ICS Alternative Crom
olyn, LTRA, Nedocromil or Theophylline
STEP 1 Preferred SABA prn
At each step Education, environmental control,
management of co-morbidities Assess Control
Step-up if needed and step-down if possible (3
months under control)
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Asthma Treatment and H1N1 Vaccine

• Inhaled steroids mainstay treatment for asthma
  control
• Some patients with asthma require high doses of
  inhaled steroids or even oral steroids
• Will the 2009 H1N1 influenza vaccine be
  adequately immunogenic in patients on high doses
  of inhaled steroids or oral steroids?

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NIAID/NHLBI Study of the 2009 H1N1 Influenza
Vaccine in Patients with Asthma
15 mcg (Day 1) 15 mcg (Day 21)
Low dose vaccine
6-month follow-up
Severe asthma (high dose steroids) N150
High dose vaccine
30 mcg (Day 1) 30 mcg (Day 21)
15 mcg (Day 1) 15 mcg (Day 21)
Low dose vaccine
Mild/moderate asthma N200
6-month follow-up
High dose vaccine
30 mcg (Day 1) 30 mcg (Day 21)

• Assessment of antibody responses 1 and 3 weeks
  after each vaccination
• Safety assessments throughout the study

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2009 H1N1 Influenza and Asthma
CAPT David Callahan, MD U.S. Public Health
Service National Center for Environmental
Health Centers for Disease Control and Prevention
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Mild Asthma and Hospitalization Risk

• 5075 of asthma is mild (usual criteria)
• 30 of asthma hospitalizations are among
  persons with mild asthma
• 3040 of asthma ED visits are severe
  exacerbations in mild asthma
• Severity is often poorly documented

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Asthma Risk Factors Associated with Death

• Previous serious exacerbation
• gt2 hospitalizations or gt3 ED visits past year
• Poorly controlled
• Difficulty perceiving symptoms of exacerbations
• Comorbidities
• Cardiovascular, psychiatric in particular
• Low SES

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People with asthma are at increased risk for
severe influenza illness

• No evidence that they are more susceptible
• Influenza infection associated with very severe
  asthma exacerbations, ICU admissions, and
  refractory exacerbations
• Vaccination reduces severe outcomes (not rates of
  asthma exacerbations)

Wark PAB, Johnston SL, Moric I, et al. Neutrophil
degranulation and cell lysis. is associated with
clinical severity in virus-induced asthma. Eur
Respir J.2002196875.
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Influenza Vaccination Coverage among People with
Asthma
Data from National Health Interview Survey

• 36 of children and adults (2005-06, NHIS)
• 29 in 2-17 age group (2004-05, NHIS)
• 40 of adults (2007-08, BRFSS)
• 42 in non-Hispanic whites
• 34 of 18-49 age group
• 25 of those without health insurance
• 19 of those without primary doctor

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2009 H1N1 and AsthmaHospitalizations

• 32 of hospitalized with 2009 H1N1 have asthma
• ICU 20 with 2009 H1N1 and asthma admitted to
  ICU
• Same ICU rate as others (non-asthma) hospitalized
  with 2009 H1N1

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ACIP Recommendations

• Seasonal flu vaccine
• 2009 H1N1 flu vaccine
• 6 months to 64 years with lung disease a priority
• Pneumococcal vaccine
• Similar recommendations for COPD

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Influenza Vaccine Dosing

• The lack of preexisting antibody cross-reactive
  with the H1N1 2009 virus among infants and
  children raises the possibility that 2 doses of
  vaccine (typically separated by 21 days) will
  be needed to provide protection.
• NIAID preliminary results of a study of children
  aged 6 months-18 years
• Among children aged 6-35 months, 3-9 years, and
  10-17 years immunized with a 15 mcg inactivated
  H1N1 2009 monovalent vaccine, 25, 36 and 76,
  respectively, developed seroprotection after a
  single dose of vaccine.
• In children aged 6 to 35 months, 100 had a
  robust immune response after the second dose
  compared with only 25 three weeks after the
  first dose.
• In children aged 3 to 9 years old, 94 had a
  robust response after the second dose compared
  with only 55 three weeks after the first dose.
• Bottom line 2 doses of 15 mcg inactivated H1N1
  monovalent vaccine for children 6 months through
  9 years old, given at least 21 days apart.

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CDC Guidance

• http//www.cdc.gov/h1n1flu/asthma_clinicians.htm
• http//www.cdc.gov/h1n1flu/asthma.htm
• Asthma Action Plan
• Asthma should be well-controlled
• Inhaled corticosteroids are protective

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CDC Guidance

• Vaccination
• 2009 H1N1 and Seasonal
• Inactivated, injectable only
• Do not use nasal spray vaccine
• Pneumococcal Vaccine
• Prompt treatment
• Plan for early contact/empiric treatment
• Oseltamivir (Tamiflu) started early

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Treatment

• Oseltamivir (Tamiflu)
• 75 mg po bid for 5 days
• Weight-based dosing for children
• http//www.cdc.gov/h1n1flu/asthma_clinicians.htm
• BEST if started within 48 hours of symptom onset
• Zanamivir (Relenza) is not recommended, because
  of the risk for adverse events, such as
  bronchospasm

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Treatment

• Rapid access to antiviral medications is
  essential
• Actions to support treatment initiation
• Informing patients of signs and symptoms of
  influenza and need for early treatment
• Ensuring rapid access to telephone consultation
  and clinical evaluation
• Considering empiric treatment of patients based
  on telephone contact

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Remember other Chronic Lung Diseases

• Persons with COPD face similar risk for severe
  outcome from influenza
• Recommendations for COPD are similar to those for
  asthma
• Asthma and COPD can be comorbidities,
  particularly in older age groups

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COPD and H1N1
Gail Weinmann, MD Division of Lung
Diseases National Heart, Lung, and Blood
Institute NIH
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What is COPD?

• A common lung disease of smokers and ex-smokers
  (and some never smokers) who experience
  difficulty breathing, at rest or on exertion,
  with or without chronic cough and sputum
  production.
• Inflammatory lung disease characterized by
  airflow limitation that is not fully reversible
• The term COPD includes
• Chronic bronchitis
• Emphysema

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COPD Statistics

• 24 million affected in the U.S.
• About half do not know they have it
• Most over age 60
• Most have multiple co-morbidities
• About 15 never smokers
• gt120,000 deaths/year (4th leading cause)
• Rates rising fastest in women
• Men and women about equal
• 900,000 disabled, working age adults
• Total cost of 37 billion/year

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Trends in Lung Disease Mortality
7
Lung Cancer
6
5.2
5
COPD
4
Percent of Total U.S. Deaths
3
Pneumonia
1.5
2
Other
1
0
1960
1970
1980
1990
2000
Year
Source CDC
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COPD High Risk For Flu Complications

• Aging immune system
• On inhaled and oral steroids
• Multiple co-morbidities
• Impaired airway defenses
• Reduced lung reserve

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COPD and the Flu

• Everyone with COPD should routinely be vaccinated
  against the seasonal flu.
• Everyone with COPD should have an updated
  pneumococcal polysaccharide vaccination (PPSV)
  according to ACIP guidelines.
• Everyone with COPD should get vaccinated for the
  2009 H1N1 influenza as supplies permit, using the
  shot (injectable) form.

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COPD and the Flu

• Persons with COPD should not get the live
  attenuated nasal spray flu vaccines (i.e.,
  FluMist).
• The inactivated 2009 H1N1 influenza vaccine can
  be administered at the same visit as any other
  vaccine, including the PPSV.

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Additional Resources

• Diseases and Conditions Index COPD
  http//www.nhlbi.nih.gov/health/dci/Diseases/Copd/
  Copd_WhatIs.html
• The COPD Learn More Breathe Better Campaign
  http//www.nhlbi.nih.gov/health/public/lung/copd/

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Conclusions

• Persons with asthma or COPD are at higher-risk of
  complications from seasonal influenza infection
• Data available thus far suggest that persons with
  asthma are at higher-risk of complications from
  2009 H1N1 influenza

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Conclusions

• Maximize asthma control, including ICS use
• Vaccinate for primary prevention
• Seasonal flu vaccine
• 2009 H1N1 flu vaccine
• Pneumococcal vaccine
• Inform patients about the signs and symptoms of
  2009 H1N1 influenza
• Treat empirically with antivirals

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CDC Interim Guidelines and Updates

• http//www.cdc.gov/h1n1flu
• http//www.cdc.gov/h1n1flu/asthma_clinicians.htm

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Questions
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