Pediatric Asthma Kimberly D. Watts MD, MS - PowerPoint Presentation

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Pediatric Asthma

Kimberly D. Watts MD, MS

Pediatric Pulmonary Medicine

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The Burden of Pediatric Asthma

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The Scope of Asthma

Most common chronic disease of childhood

Affects more than 7 million children in the United States

Approximately 9% of all US children have asthma

This rate has increased more than 160% in children under 5 in the last 20 years

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Healthcare Utilization

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The Cost of Asthma

The annual economic cost of asthma is $19.7 billion

Direct costs such as medications and indirect costs such as loss of productivity

13 million school days are missed each year

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Rising Prevalence of Asthma

Increase in asthma prevalence from 1980 to 1996 of greater than 50 %

Largest increase in patients younger than 18 years old

Estimated current asthma prevalence in general increased between 2001-2009

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Why the increasing numbers?

Improved hygiene

Less exposure to pathogens disrupting innate immunity

Increased indoor air pollution

Caused by increase in energy efficient building

Increased incidence of early onset viral infections

Increase in host susceptibility

Small lungs due to prematurity or maternal smoking

Increased recognition and awareness

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Asthma death per 1,000 people with asthma ( 2007-09)

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Pathophysiology

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Definition of Asthma

Chronic inflammatory lung disease

Cough, wheezing, dyspnea and chest tightness

Airway narrowing that is partially or completely reversible

Increased airway responsiveness to stimuli

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Asthma Pathophysiology Overview

Inflammation

Narrowed airways

Constricted muscles

Airway hyper-reactivity

Remodeled airway

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The wet dry asthma cough

Airways edema

Cellular infiltration

Eosinophils

Activated helper T cells

Mast cells

+/- neutrophils

Increased airway secretions

Secreted mucus

Desquamated lining cells

Intraluminal eosinophils

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Inflammation

Chronic inflammation occurs even in the most mild of symptomatic patients

Bronchoalveolar lavage of asthmatics demonstrates

Neutrophils, eosinophils, lymphocytes and mast cells

Cytokines including leukotrienes

Alterations in innate lung immunity

Impaired glutathione homeostasis

Decreased capacity to reduce reactive oxygen species

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Reversible Airflow Obstruction

Reduced expiratory airflow by spirometry

FEV1 < 80 % predicted and a reduced FEV1 / FVC ratio of < 0.80

Significant reversibility is an increase of >12% in FEV1 from baseline

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Airway Hyperresponsiveness

Degree to which airways narrow in response to stimuli

Methylcholine

Cold Air

Histamine

Viral upper respiratory infections

Allergens

Air pollutants

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Normal vs. Asthma Airway

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Evaluation and Diagnosis

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Clinical Presentation

Most common cause of chronic cough in children older than 3 years old is asthma

Not always accompanied by wheezing

80 % of children with asthma develop symptoms before 5 years of age

Breathlessness, chest tightness, chest pressure and chest pain

Poor school performance and fatigue

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Cough

Cough lasting more than 3 weeks

Night time cough

Cough to specific exposures

Dry and hacking cough

Productive with clear / white sputum

Usually eosinophils

With activity

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Wheezing

Polyphonic

Tends to be expiatory but can be inspiratory

Monophonic wheezes need further evaluation

Rings/slings

Malacia

When albuterol makes it worse

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Symptom Patterns

Intermittent exacerbations on a asymptomatic baseline

Chronic symptoms with worsening on exacerbations

Morning “ dipping”

Worsening of symptoms in the morning corresponding to the physiologic dip in pulmonary function

September epidemics

Viral infections, mycoplasma pneumoniae or Chlamydia pneumoniae infection

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Precipitating Factors and Risk Factors

Weather, second hand smoke, allergens and irritants

Wood fires, kerosene space heaters, room deodorizers

30 % children with food allergy have asthma

Higher rate of intubation

Children of asthmatic parents odds ratio 2.6 ( 1 parents) and 5.2 ( 2 parents)

Sleep disordered breathing 3.6 fold increase risk for severe asthma

Higher BMI associated with greater asthma severity

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Diagnosis - Spirometry

National Asthma Educations and Prevention Program recommends spirometry to be performed in patients older than 5 years old

FEV1 < 80% predicted

FEF 25-75% less than 65% correlated with reversible airflow obstruction in children with normal FEV1

Before and after bronchodilator

Increase in 12 % ( maybe 9% in children)

Normal spirometry or the lack of reversibility does not exclude the diagnosis of asthma

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Spirometry loops

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Diagnosis – Peak Flow

More variable and effort dependent

Wide variability in published predicted peak expiratory flow reference values

Can alter brand to brand

Peak flows should not be used to diagnose asthma

More helpful to monitor a patient’s response over time for a subgroup of patients

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Other Diagnostic Modalities

Impulse Oscillometry

Passive cooperation

Evaluates resistance pre and post bronchodilator

Bronchoprovocation Testing

Methylcholine, histamine , cold air , exercise

If patient fails empiric trial of asthma medsications

Chest x-ray

Congential malformations

Airspace disease

Signs of asthma

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Other Diagnostic Modalities

Sweat Chloride

Barium Swallow

TEF, reflux, vascular anomolies

Negative study cannot exclude GER

Allergy testing

Limited to seasons and suspect exposures

Exhaled nitric oxide

Levels elevated in patients with asthma

Chornic exposere to passive smoking may falsely decrease the levels

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Treatment

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Acute management

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Short Acting Beta Agonists

Relaxes smooth muscle

Overuse or regular use is associated with poor control

Theoretical concern regarding down regulation of beta receptors with chronic use

Can impact medication needed for urgent care

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Short acting medications

Albuterol

MDI with spacer or nebulizer

No role for oral albuterol given side effects

Levalbuterol

R- enantiomer – active isomer only

Approved MDI > 4 years old and neb > 6years old

Hospitalization rate lower among childrens who received levoalbuterol in the ER vs. albuterol but studies are mixed

Comparable, no evidence for superiority

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Ipratropium Bromide

Anti-cholinergic

Bronchodilator through smooth muscle relaxation

Adjuvant for albuterol in the ER

Reduce hospital admissions

Improve lung function in severe asthma

Also can use as an alternative agent to albuterol

Tracheomalacia

MDI not administered to soy or peanut allergy patients

Contains soy lecithin

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Steroids

2007 NAEPP expert panel no longer recommends doubling dose of inhaled steroids for quick relief during acute exacerbations

Not found effective in reducing severity or progression of exacerbation

Higher dose ( > 2 times the normal dose) may be an alternative to oral steroids in mild exacerbations if patient does not tolerate oral steroids

Short course of oral steroids in addition to short acting beta agonists for acute exacerbations

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Chronic Management

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Who should get controller therapy?

0 to 4 years old

Greater than 4 episodes of wheezing

Parental history of asthma

Patient with atopic dermatitis or allergies

Food allergies with eosinophilia or wheezing without colds

Require albuterol more than two days per week

Experiences severe illness < 6 weeks apart

2 rounds of steroids in 6 months

Intermittent disease with severe exacerbation

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Controller therapy 5 years and older

For any persistent asthma

Any symptoms > 2 days a week

Night time symptoms greater than 2 times a month

Albuterol more than 2 days a week

Any interference with normal activity

Requires oral steroids more than once a year

Severity and interval of exacerbations

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Intermittent - - - > Step 1

Mild - - -> Step 2

Moderate - - -> Step 3

Severe - - -> Step 3 or 4

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Starting controller therapy

Two to six week interval is needed to assess response

Adherence with current regimen needs to be assessed before escalating therapy

Included assessment of barriers

When controlled for 2 to 6 months can begin reducing regimen

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Inhaled Corticosteroids

Inhibiting steps in the inflammatory cascade

Associated with reduction in

Symptoms

Irreversible decline in lung function

Asthma exacerbations

Functional limitations

Side effects from other medications

Reduction in parameters better than with leukotriene antagonist

First line control therapy for persistent ( or step 2 or greater ) asthma

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Inhaled Corticosteroids

Fraction of the dose than systemic steroids

Minimal side effects

Almost all the trivial amount of drug absorbed is deactivated after one pass through the liver

Differences in medications

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Inhaled Corticosteroids

Minimize risk of adverse side effects

Step down treatment to lowest possible dose to maintain control

Optimize adherence to lowest dose possible

Optimize delivery

Evaluate for complicating factors

Avoid triggers

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Inhaled Steroids and Disease Progression

Did not alter disease progression

Patients 2-3 years old with > 4 episodes of wheezing- - > fluticasone or placebo

Fluticasone fewer symptoms and exacerbations

At the last observational year no significant differences

Early , intermittent intervention had no effect on disease progression from episodic to persistent wheezing

411 infants first thee years of life ICS or placebo

At 5 years of age no difference between lung function or symptoms or asthma medication use between placebo group or ICS group

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Intermittent Use of ICS

Con

Intermittent inhaled budesonide at 400 mcg BID x 7 days less effective than daily ICS in children 5-10 years old

No difference in placebo vs. high dosed ICS for 3 days at the first signs of a viral URI with wheezing

Pro

Budesonide 1 mg BID for 7 days at first onset of symptoms as effective as budesonide 0.5 mg qhs for 12-53 month old patients

Meta-analysis no difference in daily ICS vs. intermittent in need for oral steroids but daily ICS better control and more symptoms free days

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Leukotriene Receptor Agonists

Cysteinyl leukotrienes found in BAL in asthmatic patients

Inhibit production at various points in the cascade

Adjuvant therapy to ICS in patients > 1 year old

No evidence to support use as first line controller agent or as intermittent therapy

Can be used to step down therapy from ICS or in mild patient who cannot tolerate ICS

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Montelukast

VS. Placebo

2-5 years olds

Intermittent asthma associated with viral symptoms

Better than placebo with a reduced rate of exacerbations and decreased use of ICS

Vs. ICS

Meta-analysis in mild to moderate persistent asthma children ICS had better pulmonary function and better asthma control

ICS more cost effective

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Response variability

Double cross over ( 6-17 years old) – Fluticasone and montelukast

17 % responded to both medications

23 % responded to fluticasone only

5% to montelukast only

55% to neither

Inhaled steroids as the first line controller agent

Intermittent use of moneltukast was associated with some improvement but not difference from placebo in hospitalizations, albuterol use or oral steroids use

More studies needed

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Long Acting Beta Agonists

Used as an adjuvant to ICS

Should not be used for acute exacerbations

Once control is obtained, effort should be made to go to a single agent ICS

Reserved for patients who “ fail” medium dose ICS

Black box warning

May increase the chance of severe asthma episodes and asthma related deaths

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Anti IgE ( Omalizumab)

Monoclonal anti IgE

Moderate to severe asthma

Not controlled on ICS

Elevated IgE levels

Approved if > 12 year old in US

IgE levels 30 -700

Positive allergy testing

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Chronic Oral Steroids

Severe persistent asthma

Long term effects

Adrenal suppression

Weight gain

Diabetes

Hypertension

Cataracts

Delayed growth

Immune suppression

Osteoporosis

Behavioral effects

Lowest possible dose, every other day administration, trying all other modalities is preferable

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Other Therapies

Cromolyn

Systemic review found no clear therapeutic effect vs. placebo

No evidence to sport the concurrent use of cromolyn with ICS

Theophylline

Use limited secondary to potentially serious short term side effects ( arrhythmia, seizures and death)

Needs frequent serum monitoring as well as monitoring with drug interactions

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Barriers to Care

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Unequal burden of asthma

About 1 in 6 or (17%) of non-Hispanic black children had asthma in 2009

In 2001-2009 the greatest rise in asthma rates was among black children with an almost 50 % increase

About 40% of uninsured people with asthma reported not being able to afford their medications

About 11% of insured people can not afford their asthma medications

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Affects of Poverty and Race on Pediatric Asthma Prevalence

Definitions of poor, near poor and non-poor are based on federal poverty levels that take into account annual/ monthly income and family size

Prevalence data 2006-2008

MMRW, Jan. 14, 2011

Asthma Prevalence in the US

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Differences in Prevalence

African American = 12.7 %

Puerto Ricans = 25.7 %

Mexican Americans = 6.6%

Whites = 8.8%

Higher among children

Living below the poverty threshold

Living in an urban setting

Northeastern portion of the US

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Signs of Poor Control

Utilization of ER

Frequency of hospitalizations

Repeated use of oral glucocorticoids

School absenteeism

Inability to participate in physical activity

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Poor Response to Asthma Medications

Non-adherence

Inadequate inhaler technique

Ineffective drug dose or dosing interval

Complicating medical problems

Substitution of inappropriate treatment

Response variability to certain medications

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Psychosocial Factors affecting adherence

Family disagreement about diagnosis

Peer rejection

Concern about adverse side effects of controllers

Financial consequences

Disruption of family routines

Fear of inability to obtain health insurance with a pre-existing condition

Limitations of social interactions because of triggers

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Take Home Points from National Asthma Education and Prevention Program Expert Panel Report

All patients should receive

Asthma action plan

Initial assessment of asthma severity

Review of asthma level of control at follow-up visits at least every 6 months

Assessment of exposure to allergens and triggers

Asthma education by a qualified health professional

Referral to an asthma specialist when appropriate

Education regarding dangers of over use of beta agonists

Information regarding risk factors for death of asthma