Asthma in Children:Asthma in Children:Managing the Uncertainty PrincipleManaging the Uncertainty Principle

Olatunji W. Williams, M.D.

Pediatric Pulmonologist

Peyton Manning Children’s Hospital

Asthma Impact in the U.S.

Affects more than 22 million Americans

Including more than six million children

Total health care costs in billions

7070

6060

5050

4040

3030

20208585 8686 8787 8888 8989 9090 9191 9292 9393 9494

Rate/1,000 PersonsRate/1,000 Persons

YearYear

<18

18-44

45-64

65+

Total (All Ages)

<18

18-44

45-64

65+

Total (All Ages)

Age (years)Age (years)

Asthma Prevalence is Highest in Pediatrics

9595 9696

8080

Global Initiative For Asthma – Statistical Report 2005

Asthma Prevalence by AgeU.S., 1985-1996

Hospitalization Rates for Asthma by Age, U.S., 1974 - 2000

4040

3535

3030

2525

2020

1515

7474 7676 7878 8080 8282 8484 8686 8888

Rate/100,000 PersonsRate/100,000 Persons

1010

55

009090 9292 9494

<15<15

15-4415-44

45-6445-64

65+65+

9696

YearYear

9898 0000

Global Initiative For Asthma – Statistical Report 2005

What is Asthma ?

• Molecular Diagnosis– “ chronic inflammatory disorder of the airways in

which many cells and cellular elements play a role: in particular, mast cells, eosinophils, neutrophils…”

• Clinical Diagnosis– “ a disease characterized by hyper-responsiveness of

the airways to various stimuli, resulting in airway obstruction that is reversible to a significant degree “

NHLBI 2007 Asthma GuidelinesM Weinberger, Pediatric Health 2008

Asthma Pathophysiology

Airway InflammationAirway Inflammation

BronchoconstrictionBronchoconstriction

AirwayAirwayEdema & HypersecretionEdema & Hypersecretion

What Causes Asthma ?• Innate ( hygeine hypothesis )

– Involves the balance between Th1-type ( bacterial ) and Th2-type (allergic immune response)

• Exposure to other children Th1 promoting

• Less frequent antibiotic use Th1 promoting

• Country living Th1 promoting

• Genetic– Inheritable component but not fully understood

• Environmental– Airborne allergens ( alternaria and dust mites )

– Viral infections

Diagnosing Asthma

Recurrent episodes of airflow obstruction

Airflow obstruction that is reversible

Alternative diagnoses are excluded

Recurrent Airflow Obstruction

• Recurrent episodes of wheezing

• Troublesome cough at night

• Cough or wheeze after exercise

• Cough, wheeze or chest tightness after exposure to airborne allergens or pollutants

• Colds “go to the chest” or take more than 10 days to clear

Reversible Airflow Obstruction

Clinical history of response to conventional asthma therapy

SpirometryObjective confirmation of airflow obstruction and also

whether airflow obstruction in reversible

Alternative Diagnoses are Reasonably Excluded

History and Physical critical

Top six alternatives in childrenAllergic rhinitis

Recurrent viral infections

Dysphagia with aspiration

Vascular sling

Congenital airway anomaly

Cystic Fibrosis

Goals of Asthma Therapy

Symptom Control Prevent chronic troublesome symptomsDecrease need for albuterol ( < 2 /week )

Maintain near normal pulmonary function

Reduce RiskRecurrent asthma attacks, ED visits and hospitalization

Prevent loss of lung function

Asthma Care:Four Component Approach

Medications

Assessing and monitoring asthma severity and control

Education for partnership in care

Control of environmental factors and co-morbid conditions that effects asthma

Asthma Care:Four Component Approach

Medications

Assessing and monitoring asthma severity and control

Education for partnership in care

Control of environmental factors and co-morbid conditions that effects asthma

Class Warfare• Albuterol, Levalbuterol (SABA)

• Inhaled Corticosteroids (ICS)– Blecomethasone, budesonide, fluticasone

• Leukotriene Antagonists (LTRA)– Montelukast

• Combination therapy (ICS/LABA)– Fluticasone /salmeterol, blecomethasone/formoterol

• Immunotherapy– Omalizumab

Inhaled Corticosteroids

• Are the most potent and consistently effective long-term control medication for asthma – Improved symptom control

– Fewer ED visits / hospitalizations

– Decreased need for oral steroids

• Majority of patients improve on low (100mcg/day) and medium (200 – 400 mcg/day) dosing

ICS Safety

• Local Adverse Effects (oral candidiasis, dysphonia, cough)

– Dose dependent ( decreased at low dose )– Decreased with valved holding chamber use

• Systemic effects (bone density, cataracts, HPA depression)

– Rare on low to medium dose ICS. Increased with high dose ICS use

– Approximately 1 cm in linear height loss, but typically catch up growth occurs in puberty

LABA

• Is not recommended as monotherapy, but works very effectively in combination with ICS

• Approved for children > 5 y.o.

• Can be considered as an option in step-up instead of increasing ICS dose

LABA – Safety Concerns• Daily treatment with salmeterol (LABA) vs. placebo

salmeterol group exhibited: – Increased risk of asthma related deaths ( 13 vs. 3 )

• Monotherapy with Formoterol resulted in increased number of severe asthma exacerbations

• Together this has earned LABAs the infamous Black Box warning– Step down to ICS monotherapy is recommended once symptom control

is achieved (stability over 4 – 6 months)

Nelson et al 2006

Mann et al 2003

Assessing and Monitoring Asthma Severity and ControlAssessing and Monitoring Asthma Severity and Control

Severity Daily Daily Controller Controller MedicationsMedications

Other Options Other Options

(in order of cost)(in order of cost)

Step 1:Step 1:

Mild IntermittentMild Intermittent

< 2 / week: day

< 2 / month: night

• NoneNone • NoneNone

Assessing and Monitoring Asthma Severity and ControlAssessing and Monitoring Asthma Severity and Control

SeveritySeverity Daily Daily Controller Controller MedicationsMedications

Other Options Other Options

(in order of cost)(in order of cost)

Step 2:

Mild persistent

> 2 / week: day

> 2 / month: night

• Low-dose ICSLow-dose ICS •LTRALTRA

Assessing and Monitoring Asthma Severity and ControlAssessing and Monitoring Asthma Severity and Control

SeveritySeverity Daily Daily Controller Controller MedicationsMedications

Other Options Other Options (in (in order of cost)order of cost)

Step 3:Step 3:

Moderate Moderate persistentpersistent

Daily: Day> 1 / week: night

•Low - medium Low - medium dose ICS dose ICS plusplus LABALABA

•High-dose inhaled High-dose inhaled glucocorticosteroid,glucocorticosteroid, oror

• Medium-dose iMedium-dose inhaled nhaled glucocorticosteroidglucocorticosteroid plusplus leukotriene modifierleukotriene modifier

Assessing and Monitoring Asthma Severity and ControlAssessing and Monitoring Asthma Severity and Control

SeveritySeverity Daily Controller Daily Controller MedicationsMedications

Other Other OptionsOptions

Step 4Step 4

Severe Severe persistentpersistent

Throughout Throughout

the day: daythe day: day

Multiple times / Multiple times / week: nightweek: night

• High-dose ICS High-dose ICS plus plus long-long-acting inhaled acting inhaled ββ22-agonist -agonist

plusplus

- Leukotriene modifier- Leukotriene modifier

- Oral glucocorticosteroid- Oral glucocorticosteroid

- Sustained-release - Sustained-release theophyllinetheophylline

When Symptoms Aren’t Enough

Blunted response to increased respiratory load in asthma

Takashima et al, N Engl J of Med 1994

Increased ED Visits, Hospitalizations, Near-Fatal Asthma, and Deaths

Associated with Perception of Dyspnea

Magdle et al, Chest 2002

POD = Perception of dyspnea

Utilizing Spirometry in Asthma

Should be consistent with ATS standards with regards to

repeatability, technique and machine calibration recommendations

Allows objective measurement of pulmonary function

Allows stratification of risk for future asthma attacks

Obstructive Ventilatory Defect

• Disproportionate reduction in maximal airflow in relation to the maximal volume

• Implies airway narrowing during exhalation

• Earliest signs of obstructive defect are observed in the small airways

Flow - Volume Loop : Normal

Flow

Volume

Exp

irat

ion

Insp

irat

ionRVTLC

FVC

FEV1

Flow - Volume Loop : Normal

Flow

Volume

Exp

irat

ion

Insp

irat

ionRVTLC

FEV1

FEV1

Obstructive defect

Obstructive Pattern

• FVC

• FEV1

• FEV1 / FVC

Due to diseases leading to mucus plugging, bronchospasm, inflammation, or loss of elastic support of the airways (asthma, CF)

Spirometry in Asthma Management

• FEV1 < 60% is associated with a decrease in symptom free days and increase in asthma related events J Allergy Clin Immunol 2001

• FEV1 < 60% is an independent risk factor for future attacks Pediatrics 2006

Asthma Care:Four Component Approach

Medications

Assessing and Monitoring Asthma severity and control

Education for partnership in care

Control of environmental factors and co-morbid conditions that effects asthma

Education for Partnership in Care

Asthma – Basic FactsWhat is asthma ?

What is an asthma attack ?

What is airway inflammation ?

Asthma MedicationsDifferent types

How they work ( control vs. rescue )

Potential side effects

Patient / Family skillsInhaler technique ( VHC )

Awareness of symptoms

Avoiding triggers

Utilization of asthma action plan

Factors Associated with Non-Compliance in Asthma CareFactors Associated with Non-Compliance in Asthma Care

Medication Usage

Difficulties associated with inhalers

Complicated regimens

Fears about, or actual side effects

Cost

Medication Usage

Difficulties associated with inhalers

Complicated regimens

Fears about, or actual side effects

Cost

Patient/Physician

Misunderstanding/lack of information

Underestimation of severity

Attitudes toward ill health

Cultural factors

Poor communication

Patient/Physician

Misunderstanding/lack of information

Underestimation of severity

Attitudes toward ill health

Cultural factors

Poor communication

Asthma Care:Four Component Approach

Assessing and Monitoring Asthma severity and control

Medications

Education for partnership in care

Control of environmental factors and co-morbid conditions that effects asthma

Control of Environmental Factors and Co-morbid Conditions that Effects Asthma

Environmental Factors

Inhaled allergens most important

Identified by skin testing or in vitro studies

Dehumidifiers best to minimize dust mite and mold levels

Smoke exposure

HEPA filters not a magic bullet

Consideration of immunotherapy

Control of Environmental Factors and Co-morbid Conditions that Effects Asthma

Co-Morbid Conditions

Poorly controlled allergic rhinitis

Obesity

Obstructed Sleep Apnea

Vocal Cord Dysfunction

Stress / Depression

GERD

The Problem with Toddlers….

Young children are often mislabeled(chronic or wheezy bronchitis, RAD, recurrent pneumonia or GERD )

Not all wheeze or cough are caused by asthma

Lack of objective data

However……50 - 80% of asthmatics present before their 5th birthday

I can’t tell the future but…..

Asthma Predictive Index:

Major Criteria ( Any 1 )

- Parental history of asthma

- Diagnosis of atopic dermatitis

- Evidence of sensitization to aeroallergen

Minor ( Any 2 )

- Evidence of sensitization to foods

- > 4 percent peripheral blood eosinophilia

- Wheezing apart from colds

Indications for Daily Asthma Therapy in Infants and Toddlers

• Positive Asthma Index plus:– Symptoms more twice a week for more than four consecutive

weeks (or)

– Four or more episodes of wheezing in one year (or)

– Two or more episodes requiring oral steroids in six months

• Daily therapy during high risk time period can be considered (i.e. winter / viral season) with subsequent weaning of therapy

Infants and Toddlers: What to Use and Why

• Inhaled Corticosteroids (ICS) are still preferred– Either by nebulization or valved holding chamber with mask

– Budesonide FDA approved to 1 y.o. and older

• Montelukast (leukotriene antagonist) approved to 2 y.o. and older

Off label use occurs frequently but should be guided by asthma specialist

Unproven Interventions

• Chronic macrolide antibiotic therapy

• Methotrexate, Monoclonal IL-5, Cyclosporin A and IVIG

• Acupuncture

• Chiropractic therapy

• Yoga

When to Refer• Confirmation of diagnosis

• Poor symptom control after 4 – 6 weeks of therapy

• Toddlers on long term medium – high dose ICS or combination therapy

• Any patient requiring hospitalization

• For intensive asthma education

Resource Material

• NHLBI Guidelines for the Diagnosis and Management of Asthma (http://www.nhlbi.nih.gov/guidelines/asthma/)

• Global Initiative for Asthma - GINA (http://www.ginasthma.org)

• A clinical index to define risk of asthma in young children with recurrent wheezing. American Journal Respiratory Crit Care Med. 2000

• Inhaled corticosteroids should be used in infants and preschoolers with recurrent wheezing. Pediatric Allergy, Imunology, and Pulmonology 2011

• Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids. New England Journal of Medicine 2010