Transcript Asthma, Mucus and Death

Asthma in Children:
Managing 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
Asthma Prevalence is Highest in
Pediatrics
80
Rate/1,000 Persons
Age (years)
70
<18
18-44
60
45-64
50
65+
Total (All Ages)
40
Asthma Prevalence by Age
U.S., 1985-1996
30
20
85 86
87
88 89 90 91 92 93 94
Year
95 96
Global Initiative For Asthma – Statistical Report 2005
Hospitalization Rates for Asthma
by Age, U.S., 1974 - 2000
Rate/100,000 Persons
40
35
<15
15-44
45-64
65+
30
25
20
15
10
5
0
74
76
78
80
82
84
86
88
90
92
94
96
Year
Global Initiative For Asthma – Statistical Report 2005
98 00
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 Guidelines
M Weinberger, Pediatric Health 2008
Asthma Pathophysiology
Bronchoconstriction
Airway Inflammation
Airway
Edema & 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
Spirometry
Objective confirmation of airflow obstruction and also
whether airflow obstruction in reversible
Alternative Diagnoses are Reasonably
Excluded
History and Physical critical
Top six alternatives in children
Allergic rhinitis
Recurrent viral infections
Dysphagia with aspiration
Vascular sling
Congenital airway anomaly
Cystic Fibrosis
Goals of Asthma Therapy
Symptom Control
Prevent chronic troublesome symptoms
Decrease need for albuterol ( < 2 /week )
Maintain near normal pulmonary function
Reduce Risk
Recurrent 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 longterm 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 )
Nelson et al 2006
• Monotherapy with Formoterol resulted in increased
number of severe asthma exacerbations
Mann et al 2003
• 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)
Assessing and Monitoring Asthma
Severity and Control
Severity
Other Options
Daily
(in order of cost)
Controller
Medications
Step 1:
• None
Mild Intermittent
< 2 / week: day
< 2 / month: night
• None
Assessing and Monitoring Asthma
Severity and Control
Severity
Daily
Controller
Medications
Step 2:
• Low-dose ICS
Mild persistent
> 2 / week: day
> 2 / month: night
Other Options
(in order of cost)
•LTRA
Assessing and Monitoring Asthma
Severity and Control
Severity
Daily
Controller
Medications
Other Options (in
order of cost)
Step 3:
Moderate
persistent
•Low - medium
dose ICS plus
LABA
•High-dose inhaled
glucocorticosteroid, or
Daily: Day
> 1 / week: night
• Medium-dose inhaled
glucocorticosteroid
plus
leukotriene modifier
Assessing and Monitoring Asthma
Severity and Control
Severity
Daily Controller
Medications
Step 4
Severe
persistent
• High-dose
Throughout
the day: day
Multiple times /
week: night
ICS plus longacting inhaled β2-agonist
plus
- Leukotriene modifier
- Oral glucocorticosteroid
- Sustained-release
theophylline
Other
Options
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
POD = Perception of dyspnea
Magdle et al, Chest 2002
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
Expiration
Flow - Volume Loop : Normal
Flow
TLC
RV
FVC
Volume
Inspiration
FEV1
Flow - Volume Loop : Normal
Expiration
Obstructive defect
Flow
TLC
FEV1
Volume
RV
Inspiration
FEV1
Obstructive Pattern
Due to diseases leading to mucus plugging, bronchospasm,
inflammation, or loss of elastic support of the airways
(asthma, CF)
• FVC
• FEV1
• FEV1 / FVC
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 Facts
What is asthma ?
What is an asthma attack ?
What is airway inflammation ?
Asthma Medications
Different types
How they work ( control vs. rescue )
Potential side effects
Patient / Family skills
Inhaler technique ( VHC )
Awareness of symptoms
Avoiding triggers
Utilization of asthma action plan
Factors Associated with
Non-Compliance in Asthma Care
Medication Usage
Patient/Physician
Misunderstanding/lack of
information

Difficulties associated
with inhalers


Complicated regimens

Underestimation of severity

Fears about, or actual
side effects

Attitudes toward ill health

Cultural factors

Poor communication

Cost
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 Comorbid 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 Comorbid 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