Mona Mostafa El-Falaki

Professor of Pediatric Allergy & Pulmonology Head of Pediatric Allergy & Pulmonology Unit Cairo University

Increasing Prevalence of Asthma in Children/Adolescents

Finland
(Haahtela et al)

Sweden
(Aberg et al)

Japan
(Nakagomi et al)

Scotland
(Rona et al)

UK
(Omran et al)

USA
(NHIS)

New Zealand
(Shaw et al)

Australia
(Peat et al)

{1966 1989 {1979 1991 {1982 1992 {1982 1992 {1989 1994 {1982 1992 {1975 1989 {1982 1992
0 5 10 15 20 25 30 35

Prevalence (%)

Worldwide prevalence rates are increasing, on average, by 50% / decade.

(WHO, Bronchial Asthma Fact Sheet, 2000)

The prevalence of pre-school asthma is on the rise.

The

general prevalence of asthma in children aged 0 to 17 years constitutes about 33% of the entire asthmatic patient population.

The prevalence of asthma in children 4 years of age and younger rose 160% from 1980-1994
In children aged 2 to 5 years 100,000 new cases are diagnosed

each year.
CDC. Surveillance for Asthma--United States, 1960-1995 (CDC Surveillance Summaries). MMWR. 1998;47(SS-1):126). Yunginger JW et al. Community-based study of the epidemiology of asthma. Am Rev Respir Dis 1992;146:888-894.

Distribution of Ages at the Onset of Asthma Among 2499 Residents of Rochester, Minnesota

50% < 3 years 80% < 5 years

Silverstein MD et al., N. Engl J Med ,1994

Burden of Asthma One of the Most Common Chronic Illnesses in Children

Affects ~5 million children <18 years in the US Number 1 chronic illness causing school absences 14 million school days lost due to asthma

Asthma
658,000 emergency department visits for asthma in US children <15 years in 1999 Interferes with activities Estimated annual cost of treatment $3.2 billion
AAAAI. Pediatric Asthma: Promoting Best Practice University of Rochester 2004; American Lung Association. http://www.lungusa.org/site/pp.asp?c=dvLUK9O0E&b=44352.

25 20

Asthma Eczema
Rhinitis

% Diagnosed

15 10 5 0

(n=2743)

(n=4003)

(n=4034)

1964

1989

1994

CDC 1996

In a classroom of 30 children,

4 or more children are likely to have asthma and/or other allergies

Inflammation

Remodeling

Mucus Plug

Airway mucosal oedema

Definition of Asthma

Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role Chronic inflammation causes an associated increase in airway hyperresponsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning These episodes are usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment

Chronic inflammation

Histopathologic features
Structural changes

Denuded respiratory epithelium Inflammatory cell infiltration Edema Vessel dilatation &congestion Airway thickening

No asthma

Busse WW, Lemanske RF. NEJM 2001;344(5):350-62

Mild asthma

Airway Remodeling in Asthma

Airway wall thickening Subepithelial collagen deposition (Lamina reticularis) Smooth muscle hyperplasia and hypertrophy Mucus metaplasia

Epithelial hypertrophy
Vascular abnormalities Elias JA et al. J Clin Invest 1999; 104:1001

Airway inflammation in asthma

Normal

Asthmatic
P Jeffery, in: Asthma, Academic Press 1998

Vascular Adhesion and Margination of Inflammatory Cells in Allergic Airways Inflammation

Chang et al., 1997

Allergic Airways Inflammation

Early

Late
Ohkawara, Y. et al., 1997

Charcot Leyden Crystals

Creola bodies

Normal

Rapid Bronchospasm

Late, sustained reaction

Subacute/chronic inflammation

Direct acting mediators

Eosinophils Neutrophils Monocytes Epithelial cells Lymphocytes Cytokines

Onset Peak Duration Enhanced resp. Treatment response -agonists

Early Asthmatic response <10 min 10-30 min 1.5-3 hrs +/Reverses Premed-inhibits Premed-inhibits Premed no effect

Late asthmatic response 3-4 hrs 8-12 hrs > 12 hrs + Partially reverses Premed-no effect Premed-inhibits Premed-inhibits

Cromolyn Corticosteroids

Is it Asthma?

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

To establish a diagnosis of asthma, the clinician should determine that:

Episodic

symptoms of airflow obstruction (with symptoms free intervals). obstruction is at least partially reversible. number of known risk factors are present diagnoses are excluded.

Airflow

Alternative When

the child responds to anti-asthma therapy

Asthma Diagnosis

History and patterns of symptoms Physical examination Measurements of lung function Measurements of allergic status to identify risk factors

Diagnosis of Bronchial Asthma (cont.)

Markers of atopy
Positive FH Other atopic manifestations Investigation
+ve PST Serum total IgE specific IgE Perpheral blood and tissue eosinophilia Inflammatory markers e.g. S-ECP T-cell profile Th1 versus Th2

Techniques

Allergy Prick Skin Test

 Number Quality

of allergens

of allergens (purification + standardization) exposure (residence + occupation etc.) control (positive + negative control) + clinical correlation.

Patient

Quality

Interpretation

Silver birch

Alder

Hazel

Dust mite

Cat hair

Cockroach

Mite legs

Early Wheezers:Predictive Index of Developing Asthma

3 Episodes of Wheezing During Previous Year

PLUS
Parent with asthma One Major Criteria Food sensitivity Two Minor Criteria

Atopic dermatitis
Aeroallergic sensitivity

Or

Peripheral eosinophilia Wheezing not related to infection

If + , then 65% likelihood of persistent wheezing If , then 92% likelihood of not developing clinical asthma
Castro-Rodriguez J et al. Am J Resp Crit Care Med. 162:1403-6, 2001

Differential Diagnosis of Asthma in Children

Congenital malformation
(Laryngeal web ,cyst ,stenosis ,TOF ,vascular ring )

Bronchiolitis Bronchietasis Bronchopulmonary dysplasia Laryngotracheobronchitis Laryngotracheobronchomalacia Immunodeficiency syndromes Primary ciliary dyskinesia

Rhino-sinusitis Cystic fibrosis Foreign body Gastro-esophageal reflux Congenital heart disease Chronic respiratory infection Recurrent aspiration syndromes Vocal cord dysfunction

An atypical history may include:

Onset of symptoms in the neonatal period History of ventilatory support in the neonatal period. Intractable wheezing that is unresponsive to bronchodilators. Wheezing associated with feeding; vomiting The sudden onset of coughing or choking Stridor Steatorrhea

Additional or Alternative Diagnosis:

Failure thrive
Clubbing A cardiac murmur No reversibility of airflow obstruction after administration of a bronchodilator

A focal or persistent finding on chest radiograph.

Cough variant asthma

Hypersecretory asthma
Exercise induced asthma

Subclinical early asthma

Severe asthma

Pathogenesis
Genetic factors

Management

Environmental factors
Air pollution Allergens Cigarette smoking Viral infectious agents

patient education Environmental control Immunotherapy

Anti-inflammatory

Nonpharmacological therapy:

Bronchial smooth muscle contraction bronchial inflammation Airway Hyper-responsiveness ASTHMA Airflow obstruction

therapy

Bronchodilator therapy

Six-part Asthma Management Program

Control of Asthma

Minimal (ideally no) chronic symptoms

Minimal (infrequent) exacerbations

No emergency visits Minimal (ideally no) need for as needed use of

2-agonist

No limitations on activities, including exercise PEF circadian variation of less than 20 percent (Near) normal PEF Minimal (or no) adverse effects from medicine

Recommendations for the primary prevention of allergy

Unspecific Measures:
Non traumatic delivery

No exposure to tobacco smoke

Reduce air pollution

Breast feeding for as long as possible

[kjellman, NIM, 1993 & ACI News 5/5: 131-134]

When you light your cigarette in pregnancy, you're not the only one who smokes Your baby does too!

Recommendations for the primary prevention of allergy

Allergen avoidance:
Reduce exposure to major allergens Consider maternal elimination diet during breast feeding No solid foods for the first 6 months Egg and fish only after 12 months of age. Extensively hydrolyzed milk-based formula as back-up. Avoid day-care centers during infancy (risk of infection).

Asthma Management Guidelines

Treatment should be tailored for each child within the framework of international guidelines National Heart Lung and Blood Institute (NHLBI) and National Institute of Health (NIH) National Asthma Education Prevention Program (NAEPP). EPR3 (2007).

www.nhlbi.nih.gov

Global Initiative for Asthma (GINA, up dated 2007). NHLBI & WHO

www.ginasthma.org.
PRACTALL

(EAACI / AAAAI) Allergy 2008

Consensus Report .

Asthma Management and Prevention Program

Assess, Treat and Monitor Asthma The choice of treatment should be guided by: Level of asthma severity only for initiating therapy Level of asthma control

Current treatment

Pharmacological properties and availability of the various forms of asthma treatment Economic considerations

Component 4: Asthma Management and Prevention Program

Controller Medications

Inhaled glucocorticosteroids. Leukotriene modifiers - LTRA ( montelukast ). Long-acting inhaled 2-agonists LABA (SalmeterolFormeterol). Long-acing theophylline. Cromones. Long-acting oral 2-agonists. Systemic glucocorticosteroids. Anti-IgE.

Long-Term, Controller Medications

Advair

Spacers

Dont give me an inhaler; Its addictive !!!

Classification of Severity
CLASSIFY SEVERITY
Clinical Features Before Treatment
Symptoms STEP 4 Severe Persistent STEP 3 Moderate Persistent STEP 2 Mild Persistent STEP 1 Intermittent Continuous Limited physical activity Daily Attacks affect activity Nocturnal Symptoms Frequent FEV1 or PEF 60% predicted Variability > 30% 60 - 80% predicted > 1 time week Variability > 30%
80% predicted

> 1 time a week but < 1 time a day < 1 time a week Asymptomatic and normal PEF between attacks

> 2 times a month

Variability 20 - 30%

2 times a month

80% predicted Variability < 20%

The presence of one feature of severity is sufficient to place patients in that category.

Levels of Asthma Control

Characteristic Daytime symptoms Limitations of activities Nocturnal symptoms / awakening Need for rescue / reliever treatment Lung function (PEF or FEV1) Exacerbation Controlled (All of the following) None (2 or less / week) None Partly controlled (Any present in any week) More than twice / week Any 3 or more features of partly controlled asthma present in any week Uncontrolled

None
None (2 or less / week)

Any
More than twice / week < 80% predicted or personal best (if known) on any day One or more / year

Normal

None

1 in any week

LEVEL OF CONTROL
controlled

REDUCE

TREATMENT OF ACTION
maintain and find lowest controlling step
consider stepping up to gain control

partly controlled
uncontrolled INCREASE

step up until controlled

exacerbation

treat as exacerbation

REDUCE

INCREASE

TREATMENT STEPS
STEP STEP STEP STEP STEP

Estimate Comparative Daily Dosages for Inhaled Glucocorticosteroids by Age

Drug
Beclomethasone Budesonide Budesonide-Neb Inhalation Suspension Low Daily Dose (g) > 5 y Age < 5 y 200-500 200-600 100-200 100-200 250-500 Medium Daily Dose (g) > 5 y Age < 5 y >500-1000 600-1000 >200-400 >200-400 >500-1000 High Daily Dose (g) > 5 y Age < 5 y >1000 >1000 >400 >400 >1000

Ciclesonide
Flunisolide Fluticasone Mometasone furoate Triamcinolone acetonide

80 160
500-1000 100-250 200-400 400-1000

80-160
500-750 100-200 100-200 400-800

>160-320
>1000-2000 >250-500 > 400-800 >1000-2000

>160-320
>750-1250 >200-500 >200-400 >800-1200

>320-1280
>2000 >500 >800-1200 >2000

>320
>1250 >500 >400 >1200

Part 4: Establish Medication Plans for LongTerm Asthma Management in Infants and Children

Long-term treatment with inhaled glucocorticosteroids (ICS) has not been shown to be associated with any increase in osteoporosis or bone fracture. Studies including a total of over 3,500 children treated for periods of 1 13 years have found no sustained adverse effect of inhaled ICS on growth.

Six-part Asthma Management Program

Part 6: Provide Regular Follow-up Care

Continual monitoring is essential to assure that therapeutic goals are met. Frequent follow-up visits are necessary to review: Home PEF and symptom records Techniques in use of medications Risk factors and their control Once asthma control is established, follow-up visits should be scheduled (at 1 to 6 month intervals as appropriate)

Asthma Action Plan

Patient instrument Personalized Zone system Actions based on symptoms When and how to get help Influence on outcomes controversial

Adapted from NHLBI Expert Panel Guidelines (EPR-3) http://www.health.state.ny.us/diseases/asthma/pdf/4850.pdf

Part 4: Long-term Asthma Management

Pharmacologic Therapy
Reliever Medications:

Short-acting inhaled 2-agonists Systemic glucocorticosteroids Anticholinergics Methylxanthines Short-acting oral 2-agonists

Quick Relief Medications

Loosens your muscles & stops the wheezing

Albuterol for Nebulizer

PULSE OXIMETRY, PaO2, PaCO2, PEFR:

Establish Plans for Managing Exacerbations

Primary therapies for exacerbations: Repetitive administration of rapid-acting inhaled 2-agonist Early introduction of systemic glucocorticosteroids Oxygen supplementation Closely monitor response to treatment with serial measures of lung function

Emergency Department Management

Acute Asthma
Initial Assessment History, Physical Examination, PEF or FEV1 Initial Therapy Bronchodilators; O2 if needed Good Response Incomplete/Poor Response Add Systemic Glucocorticosteroids Good Response If Stable, Discharge to Home Discharge Poor Response Admit to Hospital Admit to ICU Respiratory Failure

Observe for at least 1 hour

Dosage of Drugs in Acute Asthma Attacks in Children

Inhaled 2 Agonist

Salbutamol (Ventolin) :

.Nebulizer solution 0.5%(5mg /ml) Dose: 0.1-0.15 mg/kg/dose (max. 5mg /dose) every 20 min. for 3 doses (minimum dose 1.25 mg /dose) .Metered- dose inhaler(100g/puff) Dose: 2 inhalations every 5 min. for a total of 12 puffs. . IV Dose: loading dose 1 g/kg/min. Maintenance 0.2 g/kg/min. (max. 4 g/kg/min). Only in ICU.

.Oral solution
Dose:0.6mg/kg/day divided in3-4 doses

Development of Nerves and Smooth Muscle in Human Fetal Lung

Airway branch from a human fetal lung 18 wk gestation

Sparrow et al., 1999

[McCray, 1993]

Anti-cholinergics

Ipratropium bromide (Atrovent):

Dose: 0.25mg/20min. For 3 doses then every 2-4 hours

.Nebulizer solution 0.025%(0.25mg /ml)

.Metered- dose inhaler(20g/puff)

Dose: 2-4 inhalations as needed.

Corticosteroids

Methylprednisolone (solu-medrol)
Dose in severe attacks as emergency management: 2mg/kg iv then 1- 2mg/kg/24h.

Prednisolone, Prednisone:
Dose: 1-2mg /kg/day in divided doses oral or iv

Hydrocortisone (solu-cortef)
Dose: 5mg/kg/dose every 6h

Risk Factors for Fatal or Near Fatal Asthma

History of near fatal asthma. Hospitalization or emergency visit within one year. Current use or recent withdrawal of oral corticosteroids. Overdependence on rapidly-acting inhaled beta-2 agonist. Psychological problems or denial of asthma or its severity. Non-compliance with treatment plan.

Six-part Asthma Management Program: Summary

Asthma can be effectively controlled, although it

cannot be cured

Effective asthma management programs include education, objective measures of lung function, environmental control, and pharmacologic therapy
A stepwise approach to pharmacologic therapy is recommended. The aim is to accomplish the goals of therapy with the least possible medication

Thank You

NAEPP expert panel considers initiation of a controller therapy in infants & young children who:
Require

symptomatic treatment > 2 times a wk. Have had 2 exacerbations in 6 months requiring systemic steroids. Have had > 3 wheezy episodes in the past year that lasted > 1 day and affected sleep and have risk factors for asthma (intermittent asthma with allergic sensitization). With intermittent asthma and severe exacerbation are managed as moderately severe asthma.

When Should Cough/Wheeze be Called Asthma?

When

wheeze/cough becomes recurrent When other wheeze/cough conditions have been excluded When a number of known risk factors are present When the child responds to anti-asthma therapy

PEFR Zones
Red: Below 50% of Personal Best Yellow: 50% to 80% of Personal Best Green: 80% to 100% of Personal Best

Component 4: Asthma Management and Prevention Program

Controller Medications

Inhaled glucocorticosteroids Leukotriene modifiers - LTRA ( montelukast ) Long-acting inhaled 2-agonists LABA (SalmeterolFormeterol) Long-acing theophylline Cromones Long-acting oral 2-agonists Systemic glucocorticosteroids Anti-IgE

Acute Allergen Induced Airway Remodeling

Phipps et al., AJR Cell Mol. Biol 2004