Childhood AsthmaChildhood Asthma

上海交通大学医学院附属新华医院

鲍一笑

1953-1995 （ 42

岁）

Died in Thailand due to acute asthma exacerbation

邓丽君

Died in Vienna because there is no effective treatment for asthma

1770-1827 （ 57岁）

贝多芬

IntroductionIntroduction

Definition

Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements plays a role.

The chronic inflammation is associated with 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 within the lung that is often reversible either spontaneously or with treatment.

Asthma is an inflammation indduced by allergy

AllergyEosinophils cell infiltrate

Corticosteroids

as anti-inflammatory therapy

Infection Neutrophils cell infiltrate

Red swelling, hot and pain

Antibiotics therapy

The Role of Th2 Cytokines in Allergic Cascade

The balance of Th1 and Th2

Epidemiology

　　 Prevalence↑ Death rates↑ (per 10,0000 population)

China 　 0.5-3.3% 　 36.7 　

worldwide 0.1-32% 1.3

Shanghai90 ： 1.79%00 ： 4.52%

The prevalence of asthma has been increasing since the early 1980s for all age, sex, and racial groups.

Europe and north America10%Asia 5%

The death rate1979-2000

The current asthma prevalence 2003 in USA

EtiologyEtiology

Genetic Factor

Epidemiology

• Atopy is the strongest identifiable predisposing factor. An elevated IgE level is often found in the serum of allergic patients, because IgE is the primary antibody associated with allergic reactions.

In asthma children, 30-40% have a family history of asthma,

50-60% have a family history of allergic disease.

Related gene of Asthma

More than 22 loci on 15 autosomal chromosomes have

been linked to asthma. Gene associated with IgE Genetic variation in receptors for different asthma

medications (polymorphisms in the β2-adrenergic

receptor).

Environmental Factor

Respiratory Tract Infections （ viral, bacterial,

mycoplasma ）

Inhalant Allergen

Others

About 40% of infants and young children who have wheezing with viral infections in the first few years of life will have continuing asthma through childhood.

Inhalant Allergens

Sensitization to inhalant allergens increases over time and is found in the majority of children with asthma.

Animal dander Environmental tobacco smoke

Indoor allergens Air pollutants

Dust mites Cold air, dry air

Cockroaches Exercise

Molds Strong or noxious odors or fumes

Pollens (trees, grasses, weeds) Crying, laughter, hyperventilation

Pollen

Mite

House Pet

SmokeSmoke

Exposure to tobacco smoke, especially from the mother, is

also a risk factor for asthma.

Food Allergen

Animal Protein

Fishery,product,milk,meat,egg

Oil Crop and Nuts

Peanuts

Fruit and Greengrocery

Grain

Food additive

Drug Allergen

Benzylpenicillin

Sulfonamides

Antipyretic analgesic

Anesthetic agent

Biological products

Aspirin sensitivity is uncommon in children.

Contactant allergen

• Para-phenylenediamine

• Nickel sulphate

• Mercurial

• Plastics products

• Rubber goods

• Essence

Pathogenesis

Genetic factors

Immunity factors

Psychological factors

Endocrine factors

allergen

DC、 MC、 B cell

Th2

Eos

IgE

B cell

Airwayinflammation,Hyperresponsiveness,Airway contraction,

bronchoconstriction, airway wall edema, mucus plug formation

Wheezing, Cough, Dyspnea,

IL-4

LAR

Mast cell

Excise 、 WetherHarmful gas

ECF histamine,LT,PG,PAF

PAF,LT,MBP,ECP

IL-5

EAR

Airway remodeling

Allergic inflammation

Allergic inflammation

Pathologic features

Shedding of airway epitheliumEdemaMucus plug formationMast cell activationCollagen deposition beneath the

basement membrane

Bronchospasm mucosal edema

mucus plug formation

Pathologic featuresPathologic features

AsthmaNormal

Changes of Airway Epithelium

shedding of airway

epithelium

Specimen of Bronchial Mucosa

• In the subject without asthma, the epithelium is intact;

• there is no thickening of the sub-basement membrane, and there is no cellular infiltrate.

BAIn the patient with mild asthma, there is evidence of goblet-cell hyperplasia in the epithelial-cell lining. The sub-basement membrane is thickened, with collagendeposition in the submucosal area, and there is a cellular infiltrate.

Clinical Manifestation

SymptomsSymptoms

Precursory symptoms:

Rhinocnesmus

Sneezing

Nasal obstruction

Nasal discharge

Itching of eye

Dry cough

Wheezing is the most characteristic

sign of asthma.

Patients may also have cough and shortness

of breath.

SymptomsSymptoms

Physical signs

General signs: Cyanosis, Agitation and lethargy

Chest auscultation: Prolongation of the expiratory phase and

wheezing. As the obstruction becomes more severe, wheezes become

more high pitched and breath sounds diminished.

Chest Radiograph: Bilateral hyperinflation

Others: Tachycardia and pulsus paradoxus

severe obstruction:

Flaring of nostrils, intercostal and suprasternal retractions, and use of

accessory muscles of respiration

Laboratory Examination

Clumps of eosinophils on sputum smear and blood Chest radiograph: Bilateral hyperinflation Immunologic test

(1) Allergen skin testing (2) Elevated total serum IgE levels(3) Abnormality of cytokines （ IL-3 、 IL-4 、 IL-5 ）

Pulmonary Function Test

Spirometry (in clinic)

Airflow limitation

Low FEV1 (relative to percentage of predicted norms)

FEV1/FVC ratio <0.80

Bronchodilator response (to inhaled β-agonist)

Improvement in FEV1 ≥12% or ≥200 mL

Exercise challenge

Worsening in FEV1 ≥15%

Daily peak flow or FEV 1 monitoring:

Day to day and/or AM-to-PM variation ≥20%

Lung Function Abnormalities in Asthma

FEV1, forced expiratory volume in 1 sec; FVC, forced vital capacity.

DiagnosisDiagnosis

Diagnostic Criteria of Childhood Asthma

Children older than 3 years, reccurent wheezing

Prolongation of the expiratory phase and expiratory wheezing

Improved after the use of inhaled bronchodilators

Exclusion of other diseases which can also cause wheezing, dyspnea, and cough

Diagnostic Criteria of Infant’s Asthma

1. Children younger than 3 years, more than three episodes of wheezing （ 2 score ）

2. Acute asthma exacerbation （ 1 score ）3. Prolongation of the expiratory phase and wheezing can be heard on

chest auscultation. （ 2 score ）4. Allergic disease, such as allergic rhinitis and atopic dermatitis. （ 1

score ） 5. A family history of allergic disease （ 1 score ）

≥5 score to diagnose asthma。≤4 score or just two episodes of wheezing, to diagnose suspicious asthma or asthmatic bronchitisWheezing decrease or disappear after use bronchodilators 2 score

Classification of Asthma Severity

The presence of one of the features of severity is sufficient to place a patient in the category. An individual should be assigned to the most severe grade in which any features occurs.

symptoms Nighttimesymptoms

Lung functionFEV1/PEF% predicted

PEFvariability

Step1Mildintermittent

≤2 times a week ≤2 times a month

≥80% <20%

Step2Mildpersistent

>2 times a week >2 times a month

≥80% 20%-30%

Step3Moderatepersistent

Daily symptoms >1 times a week 60%-80% >30%

Step4Severepersistent

Continual symptomsLimited physical

activity

Frequent ≤60% >30%

Differential diagnosisDifferential diagnosis

Viral bronchiolitis Foreign body Congenital laryngeal stridor Tuberculosis of trachebronchial

lymph nodes Vascular malformation Gastroesophageal Reflux

TreatmentTreatment

To control airway inflammation.

To prevent asthmatic attack.

General Measures

Avoid exposure to sensitive allergens

Give inactivated influenza vaccine

Cure respiratory tract infections

Avoid trigger factors

Self-management

education

Regular follow-up

PEFR monitoring

physical exercise

Glucocorticosteroid

ICS therapy is recommended daily as the treatment of choice for all patients with persistent asthma.

ICS therapy has been shown to reduce asthma symptoms, improve lung function, reduce AHR, reduce “rescue” medication use and, most important, reduce urgent care visits, hospitalizations.

ICS therapy may lower the risk of death due to asthma.

The role of Glucocorticosteroid

Inhaled corticosteroids

versus systemic corticosteroids : The drug nonstop to bellows

Low doses

Rapid onset of action

High security

Effectiveness

Inhalation therapy

Distribution of inhalation in lungs

Metabolic pathway of Inhaled corticosteroids

circulation

adverse effect

biological activity

80 - 90% swallow

10 - 20 % To both lungs

Intestinal Absorption

Inactivation due to first pass effect

Inhaler

Nebulizing therapy an infants

180

170

160

150

140

130

120

110

Adult height (cm)patients use inhaled corticosteroids

unimpaired child

6岁 8岁 10岁 12岁 14岁 16岁

Pedersen,1999

Effect of long-term treatment with inhaled budesonide on adult height in children with

asthma.

Children with asthma who have received

long-term treatment with budesonide attain

normal adult height.

Bronchodilators

Short-acting inhaledβ-agonist (SABA) Give their

rapid onset of action, effectiveness, and 4–6 hr duration of action.

(albuterol, levalbuterol, terbutaline, pirbuterol) Long-acting inhaledβ-agonist (LABA) have a

prolonged duration of effect of at least 12 hr. (salmeterol, formoterol)

Adverse effect of long-term use of β-agonists

Induce down regulation of the β2-receptor function.Aggravate airway inflammation and airway

hyperreactivity.Overuse of β-agonists is associated with an increased

risk of death or near-death episodes from asthma.

β2-receptor

• Corticosteroids may enhance Expression of β2-receptor

Hormone receptor

Glucocorticoids

Anti-inflammatory effect

β2-agonists may enhance Anti-inflammatory effect of of Corticosteroids

β2-agonists

Bronchiectasis effect

++++

++++

Interaction between corticosteroids and β2-agonists

The addition of LABA to ICS to is superior to doubling the dose of ICS

Other drugsOther drugs

Leukotriene receptor antagonists (LTRA). Aminophylline

Sodium Cromoglicate

Specific immunotherapy

—— hyposensitization therapy

Nonspecific immunotherapy

—— immunoloregulation therapy

ImmunotherapyImmunotherapy

• WHO issued Global initiative for

asthma (GINA) in 1994. The aims were

to set up standardization of asthmatic

treatment. It works with health care

professionals and public health officials

around the world to reduce asthma

prevalence, morbidity, and mortality.

GINA

Stepwise Approach

SummaryAsthma is a chronic inflammatory condition of the

lung airways resulting in episodic airflow obstruction. The

inflammatory cell infiltrate is the main pathologic features

includes eosinophils, lymphocytes, and neutrophils. Airway

hyperresponsiveness to nonspecific stimuli is a hallmark of

asthma. Wheezing, dry cough, and shortness of breath is the

characteristic sign of asthma.

Asthma medications include long-term control

medications combined with quick-relief medications. Anti-

inflammatory therapy is the core of modern treatment of

asthma. Corticosteroids is the most effective anti-

inflammatory agent. Inhalation therapy is the main

medication for asthma. Up to now, there is no radical

treatment

Summary

美国跳水名将洛加尼斯

American Greg Louganis

The greatest diver

美国田径全能乔伊娜

Jackie Joyner-Kersee

She earned the gold medal of heptathlon in

the 1992 Olympics.

Thanks ！