Transcript 幻灯片 1 - 上海交通大学医学院精品课程

Childhood Asthma
上海交通大学医学院附属新华医院
鲍一笑
邓丽君
1953-1995（42岁）
Died in Thailand due to acute
asthma exacerbation
贝多芬
1770-1827（57岁）
Died in Vienna because
there is no effective
treatment for asthma
Introduction
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
Allergy
Infection
Eosinophils cell infiltrate
Neutrophils cell infiltrate
Red swelling, hot and pain
Corticosteroids
as anti-inflammatory therapy
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
worldwide
Shanghai
90：1.79%
00：4.52%
0.5-3.3%
36.7
0.1-32%
1.3
Europe and north America10%
Asia
5%
The prevalence of asthma has been increasing since the early
1980s for all age, sex, and racial groups.
The death rate1979-2000
The current asthma prevalence
2003 in USA
Etiology
Genetic Factor

Epidemiology
In asthma children,
30-40% have a family history of asthma,
50-60% have a family history of allergic disease.
• 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.
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
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
Sensitization to inhalant allergens increases over time and is found in
the majority of children with asthma.
Pollen
Mite
House Pet
Smoke
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
Allergic inflammation
allergen
Excise、Wether
Harmful gas
DC、MC、B cell
IL-4
Th2
IgE
B cell
Mast cell
ECF
IL-5
histamine,LT,PG,PAF
Eos
PAF,LT,MBP,ECP
LAR
EAR
Airwayinflammation,Hyperresponsiveness,Airway contraction,
bronchoconstriction, airway wall edema, mucus plug formation
Airway
remodeling
Wheezing, Cough, Dyspnea,
Allergic inflammation
Pathologic features





Shedding of airway epithelium
Edema
Mucus plug formation
Mast cell activation
Collagen deposition beneath the
basement membrane
Pathologic features
Bronchospasm
mucosal
edema
mucus plug
formation
Changes of
Airway Epithelium
shedding of airway
epithelium
Normal
Asthma
Specimen of Bronchial Mucosa
A
•
•
In the subject without asthma, the
epithelium is intact;
there is no thickening of the subbasement membrane, and there is
no cellular infiltrate.
B
In the patient with mild asthma, there is
evidence of goblet-cell hyperplasia in the
epithelial-cell lining. The sub-basement
membrane is thickened, with collagen
deposition in the submucosal area, and
there is a cellular infiltrate.
Clinical Manifestation
Symptoms
 Precursory symptoms:
 Rhinocnesmus
 Sneezing

Nasal obstruction

Nasal discharge

Itching of eye

Dry cough
Symptoms
 Wheezing is the most characteristic
sign of asthma.
 Patients may also have cough and shortness
of breath.
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
Lung Function Abnormalities in Asthma
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%
FEV1, forced expiratory volume in 1 sec;
FVC, forced vital capacity.
Diagnosis
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 bronchitis
Wheezing decrease or disappear after use bronchodilators 2 score
Classification of Asthma Severity
symptoms
Nighttime
symptoms
Lung function
FEV1/PEF
% predicted
PEF
variability
Step1
Mild
intermittent
≤2 times a week
≤2 times a
month
≥80%
<20%
Step2
Mild
persistent
>2 times a week
>2 times a
month
≥80%
20%-30%
Step3
Moderate
persistent
Daily symptoms
>1 times a week
60%-80%
>30%
Step4
Severe
persistent
Continual symptoms
Limited physical
activity
Frequent
≤60%
>30%
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.
Differential diagnosis

Viral bronchiolitis

Foreign body

Congenital laryngeal stridor

Tuberculosis of trachebronchial
lymph nodes

Vascular malformation

Gastroesophageal Reflux
Treatment

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
Inhalation therapy
 Inhaled corticosteroids
versus systemic corticosteroids :
 The drug nonstop to bellows
 Low doses
 Rapid onset of action
 High security
 Effectiveness
Distribution
of
inhalation
in lungs
Metabolic pathway of Inhaled corticosteroids
10 - 20 %
To both lungs
circulation
biological activity
80 - 90% swallow
Intestinal
Absorption
Inactivation
adverse effect
due to first pass effect
Inhaler
Nebulizing therapy an infants
Effect of long-term treatment with inhaled
budesonide on adult height in children with
asthma.
patients use inhaled corticosteroids
180 Adult height (cm)
170
unimpaired child
160
150
140
Children with asthma
who have received
long-term treatment
with budesonide attain
normal adult height.
130
120
110
6岁
Pedersen,1999
8岁
10岁
12岁
14岁
16岁
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.
Interaction between corticosteroids and
β2-agonists
Glucocorticoids
β2-agonists
β2-receptor
+
Hormone
receptor
+
Anti-inflammatory
effect
Bronchiectasis effect
• Corticosteroids may enhance Expression of β2-receptor
β2-agonists may enhance Anti-inflammatory effect of Corticosteroids
The addition of LABA to ICS to is superior to doubling the dose of ICS
Other drugs
 Leukotriene receptor antagonists (LTRA).
 Aminophylline
 Sodium Cromoglicate
Immunotherapy

Specific immunotherapy
——

hyposensitization therapy
Nonspecific immunotherapy
——
immunoloregulation therapy
GINA
• 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.
Stepwise Approach
Summary
Asthma 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.
Summary
Asthma medications include long-term control
medications combined with quick-relief medications. Antiinflammatory therapy is the core of modern treatment of
asthma. Corticosteroids is the most effective antiinflammatory agent. Inhalation therapy is the main
medication for asthma. Up to now, there is no radical
treatment
American Greg
Louganis
The greatest diver
美国跳水名将洛加尼斯
Jackie Joyner-Kersee
She earned the gold
medal of heptathlon in
the 1992 Olympics.
美国田径全能乔伊娜
Thanks！