Bronchial Asthma

Bronchial Asthma Dr. Xing Lihua

邓丽君 1953~1995 因哮喘急性发作 病逝泰国

Beethoven 1770-1827 由于哮喘和束手 无策的医生而死 于维也纳

Outline Defination ➤ Epidemiology ➤ Pathogenesis ➤ Pathology ➤ Clinical Manifestations ➤ Diagnosis ➤ Disease management recommendations ➤

Definitio n Asthma is now defined as a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role, in particular, mast cells, eosinophils, T lymphocytes, neutrophils, and epithelial cells.

Definitio n In susceptible individuals, this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, cough, particularly at night and in the early

Definitio n These episodes are usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment. The inflammation also causes an associated increase in the existing bronchial hyperresponsiveness to a variety of stimuli.

Epidemiology ➤ morbidity

1%-13%, 1%-4% in China ➤most common chronic disease of childhood About one-half of the case develop before age 10 and another third occur before age 40 ➤higher

in developed country ➤higher in urban than in suburb ➤40% with family history

Pathogenesis: Causes Host factor (hereditary susceptibility ) FH of asthma or atopy (familial tendency for allergic reactions) Environmental factor (triggers) allergens, chemicals, smoke, cold, exercise, food additives, aspirin, extreme emotional expressions

Pathogene sis certain triggers

Pathogene sis 1. Airway Inflammation A specific type of inflammatory condition, involving, in particular, mast cells, eosinophils and T lymphocytes, which release a wide range of inflammatory mediators  These mediators act on cells in the airway, leading to contraction of smooth muscle, edema due to plasma leakage and mucus plugging 

Pathogene sis

Pathogene sis 2. Airway Hyperresponsiveness an exaggerated bronchoconstrictor response to a wide variety of stimuli leads to clinical symptoms of wheezing and dyspnea after exposure to allergens, environmental irritants, viral infections, cold air, or exercise. can be measured by inhalation challenge testing with methacholine or histamine.

Pathogene sis 3. Airflow Obstruction Acute bronchoconstriction Airway edema Chronic mucus plug formation Airway remodeling

症状tip - - -of 冰山的一角 The iceberg

Pathology

Normal

Asthma

A Panel A Specimen of Bronchial Mucosa From a Subject without Asthma. The epithelium is intact; there is no thickening of the sub-basement membrane, and there is no cellular infiltrate.

B

N Engl M .2001 ;344 (5): 350

Panel B Specimen of Bronchial Mucosa from a Subject with 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.

(A)

(A) A normal subject without asthma, showing an intact surface pseudostratified ciliated columnar epithelium. The underlying reticular basement membrane is indistinct; there are few inflammatory cells, and small amounts of bronchial smooth muscle.

(B)

Am. J. Respir. Crit. Care Med., 2000; 161(5) :1720-1745

(B) A subject with fatal asthma, showing sloughing of the surface epithelium, a prominent homogeneous thickened reticular basement membrane of hyaline appearance, an intense infiltration of the mucosa by inflammatory cells, enlargement of bronchial smooth muscle.

Airway Remodeling (structural changes) Airway wall thickening of sufficient magnitude to increase airflow resistance and enhance airway responsiveness

The episodic airway narrowing caused by three possible factors ➤ Constriction ➤ Airway ➤ The

of airway smooth muscle

edema

presence of liquids within the confines of the airway lumen

Clinical Manifestations History ➤ Shortness of breath accompanied by chest tightness, cough, wheezing and anxiety recurrent episodes may be obvious at night or in the early morning reversible either spontaneously or with treatment ➤ Variants of asthma: no wheezing, only cough or chest tightness ➤ Cold dry air may induce airway narrowing

Clinical Manifestations ➤episodes

recur following one or more triggers ➤wheezing rale as episodes ➤relief of symptoms occurs with a bronchodilator or spontaneously

Clinical Manifestations Physical Examination Vital signs: ➤ A rapid respiratory rate ---often 25- -40 bpm ➤ Tachycardia ➤ Pulsus paradoxus ( systolic blood pressure decrease >10mmHg during inspiratory period than during expiratory period)

Clinical Manifestations ➤ Using

accessory muscles of ventilation

➤ Hyperinflated ➤ Prolonged

thorax

expiratory phase

➤ Hyperresonance ➤ Wheezing

Clinical Manifestations Laboratory Findings 1.Sputum examination Eosinophils are often seen microscopically, and eosinophilic granules from disrupted cells may be seen throughout the sputum smear.

Clinical Manifestations 2.Chest x-ray Vary from normal to hyperinflation. Lung markings are commonly increased, particularly in chronic asthma. 3.Eosinophil count Eosinophilia (> 250 to 400 cells/µL) is common. In many asthmatics, the degree of eosinophilia correlates with severity of asthma.

Clinical Manifestations Laboratory Findings 4.Allergen identification measuring total serum IgE or specific IgE antibodies skin testing Use appropriately selected allergens A positive response indicates only potential allergic reactivity to the tested allergens.

Clinical Manifestations Laboratory Findings 5.Pulmonary function test bronchial

provocation test (BPT)

bronchial

dilation test (BDT)



peak expiratory flow (PEF) variability

Bronchial Provocation Test (BPT) after inhale bronchial stimulor such as metacholine or histamine, the decrease of FEV1 > 20%. (BPT +)

Bronchial Dilation Test (BDT) after inhale bronchodilator such as salbutamol, the increase of FEV1>15%; or the increase volume > 200ml .(BDT +)

Peak Expiratory Flow (PEF) Variability PEF in am (usually lowest ) and 12 hours later (usually highest), PEF variability ≥ 20% . (reversible airflow obstruction )

Diagnosis: Criteria 1. recurrent episodes of wheezing,breathlessness,or cough following one or more triggers 2. wheezing rale as episodes 3. relief of symptoms occurs with a bronchodilator or spontaneously 4. exclude other diseases 5. Pulmonary function test bronchial provocation test (+) or bronchial dilation test (+) or PEF variability ≥ 20%

1-4 or 4-5

Classification of asthma severity

Differential Diagnosis  Cardiac

asthma  Chronic asthmatic bronchitis  Lung cancer  Allergic lung diseases ： eosinophilic lung disease

Cardiac asthma Bronchial asthma history

heart disease

allergic atopy

symptoms mixed dyspnea Pink frothy sputum

expiratory dyspnea White mucous sputum

signs

moist rales in base of lung Small amounts of wheezing rale

pulmonary fullness of wheezing rale

X ray

cardiac enlargement emphysema pulmonary congestion

treatment Theophylline morphine

Theophylline adrenalin

Complications

Goals of management ➤ minimal

or no symptoms ➤ minimal asthma episodes / attacks ➤ no emergency visits to hospital ➤ minimal need for as needed β 2 agonist ➤ no

limitations on physical activities ➤ nearly normal lung function ➤ minimal or no side effects from medication

Directed at airway obstruction and inflammation

use of bronchodilators (rescue ) for acute asthma airway obstruction use of controllers for modifying the airway inflammatory environment

Treatment options Relievers: ➤short-acting β 2 agonist ➤Anticholinergics ➤methylxanthine ➤systemic steroids

Controllers: ➤inhaled steroids(ICS) ➤long-acting β 2 agonist ➤Leukotriene regulator (LTRA) ➤methylxanthine ➤mast cell stabilizers ➤systemic steroids

Relievers: short-acting β ➤ MDI

2

agonist

with a spacer or nebulizer ➤onset in 5 minutes, lasts 3-8 hours ➤equally effective ➤ tablets / syrup available for pediatrics ➤onset in 30 minutes, lasts 4-8 hrs ➤ side effects are bothersome, but transient

Relievers: anticholinergic ➤ ipratropium

bromide ➤may provide added benefit to β agonist ➤ few side effects

2

Relievers: methylxanthine Theophylline ： Bronchodilator cardiant diuresis central stimulant <1~1.2g/d

Relievers: systemic steroids ➤ prednisone

or prednisolone: ➤2 mg/kg/d ➤IV or PO ➤ generally continue for 5 days ➤simultaneously initiate inhaled steroid ➤Usually <10-14d ➤no need to taper systemic steroids

Controllers: inhaled steroids ➤ must

be scheduled ➤ takes 4 to 5 days to see benefit ➤ minimal systemic adverse effects

Controllers: long-acting β ➤ salmeterol ➤ must ➤ In

2

agonist

or albuterol

be scheduled

combination with inhaled steroid for moderate or severe persistent asthma

LABA

bronchodilation

antiinflammation

ICS

ICS

LABA

Controllers: leukotriene regulator  zafirlukast montelukast

methylxanthines ➤sustained

release theophylline

Controllers:

mast cell stabilizer ➤ cromolyn

or nedocromil ➤ must be scheduled ➤ most useful in patients with: ➤exercise induced ➤associated allergies ➤ few side effects (cough)

Controllers: systemic steroids ➤2

mg/kg/d (max 60 mg/d) ➤ numerous adverse effects ➤including growth retardation

Management plan for asthma ➤ classify

the severity of the illness ➤ identify the appropriate regimen that will maintain control of the illness ➤ review classification and management plan every 1 to 6 months ➤ gain control as quickly as possible, then adjust

Mild intermittent disease ➤ symptoms

< 1 / week ➤ nocturnal symptoms < 2 / month ➤ PEF > 80% predicted ➤ PEF variability < 20% ➨reliever: short-acting β 2 agonist PRN ➨controller: none

Mild persistent disease ➤ symptoms

> 1 / week (but not daily) ➤ symptoms may affect activity ➤ nocturnal symptoms > 2 / month ➤ PEF > 80% predicted ➤ PEF variability = 20% - 30% ➨reliever: short-acting β 2 agonist PRN ➨controller: LD inhaled steroid or mast cell stabilizer

Moderate persistent disease ➤ symptoms

daily ➤ symptoms affect activity ➤ nocturnal symptoms > 1 / week ➤ require short-acting β 2 agonist daily ➤ PEF 60% - 80% predicted ➤ PEF variability > 30% ➨reliever: short-acting β 2 agonist PRN ➨controller: MD inhaled steroid plus longacting bronchodilator

Severe persistent disease ➤ continuous

symptoms ➤ frequent exacerbations ➤ frequent nocturnal symptoms ➤ physical activities limited by asthma ➤ PEF < 60% predicted ➤ PEF variability > 30% ➨reliever: short-acting β 2 agonist PRN ➨controller: HD inhaled steroid plus longacting bronchodilator plus systemic steroids

Thanks