Bronchial AthmaBronchial AthmaBronchial AthmaBronchial Athma
Yoon Jung Oh, M.D.
The Departments of Pulmonary and Critical care Medicine
Ajou University School of Medicine
Definition
1. Variable and reversible airway obstruction
2. Airway inflammation
3. Bronchial hyperresponsiveness
Characteristics of asthma in 10 points
1. Episodic paroxysms of wheezy dyspnea2. Symptom-free periods3. Bronchial hyperresponsiveness4. Significant reversibility with beta2 agonists (≥ 20%)5. Significant reversibility with steroids (≥ 20%)6. Eosinophil inflammation7. Airway obstruction or narrowing: Increased resistance to airflow Reduced ventilatory capacity of obstructive type8. Rapid and considerable changes in lung function (peak flow variation ≥ 20%)9. Frequent nocturnal episodes and low morning peak flow values10.Frequent occurrence of allergy
Prevalence and Classification
• 4~5% of the population • Before age 10 (50%), Before age 30 (30%)• Childhood M : F = 2:1, Age 30 M : F = 1:1
AgePersonal or family history of allergic diseasesSkin testIgE level
Allergic asthma
Age 3 ~ 35Present
Positiveincreased
Idiosyncratic asthma
< age 3 or > age 35absent
Negativenormal
Pathogenesis of Asthma (1)
• Inflammatory changes in the bronchi
• The bronchial wall, its basement membrane and muscle layer are
thickened.
• There is accumulation and activation of eosinophils.
• There is shedding of ciliated epithelium.
clusters of epithelial cells(Creola bodies).
• The mucociliary clearance is grossly impaired.
• Extensive mucus plugging occludes the lumen.
• The lungs are hyperinflated with small atelectatic areas.
Smooth muscle
Mucous membrane
mucus
Normal adult
Muscular spasm
Mucosaledema
Stickymucus
Expiratory pressure
Airway inflammation : bronchoconstriction, vascular congestion, edema formation• Macrophages(antigen presenting cell)• Mast cells Primary mediator : histamine, serotonine, ECF-A Secondary mediator : LT(B,C,D,E), PGs(E2,F2,D2),bradykinin, PAF• Eosinophils (major basic protein, eosinophilic cationic protein)• Lymphocytes TH1 : IL-2 & IFN- growth and differentiation of B cell, activation of macrophages TH2 : IL-4 & IL-5 stimulate immunoglobulin secretion, eosinophil proliferation, differentiation, activation • Neutrophils
Chemotactic factor : LTB4, ECF-A, NCF-A
Pathogenesis of asthma (2)
Initial allergen exposure : allergic sensitization
Allergen
Hyperresponsiveness
Late response
Early response
Subsequent allergen exposure : allergic symptoms
Allergen
Cell membrane phospholipid
Arachidonic acid
Leukotriene A4
Leukotriene C4
Leukotriene D4
Leukotriene E4
Leukotriene B4 Prostaglandin G2
Prostaglandin H2
Thromboxane A2Prostacycline
Prostaglandin D2,E,F2
1. Allergens : dependent on IgE response House dust mite(most common) Pollen(tree, grass, weed)2. Pharmacologic stimuli aspirin, tartrazine beta-adrenergic antagonists sulfiting agents3. Environment and air pollution ozone, nitrogen dioxide, sulfur dioxide4. Occupational factors toluene diisocyanate(TDI), nickel 5. Infections : most common stimuli of acute exacerbation6. Exercise running, inhalation of cold air !! Swimming is good for asthma 7. Emotional stress
Etiology
Aspirin sensitive asthma
• Primarily affects adults• Preferential generation of leukotrienes• Begins with perennial vasomotor rhinitis hyperplastic rhinosinusitis with nasal polyps • Cross reactivity between aspirin and other NSAIDs Indomethacin, fenoprofen, naproxen, zomepirac sodium, ibuprofen, mefenamic acid, phenylbutazone!! Well tolerated drugs acetaminophen, sodium salicylate, choine salicylate, salicylamide, propoxyphene• Desensitized by daily administration of the drug Cross tolerance also develops to other NSAIDs
Pathology
• Hypertrophy of the bronchial smooth muscle• Hyperplasia of mucosal and submocosal vessels• Mucosal edema• Denudation of the surface epithelium• Pronounced thickening of the basement membrane• Eosinophilic infiltrates in the bronchial wall
Normal alveoli Hyperinflated alveoli Collapsed alveoli
Normal Lungs Asthmatic Lungs
Pathophysiology (1)
Contraction of smooth muscle,Vascular congestion Edema of the bronchial wall
Reduction of airway diameter
Increase in airway resistanceDecrease in forced expiratory volumes and flow ratesAlterations in respiratory muscle functionChanges in elastic recoilAbnormal distrubution of both ventilation and pulmonary blood flow with mismatched ratiosAltered arterial blood gas concentrations
Elastic recoil of lung Expiratory muscles
Ordinary and accessory inspiratory muscles
Asthmatic expiration with airway closure
Pathophysiology (2)
RVH, pulmonary hypertension
FVC ≤ 50% of normal
FEV1 ≤ 30% of predicted
Maximum/minimum midexpiratory flow rates ≤ 20%
Residual volume(RV) ≈ 400% of normal
Hypoxia is a universal finding but
frank ventilatory failure is relatively uncommon(10-15%)
Hypocapnia and respiratory alkalosis
Normal PaCO2 tends to be associated with quite severe levels of obstruction(impe
nding respiratory failure)
Normal Acute asthma
Pathophysiology (2)
RVH, pulmonary hypertension
FVC ≤ 50% of normal
FEV1 ≤ 30% of predicted
Maximum/minimum midexpiratory flow rates ≤ 20%
Residual volume(RV) ≈ 400% of normal
Hypoxia is a universal finding but
frank ventilatory failure is relatively uncommon(10-15%)
Hypocapnia and respiratory alkalosis
Normal PaCO2 tends to be associated with quite severe levels of obstruction(impe
nding respiratory failure)
Normal ventilation and perfusion
Ventilation/perfusion mismatch in asthma
Clinical Features
Triad : dyspnea, cough, wheezingNocturnal awakening with dyspnea and/or wheezingProlonged expirationTachypnea, tachycardia, mild systolic hypertensionOverinflated lungsUse of accessory muscles , Paradoxical pulse Extremely valuable in indicating the severity of the obstructionCough/sputum Curschmann’s spirals, eosinophils, Charcot-Leyden crystalsAtelectasisSpontaneous pneumothorax/pneumomediastinum
Mild asthma Moderate Severe
Verysevere
Sentences
DEATH
Words None
Stethosco-pic rhonchi
Audible wheezinessBreathless at rest
Speech
Use of accessory muscles
Pulsus paradoxus
Cyanosis
Confusion, loss of consciousness
Clincal signs and severity of asthma
Pulsus paradoxus
Differential Diagnosis
1. Upper airway obstruction by tumor or laryngeal edema stridor, harsh respiratory sounds localized to tracheal area absent of diffuse wheezing throughout both lung fields indirect laryngoscopy or bronchoscopy2. Glottic dysfunction narrow glottis during inspiration and expiration occasional PaCO2 retention but preserved PaO2
3. Endobronchial disease(tumor, bronchial stenosis, foreign body) persistent localized wheezing 4. Acute left ventricular failure5. Chronic bronchitis no true symptom-free periods, chronic cough,sputum 6. Recurrent pulmonary emboli lung scan, pulmonary angiography7. Carcinoid tumor8. Eosinophilic pneumonias9. Systemic vasculitis
Diagnosis
History : personal or family history of allergic diseases (eczema, rhinitis, urticaria), occupation, contact with animals
Reversible airway obstruction
≥ 15% in FEV1 following beta-adrenergic agonist
Provocation test (methacholine, histamine, cold air) ≥ 20% in FEV1
Skin tests Sputum and blood eosinophiliaSerum IgE levelsChest X-ray : hyperinflation
Questions to an asthma patient1. Do any of your patents, siblings or children have childhood eczema, asthma or h
ay fever?2. Have you ever had eczema or hay fever?3. Do you smoke/have you smoked?4. What is your occupation?5. Are you in contact with animals?6. Can you tolerate acetylsalicylic acid?7. How old were you when the disease strarted?8. Did the disease first strart with :episodes of wheezing(asthma) daily productive
cough(bronchitis), breathlessness on effort(emphysema)?9. Is there any difference between asthma : indoors/outdoors, at home/at pla
ce of work, in spring/summer/autumn/winter?10. What factors start or worsen your asthma?11. Are you ever completely free from chest symptoms?12. Have you ever been treated with steroid tablets for asthma?13. How often do you use your bronchodilator spray?14. How many days/times per month: do you have asthma symptoms? Do you wake
with asthma? Do you stay home from school/work?
Atopic dermatitis : Eczema
Keratoconjunctivits
Papillary hypertrophy in upper tarsal conjunctiva
Atopic kerato-conjunctivitis
Thickened lid margins
Eczematous skin
Allergic rhinitis
Diagnosis
History : personal or family history of allergic diseases eczema, rhinitis, urticaria, atopy
Reversible airway obstruction
≥ 15% in FEV1 following beta-adrenergic agonist
Provocation test (methacholine, histamine, cold air) ≥ 20% in FEV1
Skin tests Sputum and blood eosinophiliaSerum IgE levelsChest X-ray : hyperinflation
Reduced PEF
PEF varies ≥ 20%PEF varies ≥ 20%
Normal lung functionreduced lung function
PEF falls ≥ 20%PEF increases ≥ 20%
Dyspnea, cough
PEF increases ≥ 15%
Normal PEF
The diagnosis is
Asthma
Beta 2 inhaler
Diary with PEF for 14days
No
Corticosteroid in 14days
Diary with PEF for 14days
No
Bronchoprovocation
Not asthma
No No
NoNo
Yes
Yes Yes
Yes Yes
Diagnosis
History : personal or family history of allergic diseases eczema, rhinitis, urticaria, atopy
Reversible airway obstruction
≥ 15% in FEV1 following beta-adrenergic agonist
Provocation test (methacholine, histamine, cold air) ≥ 20% in FEV1
Skin tests Sputum and blood eosinophiliaSerum IgE levelsChest X-ray : hyperinflation
Treatment
1. Elimination of the causative agents from the environment of an allergic ast
hmatics
2. Desensitization or immunotherapy with extracts of the suspected allergen
s
3. Drug treatment
⑴ Adrenergic stimulants (epinephrine, beta2 agonist)
⑵ Methylxanthines (theophylline)
⑶ Anticholinergics (ipratropium bromide)
⑷ Glucocorticoids
⑸ Mast cell-stabilizing agents (cromolyn sodium, nedocromil)
⑹ Leukotriene antagonist
Prognosis and clinical course
Mortality rate from asthma is small.
Good prognosis for 50-80% of all patients, particularly whose disease is mild and
develops in childhood.
26-78% still have asthma 7-10 years after initial Diagnosis.
6-19% continue to have severe disease
20% spontaneous remission
Asthma is not progressive unlike other airway diseases such as chronic bronchitis.
Asthma developing irreversible changes in lung function : comorbid stimuli such as
cigarette smoking