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Title: Asthma%20for%20a%20better%20controle


1
Asthma For a better control
Dr Hatem Al Mubarak, MD, FRCPC, FACCP Pulmonary
Specialist Al Jazira and Central Hospital Abu
Dhabi, UAE
2
Asthma for a better control
  • Definition
  • Epidemiology of asthma
  • Pathophysiology and asthma evolution
  • Diagnosis of asthma
  • Asthma classification
  • Treatment of asthma
  • Clinical Scenarios and discussion

3
Definition
  • A chronic inflammatory disorder of the airways
    in which many cells play a role that causes
    recurrent episodes of wheezing, breathlessness,
    chest tightness and cough ic but variable airflow
    limitation that is at least partly reversible
    either spontaneously or with treatment. The
    inflammation also causes. These symptoms
    associates with widespread and associated
    increase in airway responsiveness to variety of
    stimuli.

4
Venn diagram of obstructive lung disease
Chronic Bronchitis
Emphysema
Airflow limitation
Asthma
5
Epidemiology and Risk Factors
  • For all age group incidence 2.65-4/1000 per
    year.
  • Children 4.3-18/1000 per year
  • Adult 2.1/1000 per year
  • Mortality (1985-1987) between 1.3-9.3 /100,000 of
    total population
  • Danish follow-up study showed cigarette smoking,
    age, presence of blood eosinophilia, impairment
    of lung function and degree of reversibility
    contribute to asthma mortality

6
Age and Sex Distribution of Asthma
16 14 12 10 8 6 4 2 0
Individuals per 1000
0 10 20 30 40 50 60 70 80
Female
Male
7
Prevalence of self-reported asthma, children aged
13-14 years
12 months prevalence of self-reported asthma with
a written questionnaire, for children aged 13-14
years . International Study of Asthma and
Allergies in Childhood (ISAAC) including 463,801
children in 56 countries
8
Asthma Evolution Hypothesis
Genetic Predis- position

Airway Inflammation
Hyper- responsiveness
Sensitisation

Asthma
Environmental Factors Maternal Smoking Indoor/outd
oor Allergens
Environmental Factors Smoking, cold
air Indoor/outdoor Allergens, viral infection
9
Asthma Evolution Hypothesis
Genetic Predis- position
Asthma
10
The Genetic of Asthma
  • 20-25 Increase in prevalence of asthma among
    first degree relative of asthmatics compare to
    general population (4)
  • Monozygotic twins (50) dizygotic twins (33)
  • Doesnt follow any medelian pattern
  • Genetic researches provided evidence of several
    atopic phenotypes (eosinophil count, skin
    testing, atopic cytokines)

11
Asthma Evolution Hypothesis
Genetic Predis- position

Asthma
Environmental Factors Maternal Smoking Indoor/outd
oor Allergens
12
Risk factors for development of asthma
Factors that contribute to asthma Factors that contribute to asthma Factors that contribute to asthma
Inherent factors Causal factors Contributing factors
Atopy Gender Hyperresponsiveness Genetic abnormalities Smoking Respiratory Infection Small birth weight Diet Air pollution Lung function Indoor allergens Outdoor allergens Occupational sensitizer
13
Atopy
  • Atopy is characterized by
  • Elevated IgE level
  • Detection of IgE against common allergens
  • Positive skin test against common allergen
  • Asthmatic are more atopic than non-asthmatic
  • Increase airway hyperresponsiveness is associated
    with increase in atopy

14
Atopy in asthma
  • House dust mite is the most common allergens
  • Increases in prevalence of asthma in New Guinea
    when adult exposed to house dust mite.
  • Association between the level of house dust mite
    in the bed room of babies during the first year
    of life and asthma in at 8 years of age.
  • Cats more than any other animals is a risk for
    asthma
  • Children expose to furry cat are at twice the
    risk for developing asthma
  • Other allergens including grass, tree pollen, and
    cockroaches

15
Asthma risk factors
  • Exercise occur because of water loss from the
    airway wall
  • Occupation e.g. wood dust, formaldehyde, latex,
    animal allergens
  • Drugs NSAID, possible biphosphonate, ß-blocker
  • Premenstrual asthma associated with late luteal
    phase

16
Smoking and asthma risk
  • Passive smoking
  • It the second major risk after atopy
  • Parental ,especially maternal, smoking is
    associated with increase risk of asthma in
    children
  • Smoking gt10cig/day increase asthma by 2.5 times
    at 12 years of age
  • Increase four-fold of the level of IgE from cord
    blood of newborn of mothers who smoke (even in
    absence of atopy)

17
Asthma evolution hypothesis
Acute Inflammation
Mediators
Symptoms
Allergen Viruses Pollution Diet
Susceptable Gene
Growth Factors
Cytokines
Tissue Remodeling
Th2 immune deviation
Chronic Inflammation
Early Environment
Cytokines
Cytokines
18
Asthma Evolution Hypothesis
Genetic Predis- position

Sensitisation
Asthma
Environmental Factors Maternal Smoking Indoor/outd
oor Allergens
19
Th1 and Th2 Balance
Bacterial Infection TB, Measles, HepA Rural
Environment
Widespread use of antibiotics Western
lifestyle Diet Sensitisation to
allergens Parasitic infection
Th1
Th2
Th0
Allergic disease
Protective immunity
20
Asthma Evolution Hypothesis
Genetic Predis- position

Airway Inflammation
Sensitisation
Asthma
Environmental Factors Maternal Smoking Indoor/outd
oor Allergens
21
Mast cell
Smooth Muscle
PGD2, LTC4/D4
Histamine, Tryptase
Eosinophils
Cytokines
Mast cell
Acute Asthma
B-cell
Chronic Asthma
APS
TH2
22
Asthma Evolution Hypothesis
Genetic Predis- position

Airway Inflammation
Hyper- responsiveness
Sensitisation

Asthma
Environmental Factors Maternal Smoking Indoor/outd
oor Allergens
Environmental Factors Smoking, cold
air Indoor/outdoor Allergens, viral infection
23
Diagnosis of Asthma
24
Case 1
  • 22 years old lady came to your office with cough
    for several weeks with no associated sputum. She
    deny any other symptoms but remember she use to
    have similar symptoms when she was young. She
    also noticed that she get tired slighter sooner
    that her class mate in sports event.
  • Examination was normal and her PEF was normal
  • Does this patient have asthma?

25
Diagnosis of asthma
Wheeze
Chest tightness
Asthma
Cough
Nocturnal symptoms
Difficulty In breathing
26
Canadian Asthma Consensus Diagnosis and
Evaluation of Asthma in Adult
  • Spirometry improvement of FEV1 by
  • 12 and 200ml from the base line after inhalation
    of short acting ß2 agonist
  • 20 and 250ml after 10-14 days on inhaled or
    systemic glucocorticosteroid
  • 20 and 250 ml with spontaneous variability
  • Peak Expiratory Flow
  • 20 or more variability between highest and
    lowest values ( morning and afternoon, before and
    after bronchodilator)

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Spirometry in asthma
Normal FVC Normal FEV1 Normal Ratio
Normal or mild low FVC low FEV1 low Ratio
Normal Asthma
30
Canadian Asthma Consensus Diagnosis and
Evaluation of Asthma in Adult
  • Airway Hyperresponsiveness
  • Methacholine neubelizer provocation test to
    evaluate the airway response
  • Positive test is there is a drop of more than 20
    of FEV1 in a methacholine concentration of less
    than 8mg/ml
  • Negative methacholine can exclude asthma

31
Methacholine Provocation Test
FEV1 Base line
PC20
20 Drop
FEV1
Normal Saline 0.25mg/ml 0.5 mg/ml
1mg/ml 2mg/ml 4mg/ml 8mg/ml
Methacholine Concentration
32
Asthma Evolution
Primary Prevention
Secondary Prevention
Secondary Prevention
Secondary Prevention
Genetic Predis- position
Regular Anti-inflammatory treatment
Avoidance
Treatment of exacerbation

Airway Inflammation
Hyper- responsiveness
Sensitisation

Asthma
Environmental Factors Maternal Smoking Indoor/outd
oor Allergens
Environmental Factors Smoking, cold
air Indoor/outdoor Allergens, viral infection
33
Current therapy for asthma
Relievers (bronchodilators) Controllers (anti-inflammatory)
ß2-Agonist Corticosteroids
Theophylline Cromones
Anticholinergics Antileukotrienes
Steroid-sparing agents -Methotrexate -Gold -Cyclosporin A
34
ß2 agonist
  • ß2 receptors are present in all smooth muscles of
    the airways
  • Direct effect causing
  • Smooth muscle relaxation
  • Reduction in neurotransmitter
  • Increase ciliary clearance
  • Decrease the microvascular leak?decrease edema
  • Salbutamol, terbutaline,fenoterole, metaprotanole
  • Does not have anti inflammatory effect
  • Drug of choice in both children and adult for the
    relief of acute asthma symptoms

35
ß2 agonist
  • Side effects
  • Mild tremor (affect on skeletal muscle receptors)
  • Tachycardia( affect on cardiovascular)
  • Hypokalemia ( increase K entry to skeletal
    muscle)
  • No evidence that it increase or induce serious
    arrhythmias or other cardiac abnormalities

36
ß2 agonist
  • No evidence that regular four times a day with
    SAß2 is better than as needed approach in any
    degree of asthma severity
  • Regular SAß2 is associated with masking
    underlying inflammation ? increase
    hyperresponsiveness ?worsening severity

37
Long acting ß2
  • It have more sustained action
  • It enhance the effect of inhaled steroids
  • Salmeterol and formoterol
  • Not recommended for relief of acute symptoms and
    exacerbation
  • Does not increase airway hyperresponsiveness and
    it have some anti-inflammatory effect

38
Theophylline
  • Phosphodiestterase inhibitors? increase in cAMP?
    bronchodilators
  • Adenosine receptors antagonist? CNS stimulation,
    cardiac arrhythmias,diuresis
  • Stimulation of adrenaline release
  • Less effective than ß2 agonist in acute
    exacerbation and it is more recommended in
    chronic asthma (especially if nocturnal symptoms
    present)

39
Anticholiergics
  • Muscarinic receptors antagonist and inhibit
    cholinergic receptors that cause
    bronchoconstrection
  • Less effective than ß2 but it has additative
    effect
  • Are more effective in acute than chronic asthma
  • More effective in asthmatic who have element of
    fixed airway
  • Ipratropium, oxitropium and tiotropium bromide

40
Affect of anticholinergic on smooth muscle
Vagus Nerve
Anticholinergic
Acetylcholine
41
Cromones
  • It may affect chloride channels that expressed in
    mast, nerve and some inflammatory cells
  • Inhibit mediators release from mast cells by
    membrane stabilization
  • Effect on sensory nerve ending in the airways
  • Prophylactic treatment and should be given
    regularly
  • Preferred agent in children

42
Antileukotrienes
  • LTC4,LTE4 and LTD4 are products of inflammatory
    cells that cause bronchoconstrition
  • 40 times more potent that histamine or
    methacholine to cause bronchoconstriction
  • Blocking leukotriens receptors cause
    bronchodilatation and decrease eosinophils
  • Zafirlukast, pranlukast and montelukast
  • Reduce allergen-exercise-cold induced asthma by
    50-70
  • Complete response in aspirin-induced asthma

43
Corticosteroids
  • Action occur through activation of
    glucocoticosteroid receptors (GCSr) which found
    in all body cells
  • When bound to receptors it decreases gene
    production for many pro and inflammatory
    cytokines
  • Systemic (parental/oral) or inhaled are the two
    major form

44
Systemic corticosteroids
  • Reserved for moderate to sever cases
  • Oral bio availability is very high with complete
    GI absorption.
  • Parental route reserved if oral rout cant be
    tolerated

45
Inhaled corticosteroid
  • They are as effective as low to moderate dose of
    systemic steroids with much lesser side effects
  • Lipophilic very high binding affinity and fast
    first pass liver metabolism
  • five inhaled corticosteroids (ICS) currently
    available
  • Fluticasone propionate (Flexotide, Flovent)
  • Beclomethasone 17,21-dipropionate ( Beclovent,
    QVAR)
  • Triamcinolone (Azmacort)
  • Flunisolide (AeroBid)
  • Budesonide (Pulmicort)

46
Corticosteroids side effects
  • Local side effect
  • oral candidiasis occur in 10
  • Increase risk with poor technique,concomitant use
    of antibiotics and reduce by use of spacer and
    rinsing mouth.
  • Dysphonia (30) in people who use their voice a
    lot
  • Doesn't have any effect on airway mucosa

47
ICS side effects
  • Hypothalamic-pituitary-adrenal axis
  • No effect was seen with doses of BDPlt1500?g/day
    or budesonide lt1600 ?g/day
  • Only 2 cases reported with adrenal insufficiency
    ( very high dose of budesonide of 6400 ?g/day)

48
ICS side effects
  • Osteoporosis
  • ICS shown to have some effect on osteocalcin
    (bone formation) and hydroxyproline (bone
    resorption) in doses of budesonidegt2000 ?g/day
  • Bone densitometry carried out in adult asthmatic
    on various doses of ICS and it showed no increase
    bone loss
  • Does not cause growth retardation in children
  • Children on ICS were shorter on average than
    children not on ICS at 2 years of age, but all of
    them had the same height at 6 years of age

49
ICS side effects
  • Posterior subcapsular cataract
  • Usually there is no risk
  • Risk slightly increase with high doses of ICS and
    use of MDI
  • Risk of lung infection
  • Risk of lung infection is not increased
  • Does not increase the risk of TB re-activation
  • Risk of skin bruising increase with height doses
    of ICS ( from 22 to 47) in older population

50
Delivery of medication
51
Case 2
  • 64 years old gentleman who was known to have
    asthma for several years on inhaled
    corticosteroids ( MDI) .
  • You are seeing him for the first time, his
    history and exam revealed moderate persistent
    asthma not will controlled because he claim he
    cant use the apparatus. Throat exam showed oral
    condidiasis and chest exam .

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Pressurized metered-dose inhaler
  • Pressurized in a crystal suspension in liquid
    mixture of chloroflucarbones(CFC)
  • The mixture boil off rabidly as soon as they
    leave the container with velocity of 30m/sec
  • Newer form ban the CFC and use non-CFC solution
  • Laryngeal deposition is 25 with some MDI

55
Laryngeal deposit with MDI
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Dry-powder inhaler
  • Depends on patient inspiratory effort
  • DPI
  • Spinhalers
  • Rotahaler
  • Diskhalers
  • Reservoir dry-powder inhalers

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Neubelizers
  • Two type of neubelizer Jet and ultrasonic
  • Ultrasonic use sound wave vibration through
    liquid to form fountain of droplets
  • Jet neubelizer result from steam of compressed
    air or oxygen that push liquid drug through small
    capillaries to become like steam
  • Usually 50 of neubelized solution is left in
    apparatus and cant be utilized

61
Deposition
Loss in air
Apparatus
GI
Lung
MDI DPI Nebulizer
62
Chronic asthma
63
Case 3
  • 29 years old male was diagnosed to have asthma
    for several years that was controlled in
    budesonide 200mcg bid with MDI. In the last week
    he noticed that he is having more cough and
    occasionally awaking up in the middle of the
    night with cough. After assessing possible
    excerbating factors what will be your next step?

64
Chronic asthma
Classification of asthma severity Classification of asthma severity Classification of asthma severity Classification of asthma severity Classification of asthma severity
step Days with symptoms Night with symptoms FEV1 or PEF PEF variability
Mild intermittent ? 2/wk ? 2/month ? 80 lt20
Mild persistent 3-6/wk 3-4/months ? 80 20-30
Moderate persistent Daily ? 5/months gt60lt80 gt30
Sever persistent Continual Frequent ?60 gt30
65
Treatment Goals
  • Achieve and maintain control of symptoms
  • Minimize frequency of asthma attacks
  • Prevent emergency visits to doctors or ER
  • Achieve and maintain normal activity level
  • Optimise asthma therapy with minimum side effects
  • Minimize the need of ß2 agonist
  • Step down use of ICS

66
Mild intermittent Asthma
If symptomsgt2/week, nocturnal gt2/month Go to next
step ?
Moderate Persistent
Rescue medication with Short ß2 agonist
Sever Persistent
Mild Persistent
67
Mild persistent asthma
If symptomsgt6/week, nocturnal gt4/month Go to next
step ?
Short ß2 agonist is needed Inhaled
corticosteroid Beclomethasone or budesonide
200-800?g Or fluticasone 100-400 ?g Or Sodium
cromolyn
Moderate Persistent
Sever Persistent
Mild intermittent
68
Moderate persistent asthma
If symptoms continual, nocturnal daily Go to next
step ?
Short ß2 agonist is needed double Inhaled
corticosteroid Beclomethasone or budesonide
800-2000?g Or fluticasone 400-1000 ?g Or Inhaled
corticosteroids with long acting ß2 agonist
Sever Persistent
Mild Persistent
Mild intermittent
69
Sever persistent asthma
Short ß2 agonist is needed double Inhaled
corticosteroid Beclomethasone or budesonide
800-2000?g Or fluticasone 400-1000 ?g Or Inhaled
corticosteroids with long acting ß2 agonist
With Theophylline or antileukutriens or high
dose Anticholinergic If worse symptoms Systemic
steroid
Moderate Persistent
Mild Persistent
Mild intermittent
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Acute Asthma
79
Case 4
  • 33 years old male presented to emergency with 3
    days of progressive dyspnea. He could not sleep
    the night before because of cough and
    breathlessness. He is known to have asthma but he
    is not taking regular treatment. He smoke a pack
    aday. He deny fever, chest pain or previous
    history of heart disease
  • Exam showed patient in moderate distress,
    BP130/90, pulse 120/min, O2 90
  • Chest exam showed decrease air entry at right
    with wheeze bilaterally
  • What is your management?

80
Clinical Features of Acute Asthma
  • History of exacerbating factors ( infection,
    allergens)
  • History of previous symptoms could be absent but
    mostly with history of uncontrolled asthma.
    Dyspnoea, orthopnea and PND could be present
  • Presence of chest pain could indicate asthma
    complication ( pneumothorax, collapse ,CAD or
    pneumomediastinum)
  • History of previous ICU or intubations considered
    high risk

81
Severity of asthma exacerbation
Symptoms Mild Moderate Sever Respiratory arrest
Dyspnea Walking Can lie down Talking Prefers sitting At rest Hunched forward
Talks in Sentences Phrases Words
Alertness May be agitated Agitated Agitated Drowsy or confuse
RR Increase Increase gt30
Accessory Muscles Not Usually Usually Paradoxical
Wheeze Moderate at end of expiration Loud Loud Absent
Pulse lt100 100-120 gt120 Bradycardia
PEF gt80 60-80 lt60
PO2 PCO2 Normal lt45 gt60 lt45 lt60 gt45
O2 sat gt95 91-95 lt90
82
Hospital management in acute asthma
Assess severity,ß2 agonist,O2, systemic steroids
Repeat assessment
Life threatening asthma
improvement
Partial or no improvement
Continue treatment
admit
Response maintain
improvement
worsening
ICU
discharge
83
Case 5
  • 26 years old lady 12 weeks pregnant came to you
    regarding her asthma treatment. She have mild
    persistent asthma taking fluticason 250mcg bid
  • She is worry about her baby as she was told that
    steroids is not good during pregnancy.
  • What will be your advice

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