ASTHMA

Dr Mayank kumar Mishra

 ASTHMA
• Asthma is a syndrome characterized by airflow obstruction
that varies markedly, both spontaneously and with treatment.

• Recurrent airflow obstruction caused by chronic airway

inflammation with a superimposed bronchospasm

• Leads to… wheezing, breathlessness and cough

• Chronic inflammation is associated with airway episodes

of wheezing, breathlessness, chest tightness, and
coughing
 SOME FACTS AND FIGURES
• Asthma is one of the most common chronic diseases globally
and currently affects approximately 300 million people
worldwide.

• In US prevalence increased from 7.3% in 2001 to 8.4% in 2010,

when 25.7 million persons had asthma.

• Over 2 million Australians have asthma – about 1 in 10 adults

and about 1 in 9 or 10 children

• Asthma morbidity and mortality is increasing

• According to the latest WHO data published in
April 2011 Asthma Deaths in Nepal reached
1,704 or 1.15% of total deaths.
 Why Is the Death Rate Increasing?
• Multifactorial
– Asthma is increasing
– Asthma is more severe
– Poor management of the disease
– Poor patient compliance
– Inadequate patient and provider response to signs
of worsening symptoms
 Facts:
• Asthma symptoms can begin at any age
• Most often misdiagnosed or
underdiagnosed in the elderly
– Fail to report symptoms because it is
thought to be normal
– Attribute the symptoms to comorbid
diseases
 Pathophysiology of Asthma
• Genetic predisposition
– Chromosome: 5Q31-Q33
• Results from repeated exposure to allergens in
the individual already equipped with the
genetic predisposition
• Upon exposure to an allergen, there is a
release of IgE antibodies
• IgE antibody binds with the antigen
• IgE/allergen complex - then attaches itself
to the mast cells on the nasal and
bronchial mucosa

• Release of numerous chemical mediators

Asthma Inflammation: Cells and Mediators
 Components of Asthma
Asthma Triggers

Allergens Exercise Irritants Viruses Weather

Smooth Muscle
Inflammation
Dysfunction

Mucus
Hypertrophy Secretion Edema
Hyperplasia
Architectural Impaired
Inflammatory Epithelial
Changes Ciliary
Mediator Release Damage
Function

Bronchial Constriction Bronchial Hyperreactivity Inflammatory Cell Infiltration

Symptoms
Exacerbations
Adapted from Creticos. Adv Stud Med. 2002;2(14):499-
 Consequences of Inflammation in Asthma
Stimulus
(Antigen, virus, pollutant, occupational agent)

Altered airway physiology Acute

↑Airflow obstruction Inflammation

Resolution

↑Airway Chronic Inflammation

dysfunction
Injury Repair

“Permanently” altered Remodeling

lung function (fixed changes in the
structure of airway)
 Risk factor and triggers involved in ASTHMA
Endogenous Factors Environmental Factors
Genetic predisposition Indoor allergens
Atopy Outdoor allergens
Airway hyperresponsiveness Occupational sensitizers
Passive smoking
Respiratory infections

TRIGGERS
Allergens
Upper respiratory tract viral infections
Exercise and hyperventilation
Cold air
Sulfur dioxide and irritant gases
Drugs (B-blockers, aspirin)
Stress
Irritants (household sprays, paint fumes)
 Diagnosis of Asthma
• History and Physical Examination
• Spirometry is needed to make diagnosis
• Measurements of allergic status to identify risk
factors
• Measurement of airway responsiveness
• Monitoring:
– Peak Flow Meters
 Symptoms and Signs of Asthma in Children and
Adults
• Coughing, particularly at night or after exercise
• Wheezing
• Chest tightness
• SOB
 Asthma Findings
• Simple spirometry confirms airflow limitation with a
reduced FEV1, FEV1/FVC ratio, and PEF
• Reversibility is demonstrated by a >12% and 200-mL
increase in FEV1 15 minutes after an inhaled short-
acting B2-agonist.

• Increased airway responsiveness to challenges with

histamine, methacoline or isocapnic hyperventillation
of cold air.
• Total serum IgE and specific IgE to inhaled allergens [radio
allergo sorbent test (RAST)] may be measured in some patients

• Skin prick tests to common inhalant allergens are positive in

allergic asthma and negative in intrinsic asthma, but are not
helpful in diagnosis.

• Exhaled NO is now being used as a noninvasive test to measure

eosinophilic airway inflammation. The typically elevated levels
in asthma are reduced by ICS, so this may be a test of
compliance with therapy
Asthma
ASTHMA MANAGEMENT
 Aims of Asthma Therapy

• Minimal (ideally no) chronic symptoms, including

nocturnal
• Minimal (infrequent) exacerbations
• No emergency visits
• Minimal (ideally no) use of a required B2-agonist

• No limitations on activities, including exercise

• Peak expiratory flow circadian variation <20%
• (Near) normal PEF
• Minimal (or no) adverse effects from medicine
 6 components of ASTHMA Mx:

1. Assess the severity of the asthma

2. Achieve best lung function
3. Maintain best lung function
4. Avoid trigger factors
5. Develop an individualized, written action plan
6. Educate and review regularly
 Environmental Control:
A useful but often ignored step
• Dust Mite Avoidance
• Pollen Avoidance
• Animal Avoidance
• Avoidance of Non-allergic Triggers
– Strong emotions
– Smoke: No smoking in house or car
– Pollution
– Cold air
– Odors
– Exercise
 Classification:
Mild Intermittent Asthma
• Symptoms < 2 days/week
• Symptoms < 2 nights/month
• PEF or FEV1 > 80%
• PEF variability < 20%
• No daily medication needed
• PRN beta agonists
• Course of systemic steroids for exacerbations
 Mild Persistent Asthma
• Symptoms > 2 days/wk but < 1x/day
• > 2 nights/month
• PEF or FEV1 > 80%
• PEF variability 20-30%
• Preferred treatment low dose inhaled
corticosteroids
• Alternatives include cromolyn, leukotriene
modifiers, or sustained release theophylline
 Moderate Persistent Asthma
• Symptoms daily
• > 1 night/week
• PEF or FEV1 > 60% and < 80%
• PEF variability > 30%
• Preferred treatment is low to medium dose inhaled
corticosteroid and a long acting inhaled beta 2
agonist
• Alternative includes increasing ICS within moderate
dose range, or low to medium dose ICS with either
leukotriene modifier or theophylline
 Severe Persistent Asthma
• Continual symptoms
• Frequent nocturnal attacks
• PEF or FEV1 < 60%
• PEF variability > 30%
• Preferred treatment is high dose inhaled
corticosteroid and long acting beta 2 agonists
• If needed, can add systemic corticosteroids
 Step Approach to Therapy
• If control is not achieved with therapy, step up
the therapy
• Once control is sustained for a minimum of 3
months, can consider stepping down the
therapy
• Regardless, therapy should be reviewed q 6
months
 Reasons for Poor Asthma Control
• Inhaler Technique
• Compliance
• Environment
• Also assess for an alternative diagnosis
• “All that wheezes is not asthma, and not all
asthma wheezes”
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 Factors Affecting Compliance
• Support of health care professional and family
• Route of drug administration (inhaled vs. oral)
• Complexity of drug regimens
• Side effects of medications
• $$ Cost $$
PHARMACOLOGICAL AGENTS TO
TREAT ASTHMA

• Reliever - bronchodilators
• Preventer - anti-inflammatory
 Beta 2 Agonists
• Most potent and rapidly acting bronchodilators
currently available for clinical use
• Given in different forms:
– short acting = Isoproterenol, Albuterol, Salbutamol,
Metaproterenol, Levalbuterol, Terbutaline.
• Salbutamol MDI 100mcg/puff 2puff TID
– long acting = Salmeterol, Formeterol
 MDI with Spacer vs. Nebulizer
• Equivalent bronchodilation can be achieved by
giving beta 2 agonist with a spacer/holding
chamber or by nebulizer therapy
• Continuous administration with a nebulizer
may be more effective in severely obstructed
adults and in those who have difficulty with an
MDI plus spacer
 Methylxanthines
• Theophylline
– Bronchodilates and increases the force with which
the diaphragm contracts
– 6 years and older
– Indicated for individuals with moderate to severe
asthma
– Numerous drug interactions and side effects

Dose: Starting 10 mg/Kg Maxm 800mg/day

 Theophylline
• Theophylline levels (normal 6-15mcg/dL)
– 15-25: GI upset, N/V, diarrhea, abdominal
pain
– 25-35: Tachycardia, occasional PVC’s
– >35: Ventricular tachycardia, seizures
 Anticholinergics

• Muscarinic receptor antagonists such as

ipratropium bromide(17 mcg/puff 2-3 puff 6
hrly), prevent cholinergic nerve-induced
bronchoconstriction and mucus secretion
• much less effective than B2-agonists in asthma
therapy
• only used as an additional bronchodilator in
patients with asthma that is not controlled by
other inhaled medications
 Glucocorticoids
• Most potent anti-inflammatory agents available
for the treatment of asthma
• ICS are by far the most effective CONTROLLERS
for asthma
• More effective than beta agonists, theophylline,
and cromolyn sodium in reducing airway hyper
responsiveness during maintenance therapy
 Inhaled Corticosteroids
• Examples
– Beclomethasone 40/80 mcg/puff
– Budesonide 90/180/200 mcg/puff
– Flunisolide 80mcg/puff
– Fluticasone 44/110/220 mcg/puff
– Mometasone 200mcg/puff
 Inhaled Corticosteroids
• Side effects
– Pharyngitis
– Dysphonia
– Oral Candidiasis
• Precautions
– High dosages: Increased systemic
absorption leading to HPA axis suppression
– Not indicated for an acute exacerbation
 To Reduce Side Effects of Inhaled
Corticosteroids
• Administer with spacers or holding chambers
• Rinse mouth after inhalation
• Use lowest possible dose to maintain control
• Children - monitor growth
 Steroids and Long Acting Beta2 Agonists

• Results in greater improvements in lung

function and symptom control than
monotherapy with escalating doses of inhaled
glucocorticoid
• Act synergistically to activate transcription
factors, decrease smooth muscle proliferation,
and impair eosinophil adhesion
 Mast Cell Stabilizers
• Cromolyn Sodium( MDI 0.8 mg/puff)
• Indications
– Asthma prophylaxis
– Prevention of bronchoconstriction before exposure
to suspected allergen
• Best for mild-moderate disease
• May be the initial choice for children
Mast Cell Stabilizers:
• Mechanism of Action
– Reduces the production of histamine and
prevents the release from the mast cell
• MDI or Nebulizer Solution
– MDI: > 5 years: 2 puffs po qid
– Nebulizer Solution: >2 years: 1 ampule qid
– Begin to work within 15 minutes of
inhalation but can take up to 2 weeks to
become effective
• Nedocromil Sodium
– for mild - moderate disease
– MDI: >6 years: 2 sprays qid (1.75mg/puff)
– Nebulizer: >2 years
• 0.5% solution; 1 ampule qid
 Leukotriene Receptor Antagonists
• Zafirlukast
– 10mg bid for ages 5-11
– 20mg bid for 12 and older
– Avoid food 1 hour before and 2 hours after taking:
Food decreases the bioavailability

• Montelukast
– 4 mg Granules once daily: 12 – 23 months
– 4 mg tablet for children 2 - 5 years of age
– 5mg od for ages 6-14
– 10mg od for ages 15 and older
Long Acting Inhaled Beta 2 Agonist
• Salmeterol (DPI 50mcg/actuation)
• >4 years of age-1 puff q 12 hours
– No role for acute exacerbations
– help children affected by the nocturnal
cough and wheezing
– Good for prevention of exercise induced
asthma

Formeterol: 12mcg/actuation
 OMALIZUMAB (Inj. 150mg/1.2ml ,s/c 2 weekly)
• Recombinant DNA-derived humanized IgG1
monoclonal antibody that selectively binds to
human immunoglobulin E (IgE).
• Inhibits the binding of IgE to the high-affinity
IgE receptor on the surface of mast cells and
basophils
• Limits the degree of release of mediators of
the allergic response.
 Omalizumab
• Indicated for adults and adolescents (12 years
and >) with moderate to severe persistent
asthma who have a positive skin test or in vitro
reactivity to aeroallergen
• And…whose symptoms are inadequately
controlled with inhaled corticosteroids
• SQ injection every 2 to 4 weeks
• Dose determined by levels of serum IgE
 6 step Asthma Mx
Step 1: Step 4:
SABA Medium dose- ICS+ LABA

Step 2: Step 5:
low dose- ICS High dose- ICS +LABA
+ Omalizumab (for allergics)

Step 3: step 6:
low dose- ICS + LABA High dose- ICS + LABA + oral corticosteroid
or + Omalizumab (for allergics)
medium dose- ICS

48
ACUTE ASTHMA EXACERBATION
SEVERE ATTACK:
• Unable to complete sentence
• RR > 25/min
• PR > 110 bpm
• PEF < 50% of predicted
LIFE THREATENING ATTACK:
• Silent chest, cyanosis, feeble respiratory effort
• Bradycardia or hypotension
• Exhaustion, confusion or coma
• PEF < 30% of predicted
• ABG: ↓ pH, PaCO2 > 36mmHg, PaO2 < 60mmHg
 Treatment: Acute Severe Asthma
• oxygen - SPO2of >90%.
• SABAs given by nebulizer
• inhaled anticholinergic may be added if not satisfactory response
to β2-agonists alone
• Systemic corticosteroids
• If refractory to inhaled therapies, a slow infusion of aminophylline
may be effective.
• Magnesium sulphate given intravenously or by nebulizer has also
been shown to be effective
• with respiratory failure, intubate and institute ventilation –
anesthesia- halothane