Asthma

Dr. Imran Masood, PhD

drimranmasood@iub.edu.pk
Asthma
Definition:
Asthma means “laboured breathing”. It is a broad term used to
refer to a disorder of the respiratory system that leads to
episodic difficulty in breathing.
Definition
 The national UK guidelines (BTS/SIGN,2009) define
asthma as a “chronic inflammatory disorder of the airways
which occur in susceptible individuals; inflammatory
symptoms are usually associated with widespread but variable
airflow obstruction and an increase in airway response to a
variety of stimuli.
Events:
The events of asthma are:
 Airway obstruction(reversible)

 Hyper-responsiveness.
Symptoms:

 Difficult breathing
 Wheezing
 Chest tightness
 Coughing
Asthma triggers
Examples of triggers are:
 Allergens: Pollens, moulds, house dust mite,

animals (dander, saliva and urine)

 Industrial chemicals: paints, hair sprays, penicillin's

 Drugs : Aspirin, ibuprofen and other prostaglandin synthetase

inhibitors(aspirin, ibuprofen, NSAIDs),β-adrenoceptor blockers(Atenolol)

Asthma triggers
 Foods: A rare cause but examples include nuts, fish, seafood, dairy
products, food colors, especially tartrazine, benzoic acid and sodium
metabisulfite
 Environmental pollutants: Traffic fumes. cigarette smoke
 Other industrial triggers: Wood or grain dust, cotton, dust, grain weevils
and mites
 Miscellaneous: Cold air, exercise, hyperventilation, viral respiratory tract
infections, emotion or stress,
Aetiology:

The two main causes of asthma symptoms are:

1. Airway hyper-responsiveness:
It is an increased tendency of the airway to react to stimuli or triggers to cause
an asthma attack.
2. Bronchoconstriction:
It is a narrowing of the airways that causes airflow obstruction.
Pathophysiology of asthma
Types of asthma:
Asthma can be classified according to the underlying pattern of airway
inflammation with the presence or absence of eosinophils in the airways.
It includes
 Extrinsic asthma when an allergen is thought to be the cause of their

asthma. More common in children where triggers, such as dust mite, cause
IgE production.
 Intrinsic asthma develops in adulthood, with symptoms triggered by non-

allergenic factors such as a viral infection, irritants which cause epithelial

damage and mucosal inflammation, emotional upset which mediates
excess parasympathetic input or exercise which causes water and heat loss
from the airways, triggering mediator release from mast cells.
Airway inflammation
Mast cell components
 Immediate reaction includes
 Mast cell components are released as a result of an IgE antibody-mediated
reaction on the surface of mast cell.
 Histamine and other mediators of inflammation are released from mast cells
for example
 Leukotriene's (C4, D4, E4) Bronchoconstriction and also causes mucus
gland to hyperactive and start producing mucous
 Prostaglandins, Vasodilation and causes more fluid to come out and
cause wall to swell up
 Bradykinnins
 Adenosine as well as
 Various chemotactic agents that attract eosinophils and neutrophils.
Macrophages
 Macrophages release prostaglandins, thromboxane
and platelet-activating factor(PAF).
 PAF sustain bronchial hyperactivity
and causes capillaries to leak plasma that leads to
mucosal edema
 PAF also facilitates the accumulation of eosinophil's

within airways
Eosinophils (late phase 12-24hrs)
 Eosinophils release various inflammatory mediators such as leukotriene
C4, and PAF, which results in epithelial damage and thick mucus
production that causes further deterioration in lung function.
 Hypertrophy and hyperplasia of bronchial smooth muscle occur by
these cell-derived mediators.
 Mucus gland hypertrophy leading to excessive mucus production and
airway plugging, airway oedema, acute bronchoconstriction and impaired
mucocilliary clearance.
Pathophysiology
Clinical manifestations
Asthma can present in a number of ways. It may be manifest as a
persistent cough but commonly described as
 Recurrent episodes of difficulty in breathing (dyspnea) associated with
wheezing(a high-pitched noise due to turbulent airflow through a narrowed
airway.)
Diagnosis or investigations
A series of routine tests has been developed to assess asthma such as
1. Forced expiratory volume(FEV)
This a most useful test for abnormalities in airway function. This is measured
by means of lung function assessment apparatus such as a spirometer. The
patient inhales as deeply as possible and then exhales forcefully and
completely into a mouthpiece connected to a spirometer.

The FEV1 is a measure of the FEV in the first second of exhalation.

Diagnosis or investigations
I. Forced vital capacity(FVC) can also be measured, which is
an assessment of the maximum volume of air exhaled with
maximum effort after maximum inspiration.
II. FEV1 is usually expressed as a percentage of the total volume
of air exhaled, reported as the FEV1/FVC ratio.
III. Tidal volume is the volume of air inspired or expired during
normal breathing.
IV. Residual volume (RV) is the volume of air left in lungs after
maximum expiration.
V. Total lung capacity = VC + RV
Normal individual can exhale at least 70% of their lung capacity in
1 sec.
Diagnosis or investigations
I. Peak flow meter is a useful means of self-assessment for
the patient. it measures peak expiratory flow( PEF) rate.
II. Peak expiratory flow rate ,the maximum flow rate that can
be forced during expiration. It can be used to assess the
improvement or deterioration in the disease as well as the
effectiveness of treatment.

A healthy average young adult

male typically has a PER of
550 to 700L/minute
 These lung function test are used to demonstrate the
presence of air flow obstruction.
 Other test include
• Skin pricking test for IgE testing for specific allergens
• X-Rays
• Eosinophilic airway inflammation can be determined by
using sputum differential count

Chest X-Rays
Treatment
The aim of asthma management is to have complete control
and have no exacerbations of disease
 BTS (The British Thoracic Society) defines asthma

control as
• No daytime symptoms

• No night time wakening

• No requirement of rescue medicines

• No asthma attack

• No limitation on activity

• Normal lung function tests FEV1 >80%

• Minimal adverse effect from medications

 Classification of asthma severity
Persistent asthma

Components Intermittent Mild Moderate Severe

of severity

Impairments Symptoms ≤2 >2 Daily Throughout

days/weeks days/week the day
but not daily

Nighttime ≤2x/weeks 3-4x/month >1x/week Often

awakenings but not 7x/week
nightly
SABA use for ≤2 >2 Daily Several times
symptom days/weeks days/week per day
control but not daily
 Persistent asthma
Components Intermittent Mild Moderate Severe
of severity

Interference None Minor Some Extremely

with normal limitation limitation limited
activity
Normal Lung function • Normal
FEV1/FVC FEV1
8-19yrs, 85% between
20-39yrs, 80% exacerbatio
40-59yrs, 75% n
60-80yrs, 70% • FEV1 • FEV1 • FEV1 • FEV1
>80% ≥80% >60% <60%
predicte predicte predicted predicted
d d • FEV1/FVC • FEV1/FVC
• FEV1/ • FEV1/ reduced reduced
FVC FVC 5% >5%
normal normal
 Persistent asthma
Component of Intermittent Mild Moderate Sever
severity
Risk Exacerbations 0-1 year ≥2 in 1
requiring oral year
systemic
corticosteroids
Consider severity and interval since last
exacerbation. Severity and frequency may fluctuate
over time for patients. Relative annual risk of
exacerbations may be related to FEV1.
 Classifying severity in patients after asthma becomes well
controlled, by lowest level of treatment required to maintain
control

Persistent asthma
Intermittent Mild Moderate Sever
Level of Step-1 Step-2 Step 3 or 4 Step 5 or 6
treatment
required to
maintain
control
Drugs used in asthma
Reliever medications
 Inhaled Short acting beta adrenoceptor agonist

(Salbutamol 200µcg)
 Inhaled anti-cholinergic agent (Ipratropium slower

onset of action)
 Long acting beta adrenoceptor agonist
 Oral bronchodilators (Theophylline)
Cont..
Preventive medication
 Anti-inflammatory agent (Corticosteroids ;

Beclomethasone or Budesonide 400µcg/day)

 Leukotriene receptor antagonist (Montelukast,

Zafirlukast)
 IgE monoclonal antibodies (Omalizumab)
 Oral corticosteroid
Stepwise management in adults of
chronic asthma

Step2: Regular preventer therapy

Add inhaled steroid 200-800µcg/day

400µcg is an appropriate starting dose for many patients
Start a dose of inhaled steroid appropriate to severity of
disease

Step1: Mild intermittent asthma

Inhaled short acting beta 2 agonists as required

Step 5: Continues or frequent use of oral
steroids
• Use daily steroid tablet in lowest dose providing adequate control
• Maintain high dose inhaled steroids at 2000 µcg/day
• Consider other treatment to minimize the use of steroid tablet
• Refer patient for specialist care.
Step 4: Persistent poor control
• Consider trials of increasing inhaled steroids upto 2000 µcg/day
• Addition of fourth drug leukotriene receptor antagonist, SR
theophylline

Step 3: Add on therapy

Add inhaled beta 2 agonists (LABA)
Assess control of asthma
• Good response to LABA
• Benefit from LABA but control still inadequate-continue LABA and
increase inhaled steroid dose to 800µcg/day
• No response to LABA- stop LABA and increase inhaled steroid to
800µcg/day. If control still inadequate institute trial of other therapy
e.g. leukotriene receptor antagonists or SR theophylline
Adjusting therapy to achieve asthma
control
Acute asthma
ADRS of some anti-asthmatic drugs
Drugs ADRs
Beta 2 agonists High doses: hypokalemia,
aggravation of angina
Inhaled corticosteroids Oral candidiasis, adrenal
suppression
Oral corticosteroids Mineralocorticoid effects include:
potassium loss, muscles
weakness, hypertension, sodium
and water retention.
Ipratropium Dry mouth
Nedocromil sodium Nausea, coughing, throat
irritation, headache
Theophylline Hyperglycemia, hypotension,
cardiac arrhythmia
Inhalation devices
 The choice of suitable inhalation devices is vital in
asthma.
 Incorrect use of inhalers will lead to sub-optimal
treatment.
Types of inhalers
 Metered dose aerosol inhaler
 Dry powder inhalers
 Nebulisers (nebuliser produces an aerosol by
blowing air or oxygen through a solution to
produce droplet of 5µm or less in size)
Metered dose aerosol inhaler
 It usually contains a solution or suspension of
active drug, with typical particle size of 2-5µm in a
liquefied propellant.
 Operation of device releases a metered dose of
drug with droplet size of 35-45µm.
 This increase in droplet size is due to propellant
which evaporates when expelled from inhaler
Advantages of MDIs
 MDIs have the advantage of being multidose, small
and widely available for most drugs used in
asthma.
 Corticosteroids administered by MDIs causes oral
candidiasis so the patient is advised to gargle with
water after using inhalation and to expel the water
from mouth afterwards
Correct technique for using MDIs
Combination inhalers
 Corticosteroids and long-acting beta agonists
Some inhaled asthma medication combinations contain
both a corticosteroid and a bronchodilator:
• Fluticasone and Salmeterol (Advair Diskus)
• Budesonide and Formoterol (Symbicort)
• Mometasone and Formoterol (Dulera)
• Fluticasone and Vilanterol (Breo)
• Formeterol and Beclomethasone (Foster)
 Long-acting beta agonists (LABAs)
The most commonly used LABA for asthma is salmeterol
(Serevent).
 Quick relief drugs

Albuterol (ProAir HFA, Ventolin HFA, others)

Levalbuterol (Xopenex HFA)
Refrences:
 Clinical pharmacy and therapeutics Rogger
Walker 5th edition
 Applied therapeutics 9th edition (Marry Anne

Koda-Kimble)