Pathophysiology and management Dr Deepak Aggarwal MD, FCCP Asst. Professor Pulmonary medicine What is Asthma…..Definition ( GINA) •Asthma is –A… [629786]

Bronchial  Asthma
Pathophysiology and  management  
Dr Deepak Aggarwal
MD, FCCP
Asst. Professor
Pulmonary  medicine

What is Asthma…..Definition  ( GINA)
•Asthma is 
–A chronic inflammatory  disorder of the airways in 
which many cells and cellular elements  play a role. 
–The chronic inflammation  is associated  with airway 
hyper‐responsiveness that leads to recurrent  episodes 
of wheezing  , breathlessness,  chest tightness  and 
coughing particularly  at night or early morning. 
–These episodes are usually associated  with widespread,  
but variable airflow obstruction  within the lung that is 
often reversible  either spontaneously  or with 
treatment

Causes/ Risk factors
ENVIRONMENTAL  RISK 
FACTORS
GENETIC SUSCEPTIBILITY  AND
GENE‐ENVIRONMENT  INTERACTIONS
Perinatal Factors
Indoor and Outdoor Allergens
Smoking and Environmental  Tobacco 
SmokeOther Pollutants
Race/Ethnicity  and Socioeconomic  
StatusObesityRespiratory  Illnesses

How Asthma develops…..

PATHOGENESIS

PATHOGENESIS

ASTHMA ‐PATHOPHYSIOLOGY
Asthma
Genetic predisposition
Intrinsic vulnerability
Atopy/allergy  Inflammation  underlies  disease 
processes
Phenotype  varies by individual  
and over time Clinical symptoms  also vary by 
individual  and over time

PATHOLOGY

Asthma: Pathological  changes

Pathology  and consequences

COPD
Neutrophils
No airway 
hyperresponsiveness
Less bronchodilator
response
Limited steroid
responseWheezy 
bronchitis  10%Asthma
Eosinophils
Airway 
hyperresponsiveness
Bronchodilator
response
Steroid
response
CD4+ T-lymphocytes CD8+ T-lymphocytes
Completely
reversibleincompletely
irreversible

Physiologic  Differences
Asthma
•Normal DLCO
•Normal lung volume
•Normal elastic recoilCOPD
•Abnormal  DLCO
•Hyperinflation
•Decreased  elastic recoil
Sciurba FC, CHEST 2004;117S ‐124S

Reversible  airflow obstruction + ++ +
Airway inflammation + ++ +  +
Mucus hypersecretion ++  + +
Goblet cell metaplasia +  + +
Impaired mucus clearance + ++  +
Epithelial  damage ++ —
Alveolar destruction —+ +
Smooth muscle hypertrophy + + —
Basement  membrane  thickening +++ —Disease Pathology Asthma COPD

Asthma‐Classic presentation
•Intermittent  episodic, acute/subacute onset
•Breathlessness/chest  tightness usually with 
wheeze 
•Cough nocturnal  or early morning.
•Diurnal and seasonal variation
•History of atopy, family history 
•Polyphonic  wheeze, prolonged  expiration
•However,  the examination  can be normal.

Differential  diagnosis

DIAGNOSIS

18Cough, wheezing
and
Breathlessness
Minimal or no expectoration
Associated chest tightnessExpectoration
mucoid or
mucopurulentAssociated fever,
chest pain,
constitutional symptoms
Symptoms variable,
Intermittent, recurrent, seasonal, worse at night and provoked by triggers
History of atopy in self or
atopy/eczema in familySymptoms chronic/
progressive/persistentSUSPECT OTHER
DIAGNOSES OR
COMPLICATIONS
History of smoking
(active or ETS exposure)
Breath Sound intensity normal
Prominent rhonchi – bilateral,
diffuse, polyphonic, expiratory
MANAGE AS
ASTHMAHyperinflation, pursed lip
breathing, diminished
intensity of breath soundsLocalized signs Normal
SUSPECT OTHER
DIAGNOSES OR
COMPLICATIONSSputum for AFB (x3)
Positive Negative
TUBERCULOSIS
(Refer to RNTCP)MANAGE AS
COPDReferral

Key indicators for considering a
diagnosis of asthma
•Typical history
•Intermittent symptoms (reversible)
•Association of symptoms to weather changes, dust,
smoke, exercise, viral infection, animals with fur or feathers,
house-dust mites, mold, pollen, strong emotional expression
(laughing or crying hard), airborne chemicals or dust
•Diurnal variation
•Family history
•Presence of atopy, allergic rhinitis, skin allergies

Routine Investigations
•Hemogram including  eosinophil count
•Blood gas analysis
•X‐ray chest
•Serum electrolytes  (Mg, Na, K)
•Spirometry
•Other test to rule out specific diseases

Spirometry
•Spirometry measurements (FEV 1, FVC, FEV 1/FVC)
before and after bronchodialator helps determine whether there is airflow obstruction and whether it is
reversible over the short term
•(12% in increase in FEV1 and absolute increase in
200ml after 200ug of salbutamol inhalation)

Spirometry
•Spirometry should be done
–at the time of initial assessment
–after treatment is initiated and symptoms and peak
expiratory flow (PEF) have been stabilized
–at least every 1 to 2 years to assess the
maintenance of airway function

TREATMENT

24Goals of Asthma Therapy
•Prevent recurrent  exacerbations  and minimize the 
need for emergency  department  visits or 
hospitalizations
•Maintain (near‐) “normal” pulmonary  function
•Maintain normal activity levels (including  exercise 
and other physical activity)
•Provide optimal pharmacotherapy  with minimal or 
no adverse effects

25
GINA Levels of Asthma Control
Characteristic ControlledPartly controlled
(Any present in any week)Uncontrolled
Daytime symptomsNone (2 or less /
week)More than
twice / week
3 or more
features of partly controlled asthma present in any weekLimitations of
activitiesNone Any
Nocturnal
symptoms /
awakeningNone Any
Need for rescue /
“reliever” treatmentNone (2 or less /
week)More than
twice / week
Lung function
(PEF or FEV
1)Normal< 80% predicted or
personal best (if
known) on any day
Exacerbation None One or more / year 1 in any week

Levels of 
prevention

Asthma drug classification

What are Controllers?
Control/treat  chronic 
inflammation
Prevent future attacks
Long term control
Prevent airway 
remodeling

What Are Relievers?
‐ Rescue medications  to treat 
acute bronchospasm
‐ Quick relief of symptoms
‐ Used during acute attacks
‐ Action usually lasts 4‐6 hrs

Methods of Medication Delivery
Metered-dose inhaler (MDI)
Spacer/holding chamber/face mask
Dry-powder inhaler (DPI)
Nebulizer
Oral Medication
Tablets, Liquids
Intravenous Medication
IV Corticosteroids, IV Aminophylline

CONTROLLERS
Inhaled Corticosteroids
Treatment of choice for long-term control of
persistent asthma
Benefits
Reduced airway inflammation through topical activity
Decreases airway hyper-responsiveness.
Improve lung function and quality of life
Reduce the frequency of exacerbations
Reduced use of quick-relief medicine
**NEVER FOR RESCUE PURPOSES**

CONTROLLERS
Corticosteroids
•Inhaled
Beclomethasone
Fluticasone
Triamcinolone
Budesonide
Flunisolide

Anti-inflammatory Effect of Glucocorticoid

Estimated  Comparative  Daily Dosages for 
Adults of Inhaled Corticosteroids
DrugLow Dose
Step 2Medium Dose
Step 3High Dose
Step 4
Beclomethasone 1-3 puffs
80 – 240 mcg3-6 puffs
240 – 480 mcg>6 puffs
> 480 mcg
Budesonide DPI 1-3 puffs
200 – 600 mcg3-6 puffs
600 – 1,200 mcg> 6 puffs
> 600 mcg
Flunisolide 2-4 puffs
500–1,000 mcg4-8 puffs
1,000–2,000 mcg> 8 puffs
> 2,000 mcg
Fluticasone 2-6 puffs (44)
88-264 mcg2-6 puffs (110)
264-660 mcg> 6 puffs (110)
> 660 mcg
Triamcinolone 4-10 puffs
400-1,000 mcg10-20 puffs
1,000–2,000 mcg> 20 puff
> 2,000 mcg

Corticosteroid Side Effects
Inhaled Local
•Dysphonia
•Cough/throat  irritation
•Thrush
•Impaired growth (high 
dose)?Systemic (oral, IV)
•Fluid retention
•Muscle weakness
•Ulcers
•Malaise
•Impaired wound healing
•Nausea/Vomiting,  HA
•Osteoporosis  (adults)
•Cataracts  (adults)
•Glaucoma  (adults)

CONTROLLERS
Long-acting Beta2-agonists
Salmeterol, Formoterol
Indication: Daily long-term control
Advantages
Blunt exercise induced symptoms for longer time
Decrease nocturnal symptoms
Improve quality of life
Combination therapy beneficial when added to
inhaled corticosteroids

CONTROLLERS
Long-acting Beta2-agonists
NOTfor acute symptoms or exacerbations
Onset of effect 30 minutes
Peak effect 1-2 hours
Duration of effect up to 12 hours
NOTa substitute for anti-inflammatory
therapy
NOTappropriate for monotherapy

Useful Beta Adrenergic  Effects
•Relax bronchial  smooth muscle
•Inhibit mediator release from mast cells, eosinophils,  
macrophages
•Decrease mucous secretion  (submucosal gl)
•Increase mucociliary transport
•Inhibit bronchial  oedema
•Inhibit cholinergic  transmisssion
•Decrease airway hyperresponsiveness

CONTROLLERS
Leukotriene Modifiers
Cysteinyl Leukotriene Receptor Antagonists
Montelukast – Once a day dose
Zafirlukast – Twice daily – Empty Stomach
5-Lipoxygenase inhibitors
Zileuton – Four times daily
 Many drug interactions

Add‐on Controllers
Leukotriene Modifiers
Montelukast
–Improves  lung function and asthma control
–May protect against exercise induced bronchoconstriction
–Not as effective as inhaled corticosteroids
–No food restrictions

RELIEVERS
Short-Acting Beta -agonist
•Salbutamol
•Terbutaline
•levosalbutamol

RELIEVERS
Short-Acting Beta2-Agonists
Most effective medication for relief of acute
bronchospasm
Increased need for these medications indicates
uncontrolled asthma (and inflammation)
Use “as needed” as regular use
May lower effectiveness
May increase airway hyperresponsiveness

RELIEVERS
Short-Acting Beta2-Agonists
Side Effects:
Increased Heart Rate
Palpitations
Nervousness
Sleeplessness
Headache
Tremor

Unwanted  Beta Adrenergic  Effects
•Hypokalemia  (K shift into muscle tissue)
•Hyperglycemia  (glycogenolysis)
•Hypoxia (pulmonary  vasodilation  causing 
increased  ventilation/perfusion  
mismatch)

Oral Steroid Short Course
•Prednisone  30‐40mg x 10‐14 days 
for acute exacerbation  of Asthma
•no weaning of dose unless long 
term use

Step 1 Treatment for Adults and
Children > 5: Mild Intermittent
Controller  – Daily
‐Not needed
Reliever –Q u i c k Relief
‐Short‐acting inhaled beta2‐agonist
‐Increasing  use, or use more than 
2x/week, may indicate need for 
long‐term‐control therapy
‐STEP 1

Step 2 Treatment for Adults and
Children > 5: Mild Persistent
STEP 2Controller  –P r e f e r r e d  Daily
‐Low dose inhaled corticosteroid  
Alternatives
‐leukotriene modifier,  
OR
‐Sustained ‐release theophylline

Step 3 Treatment for Adults and
Children > 5: Moderate Persistent
Controller  –P r e f e r r e d  Daily
‐Low to medium dose inhaled 
corticosteroid  (medium dose) and 
long‐acting beta2‐agonist
Alternatives  
‐Increase inhaled corticosteroids  to medium‐
dose range
OR
‐Low to medium dose inhaled corticosteroid  
(medium dose) and either leukotriene
modifier or theophyllineSTEP 3

Step 3 Treatment for Adults and
Children > 5: Moderate Persistent
(patients with recurring severe exacerbations)
Controller  
‐Medium dose inhaled corticosteroid  
(medium dose) and long‐acting beta2‐
agonist
Alternatives  
‐Medium dose inhaled corticosteroid  
(medium dose) and either leukotriene
modifier or theophylline
‐High dose inhaled corticosteroid
‐Consider referral to a specialistSTEP 4

Step 4 Treatment for Adults and
Children > 5: Severe Persistent
Controller  – Daily
‐High‐dose inhaled corticosteroid  AND
‐Long‐acting inhaled beta2‐agonist 
AND , if needed,
‐Add leukotriene antagonists  & 
theophylline
‐Corticosteroid  tablets STEP 5

Monitor Asthma Control

53Treating to Maintain Asthma Control
Stepping down treatment  when asthma is controlled
When controlled  on medium‐to high‐dose inhaled 
glucocorticosteroids:   50% dose reduction  at 3 
month intervals (Evidence  B)
When controlled  on low‐dose inhaled 
glucocorticosteroids:   switch to once‐daily dosing 
(Evidence  A)

54Treating to Maintain Asthma Control
Stepping up treatment  in response to loss of control
Rapid‐onset, short‐acting or long‐acting inhaled β2‐
agonist bronchodilators  provide temporary  relief
Need for repeated dosing over more than one/two 
days signals need for possible increase in controller  
therapy

As soon as good control:
• Reduce oral steroids first, then stop
• Reduce relievers before controllers  
When good control for 3+ months:
• Reduce inhaled steroidsManaging  the well controlled  patient

Therapy to avoid!
•Sedatives  & hypnotics
•Cough syrups
•Anti‐histamines
•Immunosuppressive  drugs
•Immunotherapy
•Maintenance  oral prednisone  >10mg/day

Managing  partly/uncontrolled  asthma
•C h e c k the inhaler technique
•C h e c k adherence  and understanding  of 
medication
• Consider  aggravation  by:
–Exposure to triggers/allergens  at home or work
–Co‐morbid conditions:  GI reflux,rhinitis/sinusitis,  
cardiac problem
–Medications:  Beta‐blockers, NSAIDs, Aspirin

The Asthma Action Plan
•Helps patients/caregivers manage asthma
Uses Peak Flows
Spells out medication instructions
•Green Zone 80-100% Peak Flow
•Yellow Zone 50-80% Peak Flow
•Red Zone Below 50% Peak Flow

Medication Delivery Demonstrations
Breath Actuated Inhalers
Metered Dose Inhalers with Spacer/Holding Chamber
Dry Powder Inhalers
Nebulizers

pMDIs
Advantages                  Disadvantages
Small and portable    difficult to learn technique
Unsuitable  for children < 5‐6     
Quick to use                  Unsuitable  for the elderly, 
Cold jet may irritate throat
Limited amount of drug 
delivered  per puff

Spacers and Holding
Chambers
A spacer device enhances  delivery by 
decreasing  the velocity of the particles and 
reducing the number of large particles, 
allowing smaller particles of drug to be inhaled.
A spacer device with a one-way valve, i.e., holding chamber,
eliminates the need for the patient to coordinate actuation with inhalation and optimizes drug delivery.
A simple spacer device without a valve requires coordination
between inhalation and actuation.

DPIs
•Generally  easier to use
•A minimal inspiratory flow  rate is necessary  to inhale 
from a DPI; difficult for some pts to use during an 
exacerbation
•More ecological  than MDIs
•Storage may be difficult in humid climates

Nebulizer
Advantages Disadvantages
No Coordination   required Cumbersome
Can be used for all ages Expensive
Effective in severe asthma Noisy
Treatment takes  time

Which inhalation  device for which 
patient?
•Infants and children       pMDI+spacer,  nebulizer
up 5 y/o 
•Children 5‐9 y/o              pMDI+spacer,  nebulizer,  DPI
•Competent  older             pMDI, DPI
children and adults
•Incompetent  older          pMDI+spacer,  nebulizer
children/adults

Key Messages
•Asthma is common and can start at any age
•Asthma can be effectively  controlled
•Effective asthma management  programs  include 
education,  objective measures  of lung function, 
environmental  control, and pharmacologic  therapy.
•A stepwise approach  to pharmacologic  therapy is 
recommended.  
•The aim is to accomplish  the goals of therapy with the 
least possible medication.

Thank you