Asthma

Prevalence of Asthma Asthma affects 300 million adults and

children worldwide

Estimated prevalence of asthma is increasing 50% per decade

WHO: 15-20 million asthmatics in India

Children: 12% and Adults 5%’

Parts of the Respiratory System

The microscopic structure of the airwaysThe airways from the windpipe down to the smallest air passages that supply

the air sacs, have a similar microscopic structure

Ciliated columnar epithelium

Goblet cell

Basement membrane

Blood cellSmooth muscle layer

Spongy layer

Bronchial gland

Classification of the nervous system

Nervous system

Peripheral Central

Somatic Autonomic

Sympathetic Parasympathetic

Sympathetic receptors

Alpha- Beta-

1 2 1 2

Lungs

Where are beta receptors located?

Location Smooth muscle cells Mast cells Eosinophils Lymphocytes Nerve endings Epithelial cells

Relaxation

Anti-inflammatory

Mucus enhancement

Effects

Parasympathetic receptors

Muscarinic - M

M1, M2, M3

Smooth muscle

mucus glands

Ciliary epithelium

Blood vessels

Bronchoconstriction

Mucus secretions

Ciliary activity

Dilation Oedema

Inflammatory Cells

R B C s

E os in op h ils N eu trop h ils B asop h ils --> M as t ce lls

G ran u locytes

L ym p h ocytesT ce lls & B ce lls

M on ocytes - M ac rop h ag es

A g ran u locytes

W B C s P la te le ts

C e lls

Asthma - Definition

Asthma is a Chronic inflammatory

disease characterized by

Airway hyperesponsiveness to a

variety of stimuli resulting in Bronchospasm

which reverses spontaneously - on treatment

Basic Cellular Mechanisms

FIRST EXPOSURE Sensitisation process

SECOND EXPOSURE Early allergic reaction Late allergic reaction

Allergic Response

SENSIT IZATION PH ASE

1st exposure

Enters the body

Allergen Body produces IgE antibodies

Antibodies + Allergens

Excess antibodiesBind to mast cells

Inflammatory mediators (histamine)(not released)

Produce

Y Y

YY

Y

YYY

YY

Y

Y

M astcell

Sensitization

Allergic Response

2nd exposure

IgE antibody

A llergen

Histamine

ChemotacticFactors

EA RLY ALLERG IC RESPON SE(EAR)

5-30 minutesafter exposure

Allergic Response

2nd exposure C hem otacticF actors

Migration & Activation

Basophils NeutrophilsEOSINOP HILS

Secondary Mediators ECP ; MBP

Damage to Epithelial cells (this exposes the parasympathetic nerves)

LATE A LLERG IC R ESPO N SE (LA R)

INFLAM M ATIO N

Mucus productionBronchoconstriction

Ciliary activityVasodilation

}

REDNESS, SWELLING

between 3-11 hours after exposure

Bronchospasm

Histamine

Leukotrienes

Acetylcholine

Effects of inflammation in the airways

Airway remodelling: the structural changes in the airways chronic untreated inflammation leads to irreversible changes in the structure of airways.

Fibrosis: Formation of fibrous tissue (destruction of lung tissue)

Goblet cell hyperplasia: Increase in the number of goblet cells

Neovascularization: Formation of new blood vessels

Smooth muscle cell hypertrophy: Increase in the size of smooth muscle cells

Basement Membrane Thickening Bronchial Gland Hyperplasia: Increase

in the cells of bronchial gland

Acute Effects Bronchoconstriction Plasma leakage Vasodilation Mucus secretion Nerve activation

Chronic Effects(Airway remodelling) Fibrosis Smooth muscle cell

hypertrophy Goblet cell hyperplasia New blood vessel

formation

Nocturnal Asthma

Nighttime symptoms of wheezing, cough, breathlessness is known as nocturnal asthma.

70% of deaths due to asthma occur

at night

Asthma attacks often occur

between2 and 4 am

Nocturnal Asthma

Causes of Nocturnal Asthma

Exposure to dust mite, animal dander

Gastro-oesophageal reflux

Post nasal drip

Decreased cortisol levels

Increased parasympathetic activity

Increased sensitivity to histamine

Diagnosing Asthma

Medical history

Physical examination

Measurements of lung function

Trial use of asthma medications

Peak Flow Meter

Diagnose asthma

To determine effectiveness of therapy

Identify factors which worsen asthma

Warn of an impending attack

Interpretation of PEFR

15-20% increase in the peak flow when

measured after administering a

bronchodilator, it indicates a significant

degree of reversible airflow obstruction.

Diurnal variability of >20% is indicative of

Asthma.

Spirometry

Patient blows into spirometer. The device measures and records maximum air flow, lung volume, and other parameters which are important in understanding the individual’s pulmonary (lung) function

FEV1

The spirometer mainly measures the FEV1 i.e.

the volume of air that a person can exhale out forcefully in the first second.

The FEV1 values are reduced in case of

asthmatics

Generally in mild cases it is <80% of the normal

Bronchodilator Reversibility testing

Diagnose asthma (Reversibility test)

Measure PEFR

Administer fast acting bronchodilator (Salbutamol 2 puffs)

Measure PEFR after 15-20 mins

15% improvement in peak flow reading

Two clinical properties of bronchodilators

Bronchodilation

Ability to dilate constricted bronchi

Bronchoprotection

Ability to prevent bronchi from going into

spasm after exposure to allergen or any

stimulus

Evaluation of bronchodilators

Bronchodilation Symptoms FEV1/PEFR

Bronchoprotection – can be assessed by methacholine challenge test PD20 /PD15

RELIEVERS Short acting 2 agonists

SalbutamolLevosalbutamol Terbutabaline

Anti-cholinergicsIpratropium bromide

XanthinesTheophylline Aminophylline

Adrenaline injections

PREVENTERSCorticosteroids

ORAL

Prednisolone, Betamethasone

INHALED

BeclomethasoneBudesonideFluticasone

PREVENTERS

Long acting 2 agonistsBambuterol – ORALSalmeterolFormoterol

Anti-leukotrienesMontelukast Zafirlukast

Xanthines

Theophylline SR

Mast cell stabilisers

Sodium cromoglycate

PREVENTERS

Classification of Severity-GINACLASSIFY SEVERITY

Clinical Features Before Treatment

SymptomsSymptoms NocturnalNocturnalSymptomsSymptoms FEVFEV1 1 or PEFor PEF

STEP 4STEP 4

Severe Severe PersistentPersistent

STEP 3STEP 3

Moderate Moderate PersistentPersistent

STEP 2STEP 2

Mild Mild PersistentPersistent

STEP 1STEP 1

IntermittentIntermittent

ContinuousContinuous

Limited physical Limited physical activityactivity

DailyDailyAttacks affect activityAttacks affect activity

> 1 time a week > 1 time a week but < 1 time a day but < 1 time a day

< 1 time a week< 1 time a week

Asymptomatic and Asymptomatic and normal PEF normal PEF between attacksbetween attacks

FrequentFrequent

> 1 time week> 1 time week

> 2 times a month> 2 times a month

2 times a month2 times a month2 times a month2 times a month

60% predicted60% predicted

Variability > 30%Variability > 30%

60 - 80% predicted 60 - 80% predicted

Variability > 30%Variability > 30%

80% predicted80% predicted

Variability 20 - 30%Variability 20 - 30%

80% predicted80% predicted

Variability < 20%Variability < 20%

The presence of one feature of severity is sufficient to place patient in that category.The presence of one feature of severity is sufficient to place patient in that category.

Goals of Asthma Therapy Minimal (ideally no) chronic symptoms Minimal (infrequent) exacerbations No emergency visits Minimal (ideally no) need for “as needed” use of

β2-agonist No limitations on activities, including exercise PEF circadian variation of less than 20 percent (Near) normal PEF Minimal (or no) adverse effects from medicine

Stepwise Approach to Asthma Therapy - AdultsStepwise Approach to Asthma Therapy - Adults

Alternative controller and reliever medications may be considered Alternative controller and reliever medications may be considered

Reliever: Rapid-acting inhaled β2-agonist prn

Preventer: Daily inhaledcorticosteroid

Preventer: Daily inhaled

corticosteroid Daily long-acting

inhaled β2-agonist

Preventer: Daily inhaled

corticosteroid Daily long –acting

inhaled β2-agonist plus (if needed)

When asthma is controlled, reduce therapy

Monitor

STEP 1:STEP 1:IntermittentIntermittent

STEP 2:STEP 2:Mild PersistentMild Persistent

STEP 3:STEP 3: Moderate Moderate PersistentPersistent

STEP 3:STEP 3: Moderate Moderate PersistentPersistent

STEP 4:STEP 4:Severe Severe

PersistentPersistentSTEP DownSTEP DownSTEP DownSTEP Down

Outcome: Asthma Control Outcome: Best Possible Results

Preventer:None

-Theophylline-SR -Anti-Leukotriene -Long-acting inhaled β2- agonist -Oral corticosteroid