BronchialAsthma

Pathophysiology andmanagement

DrDeepakAggarwal
MD,FCCP
Asst.Professor
Pulmonarymedicine
 WhatisAsthma..Definition(GINA)

Asthmais
Achronicinflammatorydisorderoftheairwaysin
whichmanycellsandcellularelementsplayarole.
Thechronicinflammationisassociatedwithairway
hyperresponsiveness thatleadstorecurrentepisodes
ofwheezing,breathlessness,chesttightnessand
coughingparticularlyatnightorearlymorning.
Theseepisodesareusuallyassociatedwithwidespread,
butvariableairflowobstructionwithinthelungthatis
oftenreversibleeitherspontaneouslyorwith
treatment
 Causes/Riskfactors

GENETICSUSCEPTIBILITYAND ENVIRONMENTALRISK
GENEENVIRONMENTINTERACTIONS FACTORS

Perinatal Factors
IndoorandOutdoorAllergens
SmokingandEnvironmentalTobacco
Smoke
OtherPollutants
Race/EthnicityandSocioeconomic
Status
Obesity
RespiratoryIllnesses
HowAsthmadevelops..
PATHOGENESIS
PATHOGENESIS
 ASTHMA PATHOPHYSIOLOGY

Asthma

Geneticpredisposition Inflammationunderliesdisease
processes
Intrinsicvulnerability Clinicalsymptomsalsovaryby
Atopy/allergy Phenotypevariesbyindividual individualandovertime
andovertime
PATHOLOGY
Asthma:Pathologicalchanges
Pathologyandconsequences
 COPD Asthma
Neutrophils Eosinophils
CD4+ T-lymphocytes CD8+ T-lymphocytes
Noairway Wheezy Airway
hyperresponsiveness bronchitis10% hyperresponsiveness

Lessbronchodilator Bronchodilator
response response

Limitedsteroid Steroid
response response

incompletely Completely
irreversible reversible
 PhysiologicDifferences
Asthma COPD
NormalDLCO AbnormalDLCO

Normallungvolume Hyperinflation

Normalelasticrecoil Decreasedelasticrecoil

SciurbaFC,CHEST2004;117S124S
DiseasePathology Asthma COPD
Reversibleairflowobstruction +++ +
Airwayinflammation ++ + ++
Mucushypersecretion + +++
Gobletcellmetaplasia + ++
Impairedmucusclearance ++ ++
Epithelialdamage ++
Alveolardestruction ++
Smoothmusclehypertrophy ++

Basementmembranethickening +++
 AsthmaClassicpresentation
Intermittentepisodic,acute/subacute onset
Breathlessness/chesttightnessusuallywith
wheeze
Coughnocturnalorearlymorning.
Diurnalandseasonalvariation
Historyofatopy,familyhistory
Polyphonicwheeze,prolongedexpiration
However,theexaminationcanbenormal.
Differentialdiagnosis
DIAGNOSIS
 Cough, wheezing
and
Breathlessness

Expectoration Associated fever,

Minimal or no expectoration
Associated chest tightness
mucoid or chest pain,
mucopurulent constitutional symptoms

Symptoms variable, SUSPECT OTHER

Intermittent, recurrent, Symptoms chronic/
seasonal, worse at night
DIAGNOSES OR
progressive/persistent COMPLICATIONS
and provoked by triggers

History of atopy in self or History of smoking

atopy/eczema in family (active or ETS exposure)

Breath Sound intensity normal Hyperinflation, pursed lip

Prominent rhonchi bilateral, breathing, diminished Normal Localized signs
diffuse, polyphonic, expiratory intensity of breath sounds

SUSPECT OTHER
MANAGE AS
Sputum for AFB (x3) DIAGNOSES OR
ASTHMA COMPLICATIONS

Positive Negative Referral

TUBERCULOSIS MANAGE AS
(Refer to RNTCP) COPD 18
 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
 RoutineInvestigations
Hemogram includingeosinophil count
Bloodgasanalysis
Xraychest
Serumelectrolytes(Mg,Na,K)
Spirometry
Othertesttoruleoutspecificdiseases
 Spirometry

Spirometry measurements (FEV1, FVC, FEV1/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
 GoalsofAsthmaTherapy
Preventrecurrentexacerbationsandminimizethe
needforemergencydepartmentvisitsor
hospitalizations
Maintain(near)normalpulmonaryfunction
Maintainnormalactivitylevels(includingexercise
andotherphysicalactivity)
Provideoptimalpharmacotherapywithminimalor
noadverseeffects

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 GINALevelsofAsthmaControl
Partly controlled
Characteristic Controlled Uncontrolled
(Any present in any week)

None (2 or less / More than

Daytime symptoms
week) twice / week
Limitations of 3 or more
None Any
activities features of
Nocturnal partly
symptoms / None Any controlled
awakening asthma
present in
Need for rescue / None (2 or less / More than
any week
reliever treatment week) twice / week
< 80% predicted or
Lung function
Normal personal best (if
(PEF or FEV1)
known) on any day

Exacerbation None One or more / year 1 in any week

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 Levelsof
prevention
Asthmadrugclassification
 WhatareControllers?
Control/treatchronic
inflammation

Preventfutureattacks

Longtermcontrol

Preventairway
remodeling
 WhatAreRelievers?
Rescuemedicationstotreat
acutebronchospasm
Quickreliefofsymptoms
Usedduringacuteattacks
Actionusuallylasts46hrs
 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
 EstimatedComparativeDailyDosagesfor
AdultsofInhaledCorticosteroids
Drug Low Dose Medium Dose High Dose
Step 2 Step 3 Step 4
Beclomethasone 1-3 puffs 3-6 puffs >6 puffs
80 - 240 mcg 240 - 480 mcg > 480 mcg

Budesonide DPI 1-3 puffs 3-6 puffs > 6 puffs

200 600 mcg 600 1,200 mcg > 600 mcg

Flunisolide 2-4 puffs 4-8 puffs > 8 puffs

5001,000 mcg 1,0002,000 mcg > 2,000 mcg

Fluticasone 2-6 puffs (44) 2-6 puffs (110) > 6 puffs (110)
88-264 mcg 264-660 mcg > 660 mcg

Triamcinolone 4-10 puffs 10-20 puffs > 20 puff

400-1,000 mcg 1,0002,000 mcg > 2,000 mcg

 Corticosteroid Side Effects
InhaledLocal Systemic(oral,IV)
Dysphonia Fluidretention
Muscleweakness
Cough/throatirritation Ulcers
Thrush Malaise
Impairedgrowth(high Impairedwoundhealing
dose)? 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
NOT for acute symptoms or exacerbations
Onset of effect 30 minutes

Peak effect 1-2 hours

Duration of effect up to 12 hours

NOT a substitute for anti-inflammatory

therapy
NOT appropriate for monotherapy
 UsefulBetaAdrenergicEffects
Relaxbronchialsmoothmuscle
Inhibitmediatorreleasefrommastcells,eosinophils,
macrophages
Decreasemucoussecretion(submucosal gl)
Increasemucociliary transport
Inhibitbronchialoedema
Inhibitcholinergictransmisssion
Decreaseairwayhyperresponsiveness
 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
 AddonControllers
Leukotriene Modifiers
Montelukast

Improveslungfunctionandasthmacontrol
Mayprotectagainstexerciseinducedbronchoconstriction
Notaseffectiveasinhaledcorticosteroids
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
 UnwantedBetaAdrenergicEffects

Hypokalemia(Kshiftintomuscletissue)
Hyperglycemia(glycogenolysis)
Hypoxia(pulmonaryvasodilationcausing
increasedventilation/perfusion
mismatch)
 OralSteroidShortCourse

Prednisone3040mgx1014days
foracuteexacerbationofAsthma
noweaningofdoseunlesslong
termuse
 Step 1 Treatment for Adults and
Children > 5: Mild Intermittent
Controller Daily
Notneeded

Reliever QuickRelief STEP1

Shortactinginhaledbeta2agonist

Increasinguse,orusemorethan
2x/week,mayindicateneedfor
longtermcontroltherapy

 Step 2 Treatment for Adults and

Children > 5: Mild Persistent
Controller PreferredDaily
Lowdoseinhaledcorticosteroid
STEP2
Alternatives
leukotriene modifier,
OR
Sustainedreleasetheophylline
 Step 3 Treatment for Adults and
Children > 5: Moderate Persistent
Controller PreferredDaily
STEP3
Lowtomediumdoseinhaled
corticosteroid(mediumdose)and
longactingbeta2agonist

Alternatives
Increaseinhaledcorticosteroidstomedium
doserange
OR
Lowtomediumdoseinhaledcorticosteroid
(mediumdose)andeitherleukotriene
modifierortheophylline
 Step 3 Treatment for Adults and
Children > 5: Moderate Persistent
(patients with recurring severe exacerbations) STEP4

Controller
Mediumdoseinhaledcorticosteroid
(mediumdose)andlongactingbeta2
agonist

Alternatives
Mediumdoseinhaledcorticosteroid
(mediumdose)andeitherleukotriene
modifierortheophylline
Highdoseinhaledcorticosteroid

Considerreferraltoaspecialist
 Step 4 Treatment for Adults and
Children > 5: Severe Persistent
STEP 5

Controller Daily

HighdoseinhaledcorticosteroidAND
Longactinginhaledbeta2agonist
AND,ifneeded,

Addleukotriene antagonists&
theophylline

Corticosteroidtablets
MonitorAsthmaControl
 Treating to Maintain Asthma Control

Steppingdowntreatmentwhenasthmaiscontrolled

Whencontrolledonmedium tohighdoseinhaled
glucocorticosteroids:50%dosereductionat3
monthintervals(EvidenceB)
Whencontrolledonlowdoseinhaled
glucocorticosteroids:switchtooncedailydosing
(EvidenceA)

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 Treating to Maintain Asthma Control

Steppinguptreatmentinresponsetolossofcontrol
Rapidonset,shortactingorlongactinginhaled2
agonistbronchodilatorsprovidetemporaryrelief
Needforrepeateddosingovermorethanone/two
dayssignalsneedforpossibleincreaseincontroller
therapy

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Managingthewellcontrolledpatient

Assoonasgoodcontrol:
Reduceoralsteroidsfirst,thenstop
Reducerelieversbeforecontrollers

Whengoodcontrolfor3+months:
Reduceinhaledsteroids
 Therapytoavoid!

Sedatives&hypnotics
Coughsyrups
Antihistamines
Immunosuppressivedrugs
Immunotherapy
Maintenanceoralprednisone>10mg/day
Managingpartly/uncontrolledasthma
Checktheinhalertechnique
Checkadherenceandunderstandingof
medication
Consideraggravationby:
Exposuretotriggers/allergensathomeorwork
Comorbidconditions:GIreflux,rhinitis/sinusitis,
cardiacproblem
Medications:Betablockers,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

AdvantagesDisadvantages

Smallandportabledifficulttolearntechnique
Unsuitableforchildren<56

QuicktouseUnsuitablefortheelderly,
Coldjetmayirritatethroat
Limitedamountofdrug
deliveredperpuff
 Spacers and Holding
Chambers

Aspacerdeviceenhancesdeliveryby
decreasingthevelocityoftheparticlesand
reducingthenumberoflargeparticles,
allowingsmallerparticlesofdrugtobeinhaled.
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

Generallyeasiertouse
Aminimalinspiratory flowrateisnecessarytoinhale
fromaDPI;difficultforsomeptstouseduringan
exacerbation
MoreecologicalthanMDIs
Storagemaybedifficultinhumidclimates
 Nebulizer

Advantages Disadvantages

NoCoordinationrequired Cumbersome

Canbeusedforallages Expensive
Effectiveinsevereasthma Noisy
Treatment takestime
 Whichinhalationdeviceforwhich
patient?

InfantsandchildrenpMDI+spacer,nebulizer
up5y/o
Children59y/opMDI+spacer,nebulizer,DPI
CompetentolderpMDI,DPI
childrenandadults
IncompetentolderpMDI+spacer,nebulizer
children/adults
 KeyMessages

Asthmaiscommonandcanstartatanyage

Asthmacanbeeffectivelycontrolled

Effectiveasthmamanagementprogramsinclude
education,objectivemeasuresoflungfunction,
environmentalcontrol,andpharmacologictherapy.

Astepwiseapproachtopharmacologictherapyis
recommended.

Theaimistoaccomplishthegoalsoftherapywiththe
leastpossiblemedication.
Thankyou