Asthma Module 1 Session 1 | 24/03/2010 | All

AsthmaAsthma

George Chalmers Glasgow Royal Infirmary

Asthma factsAsthma facts• 5.4 million people in UK on treatment for asthma5.4 million people in UK on treatment for asthma• 1.1 million children in UK on treatment for asthma1.1 million children in UK on treatment for asthma

– 1 in 11 children1 in 11 children– 1/3 of all long-term childhood illnesses1/3 of all long-term childhood illnesses

• Person with asthma - 1 in 5 households in UKPerson with asthma - 1 in 5 households in UK

• 56% of asthmatics are sensitive to pet allergens56% of asthmatics are sensitive to pet allergens• Est. 75% of hospital asthma admissions are “avoidable”Est. 75% of hospital asthma admissions are “avoidable”• Smoking in pregnancy Smoking in pregnancy - 35% increased risk of wheeze in child- 35% increased risk of wheeze in child

• Asthma costs the NHS over £996 MillionAsthma costs the NHS over £996 Million

What is asthma?What is asthma?

DefinitionsDefinitions

Bronchial anatomyBronchial anatomy

Internet encyclopedia of science

Anatomy of asthmaAnatomy of asthma

Asthma - diagnosisAsthma - diagnosis

• ClinicalClinical diagnosis diagnosis• SymptomsSymptoms

– Wheeze, breathlessness, cough, allergyWheeze, breathlessness, cough, allergy• Airway narrowing Airway narrowing

– VariableVariable over time over time– GeneralisedGeneralised not localised (e.g. tumour/foreign body) not localised (e.g. tumour/foreign body)


• COPDCOPD

– airflow obstruction due to airflow obstruction due to chronic bronchitis or chronic bronchitis or emphysemaemphysema

– the airflow obstruction is the airflow obstruction is generally progressivegenerally progressive

– maymay be accompanied by be accompanied by airway hyper-reactivity airway hyper-reactivity

– maymay be partially reversible be partially reversible

• AsthmaAsthma

– Variable airflow obstructionVariable airflow obstruction

– Associated with airway Associated with airway hyperreactivityhyperreactivity

– Reversible with treatmentReversible with treatment

How do you measure airflow How do you measure airflow obstruction?obstruction?

Lung Function – Peak Flow RatesLung Function – Peak Flow Rates

Spirometry & Pulmonary Function testsSpirometry & Pulmonary Function tests

SpirometrySpirometry

SpirometrySpirometry

FEV1

Spirometry – confirm airflow obstructionSpirometry – confirm airflow obstruction

• Reduced FEV1Reduced FEV1– Forced expiratory volume in Forced expiratory volume in

1 second1 second

Reduced FVCReduced FVCForced vital capacityForced vital capacity

Reduced FEV1/FVC ratioReduced FEV1/FVC ratioRatio < 70%Ratio < 70%

Flow volume loopsFlow volume loops

Normal Airflow obstruction

Airway HyperreactivityAirway Hyperreactivity• PharmacologicalPharmacological

– HistamineHistamine– MethacholineMethacholine

• OccupationalOccupational– Agents encountered at workAgents encountered at work

• AllergenAllergen– House dust miteHouse dust mite

O’Byrne – Chest 2003

Asthma - diagnosisAsthma - diagnosis

• Clinical diagnosisClinical diagnosis• Confirmatory testsConfirmatory tests

– Peak flow variabilityPeak flow variability– SpirometrySpirometry– Bronchial Bronchial

hyperreactivityhyperreactivity• AtopyAtopy

– Total IgETotal IgE– Specific IgESpecific IgE– Skin testsSkin tests

200

300

400

500

M T W Th Fr Sat Su Th Fr Sa Su

untreated treated

PeakExpiratory

Flow(l/min)

Skin testing for atopySkin testing for atopy

Is asthma increasing?Is asthma increasing?

Copyright ©2007 BMJ Publishing Group Ltd.

Ross Anderson, H et al. Thorax 2007;62:85-90

Patients consulting general practitioners for asthma per 10 000 population, England and Wales, 1955-1998.

Data from the GP Research Database (GPRD) and Morbidity Statistics in General Practice (MSGP).



Hospital admissions for asthma by age, England and Wales 1958-2003.



Mortality from asthma by age, England and Wales, 1955-2004. y, year.

What causes asthma?What causes asthma?

Airflow ObstructionAirflow Obstruction

Asthma - inflammatory conditionAsthma - inflammatory condition

• Airway inflammationAirway inflammation– Lymphocytes, Lymphocytes,

eosinophils & mast cellseosinophils & mast cells• Epithelial denudationEpithelial denudation• Submucosal infiltrationSubmucosal infiltration

– Lymphocytes (Th2) & Lymphocytes (Th2) & eosinophilseosinophils

• Subepithelial fibrosisSubepithelial fibrosis– Airway remodellingAirway remodelling

• Mucus productionMucus production

Lymphocyte eosinophils

AllergyAllergy

GeneticsGeneticsGenome screen for asthma / asthma-related intermediate phenotypes

Carrol W, Paed Resp Rev 2005

Asthma

Total IgE

Eosinophils

% FEV1

BHR

Skin prick – allergen mixLOD

Score

Tantisara & Weiss

Tantisara & Weiss

AllergensViruses

Inhalants (smoking)

Drugs

What triggers asthma?What triggers asthma?

Triggers of asthmaTriggers of asthma• InfectionsInfections• AllergensAllergens• Occupational agentsOccupational agents• ExerciseExercise• Cold airCold air• HyperventilationHyperventilation• DrugsDrugs• FoodsFoods• Psychological factorsPsychological factors

Symptomsof asthma

Susceptibleairway

Trigger Factors

How do you treat asthma?How do you treat asthma?

Rational treatmentRational treatment

• Right Right patientpatient– Is the diagnosis correct? - Asthma/COPD/otherIs the diagnosis correct? - Asthma/COPD/other

• Right Right drugs drugs – Evidence basedEvidence based

• Right Right timetime– Appropriate assessment of e.g. severityAppropriate assessment of e.g. severity

• Right Right means of deliverymeans of delivery– Oral, IV, inhaled, subcutaneousOral, IV, inhaled, subcutaneous

Drugs in airflow obstructionDrugs in airflow obstruction

• Which drugs?Which drugs?• What response?What response?

– BronchodilationBronchodilation– Suppression of inflammation / mucus secretionSuppression of inflammation / mucus secretion

• Which route of delivery?Which route of delivery?– Inhaled / nebulisedInhaled / nebulised– OralOral– intravenousintravenous

• Side effects?Side effects?

Short-acting Short-acting 22-agonist bronchodilators-agonist bronchodilators

• SalbutamolSalbutamol• TerbutalineTerbutaline

• ““RelieverReliever” inhalers” inhalers

• Relax airway muscle toneRelax airway muscle tone– ““opens” airwaysopens” airways– resistance to air flowresistance to air flow

Long-acting bronchodilatorsLong-acting bronchodilators

• Long-acting Long-acting 22 agonists agonists

– SalmeterolSalmeterol– FormoterolFormoterol

• 12 hr (+) duration of action12 hr (+) duration of action

Clinical effects of Clinical effects of 22 agonists agonists

• PositivePositive– Smooth muscle relaxationSmooth muscle relaxation– vascular permeabilityvascular permeability– mucociliary clearancemucociliary clearance– inflammatory mediatorsinflammatory mediators– cholinergic transmissioncholinergic transmission

• Negative (potentially)Negative (potentially)– Tachycardia (palpitations)Tachycardia (palpitations)– KK++

– TremorTremor– tachyphylaxistachyphylaxis

• Negative effects more Negative effects more pronounced with pronounced with dosedose

Anticholinergic bronchodilatorsAnticholinergic bronchodilators

• smooth muscle tone (vagal)smooth muscle tone (vagal)• secretionssecretions• e.g. e.g. ipratropium bromideipratropium bromide (Atrovent (Atrovent®®))

– Less effective than Less effective than 22 agonists agonists

– May be useful in addition to May be useful in addition to 22 agonists agonists

– Few side effectsFew side effects• Theoretically Theoretically dry eyes, mouth, urinary retention dry eyes, mouth, urinary retention• Poor mucosal absorption limits side-effectsPoor mucosal absorption limits side-effects

SteroidsSteroids

• Inhaled steroidsInhaled steroids• ““Preventer” inhalersPreventer” inhalers

– BeclomethasoneBeclomethasone– Fluticasone propionateFluticasone propionate– BumetanideBumetanide– MometasoneMometasone– CiclesonideCiclesonide

Combination inhalersCombination inhalers

• Combined inhaled steroid and LABDCombined inhaled steroid and LABD– Seretide = Fluticasone + SalmeterolSeretide = Fluticasone + Salmeterol– Symbicort = Budesonide + Formoterol Symbicort = Budesonide + Formoterol

• Some evidence of increased efficacySome evidence of increased efficacy• Probably increased concordance (compliance)Probably increased concordance (compliance)• Decreased flexibility - ability to vary dose in self Decreased flexibility - ability to vary dose in self

managementmanagement

Steroids - cellular effectsSteroids - cellular effects

Steroids - anti-inflammatory effectSteroids - anti-inflammatory effect

0

100

200

300

400

500

1 2 3 4 5 6 7 8 9 10 11 12 13 14

Pea

k fl

ow

(L

/min

)

1 2 3 4 5 6 7 8 9 10 11 12 13 14

Pea

k fl

ow

(L

/min

)

Days

Prednisolone 30 mg o.m. x 14 days

Prednisolone 30 mg o.m. x 14 days

COPD

ASTHMA

0

100

200

300

400

500

TRIAL OF STEROIDSTRIAL OF STEROIDS

Steroids - side effects - oral (?inhaled)Steroids - side effects - oral (?inhaled)

• Adrenal suppressionAdrenal suppression– Dose, duration and frequency dependentDose, duration and frequency dependent

• Bone metabolism (Osteoporosis)Bone metabolism (Osteoporosis)– HPA axis, CaHPA axis, Ca++ absorption, renal tubular Ca absorption, renal tubular Ca++ reabsorption reabsorption

– Slow, dose-dependent Slow, dose-dependent • GrowthGrowth• EyesEyes• Metabolic effectsMetabolic effects

– Glucose toleranceGlucose tolerance

Asthmatic smokers - Peak flow rates Asthmatic smokers - Peak flow rates (PFR)(PFR)

-20

0

20

40

Mean (SE) changein morning PFR

followingtreatment period

(L/min)

*/**

NON-SMOKERS SMOKERS

placebo fluticasone placebo fluticasone

* greater than placebo** greater than smokers' fluticasone response

Leukotriene antagonistsLeukotriene antagonists

• BronchodilatorBronchodilator• Protect vs broncho-Protect vs broncho-

constrictionconstriction• bronchial bronchial

hyperreactivityhyperreactivity• Anti-inflammatory Anti-inflammatory

actionaction

placebo

LKT antagonist

Inhaled steroid

Magnesium sulphateMagnesium sulphate

• Evidence of bronchodilator effectEvidence of bronchodilator effect• Evidence of clinical effect only in acute severe asthmaEvidence of clinical effect only in acute severe asthma

– PFR by c. 50 l/minPFR by c. 50 l/min– FEV1 by c. 10%FEV1 by c. 10%

• No effect on hospital admission except in severe groupNo effect on hospital admission except in severe group

• Dose 2g IV over 20 minutesDose 2g IV over 20 minutes

Management of asthmaManagement of asthma

Adults

Non-Pharmacological ManagementNon-Pharmacological Management• Primary preventionPrimary prevention

– Breast FeedingBreast Feeding– Allergen avoidanceAllergen avoidance– Nutritional supplementsNutritional supplements– Avoid tobacco smokeAvoid tobacco smoke

• Secondary preventionSecondary prevention– Avoid triggersAvoid triggers– Allergen avoidanceAllergen avoidance

• Limited evidence HDMLimited evidence HDM• No evidence for petsNo evidence for pets

– Avoid smokingAvoid smoking– ImmunotherapyImmunotherapy– Buteyko (symptoms)Buteyko (symptoms)– Air ionisersAir ionisers

Exercise is good for you!Exercise is good for you!

Occupational asthmaOccupational asthma• Respiratory SensitisersRespiratory Sensitisers

– ““cause” asthmacause” asthma

• IsocyanatesIsocyanates• FlourFlour• Wood dustsWood dusts• Colophony (soldering)Colophony (soldering)• LatexLatex• Animal dustAnimal dust

– Labs, farms, shellfishLabs, farms, shellfish

Paediatric AsthmaPaediatric Asthma

Paediatric asthmaPaediatric asthma

Children age 5-12 yrs

Children Less than 5 yrs

SummarySummary• What is asthma?What is asthma?• What “causes” it?What “causes” it?

– GeneticsGenetics– EnvironmentEnvironment– Association with allergyAssociation with allergy– inflammationinflammation

• How to measure lung How to measure lung functionfunction– Airflow obstructionAirflow obstruction

• Management of asthmaManagement of asthma– PharmacologyPharmacology– Guidelines – stepsGuidelines – steps

• Step up Step up and and step downstep down

For further InformationFor further Information• Asthma UKAsthma UK

– www.asthma.org.ukwww.asthma.org.uk

• British Thoracic SocietyBritish Thoracic Society– www.brit-thoracic.org.ukwww.brit-thoracic.org.uk

Asthma Module 1 Session 1 | 24/03/2010 | All

Health & Medicine

Transcript of Asthma Module 1 Session 1 | 24/03/2010 | All