CHRONIC OBSTRUCTIVE CHRONIC OBSTRUCTIVE PULMONARY DISEASE PULMONARY DISEASE Treatment OpportunitiesTreatment Opportunitiesin a Heartsink Diseasein a Heartsink Disease

Jim ReidJim Reid

COPD – Treatment COPD – Treatment OpportunitiesOpportunities

Target of treatmentTarget of treatment To improve quality of lifeTo improve quality of life To improve lung functionTo improve lung function To prevent deteriorationTo prevent deterioration To prevent exacerbationsTo prevent exacerbations To reduce shortness of breathTo reduce shortness of breath To decrease mortalityTo decrease mortality

COPD – Treatment COPD – Treatment OpportunitiesOpportunities

Causative elementsCausative elements Oxidative stress associated with Oxidative stress associated with

neutrophil infiltrationneutrophil infiltration Elastin breakdownElastin breakdown Narrowing of small airways – Narrowing of small airways –

inflammation and scarringinflammation and scarring Increase in goblet cell size and Increase in goblet cell size and

number.number.

COPD – Treatment COPD – Treatment OpportunitiesOpportunities

The common denominator is The common denominator is cigarette smoke.cigarette smoke.

COPDCOPD

COPD – Treatment COPD – Treatment OpportunitiesOpportunities

Other CausesOther Causes Burning of biomass fuelsBurning of biomass fuels Industrial pollutionIndustrial pollution Mining – coal, silica etcMining – coal, silica etc Car exhaust pollution. Car exhaust pollution.

AIR POLLUTIONAIR POLLUTION

Air pollution resulting from the burning of wood and Air pollution resulting from the burning of wood and other biomass fuels is estimated to kill two million other biomass fuels is estimated to kill two million

women and children each year.women and children each year.

GOLD 2006GOLD 2006

COPD – Treatment COPD – Treatment OpportunitiesOpportunities

Opportunity # 1Opportunity # 1 Smoking cessationSmoking cessation Adequate ventilation if exposed Adequate ventilation if exposed

to biomass burning – Cooking.to biomass burning – Cooking. Avoidance of exposure to Avoidance of exposure to

industrial pollution etcindustrial pollution etc Adequate breathing protection. Adequate breathing protection.

COPD – Treatment COPD – Treatment OpportunitiesOpportunities

Opportunity # 1Opportunity # 1

Influenza VaccinationInfluenza Vaccination Pneumococcal Vaccination.Pneumococcal Vaccination.

COPD – Treatment COPD – Treatment OpportunitiesOpportunities

COPD - a chronic inflammatory COPD - a chronic inflammatory disease – large numbers of disease – large numbers of

neutrophils, neutrophils, macrophages, macrophages, CD8 T lymphocytesCD8 T lymphocytes

COPD – Treatment COPD – Treatment OpportunitiesOpportunities

Inflammation leads toInflammation leads to

FibrosisFibrosis Small airway narrowingSmall airway narrowing Decrease in FEV1.Decrease in FEV1.

COPD – Treatment COPD – Treatment OpportunitiesOpportunities

DifficultiesDifficulties

DiagnosisDiagnosis Progression - outcomeProgression - outcome

COPD – Treatment COPD – Treatment OpportunitiesOpportunities

DiagnosisDiagnosis

SymptomsSymptoms SpirometrySpirometryProgression of symptoms with Progression of symptoms with

increase in airway wall thickness, increase in airway wall thickness, decrease in surface area, decrease in surface area, resulting in decrease in FEV1. resulting in decrease in FEV1.

COPD DiagnosisCOPD Diagnosis

HISTORYHISTORY COPDCOPD ASTHMASTHMAA

Smoker or ex Smoker or ex smokersmoker

Nearly Nearly alwaysalways

VariableVariable

““Chesty Chesty Childhood”Childhood”

InfrequentInfrequent OftenOften

Chronic Cough Chronic Cough and Sputumand Sputum

CommonCommon InfrequentInfrequent

BreathlessnessBreathlessness Gradual and Gradual and ProgressiveProgressive

IntermittentIntermittent

COPD DiagnosisCOPD DiagnosisINVESTIGATIOINVESTIGATIONN

COPDCOPD ASTHMAASTHMA

FEV1FEV1 Always Always ReducedReduced

VariableVariable

Daily Daily Variations in Variations in

PEFRPEFR

MinimalMinimal ““Morning dip Morning dip + day to day+ day to day

Objective Objective Response to Response to

SABASABA

Nil / PartialNil / Partial Partial / Partial / CompleteComplete

Objective Objective Response to Response to

Corticosteroid Corticosteroid TrialTrial

Partial Partial Response in Response in

10 - 20%10 - 20%

Good Good Response in Response in

MajorityMajority

COPD – Treatment COPD – Treatment OpportunitiesOpportunities

OutcomeOutcome

Impossible to predict progression Impossible to predict progression or outcome of disease in patient or outcome of disease in patient with Gold stage 0. with Gold stage 0.

COPD – Treatment COPD – Treatment OpportunitiesOpportunities

ComorbiditiesComorbidities

Co - morbities increase with Co - morbities increase with progression of the disease – progression of the disease – decreased lung function, reduced decreased lung function, reduced exercise tolerance, muscle exercise tolerance, muscle catabolismcatabolism

COPD – Treatment COPD – Treatment OpportunitiesOpportunities

Opportunity # 2Opportunity # 2

BronchodilatationBronchodilatation

The cornerstone of treatmentThe cornerstone of treatment

COPD – Treatment COPD – Treatment OpportunitiesOpportunities

Bronchodilator choiceBronchodilator choice Short acting beta agonistShort acting beta agonist Long Acting beta agonistLong Acting beta agonist Anticholinergic – long or short Anticholinergic – long or short

actingacting CombinationCombination TheophyllineTheophylline

COPD – Treatment COPD – Treatment OpportunitiesOpportunities

Bronchodilator ChoiceBronchodilator Choice

ConsiderConsider PricePrice Effectiveness including side Effectiveness including side

effectseffects Individual Properties.Individual Properties.

COPD – Treatment COPD – Treatment OpportunitiesOpportunities

Tiotropium (Spiriva)Tiotropium (Spiriva) Long term maintainenceLong term maintainence Previous trial (Sample or Previous trial (Sample or

Atrovent)Atrovent) Grade 4 or 5 MRC dyspnoea scaleGrade 4 or 5 MRC dyspnoea scale Smoking and influenza addressed. Smoking and influenza addressed. FEV1 60% or less predicted. FEV1 60% or less predicted.

COPD – Treatment COPD – Treatment OpportunitiesOpportunities

TiotropiumTiotropium Available for moderate to severe Available for moderate to severe

asthma.asthma. Reduction in exacerbationsReduction in exacerbations Reduction in sputum productionReduction in sputum production No increase in pneumoniaNo increase in pneumonia

COPD – Treatment COPD – Treatment OpportunitiesOpportunities

Treatment of InflammationTreatment of Inflammation Inflammatory basis of asthma Inflammatory basis of asthma

known since the time of Osler known since the time of Osler (1900)(1900)

Emphasis of treatment for 70 Emphasis of treatment for 70 years was bronchodilatationyears was bronchodilatation

Inflammation not targeted till mid Inflammation not targeted till mid 1960’s. 1960’s.

COPD – Treatment COPD – Treatment OpportunitiesOpportunities

Inhaled Corticosteroids in COPDInhaled Corticosteroids in COPD Ineffective in neutrophil induced Ineffective in neutrophil induced

inflammationinflammation

HoweverHowever IHCs in significant COPD have IHCs in significant COPD have

been shown to reduce been shown to reduce exacerbation rate.exacerbation rate.

COPD – Treatment COPD – Treatment OpportunitiesOpportunities

Importance of ExacerbationsImportance of Exacerbations While lung function steadily While lung function steadily

declines with age, it declines declines with age, it declines more rapidly in sufferers of COPD. more rapidly in sufferers of COPD.

With each exacerbation, lung With each exacerbation, lung function never quite returns to function never quite returns to the previous statethe previous state

COPD – Treatment COPD – Treatment OpportunitiesOpportunities

ExacerbationsExacerbations If exacerbations can be reduced, If exacerbations can be reduced,

deterioration in lung function deterioration in lung function maymay be be reduced.reduced.

This seems to only be relevant in GOLD This seems to only be relevant in GOLD stage 3 and 4. stage 3 and 4.

IHC in severe COPD reduces IHC in severe COPD reduces exacerbations but increases pneumonia exacerbations but increases pneumonia incidence. incidence.

There is no evidence change in disease There is no evidence change in disease outcome! outcome!

Van Schayck & Reid 2006Van Schayck & Reid 2006

COPD – Treatment COPD – Treatment OpportunitiesOpportunities

INHALED CORTICOSTEROIDS – 2011INHALED CORTICOSTEROIDS – 2011 There is increasing claims that IHCs may There is increasing claims that IHCs may

influence disease outcome in influence disease outcome in severesevere COPD. COPD. Evidence is not strongEvidence is not strong

Used in higher doses than in asthma (500Used in higher doses than in asthma (500μμg g bd fluticasone or 800bd fluticasone or 800μμg bd budesonide)g bd budesonide)

Reduce number of exacerbations which can Reduce number of exacerbations which can cause progressive deterioration of lung cause progressive deterioration of lung function, but increase incidence of pneumonia.function, but increase incidence of pneumonia.

Increasing evidence that combination IHC and Increasing evidence that combination IHC and LABA have symbiotic action and are more LABA have symbiotic action and are more effective together than when used separately. effective together than when used separately. (As in asthma) (As in asthma)

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COPD – Treatment COPD – Treatment OpportunitiesOpportunities

Opportunity # 3Opportunity # 3

Inhaled corticosteroids Inhaled corticosteroids in selected in selected patients.patients.

COPD – Treatment COPD – Treatment OpportunitiesOpportunities

Opportunity # 4 - TheophyllineOpportunity # 4 - Theophylline Some patients may benefitSome patients may benefit Now 3Now 3rdrd line treatment line treatment Narrow therapeutic window and Narrow therapeutic window and

potential for toxicity. potential for toxicity. Start low – go slowStart low – go slow Blood levels after 1 week on increased Blood levels after 1 week on increased

dose till plateau reacheddose till plateau reached Levels should be maintained 40 – 60 Levels should be maintained 40 – 60

microl / L. microl / L.

COPD – Treatment COPD – Treatment OpportunitiesOpportunities

Opportunity # 5Opportunity # 5

REHABILITATIONREHABILITATION

Exercise training - WalkingExercise training - Walking NutritionNutrition EducationEducation

GOALSGOALS Reduce symptomsReduce symptoms Improve quality of lifeImprove quality of life

COPD – Treatment COPD – Treatment OpportunitiesOpportunities

Opportunity # 6Opportunity # 6 OxygenOxygen Long term oxygen increases survival.Long term oxygen increases survival.

Goal to > PO2 to 60mmHg. Goal to > PO2 to 60mmHg. Suitable only for stage 4 disease if Suitable only for stage 4 disease if PaOPaO2 2 is <55mm Hg. is <55mm Hg.

Lung reduction SurgeryLung reduction Surgery Lung transplant.Lung transplant.

COPD – Treatment COPD – Treatment OpportunitiesOpportunities

Opportunity # 7Opportunity # 7

EXACERBATIONSEXACERBATIONS Antibiotics for infective episodesAntibiotics for infective episodes Regular bronchodilatationRegular bronchodilatation Glucocorticoids Glucocorticoids

COPD – Palliative CareCOPD – Palliative Care

A new concept with application to A new concept with application to COPDCOPD

The disease is incurable and has a The disease is incurable and has a terminal phaseterminal phase

Concept needs careful planning, a Concept needs careful planning, a team approach, with team team approach, with team consensus. consensus.

Needs frank, pragmatic, sensitive Needs frank, pragmatic, sensitive approach.approach.

COPD – Treatment COPD – Treatment OpportunitiesOpportunities

The FutureThe Future Inhibition of inflammationInhibition of inflammation

– Phosphodiesterase inhibition. Theophylline Phosphodiesterase inhibition. Theophylline is a non targeted PDE inhibitoris a non targeted PDE inhibitor

– Leukotriene B4 InhibitorsLeukotriene B4 Inhibitors– Chemokine InhibitorsChemokine Inhibitors– Tumour Necrosis Factor Inhibitors.Tumour Necrosis Factor Inhibitors.– Interleukin -10 – (A cytokine with anti-Interleukin -10 – (A cytokine with anti-

inflammatory actionsinflammatory actions