Optimizing Management of asthma and COPD.ppt

Brief Overview on "Optimizing management of asthma and COPD" including importance of optimizing management, pathogenesis of asthma and COPD, exacerbations, treatment of exacerabtions, management strategies etc.

1. Dr. Surinder K Jindal
www.jindalchest.com

2. Definition of COPD & Asthma
COPDis a preventable and treatable disease with some significant
extrapulmonary effects that may contribute to the severity in individual patients.
It is characterized by airflow limitation that is not fully reversible. The airflow
limitation is usually progressive and associated with an abnormal inflammatory
response of the lung to noxious particles or gases.
Asthma -Chronic Inflammatorydisorder of airways
characterized byEpisodic, Reversiblebronchospasm
resulting from an exaggerated bronchoconstrictor response
to various stimuli.

3. •Differentcauses
•Differentinflammatorycells
•Differentmediators
•Differentinflammatoryconsequences
•Differentsites
COPD IS NOT ASTHMA
•Different response to treatment

4. Inflammation
Asthma COPD
Inflammatory cells Mast cell, Eosinophil Neutrophil
CD4+ cells CD8+ cells
Macrophages + Macrophages ++
Inflammatory LTB4, histamine LTB4
mediators IL-4, IL-5, IL-13 TNF-a
Oxidative stress + Oxidative stress +++
Inflammatory effect All airways Peripheral airways
AHR +++ AHR ±
Epithelial shedding Epithelial metaplasia
Fibrosis + Fibrosis ++
No parenchymal
involvement
Parenchymal destruction
Mucus secretion + Mucus secretion +++
Response to steroid +++ ±

5. LUNG INFLAMMATION
COPD PATHOLOGY
Oxidative
stress Proteinases
Repair
mechanisms
Anti-proteinases
Anti-oxidants
Host factors
Amplifying mechanisms
Cigarette smoke
Biomass particles
Particulates
Source: Peter J. Barnes, MD
Pathogenesis of
COPD

6. INFLAMMATION
Airflow Limitation
SYMPTOMS
Cough Wheeze
Dyspnoea
TRIGGERS
Allergens, Exercise,
Cold Air, SO2 Particulates
Asthma
Pathogenesis:
Airway
Hyperresponsiveness
Genetic*
INDUCERS
Allergens,Chemical sensitisers,
Air pollutants, Virus infections

7. Investigations
Asthma COPD
Chest radiograph Normal Suggestive
Spirometry Obstructive defect Obstructive defect
Good reversibility Poor reversibility
AHR Very common May be present
DLCO Normal / Increased Decreased
Lung elastic recoil Normal Increased
Thoracic CT scan Airway wall thickeningAirway wall thickening
Mucus plugs (ABPA) Emphysema
Air trapping ± Air trapping
In general, investigations are poor discriminators

8. The Overlap
COPD
Neutrophils
No airway
hyperresponsiveness
Less bronchodilator
response
Limited steroid
response
Wheezy
bronchitis
10%
Asthma
Eosinophils
Airway
hyperresponsiveness
Bronchodilator
response
Steroid
response

9. Basic Principles of Management of Asthma
And COPD
Removal/Avoidanceofrisk-factor/s
Pharmacotherapy
Bronchodilators
Anti-inflammatorydrugs
(Corticosteroids)
Supportivetherapy
Non-pharmacologicalmanagements
ManagementofAcuteExacerbations
ManagementofComplications

10. Bronchodilators
Bronchodilatormedications-centraltosymptommanagement
Reducebreathlessness,improvelungfunction,improveHRQOL
Inhaledtherapyispreferred
Choicebetweenβ2-agonist(shortactingandlong-acting),anticholinergic
agents,theophyllineoracombinationofthesedrugs

11. Inhalers vs Oral drugs
Inhalationroutepreferred
MDI,DPI,ornebulizedaerosol
MDIwithspacer-preferreddevice
DPIeasiertouse,butcostlier
Patientsshouldbeinstructedregardingproperuseoftheinhalerdeviceand
techniqueshouldbecheckedregularly
Cochrane Database Syst Rev 2002; 1: CD002170

12. Bronchodilators
Therapy-availabilityandindividualresponseintermsofsymptomrelief
andsideeffects
Prescribed-onas-neededorregularbasistopreventorreducesymptoms
Long-actingdrugsaremoreconvenient
Combinationofβ2-agonistandanticholinergicagents-betterthaneither
druggivenalone(lungfunction)
Eur Respir J 2005; 25: 1084-1106

13. Anti-inflammatory Drugs
Corticosteroids:
Inhaled(Beclomethasone,Budesonide,
Fluticasone,Mometasone,Triamcinalone)
Oral(Prednisone,Prednisolone,
Dexamethasone,Methylprednisolone)
Parenteral(Hydrocortisone,
Methylprednisolone,Dexamethasoneetc)
Immunosuppressants
Immunomodulators

14. What are your objectives while treating a
patient with COPD?
No treatment has shown to reverse the pre-existing changes
that have occurred in COPD

15. Four Components of COPD
Management
1.Assessandmonitordisease
2.Reduceriskfactors
3.ManagestableCOPD
Education
Pharmacologic
Non-pharmacologic
4.Manageexacerbations

16. Objectives
Prevent disease progression
Relieve symptoms
Improve exercise tolerance
Improve health status
Prevent and treat exacerbations
Prevent and treat complications
Reduce mortality
Minimize side effects from treatment
Am J Respir Crit Care Med 2001; 163: 1256-1276

17. Management of stable COPD
NoneoftheexistingmedicationsforCOPDhasbeenshowntomodifythe
long-termdeclineinlungfunctionthatisthehallmarkofthisdisease
(EvidenceA)
Therefore,pharmacotherapyforCOPDisusedtodecreasesymptoms
and/orcomplications

18. Basic considerations
Heterogeneouscondition
Allpatientsshouldbeviewedasindividuals-presentation,history,
symptoms,disability;responsetodrugs
Importantfactors-acceptability,adverseeffects,efficacy
Drugtitration-airflowobstruction,symptoms,exercisetolerance,
frequencyofexacerbations

19. Which bronchodilator???
1. Theophylline
2. Ipratropium
3. Tiotropium
4. Beta-2 agonists

20. Bronchodilator in COPD
Predominantparasympathetictone–firstchoice–anticholinergic
TiotropiumorIpratropium
TiotropiumreducedtheCOPDexacerbation(OR0.74;95%CI0.66to
0.83)andhospitalizations(OR0.64;95%CI0.51to0.82)comparedto
placebooripratropium
Combinationoftiotropiumandformoterolideal
Cochrane Database Syst Rev 2005; 2: CD002876

21. Cochrane Database Syst Rev 2005; 2: CD002876

22. Commonly used bronchodilators
Drugs MDI/DPI (μg/dose) Oral (mg)
Beta agonists
Salbutamol 100-200 2-4mg tid/qid
Terbutaline 250-500 2.5-5 mg tid
Salmeterol 25-50
Formoterol 6-12
Bambuterol 10-20mg/day
Anticholinergics
Ipratropium 40-160
Tiotropium 18
Methylxanthines
Theophyllines 200-600 mg/day

23. IstherearoleforICSinCOPD?
1.Yes
2.No
3.Limited
4.Acuteexacerbation
Is there a role for ICS in COPD?

24. Inhaled corticosteroids in COPD
Anti-inflammatoryeffectswithICSinCOPD
include:
Attenuationofneutrophilactivation&
recruitment
Reductionofneutrophilchemotaxis
ReductionintheCD8/CD4ratio
ReductioninIL-8levels
Reductionineosinophils&RANTES,
associatedwithexacerbationsofCOPD.
Decreasedsymptoms
Decreasednumberandseverityof
exacerbations
Improvedhealthstatus
Reductionofcardiacevents-IHD
Decreasedmortality(?)
Options:beclomethasone,budesonide,fluticasone,triamcinolone
Oralglucocorticosteroidsnotrecommendedforlong-termuseinCOPD

25. Cochrane review on
efficacy of the use of ICS in COPD
Forty-sevenprimarystudieswith13,139participantsmettheinclusion
criteria.
LongtermuseofICS(>sixmonths)didnotsignificantlyreducetherate
ofdeclineinFEV1inCOPDpatients
LongtermuseofICSreducedthemeanrateofexacerbations
Therewasanincreasedriskoforopharyngealcandidiasisandhoarseness.
Nomajoreffectonfracturesandbonemineraldensityover3years.
Cochrane Database Syst Rev. 2007 Apr 18;(2):CD002991.

26. 1.Mucolytics
2.Immunomodulators
3.Antibiotics
4.Respiratorystimulants
What other therapies can be used in
patients with COPD?

27. Other drugs
Vaccines–InfluenzaandPneumococcus–inallpatients
Oralmucolytics-reducetheviscosityofsputum,noeffectonlungfunction
Oralimmunostimulatoryagent–OM-85BV(extractof8bacteria)-
recurrentexacerbations
Antioxidants-N-acetylcysteine-noclearrole
Am J Respir Crit Care Med 2001; 163: 1256-1276

28. Other drugs
Respiratorystimulants–almitrineanddoxapram–norole
Antibiotics–noroleinstableCOPD
Others-Nedocromil,leukotrienemodifiersandalternateformsof
medicine-noclearrole
Am J Respir Crit Care Med 2001; 163: 1256-1276

29. IV: Very SevereIII: SevereII: ModerateI: Mild
Therapy at Each Stage of COPD
FEV
1
/FVC < 70%
FEV
1
>80%
predicted
FEV
1
/FVC < 70%
50% <FEV
1
< 80%
predicted
FEV
1
/FVC < 70%
30% <FEV
1
< 50%
predicted
FEV
1
/FVC < 70%
FEV
1
< 30% predicted
orFEV
1
< 50% predicted
plus chronic
respiratory failure
Addregular treatment with one or more long-acting
bronchodilators (when needed); Addrehabilitation
Addinhaled glucocorticosteroids if
repeated exacerbations
Active reduction of risk factor(s); influenza vaccination
Addshort-acting bronchodilator (when needed)
Addlong term oxygenif chronic
respiratory failure. Consider
surgical treatments

30. Management of Stable COPD
Non-Pharmacologic Treatments
Rehabilitation:AllCOPDpatientsbenefitfromexercisetrainingprograms,
improvingwithrespecttobothexercisetoleranceandsymptomsofdyspnea
andfatigue(EvidenceA).
OxygenTherapy:Thelong-termadministrationofoxygen(>15hoursperday)
topatientswithchronicrespiratoryfailurehasbeenshowntoincreasesurvival
(EvidenceA).

31. Exacerbations
What are they?
An event which in the natural course of the disease characterized by a
change in the patient’s baseline dyspnea, cough and/or sputum and beyond
the normal day-to-day variations
Acute in onset
May warrant a change in regular medication
•Patientsarelivingwithdaily
breathlessnessandcough
•Fearaboutworsening
•Unpredictable

32. Exacerbations result in worsening
of quality of life: Data from GLOBE study
Am J Med 2006;119(10A):S38-S45

33. Treatment of exacerbation
Inhaledbronchodilators:salbutamol/ipratropium
Oralprednisolone30-40mgfor7-10days
Antibiotics
–respiratoryquinolones,macrolides,co-amoxyclav,2
o
or3
o
cephalosporins
–FEV
1<35%withrecurrentcoursesoforalsteroidsetc:FQwith
antipseudomonalactivity

34. Acute exacerbations are defining moments in a COPD
patient particularly if hospitalization is needed
Patient
Death
Worsening quality of life
Costs
Disease
Accelerated progression
Enhanced airway inflammation
Adverse effects of oral steroids
It is no less serious than an acute myocardial infarction

35. Goals of Asthma Management
1.Minimal(ideallyno)symptoms
2.Minimal(orno)symptomsonexercise
3.Minimalneedforrelievers
4.Noexacerbations
5.Nolimitationofphysicalactivity
6.Normal(ornearnormal)PFT
7.Minimalsideeffectsofdrugs
8.Preventionofirreversibleobstruction
9.Preventasthmarelatedmortality

36. Stage-wise Control
1.Daytimesymptoms<1/week Relievers
andnighttime<2/month
2.Needforrelievers<1/week Controllers
3.Needforrelievers<3/day Doctorvisit
4.Requirementfordrugs (aspertable)
5.Maintenanceofgoalsfor Stepdown
atleast3months (25%reductionindosages)

37. Anti-asthma Drugs
I.Controllers
Glucocorticoids–Inhaled/Systemic
Inhaledlongacting-2agonists
Oraltheophyllines
Leukotrienereceptorantagonists
Cromones
Orallongacting-2agonist
II.Relievers
Rapidacting2agonists
Oralglucocorticoids
Inhaledanticholinergics
Oralshortacting2agonists

38. GINA Guidelines for Asthma
Mildintermittent :
Mildpersistent :
Moderatepersistent :
SeverePersistent :
SOS bronchodilators
ICS + LABA + LTRA
+ AC + OS
ICS + LABA/LTRA
combination
ICS/LTRA
At each step SOS bronchodilator therapy is required
GINA 2004

39. Asthma Control vs. Severity
AsthmaControl
Clinicalstatusofdisease(with
ongoingtherapy)
Patient-centeredapproach
AsthmaSeverity
Underlyingdisease(asthma)
(inabsenceofanytreatment)
Physician-centeredapproach

40. Asthma: Levels of Control
Controlled
(All of the
following)
Partly Controlled
(Any measure
present)
Un-controlled
Nocturnal symptoms
or awakening
None Any ≥ 3 features of
partly
controlled
asthma
Daytime symptoms ≤2 per week > 2 per week
Limitation of activitiesNone Any
Need for reliever or
rescue treatment
≤2 per week > 2 per week
FEV1 or PEF Normal <80% predicted
42
Adapted from GINA (Global Initiative for Asthma) guidelines 2010

41. Asthma Management
Maintain“wellcontrolled”state
Adddrugs,step-wise,determinedbycontrol
ICS&LABAsconstitutethecornerstoneoftreatment
UseofSABA,asneeded
SMARTapproach(UseofsingleinhalerformaintenanceandSOSuse)

42. Difficult Asthma
Asthmawhichisdifficulttocontrolwithmaximumtreatment
recommendedasappropriateforthatstage…
Persistenceofsymptoms,frequentexacerbationsorairwayobstruction
despitehigh(oroptimum)medication

43. Considerations in Management
of SR/SD Asthma
Correctdiagnosticworkup
SRasthmaticsdorespondtobronchodilatortherapyandsuchmedications
shouldbeinstitutedearlyasrescuetherapy.
Presenceofpersistentairwayinflammationpredisposesthemtoairway
remodelingandlongtermirreversibleairwaysdiseases.Thusitisof
paramountimportancetotreattheirinflammationearlyandeffectively.

44. SUMMARY-Asthma
Airwayinflammation,aprominentfeatureinasthma,needstobetargetedwith
effectivemedicationtoachieveasthmacontrol.
Appropriateguidelinesneedtobefollowedforbestresults.ICSina
combinationwithLABAsremainthecornerstoneoftreatment.
Amajorunmetneedistotreatpatientswithsevereasthmawhoarerelatively
corticosteroid-resistantmoreeffectively.
Anumberofpharmaceuticalapproachescurrentlyinclinicaldevelopment,
showpromiseintargetingspecificcytokines,inflammatorycells,or
inflammatorymechanisms.

45. Summary -COPD
CurrenttherapyforCOPDremainssub-optimal
ConcomitantuseofLABAswithICSinfluencesbothairflowobstruction&
airwayinflammation.TheuseofICS&LABAincombinationforsevereCOPD
helpinachievingpatientcenteredoutcomes.
Theclinicalbenefitsaremanifestedbythereductioninthenumberandseverity
ofexacerbations,lungfunctionimprovement&improvedhealthstatusof
COPDpatients

46. Conclusion
Budesonide/formoterolwasshowntobeaneffectivetreatmentforthe
managementofmoderate-to-severeCOPDin:
•Reducingsevereexacerbations
•Providingearlyandsustainedimprovementsinlungfunctionand
symptoms,Improvementsinhealth-relatedqualityoflife.
•Budesonide/formoteroldemonstratedasimilarsafetyprofiletoplacebo.
Szafransky Eu Resp J 2003;21:74-

47. Important Treatment Recommendations
GINA NIH BTS
1Management steps 4 4 5
2Inhaled CS Steps
2 to 4
Low doses
Step 2
Steps
2 to 5
3Add on Therapies
LABA Steps
3 and 4
Step 2
onwards
Step 3
onwards
SR Theophylline Step 4 -do- -do-
LT modifiers -do- -do- -do-
Oral CS -do- -do- Step 5

48. PDE-4 Inhibitors
Roflumilast,orallyactivePDE-4inhibitor,dose-relatedinhibitionoflate-
phasebronchospasmfollowingallergenchallengeinmildasthma
Improvementsinlungfunction(FEV1),asthmasymptoms,andreductions
inrescuemedicationuse,vsICS
Ciclamilast-mediatesAHRthroughinhibitionofPDE-4DmRNA
expressionanddown-modulationofPDE-4activity,reducedinflammation
andmucushypersecretion
Ann Allergy Asthma Immunol 2006; 96:679–686
Eur J Pharmacol 2006; 547:125–135

49. A new paradigm: A systemic disease,
needs a systemic approach
Asthmaisasystemicdisease
Required:
Newclassesthatareeffectiveinseverepoorlycontrolledasthma
Anoraltreatmentthatisaseffectiveasinhaledcorticosteroidswithoutany
sideeffects
Drugsthatmodifyorevencurethedisease
J Allergy Clin Immunol 2007

50. Well Controlled asthma
Noorminimalsymptoms
Minimaluseofrescuemedication
Nosignificantlimitationinactivity
(Near)normallungfunction
GINA-2006

51. Algorithmic Management of Acute Severe Asthma
Unable to complete a sentence in one breath, RR > 30/minute, use of
accessory muscles of respiration, HR > 120/minute, pulsusparadoxus> 25
mm Hg, extensive wheeze, PEFR < 50%, PaO2 < 60 mm Hg, PaCO2 > 45
mm Hg
Salbutamol2.5 mg q 15 minutes + Ipratropium250 mcg q 15 minutes + PO
prednisolone40-60 mg/day
Sustained improvement at 1hour-
Discharge on oral steroids and
bronchodilators
No improvement-ADMISSION IN
HOSPITAL OR ICU

52. Management of SRA/SDA
Highdoseinhaledcorticosteroidsarethefirstlineoption
Omalizumabiseffectiveinreducingoralcorticosteroidrequirementsin
allergicasthma
Methotrexate,gold,andcyclosporinehavecorticosteroidsparingeffects
clinicallythatmustbeweighedagainstaseriousadverseeffectprofile
Nebulizeddiureticsandlidocaine,withalowadverseeffectprofile,offer
promisingresultsbutrequirefurtherstudy
Randhawaet al. –30 yrs review

53. Acute asthma: Algorithmic management
Good Response
Observe for at
least 1 hour
If Stable,
Discharge to
Home
Initial Assessment
History, Physical Examination, PEF or FEV
1
Initial Therapy
Bronchodilators; O
2if needed
Incomplete/Poor Response
Add Systemic Glucocorticosteroids
Good Response
Discharge Poor Response
Admit to Hospital
Respiratory Failure
Admit to ICU

54. Use of ACT
Differentpopulationsandsub-populations(Literacy,language,socio-
economicfactors,urban/ruralresidence,age,sexetc.)
Primaryhealth-caresettings
Abandoninglungfunctionmeasurements
Under-assessmentandundertreatment

55. GINA Classification of Control
Controlled
 Noorminimalsymptoms
 Minimaluseofrescuemedication
 Nosignificantlimitationinactivity
 (Near)normallungfunction
Partlycontrolled
Poorlycontrolled
GINA-2006

56. A new paradigm: A systemic disease
needs a systemic approach
Asthmaisasystemicdisease
Newclassesthatareeffectiveinseverepoorlycontrolledasthma
Anoraltreatmentthatisaseffectiveasinhaledcorticosteroidswithoutany
sideeffects
Drugsthatmodifyorevencurethedisease
J Allergy Clin Immunol 2007;120:1269-75

57. Instruments for control measurements
AsthmaControlTest(ACT)
AsthmaControlQuestionnaire(ACQ)
AsthmaTherapyAssessmentQuestionnaire(ATAQ)
AsthmaControlScoringSystem(ACSS)
Asthma-symptomdiary