Download - Phenotypes of Asthma Elisabeth
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Elisabeth BelElisabeth Bel
Dept. Respiratory MedicineDept. Respiratory Medicine
Academic Medical CentreAcademic Medical Centre
University of AmsterdamUniversity of Amsterdam
PhenotypesPhenotypes ofofasthmaasthma
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HeterogeneityHeterogeneity ofofasthmaasthma
allergicallergic
severesevere intrinsicintrinsic
steroidsteroid resistantresistant
eosinophiliceosinophilic
exacerbationexacerbation proneprone
ChildhoodChildhood onsetonset
psychogenicpsychogenicbrittlebrittle
aspirinaspirin--inducedinduced
prepre--menstrualmenstrual
fixedfixed obstructionobstruction
occupationaloccupational
AdultAdult
onsetonset
neutrophilicneutrophilic
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33 patientspatients withwith uncontrolleduncontrolled asthmaasthma
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femalefemale 5050 yryr Diagnosis ofDiagnosis ofasthmaasthma sincesince 44 yearsyears Last 2Last 2 yearsyears increasinglyincreasingly symptomaticsymptomatic
HighHigh
dosedose
ICS plus LABA plus SABAICS plus LABA plus SABA
OralOral corticosteroidscorticosteroids > 50% of the time> 50% of the time
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AdditionalAdditional informationinformation
1.1. NeverNever smokersmoker
2.2. ProfessionProfession:: secretarysecretary
3.3. RecentlyRecently divorceddivorced, 4, 4 childrenchildren
4.4. AllergicAllergic rhinitisrhinitis ((grassgrass pollen ++)pollen ++)
5.5. BMI 35BMI 35
6.6. FEVFEV11 65 %65 %predpred. 12%. 12% reversibilityreversibility
7.7. inducedinduced sputum: fewsputum: few inflammatoryinflammatory cellscells
8.8. R/R/ metforminmetformin, HRT, paracetamol, HRT, paracetamol
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HowHow manymany contributingcontributing factors?factors?
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AdditionalAdditional informationinformation
1.1. NeverNever smokersmoker
2.2. ProfessionProfession:: secretarysecretary
3.3. RecentlyRecently divorceddivorced, 4, 4 childrenchildren
4.4. AllergicAllergic rhinitisrhinitis ((grassgrass pollen ++)pollen ++)
5.5. BMI 35BMI 35
6.6. FEVFEV11 65 %65 %predictedpredicted, 12%, 12% reversibilityreversibility
7.7. inducedinduced sputum: fewsputum: few inflammatoryinflammatory cellscells
8.8. R/R/ metforminmetformin, HRT, paracetamol, HRT, paracetamol
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66 contributingcontributing factors!factors!
1.1. NeverNever smokersmoker
2.2. ProfessionProfession:: secretarysecretary
3.3. RecentlyRecently divorceddivorced,, 44 childrenchildren
4.4. AllergicAllergic rhinitisrhinitis ((grassgrass pollen ++)pollen ++)
5.5. BMI 35BMI 35
6.6. FEVFEV11 65 %65 %predictedpredicted, 12%, 12% reversibilityreversibility
7.7. inducedinduced sputum: fewsputum: few inflammatoryinflammatory cellscells
8.8. R/R/ metforminmetformin,, HRTHRT,, paracetamolparacetamol
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AtopicAtopic andand nonatopicnonatopic rhinitisrhinitis
ShabaanShabaan et al Lancet 2008; 372: 1049et al Lancet 2008; 372: 1049 5757
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PregnanciesPregnancies,, pillpill andand hormonehormone
replacementreplacement therapytherapy
J enkinsJ enkins MA et alMA et al ClinClin Exp Allergy 2006;36:609Exp Allergy 2006;36:609--13.13.
RomieuRomieu et al, Thorax 2010;et al, Thorax 2010; 65: 29265: 292--297297
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ObesityObesity
BeutherBeuther et al AJ RCCM 2007;et al AJ RCCM 2007;175:661175:661 666666
VonVon BehrenBehrenJ et al; Thorax 2009; 64: 889J et al; Thorax 2009; 64: 889--9393
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frequentfrequent useuse ofofacetaminophenacetaminophen
ShaheenShaheen et alet al EurEurRespirRespirJJ 2008;32:12312008;32:1231 12361236
BarrBarr et alet al AJ RCCM 2004;AJ RCCM 2004; 169. 836169. 836 841841
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StressfullStressfull lifelife eventsevents
Wright RJ et al JWright RJ et al J EpidemiolEpidemiol Community HealthCommunity Health 2010;64:6302010;64:630--55
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MultipleMultiple endocrineendocrine hitshits
AtwoodAtwood && BowenBowen.. AgeingAgeing ResRes RevRev 2008;1142008;114--2525
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BestBest treatmenttreatment optionoption??
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BestBest treatmenttreatment optionoption1.1. ExtrafineExtrafine ICSICS
2.2. AntiAnti leukotrienesleukotrienes
3.3. ContinuousContinuous lowlow dosedose oraloral corticosteroidscorticosteroids4.4. OmalizumabOmalizumab
5.5. MacrolidesMacrolides
6.6. ThermoplastyThermoplasty
7.7. WeightWeight controlcontrol reduce oral corticosteroids
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DownDown--titratingtitrating oraloral corticosteroidscorticosteroids byby useuse ofof
NONO--guidedguided internetinternet strategystrategy
HashimotoHashimoto et al. Thorax inet al. Thorax in presspress
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Effect ofEffect ofbariatricbariatric surgerysurgery onon asthmaasthma severityseverity
ReddyReddy et alet al ObesObes SurgSurg 2011:21:2002011:21:200--66..
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male 40male 40 yryr Diagnosis ofDiagnosis ofasthmaasthma sincesince 44 yearsyears 44--66 severesevere exacerbationsexacerbations // yryr HighHigh dosedose ICS plus LABA plus SABAICS plus LABA plus SABA OralOral corticosteroidscorticosteroids > 50% of the time> 50% of the time
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AdditionalAdditional informationinformation
1.1. exex smokersmoker ((stoppedstopped 55 yearsyears agoago))
2.2. ProfessionProfession:: policemanpoliceman, 2, 2 dogsdogs
3.3. SingleSingle
4.4. skinskin prickprick test: housetest: house dustdust mitemite ++++
5.5. BMI 26BMI 26
6.6. inducedinduced sputum: 70%sputum: 70% neutrophilsneutrophils
7.7. FEVFEV11 65 %65 %predpred. 15%. 15% reversibilityreversibility8.8. R/R/ furosemidefurosemide,, sotalolsotalol
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HowHow manymany contributingcontributing factors?factors?
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AdditionalAdditional informationinformation
1.1. exex smokersmoker ((stoppedstopped 55 yearsyears agoago))
2.2. ProfessionProfession:: policemanpoliceman, 2, 2 dogsdogs
3.3. SingleSingle
4.4. skinskin prickprick test: housetest: house dustdust mitemite ++++
5.5. BMI 26BMI 26
6.6. inducedinduced sputum: 70%sputum: 70% neutrophilsneutrophils
7.7. FEVFEV11 65 %65 %predpred. 15%. 15% reversibilityreversibility8.8. R/R/ furosemidefurosemide,, sotalolsotalol
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44 contributingcontributing factorsfactors
1.1. exex smokersmoker ((stoppedstopped 55 yearsyears agoago))
2.2. ProfessionProfession:: policemanpoliceman, 2, 2 dogsdogs
3.3. SingleSingle
4.4. skinskin prickprick test:test: househouse dustdust mitemite ++++
5.5. BMI 26BMI 26
6.6. inducedinduced sputum: 70%sputum: 70% neutrophilsneutrophils !!!!
7.7. FEVFEV11 65 %65 %predpred. 15%. 15% reversibilityreversibility8.8. R/R/ furosemidefurosemide,, sotalolsotalol
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TrafficTraffic relatedrelated airair pollutionpollution
KKnzlinzli et alet al ThoraxThorax 2009;64;6642009;64;664--670670
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BestBest treatmenttreatment optionoption??
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BestBest
treatmenttreatment
optionoption
1. Extrafine ICS
2. Anti leukotrienes
3. Continuous low dose oral corticosteroids4. Omalizumab
5. Macrolides
6. Thermoplasty
7. Weight control
????
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ClarithromycinClarithromycin inin neutrophilicneutrophilic asthmaasthma
SimpsonSimpson et alet al AJ RCCM 2008:15;177:148AJ RCCM 2008:15;177:148--55.55.
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ClarithromycinClarithromycin inin neutrophilicneutrophilic asthmaasthma
SimpsonSimpson et alet al AJ RCCM 2008:15;177:148AJ RCCM 2008:15;177:148--55.55.
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macrolidesmacrolides inin chronicchronic stablestable asthmaasthma
Kraft MKraft M et alet al ChestChest 2002:121:17822002:121:1782--88.
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PersistentPersistent infectionsinfections implicatedimplicated inin
thethe developmentdevelopment ofof intrinsicintrinsic asthmaasthma
DahlbergDahlberg & Busse& Busse ClinClin Exp Allergy 2009; 39: 1324Exp Allergy 2009; 39: 1324 13291329
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femalefemale 4545 yryr Diagnosis ofDiagnosis ofasthmaasthma sincesince 1010 yearsyears
HighHigh dosedose ICS plus LABA plus SABAICS plus LABA plus SABA OralOral corticosteroidscorticosteroids > 50% of the time> 50% of the time PoorPoor qualityquality ofoflifelife
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AdditionalAdditional informationinformation
1.1. nevernever smokersmoker
2.2. ProfessionProfession:: cleaningcleaning ladylady
3.3. MarriedMarried, 2, 2 childrenchildren
4.4. chronicchronic sinusitissinusitis withwith nasalnasal polypspolyps
5.5. skinskin prickprick test:test: negativenegative
6.6. BMI 27BMI 27
7.7. inducedinduced sputum: 20%sputum: 20% eoeo, 50%, 50% neutroneutro8.8. FEVFEV11 65 %65 %predpred. 3%. 3% reversibilityreversibility
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HowHow manymany contributingcontributing factors?factors?
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AdditionalAdditional informationinformation
1.1. nevernever smokersmoker
2.2. ProfessionProfession:: cleaningcleaning ladylady
3.3. MarriedMarried, 2, 2 childrenchildren
4.4. chronicchronic sinusitissinusitis withwith nasalnasal polypspolyps
5.5. skinskin prickprick test:test: negativenegative
6.6. BMI 27BMI 27
7.7. inducedinduced sputum: 20%sputum: 20% eoeo, 50%, 50% neutroneutro8.8. FEVFEV11 65 %65 %predpred. 3%. 3% reversibilityreversibility
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22 aggravatingaggravating factorsfactors
1.1. nevernever smokersmoker
2.2. ProfessionProfession:: cleaningcleaning ladylady
3.3. MarriedMarried, 1, 1 childchild
4.4. chronicchronic sinusitissinusitis withwith nasalnasal polypspolyps
5.5. skinskin prickprick test:test: negativenegative
6.6. BMI 27BMI 27
7.7. inducedinduced sputum: 20%sputum: 20% eoeo !!!!, 50%, 50% neutroneutro8.8. FEVFEV11 65 %65 %predpred. 3%. 3% reversibilityreversibility
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Houshold cleaning products useincreases asthma risk
ZockZock et al Am Jet al Am J RespirRespir CritCrit Care Med 2007;176:735Care Med 2007;176:735 741741
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SinusSinus diseasedisease isis associatedassociated withwith
frequentfrequent exacerbationsexacerbations
ten Brinke Aten Brinke A et alet al., ERJ 2005;26:812., ERJ 2005;26:812 818818
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PatientsPatients withwith CRS haveCRS have higherhigher
eosinophilseosinophils inin peripheralperipheral bloodblood
SteinkeSteinke et alet al. J Allergy. J Allergy ClinClin ImmunolImmunol 2003;111:3422003;111:342--99
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CTCT--sinus score is associated with sputumsinus score is associated with sputum
eosinophilseosinophils and exhaled NOand exhaled NO
ten Brinketen Brinke et alet al , J Allergy, J Allergy ClinClin ImmunolImmunol, 2002, 2002;109:621;109:621--66
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CTCT--sinussinus score isscore is associatedassociated withwith
degreedegree of airof air trappingtrapping
ten Brinke,ten Brinke, J AllergyJ Allergy ClinClin ImmunolImmunol, 2002, 2002;109:621;109:621--66ten Brinketen Brinke et alet al , J Allergy, J Allergy ClinClin ImmunolImmunol, 2002, 2002;109:621;109:621--66
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InflammationInflammation in distalin distal airwaysairways inin
severesevere asthmaasthma
Mauad et al. J Allergy Clin Immunol 2007;2:333-339
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BestBest treatmenttreatment optionoption??
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BestBest treatmenttreatment optionoption
1. Extrafine ICS
2. Anti leukotrienes
3. Continuous low dose oral corticosteroids4. Omalizumab
5. Macrolides
6. Thermoplasty
7. Weight control
+ nasal corticosteroids
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Effect of CRS treatment on asthmaEffect of CRS treatment on asthma
(% change compared to baseline)(% change compared to baseline)
RagabRagab et al.et al. EurEur RespirRespirJ 2006; 28: 68J 2006; 28: 68 7474
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Effect ofEffect ofextrafineextrafine ICSICS onon largelarge andand
smallsmall airwaysairways inflammationinflammation
HauberHauber HP et al, J AllergyHP et al, J Allergy ClinClin ImmunolImmunol 2003;112:582003;112:58--6363
Small airways
Large airways
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Effect ofEffect ofextraextra--finefine ICSICS onon
asthmaasthma exacerbationsexacerbations
BatemanBateman E. et al.E. et al. PulmPulm PharmPharmTherTher 2008; 21: 4892008; 21: 489--498498
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30pre post
0
25
50
75
S
putum
eosinophils
(%)
pre post
p
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33 clinicalclinical phenotypesphenotypes ofofasthmaasthma
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HaldarHaldar et al AJ RCCM 2008;178:218et al AJ RCCM 2008;178:218--224224
COPD?COPD?
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AuffrayAuffray et alet al Genome Med 2009;1:2Genome Med 2009;1:2
Patient reported
Clinical
Functional
Cellular
Molecular
Future ofFuture ofphenotypingphenotyping: Systems Medicine: Systems Medicine