Phenotypes of Asthma Elisabeth

7/28/2019 Phenotypes of Asthma Elisabeth

1/53

Elisabeth BelElisabeth Bel

Dept. Respiratory MedicineDept. Respiratory Medicine

Academic Medical CentreAcademic Medical Centre

University of AmsterdamUniversity of Amsterdam

PhenotypesPhenotypes ofofasthmaasthma


2/53

HeterogeneityHeterogeneity ofofasthmaasthma

allergicallergic

severesevere intrinsicintrinsic

steroidsteroid resistantresistant

eosinophiliceosinophilic

exacerbationexacerbation proneprone

ChildhoodChildhood onsetonset

psychogenicpsychogenicbrittlebrittle

aspirinaspirin--inducedinduced

prepre--menstrualmenstrual

fixedfixed obstructionobstruction

occupationaloccupational

AdultAdult

onsetonset

neutrophilicneutrophilic


3/53

33 patientspatients withwith uncontrolleduncontrolled asthmaasthma


4/53

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


5/53

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


6/53

HowHow manymany contributingcontributing factors?factors?


7/53




3.3. RecentlyRecently divorceddivorced, 4, 4 childrenchildren


5.5. BMI 35BMI 35

6.6. FEVFEV11 65 %65 %predictedpredicted, 12%, 12% reversibilityreversibility


8.8. R/R/ metforminmetformin, HRT, paracetamol, HRT, paracetamol


8/53

66 contributingcontributing factors!factors!



3.3. RecentlyRecently divorceddivorced,, 44 childrenchildren


5.5. BMI 35BMI 35

6.6. FEVFEV11 65 %65 %predictedpredicted, 12%, 12% reversibilityreversibility


8.8. R/R/ metforminmetformin,, HRTHRT,, paracetamolparacetamol


9/53

AtopicAtopic andand nonatopicnonatopic rhinitisrhinitis

ShabaanShabaan et al Lancet 2008; 372: 1049et al Lancet 2008; 372: 1049 5757


10/53

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


11/53

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


12/53

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


13/53

StressfullStressfull lifelife eventsevents

Wright RJ et al JWright RJ et al J EpidemiolEpidemiol Community HealthCommunity Health 2010;64:6302010;64:630--55


14/53

MultipleMultiple endocrineendocrine hitshits

AtwoodAtwood && BowenBowen.. AgeingAgeing ResRes RevRev 2008;1142008;114--2525


15/53

BestBest treatmenttreatment optionoption??


16/53

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


17/53

DownDown--titratingtitrating oraloral corticosteroidscorticosteroids byby useuse ofof

NONO--guidedguided internetinternet strategystrategy

HashimotoHashimoto et al. Thorax inet al. Thorax in presspress


18/53

Effect ofEffect ofbariatricbariatric surgerysurgery onon asthmaasthma severityseverity

ReddyReddy et alet al ObesObes SurgSurg 2011:21:2002011:21:200--66..


19/53

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


20/53


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


21/53



22/53




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



23/53

44 contributingcontributing factorsfactors



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 !!!!



24/53


25/53

TrafficTraffic relatedrelated airair pollutionpollution

KKnzlinzli et alet al ThoraxThorax 2009;64;6642009;64;664--670670


26/53


27/53



28/53

BestBest

treatmenttreatment

optionoption

1. Extrafine ICS

2. Anti leukotrienes

3. Continuous low dose oral corticosteroids4. Omalizumab

5. Macrolides

6. Thermoplasty

7. Weight control

????


29/53

ClarithromycinClarithromycin inin neutrophilicneutrophilic asthmaasthma

SimpsonSimpson et alet al AJ RCCM 2008:15;177:148AJ RCCM 2008:15;177:148--55.55.


30/53

ClarithromycinClarithromycin inin neutrophilicneutrophilic asthmaasthma

SimpsonSimpson et alet al AJ RCCM 2008:15;177:148AJ RCCM 2008:15;177:148--55.55.


31/53

macrolidesmacrolides inin chronicchronic stablestable asthmaasthma

Kraft MKraft M et alet al ChestChest 2002:121:17822002:121:1782--88.


32/53

PersistentPersistent infectionsinfections implicatedimplicated inin

thethe developmentdevelopment ofof intrinsicintrinsic asthmaasthma

DahlbergDahlberg & Busse& Busse ClinClin Exp Allergy 2009; 39: 1324Exp Allergy 2009; 39: 1324 13291329


33/53

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


34/53


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


35/53



36/53




3.3. MarriedMarried, 2, 2 childrenchildren



6.6. BMI 27BMI 27

7.7. inducedinduced sputum: 20%sputum: 20% eoeo, 50%, 50% neutroneutro8.8. FEVFEV11 65 %65 %predpred. 3%. 3% reversibilityreversibility


37/53

22 aggravatingaggravating factorsfactors



3.3. MarriedMarried, 1, 1 childchild



6.6. BMI 27BMI 27

7.7. inducedinduced sputum: 20%sputum: 20% eoeo !!!!, 50%, 50% neutroneutro8.8. FEVFEV11 65 %65 %predpred. 3%. 3% reversibilityreversibility


38/53

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


39/53

SinusSinus diseasedisease isis associatedassociated withwith

frequentfrequent exacerbationsexacerbations

ten Brinke Aten Brinke A et alet al., ERJ 2005;26:812., ERJ 2005;26:812 818818


40/53

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


41/53

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


42/53

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


43/53

InflammationInflammation in distalin distal airwaysairways inin

severesevere asthmaasthma

Mauad et al. J Allergy Clin Immunol 2007;2:333-339


44/53



45/53

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


46/53

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


47/53

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


48/53

Effect ofEffect ofextraextra--finefine ICSICS onon

asthmaasthma exacerbationsexacerbations

BatemanBateman E. et al.E. et al. PulmPulm PharmPharmTherTher 2008; 21: 4892008; 21: 489--498498


49/53

30pre post

0

25

50

75

S

putum

eosinophils

(%)

pre post

p


50/53

33 clinicalclinical phenotypesphenotypes ofofasthmaasthma


51/53


52/53

HaldarHaldar et al AJ RCCM 2008;178:218et al AJ RCCM 2008;178:218--224224

COPD?COPD?


53/53

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

Documents

Phenotypes of Asthma Elisabeth