Cat and dog allergens

1December2017Thansinee Saetae,MD

PediatricallergyandImmunologyUnitKingChulalongkornMemorialHospital

http://biologyvermontschool.blogspot.com/2013/03/bio-classification-classify-al-least-2.html

CatandDogAllergen

Pomés Aetal.Curr AllergyAsthmaRep.2016;16:43

• Fel d1isa38kD tetramericglycoproteinwithastructuresimilartothatofuteroglobulin.• IgE fromover90%ofcat-sensitizedindividualsreactswiththismajorcatallergen.• Fel d1isproducedinsebaceous,anal,andsalivaryglandsandtransferredtothefur bygrooming.• AirborneFel d1ismostly associatedwithlargerparticles(>9μm)• 23% ofairborneFel d1iscarriedonsmallparticles(<4.7μm diameter)thatstaysuspendedintheairforseveraldays,favoringdistributionoftheallergenintheenvironment.


• Othersrelevantcatallergens• Fel d3:Cysteineproteaseinhibitorreactwith10% ofIgE fromcat-allergicpatients.• Fel d6: CatIgMislesswelldocumented.

Pomés Aetal.Curr AllergyAsthmaRep2016;16:43Gronlund Hetal.Int ArchAllergyImmunol 2010;151:265–274Konradsen etal.JAllergyClin Immunol 2015;135:616-25.Sarbjit S.Saini.Middleton's8thedition.

90%

63%

37%

15-40%

40%

HighIgE levelstoFel d1couldbeamarkerofincreasedasthmarisk.

HighIgE levelstoFel d4havebeenassociatedwithatopicdermatitis.

• A proportionoftheairborneallergen(10%to40%)wasbeingcarriedonsmallerparticles(lessthan5μm indiameter).

• Theaerodynamicbehavioroftheseparticlesandshowthattheyaredynamicallyequivalenttospheresof1to7μm indiameter.• Itisimportanttorealizethataflat“flake”ofdandermaypotentiallyhaveanaerodynamicsizesmaller thanitsrealsize.

• Approximately60% ofairborneFel d1 settlesoutwithin2daysofdisturbance,leavingsmallerparticlesthatcanremainairborneforupto14daysorlonger.

J.Portnoyetal.AnnAllergyAsthmaImmunol 2012;2018:223.e1–223.e15Sarbjit S.Saini.Middleton's8thedition.

• ThepresenceofacatcanincreaseairborneFel d1within30minutes.

• Indeed,recentestimatessuggestthatthequantitiesofcatallergeninhaledare10to50timeshigherthanmiteallergen.

• Thesizeoftheseparticleshassomeimportant consequences.• Smallparticlesfallslowlyandcanbekeptairbornebyanymovementinthehouse.• Increasedventilationhelpstoremovesmallparticlesfromahouse.• Airfiltrationwitharoomaircleanermaybeausefulmethodofreducingexposuretoallergenonsmallparticles.

J.Portnoyetal.AnnAllergyAsthmaImmunol 2012;2018:223.e1–223.e15Sarbjit S.Saini.Middleton's8thedition.

• Morethan90% ofallpeoplewhohaverespiratorytractsymptomsrelatedtocatexposurehaveIgE antibodiesspecificforFel d1.• MeasurementsofFel d1intheenvironmentprovideanexcellentmodelforcatexposurerelevanttoasthma orrhinitis.• Peptides derivedfromFel d1havebeenproposedasanalternativetocatextractforimmunotherapy.• Fel d1 itselfhasno importantcross-reactivities andindeedhasverylittlehomologywithanyknownallergensexceptCanf4.

Sarbjit S.Saini.Middleton's 8thedition.

• Otherallergensfromcataremoreimportantinrelationtofoodallergy thantoinhalantsymptoms.

Fel d2,Catalbumincross-reacts immunologicallywithseveral differentmammalianalbumins,includingthoseofdog,pork,andbeefà adult-onsetallergicreactionstoporkPork-CatSyndromePatientswiththissyndromesensitizedtoalbuminsfromanimaldanderreportsymptomsaftertheconsumptionofporkbecauseofthecross-reactivityofalbuminsfromdifferentspecies.

Konradsen etal.JAllergyClin Immunol 2015;135:616-25.Sarbjit S.Saini.Middleton's8thedition.

• Fel d5w,catIgA• Thealpha-gal–specificIgE antibodieswerestronglyassociatedwithdelayedanaphylaxistoredmeat.• IgE antibodiestoalpha-galwillbindtocatIgA(Fel d5w),beefthyroglobulin• ThepresenceofIgE antibodiestoalpha-galcanleadtomisleading resultsonIgE assaysorskintestsusingcatextracts.• IgE antibodiestoalpha-galdonotcreateariskforasthmaorotherinhalantsymptoms.


Konradsen etal.JAllergyClin Immunol 2015;135:616-25.

• Dogscanbeapotentsourceofallergen,• appearstobelesscommonthancatallergyasacauseofasthma.

• Manydogsarekeptoutside andbecomedirty(actually,muchworse),sowashingdogsisacommonpractice.• Acommonsourcesofdogallergensaredanderandsaliva.• Fourofsixcurrentlyidentifieddogallergens arelipocalins.• Canf1,Canf2,Canf4,andCanf6

Sarbjit S.Saini.Middleton's 8thedition.Pomés Aetal.Curr AllergyAsthmaRep.2016;16:43

• About∼70%ofdog- allergicindividualshaveIgE antibodiesspecifictothemajordogallergenCanf1.• Canf1isdetectableinonethirdofhomeswithoutadog.• Thesize distributionofparticlesassociatedwithCanf1issimilar tothatofFel d1.• Awidevariability inCanf1levelscanbefoundbetweendogbreeds,• butthereisno evidenceforahypoallergenicbreed.


• Canf5(prostatickallikrein,arginineesterase),derivedfromdogurine isalsoconsideredamajorallergen,withupto70% ofdog- allergicpatientshavingCanf5-specificIgE.• 38%ofdog-allergicpatientsweremonosensitized toCanf5.

• Otherrelevantdogallergens• Canf2(lipocalin)

• reactwith20–30%ofIgE fromdog- allergicpatients.• Canf4(lipocalin)

• reactwith15–50%ofIgE fromdog- allergicpatients.• Canf6(lipocalin)

• reactwith38%ofIgE fromdog- allergicpatients.• Canf3(dogalbumin)

• reactwith81% ofIgE fromdog- allergicpatients.

Significantinhalantallergens

Sarbjit S.Saini.Middleton's8thedition. Mattsson etal.JAllergyClin Immunol 2009;123:362-8.Pomés Aetal.Curr AllergyAsthmaRep.2016;16:43

D.M.SmithandC.A.Coop.AnnAllergyAsthmaImmunol 2016;116:188-193

ImmuneresponsetoCatandDogallergen

• Theimmuneresponsetodomesticanimalallergensincludes• Tcells• IgE antibodies• differentisotypesofantibodies.

• Atpresent,boththesignificanceofIgE antibodiesandthetechniquesformeasuringIgE antibodylevelsarebetterestablishedthanthetechniquesfordescribinganyotheraspectoftheimmuneresponse.


• T-cellresponses• A widerangeofstudieshavebeencarriedoutonT-cellresponsestocatallergensusingboththeproteinFel d1andoverlappingpeptidesderivedfromFel d1.• ThesestudiesdemonstratedthatresponsestoFel d1are,broadlyspeaking,ofaTH2type.• AlthoughitispossiblethattherearepatientswhohavesymptomsrelatedtocatordogallergenexposureonthebasisofaT-cellresponsewithoutanassociatedIgE antibodyresponse,thishasnotbeendemonstrated.


• IgGantibodyresponses• TherearemixeddataabouttheisotypesotherthanIgE andIgG4.• ManypublicationsreportdetectableIgG4antibodiesinmostallergicandnon-allergicsubjects incontrasttoextensiveearlierdata.• Althoughtheresultsmightnotberelevanttotheclinicalevaluationofpatients,theyareimportanttounderstandingtheimmuneresponsetocatallergensinthoseatopicchildrenwholiveinahousewithacat butdonotbecomesymptomaticonexposuretocatallergens.


• IgGantibodyresponses (Cont.)• Thedissociationofallergen-specificIgE andIgGresponsestocat,dog,andhorsewasreported,• indicatingthatnonsequential class-switchmechanismsareoperativeinpatientswithanimalallergyandmightexplainwhynaturallyoccurringallergen-specificIgGisnotalwaysprotective.• MeasurementofIgGantibodiesmightalsoberelevanttounderstandingwhysomesubjectsexperienceincreasedsymptomsonenteringahousewithananimalafter aperiodofdecreasedexposure.


Studydesign:Prospectivecohortstudy

Participants:97collegestudentswhotoleratedlivinginahousewithacat

Intervention:Decreaseexposuretocatallergen

Theprimaryoutcome:Thechangeinantibodytitersovertime.

Measure:Skinpricktest:

atbaselineSpecificIgE tocat:

atbaseline,8monthsSpecificIgE toFel d1:

atbaseline,8monthsIgGtoFel d1à IgG4toFel d1:

atbaseline,8monthsE.A.Erwinetal.AnnAllergyAsthmaImmunol 2014;112:545-550

• HavingIgGwithoutevidenceofsensitizationwasthemost frequentlyobservedimmuneresponse tocat(n=32).

• NoneofthestudentswhohadIgG butwerenotsensitizedtocathadwheezing.

E.A.Erwinetal.AnnAllergyAsthmaImmunol 2014;112:545-550


• Non-sensitized individualswithIgGtoFel d1experiencedasignificantdecreaseinIgGtiterswithdecreasedexposuretocatallergen(p=0.02).

• Forthosestudents(n= 21)whowerefollowedupforasecondyear,levelsofIgGantibodytoFel d1haddecreasedfurther.

• Non- sensitizedindividuals, IgG4 alsodecreased(P<.001)during 8monthsofdecreasedcatexposure.

• None oftheindividualshaving IgGtoFel d1withoutsensitization tocatdevelopedapositiveserumIgEantibodyassayorapositiveskinpricktestresulttocatduring 1yearor2years.

ChangesinAntibodyTiterstoFel d1inNon-sensitizedIndividuals


• SpecificIgE titerstocatdidnotdecreasesignificantlyduring prolonged, decreasedexposuretocatallergen.

• IgGantibodytoFel d1decreasedsignificantly duringthe8-monthstudyperiod (P<.001)

AntibodyChangesinCatSensitizedIndividuals

RatiosofcatspecificIgGtoIgE antibodies


TherewasahighlysignificantdecreaseintheratioofIgGtoIgEantibodies after8months,decreasedexposuretocatallergen.

• Conclusion:Underconditionsofmarkeddecreaseinexposure,• No participantsdevelopednew-onsetsensitization.• Amongtheindividualssensitizedatstudyentry,thereweremajordecreasesintheratioofIgGtoIgE.


TheeffectofCatsorDogsinthehome

• Themajorcatallergen,Fel d1,remainsairborne formanyhoursafteranydisturbance.• Asaresult,estimatesofthequantitiesofcat(ordog)allergensinhaledinahousewithananimalaremuchhigher,atapproximately1μg/day,thancomparableestimatesofDerp1inhaledof10ng/day.• Inaddition,theparticlesofdandercarryingcatallergensappeartobe“sticky,”whichmeansthattheyareconsistentlycarriedonclothingfromhouseswithananimaltootherbuildings.


• Inacommunitywhere20%ormoreofthefamilieshaveanimals,theseallergenswillbeeasily measurableindustfromschools orinhomeswithoutacat.• Sensitizationtocatscanoccurwithoutdirectexposuretotheanimals.• Insomestudies,75%ofthechildrenwhoareallergictocats havenever livedinahousewithacat.


• In1998,Hesselmar andBjorksten reportedthatchildrenraisedinahousewithacatwerelesslikelytobecomeallergictocats.• Thisresultwasgreetedwithastonishment;however,severalothergroupsofinvestigatorsfoundstrongevidencesupportingthatobservation.• Manyofthe“non-allergic”childrenwholivedinahousewithacathadmadeIgGandIgG4 antibodiestoFel d1.• Thisresponseisofinterestinthatithasmoreofthefeaturesofa“modifiedTh2”responsethanofashifttoTh1.

• Theeffectofexposuretoacatinearlylifecanbebothallergen-specific andlong-lasting.


Studydesign: Meta– analysisObjective:Toexaminetheassociationsbetweenpetkeepinginearlychildhoodandasthmaandallergiesinchildrenaged6–10years.Participants:Dataof11prospectiveEuropeanbirthcohortsthatrecruitedatotalofover22,000childreninthe1990s.

Exposuredefinition:Ownershipofonlycats,dogs,birds,rodents,orcats/dogscombinedduringthefirst2yearsoflife.Outcomes:Allergicasthma,AllergicrhinitisandAllergicsensitizationduring6–10yearsofage.

Lodrup Carlsen KCetal.PLoS One2012;7:e43214.

Pets and Asthma

PLOS ONE | www.plosone.org 6 August 2012 | Volume 7 | Issue 8 | e43214

Pets and Asthma



OR=1.09

OR=0.79

Pets and Asthma



OR=0.91

Pets and Asthma


Pets and Asthma



OR=0.65

OR=0.87

Pets and Asthma



OR=0.68

Pets and Asthma



Pets and Asthma


OR=1.02

OR=0.77

Pets and Asthma



OR=0.79


Conclusion:• Petownershipinearlylifedidnot appeartoeitherincreaseorreducetheriskofasthma orallergicrhinitissymptomsinchildrenaged6–10.• Advice fromhealthcarepractitionerstoavoidortospecificallyacquirepetsforprimarypreventionofasthmaorallergicrhinitisinchildrenshouldnotbegiven.

• Anissueofsomeclinicalimportanceiswhethertheeffectofadog inthehouseisthesameastheeffectofacat.• Highlevelsofendotoxininthehomewereinversely relatedtoallergensensitization.• Severaldetailedstudieshaveshownthatacat inthehomedoesnotincreaseendotoxineitherinfloordustorinairborneform.• Thepresenceofoneormoredogsinthehousedoesincreaseairborneendotoxin,andinsomestudies,earlyexposuretodogs appearedtohaveaninhibitoryeffectonallergyingeneral.


• Althoughundoubtedlyindividualdifferenceswillaffecttheresponseto animalexposure,twoverydifferentmechanismsmaybeinvolved.• Thefirstistheshift,inducedbyhigherexposure,togerminalcenterproductionofBcells,whichfavorsIgG4productionandmaybeamajorcomponentoftheallergen-specifictolerance inducedbyearlyexposuretocatallergens.• Thesecondmechanismisincreasedendotoxin orincreasedbacterialdiversityinthehome,withconsequenteffectsonthemicrobiomeofthechildduringearlydevelopment.• Thesecondmechanismwouldnotbeallergen- specificandismorelikelywithadogthanwithacat.


Environmentalassessmentandexposurecontrol

Practice Parameter

Environmental assessment and exposure control: a practice parameter—furry animalsChief Editors: Jay Portnoy, MD, Kevin Kennedy, MPH, James Sublett, MD

Members of the Joint Task Force onPractice Parameters:David Bernstein,MD, Joann Blessing-Moore,MD, Linda Cox,MD, David Khan,MD, David Lang,MD, RichardNicklas,MD, John Oppenheimer, MD, Jay Portnoy, MD, Christopher Randolph, MD, Diane Schuller, MD, Sheldon Spector, MD, Stephen A. Tilles, MD, Dana Wallace, MDPractice ParameterWork Group: James Sublett, MD, cochair, Kevin Kennedy, MPH, cochair, Charles Barnes, PhD, David Bernstein, MD, Jonathan Bernstein, MD, Carl Grimes,Elizabeth Matsui, MD, Jeffrey D. Miller, MD, J. David Miller, PhD, Wanda Phipatanakul, MD, MS, James Seltzer, MD, P. Brock Williams, PhDInvited Reviewers: Jack Armstrong, Hans Gr×nlund, PhD, Kraig W. Jacobson, MD, Jill A. Poole, MD, Matthew A Rank, MD, Megan Taylor, MDThis parameter was developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma and Immunology, the American College of Allergy,Asthmaand Immunology, and the Joint Council of Allergy, Asthmaand Immunology.The American Academy of Allergy, Asthma and Immunology (AAAAI) and the American College of Allergy, Asthma and Immunology (ACAAI) have jointly accepted responsibility forestablishing “Environmental Assessment and Remediation: A Practice Parameter.” This is a complete and comprehensive document at the current time. The medical environment is achangingenvironment, andnotall recommendationswillbeappropriate forallpatients.Because thisdocument incorporatedtheeffortsofmanyparticipants,nosingle individual, includingthosewhoservedontheJointTaskForce, isauthorizedtoprovideanofficialAAAAIorACAAIinterpretationofthesepracticeparameters.Anyrequestforinformationaboutoraninterpretationof these practice parameters by the AAAAI or ACAAI should be directed to the executive offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma and Immunology. Theseparameters are not designed for use bypharmaceutical companies in drugpromotion.Reprints: Joint Council of Allergy, Asthmaand Immunology, 50NBrockway St, #3-3 Palatine, IL 60067.Disclosures: The following is a summaryof interests disclosedonWorkGroupmembers’ Conflict of InterestDisclosure Statements (not including information concerning familymemberinterests). Completed Conflict of Interest Disclosure Statements are available on request. Dr. Sublett is the owner of AllergyZone. Dr. Portnoy is a speaker and consultant for ThermoFisher(Phadia). Dr. Barnes is a consultant for and has received research funding from Clorox Corporation. Mr. Grimes is the owner of Healthy Habitats LLC. Dr. Matsui is speaker for IndoorBioTechnologies.Dr.Miller is theownerofMission:Allergy Inc.Dr. Seltzer is thePresident of JamesM. Seltzer, Assoc. TheotherWorkGroupmembershaveno conflicts todisclose. The JointTask Force recognizes that experts in a field are likely to have interests that could come into conflictwith development of a completely unbiased and objective practice parameter. To takeadvantage of that expertise, a process has beendeveloped to prevent potential conflicts from influencing thefinal document in a negativeway.At theworkgroup level,memberswhohaveapotential conflictof interest eitherdonotparticipate indiscussions concerning topics related to thepotential conflictor, if theywrite a sectiononthattopic, theworkgroupcompletelyrewritesitwithouttheir involvementtoremovepotentialbias. Inaddition,theentiredocumentisreviewedbytheJointTaskForce,andanyapparentbias is removedat that level. Finally, thepracticeparameter is sent for reviewbothby invited reviewersandbyanyonewithan interest in the topicbyposting thedocumenton thewebsitesof theACAAI and theAAAAI.In particular, the 2 owners of companies that produce products discussed in this practice parameter are Jeffrey D. Miller, MD, and James Sublett, MD. DrMiller wrote an initial section onmattress encasings. This section was then completely rewritten by other members of the work groupwithout his participation. Dr Sublett wrote a preliminary draft of the section on airfiltration. That sectionwas also subsequently rewritten by othermembers of thework groupwithout his participation. Neither participant provided subsequent input into those sections.The Joint Task Force has made a concerted effort to acknowledge all contributors to this parameter. If any contributors have been excluded inadvertently, the Task Force will ensure thatappropriate recognition of such contributions ismade subsequently.Work Group Cochairs: James Sublett,MD, FamilyAllergy andAsthma, Louisville, Kentucky; KevinKennedy,MPH, Center for EnvironmentalHealth, Children’sMercyHospitals &Clinics,KansasCity,Missouri; JointTaskForceLiaison:JayM.Portnoy,MD,SectionofAllergy,Asthma& Immunology, TheChildren’sMercyHospitals&ClinicsDepartmentofPediatrics,UniversityofMissouri–KansasCity School ofMedicine,KansasCity,Missouri; JointTaskForceMembers:David I. Bernstein,MD,DepartmentofClinical,MedicineandEnvironmentalHealth,DivisionofAllergy/Immunology,UniversityofCincinnati,CollegeofMedicine,Cincinnati,Ohio; JoannBlessing-Moore,MD,Departmentof Immunology,StanfordUniversityMedicalCenter,PaloAlto,California; Linda Cox, MD, Department of Medicine, Nova Southeastern University College of Osteopathic Medicine, Davie, Florida; David A. Khan, MD, Department of Internal Medicine,University of Texas, Southwestern Medical Center, Dallas, Texas; David M. Lang, MD, Allergy/Immunology Section, Division of Medicine, Allergy and Immunology Fellowship TrainingProgram, Cleveland Clinic Foundation, Cleveland, Ohio; Richard A. Nicklas, MD, Department of Medicine, George Washington Medical Center, Washington, DC; John Oppenheimer, MD,Departmentof InternalMedicine,NewJerseyMedicalSchool,PulmonaryandAllergyAssociates,Morristown,NewJersey; JayM.Portnoy,MD,SectionofAllergy,Asthma&Immunology,TheChildren’s Mercy Hospitals & Clinics, Department of Pediatrics, University of Missouri–Kansas City School of Medicine, Kansas City, Missouri; Christopher C. Randolph, Department ofPediatrics,YaleAffiliatedHospitals,Center forAllergy,Asthma,&ImmunologyWaterbury,Connecticut;DianeE.Schuller,MD,DepartmentofPediatrics,PennsylvaniaStateUniversityMiltonS.HersheyMedical College,Hershey, Pennsylvania; SheldonL. Spector,MD,DepartmentofMedicine,UCLASchool ofMedicine, LosAngeles, California; StephenA. Tilles,MD,DepartmentofMedicine,UniversityofWashington,SchoolofMedicine,Redmond,Washington;DanaWallaceMD,DepartmentofMedicine,NovaSoutheasternUniversityCollegeofOsteopathicMedicine,Davie, Florida;ParameterWorkGroupMembers:CharlesBarnes,PhD,AllergyResearch,TheChildren’sMercyHospitals&ClinicsKansasCity,Missouri;David I.Bernstein,MD,Departmentof Clinical Medicine, Division of Immunology, University of Cincinnati College of Medicine, Cincinnati, Ohio; Jonathan A. Bernstein, MD, Department of Internal Medicine, Division ofImmunology/Allergy Section, University of Cincinnati College of Medicine, Cincinnati, Ohio; Carl Grimes, CIEC, Healthy Habitats LLC, Denver, Colorado; Elizabeth Matsui, MD, MHS,Department of Pediatrics, Johns Hopkins School ofMedicine, Baltimore,Maryland; Jeffrey D.Miller, MD, Department of Pediatrics, NewYorkMedical College, Valhalla, NewYork; J. DavidMiller,PhD,DepartmentofBiochemistry,CarltonUniversity,Ottawa,Ontario,Canada;WandaPhipatanakul,MD,MS,DepartmentofPediatrics,DivisionofAllergyandImmunology,HarvardMedical School, Children’s Hospital Boston, Boston, Massachusetts; JamesM. Seltzer, MD, RelianceMedical Group, Department of Allergy and Immunology,Worcester, Massachusetts; P.BrockWilliams,PhD,DepartmentofAllergy/Immunology,UniversityofMissouri–KansasCitySchoolofMedicineandTheChildren’sMercyHospitals&Clinics,KansasCity,Missouri; InvitedReviewers: Jack Armstrong, MD, Medical Arts Allergy, P.C., Carlisle, Pennsylvania; Hans Gr×nlund, PhD, Department of Immunology, Clinical Immunology and Allergy Unit KarolinskaInstitute,Stockholm,Sweden;KraigW.Jacobson,MD,CPI,OregonAllergyAssociates,AllergyandAsthmaResearchGroup,Eugene,Oregon;JillA.Poole,MD,DepartmentofMedicine,DivisionofAllergy, Asthma& Immunology,University ofNebraskaMedical Center,Omaha,Nebraska;MatthewARank,MD,DivisionofAllergicDiseases,MayoClinic, Rochester,Minnesota;MeganTaylor,MD, Allergy&AsthmaCare, Jenkintown, Pennsylvania.

Ann Allergy Asthma Immunol 108 (2012) 223.e1–223.e15

Contents lists available at SciVerse ScienceDirect

1081-1206/12/$36.00 - see front matter ! 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.doi:10.1016/j.anai.2012.02.015

• A desireforcompanionship oftenoverride themedicallyprudentadvicetoavoidexposuretodogsandcatsforasensitizedperson.

• Thebottomlineisthatpatientslovetheirpets.Theyarepartofthefamily.• Petownershipislikelytopersist.• Allergists needtobeabletoadvisetheirpatientshowtolivewiththepet

whileremainingashealthyaspossible.

• Removalofcatsisrecommendedtodecreaseoverallexposure.• However,completeremovalofallcatsisnecessarytominimizecatallergenexposureinahome.(C)

• Catcharacteristics, suchaslengthofhair,sex,reproductivestatus,andtimespentindoors, arenotassociatedwithlevelsofFel d1intheenvironment.• Therefore,interventionsrelatedtothesefactorscannotberecommended.(C)

• Dataabouttheeffectofneutering adogorcatareinconsistent,• Nospecificrecommendationscanbemadeatthistimeaboutperformingsuchaproceduretoreduceallergenexposure.(D)

J.Portnoyetal.AnnAllergyAsthmaImmunol 2012;2018:223.e1–223.e15

• Because1ormorecatallergensarepresentinallcats,patientsshouldnotbeadvisedthatitissafe toobtaina nonallergenic cat.(C)

• Measurementofcatallergensinsettleddustshouldnotbeusedasasurrogateforairborneexposure.(C)• Carpets arethemajorreservoirforpetallergensinhomeswithpets• DustfromlivingroomscontainssignificantlyhigherconcentrationsofbothFel d1

andCanf1thandustfrombathrooms,kitchens,andbedrooms,althoughthebedsmaycontainevenhigherconcentrationsofFel d1.

• Toreducetransportofcatallergen,peopleshouldconsiderchangingtheirclothes whentravelingfromahighcatallergenenvironmenttoalowcatallergenenvironment.(C)


• Because1ormoredogallergensarepresentinalldogs,patientsshouldnotbeadvisedthatitissafe toobtainanonallergenic dog. (C)• Dogsshouldbeexcluded fromroomsinwhichreducedexposureisdesired.(C)• Thenumberofdogsinthehomeisnotrelatedtodogallergenlevels.• Homeswithoutdoordogshavehigher dogallergenlevelsthanhomeswithoutanydogsbutlower levelsthanhomeswithindoordogs.• Upholsteredchairsinhospitalsareanimportantreservoirofcatanddogallergen.• Specialdaycarecenterswithchildrenwhodon’thavedogsorcats havelowerconcentrationsofbothdogandcatallergen thandaycarecenterswithchildrenwholivewithadogorcat.


• AlthoughexposuretoelevatedcatallergenFel d1concentrationsbefore3monthsofagemayreducethelikelihoodofdevelopingcatsensitization,• theriskreductionisnotsufficienttojustifyadecisiontogetacattoavoidIgE sensitization. (C)

• AlthoughexposuretoelevateddogallergenCanf1concentrationsbefore3monthsofagemayreducethelikelihoodofdevelopingdogsensitization,• theriskreductionisnotsufficienttojustifyadecisiontogetadogtoavoidIgE sensitization. (C)


• Catexposureshouldbeminimized incatsensitizedindividualstoreducethelikelihoodofdevelopingasthma.(C)• Dogexposureshouldbeminimizedindogsensitizedindividualstoreducethelikelihoodofdevelopingasthma.(C)


• Exposuretocatallergensshouldbeminimized toreducethelikelihoodofanasthmaexacerbation incatsensitizedschoolchildrenandadultswhoalreadyhaveasthma.(A)

• Exposuretodogallergensshouldbeminimized toreducethelikelihoodofanasthmaexacerbation indogsensitizedschoolchildrenandadultswhoalreadyhaveasthma.(A)

• Patientsshouldbeaskedwhetherthereisadogorcatinthehousebecauseanaffirmativeanswerisassociatedwithgreaterexposuretodogorcatallergens.(C)• PatientswithallergicdisordersshouldbeevaluatedforsensitizationtocatanddogallergensbyskinpricktestingorinvitrotestingforcatanddogspecificIgE. (C)


• Patientsshouldbeadvisedtoconsiderremovingthecatordogfromtheenvironment,ifpresent,toimproverespiratoryhealth. (A)• To reduceexposuretocatallergenswiththecatstilllivinginthehouse,acombinationofmeasures,suchasremovingreservoirs,keepingthecatoutofthebedroom,washingthecat,aircleaningwithaHEPA roomaircleaner,improvingventilation,andmattressandpillowcovers,maybehelpful.(C)


• Chemicaltreatments,suchastannicacid,canbeappliedtocarpet togiveshort-termreductionofcatallergen,butthisisnotsustainedandthereisnoevidencethatitimprovesrespiratoryhealth.(C)• Useofhypochloritebleachtodenatureindoorallergenscanreduceallergenexposure,improvequalityoflife,andreducethelikelihoodofdevelopingatopy,butitcanalsoleadtoincreasedrespiratorysymptoms inindividualsusingit.(C)


• Washingcatsordogsatleastweekly canreduceairbornecatFel d1ordogCanf1;however,theclinicalbenefitisyettobeprovenandtheeffectofwashingisnotsustained.(B)• Somewoven microfiberbedencasings,generallythosewithameanporesizeof6morless,blockcatallergenfrompenetratingthefabricthoughtherespiratoryhealth benefitfromtheiruseisunclear. (C)• Nonwovenmicrofiberencasingscollectallergenontheirsurfaceovertime,includingcatandmiteallergens.Becausetheycannotbewashed,theyareunsuitableforallergenavoidance.(C)


• Long-termregularuseofhigh-efficiencyorcentralvacuumcleanersisassociatedwithreducedexposuretoFel d1andCanf1inhomeswithcatsordogslivinginthem,althoughthehealtheffectsareuncertain.(B)• HEPAaircleanersruncontinuouslyovertimecanreduceexposuretodogandcatallergenconcentrations,buttheclinicalbenefitsareunknown. (B)• Dogandcatallergensarerelativelystabletodryheatsodryheatshouldnotbeusedspecificallytoreduceexposure.(C)



28 Indoor Allergens 465

allergen level of 40 ng/m3, the onset of lung symptoms would be predicted to occur within 15 minutes. With reduction of this level to 2 ng/m3 or less (which appears to be possible), the same dose would be inhaled in approximately 5 hours. Although measurement of airborne cat allergen could theoretically be used as a true index of exposure, reservoir measurements remain the standard for assessing both exposure and the effec-tiveness of avoidance measures.

Avoidance measures for dogs appear to be similar in general to those for cats—that is, keeping the dog out of the house and controlling accumulation in reservoirs. In addition, using HEPA room filters and washing the animal have each been shown to decrease airborne dog allergen.127

COCKROACH AND OTHER ALLERGENS

For most other allergens, there are only case reports of benefit from avoidance measures. For domestic or wild rodents, the measures are obvious, and the primary problems may be per-suading the family to admit to the presence of a caged animal or agree to remove it. Although the best-recognized source of allergens related to inner city asthma is the German cockroach, other allergens, especially mites, also are important. In the Midwest and Northeast, mice and rats also may be important sources of allergens, and skin testing with rodent extracts should be routine in clinics that treat patients living in cities in these regions.

Avoidance measures for cockroach allergens have been shown to be effective when applied as part of an overall avoid-ance plan.26 The primary strategies are (1) use of poison bait, (2) careful housekeeping to enclose all sources of food for the insects, (3) cleaning to remove any accumulated allergen, and (4) sealing as many access points to the house as possible. Bait for killing cockroaches ranges from boric acid, which can kill mites by damaging the foregut, to a variety of chemicals includ-ing hydramethylnon, abamectin, and fipronil.118,128 Baits can be applied as traps or in the form of paste. Spraying with insecti-cides generally is ineffective and has the additional problem that the volatile organic substances used often are irritating to patients with asthma.

For indoor fungi, the situation is confusing. It is not clear that spore counts are consistent from day to day or how they relate to allergen exposure. Simple assays for allergens derived from Aspergillus (Asp f 1) and Alternaria (Alt a 1) have been developed, but the use of these assays to measure allergens in houses has been disappointing. Many spores are not viable, and some allergens may be expressed only after the spore germi-nates. At present, reasonable recommendations include control-ling humidity, removing sites for fungal growth, cleaning surfaces with fungicides, and avoidance of basement living envi-ronments by allergic individuals.

Although the importance of bacteria as a source of allergens generally is discounted, this is largely because of the lack of good evidence in favor of the concept, rather than reflecting clear evidence against their role. By contrast, extensive evidence shows that endotoxins produced by gram-negative bacteria can influence allergic disease. The endotoxins produced by bacteria are a complex group of lipids. Most available data relate to measurements inside houses and from buildings using the Limulus amebocyte assay, which is a nonspecific assay for endo-toxin.99 In different studies, endotoxin has been proposed to reduce or increase allergic disease. In farming villages, children

effective at killing mites, so the problem is to achieve suf-ficient effect in a carpet. In addition to acaricides, applica-tion of 1% or 3% tannic acid has been recommended as a method of denaturing mite allergens. Again, reduction of mite allergen can be achieved, but tannic acid does not kill mites, so the effect can only be temporary.

A special problem is posed by carpets fitted onto unventi-lated floors, as in basements or the ground floor of houses built on concrete slabs. Under these circumstances, water can accu-mulate either because of condensation onto the cold surface of the concrete or because of leakage (either domestic or rain water from outside). In either case, once the carpet is wet, it will stay wet, and if the temperature rises, it will become an excellent environment for the growth of both fungi and mites.

DOMESTIC ANIMALS

Although removing the cat is an effective way to reduce expo-sure to cat allergen, many domestic animals are full members of the family, so recommending their removal requires great tact. Removal of the cat(s) from a home leads to progressive reductions in the concentration of Fel d 1 in the house, although as long as 4 months after removal may be required for the levels in carpet dust to fall below 8 μg/g.126 Thus it is not surprising that many cat-allergic patients develop symptoms when they move into a house where a cat previously had been present. Keeping the cat outdoors is an alternative and will reduce cat allergen; however, there is likely to be significant allergen brought into the house by passive transfer. On the other hand, some patients maintain that cats do not cause symptoms if they have polished floors and air filtration and wash the cat regularly. Detailed experiments with cats showed that the combination of polished floors, air filtration, vacuum cleaning, and regular washing of the cat could significantly reduce airborne cat aller-gen42 (Box 28-3). Subsequent experiments were not as success-ful, and it now appears that washing the cat twice a week would be required to maintain a decrease in airborne allergen. None-theless, washing the animal can remove 5 to 30 mg of Fel d 1 and may be an effective method of decreasing accumulation of cat allergen in the house.

Up to 40% of airborne cat allergen is associated with parti-cles that are similar in size to those generated by a nebulizer, which makes it possible to make comparisons between natural exposure and bronchial provocation. Inhaling 10 ng of Fel d 1 on droplets approximately 2 μm in diameter in a provocation experiment will produce a measurable fall in FEV1 in sensitive patients. Thus if such a patient was in a house with an airborne

• Removal of cat from the home*• Measures to reduce allergen with cat in situ

1. Reduce reservoirs for cat allergen (e.g., carpets, sofas).2. Use vacuum cleaners with effective filtration system.3. Increase ventilation or use high-efficiency particulate air

(HEPA) filters to remove small airborne particles.4. Wash cat weekly, if possible.

BOX 28-3 AVOIDANCE MEASURES FOR CAT ALLERGENS

*Reducing allergen levels requires about 12 to 16 weeks after cat is removed.

CatandDogImmunotherapy

• Althoughthebesttreatmentforanimalallergyisavoidance.• Thisisnotalwayspossible.

• Exposuretobothdogandcatallergenhasbeenshowntobeubiquitousandcanoccurevenwithoutananimalinthehome.• Makingavoidanceevenmoredifficult.

• Becauseimmunotherapy hasbeenshowntobeeffective forcatanddog• Thedecisiontoincludedogorcatallergeninanallergenimmunotherapyextractshouldbeconsideredinthosecircumstancesinwhichthereisexposure.

Coxetal.JAllergyClin Immunol 2011;127:S1-55

• Themajorallergencontentofcatextractsisrelativelylow, requiringlargeramountstobegiventhanforpollensorhousedustmite.• Themajorallergencontentofmostdogextractsistoolowtoalloweffectivedosing,evenwithundilutedmanufacturers’extracts.• However,inonestudyusinganextractcontainingapproximately161mg/mLCanf1(Hollister-Stier Laboratories,Spokane,Wash),therewasasignificantdoseresponseofimmunologicparameters similartothatdemonstratedwithotherallergens.


• Fel d1isnowavailableasanadditionalrecombinantallergenandsupplementaldiagnostictoolforthediagnosisofcatallergy.• Thissinglemajorcatallergenhasshowntobeasgoodascatdanderextract inidentifyingpatients.• TheIgE levelsinrFel d1maybeusefulasincreasedlevelsinchildrenseemtobeapotentialriskfactorforallergicasthma.

Gronlund Hetal.Int ArchAllergy Immunol 2010;151:265–274

• Fel d1isanidealmodelallergenforthedevelopmentofnewstrategies forallergen-specifictreatmentofallergyandasthma.• Fel d1hypoallergens• Peptide-basedimmunotherapy:

• T-cellepitope-containingpeptides• EngineeredFel d1proteinswithimmunomodulatoryfunction:

• FormulationsconsistingofFel d1coupledtoanimmunomodulatoryproteinorcarrier.

• ResultsreportedfromstudiesevaluatingtheseapproachesinexperimentalinvitroandinvivosystemsaswellasinclinicaltrialswithFel d1peptidesbearpromisethatsafer,morespecificandefficientwaystotreatcat-allergicpatientswillbeavailableinthefuture.

Gronlund Hetal.Int ArchAllergy Immunol 2010;151:265–274

Studydesign:• Randomized,double-blind,placebo-controlled,parallel-groupclinicaltrial

Subjects:• 18- 65years,hadahistoryofrhinoconjunctivitisonexposuretocatsforatleast1year

Studymedication:Cat-PAD:6-nmol,3-nmolCat-PAD:Cat-peptideantigendesensitization• anequimolarmixtureof7peptides• derivedfromFel d1

• Peptideimmunotherapy usessyntheticpeptidesconsistingofT-cellepitopesderivedfrommajorallergensandautoantigenstoinduceantigen-specifictolerance.

• DeliveryofT-cellepitopesintradermally isthoughttoleadtotheinductionofTcellswitharegulatoryphenotype,whichresultsindownregulationoftheresponsetoantigen.

Pateletal.JAllergyClin Immunol 2013;131:103-9

• Intervention: 3groups

• Primaryefficacymeasurement:themeanchangeinTRSSsat50to54weeksfrom1houronwardondays2to4oftheposttreatmentchallenge(PTC)comparedwithbaselinevalues



Baseline

18-22wksafter

treatment

50-54wksafter

treatment

MeanTRSSsscore

• Results:• Greaterefficacywith4administrationsofa6-nmoldose4weeksapart• Thetreatmenteffectof6nmol persisted1yearafterthestartoftreatmentandwassignificantly differentfrom• 3-nmol(P=0.0342)andplacebo(P=0.0104)

• Conclusions:• AshortcourseofCat-PAD improvestheocularandnasalcomponentsofrhinoconjunctivitis symptomsinsubjectswithcatallergy,withthetreatmenteffectpersisting1year afterthestartoftreatment.


P.Couroux etal.Clinical&ExperimentalAllergy2015;45:974–981

• Studiesinvestigatingdogallergenimmunotherapyduringthepast40yearshavefailed todemonstrateanyclearlyreproducibleclinicalevidencetoconfirmitseffectivenessinamelioratingsymptomsofrhinitisandasthma.• VariabilityofDogExtracts

• In1996reportnotedthat• Canf1 levels intheseextractsranged from3.8to170mg/mL.• Themajordustmiteallergens,Derp1andDerp2,weredetectable inallcommercialdogextracts.

• Thepossibility offalsepositiveswithskinpricktestingfordogallergy.• In2001comparedthenewestAPdogextracttothetraditionalaqueousdogextract

• 48%testedpositivetoAPdog.Only28%testedpositivetoconventionaldogextracts.• AllpatientswhotestedpositivetoconventionalextractsalsowerepositivetoAPdog,withasignificantly largermeanwhealdiameter.

• 41%whotestedpositivetoAPdogtestednegativetoconventionaldogextracts.• Thesedataperpetuatedquestionsaboutfalsenegative.


• StabilityofDogExtracts• In1998showedthat

• Canf1wasrelativelythermostable,with50%oftheallergenremainingafter60minutesof140Cdryheat.

• In2009,thestabilityandcompatibilityofAPandconventionaldogextractswereinvestigated• Canf1levelsremainedat94%to119%andCanf3retained79%to94%potencyfor3dayswhenkeptbetween21Cand45C,showingstandardshippingmethodswithoutrefrigerationareacceptableforextracts.

• Theextractswith50%glycerinretainedtheirpotency,whereastheextractswithnomorethan10%glycerinshowedsignificantdegradation.


• CurrentPrescribingTrends• Anationwidesurveyin2006 showedtheperspectiveofhowallergists acrosstheUnitedStateswereintegratingtheseconflictingandconfusingdataandusingthemindailypractice.• Responsesshowedthemaintenanceweight-to-volumeratiovariedwidelyfrom1:10to1:1,000 withthemostcommonconcentrationbeing1:100(24.3%).

• Mostallergistsbelievethatdogimmunotherapywillprovideatleastsomerelief fromallergicrhinitis(91.9%)andasthma (89.6%)

• 86% wouldbewillingtooffer immunotherapytotreatoccupationalallergy.• Thisratedecreasesto81% ifthepatientisunabletoremovethedogforpurelyemotionalreasons.

• Tocomparewith1987whenonly65%ofboard-certifiedallergists inprivatepracticeperceivedimprovementinallergicrhinitisorasthmasymptomswithcatordogimmunotherapy.


• Futureresearchisnecessarytoproducemorepotentandcomplexextractsthatcouldbetailoredtoanindividual patient’spatternofdogsensitization.• Thefirststepwouldbetoproduceastandardizedextractforclinicaluse.

• Additionaltrialscouldbedesignedtoevaluatetheefficacyofdogallergenimmunotherapy inimprovingclinicalendpointsforpatients.• Properlypoweredstudieswithconsistentallergenextractsalsowouldfacilitateidentificationoftheoptimaldoserequiredtoproducetheseeffects.• Thecurrentrecommendationonimmunotherapydosingfornonstandardizeddogextractsis15ug ofCanf1perdose.• 0.5-mLdoseusingfull-strength(1:100w/v)APdogextract


Cat and dog allergens

Health & Medicine

Transcript of Cat and dog allergens