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1	December	2017
Thansinee Saetae,	MD
Pediatric	allergy	and	Immunology	Unit
King	ChulalongkornMemorial	Hospital
http://biologyvermontschool.blogspot.com/2013/03/bio-classification-classify-al-least-2.html
Cat	and	Dog	Allergen
Pomés A	et	al.	Curr Allergy	Asthma	Rep.	2016;16:43
• Fel d	1	is	a	38	kD tetrameric	glycoprotein with	a	structure	similar	to	
that	of	uteroglobulin.
• IgE from	over	90	%	of	cat-sensitized	individuals	reacts	with	this	major	
cat	allergen.
• Fel d	1	is	produced	in	sebaceous,	anal,	and	salivary	glands	and	
transferred	to	the	fur by	grooming.
• Airborne	Fel d	1	is	mostly associated	with	larger	particles	(>9	μm)
• 23	% of	airborne	Fel d	1	is	carried	on	small	particles	(<4.7	μm diameter)	that	
stay	suspended	in	the	air	for	several	days,	favoring	distribution	of	the	
allergen	in	the	environment.
Pomés A	et	al.	Curr Allergy	Asthma	Rep.	2016;16:43
• Others	relevant	cat	allergens
• Fel d	3:	Cysteine	protease	inhibitor	react	with	10	% of	IgE from	cat-allergic	patients.	
• Fel d	6: Cat	IgM	is	less	well	documented.	
Pomés A	et	al.	Curr Allergy	Asthma	Rep	2016;16:43
Grönlund H	et	al.	Int Arch	Allergy	Immunol 2010;151:265–274
Konradsen et	al.	J	Allergy	Clin Immunol 2015;135:616-25.	
Sarbjit S.	Saini.	Middleton's	8th	edition.	
90%
63%
37%
15-40%
40%
High	IgE levels	to	Fel d	1	could	be	a	marker	of	increased	asthma	risk.	
High	IgE levels	to	Fel d	4	have	been	associated	with	atopic	dermatitis.
• A proportion	of	the	airborne	allergen	(10%	to	40%)	was	being	carried	on	
smaller	particles	(less	than	5	μm in	diameter).	
• The	aerodynamic	behavior	of	these	particles	and	show	that	they	are	
dynamically	equivalent	to	spheres	of	1	to	7	μm in	diameter.	
• It	is	important	to	realize	that	a	flat	“flake”	of	dander	may	potentially	have	an	
aerodynamic	size	smaller than	its	real	size.	
• Approximately	60% of	airborne	Fel d	1 settles	out	within	2	days	of	
disturbance,	leaving	smaller	particles	that	can	remain	airborne	for	up	to	14	
days	or	longer.	
J.	Portnoy	et	al.	Ann	Allergy	Asthma	Immunol 2012;2018:223.e1–223.e15
Sarbjit S.	Saini.	Middleton's	8th	edition.
• The	presence	of	a	cat	can	increase	airborne	Fel d	1	within	30	minutes.	
• Indeed,	recent	estimates	suggest	that	the	quantities	of	cat	allergen	inhaled	
are	10	to	50	times	higher	than	mite	allergen.	
• The	size	of	these	particles	has	some	important consequences.	
• Small	particles	fall	slowly	and	can	be	kept	airborne	by	any	movement	in	the	house.	
• Increased	ventilation	helps	to	remove	small	particles	from	a	house.	
• Air	filtration	with	a	room	air	cleaner	may	be	a	useful	method	of	reducing	exposure	
to	allergen	on	small	particles.	
J.	Portnoy	et	al.	Ann	Allergy	Asthma	Immunol 2012;2018:223.e1–223.e15
Sarbjit S.	Saini.	Middleton's	8th	edition.
• More	than	90% of	all	people	who	have	respiratory	tract	symptoms	
related	to	cat	exposure	have	IgE antibodies	specific	for	Fel d	1.	
• Measurements	of	Fel d	1	in	the	environment	provide	an	excellent	
model	for	cat	exposure	relevant	to	asthma or	rhinitis.	
• Peptides derived	from	Fel d	1	have	been	proposed	as	an	alternative	
to	cat	extract	for	immunotherapy.	
• Fel d	1 itself	has	no important	cross-reactivities and	indeed	has	very	
little	homology	with	any	known	allergens	except	Can	f	4.	
Sarbjit S.	Saini.	Middleton's	 8th	edition.
• Other	allergens	from	cat	are	more	important	in	relation	to	food	
allergy than	to	inhalant	symptoms.
Fel d	2,	Cat	albumin
cross-reactsimmunologically	with	several different	
mammalian	albumins,	including	those	of	dog,	pork,	
and	beef	à adult-onset	allergic	reactions	to	pork	
Pork-Cat	Syndrome
Patients	with	this	syndrome	sensitized	to	albumins	
from	animal	dander	report	symptoms	after	the	
consumption	of	pork	because	of	the	cross-reactivity	
of	albumins	from	different	species.	
Konradsen et	al.	J	Allergy	Clin Immunol 2015;135:616-25.
Sarbjit S.	Saini.	Middleton's	8th	edition.
• Fel d	5w,	cat	IgA
• The	alpha-gal–specific	IgE antibodies were	strongly	associated	with	delayed	
anaphylaxis	to	red	meat.	
• IgE antibodies	to	alpha-gal will	bind	to	cat	IgA	(Fel d	5w),	beef	thyroglobulin
• The	presence	of	IgE antibodies	to	alpha-gal	can	lead	to	misleading results	on	
IgE assays	or	skin	tests	using	cat	extracts.	
• IgE antibodies	to	alpha-gal	do	not	create	a	risk	for	asthma	or	other	inhalant	
symptoms.
Sarbjit S.	Saini.	Middleton's	 8th	edition.
Konradsen et	al.	J	Allergy	Clin Immunol 2015;135:616-25.
• Dogs	can	be	a	potent	source	of	allergen,	
• appears	to	be	less	common	than	cat	allergy	as	a	cause	of	asthma.	
• Many	dogs	are	kept	outside and	become	dirty	(actually,	much	worse),	
so	washing	dogs	is	a	common	practice.	
• A	common	sources	of	dog	allergens	are	dander	and	saliva.
• Four	of	six	currently	identified	dog	allergens are	lipocalins.	
• Can	f	1,	Can	f	2,	Can	f	4,	and	Can	f	6
Sarbjit S.	Saini.	Middleton's	 8th	edition.		
Pomés A	et	al.	Curr Allergy	Asthma	Rep.	2016;16:43
• About	∼70	%	of	dog- allergic	individuals	have	IgE antibodies	specific	to	
the	major	dog	allergen	Can	f	1.	
• Can	f	1	is	detectable	in	one	third	of	homes	without	a	dog.	
• The	size distribution	of	particles	associated	with	Can	f	1	is	similar to	
that	of	Fel d	1.	
• A	wide	variability in	Can	f	1	levels	can	be	found	between	dog	breeds,	
• but	there	is	no evidence	for	a	hypoallergenic	breed.	
Pomés A	et	al.	Curr Allergy	Asthma	Rep.	2016;16:43
• Can	f	5	(prostatic	kallikrein,	arginine	esterase),	derived	from	dog	urine is	
also	considered	a	major	allergen,	with	up	to	70% of	dog- allergic	patients	
having	Can	f	5-specific	IgE.	
• 38	%	of	dog-allergic	patients	were	monosensitizedto	Can	f	5.	
• Other	relevant	dog	allergens	
• Can	f	2	(lipocalin)	
• react	with	20–30%	of	IgE from	dog- allergic	patients.
• Can	f	4	(lipocalin)	
• react	with	15–50%	of	IgE from	dog- allergic	patients.
• Can	f	6	(lipocalin)
• react	with	38%	of	IgE from	dog- allergic	patients.
• Can	f	3	(dog	albumin)
• react	with	81	% of	IgE from	dog- allergic	patients.	
Significant	inhalant	allergens
Sarbjit S.	Saini.	Middleton's	8th	edition.		
Mattsson et	al.	J	Allergy	Clin Immunol 2009;123:362-8.	
Pomés A	et	al.	Curr Allergy	Asthma	Rep.	2016;16:43
D.M.	Smith	and	C.A.	Coop.	Ann	Allergy	Asthma	Immunol 2016;116:188-193
Konradsen et	al.	J	Allergy	Clin Immunol 2015;135:616-25.
Immune	response	to	
Cat	and	Dog	allergen
• The	immune	response	to	domestic	animal	allergens	includes	
• T	cells	
• IgE antibodies
• different	isotypes	of	antibodies.	
• At	present,	both	the	significance	of	IgE antibodies	and	the	techniques	
for	measuring	IgE antibody	levels	are	better	established	than	the	
techniques	for	describing	any	other	aspect	of	the	immune	response.	
Konradsen et	al.	J	Allergy	Clin Immunol 2015;135:616-25.
• T-cell	responses
• A wide	range	of	studies	have	been	carried	out	on	T-cell	responses	
to	cat	allergens	using	both	the	protein	Fel d	1	and	overlapping	
peptides	derived	from	Fel d	1.	
• These	studies	demonstrated	that	responses	to	Fel d	1	are,	broadly	
speaking,	of	a	TH2	type.	
• Although	it	is	possible	that	there	are	patients	who	have	symptoms	
related	to	cat	or	dog	allergen	exposure	on	the	basis	of	a	T-cell	
response	without	an	associated	IgE antibody	response,	this	has	
not	been	demonstrated.
Konradsen et	al.	J	Allergy	Clin Immunol 2015;135:616-25.
• IgG	antibody	responses
• There	are	mixed	data	about	the	isotypes	other	than	IgE and	IgG4.
• Many	publications	report	detectable	IgG4	antibodies	in	most	allergic	and	
non-allergic	subjects in	contrast	to	extensive	earlier	data.	
• Although	the	results	might	not	be	relevant	to	the	clinical	evaluation	of	
patients,	they	are	important	to	understanding	the	immune	response	to	cat	
allergens	in	those	atopic	children	who	live	in	a	house	with	a	cat but	do	not	
become	symptomatic	on	exposure	to	cat	allergens.
Konradsen et	al.	J	Allergy	Clin Immunol 2015;135:616-25.
• IgG	antibody	responses (Cont.)
• The	dissociation	of	allergen-specific	IgE and	IgG	responses	to	cat,	
dog,	and	horse	was	reported,	
• indicating	that	nonsequential class-switch	mechanisms	are	operative	in	
patients	with	animal	allergy	and	might	explain	why	naturally	occurring	
allergen-specific	IgG	is	not	always	protective.
• Measurement	of	IgG	antibodies	might	also	be	relevant	to	understanding	
why	some	subjects	experience	increased	symptomson	entering	a	house	
with	an	animal	after a	period	of	decreased	exposure.	
Konradsen et	al.	J	Allergy	Clin Immunol 2015;135:616-25.
Study	design:
Prospective	cohort	study
Participants:
97	college	students	who	tolerated	living	in	
a	house	with	a	cat
Intervention:
Decrease	exposure	to	cat	allergen
The	primary	outcome:	
The	change	in	antibody	titers	over	time.	
Measure:
Skin	prick	test:	
at	baseline
Specific	IgE to	cat:	
at	baseline,	8	months
Specific	IgE to	Fel d	1:	
at	baseline,	8	months
IgG	to	Fel d	1	à IgG4	to	Fel d	1:	
at	baseline,	8	months
E.A.	Erwin	et	al.	Ann	Allergy	Asthma	Immunol 2014;112:545-550
• Having	IgG	without	evidence	of	sensitization	was	the	most frequently	observed	
immune	response to	cat	(n	=	32).
• None	of	the	students	who	had	IgG but	were	not	sensitized	to	cat	had	wheezing.
E.A.	Erwin	et	al.	Ann	Allergy	Asthma	Immunol 2014;112:545-550
E.A.	Erwin	et	al.	Ann	Allergy	Asthma	Immunol 2014;112:545-550	
• Non-sensitized individuals	with	IgG	to	Fel d	1	experienced	
a	significant	decrease	in	IgG	titers	with	decreased	
exposure	to	cat	allergen	(p=0.02).	
• For	those	students	(n	= 21)	who	were	followed	up	for	a	
second	year,	levels	of	IgG	antibody	to	Fel d	1	had	
decreased	further.	
• Non- sensitized	individuals,	 IgG4 also	decreased	(P	<	.001)	
during	 8	months	of	decreased	cat	exposure.	
• None of	the	individuals	having	IgG	to	Fel d	1	without	
sensitization to	cat	developed	a	positive	serum	IgE
antibody	assay	or	a	positive	skin	prick	test	result	to	cat	
during	 1	year	or	2	years.	
Changes	in	Antibody	Titers	to	Fel d	1	in	Non-sensitized	Individuals
E.A.	Erwin	et	al.	Ann	Allergy	Asthma	Immunol 2014;112:545-550	
• Specific	IgE titers	to	cat	did	not	decrease	
significantly	during	 prolonged,	 decreased	
exposure	to	cat	allergen.
• IgG	antibody	to	Fel d	1	decreased	significantly during	
the	8-month	study	period	(P	<	.001)
Antibody	Changes	in	Cat	Sensitized	Individuals
Ratios	of	cat	specific	IgG	to	IgE antibodies	
E.A.	Erwin	et	al.	Ann	Allergy	Asthma	Immunol 2014;112:545-550	
There	was	a	highly	significant	
decrease	in	the	ratio	of	IgG	to	IgE
antibodies after	8	months,	
decreased	exposure	to	cat	allergen.
• Conclusion:	Under	conditions	of	marked	decrease	in	exposure,
• No participants	developed	new-onset	sensitization.	
• Among	the	individuals	sensitized	at	study	entry,	there	were	major	decreases	
in	the	ratio	of	IgG	to	IgE.	
E.A.	Erwin	et	al.	Ann	Allergy	Asthma	Immunol 2014;112:545-550
The	effect	of	Cats	or	Dogs	
in	the	home
• The	major	cat	allergen,	Fel d	1,	remains	airborne for	many	hours	
after	any	disturbance.
• As	a	result,	estimates	of	the	quantities	of	cat	(or	dog)	allergens	
inhaled	in	a	house	with	an	animal	are	much	higher,	at	approximately	
1	μg/day,	than	comparable	estimates	of	Der	p	1	inhaled	of	10	
ng/day.	
• In	addition,	the	particles	of	dander	carrying	cat	allergens	appear	to	be	
“sticky,”	which	means	that	they	are	consistently	carried	on	clothing	
from	houses	with	an	animal	to	other	buildings.	
Sarbjit S.	Saini.	Middleton's	 8th	edition.
• In	a	community	where	20%	or	more	of	the	families	have	animals,	
these	allergens	will	be	easily measurable	in	dust	from	schools or	in	
homes	without	a	cat.	
• Sensitization	to	cats	can	occur	without	direct	exposure	to	the	
animals.	
• In	some	studies,	75%	of	the	children	who	are	allergic	to	cats have	never lived	
in	a	house	with	a	cat.	
Sarbjit S.	Saini.	Middleton's	 8th	edition.
• In	1998,	Hesselmar and	Bjorksten reported	that	children	raised	in	a	
house	with	a	cat were	less	likely	to	become	allergic	to	cats.
• This	result	was	greeted	with	astonishment;however,	several	other	groups	of	
investigators	found	strong	evidence	supporting	that	observation.
• Many	of	the	“non-allergic”	children	who	lived	in	a	house	with	a	cat	had	made	
IgG	and	IgG4 antibodies	to	Fel d	1.	
• This	response	is	of	interest	in	that	it	has	more	of	the	features	of	a	“modified	
Th2”	response	than	of	a	shift	to	Th1.	
• The	effect	of	exposure	to	a	cat	in	early	life	can	be	both	allergen-
specific and	long-lasting.
Sarbjit S.	Saini.	Middleton's	 8th	edition.
Study	design: Meta	– analysis
Objective:
To	examine	the	associations	between	pet	
keeping	in	early	childhood	and	asthma	and	
allergies	in	children	aged	6–10	years.	
Participants:
Data	of	11	prospective	European	birth	cohorts	
that	recruited	a	total	of	over	22,000	children	
in	the	1990s.	
Exposure	definition:
Ownership	of	only	cats,	dogs,	birds,	
rodents,	or	cats/dogs	combined	during	the	
first	2	years	of	life.	
Outcomes:	
Allergic	asthma,	Allergic	rhinitis	and	Allergic	
sensitization	during	6–10	years	of	age.	
Lodrup Carlsen KC	et	al.	PLoS One	2012;7:e43214.
Pets
Pets and
Lodrup Carlsen KC	et	al.	PLoS One	2012;7:e43214.	
OR=	1.09
OR=	0.79
Lodrup Carlsen KC	et	al.	PLoS One	2012;7:e43214.	
OR=	0.91
PetP
Lodrup Carlsen KC	et	al.	PLoS One	2012;7:e43214.	
OR=	0.65
OR=	0.87
Lodrup Carlsen KC	et	al.	PLoS One	2012;7:e43214.	
OR=	0.68
P
Lodrup Carlsen KC	et	al.	PLoS One	2012;7:e43214.	
P
OR=	1.02
OR=	0.77
Lodrup Carlsen KC	et	al.	PLoS One	2012;7:e43214.	
OR=	0.79
Lodrup Carlsen KC	et	al.	PLoS One	2012;7:e43214.	
Conclusion:	
• Pet	ownership	in	early	life	did	not appear	to	either	increase	or	reduce	the	risk	
of	asthma or	allergic	rhinitis	symptoms	in	children	aged	6–10.	
• Advice from	health	care	practitioners	to	avoid	or	to	specifically	acquire	pets	for	
primary	prevention	of	asthma	or	allergic	rhinitis	in	children	should	not	be	given.
• An	issue	of	some	clinical	importance	is	whether	the	effect	of	a	dog in	
the	house	is	the	same	as	the	effect	of	a	cat.	
• High	levels	of	endotoxin	in	the	home	were	inversely related	to	
allergen	sensitization.
• Several	detailed	studies	have	shown	that	a	cat in	the	home	does	not	increase	
endotoxin	either	in	floor	dust	or	in	airborne	form.
• The	presence	of	one	or	more	dogs	in	the	house	does	increase	airborne	
endotoxin,	and	in	some	studies,	early	exposure	to	dogs appeared	to	have	an	
inhibitory	effect	on	allergy	in	general.	
Sarbjit S.	Saini.	Middleton's	 8th	edition.
• Although	undoubtedly	individual	differences	will	affect	the	response	
to animal	exposure,	two	very	different	mechanisms may	be	involved.	
• The	first	is	the	shift,	induced	by	higher	exposure,	to	germinal	center	
production	of	B	cells,	which	favors	IgG4	production	and	may	be	a	major	
component	of	the	allergen-specific	tolerance induced	by	early	exposure	to	
cat	allergens.
• The	second mechanism	is	increased	endotoxin or	increased	bacterial	
diversity	in	the	home,	with	consequent	effects	on	the	microbiomeof	the	
child	during	early	development.
• The	second	mechanism	would	not	be	allergen- specific	and	is	more	likely	with	a	dog	
than	with	a	cat.	
Sarbjit S.	Saini.	Middleton's	 8th	edition.
Environmental	assessment	
and	exposure	control
Practice Parameter
Environmental assessment and exposure control: a practice parameter—furry animals
Chief Editors: Jay Portnoy, MD, Kevin Kennedy, MPH, James Sublett, MD
Members of the Joint Task Force on Practice Parameters: David Bernstein, MD, Joann Blessing-Moore, MD, Linda Cox, MD, David Khan, MD, David Lang, MD, Richard Nicklas,
MD, John Oppenheimer, MD, Jay Portnoy, MD, Christopher Randolph, MD, Diane Schuller, MD, Sheldon Spector, MD, Stephen A. Tilles, MD, Dana Wallace, MD
Practice Parameter Work 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, PhD
Invited Reviewers: Jack Armstrong, Hans Gr×nlund, PhD, Kraig W. Jacobson, MD, Jill A. Poole, MD, Matthew A Rank, MD, Megan Taylor, MD
This 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,
Asthma and Immunology, and the Joint Council of Allergy, Asthma and Immunology.
The American Academy of Allergy, Asthma and Immunology (AAAAI) and the American College of Allergy, Asthma and Immunology (ACAAI) have jointly accepted responsibility for
establishing “Environmental Assessment and Remediation: A Practice Parameter.” This is a complete and comprehensive document at the current time. The medical environment is a
changingenvironment,andnotallrecommendationswillbeappropriateforallpatients.Becausethisdocumentincorporatedtheeffortsofmanyparticipants,nosingleindividual,including
thosewhoservedontheJointTaskForce,isauthorizedtoprovideanofficialAAAAIorACAAIinterpretationofthesepracticeparameters.Anyrequestforinformationaboutoraninterpretation
of 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. These
parameters are not designed for use by pharmaceutical companies in drug promotion.
Reprints: Joint Council of Allergy, Asthma and Immunology, 50 N Brockway St, #3-3 Palatine, IL 60067.
Disclosures: The following is a summary of interests disclosed on Work Group members’ Conflict of Interest Disclosure Statements (not including information concerning family member
Ann Allergy Asthma Immunol 108 (2012) 223.e1–223.e15
Contents lists available at SciVerse ScienceDirect
• A desire	for	companionship often	override the	medically	prudent	advice	to	
avoid	exposure	to	dogs	and	cats	for	a	sensitized	person.	
• The	bottom	line	is	that	patients	love	their	pets.	They	are	part	of	the	family.
• Pet	ownership	is	likely	to	persist.
• Allergists need	to	be	able	to	advise	their	patients	how	to	live	with	the	pet	
while	remaining	as	healthy	as	possible.
• Removal	of	cats	is	recommended	to	decrease	overall	exposure.
• However,	complete	removal	of	all	cats	is	necessary	to	minimize	cat	allergen	
exposure	in	a	home.	(C)	
• Cat	characteristics, such	as	length	of	hair,	sex,	reproductive	status,	
and	time	spent	indoors, are	not	associated	with	levels	of	Fel d	1	in	
the	environment.
• Therefore,	interventions	related	to	these	factors	cannot	be	recommended.	(C)	
• Data	about	the	effect	of	neutering a	dog	or	cat	are	inconsistent,	
• No	specific	recommendations	can	be	made	at	this	time	about	performing	
such	a	procedure	to	reduce	allergen	exposure.	(D)	
J.	Portnoy	et	al.	Ann	Allergy	Asthma	Immunol 2012;2018:223.e1–223.e15
• Because	1	or	more	cat	allergens	are	present	in	all	cats,	patients	should	not	
be	advised	that	it	is	safe to	obtain	a nonallergenic cat.	(C)
• Measurement	of	cat	allergens	in	settled	dust	should	not	be	used	as	a	
surrogate	for	airborne	exposure.	(C)	
• Carpetsare	the	major	reservoir	for	pet	allergens	in	homes	with	pets	
• Dust	from	living	rooms	contains	significantly	higher	concentrations	of	both	Fel d	1	
and	Can	f	1	than	dust	from	bathrooms,	kitchens,	and	bedrooms,	although	the	beds	
may	contain	even	higher	concentrationsof	Fel d	1.	
• To	reduce	transport	of	cat	allergen,	people	should	consider	changing	their	
clothes when	traveling	from	a	high	cat	allergen	environment	to	a	low	cat	
allergen	environment.	(C)	
J.	Portnoy	et	al.	Ann	Allergy	Asthma	Immunol 2012;2018:223.e1–223.e15
• Because	1	or	more	dog	allergens	are	present	in	all	dogs,	patients	
should	not	be	advised	that	it	is	safe to	obtain	a	nonallergenic dog. (C)
• Dogs	should	be	excluded from	rooms	in	which	reduced	exposure	is	
desired.	(C)	
• The	number	of	dogs	in	the	home	is	not	related	to	dog	allergen	levels.	
• Homes	with	outdoor	dogs	have	higher dog	allergen	levels	than	homes	
without	any	dogs	but	lower levels	than	homes	with	indoor	dogs.	
• Upholstered	chairs	in	hospitals	are	an	important	reservoir	of	cat	and	dog	
allergen.	
• Special	daycare	centers	with	children	who	don’t	have	dogs	or	cats have	
lower	concentrations	of	both	dog	and	cat	allergen than	daycare	centers	with	
children	who	live	with	a	dog	or	cat.	
J.	Portnoy	et	al.	Ann	Allergy	Asthma	Immunol 2012;2018:223.e1–223.e15
• Although	exposure	to	elevated	cat	allergen	Fel d	1	concentrations	
before	3	months	of	age	may	reduce	the	likelihood	of	developing	cat	
sensitization,	
• the	risk	reduction	is	not	sufficient	to	justify	a	decision	to	get	a	cat	to	avoid	
IgE sensitization. (C)	
• Although	exposure	to	elevated	dog	allergen	Can	f	1	concentrations	
before	3	months	of	age	may	reduce	the	likelihood	of	developing	dog	
sensitization,	
• the	risk	reduction	is	not	sufficient	to	justify	a	decision	to	get	a	dog	to	avoid	
IgE sensitization. (C)	
J.	Portnoy	et	al.	Ann	Allergy	Asthma	Immunol 2012;2018:223.e1–223.e15
• Cat	exposure	should	be	minimizedin	cat	sensitized	individuals	to	reduce	the	
likelihood	of	developing	asthma.	(C)	
• Dog	exposure	should	be	minimized	in	dog	sensitized	individuals	to	reduce	the	
likelihood	of	developing	asthma.	(C)	
J.	Portnoy	et	al.	Ann	Allergy	Asthma	Immunol 2012;2018:223.e1–223.e15	
• Exposure	to	cat	allergens	should	be	minimizedto	reduce	the	likelihood	of	an	
asthma	exacerbation in	cat	sensitized	schoolchildren	and	adults	who	already	
have	asthma.	(A)	
• Exposure	to	dog	allergens	should	be	minimizedto	reduce	the	likelihood	of	an	
asthma	exacerbation in	dog	sensitized	schoolchildren	and	adults	who	already	
have	asthma.	(A)
• Patients	should	be	asked	whether	there	is	a	dog	or	cat	in	the	house	
because	an	affirmative	answer	is	associated	with	greater	exposure	to	
dog	or	cat	allergens.	(C)	
• Patients	with	allergic	disorders	should	be	evaluated	for	sensitization	
to	cat	and	dog	allergens	by	skin	prick	testing	or	in	vitro	testing	for	cat	
and	dog	specific	IgE. (C)	
J.	Portnoy	et	al.	Ann	Allergy	Asthma	Immunol 2012;2018:223.e1–223.e15
• Patients	should	be	advised	to	consider	removing	the	cat	or	dog	from	
the	environment,	if	present,	to	improve	respiratory	health. (A)	
• To reduce	exposure	to	cat	allergens	with	the	cat	still	living	in	the	
house,	a	combination	of	measures,	such	as	removing	reservoirs,	
keeping	the	cat	out	of	the	bedroom,	washing	the	cat,	air	cleaning	
with	a	HEPA room	air	cleaner,	improving	ventilation,	and	mattress	
and	pillow	covers, may	be	helpful.	(C)	
J.	Portnoy	et	al.	Ann	Allergy	Asthma	Immunol 2012;2018:223.e1–223.e15
• Chemical	treatments,	such	as	tannic	acid,	can	be	applied	to	carpet to	
give	short-term	reduction	of	cat	allergen,	but	this	is	not	sustained	
and	there	is	no	evidence	that	it	improves	respiratory	health.	(C)	
• Use	of	hypochlorite	bleach	to	denature	indoor	allergens	can	reduce	
allergen	exposure,	improve	quality	of	life,	and	reduce	the	likelihood	
of	developing	atopy,	but	it	can	also	lead	to	increased	respiratory	
symptoms in	individuals	using	it.	(C)	
J.	Portnoy	et	al.	Ann	Allergy	Asthma	Immunol 2012;2018:223.e1–223.e15
• Washing	cats	or	dogs	at	least	weekly can	reduce	airborne	cat	Fel d	1	
or	dog	Can	f	1;	however,	the	clinical	benefit	is	yet	to	be	proven	and	
the	effect	of	washing	is	not	sustained.	(B)	
• Some	woven microfiber	bed	encasings,	generally	those	with	a	mean	
pore	size	of	6	m	or	less,	block	cat	allergen	from	penetrating	the	fabric	
though	the	respiratory	health benefit	from	their	use	is	unclear. (C)	
• Nonwoven	microfiber	encasings	collect	allergen	on	their	surface	
over	time,	including	cat	and	mite	allergens.	Because	they	cannot	be	
washed,	they	are	unsuitable	for	allergen	avoidance.	(C)	
J.	Portnoy	et	al.	Ann	Allergy	Asthma	Immunol 2012;2018:223.e1–223.e15
• Long-term	regular	use	of	high-efficiency	or	central	vacuum	cleaners	
is	associated	with	reduced	exposure	to	Fel d	1	and	Can	f	1	in	homes	
with	cats	or	dogs	living	in	them,	although	the	health	effects	are	
uncertain.	(B)	
• HEPA	air	cleaners	run	continuously	over	time	can	reduce	exposure	to	
dog	and	cat	allergen	concentrations,	but	the	clinical	benefits	are	
unknown. (B)	
• Dog	and	cat	allergens	are	relatively	stable	to	dry	heat	so	dry	heat	
should	not	be	used	specifically	to	reduce	exposure.	(C)	
J.	Portnoy	et	al.	Ann	Allergy	Asthma	Immunol 2012;2018:223.e1–223.e15
Sarbjit S.	Saini.	Middleton's	 8th	edition.		
houses ha
some alle
nates.At p
ling hum
surfaces w
ronments
Althou
generally
good evid
clear evid
shows tha
influence
are a com
measurem
Limulus a
toxin.99
In
reduce or
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.
Cat	and	Dog	Immunotherapy
• Although	the	best	treatment	for	animal	allergy	is	avoidance.
• This	is	not	always	possible.	
• Exposure	to	both	dog	and	cat	allergen	has	been	shown	to	be	ubiquitous	
and	can	occur	even	without	an	animal	in	the	home.	
• Making	avoidance	even	more	difficult.
• Because	immunotherapy has	been	shown	to	be	effective for	cat	and	dog
• The	decision	to	include	dog	or	cat	allergen	in	an	allergen	immunotherapy	extract	
should	be	considered	in	those	circumstances	in	which	there	is	exposure.	
Cox	et	al.	J	Allergy	Clin Immunol 2011;127:S1-55
• The	major	allergen	content	of	cat	extracts	is	relatively	low, requiring	
larger	amounts	to	be	given	than	for	pollens	or	house	dust	mite.	
• The	major	allergen	content	of	most	dog	extracts	is	too	low	to	allow	
effective	dosing,	even	with	undiluted	manufacturers’	extracts.	
• However,	in	one	study	using	an	extract	containing	approximately	161	mg/mL	
Can	f	1	(Hollister-Stier Laboratories,	Spokane,	Wash),	there	was	a	significant	
dose	response	of	immunologic	parameters similar	to	that	demonstrated	with	
other	allergens.
Cox	et	al.	J	Allergy	Clin Immunol 2011;127:S1-55
Cox	et	al.	J	Allergy	Clin Immunol 2011;127:S1-55
• Fel d	1	is	now	available	as	an	additional	recombinant	allergen	and	
supplemental	diagnostic	tool	for	the	diagnosis	of	cat	allergy.	
• This	single	major	cat	allergen	has	shown	to	be	as	good	as	cat	dander	
extract in	identifying	patients.	
• The	IgE levels	in	rFel d	1	may	be	useful	as	increased	levels	in	children	
seem	to	be	a	potential	risk	factor	for	allergic	asthma.	
Grönlund H	et	al.	Int Arch	Allergy	Immunol 2010;151:265–274
• Fel d	1	is	an	ideal	model	allergen	for	the	development	of	new	strategies for	
allergen-specific	treatment	of	allergy	and	asthma.	
• Fel d	1	hypoallergens
• Peptide-based	immunotherapy:	
• T-cell	epitope-containing	peptides
• Engineered	Fel d	1	proteins	with	immunomodulatory	function:	
• Formulations	consisting	of	Fel d	1	coupled	to	an	immunomodulatory	protein	or	carrier.	
• Results	reported	from	studies	evaluating	these	approaches	in	experimental	in	
vitro	and	in	vivo	systems	as	well	as	in	clinical	trials	with	Fel d	1	peptides	bear	
promise	that	safer, more	specific	and	efficient ways	to	treat	cat-allergic	patients	
will	be	available	in	the	future.	
Grönlund H	et	al.	Int Arch	Allergy	Immunol 2010;151:265–274
Study	design:	
• Randomized,	double-blind,	placebo-controlled,	parallel-group	clinical	trial
Subjects:	
• 18- 65	years,	had	a	history	of	rhinoconjunctivitison	exposure	to	cats	for	at	least	1	year
Study	medication:	Cat-PAD:		6-nmol,	3	-nmol
Cat-PAD:	Cat-peptide	antigen	desensitization	
• an	equimolar	mixture	of	7	peptides	
• derived	from	Fel d	1
• Peptide	immunotherapy uses	synthetic	peptides	consisting	of	
T-cell	epitopes	derived	from	major	allergens	and	autoantigens	
to	induce	antigen-specific	tolerance.	
• Delivery	of	T-cell	epitopes	intradermallyis	thought	to	lead	to	
the	induction	of	T	cells	with	a	regulatory	phenotype,	which	
results	in	downregulation	of	the	response	to	antigen.	
Patel	et	al.	J	Allergy	Clin Immunol 2013;131:103-9
• Intervention: 3	groups
• Primary	efficacy	measurement:	the	mean	change	in	TRSSs	at	50	to	54	
weeks	from	1	hour	onward	on	days	2	to	4	of	the	posttreatment	challenge	
(PTC)	compared	with	baseline	values
Patel	et	al.	J	Allergy	Clin Immunol 2013;131:103-9
Patel	et	al.	J	Allergy	Clin Immunol 2013;131:103-9
Patel	et	al.	J	Allergy	Clin Immunol 2013;131:103-9	
Baseline
18-22	wks
after	
treatment
50-54	wks
after	
treatment
Mean	TRSSs	score
• Results:	
• Greater	efficacy	with	4	administrations	of	a	6-nmol	dose	4	weeks	apart
• The	treatment	effect	of	6	nmol persisted	1	year	after	the	start	of	treatment	
and	was	significantly different	from	
• 3-nmol	(P=	0.0342)	and	placebo	(P=	0.0104)
• Conclusions:	
• A	short	courseof	Cat-PAD improves	the	ocular	and	nasal	components	of	
rhinoconjunctivitis symptoms	in	subjects	with	cat	allergy,	with	the	treatment	
effect	persisting	1	year after	the	start	of	treatment.	
Patel	et	al.	J	Allergy	Clin Immunol 2013;131:103-9
P.	Couroux et	al.
Clinical	&	Experimental	Allergy	2015;45:974–981
D.M.	Smith	and	C.A.	Coop.	Ann	Allergy	Asthma	Immunol 2016;116:188-193
• Studies	investigating	dog	allergen	immunotherapy	during	the	past	40	years	
have	failed to	demonstrate	any	clearly	reproducible	clinical	evidence	to
confirm	its	effectiveness	in	ameliorating	symptoms	of	rhinitis	and	asthma.	
• Variability	of	Dog	Extracts	
• In	1996	report	noted	that	
• Can	f	1 levels	in	these	extracts	ranged from	3.8	to	170	mg/mL.
• The	major	dust	mite	allergens,	Der	p	1	and	Der	p	2,	were	detectable in	all	commercial	dog	
extracts.	
• The	possibility	of	false	positives	with	skin	prick	testing	for	dog	allergy.	
• In	2001	compared	the	newest	AP	dog	extract	to	the	traditional	aqueous	dog	extract
• 48%	tested	positive	to	AP	dog.	Only	28%tested	positive	to	conventional	dog	extracts.	
• All	patients	who	tested	positive	to	conventional	extracts	also	were	positive	to	AP	dog,	with	a	
significantly	larger	mean	wheal	diameter.	
• 41%	who	tested	positive	to	AP	dog	tested	negative	to	conventional	dog	extracts.	
• These	data	perpetuated	questions	about	false	negative.
D.M.	Smith	and	C.A.	Coop.	Ann	Allergy	Asthma	Immunol 2016;116:188-193
• Stability	of	Dog	Extracts	
• In	1998	showed	that	
• Can	f	1	was	relatively	thermostable,	with	50%	of	the	allergen	remaining	after	60	minutes	
of	140	C	dry	heat.	
• In	2009,	the	stability	and	compatibility	of	AP	and	conventional	dog	extracts	
were	investigated	
• Can	f	1	levels	remained	at	94%	to	119%	and	Can	f	3	retained	79%	to	94%	potency	for	3	
days	when	kept	between	21	C	and	45	C,	showing	standard	shipping	methods	without	
refrigeration	are	acceptable	for	extracts.	
• The	extracts	with	50%	glycerin	retained	their	potency,	whereas	the	extracts	with	no	
more	than	10%	glycerin	showed	significant	degradation.
D.M.	Smith	and	C.A.	Coop.	Ann	Allergy	Asthma	Immunol 2016;116:188-193
• Current	Prescribing	Trends	
• A	nationwide	survey	in	2006 showed	the	perspective	of	how	allergists across	
the	United	States	were	integrating	these	conflicting	and	confusing	data	and	
using	them	in	daily	practice.	
• Responses	showed	the	maintenance	weight-to-volume	ratio	varied	widely	from	1:10	to	
1:1,000 with	the	most	common	concentration	being	1:100	(24.3%).	
• Most	allergists	believe	that	dog	immunotherapy	will	provide	at	least	some	relief from	
allergic	rhinitis	(91.9%)	and	asthma (89.6%)
• 86% would	be	willing	to	offer immunotherapy	to	treat	occupational	allergy.	
• This	rate	decreases	to	81% if	the	patient	is	unable	to	remove	the	dog	for	purely	
emotional	reasons.
• To	compare	with	1987 when	only	65%	of	board-certified	allergists in	private	
practice	perceived	improvement	in	allergic	rhinitis	or	asthma	symptoms	with	
cat	or	dog	immunotherapy.
D.M.	Smith	and	C.A.	Coop.	Ann	Allergy	Asthma	Immunol 2016;116:188-193
• Future	research	is	necessary	to	produce	more	potent	and	complex	extracts	that	
could	be	tailored	to	an	individual patient’s	pattern	of	dog	sensitization.
• The	first	step	would	be	to	produce	a	standardized	extract	for	clinical	use.	
• Additional	trials	could	be	designed	to	evaluate	the	efficacy	of	dog	allergen	
immunotherapy in	improving	clinical	end	points	for	patients.
• Properly	powered	studies	with	consistent	allergen	extracts	also	would	facilitate	
identification	of	the	optimal	dose	required	to	produce	these	effects.
• The	current	recommendation	on	immunotherapy	dosing	for	nonstandardized
dog	extracts	is	15	ug of	Can	f	1	per	dose.
• 0.5-mL	dose	using	full-strength	(1:100	w/v)	AP	dog	extract	
D.M.	Smith	and	C.A.	Coop.	Ann	Allergy	Asthma	Immunol 2016;116:188-193
Cat and dog allergens

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