- Welcome everyone to Wednesday
Nite @ the Lab.
I'm Tom Zinnen.
I work here at the UW-Madison Bi
otechnology Center.
I also work for the Division
of Extension,
and on behalf of those folks
and our other co-organizers,
Wisconsin Public Television,
Wisconsin Science Alliance,
and the Wisconsin Alumni Associa
tion,
thank you very much for coming
to Wednesday Nite @ the Lab.
We do this every Wednesday night,
50 times a year.
Tonight, it's my pleasure to int
roduce to you
Anne Marie Singh.
She's a professor in the Depa
rtment of Pediatrics here.
She was born in Buffalo, New Yor
k,
and went to high school in Willia
msville, New York,
which is a suburb of Buffalo.
Then she went to the Universi
ty of Rochester
and got her undergraduate degree
in chemistry.
She went to the Albert Einstein C
ollege of Medicine
in New York City to get her MD d
egree,
she did a residency in Philadelp
hia,
and then she came to UW-Madis
on to do a fellowship.
And that was the one in allergy?
- Anne Marie: Yes.
- Great.
Then she was on the faculty
at Northwestern University's med
ical school
in Chicago for nine years.
And then in 2017, she returned h
ere to UW-Madison,
and is again in the Department o
f Pediatrics.
Tonight, she's gonna talk with us
about something, if I might add,
we're all itching to hear about.
[audience laughing]
Yes, she's here to talk with us a
bout
insights in pediatric food aller
gies.
As somebody who had tiny little f
ood allergies,
but a lot of shots when I was
growing up,
it's gonna be very interesting to
hear
how things have changed in t
he last 50 years.
So please join me in welcoming
Anne Marie Singh to Wednesday Ni
te @ the Lab.
[audience applauding]
- Okay, great.
Thank you everyone for coming ton
ight
and thank you for that very k
ind introduction.
So tonight I'm gonna be talking
about food allergy and insights i
n
pediatric food allergy.
And so the first half of my talk,
I want to talk about the disease,
basically the clinical disease,
what is a food allergy,
what's not a food allergy,
how we diagnose food allergy,
what's coming down the pike
with treatments, and kind of wher
e we are
with the clinical care of food a
llergy.
So that'll be the first half
of the talk.
The second half of the talk I
want to talk,
it'll be a little bit more r
esearch-focused,
and kind of the burning question
I'm imagining on many people in t
he audience today,
and also among many allergists,
is it seems like there's a lot mo
re
food allergy than there used to
be.
And the question is, is that true
?
Is there really more food allerg
y
than there used to be?
And if so, why?
And then, what can we do about it
?
So then, I want to talk about th
e future of food allergy.
Can we prevent food allergy?
And what are some of the treatme
nts
that are going on for food aller
gy?
And near and dear to my heart is
what is UW doing about this, righ
t?
So how can we contribute to the f
ood allergy field?
Okay, so what is food allergy?
So this is the medical definition
that I have on the top of the
slide here.
And this is kind of based on
the clinical practice guidelines,
and food allergy is defined
as an adverse health effect
that arises from a specific immun
e response,
and occurs reproducibly on expo
sure to a given food.
So that's a lot of information
packed into one sentence.
But I tried to highlight the key
things.
So the first thing is, it's an im
mune response.
So this is an immune-mediated
phenomenon,
or something that's happening
and your immune system is get
ting turned on
when reacting to a food.
It has to occur reproducibly,
which means it needs to happen
every single time you eat the fo
od.
And not sometimes and not others
in most cases.
And it's on a given food.
So, when we think about an adver
se food reaction,
there are many reasons why a pers
on might eat something
and it can make them not feel wel
l, right.
There are many many reasons,
some of which are food allergy.
And so when we think about this i
s,
and I know he mentioned this,
but I'm a pediatric allergis
t immunologist,
so let me just back up and say t
hat.
So that's the lens from which I'
m speaking today.
So when we think about someon
e who says,
"Oh, I ate a peanut and I di
dn't feel well,"
the first question we try to answ
er is,
does this sound like this is an
immune reaction?
Was it immune-mediated or was
it nonimmune-mediated?
And so when we think about an imm
unologic reaction,
there can be different types
of an immunologic reaction.
And almost everything that I'm g
onna
talk about today is the left
part of the slide,
which is an IgE mediated reactio
n.
So our immune systems make diffe
rent
types of antibodies and we all k
now,
antibodies help us fight infectio
n and things.
And that's usually IgG,
and IgE are the antibodies that
were originally made
to help us fight parasites.
Well, in the U.S. hopefully, man
y of us
are free of parasitic infections
,
and IgE now is really considered
the allergic antibody.
And so, but IgE mediated foo
d allergies
are often hives or urticaria or a
naphylaxis,
but there are also non-IgE mediat
ed food allergies
that I'm not gonna talk about t
oday.
And the one that is probably
most familiar
to everybody in this group would
be like celiac disease.
So this is an immune-mediated re
action to wheat,
but it's not IgE mediated.
And so that's kind of why
it's in the non-IgE mediated gro
up.
When we think about other types
of adverse food reactions,
these are kind of a lot of the t
hings
that fit into the non-immunologi
c.
So something that's really easy
to understand.
If you eat rotten eggs and yo
u get vomiting and diarrhea,
obviously that's not a food aller
gy.
That was food poisoning.
You got sick from eating rotten
eggs.
So just because you eat somethin
g
and it doesn't make you feel good
,
doesn't make it a food allergy.
And so there are known things lik
e food poisoning
or scromboid fish poisoning.
There are pharmacologic reac
tions.
If you drink a lot of coffee
and get jittery,
that's not very surprising.
That's from the caffeine in
the coffee.
There are enzyme deficiencies,
so lactose intolerance or lac
tose deficiency.
And then there are other disorder
s, like
if you can't digest your food pr
operly
because you're missing some pancr
eatic enzymes,
or if you have liver disease or t
hings like that,
you can have reactions to foods,
but that would not be considered
a food allergy,
at least the type of food allerg
y
I'm gonna be talking about today.
So as an allergist, we talk a lo
t about
what is a food allergy versus
an intolerance.
And so when I ask a patient,
"Tell me what happens when you e
at that food,"
or "Tell me what happened when y
ou ate that."
These are some of the clues that
I'm listening for
to try to help distinguish if som
eone's having
an allergic reaction or an intole
rance.
So if you remember from that defi
nition,
I said it happens reproducibly a
nd reliably
every single time you eat the fo
od.
And so that means,
even if you only eat a small amou
nt of the food,
so a trace amount of the food sho
uld trigger reaction
if it's an allergy.
If it's a more of a dose-depende
nt reaction,
meaning I eat a little bit an
d I'm fine,
but if I eat a lot, that's w
hen I get sick,
that's more likely to put you in
the intolerance.
We talked about the immune-media
ted
and nonimmune-mediated,
and not always reproducible and
reproducible.
I put a little asterisk in h
ere because
for the reproducible and immediat
e,
because when we talk about update
s in the last 50 years,
this is one of the biggest upda
tes that we've found,
and I'm not gonna talk too muc
h more
about it later in the talk, but
that's
especially in children,
there are children who are allerg
ic to milk or egg
who can't drink a glass of milk
or can't have cheese or ice crea
m,
but they can eat milk if it's coo
ked,
what we call extensively heated m
ilk,
or baked in a cookie or a muffin
or something like that.
And the same is true for egg, and
now very new,
there was just recently an articl
e
inThe New York Timesabout it
.
There's a delayed allergy to red
meat,
and that has to do with the sali
va from a tick bite.
So, and it's the lone star tick a
nd it's usually in
Appalachia, and surprisingly it's
also in Wisconsin,
but it's more common in Appalachi
a,
and these patients will get
a delayed reaction
to red meat.
So normally it's a trace amount,
reproducible and immediate,
but there are a couple of except
ions
out there that I just highlighted
.
Okay, so now we've talked about
what a food allergy is.
So it's an immune-mediated respon
se,
that's that IgE mediated or that
allergic antibody mediated.
And so the symptoms can range fr
om atopic dermatitis
or allergic skin disease,
all the way to a life-threatening
reaction
called anaphylaxis.
And I'm gonna talk about that in
a
little bit more detail on a c
ouple of slides.
We just talked about how this
is different than a food intol
erance
or food sensitization.
And for the research part of the
talk,
I'm just gonna, early in lif
e food allergies,
often co-expressed or at the same
time,
children will often have that all
ergic skin disease
or atopic dermatitis and food all
ergy.
So I'm just laying the groundwork
now,
'cause we're gonna revisit that i
n the
second half of the talk.
There are eight foods that will
trigger
over 90% of this IgE mediated
food allergy,
and they're listed on the slide.
So milk, egg, wheat, soy,
peanuts, tree nuts, fish, and
shellfish.
And that's just a little graphic
of all the top allergens.
What's really interesting
about the food allergy world now,
is there are now
what we're calling emerging aller
gens,
or there are now foods that m
aybe 10 years ago
didn't cause food allergy,
but it's causing food allergy tod
ay.
And this is a puzzle, and we don'
t really understand why.
And sesame and some of the seeds
is
one of the most common emerging
ones.
Legumes including lentils,
chickpeas, beans, peas, green be
an,
that's another one of the emergi
ng food allergens,
and particularly in adults,
less so than in children,
there's this emerging fruit alle
rgy
including to kiwi and avocado,
and then there's been some case
reports
in Europe at least of apple all
ergy,
hasn't made it to the U.S. really
yet, but in Europe.
So not only we're gonna talk
about food allergy is increasing,
but now we're developing allergie
s to more foods.
And this is a puzzle for the food
allergy community.
So this is a lot of information,
and I just kind of put it up
here to highlight
that depending on your age,
there are usually different trig
gers.
So young children are most often
allergic to the egg, milk, and th
en soy and wheat,
and then peanuts, tree nuts, and
seeds.
But if you think about adult
food allergy,
that's more likely to be nuts and
fish.
So peanuts, tree nuts, fish,
and shellfish.
And what's really interesting,
and this is an area of resea
rch in my lab,
is most children will actually
outgrow their food allergy,
especially if it's to milk, egg,
wheat, or soy.
So if you have a fish or a nut a
llergy,
you're less likely to outgrow tha
t
and more likely for that to be
lifelong.
But if you're allergic to on
e of the
other foods, milk, egg, wheat, or
soy,
that's almost universally outgro
wn.
The sad part is, just like with
everything
with food allergy, is this n
atural tolerance
or this ability to outgrow food a
llergy
is occurring later in life.
So when I was a fellow here,
as you heard in the introduction
,
that was in 2005, I was taug
ht by my teachers
all children will outgrow their
food allergy by the time they sta
rt kindergarten.
It's just a disease that everybo
dy outgrows.
Obviously, now everyone in t
his room knows
this is not true anymore,
and food allergies are persisting
into adulthood,
and that people aren't outgr
owing them
as quickly as they used to.
And this is a question in the fo
od allergy field.
So what are the symptoms of a foo
d allergy?
And I kind of listed them here,
and they can basically affect any
organ system.
Symptoms usually occur within min
utes,
and they typically occur with
in two hours.
So normally, it will happen
within 15 to 30 minutes of e
ating a food,
but can happen up to two hours.
And when we talk about what sympt
oms,
it can affect any organ system,
and I kind of have them up on the
slide,
you know, itching, flushing, hive
s,
swelling, rash, itching or t
earing of the eyes,
coughing, wheezing, sneezing,
difficulty breathing,
the dreaded throat closing of an
anaphylactic reaction.
It can affect the GI system, n
ausea,
vomiting, belly pain [coughing] e
xcuse me.
The cardiovascular system,
heart racing, heart slowing,
changes in blood pressure and
dizziness.
And then in the neurologic syste
m,
food allergy patients will often
describe
what's described in the medical
textbooks
as this impending sense of doom,
which for whatever reason,
they eat a food and they're like
,
they don't feel well and they th
ink
something really bad is gonna hap
pen,
and they can get panicked.
And this has got to do with a neu
rological change
that happens when they eat th
e food allergy.
So here are some pictures of some
of
the patients that I've taken car
e of.
So here in the upper left, if I c
an get my mouse here,
is a little girl who was eating
actually beans and legumes,
and this is a picture that her m
om gave me,
and you can see she's got so
me eye swelling,
and some lip swelling, but sh
e's happy.
She's fine, right.
We'll treat her, she's gonna
get better.
Here's another patient,
and here you can see this diffuse
itchy rash,
or the urticaria or hives.
This is a patient from a food ch
allenge
and we can see again, lip sw
elling and hives.
It's hard to appreciate it i
n the picture,
but there's some redness of the
eyes, and some tearing.
Here's again some lip swelling,
and then this patient on the lef
t,
I'm a little bit more concerned a
bout,
because they have rash and l
ip swelling,
but obviously they're not really
,
they're really sleepy,
their mental status,
their mental ability, they're di
fficult to arouse.
And obviously, I was concerned en
ough.
It's hard to see, I can't get
there.
Oh there it is, in the corner her
e,
this is a blood pressure cuff
because she started to drop her b
lood pressure,
and the patient did well,
but she required multiple doses
of epinephrin,
she got better and she's fine.
But these are all kind of the
different things
that can happen in food allergy.
So what happened with that last
patient
that's different than the other
patients
in the picture?
And that last patient had anaphy
laxis.
So when people talk about and
anaphylactic reaction,
or what is anaphylaxis?
The medical definition is two or
more organ systems
that get affected, or a single o
rgan system
that's life-threatening.
And there are certain foods
that are more associated with ana
phylaxis than others.
And peanuts, tree nuts, and seaf
ood
are more common throughout
all of food allergy patients,
and in the really young children
,
it's more likely to be milk and e
gg.
And so that patient that I showed
in the picture,
that was to egg in that little
girl.
Unfortunately, anaphylaxis remain
s potentially fatal,
and there are about 150 deaths p
er year
in the United States.
And there are some risk fact
ors associated with
who is more likely to die of an
anaphylactic reaction.
And that's a patient who has asth
ma,
a patient who doesn't get the pr
oper treatment,
so they don't get their epinephr
in.
Obviously, if they've had a prev
ious severe reaction,
you're at risk for another severe
reaction.
And then adolescents and young ad
ults.
And the thought is in that age gr
oup,
it's the typical age group
when they don't want anything to
be wrong with them,
they don't want to be different
than their friends or peers,
so they don't tell anybody they d
on't feel well,
they don't give themselves their
epinephrin,
and then that's kind of what can
lead to a fatal reaction.
And then if you don't have s
kin involvement,
then sometimes people get confus
ed, like,
"Oh, but I don't have hives,
I'm not itching.
"This can't be a food allergy."
And then that can be a risk fact
or.
Okay, so how do we diagnose f
ood allergy?
So, the gold standard is an ora
l food challenge,
and that's where the patient
comes into my clinic, and they e
at
escalating amounts of a trigger
food
over several hours.
So I did two of these on Tuesday
,
in my clinic on Tuesday,
where I'm trying to see
if someone truly is food allergic
, or more likely
when I do this clinically,
it's because I think someone
has outgrown their food allergy
and I want to prove to
the family and to myself
that it's safe for them to eat,
and they'll come in.
And so for a peanut challenge,
they'll bring in peanut butter
or they'll bring in PB2.
Have you guys seen that now?
That like dehydrated peanut powde
r,
and they literally start with
milligrams,
and they eat milligrams,
like a tiny tiny amount of the fo
od,
and they wait 15 minutes and I wa
tch them,
and if that goes okay, then they
eat a little bit more,
and then they wait 15 more minute
s,
and they eat a little bit more,
until after
about between four and seven step
s,
they've consumed a whole serving,
and then they stay with me for a
t least two hours,
and I make sure they don't have
a delayed reaction.
So that's what an oral food c
hallenge is.
So obviously, this is risky, righ
t?
I'm feeding someone they can be
potentially allergic to.
It causes significant anxiety in
parents
and children, and it's time-cons
uming,
labor-intensive, and expensive.
So we often try to make the di
agnosis
in other ways.
And so we'll do that based on
the clinical history
and confirmatory testing.
So there's two types of conf
irmatory testing,
and there's skin testing and IgE
testing.
And I'm sorry, the pictures don'
t show very well,
but I just kind of,
for anyone who has not had al
lergy testing,
I wanted to put these pictures i
n,
just so you could see what it's
like.
So basically we usually do it
on the kind of front of your fore
arm,
and we put like little drops of p
urified antigen
or purified protein from the fo
od on your arm.
And then we do a little prick.
So what the caretaker is holding
there is this little tiny,
I always tell the little kids,
it's like a fork,
but you know it's like a litt
le metal fork.
It's not quite a needle.
And then we do a little scratch
under the first layer of skin,
and then we look to see in the l
ower picture here
if the skin reacts.
And so if we get a big red hive,
that's considered a positive tes
t.
If nothing happens here,
that would be a negative test.
And so then we use the skin testi
ng
in combination with the clinical
history,
using those clinical clues
that I showed earlier in the tal
k
to decide whether or not I think
somebody has a food allergy or n
ot.
And if I'm not sure,
or the parent's not convinced,
or no one's convinced,
then we go to the food challenge
.
So that's how we diagnose foo
d allergy.
What about the treatment of food
allergy?
So unfortunately,
there are no approved treatments
for food allergy.
So most of the treatments, or wh
at happens when I diagnose
someone with food allergy is edu
cation,
education, education.
So teaching a patient and their
family
how do they live with this diagno
sis.
And the issues that you have whe
n you're a toddler,
or you're going to daycare or pre
school,
are different than the issues
than if you transition to school
,
which are different than the iss
ues
when you're a teenager and yo
u're start leaving,
you're not under the control of y
our parents,
which are different than when we
say goodbye
and we kiss our kids and send the
m to college.
And then they're responsible for
all their own foods.
So a lot of what I do is teachin
g families
how to live with the food allergy
.
And the main thing I have to say
is strict avoidance.
So you can't eat this food.
You have to read every label,
you have to be cautious of c
ross-contamination,
you have to be cautious of h
idden ingredients.
I do a lot of nutritional co
unseling.
I work really closely with the pe
diatric nutritionist
in my clinic,
and we ensure that feeding and nu
tritional needs
are being met, and then they get
this emergency plan,
because unfortunately, if you lo
ok at the research,
20% of patients will have
an accidental ingestion per year
.
So I need to prepare my pati
ents for when you--
not if, when you accidentally get
in touch
with the food that you're suppose
d to avoid,
what should you do?
And so this is a picture of, ever
y patient that I see
leaves with an action plan
and it basically says, if you hav
e
these symptoms, do this.
If you have these are the more s
evere symptoms,
it says inject epinephrin imm
ediately,
call 911, blah, blah, blah.
And then the patients need to ca
rry
an epinephrine autoinjector.
So here are pictures of the two
major epinephrin autoinjectors.
And basically I teach them
how to use these devices.
So they need to carry these devi
ces and
take them with them everywhere t
hey go.
So if you don't have a food alle
rgy
but you host a grandchild or a ch
ild
or someone at your house,
you may see these when they come
.
And I teach them how to use it,
and then we follow them to keep g
oing,
how you live with the disease.
And then as I said, I always try
to be hopeful,
like, you will likely outgrow th
is disease,
but we have to follow you closely
,
and see when that will happen.
So what does avoidance really
mean?
I mentioned this already.
You have to read every label,
even foods that you may have
eaten before,
in case the food manufacturer cha
nges
how they do it.
I counsel patients on specia
l circumstances.
How do you go out to eat with a f
ood allergy?
I talk to them about, we practi
ce in the office.
What are you gonna say to the wai
ter?
What are you gonna tell your frie
nd
at the table in kindergarten?
Like these are the things we kin
d of go through.
We talk about birthday partie
s, play dates.
The official recommendation
is that you're supposed to avoid
foods with advisory labeling,
so may contain or processed in a
facility with peanuts.
So here's an example of what i
f someone comes in
and they have a milk allergy.
And so this on this slide,
these are all the different ways
milk might be listed on an in
gredient list.
So I took this out of the slide
'cause I didn't want to bog it d
own.
But when a patient sees me,
they get a food-specific handout
that says,
Oh, you're allergic to peanut,
I print out the peanut handout,
you're allergic to milk,
I print out the milk handout.
and it kind of walks patients thr
ough,
these are some of the hidden wor
ds
that equal milk or milk protein
that could be an allergy too.
So, so here's an example of all t
he
different ways that milk could b
e listed.
So that is kind of the first
half of the talk
where I wanted to talk about cl
inically,
what is food allergy,
how we diagnose it,
and what I spend a lot of tim
e in my office
talking to patients about.
So now I'm gonna move on to
the second half of the talk,
which is a little bit more of th
e research,
and that's state of the art, and
what's
going on with food allergy.
So how common is food allergy, ri
ght?
So they talk about a food all
ergy epidemic.
So 32 million Americans are thou
ght to have food allergy,
which means 1 in 13 children and
1 in 10 adults.
So I can tell you when I wen
t to school,
I can think of maybe one person,
in all of my childhood, that h
ad a food allergy.
It just wasn't something that
I lived with or knew much about.
And these statistics bear out.
I have two children,
they're both school-aged,
and there's always a food all
ergic children
in every class, every single
birthday party,
there's somebody with a food
, food allergy now,
and it's just a part of their li
fe.
So like for my kids,
I remember when my daughter want
ed the birthday party,
she came home one day, she's like
, "I want to invite
"Henry to my party, but Mom,
"he can't eat peanuts and wheat.
"
And she knows, and they all
know, and I'm like,
"Okay, we'll make that happen."
I figure if I can't make that ha
ppen
for that child, nobody can, righ
t?
[audience laughing]
So I can make this happen for
that child.
So food allergy is more common.
377% is the increase in like,
insurance diagnosis codes for me
dical claims
of anaphylactic food reactions
between 2007 and 2016, so it re
ally is increasing.
This is just some of the nuance.
Self-reported food allergy is abo
ut 10 to 18%.
Physician-diagnosed food allergy
is somewhere between 3 and 8%.
And so we think the prevalence i
s about
8% of Americans have a food alle
rgy.
So what is this epidemic?
So the incidence of food all
ergy continues
to increase, despite our best pub
lic health efforts.
And I kind of walked through some
of this.
We don't need to belabor this.
So why is food allergy increasing
?
And so, these are kind of som
e of the thoughts
in the food allergy community
about why there is so much m
ore food allergy.
And one of the reasons is inc
reased awareness.
Everyone now knows about food all
ergies.
Everyone's on the radar for it,
and we pay attention to it.
And so maybe because there's so m
uch more awareness,
there's increased recognition.
And I think that's probably true,
because we're recognizing milder
disease
and more of the younger kids
that outgrow it more quickly.
So I definitely believe that
to be true.
We know from some of these birth
cohort studies
and these population-based studi
es,
that more patients who get sensit
ized become allergic.
So I didn't talk about this earli
er,
but you can sometimes have IgE a
ntibody
to a food before you develop the
food allergy,
and more people are crashing thro
ugh that checkpoint
and going from sensitized to bec
oming allergic.
And so one of the example,
there's this very big health nut
study,
it was a population-based study
where they looked at young ch
ildren who are
comprehensively evaluated, and 10
.4% at age 1
were allergic to egg, peanut, or
sesame.
There's another part to this sto
ry,
and that's if we recognize more f
ood allergy,
we're taking that food out of the
person's diet,
and now we know, which I'm gonna
show
some of the research in a few sli
des,
that oral exposure, if you can
handle it
and it doesn't cause a reaction,
can be protective
or almost a form of therapy.
So maybe by recognizing more
food allergy,
we're being more cautious, and th
en
we could also be making the prob
lem worse in that way.
And then obviously, if I grew
up and there are
no food allergy in my children,
it's a part of their lives, food
allergy,
that genetics doesn't,
human genetics don't change tha
t quickly
in one generation.
Then there has to be some change
s in our environment.
Something about our environment
and
our environmental exposures
is leading to
this increase in food allergy.
So why are more children developi
ng food allergies
is the cocktail party question,
the clinical question.
And so if I turn that into a res
earch question,
what are the environmental ex
posures
that alter food allergy risk?
And so I'm going to bring up t
he hygiene hypothesis.
So the hygiene hypothesis is thi
s hypothesis
that was actually proposed in the
late 80s, 1989,
by a British epidemiologist name
d William Strachan,
and basically it was based on the
se observations
that he saw that children
who had more viral infections,
or children who had older siblin
gs,
or children who grew up on a far
m,
these dirty environments,
were less likely to develop asthm
a.
And so that became the hygien
e hypothesis,
that maybe we're too clean,
and because we're too clean,
our immune system wasn't fightin
g
what it was designed to fight.
And so now it starts fighting thi
ngs
that it's not supposed to fight.
So we're not eating dirt anymore
.
[audience laughing]
And so then we can get dirty.
And so here are some of the fact
ors.
So you know, less exposure to an
imals, pets and livestock,
older siblings was a risk factor.
And then these viral infections e
arly in life.
And so this is kind of showing t
his
in kind of a mechanistic way,
and the important thing to take
from the hygiene hypothesis
is emphasizing that the immu
ne system changes.
So you're not born with an immune
system
that you keep forever,
that your immune system is prone
to these influences in the envir
onment,
and that different exposures can
infect your
immune system in different ways.
All right.
So what's important about the hy
giene hypothesis
is that all the factors
have really been investigated
for asthma
and nobody had ever looked,
are the same things that are a ri
sk factor for asthma
an important risk factor for foo
d allergy?
So the question I wanted to ask,
do hygiene hypothesis factors af
fect oral tolerance
in the food allergy balance?
And so to answer this question,
I collaborated with an epidemiolo
gist in Chicago,
Lurie Children's, and we did thi
s
Children's Memorial food allergy
study,
where we enrolled over a thou
sand families,
and we tried to look at what
are the factors
that are associated with food al
lergy.
So there are a thousand fami
lies and so,
both parents and siblings wer
e enrolled.
And you can see on the slide,
527 don't have food allergy.
832 of the children do have food
allergy.
953 don't have asthma, and 40
6 have asthma.
So these are the same children.
We just divided them
into whether they had food a
llergy or asthma,
because as I mentioned,
everything about the hygiene hypo
thesis
previously had been about asthma.
So we looked at these hygiene hy
pothesis factors,
age, gender, ethnicity, inco
me structure,
maternal food allergy.
And then you know did they go to
daycare?
Were they delivered vaginally or
by C-section,
were they breastfed?
Did they have pet exposures,
do they have infections?
And basically, when we looked at
all of these things,
and all of these things
have been associated with asthma
risk,
the only one of these factors
that were associated with foo
d allergy risk
was maternal food allergy,
or if the child had other al
lergic disease.
So this is kind of our first clue
that
maybe the hygiene hypothesis
is different
in food allergy than it is for as
thma.
So then we wanted to hone in
on this early life infection,
because early life infection has
been
the strongest predictor of a
sthma risk
in the hygiene hypothesis.
So this graph, on the bottom,
you can see these are all the hy
giene hypothesis factors
that have previously been publish
ed
to be associated with asthma,
and our study recapitulates thos
e findings.
So children without asthma are i
n blue,
children with asthma are in red.
And you can see if you got
antibiotics early in life,
if you had more common colds
early in life,
more severe lower respirator
y infections.
RSV stands for respiratory syncyt
ial virus infections.
If he had ear infections, pn
eumonias or skin infections,
just like you would expect,
those children with those infect
ions
were more likely to have asthma.
When we look at these exact same
children,
and we look at these exact same
factors,
you can see that the,
all of the statistical signif
icance goes away.
So these children,
these are not risk factors for fo
od allergy
except for skin infection.
So that said to me, there's some
thing different
about a skin infection
that could be relating to foo
d allergy risk.
So that led to the next question.
So why would skin infection
be associated with food allergy r
isk?
And so as a pediatric allergist,
or as a pediatrician,
when we think about skin infecti
on
in the first year of life,
children who have allergic s
kin disease,
or an atopic dermatitis or eczema
,
are much more likely to have
a skin infection
than children who don't.
So I kind of turn this to bring
it into
something that I can study.
How does eczema or atopic derma
titis
diagnosis affect food allergy ris
k?
So to answer this question,
I started collaborating with
some of the
researchers here, and we looked
at the
childhood origins of asthma birth
cohort.
So this is a high risk.
These children are enrolled
in a clinical study before birth
,
so the pregnant mothers enro
ll their children,
and these children were followed
prospectively from birth, and now
they're no longer children anymo
re.
They're turning 18, 19, and 20 r
ight now.
And so, and then every year t
hey come in
for clinical visits, and we kind
of can
get some information about the na
tural history
or what happens with their disea
se.
And what we found was that child
ren with eczema
are much more likely to deve
lop food allergy.
So if you remember from that slid
e
really early in the talk,
I talked about how food allergy
and eczema are often co-expressed
.
I'm afraid to touch my mouse,
but so that's at year one, right?
If you look at the year one bar,
children if you had a food allerg
y, the yes, the red.
Sorry, if you had eczema, which
is the red bar,
then you are much more likely to
have food allergies.
So that year one bar was kind of
known,
and been published, and we furth
ered
that observation to show that no
t only
do you have risk at year one,
but that risk persists at least
throughout childhood.
So if you have eczema as a baby,
your risk of food allergy pe
rsists throughout childhood,
all the way through age 18.
We tried to quantify that risk b
y doing an odds ratio,
and the odds ratio of having
a food allergy is close to 10.
It's a log scale at the bottom.
So if you have eczema, you have a
bout between a
7 and then 10 times risk.
I'm sorry, if you have eczema
in the first year of your life,
you have about a 7 to 10 times ri
sk
of having food allergy.
So what are the mechanisms
that could be causing food aller
gy,
and why is eczema associated with
food allergy,
was the next research question.
So this is the only immunology
slide I'm gonna put in,
and I'm not gonna say too much a
bout it,
except to say the top is the envi
ronmental exposures.
You can see bacteria up on the ri
ght,
and food antigens and stuff in t
he middle.
And then those things get uptake
n by our immune system.
And there's this crucial cell
that's the green cells
right in the middle of the figur
e.
And those are your regulatory T c
ells.
So regulatory T cells are the ce
lls
that are thought to be really cr
ucial
in turning immune systems,
turning on the immune system or
turning it off.
So they're called regulatory T c
ells,
because they regulate the immune
system.
They turn it on or they turn it
off.
And so that led me to hypothesiz
e
that these regulatory T cells we
re crucial in food allergy,
and that food allergy may be hap
pening
because you don't have enough reg
ulatory T cells
or they don't work.
So we asked the question,
are these cells different
in children with or without food
allergy?
And I did this project with a fel
low, Ben Prince,
who worked with me in my lab
and he's now faculty at Ohio Stat
e,
and we looked at 55 children.
And to make a long story short,
what we find is that regulatory T
cells
are important, but only if yo
u're little.
You have to be less than six
years of age,
less than six years old,
and then the regulatory T cells
seem to be important.
So the purple dots on the left sh
ow
that younger children who do not
have food allergy
have more regulatory T cells
than children with food allergy,
which are the red dots.
And that's really important at
zero to six years of age.
But if you look after six years
of age,
that difference seems to go away
, and maybe even flip flops.
So this is, we're only talking
about regulatory T cell number.
Do these regulatory T cells work
?
So without going into a whole lo
t of detail
about the immunology piece,
but we look to see what chemicals
these regulatory T cells can make
,
and how that works for their func
tion.
And we do find in the, at the
younger ages,
there's no difference
in how the regulatory T cells fu
nction.
They seem to work okay in the you
nger children,
but they have fewer of them.
And the older children,
when I said the numbers seem
to flip flop,
like maybe they had more if they
had food allergy,
but the problem is, they don't w
ork.
So even though they have more nu
mbers,
the cells that are there
don't do what they're supposed t
o do.
So they don't secrete the messen
gers
they're supposed to secrete.
They don't suppress the immune s
ystem
the way they're supposed to supp
ress.
So now where my research is
going now,
is trying to understand what is i
t
about those skin infections or ec
zema
that's affecting the regulatory
T cells.
And so we're doing a lot of work
about the microbiome and the bact
eria on the skin
of children who have skin inflamm
ation
compared to children who don't ha
ve
skin inflammation, and how that
affects their immune system,
particularly these regulatory T c
ells.
Okay.
So, if there's no treatment,
maybe we could prevent food aller
gy.
So can we prevent this from happ
ening,
the the kid in school
who has to go to school in a
space suit?
And so I want to spend just
a couple minutes,
this is a really exciting develop
ment
in the field of food allergy.
So there is a group,
Gideon Lack and his group.
He had this really talented po
stdoc who was from Israel,
and then he went to the U.K.
for his postdoc.
And what he observed was,
in Israel, there was no peanut al
lergy.
And then he got to London and
he was like,
"What is peanut allergy,
"and why is everybody allergic t
o peanut allergy?"
And so he did a study to do an a
ssessment
of Jewish children in the U.K.
versus Jewish children in Israel
.
And he found that the prevalence
of peanut allergy
was over 10 times higher in the U
.K. than in Israel.
And so he had this hypothesis,
because he said, Israeli children
eat the snack called Bamba.
So that's the picture there.
And it's similar,
it's basically their teething bis
cuit.
So as babies are learning to teet
h,
they're given this Bamba, this t
eething biscuit,
you know in the U.S. we give
Cheerios or puffs
to all the little kids.
In Israel, they don't do Cheerio
s.
They do Bamba, and Bamba is made
from peanut flour.
And so he had this hypothesis
that there was something
about this early introduction
of peanuts
that might be preventing food al
lergy.
So he had this hypothesis
that dietary introduction of p
eanut before 11 months
would prevent food allergy.
So they did a randomized open lab
el study,
where high-risk infants are enro
lled.
That's the bottom.
They go through an oral food c
hallenge, and then
if they are not allergic to pean
ut,
they're either randomized to ear
ly introduction,
so to eat peanut early in life
, or peanut avoidance.
So I, the public health advi
ce at this time
was peanut avoidance.
So we were telling people,
don't feed peanut to your child
'cause it could give them an alle
rgy.
And so this was really
a provocative hypothesis and ide
a.
And what he found was that the c
hildren
that were randomized to the
peanut consumption,
so that's the consumption group,
no matter if they were sensitized
or not sensitized.
So that's the skin prick negative
,
skin prick positive.
Or if you take everybody,
there was an overall 81% reductio
n in peanut allergy
in the children that were random
ized
to early peanut introduction.
So this was a landmark study.
It led the AAP, the American Acad
emy of Pediatrics,
in 2015, to rewrite the infant f
eeding guidelines.
And now we say, you should give y
our child peanut
before one year, and if you're hi
gh risk,
you should do it before four
months of age.
So this is completely different
than probably when you all had ch
ildren
and completely different from whe
n I had my children.
So this has kind of been turned
around.
There are some questions about th
is though,
and that's does this hold for a
ll foods?
And so they did a follow-up stud
y,
and I took the data out, called t
he eat study,
and it does not hold for all foo
ds.
So they tried this exact same stu
dy design,
and the children were randomized
to consume all those milk, egg, f
ish,
wheat, and peanut versus not.
So that's, and they didn't find
a statistically significant diff
erence in food allergy
between the groups, and there's
a lot of possibilities for that.
And one of them could be it was
just too hard.
Like you have a newborn, and you
want me
to try to introduce five differe
nt
complementary foods twice a week
?
So they had a lot of trouble
with adherence.
Like the new parents weren't able
to adhere to that.
But also, it looks like early
introduction
only works for some foods and no
t others.
And so there's a lot of work
now in the field
to say what foods does it work f
or?
What foods doesn't it work for?
When should we be doing it?
And the newest data's coming out
that's showing,
maybe this will be helpful for eg
g,
but it doesn't seem to be helpful
for milk, soy, wheat, or fish.
But there's more to come.
So just because it's true for pea
nut,
doesn't mean it's true for every
thing.
So I just kind of wanted to
mention that.
Okay, so this was super exci
ting in the allergy world.
We finally have a way to prevent
at least peanut allergy.
And now, now what?
And so I want to spend the next
just like two slides talking abou
t the future.
And so the future, now, what are
the--
I said there are no FDA appr
oved therapies.
What are some investigational th
erapies?
And so one you may start hearing
about
is oral immunotherapy.
And in fact there was just a rea
lly big article
inThe New York Timesmagazine
,
if anybody saw that about this.
And what this is,
is we feed the children some
thing they're allergic to.
And we do escalating amounts.
That's the initiation phase,
and then build-up phase.
And so we increased the amount,
the dose of say peanut,
that they eat every single day,
and then there's a maintenance ph
ase.
We get them to 300 milligrams of
peanut protein,
which is the equivalent of a
peanut.
And they eat that every single d
ay
for a period of well, we don't r
eally know,
but the studies have all been bet
ween 6 and 24 months.
And then if you make it throu
gh all of that,
then you can have at least a p
eanut.
So that can take away some of th
e fear.
And interestingly, some of the ch
ildren
could go on and eat 10 times tha
t.
So not just one peanut, actu
ally 30 times that.
They can eat 30 peanuts, but some
patients can't.
And so we can't predict who gets
what we call desensitized,
versus who does not get desensit
ized.
The other interesting piece of t
hat
is some patients can develop what
's called
sustained unresponsiveness.
And all that means is,
if you take away the daily peanut
,
some people remain unresponsive
and some people don't.
And if you notice I'm saying,
some get desensitized, some d
on't,
some get sustained unresponsivene
ss, some don't.
And that is true, and unfortunat
ely
we have no way of predicting
who's gonna fall into what bucket
s.
So this is an area that people
are really looking into.
How can we predict who is this t
herapy gonna work for,
how we can predict
how well it's gonna work for
each patient.
And the reason why this is impo
rtant
is if you look on the right,
the dropout rate, it's really hi
gh
because I'm giving you basica
lly a poison.
I am giving you something that y
ou are allergic to.
100% of patients will have side
effects.
The question is, can you live w
ith them?
And so maybe the side effect
is mild enough,
you get an hour worth of abdomin
al pain
or belly pain every single day,
and that's worth it to you.
But up to 20 to 30% of patients w
ill anaphylax,
or have that severe reaction fro
m the therapy.
And so some of the patients say,
"You know what?
"It was better to avoid.
"I feel sick every single day.
"I don't like this therapy, I don
't want it."
And some, it's worth it to them.
And that's obviously a personal c
hoice.
Everyone can make their own choi
ce.
So this has been submitted for FD
A approval.
It's compound AR-101,
if you see anything in the ne
ws about that.
So it's been submitted for ap
proval.
It's hopeful and it's exciting,
but obviously,
this is not going to be the golde
n ticket, right?
There are a lot of questions
and unknowns
and a lot of side effects associ
ated with it.
I went through all of this, so
I don't need to say this.
And so then the other therap
y that is pending
is epicutaneous immunotherapy or
EPIT, or the patch.
And so this would be peanut patc
h,
and this is where peanut protein
is placed on this little sticker
.
And then you change the amount,
you change the patch every single
day for 24 hours,
and then we see if we can do,
instead of having to swallow the
food,
is the patch application good eno
ugh?
And what's nice about the pa
tch is no one's anaphylaxing
'cause they're not swallowing any
thing.
They may get some itchiness from
the patch.
But what's not so nice about the
patch
is it doesn't work as well.
So it can increase your threshold
.
So if you took a bite of somethin
g and spit it out,
maybe you won't have a reaction,
but it doesn't let you eat a pe
anut.
It does not let you eat the birt
hday cake
at the birthday party.
It does not let you eat the Chin
ese food.
And so again, it becomes a ri
sk benefit.
Like, is that amount of benefit e
nough
for that patient that they want
to do it?
And again, these are all investig
ational therapies.
So what is the UW doing to contri
bute to all of this?
And so about in February of
this year,
we were awarded a clinical and r
esearch
Center of Excellence.
So UW is now on the map, you can
see.
So, I'm the director of the cente
r.
And so that means that we provid
e,
it's national recognition
that we are a leading clinical
center for food allergy.
And it also means we are a parti
cipant
in these investigational therapie
s
that we've talked about.
And that we're performing cuttin
g-edge research,
some of which that I showed you t
oday,
about what causes food allergy,
what are the immune mechanisms o
f food allergy.
And so that's really an excit
ing development
for the UW that I'm really excit
ed about.
So to summarize, food allergy
is a failure of oral tolerance
and it's an immune-mediated re
action
that occurs predictably and
reliably
on exposure to a food trigger.
This is different than an intole
rance.
Food allergy is increasing in bot
h children and adults
in the U.S. and throughout the w
orld.
And we don't really know why,
but we think there are some ke
y environmental exposures,
such as oral exposure or bac
terial exposures,
or the microbiome that could be p
laying a role in this.
There are no treatments.
Families have to strictly avoid
the food in all situations,
and this significantly affect
s their quality of life.
But there's hope.
Oral exposure can be protective,
especially early in life, at lea
st to peanut.
And we can maybe prevent food all
ergy.
And as I highlighted, there
are two therapies
that are very close.
We're hoping for 2020 FDA approva
l.
So with that, I'm gonna end.
And this is a cartoon that was d
riven,
Dr. Gupta, whose picture was on
one of the early slides,
this was one of her patients and
she published it.
And it's basically showing the op
timism
in these food allergy patients.
And so here's the mom saying to
the child,
"When I was your age, there were
no food allergies."
So that's what I say to my k
ids all the time,
"When I was your age, there were
no food allergies."
And they're all confused
'cause food allergy's a part of
their daily life.
And now my hope is, through the
work going on
right here at the UW,
is that when that child grows up
,
they can say, "When I was your a
ge,
"there were food allergies."
And now that child is all confuse
d
'cause they don't know what a
food allergy is.
So with that, thank you for
your attention,
and I'd be happy to take any que
stions.
[audience applauding]