Food allergies in children:

A review of diagnostic tools and treatment

Brooke M. Warren

Nutrition 780 Critical Issues in Nutrition

May 3, 2013
Table of Contents

1. Introduction..1
1.1: Prevalence.1
1.2: Consequences of childhood food allergy..2
1.3: Food allergy & the immune system......3
2. Diagnosis......5
2.1: Sensitization patterns5
2.2: Diagnosis of Food Allergy6
a: Hens Egg.7
b. Cows Milk..8
c. Peanuts.9
3. Treatment of Food Allergy10
3.1: Avoidance...10
3.2: Specific Oral Desensitization..11
3.3: Maternal Antibody Transfer...12
4. Conclusion.13
5. Appendix
6. References

"
1. Introduction:
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Food allergy is major health concern for both children and adults that can lead to life-
threatening consequences. Internationally, the prevalence of food allergy (FA) in children is
reported to range from 3.1% to 10.5% (1-10). Actual prevalence rates may differ because many
of the studies, detailed in Table 1, used only self-reported data to determine prevalence (1,3,5,6).
The studies that relied solely on this type of data tended to have higher estimated prevalence
rates than the studies that also implemented skin prick test (SPT), double blind, placebo
controlled food challenges (DBPCFC), and/or allergen specific IgE test (sIgE) (2,4,7-10).
Allergen-specific IgE antibodies are made in response to the presence of an allergen. Levels tend
to be much higher in people who are sensitized and/or allergic than those that are not. Two recent
prevalence studies on FA in the United States indicate that between 3.9% and 9.8% of children
aged seventeen and younger suffer from a food allergy (2.5). Braum et al used data from the
National Health Interview Survey (NHIS) and the National Health and Nutrition Examination
Survey (NHANES) to look at the change in FA prevalence from 1997 to 2007. They used sIgE
for peanut, egg, and milk to verify self-reported FA. SPT and DBPCFC were not used to verify
FA. They found that the prevalence of FA in the United States has increased significantly from
3.3% to 3.9% (2). The most common foods which children are sensitized to are milk, peanut,
and hens egg with 12.2%, 9.3%, and 6.7%, respectively, of children exhibiting serum IgE
antibodies. Gupta et al published a cross-sectional, population-based study in 2012 looking at the
geographic variability among food allergies in children in the United States. This study,
consisting of 38,465 participants, used a survey method and did not confirm results with a SPT,
DBPCFC, or sIgE. A probability based sample statistic was used to identify and correct for any
sampling bias. Gupta et al found that the prevalence of food allergies in children ranged
#
significantly from 6.2% in rural area to 9.8% in urban areas (5). There was a significant
difference in the rates of peanut and egg allergies, with urban areas seeing a higher prevalence of
both. There was not a significant difference in the rates of milk allergy between children in rural
and urban areas (5).
1.b Consequences of Childhood FA
FA in children affects more than just the foods they can eat. FA diagnosis in correlated
with a decreased health-related quality of life in both children and caregivers (11-14). A nested
case-control study of 1,378 nine year olds in Sweden found that children with FA had a lower
self-reported quality of life (QOL) than children with other allergic diseases in the sub-categories
of physical functioning, social limitations, and general health (11). This same study found that
children with allergies to two or more different foods had an even more significantly decreased
quality of life than children allergic to only one food (11). Children with a perceived FA (not
necessarily physician diagnosed) reported more limitations of social activities than the general
population and children with type 1 diabetes (12). Children with nut allergies reported similar
QOL in physical health and school related domains similar children without FA but had
significantly lower emotional and social QOL (13). Caregivers of children with FA also show a
decreased QOL. These caregivers report feelings of guilt and worry and unresolved sorrow and
anger. The caregiver QOL was not related to the childs gender, number of different allergies,
need for epinephrine, or other related medical condition. Their QOL was significantly related to
the childs age, with caregivers with younger children (<8) showing a significantly decreased
QOL compared to caregiver with children over age 8 (14).
Food allergies can greatly effect a childs nutrient intake. A cross-sectional study using
children diagnosed with a food allergy by either SPT, DBPCFC, or sIgE found that children with
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FA were more likely to be less than the 25
th
percentile in height-for-age than children without
FA (15-17). When height-for-age and weight-for-age data was standardized using z-scores, it
was found that children with FA had significantly lower scores than children without FA (15).
Children with three or more FA were significantly smaller than children with only one FA (15).
The number of children with FA who did not meet the DRI for calcium and vitamin D was
significantly greater than in children without FA. Among children with FA, those with an allergy
to milk or who were allergic to two or more foods had the lowest intake of calcium and vitamin
D (16). Children with a cows milk allergy have significantly lower whole body bone mineral
content and bone mineral density than children without a cows milk allergy (17).
In addition to the psycho-social and health consequences discussed above, FA can have a
significant financial impact. Very little research has been done looking at the direct and indirect
cost of FA. One recent study looking at the cost of several allergic diseases from birth to two
years in Finland investigated the cost of raising a child with a cows milk allergy, atopic
dermatitis, and asthma. The data was collected as part of an on-going prospective mother-infant
study. Costs that were included in the totals were: time, lost work, travel, infant formulas,
medications, private specialists, hospital in-patient, hospital outpatient, and primary care. The
results showed that the costs associated with raising an infant with a FA were 3.5 times higher
than those associated with asthma, 11 times higher than atopic dermatitis, and 318 times higher
than raising a healthy infant (18).
1.c FA and the Immune System
FA is distinct from food intolerances in that FA involves the evocation of the immune
system. The immune system consists of two components: the innate immune system and the
adaptive immune system (19). Innate immunity consists of cells that a healthy person is born
%
with including epithelial cells, phagocytes, and natural killer cells. This system tends to be
activated within hours of contact with an allergen and do not change over the course of a
persons lifetime (20). The adaptive immune system is stimulated when a foreign microbe or
particle enters the body. The system then adapts to the presence of the foreign element and is
activated within minutes. The adaptive immune system can be spilt into two different types,
humoral and cell-mediated (19). Humoral immunity is mediated by proteins called anti-bodies,
which are produced by B-lymphocytes. Cell-mediated immunity is control by T lymphocytes
(20).
There are two main events that occur in the development of a type 1 hypersensitivity
(FA). The first involves the sensitization to an allergen. This allergen is also know as an antigen.
A protein found in the cytosol called ubiquitin detects the antigen. The antigen is then broken
down into peptide fragments. These degraded peptide fragments are presented by major
histocompatibility complex class II and recognized by nave CD4+ T cells. The CD4+ T-cells
then differentiate into th2 cells, which secrete cytokines called IL-4 and IL-13 (20). Cytokines
act as intercellular messengers. Il-4 and IL-13 stimulate B-cells to produce allergen-specific IgE
antibodies (21). The IgE antibodies then attach to mast cells in the tissues and basophils in the
blood via FceR1 (fragment crystallizable epsilon region R1) (22) . There are generally no
symptoms involved in this first exposure. During any subsequent exposures, the allergen will
cross-link to two cell-bound IgE molecules forming an allergen-IgE-FceR1 complex. The cross-
linking stimulates a series of events that ultimately leads to an increase in the Ca
++
. The
increased Ca
++
leads to the degranulation of the mast cells and basophils. The degranulation
causes the release of chemical mediators including prostaglandins, cytokines, leukotrienes, and
histamine. These mediators cause smooth muscle dilation, capillary disruption, swelling, and
&
other allergic symptoms including anaphylaxis (20). These subsequent exposures can also trigger
the formation of other antibodies including IgA and IgG. IgA antibodies are primarily found in
mucus secretions such as those produced by the gastrointestinal tract. IgG antibodies are unique
in that they are the only antibodies that can be passed across the placenta. The IgG4 subtype
tends to be higher when someone has developed a tolerance for an allergen that they were
previously allergic to (21).
2. Sensitization & Diagnosis
2.1 Sensitization Patterns
Sensitization to food allergens does not necessarily mean that a child will develop a FA,
but it is a risk factor (23). Understanding the correlation between sensitization and clinical FA is
important in developing alternative diagnostic tools. A 2009 prospective cohort study performed
by Schnabel et al obtained blood samples from 1,082 German children enrolled in the LISA
(Influences of life-style-related factors on the immune system and the development of childhood
allergies) birth cohort. The samples were obtained when the children were 2 years old and again
at age 6. The parents completed questionnaires at birth and ages 2, 4, and 6. Allergen-specific
IgE antibodies were measured using a mixture of common food allergens (fx5: hens egg, cows
milk, peanut, soybean, wheat flour, and codfish). If this screening test was positive, it was
followed by measurements for individual allergens. The authors chose to only test for hens egg,
cows milk, and peanuts individually because previous prevalence studies had indicated that they
are the most common FA (23). Sensitization to food allergens (fx5) and to the three individual
allergens were classified into three groups: No sensitization (no sIgE at 2 or 6 years), early onset
(sIgE only at 2 years), last onset (sIgE only at 6 years), and persistent (sIgE at 2 and 6 years).
Doctor-diagnosed food allergy was assessed at age six. Investigators then performed a multiple
'
logistic regression analyses to look at the association between sensitization phenotypes and food
allergy diagnosis. The results showed an increased sensitization to peanuts from two to six years
of age (2.1% to 5.2%). Children with peanut allergies were more likely to fall into the late-onset
phenotype. In comparison, sensitization to hens egg and cows milk decreased from age two to
six (hens egg: 5.7% to 2.7%. cows milk: 5.0% to 4.3%). Children with allergies to hens eggs
and cows milk were likely to fall into the early-onset phenotype (26). The persistent phenotype
was more common in boys than girls and in children with atopic parents. The results of the
descriptive analysis indicate that early-onset and persistent sensitization was associated with a
higher prevalence of doctor-diagnosed food allergy at the age of 6. After adjustment for study
region, gender, parental education, and parental atopic disease, there was no significant change
in the results (23).
2.b Diagnosis of Food Allergy
Currently the gold standard for diagnosis of FA is the double-blind placebo controlled
food challenge (DBPCFC) (20,23,24,25,26). In a DBPCFC neither the patient nor the
investigator is aware of what food the child is given. The test food is disguised within another
food that is known not to cause any atopic symptoms. The test uses increasing doses of the
suspected food to determine if there is any tolerance. These tests are performed in a clinical
setting under the supervision of a physician (25). There are, however, several downfalls to the
use of DBPCFC. First and foremost, these challenges are extremely time-consuming and very
expensive (25). They can cause undue stress and anxiety on both the child and their caregiver
because of the associated risk of a severe allergic reaction (12). Additionally, there is no specific
criteria or guidelines on when to declare the challenge positive or negative. False negatives can
be caused by inadvertent anti-histamine use before a challenge. False positives may arise if the
(
child does not strictly avoid the offending food in the weeks leading up to the challenge (25).
Research is now looking at alternative tests that can be used to diagnosis FA that are cheaper and
less stressful for the child. Most of the current research has been focused on the three most
prevalent FA in children; Hens eggs, cows milk, and peanuts (2).
Hens Egg
A 2010 retrospective study performed by Ahrens et al aimed to correlate hens egg (HE)
specific IgE, IgG, and IgG4 levels with the outcome of a DBPCFC in patients with suspected HE
allergy. Serum samples were gathered from 150 children (aged 5 months to 14 years) who had
undergone a DBPCFC. The DBPCFC were prepared and randomized by a clinical dietician and
consisted of seven gradually increasing titration steps with a cumulative dose of 6.2g of HE
protein. HE-specific IgE, IgG, and IgG4 were measured in all 150 children. The children were
split into three groups for comparison purposes: 1) HE-sensitized and allergic (median age 22
months), 2) HE-sensitized but tolerant (median age 29 months), and 3) non-sensitized and
tolerant (median age 30 months) (26). HE-specific IgE levels were significantly higher in group
1 than in group 2. In group 3, no HE-specific IgE was detected. Ahrens et al used a cut-off point
proposed by Sampson et al (27) of 12 kU/L HE-specific IgE. Using this cut-off, all children in
this study were correctly identified as HE allergic using specific IgE. There were no significant
differences in IgG and IgG4 levels between the three groups (26). The authors suggest that HE-
specific IgE levels could be used in place of a DBPCFC for patients above the cut-off level of 12
kU/L. For patients who fall below this cut-off, a DBPCFC would still be needed to diagnose a
suspected FA.
Okamoto et al performed a similar study to that of Ahrens et al, but found differing
results. This retrospective study involving 105 children aimed to investigate whether HE-specific
)
IgG4 could be used as a marker for the outcome of a DBPCFC. Unlike the Ahrens et al study,
patients with atopic dermatitis were excluded from this study. The median age of all patients was
5 years with a range of 1 to 13 years. Serum sample were taken from all patients on the day of
the food challenge. Of the 105 participants, 60 had a positive food challenge (PFC) and 45 had a
negative food challenge (NFC). The median HE-specific IgE level on the NFC group was 5.15
kU/L and was significantly lower than the median level in the PFC group at 14.45 kU/L. The
median level of IgG4 in the NFC group (2.17 mgA/L) was significantly higher than the level
determined in the PFC group (0.29 mgA/L). Overall patients with a NFC had a significantly
lower IgE/IgG4 ratio than patients with a PFC (28). Okamoto et al discuss the discrepancies
between their results and those of Ahrens et al. They believe that the main reason for the
differences may be the age of the participants. The participants in the Ahrens et al study had a
median age of 2 years. It has been documented that children under the age of two have a limited
ability to produce IgG4 (29). Nevertheless, the research indicates that the use of HE-specific IgE
and IgE/IgG4 ratios is a diagnostic tool that can be used in place of the DBPCFC for some
patients.
Cows Milk
A 2010 study by DUrbano et al aimed to assess the clinical performance of an
component-based allergen-microarray for detection of allergen specific IgE in children with a
challenge proven/excluded cows milk allergy, in comparison with a traditional serum IgE assay.
The traditional assay is the ImmunoCAP system that detected specific IgE antibodies for !-
lactalbumin, "-lactoglobulin, and casein. The allergen microarray assay was capable of detecting
!-lactalbumin, "-lactoglobulin A, "-lactoglobulin B, bovine serum albumin, IgG bovine, casein,
!-casein, "-casein, #-casein, and lactoferrin. Food challenge tests were conducted at a
*
specialized allergy clinic. A total of 104 children (median age of 4.9) were enrolled in the study.
55% of patients with a suspected cows milk allergy had a positive food challenge test.
Investigators used the outcome of the food challenge as the reference parameter. There was not a
significant difference in the ability of the different assays to predict the outcome of the food
challenge. There was a significant positive predictive value when the two assays were used
sequentially (30). The authors used the cut-off point proposed by Sampson et al (27) of 16.6
kU/L for cows milk specific IgE. This level was determined using the ImmunoCAP system.
Thirteen out of 14 participants who has levels >16.6 kU/L had a positive food challenge. Only 19
of the 44 patients with a specific IgE level <16.6 kU/L (30) had a positive DBPCFC. These 44
patients were then tested using the microarray. It was determined that casein had the highest
positive predictive value out of all the allergens in the assay. A cut-off value of 0.60 ISU was
used. Of the 15 patients with levels above the cut-off point, 14 tested positive in a food
challenge. Of the 29 patients with levels below the cut-off, only 5 tested positive during the food
challenge (30). These results indicate that although these tests cannot completely eliminate the
need for DBPCFC, they could greatly reduce the number of children that need to undergo them.
Peanuts
A 2007 case-control study looked to determine whether combining the results of a skin
prick test (SPT), immediate skin application (I-SAFT), and specific IgE testing improves their
ability to diagnose peanut allergy (31). These tests, by themselves, only indicate peanut
sensitization and not clinical allergy (32). Children were recruited from a population attending
the Allergy Clinic at Sydney Childrens Hospital. Inclusion criteria included having a positive
SPT to peanuts. A positive test was defined as one that produced a wheal 3 x 3mm larger than
the saline control. Eighty-four children with a positive SPT were recruited and underwent an I-
"+
SAFT, peanut-specific IgE, and food challenge. The I-SAFT test involved placing 1 gram of
natural peanut butter on a 2.5cm cardboard and then applying the peanut butter directly to the
skin. A placebo ointment was also applied in the same manner for comparison. A blind clinician
interpreted the results. The investigators analyzed two different test combinations. The first was
a SPT $8mm, a positive I-SAFT test, and a peanut specific IgE level $ 0.35kU/l. The second
combination consisted of a SPT $8mm, a positive I-SAFT test, and a peanut-specific IgE
$0.35kU/L but < 10kU/l. The 10 kU/l cutoff was chosen because anything above this level has
been shown to be predictive of peanut allergy (32). When the tests were looked at individually
only a SPT $15mm or a peanut-specific IgE level of $10kU/L were significantly correlated with
a positive food challenge. The specific IgE level is in line with the levels proposed by Sampson
et al (33). Both combinations of tests described above were significantly more specific than any
of the individual tests. When investigators adjusted for factors significantly associated with the
outcome of a peanut food challenge (mean SPT wheal size, I-SAFT results, peanut-specifc IgE
levels, and previous reaction) using a logistic regression model, only the specific-IgE level was
predictive of the outcome of the challenge. Johannsen et al replicated these results in a case-
control study published in 2011.
3. Treatment of FA
3.1 Avoidance
From the mid 1980s until the mid 2000s, the avoidance method was the only treatment
available for people with IgE-mediated FA. Recommendations were also made to avoid food
allergens in early life in order to reduce the risk developing a FA (34). These recommendations
were partially based on several reviews published in the 1980s that suggested that once
sensitization occurs, strict avoidance is required to prevent further sensitization and expedite the
""
development of tolerance (35,36). These recommendations have been correlated with an
increasing prevalence of sensitization (9), referrals for allergy specialists (37), and
hospitalizations related to anaphylaxis (38). Avoidance diets have also been correlated with
inadequate nutrient intake and impaired growth in some children (16).
3.2 Specific Oral Desensitization
Oral desensitization therapy (ODT) involves a two-part process: desensitization and
maintenance. The protocol for ODT depends on the specific allergen. Suggested protocols for
hens egg, cows milk, and peanuts can be found in Table 2 (39-41). The goal of this therapy is
to increase a persons tolerance to a specific allergen and then maintain that tolerance (42). This
therapy may not cure a person of their allergy, but can increase their tolerance to the point that
they dont have to worry as much about accidental exposure resulting in life-threatening
reactions (40). There are two types of ODT; rush and prolonged. In the rush method, the
desensitization occurs over the span a few days followed by the maintenance period (39). In the
prolonged method, the desensitization occurs over a span of months (41). Recently, there has
been in increase in research on the safety and efficacy of this type of treatment (table 3 (39-43)).
The first randomized, placebo controlled, double-blinded study on ODT in children with
peanut allergy was published in 2011 by Varchney et al. The aim of their study was to see of
subjects receiving ODT could consume a greater amount of peanut protein than those receiving
the placebo. Subjects were excluded if they had a history of anaphylaxis, poorly controlled atopic
dermatitis, or the inability to discontinue antihistamines. All participants underwent a DBPCFC
prior to treatment. Participants in the treatment group took a median time of 12.4 months to
complete treatment and the placebo group took a median time of 11.7 months. At the end of the
therapy, subjects in the treatment group were able to ingest a significantly greater amount of
"#
peanuts during a DBPCFC than the placebo group (p<0.001) (41). The authors discuss how the
outcome of this trial could lead to future research that includes subjects with more severe
symptoms including anaphylaxis and uncontrolled atopic dermatitis.
Burks et al performed a double blind, randomized, placebo controlled study to determine
the effectiveness and safety of oral desensitization and its capacity to sustain tolerance in
children with egg allergy. Children were eligible to participate if they were 5-18 years old and
had a convincing clinical history of egg allergy (defined as development of allergic symptoms
within 2 hours of ingesting egg), and had a serum egg-specific IgE of 5kU/L for children over
age 6 and 12 kU/l for children under age 6. Exclusion criteria included diagnosis of asthma or
severe atopic dermatitis. A DBPCFC was not performed at baseline. A DBPCFC was performed
at 10 and 22 months post-desensitization. There was a significant difference (p<0.001) in the
tolerance between groups at 10 months. This significant difference persisted at 24 month. The
experimental group had a significant reduction in SPT weal size and egg-specific IgE at 22
months compared to the control group (39). The major limitation to this study was that they did
not do a DBPCFC at baseline so true antecedent conditions could not be confirmed. They also
excluded children with asthma and atopic dermatitis, conditions that are often associated with
more severe forms of FA (20). To this authors knowledge, Burks et al, was the first to study egg
ODT using a double blind, randomized, placebo controlled design, so more trials are needed to
confirm these results.
3.3 Maternal Antibody Transfer
Some of the latest research on food allergies has moved away from treatment per say and
is looking at ways to prevent children from acquiring FA in the first place. This exciting field is
currently focusing on high-risk individuals, such as fetuses of mothers who are peanut allergic.
"$
It is well document that having atopic parents is a risk factor for a child developing allergies and
this seems to be particularly true with severe peanut allergy (47).
A murine study performed by Lopez-Exposito et al aimed to assess whether maternal
feeding of peanuts alone protects against peanut sensitization in offspring compared to the effect
of a mucosal adjuvant co-administered with peanut in mothers who are peanut allergic (48).
Mucosal adjuvants are agents that modify the effect of another agent (49). In this study, the
adjuvant used was cholera toxin (CT). CT, when administered with peanut (PN), has the ability
to increase the immune response. It also allows for a response to occur with a smaller amount of
PN. Lopez-Exposito et al divided the female mice into four groups: 1) PN + CT, 2) PN only, 3)
CT only, and 4) unimmunized. They were then allowed to breed. All the experimental groups
were sensitized on a weekly basis throughout their three-week pregnancy and three week
lactation period. The pups were sensitized with both PN + CT weekly starting at weaning age.
The mothers were sacrificed after weaning and the pups were sacrificed 8 weeks after weaning.
Tests showed that the CT + PN mothers had significantly more PN-specific IgG, IgGa,and IgA
in their breast milk. The offspring of CT+PN mothers had significantly lower PN-specific IgE
and significantly higher IgG2a/IgG1 ratios than the other pup (48). These results indicate that
pups of mothers who were sensitized to PN and received the adjuvant had a lower risk of
developing a PN allergy. The obvious limitation to this study is that the subjects were mice. A
study funded by the National Institute of Allergy and Infectious disease just wrapped up a similar
study on human and the results should be published within the next year.
4. Conclusion
FA are a prevalent and debilitating disorder that affects between 3.9-9.8% of children in
the United States (2,5). The wide range in numbers reported by the two most recent prevalence
"%
studies performed on children in the United States are likely due to the vastly different methods
used by the two sets of researchers. Branum et al relied on information gathered from two well-
documented national health studies, NHIS and NHANES. They verified the self-reported data
using blood samples collected during the 2004-2005 NHANES survey (2). Gupta et al used only
data collected from self-reported questionnaire (5). Due to the tendency of the self-reported
prevalence rates to be over-estimated, the true prevalence of FA in children is likely to be closer
to the 3.9% reported by Branum et al.
Regardless of the exact percentages, FA is an issue that many children must deal with on
a day-to-day basis. It is well documented that children with FA have a decreased quality of life
compared to children without a FA (11-14). The caregivers of children with FA also experience a
decreased quality of life and feelings of guilt and constant worry (13). These feelings of worry
can be extremely troublesome when children undergo testing for FA via the DBPCFC.
Nutritionally, children with FA are at a increased risk for stunted growth due to the inability to
eat certain foods. FA children tend to be smaller and shorter than children without FA (15,16).
FA also place a burden families financially due to costs associated with special food, doctors
appointments, lost work hours, travel, and medication (18). A better way of diagnosing and
treating FA in children is needed to help decrease some of the adverse consequences experienced
by both the child and their family.
Currently the gold-standard for diagnosing FA is the DBPCFC (20,23,24,25,26). These
tests are extremely time-consuming and expensive (25). They can be traumatic for the child and
caregivers due to the risk of a severe reaction (12). The current research indicates that testing for
allergen-specific IgE levels may offer the best chance of an alternative diagnostic tool. Much of
this research uses cut-off points proposed by Sampson et al (27). Unfortunately, there is great
"&
variability in the specific-IgE levels from person to person and the presence of specific-IgE only
indicates sensitization and not clinical allergy. More double blind, placebo controlled,
randomized studies are need to specify certain cut-offs above which a DBPCFC would be
deemed unnecessary. Unfortunately there will be some patients whose specific-IgE level fall
below any cutoffs who will still need to undergo a food challenge, but the goal should be to
reduce the numbers who do.
Until recently, avoidance of the allergen has been the only treatment available for food
allergies. The research on oral desensitization therapy (ODT) seems to indicate that this may be
the treatment of the future. The majority of the current research in this area has been done on
hens eggs, cows milk, and peanuts. The results of multi-year follow up studies are indicating
that this treatment protocol is an effective and safe long-term solution to FA. Much of the current
research has only focused on moderate cases of FA and has excluded patients with severe
anaphylaxis and uncontrolled atopic dermatitis. More double blind, placebo controlled clinical
trials need to be done to determine protocols for a wider range of FA severities. The future goals
of research are going beyond just treating FA, but preventing them from occurring. Animal
studies have indicated that giving small doses of allergens in combination with a mucosal
adjuvant to pregnant mothers may have a protective effect on their offspring. The first human
trial has just wrapped up and the publication of the finding is being eagerly awaited.
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6
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g
e
s

4
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8
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n
u

1
4
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6

a
g
e
s

>

1
9


-
6
.
9
%

o
f

c
a
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s

w
e
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e

c
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n
f
i
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m
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u

b
y

e
x
p
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t
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t
o

h
a
v
e

a

F
A

-
S
.
4
%

o
f

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g
e
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S


-
7
.
7
%

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f

a
g
e
s

4
-
1
8

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6
.
4
%

o
f

a
g
e

>
1
9

-

T
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p

f
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u

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l
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e
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g
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e
s

w
e
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e

s
h
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m
p

(
S
1
.
6
%
)
,

c
i
a
b

(
S
4
%
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a
n
u

f
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s
h

(
1
9
%
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0
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h
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i

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l
l
e
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g
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e
s

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n
c
l
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p
e
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u
t

(
9
.
9
%
)

a
n
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e
g
g

(
6
%
)


F
A
:

F
o
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u

A
l
l
e
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g
y
,

N
A
F
B
:

N
o
n
-
a
l
l
e
i
g
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c

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u

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y
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e
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n
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v
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y
,

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F
R
:

A
u
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s
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-
f
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o
u

i
e
a
c
t
i
o
n
,

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B
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C
F
C
:

B
o
u
b
l
e
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b
l
i
n
u
,

p
l
a
c
e
b
o
-
c
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t
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l
l
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f
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u

c
h
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l
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e
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g
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,

0
R
:

0
u
u
s

R
a
t
i
o
,

S
P
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:

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k
i
n

P
i
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c
k

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e
s
t
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0
F
C
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0
p
e
n

f
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o
u

c
h
a
l
l
e
n
g
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P
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:

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k
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n

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i
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c
k

T
e
s
t
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g
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:

S
p
e
c
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f
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c

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g
E


T
a
b
l
e

2
:

P
r
o
p
o
s
e
d

O
r
a
l

D
e
s
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n
s
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t
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T
h
e
r
a
p
y

P
r
o
t
o
c
o
l
s

H
e
n

s

E
g
g

(
3
9
)

C
o
w

s

M
i
l
k

(
4
0
)

P
e
a
n
u
t
s

(
4
1
)

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7

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5

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D
a
y

1
:

4

d
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(
0
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0
0
1
m
l
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0
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5
m
l
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0
.
0
1
m
l
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0
.
0
5
m
l
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a
d
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d

e
v
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y

h
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r

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a
y

2
:

4

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v
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y

4
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y

5
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8
m
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0

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c
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w
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a
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t

h
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-

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k

1
:

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d
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p

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f

1
:
2
5

d
i
l
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C
M

-

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k

2
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2

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p
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M

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3
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4

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M

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4
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8

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f

1
:
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5

d
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C
M

-

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k

5
:

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6

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p
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5

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C
M

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k

6
:

3
2

d
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f

1
:
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5

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C
M

-

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k

7
:

6
4

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1
:
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d

C
M

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k

8
:

5

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M

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k

9
:

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0

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p
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f

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C
M

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k

1
0
:

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0

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1
:

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l

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1
2
:

4
m
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C
M

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k

1
3
:

8
m
l

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d
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d

C
M

-

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k

1
4
:

1
6
m
l

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d
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C
M

-

W
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k

1
5
:

3
2
m
l

u
n
d
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d

C
M

-

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k

1
6
:

6
4
m
l

u
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d
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d

C
M

-

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k

1
7
:

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m
l

u
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k

1
8
:

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0
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p
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n

p
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-

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t
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s

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n
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r

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-

D
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s
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g

b
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g
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s

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t

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.
1
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g

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t
s

p
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n

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e

d
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d

e
v
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y

3
0

m
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s

u
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6

m
g

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a
c
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y
m
p
t
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m
s

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c
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r

-
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t
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d
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s
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h
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e

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g

H
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e

d
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:


-

P
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d
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p
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y

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P
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m
a
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B
u
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d
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p

v
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-

S
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b
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m
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y

4
4

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D
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e

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5
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%

u
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t
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t
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e

7
5
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g

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s

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d

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2
5
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3
%

u
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t
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e

4
,
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0
0
m
g

m
a
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e

d
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s

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d

M
a
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n
c
e

p
h
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e
:

-

P
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s

c
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s
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m
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m
a
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t
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d
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o
n
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p
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y


T
a
b
l
e

3
:

S
u
m
m
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y

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f

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s
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d
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t
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r
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p
y

R
e
f
e
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A
l
l
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n

O
b
j
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c
t
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S
t
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y

T
y
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P
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M
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R
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s
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P
a
t
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a

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t

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l

(
4
3
)

2
0
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3


M
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a
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T
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P
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5
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(
a
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e

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o

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l
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-
1
9
/
2
9

p
a
t
i
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