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European Academy of Allergy and Clinical Immunology

Supplementary materials

Food Allergy and Anaphylaxis Guidelines

European Academy of Allergy and Clinical Immunology

EAACI GUIDELINES Food Allergy and Anaphylaxis

Editors

Antonella Muraro

Graham Roberts

Editorial BoardIoana Agache

Carsten Bindslev-JensenAndy Clark

Anthony DuboisSusanne Halken

Karin Hoffmann-Sommergruber Aziz Sheikh

Thomas WerfelMargitta Worm


EAACI

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3rd Floor

8050 Zurich

Switzerland

The European Academy of Allergy and Clinical Immunology, EAACI, is a non-profit organisation active in the field of allergic and immunologic diseases such as asthma, rhinitis, eczema, occupational allergy, food and drug allergy and anaphylaxis. EAACI was founded in 1956 in Florence and has become the largest medical association in Europe in the field of allergy and clinical immunology. It includes over 7800 members from 121 countries, as well as 47 National Allergy Societies.

© - European Academy of Allergy and Clinical Immunology (EAACI) 2014

All rights reserved.

To all the members of EAACIand to our patients

Contents

Food allergy: diagnosis and managementE-3 The epidemiology of food allergy in Europe: systematic review and meta-analysisE-35 Prevalence of common food allergies in Europe: systematic review and meta-

analysisE-65 The diagnosis of food allergy: systematic review and meta-analysisE-75 Acute and long-term management of food allergy: systematic review

1

2 Primary prevention of food allergyE-109 Primary prevention of food allergy in children and adults: systematic review3 Quality of life in food allergy E-139 Disease-specific health-related quality of life instruments for IgE-mediated food allergy: systematic review4 Anaphylaxis E-151 The epidemiology of anaphylaxis in Europe: systematic reviewE-185 Management of anaphylaxis: systematic review

FOOD ALLERGY DIAGNOSIS

AND MANAGEMENT

1SECTION


BI Nwaru1, L Hickstein2, SS Panesar3, A Muraro4, T Werfel5, V Cardona6, AEJ Dubois7, S Halken8, K Hoffmann-Sommergruber9, LK Poulsen10, G Roberts11-13, R Van Ree14, BJ Vlieg-Boerstra15, A Sheikh3, 16 on

behalf of The EAACI Food Allergy & Anaphylaxis Guidelines Group

EAACI Food Allergy & Anaphylaxis Guidelines Group: CA Akdis, R Alvarez, K Beyer, C Bindslev-Jensen, V Cardona, P Demoly, A Dubois, P Eigenmann, M Fernandez Rivas, A Host, E Knol, G Lack, MJ Marchisotto, B

Niggeman, N Papadopolous, I Skypala, M Worm

1.1THE EPIDEMIOLOGY

OF FOOD ALLERGY IN EUROPE

SYSTEMATIC REVIEW AND META-ANALYSIS


AFFILIATIONS1 School of Health Sciences, University of Tampere, Finland

2 Institute for Medical Informatics, Biometry and Epidemiology, University of Munich, Germany3 Allergy & Respiratory Research Group, Center for Population Health Sciences, The University of Edinburgh, UK

4 Department of Pediatrics, Center for Food Allergy Diagnosis and Treatment, Veneto Region, University of Padua, Italy5 Hannover Medical School, Hanover, Germany

6 Hospital Valld’Hebron, Barcelona, Spain7 Department of Paediatrics, Division of Paediatric Pulmonology and Paediatric Allergy, University Medical Centre Groningen,

University of Groningen, Groningen, The Netherlands8 Odense University Hospital, Odense C, Denmark

9 Department of Pathophysciology and Allergy Research Medical University of Vienna, Vienna, Austria10 Laboratory of Medical Allergology, Allergy Clinic, Copenhagen University Hospital, Hellerup, Denmark

11 David Hide Asthma and Allergy Research Centre, St Mary’s Hospital, Newport, Isle of Wight, UK12 NIHR Southampton Respiratory Biomedical Research Unit, University of Southampton and University Hospital Southampton

NHS Foundation Trust, UK13 Human Development and Health and Clinical and Experimental Sciences Academic Units, Faculty of Medicine, University of

Southampton, UK14 Departments of Experimental Immunology and of Otorhinolaryngology, Academic Medical Center, University of Amsterdam,

The Netherlands15 Department of Pediatric Respiratory Medicine and Allergy, Emma Children’s Hospital, Academic Medical Center, University of

Amsterdam, The Netherlands16 Division of General Internal Medicine and Primary Care Brigham and Women’s Hospital/Harvard Medical School, Boston, MA,

USA

E-5EAACI

Epidemiology of food allergy in Europe: a review


METHODSSearch strategyArticles were retrieved using a highly sensitive search strategy implemented in four electronic databases (OVID MEDLINE, OVID EMBASE, CINAHL, and ISI Web of Science). The search strategy was devised on OVID MEDLINE and then adapted for the other databases (see Box E1). Systematic reviews were retrieved by using the systematic review filter developed at McMaster University Health Information Research Unit (HIRU) (http://hiru.mcmaster.ca/hiru/HIRU_Hedges_MEDLINE_Strategies.aspx#Reviews). We also adapted the search filter from York University Centre for Reviews and Dissemination (http://www.york.ac.uk/inst/crd/intertasc/epidemiological_studies.html) to retrieve the characteristics describing the epidemiology of FA. The McMaster filter (http://hiru.mcmaster.ca/hiru/HIRU_Hedges_EMBASE_Strategies.aspx#Prognosis) was applied for retrieving studies on prognostic factors. Additional references were located byhand search. Unpublished work and research in progress were searched through discussion with experts in the field. There were no language restrictions, and where possible the literature in languages other than English was translated. The literature we were unable to translate is shown in the PRISMA flow diagram (Figure 1).

Inclusion and exclusion criteriaAs per the study design, we included systematic reviews and meta-analyses, cohort studies, case-control studies, cross-sectional studies, and routine healthcare studies. We excluded review and discussion papers, non-research letters and editorials, case studies and case series, animal studies, and all randomized controlled trials. Our initial inclusion criteria were broad by including studies published worldwide between January 1990 and September 2012. However, after assessing the large amount of articles, we made further restrictions to include studies published only in Europe (based on the United Nations definition (http://unstats.un.org/unsd/methods/m49/m49regin.htm#europe accessed on December 28, 2012) between January 1, 2000 and September 30, 2012, with the exception of Greenland and Turkey, which were included in the review because we believe they are culturally and politically more European than North American and Asia, respectively.

Term Definition

1 exp Food Hypersensitivity/

2 food allerg*.mp.

3 food hypersensitivity.mp.

4 food hypersensitivities.mp.

5 allergy, food.mp.

6 (rat or rats or cow or cows or chicken? or horse or horses or mice or mouse or bovine or animal$).ti.

7 exp animals/ not humans.sh.

8 6 or 7

9 *Incidence/

10 *Prevalence/

11 (incidence or prevalence or epidemiol$).ti.

12 epidemiologic methods/

13 *cohort studies/

14 controlled clinical trial.pt.

15 *case-control studies/

16 exp Food Hypersensitivity/ep [Epidemiology]

17 exp Hospitalization/

18 exp Hospitalization/sn, td [Statistics & Numerical Data, Trends]

19 exp Mortality/sn, td [Statistics & Numerical Data, Trends]

20 exp Epinephrine/ad, tu, th [Administration & Dosage, Therapeutic Use, Therapy]

21 exp "Cause of Death"/

22 ((adrenaline or epinephrine) adj3 (dispens$ or prescrib$)).tw.

23 or/9-22

24 or/1-5

25 23 and 24

26 25 not 8

27 limit 26 to yr="1990 - 2012"

Box E1 Ovid Medline search strategy


E-6 EAACI Supplementary materials

Analysis, synthesis and reportingWe recalculated all the frequency estimates of FA occurrence if adequate data were provided by authors. If any discrepancies were observed between our recalculated estimates and those of the authors, we reported our recalculated estimates. Our recalculated estimates were based on the minimal measured events rather than extrapolated estimates. In studies where inadequate data were given to enable recalculation, we reported the estimates provided by the authors. Where needed and possible, we contacted authors of primary studies for clarifications. The 95% confidence intervals (95% CI) of our recalculations were computed by using the Wilson score method without continuity correction (15). Different reports from the same primary study were reported as one study. Although several specific food allergies were reported across the studies, the focus of the current report is to present the estimates for ‘any FA’. The other specific foods will be presented in a future report. In studies reporting estimates of sensitization to food allergy alongside cross-reactivity to pollen (wheat and grass), we always used the true estimates without pollen cross-reactivity, where possible.

We performed a random-effects meta-analysis for clinically and methodologically comparable studies to estimate the frequency of FA. The following outcomes were considered: 1. point and life-time prevalence of self-reported FA; 2. point prevalence of specific IgE positivity; 3. point prevalence of SPT positivity; 4. point prevalence of symptoms plus IgE positivity; 5. point prevalence of symptoms plus SPT positivity; 6. point prevalence of clinical history or OFC/DBPCFC-positivity; 7. point prevalence of positive response to food challenge (open food challenge [OFC] or DBPCFC). For outcomes 6 and 7 above, where a study reported estimates for both OFC and DBPCFC, the DBPCFC estimates were always used; otherwise OFC estimates were used if DBPCFC was not done in the study. We did not present pooled estimates for cumulative incidence of FA due to inconsistencies and very few data across studies.

We aimed to present stratified pooled estimates by different age groups (1 year and under, 2-5 years, 6-10 years, 11-17 years, 18-60 years, and older than 60 years). However, due to several overlapping ages of participants across the studies, the age-stratified pooled estimates were more feasibly computed for the age groups 0-17 years (children) and 18 years

and over (adults). A study with overlap between these two age groups was included in either age group if the age distribution was skewed to that age group. For studies that gave frequency estimates at different ages for the same individuals, we used the estimates for the highest age in computing the pooled estimates. We also present the pooled estimates stratified by geographical region in Europe (i.e., East, West, South, North, and ‘Europe’; the last group being for studies that included several European countries and gave overall estimate for all the countries and in which it was not possible to calculate the frequency for each country studied) using the classification by the UN (http://unstats.un.org/unsd/methods/m49/m49regin.htm#europe accessed December, 2012). Due to methodological differences across the studies investigating the risk and prognostic factors for FA (varied risk and prognostic factors studied, differences in study design, differences in statistical methods employed across studies, differences in factors considered for adjustment, and others), we did not perform meta-analysis for these studies.

RESULTS

Study characteristicsThe characteristics, main results, and the overall risk of bias grading of the studies included for review are shown in Table E1. Of the 56 studies reviewed, 31 were cross-sectional, 19 cohort, three were systematic reviews, and three case-control studies. Over 50% of the studies were conducted in northern European countries. A majority of the studies (n=37) were undertaken only in children. Ten studies assessed FA only by self-report, 10 only by specific-IgE or SPT positivity, while the remainder was a combination of self-report, specific-IgE or SPT sensitization, and food challenge. Twenty-six of the studies undertook food challenges for verifying FA, and 22 of these employed DBPCFC. A majority of the studies (n=49) reported point prevalence as the occurrence measure for estimating the frequency of FA. The majority of studies had a moderate risk of bias (Table E2).

Frequency of FASelf-reported FA: details of studiesEighteen of the 27 studies on self-reported FA included children (i.e., < 18 years). Two studies

E-7EAACI



reported cumulative incidence in children: one study from Denmark reported the cumulative incidence of self-reported FA by the age of 6 years as 11.6% (27-29), whereas one study from the UK reported estimate of 25.8% by the age of 1 year and 28.1% by the age of 3 years (85-87). The lowest (1.6%) and highest (38.7%) point prevalence of FA were reported in Italy (20) and Norway (52), respectively (Figure E1). The lowest and highest life-time prevalence of FA was found in Turkey (5.7%) (59) and Poland (41.8%) (53), respectively (Table E3). The range of point prevalence of self-reported FAfor all age groups was 1.6% to 38.7% and the highest point prevalence was found in the age group 2-5 years (Table 1). The range of life-time prevalence of self-reported FA for all age groups was 5.7% to 41.8% and the highest life-time prevalence was found in the age group 6-10 years (Table E3).

FA by positive SPT or IgE to specific food allergens: details of studies

Of the 18 studies (17-19,27-29,35-42,47,50-52,61-64,67-70,76,77,81,82,85-88) that defined FA by means of specific sensitization (positive SPT or IgE) to food allergens, 12 were undertaken among children (Table E4). The frequency of FA as defined by positive specific-IgE was generally higher than corresponding positive SPT, and often the correlation between the two types of tests was low. The cumulative incidence of positive SPT or specific-IgE to at least one food by the age of 4 years was reported to be 5.5% in Finland (69). The cumulative incidence of positive specific-IgE by 6 years was 47.3% in Denmark (27-29), while that of positive SPT was 5.3% by the age of 3 years in the UK (Table E4) (85-87). The point prevalence of positive SPT to at least one food was lowest in France (1.8%) (67) and highest in the UK (7.7%) (88). In general, the point prevalence of SPT positivity was highest in Northern Europe than other regions (Figure E3), with only one study each being undertaken in Western and Southern Europe. No study was found from Eastern Europe on FA by SPT positivity to any specific food allergen. Studies on specific-IgE positivity to food allergens were from only Northern and Western Europe. The point prevalence of positive specific-IgE was lowest in Finland (2.0%) (41) and highest in Germany, Italy, Norway, and Denmark (each country having approximately 22%) (Table E4) (18). In general, the point prevalence was higher in Western than in Northern Europe (Figure E2), although only

one study was undertaken in Western Europe. The range of the prevalence of positive SPT positivity for all age groups was 1.8% to 6.1%, with the highest prevalence in the age group the 6-10 years; that of positive specific-IgE ranged from 2.0% to 52.0%, the age group 6-17 also having the highest prevalence (Table 1).

FA defined by symptoms plus allergic sensitization and by clinical history or food challenge

Nine studies (23,48,53,60,67,68,78-80,85-88) defined FA based on symptoms plus sensitization (SPT and IgE) to specific food allergens (n=5) or based on convincing clinical history or positivity to food challenge (OFC or DBPCFC) (n=4) (Table E5). All of these studies were among children and a majority from Northern Europe (n=6) (23,48,53,68,85-88). FA based on symptoms plus sensitization involved subjects who were symptomatic for FA (usually by self-report) and subsequently had positive results when they underwent SPT or IgE tests. On the other hand, FA based on clinical history or food challenge was defined as either having a convincing clinical history (without any food challenge) or being positive with food challenge.

The pooled point prevalence of symptoms plus positive IgE to at least one food was similar in Northern and Western Europe (Figure 3). The lowest (2.2%) and highest (4.6%) point prevalence of symptoms plus positive specific-IgE to at least one food were both found in Germany (78-80). The range of the point prevalence of symptoms plus positive specific-IgE by age group was 1.3% to 4.6%, those 1 year and less having the lowest frequency (Table 1).

The point prevalence of symptoms plus SPT positivity was just highest in Southern Europecompared toother regions (Figure 4). The lowest point prevalence was found in France (0.1%) (66) and the highest in Germany (13.1%) (77-79). The range of the point prevalence of symptoms plus positive SPT by age group was0.1% to 13.1%, the age groups 6-10 and 11-17 years having the lowest estimates.

The overall pooled point prevalence of clinical history or food challenge positivity was lowest in the UK (1.1%) (87) and highest in Norway (6.8%) (53) (Table E5). The range of the point prevalence of clinical history or food challenge by age group was 1.1% to 6.8%, the age group 2-5 years having the highest frequency (Table 1). Differences may be explained by the use of



OFC versus DBPCFC.

There was significant heterogeneity between the studies (P < 0.05 for I2) despite stratification by age and region.

Challenge-verified FA: details of studies

Of the 12 primary studies (23,27-29,34,48,60,65,66,68-70,78-80,85-88) that assessed FA by performing food challenge (OFC or DBPCFC), eight only included children (23,27-29,48,60,68-70,85-88) and nine came from Northern Europe (23,27-29,48,65,66,68-70,85-88), two from Southern Europe (34,60), and one from Western Europe (78-80) (Table E6). Three of the studies reported cumulative incidence of challenge positive FA by 1 year (1.5% [95% CI 0.9-2.5]) (27-29), by 4 years (3.3% [95% CI 2.8-3.9]) (69,70), and by 6 years (3.6% [95% CI 2.3-5.4]) (85-87). The lowest point prevalence of challenge-verified FA was found in the UK (almost zero per cent) (85-87) while the highest was found in Germany (5.7%) (78-80) (Table E6). The range of the point prevalence of challenge-verified FA was from 0% to 5.7%, with the age group 11-17 having the highest frequency (Table 1). There was significant heterogeneity between the

studies (P < 0.05 for I2) even after stratification by age and region.

Cumulative incidence

Only one of the nine studies in these categories reported estimates for cumulative incidence (84-86), showing that the cumulative incidence of FA by the age of 3 years was 6.0% (95% CI 4.6-6.7) based on clinical history or OFC positivity and 5.0% (95% CI 3.8-6.5) based on clinical history or DBPCFC positivity.

Risk and prognostic factors for FAAlthough a number of the reviewed studies examined the risk and prognostic factors for self-reported FA and sensitization to specific food allergen, a priori, we were interested in studying the risk and prognostic factors for clinician-diagnosed or objectively-verified FA, which is expected to give stronger evidence for causality and would be more meaningful for clinical intervention. Thirteen studies (22,24-26,32,34,40,46,53,58,68-70,73,84-87) were found of which 11 were among children (Table 3). Due to several methodological differences between the studies, they were not combined in a meta-analysis.

E-9EAACI



Tabl

e E1

The

mai

n fe

atur

es, m

ain

resu

lts o

f fre

quen

cy o

f FA

, and

ove

rall

risk

of b

ias

asse

ssm

ent o

f the

stu

dies

incl

uded

in th

e sy

stem

atic

revi

ew

on th

e ep

idem

iolo

gy o

f FA

in E

urop

e: s

tudi

es p

ublis

hed

1 J

anua

ry 2

00

0 -

30

Sep

tem

ber

20

12

Refe

renc

e,

coun

try

Stud

y de

sign

Stud

y po

pula

tion

N (c

hild

ren/

adul

ts; s

ourc

e of

st

udy

popu

latio

n)A

ge o

f su

bjec

tsO

utco

me

stud

ied

and

asse

ssm

ent m

etho

dO

ccur

renc

e m

easu

re(s

)

Mai

n re

sults

of t

he

freq

uenc

y of

FA

(FA

)Pe

rcen

tage

(95

% C

I)

Ove

rall

risk

of b

ias

asse

ssm

ent

Num

ber

appr

oach

edN

umbe

r pa

rtic

ipat

edO

utco

me(

s) s

tudi

edM

etho

d of

out

-co

me

asse

ssm

ent1

Ban

t et a

l. 2

00

8,

Pola

nd

Cros

s-se

ctio

nal

stud

y

Not

in

dica

ted

15

61

8-2

7

year

s ol

dA

ny fo

od a

llerg

enSP

T, s

IgE

Poin

t pr

eval

ence

Poin

t pre

vale

nce

of

sIgE

pos

itivi

ty to

ast

le

ast o

ne F

A: 1

1%

Mod

erat

e

Bur

ney

et a

l. 2

01

0; W

oods

et

al. 2

00

1, E

urop

e,

Uni

ted

Stat

es

of A

mer

ica,

A

ustr

alia

, New

Ze

alan

d

Cros

s-se

ctio

nal

stud

y

Not

in

dica

ted

17

28

02

0-4

4

yrs

old

Any

FA

, fish

, egg

, cow

’s

milk

, mus

tard

, mel

on, p

op-

py s

eed,

soy

a, s

unflo

wer

, w

alnu

t, ba

nana

, pea

nut,

buck

whe

at, r

ice,

tom

ato,

co

rn, c

eler

y, k

iwifr

uit,

car-

rot,

sesa

me,

app

le, w

heat

, sh

rim

p, p

each

, haz

elnu

t

Self-

repo

rted

, sI

gE

Poin

t and

lif

e-tim

e pr

eval

ence

Poin

t pre

vale

nce

of

sIgE

pos

itivi

ty to

at

leas

t one

FA

for

all

coun

trie

s 1

2.3

%

Mod

erat

e

Caffa

relli

et a

l. 2

01

1, I

taly

Cros

s-se

ctio

nal

stud

y9

00

62

55

-14

ye

ars

old

Any

FA

, cow

’s m

ilk,

egg,

tom

ato,

pea

nut,

whe

at, c

hoco

late

, kiw

i, st

raw

berr

y, m

elon

, or

ange

, haz

elnu

t, se

sam

e

Self-

repo

rted

Poin

t and

lif

e-tim

e pr

eval

ence

Poin

t pre

vale

nce

of

self-

repo

rted

FA

:1

.6%

(0.9

-2.9

)M

oder

ate

Chaf

en e

t al.

20

10

, Wor

ld-

wid

e

Syst

emat

ic

revi

ew

12

37

8

stud

ies

iden

tified

72

stu

dies

in

clud

edA

ll ag

e gr

oups

Cow

’s m

ilk, e

gg, p

eanu

t, fis

h, s

hellfi

sh

Self-

repo

rted

, ph

ysic

ian-

diag

nosi

s, S

PT,

sIgE

, OFC

, D

BPC

FC

Poin

t, pe

riod

, lif

e-tim

e pr

eval

ence

; cu

mul

ativ

e in

cide

nce,

in

cide

nce

rate

The

sam

e fr

eque

ncy

estim

ates

as

give

n in

Ro

na e

t al.

20

07

Stro

ng

Colv

er e

t al.

20

05

, UK

and

Ir

elan

d

Cros

s-se

ctio

nal

stud

y 1

30

28

93

31

30

28

93

3Ch

ildre

n<

16

ye

ars

Any

food

alle

rgic

re

actio

nPh

ysic

ian

diag

nosi

sPo

int

prev

alen

ce

Freq

uenc

y es

timat

es

not o

btai

nabl

e fr

om

the

stud

yM

oder

ate

Du

Toit

et a

l. 2

00

8, U

K a

nd

Isra

el

Cros

s-se

ctio

nal

stud

y1

07

86

88

26

4-1

8

year

s ol

d

Pean

ut, s

esam

e, tr

ee

nuts

, egg

, milk

Self-

repo

rted

, cl

inic

al h

isto

ry,

OFC

Poin

t pr

eval

ence

Poin

t pre

vale

nce

of D

B-

PCFC

-con

firm

ed p

eanu

t al

lerg

y: 0

.4%

(0.3

-0.6

) in

UK

and

Isra

el

Mod

erat

e

Dub

akie

ne e

t al.

20

12

, Lith

uani

aCo

hort

st

udy

15

58

15

58

6-1

2

mon

ths

old

Any

FA

, milk

, egg

, whe

at,

pean

ut, p

otat

o, a

nd fi

sh

Self-

repo

rted

, SP

T, s

IgE,

D

BPC

FC

Poin

t pr

eval

ence

Poin

t pre

vale

nce

of

DB

PCFC

-con

firm

ed

FA: 0

.3%

(0.1

-0.7

)M

oder

ate



Refe

renc

e,

coun

try

Stud

y de

sign

Stud

y po

pula

tion

N (c

hild

ren/

adul

ts; s

ourc

e of

st

udy

popu

latio

n)A

ge o

f su

bjec

tsO

utco

me

stud

ied

and

asse

ssm

ent m

etho

dO

ccur

renc

e m

easu

re(s

)

Mai

n re

sults

of t

he

freq

uenc

y of

FA

(FA

)Pe

rcen

tage

(95

% C

I)

Ove

rall

risk

of b

ias

asse

ssm

ent

Num

ber

appr

oach

edN

umbe

r pa

rtic

ipat

edO

utco

me(

s) s

tudi

edM

etho

d of

out

-co

me

asse

ssm

ent1

Egge

sbø

et a

l. 2

00

3, 2

00

1a

and

20

01

b,

Nor

way

Coho

rt

stud

y4

97

33

75

42

.5

year

s ol

d

Any

FA

, cow

’s m

ilk,

hen’

s eg

g, fi

sh, n

uts,

ce

real

s, c

hoco

late

, fru

its,

vege

tabl

es

Self-

repo

rted

, ph

ysic

ian

diag

nosi

s, S

PT,

sIgE

, OFC

, D

BPC

FC

Poin

t pr

eval

ence

, cu

mul

ativ

e in

cide

nce

Poin

t pre

vale

nce

of

OFC

/DBP

CFC-

confi

rmed

eg

g al

lerg

y 0

.3%

(0.2

-0

.6) a

nd m

ilk a

llerg

y 0

.4%

(0.2

-0.7

)

Mod

erat

e

Elle

r et

al.

20

09

, K

jaer

et a

l. 2

00

8,

John

ke e

t al.

20

06

, Den

mar

k

Coho

rt

stud

y1

09

55

62

6 y

ears

ol

d

Any

FA

, cow

’s m

ilk, h

en’s

eg

g, p

eanu

t, w

heat

, co

dfish

, so

y, s

hrim

p, h

a-ze

lnut

, Bra

zil n

ut, c

eler

y

Self-

repo

rted

, SP

T, s

IgE,

OFC

, D

BPC

FC

Poin

t pr

eval

ence

, cu

mul

ativ

e in

cide

nce

Poin

t pre

vale

nce

of O

FC/

DB

PCFC

-co

nfirm

ed F

A a

t 6

year

s: 1

.2%

(0.5

-2.9

)

Mod

erat

e

Falc

aõ e

t al.

20

04

,Po

rtug

al

Cros

s-se

ctio

nal

stud

y1

56

56

59

>3

9

year

s ol

d

Any

FA

, fre

sh fr

uits

, m

eat,

fish,

egg

s, o

ctop

us

and

squi

d, c

hoco

late

, m

ilk, s

pice

s, le

gum

es

Self-

repo

rted

Poin

t pr

eval

ence

Poin

t pre

vale

nce

of

self-

repo

rted

FA

: 5

.2%

(3.7

-7.1

)M

oder

ate

Flok

stra

-de

Blo

k et

al.

20

11

, The

N

ethe

rland

s

Cros

s-se

ctio

nal

stud

y

No

info

rmat

ion

22

84

11

-20

ye

ars

old

Any

FA

Self-

repo

rted

Poin

t pr

eval

ence

Poin

t pre

vale

nce

of

self-

repo

rted

FA

: 2

.1%

(1.6

-2.8

)W

eak

Fox

et a

l. 2

00

9,

UK

Case

-co

ntro

l st

udy

13

3 c

ases

, 3

10

co

ntro

ls

13

3 c

ases

, 3

10

con

trol

s<

4

year

sPe

anut

alle

rgy

SPT,

sIg

E,

DB

PCFC

Poin

t pr

eval

ence

Case

-con

trol

stu

dy:

freq

uenc

y es

timat

es

not g

iven

Mod

erat

e

Fron

gia

et a

l 2

00

5, I

taly

Cros

s-se

ctio

nal

stud

y5

04

04

60

21

-2

year

s ol

d

Any

FA

, pea

nut,

egg,

m

ilk, t

omat

oSe

lf-re

port

edLi

fetim

e pr

eval

ence

Life

time

prev

alen

ce

of F

A: 7

.8%

(7.0

-8

.6)

Mod

erat

e

Gel

inci

k et

al.

20

08

, Tur

key

Cros

s-se

ctio

nal

stud

y1

70

64

11

81

6≥

18

ye

ars

old

Any

FA

, any

non

-alle

rgic

fo

od h

yper

sens

itivi

ty, t

o-m

atoe

s, h

en’s

egg

, cac

ao,

oran

ge, e

ggpl

ant,

pean

ut,

stra

wbe

rry,

car

rot,

bana

na,

haze

lnut

, pea

r, s

pina

ch,

red

chili

, bla

ck p

eppe

r,

food

add

itive

s, c

hoco

late

, w

alnu

t, po

tato

, fish

Self-

repo

rted

, SP

T, s

IgE,

D

BPC

FC

Poin

t and

lif

e-tim

e pr

eval

ence

Poin

t pre

vale

nce

of

DB

PCFC

-con

firm

ed

FA: 0

.1%

(0.1

-0.2

)M

oder

ate

Gru

ndy

et a

l. 2

00

2, U

KCo

hort

st

udy

28

58

12

73

3-4

ye

ars

old

Pean

ut a

llerg

ySe

lf-re

port

, SPT

, O

FCPo

int

prev

alen

ce

Poin

t pre

vale

nce

of

OFC

-con

firm

ed p

eanu

t al

lerg

y: 0

.6%

(0.3

-1.2

)M

oder

ate

Tabl

e E1

(co

ntin

ued)

E-11EAACI



Refe

renc

e,

coun

try

Stud

y de

sign

Stud

y po

pula

tion

N (c

hild

ren/

adul

ts; s

ourc

e of

st

udy

popu

latio

n)A

ge o

f su

bjec

tsO

utco

me

stud

ied

and

asse

ssm

ent m

etho

dO

ccur

renc

e m

easu

re(s

)

Mai

n re

sults

of t

he

freq

uenc

y of

FA

(FA

)Pe

rcen

tage

(95

% C

I)

Ove

rall

risk

of b

ias

asse

ssm

ent

Num

ber

appr

oach

edN

umbe

r pa

rtic

ipat

edO

utco

me(

s) s

tudi

edM

etho

d of

out

-co

me

asse

ssm

ent1

Gup

ta e

t al.

20

07

, 20

04

, 2

00

3, U

K

Cros

s-se

ctio

nal

stud

y

Not

in

dica

ted

Not

indi

cate

dA

ll ag

e gr

oups

Any

FA

Phys

icia

n di

agno

sis

Cum

ulat

ive

inci

denc

ePl

ease

see

resu

lts in

Ta

ble

7 (t

ime

tren

ds)

Mod

erat

e

Høs

t et a

l. 2

00

2,

Den

mar

kCo

hort

st

udy

17

58

17

49

15

ye

ars

old

Any

FA

, cow

’s m

ilk

alle

rgy

SPT,

sIg

E, O

FC,

DB

PCFC

Poin

t pr

eval

ence

Poin

t pre

vale

nce

of

hist

ory

or O

FC/D

BP-

CFC-

confi

rmed

milk

al

lerg

y 2

.2%

(1.6

-3.0

)

Mod

erat

e

Hou

riha

ne e

t al.

20

07

, UK

Cros

s-se

ctio

nal

stud

y5

07

21

12

54

-5

year

s ol

dPe

anut

alle

rgy

SPT,

sIg

E,

DB

PCFC

Poin

t pr

eval

ence

Poin

t pre

vale

nce

of

DB

PCFC

-con

firm

ed

pean

ut a

llerg

y: 1

.4%

(0

.8-2

.3)

Mod

erat

e

Isol

auri

et a

l. 2

00

4, F

inla

nd

Cros

s-se

ctio

nal

stud

y4

00

4

00

7, 2

7,

47

, 67

ye

ars

Any

FA

, milk

Self-

repo

rted

, sI

gE

Life

time

prev

alen

ce

and

poin

t pr

eval

ence

Poin

t pre

vale

nce

of

sIgE

pos

itivi

ty to

at

leas

t one

FA

at 6

7

year

s: 9

% (5

-18

)

Mod

erat

e

Joha

nsso

n et

al.

20

05

, Sw

eden

an

d N

orw

ay

Cros

s-se

ctio

nal

stud

y

Not

in

dica

ted

Swed

en 1

00

2;

Nor

way

50

0A

dults

Any

FA

, pea

nut,

soya

be

an, e

gg w

hite

, cow

’s

milk

, cod

fish

, whe

at fl

our,

pe

nici

lloyl

G, s

uxam

etho

ni-

um, l

atex

, haz

el n

ut

sIgE

Poin

t pr

eval

ence

Poin

t pre

vale

nce

of

sIgE

pos

itivi

ty to

at

leas

t one

FA

for

both

N

orw

ay a

nd S

wed

en

3.6

% (2

.8-4

.7)

Mod

erat

e

Julg

e et

al.

20

01

, Vas

ar e

t al

. 20

00

, Est

onia

Coho

rt

stud

y4

55

29

85

yea

rsEg

g w

hite

, cow

’s m

ilkSP

T, s

IgE

Poin

t pr

eval

ence

Poin

t pre

vale

nce

of

SPT

posi

tivity

to e

gg

at 5

yea

rs 0

% a

nd

sIgE

pos

itivi

ty to

egg

at

5 y

ears

2.4

%

Mod

erat

e

Kan

ny e

t al.

20

01

, Fra

nce

Cros

s-se

ctio

nal

stud

y4

40

00

31

11

0≤

60

ye

ars

Any

FA

Self-

repo

rted

Poin

t pr

eval

ence

Poin

t pre

vale

nce

of s

elf-

repo

rted

FA

3

.5%

(3.3

-3.7

)M

oder

ate

Kot

z et

al.

20

11

, U

KCo

hort

st

udy

29

58

36

62

95

83

66

All

age

grou

psPe

anut

alle

rgy

Ph

ysic

ian

diag

nosi

s

Life

-tim

e pr

eval

ence

, in

cide

nce

rate

Plea

se s

ee re

sults

in

Tabl

e 7

(tim

e tr

ends

)M

oder

ate

Kra

use

et a

l. 2

00

2, G

reen

land

Cros

s-se

ctio

nal

stud

y1

21

31

06

85

-18

ye

ars

old

Any

FA

, egg

, milk

, fish

, pe

anut

, whe

at, s

oysI

gEPo

int

prev

alen

ce

Poin

t pre

vale

nce

of s

IgE

posi

tivity

to a

t lea

st o

ne

FA: 4

.1%

(3.0

-5.5

)M

oder

ate

Tabl

e E1

(co

ntin

ued)



Refe

renc

e,

coun

try

Stud

y de

sign

Stud

y po

pula

tion

N (c

hild

ren/

adul

ts; s

ourc

e of

st

udy

popu

latio

n)A

ge o

f su

bjec

tsO

utco

me

stud

ied

and

asse

ssm

ent m

etho

dO

ccur

renc

e m

easu

re(s

)

Mai

n re

sults

of t

he

freq

uenc

y of

FA

(FA

)Pe

rcen

tage

(95

% C

I)

Ove

rall

risk

of b

ias

asse

ssm

ent

Num

ber

appr

oach

edN

umbe

r pa

rtic

ipat

edO

utco

me(

s) s

tudi

edM

etho

d of

out

-co

me

asse

ssm

ent1

Kri

stin

sdot

tir e

t al

. 20

11

, Ice

land

Coho

rt

stud

yN

o in

form

atio

n1

34

11

yea

r ol

d

Any

FA

, hen

’s e

gg, c

ow’s

m

ilk, p

eanu

t, fis

h, w

heat

, so

y, s

hrim

p, c

ranb

erry

, po

tato

, pin

eapp

le, a

lmon

d,

nutr

amig

en, g

reen

pea

s

Self-

repo

rted

, SP

T, s

peci

fic

sIgE

, DB

PCFC

Poin

t pr

eval

ence

Poin

t pre

vale

nce

of

DB

PCFC

-con

firm

ed

FA: 1

.9%

(1.3

-2.7

)M

oder

ate

Kuc

ukos

man

oglu

et

al.

20

08

, Tu

rkey

Cros

s-se

ctio

nal

stud

y1

41

51

01

58

-18

m

onth

sEg

g al

lerg

ySP

TPo

int

prev

alen

ce

Poin

t pre

vale

nce

of

SPT

posi

tivity

to e

gg

1.9

% (1

.2-2

.9)

Mod

erat

e

Kur

ulaa

ratc

hy e

t al

. 20

05

, Ars

had

et a

l. 2

00

1, T

ariq

et

al.

20

00

, UK

Coho

rt

stud

y1

53

61

45

64

yea

rs

old

Any

FA

, milk

, egg

, pe

anut

, cod

, whe

at, s

oya

SPT

Poin

t pr

eval

ence

, cu

mul

ativ

e in

cide

nce

Poin

t pre

vale

nce

of

SPT

posi

tivity

to a

t le

ast o

ne F

A: 3

.5%

Mod

erat

e

Kven

shag

en e

t al.

20

09

, Nor

way

Coho

rt

stud

yN

ot

indi

cate

d6

09

2 y

ears

ol

dA

ny F

A, e

gg, m

ilk,

pean

ut, h

azel

nut

Self-

repo

rted

, SP

T, s

IgE,

OFC

, D

BPC

FC

Poin

t pr

eval

ence

Poin

t pre

vale

nce

of

Clin

ical

his

tory

or

OFC

/DB

PCFC

FA

6

.8%

(5.0

-9.4

)

Mod

erat

e

Maj

kow

ska-

Woj

ciec

how

ska

et

al. 2

00

9, P

olan

d

Cros

s-se

ctio

nal

stud

y 3

26

02

14

87

-10

ye

ars

old

Any

FA

, milk

, cho

cola

te,

dair

y, s

traw

berr

ies,

egg

s,

tom

atoe

s, c

ocoa

, nut

s,

frui

ts, o

rang

es

Self-

repo

rted

Life

-tim

e pr

eval

ence

Life

-tim

e pr

eval

ence

of

FA

41

.6%

(39

.5-

43

.7)

Mod

erat

e

Mar

klun

d et

al.

20

04

, Sw

eden

Cros

s-se

ctio

nal

stud

y2

06

41

48

81

3-2

1

year

s ol

d

Any

food

hy

pers

ensi

tivity

Se

lf-re

port

edPo

int

prev

alen

ce

Poin

t pre

vale

nce

of

self-

repo

rted

FA

: 1

8.7

% (1

6.8

-20

.8)

Mod

erat

e

Mat

rica

rdi e

t al.

20

07

, Ger

man

yCo

hort

st

udy

76

09

13

14

2-1

0

year

s ol

d

Cow

’s m

ilk, h

en’s

egg

, so

y, a

nd w

heat

sIgE

Poin

t pr

eval

ence

Poin

t pre

vale

nce

of

sIgE

pos

itivi

ty to

at

leas

t one

FA

at 1

0

year

s: m

ilk 1

.0%

(0

.5-2

.3),

egg

0.9

%

(0.4

-2.0

), so

y 6

.1%

(4

.4-8

.3),

whe

at

8.8

% (6

.8-1

1.4

)

Mod

erat

e

Mos

sako

wsk

a et

al

. 20

08

, Pol

and

Cros

s-se

ctio

nal

stud

y

Not

in

dica

ted

30

1>

10

0

year

s ol

d

Stra

wbe

rrie

s, b

anan

as, o

r-an

ges,

egg

s, p

eppe

r, ga

rlic,

ch

amom

ile, i

ce c

ream

Self-

repo

rted

Poin

t pr

eval

ence

Poin

t pre

vale

nce

of

FA: 3

.3%

(1.8

-6.0

)M

oder

ate

Tabl

e E1

(co

ntin

ued)

E-13EAACI



Refe

renc

e,

coun

try

Stud

y de

sign

Stud

y po

pula

tion

N (c

hild

ren/

adul

ts; s

ourc

e of

st

udy

popu

latio

n)A

ge o

f su

bjec

tsO

utco

me

stud

ied

and

asse

ssm

ent m

etho

dO

ccur

renc

e m

easu

re(s

)

Mai

n re

sults

of t

he

freq

uenc

y of

FA

(FA

)Pe

rcen

tage

(95

% C

I)

Ove

rall

risk

of b

ias

asse

ssm

ent

Num

ber

appr

oach

edN

umbe

r pa

rtic

ipat

edO

utco

me(

s) s

tudi

edM

etho

d of

out

-co

me

asse

ssm

ent1

Nic

olao

u et

al.

20

10

, UK

Coho

rt

stud

y1

49

91

08

58

yea

rs

old

Pean

ut, m

ilk, e

gg, fi

sh,

tree

nut

Self-

repo

rted

, SP

T, s

IgE,

OFC

, D

BPC

FC

Poin

t and

lif

etim

e pr

eval

ence

Poin

t pre

vale

nce

of O

FC-c

onfir

med

pe

anut

alle

rgy:

0.7

%

(0.3

-1.4

)

Mod

erat

e

Nig

gem

ann

et a

l. 2

01

1, G

erm

any

Cros

s-se

ctio

nal

stud

y2

67

87

17

64

10

-17

ye

ars

old

Pean

ut a

llerg

ysI

gEPo

int

prev

alen

ce

Poin

t pre

vale

nce

of

sIgE

pos

itivi

ty to

pea

-nu

t alle

rgen

10

.9%

Mod

erat

e

Orh

an e

t al.

20

09

, Tur

key

Cros

s-se

ctio

nal

stud

y3

50

02

73

96

-9

year

s ol

d

Any

FA

, coc

oa, h

en’s

egg

, be

ef, c

ow’s

milk

, fish

, to-

mat

o, h

azel

nut,

kiw

i, bl

ack

pepp

er, c

hick

pea,

pea

nut,

wal

nut,

corn

, ban

ana,

st

raw

berr

y, p

otat

o

Self-

repo

rted

, SP

T, O

FC,

DB

PCFC

Life

-tim

e an

d po

int

prev

alen

ce

Poin

t pre

vale

nce

of

DB

PCFC

-con

firm

ed

FA 0

.7%

(0.5

-1.1

)M

oder

ate

Öst

blom

et a

l. 2

00

8a,

20

08

b,

20

08

c an

d A

lmqv

ist e

t al.

20

05

, Sw

eden

Coho

rt

stud

y7

22

14

08

94

-8

year

s ol

d

Any

FA

, cow

’s m

ilk, c

itrus

, pe

anut

, tre

e nu

ts/a

lmon

d,

hen’

s eg

g, s

tone

frui

t, ch

oc-

olat

e, fi

sh, p

ea, s

oy b

ean,

w

heat

, ban

ana,

cod

fish

Self-

repo

rted

, sI

gE

Poin

t and

pe

riod

pr

eval

ence

Poin

t pre

vale

nce

of

sIgE

pos

itivi

ty to

at

leas

t one

FA

at 8

ye

ars:

13

.8%

(12

.5-

15

.4)

Mod

erat

e

Ost

erba

lle e

t al.

20

09

, Den

mar

k

Cros

s-se

ctio

nal

stud

y1

09

48

43

Mea

n ag

e 2

2

year

s

Any

FA

, ad

ditiv

es, c

odfis

h,

cow

’s m

ilk, h

en’s

egg

, oc

topu

s, p

eanu

t, sh

rim

p,

soy,

whe

at,

beer

, che

ese,

re

d w

ine

(oth

er s

econ

dary

fo

od a

llerg

ies

also

repo

rt-

ed in

the

pape

r

Self-

repo

rted

, SP

T, O

FC,

DB

PCFC

Poin

t pr

eval

ence

Poin

t pre

vale

nce

of O

FC/D

BPC

FC-

confi

rmed

FH

S: 1

.8%

(1

.1-2

.9)

Mod

erat

e

Ost

erba

lle e

t al.

20

05

, Den

mar

kCo

hort

st

udy

Not

in

dica

ted

18

34

Child

ren

and

adul

ts

Any

FA

, add

itive

s,

codfi

sh, c

ow’s

milk

, hen

’s

egg,

pea

nut,

shri

mp,

soy

, w

heat

, fru

it/ve

geta

bles

Self-

repo

rted

, ph

ysic

ian

diag

nosi

s, S

PT,

sIgE

, OFC

, D

BPC

FC

Poin

t pr

eval

ence

Poin

t pre

vale

nce

of

OFC

/DB

PCFC

-con

-fir

med

FH

S: a

t 3 y

ears

2

.3%

(1.3

-4.0

); ad

ults

3

.2%

(2.3

-4.5

)

Mod

erat

e

Pena

rd-M

oran

d et

al.

20

05

, Fr

ance

Cros

s-se

ctio

nal

stud

y9

61

57

78

19

-11

ye

ars

old

Any

FA

, nut

s, fr

uits

or

vege

tabl

es, e

gg, m

ilk,

pean

ut, fi

sh, s

eafo

od

Self-

repo

rted

, SP

TPo

int

prev

alen

ce

Poin

t pre

vale

nce

of

sym

ptom

s pl

us S

PT

posi

tivity

to a

t lea

st o

ne

FA: 0

.1%

(0.1

-0.3

)

Mod

erat

e

Tabl

e E1

(co

ntin

ued)



Refe

renc

e,

coun

try

Stud

y de

sign

Stud

y po

pula

tion

N (c

hild

ren/

adul

ts; s

ourc

e of

st

udy

popu

latio

n)A

ge o

f su

bjec

tsO

utco

me

stud

ied

and

asse

ssm

ent m

etho

dO

ccur

renc

e m

easu

re(s

)

Mai

n re

sults

of t

he

freq

uenc

y of

FA

(FA

)Pe

rcen

tage

(95

% C

I)

Ove

rall

risk

of b

ias

asse

ssm

ent

Num

ber

appr

oach

edN

umbe

r pa

rtic

ipat

edO

utco

me(

s) s

tudi

edM

etho

d of

out

-co

me

asse

ssm

ent1

Pere

ira e

t al.

20

05

, UK

Cros

s-se

ctio

nal

stud

y3

14

41

53

21

1 a

nd

15

yea

r ol

d

Any

FA

, milk

, egg

, whe

at,

fish,

pea

nut,

sesa

me,

tr

ee n

uts,

add

itive

s,

shel

lfish

Self-

repo

rted

, ph

ysic

ian

diag

nosi

s, S

PT,

OFC

, DB

PCFC

Poin

t pr

eval

ence

Poin

t pre

vale

nce

for

all c

hild

ren:

OFC

-con

-fir

med

FA

2.3

% (1

.6-

3.2

) DB

PCFC

-con

-fir

med

1.8

% (1

.2-2

.6

Mod

erat

e

Pyrh

önen

et a

l. 2

01

1 a

nd 2

00

9,

Finl

and

Coho

rt

stud

y 5

97

33

89

90

-4

year

s ol

d

Any

FA

, milk

, egg

, whe

at,

barle

y or

rye

, nu

t, fis

h,

citr

us fr

uit

Self-

repo

rted

, ph

ysic

ian-

diag

nosi

s, S

PT,

sIgE

, OFC

Life

-tim

e pr

eval

ence

, cu

mul

ativ

e in

cide

nce

Life

time

prev

alen

ce o

f se

lf-re

port

ed p

hysi

-ci

an-d

iagn

osed

FA

3

0.3

% (2

8.7

-31

.9)

Cum

ulat

ive

inci

denc

e of

O

FC-c

onfir

med

FA

by

4

year

s: 3

.3%

(2.8

-3.9

)

Mod

erat

e

Pyzi

ak a

nd

Kam

er 2

01

1,

Pola

nd

Cros

s-se

ctio

nal

stud

y1

15

83

6-1

7

year

s ol

d

Any

FA

, cow

’s m

ilk, h

en’s

eg

g, s

oy, p

ork,

bee

fSe

lf-re

port

ed,

sIgE

, SPT

, OFC

Poin

t pr

eval

ence

Freq

uenc

y es

timat

es

not g

iven

in th

e st

udy

Mod

erat

e

Ran

ce e

t al.

20

05

, Fra

nce

Cros

s-se

ctio

nal

stud

y3

50

02

71

6M

ean

age

8.9

ye

ars

Any

FA

, cow

’s m

ilk, e

gg,

kiw

i, pe

anut

, fish

, tre

e nu

t, sh

rim

pSe

lf-re

port

edPo

int a

nd

life-

time

prev

alen

ce

Poin

t pre

vale

nce

of

self-

repo

rted

FA

: 4.7

(3

.9-5

.5)

Mod

erat

e

Robe

rts

et a

l. 2

00

5 a

nd L

ack

et a

l. 2

00

3, U

K

Coho

rt

stud

y1

39

71

12

09

0

0-7

ye

ars

Egg,

milk

, cod

fish

, soy

a,

sesa

me,

pea

nut,

tree

nut

, ca

shew

, alm

ond,

wal

nut,

haze

lnut

, bra

zil n

ut, p

ecan

nu

t

Self-

repo

rted

, SP

T, D

BPC

FCPo

int

Prev

alen

ce

Poin

t pre

vale

nce

of

DB

PCFC

-con

firm

ed

pean

ut a

llerg

y: 0

.2%

(0

.1-0

.3)

Mod

erat

e

Rona

et a

l. 2

00

7,

Wor

ld-w

ide

Syst

emat

ic

revi

ew9

34

stu

dies

id

entifi

ed

Num

ber

of s

tudi

es

incl

uded

in

revi

ew n

ot

indi

cate

d

All

age

grou

ps

Any

FA

, cow

’s m

ilk,

hen’

s eg

g, p

eanu

t, fis

h,

shel

lfish

Self-

repo

rted

, ph

ysic

ian-

diag

nosi

s, S

PT,

sIgE

, OFC

, D

BPC

FC

Poin

t, pe

riod

, lif

e-tim

e pr

eval

ence

, cu

mul

ativ

e in

cide

nce

and

inci

denc

e ra

te

Ran

ge o

f pre

vale

nce

of S

PT o

r sI

gE to

at

leas

t one

FA

: 2%

-5%

SPT

only

: 7%

-17

%

IgE

only

: 4%

-6%

Mod

erat

e

Ronc

hett

i et a

l. 2

00

8, I

taly

Cros

s-se

ctio

nal

stud

y

Not

in

dica

ted

38

0

9 a

nd

13

ye

ars

old

Any

FA

, cow

’s m

ilk, h

en’s

eg

g, to

mat

o, w

heat

flou

rSP

TPo

int

prev

alen

ce

Poin

t pre

vale

nce

of

SPT

posi

tivity

to a

t le

ast o

ne F

A fo

r all

chil-

dren

4.2

% (2

.6-6

.7)

Mod

erat

e

Tabl

e E1

(co

ntin

ued)

E-15EAACI



Refe

renc

e,

coun

try

Stud

y de

sign

Stud

y po

pula

tion

N (c

hild

ren/

adul

ts; s

ourc

e of

st

udy

popu

latio

n)A

ge o

f su

bjec

tsO

utco

me

stud

ied

and

asse

ssm

ent m

etho

dO

ccur

renc

e m

easu

re(s

)

Mai

n re

sults

of t

he

freq

uenc

y of

FA

(FA

)Pe

rcen

tage

(95

% C

I)

Ove

rall

risk

of b

ias

asse

ssm

ent

Num

ber

appr

oach

edN

umbe

r pa

rtic

ipat

edO

utco

me(

s) s

tudi

edM

etho

d of

out

-co

me

asse

ssm

ent1

Sand

in e

t al.

20

05

, Sw

eden

an

d Es

toni

a

Case

-co

ntro

l st

udy

All

98

5Sw

eden

6

45

Esto

nia

34

0

All

77

0Sw

eden

48

3Es

toni

a 2

87

10

-11

ye

ars

old

Any

FA

; app

le, p

each

, ki

wi,

or c

arro

t; nu

t or

pea

nut;

oran

ge,

man

dari

n or

tom

ato;

m

ilk, e

gg, fi

sh o

r w

heat

Self-

repo

rt, s

IgE

Poin

t pr

eval

ence

Poin

t pre

vale

nce

of s

IgE

posi

tivity

to

at le

ast o

ne F

A fo

r Es

toni

a an

d Sw

eden

1

3.9

% (1

1.3

-16

.9)

Mod

erat

e

Schä

fer

et a

l. 2

00

1, G

erm

any

Nes

ted

case

-co

ntro

l st

udy

25

39

15

37

25

-74

Any

FA

Self-

repo

rted

, SP

T

Poin

t pr

eval

ence

, lif

etim

e pr

eval

ence

Poin

t pre

vale

nce

of S

PT

posi

tivity

to a

t lea

st o

ne

FA in

the

popu

latio

n of

the

alle

rgy

MO

NIC

A

stud

y: 1

6.8

%

Mod

erat

e

Schn

abel

et a

l. 2

01

0, G

erm

any

Coho

rt

stud

y3

09

71

08

26

yea

rs

old

Any

FA

Self-

repo

rted

, sI

gEPo

int

prev

alen

ce

Poin

t pre

vale

nce

of

sIgE

pos

itivi

ty to

at

leas

t one

FA

at 6

ye

ars:

11

.7%

(10

.0-

13

.8)

Mod

erat

e

Soos

t et a

l. 2

00

9

and

Zube

rbie

r et

al

. 20

04

, Roe

hr

et a

l. 2

00

4,

Ger

man

y

Cros

s-se

ctio

nal

stud

y1

33

00

All:

40

93

Age

0-1

7

year

s: 7

39

Age

18

-79

ye

ars:

32

27

0-7

9

year

s ol

d

Any

FA

, veg

etab

les,

leg-

umes

, soy

, spi

ces,

fish

, ce

real

s, m

eat a

nd fa

t, st

onef

ruit,

cho

cola

te/

swee

ts, c

ow’s

milk

, hen

’s

egg,

pip

frui

t, nu

ts, v

eg-

etab

le o

il, c

arro

t, ce

lery

, se

sam

e, a

pple

, app

le,

haze

lnut

, pot

ato,

whe

at,

pean

ut, w

alnu

t, sh

rim

p

Self-

repo

rted

, ph

ysic

ian

diag

nosi

s, S

PT,

sIgE

, OFC

, SB

PCFC

, DB

PCFC

Poin

t and

lif

e-tim

e pr

eval

ence

Poin

t pre

vale

nce

of O

FC/D

BPC

FC-

confi

rmed

FA

:A

ll: 2

.8%

(2.4

-3.4

)Ch

ildre

n: 4

.2%

(3.0

-5

.9)

Adu

lts: 2

.9%

(2.3

-3

.5)

Mod

erat

e

Stei

nke

et a

l. 2

00

7, E

urop

e

Cros

s-se

ctio

nal

stud

y

Not

in

dica

ted

40

42

6<

18

ye

ars

Any

FA

, fish

, sea

food

, w

heat

, mea

t, eg

gs,

milk

, fru

its, l

egum

es,

vege

tabl

es, n

uts

Self-

repo

rted

Poin

t pr

eval

ence

Poin

t pre

vale

nce

of

self-

repo

rted

FA

: A

ll co

untr

ies:

5.0

%

(4.5

-5.4

)

Mod

erat

e

Vent

er e

t al.

20

10

, UK

Coho

rt

stud

y5

28

33

38

23

-4

year

s ol

dPe

anut

alle

rgy

Phys

icia

n di

agno

sis,

SPT

, sI

gE, O

FC,

DB

PCFC

Poin

t pr

eval

ence

Poin

t pre

vale

nce

of O

FC-c

onfir

med

pe

anut

alle

rgy:

0.3

%

(0.1

-1.0

)

Mod

erat

e

Tabl

e E1

(co

ntin

ued)



Refe

renc

e,

coun

try

Stud

y de

sign

Stud

y po

pula

tion

N (c

hild

ren/

adul

ts; s

ourc

e of

st

udy

popu

latio

n)A

ge o

f su

bjec

tsO

utco

me

stud

ied

and

asse

ssm

ent m

etho

dO

ccur

renc

e m

easu

re(s

)

Mai

n re

sults

of t

he

freq

uenc

y of

FA

(FA

)Pe

rcen

tage

(95

% C

I)

Ove

rall

risk

of b

ias

asse

ssm

ent

Num

ber

appr

oach

edN

umbe

r pa

rtic

ipat

edO

utco

me(

s) s

tudi

edM

etho

d of

out

-co

me

asse

ssm

ent1

Vent

er a

l 20

08

; D

ean

et a

l. 2

00

7;

Vent

er e

t al.

20

06

, UK

Coho

rt

stud

y1

06

39

69

3 y

ears

ol

dA

ny F

A, m

ilk, e

gg, fi

sh,

pean

ut, s

esam

e, w

heat

Self-

repo

rt, S

PT,

OFC

, DB

PCFC

Poin

t and

pe

riod

pr

eval

ence

, cu

mul

ativ

e in

cide

nce

Poin

t pre

vale

nce

of

OFC

-con

firm

ed F

A

at 3

yea

rs: 0

.8%

(0

.4-1

.6)

Mod

erat

e

Vent

er e

t al.

20

06

, UK

Cros

s-se

ctio

nal

stud

y1

44

07

98

6 y

ears

ol

d

Any

FA

, milk

, pea

nut,

egg,

add

itive

s &

col

our-

ings

, tre

e nu

ts, w

heat

, st

raw

berr

y, s

esam

e, fi

sh,

choc

olat

e, b

anan

a

Self-

repo

rt, S

PT,

OFC

, DB

PCFC

Poin

t pr

eval

ence

Poin

t pre

vale

nce

of

OFC

-con

firm

ed F

A

1.3

% (0

.7-2

.3) a

nd

DB

PCFC

-con

firm

ed

FA 0

.4%

(0.1

-1.1

)

Mod

erat

e

von

Her

tzen

et

al. 2

00

6, F

inla

nd

and

Rus

sia

Cros

s-se

ctio

nal

stud

y

Finl

and:

5

46

chi

ld-

mot

her

pair

s

Finl

and:

41

3

child

ren,

40

9

mot

hers

7-1

6

year

s ch

ildre

n

Fish

, egg

, whe

at, c

ow’s

m

ilk, p

eanu

t, ha

zeln

utSP

TPo

int

prev

alen

ce

Poin

t pre

vale

nce

of S

PT p

ositi

vely

to

pea

nut a

llerg

en:

child

ren:

8.2

%

(5.8

-11

.5),

mot

hers

: 1

0.1

% (7

.4-1

3.6

)

Mod

erat

e

Zuid

mee

r et

al.

20

08

, Wor

ld-

wid

e

Syst

emat

ic

revi

ew3

96

stu

dies

id

entifi

ed3

3 s

tudi

es

incl

uded

All

age

grou

psFr

uits

, veg

etab

les,

tree

nu

ts, s

oy, w

heat

Self-

repo

rted

, ph

ysic

ian-

diag

-no

sis,

SPT

, sIg

E,

OFC

, DB

PCFC

Poin

t, pe

riod

, and

lif

e-tim

e pr

eval

ence

Poin

t pre

vale

nce

of

DB

PCFC

-con

firm

ed

alle

rgy

to v

eget

able

s:

1.4

%

Mod

erat

e

DB

PCFC

: dou

ble-

blin

d, p

lace

bo-c

ontr

olle

d fo

od c

halle

nge;

OFC

: ora

l foo

d ch

alle

nge;

sIg

E: s

peci

fic im

mun

oglo

bulin

E te

st; S

PT: s

kin

pric

k te

st fo

r se

nsiti

zatio

n to

spe

cific

fo

od a

llerg

ens

Tabl

e E1

(co

ntin

ued)

E-17EAACI



Tabl

e E2

Qua

lity

asse

ssm

ent o

f stu

dies

incl

uded

in th

e sy

stem

atic

revi

ew: i

nclu

ded

stud

ies

1 J

anua

ry 2

00

0 -

30

Sep

tem

ber

20

12

Refe

renc

e, c

ount

ryO

vera

ll ri

sk o

f bia

s as

sess

men

t

Com

pone

nts

of r

isk

of b

ias

asse

ssm

ent

Stud

y de

sign

Sele

ctio

n bi

asEx

posu

re a

sses

smen

tO

utco

me

asse

ssm

ent

Ban

t et a

l. 2

00

8, P

olan

dM

oder

ate

Stro

ngW

eak

Not

app

licab

leM

oder

ate

Bur

ney

et a

l. 2

01

0; W

oods

et a

l. 2

00

1,

Euro

pe, U

SA, A

ustr

alia

, New

Zea

land

Mod

erat

eM

oder

ate

Mod

erat

eM

oder

ate

Mod

erat

e

Caffa

relli

et a

l. 2

01

1, I

taly

Mod

erat

eSt

rong

Mod

erat

eM

oder

ate

Wea

k

Chaf

en e

t al.

20

10

, Wor

ld-w

ide

Stro

ngSt

rong

Mod

erat

eN

ot a

pplic

able

Stro

ng

Colv

er e

t al.

20

05

, UK

and

Irel

and

Mod

erat

eM

oder

ate

Wea

kM

oder

ate

Mod

erat

e

Du

Toit

et a

l. 2

00

8, U

K a

nd Is

rael

Mod

erat

eM

oder

ate

Mod

erat

eM

oder

ate

Stro

ng

Dub

akie

ne e

t al.

20

12

, Lith

uani

aM

oder

ate

Stro

ngM

oder

ate

Mod

erat

eSt

rong

Egge

sbø

et a

l. 2

00

3, 2

00

1a,

20

01

b, N

orw

ayM

oder

ate

Stro

ngM

oder

ate

Mod

erat

eSt

rong

Elle

r et

al.

20

09

, Kja

er e

t al.

20

08

, Joh

nke

et

al. 2

00

6, D

enm

ark

Mod

erat

eSt

rong

Mod

erat

eN

ot a

pplic

able

Stro

ng

Falc

aõ e

t al.

20

04

, Por

tuga

lM

oder

ate

Stro

ngM

oder

ate

Not

app

licab

leW

eak

Flok

stra

-de

Blo

k et

al.

20

11

, The

Net

herla

nds

Wea

kSt

rong

Wea

kN

ot a

pplic

able

Wea

k

Fox

et a

l. 2

00

9, U

KM

oder

ate

Stro

ngM

oder

ate

Mod

erat

eSt

rong

Fron

gia

et a

l 20

05

, Ita

lyM

oder

ate

Stro

ngM

oder

ate

Not

app

licab

leW

eak

Gel

inci

k et

al.

20

08

, Tur

key

Mod

erat

eM

oder

ate

Wea

kM

oder

ate

Stro

ng

Gru

ndy

et a

l. 2

00

2, U

KM

oder

ate

Stro

ngM

oder

ate

Not

app

licab

leSt

rong

Gup

ta e

t al.

20

07

, 20

04

, 20

03

, UK

Mod

erat

eSt

rong

Wea

kN

ot a

pplic

able

Mod

erat

e

Høs

t et a

l. 2

00

2, D

enm

ark

Mod

erat

eSt

rong

Mod

erat

eN

ot a

pplic

able

Stro

ng

Hou

riha

ne e

t al.

20

07

, UK

Mod

erat

eM

oder

ate

Wea

kM

oder

ate

Stro

ng

Isol

auri

et a

l. 2

00

4, F

inla

ndM

oder

ate

Stro

ngM

oder

ate

Mod

erat

e M

oder

ate

Joha

nsso

n et

al.

20

05

, Sw

eden

and

Nor

way

Mod

erat

eM

oder

ate

Wea

kN

ot a

pplic

able

Mod

erat

e

Julg

e et

al.

20

01

, Vas

ar e

t al.

20

00

, Est

onia

Mod

erat

eSt

rong

Mod

erat

eM

oder

ate

Mod

erat

e

Kan

ny e

t al.

20

01

, Fra

nce

Mod

erat

eSt

rong

Mod

erat

eM

oder

ate

Wea

k



Refe

renc

e, c

ount

ryO

vera

ll ri

sk o

f bia

s as

sess

men

t

Com

pone

nts

of r

isk

of b

ias

asse

ssm

ent

Stud

y de

sign

Sele

ctio

n bi

asEx

posu

re a

sses

smen

tO

utco

me

asse

ssm

ent

Kot

z et

al.

20

11

, UK

Mod

erat

eM

oder

ate

Mod

erat

eM

oder

ate

Mod

erat

e

Kra

use

et a

l. 2

00

2, G

reen

land

Mod

erat

eSt

rong

Mod

erat

eN

ot a

pplic

able

Mod

erat

e

Kri

stin

sdot

tir e

t al.

20

11

, Ice

land

Mod

erat

eSt

rong

Mod

erat

eN

ot a

pplic

able

Stro

ng

Kuc

ukos

man

oglu

et a

l. 2

00

8, T

urke

yM

oder

ate

Stro

ngM

oder

ate

Not

app

licab

leM

oder

ate

Kur

ulaa

ratc

hy e

t al.

20

05

, Ars

had

et a

l. 2

00

1, T

ariq

et a

l. 2

00

0, U

KM

oder

ate

Stro

ngM

oder

ate

Not

app

licab

leM

oder

ate

Kven

shag

en e

t al.

20

09

, Nor

way

Mod

erat

eSt

rong

Mod

erat

eM

oder

ate

Stro

ng

Maj

kow

ska-

Woj

ciec

how

ska

et a

l. 2

00

9,

Pola

ndM

oder

ate

Stro

ngM

oder

ate

Not

app

licab

leW

eak

Mar

klun

d et

al.

20

04

, Sw

eden

Mod

erat

e St

rong

M

oder

ate

Not

app

licab

leW

eak

Mat

rica

rdi e

t al.

20

07

, Ger

man

yM

oder

ate

Stro

ngM

oder

ate

Not

app

licab

leM

oder

ate

Mos

sako

wsk

a et

al.

20

08

, Pol

and

Mod

erat

eSt

rong

Mod

erat

eN

ot a

pplic

able

Wea

k

Nic

olao

u et

al.

20

10

, UK

Mod

erat

eSt

rong

Mod

erat

eM

oder

ate

Stro

ng

Nig

gem

ann

et a

l. 2

01

1, G

erm

any

Mod

erat

eSt

rong

Mod

erat

eN

ot a

pplic

able

Mod

erat

e

Orh

an e

t al.

20

09

, Tur

key

Mod

erat

eSt

rong

Mod

erat

eN

ot a

pplic

able

Stro

ng

Öst

blom

et a

l. 2

00

8a,

20

08

b, 2

00

8c;

A

lmqv

ist e

t al.

20

05

, Sw

eden

Mod

erat

eSt

rong

Mod

erat

eN

ot a

pplic

able

Mod

erat

e

Ost

erba

lle e

t al.

20

09

, Den

mar

kM

oder

ate

Stro

ngM

oder

ate

Not

app

licab

leSt

rong

Ost

erba

lle e

t al.

20

05

, Den

mar

kM

oder

ate

Stro

ngM

oder

ate

Not

app

licab

leSt

rong

Pena

rd-M

oran

d et

al.

20

05

, Fra

nce

Mod

erat

eM

oder

ate

Mod

erat

eM

oder

ate

Mod

erat

e

Pere

ira e

t al.

20

05

, UK

Mod

erat

eSt

rong

Mod

erat

eN

ot a

pplic

able

Stro

ng

Pyrh

önen

et a

l. 2

01

1 a

nd 2

00

9, F

inla

ndM

oder

ate

Mod

erat

eM

oder

ate

Mod

erat

eSt

rong

Pyzi

ak a

nd K

amer

20

11

, Pol

and

Mod

erat

e M

oder

ate

Wea

k M

oder

ate

Stro

ng

Ran

ce e

t al.

20

05

, Fra

nce

Mod

erat

eSt

rong

Mod

erat

eN

ot a

pplic

able

Wea

k

Tabl

e E2

(co

ntin

ued)

E-19EAACI



Refe

renc

e, c

ount

ryO

vera

ll ri

sk o

f bia

s as

sess

men

t

Com

pone

nts

of r

isk

of b

ias

asse

ssm

ent

Stud

y de

sign

Sele

ctio

n bi

asEx

posu

re a

sses

smen

tO

utco

me

asse

ssm

ent

Robe

rts

et a

l. 2

00

5 a

nd L

ack

et a

l. 2

00

3, U

KM

oder

ate

Stro

ngM

oder

ate

Mod

erat

eSt

rong

Rona

et a

l. 2

00

7, W

orld

-wid

eM

oder

ate

Stro

ngM

oder

ate

Not

app

licab

leSt

rong

Ronc

hett

i et a

l. 2

00

8, I

taly

Mod

erat

eM

oder

ate

Mod

erat

eN

ot a

pplic

able

Mod

erat

e

Sand

in e

t al.

20

05

, Sw

eden

and

Est

onia

Mod

erat

eM

oder

ate

Mod

erat

eN

ot a

pplic

able

Mod

erat

e

Soos

t et a

l. 2

00

9 a

nd Z

uber

bier

et a

l. 2

00

4,

Roeh

r et

al.

20

04

, Ger

man

yM

oder

ate

Mod

erat

eM

oder

ate

Mod

erat

eSt

rong

Schn

abel

et a

l. 2

01

0, G

erm

any

Mod

erat

eSt

rong

Mod

erat

eM

oder

ate

Mod

erat

e

Schä

fer

et a

l. 2

00

1, G

erm

any

Mod

erat

eSt

rong

Mod

erat

eN

ot a

pplic

able

Mod

erat

e

Stei

nke

et a

l. 2

00

7, E

urop

eM

oder

ate

Stro

ngM

oder

ate

Not

app

licab

leW

eak

Vent

er e

t al.

20

10

, UK

Mod

erat

eSt

rong

Mod

erat

eM

oder

ate

Stro

ng

Vent

er e

t al.

20

08

; Dea

n et

al.

20

07

; Ven

ter

et a

l. 2

00

6, U

KM

oder

ate

Stro

ngM

oder

ate

Mod

erat

eSt

rong

Vent

er e

t al.

20

06

, UK

Mod

erat

eSt

rong

Mod

erat

eN

ot a

pplic

able

Stro

ng

von

Her

tzen

et a

l. 2

00

6, F

inla

nd a

nd R

ussi

aM

oder

ate

Mod

erat

eM

oder

ate

Mod

erat

eM

oder

ate

Zuid

mee

r et

al.

20

08

, Wor

ld-w

ide

Mod

erat

eSt

rong

Wea

kN

ot a

pplic

able

Stro

ng

The

over

all r

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