1
Ti le: Blood Eosinophil Coun as P edic o o As hma Exace ba ion. A Me a-analysis
Sho i le: Blood Eosinophil Coun and As hma Exace ba ion
Na meen Mallah, MSc1,2; San iago Rod iguez-Segade, MD3; F ancisco-Ja ie Gonzalez-
Ba cala, MD3,4,5,6; Bahi Takkouche, PhD1,2,6
1Depa men o P e en i e Medicine, Uni e si y o San iago de Compos ela, San iago de Compos ela,
Spain.
2Cen o de In es igación Biomédica en Red de Epidemiología y Salud Pública (CIBER-ESP), Ca los III
Heal h Resea ch Ins i u e, Mad id, Spain.
3Depa men o Respi a o y Medicine, Uni e si y Hospi al o San iago de Compos ela (CHUS), San iago
de Compos ela, Spain.
4Depa men o Medicine, Uni e si y o San iago de Compos ela, San iago de Compos ela, Spain.
5Spanish Biomedical Resea ch Ne wo king Cen e (CIBER-ES), Ca los III Heal h Resea ch Ins i u e,
Mad id, Spain.
6Heal h Resea ch Ins i u e o San iago de Compos ela (IDIS), San iago de Compos ela, Spain.
Co esponding Au ho : D . F ancisco-Ja ie Gonzalez-Ba cala, Depa men o Respi a o y
Medicine, Uni e si y Hospi al o San iago de Compos ela (CHUS), San iago de Compos ela,
15706, Spain ( ancisco.ja ie [email p o ec ed]).
Au ho s′ Con ibu ions: NM conduc ed he li e a u e e iew, ex ac ed, analyzed, and
in e p e ed he da a, and designed and w o e he manusc ip . SR-S pa icipa ed in he s udies
2
localiza ion. NM and BT ex ac ed he da a. FJG-B concei ed he esea ch idea and esol ed
disag eemen s abou a icles՚ selec ion. BT designed he s udy and supe ised he da a analysis
and in e p e a ion. All au ho s e iewed and e ised he manusc ip and app o ed i o
publica ion.
Acknowledgmen s: We a e g a e ul o he ollowing au ho s who answe ed ou que ies abou
hei s udies: Da id B. P ice (Cen e o Academic P ima y Ca e, The Ins i u e o Applied Heal h
Sciences, Uni e si y o Abe deen, Abe deen, UK; Resea ch in Real-Li e, Camb idge, UK), Lo en
C. Denlinge (Uni e si y o Wisconsin, Madison, Wisconsin) and Kyoung-Hee Sohn (Ins i u e o
Alle gy and Clinical Immunology, Seoul Na ional Uni e si y Medical Resea ch Cen e , Seoul
Na ional Uni e si y College o Medicine, Seoul, Ko ea).
Con lic o in e es : none decla ed
Funding sou ces: no unding was equi ed o his s udy.
Wo d Coun (Abs ac ): 247
Wo d Coun (Tex ): 3047
3
ABSTRACT
Backg ound: E idence abou he associa ion o high blood eosinophil coun wi h as hma
exace ba ion is inconsis en and unclea . The objec i e o his me a-analysis is o de e mine
whe he ele a ed blood eosinophils coun p edic s as hma exace ba ion.
Me hods: We sea ched MEDLINE, EMBASE, and addi ional da abases, wi hou any language
es ic ion. We also checked he e e ence lis s o he included s udies and o ele an sys ema ic
e iews. The main ou come was he occu ence o as hma exace ba ion. We calcula ed global
pooled Odds Ra ios (ORs) and hei 95% Con idence In e als (CIs) and pe o med p ede ined
subg oup analyses. We app aised he quali y o he s udies using Newcas le-O awa Scale,
examined he he e ogenei y be ween s udies, assessed publica ion bias and ca ied ou sensi i i y
analyses.
Resul s: Among 1567 e ie ed publica ions, 23 obse a ional s udies comp ising 155,772
pa icipan s me he inclusion c i e ia. High blood eosinophil coun was associa ed wi h highe
odds o as hma exace ba ion [OR: 1.31 (95%CI: 1.16, 1.49)], speci ically wi h as hma- ela ed
ou pa ien isi s [OR: 1.46 (95%CI: 1.25, 1.70)] and eme gency depa men isi s [OR: 1.63
(95%CI: 1.29, 2.07)]. A signi ican associa ion was obse ed s a ing om an eosinophils’ cu -o
alue o 200 cells/μl. The associa ion was obse ed o coho s udies [OR: 1.30 (95%CI: 1.13,
1.49)], No h-Ame ican s udies [OR: 1.43 (95%CI: 1.31, 1.57)], Asian popula ions [OR: 1.67
(95%CI: 1.34, 2.08)] child en [OR: 1.38 (95%CI: 1.22, 1.56)], and s udies ha adjus ed o inhaled
co icos e oids he apy [OR: 1.42 (95%CI: 1.28, 1.56)].
Conclusions: Blood eosinophil coun s ≥ 200 cells/µl a e associa ed wi h as hma exace ba ion.
Blood eosinophil coun is a modi iable ac o ha could be add essed in as hma managemen
s a egies.
Keywo ds: as hma exace ba ion, blood eosinophils, me a-analysis
4
Abb e ia ions: CCI: Cha lson Como bidi y Index; CI: Con idence In e al; CRP: C-Reac i e
P o ein; FEV1: Fo ced Expi a o y Volume in 1 second; FeNO: F ac ional Exhaled Ni ic Oxide;
ICS: Inhaled Co icos e oids; NOS: Newcas le-O awa Scale; OR: Odds Ra io; PEF: Peak
Expi a o y Flow; RR: Rela i e Risk
5
INTRODUCTION
As hma is a p ominen ch onic disease ha a ec s 235 million indi iduals wo ldwide and
ep esen s he mos common ch onic disease among child en.1,2 When exace ba ed, i equi es
u gen medical assis ance o p e en se ious ou comes including dea h.3 As hma exace ba ion
occu s in highe equency and wi h mo e se e i y when as hma is no con olled; ne e heless, i
may also a ec pa ien s on as hma ea men .4 The global mo ali y a e om as hma was 0.19
pe 100,000 indi iduals in 2012, wi h s alled imp o emen s in lowe ing mo ali y o e he pas
decade.5 Indeed, in 2016, as hma was classi ied as he 23 d leading cause o p ema u e mo ali y.6
The Global As hma Repo 2018 es ima es ha 1000 people die e e y day om as hma
wo ldwide.6 As hma p e alence is s ill g owing in many coun ies, imposing majo consequences
on public heal h, socie y and economy.6 These obse a ions emphasize he need o be e
unde s and p edisposing ac o s o p edic he occu ence and se e i y o as hma exace ba ion.
Inc eased clinical in e es in he use o eosinophil coun as a p edic o o as hma wo sening was
obse ed in he ecen li e a u e. Howe e , o each app op ia e clinical decisions, a ca e ul
in e p e a ion o he a ailable e idence is equi ed. Findings conce ning blood eosinophils and
as hma exace ba ion di e ged widely ac oss s udies, as he di ec ions and he magni udes o
measu es o e ec we e inconsis en . While some s udies did no ind a co ela ion be ween
inc eased blood eosinophil coun and as hma se e i y,7,8 o he s epo ed a bo de line e ec ,9-11 o
a posi i e associa ion which magni ude a ied g ea ly be ween s udies, anging be ween 30% and
150% inc ease in he isk o as hma wo sening.12-19 On he o he side, some au ho s epo ed
opposi e indings which associa ed ele a ed le els o blood eosinophils wi h a lowe isk o
as hma exace ba ion.20,21 In ligh o hese con adic o y obse a ions, and aking in o accoun ha
blood eosinophil coun may be lowe ed h ough adequa e he apy, we conside ed ha he e was a
6
need o a me a-analysis ha assesses he associa ion be ween blood eosinophil coun and as hma
exace ba ion, and explo es he h eshold o blood eosinophils which po en ially induces as hma
wo sening.
METHODS
Da a sou ces and sea ches
We pe o med a sys ema ic e iew and me a-analysis o blood eosinophil coun s as p edic o s o
he isk o as hma exace ba ion. As hma exace ba ion is also some imes e e ed as as hma
a ack.22,23 We de ined as hma exace ba ion (o as hma a ack) as a de e io a ion in as hma
equi ing any o he ollowing: ea men wi h an o al co icos e oid, isi o an eme gency
depa men , ou pa ien isi , o hospi aliza ion. We included s udies ha asce ained as hma
exace ba ions using sel -assessmen ools. Howe e we la e s a i ied he analysis based on he
mean used o ou come asce ainmen .
We sea ched he ollowing da abases since hei incep ion un il May 2020: MEDLINE,
EMBASE, Con e ence P oceedings Ci a ion Index- Science, he i e egional bibliog aphic
da abases o he Wo ld Heal h O ganiza ion; as well as he Open Access Thesis and
Disse a ions. We did no apply any es ic ion on language o publica ion da e. In MEDLINE we
applied he sea ch syn ax: ("As hma"[Mesh] AND "Eosinophils"[Mesh] AND (exace ba ion OR
wo sening)), which we hen adap ed o o he da abases. We comple ed ou sea ch by using he
e ms: as hma, blood eosinophil, exace ba ion, wo sening, a ack, as ee ex wo ds, and by
checking manually he e e ence lis s o he eligible s udies as well as ha o o he ele an
sys ema ic e iews.
7
S udy selec ion
Two esea che s (NM and SR-S) independen ly e iewed he i les and abs ac s o he e ie ed
s udies and subsequen ly selec ed he po en ially eligible ones o a ull- ex e ision.
Disag eemen s we e esol ed by e e ing o a hi d esea che (FJG-B).
We included obse a ional s udies ha epo ed Odds Ra io (OR) o Rela i e Risk (RR) o he
associa ion be ween high blood eosinophil coun and as hma exace ba ion. We excluded s udies
in which he compa ison g oup was limi ed o heal hy subjec s. In he case o duplica ed epo s,
we conside ed he mos comple e and upda ed e sion. The s udy p o ocol is egis e ed in he
In e na ional P ospec i e Regis e o Sys ema ic Re iews (PROSPERO) (CRD42020157743).
Da a ex ac ion and quali y assessmen
Two epidemiologis s (NM and BT) ex ac ed da a on: 1) s udy sou ce: i s au ho ’s name and
publica ion yea ; 2) s udy cha ac e is ics: coun y, s udy design, blood eosinophil cu -o limi ,
sample size, pa icipan s’ inclusion and exclusion c i e ia, e ec measu e and 95% con idence
in e al (CI), and adjus men a iables; 3) pa ien s’ cha ac e is ics: age and sex; and 4) as hma
exace ba ion de ini ions: hospi al admission, eme gency depa men isi , ou pa ien isi and/o
inc eased co icos e oids ea men . When ele an da a we e incomple e o no a ailable, we
con ac ed he co esponding au ho o eques he missing in o ma ion.8,9,14,15,24-28
To assess he me hodological quali y o he s udies, we used he Newcas le-O awa Scale (NOS)
o coho and case-con ol s udies,29 and an adap ed NOS e sion o he e alua ion o c oss-
sec ional s udies.30 NOS is a widely used ool o e alua e he me hodological aspec s o
obse a ional s udies such as samples՚ ep esen a i eness, pa icipa ion a e, con ol o
con ounding ac o s, and asce ainmen o exposu e and ou come. Quali y sco ing was pe o med
8
independen ly by wo e iewe s and he a e age sco e be ween e iewe s was assigned o he
s udies. A maximum o 8 poin s was a ibu ed o each s udy.(e-Appendix 1) Disag eemen
be ween a e s was measu ed by he Bland-Al man limi s o ag eemen me hod.31
Da a syn hesis and s a is ical analysis
We weigh ed he s udy-speci ic adjus ed measu es o e ec by he in e se o hei a iance o
ob ain a pooled OR. When a ious h esholds o blood eosinophil coun we e epo ed, we used
400 cells/μl as a cu -o limi .32 When e ec measu es we e epo ed o di e en subg oups
wi hin he same s udy, we pooled he di e en es ima es in o de o ob ain one global OR pe
s udy.
We compu ed ixed and andom e ec models bu conside ed only he la e when he e ogenei y
was de ec ed. We checked o he e ogenei y using De Simonian and Lai d’s Q es and
quan i ied i using Ri, he p opo ion o o al a iance due o be ween-s udy a iance.33 We
in e p e ed Ri alues as ollows: low he e ogenei y (Ri<0.4), mode a e he e ogenei y (0.4≤
Ri≤0.75), and high he e ogenei y (Ri>0.75). Finally, we s a i ied he analysis acco ding o s udy
design, ype o coho s udy, quali y sco e, age ca ego y, geog aphical loca ion, blood
eosinophils’ cu -o limi , as hma exace ba ion de ini ions (indica o s), me hods o as hma
exace ba ion asce ainmen , and equency o as hma a acks. We planned a p io i all hese
subg oup analyses.
We explo ed he p esence o publica ion bias, i s isually using a unnel plo and hen, mo e
o mally, using Egge ’s eg ession es . We also ca ied ou a sensi i i y analysis assuming ha
c oss-sec ional s udies a e he leas likely o be published when hey show a null associa ion. We
ecalcula ed he pooled OR assuming ha : 1) he c oss-sec ional s udies included in ou me a-
9
analysis ep esen only hal o he s udies ha ha e e e been conduc ed on his opic, 2) he
unpublished c oss-sec ional s udies ound a null associa ion o OR = 1 and 3) he p e alence o
as hma exace ba ion in he unpublished s udies was equal o he a e age p e alence o he
published ones.
In addi ion, o u he assess publica ion bias, we pe o med a “ im and ill” analysis.34
We ca ied ou he analyses using he so wa e HEpiMA e sion 2.1.3,35 and STATA e sion 12
(S a a Co p, College S a ion, TX, USA).
RESULTS
Li e a u e sea ch and s udy cha ac e is ics
We iden i ied 1567 s udies in ou sea ch (Figu e 1). Twen y- h ee s udies wi h a o al popula ion
o 155772 pa ien s me ou inclusion c i e ia (Table 1 and Figu e 2). Fou s udies we e no
conside ed eligible o his me a-analysis because hey did no use any speci ic cu -o alue o
blood eosinophil coun .9,24,26,27 One o he ou s udies measu ed he associa ion using pe cen age
o blood eosinophils ins ead o coun s,9 and 3 o he s udies p o ided con inuous e ec
measu es.24,26,27
We me ged da a om di e en s udies ca ied ou in he same popula ion as explained in
eAppendix 2.
We classi ied one coho s udy as c oss-sec ional gi en ha he blood eosinophil es was
pe o med a admission o he hospi al, and hence no ollow-up s age was ca ied ou .20
16
Addi ional analyses o ou da a ha e shown ha misclassi ica ion o he ou come due o sel -
asce ainmen o as hma exace ba ion and misclassi ica ion o blood eosinophil coun a e
unlikely o explain ou esul s (da a no shown).
We also ound a la ge amoun o he e ogenei y be ween s udies ha emained p esen in many
subg oup analyses. This he e ogenei y was o a ce ain poin expec ed, due o he wide ange o
cu -o limi s and he di e ences in he de ini ions o as hma wo sening used in he s udies. We,
he e o e, based ou in e p e a ion on andom e ec s es ima es as ecommended.58,59 Me a-
analysis expe s emphasize ha no deg ee o he e ogenei y can be deemed unaccep able,
p o ided he eligibili y c i e ia a e clea and he da a a e co ec ,58 and ha he e ogenei y in me a-
analysis, due o he di e ences in me hods and popula ions, should be iewed as he
“expec a ion, a he han he excep ion”.60
Finally, due o he lack o da a, i was no possible o assess whe he he inc ease in he odds o
as hma exace ba ion was associa ed in a dose- esponse ashion o he inc ease in he coun o
blood eosinophils.
As hma is a equen li e-long in lamma o y diso de ha causes a global subs an ial bu den o
disease. Eosinophilic in lamma ion in as hma pa ien s is a well-cha ac e ized ea u e o he
disease. We showed ha he occu ence o as hma exace ba ion is ela ed o inc eased le els o
blood eosinophils, a modi iable exposu e ac o . Fu u e esea ch is needed o in es iga e his
associa ion in unde s udied ulne able popula ions including elde ly pa ien s. The indings o his
me a-analysis could p o e use ul in he managemen o as hma.
17
DATA AVAILABILITY
The da a ha suppo he indings o his s udy a e openly a ailable in “FigSha e” a :
h ps:// igsha e.com/s/e7c1358ae298d033 a91
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32
Table 2. Pooled OR and 95% CI o inc eased blood eosinophil coun and as hma exace ba ion
Numbe
o s udies
OR (95% CI)
Fixed e ec s
OR (95% CI)
Random e ec s
Ri‡
Q es
p- alue
All s udies
22†
1.39 (1.35, 1.44)
1.31 (1.16, 1.49)
0.90
<0.0001
S udy design
Coho
15
1.40 (1.36, 1.45)
1.30 (1.13, 1.49)
0.92
<0.0001
C oss-Sec ional
6
1.31 (1.13, 1.51)
1.27 (0.94, 1.72)
0.73
0.003
Coho s udy ype
P ospec i e
7
1.42 (1.37, 1.46)
1.35 (1.17, 1.56)
0.92
<0.0001
Re ospec i e
8
1.26 (1.13, 1.41)
1.29 (0.95, 1.76)
0.86
<0.0001
Age ca ego y
Only child en
4
1.38 (1.22, 1.56)
1.38 (1.22, 1.56)
0.00
0.64
Exace ba ion
asce ainmen
Medical Reco d
18
1.40 (1.36, 1.44)
1.30 (1.13, 1.50)
0.93
<0.0001
Sel -Repo ing
4
1.40 (1.17, 1.67)
1.40 (1.17, 1.67)
0.00
0.42
Adjus men o ICS
ea men
No adjus ed o ICS o
unspeci ied
7
1.08 (0.94, 1.24)
1.13 (0.73, 1.74)
0.90
<0.0001
Adjus ed o ICS
15
1.42 (1.38, 1.46)
1.42 (1.28, 1.56)
0.79
0.001
Quali y Sco e
< 4 poin
11
1.39 (1.35, 1.44)
1.21 (0.93, 1.59)
0.98
<0.0001
≥ 4 poin s
11
1.44 (1.33, 1.55)
1.44 (1.33, 1.55)
0.00
0.86
Geog aphical loca ion
Eu ope
12
1.39 (1.35, 1.44)
1.19 (0.95, 1.50)
0.97
<0.0001
No h Ame ica
7
1.43 (1.31, 1.57)
1.43 (1.31, 1.57)
0.00
0.54
Asia
3
1.67 (1.34, 2.08)
1.67 (1.34, 2.08)
0.00
0.70
Blood eosinophils cu -o
limi
150
4
1.21 (1.08, 1.34)
1.16 (0.77, 1.74)
0.93
<0.0001
200
5
1.16 (1.11, 1.22)
1.22 (1.02, 1.46)
0.92
<0.0001
250
3
1.24 (1.18, 1.29)
1.42 (1.09, 1.83)
0.95
0.005
300
11
1.29 (1.24, 1.35)
1.23 (1.08, 1.41)
0.83
<0.0001
350
2
1.34 (1.28, 1.41)
1.34 (1.28, 1.41)
0.00
0.56
400
12
1.41 (1.34, 1.48)
1.41 (1.23, 1.62)
0.78
<0.0001
>400
3
1.54 (1.46, 1.61)
1.54 (1.46, 1.61)
0.00
0.70
De ini ion o as hma
exace ba ion
As hma ela ed
hospi aliza ion
8
0.99 (0.86, 1.15)
1.40 (0.82, 2.40)
0.92
<0.0001
As hma ela ed eme gency
oom isi
3
1.63 (1.29, 2.07)
1.63 (1.29, 2.07)
0.00
0.58
As hma ela ed ou pa ien
acu e isi s
2
1.46 (1.25, 1.70)
1.25 (0.71, 2.20)
0.90
0.14
F equency o as hma
a ack
F equen (≥2)
5
1.47 (1.38, 1.56)
1.28 (0.94, 1.74)
0.92
0.05
Less equen
4
1.04 (0.90, 1.20)
0.95 (0.70, 1.29)
0.71
0.04
†: The o al numbe o s udies is 22, as 2 coho s udies we e analyzed oge he (e-Appendix 2).
‡: P opo ion o o al a iance due o be ween-s udy a iance
33
Figu e Legends
Figu e 1. Flow diag am o s udies՚ localiza ion and selec ion
Figu e 2. S udy-speci ic and pooled Odds Ra ios o blood eosinophil coun and as hma
exace ba ion
Figu e 3. Funnel plo o Odds Ra ios o blood eosinophil coun and as hma exace ba ion
34
Appendices
e-Appendix 1: Quali y Assessmen o included s udies
We assessed he ollowing aspec s ha we e common be ween he h ee s udy designs: 1) i he me hod used o
coun blood eosinophils was desc ibed (1 poin ), else (0 poin ); 2) i as hma exace ba ion was de e mined based
on medical eco ds (1 poin ), else (0 poin ).
Fo coho s udies we also de e mined: 1) i he exposed coho was ep esen a i e o he popula ion (1 poin ),
else (0 poin ); 2) i non-exposed pa ien s we e ec ui ed om he same popula ion as he exposed pa ien s (1
poin ), else (0 poin ); 3) i included pa ien s we e ee om as hma exace ba ion e en s when ec ui ed (1 poin ),
else (0 poin ); 4) i he measu e o e ec was adjus ed o sex, age, weigh , as hma ea men and smoking habi s
(1 poin ), else (0 poin ); 5) i pa ien s we e ollowed up o a minimum o 1 yea (1poin ), else (0 poin ); 6) i he
p opo ion o pa ien s who le he s udy o we e los o ollow up was ≤ 20% (1 poin ), else (0 poin ).
Fo case-con ol s udies, we de e mined: 1) i cases we e ep esen a i e o pa ien s wi h as hma exace ba ion in
he popula ion (1 poin ), else (0 poin ); 2) i con ols we e selec ed om he same popula ion as he cases (1
poin ), else (0 poin ); 3) i blood eosinophil coun in con ols was asce ained using he same me hod as ha
applied o cases (1 poin ), else (0 poin ); 4) i pa icipa ion a e was ≥ 80% (1 poin ), else (0 poin ).
Fo c oss-sec ional s udies we checked: 1) i he sample was ep esen a i e o he whole popula ion (1 poin ),
else (0 poin ); 2) i he esponse a e was epo ed (1 poin ), else (0 poin ); 3) i he s a is ical analysis was well
desc ibed and app op ia e (1 poin ), else (0 poin ); 4) i he sample size was jus i ied (1 poin ), else (0 poin ).
The compa abili y in case-con ol and c oss-sec ional s udies was a ed as ollows: 1) i he measu emen o
e ec was adjus ed o as hma ea men (1 poin ), else (0 poin ); 2) i he measu emen o e ec was adjus ed
o sex, age, weigh , and smoking habi s (1 poin ), else (0 poin ).
When de ails on a speci ic i em we e no p o ided, we g aded his i em wi h 0 poin .
Finally, we summed he poin s ac oss he i ems in o de o ob ain a global quali y sco e o a maximum 8 poin s.
e-Appendix 2: Fu he de ails on di e en publica ions using he same popula ion
Two di e en publica ions using he same popula ion we e conside ed o ou me a-analysis as hey measu ed a
di e en ou come. The i s publica ion measu ed he isk o “any as hma exace ba ion” while he second
assessed he isk o “ equen as hma exace ba ion”.1,2 The esul s o hese s udies we e ne e pooled in he same
g oup. We used he i s one o he o e all pooled es ima ion and all he subg oup analyses,1 excep o he
subg oup “F equency o as hma a acks” in which we used he second publica ion in he ca ego y “ equen ” (≥ 2
a acks).2 A hi d publica ion by he same g oup was included in his me a-analysis a e con i ming wi h he
au ho ha he e was no o e lap be ween he popula ion o his s udy,3 and ha o he p e ious wo s udies.1,2
O he 3 s udies, published by he same i s au ho (Zeige RS), we e un ela ed and encompassed di e en
popula ions.4-6 One o hese s udies in ol ed adul pa ien s ec ui ed be ween 2009 and 2010,4 whe eas he
second publica ion included pa ien s ≥ 12 yea s o age a e 2012.5 The hi d s udy included a popula ion o
child en aged 5 o 11 yea s old.6
Online-Only Re e ences
1. P ice DB, Rigazio A, Campbell JD, Bleecke ER, Co igan CJ, Thomas M, e al. Blood eosinophil
coun and p ospec i e annual as hma disease bu den: a UK coho s udy. Lance Respi Med.
2015;3(11):849-858. doi: 10.1016/S2213-2600(15)00367-7
2. P ice D, Wilson AM, Chisholm A, Rigazio A, Bu den A, Thomas A, e al. P edic ing equen as hma
exace ba ions using blood eosinophil coun and o he pa ien da a ou inely a ailable in clinical
p ac ice. J As hma Alle gy. 2016;9:1-12. doi: 10.2147/JAA.S97973
3. P ice DB, Bosnic-An ice ich S, Pa o d ID, Roche N, Halpin DMG, Bje me L, e al. Associa ion o
ele a ed ac ional exhaled ni ic oxide concen a ion and blood eosinophil coun wi h se e e as hma
exace ba ions. Clin T ansl Alle gy. 2019;9:41. doi: 10.1186/s13601-019-0282-7
4. Zeige RS, Scha z M, Li Q, Chen W, Kha y DB, Gossage D, e al. High blood eosinophil coun is a
isk ac o o u u e as hma exace ba ions in adul pe sis en as hma. J Alle gy Clin Immunol P ac .
2014;2(6):741-750. doi: 10.1016/j.jaip.2014.06.005
5. Zeige RS, Scha z M, Dalal AA, Chen W, Sadiko a E, Su uki RY, e al. Blood eosinophil coun and
ou comes in se e e uncon olled as hma: a p ospec i e s udy. J Alle gy Clin Immunol P ac .
2017;5(1):144-153:e8. doi: 10.1016/j.jaip.2016.07.015
6. Zeige RS, Scha z M, Li Q, Chen W, Kha y DB, Gossage D, T an TN. The associa ion o blood
eosinophil coun s o u u e as hma exace ba ions in child en wi h pe sis en as hma. J Alle gy Clin
Immunol P ac . 2015; 3(2):283-287. doi: 10.1016/j.jaip.2014.10.009
.
Reco ds iden i ied h ough da abase
sea ching (n = 1567)
EMBASE: 492
Medline: 695
WOS P oceedings: 293
WHO da abases: 70
OATD: 17
Sc eening
Included
Eligibili y
Iden i ica ion
Addi ional eco ds iden i ied h ough
o he sou ces
(n = 75)
Reco ds a e duplica es emo ed
(n = 1132)
Reco ds sc eened
(n = 1132)
Reco ds excluded
(n = 995)
Full- ex a icles assessed o
eligibili y
(n = 137)
S udies included in
quali a i e syn hesis
(n = 23)
S udies included in
quan i a i e syn hesis
(me a-analysis)
(n = 23)
Full- ex a icles excluded, wi h
easons
(n = 114)
Do no measu e he di ec
associa ion be ween blood
eosinophils coun and as hma
exace ba ion (41)
Insu icien da a o he me a-
analysis (49)
OR canno be calcula ed om
dicho omous a iables (4)
Duplica ed da a abou he same
popula ion (1)
Con e ence p oceedings ha we e
published la e as ull ex a icles
(13)
Re iew a icles (6)
O e all
Zeige e al, 2015
Sohn e al, 2020
Mogensen e al, 2018
Nagasaki e al, 2019
T an e al, 2014
Malino schi e al, 2016
Vel ho e e al, 2009
P ice e al, 2015 & 2016
Shah e al, 2019
Pola-Bibian e al, 2017
P ice e al, 2019
Yii e al, 2019
Zeige e al, 2017
Casciano e al, 2016
Tu ne e al, 2018
Ke kho e al, 2018
Vedel-K ogh e al, 2017
Zeige e al, 2014
Gonzalez-Ba cala e al, 2018
S udy
Wes e ho e al, 2016
Belda e al, 2001
Hakansson e al, 2019
1.31 (1.16, 1.49)
1.40 (1.02, 1.94)
OR (95% CI)
1.69 (1.29, 2.20)
1.56 (1.15, 2.01)
1.25 (0.58, 2.67)
1.23 (0.92, 1.64)
1.25 (0.76, 2.07)
15.30 (3.90, 60.00)
1.42 (1.36, 1.47)
1.52 (1.30, 1.77)
0.46 (0.33, 0.64)
1.53 (1.09, 2.15)
1.80 (1.10, 2.90)
1.40 (1.02, 1.90)
3.06 (1.14, 8.22)
1.46 (1.20, 1.78)
1.49 (1.04, 2.13)
1.37 (1.18, 1.60)
1.31 (1.07, 1.60)
0.59 (0.37, 0.92)
2.94 (1.10, 8.10)
4.50 (1.80, 38.00)
0.64 (0.50, 0.90)
100.00
5.20
Weigh
5.79
5.66
2.06
5.55
3.54
0.79
7.69
6.96
5.10
5.01
3.67
5.31
1.38
6.54
4.82
6.98
6.50
3.93
1.35
0.64
5.50
1.31 (1.16, 1.49)
1.40 (1.02, 1.94)
OR (95% CI)
1.69 (1.29, 2.20)
1.56 (1.15, 2.01)
1.25 (0.58, 2.67)
1.23 (0.92, 1.64)
1.25 (0.76, 2.07)
15.30 (3.90, 60.00)
1.42 (1.36, 1.47)
1.52 (1.30, 1.77)
0.46 (0.33, 0.64)
1.53 (1.09, 2.15)
1.80 (1.10, 2.90)
1.40 (1.02, 1.90)
3.06 (1.14, 8.22)
1.46 (1.20, 1.78)
1.49 (1.04, 2.13)
1.37 (1.18, 1.60)
1.31 (1.07, 1.60)
0.59 (0.37, 0.92)
2.94 (1.10, 8.10)
4.50 (1.80, 38.00)
0.64 (0.50, 0.90)
100.00
5.20
Weigh
5.79
5.66
2.06
5.55
3.54
0.79
7.69
6.96
5.10
5.01
3.67
5.31
1.38
6.54
4.82
6.98
6.50
3.93
1.35
0.64
5.50
Fa o lowe odds Fa o highe odds
1.0167 1 60
OR (95%CI)
