Allergy Clin Immun Int 18_1_2006 (1)

ReseorchTrends
EncosingStudyin
Mite-ollergic Potients
One-Yeor,Double-blind,Plocebo
ond Environmenf-conlrolled
Investigotion
by RandolfBrehler & Frans Kniest
t s d . l s , ! x , . / : T h e r e d u c r b no l h o u s . d u s tm i l c ( H l ) N l ) a l l e r
g e | e x p o s u r ci s c s h b l i s h c di n t b c m x n r g e D r e notf H I ) \ 1 a l (
\. r..i fHt'\lt- \c
. b r, . .
n o l w e l l d o c u n c n l c dT. h e f t r r p o s co f t h i s ! l u d ! l v a sr o e v a l u a t e t l r ee f l j c a c ) o l e r ) c a s m D
g u t t r c s s c st .i l l ( ^ ! s . r n d d u v e t s
o f b l a n k e t sa s a s i n g l em e . r s u r ca g r i n s Ln i l c ! l l c r g y s ) . r t )
,l'l.|io*: hr thii onc ycar. phcebo coflrolled. double-blird
studr-.milc rllcrgic \,olu.reefs encasedbedding rn allcrgcD
nnpcnnc{bl. or peDne.rblecoveN.The selerlry ol clinrcrl al
lcrgy syntknns wls mcasured D tef.rs ofa daily slmploln
s c o r ea l l h e b c g i n D i n g
r D . l a tt h c . r d o l l h e n i a l \ V ea l s ox n a l y z e d o m l n g p e r h l l d ! \ r l u c s a . d . o s i n o f h l l c r t l o n i cp r o l e i n ( E C P Il e l e l s .
l . s r / / f r A c l i n i c a lb e r e l i l $ , a sd o c u n e l l . c ll i ) r a l l ! o l u . t c c r s
n s r . ga l l e l g e r - i m p e r o r e a cb ol e\ c r s .x D dl i r I o f I I v o h n t e c r s
u s i n gp e r m e a b l pe l a c e b oc o r e r sT. h c r . $ ? s a s r N ( i s t i c r l sl vi g
nificr.t dccreasein the scofeolrhe slmplom lord only in lhc
g r o u p 0 1 \ o l u n t c c b u s i n gl h e i n r f e r n e a b l ec o v e r . S i g n i l i c a n l c l l c c l so n m o m i n g p c a kf l o s r n d E ( P ! a l L r e s$ e r e n o l
t o. l . . r),
.
,J 1. ..i ,r. c.r reduce allelgy s)ffplonrs in nitc all.rgic prlients l-bf soDe palienis rhis can be rn adcquatclhcrapl o. its ow. We thereforc
f e c o n r n e n dl h e j n s r r l l a l i o |o l c c a s . n c n ( sr s r f i r s t s t c f i n
t h c m a n a g . m e . to f m i t e a l l e f g y
lntroduction
Housc dusl mite (HDM) alLergenshave been proven 1(]be
the most impo.tiDt indoor allergens.High nite allergenlevels
are a risk I'aclor for thc dcvelopment of alleryic fhinitis and
aslhma.A dose-responsc
rclationshipbetveenthe concentration
of ni|e allergensin housedusi and the dsk ofsensitization has
becn rcportcdand the thresholdconcentrationhasbe€nestilnal'
cd to bc > 2pg of the allergerof Dernatophuqoi.lesptetury,ssi
,m (Der p l)/g dust ll. Exposufe to low allergen concentrations over longer pcriods may also induce mite allergy in
susceptibleindividuals [2] Der p I conccntr.ttionshigher than
l0 Jrg/gdust can causeacule asthna synptoms in previously
patients[1].
mrte-sensrtized
Thc rcductioDof mite allergenexposureis thereforeof rlnporlance1opreventthc dcvclopmentof mite allergy and to control allergy synptoms in palientswho arc xheady sensitiTedto
mites. Encasing bedding in allergen-lmpermcablccoveN has
been shown 1o be consistentlyefiective in reducing mile aller
gen lelels, but the control of allergy symptons by these mea
sufesis still controv€rsial[3 12]. The prrpose ofour one-year
randomized,double-blin4 placeboconholled study was to examine the clinical effect of allergen impcrmeable but vapor,
penneablecovers (Allergocovera)1br natlresscs.pilbws, and
duvetson mite allergy symptoms.
,(r,_rwr?^:housc dusLmilc. allcrgy. piu,cntio. .reasures,elr..1lltts\ ( lut hnniobl Int
.l lfb ttAllttgt Ot.qat)|tj:
1 8 1 1 51 9
Nlaterial and Nlethods
,{ller rpprovalofou. studyprotocolby the ErhjcsCommiitcc ofthe Universityof MuenstetGermany,
a tolal of 32 nrirc
O 2006Hogrefe& rlube.tublishcN
D O r :1 0 . r 0 2 7 , 0 8r3982 5 . 1 E . 1 . 1 5
A ers: Cln1hn"turollht Jwon.lAlleryrOry, |8l (20t)6)
l5
ReseorchTrends
l6
allerSicindividualscnteredthesrudy(l I femalesand2l males. velopingsevereasthoaduringthe study periodand in such
rge | 2 /'8 )ears.nrcJnl-.2 )cxrsr.l he\.lunreer:$ererecrurt- casesthestudyrvasto endforthesepaii€nts.
ed throughannounccmenls
in thc localncwspapers.
At the end oflhe siudy after 12 months,patientsagrin
Inclusioncrilcriafor rhc12 \'oluntccrs
were:
recordedtheir symptoms,morning pcak flow. and medicarion in dflly logso\cr d r\ro $eek p(riod Pa(icnls
$eree).. Positiveskin prick tests (SPT) with housedust mite
anined clinically, l ng tunction lests were performed,and
(HDM) extracts.
bloodsampleswerctakento analyzecosinophilcationicpro. SpecificIgE antibodies
to HDM.
tein(ECP).
. A historyofrhinoconjunctivilis
dueto HDM allergyEncasings
Enteringlhe studytheydid not have:
.
.
.
.
In theactivegroup,mattresses,
pillows,andduvetsor blankcts werecoveredwith Allergocover"(Allergophannai,ReinClinicallyrelevantsensitizations
to oth€rindoorallergens bek, Gennany),a tightly woven mitc allergen-imp€rmeablc
Asthmathatrequiredcontinuous
therapy
polyeslermembrane
pcrmeableto air and vater vapor.ln th€
Therapywith syst€miccorticostcroids
or immunosuppres- controlgrcup.volunlecrs
usedplacebocoversofloosclywoven
cottonproduccdby lhc samecompany.Volunteers
had to use
Specificimmunorherapy
{SlTr dunngIhe prc!iou.rwo
normalsheelson thelop ofthe encasings
for mattresses,
duvets.
years.
andpillowsandwereinslructednol to washihe encasings
duF
ing thestudyperiod.
(lolleclion
andAnalrsis
of DustSampl€s
Slud] l)csign
The srudyvas pcrformedin a randomiTedplacebo-conMatlrcssdustwascollectedby oncofthe investigaton
using
trollcd. doubleblind, parallel-groupdesign-For all volun- a vacuumcleaner(KArcher
260| plus.I200Wau)wnh a spccial
teers.the sludystancdin December1999andendedafteronc filter dcvice(ALK, Copcnhagen,
Denmark).
Thc dus.wascollecledby vacuumingI nr:ofthe matlress
surfacefor4 nin. Additionnlly,dustsanpleswcrecollectcdfrom carpetsanduphol,
After the screeningprocedrre(clinical evaluation.skin steredfurniturein thebedroomsTheguanineconcentralion
was
tests,lung functionlcsts.and analysisof rnite-specificim- analyzedin the dust samplcsusingthc Acarex-Tcst-,
(AllcrmunoglobulinE (l8E) antibodies)
volunteers
rccordeda clini- gopharma.
Rejnbek,Gcrmany);
test.esullswererecordedsemical symptomscorein a dailylog lbr l4 days.Thcynotedmorn- quantitalively
in 3 classes.
ing pcak flow valuesand antiallcrgicdrug medicationand
scorcdnosesymptoms(nasaldischarge,nasalirching,nasal
obstruction),eye symptoms(ilchin8,runningeyes,redness), Skin lcsts
lung symp|ons(cough.wheezing.dyspnoca)and skin symptoms(itching,cxudalion.eczema)itheseitemswercscoredon
Skir prick testswereperfomedon thevolarlbrcarmswith
a four-pointscalcwith a scoreof 0 denotingno symptomsat cxtracts liom Dernabphagoides pten'nyssinus, D. farinae,
all and a scoreof I denotingvery scrioussymptoms.During birch pollcn,grassand herbalpollenmixcs.cat dander,C/athis 1ime,we visitcdthe homesofthc volunteenandcollected dospotiunt.andAltenlaia (Allcrgophanm.Reinbek.Germany
housedustsamplesfrom mattresscs,
carpets,andupholstered / ALK, Copenhagen.
Dennark).Whealdiametersweremeaturniturein the bedrooms.
At thc screening
visit, we recorded sured20 min after skin puncturing.Wheal diamcters3 mm
the dimensions
pillows.andduvetsor blank€ls. gr€aterthanthe negativecontrolwereconsid€red
of ma(rcsses,
to be posiand senta lisl of the meas$emenls
(Allerto Allergopharma
gopharmaJoachimGanzerKC. Reirbck.Germany).
wherethe
voluntecrs
wererandomized
to receivecitheraclivcor placcbo
encasings.
Subsequcntly,
aflcr the basclineperiod the covcrs
pilbws, andduvetsor blanletswcrehandcdout
formallresses,
in numberedpackages.
The voluntcerswere rcsponsiblefor
Allergcn-specificI8E antibodies(grass,tree, and herb
puttingthecoverson theirbcdding.
Thcy$ereinstructed
not to pollenmixcs.D. pterony.\\inuslhrinac.
moulds,and cat danchangenoorsurlhccs,
carpets.
andupholstered
lirrDitureduring der) were nnalyzedby the CAP-FEIA method(Plrannacia,
Freiburg,Germany).Valucsabove0.35 ku/l werc considered
At 3, 6. and9 months,patientswerere exanincdandinterviewedaboutasthmasymptoms.
Thestudyprotocolprescribcd
ECPwasaflalyzedin scrumsamples
takenin vacuunrconthattherandomizalion
codewasto bebrokenfor volunteers
dc- taincrs(tsD VicutainerSSTrMplus, BD Vaculainersystems,
A eryrCliltltuntubth
Jtvotld,llk!.t Ory.I8/l t2006)
ReseorchTrends
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'IAor-E
I
, NrrHornrs,\ND
S E M r - e u A N r r r , \ ' r 'G
r vtrr ^ N I N EC o N o i N l R A r t o N
A ( i r , . T r r \ L S E R U NI ci E . I I r f r n \ p c rr r r . I G F A
(Br,rwrriNCr.\ssrisorol)rxrrrri\'l^lrREssEsoFVorrJNtr:riRsrNIHEAcrlvE,\NDPIAcFBoGRouPs,\rrHtrBEarN
o r r f l r ;i l L l ) f
lgE (kU/l)anlibodies
ro
Specifrc
Age (years)
Guaninclass
Group
lgE(ku/l)
24
26
32
32
32
36
,13
62
68
t2
29
33
35
39
50
5l
51
65
80.8
39.1
ll.9
42.1
13.4
110.0
143.0
36.4
26.9
39.4
38.6
165.0
60.7
321.0
I t0.0
25.0
20.0
24.0
193.0
ll5.{J
53.1
3.7
3.5
14.0
l t.l
9.1
'7.3
2.1
15.1
5.5
3.21
1.5
5.1
5.9
q6.3
2.4
14.7
6.2
2.5
2.2
3.5
7.3
> t00.0
I5.0
78.5
70.2
1.4
3.8
t.0
15.4
63.6
75.5
l.l
3.4
0.6
11.2
'7.4
| 1.2
12.7
Plynoutfi. UK). Blood samplesncrc ccntrifuged exaclly I h
after being takcn. Sera$ere frozcn al -70 "C until anaiyzedlbr
ECP !ith the DPC hnnunolile-syslcnr (DPC. tsad Nauheiln,
ccmrny).
9.2
2.5
I
3
2
I
2
3
I
3
I
I
I
I
1.5
2.5
2.5
3
3
3
Resulls
Out of 16 volunteersin each of thc rctive and placebo
gfoups.I I in eachgroupcompleted
rhc study.Thoselostfron
whomo!€d 2 pati€nts
ex€luded
due
thestudy$€re4 vohrntccrs
O u t c o m eP a r r m c t e r !
ro theuseofnelvmalrrcsscs
andbeddings
duringthestudyperifordle mallress,
anothThe prnnrry outcomeparamelerin this study $zs the effecl 04 I patienhvhouscdonlytheencasing
for only partofthe wholesrudypener $'housedtheencasrrgs
ofthc cndsing on the symptom load dclrred $ thc sum ofthc
fie clinicalsynrptonsinsufficiently
od I patieniwho recorded
scoreslbr nosc.cyc. lung, and skin synlplons and the usc ofanperiods,and I palicnlwho withdrewinliallergic drugs SccoDdaryoulcome prtameterswere changcs du ng the obseNation
a significantmould
1i,medconsent.Onevolunteerdeveloped
i n r h em o r n r n gt ( l l f l , ' q ! u l r e . J n J l - ( | l e \ e l .
allcrgydiagnosedI monlhsafter enteringthc study.Moulds
\€re presentin the roomwherethc palicnlslept-A continuous
asthmatherapywasinitiatedbcforcthc srudyend€d.Therefore
Dataanrllsis
{€ p.esenttheresuhsof2l volunleers
complclingthe study.
Statislical analyscs{ere pe.fornred wilh SPSS I1.0 slandard lersion. The Mann'Whihcy-lj-tcsl was usedto test difteF
ences between the aclive and fhccbo groups. We estimated
the effeclivenessof the co!crs $,ithin lhe groups by meansol
the wilcoxon rank rcst. P values < 0.05 were conslderedsignificant.
Therewcrcno significantditrerences
belweenthetwo study
groupsat the bcginnrDg
of the studywidr regardto age,sex,
rhinoconjunctivitis,
Asthmasymptomand medicationscorcs,
lvholcserumIgll rnd mile-sp€cificIgE antibodylevcls.or alandbedroomcarpclsandsanitation
lcrgcnicloadofnraltrcsses
1 e'At (-|tu ltururolh
J lli'dl All.tlt
Ory. l\ll
Q006)
ResearchTrends
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(.|\|(\ll:r||(\l'Nl||r'A|jl-lt(ilN'rNP||\||\Bl|.lr\i\|.CRotjPl\N|,\1llLAIIlI)r\(j'll()(iR(U|]
(i^ rR\ \r B\sr \r \\r,,\r. k rrNl0\rH\
Acti\c grcup
B.tsclnrescoro l2 'nonlh scorc
:1.2+ 3.8
2 . 1 9+ 1 . 8
Srmptomload
Elc slrrrproms
, 2.u
1.8.1
I 1.4)
0.7.1
-il:r+ 100
l i . 9r u . l
Af(tsrllcrgic
drugusc
(tg l)
F,CP
0 . 2+ 0 3
1 . 0L 2 I
0 . t 9E 0 . 1
519I 9:l
15.1:7l
B a s e l r n sc c o r e
0.005
0.07'l
0.0i6
0.018
0.09r
0..199
6.62+ 3.5
+ l.l
2..16
0 . 8 8, l . l
l.2l:1.0
r . 5 5= t . 8
0.5t+06
t 5 . 8 +t 2 . - 1
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l2inonth scofc
6.54+3.9
2..10+ I l
0.95+ t.:l
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[.929
0.505
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16.5
l h c { } n r f t o n rl o a d i s l l c s u n ro f n o s e .c } c . i L r n gs. k i n s y n r o r n sr D d d n t i a l l c r ! i cd r u gu s e .N l e n s c o r e s+ S D r r c g i v e n .
n r e a s u r cu\ l e d p r i o . r ( )t h c r r x o l t h . n u ( l ! ( \ . . T r b l e
I).
dings are ihc nNsr inportrnl rcscr\oirs ofhouse dun nit.t and
t h e i r r l l c r s c n s .r h h o u g ho r h c rr c \ r i l c o b i e c r \l i k c l i \ n r g r o o n r
, ^ n r l r s i so l r h cd r i l y l o l s l l o m d r c b c r i D r i n gr n d t h e c r ) d , ) l ' t i ' r n i l u r cl l . 1 l .$ l i s l l . 1 l ., u r l l i \ i n g r o o n rc r r p c l sl l 5 l c d nf o m r
t h c ( l | d y $ r o $ e dl h r Ll h c r r $ u s a s t a t i s t i c r l lhy i g h l ys g f i l r e l I l
n r a l nl b c i o i l l l ) N I ; r l e s t a t i o ni n h o n c s . 1 no u r s r u c l yt .h c n r a t
decNrsr r. sr"rrplornLoir(lliorlr 7.8.1lo -l.l (/, 0.i)0j) in rhc Iet r e s s e so J . r L l! o l u n r e e r s$ c r c H I I M - i n l i s t c d x n d 5 0 9 / "\ ' c f c
t i \ e g r ) L L pA d e c r e a sieI r h c t l e b o g r o u n l l u n 6 . 6 2r o ( ' . 5 1 h i g h l y i n l c s l c d( ' l 0 r r g s g u a n i r e ) .O f t h c d o s rs n m p l e sc o l
\r\ nor significanr Thc nr.irDsl'Inpto]nlortls lirr thc mdn i(lurl
l.ct.d l_r'orrnon bcdding ircn)s {rch as lirrnirrr,i. carpets..tc.
( . ! e n l ) d n r d c do \ e r t h e 1 $ o \ o l u n r e e rg r o u p s ) 5
orgnnsrnd lhe seco|drn .rd poinls ol rhc nud\ arc gi\!n in
. 9'd !ho$cd r
l i b l c : . . ^ n r l ) s i s o l t h c l r l d N i d u a lc o n r l o r c n r so f t h e s c o r f s i g r i f i c a n ll l l ) N 1a l l e r g c nl o r ( 1 .I h e e r c c p l i o n r li n r p o r l r D c oc f
sh$\c(lr sigrificinl ctccfclseonl)- lbr thc nrcanclc (/) 0.0-16) . r i t e a l l c r g c r rlsn b e d d l n gc r n b c c r p l a i l c d b y t h c l N c tr h a ln r i t c
x n d l u r g s y n r p t o r n(s1 , 0 0 2 8 ) o l t h . ! o l | l r e c r sr n t h e ! r r \ o rllergensbclo.rc.rirbome oIlly lilef the dlstu rrnc. ol dust duc
1 l r ( \ r t A r c d u c e ds v n r t r o r nl o t l d$ a s d o c u n r c r l l .ldo . a l l p N t i c n r s . ' , J i ! , t , l
, r \ . , ' e r r h . \ l ( h L r . r l . .r . r L h r .
ofth. acti\e gr)up ln lhr fh.cbo qroup.lhc reoredecr.rscd li)r
- . '\ o l u r r e . A r d i n c r e r \ c ( l| ; r I ( s e eF r s u r cl l . \ l o r n u r g f . r k
h r l 0 { l l . r $ o ( l o c h r a r ef c \ i c $ j s e r e p u b l i s h c df o c L r s i nogn
f l o \ l n d I t I ' \ a ] L r e si n c f . r s ] r di r b o l h p r l i c n lg j . ( r u p s .
drffcrenl Lll)l\1 coDtrolnrers fcs rn the rninngcnlcnt olaslhmr
t
f : l l a n d p c f c f n i " f h n r i t i sl 4 l ( [ r e r o H D N L A s i s , r i i i c . r Di m
p r o ! e . r e n lo l . r s t h ' n as v l D p l o r n(s2 9 l r i a l s )o r I s i g i l i c r D t r c
d u c t i o no l d r i n i r i ss v n r p l o n r(s. 1 r f i a l s )d u c ( , l l l ) N I n \ o i d r n c c
nr.riur$ $rs nol rcpofted
l)isrus\ion
I D t \ o f c e e r r l l lt u b l i s h . ( l n u d i . s o n H I ) \ 4 . l l l c r g i c v o l L r r r r e e r sc n c r s l n gb c d d i n gi n i f r f c r n r c a b l ec o v c r s$ i l s n o l e f f e c l f o u f n i l o m i T e dt ). | r ! . b o c o n r r o i l c d
c l f i c r l s t u d yi n ( ) ! i . . l . I R ( . | , , f J . , , r . ,1 5 1 , , , l l e r s i .- | i r I . , .
pr.rr.
i n g \ o l U n t . . f \ $ i t h a l l c f g i c r i n o c o l r l u n c li li \i { d u er o I l D N , l. l
s lrL r d )b,) , f e r r e e h o r s r
1 6 l .I n r h e p L r e . b oc o n r r o l l c d| n r L h i c e n t e
l . . g \ . r l l f r r i . n t j h . d I c l i n i e r lb e n e f nl i o r r rr h c u s eo l . r 1 l . r s ! r r - i o d c o l l . r g u c s[ 6 ] . t h c u s eo l i D r p c r n r e a bcl eo \ c r s l i r b e d d i n s
n n p c r n r c x b l c o \ c r s l i r n n t t r c s s e sp- j l l ( ^ \ s . n d d u \ e l s . l h c
l e d t o a r c d u c l i o ni n r n i l c r l l c r s c n c \ p o s u r e .t r L uD c \ . r d r e l e s s
s ) n r p r u n k r a d .d e f n r c dN sr h e s u n ro f s y n r p r o Dl rn d m e d i c L r t i t ' r r n e i l h e rr r h l n l l i s - s p e c i l i cr i s u ! l - r n r l o g u c s . o r c n o r a d a i l y
s c o r c ss. h ( J r e dl r s L a n s l i c . l lsyr g D i l i c u td c c r c . r sA
c D . r l y z i nlgh c s , ! l n p l ( ) ns c o f c$ , e f ea l i c c t c d l r r o u r s L u d r w c L r s c d{ s i m i l a l
e l l i c r s o r l l h e b a ! \ o f s ) 1 1 n l o n rosf i n d l \ i d u l r l r g e to r g a n sr c - s c o r e 1 i ) r f r L r r r t L sSy l l 1 p t ( n r lrsc c o f t l c do n t t ( L r i l y b r s i s r n d
\crlc(l r rlgllilicanr dccrc.r\. onl) for tlre seof.i ofrhe c)c irnd l b u n d l h r l t h t s c o r es a s ' r o t l l l . c t . d s i ! n i I c n r r l l v .l n c o n l r n n
l u n s s \ n r o n r s l . l i n g a l l c r g . np e n D e a b lf(h c e b o c o \ r r s . r h c r o I \ ( . r , r l \ l \ T , l ( . 1 ! r . r . , ' ( l ' , , \ ' r r u c . r h ( r r . , i, . u r L ^ I r (
s \ m p r o n rk r u dd c c r . l s c di n I \ . l u n t e e f r n d i D c r c a s ei d
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