pm2013-618576
Post on 02-Apr-2018
215 Views
Preview:
TRANSCRIPT
-
7/27/2019 PM2013-618576
1/9
Hndaw Pblshn CopoatonPlmonay MdcnVolm 2013, Atcl ID 618576, 9 pashttp://dx.do.o/10.1155/2013/618576
Research ArticleComparison Study of Airway Reactivity Outcomes due toa Pharmacologic Challenge Test: Impulse Oscillometry versusLeast Mean Squared Analysis Techniques
Elena Rodriguez,1,2,3 Charrell M. Bullard,4 Milena H. Armani,1
Thomas L. Miller,5 and Thomas H. Shaffer1,2,5
1 Nemours Research Lung Center, Nemours/Alred I. duPont Hospital or Children, Wilmington, DE 19803, USA2 Nemours Biomedical Research, Nemours/Alred I. duPont Hospital or Children, Wilmington, DE 19803, USA3 Division o Clinical Pharmacology, Tomas Jeferson University, Philadelphia, PA 19107, USA4 Division o Neonatology, Tomas Jeferson University Hospital, Philadelphia, PA 19107, USA5 Department o Pediatrics, Tomas Jeferson University, Philadelphia, PA 19107, USA
Cospondnc shold b addssd to Elna Rodz; mod@nmos.o
Rcvd 31 Dcmb 2012; Rvsd 6 Mach 2013; Accptd 7 Mach 2013
Acadmc Edto: S. L. Johnston
Copyht 2013 Elna Rodz t al. Ts s an opn accss atcl dstbtd nd th Catv Commons AttbtonLcns, whch pmts nstctd s, dstbton, and podcton n any mdm, povdd th onal wok s poplyctd.
T tchnq o masn tansplmonay pss and spatoy afow wth manomty and pnmotachoaphy sn thlast man sqad analyss (LMS) has bn sd boadly n both pclncal and clncal sttns o th valaton o nonatal s-patoy ncton dn tdalvolm bathno lntss and away ctonal mchancal popts masmnts.Whasth tchnq o masn spatoy ncton sn th mpls oscllaton tchnq (IOS) nvolvs th assssmnt o th la-tonshp btwn pss andfow sn an mpls snalwth a an o qncs, qs lss coopatonand povds monomaton on total spatoy systm sstanc (chst wall, ln tss, and aways). T psnt stdy psnts a pclncalanmal stdy to dtmn whth ths spatoy ncton tchnqs (LMS and IOS) a compaabl n dtctn chans nspatoy sstanc dvd om a dct phamacolocal challn.
1. Introduction
T s o anmal modls o stdyn spatoy mchancs
nd away challn tsts has ld to a sddn ncaso nomaton adn th bhavo o th dnt aaso th spatoy systm. Dspt th la amont o -sach n th adlt and pdatc ops, w stll lack sn-cant knowld n th nonatal sbop. T psnt stdypsnts a pclncal anmal stdy to dtmn whthtwo spatoy ncton tchnqs a compaabl n d-tctn chans n spatoy sstanc dvd om a dctphamacolocal challn.
T tchnq o masn tansplmonay pssand spatoy afow wth sophaal manomty, awaymanomty, and pnmotachoaphy has bn pvoslydscbd [1]. ansplmonay pss dvd om
poxmal away psss and ntaplmonay sophaalpss dtctd om a wat-lld catht [2, 3] amasd by dntal pss tansdcs. T afow s
masd wth a low dad-spac volm pnmotachomtanda dntal psstansdc. T last man sqadanalyss (LMS) has bn sd boadly n both pclncal andclncal sttns o th valaton o nonatal ln nctondn tdal volm bathn [1, 4, 5].
T tchnq o masn spatoy ncton snocd oscllaton tchnq (FO), o mpls oscllomty,nvolvs th assssmnt o th latonshp btwn pssand fow sn a ocd/mpls snal composd wth aan o qncs. T spons to ths snal s calld thspatoy mpdanc, whch s th qncy-dpndnt -latonshp btwn tansspatoy pss and fow. Tmpdanc o th spatoy systm nclds th spatoy
http://dx.doi.org/10.1155/2013/618576http://dx.doi.org/10.1155/2013/618576 -
7/27/2019 PM2013-618576
2/9
-
7/27/2019 PM2013-618576
3/9
Plmonay Mdcn 3
montod and mantand at 37-38C on a adant wambd (Rsscta; Hll-Rom A-Shlds, Hatboo, PA, USA).Onc th physoloc stablty o th anmal was conmdby th analyss o th atal blood chmsty (Stat pol;Nova Bomdcal, Waltham, MA, USA), ECG, and bloodpss monton; th anmals spatoy masmnts
w codd as dscbd blow. Intavnos mdazolamwas sd as an anxolytc to as th wok o bathn. Fol-lown th complton o th potocol, anmals w tha-nzd wth pntobabtal (50 m/k) and satatd potassmchlod (2 mEq). All pocds o th anmal ppaatonw appovd by th Instttonal Anmal Ca and UsCommtt. Fnctonal spatoy paamts o ntstw codd a th anmal was stablzd. T plt thnwas connctd to th PEDS cct o basln mas-mnts. Immdatly ollown LMS basln assssmnt(ava o 5 mn), th plt wasconnctd to th IOS systmo basln oscllatoy masmnts, and tstn was p-omd as soon as th tansspatoy pss tnd to10cmH
2O as dscbd blow. Also, F 1 llstats th
tst paadm that was ollowd n od to compa s-patoy ncton assssmnt btwn th LMS and IOSmthods both bo and a phamacolocally ndcdaway constcton.
2.2. Respiratory Function Assessment-Least Mean SquaredAnalysis. Fo th convntonal tdal bathn sstancmasmnts, th E was connctd to th pnmota-chomt pot. A th-valv stopcock was sd to block thpss pot. T natv fow pot was manally occlddto pvnt fow atact snc th was no addtonal fow va
vntlato tbn. A wat-lld balloon was placd va th
moth nto th sophas to mas th ntathoacc ps-s dn spaton. Optmm placmnt o th balloonwas conmd by al-tm monton o pss tacns,sn cta o maxmm natv dfcton dn nsp-aton wth mnmm cadac atacts. Only spontanosbaths (at last 10 baths) w analyzd, and baths wthdstoton o th snal w xcldd om th ava data.
Plts w obsvd o 30 sconds on th cct. Rs-patoy volms w dtmnatd by lctonc ntatono fow snals, and th ollown paamts w calclatd:dynamc plmonay sstanc () n cmH
2O/L/s, spa-
toy at, tdal volm, and mnt vntlaton. Rsstancvals w codd whl postv pss was appld
to ndc opposton to fow and calclatd by last mansqad (LMS) alothms ncopoatd nto th comptsystm.
2.3. Respiratory Function Assessment-Impulse OscillometryAnalysis. T mpdanc o th total spatoy systm wasmasd sn a commcally avalabl IOS that has bndscbd pvosly. Dn tdal bathn thoh an E,an mpls nato dlvd b plss at ntvals o0.2 sc, spmposd on th spontanos bathn pattn.T dtalzd pss and fow snals w d nto th astFo tansomaton, wh 32 sampls w consdd.Fo xpmntal poposs, no systm cocton was sd.
Pharmacologic challenge
Baseline PFT
LMS IOSLMS IOS
Post PFT
1 mg/kg/hr
BL = 7 0 2Time (hr)
Pig preparation andstabilization period
(1 hr)
Bethanechol1 mg/kg twice
infusion
Test paradigm
Figure 1: A schmatc daam llstatn th cnt tst paa-dm. LMS, last man sqas; IOS, mpls oscllatoy systm;PF, plmonay ncton tstn; , nmb o anmals; BL, bas-ln; Post, a bthanchol admnstaton. m btwn th stand scond bthanchol doss was 10 mn.
Daly calbaton sn a calbaton pmp (3.0 0.01 L SD,Ja; Hochb, Gmany) and a nc mpdanc o10cmH
2O/L/s w pomd, and a maxmm o o 10%
was pmttd. Plts w connctd va E adapt to thpnmotach o thIOS, w tstd o 30 sconds on th c-ct wth a tansspatoy pss o 10 cmH
2O, and w
savd o lat valaton; poch o masmnts was ds-cadd th tm fow and pss pattn n th pmaydata tm and tm slts tnds showd ntpton o thoscllatoy snal, whch occd occasonally (appox-matly 1015%) n th cnt stdy. In th valaton phas,th mnmm tm pod o potn ths masmntswas 2 sconds. T mpdanc o th spatoy systm (s )and s n cmH2O/L/s w calclatd at 3, 5, 10, 15, 20, 25,and 35 Hz. Rplcat oscllatoy vals w pomd byJLAB 4.65.1.0 sowa (Ech Ja GmbH, Wzb, Gmany) and analyzd by JLAB 5.20.0.52 sowa (VIASYSHalthca GmbH, Hochb, Gmany). Snc paamtsw assssd wthn th sam plt ov tm/dlta chans,a cocton o th mpdanc o th E was not ndd.
Each plt povdd a matchd st o data om th Mas-tScn PF IOS (Ja, Hochb, Gmany) and thPEDS plmonay ncton nt (MAS, Hatld, PA) o th
oscllomty and LMS analyss, spctvly. Each plt wasmasd wth ach dvc nd two condtons: basln(p) and a ntvnton (post).
Follown basln mass,bthancholwas sd as thntvnton to phamacolocally ndc bonchoconstc-ton and sbsqnt lvatd away sstanc. Bthancholpowd (cabamyl--mthylcholn, Sma-Aldch) wasmxd wth saln (5 m o bthanchol : 1 mL o saln) andadmnstd as two ntavnos njctons at a dos o1 m/k o bthanchol chlod n 0.2 mL/k o saln st10 mn apat to achv an ncas n th spatoy ss-tanc. Dcay n th lvatd sstanc was compnsatd wthan nson o 1 m/k/h o bthanchol chlod statd
-
7/27/2019 PM2013-618576
4/9
4 Plmonay Mdcn
thoh th vnos ln ollown th ntal bols. Ts dos-n mn was adaptd om a pvosly dscbd pltpotocol [30]. o compa th two mthodolos dscbdhn, w w ntstd n stablshn a la an o pl-monay chans (basln to maxmm dos spons wth-ot vokn sncant cadovascla chans) nstad o a
standad dos spons assssmnt wth small plmonaychans.Bthanchol bols and mantnanc dos w vn as
dscbd abov. Plts w obsvd ntl stabl boncho-constcton was assmd (35 mn a th scond dos)whn sstanc ncasd at last 40% om basln. Post-ntvnton LMS masmnts w obtand, ollowd byIOS masmnts, to pvnt any navoabl ct omth mplss on LMS paamts. Paamts o ntstw docmntd o ach tchnq, ach tm n th samsqnc.
2.4. Statistics. Contnos vaabls w smmazd ov-
all by man and standad o o th man (SEM), nlssndcatd othws. All assmptons w tstd o nomal-ty; n th cas o volaton o any assmpton, nonpaamtctsts w pomd. T dlta chans w compad snpad -tst o th dpndnt contnos nomal vaablso Wlcoxon snd ank tst o th nonnomal dpndnt
vaabls, tstn o postv man o mdan dncs,spctvly. Sncanc was st at alpha lvl o 0.05 (1-sdd). A compaatv analyss o amnt btwn th twomthods was dtald o th phamacolocal challnsn th Bland-Altman plot analyss; th bas, o th avao th dncs, and th 95% lmts o amnt (LOA)w potd o all qncs alon wth th lna -
sson analyss (2
, slop, and vals). Statstcal analysswas don sn a combnaton o statstcal sowa packas(GaphPad Psm vson 5.02 o Wndows; GaphPad So-wa, San Do, CA, USA, and SPSS vson 19; IBM, Ch-cao, IL, USA).
3. Results
In ths anmal modl, masmnts o spatoy mchan-cs w possbl, and dtcton o an ncas n sstancwas achvd wth both systms a bthanchol admns-taton n svn o th plts. On anmal dd dn thpostbthanchol masmnts (post) sconday to ca-
dac ast. Follown ntavnos (IV) admnstaton obthanchol, a small bt statstcally sncant dcas wassn n hat at (man SD, 15112 vss 1336, 12%, = 0.03) and atal pss (man SD, 79 5 vss675, 15%, = 0.002) o th mann 7 plts; althohths chans w not physolocally lvant o hmody-namc nstablty, th w no sncant chans n sp-atoy at, tdal volm, and mnt vntlaton ollownbthanchol admnstaton.
Rspatoy mchancs masmnts showd a sn-cant ncas n dynamc plmonay sstanc masd byth LMS (+53%, = 0.003) ollown bthanchol admns-taton (F 2). Pss-volm loops also vd that,
whn compad wth basln, bthanchol admnstatonsltd n ncasd pss qmnts as wll as awdnn and dcas n th slop o th pss-volmloops.
Follown bthanchol admnstaton, a sncant ov-all ncas n th spatoy sstanc masd by IOS was
dmonstatd by postv chans n s om 10 to 25 Hz(+96%, = 0.018; F 3). Sncant ncass n spc-c spatoy sstancs w dmonstatd by postvchans n th ntmdat qncy spctm (qn-cs: s 10Hz [+106%, = 0.031], s 15Hz [+96%, = 0.013],s 20Hz [+95%, = 0.026], and s 25Hz [+85%, = 0.037]).No statstcally sncant dncs btwn th p-bthanchol (p) and postbthanchol (post) otcoms oany mann qncs w obsvd: s 3Hz (+67%, =0.131), s 5Hz (+67%, = 0.09), and s 35Hz (+95%, =0.084), and th sstanc spctm o s dmonstatdncasd postv qncy dpndnc (F 4).
T Bland-Altman analyss dmonstatd that 95% o thdncs btwn mthods (IOS and LMS) lay wthn 1.96SD om th man dnc ndcatd by th LOA. Ovall,th was a consstnt lna slopd tnd wth a systmatcbas (natv bas psntd at low vals and postvbas psntd at hh vals o th masmnt an)acossth Bland-Altmanplots, bt wthn thLOA (F 5);ths ct bcoms lss basd towads low qncs(Fs 5(a) and 5(b)) asdo th slops oth lnassonanalyss.
4. Discussion
In th psnt stdy, w dmonstatd that both spatoyncton tchnqs assssd th cts o ntavnosbthanchol on th spatoy systm. O slts showdthat dlta chans o oscllomtc sstancs n th mddlqncy an (s 10, 106%; s 15, 96%; s 20, 95%; s 25,85%) w hh than LMS dynamc plmonay sstanc(, 53%).
T smooth mscl o th spatoy tact has both paa-sympathtc and sympathtc nnvatons; cabamyl--mthylcholn (bthanchol) s a choln st and an aonsto mscanc cptos that stmlats ths cptos on thsmooth mscl o th spatoy tact, casn away na-own and phaps tss constcton. Bthanchol blonsto th sam op o ds as actylcholn, cabachol, and
mthacholn [39]. T plt modl sd n ths stdy waschosn basd on ts compaabl sz to th nonat/pdatchman and ts common s o th nvstaton o vntla-toy thaps [3137].
In addton, bthanchol-ndcd away challns havbn pvosly potd as an appopat xpmntalntvnton n th laboatoy [4044], and smla analos(.., mthacholn) hav bn sd o clncal sach p-poss [4547]. In hmans, bthanchol s appovd only ooal admnstaton s; n vtnay mdcn, t s avalablas an njcton o sbctanos (SC), ntamscla, o IVadmnstaton. Cadac ast s a sv, a advs ac-ton docmntd n hmans, and n anmals, t s a lkly
-
7/27/2019 PM2013-618576
5/9
Plmonay Mdcn 5
40
30
20
10
0
Resistance
(c
mH2
O/L/s)
Pre Post
Bethanechol
= 0.003
Figure 2: Plots o man vals o dynamc plmonay sstanc(sstanc) bo (p) and a (post) bthanchol o ach plt. = 0.003, pad -tst on tald.
= 0.018
40
50
30
20
10
0 Pre Post
Rrs1025Hz
(cmH2
O/L/s)
Figure 3: Plots o man vals o spatoy sstanc (s ) om10 Hz to 25 Hz bo (p) and a (post) bthanchol o achplt. = 0.018, pad -tst on tald o th ava.
sv cholnc acton vn IV o n ovdosa. It scommndd that atopn b mmdatly avalabl whnvn IV o SC [4851].
A bthanchol admnstaton, a at pcnta ochan was sn n away sstanc manly psntd bys 10s 25 (+10685%) whn compad wth th ln sst-
anc mostly psntd bys 3s 5 (+6963%), ndcatna at nonpphal away constcton spons thanpphal away/ln tss spons. Radn th lntss contbton vss away contbtons to th totalspatoy sstanc, dncs n th d o tss v-ss away contbton xstbtwn spcs [52, 53], ncld-n hmans [54], and wthnndcd-physolocaland pha-macolocal condtons [44]; ths, caton shold b takn ntanslatn ths ndns btwn spcs.
It s wdly conzd that th s o an sophaal bal-loon o sstanc masmnts spaats th ln andchst wall componnt, tho, xcldn th chst wallsstanc [4], whl s nclds th sstanc o th chst
Post
Pre
Frequency (Hz)
3 5 10 15 20 25 35
80
60
40
20
0
= 0.0002
Rrs
(cm
H2
O/L/s)
Figure 4: Plots o man (SEM) vals o spatoy sstanc(s ), as a ncton o oscllatoy qncy, bo (p) and a(post) bthanchol
( = 7 ). As shown, sncant dncs n
th mddl oscllatoy qncs an a dsplayd (
< 0.05);pad -tst on tald at ach qncy and ovall ( = 0.0002).
wall (.., ln sstanc) and away sstanc. T lowth spcc oscllatoy qncy s, th mo snstv thmasmnt s to th pphy o th spatoy systm.Masmnt o th sstanc sn mthods that qplacmnt o an sophaal balloon o spatoy nctontstn pocds to assss th spatoy systm n no-nats s not asy. Nonnvasvspatoy ncton tchnqs(.., mpls oscllomty) q lss patnt coopatonand povd mo nomaton abot th total spatoysystm sstanc [19].
W also dmonstatd that no pas n bathn wasncssay o codn labl data at low qncs os sn th mpls oscllaton tchnq n nonatal pltsspontanosly bathn thoh an E. In ths ad, thHn-B nfaton fx and ac mask w not sdn o stdy n compason to pvosly ctd stds n n-sdatd nonats/nants [28, 29].
T Bland-Altman analyss showd ood amnt bt-wn th two tchnqs (IOS andLMS) omasn sst-anc popts, and th amnt btwn ths tchnqs
dpndd on th oscllaton qncy. Fom a mchanstcvw pont, masd by th LMS n th stdy psntssstanc o th ln tss and away ctonal mchancalpopts, whas s masd by IOS psnts total s-patoy sstanc, so th two tchnqs a not dctlyntchanabl at low qncs. Howv, as mntondn Scton 3, th bas and slop dcas towads low q-ncs. In ths ad, spatoy sstanc at 5 Hz (s 5)and spatoy sstanc at 3 Hz (s 3) may b closlyntchanabl n th appopat sttns. Howv, thdnc o 1.96 SD om th man dnc o s 35(F 5()) was dmonstatd to b naccptabl o nt-chanablty.
-
7/27/2019 PM2013-618576
6/9
6 Plmonay Mdcn
28.75
Mean1.03
Slope = 2.36 0.72
= 0.67, value: 0.024
70605040302010
0
20
30
40
50Diferencein%change
(LMS-IOS)
10
10 5 0 5 10 15 20 25 30 35 40
Average in % change by LMS and IOS
30.75
+1.96 SD
1.96 SD
Rrs 3Hz
(a)
70605040302010
0
20
30
40
50
10 5 0 5 10 15 20 25 30 35 40
Average in % change by LMS and IOS
Dif
erencein%change
(LMS-IOS)
25.67
Mean0.67
27.02
Slope = 2.2 0.82
= 0.56, value: 0.051
10
+1.96 SD
1.96SD
Rrs 5Hz
(b)
10 5 0 5 10 15 20 25 30 35 40
Average in % change by LMS and IOS
Mean
2
= 0.67, value: 0.024Slope = 2.39 0.7
25.96
33.43
3.73
70605040302010
010
20
30
40
50
Diferencein%change
(LMS-IOS)
+1.96 SD
Rrs 10Hz
1.96 SD
(c)
70605040302010
010
20
30
40
50
10 5 0 5 10 15 20 25 30 35 40
Average in % change by LMS and IOS
Mean
31.01
4.33
22.34
2
= 0.62, value: 0.034Slope = 2.84 0.9
Dif
erencein%change
(LMS-IOS) +1.96 SD
Rrs 15Hz
1.96 SD
(d)
Mean
Slope = 2.83 0.6
5.95
40.31
28.4
70605040302010
010
10
2030
40
50
5 0 5 10 15 20 25 30 35 40
Average in % change by LMS and IOS
Difer
encein%cha
llenge
(LMS-IOS)
2
= 0.81, value: 0.005+1.96 SD
Rrs 20Hz
1.96 SD
()
Mean
33.88
49.94
8.02
70605040302010
010
2030
40
50Diferencein%cha
llenge
(LMS-IOS)
10 5 0 5 10 15 20 25 30 35 40
Average in % change by LMS and IOS
2
= 0.87, value: 0.002+1.96 SD
Slope = 2.59 0.4Rrs 25Hz
1.96 SD
()
70605040302010
010
20
30
40
50Diferencein%cha
llenge
(LM
S-IOS)
10 5 0 5 10 15 20 25 30 35 40
Average in % change by LMS and IOS
Mean
67.92
9.88
48.15
Slope = 2.06 0.22
= 0.91, value: 0.0009+1.96 SDRrs 35Hz
1.96 SD
()
Figure 5: Bland-Altman plots constctd om th last man sqa (LMS) and mpls oscllomty (IOS) data at ach spcc qncy(pcnta o chan) wth man (bas), LOA, and bst-t vals o lnasson (slop, 2, val) a admnstaton o ntavnosbthanchol. LOA, lmt o amnt; Upp LOA, man dnc (bas) + 1.96 SD; Low LOA, man dnc (bas) 1.96 SD; 2, sqas. T val s tstn th nll hypothss that th ovall slop s zo.
-
7/27/2019 PM2013-618576
7/9
Plmonay Mdcn 7
Lk many plmnay stds, th psnt stdy hassom xpmntal lmtatons. Alon ths lns, th cntstdy s an xpmntal pclncal modl compan thIOS and th LMS appoach as an ndcato o away ac-tvty bhavo to a phamacoloc ntvnton n a smallnmb o anmals. Addtonal wok s qd n th po-
manc, podcblty, and saty o th oscllaton tchn-q, ncldn valdaton and qalcaton as a bomak,bo t can b poposd o standad clncal pactc n thnonatal poplaton.
5. Conclusions
In conclson, w docmntd sncant away actvtysn both spatoy ncton tchnqsand dmonstatdth mantd o th chan n away sstanc componntat basln and a admnstaton o ntavnos bthan-chol. In a smla scnao, th masmnts o spatoysstanc om th mpls oscllaton tchnq (om 3 Hz
to25 Hz) may b sdn l o th dynamc plmonayss-tanc masmnts om th LMS tchnq to dtmnsstanc chans sconday to ndcd away actvtydn spontanos baths.
T IOS tchnq as a nonnvasv mans o valatnth dnt componnts o th spatoy systm and pl-monay mchancsn th nonatal sttn s vy appaln; tvs th nomaton thoh a an o sstanc valspsntn th away, tss, and chst mchancal pop-ts. Howv, th modcaton n th tchnq stp,ncopoaton o th appopat ncs vals o thnonatal poplaton, and collaboaton wth xpncdphyscans and scntsts n spatoy physoloy/spa-
toy ncton tchnqs a qd bo boad clncals s psd n th nonatal poplaton.
Funding
Ts stdy was ndd thoh Nmos Rsach Po-ams/Nmos Fondaton, NIH COBRE Gant no. 8P20 GM103464 (. H. Sha), and NIH Gant no. 532GM008562-17 (E. Rodz) pdatc phamacoloy llowndd by NICHD nd th Bst Phamactcals o Chl-dn Act. Ts wok was pomd at th Nmos/Ald I.dPont Hosptal o Chldn.
Acknowledgment
T athos thank Ms. Ann Hsk oh assstanc wth thanmal scal ppaaton.
References
[1] V. K. Bhtan,E. M. Sv, S. Abbas, and.H. Sha, Evala-ton o nonatal plmonay mchancs and ntcs: a twoacto lastman sqa analyss, Pediatric Pulmonology,vol.4,no. 3, pp. 150158, 1988.
[2] C. S. Badsmo, P. Hlms, J. Stocks, D. J. Hatch, and M.Slvman, Impovd sophaal balloon tchnq o s n
nants, Journal o Applied Physiology Respiratory Environmen-tal and Exercise Physiology, vol. 49, no. 4, pp. 735742, 1980.
[3] A. Bayd, P. K. Bhaks, and W. A. Zn, A smpl mthodo assssn th valdty o th sophaal balloon tchnq,American Review o Respiratory Disease, vol.126, no. 5,pp. 788791, 1982.
[4] V. K. Bhtan, . H. Sha, and D. Vdyasaa, Eds., NeonatalPulmonary Function esting: Physiological, echnical and Clini-cal Considerations, Pnatoloy Pss, Ithaca, NY, USA, 1988.
[5] L. S. Goldsmth, J. S. Gnspan, S. D. Rbnstn, M. R.Wolson, and . H. Sha, Immdat mpovmnt n lnvolm a xonos sactant: alvola ctmnt vssncasd dstnton, Journal o Pediatrics, vol. 119, no. 3, pp.424428, 1991.
[6] A. B. Dbos, A. W. Body, D. H. Lws, and B. F. Bss J.,Oscllaton mchancs o lns and chst n man, Journal oApplied Physiology, vol. 8, no. 6, pp. 587594, 1956.
[7] H. J. Smth, P. Rnhold, and M. D. Goldman, Focd osclla-ton tchnq and mpls oscllomty, European RespiratoryMonograph, vol. 31, pp. 72105, 2005.
[8] H. Bsaad andB. Kl, Lnnctonmasmnt n awakyon chldn, European Respiratory Journal, vol.8, no. 12, pp.20672075, 1995.
[9] C. Dlacot, H. Lono, M. Hv-Gllot, P. Rnt, A. Ha,andB. Hosst, Us o th ocd oscllaton tchnq to assssaway obstcton and vsblty n chldn, AmericanJournal o Respiratory and Critical Care Medicine, vol. 161, no.3, pat 1, pp. 730736, 2000.
[10] F. M. Dcham andG. M. Davs, Rspatoy sstanc n thmncy dpatmnt: a podcbl and sponsv maso asthma svty, Chest, vol. 113, no. 6, pp. 15661572, 1998.
[11] B. Kl and H. Bsaad, Masmnt o ln ncton nawak 24-ya-old asthmatc chldn dn mthacholnchalln and act asthma: a compason o th mpls oscl-
laton tchnq, th ntpt tchnq, and tansctanosmasmnt o oxyn vss whol-body plthysmoaphy,Pediatric Pulmonology, vol. 21, no. 5, pp. 290300, 1996.
[12] B. Kl and H. Bsaad, Rpatablty o mthacholn chal-lns n 2- to 4-ya-old chldn wth asthma, sn a nwtchnq o qanttatv dlvy o aosol, Pediatric Pul-monology, vol. 23, no. 4, pp. 278286, 1997.
[13] B. Kl and H. Bsaad, Spcc away sstanc, ntptsstanc, and spatoy mpdanc n halthy chldn ad27 yas, Pediatric Pulmonology, vol. 25, no. 5, pp. 322331,1998.
[14] B. Kl and H. Bsaad, Ln ncton and shot-tm ot-com n yon asthmatc chldn, European Respiratory Jour-nal, vol. 14, no. 5, pp. 11851189, 1999.
[15] B. Kl, K. G. Nlsn, andH. Bsaad, Obsv vaablty oln ncton masmnts n 26-y-old chldn, EuropeanRespiratory Journal, vol. 16, no. 3, pp. 472475, 2000.
[16] D. Stansc, N. E. Moavo, C. Vt, and L. Bass, F-qncy dpndnc o spatoy sstanc n halthy chl-dn, Journal o Applied Physiology Respiratory Environmentaland Exercise Physiology, vol. 47, no. 2, pp. 268272, 1979.
[17] E. Oostvn, D. MacLod, H. Lono t al., T ocd osclla-ton tchnq n clncal pactc: mthodoloy, commnda-tons and t dvlopmnts, European Respiratory Journal,vol. 22, no. 6, pp. 10261041, 2003.
[18] J. J. Pllow, P. D. Sly, and Z. Hantos, Monton o ln volmctmnt and dctmnt sn oscllatoy mchancs
-
7/27/2019 PM2013-618576
8/9
8 Plmonay Mdcn
dn hh-qncy oscllatoy vntlaton n th ptmlamb, Pediatric Critical Care Medicine, vol. 5, no. 2, pp. 172180,2004.
[19] E. Rodz, M. B.Bob, L. Davyt al., Rspatoy mchan-cs n an nant wth pnatal lthal hypophosphatasa tatdwth hman combnant nzym placmnt thapy, Pedi-atric Pulmonology, vol. 47, pp. 917922, 2012.
[20] U. Fy, M. Slvman, R. Kam, and A. C. Jackson, Hh-qncy spatoy mpdanc masd by ocd-osclla-ton tchnq n nants, American Journal o Respiratory andCritical Care Medicine, vol. 158, no. 2, pp. 363370, 1998.
[21] K. N. Dsa, W. Bh, M. Wllmn t al., Masmnt ototal spatoy mpdanc n nants by th ocd oscllatontchnq,Journal o Applied Physiology, vol.71, no. 2,pp. 770776, 1991.
[22] K. N. Dsa, M. Cabhs, J. Nadts, and K. P. van dWostjn, Infnc o pp away shnt on total spatoympdanc n nants,Journal o Applied Physiology, vol. 87, no.3, pp. 902909, 1999.
[23] K. N. Dsa, M. Wllmn, H. P. Van Bv, W. D Back, and
P. A. Vm, Evalaton o nasal mpdanc sn th ocdoscllaton tchnq n nants, Pediatric Pulmonology, vol. 11,no. 1, pp. 17, 1991.
[24] U. Fy, Focd oscllaton tchnq n nants and yonchldn, Paediatric Respiratory Reviews, vol. 6, no. 4, pp. 246254, 2005.
[25] G. L. Hall, Z. Hantos, J. H. Wldhab, F. Ptak, and P. D. Sly,Mthacholn sponsvnss n nants assssd wth lowqncy ocd oscllaton and ocd xpaton tchnqs,Torax, vol. 56, no. 1, pp. 4247, 2001.
[26] C. J. Lant and P. D. Sly, Chans n spatoy mchancswth a, Journal o Applied Physiology, vol. 74, no. 1, pp. 369378, 1993.
[27] . H. Sha, V. K. Bhtan,M. R. Wolson, R. B. Pnn, and N. N.an, In vvo mchancal popts o th dvlopn away,Pediatric Research, vol. 25, no. 2, pp. 143146, 1989.
[28] G. L. Hall, Z. Hantos, F. Ptak t al., Away and spatoytss mchancs n nomal nants, American Journal o Res-piratory and Critical Care Medicine, vol. 162, no. 4, pat 1, pp.13971402, 2000.
[29] J. J. Pllow, J. Stocks, P. D. Sly, and Z. Hantos, Pattonno away and panchymal mchancs n nsdatd nwbonnants, Pediatric Research, vol. 58, no. 6, pp. 12101215, 2005.
[30] . L. Mll, C. J. Snhas, . I. Shman, J. S. Gnspan, and. H. Sha, Physoloc mplcatons o hlm as a caas o nhald ntc oxd n a nonatal modl o Bthancol-ndcd bonchoconstcton, Pediatric Critical Care Medicine,vol. 7, no. 2, pp. 159164, 2006.
[31] E. A. Mats, J. Hldbandt, J. C. Jackson, P. aczy-Honoch,and M. P. Hlastala, Shnt and vntlaton-pson dstb-ton dn patal lqd vntlaton n halthy plts, Journalo Applied Physiology, vol. 82, no. 3, pp. 933942, 1997.
[32] M. A. Enon, M. C. Papo, C. L. Lach t al., Ronal pl-monay blood fow dn patal lqd vntlaton n nomaland act olc acd-ndcd ln-njd plts, Critical CareMedicine, vol. 27, no. 12, pp. 27162723, 1999.
[33] D. M. Stnhon, M. C. Papo, A. . Rotta, A. Aljada, B. P.Fhman, and P. Dandona, Lqd vntlaton attnats pl-monay oxdatv dama, Journal o Critical Care, vol. 14, no.1, pp. 2028, 1999.
[34] S. Wol, H. Lohbnn, . Bsch t al., Idal PEEP s sp-o to hh dos patal lqd vntlaton wth low PEEP nxpmntal act ln njy, Intensive Care Medicine, vol. 27,no. 12, pp. 19371948, 2001.
[35] R. K. M. Kshnan, P. A. Mys, C. Wowa, R. Gotz, G.Scha, and M. C. Mamml, Standadzd ln ctmntdn hh qncy and convntonal vntlaton: smlapathophysoloc and nfammatoy sponss n an anmalmodl o spatoy dstss syndom, Intensive Care Medi-cine, vol. 30, no. 6, pp. 11951203, 2004.
[36] J. L. Nold, P. A. Mys, C. . Wowa t al., Dcasd lnnjy a sactant n plts tatd wth contnos pos-tv away pss o synchonzd ntmttnt mandatoyvntlaton, Neonatology, vol. 92, no. 1, pp. 1925, 2007.
[37] A. L. Lampland, P. A. Mys, C. . Wowa, E. C. Swanson, andM. C. Mamml, Gas xchan and ln nfammaton snnasal ntmttnt postv-pss vntlaton vss syncho-nzd ntmttnt mandatoy vntlaton n plts wth salnlava-ndcd ln njy: an obsvatonal stdy, CriticalCare Medicine, vol. 36, no. 1, pp. 183187, 2008.
[38] . L. Mll, . J. Blackson, . H. Sha, and S. M. och,achal as nsaton-amntd contnos postv a-way pss n a spontanosly bathn modl o nonatalspatoy dstss, Pediatric Pulmonology, vol. 38, no. 5, pp.386395, 2004.
[39] J.L. Schlatt andJ. L. Saln, Bthancholchlodoal sol-tons: stablty and s n nants, Annals o Pharmacotherapy,vol. 31, no. 3, pp. 294296, 1997.
[40] E. N. Kklkan, M. R. Wolson, and . H. Sha, Canpotntats away sponsvnss n th nonatal lamb, Pedi-atric Pulmonology, vol. 12, no. 1, pp. 1722, 1992.
[41] V. K. Bhtan, R. J. Koslo, and . H. Sha, T ct otachal, smooth mscl ton on nonatal away collapsblty,Pediatric Research, vol. 20, no. 6, pp. 492495, 1986.
[42] R. B. Pnn, M. R. Wolson, and . H. Sha, Ect o tachalsmooth mscl ton on collapsblty o mmat aways,Journal o Applied Physiology, vol. 65, no. 2, pp. 863869, 1988.
[43] R. B. Pnn, M. R. Wolson, and . H. Sha, Infnc osmooth mscl ton and lontdnal tnson on th collaps-blty o mmat aways, Pediatric Pulmonology, vol. 5,no. 3,pp. 132138, 1988.
[44] H. B. Pantch, I. almac, J. Hckman, M. R. Wolson, and .H. Sha, Qanttatv bonchoscopc assssmnt o awaycollapsblty n nwbonlamb tacha, PediatricResearch, vol.43, no. 6, pp. 832839, 1998.
[45] H. B.Pantch, E. N. Kklkan, R. A. Motly, M. R. Wolson, andD. V. Schdlow, Ect o altn smooth mscl ton on max-mal xpatoy fows n patnts wth tachomalaca, PediatricPulmonology, vol. 9, no. 3, pp. 170176, 1990.
[46] S. M. Stck, D. J. n, and P. N. LSo, Ln ncton andbonchal challns n nants: patablty o hstamn andcompason wth mthacholn challns, Pediatric Pulmono-logy, vol. 16, no. 3, pp. 177183, 1993.
[47] C. Dlacot, M. R. Bnost, S. Wanssyckl t al., Rpata-blty o ln ncton tsts dn mthacholn challn nwhzy nants, Torax, vol. 53, no. 11, pp. 933938, 1998.
[48] J.L. Schlatt andJ. L. Saln, Bthancholchlodoal sol-tons: stablty and s n nants, Annals o Pharmacotherapy,vol. 31, no. 3, pp. 294296, 1997.
[49] L. V. Alln J. andM. A. Eckson,Stabltyo bthanchol chlo-d,pyaznamd,qndn slat, ampn,and ttacycln
-
7/27/2019 PM2013-618576
9/9
Plmonay Mdcn 9
hydochlod n xtmpoanosly compondd oal lqds,American Journal o Health-System Pharmacy, vol. 55, no. 17, pp.18041809, 1998.
[50] M. C. Nahata, V. B. Pa, and . F. Hppl, Eds., Pediatric DrugFormulations, Havy Whtny Books, Cncnnat, Oho, USA,5th dton, 2004.
[51] D. C. Plmb, Veterinary Drug Handbook, Iowa Stat Pss, St.Pal, Mnn, USA, 4th dton, 2002.
[52] Z. Hantos, B. Daoczy, B. Sk, and S. Nay, Low-qncyspatoy mchancal mpdanc n th at,Journal o AppliedPhysiology, vol. 63, no. 1, pp. 3643, 1987.
[53] Z. Hantos,B. Daoczy, B. Sk, S. Nay, andJ. J.Fdb, Inptmpdancand pphalnhomonty o do lns,Journalo Applied Physiology, vol. 72, no. 1, pp. 168178, 1992.
[54] B. G. Fs J., J. Mad, and L. H. Op, Pattonn o spa-toy fow sstanc n man, Journal o Applied Physiology, vol.19, pp. 653658, 1964.
top related