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T*
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T*
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T*
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T*
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T*
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T*
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T*
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T*
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T*
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T*
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T*
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T*
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[([7)13.9(].)]TJ
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[(In)-612(guinea-pigs)-11.1(,)-603.6(leukot)-9.7(riene)-611.8(\(L)78.1(T\)D)]TJ
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(4)Tj
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[(causes)-617.1(eosinophil)]TJ
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T*
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(4)Tj
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(and)Tj
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(D)Tj
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(4)Tj
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[(phils)-282.9(in)-277.1(asthm)-10.9(atic)-281.8(patients)-282.7([12])-285.1(and)-275.8(blunt)-8.6(s)-275.1(the)-283.9(increase)-286(in)]TJ
T*
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T*
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[(tr)17.3(ie)18.4(ne)]TJ
7.472 0 0 6.641 80.05 110.891 Tm
(1)Tj
9.963 0 0 9.963 87.477 112.535 Tm
[(\(C)14.9(ys)14.4(L)97.5(T)]TJ
7.472 0 0 6.641 116.844 110.891 Tm
(1)Tj
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[(th)18.9(ei)18.4(r)-212.9(p)0(r)19.6(e)0(s)19.6(t)0(u)18.9(d)0(y)-200.7(t)0(r)17.3(e)0(a)14.7(t)0(m)15.7(e)0(n)20.8(t)0(,)-197(t)0(o)-197.4(r)0(e)13.5(c)0(o)20.8(r)0(d)-202.3(s)0(y)20(m)0(p)18.1(t)0(o)13.2(m)0(s)16.9(,)-205.2(th)18.9(e)-206(u)0(s)14.4(e)-206(of)-196.6(as)13.9(-)]TJ
0 -1.0528 TD
[(ne)15.1(ed)20.8(ed)]TJ
/F8 1 Tf
2.9875 0 TD
(b)Tj
/F3 1 Tf
7.472 0 0 6.641 93.487 348.491 Tm
(2)Tj
9.963 0 0 9.963 97.115 350.135 Tm
[(-a)19.2(go)15.5(ni)18.9(st)17.7(s,)-212.9(an)15.1(d)-222.7(m)0(o)18.1(r)0(n)13.9(i)0(n)18.9(g)-222.7(an)20.8(d)-222.7(e)0(v)15.1(e)0(n)15.1(i)13.9(ng)-217.8(pe)20.8(ak)-218.2(ex)20.8(pi)18.9(ra)13.5(-)]TJ
-3.898 -1.0471 TD
[(to)18.9(ry)-190.9(fl)17.3(ow)-187.6(\(P)20.4(EF)17.9(\))-195.8(o)0(n)-189.3(a)-194.7(da)15.1(i)13.9(l)0(y)-191.7(d)0(i)18.9(a)0(r)19.2(y)-194.2(ca)14.7(rd)19.6(.)-199.6(A)12.4(dd)15.5(it)16.5(io)18.9(na)15.1(l)13.9(l)0(y)75.8(,)-193.9(pa)20.8(ti)16.5(en)15.1(ts)]TJ
0 -1.0527 TD
[(re)19.2(fr)12.4(ai)18.4(ne)20.8(d)-359.3(f)0(r)18(o)0(m)-351.8(i)0(n)13.2(h)0(a)20.8(l)0(e)18.4(d)-359.3(sa)13.9(lb)18.9(ut)18.9(am)17.7(ol)-351(an)15.1(d)-359.3(c)0(a)20.4(f)20.4(f)0(e)13.5(i)0(n)18.9(a)0(t)18.4(e)0(d)-349.1(b)0(e)15.1(v)0(e)15.1(r)20.4(-)]TJ
0 -1.0471 TD
[(ag)15.1(es)-264.9(fo)19.6(r)-275.5(a)0(t)-266.1(l)0(e)18.4(a)0(s)13.9(t)-270.6(6)-273.9(h)0(,)-268.6(a)0(n)20.8(d)-273.9(an)15.1(y)-273.9(a)0(n)15.1(t)0(i)22.2(h)0(i)13.2(s)0(t)17.7(a)0(m)17.7(i)0(n)18.9(e)-274.3(me)17.7(di)13.2(ca)20.4(ti)16.5(on)-263.3(fo)13.9(r)]TJ
0 -1.0527 TD
[(at)-351.4(le)12.8(as)19.6(t)-361.7(4)0(8)-354.3(h)0(,)-348.3(b)0(e)15.1(f)0(o)19.6(r)0(e)-356.3(a)-359.7(st)17.7(ud)15.5(y)-359.3(v)0(i)18.9(s)0(i)17.7(t)0(,)-356.3(a)0(n)20.8(d)-365(co)20.8(nt)18.9(ac)14.7(te)18.4(d)-365(a)-359.7(st)17.7(ud)15.5(y)]TJ
0 -1.0471 TD
[(ph)15.5(ys)20(ic)18.4(ia)18.4(n)-279.6(i)13.9(f)-275.5(a)-280(de)20.8(te)18.4(ri)17.3(or)13.9(at)18.5(io)18.9(n)-273.9(i)0(n)-265.7(s)0(y)14.4(m)0(p)18.1(t)0(o)18.9(m)0(s)-267.6(o)0(r)-264.9(P)0(E)17.9(F)-278.8(oc)20.8(cu)15.1(rr)18(ed)15.1(.)]TJ
0 -1.0527 TD
[(Qu)17.3(al)18.4(if)17.3(yi)13.2(ng)-200.7(pa)15.1(t)13.9(i)0(e)12.8(n)0(t)18.9(s)-212.5(un)21.2(de)15.1(rw)15.7(en)20.8(t)-213.7(a)0(l)18.4(l)0(e)12.8(r)20.4(gy)-200.7(sk)14.3(in)-203.1(te)18.4(st)17.7(in)18.9(g)-211.3(a)0(n)15.1(d)-211.3(sp)14.4(u-)]TJ
0 -1.0471 TD
[(tu)18.9(m)-225.8(i)0(n)18.9(d)0(u)15.5(c)0(t)18.5(i)0(o)18.9(n)0(,)-217.4(a)0(n)20.8(d)-228.4(w)12.4(e)0(r)13.5(e)-223.1(al)18.4(lo)18.9(ca)14.7(te)18.4(d)-222.7(r)0(a)13.5(n)0(d)21.2(o)0(m)18.1(l)0(y)-220.2(a)0(c)20.4(c)0(o)15.1(r)0(d)19.6(i)0(n)18.9(g)-222.7(to)-220.2(a)]TJ
25.1977 49.6557 TD
[(co)15.1(mp)18.1(ut)18.9(er)24.9(-g)19.6(en)15.1(er)19.2(at)18.5(ed)-377.5(sc)19.6(he)15.1(du)21.2(le)-374.2(to)-373.8(re)13.5(ce)20.4(iv)18.9(e)-382.4(e)0(i)12.8(t)0(h)18.9(e)0(r)-373.4(m)0(o)18.1(n)0(t)18.9(e)0(l)12.8(u)0(k)21.2(-)]TJ
0 -1.0471 TD
[(as)13.9(t)-367.3(1)0(0)-360(m)0(g)-363.2(o)0(r)-355.9(m)0(a)12(t)0(c)18.5(h)0(i)18.9(n)0(g)-360(i)0(m)15.7(a)0(g)20.8(e)-371.1(pl)18.9(ac)14.7(eb)20.8(o)-370.7(t)0(a)18.4(b)0(l)18.9(e)0(t)12.8(s)-366.2(on)15.5(ce)-360.8(da)20.8(il)16.5(y)]TJ
0 -1.0528 TD
[(at)-294.5(be)15.1(dt)18.9(im)15.7(e.)-291.8(Sp)16.3(ut)18.9(um)-294.9(wa)16.9(s)-303.6(i)0(n)13.2(d)0(u)21.2(c)0(e)14.7(d)-302.4(ag)20.8(ai)18.5(n)-308.1(1)-302.4(an)20.8(d)-302.4(4)-302.4(w)0(e)16.9(e)0(k)15.1(s)-303.6(af)19.2(-)]TJ
0 -1.0471 TD
[(te)12.8(r)-474.7(t)0(r)17.3(e)0(a)14.7(t)13.9(me)12(nt)-464.8(al)18.4(lo)13.2(ca)20.4(ti)16.5(on)15.5(.)-472.7(C)0(l)14.1(i)0(n)18.9(i)0(c)18.4(a)0(l)-470.9(e)0(f)30.6(f)0(i)17.3(c)0(a)14.7(c)0(y)-462.9(m)0(e)12(a)0(s)19.6(u)0(r)19.6(e)0(m)12(e)0(n)20.8(t)0(s)]TJ
0 -1.0528 TD
[(\(F)14.7(EV)]TJ
7.97 0 0 7.97 330.86 729.808 Tm
(1)Tj
9.963 0 0 9.963 334.772 729.808 Tm
[(,)-330.4(P)11.4(EF)86.2(,)-330.4(d)0(a)20.8(y)0(t)18.9(i)0(m)15.7(e)-331.2(as)13.9(th)18.9(ma)-323.7(sy)20(mp)18.1(to)13.2(ms)16.9(\))-326.7(w)0(e)11.2(r)0(e)-322.2(p)0(e)20.8(r)0(f)18(o)0(r)13.9(m)0(e)17.7(d)]TJ
-2.5551 -1.0471 TD
[(ov)15.5(er)-595.3(th)18.9(e)-604.4(4)0(-)19.6(w)0(e)16.9(e)0(k)-593.8(t)0(r)17.3(e)0(a)20.4(t)0(m)15.7(e)0(n)15.1(t)-600.7(pe)15.1(ri)17.3(od)21.2(.)-603.6(B)0(l)19.8(o)0(o)15.5(d)-604(sa)19.6(fe)19.2(ty)-595.7(te)18.5(st)17.7(s)]TJ
0 -1.0528 TD
[(\(i)17.3(nc)15.1(lu)18.8(di)18.9(ng)-314.5(eo)20.8(si)17.7(no)15.5(ph)21.2(il)-313.6(co)20.8(un)15.5(ts)17.7(\))-321(w)12.4(er)13.5(e)-319.8(p)0(e)20.8(r)0(f)18(o)0(r)13.9(m)0(e)17.7(d)-319.4(at)-311.6(pr)19.6(es)13.9(t)13.9(u)0(d)15.5(y)]TJ
0 -1.0471 TD
[(an)15.1(d)-325.1(2)-325.1(a)0(n)20.8(d)-325.1(4)-325.1(w)12.4(ee)14.7(ks)-315.7(af)19.2(te)12.8(r)-321(a)0(l)18.5(l)0(o)13.2(c)0(a)20.4(t)0(i)16.5(o)0(n)15.5(.)]TJ
/F5 1 Tf
0 -2.4583 TD
[(Clini)-10(cal)-335.1(meas)-8.6(ur)31.4(emen)-7.8(ts)]TJ
/F3 1 Tf
1.0015 -1.747 TD
[(Pa)15.9(ti)16.5(en)15.1(ts)-397.8(re)19.2(co)15.1(rd)19.6(ed)-394.6(th)13.2(e)-405.2(n)0(u)21.2(m)0(b)12.4(e)0(r)-396.2(o)0(f)-395.8(a)0(s)13.9(-)0(n)19.6(e)0(e)14.7(d)0(e)20.8(d)]TJ
/F8 1 Tf
17.7659 0 TD
(b)Tj
/F3 1 Tf
7.472 0 0 6.641 501.732 654.86 Tm
(2)Tj
9.963 0 0 9.963 505.36 656.56 Tm
[(-a)19.2(go)15.5(ni)18.8(st)]TJ
-19.6779 -1.0527 TD
[(pu)15.5(f)20.4(f)0(s)-374.2(u)0(s)14.4(e)0(d)20.8(,)-387.3(mo)18.1(rn)19.6(in)13.2(g)-382(a)0(n)20.8(d)-387.7(ev)20.8(en)15.1(in)18.9(g)-382(P)0(E)17.9(F)-386.9(\(t)17.3(he)-371.8(be)15.1(st)-375(of)-373(th)13.2(re)19.2(e)]TJ
T*
[(me)12(as)19.6(ur)19.6(es)-316.1(us)20(in)18.9(g)-325.1(a)-319.8(Mi)16.9(ni)18.9(-W)46.9(ri)17.3(gh)15.5(t)-321.8(p)0(e)15.1(a)0(k)-309.2(f)0(l)17.3(o)0(w)-312.8(m)0(e)12(t)13.9(er)-316.5(\(C)14.9(le)18.4(me)17.7(nt)]TJ
0 -1.0471 TD
[(Cl)14.1(ar)19.2(k)-404.8(I)0(n)19.6(c)0(.)15.5(,)-404.4(C)11.6(o)0(l)13.2(u)0(m)18.1(b)0(u)21.2(s)0(,)-395(O)0(H)13.4(,)-404.4(U)12.4(S)0(A)12.4(\))0(\))18(,)-404.4(an)20.8(d)-404.8(d)0(a)15.1(y)0(t)18.9(i)0(m)15.7(e)-399.5(as)14(th)18.9(ma)]TJ
0 -1.0528 TD
[(sy)14.4(mp)18.1(to)18.8(m)-459.2(s)0(c)19.6(o)0(r)14(e)0(s)-447(o)0(n)-445.4(a)-462.1(da)20.8(il)16.5(y)-456(d)0(i)18.9(a)0(r)13.5(y)-456(ca)20.4(rd)-452.7(va)20.8(li)16.5(da)15.1(te)18.4(d)-456(f)0(o)19.6(r)-457.6(it)16.5(s)]TJ
0 -1.0471 TD
[(me)12(as)19.6(ur)19.6(em)12(en)20.8(t)-481.1(a)0(n)15.1(d)-478.8(li)16.5(ng)15.5(ui)18.9(st)17.7(ic)-470.9(pr)14(op)21.2(er)13.5(ti)16.5(es)-469.7([2)13.9(4].)-481.5(Spirometr)-11.9(y)]TJ
0 -1.0528 TD
[(was)-349.3(perfor)-9.8(med)-341.6(a)-6.9(ccording)-346.6(to)-345.3(Ameri)-9.6(can)-344.5(Tho)-6.4(racic)-344.7(So)-6.4(ciety)]TJ
0 -1.0471 TD
[(crit)-9.8(eria)-303.7([25])-302.2(betwe)-10.9(en)-297.8(06:00)-307.8(h)-296.7(and)-304.3(09:00)-302.1(h,)-302.7(~8\26110)-302.9(h)-302.4(after)]TJ
0 -1.0528 TD
[(the)-283.9(previous)-284.8(\(bedt)-8.2(ime\))-283.7(dose)-277.8(of)-282(study)-280.5(drug.)-278.2(Fo)-6.4(r)-275.5(each)-283.1(time)]TJ
0 -1.0471 TD
[(point)-8.6(,)-358.9(the)-363.6(best)-365.5(FEV)]TJ
7.97 0 0 7.97 389.65 562.394 Tm
(1)Tj
9.963 0 0 9.963 397.19 562.394 Tm
[(va)-7.6(lue)-363.6(from)-362.2(at)-362.8(least)-369.1(three)-367.1(measure-)]TJ
-8.8204 -1.0528 TD
[(ment)-9(s)-502.7(was)-508.6(used)-505.4(for)-511.9(analysis.)-509.5(Rev)-7.4(ersibility)-512.1(was)-508.6(deter-)]TJ
0 -1.0471 TD
[(min)-7.8(ed)-485.6(by)-490.9(adminis)-9.1(tering)-489.3(salbu)-7.8(tamol)-490.1(200)]TJ
/F8 1 Tf
17.2196 0 TD
(m)Tj
/F3 1 Tf
0.5747 0 TD
[(g)-484.5(throu)-7.8(gh)-485.2(a)]TJ
-17.7943 -1.0528 TD
[(spacer)-259(dev)-8.4(ice)-250.2(\(Ae)-8.2(rocham)-10.1(ber)]TJ
7.472 0 0 6.641 422.305 535.408 Tm
0.0001 Tc
(TM)Tj
9.963 0 0 9.963 433.417 530.986 Tm
0 Tc
[(;)-253.5(Monagh)-6.9(an)-252.3(Medi)-7.8(cal)-255.9(Cor-)]TJ
-12.4566 -1.0471 TD
[(porat)-8.2(ion,)-460.3(Platt)-10.6(sburgh,)-451.6(NY)121.5(,)-461.3(USA\))-461.3(and)-463.6(meas)-8.2(uring)-463(FEV)]TJ
7.97 0 0 7.97 532.516 520.554 Tm
(1)Tj
9.963 0 0 9.963 309.316 510.066 Tm
[(10\261)-8(30)-223.5(min)-229.7(later)45.9(.)-222.3(Allergy)-226.6(skin)-228.6(tests)-227.6(wer)-8.2(e)-223.1(carried)-234.1(out)-226.6(by)-223.5(the)]TJ
T*
[(skin)-251.3(prick)-252.9(technique)-251.8(wi)-7.8(th)-242.9(a)-245.9(min)-7.8(imum)-250.7(of)-236.4(five)-252.1(aeroallergen)]TJ
0 -1.0527 TD
[(extra)-8.6(cts)-313.6(appropr)-8.9(iate)-315.9(to)-311.2(the)-312.4(geograp)-7.7(hical)-316.7(location.)-316(A)-232.3(weal)]TJ
0 -1.0471 TD
[(diam)-9(eter)-252.5(at)-249(least)-255.3(3)-245.5(m)0(m)-252.5(larger)-244.3(than)-250.5(the)-249.8(dilu)-7.8(ent)-249.8(contr)-8.2(ol)-248.6(was)]TJ
0 -1.0528 TD
[(con)-8.4(sidered)-341.4(positive)-9.1(.)]TJ
/F5 1 Tf
0 -2.4526 TD
[(Spu)-8(tum)-333(and)-338(blood)-336.3(exam)-7.8(ination)]TJ
/F3 1 Tf
1.0015 -1.7527 TD
[(St)14(ud)21.2(y)-438.9(s)0(i)17.7(t)0(e)-425.4(p)0(e)15.1(r)0(s)18.4(o)0(n)15.5(n)0(e)20.8(l)-441.3(w)12.4(e)0(r)13.5(e)-433.7(tr)17.3(ai)18.5(ne)15.1(d)-438.9(t)0(o)-425(p)0(e)15.1(r)0(f)18(o)0(r)19.6(m)-436.4(sp)14.3(ut)18.9(um)]TJ
-1.0015 -1.0471 TD
[(in)13.2(du)21.2(ct)18.5(io)13.2(n)-353.6(a)0(n)15.1(d)-353.6(pr)19.6(oc)15.1(es)19.6(si)17.7(ng)-348.7(in)-345.3(a)-354(s)0(t)12(a)0(n)20.8(d)0(a)15.1(r)0(d)19.6(i)0(z)18.4(e)0(d)-349.1(m)0(a)17.7(n)0(n)15.5(e)0(r)70.4(.)-353.2(Sp)16.3(u-)]TJ
0 -1.0528 TD
[(tu)13.2(m)-345.3(w)0(a)16.9(s)-349.1(in)18.9(du)15.5(ce)14.7(d)-347.9(a)0(s)-338.9(d)0(e)20.8(s)0(c)13.9(r)0(i)17.3(b)0(e)20.8(d)-347.9(by)-343(P)]TJ
6.974 0 0 6.974 451.729 405.411 Tm
(IN)Tj
/F5 1 Tf
9.963 0 0 9.963 462.444 405.411 Tm
[(et)-340.1(al)]TJ
/F3 1 Tf
1.7982 0 TD
[(.)-347.5([)0(2)19.6(2)0(])-350.2(with)-364.6(an)]TJ
-17.1684 -1.0471 TD
[(aeroso)-8.2(l)-264.9(o)0(f)-259.2(hype)-9.1(rtonic)-267.4(saline)-267.4(\(3,)-259.6(4)-262.5(and)-264.5(5%\))-268(generated)-268.5(by)-263.3(a)]TJ
0 -1.0527 TD
[(Fisone)-7.8(b)]TJ
7.472 0 0 6.641 340.724 388.913 Tm
0.0001 Tc
(TM)Tj
9.963 0 0 9.963 354.671 384.491 Tm
0 Tc
[(u)-6.5(ltrasonic)-290.7(nebuli)-9.7(zer)-283.5(\(Can)-9.8(adian)-285.8(Medi)-7.8(cal)-284.3(Prod-)]TJ
-4.5524 -1.0471 TD
[(ucts)-263.1(Ltd.,)-259.9(Markh)-7.8(am,)-261.5(Ontari)-9.6(o,)-257.2(Can)-7.4(ada\).)-261.9(Sputum)-259.7(separa)-8.6(ted)]TJ
0 -1.0528 TD
[(from)-225.6(sali)-9.4(va)-218.2(was)-224.1(proces)-8.2(sed)-225.8(as)-219.4(descri)-10.6(bed)-218.9(by)-223.5(P)]TJ
6.974 0 0 6.974 482.683 363.572 Tm
0.0001 Tc
[(IZZICHIN)-15.9(I)]TJ
/F5 1 Tf
9.963 0 0 9.963 517.039 363.572 Tm
0 Tc
[(et)-220.6(al)]TJ
/F3 1 Tf
1.7015 0 TD
(.)Tj
-22.5516 -1.0471 TD
[([19].)-262.7(Briefly)55.6(,)-256.5(sputum)-256(was)-258.2(treated)-263.3(by)-251.9(adding)-257.7(four)-262.3(volumes)]TJ
0 -1.0528 TD
[(of)-464.1(0.1%)-460.3(dith)-7.8(iothreit)-11.9(ol)-459.2(\(DTT\),)-463.4(sputa)-7.8(lysin)-465(10%)-459.9(\(C)-7.8(albio-)]TJ
0 -1.0471 TD
[(che)-8.8(m)-481.9(Corp.,)-488.1(San)-479.9(Di)-7.8(ego,)-481.1(CA,)-488.6(USA\))-484(foll)-9.4(owed)-485.4(by)-479.5(four)]TJ
0 -1.0528 TD
[(volum)-9.3(es)-566.5(of)-560.8(Dul)-8.6(becco)]TJ
/F10 1 Tf
9.1333 0 TD
(')Tj
/F3 1 Tf
0.2162 0 TD
[(s)-565.3(phospha)-6.9(te-bu)-8.2(ffered)-562.2(saline)-569(\(D-)]TJ
-9.3496 -1.0471 TD
[(PBS\))-7.8(.)-210.9(The)-211.7(suspen)-7.4(sion)-211.5(was)-212.7(filtered)-216.4(throu)-7.8(gh)-212.1(a)-206(48-)]TJ
/F8 1 Tf
18.9723 0 TD
(m)Tj
/F3 1 Tf
0.5747 0 TD
[(m)-208.8(nylon)]TJ
-19.547 -1.0527 TD
[(gau)-8.4(ze)-224.3(\(BBSH)-228.5(Tho)-6.4(mpson,)-224.8(Sc)-6.8(arboroug)-9.7(h,)-223.1(Ontari)-9.6(o,)-223.1(Canada\))]TJ
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[(3%)-618.5(\(c)13.5(on)21.2(si)17.7(de)15.1(re)19.2(d)-626.7(s)0(i)17.7(g)0(n)15.5(i)0(f)17.3(i)0(c)18.4(a)0(n)20.8(t)0(l)16.5(y)-626.7(el)18.4(ev)15.1(at)18.4(ed)-616.5([2)19.6(7]\))-631.4(to)]TJ
-3.0558 -1.0527 TD
[(exclud)-7.8(e)-314.2(baseline)-320.6(values)-321.9(too)-312(low)-321.6(to)-311.2(show)-321.2(meaningful)-325.2(de-)]TJ
0 -1.0471 TD
[(creases)-358.1(durin)-7.8(g)-347.9(treatmen)-11.1(t.)-350.6(T)29.3(reatment)-358.2(by)-354.3(baseline)-354.7(inte)-8.2(rac-)]TJ
0 -1.0528 TD
[(tion)-309.4(was)-309.4(also)-314.3(evaluated)-314.8(as)-310.4(was)-309.4(the)-306.7(change)-313.1(from)-311(basel)-8.2(ine)]TJ
0 -1.0471 TD
[(to)-294.1(the)-289.6(W)72(e)0(e)-8(k-1)-288.4(\(fir)-10.2(st)-289.6(visit)-296.7(after)-294.7(allo)-8.2(cation\))-297(value)-291.5(using)-297.6(the)]TJ
0 -1.0527 TD
[(same)-349.6(model)-9.7(.)-341.8(The)-348.2(average)-350(treat)-11(ment)-344.7(p)-6.5(eriod)-349.6(change)-347.2(from)]TJ
0 -1.0471 TD
[(basel)-8.2(ine)-346.5(for)-352.6(peripheral)-352.5(blood)-353.3(eosin)-7.8(ophils)-352(was)-349.2(also)-348.5(com-)]TJ
0 -1.0528 TD
[(pared)-364.7(between)-360(treat)-11(ment)-361.8(groups)-360.2(using)-360.2(this)-361.8(model.)-362.9(Post-)]TJ
T*
[(alloca)-10.6(tion)-457.4(sputu)-7.4(m)-459.2(eosino)-8.6(phil)-457.4(data)-461.5(wer)-8.2(e)-456.4(exclud)-7.8(ed)-457.2(from)]TJ
0 -1.0471 TD
[(analys)-9(is)-642.4(if)-642.8(prespe)-8.2(cified)-643.4(crit)-9.8(eria)-645.2(confoun)-7.3(ding)-642.8(efficacy)]TJ
0 -1.0527 TD
[(meas)-8.2(urements,)-396.9(such)-391.6(as)-390.1(an)-388.9(upper)-392.8(respirato)-11.1(ry)-390.1(tract)-392.2(infec)-8.6(-)]TJ
0 -1.0471 TD
[(tion,)-366.7(occurr)-8.6(ed.)-366.5(For)-361.6(clin)-8.2(ical)-367.1(endpoints,)-372.1(the)-363.6(average)-367.1(treat)-11(-)]TJ
0 -1.0527 TD
[(ment)-384.6(perio)-8.2(d)-382(changes)-383.3(\(dayt)-8.2(ime)-383.8(symp)-7.4(tom)-383.4(score,)-383.4(PEF\))-388.5(or)]TJ
0 -1.0471 TD
[(average)-446.7(per)-442.5(cent)-438.7(chan)-9.6(ges)-436.4(\(FE)-7.2(V)]TJ
7.97 0 0 7.97 189.241 175.294 Tm
(1)Tj
9.963 0 0 9.963 193.209 175.294 Tm
(,)Tj
/F8 1 Tf
0.6886 0 TD
(b)Tj
/F3 1 Tf
7.472 0 0 6.641 205.568 173.65 Tm
(2)Tj
9.963 0 0 9.963 209.31 175.294 Tm
[(-agoni)-9(st)-443.3(use\))-438.7(wer)-8.2(e)]TJ
-15.1596 -1.0528 TD
[(summari)-11.5(zed)-270.6(\(mea)-8.6(n\213)]TJ
6.974 0 0 6.974 139.238 164.806 Tm
0.0001 Tc
(SD)Tj
9.963 0 0 9.963 148.139 164.806 Tm
0 Tc
[(\))-269.8(and)-270.2(compa)-7.8(red)-266.1(b)-6.5(etween)-273.9(treatmen)-11.1(t)]TJ
-9.0195 -1.0471 TD
[(groups)-434.2(u)-6.5(sing)-433.4(an)-428.7(ana)-8.8(lysis)-432.1(of)-435.6(variance)-438.5(\(ANO)-10.7(V)126.2(A)0(\))-433.8(model)]TJ
0 -1.0528 TD
[(includ)-9.7(ing)-363.2(factors)-371.4(for)-364(treatmen)-11.1(t)-361.7(and)-366.9(centr)-8.6(e.)-360.1(The)-365.3(betw)-9.8(een)]TJ
0 -1.0471 TD
[(treatmen)-11.1(t)-390.1(differences)-393.9(were)-396.3(summari)-11.5(zed)-390.1(as)-390.1(least)-397.5(square)-8.2(s)]TJ
0 -1.0528 TD
[(means)-100(and)-99.4(95%)-101.4(confidence)-104.3(inte)-8.2(rvals)-100.4(\(CI\))-97.9(using)-104.1(the)-96.1(ANO)-8.4(V)126.2(A)]TJ
0 -1.0471 TD
[(model)-9.7(.)-381.7(All)-392.2(available)-391.2(data)-393.2(were)-390.7(used)-385.9(for)-392.4(the)-386.3(analys)-9(is)-386.4(of)]TJ
25.1977 46.7763 TD
[(clin)-8.2(ical)-190.7(endpoi)-7.4(nts.)-188.3(A)-186.8(p-val)-8.2(ue)]TJ
/F9 1 Tf
11.4665 0 TD
(#)Tj
/F3 1 Tf
0.8308 0 TD
[(0.05)-190.5(was)-189.9(consi)-7.8(dered)-188.3(stat)-9.4(is-)]TJ
-12.2973 -1.0528 TD
[(tica)-8.6(lly)-337.1(signifi)-9.6(cant.)]TJ
1.0015 -1.0471 TD
[(Th)17.1(e)-291.4(s)0(t)17.7(u)0(d)21.2(y)-291(wa)16.9(s)-286.5(d)0(e)15.1(s)0(i)17.7(g)0(n)21.2(e)0(d)-280.8(w)0(i)14.9(t)0(h)-277.1(a)-291.4(tr)17.3(ea)20.4(tm)15.7(en)15.1(t)-287.7(g)0(r)19.6(o)0(u)15.5(p)-285.3(sa)14(mp)18.1(le)]TJ
-1.0015 -1.0528 TD
[(si)17.7(ze)-230(of)-230.7(n)]TJ
/F8 1 Tf
3.2891 0 TD
(=)Tj
/F3 1 Tf
0.5406 0 TD
[(18)-229.2(to)-231.5(ha)20.8(ve)-229.6(80)15.5(%)-242.1(p)0(o)21.2(w)0(e)16.9(r)-241.4(\()]TJ
6.974 0 0 6.974 440.674 547.143 Tm
0.0001 Tc
(SD)Tj
/F8 1 Tf
9.963 0 0 9.963 449.405 547.143 Tm
0 Tc
(=)Tj
/F3 1 Tf
0.5406 0 TD
[(65)15.5(%)-242.1(\()0(l)17.3(o)0(g)-229.2(s)0(c)19.6(a)0(l)18.5(e)0(\))-231.1(a)0(t)-231.9(a)0(n)]TJ
/F8 1 Tf
-14.6019 -1.0471 TD
(a=)Tj
/F3 1 Tf
1.1723 0 TD
[(0.)15.9(05)21.2(,)-233.7(t)0(w)14.9(o)0(-)19.6(t)0(a)12.8(i)0(l)16.5(e)0(d)-223.9(t)0(e)18.4(s)0(t)17.7(\))-235.7(to)-231.5(de)20.8(te)18.4(ct)-231.9(a)-234.5(r)0(e)19.2(d)0(u)15.5(c)0(t)18.4(i)0(o)18.9(n)-239.8(of)-225.1(50)21.2(%)-242.1(i)0(n)-225.8(t)0(h)18.9(e)]TJ
-1.1723 -1.0528 TD
[(ch)15.1(an)15.1(ge)-497(fr)12.4(om)-499.8(ba)15.1(se)19.6(li)16.5(ne)-502.7(in)-499(th)13.2(e)-507.6(p)0(e)15.1(r)0(c)19.2(e)0(n)15.1(t)0(a)18.4(g)0(e)-502.7(o)0(f)-503.9(e)0(o)20.8(s)0(i)17.7(n)0(o)15.5(p)0(h)21.2(i)0(l)16.5(s)]TJ
T*
[(be)15.1(tw)14.9(ee)20.4(n)-325.1(t)0(r)17.3(e)0(a)14.7(t)0(m)15.7(e)0(n)20.8(t)-327.5(gr)19.6(ou)21.2(ps)14.4(.)]TJ
/F7 1 Tf
9.8617 -2.4356 TD
[(Res)-7.8(ults)]TJ
/F5 1 Tf
-9.8617 -1.8494 TD
[(Pat)-8.8(ient)-332.6(allo)-7.8(cation)-339.8(and)-338(exclusion)-338.4(fr)23.3(om)-335.5(sputum)-336.4(analys)-8.6(is)]TJ
/F3 1 Tf
1.0015 -2.0998 TD
[(Fo)16.3(rt)17.3(y)-319.4(e)0(l)18.5(i)0(g)18.8(i)0(b)18.8(l)0(e)-311.6(p)0(a)20.8(t)0(i)16.5(e)0(n)15.1(t)0(s)-306.7(w)0(e)16.9(r)0(e)-310.8(r)0(a)19.2(n)0(d)15.5(o)0(m)18.1(i)0(z)18.4(e)0(d)-309.2(t)0(o)-305.5(a)0(c)14.7(t)0(i)16.5(v)0(e)-309.2(t)0(r)17.3(e)0(a)20.4(t)0(-)]TJ
-1.0015 -1.0528 TD
[(me)12(nt)-260(\(1)19.6(9)-268.2(t)0(o)-260(m)0(o)18.1(n)0(t)13.2(e)0(l)18.5(u)0(k)21.2(a)0(s)13.9(t)0(,)-259.6(2)0(1)-257.6(t)0(o)-260(p)0(l)18.8(a)0(c)14.7(e)0(b)20.8(o)0(\))13.9(.)-267.8(Th)17.1(re)19.2(e)-268.6(p)0(a)15.1(t)0(i)16.5(e)0(n)20.8(t)0(s)-261.2(i)0(n)]TJ
0 -1.0471 TD
[(th)13.2(e)-615.8(m)0(o)18.1(n)0(t)18.9(e)0(l)12.8(u)0(k)21.2(a)0(s)19.6(t)-617.7(gr)14(ou)21.2(p)-621(d)0(i)18.9(d)-615.3(no)15.5(t)-617.7(h)0(a)20.8(v)0(e)-610.8(W)83.4(ee)14.7(k-)19.6(4)-615.3(s)0(p)14.3(u)0(t)18.9(u)0(m)]TJ
0 -1.0527 TD
[(sa)13.9(mp)18.1(le)18.4(s)-519.8(a)0(v)15.1(a)0(i)18.5(l)0(a)18.4(b)0(l)18.9(e)0(.)-508(T)69.1(wo)-511.9(of)-509.6(th)18.9(es)19.6(e)-519(p)0(a)15.1(t)0(i)16.5(e)0(n)20.8(t)0(s)-511.6(w)0(e)16.9(r)0(e)-510(d)0(i)18.9(s)0(c)13.9(o)0(n)21.2(-)]TJ
0 -1.0471 TD
[(ti)16.5(nu)15.5(ed)20.8(,)-387.3(o)0(n)21.2(e)-382.4(ow)17.3(in)13.2(g)-382(t)0(o)-373.8(a)0(n)-371.8(a)0(d)15.1(v)0(e)15.1(r)0(s)18.4(e)-382.4(ev)20.8(en)15.1(t)-384.4(\()0(a)19.2(b)0(d)15.5(o)0(m)18.1(i)0(n)18.9(a)0(l)-374.2(p)0(a)15.1(i)0(n)18.8(\))]TJ
0 -1.0528 TD
[(an)15.1(d)-450.3(o)0(n)15.5(e)-450.7(ow)17.3(in)18.9(g)-456(t)0(o)-442.1(a)-450.7(pr)13.9(ot)18.9(oc)15.1(ol)-442.1(de)20.8(vi)13.2(at)18.5(io)18.9(n.)-445(D)12.4(a)0(t)12.8(a)-450.7(fr)18(om)-442.8(on)15.5(e)]TJ
0 -1.0471 TD
[(pl)13.2(ac)20.4(eb)15.1(o)-370.7(p)0(a)20.8(t)0(i)16.5(e)0(n)15.1(t)-367.3(we)16.9(re)-362(ex)15.1(cl)18.4(ud)15.5(ed)-360.4(fr)18(om)-363.2(sp)14.3(ut)18.9(um)-363.2(an)20.8(al)18.5(ys)14.4(is)-363.6(be)20.8(-)]TJ
0 -1.0528 TD
[(ca)14.7(us)20(e)-228.8(a)0(n)-212.5(u)0(p)15.5(p)0(e)20.8(r)-224.3(re)19.2(sp)14.4(ir)17.3(at)18.5(or)19.6(y)-228.4(t)0(r)17.3(a)0(c)20.4(t)-225.1(in)18.8(fe)13.5(ct)18.5(io)18.9(n)-222.7(o)0(c)15.1(c)0(u)20.8(r)0(r)12.3(e)0(d)-212.5(w)0(i)14.9(t)0(h)18.8(i)0(n)-214.5(5)]TJ
0 -1.0471 TD
[(da)15.1(ys)-378.3(af)13.5(te)18.4(r)-389.3(r)0(a)13.5(n)0(d)21.2(o)0(m)18.1(i)0(z)12.8(a)0(t)18.5(i)0(o)18.9(n)-387.7(\(p)13.9(re)19.2(sp)14.4(ec)20.4(if)17.3(ie)18.4(d)-393.4(c)0(r)19.2(i)0(t)16.5(e)0(r)19.2(i)0(a)12.8(\))0(.)-378.3(A)0(l)14.9(l)-390.1(al)18.5(lo)18.8(-)]TJ
0 -1.0528 TD
-0.0177 Tc
[(c)-17.7(a)-3(t)-17.7(e)0.7(d)-598.9(p)-17.7(at)-17.7(ie)-17.7(nt)-17.7(s)-591.9(w)-17.7(er)-17.7(e)-596(i)-17.7(nc)-17.7(lu)-17.7(de)-17.7(d)-588.7(i)-17.7(n)-590.7(c)-17.7(li)-17.7(n)-4.5(i)-17.7(ca)-17.7(l)-591.1(e)-17.7(nd)-17.7(po)-17.7(in)-17.7(t)-590.7(a)-17.7(nd)]TJ
0 -1.0471 TD
0 Tc
[(sa)13.9(fe)19.2(ty)-316.9(an)20.8(al)12.8(ys)20(es)19.6(.)]TJ
/F5 1 Tf
0 -2.8396 TD
[(Effect)-341(of)-339.6(montelu)-8.7(kast)-337.1(on)-331.6(sputu)-7.4(m)-334.8(and)-338(blood)-336.2(cell)-338.7(counts)]TJ
/F3 1 Tf
1.0015 -1.8494 TD
[(Th)17.1(e)-325.5(c)0(h)15.1(a)0(r)19.2(a)0(c)14.7(t)0(e)18.4(r)0(i)17.3(s)0(t)17.7(i)0(c)18.4(s)-326.3(of)-316.1(sp)20(ut)13.2(um)-312(ce)14.7(ll)16.5(s)-320.6(i)0(n)-316.9(e)0(a)14.7(c)0(h)-314.9(g)0(r)19.6(o)0(u)15.5(p)-325.1(we)16.9(re)]TJ
-1.0015 -1.0471 TD
[(ex)15.1(am)17.7(in)18.8(ed)-309.2(be)15.1(fo)19.6(re)-310.8(tr)17.3(ea)14.7(tm)15.7(en)20.8(t.)-310.8(El)14.7(ev)20.8(en)-309.2(pa)15.1(ti)16.5(en)20.8(ts)-312.4(in)-305.5(th)13.2(e)-314.2(m)0(o)12.4(n)0(t)18.9(e)0(-)]TJ
0 -1.0528 TD
[(lu)13.2(ka)20.8(st)-460.3(gr)13.9(ou)21.2(p)-467.4(a)0(n)15.1(d)-467.4(17)-462.5(i)13.9(n)-473.1(th)18.9(e)-467.8(p)0(l)18.9(a)0(c)14.7(e)0(b)20.8(o)-473.1(gr)19.6(ou)21.2(p)-473.1(h)0(a)20.8(d)-467.4(sp)14.3(ut)18.9(um)]TJ
0 -1.0471 TD
[(eo)15.1(si)17.7(no)15.5(ph)21.2(il)16.5(s)]TJ
/F8 1 Tf
4.7402 0 TD
(>)Tj
/F3 1 Tf
0.5463 0 TD
[(3%)-299.8(at)-305.9(ba)20.8(se)13.9(li)16.5(ne)-297.8(vi)13.2(si)17.7(t.)-299.4(Co)16.5(mp)18.1(ar)13.5(ed)-297.8(wi)14.9(th)-299.8(mo)12.4(nt)18.9(e-)]TJ
-5.2865 -1.0527 TD
[(lu)13.2(ka)20.8(st)17.7(,)-421.5(t)0(h)18.8(e)-422.3(pr)13.9(op)21.2(or)19.6(ti)16.5(on)-411.2(of)-412.8(sp)14.4(ut)18.8(um)-414.4(eo)20.8(si)17.7(no)15.5(ph)15.5(il)22.2(s)-423.1(a)0(t)-414(b)0(a)20.8(s)0(e)13.9(l)0(i)16.5(n)0(e)]TJ
0 -1.0471 TD
[(wa)16.9(s)-474.3(h)0(i)18.9(g)0(h)21.2(e)0(r)-464.5(i)0(n)-459.2(t)0(h)18.8(e)-473.5(pl)18.9(ac)20.4(eb)15.1(o)-467.4(g)0(r)14(o)0(u)21.2(p)-473.1(w)12.4(h)0(e)15.1(t)0(h)18.9(e)0(r)-464.5(i)0(n)18.8(c)0(l)18.4(u)0(d)15.5(i)0(n)18.9(g)-467.4(al)18.5(l)]TJ
0 -1.0528 TD
[(su)14.4(bj)18.9(ec)14.7(t)13.9(s)-309.2(\(t)17.3(ab)20.8(le)-294.5(2\))-310.4(or)-310.4(an)-7.6(alysing)-319(only)-318.4(patients)-322.5(with)-319(sputum)]TJ
T*
[(eosin)-7.8(ophil)-8.6(s)]TJ
/F8 1 Tf
4.928 0 TD
(>)Tj
/F3 1 Tf
0.5577 0 TD
[(3%)-402.2(\(mean)-407.7(eosinophil)-10.7(s)-400.3(o)0(f)-401.5(10.6)-401(and)-401(17.1%)]TJ
-5.4857 -1.0471 TD
[(for)-341.2(monteluk)-8.7(ast)-336.3(and)-338.4(placebo)-8.9(,)-330.4(respec)-8.6(tively\).)]TJ
1.0015 -1.0527 TD
[(Wh)14.4(il)16.5(e)-223.1(t)0(h)18.9(e)0(r)13.5(e)-223.1(wa)16.9(s)-223.9(s)0(o)20(m)0(e)-221.3(v)0(a)20.8(r)0(i)17.3(a)0(b)15.1(i)0(l)16.5(i)0(t)22.2(y)-228.4(in)-214.5(re)19.2(sp)14.4(on)21.2(se)19.6(,)-228(t)0(h)18.9(e)-223.1(ef)24.9(fe)19.2(ct)18.4(s)]TJ
-1.0015 -1.0471 TD
[(of)-230.7(tr)17.3(ea)20.4(tm)15.7(en)15.1(t)-236.5(o)0(n)-223.5(s)0(p)14.4(u)0(t)18.9(u)0(m)-226.6(e)0(o)15.1(s)0(i)17.7(n)0(o)21.2(p)0(h)15.5(i)0(l)16.5(s)-235.3(in)-225.8(mo)18.1(st)-227(pa)15.1(ti)16.5(en)20.8(ts)-227(wi)14.9(th)18.8(in)]TJ
0 -1.0527 TD
[(ea)14.7(ch)-149.9(gr)19.6(ou)15.5(p)-160.1(w)12.4(er)13.5(e)-160.5(s)0(i)17.7(m)0(i)21.4(l)0(a)12.8(r)60.2(.)-154(F)0(o)16.3(u)0(r)-151.1(w)0(e)16.9(e)0(k)20.8(s)-161.3(of)-151.1(tr)17.3(ea)20.4(tm)15.7(en)15.1(t)-156.8(w)0(i)14.9(t)0(h)-151.9(m)0(o)18.1(n)0(-)]TJ
0 -1.0471 TD
[(te)12.8(lu)18.9(ka)20.8(st)-460.3(si)17.7(gn)15.5(if)17.3(ic)18.5(an)20.8(tl)16.5(y)-467.4(r)0(e)13.5(d)0(u)21.2(c)0(e)14.7(d)-467.4(t)13.9(h)0(e)-462.9(p)0(e)20.8(r)0(c)13.5(e)0(n)20.8(t)0(a)18.4(g)0(e)-457.2(o)0(f)-458.4(s)0(p)14.3(u)0(t)18.9(u)0(m)]TJ
0 -1.0528 TD
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0 -1.0471 TD
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[(si)17.7(mi)15.7(la)18.4(r)-298.3(b)0(e)20.8(t)0(w)14.9(e)0(e)14.7(n)-296.7(mo)18.1(nt)18.9(el)18.4(uk)15.5(as)19.6(t)-299.1(a)0(n)20.8(d)-296.7(pl)18.9(ac)14.7(eb)20.8(o.)-291.4(N)12.4(o)-296.7(pa)15.1(ti)16.5(en)20.8(t)-299.1(w)0(a)16.9(s)]TJ
T*
[(di)18.9(sc)13.9(on)21.2(ti)16.5(nu)15.5(ed)-314.9(du)21.2(e)-325.5(t)0(o)-316.9(a)-325.5(l)13.9(a)0(b)15.1(o)0(r)19.6(a)0(t)12.8(o)0(r)19.6(y)-325.1(ad)20.8(ve)15.1(rs)18.4(e)-325.5(e)0(x)20.8(p)0(e)15.1(r)0(i)17.3(e)0(n)15.1(c)0(e)20.4(.)]TJ
/F7 1 Tf
34.3652 41.8597 TD
[(Discu)-10.9(ssion)]TJ
/F3 1 Tf
-8.1659 -2.0998 TD
[(In)-156.8(th)18.8(is)-158.7(ra)19.2(nd)15.5(om)18.1(iz)18.4(ed)-155.6(tr)17.3(ia)18.4(l,)-151.5(da)15.1(il)16.5(y)-160.1(t)0(r)17.3(e)0(a)14.7(t)0(m)15.7(e)0(n)20.8(t)-168.2(w)12.4(i)0(t)16.5(h)-165.8(mo)18.1(nt)18.9(el)18.5(uk)15.5(as)19.6(t)]TJ
-1.0015 -1.0755 TD
[(fo)13.9(r)-406.4(4)-410.5(we)16.9(ek)20.8(s)-411.7(r)0(e)19.2(d)0(u)15.5(c)0(e)20.4(d)-410.5(sp)20(ut)18.9(um)-403(an)15.1(d)-404.8(b)0(l)18.9(o)0(o)15.5(d)-404.8(eo)15.1(si)17.7(no)15.5(ph)21.2(il)16.5(s)-406(a)0(n)15.1(d)]TJ
T*
[(im)15.7(pr)13.9(ov)21.2(ed)-161.3(cl)18.4(in)18.8(ic)18.4(al)-158(as)13.9(t)13.9(h)0(m)12.4(a)-166.2(co)20.8(nt)13.2(ro)19.6(l)-168.2(c)0(o)20.8(m)0(p)18.1(a)0(r)13.5(e)0(d)-155.6(w)0(i)14.9(t)0(h)-157.6(p)0(l)18.9(a)0(c)14.7(e)0(b)20.8(o)0(.)-160.5(A)]TJ
T*
[(sm)16.9(al)12.8(l)-122.6(e)0(f)30.6(f)0(e)13.5(c)0(t)-112.4(o)0(n)-115.3(s)0(p)20(u)0(t)13.2(u)0(m)-112.8(e)0(o)15.1(s)0(i)17.7(n)0(o)21.2(p)0(h)15.5(i)0(l)16.5(s)-121.5(wa)16.9(s)-121.5(s)0(e)14(e)0(n)-110.1(a)0(f)13.5(t)0(e)18.4(r)-121.9(1)-126(w)0(e)16.9(e)0(k)-115.8(a)0(n)20.8(d)]TJ
T*
[(th)13.2(is)-249.8(wa)16.9(s)-263.7(s)0(i)17.7(g)0(n)15.5(i)13.9(fi)11.6(ca)20.4(nt)-254.3(af)19.2(te)18.4(r)-264.1(4)-262.5(we)16.9(ek)15.1(s)-258(o)0(f)-253.5(t)0(h)18.8(e)0(r)13.5(a)0(p)20.8(y)67.5(.)-256.5(T)0(h)17.1(e)0(s)13.9(e)-262.9(re)19.2(su)20(lt)16.5(s)]TJ
T*
[(ra)13.5(is)17.7(e)-166.2(t)0(h)18.8(e)-171.9(po)21.2(ss)18.9(ib)13.2(il)22.2(it)16.5(y)-171.5(t)0(h)18.9(a)0(t)-158(t)0(h)18.9(e)-171.9(de)20.8(cr)19.2(ea)14.7(se)19.6(s)-172.7(i)13.9(n)-171.5(s)0(p)20(u)0(t)18.9(u)0(m)-164(e)0(o)20.8(s)0(i)17.7(n)0(o)15.5(p)0(h)21.2(i)0(l)16.5(s)]TJ
T*
[(mi)15.7(gh)15.5(t)-321.8(h)0(a)15.1(v)0(e)-314.9(c)0(o)20.8(n)0(t)13.2(r)0(i)17.3(b)0(u)21.2(t)0(e)18.4(d)-325.1(to)-316.9(th)18.8(e)-325.5(c)0(l)18.5(i)0(n)18.9(i)0(c)12.8(a)0(l)-311.6(i)0(m)15.7(p)0(r)13.9(o)0(v)21.2(e)0(m)17.7(e)0(n)15.1(t)0(.)]TJ
1.343 -1.0471 TD
[(Th)17.1(is)-323.8(is)-323.8(th)18.9(e)-331.2(f)0(i)17.3(r)0(s)18.4(t)-333.2(re)19.2(po)15.5(rt)-324.2(of)-321.8(th)18.8(e)-331.2(e)0(f)24.9(f)0(e)19.2(c)0(t)-323(o)0(f)-321.8(m)0(o)12.4(n)0(t)18.9(e)0(l)18.4(u)0(k)15.5(a)0(s)19.6(t)-333.2(on)]TJ
-1.343 -1.0755 TD
[(ai)12.8(rw)15.7(ay)-201.1(eo)15.1(si)17.7(no)21.2(ph)15.5(il)16.5(ic)-203.5(in)13.2(fl)17.3(am)17.7(ma)17.7(ti)16.5(on)-206.4(in)-203.1(hu)15.5(ma)17.7(ns)20(.)-216.6(T)0(h)17.1(e)-211.7(de)15.1(cr)19.2(ea)14.7(se)]TJ
T*
[(in)-299.8(eo)20.8(si)17.7(no)15.5(ph)21.2(il)16.5(s)-303.6(w)0(a)16.9(s)-303.6(id)18.9(en)15.1(ti)16.5(fi)17.3(ed)-292.2(by)-297.4(th)18.8(e)-302.8(r)0(e)19.2(p)0(e)15.1(a)0(t)18.4(e)0(d)-297.8(e)0(x)20.8(a)0(m)17.7(i)0(n)13.2(a)0(t)18.5(i)0(o)18.8(n)]TJ
T*
[(of)-208(in)18.9(du)15.5(ce)20.4(d)-217(s)0(p)20(u)0(t)18.9(u)0(m)12.4(,)-210.9(a)-217.4(m)0(e)17.7(t)0(h)18.9(o)0(d)-206.4(w)0(h)17.3(i)0(c)18.4(h)-217(is)-204.3(no)15.5(ni)18.9(nv)21.2(as)14(iv)18.8(e)-217.4(a)0(n)20.8(d)-217(ha)20.8(s)]TJ
T*
[(be)15.1(en)-400.3(sh)20(ow)17.3(n)-404.8(t)0(o)-402.3(b)0(e)-394.6(s)0(u)14.4(c)0(c)20.4(e)0(s)19.6(s)0(f)12.8(u)0(l)18.9(,)-404.4(re)13.5(li)22.2(ab)15.1(le)-397(an)15.1(d)-404.8(r)0(e)13.5(s)0(p)20(o)0(n)21.2(s)0(i)17.7(v)0(e)-400.3(t)0(o)]TJ
T*
[(ch)15.1(an)15.1(ge)-275.1(wi)14.9(th)-277.1(tr)17.3(ea)14.7(t)13.9(m)0(e)12(n)0(t)-277.1([)0(2)19.6(8].)-288(The)-302.7(effect)-290.2(of)-299(mont)-8.6(elukast)-302.3(on)]TJ
T*
[(blood)-245.2(eosinoph)-10.1(ils)-235.9(has)-242.9(also)-240.3(been)-242.9(demonstra)-10.3(ted)-238.4(in)-237.2(p)-6.5(revious)]TJ
0 -1.0698 TD
[(studi)-9.8(es)-333.2([16,)-340(17].)]TJ
1.0015 -1.0527 TD
[(Th)17.1(e)-240.2(r)0(e)19.2(s)0(u)20(l)0(t)16.5(s)0(,)-224.3(n)0(o)15.5(t)-236.5(co)20.8(nf)13.9(ou)21.2(nd)15.5(ed)-223.9(by)-229.2(ot)18.9(he)20.8(r)-235.7(a)0(s)13.9(t)0(h)18.9(m)0(a)-227(t)0(r)17.3(e)0(a)14.7(t)13.9(me)12(nt)18.9(s,)]TJ
-1.0015 -1.0755 TD
[(we)16.9(re)-305.1(ob)15.5(ta)18.4(in)18.8(ed)-303.5(in)-299.8(pa)15.1(ti)16.5(en)20.8(ts)-301(wi)14.9(th)-299.8(ch)15.1(ro)19.6(ni)13.2(c)-308.5(a)0(s)19.6(t)0(h)13.2(m)13.2(a)-314.2(an)20.8(d)-313.8(w)0(i)14.9(t)0(h)-299.8(a)]TJ
T*
[(re)13.5(la)18.4(ti)16.5(ve)20.8(ly)-419.3(sm)11.2(al)18.5(l)-429.9(s)0(a)19.6(m)0(p)18.1(l)0(e)-419.7(s)0(i)17.7(z)0(e)14.7(.)-427.2(Mo)19.3(nt)13.2(el)18.5(uk)21.2(as)13.9(t)-429.9(t)13.9(re)13.5(at)18.5(me)17.7(nt)18.8(,)-432.9(d)0(e)20.8(-)]TJ
T*
[(sp)14.4(it)16.5(e)-587.3(a)-587.3(l)0(o)18.8(w)0(e)11.2(r)-588.5(ba)20.8(se)13.9(li)22.2(ne)15.1(,)-586.5(d)0(e)15.1(c)0(r)19.2(e)0(a)14.7(s)0(e)19.6(d)-586.9(sp)14.3(ut)18.9(um)-579.4(eo)15.1(si)17.7(no)21.2(ph)15.5(il)16.5(s,)]TJ
T*
[(wh)17.3(il)16.5(e)-274.3(a)0(n)-269.4(i)0(n)18.9(c)0(r)19.2(e)0(a)14.7(s)0(e)-264.9(w)0(a)16.9(s)-275.1(ob)15.5(se)19.6(rv)14(ed)-263.7(in)-265.7(th)18.9(e)-274.3(p)0(l)13.2(a)0(c)20.4(e)0(b)15.1(o)-273.9(gr)19.6(ou)15.5(p.)-262.9(Th)17.1(e)]TJ
T*
[(di)13.2(re)19.2(ct)18.4(io)18.9(n)-279.6(o)0(f)-264.9(t)0(h)18.9(e)-274.3(ch)15.1(an)20.8(ge)15.1(s,)-264.1(de)15.1(sp)20(it)16.5(e)-274.3(b)0(a)15.1(s)0(e)19.6(l)0(i)16.5(n)0(e)-263.7(d)0(i)18.9(f)14.7(fe)19.2(re)19.2(nc)15.1(es)19.6(,)-279.2(p)0(r)19.6(o)0(-)]TJ
0 -1.0698 TD
[(vi)13.2(de)20.8(d)-387.7(s)0(t)17.7(r)0(o)13.9(n)0(g)-377.1(e)0(v)15.1(i)0(d)18.9(e)0(n)20.8(c)0(e)-383.6(f)0(o)19.6(r)-389.3(a)-388.1(t)0(r)17.3(e)0(a)14.7(t)0(m)15.7(e)0(n)20.8(t)-390.1(ef)24.9(fe)19.2(ct)-379.9(by)-377.1(wo)17.3(rk)13.9(in)18.8(g)]TJ
0 -1.0755 TD
[(ag)15.1(ai)18.4(ns)14.3(t)-293.4(c)0(h)20.8(a)0(n)15.1(g)0(e)20.8(s)-292.2(ex)15.1(pe)15.1(ct)18.5(ed)]TJ
/F5 1 Tf
10.2259 0 TD
[(vi)12.8(a)]TJ
/F3 1 Tf
1.4852 0 TD
[(re)19.2(gr)13.9(es)19.6(si)17.7(on)-286.1(to)-282.7(th)18.8(e)-297.1(m)0(e)17.7(a)0(n)-286.5([)0(2)19.6(9].)]TJ
-11.7112 -1.0755 TD
[(In)-293.3(the)-295.3(absence)-298.4(of)-293.3(a)-291.4(treatmen)-11.1(t)-287.7(effect,)-290.6(the)-295.3(regression)-300.9(to)-288.4(the)]TJ
T*
[(mean)-524.8(woul)-9.4(d)-518.6(cause)-524.1(changes)-525.6(in)-521.8(the)-517.2(op)-7.2(posite)-523.1(direc)-8.6(tion,)]TJ
T*
[(reduci)-9.4(ng)-360(the)-357.9(treatmen)-11.1(t)-356(effect.)-353.2(Fu)-6.4(ture)-360.2(studies)-360(mig)-7.8(ht)-356.7(con-)]TJ
T*
[(sider)-362.2(stratifying)-364.1(pati)-8.2(ents)-354.2(by)-354.3(basel)-8.2(ine)-352.2(eo)-7.6(sinophil)-355.9(p)-6.5(ercent-)]TJ
T*
[(age)-8.8(s,)-332.4(to)-334(ensure)-338.2(they)-341.6(are)-334.7(simil)-9.6(ar)-333.6(in)-334(the)-340.8(treatmen)-11.1(t)-333.2(groups)-7.4(.)]TJ
1.0015 -1.0471 TD
[(St)14(an)20.8(da)15.1(rd)19.6(,)-489.8(s)0(t)17.7(u)0(d)21.2(y)0(-)13.9(w)0(i)14.9(d)0(e)-474.3(m)0(e)12(t)13.9(ho)15.5(do)15.5(l)13.9(o)0(g)15.5(y)-490.2(t)13.9(o)-490.2(en)20.8(su)14.4(re)-475.8(sp)14.3(ut)18.9(um)]TJ
-1.0015 -1.0755 TD
[(in)13.2(du)21.2(ct)18.5(io)13.2(n)-399.1(a)0(n)15.1(d)-399.1(pr)13.9(oc)20.8(es)13.9(si)17.7(ng)-394.2(co)20.8(ns)20(is)12(t)13.9(e)0(n)15.1(c)0(y)-394.6(w)0(a)16.9(s)-400.3(em)12(pl)18.9(oy)21.2(ed)15.1(;)-401.5(a)0(l)18.5(l)]TJ
T*
[(te)12.8(ch)20.8(ni)18.9(ci)12.8(an)20.8(s)-400.3(w)0(e)16.9(r)0(e)-396.2(t)0(r)17.3(a)0(i)18.5(n)0(e)15.1(d)-399.1(ce)14.7(nt)18.9(ra)19.2(ll)16.5(y)73.2(.)-404.4(T)12.2(h)0(e)-394.6(u)0(s)20(e)-405.2(of)-390.1(tw)14.9(o)-399.1(i)0(n)13.2(d)0(e)20.8(-)]TJ
T*
[(pe)15.1(nd)15.5(en)20.8(t)-185.2(a)0(n)20.8(d)-188.6(hi)18.9(gh)21.2(ly)-180.3(t)13.9(r)0(a)13.5(i)0(n)18.8(e)0(d)-178.3(h)0(a)20.8(e)0(m)17.7(a)0(t)12.8(o)0(l)18.9(o)0(g)21.2(y)-188.6(t)13.9(e)0(c)14.7(h)0(n)15.5(i)13.9(ci)12.8(an)20.8(s)-184.1(t)0(o)-174.6(r)0(e)13.5(a)0(d)]TJ
T*
[(th)13.2(e)-302.8(c)0(y)15.1(t)0(o)18.8(s)0(p)20(i)0(n)13.2(s)-303.6(mi)15.7(ni)18.9(mi)15.7(ze)14.7(d)-302.4(p)0(o)15.5(t)0(e)18.4(n)0(t)18.8(i)0(a)18.4(l)-310.4(so)20(ur)13.9(ce)20.4(s)-309.2(o)0(f)-293.3(b)0(i)18.9(a)0(s)14(.)-302(A)-238(v)0(a)20.8(l)0(i)16.5(-)]TJ
T*
[(da)15.1(ti)16.5(on)-223.5(of)-225.1(th)18.8(es)19.6(e)-234.5(s)0(a)19.6(m)0(e)-227(t)0(w)14.9(o)-234.1(sl)17.7(id)18.9(e)-234.5(r)0(e)19.2(a)0(d)15.1(e)0(r)19.2(s)-235.3(ha)20.8(d)-234.1(p)0(r)19.6(e)0(v)15.1(i)0(o)18.9(u)0(s)14.3(l)13.9(y)-234.1(b)0(e)15.1(e)0(n)]TJ
T*
[(sh)14.4(ow)17.3(n)-325.1(t)0(o)-311.2(b)0(e)-314.9(h)0(i)13.2(g)0(h)21.2(l)0(y)-316.9(r)0(e)19.2(p)0(e)15.1(a)0(t)18.4(a)0(b)15.1(l)0(e)-311.6(a)0(n)15.1(d)-325.1(co)20.8(nc)15.1(or)19.6(da)15.1(nt)-311.2([1)13.9(9].)]TJ
1.0015 -1.0471 TD
[(An)-290(in)18.9(hi)13.2(bi)18.9(ti)16.5(on)-286.1(of)-287.7(eo)15.1(si)17.7(no)21.2(ph)15.5(il)-285.1(ch)15.1(em)17.7(ot)18.9(ax)15.1(is)-289.6(by)-286.1(mo)18.1(nt)18.9(el)18.5(uk)15.5(as)19.6(t)]TJ
-1.0015 -1.0755 TD
[(ma)12(y)-382(e)0(x)20.8(p)0(l)18.9(a)0(i)18.4(n)-382(th)13.2(e)-376.8(r)0(e)13.5(s)0(u)20(l)0(t)16.5(s)-383.2(in)-373.8(th)18.9(is)-369.3(st)17.7(ud)15.5(y)73.2(.)-381.6(Cy)16.5(sL)101.3(T)69.1(s)-377.5(ha)15.1(ve)-371.8(be)15.1(en)]TJ
T*
[(sh)14.4(ow)17.3(n)-484.5(t)0(o)-476.2(a)0(t)18.4(t)0(r)17.3(a)0(c)14.7(t)-486.8(eo)20.8(si)17.7(no)15.5(ph)21.2(il)16.5(s,)-480.3(an)20.8(d)-484.5(L)91.8(T)-426(a)0(n)20.8(t)0(a)18.4(g)0(o)15.5(n)0(i)18.9(s)0(t)17.7(s)-485.7(co)15.1(ul)18.8(d)]TJ
ET
0 0 0 1 K
0 J 0 j 0.5 w 3.864 M []0 d
/GS3 gs
1 i 
102.18 632.169 m
102.18 774.072 l
98.325 774.072 m
102.18 774.072 l
99.827 771.13 m
102.18 771.13 l
99.827 767.815 m
102.18 767.815 l
99.827 761.366 m
102.18 761.366 l
99.827 764.307 m
102.18 764.307 l
98.392 758.572 m
102.247 758.572 l
99.895 755.63 m
102.247 755.63 l
99.895 752.315 m
102.247 752.315 l
99.895 745.866 m
102.247 745.866 l
99.895 748.807 m
102.247 748.807 l
98.459 743.072 m
102.314 743.072 l
99.961 740.131 m
102.314 740.131 l
99.961 736.815 m
102.314 736.815 l
99.961 730.366 m
102.314 730.366 l
99.961 733.307 m
102.314 733.307 l
98.526 727.288 m
102.381 727.288 l
100.028 724.347 m
102.381 724.347 l
100.028 721.032 m
102.381 721.032 l
100.028 714.583 m
102.381 714.583 l
100.028 717.524 m
102.381 717.524 l
98.309 711.289 m
102.165 711.289 l
99.812 708.347 m
102.165 708.347 l
99.812 705.032 m
102.165 705.032 l
99.812 698.583 m
102.165 698.583 l
99.812 701.524 m
102.165 701.524 l
98.376 695.289 m
102.232 695.289 l
99.879 692.348 m
102.232 692.348 l
99.879 689.032 m
102.232 689.032 l
99.879 682.583 m
102.232 682.583 l
99.879 685.524 m
102.232 685.524 l
98.443 679.789 m
102.299 679.789 l
99.946 676.848 m
102.299 676.848 l
99.946 673.532 m
102.299 673.532 l
99.946 667.083 m
102.299 667.083 l
99.946 670.024 m
102.299 670.024 l
98.51 664.005 m
102.366 664.005 l
100.013 661.064 m
102.366 661.064 l
100.013 657.749 m
102.366 657.749 l
100.013 651.299 m
102.366 651.299 l
100.013 654.241 m
102.366 654.241 l
98.227 648.005 m
102.082 648.005 l
99.729 645.064 m
102.082 645.064 l
100.013 641.749 m
102.366 641.749 l
99.729 635.3 m
102.082 635.3 l
99.729 638.241 m
102.082 638.241 l
98.51 632.005 m
102.366 632.005 l
107.651 632.131 m
182.151 632.131 l
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(l)Tj
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0.0472 1.0833 TD
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(l)Tj
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(l)Tj
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(l)Tj
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(l)Tj
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(l)Tj
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(l)Tj
ET
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169.035 644.948 m
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208.894 745.866 m
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207.525 727.288 m
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209.028 724.347 m
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209.028 721.032 m
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209.028 717.524 m
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207.309 711.289 m
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211.164 708.347 l
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208.811 698.583 m
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208.878 692.348 m
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208.878 689.032 m
211.231 689.032 l
208.878 682.583 m
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208.878 685.524 m
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208.945 676.848 m
211.298 676.848 l
208.945 673.532 m
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208.945 667.083 m
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208.945 670.024 m
211.298 670.024 l
207.51 664.005 m
211.365 664.005 l
209.012 661.064 m
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211.082 648.005 l
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208.729 635.3 m
211.082 635.3 l
208.729 638.241 m
211.082 638.241 l
207.51 632.005 m
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BT
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ET
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224.65 629.631 m
224.65 632.131 l
281.65 629.631 m
281.65 632.131 l
217.65 632.131 m
289.8 632.131 l
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BT
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(l)Tj
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(l)Tj
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(l)Tj
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(l)Tj
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(l)Tj
-9.5 -0.5416 TD
(l)Tj
0 -1.2083 TD
(l)Tj
-0.0417 -12.9584 TD
(l)Tj
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(l)Tj
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(l)Tj
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(l)Tj
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(l)Tj
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(l)Tj
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(l)Tj
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(l)Tj
-0.0361 0.0833 TD
(l)Tj
-0.0056 0.1667 TD
(l)Tj
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(l)Tj
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(l)Tj
-9.4528 1.375 TD
(l)Tj
-0.0056 0.1667 TD
(l)Tj
0.0056 -14 TD
(l)Tj
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(l)Tj
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(l)Tj
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(l)Tj
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(l)Tj
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(l)Tj
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(l)Tj
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(l)Tj
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(l)Tj
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(l)Tj
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(l)Tj
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(70)Tj
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(a\))Tj
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[(Pre)-4124(Post)]TJ
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(Montelukast)Tj
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[(Pre)-4124(Post)]TJ
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ET
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174.651 631.881 m
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224.65 631.732 m
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281.65 631.732 m
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BT
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(=)Tj
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[(16\);)-335.6(and)-327(b\))-337.4(placebo)-326.1(\(n)]TJ
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[(20\))-328.2(on)]TJ
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[(sputum)-332.7(eosinophils)-333.9(at)-338.6(baseline)-334.6(\(Pre\))-335.3(and)-341.2(after)-338.7(4)-339.4(weeks)-332.6(\(Post\))-337.7(of)-337.4(therapy)64(.)]TJ
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0 -1.0599 TD
[(mean)-430.9(values.)-436(The)-436.4(percentage)-431.7(of)-437(eosinoph)14.3(ils)-440.7(\(mean\213)]TJ
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(SD)Tj
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[(\))-439.1(decreased)-432.6(from)]TJ
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[(14.54\21314.40)-322.1(to)-325.4(17.90\21319.79)-322.1(in)-332.5(the)-329.4(placebo)-326.1(group)-331.1(\(p)]TJ
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445.566 695.126 m
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399.816 626.127 m
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445.316 626.127 m
445.316 629.126 l
535.315 626.127 m
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490.315 626.127 m
490.315 629.126 l
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BT
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[(T)30(reatment weeks)]TJ
ET
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533.92 697.376 534.815 696.481 534.815 695.376 c
534.815 694.272 533.92 693.376 532.815 693.376 c
531.711 693.376 530.815 694.272 530.815 695.376 c
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536.386 664.376 537.282 663.481 537.282 662.376 c
537.282 661.272 536.386 660.376 535.282 660.376 c
534.177 660.376 533.282 661.272 533.282 662.376 c
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355.066 700.126 m
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358.171 702.126 359.066 701.231 359.066 700.126 c
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355.961 698.126 355.066 699.022 355.066 700.126 c
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447.566 710.522 446.67 709.626 445.566 709.626 c
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448.17 680.876 449.066 679.981 449.066 678.876 c
449.066 677.772 448.17 676.876 447.066 676.876 c
445.961 676.876 445.066 677.772 445.066 678.876 c
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BT
0 10 -10 0 318.301 648.146 Tm
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(Changes in blood eosinophils)Tj
2.8069 -1 TD
(10)Tj
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(6)Tj
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( cells\341mL)Tj
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(-1)Tj
ET
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347.816 629.627 m
347.816 770.842 l
S
BT
10 0 0 10 327.6 767.693 Tm
/GS4 gs
(  0.2)Tj
ET
/GS3 gs
344.316 770.626 m
347.816 770.626 l
S
BT
10 0 0 10 327.6 732.193 Tm
/GS4 gs
(  0.1)Tj
ET
/GS3 gs
344.316 735.126 m
347.816 735.126 l
S
BT
10 0 0 10 328.45 696.693 Tm
/GS4 gs
(    0)Tj
ET
/GS3 gs
344.316 699.626 m
347.816 699.626 l
S
BT
10 0 0 10 328.45 661.76 Tm
/GS4 gs
(-0.1)Tj
ET
/GS3 gs
344.316 664.693 m
347.816 664.693 l
S
BT
10 0 0 10 327.6 626.544 Tm
/GS4 gs
(-0.2)Tj
ET
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344.316 629.477 m
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354.816 629.627 m
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354.816 626.627 m
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447.316 668.376 m
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535.065 648.376 m
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442.816 729.626 m
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532.315 647.626 m
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529.815 679.626 m
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529.815 712.126 m
535.815 712.126 l
S
BT
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7.97 0 0 7.97 309.316 587.622 Tm
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14.7242 0 TD
(*)Tj
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[(\))-296.8(and)-291.4(placebo)-290.5(\()]TJ
/F13 1 Tf
6.039 0 TD
(s)Tj
/F3 1 Tf
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[(\))-296.8(o)0(n)-294.6(peripheral)]TJ
-22.5984 -1.067 TD
[(blood)-326.2(eosinophils)-319.7(at)-331.5(baseline)-320.4(\(BL\))-326.6(and)-327(2)-325.1(and)-327(4)-332.2(weeks)-318.4(after)-331.6(allocation.)]TJ
0 -1.0599 TD
[(V)99.2(ertical)-267(bars)-262.3(represent)-266.5(mean\213)]TJ
5.579 0 0 5.579 403.257 570.671 Tm
(SEM)Tj
7.97 0 0 7.97 414.652 570.671 Tm
[(.)-269.3(Over)-263.5(the)-272.5(4-week)-258.3(period,)-265.3(montelukast)]TJ
-13.2162 -1.0599 TD
[(caused)-504.8(a)-509(significant)-497.9(\(p)]TJ
/F8 1 Tf
9.6241 0 TD
(=)Tj
/F3 1 Tf
0.5548 0 TD
[(0.009\))-500.8(reduction)-496.2(compared)-499.9(with)-503.9(placebo)-503.9(in)]TJ
-10.1789 -1.067 TD
[(peripheral)-329.6(blood)-326.2(eosinophils.)]TJ
8.966 0 0 8.966 527.527 797.499 Tm
(15)Tj
7.472 0 0 7.472 194.91 797.499 Tm
0.0001 Tc
[(LEUKOTRIEN)-13.5(ES)-331(AND)-334.5(SPUT)-9.3(UM)-331.7(EOSINOP)-11.5(HILIA)-335.6(I)0.1(N)-333.2(ASTH)-10.2(MA)]TJ
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BT
/F3 1 Tf
9.963 0 0 9.963 58.28 357.449 Tm
0 g
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[(po)15.5(te)18.4(nt)18.9(ia)18.4(ll)16.5(y)-182.9(b)0(l)18.9(o)0(c)20.8(k)-182.9(th)18.9(es)19.6(e)-183.3(e)0(f)30.6(f)0(e)13.5(c)0(t)18.4(s)0(.)-173.1(F)11.4(or)-173.8(ex)20.8(am)17.7(pl)13.2(e,)-166.6(S)]TJ
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0.0001 Tc
[(P)96.9(ADA)]TJ
/F5 1 Tf
9.963 0 0 9.963 253.644 357.449 Tm
0 Tc
[(et)-175(al)]TJ
/F3 1 Tf
1.6332 0 TD
0.1768 Tc
[(.[)176.8(7)190.7(])]TJ
-21.2428 -1.0698 TD
0 Tc
[(showe)-9.3(d)-211.3(L)86.2(TD)]TJ
7.472 0 0 6.641 109.134 345.09 Tm
0 Tw
(4)Tj
9.963 0 0 9.963 114.973 346.79 Tm
[(to)-214.5(be)-212.5(a)-211.7(potent)-220.3(and)-213.2(selec)-8.6(tive)-213.1(chemo)-7.8(attractan)-11.5(t)]TJ
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[(for)-443.7(human)-439.8(eosin)-7.8(ophil)-8.6(s)-434.4(a)0(t)-442.5(physi)-7.4(ologically)-444.7(relev)-8.6(ant)-443.2(con-)]TJ
T*
[(centr)-8.6(ations.)-227.6(Using)-227.6(radio)-8.2(labelled)-230.7(eosin)-7.8(ophils)-226.8(in)-225.8(guinea)-7.8(-pig)]TJ
T*
[(conjun)-7.4(ctiva,)-470.7(C)]TJ
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(HAN)Tj
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0 Tc
[(et)-470.9(al)]TJ
/F3 1 Tf
1.9519 0 TD
[(.)-467([9])-466.4(show)-8.2(ed)-468.6(adminis)-9.1(tration)-475.4(of)]TJ
-9.9471 -1.0698 TD
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[(LT)-80.5(D)]TJ
7.472 0 0 6.641 76.705 302.457 Tm
0 Tc
(4)Tj
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[(induce)-7.8(d)-365(a)-365.4(2.5-fol)-10.5(d)-359.3(incre)-8.6(ase)-368.5(in)-362.4(conjun)-7.4(ctiv)-8.2(al)-362.8(radio)-8.2(-)]TJ
-2.5835 -1.0698 TD
[(activity)-483.1(\(a)-470.2(meas)-8.2(ure)-470.9(of)-475.4(eosin)-7.8(ophil)-475.2(chemo)-7.8(taxis\))]TJ
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[(in)-476.2(vivo)]TJ
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2.8965 0 TD
(.)Tj
-22.5516 -1.0698 TD
[(Utilizing)-245(aeroso)-8.2(lized)-237(L)80.5(T)0(D)]TJ
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(4)Tj
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(,U)Tj
6.974 0 0 6.974 176.995 282.841 Tm
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[(ND)-10.9(ER)50.7(WOOD)]TJ
/F5 1 Tf
9.963 0 0 9.963 219.515 282.841 Tm
0 Tc
[(et)-237.6(al)]TJ
/F3 1 Tf
1.7129 0 TD
[(.)-233.7([8])-238.8(demon)-7.4(-)]TJ
-17.8968 -1.0698 TD
[(strated)-326.7(inhal)-9(ed)-320.6(L)86.2(T)57.7(s)-320.6(elevated)-325.5(BAL)-322.3(eosin)-7.8(ophils)-323.5(in)-322.6(guinea)-7.8(-)]TJ
T*
[(pig)-152.6(airways;)-155(incre)-8.6(ased)-153(eosinophil)-158.6(numbe)-7.4(rs)-146.6(wer)-8.2(e)-149.1(confirmed)]TJ
T*
[(histolog)-8.7(ical)-8.6(ly)-311.2(in)-311.2(the)-312.4(bronchi)-9.7(al)-311.6(e)-6.9(pithelium)-321.5(and)-310(subepi)-8.6(the-)]TJ
T*
[(lium.)-364.2(Final)-8.2(ly)64.4(,)-358.9(L)]TJ
6.974 0 0 6.974 121.89 240.208 Tm
0.0001 Tc
(AITINEN)Tj
/F5 1 Tf
9.963 0 0 9.963 153.468 240.208 Tm
0 Tc
[(et)-357.1(al)]TJ
/F3 1 Tf
1.838 0 TD
[(.)-358.9([10])-359.1(show)-8.2(ed)-360.4(inhaled)-363.7(L)80.5(T)0(E)]TJ
7.472 0 0 6.641 281.707 238.564 Tm
(4)Tj
9.963 0 0 9.963 58.28 229.55 Tm
[(incre)-8.6(ased)-403.4(eosin)-7.8(ophils)-408.9(\(but)-405.4(not)-403(mast)-408.5(cells,)-403.6(lym)-7.8(phocyt)-7.4(es,)]TJ
0 -1.0698 TD
[(plasma)-256.8(cells)-255.3(or)-247.8(macr)-8.6(ophages)-7.3(\))-247.1(i)0(n)-248.6(the)-255.5(lamina)-252.3(propri)-10.1(a)-245.9(o)-6.5(f)-247.1(the)]TJ
T*
[(airways)-345.3(of)-333.2(patients)-345.3(with)-336.1(asthma.)]TJ
1.0015 -1.0471 TD
[(Co)16.5(rt)17.3(ic)18.4(os)14.4(te)18.4(ro)19.6(id)18.9(s)-497(a)0(n)15.1(d)-495.8(an)15.1(ti)16.5(le)18.4(uk)21.2(ot)13.2(ri)17.3(en)20.8(e)-501.9(a)0(g)20.8(e)0(n)15.1(t)0(s)-488.8(h)0(a)20.8(v)0(e)-491.3(b)0(e)20.8(e)0(n)]TJ
-1.0015 -1.0698 TD
[(sh)20(ow)17.3(n)-188.6(t)0(o)-174.6(a)0(f)24.9(f)0(e)19.2(c)0(t)-180.7(s)0(p)20(u)0(t)18.9(u)0(m)-181.1(e)0(o)15.1(s)0(i)17.7(n)0(o)21.2(p)0(h)15.5(i)0(l)16.5(s)-184.1(in)-174.6(pa)15.1(ti)16.5(en)20.8(ts)-181.5(w)12.4(i)0(t)16.5(h)-188.6(as)19.6(th)18.9(ma)12(.)]TJ
T*
[(In)-236.4(a)-245.9(3)0(-)19.6(w)0(e)16.9(e)0(k)-235.2(p)0(l)18.9(a)0(c)14.7(e)0(b)20.8(o)0(-)13.9(c)0(o)20.8(n)0(t)13.2(r)0(o)19.6(l)0(l)16.5(e)0(d)-235.2(s)0(t)17.7(u)0(d)21.2(y)67.5(,)-239.4(i)0(n)13.2(h)0(a)20.8(l)0(e)18.4(d)-245.5(be)15.1(cl)18.4(om)18.1(et)18.4(ha)15.1(-)]TJ
T*
[(so)20(ne)-115.7(\(1)13.9(,0)21.6(00)]TJ
/F8 1 Tf
4.5695 0 TD
(m)Tj
/F3 1 Tf
0.5634 0 TD
[(g)-126(d)0(a)20.8(i)0(l)16.5(y)0(\))-116.9(d)0(e)20.8(c)0(r)13.5(e)0(a)20.4(s)0(e)13.9(d)-120.3(sp)20(ut)13.2(um)-112.8(eo)15.1(si)17.7(no)21.2(ph)15.5(il)16.5(s)-121.5(b)0(y)-115.3(7)0(3)15.5(%)0(,)]TJ
-5.1329 -1.0698 TD
[(\(4)19.6(5%)-208.8(de)15.1(cr)19.2(ea)20.4(se)-208(wi)14.9(th)-203.1(pl)18.9(ac)14.7(eb)15.1(o)-211.3(t)0(r)17.3(e)0(a)14.7(t)13.9(me)12(nt)18.9(,)-210.9(n)0(e)15.1(t)-213.7(di)18.9(f)14.7(f)0(e)19.2(r)0(e)19.2(n)0(c)15.1(e)-211.7(28)15.5(%\))]TJ
T*
[([3)19.6(0].)-282.3(Simi)-10.2(larly)57.7(,)-290.6(inhaled)-295.4(beclometh)-10.3(asone)-296(\(1,000)]TJ
/F8 1 Tf
19.0747 0 TD
(m)Tj
/F3 1 Tf
0.5691 0 TD
(g)Tj
/F11 1 Tf
0.5008 0.1992 TD
(.)Tj
/F3 1 Tf
0.2731 -0.1992 TD
(day)Tj
7.472 0 0 6.641 276.038 148.932 Tm
(-1)Tj
9.963 0 0 9.963 282.217 144.51 Tm
(\))Tj
-22.4777 -1.0698 TD
[(reduced)-247.2(sputum)-244.6(eosinophil)-10.7(s)-235.3(i)0(n)-237.2(a)-240.2(4-week)-244.2(study)-240.7(compa)-7.8(ring)]TJ
T*
[(beclom)-10.9(ethasone)-289.7(with)-290.6(salmeter)-12.3(ol)-282.7([31],)-285.5(an)-7.6(d)-279.6(treat)-11(ment)-287.8(with)]TJ
T*
[(budeson)-6.9(ide)-568.4(\(400)]TJ
/F8 1 Tf
7.4945 0 TD
(m)Tj
/F3 1 Tf
0.5747 0 TD
(g)Tj
/F11 1 Tf
0.5008 0.1992 TD
(.)Tj
/F3 1 Tf
0.2731 -0.1992 TD
(day)Tj
7.472 0 0 6.641 160.724 116.957 Tm
(-1)Tj
9.963 0 0 9.963 172.46 112.535 Tm
[(for)-568.8(7)-569.8(days\))-564.7(a)-6.9(ttenuated)-572.9(the)]TJ
13.737 24.5832 TD
[(incre)-8.6(ase)-294.5(in)-288.4(eosin)-7.8(ophils)-295.1(after)-294.7(anti)-8.2(gen)-292.9(challenge)-297.8([3].)-296.1(In)-287.7(the)]TJ
0 -1.0698 TD
[(presen)-8.2(t)-418.6(study)55.2(,)-415.8(the)-420.5(48%)-420.1(decreas)-9.7(e)-416.6(i)0(n)-419.3(sputu)-7.4(m)-419.3(eosin)-7.8(ophils)]TJ
T*
[(after)-573.6(mont)-8.6(elukast)-569.8(treatmen)-11.1(t)-566.5(\(com)-8.2(pared)-569.6(with)-569.4(the)-568.4(23%)]TJ
T*
[(incre)-8.6(ase)-385.6(after)-385.8(placeb)-8.2(o\))-384.4(is)-380.7(simil)-9.6(ar)-379.1(in)-385.2(magni)-9.7(tude)-381.4(\(net)-388.7(dif-)]TJ
T*
[(ference)-254.8(of)-247.8(71%\))-251.7(to)-248.6(the)-249.8(effects)-246.6(seen)-249.7(with)-250.7(corticost)-11.9(eroids)-249.2(in)]TJ
T*
[(other)-372.4(studies;)-368.8(howe)-7.4(ver)29.9(,)-364.6(direc)-8.6(t)-361.7(withi)-9.2(n-study)-369(compa)-7.8(risons)]TJ
T*
[(are)-516.8(necess)-8.2(ary)-516.4(to)-516.1(confi)-8.2(rm)-512.7(this)-515.5(inte)-8.2(rpretati)-11.6(on.)-514.1(An)-511.9(addi-)]TJ
T*
[(tion)-7.8(al,)-403(interest)-11.1(ing)-403(observ)-7.8(ation)-401.6(in)-402.2(the)-403.4(presen)-8.2(t)-401.5(trial)-405.6(is)-403.4(the)]TJ
T*
[(large)-412.6(improvem)-11.1(ent)-414.8(observ)-7.8(ed)-417.3(in)-413.6(most)-419.5(clin)-8.2(ical)-418.3(endpoints)]TJ
T*
[(\(PE)-7.2(F)74(,)]TJ
/F8 1 Tf
2.538 0 TD
(b)Tj
/F3 1 Tf
7.472 0 0 6.641 340.101 259.88 Tm
(2)Tj
9.963 0 0 9.963 343.842 261.524 Tm
[(-agoni)-9(st)-323.8(use,)-328.6(symptom)-9.5(s\))-323(whi)-8.6(ch,)-321(o)-6.5(n)-319.4(average,)-333.3(are)]TJ
-3.4655 -1.0698 TD
[(great)-8.6(er)-219.8(than)-222.1(the)-221.3(effect)-216.2(seen)-221.3(in)-220.2(other)-224.4(mont)-8.6(elukast)-222.6(trials)-225.5([16,)]TJ
T*
[(17].)-499.3(The)-496.2(explan)-7.8(ation)-498.4(for)-494.9(this)-498.4(observ)-7.8(ation)-498.4(is)-494.5(unknow)-8.5(n)]TJ
T*
[(\(and)-346.5(may)-347.3(be)-343.4(a)-342.6(chance)-347.6(varia)-8.6(tion\),)-346.3(but)-346.1(may)-347.3(be)-343.4(due)-344.1(to)-339.7(the)]TJ
T*
[(selec)-8.6(tion)-252.5(of)-247.8(pati)-8.2(ents)-251.7(with)-250.7(more)-252.9(substanti)-11.1(al)-249(airway)-258(eosino-)]TJ
T*
[(phil)-7.8(ic)-459.6(infl)-9.4(ammati)-10.7(on.)-462.8(However)24.2(,)-461.3(the)-466(correlati)-12.7(on)-462.5(between)]TJ
T*
[(imp)-7.8(rovem)-9(ents)-468(in)-464.8(sputum)-472.2(eosinophil)-10.7(s)-462.9(and)-469.3(clinical)-472.1(end-)]TJ
T*
[(point)-8.6(s)-468.6(was)-468.8(gene)-9.6(rally)-471.5(modes)-8.5(t;)-467.2(the)-471.7(relations)-11.9(hip)-471.3(between)]TJ
T*
[(cha)-8.8(nges)-334.7(in)-339.7(clinical)-346.9(endpoints)-343.3(and)-338.4(airways)-345.3(eosinophil)-10.7(s)-332(i)0(s)]TJ
T*
[(unk)-8(nown)-337(and)-332.7(awai)-10.2(ts)-335.1(further)-343(clinical)-341.2(trials.)]TJ
1.0015 -1.0471 TD
[(Th)17.1(is)-397.8(st)17.7(ud)21.2(y)-404.8(w)0(a)16.9(s)-406(ne)20.8(it)16.5(he)15.1(r)-400.7(d)0(e)15.1(s)0(i)17.7(g)0(n)21.2(e)0(d)-394.6(n)0(o)15.5(r)-400.7(po)15.5(we)16.9(re)19.2(d)-404.8(t)0(o)-396.6(p)0(r)19.6(o)0(-)]TJ
-1.0015 -1.0698 TD
[(sp)14.4(ec)20.4(ti)16.5(ve)15.1(ly)-186(de)15.1(te)18.4(rm)16.5(in)18.9(e)-200.3(t)0(h)18.8(e)-194.6(co)15.1(rr)18(el)18.4(at)12.8(i)13.9(o)0(n)-189.3(b)0(e)15.1(t)0(w)14.9(e)0(e)20.4(n)-199.9(sp)20(ut)18.9(um)-192.5(ma)17.7(rk)19.6(-)]TJ
T*
[(er)13.5(s)-223.9(a)0(n)15.1(d)-222.7(cl)18.4(in)13.2(ic)18.4(al)-214.9(ou)15.5(tc)18.4(om)18.1(es)13.9(.)-222.3(T)0(h)17.1(e)0(r)19.2(e)0(f)13.5(o)0(r)19.6(e)0(,)-217.8(t)0(h)18.8(e)-228.8(w)12.4(e)0(a)14.7(k)-228.4(co)20.8(rr)18(el)12.8(at)18.4(io)18.8(ns)]TJ
T*
[(be)15.1(tw)14.9(ee)20.4(n)-342.2(i)0(m)15.7(p)0(r)19.6(o)0(v)15.5(e)0(m)17.7(e)0(n)20.8(t)-344.6(in)-328.3(sp)14.4(ut)18.9(um)-329(eo)15.1(si)17.7(no)21.2(ph)15.5(il)16.5(s)-337.7(a)0(n)15.1(d)-336.5(cl)12.8(in)18.9(ic)18.4(al)]TJ
T*
[(ou)15.5(tc)18.4(om)18.1(es)-390.1(is)-386.4(li)16.5(ke)20.8(ly)-385.2(to)-390.9(be)-383.2(an)-388.9(ef)30.6(fe)13.5(ct)-385.6(of)-384.4(th)18.9(e)-399.5(s)0(m)16.9(a)0(l)18.4(l)-395.8(ra)19.2(ng)15.5(e)-393.8(o)0(f)]TJ
ET
0 0 0 1 K
0 J 0 j 0.5 w 3.864 M []0 d
/GS3 gs
1 i 
276.913 463.132 m
276.913 495.132 l
233.697 448.632 m
233.697 470.132 l
189.981 457.132 m
189.981 475.132 l
143.981 464.632 m
143.981 478.132 l
101.197 458.632 m
144.197 471.132 l
189.697 466.132 l
233.197 459.632 l
276.696 478.132 l
95.697 585.631 m
95.697 439.601 l
S
BT
/F19 1 Tf
10 0 0 10 63.198 582.848 Tm
0 0 0 1 k
/GS4 gs
(c\))Tj
ET
/GS3 gs
98.697 439.849 m
279.114 439.849 l
98.197 435.849 m
98.197 439.849 l
S
BT
10 0 0 10 94.197 424.849 Tm
/GS4 gs
(BL)Tj
6.55 -1.05 TD
[(T)30(reatment  weeks)]TJ
ET
/GS3 gs
143.697 507.349 m
147.947 507.349 l
S
BT
10 0 0 10 73.981 582.631 Tm
/GS4 gs
(  70)Tj
ET
/GS3 gs
90.981 585.848 m
95.697 585.848 l
S
BT
10 0 0 10 73.981 563.632 Tm
/GS4 gs
(  60)Tj
ET
/GS3 gs
90.981 566.848 m
95.697 566.848 l
S
BT
10 0 0 10 73.981 545.766 Tm
/GS4 gs
(  50)Tj
ET
/GS3 gs
90.981 548.982 m
95.697 548.982 l
S
BT
10 0 0 10 73.981 527.616 Tm
/GS4 gs
(  40)Tj
ET
/GS3 gs
90.981 530.833 m
95.697 530.833 l
S
BT
10 0 0 10 73.981 509.467 Tm
/GS4 gs
(  30)Tj
ET
/GS3 gs
90.981 512.683 m
95.697 512.683 l
S
BT
10 0 0 10 73.981 490.751 Tm
/GS4 gs
(  20)Tj
ET
/GS3 gs
90.981 493.967 m
95.697 493.967 l
S
BT
10 0 0 10 73.981 472.601 Tm
/GS4 gs
(  10)Tj
ET
/GS3 gs
90.981 475.818 m
95.697 475.818 l
S
BT
10 0 0 10 73.981 454.735 Tm
/GS4 gs
(    0)Tj
ET
/GS3 gs
90.981 457.952 m
95.697 457.952 l
S
BT
10 0 0 10 73.131 436.302 Tm
/GS4 gs
( -10)Tj
ET
/GS3 gs
90.981 439.518 m
95.697 439.518 l
S
BT
0 10 -10 0 68.181 483.632 Tm
/GS4 gs
(PEF)Tj
0 8 -8 0 68.181 499.582 Tm
(a.m.)Tj
0 10 -10 0 68.181 512.342 Tm
(  L\341min)Tj
0 8 -8 0 65.913 536.952 Tm
(-1)Tj
ET
/GS3 gs
143.996 435.849 m
143.996 439.849 l
S
BT
10 0 0 10 141.496 424.849 Tm
/GS4 gs
(1)Tj
ET
/GS3 gs
189.079 435.849 m
189.079 439.782 l
S
BT
10 0 0 10 187.579 424.849 Tm
/GS4 gs
(2)Tj
ET
/GS3 gs
234.496 435.849 m
234.496 439.849 l
S
BT
10 0 0 10 232.496 424.849 Tm
/GS4 gs
(3)Tj
ET
/GS3 gs
279.114 436.416 m
279.114 439.916 l
S
BT
10 0 0 10 276.114 425.416 Tm
/GS4 gs
(4)Tj
ET
/GS3 gs
278.913 564.848 m
283.163 564.848 l
236.697 575.098 m
240.947 575.098 l
278.946 527.848 m
283.196 527.848 l
236.697 536.348 m
240.947 536.348 l
190.447 554.098 m
194.697 554.098 l
190.23 513.098 m
194.481 513.098 l
274.947 495.599 m
279.196 495.599 l
274.696 462.849 m
278.946 462.849 l
231.447 470.599 m
235.697 470.599 l
S
0 0 0 0 k
97.197 458.599 m
97.197 459.841 98.205 460.849 99.447 460.849 c
100.69 460.849 101.697 459.841 101.697 458.599 c
101.697 457.356 100.69 456.349 99.447 456.349 c
98.205 456.349 97.197 457.356 97.197 458.599 c
b
231.447 448.349 m
235.697 448.349 l
S
0 0 0 1 k
278.946 545.598 m
278.946 546.841 279.954 547.848 281.196 547.848 c
282.439 547.848 283.446 546.841 283.446 545.598 c
283.446 544.356 282.439 543.348 281.196 543.348 c
279.954 543.348 278.946 544.356 278.946 545.598 c
b
0 0 0 0 k
274.696 478.099 m
274.696 479.341 275.704 480.349 276.946 480.349 c
278.189 480.349 279.196 479.341 279.196 478.099 c
279.196 476.856 278.189 475.849 276.946 475.849 c
275.704 475.849 274.696 476.856 274.696 478.099 c
b
187.697 456.849 m
191.947 456.849 l
S
0 0 0 1 k
236.947 554.598 m
236.947 555.841 237.954 556.848 239.197 556.848 c
240.439 556.848 241.447 555.841 241.447 554.598 c
241.447 553.356 240.439 552.348 239.197 552.348 c
237.954 552.348 236.947 553.356 236.947 554.598 c
b
0 0 0 0 k
231.197 459.599 m
231.197 460.841 232.204 461.849 233.447 461.849 c
234.689 461.849 235.697 460.841 235.697 459.599 c
235.697 458.356 234.689 457.349 233.447 457.349 c
232.204 457.349 231.197 458.356 231.197 459.599 c
b
187.697 475.599 m
191.947 475.599 l
S
0 0 0 1 k
189.947 532.598 m
189.947 533.841 190.954 534.848 192.197 534.848 c
193.44 534.848 194.447 533.841 194.447 532.598 c
194.447 531.356 193.44 530.348 192.197 530.348 c
190.954 530.348 189.947 531.356 189.947 532.598 c
b
0 0 0 0 k
187.697 466.099 m
187.697 467.341 188.704 468.349 189.947 468.349 c
191.19 468.349 192.197 467.341 192.197 466.099 c
192.197 464.856 191.19 463.849 189.947 463.849 c
188.704 463.849 187.697 464.856 187.697 466.099 c
b
141.697 478.349 m
145.947 478.349 l
S
0 0 0 1 k
143.447 524.598 m
143.447 525.841 144.454 526.848 145.697 526.848 c
146.94 526.848 147.947 525.841 147.947 524.598 c
147.947 523.356 146.94 522.348 145.697 522.348 c
144.454 522.348 143.447 523.356 143.447 524.598 c
b
0 0 0 0 k
141.697 471.099 m
141.697 472.341 142.704 473.349 143.947 473.349 c
145.19 473.349 146.197 472.341 146.197 471.099 c
146.197 469.856 145.19 468.849 143.947 468.849 c
142.704 468.849 141.697 469.856 141.697 471.099 c
b
141.947 464.349 m
146.197 464.349 l
S
0 0 0 1 k
98.947 458.599 m
98.947 459.841 99.955 460.849 101.197 460.849 c
102.44 460.849 103.447 459.841 103.447 458.599 c
103.447 457.356 102.44 456.349 101.197 456.349 c
99.955 456.349 98.947 457.356 98.947 458.599 c
b
101.197 458.632 m
145.697 524.132 l
192.197 532.632 l
239.697 554.632 l
281.196 545.632 l
145.697 507.632 m
145.697 541.632 l
192.331 513.132 m
192.331 553.632 l
238.98 536.632 m
238.98 574.631 l
281.263 528.132 m
281.263 564.632 l
143.447 542.098 m
147.697 542.098 l
395.629 488.132 m
395.629 529.632 l
442.345 499.132 m
442.345 560.132 l
440.629 514.132 m
440.629 590.632 l
486.129 442.882 m
486.129 521.632 l
528.061 547.632 m
528.061 468.632 l
351.413 507.132 m
395.912 511.132 l
440.912 552.632 l
486.412 484.132 l
528.412 507.632 l
347.413 608.131 m
347.413 439.885 l
S
BT
10 0 0 10 315.48 601.848 Tm
/GS4 gs
(d\))Tj
ET
/GS3 gs
350.413 439.849 m
530.829 439.849 l
349.913 435.849 m
349.913 439.849 l
S
BT
10 0 0 10 345.913 424.849 Tm
/GS4 gs
(BL)Tj
6.55 -1.05 TD
[(T)30(reatment  weeks)]TJ
-8.5933 18.7284 TD
(  12)Tj
ET
/GS3 gs
342.48 604.848 m
347.196 604.848 l
395.711 435.849 m
395.711 439.849 l
S
BT
10 0 0 10 393.212 424.849 Tm
/GS4 gs
(1)Tj
ET
/GS3 gs
440.794 435.849 m
440.794 439.782 l
S
BT
10 0 0 10 439.294 424.849 Tm
/GS4 gs
(2)Tj
ET
/GS3 gs
486.211 435.849 m
486.211 439.849 l
S
BT
10 0 0 10 484.211 424.849 Tm
/GS4 gs
(3)Tj
ET
/GS3 gs
530.829 436.416 m
530.829 439.916 l
S
BT
10 0 0 10 527.829 425.416 Tm
/GS4 gs
(4)Tj
-20.2284 16.0717 TD
(  10)Tj
ET
/GS3 gs
342.547 589.348 m
347.263 589.348 l
S
BT
10 0 0 10 325.614 570.348 Tm
/GS4 gs
(    8)Tj
ET
/GS3 gs
342.614 573.565 m
347.33 573.565 l
S
BT
10 0 0 10 325.681 553.147 Tm
/GS4 gs
(    6)Tj
ET
/GS3 gs
342.681 556.364 m
347.397 556.364 l
S
BT
10 0 0 10 325.748 536.797 Tm
/GS4 gs
(    4)Tj
ET
/GS3 gs
342.748 540.013 m
347.464 540.013 l
S
BT
10 0 0 10 325.815 520.163 Tm
/GS4 gs
(    2)Tj
ET
/GS3 gs
342.815 523.379 m
347.531 523.379 l
S
BT
10 0 0 10 325.882 504.096 Tm
/GS4 gs
(    0)Tj
ET
/GS3 gs
342.882 507.313 m
347.598 507.313 l
342.665 490.962 m
347.382 490.962 l
342.732 474.895 m
347.448 474.895 l
342.799 458.261 m
347.515 458.261 l
342.866 439.927 m
347.582 439.927 l
S
BT
10 0 0 10 327.65 487.746 Tm
/GS4 gs
(  -2)Tj
-0.0217 -1.6067 TD
(  -4)Tj
0.0067 -1.6634 TD
(  -6)Tj
0.035 -1.8335 TD
(  -8)Tj
0 10 -10 0 319.58 498.848 Tm
(FEV)Tj
0 8 -8 0 319.58 514.798 Tm
(1)Tj
0 10 -10 0 319.58 518.446 Tm
(  % change)Tj
ET
/GS3 gs
525.912 468.349 m
530.162 468.349 l
484.162 442.681 m
488.412 442.681 l
S
0 0 0 0 k
348.913 507.598 m
348.913 508.841 349.92 509.848 351.163 509.848 c
352.405 509.848 353.413 508.841 353.413 507.598 c
353.413 506.356 352.405 505.348 351.163 505.348 c
349.92 505.348 348.913 506.356 348.913 507.598 c
b
530.912 586.348 m
535.162 586.348 l
S
0 0 0 1 k
530.662 561.098 m
530.662 562.341 531.669 563.348 532.912 563.348 c
534.154 563.348 535.162 562.341 535.162 561.098 c
535.162 559.856 534.154 558.848 532.912 558.848 c
531.669 558.848 530.662 559.856 530.662 561.098 c
b
0 0 0 0 k
525.912 507.098 m
525.912 508.341 526.919 509.348 528.162 509.348 c
529.404 509.348 530.412 508.341 530.412 507.098 c
530.412 505.856 529.404 504.848 528.162 504.848 c
526.919 504.848 525.912 505.856 525.912 507.098 c
b
525.945 547.815 m
530.195 547.815 l
S
0 0 0 1 k
485.662 552.598 m
485.662 553.841 486.669 554.848 487.912 554.848 c
489.155 554.848 490.162 553.841 490.162 552.598 c
490.162 551.355 489.155 550.348 487.912 550.348 c
486.669 550.348 485.662 551.355 485.662 552.598 c
b
0 0 0 0 k
483.912 483.599 m
483.912 484.841 484.919 485.849 486.162 485.849 c
487.404 485.849 488.412 484.841 488.412 483.599 c
488.412 482.356 487.404 481.349 486.162 481.349 c
484.919 481.349 483.912 482.356 483.912 483.599 c
b
530.662 538.598 m
534.912 538.598 l
S
0 0 0 1 k
396.662 565.098 m
396.662 566.34 397.67 567.348 398.912 567.348 c
400.155 567.348 401.162 566.34 401.162 565.098 c
401.162 563.855 400.155 562.848 398.912 562.848 c
397.67 562.848 396.662 563.855 396.662 565.098 c
b
0 0 0 0 k
438.412 552.098 m
438.412 553.341 439.419 554.348 440.662 554.348 c
441.905 554.348 442.912 553.341 442.912 552.098 c
442.912 550.856 441.905 549.848 440.662 549.848 c
439.419 549.848 438.412 550.856 438.412 552.098 c
b
485.912 573.848 m
490.162 573.848 l
S
0 0 0 1 k
440.162 528.598 m
440.162 529.841 441.169 530.848 442.412 530.848 c
443.655 530.848 444.662 529.841 444.662 528.598 c
444.662 527.356 443.655 526.348 442.412 526.348 c
441.169 526.348 440.162 527.356 440.162 528.598 c
b
0 0 0 0 k
393.412 511.099 m
393.412 512.341 394.42 513.349 395.662 513.349 c
396.905 513.349 397.912 512.341 397.912 511.099 c
397.912 509.856 396.905 508.849 395.662 508.849 c
394.42 508.849 393.412 509.856 393.412 511.099 c
b
0 0 0 1 k
351.379 507.598 m
351.379 508.841 352.386 509.848 353.629 509.848 c
354.872 509.848 355.879 508.841 355.879 507.598 c
355.879 506.356 354.872 505.348 353.629 505.348 c
352.386 505.348 351.379 506.356 351.379 507.598 c
b
353.413 508.132 m
398.912 565.631 l
442.412 529.132 l
487.912 553.132 l
532.912 561.632 l
398.912 542.632 m
398.912 590.131 l
487.912 533.132 m
487.912 573.632 l
532.978 538.632 m
532.978 586.132 l
485.662 532.848 m
489.912 532.848 l
483.945 521.815 m
488.195 521.815 l
438.412 590.848 m
442.662 590.848 l
396.662 590.598 m
400.912 590.598 l
396.912 542.348 m
401.162 542.348 l
440.162 560.598 m
444.412 560.598 l
438.412 513.848 m
442.662 513.848 l
439.912 498.848 m
444.162 498.848 l
393.412 529.781 m
397.662 529.781 l
393.412 487.849 m
397.662 487.849 l
144.414 726.631 m
144.414 748.881 l
235.73 718.881 m
235.73 763.63 l
276.98 686.631 m
276.98 737.131 l
276.663 711.631 m
235.413 741.381 l
189.413 704.381 l
144.164 737.131 l
100.414 737.131 l
189.697 689.881 m
189.697 715.631 l
S
BT
0 10 -10 0 67.914 652.131 Tm
/GS4 gs
(Daytime symptom score)Tj
ET
/GS3 gs
95.414 768.13 m
95.414 626.1 l
S
BT
10 0 0 10 73.698 754.414 Tm
/GS4 gs
( 0.2)Tj
ET
/GS3 gs
90.697 757.63 m
95.414 757.63 l
S
BT
10 0 0 10 73.764 733.914 Tm
/GS4 gs
(    0)Tj
ET
/GS3 gs
90.197 737.131 m
94.914 737.131 l
S
BT
10 0 0 10 72.698 714.548 Tm
/GS4 gs
(-0.2)Tj
ET
/GS3 gs
89.981 717.765 m
94.697 717.765 l
S
BT
10 0 0 10 72.765 694.332 Tm
/GS4 gs
(-0.4)Tj
ET
/GS3 gs
90.048 697.548 m
94.764 697.548 l
S
BT
10 0 0 10 72.832 673.832 Tm
/GS4 gs
(-0.6)Tj
ET
/GS3 gs
90.115 677.048 m
94.831 677.048 l
S
BT
10 0 0 10 72.899 653.049 Tm
/GS4 gs
(-0.8)Tj
ET
/GS3 gs
90.182 656.265 m
94.898 656.265 l
S
BT
10 0 0 10 72.682 633.116 Tm
/GS4 gs
(-1.0)Tj
ET
/GS3 gs
89.965 636.332 m
94.682 636.332 l
S
BT
10 0 0 10 62.914 754.63 Tm
/GS4 gs
(a\))Tj
ET
/GS3 gs
98.414 626.631 m
277.413 626.631 l
97.914 622.631 m
97.914 626.631 l
145.414 622.631 m
145.414 626.631 l
191.913 622.631 m
191.913 626.564 l
235.913 622.631 m
235.913 626.631 l
277.413 622.631 m
277.413 626.131 l
S
0 0 0 0 k
274.663 711.631 m
274.663 712.873 275.67 713.881 276.913 713.881 c
278.156 713.881 279.163 712.873 279.163 711.631 c
279.163 710.388 278.156 709.381 276.913 709.381 c
275.67 709.381 274.663 710.388 274.663 711.631 c
b
0 0 0 1 k
274.663 651.131 m
274.663 652.374 275.67 653.381 276.913 653.381 c
278.156 653.381 279.163 652.374 279.163 651.131 c
279.163 649.888 278.156 648.881 276.913 648.881 c
275.67 648.881 274.663 649.888 274.663 651.131 c
b
233.163 652.131 m
233.163 653.374 234.171 654.381 235.413 654.381 c
236.656 654.381 237.663 653.374 237.663 652.131 c
237.663 650.888 236.656 649.881 235.413 649.881 c
234.171 649.881 233.163 650.888 233.163 652.131 c
b
0 0 0 0 k
233.413 741.381 m
233.413 742.623 234.421 743.631 235.663 743.631 c
236.906 743.631 237.913 742.623 237.913 741.381 c
237.913 740.138 236.906 739.131 235.663 739.131 c
234.421 739.131 233.413 740.138 233.413 741.381 c
b
0 0 0 1 k
189.163 643.881 m
189.163 645.124 190.171 646.131 191.413 646.131 c
192.656 646.131 193.663 645.124 193.663 643.881 c
193.663 642.638 192.656 641.631 191.413 641.631 c
190.171 641.631 189.163 642.638 189.163 643.881 c
b
0 0 0 0 k
187.414 704.381 m
187.414 705.623 188.421 706.631 189.664 706.631 c
190.906 706.631 191.913 705.623 191.913 704.381 c
191.913 703.138 190.906 702.131 189.664 702.131 c
188.421 702.131 187.414 703.138 187.414 704.381 c
b
0 0 0 1 k
143.914 656.631 m
143.914 657.874 144.921 658.881 146.164 658.881 c
147.406 658.881 148.414 657.874 148.414 656.631 c
148.414 655.388 147.406 654.381 146.164 654.381 c
144.921 654.381 143.914 655.388 143.914 656.631 c
b
0 0 0 0 k
142.164 736.881 m
142.164 738.123 143.171 739.131 144.414 739.131 c
145.656 739.131 146.664 738.123 146.664 736.881 c
146.664 735.638 145.656 734.631 144.414 734.631 c
143.171 734.631 142.164 735.638 142.164 736.881 c
b
97.881 737.314 m
97.881 738.556 98.888 739.564 100.131 739.564 c
101.373 739.564 102.381 738.556 102.381 737.314 c
102.381 736.071 101.373 735.064 100.131 735.064 c
98.888 735.064 97.881 736.071 97.881 737.314 c
b
0 0 0 1 k
99.548 737.314 m
99.548 738.556 100.555 739.564 101.798 739.564 c
103.041 739.564 104.048 738.556 104.048 737.314 c
104.048 736.071 103.041 735.064 101.798 735.064 c
100.555 735.064 99.548 736.071 99.548 737.314 c
b
101.914 737.381 m
145.914 656.631 l
191.413 644.131 l
235.413 652.381 l
276.913 651.131 l
187.414 716.131 m
191.663 716.131 l
274.696 632.131 m
278.946 632.131 l
274.696 671.631 m
278.946 671.631 l
232.947 633.881 m
237.197 633.881 l
188.947 629.631 m
193.197 629.631 l
233.197 670.631 m
237.447 670.631 l
189.197 659.881 m
193.447 659.881 l
143.947 641.381 m
148.197 641.381 l
144.197 671.564 m
148.447 671.564 l
274.696 737.631 m
278.946 737.631 l
274.696 686.381 m
278.946 686.381 l
233.447 763.814 m
237.697 763.814 l
142.197 726.631 m
146.447 726.631 l
142.447 749.38 m
146.697 749.38 l
233.447 718.881 m
237.697 718.881 l
187.447 689.631 m
191.697 689.631 l
235.346 634.131 m
235.346 670.131 l
276.879 632.381 m
276.879 671.131 l
191.413 629.631 m
191.413 659.381 l
146.13 641.631 m
146.13 671.381 l
351.413 697.131 m
394.412 701.131 l
439.412 671.631 l
485.412 729.631 l
526.912 707.631 l
394.446 689.381 m
394.446 712.631 l
527.195 682.631 m
527.195 732.131 l
485.296 692.881 m
485.296 767.38 l
439.412 660.381 m
439.412 678.631 l
347.413 773.13 m
347.413 626.1 l
S
BT
10 0 0 10 314.413 770.63 Tm
/GS4 gs
(b\))Tj
ET
/GS3 gs
350.413 626.631 m
529.412 626.631 l
349.913 622.631 m
349.913 626.631 l
397.412 622.631 m
397.412 626.631 l
529.412 622.631 m
529.412 626.131 l
442.211 622.631 m
442.211 626.564 l
486.778 622.631 m
486.778 626.631 l
S
BT
10 0 0 10 325.696 770.414 Tm
/GS4 gs
(  80)Tj
ET
/GS3 gs
342.696 773.63 m
347.413 773.63 l
S
BT
10 0 0 10 325.696 753.414 Tm
/GS4 gs
(  60)Tj
ET
/GS3 gs
342.696 756.63 m
347.413 756.63 l
S
BT
10 0 0 10 325.696 735.847 Tm
/GS4 gs
(  40)Tj
ET
/GS3 gs
342.696 739.064 m
347.413 739.064 l
S
BT
10 0 0 10 325.696 716.58 Tm
/GS4 gs
(  20)Tj
ET
/GS3 gs
342.696 719.796 m
347.413 719.796 l
S
BT
10 0 0 10 325.696 695.327 Tm
/GS4 gs
(    0)Tj
ET
/GS3 gs
342.696 698.543 m
347.413 698.543 l
342.696 677.858 m
347.413 677.858 l
342.696 657.173 m
347.413 657.173 l
342.696 635.921 m
347.413 635.921 l
S
BT
10 0 0 10 324.846 674.642 Tm
/GS4 gs
( -20)Tj
0 -2.0685 TD
( -40)Tj
0 -2.1252 TD
( -60)Tj
/F22 1 Tf
0 10 -10 0 319.413 652.631 Tm
(b)Tj
/F19 1 Tf
0 8 -8 0 321.681 658.121 Tm
(2)Tj
0 10 -10 0 319.413 661.769 Tm
(-agonist use  % change)Tj
ET
/GS3 gs
526.912 635.131 m
526.912 636.374 527.919 637.381 529.162 637.381 c
530.404 637.381 531.412 636.374 531.412 635.131 c
531.412 633.888 530.404 632.881 529.162 632.881 c
527.919 632.881 526.912 633.888 526.912 635.131 c
b
0 0 0 0 k
524.912 708.131 m
524.912 709.373 525.919 710.381 527.162 710.381 c
528.404 710.381 529.412 709.373 529.412 708.131 c
529.412 706.888 528.404 705.881 527.162 705.881 c
525.919 705.881 524.912 706.888 524.912 708.131 c
b
0 0 0 1 k
395.412 643.381 m
395.412 644.624 396.42 645.631 397.662 645.631 c
398.905 645.631 399.912 644.624 399.912 643.381 c
399.912 642.138 398.905 641.131 397.662 641.131 c
396.42 641.131 395.412 642.138 395.412 643.381 c
b
0 0 0 0 k
483.195 729.881 m
483.195 731.123 484.203 732.131 485.445 732.131 c
486.688 732.131 487.695 731.123 487.695 729.881 c
487.695 728.638 486.688 727.631 485.445 727.631 c
484.203 727.631 483.195 728.638 483.195 729.881 c
b
0 0 0 1 k
484.162 634.131 m
484.162 635.374 485.169 636.381 486.412 636.381 c
487.655 636.381 488.662 635.374 488.662 634.131 c
488.662 632.888 487.655 631.881 486.412 631.881 c
485.169 631.881 484.162 632.888 484.162 634.131 c
b
0 0 0 0 k
392.162 701.381 m
392.162 702.623 393.17 703.631 394.412 703.631 c
395.655 703.631 396.662 702.623 396.662 701.381 c
396.662 700.138 395.655 699.131 394.412 699.131 c
393.17 699.131 392.162 700.138 392.162 701.381 c
b
0 0 0 1 k
439.412 636.881 m
439.412 638.124 440.42 639.131 441.662 639.131 c
442.905 639.131 443.912 638.124 443.912 636.881 c
443.912 635.639 442.905 634.631 441.662 634.631 c
440.42 634.631 439.412 635.639 439.412 636.881 c
b
0 0 0 0 k
437.162 671.381 m
437.162 672.624 438.17 673.631 439.412 673.631 c
440.655 673.631 441.662 672.624 441.662 671.381 c
441.662 670.138 440.655 669.131 439.412 669.131 c
438.17 669.131 437.162 670.138 437.162 671.381 c
b
397.629 635.881 m
397.629 650.631 l
441.662 628.381 m
441.662 645.131 l
486.412 628.131 m
486.412 642.631 l
529.162 628.131 m
529.162 643.631 l
392.196 713.131 m
396.446 713.131 l
392.196 689.131 m
396.446 689.131 l
395.446 651.131 m
399.696 651.131 l
395.479 635.881 m
399.729 635.881 l
483.445 767.631 m
487.695 767.631 l
524.945 732.631 m
529.195 732.631 l
524.945 682.381 m
529.195 682.381 l
483.195 692.631 m
487.445 692.631 l
437.195 679.131 m
441.446 679.131 l
437.195 660.131 m
441.446 660.131 l
527.195 627.881 m
531.445 627.881 l
527.195 644.131 m
531.445 644.131 l
484.195 627.881 m
488.445 627.881 l
484.195 642.881 m
488.445 642.881 l
439.479 628.381 m
443.729 628.381 l
439.729 645.314 m
443.979 645.314 l
S
349.663 697.597 m
349.663 698.84 350.67 699.847 351.913 699.847 c
353.155 699.847 354.163 698.84 354.163 697.597 c
354.163 696.355 353.155 695.347 351.913 695.347 c
350.67 695.347 349.663 696.355 349.663 697.597 c
b
0 0 0 1 k
351.413 697.381 m
351.413 698.624 352.42 699.631 353.663 699.631 c
354.905 699.631 355.913 698.624 355.913 697.381 c
355.913 696.138 354.905 695.131 353.663 695.131 c
352.42 695.131 351.413 696.138 351.413 697.381 c
b
353.413 697.131 m
397.412 643.631 l
441.412 637.131 l
486.412 634.131 l
528.912 635.131 l
S
BT
/F3 1 Tf
7.97 0 0 7.97 58.28 404.164 Tm
0 g
/GS2 gs
[(Fig.)-312.9(3.)-316.9(\261)-310.9(The)-315.5(eff)14.1(ect)-314.1(of)-316.1(montelukast)-310.7(\()]TJ
/F6 1 Tf
14.7526 0 TD
(*)Tj
/F3 1 Tf
0.9958 0 TD
[(\))-318.2(and)-312.8(placebo)-311.8(\()]TJ
/F13 1 Tf
6.1031 0 TD
(s)Tj
/F3 1 Tf
0.8322 0 TD
[(\))-318.2(on:)-309.1(a\))-322.2(daytime)-308.4(symptoms)11.5(;)-320.4(b)0(\))]TJ
/F8 1 Tf
12.5903 0 TD
(b)Tj
/F3 1 Tf
5.977 0 0 5.313 343.786 402.86 Tm
(2)Tj
7.97 0 0 7.97 346.79 404.164 Tm
[(-agonis)12(t)-320.4(use)-314(\(puf)15.2(fs)]TJ
/F11 1 Tf
7.4617 0.249 TD
(.)Tj
/F3 1 Tf
0.2703 -0.249 TD
(day)Tj
5.977 0 0 5.313 419.868 407.735 Tm
(-1)Tj
7.97 0 0 7.97 424.8 404.164 Tm
[(\);)-311.4(c\))-315.1(morning)-315.3(peak)-309.7(expiratory)-309.3(flow)]TJ
-45.9864 -0.9958 TD
(\(PEF)Tj
6.376 0 0 6.376 74.438 396.227 Tm
(a.m.)Tj
7.97 0 0 7.97 85.323 396.227 Tm
[(\);)-346.9(and)-334.1(d\))-344.5(forced)-341.4(expiratory)-337.7(volume)-337.6(in)-339.6(one)-341.2(second)-342.2(\(FEV)]TJ
6.376 0 0 6.376 265.663 396.227 Tm
(1)Tj
7.97 0 0 7.97 268.838 396.227 Tm
[(\))-346.6(over)-339.3(the)-336.5(4-week)-343.7(treatment)-334.2(period.)-343.5(V)106.3(ertical)-338.1(bars)-340.5(represent)-344.7(mean\213)]TJ
5.579 0 0 5.579 482.003 396.227 Tm
(SEM)Tj
7.97 0 0 7.97 496.176 396.227 Tm
[(change)-332.9(from)]TJ
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