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[(the)-333.6(treatment)-338.8(of)-333.2(asthm)-8.2(a)]TJ
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(b)Tj
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(2)Tj
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[(-a)19.2(go)15.5(n-)]TJ
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[(that)-292.7(long-acti)-10.7(ng)-280.4(agonis)-8.6(ts)-283.9(are)-289.2(only)-284.3(prescr)-9.8(ibed)-284.7(when)-291.9(short-)]TJ
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[(dose)-300.6(of)-299(400)-8(\261800)]TJ
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(m)Tj
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T*
[(lu)18.9(ng)-189.3(fu)13.9(nc)20.8(ti)16.5(on)-189.3(an)20.8(d)-199.9(s)0(y)14.4(m)0(p)18.1(t)0(o)18.9(m)0(s)-188(a)0(t)-192.1(a)-200.3(ti)16.5(me)-187.2(wh)17.3(en)-189.7(th)18.9(e)-200.3(l)0(o)18.9(n)0(g)15.5(-)0(a)19.2(c)0(t)18.4(i)0(n)13.2(g)]TJ
0 -1.0698 TD
[(ag)15.1(on)21.2(is)17.7(ts)-357.9(we)16.9(re)-356.3(st)12(i)13.9(l)0(l)-359.1(a)0(c)14.7(t)0(i)16.5(v)0(e)-354.7(t)0(o)-356.7(s)0(o)14.4(m)0(e)-357.9(e)0(x)20.8(t)0(e)18.4(n)0(t)13.2(.)-364.6(T)12.2(h)0(u)15.5(s)0(,)-355.2(a)0(l)12.8(t)13.9(ho)15.5(ug)15.5(h)]TJ
0 -1.0755 TD
[(sy)20(mp)12.4(to)18.9(ms)-330.2(ma)17.7(y)-342.2(h)0(a)20.8(v)0(e)-332(d)0(e)15.1(c)0(r)19.2(e)0(a)14.7(s)0(e)19.6(d)-342.2(an)20.8(d)-342.2(l)0(u)18.9(n)0(g)-331.6(f)0(u)19.6(n)0(c)15.1(t)0(i)22.2(o)0(n)-331.6(i)0(m)15.7(p)0(r)13.9(o)0(-)]TJ
T*
[(ve)15.1(d)-251.2(d)0(u)15.5(r)0(i)17.3(n)0(g)-246.2(t)13.9(he)-246.6(us)14.4(e)-251.6(o)0(f)-247.8(t)0(h)18.9(e)0(s)19.6(e)-257.2(dr)19.6(ug)15.5(s,)-247(t)13.9(h)0(e)15.1(r)0(e)-248.2(s)0(t)17.7(i)0(l)16.5(l)-253.5(re)19.2(ma)17.7(in)13.2(s)-252.3(a)-257.2(ri)17.3(sk)]TJ
T*
[(th)18.9(at)-118.1(th)18.9(es)13.9(e)-126.4(o)0(u)21.2(t)0(c)18.4(o)0(m)12.4(e)0(s)-116.9(a)0(r)19.2(e)-126.4(ma)17.7(sk)14.4(in)18.9(g)-126(p)0(o)21.2(s)0(s)13.2(i)0(b)18.9(l)0(e)-118.1(u)0(n)21.2(d)0(e)15.1(r)0(l)17.3(y)0(i)18.9(n)0(g)-115.3(i)0(n)13.2(f)0(l)17.3(a)0(m)17.7(-)]TJ
0 -1.0698 TD
[(ma)17.7(to)18.9(ry)-276.3(pr)14(oc)20.8(es)13.9(se)19.6(s)-286.5(o)0(r)-270.6(t)0(h)13.2(e)-280(in)13.2(cr)19.2(ea)14.7(se)-270.6(th)13.2(er)19.2(eo)15.1(f.)-270.2(Wh)14.4(en)-275.1(co)15.1(nt)18.9(ro)19.6(l)-287.7(o)0(f)]TJ
0 -1.0755 TD
[(as)19.6(th)13.2(ma)-278.2(is)-278.2(th)18.9(e)-291.4(p)0(r)19.6(i)0(m)15.7(a)0(r)19.2(y)-291(ai)18.5(m)-288.4(o)0(f)-282(a)-285.7(st)17.7(ud)21.2(y)67.5(,)-284.9(it)-279.4(is)-278.2(pa)15.1(rt)17.3(ic)18.4(ul)18.9(ar)13.5(ly)-277.1(im)15.7(-)]TJ
T*
[(po)15.5(rt)17.3(an)20.8(t)-236.5(t)0(o)-220.2(k)0(n)15.5(o)0(w)-227.4(w)12.4(he)15.1(th)18.9(er)-225.5(or)-225.1(no)21.2(t)-236.5(e)0(x)20.8(a)0(c)14.7(e)0(r)19.2(b)0(a)15.1(t)0(i)16.5(o)0(n)21.2(s)-235.3(oc)15.1(cu)20.8(r)-235.7(d)0(u)21.2(r)0(i)17.3(n)0(g)]TJ
0 -1.0698 TD
[(th)18.9(e)-166.2(l)0(o)18.9(n)0(g)15.5(-)0(t)17.3(e)0(r)19.2(m)-168.9(us)20(e)-166.2(o)0(f)-156.8(t)0(h)18.9(e)0(s)13.9(e)-160.5(dr)14(ug)21.2(s.)-156(It)-159.1(wa)16.9(s)-167(e)0(s)19.6(p)0(e)15.1(c)0(i)18.4(a)0(l)18.4(l)0(y)-157.6(i)0(n)-157.6(v)0(i)18.9(e)0(w)-159.5(o)0(f)]TJ
25.1977 42.9067 TD
[(th)13.2(is)-369.3(th)18.9(at)-368.5(th)18.9(e)-382.4(F)11.4(or)19.6(mo)12.4(te)18.4(ro)19.6(l)-378.7(a)0(n)15.1(d)-376.3(Co)16.5(rt)17.3(ic)18.5(os)20(te)12.8(ro)19.6(id)18.8(s)-377.5(E)0(s)15.9(t)0(a)18.4(b)0(l)18.9(i)0(s)12(h)0(i)18.9(n)0(g)]TJ
0 -1.0471 TD
[(Th)17.1(er)13.5(ap)20.8(y)-177.2(\()0(F)88.7(A)0(C)18.3(E)0(T)13(\))-173.1(st)17.7(ud)15.5(y)-177.2(w)0(a)16.9(s)-178.4(se)19.6(t)-179.6(u)0(p)15.5(:)-173.9(a)-177.6(1)0(2)15.5(-)0(m)16.5(o)0(n)21.2(t)0(h)-168.9(t)0(r)17.3(i)0(a)12.8(l)-173.9(du)15.5(ri)17.3(ng)]TJ
0 -1.0528 TD
[(wh)17.3(ic)12.8(h)-353.6(t)0(h)13.2(e)-354(ef)24.9(fe)19.2(ct)12.8(s)-354.8(o)0(f)-350.2(v)0(a)15.1(r)0(i)17.3(o)0(u)21.2(s)-360.5(do)21.2(se)14(s)-354.8(o)0(f)-350.3(a)0(n)-349.1(i)0(n)13.2(h)0(a)20.8(l)0(e)18.4(d)-359.3(co)15.1(rt)17.3(ic)18.4(o-)]TJ
0 -1.0471 TD
[(st)17.7(er)13.5(oi)18.9(d)-143(\()0(b)19.6(u)0(d)15.5(e)0(s)19.6(o)0(n)15.5(i)0(d)18.9(e)-143.4(20)15.5(0)]TJ
/F6 1 Tf
9.3097 0 TD
[(ve)20.4(rs)18.8(us)]TJ
/F5 1 Tf
2.6233 0 TD
[(80)15.5(0)]TJ
/F3 1 Tf
1.6275 0 TD
(m)Tj
/F5 1 Tf
0.5634 0 TD
[(g)-143(d)0(a)15.1(i)0(l)22.2(y)0(\))13.9(,)-142.6(po)21.2(ss)13.2(ib)18.9(ly)-134.8(co)20.8(m-)]TJ
-14.1239 -1.0528 TD
[(bi)13.2(ne)20.8(d)-251.2(w)12.4(it)16.5(h)-251.2(a)-245.9(lo)18.8(ng)15.5(-a)19.2(ct)18.5(in)18.9(g)]TJ
/F3 1 Tf
9.7536 0 TD
(b)Tj
/F5 1 Tf
7.472 0 0 6.641 411.874 728.164 Tm
(2)Tj
9.963 0 0 9.963 415.502 729.808 Tm
[(-a)13.5(dr)19.6(en)15.1(er)30.6(gi)18.9(c)-251.6(a)0(g)20.8(o)0(n)15.5(i)0(s)17.7(t)-247.8(\(f)18(or)13.9(mo)18.1(te)18.4(ro)19.6(l)]TJ
-10.6584 -1.0471 TD
(24)Tj
/F3 1 Tf
1.3999 0 TD
(m)Tj
/F5 1 Tf
0.5634 0 TD
[(g)-410.5(d)0(a)15.1(i)13.9(ly)13.2(\),)-395.4(we)16.9(re)-401.9(st)17.7(ud)15.5(ie)18.4(d)-404.8(i)0(n)-402.2(8)0(5)21.2(2)-410.5(as)19.6(th)13.2(ma)-397.7(pa)15.1(ti)16.5(en)20.8(ts)-397.8([2)14(0].)]TJ
-1.9632 -1.0528 TD
[(Rem)-10.6(arkably)58.2(,)-222.3(the)-221.3(long-ac)-10.1(ting)-218.4(agon)-9.1(ist)-218.8(did)-220.9(not)-220.9(on)-7.2(ly)-220.2(improve)]TJ
0 -1.0471 TD
[(lung)-403.8(function)-405.5(and)-395.3(dec)-8.8(rease)-400.5(symp)-7.4(toms)-396.7(bu)-7.2(t)-395.8(also)-399.7(reduced)]TJ
0 -1.0527 TD
[(the)-306.7(n)-6.5(umber)-304.9(o)-6.5(f)-304(mild)-306.9(and)-310(severe)-310.2(exacerba)-9.7(tions)-305.7(\(by)-311.2(40)-303.1(and)]TJ
T*
[(29%)-380.2(respec)-8.6(tive)-8.2(ly\).)-376.5(This)-380.6(was)-377.7(the)-380.7(case)-381(with)-381.6(not)-380.2(only)-375.3(the)]TJ
0 -1.0471 TD
[(high)-267.2(dose)-260.7(of)-259.2(the)-261.2(inhal)-9(ed)-258(corticost)-11.9(eroid)-264.3(\(800)]TJ
/F3 1 Tf
17.6293 0 TD
(m)Tj
/F5 1 Tf
0.5747 0 TD
[(g)-262.5(daily\))-261.7(but)]TJ
-18.2041 -1.0528 TD
[(also)-285.9(the)-283.9(low)-281.7(dose)-283.5(\(200)]TJ
/F3 1 Tf
9.3496 0 TD
(m)Tj
/F5 1 Tf
0.5747 0 TD
[(g)-279.6(dail)-8.2(y\).)-282.3(This)-283.9(last)-282.6(observ)-7.8(ation)-287.8(is)]TJ
-9.9243 -1.0471 TD
[(highl)-8.6(y)-211.3(relevant,)-213.2(b)-6.5(ecause)-212.2(this)-213.9(might)-216.6(imply)-210.9(that)-213.1(the)-215.6(addition)]TJ
0 -1.0527 TD
[(of)-230.7(a)-228.8(long-)-7.8(acti)-8.6(ng)]TJ
/F3 1 Tf
6.4702 0 TD
(b)Tj
/F5 1 Tf
7.472 0 0 6.641 379.275 633.997 Tm
(2)Tj
9.963 0 0 9.963 383.017 635.641 Tm
[(-agoni)-9(st)-227(could)-234.2(be)-229.6(useful)-237.8(from)-231.3(the)-232.7(mild-)]TJ
-7.3977 -1.0471 TD
[(persi)-9.4(stent)-363(asthma)-359.2(stage)-366.7(\(phase)-361(2)-353.6(i)0(n)-362.4(figure)-357.7(1)-6.5(,)-353.2(in)-356.7(which)-363.3(a)]TJ
0 -1.0527 TD
[(low)-350(dose)-346.1(of)-350.3(corticost)-11.9(eroids)-351.6(is)-346.5(adminis)-9.2(tered\).)-347.1(Thi)-8.8(s)-343.4(might)]TJ
0 -1.0471 TD
[(lead)-148.5(to)-140.5(long-)-7.8(acti)-8.6(ng)-138.1(agon)-9.2(ists)-141.1(being)-148.9(introduced)-151.4(at)-146.6(a)-143.4(much)-143.2(ear-)]TJ
0 -1.0528 TD
[(lier)-351.2(stage)-8.2(.)-347.5(Short-acti)-12.3(ng)-348.7(agonists)-349.4(mig)-7.8(ht)-345.3(then)-353(be)-343.4(prim)-10.2(arily)]TJ
0 -1.0471 TD
[(reser)-9(ved)-275.8(for)-272.9(intermi)-11.9(ttent)-273.1(asthm)-10.9(a)-268.6(and)-275.8(the)-272.5(long-)-7.8(acting)-277.6(ones)]TJ
0 -1.0527 TD
[(for)-267.3(persi)-9.4(stent)-266.2(asthm)-10.9(a.)-263.3(It)-267.3(should)-269.9(be)-263.7(stressed,)-270.9(howe)-7.4(ver)29.9(,)-267.8(that)]TJ
0 -1.0471 TD
[(long-)-7.8(actin)-9.4(g)-461.7(agonis)-8.6(ts)-466(should)-469.1(always)-473.8(be)-462.9(admi)-9(nistered)-469.7(in)]TJ
0 -1.0528 TD
[(combi)-9.7(nation)-169.1(with)-171.1(inhaled)-170.2(corticost)-11.9(eroid)-8.2(s.)-161.7(The)-166.2(dose)-169.7(of)-168.2(ster-)]TJ
0 -1.0471 TD
[(oids)-302.5(may)-296.1(be)-297.8(incre)-8.6(ased)-295.3(consi)-7.8(stent)-300.4(with)-296.3(the)-301(severity)-304.7(of)-293.3(the)]TJ
0 -1.0527 TD
[(asthm)-10.9(a;)-214.9(the)-215.6(F)68.3(ACET)-156.5(study)-217.9(also)-217.6(show)-8.2(s)-212.5(that)-218.8(a)-217.4(higher)-219.5(dose)-215.2(of)]TJ
0 -1.0471 TD
[(inhal)-9(ed)-332(co)-7.6(rticosteroid)-12.5(s)-332(resul)-9.4(ts)-335.2(in)-334(few)-8.2(er)-333.6(exacerba)-9.7(tions.)]TJ
/F6 1 Tf
0 -3.5566 TD
[(Pos)-7.6(sible)-334.5(a)-6.5(daptation)-338.4(of)-339.6(the)-335.1(phased)-336.2(plan)]TJ
/F5 1 Tf
1.0015 -2.7485 TD
[(Th)17.1(e)-428(c)0(o)20.8(n)0(s)14.4(i)13.9(de)15.1(ra)19.2(ti)16.5(on)15.5(s)-423.1(m)0(e)17.7(n)0(t)18.9(i)0(o)18.9(n)0(e)15.1(d)-421.9(ab)15.1(ov)21.2(e)-428(m)0(a)17.7(y)-421.9(le)18.4(ad)-417.4(in)-413.6(th)18.9(e)]TJ
-1.0015 -1.0528 TD
[(lo)13.2(ng)-200.7(ru)13.9(n,)-200.3(to)-203.1(ad)15.1(ap)20.8(ta)12.8(ti)22.2(on)-206.4(of)-202.3(th)13.2(e)-211.7(p)0(h)21.2(a)0(s)14(e)0(d)-201.1(p)0(l)13.2(a)0(n)-201.1(\()0(f)18(i)0(g)18.9(.)-216.6(2\).)-214.1(It)-221.7(shoul)-7.4(d)]TJ
0 -1.0471 TD
[(be)-269.4(empha)-7.8(sized)-275.7(that)-270(such)-272.1(adapta)-8.2(tion)-269.6(cannot)-275.2(be)-269.4(carried)-273.9(out)]TJ
0 -1.0527 TD
[(wi)-7.8(thout)-219.1(first)-223.5(having)-217.9(obtai)-9(ned)-213.2(the)-221.3(results)-225(of)-213.7(wel)-9(l)-213.7(contr)-8.2(olled)]TJ
0 -1.0471 TD
[(tri)-8.6(als)-313.6(conduct)-8.5(ed)-314.9(over)-318(a)-314.2(perio)-8.2(d)]TJ
/F3 1 Tf
12.3599 0 TD
(>)Tj
/F5 1 Tf
0.552 0 TD
[(12)-314.5(months.)-319(T)63.4(o)-313.8(prevent)-323.1(a)]TJ
-12.9119 -1.0527 TD
[(dec)-8.8(rease)-377.7(in)-373.8(compl)-9.7(iance)-377.3(wi)-7.8(th)-373.8(regard)-378.5(to)-379.5(inhaled)-380.8(corticos-)]TJ
0 -1.0471 TD
[(teroi)-10.6(ds)-537.6(a)-6.9(s)-536.9(a)-541.8(resul)-9.4(t)-538.1(o)0(f)-543.7(the)-545.7(efficacy)-536.8(of)-543.7(long-)-7.8(acting)]TJ
/F3 1 Tf
21.5501 0 TD
(b)Tj
/F5 1 Tf
7.472 0 0 6.641 529.512 393.335 Tm
(2)Tj
9.963 0 0 9.963 533.253 395.036 Tm
(-)Tj
-22.4777 -1.0528 TD
[(ago)-8.4(nists,)-227.6(the)-232.7(adminis)-9.1(tration)-230.7(of)-230.8(inhaled)-232.8(corticost)-11.9(eroids)-232.1(and)]TJ
0 -1.0471 TD
[(long-)-7.8(actin)-9.4(g)]TJ
/F3 1 Tf
4.8484 0 TD
(b)Tj
/F5 1 Tf
7.472 0 0 6.641 363.175 372.416 Tm
(2)Tj
9.963 0 0 9.963 366.916 374.116 Tm
[(-agonists)-334.7(in)-334(a)-331.2(fixed)-332.6(combi)-9.7(nation)-334.1(migh)-8.6(t)-327.5(b)0(e)]TJ
-5.7816 -1.0528 TD
[(con)-8.4(sidered.)-529.5(Thi)-8.8(s)-525.5(may)-529.4(involve)-534(variou)-9(s)-525.5(dosages)-532.1(of)-526.7(the)]TJ
0 -1.0471 TD
[(inhal)-9(ed)-383.2(corticost)-11.9(eroid,)-384.2(dependi)-8.5(ng)-382.8(on)-377.1(the)-386.3(severity)-390(of)-378.7(the)]TJ
0 -1.0527 TD
[(asthm)-10.9(a.)-229.2(Lab)-6.8(elling)-234.1(these)-241.5(various)-238.5(dosages)-236.2(with)-233.7(vario)-8.2(us)-230.3(co)-7.6(l-)]TJ
0 -1.0471 TD
[(ours,)-194(for)-187.6(instance)-189.7(green,)-194.4(orange)-189.1(and)-184.8(red)-192.1(\(comparabl)-11.9(e)-183.3(t)0(o)-186(the)]TJ
0 -1.0527 TD
[(colour)-9(s)-343.4(corres)-9.8(pondin)-7(g)-342.2(t)0(o)-345.3(the)-346.5(peak)-345.3(flow)-346.7(ranges)-349.6(in)-345.4(recent)]TJ
0 -1.0471 TD
[(self)-8.6(-mana)-9.4(gement)-341(plans\),)-340.6(could)-336.7(be)-337.7(considered.)]TJ
1.0015 -1.0527 TD
[(Re)16.1(ce)14.7(nt)18.8(ly)81.4(,)-250.8(i)0(t)-245.3(h)0(a)15.1(s)-246.7(be)15.1(en)-240.9(su)14.4(gg)21.2(es)13.9(te)18.4(d)-251.2(t)0(h)18.8(a)0(t)18.5(,)-250.8(wh)17.3(en)-246.6(a)-251.6(l)0(o)18.8(n)0(g)-240.5(a)0(c)14.7(t)0(i)16.5(n)0(g)]TJ
/F3 1 Tf
-1.0015 -1.0528 TD
(b)Tj
/F5 1 Tf
7.472 0 0 6.641 314.759 288.737 Tm
(2)Tj
9.963 0 0 9.963 318.387 290.381 Tm
[(-a)19.2(go)15.5(ni)18.9(st)-352.2(\(f)18(or)19.6(mo)18.1(te)12.8(ro)19.6(l\))-346.9(is)-352.2(us)20(ed)-349.1(on)-348.7(de)20.8(ma)12(nd)21.2(,)-358.9(i)0(t)-347.7(a)0(l)18.4(s)0(o)-349.8(m)0(i)15.7(g)0(h)21.2(t)]TJ
-0.9105 -1.0471 TD
[(im)15.7(pr)13.9(ov)21.2(e)-274.3(q)0(u)21.2(a)0(l)12.8(i)0(t)22.2(y)-273.9(of)-264.9(li)16.5(fe)-259.6(an)15.1(d)-268.2(a)0(s)14(t)0(h)18.8(m)0(a)-261.2(c)0(o)15.1(n)0(t)18.9(r)0(o)13.9(l)-270.6([2)19.6(1,)-274.3(22].)-283.1(How-)]TJ
0 -1.0528 TD
[(eve)-8.8(r)31.8(,)-239.4(this)-242.3(eviden)-7.8(ce)-241.3(is)-244.1(thus)-245.6(far)-244.9(not)-238(sufficient)-247.6(to)-237.2(propos)-7.4(e)-240.2(the)]TJ
0 -1.0471 TD
[(intr)-9.4(oduction)-238.9(of)-230.7(long-)-7.8(acting)]TJ
/F3 1 Tf
10.8917 0 TD
(b)Tj
/F5 1 Tf
7.472 0 0 6.641 423.326 257.386 Tm
(2)Tj
9.963 0 0 9.963 427.068 259.03 Tm
[(-agoni)-9(st)-232.7(even)-231.5(earli)-11(er)-231.2(than)-233.5(in)]TJ
-11.8193 -1.0528 TD
[(pha)-8.4(se)-333.2(2.)]TJ
/F7 1 Tf
0.6601 -3.5509 TD
[(The)-336.7(place)-342(of)-333.2(long-a)-7.8(cting)]TJ
/F3 1 Tf
10.7551 0 TD
(b)Tj
/F7 1 Tf
7.472 0 0 6.641 428.598 211.464 Tm
(2)Tj
9.963 0 0 9.963 432.34 213.165 Tm
[(-adrenergic)-331.5(agon)-8(ists)-333.8(in)]TJ
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