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[(la)18.4(bo)15.5(ra)19.2(to)18.9(ry)-230.8(on)-223.5(ei)18.4(gh)15.5(t)-230.8(o)0(c)15.1(c)0(a)14.7(s)0(i)17.7(o)0(n)21.2(s)0(.)-224.3(T)0(h)17.1(e)-234.5(sc)13.9(re)19.2(en)15.1(in)18.9(g)-234.1(w)0(a)16.9(s)-235.3(fo)19.6(ll)16.5(ow)17.3(ed)]TJ 0 -1.0698 TD [(by)-422.6(t)13.9(h)0(r)13.9(e)0(e)-417.7(5)0(-)13.9(d)0(a)20.8(y)-433.3(tr)17.3(ea)20.4(tm)15.7(en)15.1(t)-429.9(p)0(e)20.8(r)0(i)17.3(o)0(d)15.5(s)-428.7(wi)20.6(th)-425(a)-428(m)0(i)15.7(n)0(i)18.9(m)0(u)18.1(m)-430.7(of)-424.2(1)]TJ 0 -1.0755 TD [(we)16.9(ek)-206.8(wa)16.9(sh)-207.6(ou)15.5(t)-219.4(p)0(e)20.8(r)0(i)17.3(o)0(d)-206.4(i)0(n)-208.8(b)0(e)15.1(t)0(w)20.6(e)0(e)14.7(n)0(.)-206(Z)0(a)16.7(f)0(i)17.3(r)0(l)17.3(u)0(k)15.5(a)0(s)19.6(t)-219.4(an)20.8(d)-217(a)-217.4(ma)17.7(tc)12.8(h-)]TJ T* 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[(pe)15.1(rf)18(or)19.6(me)17.7(d)-308.1(a)0(t)-300.2(3)-308.1(h)-308.1(f)0(o)13.9(l)13.9(l)0(o)13.2(w)12.4(in)13.2(g)-308.1(t)0(h)18.9(e)-308.5(fi)17.3(rs)18.4(t)-310.4(d)0(o)21.2(s)0(e)-299(o)0(f)-299(t)0(r)17.3(e)0(a)14.7(t)0(m)15.7(e)0(n)20.8(t)0(.)-299.4(A)0(t)]TJ T* [(th)18.9(e)-274.3(e)0(n)15.1(d)-273.9(of)-270.6(ea)20.4(ch)-269.4(5)-273.9(d)0(a)15.1(y)-273.9(tr)17.3(ea)20.4(tm)15.7(en)15.1(t)-276.3(p)0(e)20.8(r)0(i)17.3(o)0(d)-269(c)0(o)15.1(l)13.9(d)-279.6(a)0(i)18.4(r)-275.5(ch)15.1(al)18.4(le)18.4(ng)15.5(es)]TJ T* [(we)16.9(re)-276.7(do)15.5(ne)-275.1(3,)-280(8,)-274.3(12)21.2(,)-284.9(2)0(4)-280.4(h)-285.3(fo)19.6(ll)16.5(ow)17.3(in)18.9(g)-285.3(t)0(h)13.2(e)-285.7(la)18.4(st)-278.2(mo)18.1(rn)19.6(in)13.2(g)-285.3(d)0(o)21.2(s)0(e)13.9(.)]TJ T* [(S)11.4(u)0(b)15.5(j)0(e)18.4(c)0(t)18.4(s)-263.7(at)18.4(te)12.8(nd)21.2(ed)-252.3(th)13.2(e)-257.2(c)0(l)12.8(i)0(n)18.9(i)0(c)-254.7(a)0(t)-249(t)0(h)13.2(e)-262.9(sa)19.6(me)-255.5(ti)16.5(me)-255.5(of)-247.8(da)15.1(y)-262.5(\()0(\213)15.1(2)-262.5(h\))]TJ T* [(fo)19.6(r)-298.3(e)0(a)20.4(c)0(h)-286.5(v)0(i)18.9(s)0(i)17.7(t)0(.)-288.1(I)0(n)-287.7(c)0(a)20.4(s)0(e)-287.7(o)0(f)-287.7(l)13.9(ow)-290(ou)21.2(td)13.2(oo)21.2(r)-298.3(t)13.9(em)12(pe)20.8(ra)13.5(tu)18.9(re)19.2(s)-297.9(\()0(u)19.6(n)0(d)15.5(e)0(r)]TJ T* (10)Tj /F10 1 Tf 0.9845 0 TD 0 Tw (8)Tj /F9 1 Tf 0.3756 0 TD [(C)11.6(\))-355.2(th)18.9(e)-354(p)0(a)15.1(t)13.9(ie)12.8(nt)18.9(s)-354.8(h)0(a)20.8(d)-353.6(to)-345.3(ta)18.4(ke)-343.4(a)-354(r)0(e)19.2(s)0(t)-346.5(f)0(o)19.6(r)-355.2(60)-343(mi)15.7(n)-347.9(a)0(t)-345.7(r)0(o)13.9(o)0(m)]TJ -1.36 -1.0698 TD [(te)18.4(mp)18.1(er)13.5(at)18.4(ur)19.6(e)-325.5(a)0(f)13.5(t)0(e)18.4(r)-321(th)13.2(ey)-314.9(ar)19.2(ri)17.3(ve)15.1(d)-319.4(a)0(t)-317.3(t)0(h)18.9(e)-325.5(ce)14.7(nt)18.9(re)19.2(.)]TJ /F3 1 Tf 0 -3.3005 TD [(Lung)-338(function)-343.7(measur)28.5(emen)-7.8(t)]TJ /F9 1 Tf 1.0015 -1.6503 TD [(FE)17.9(V)]TJ 7.97 0 0 7.97 86.683 155.452 Tm (1)Tj 9.963 0 0 9.963 93.203 155.452 Tm [(ba)15.1(se)19.6(li)16.5(ne)15.1(-t)17.3(es)19.6(ts)-249.8(co)15.1(ns)20(is)17.7(te)18.4(d)-256.8(o)0(f)-247.8(t)0(h)13.2(r)0(e)19.2(e)-257.2(fo)19.6(rc)13.5(ed)-246.6(ex)15.1(pi)18.9(ra)19.2(to)13.2(ry)]TJ -3.5054 -1.0755 TD [(ma)17.7(no)15.5(eu)20.8(vr)14(es)-327.5(ca)20.4(rr)12.4(i)13.9(e)0(d)-332(o)0(u)21.2(t)-338.9(ac)20.4(co)15.1(rd)19.6(in)13.2(g)-336.5(t)13.9(o)-336.5(s)0(t)17.7(a)0(n)15.1(d)0(a)15.1(r)0(d)-327.5(p)0(r)19.6(o)0(c)15.1(e)0(d)20.8(u)0(r)13.9(e)0(s)]TJ T* [([1)19.6(4])-424.2(with)-438.5(an)-428.7(elect)-9.8(ronic)-435(spiromet)-11.5(er)-430.3(\(Z)-7.2(AN)-430.5(Hand)-7.4(y;)-430.7(ZAN)]TJ T* [(Co.,)-183.4(Ober)-9(thulba,)-186.5(Ger)-8.2(many\))-9(.)]TJ /F8 1 Tf 11.2047 0 TD (b)Tj /F9 1 Tf 7.472 0 0 6.641 175.408 121.663 Tm (2)Tj 9.963 0 0 9.963 179.15 123.307 Tm [(-agonists)-192.4(were)-185.8(withhel)-11.1(d)-182.9(for)]TJ /F11 1 Tf -12.1322 -1.0755 TD ($)Tj /F9 1 Tf 0.8365 0 TD [(6)-330.8(h)-336.5(before)-338.6(each)-340(spiromet)-11.5(ry)-333.2(test.)]TJ /F3 1 Tf 24.3612 35.7025 TD [(Isocap)-7.8(nic)-340.8(hyperve)-8.1(ntilation)-343.1(challenge)-342.9(with)-336.9(cold)-335.9(air)]TJ /F9 1 Tf 1.0015 -1.6503 TD [(Th)17.1(e)-450.7(d)0(e)15.1(t)13.9(ai)12.8(le)18.5(d)-444.6(t)0(e)12.8(c)0(h)20.8(n)0(i)18.9(q)0(u)15.5(e)-450.7(ha)20.8(s)-445.8(b)0(e)15.1(e)0(n)-440.1(d)0(e)20.8(s)0(c)13.9(r)0(i)17.3(b)0(e)20.8(d)-450.3(el)18.4(se)14(w)12.4(h)0(e)15.1(r)0(e)]TJ -1.0015 -1.0527 TD [([1)13.9(5\26117].)-540.7(Briefly)55.6(,)-546.7(chall)-9.4(enges)-546.4(wer)-8.2(e)-547.5(conduct)-8.5(ed)-548.2(with)-546.7(the)]TJ 0 -1.0471 TD [(subje)-7.8(ct)-254.7(stand)-7.8(ing)-255.1(and)-253.1(breat)-8.6(hing)-255.8(cold,)-256.6(dry)-254.3(air)-257.1(from)-259.8(the)-255.5(hos-)]TJ 0 -1.0527 TD [(pita)-8.2(l)]TJ /F10 1 Tf 1.7584 0 TD (')Tj /F9 1 Tf 0.2162 0 TD [(s)-332(c)-6.9(ompressed)-344.8(air)-336.7(supply)60.1(,)-336.1(which)-340.6(was)-337.9(chilled)-343.3(to)-334(app-)]TJ -1.9746 -1.0471 TD [(roxim)-10.9(ately)-276.8(-17)]TJ /F10 1 Tf 5.884 0 TD (8)Tj /F9 1 Tf 0.387 0 TD [(C)-272.9(b)0(y)-269(a)-274.3(heat)-273.7(exchange)-7.7(r)-269.8(\(RHE-T)49.3(est;)-271.2(Jaeger)]TJ -6.271 -1.0527 TD [(Co.)-6.6(,)-262.1(H)0(o)]TJ 2.7485 0 TD [(\310)-82(chb)-8.4(erg,)-255.1(Germany\))-11.5(,)-262.1(through)-265.4(a)-262.9(t)0(w)-7.8(o)-262.5(way)-262.7(valve)-268.8(with)]TJ -2.7485 -1.0471 TD [(separa)-8.6(ted)-272.5(ports)-276.4(for)-267.2(inspi)-9.8(ration)-273.1(and)-270.1(expir)-8.2(ation.)-271.1(The)-274.3(inspir-)]TJ 0 -1.0528 TD [(atory)-264.3(port)-263.1(was)-258.2(atta)-8.6(ched)-259.9(to)-260(an)-258(air)-257.1(flow)-261.4(syst)-7.8(em,)-261.5(which)-260.9(con-)]TJ 0 -1.0471 TD [(tain)-8.2(ed)-206.8(a)-211.7(mechanism)-217.1(for)-210.3(indi)-7.8(cating)-209.3(the)-209.9(subje)-7.8(ct)]TJ /F10 1 Tf 17.7545 0 TD (')Tj /F9 1 Tf 0.2162 0 TD [(s)-206.8(v)0(e)-7.6(ntilation)]TJ -17.9708 -1.0528 TD [(rate)-275.3(and)-275.8(thus)-274.1(allowi)-10.4(ng)-269(the)-272.5(subje)-7.8(ct)-271.8(to)-271.4(mai)-8.2(ntain)-270.7(the)-278.2(desired)]TJ 0 -1.0471 TD [(rate.)-309.8(T)63.4(o)-308.1(determin)-10.7(e)-302.8(the)-306.7(provoca)-7.7(tive)-304.1(venti)-9(lation)-308(rate)-309.4(requi-)]TJ 0 -1.0528 TD [(red)-237.6(to)-231.5(induce)-235.4(a)-234.5(10%)-232.3(fall)-237.4(in)-231.5(FEV)]TJ 7.97 0 0 7.97 434.041 336.756 Tm (1)Tj 9.963 0 0 9.963 440.334 336.756 Tm (\(PV)Tj 7.97 0 0 7.97 456.264 336.756 Tm (10)Tj 9.963 0 0 9.963 464.201 336.756 Tm [(\))-230(and)-236(a)-228.8(20%)-238(fall)-231.7(in)]TJ -15.5466 -1.0527 TD (FEV)Tj 7.97 0 0 7.97 328.082 326.268 Tm (1)Tj 9.963 0 0 9.963 334.942 326.268 Tm [(\(P)-8(V)]TJ 7.97 0 0 7.97 350.872 326.268 Tm (20)Tj 9.963 0 0 9.963 358.809 326.268 Tm [(\))-298.3(each)-300.2(subje)-7.8(ct)-294.5(breat)-8.6(hed)-298.6(for)-295.7(succes)-8.2(sive)-302.9(3-min)]TJ -4.9678 -1.0471 TD [(perio)-8.2(ds)-275.9(at)-271.8(a)-274.3(ventilat)-10.7(ion)-272.1(rate)-281(that)-275.7(started)-281.2(at)-271.8(20)-274.7(L)]TJ /F7 1 Tf 18.6593 0.1992 TD (.)Tj /F9 1 Tf 0.2675 -0.1992 TD (min)Tj 7.472 0 0 6.641 513.297 320.258 Tm (-1)Tj 9.963 0 0 9.963 522.142 315.836 Tm (and)Tj -21.3623 -1.0527 TD [(was)-377.7(increased)-377.8(by)-371.4(10)-371.4(L)]TJ /F7 1 Tf 9.3666 0.2049 TD (.)Tj /F9 1 Tf 0.2731 -0.2049 TD (min)Tj 7.472 0 0 6.641 420.718 309.827 Tm (-1)Tj 9.963 0 0 9.963 430.583 305.348 Tm [(at)-368.5(the)-375(start)-376(of)-367.3(each)-374.1(subse-)]TJ -12.1721 -1.0471 TD [(que)-8.4(nt)-345.3(perio)-8.2(d.)-348.3(Cold)-357.3(air)-348.1(cha)-8.8(llenges)-353.5(wer)-8.2(e)-348.3(performed)-357(when)]TJ 0 -1.0527 TD [(basel)-8.2(ine)-460.3(FEV)]TJ 7.97 0 0 7.97 364.932 284.428 Tm (1)Tj 9.963 0 0 9.963 373.436 284.428 Tm (was)Tj /F8 1 Tf 1.9974 0 TD (>)Tj /F9 1 Tf 0.552 0 TD [(70%)-459.9(of)-452.7(predi)-8.2(cted)-455.8(and)-457.9(term)-10.6(inated)]TJ -8.9854 -1.0471 TD [(when)-337.4(a)-331.2(drop)-329(in)-334(FEV)]TJ 7.97 0 0 7.97 392.938 273.997 Tm (1)Tj 9.963 0 0 9.963 400.195 273.997 Tm (of)Tj /F11 1 Tf 1.1495 0 TD ($)Tj /F9 1 Tf 0.8365 0 TD [(20%)-334.7(from)-333.8(basel)-8.2(ine)-329.4(occurr)-8.6(ed.)]TJ -11.108 -1.0528 TD (FEV)Tj 7.97 0 0 7.97 328.082 263.509 Tm (1)Tj 9.963 0 0 9.963 334.828 263.509 Tm [(was)-286.7(recorded)-289.3(30)-280.4(s)-280.8(after)-289(the)-283.9(end)-281.5(of)-282(each)-283.1(ven)-8.4(tilation)]TJ -2.5607 -1.0471 TD [(perio)-8.2(d)-217(and)-224.6(after)-226.4(1.5,)-218.5(3,)-217.4(5)-222.7(and)-218.9(6.5)-223.8(min)-218.4(in)-220.2(order)-223.6(to)-220.2(d)-6.5(etect)-220.3(the)]TJ 0 -1.0528 TD [(maxi)-9(mum)-281.7(respon)-7.8(se.)-282.3(The)-280(CO)]TJ 7.472 0 0 6.641 424.12 240.945 Tm (2)Tj 9.963 0 0 9.963 430.583 242.589 Tm [(con)-8.4(tent)-281.4(of)-276.3(inspi)-9.8(red)-277.4(air)-285.5(was)]TJ -12.1721 -1.0471 TD [(adjus)-7.8(ted)-283.9(to)-282.7(maintain)-284.7(isoca)-8.2(pnic)-284.7(hyperve)-7.7(ntilation.)-287(Su)-6.4(bjects)]TJ 0 -1.0527 TD [(wer)-8.2(e)-371.1(not)-374.6(allowed)-379(to)-373.8(perfor)-9.8(m)-368.1(any)-378.3(exercise)-377.1(prior)-379.3(to)-373.8(their)]TJ 0 -1.0471 TD [(atte)-8.6(ndance.)-313.5(This)-306.7(incl)-8.2(uded)-310.7(cycling,)-312.9(running)-310.9(or)-310.4(swimming)]TJ 0 -1.0528 TD [(in)-487.6(the)-488.8(morn)-7.8(ing)-488.4(of)-486.8(the)-488.8(visi)-9(t)-486.8(and)-486.4(between)-496.6(the)-488.8(different)]TJ 0 -1.0471 TD [(exe)-8.8(rcise-testi)-13.3(ngs)-333.5(of)-338.9(the)-335.1(day)59.9(.)]TJ /F3 1 Tf 0 -3.0103 TD [(Safet)-9(y)-331.2(asses)-7.8(sme)-7.8(nts)]TJ /F9 1 Tf 1.0015 -1.6503 TD [(Sa)15.9(fe)13.5(ty)-271.4(wa)16.9(s)-286.5(d)0(e)15.1(t)13.9(er)13.5(mi)15.7(ne)20.8(d)-285.3(d)0(u)15.5(r)0(i)17.3(n)0(g)-274.7(e)0(a)20.4(c)0(h)-275.1(v)0(i)18.9(s)0(i)12(t)-282(by)-274.7(a)-285.7(r)0(e)19.2(v)0(i)18.9(e)0(w)-279(o)0(f)]TJ -1.0015 -1.0471 TD [(su)14.4(bj)18.9(ec)14.7(t)]TJ /F10 1 Tf 2.7372 0 TD (')Tj /F9 1 Tf 0.2105 0 TD [(s)-275.1(s)0(t)17.7(a)0(t)18.5(e)-280(of)-264.9(he)20.8(al)12.8(t)13.9(h)0(,)-268.6(a)0(n)-263.7(i)0(n)18.9(t)0(e)12.8(r)0(v)19.6(i)0(e)18.4(w)-277.8(fo)19.6(r)-275.5(s)0(u)14.4(b)0(j)18.9(e)0(c)20.4(t)0(i)16.5(v)0(e)-269.4(s)0(y)20(m)0(p)18.1(-)]TJ -2.9477 -1.0528 TD [(to)13.2(ma)17.7(to)18.9(lo)18.8(gy)78.1(,)-364.6(r)0(o)19.6(u)0(t)18.9(i)0(n)13.2(e)-359.7(la)12.8(bo)21.2(ra)13.5(t)13.9(o)0(r)13.9(y)-365(te)18.4(st)17.7(s)-366.2(a)0(n)20.8(d)-365(re)13.5(co)20.8(rd)13.9(i)13.9(n)0(g)-360(o)0(f)-355.9(a)0(d)20.8(-)]TJ 0 -1.0471 TD [(ve)15.1(rs)18.4(e)-325.5(e)0(v)15.1(e)0(n)20.8(t)0(s)17.7(.)]TJ ET 1 i 58.28 768.302 478.205 -0.51 re f 58.28 742.393 478.205 -0.51 re f 58.28 536.655 478.205 -0.51 re f BT /F2 1 Tf 8.966 0 0 8.966 58.28 772.667 Tm [(Table)-331.9(1.)-336.7(\261)-668.3(Patient)]TJ /F10 1 Tf 8.3083 0 TD (')Tj /F2 1 Tf 0.2213 0 TD [(s)-334.6(characteristics)]TJ /F9 1 Tf -8.5296 -1.7135 TD (Pt)Tj 0 -1.0496 TD (No.)Tj 4.445 1.0496 TD (Sex)Tj -0.1138 -1.0496 TD (M/F)Tj 3.465 1.0496 TD (Height)Tj 0.7461 -1.0496 TD (cm)Tj 3.7115 1.0496 TD (Age)Tj 0.2213 -1.0496 TD (yrs)Tj 3.1931 1.0496 TD [(Exsmoker)-1761(Aller)12.7(gy)-2515.5(PC)]TJ 7.173 0 0 7.173 311.017 757.304 Tm (20)Tj 8.966 0 0 8.966 293.329 747.893 Tm (mg)Tj /F7 1 Tf 1.2646 0.2213 TD (.)Tj /F9 1 Tf 0.2719 -0.2213 TD (mL)Tj 6.725 0 0 5.977 319.464 751.861 Tm (-1)Tj 8.966 0 0 8.966 345.09 757.304 Tm (PV)Tj 7.173 0 0 7.173 356.485 757.304 Tm (20)Tj 8.966 0 0 8.966 340.724 747.893 Tm (L)Tj /F7 1 Tf 0.607 0.2213 TD (.)Tj /F9 1 Tf 0.2719 -0.2213 TD (min)Tj 6.725 0 0 5.977 362.438 751.861 Tm (-1)Tj 8.966 0 0 8.966 385.342 757.304 Tm (VC)Tj 0.392 -1.0496 TD (L)Tj 2.9338 1.0496 TD (FEV)Tj 7.173 0 0 7.173 431.943 757.304 Tm (1)Tj 8.966 0 0 8.966 422.646 747.893 Tm (L)Tj 3.5155 1.0496 TD (FEV)Tj 7.173 0 0 7.173 471.005 757.304 Tm (1)Tj 8.966 0 0 8.966 451.332 747.893 Tm [(%)-328.8(pred)]TJ 4.6726 1.0496 TD (Medication)Tj -48.5094 -3.054 TD [(1)-4412.9(F)-2931.9(168)-2685.7(45)-3931.8(-)-4951.3(-)-3743.6(0.26)-3542.2(36.1)-2397.8(4.12)-2024.7(2.56)-2846.7(88.0)-4016.4(B)]TJ 0 -1.0559 TD [(2)-4242.2(M)-2769.6(185)-2685.7(28)-3931.8(-)-4831.2(+)-3623.8(0.28)-3542.2(44.8)-2397.8(5.16)-2024.7(4.22)-2846.7(90.8)-4016.4(B)]TJ T* 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[(ve)15.1(nt)18.9(il)16.5(at)18.4(io)18.9(n)-347.9(c)0(u)15.1(r)0(v)19.6(e)-354(on)21.2(ly)-345.3(w)12.4(h)0(e)15.1(r)0(e)-339.3(t)0(h)13.2(e)-348.3(la)18.4(st)-340.8(po)15.5(in)18.9(t)-350.3(o)0(n)-343(t)0(h)18.8(e)-348.3(ve)15.1(nt)18.9(il)16.5(-)]TJ 0 -1.0755 TD [(at)18.4(io)18.9(n)-438.9(c)0(u)20.8(r)0(v)13.9(e)-433.7(wa)16.9(s)-434.4(g)0(r)13.9(e)0(a)20.4(t)0(e)12.8(r)-434.8(th)18.9(an)-428.7(or)-424.2(eq)15.1(ua)20.8(l)-435.6(t)0(o)-425(5)0(%)-430.7(a)0(n)15.1(d)-433.3(15)21.2(%,)]TJ T* [(re)19.2(sp)14.4(ec)20.4(ti)16.5(ve)15.1(ly)81.4(,)-319.1(f)0(a)19.2(l)0(l)-307.9(i)0(n)-311.2(F)11.4(EV)]TJ 7.97 0 0 7.97 154.772 604.176 Tm (1)Tj 9.963 0 0 9.963 158.627 604.176 Tm [(.)-319.1(I)0(f)-306.3(t)0(h)13.2(e)-314.2(ve)15.1(nt)18.9(il)16.5(at)18.5(io)18.9(n)-319.4(r)0(a)19.2(t)0(e)-311.6(f)0(o)19.6(r)-321(P)11.4(V)]TJ 7.97 0 0 7.97 277.568 604.176 Tm (10)Tj 9.963 0 0 9.963 58.28 593.461 Tm [(ca)14.7(l)13.9(c)0(u)15.1(l)0(a)18.4(t)0(e)18.4(d)-239.8(by)-234.8(ex)20.8(tr)17.3(ap)15.1(ol)18.9(at)18.4(io)18.9(n)-239.8(w)0(a)16.9(s)]TJ /F8 1 Tf 12.4964 0 TD (>)Tj /F9 1 Tf 0.5463 0 TD [(80)-229.2(L)]TJ /F7 1 Tf 1.821 0.2049 TD (.)Tj /F9 1 Tf 0.2731 -0.2049 TD [(mi)15.7(n)]TJ 7.472 0 0 6.641 224.164 597.883 Tm (-1)Tj 9.963 0 0 9.963 232.611 593.461 Tm [(th)18.9(e)-240.2(v)0(a)15.1(l)0(u)18.9(e)-240.2(wa)16.9(s)]TJ -17.4984 -1.0698 TD [(se)19.6(t)-344.6(a)0(t)-334.4(8)0(5)-331.6(L)]TJ /F7 1 Tf 4.3874 0.1992 TD (.)Tj /F9 1 Tf 0.2675 -0.1992 TD [(mi)15.7(n)]TJ 7.472 0 0 6.641 119.735 587.225 Tm (-1)Tj 9.963 0 0 9.963 125.745 582.803 Tm [(.)-336.1(T)0(h)17.1(e)-342.6(ce)14.7(ns)20(or)13.9(ed)-332(va)20.8(lu)18.9(es)-333.2(mi)15.7(gh)15.5(t)-344.6(h)0(a)20.8(v)0(e)-332(i)0(n)18.9(t)0(r)17.3(o)0(-)]TJ -6.7718 -1.0755 TD [(du)15.5(ce)20.4(d)-211.3(s)0(o)14.4(m)0(e)-204.2(b)0(i)18.9(a)0(s)-202.3(i)0(n)18.9(t)0(o)-208.8(t)13.9(he)-206.8(tr)17.3(ea)20.4(tm)15.7(en)15.1(t)-213.7(c)0(o)20.8(m)0(p)18.1(a)0(r)13.5(i)0(s)17.7(o)0(n)21.2(s)-212.5(bu)15.5(t)-213.7(s)0(h)20(o)0(u)15.5(l)0(d)]TJ T* [(ha)15.1(ve)-292.2(in)18.8(tr)11.6(od)21.2(uc)15.1(ed)-292.2(le)12.8(ss)-294.1(bi)18.9(as)-299(th)18.9(an)-297.8(om)18.1(it)16.5(ti)22.2(ng)-297.4(th)18.9(es)13.9(e)-302.8(v)0(a)15.1(l)0(u)18.8(e)0(s)-293.3(f)0(r)12.4(o)0(m)]TJ 0 -1.0698 TD [(th)18.9(e)-325.5(a)0(n)15.1(a)0(l)18.4(y)0(s)20(i)0(s)-318.1(a)0(l)18.4(t)0(o)18.9(g)0(e)15.1(t)0(h)18.9(e)0(r)70.4(.)-324.7(Wh)14.4(er)19.2(e)-325.5(e)0(x)20.8(t)0(r)17.3(a)0(p)15.1(o)0(l)18.9(a)0(t)18.4(i)0(o)13.2(n)-319.4(wa)16.9(s)-326.3(n)0(o)15.5(t)-321.8(po)15.5(s-)]TJ 0 -1.0755 TD [(si)17.7(bl)18.9(e,)-246.2(a)-251.6(c)0(e)14.7(n)0(s)20(o)0(r)14(e)0(d)-240.9(v)0(a)15.1(l)0(u)18.9(e)-257.2(eq)20.8(ua)15.1(l)-253.5(t)0(o)-242.9(t)0(h)18.9(e)-257.2(hi)18.9(gh)21.2(es)13.9(t)-253.5(v)0(e)20.8(n)0(t)13.2(i)0(l)16.5(a)0(t)18.4(i)0(o)18.8(n)-251.2(ra)13.5(te)]TJ T* [(wa)16.9(s)-326.3(u)0(s)20(e)0(d)15.1(.)]TJ 1.0015 -1.0471 TD [(Be)16.1(ca)14.7(us)20(e)-336.9(o)0(f)-327.5(t)0(h)13.2(e)-336.9(la)18.4(r)20.4(g)0(e)-332(p)0(r)19.6(o)0(p)15.5(o)0(r)19.6(t)0(i)16.5(o)0(n)-331.6(o)0(f)-327.5(c)0(e)20.4(n)0(s)14.4(o)0(r)19.6(e)0(d)-332(P)11.4(V)]TJ 7.97 0 0 7.97 259.2 518.853 Tm (20)Tj 9.963 0 0 9.963 270.425 518.853 Tm [(va)15.1(l-)]TJ -21.294 -1.0755 TD [(ue)15.1(s)-235.3(a)-240.2(no)15.5(np)21.2(ar)13.5(am)17.7(et)18.5(ri)17.3(c)-240.2(a)0(n)15.1(a)0(l)18.5(y)0(s)20(i)0(s)-232.7(b)0(y)-229.2(a)-240.2(F)11.4(r)0(i)17.3(e)0(d)15.1(m)0(a)17.7(n)]TJ /F10 1 Tf 17.0489 0 TD (')Tj /F9 1 Tf 0.2049 0 TD [(s)-241(C)0(h)16.5(i)0(-)17.3(S)11.4(qu)15.5(ar)19.2(ed)]TJ -17.2537 -1.0755 TD [(te)18.4(st)-357.9(wa)16.9(s)-366.2(p)0(e)15.1(r)0(f)18(o)0(r)19.6(m)0(e)12(d)-365(us)20(in)18.9(g)-370.7(S)11.4(AS)]TJ 7.472 0 0 6.641 180.624 501.846 Tm 0.0001 Tc (TM)Tj 9.963 0 0 9.963 195.307 497.423 Tm 0 Tc [(PR)17.3(OC)-363(F)11.4(R)0(E)18.1(Q)-368.9(\(S)14.7(A)12.4(S)]TJ 7.472 0 0 6.641 274.394 501.846 Tm 0.0001 Tc (TM)Tj 9.963 0 0 9.963 58.28 486.765 Tm 0 Tc [(In)19.6(st)17.7(it)16.5(ut)13.2(e)-354(I)0(n)19.6(c)0(.)15.5(,)-353.2(Ca)16.1(ry)82.2(,)-358.9(N)0(C)18.3(,)-358.9(U)12.4(S)0(A)12.4(\))-355.2(to)-345.3(te)18.4(st)-346.5(fo)13.9(r)-355.2(d)0(i)18.9(f)20.4(fe)13.5(re)19.2(nc)15.1(es)-344.6(be)15.1(-)]TJ T* [(tw)14.9(ee)20.4(n)-416.2(e)0(a)20.4(c)0(h)-406(z)0(a)20.4(f)0(i)17.3(r)0(l)17.3(u)0(k)15.5(a)0(s)19.6(t)-412.9(tr)17.3(ea)14.7(tm)15.7(en)20.8(t)-412.9(a)0(n)15.1(d)-410.5(pl)13.2(ac)20.4(eb)15.1(o)-410.5([)0(1)19.6(5].)-418.9(This)]TJ T* [(test)-322.4(assum)-9.7(es)-321.8(that)-321.2(there)-327.3(are)-317.7(no)-320.2(sequen)-12.3(ce,)-321.4(period)-321.9(or)-321.8(carry-)]TJ T* [(over)-215.6(effects.)-207.2(This)-215.6(assumpti)-11.1(on)-212.1(was)-212.7(reason)-8.2(able)-211.1(given)-217.2(by)-212.1(the)]TJ 0 -1.0698 TD [(nonsi)-7.4(gnificant)-420.4(resul)-9.4(ts)-414.8(of)-418.5(the)-414.8(param)-9.4(etric)-420.7(analys)-9(es)-412.8(of)-418.5(the)]TJ 0 -1.0755 TD (PV)Tj 7.97 0 0 7.97 70.98 433.247 Tm (10)Tj 9.963 0 0 9.963 82.431 433.247 Tm [(values.)-356.5(The)-353.9(extent)-357.3(of)-355.9(values)-356.1(for)-358.3(PV)]TJ 7.97 0 0 7.97 228.246 433.247 Tm (10)Tj 9.963 0 0 9.963 239.698 433.247 Tm [(censor)-8.2(ed)-354.7(at)]TJ -18.2098 -1.0755 TD [(the)-255.5(highes)-8.6(t)-247.8(venti)-9(lation)-256.8(rate)-258.2(and)-253.1(at)-254.7(85)-251.9(L)]TJ /F7 1 Tf 15.3019 0.1992 TD (.)Tj /F9 1 Tf 0.2731 -0.1992 TD (min)Tj 7.472 0 0 6.641 228.813 426.954 Tm (-1)Tj 9.963 0 0 9.963 237.487 422.532 Tm [(was)-258.2(8%)-254.3(and)]TJ -17.9878 -1.0698 TD [(a)-354(parametri)-13.5(c)-348.3(a)0(n)-7.6(alysis)-353.6(by)-354.3(analys)-9(is)-352.2(of)-355.9(variance)-358.8(\(ANO)-10.7(V)126.2(A)0(\))]TJ 0 -1.0755 TD [(model)-9.7(s)-480(was)-491.5(fitted)-491.7(to)-481.9(the)-488.8(data)-489.9(for)-489.2(PV)]TJ 7.97 0 0 7.97 216.964 401.159 Tm (10)Tj 9.963 0 0 9.963 229.776 401.159 Tm [(using)-485.4(SAS)]TJ 7.472 0 0 6.641 274.28 405.581 Tm 0.0001 Tc (TM)Tj 9.963 0 0 9.963 58.28 390.444 Tm 0 Tc [(PROC)-470.9(FREQ)-470.3(\(SAS)]TJ 7.472 0 0 6.641 140.315 394.866 Tm 0.0001 Tc (TM)Tj 9.963 0 0 9.963 156.076 390.444 Tm 0 Tc [(Institu)-9.6(te)-465.2(Inc.\).)-468.3(Separat)-9.7(e)-462.1(model)-9.7(s)]TJ -9.8162 -1.0755 TD [(were)-225.6(fitted)-224.3(to)-225.8(the)-221.3(data)-222.5(from)-225.6(each)-220.5(tim)-10.2(e)-217.4(point.)-225.2(The)-223.1(effects)-218.2(of)]TJ 0 -1.0698 TD [(patien)-10.1(ts)-545.7(\(between)-555.8(patients\))-558.2(and)-543.3(the)-551.4(effects)-542.5(of)-549.4(perio)-8.2(d,)]TJ 0 -1.0755 TD [(treatmen)-11.1(t)-242.2(and)-241.7(first)-246.3(order)-246.4(carry-)-10.2(over)-244.1(\(within)-245.6(pati)-8.2(ents\))-242.7(wer)-8.2(e)]TJ T* [(includ)-9.7(ed)-286.5(in)-288.4(the)-295.3(models.)-296.6(The)-291.3(assumpti)-11.1(ons)-288(of)-293.3(the)-289.6(ANO)-8.4(V)126.2(A)]TJ 0 -1.0698 TD [(were)-396.3(valid)-390.2(for)-392.4(the)-392(analysis)-395.3(of)-390.1(PV)]TJ 7.97 0 0 7.97 196.554 336.983 Tm (10)Tj 9.963 0 0 9.963 208.346 336.983 Tm [(at)-391.3(each)-391.2(time)-392.6(point)-8.6(.)]TJ -15.0629 -1.0755 TD [(First)-545.5(order)-542.3(carry-)-10.2(over)29.1(,)-541(perio)-8.2(d)-535.7(a)0(n)-7.6(d)-535.7(treatmen)-11.1(t)-543.7(sequenc)-7.7(e)]TJ T* [(were)-265.5(nonsi)-7.4(gnificant)-272.5(in)-265.7(all)-263.5(models,)-268.2(for)-267.2(PV)]TJ 7.97 0 0 7.97 222.236 315.553 Tm (10)Tj 9.963 0 0 9.963 232.838 315.553 Tm [(as)-259.2(wel)-9(l)-259.2(a)0(s)-264.9(for)]TJ -17.5212 -1.0698 TD [(basel)-8.2(ine)-312.4(FEV)]TJ 7.97 0 0 7.97 112.422 304.894 Tm (1)Tj 9.963 0 0 9.963 116.391 304.894 Tm [(.)-307.7(Addi)-9.4(tionally)-317.6(the)-312.4(maximum)-319.2(fall)-311.4(in)-311.2(FEV)]TJ 7.97 0 0 7.97 278.986 304.894 Tm (1)Tj 9.963 0 0 9.963 282.954 304.894 Tm (,)Tj -22.5516 -1.0755 TD [(at)-562(a)-564.5(venti)-9(lation)-569.8(rate)-565.5(of)-560.8(30)-564.9(L)]TJ /F7 1 Tf 12.6615 0.1992 TD (.)Tj /F9 1 Tf 0.2675 -0.1992 TD (min)Tj 7.472 0 0 6.641 202.507 298.601 Tm (-1)Tj 9.963 0 0 9.963 214.242 294.179 Tm [(was)-565.5(analys)-9(ed)-565.3(by)]TJ -15.6547 -1.0755 TD [(ANO)-8.4(V)126.2(A)-465.6(as)-469.7(described)-474.2(for)-466.4(PV)]TJ 7.97 0 0 7.97 181.587 283.464 Tm (10)Tj 9.963 0 0 9.963 189.524 283.464 Tm [(.)-467(The)-467.7(mean)-467.9(percent)-10.5(age)]TJ -13.1736 -1.0755 TD [(prote)-8.2(ction)-213.8(of)-213.7(active)-215.4(treatmen)-11.1(t)-213.7(over)-209.9(placeb)-8.2(o)-211.3(was)-212.7(calcul)-10.6(ated)]TJ 0 -1.0698 TD [(by:)-511.1(\(mea)-8.6(n)-507.2(acti)-8.6(ve-mean)-517.8(placebo)-8.9(\)/mean)-513.3(placeb)-8.2(o)]TJ /F10 1 Tf 20.0421 0 TD (6)Tj /F9 1 Tf 1.0072 0 TD (100.)Tj -21.0493 -1.0755 TD [(Differences)-289.7(in)-282.7(basel)-8.2(ine)-283.9(values)-287.8(of)-287.6(FEV)]TJ 7.97 0 0 7.97 210.331 251.376 Tm (1)Tj 9.963 0 0 9.963 214.299 251.376 Tm [(,)-284.9(before)-287.4(chall)-9.4(enge)]TJ -15.6604 -1.0755 TD [(for)-216(the)-215.6(three)-219.2(treatmen)-11.1(t)-213.7(perio)-8.2(ds)-213.3(were)-219.9(analysed)-221.4(by)-212.1(ANO)-8.4(V)126.2(A)0(,)]TJ 0 -1.0698 TD (FEV)Tj 7.97 0 0 7.97 76.989 230.003 Tm (1)Tj 9.963 0 0 9.963 80.957 230.003 Tm [(,)-290.6(values)-299.2(before)-298.8(and)-292.9(3)-291(h)-291(after)-300.4(medicatio)-12.7(n)-291(were)-293.9(com-)]TJ -2.2762 -1.0755 TD [(pared)-342(by)-331.6(t-test)-339.3(for)-341.2(dependen)-7.3(t)-333.2(samp)-7.8(les.)]TJ 1.0015 -1.0528 TD [(Ac)16.9(co)15.1(rd)19.6(in)18.9(g)-535.7(t)0(o)-527.4(t)0(h)18.9(e)-536.1(st)17.7(ud)15.5(y)-530(d)0(e)15.1(s)0(i)17.7(g)0(n)-525.1(f)0(i)17.3(v)0(e)-525.5(h)0(y)15.5(p)0(e)20.8(r)0(v)13.9(e)0(n)20.8(t)0(i)16.5(l)0(a)18.4(t)0(i)16.5(o)0(n)]TJ -1.0015 -1.0698 TD [(ch)15.1(al)18.5(le)18.4(ng)15.5(es)-236.4(we)16.9(re)-242.5(pe)20.8(rf)12.4(or)19.6(me)17.7(d)-251.2(f)0(o)19.6(r)-247.1(ea)14.7(ch)-240.9(pa)20.8(ti)16.5(en)15.1(t)-247.8(u)0(n)21.2(d)0(e)15.1(r)-247.1(pl)18.9(ac)14.7(eb)20.8(o.)]TJ 0 -1.0755 TD [(Be)16.1(ca)20.4(us)14.4(e)-336.9(t)0(h)18.9(e)0(s)19.6(e)-336.9(fi)17.3(ve)-326.3(va)15.1(lu)18.9(es)-327.5(di)18.9(d)-336.5(n)0(o)15.5(t)-333.2(di)13.2(f)20.4(f)0(e)19.2(r)-338.1(st)17.7(at)18.4(is)17.7(ti)16.5(ca)14.7(ll)16.5(y)-330.8(f)0(r)12.4(o)0(m)]TJ T* [(ea)14.7(ch)-195.4(ot)18.9(he)15.1(r)43.2(,)-210.9(th)18.9(e)-206(a)0(u)15.1(t)0(h)18.9(o)0(r)19.6(s)-206.8(ca)14.7(lc)18.4(ul)18.9(at)12.8(ed)-195.4(th)18.9(ei)12.8(r)-207.2(m)0(e)17.7(a)0(n)-195.4(v)0(a)15.1(l)0(u)18.8(e)0(s)-202.3(a)0(n)20.8(d)-205.6(th)13.2(e)]TJ 0 -1.0698 TD [(co)15.1(rr)18(es)19.6(po)15.5(nd)21.2(in)18.9(g)-234.1(9)0(5)15.5(%)-236.4(up)21.2(pe)15.1(r)-235.7(p)0(r)19.6(e)0(d)20.8(i)0(c)12.8(t)0(i)16.5(o)0(n)-223.5(l)0(i)16.5(m)0(i)21.4(t)0(s)-227(u)0(s)14.4(i)13.9(ng)-229.2(S)11.4(t)0(u)18.9(d)0(e)15.1(n)0(t)]TJ /F10 1 Tf 22.2045 0 TD (')Tj /F9 1 Tf 0.2105 0 TD (s)Tj -22.4151 -1.0755 TD [(t-)17.3(di)18.9(st)17.7(ri)17.3(bu)15.5(ti)16.5(on)-490.9(\(o)13.9(ne)-491.3(ta)12.8(i)13.9(l)0(e)12.8(d)0(\))-492.5(a)0(s)-492.5(d)0(e)15.1(s)0(c)19.6(r)0(i)17.3(b)0(e)15.1(d)-501.5(be)15.1(fo)19.6(re)-498.6([1)19.6(6].)-504.3(By)]TJ T* [(these)-395.2(parameter)-11.5(s,)-389.3(variabili)-13.1(ty)-385.2(of)-390.1(the)-392(respon)-7.8(se)-390.1(to)-385.2(cold)-392.8(air)]TJ T* [(challe)-10.6(nge)-236(could)-234.2(be)-235.2(charact)-10.9(erize)-9(d)-234.1(o)0(n)-234.8(a)0(n)-235.2(individua)-8.7(l)-236.5(basis)-236.6(in)]TJ 0 -1.0698 TD [(order)-451.3(to)-447.8(identify)-453.4(respon)-7.8(ders)-450.1(and)-446.6(n)-6.5(onresponders)-453.7(in)-447.8(this)]TJ 0 -1.0755 TD [(study)55.2(.)]TJ /F5 1 Tf 35.0595 66.1583 TD [(Res)-7.8(ults)]TJ /F3 1 Tf -9.8617 -2.0998 TD [(Pr)27.3(emed)-7.8(ication)-337.2(lung)-341.2(function)-343.7(and)-332.3(effe)-8.6(ct)-334.4(on)-331.6(airway)-343.3(tone)]TJ /F9 1 Tf 1.0015 -1.8494 TD [(Th)17.1(er)13.5(e)-354(w)12.4(er)13.5(e)-354(n)0(o)-343(s)0(i)17.7(g)0(n)21.2(i)0(f)17.3(i)0(c)12.8(a)0(n)20.8(t)-356(di)18.9(f)20.4(f)0(e)19.2(r)0(e)13.5(n)0(c)20.8(e)0(s)-344.6(i)0(n)-345.3(p)0(r)19.6(e)0(d)15.1(r)0(u)19.6(g)-353.6(ba)15.1(se)19.6(-)]TJ -1.0015 -1.0527 TD [(li)16.5(ne)-297.8(FE)17.9(V)]TJ 7.97 0 0 7.97 345.26 721.814 Tm (1)Tj 9.963 0 0 9.963 352.29 721.814 Tm [(fo)19.6(r)-309.7(t)0(h)18.8(e)-302.8(th)13.2(re)19.2(e)-302.8(t)0(r)17.3(e)0(a)14.7(t)0(m)15.7(e)0(n)20.8(t)-310.4(pe)20.8(ri)17.3(od)15.5(s)-303.6(o)0(r)-299(b)0(e)20.8(t)0(w)14.9(e)0(e)14.7(n)-302.4(fi)17.3(rs)18.4(t)]TJ -4.3134 -1.0471 TD [(do)15.5(se)-310.4(an)20.8(d)-319.4(l)0(a)18.4(s)0(t)-306.7(d)0(o)15.5(s)0(e)-310.4(a)0(t)-305.9(s)0(t)17.7(e)0(a)14.7(d)0(y)-308.8(s)0(t)17.7(a)0(t)18.5(e)0(.)-308.8(B)11.6(ef)13.5(or)19.6(e)-319.8(f)0(i)17.3(r)0(s)18.4(t)-316.1(do)15.5(se)-310.4(m)13.2(e)0(a)14.7(n)]TJ 0 -1.0527 TD (\213)Tj 6.974 0 0 6.974 314.646 700.894 Tm [(SE)17.9(M)]TJ 9.963 0 0 9.963 332.164 700.894 Tm [(FE)17.9(V)]TJ 7.97 0 0 7.97 350.589 700.894 Tm (1)Tj 9.963 0 0 9.963 357.959 700.894 Tm [(wa)16.9(s)-343.4(3)0(.)21.6(5)0(4)15.5(\213)11.8(0.)15.9(15)15.5(,)-336.1(3)0(.)15.9(6)0(8)21.2(\213)0(0)16.7(.)0(1)15.9(5)-336.5(an)15.1(d)-342.2(3)0(.)21.6(5)0(9)15.5(\213)11.8(0.)15.9(13)-331.6(fo)19.6(r)]TJ -4.8825 -1.0471 TD [(tr)17.3(ea)14.7(tm)15.7(en)20.8(t)-304.7(p)0(e)15.1(r)0(i)17.3(o)0(d)-291.7(8)0(0)-297.4(m)0(g)]TJ /F3 1 Tf 9.6 0 TD [(b.)15.9(i)13.9(.)0(d)15.9(.)]TJ /F9 1 Tf 2.2762 0 TD [(20)-297.4(mg)]TJ /F3 1 Tf 2.8624 0 TD [(b.)21.6(i.)13.5(d.)]TJ /F9 1 Tf 2.2762 0 TD [(za)14.7(fi)17.3(rl)17.3(uk)21.2(as)14(t)-299.1(a)0(n)15.1(d)]TJ -17.0147 -1.0527 TD [(pl)13.2(ac)20.4(eb)15.1(o.)-211.7(Be)16.1(fo)19.6(re)-214.1(la)12.8(st)-210(do)15.5(se)-213.7(co)15.1(rr)18(es)19.6(po)15.5(nd)21.2(in)13.2(g)-222.7(v)0(a)20.8(l)0(u)18.8(e)0(s)-213.7(w)0(e)16.9(r)0(e)-219.8(3)0(.)21.6(6)0(3)15.5(\213)]TJ 0 -1.0471 TD [(0.)15.9(15)15.5(,)-210.9(3)0(.)15.9(6)0(5)21.2(\213)0(0)16.7(.)0(1)15.9(4)-211.3(an)15.1(d)-211.3(3)0(.)15.9(6)0(1)21.2(\213)0(0)16.7(.)0(1)15.9(4)0(.)-206(T)12.2(hr)13.9(ee)-207.2(ho)21.2(ur)13.9(s)-212.5(a)0(f)19.2(t)0(e)12.8(r)-212.9(fi)17.3(rs)18.4(t)-213.7(d)0(o)15.5(s)0(e)]TJ 0 -1.0527 TD [(me)12(an)-201.1(\(9)19.6(5%)-203.1(co)15.1(nf)19.6(id)18.8(en)15.1(ce)-201.5(in)18.8(te)18.4(rv)14(al)-197.8(\(C)14.9(I\))18(\))-212.9(i)0(n)18.9(c)0(r)13.5(e)0(a)20.4(s)0(e)-202.3(o)0(f)-202.3(F)11.4(EV)]TJ 7.97 0 0 7.97 515.225 659.055 Tm (1)Tj 9.963 0 0 9.963 521.291 659.055 Tm [(wa)16.9(s)]TJ -21.277 -1.0471 TD [(6.)15.9(2)-245.5(\()0(2)19.6(.)0(3)21.6(\261)0(1)15.5(0)0(.)15.9(1)0(\))-230.7(%)-247.8(wi)20.6(th)-237.2(za)14.7(fi)17.3(rl)17.3(uk)21.2(as)13.9(t)-242.2(8)0(0)-234.8(m)0(g)18.1(,)-245.1(w)12.4(h)0(i)13.2(c)0(h)-229.6(w)0(a)16.9(s)-246.7(st)17.7(at)18.5(is)17.7(-)]TJ 0 -1.0527 TD [(ti)16.5(ca)14.7(ll)16.5(y)-342.2(h)0(i)13.2(g)0(h)21.2(e)0(r)-339.3(a)0(s)-338.9(c)0(o)20.8(m)0(p)12.4(a)0(r)19.2(e)0(d)-337.7(t)0(o)-339.7(p)0(l)18.9(a)0(c)14.7(e)0(b)20.8(o)-347.9(\(p)]TJ /F8 1 Tf 16.2181 0 TD (=)Tj /F9 1 Tf 0.5463 0 TD [(0.)21.6(02)15.5(\).)-338.5(T)12.2(h)0(e)-337.7(c)0(o)15.1(r)20.4(-)]TJ -16.7644 -1.0471 TD [(re)13.5(sp)20(on)15.5(di)18.9(ng)-223.5(va)20.8(lu)18.9(es)-225.1(fo)19.6(r)-230(z)0(a)14.7(f)0(i)17.3(r)0(l)17.3(u)0(k)21.2(a)0(s)13.9(t)-230.8(20)-217.8(mg)-226.6(we)16.9(re)-219.8(3.)15.9(7)-228.4(\()0(1)14(.)0(1)21.6(\261)0(6)15.5(.)0(2)21.6(\))]TJ 0 -1.0527 TD [(%)-367.3(w)0(h)17.3(i)0(c)18.4(h)-365(w)12.4(a)0(s)-355.9(n)0(o)15.5(t)-361.7(st)17.7(at)18.4(is)17.7(ti)16.5(ca)20.4(ll)16.5(y)-365(d)0(i)18.9(f)20.4(fe)13.5(re)19.2(nt)-351(fr)12.4(om)-351.8(th)18.9(e)-365.4(i)0(n)18.8(c)0(r)19.2(e)0(a)14.7(s)0(e)]TJ 0 -1.0471 TD [(\(1)13.9(.6)-314.1(\(-)18(1.)15.9(4\261)21.2(4.)15.9(5\))-316.1(%\))-312.8(un)15.5(de)20.8(r)-326.7(p)0(l)18.9(a)0(c)14.7(e)0(b)20.8(o)0(.)]TJ /F3 1 Tf 0 -2.7542 TD [(Effect)-341(on)-337.3(isoca)-7.8(pnic)-335.9(hyperve)-8.2(ntilatio)-12.3(n)-330.8(with)-336.9(cold)-341.6(air)]TJ 0 -1.8494 TD [(Maxi)-8.2(mum)-300.4(per)24.6(centage)-304.8(fall)-300.4(in)-294.1(for)28.3(c)-6.9(e)0(d)-297.8(expiratory)-306.2(volume)-301.9(in)]TJ 0 -1.0527 TD [(one)-224.6(second)-228.5(at)-220.2(3)-222.7(h)-222.7(post)-222.9(fir)-8.2(st)-221.3(dose)-226.6(at)-220.2(a)-222.7(ventilat)-10.7(ion)-220.9(rate)-229(of)-220.2(30)]TJ 0 -1.0471 TD (L)Tj /F7 1 Tf 0.5577 0.1992 TD (.)Tj /F3 1 Tf 0.2675 -0.1992 TD [(mi)-7.8(n)]TJ 7.472 0 0 6.641 332.447 544.422 Tm (-1)Tj 9.963 0 0 9.963 338.57 540 Tm (.)Tj /F9 1 Tf 0.5577 0 TD [(Th)17.1(e)-302.8(m)0(e)17.7(a)0(n)-292.1(\()0(9)19.6(5)0(%)-294.1(C)11.6(I\))-294.9(fa)19.2(ll)-290.8(in)-288.4(FE)12.2(V)]TJ 7.97 0 0 7.97 471.005 540 Tm (1)Tj 9.963 0 0 9.963 477.978 540 Tm -0.0175 Tc [(a)-17.5(t)-312(a)-314.6(v)-17.5(en)-17.5(ti)-17.5(la)-17.5(ti)-17.5(on)]TJ -16.9294 -1.0527 TD 0 Tc [(ra)13.5(te)-288.8(of)-293.3(30)-291.7(L)]TJ /F7 1 Tf 4.7402 0.1992 TD (.)Tj /F9 1 Tf 0.2731 -0.1992 TD [(mi)15.7(n)]TJ 7.472 0 0 6.641 374.343 533.934 Tm (-1)Tj 9.963 0 0 9.963 383.357 529.512 Tm [(wa)16.9(s)-303.6(1)0(4)21.2(.)0(8)-291.4(\()0(1)48.1(1)0(.)21.6(7)0(\261)15.5(1)0(9)21.2(.)0(1)15.9(\))-298.3(%)-304.7(i)0(n)-288.4(t)0(h)18.8(e)-302.8(pl)18.8(ac)20.4(eb)15.1(o)]TJ -7.4319 -1.0527 TD [(gr)13.9(ou)21.2(p)-330.8(c)0(o)15.1(m)0(p)18.1(a)0(r)13.5(e)0(d)-320.6(t)0(o)-322.6(9)0(.)21.6(1)-330.8(\(5)13.9(.3)21.6(\2611)15.5(3.)21.6(1\))-327.5(an)20.8(d)-330.8(1)0(0)15.5(.)0(5)-319.8(\()0(6)19.6(.)0(7)15.9(\261)0(1)21.2(4)0(.)15.9(4)0(\))-321.8(i)0(n)]TJ 0 -1.0471 TD [(th)13.2(e)-194.6(z)0(a)14.7(f)0(i)17.3(r)0(l)17.3(u)0(k)21.2(a)0(s)14(t)-196.6(80)-189.3(mg)-186.8(an)15.1(d)-194.2(2)0(0)-189.3(m)0(g)-186.8(g)0(r)13.9(o)0(u)21.2(p)-199.9(re)19.2(sp)14.4(ec)20.4(ti)16.5(ve)15.1(l)13.9(y)-199.9(\(f)18(ig)18.8(.)-199.6(1\).)]TJ 0 -1.0528 TD [(Mean)-364.3(percent)-10.5(age)-361.6(prote)-8.2(ction)-361.8(of)-361.6(38.4%)-364.3(for)-364(zafir)-10.2(lukast)-363.7(80)]TJ 0 -1.0471 TD [(mg)-203.8(was)-195.6(stat)-9.4(istically)-202.9(signi)-9.8(ficant)-205.2(improvem)-11.1(ent)-198.6(over)-198.5(placeb)-8.2(o)]TJ 0 -1.0528 TD (\(p)Tj /F8 1 Tf 0.8251 0 TD (=)Tj /F9 1 Tf 0.5577 0 TD [(0.016\).)-438.7(Fo)-6.4(r)-434.8(z)-6.9(afirlukas)-11.1(t)-435.6(2)0(0)-439.7(m)0(g)-442.8(mean)-445.2(protectio)-10.7(n)-438.9(was)]TJ -1.3828 -1.0471 TD [(29.1)-8.4(%)-333.2(\()0(p)]TJ /F8 1 Tf 3.7387 0 TD (=)Tj /F9 1 Tf 0.552 0 TD (0.062\).)Tj /F3 1 Tf -4.2907 -2.3047 TD (PV)Tj 7.97 0 0 7.97 321.392 443.792 Tm (20)Tj 9.963 0 0 9.963 331.54 443.792 Tm [(at)-220.2(3)-222.7(h)-217(post)-222.9(first)-223.9(dose)-226.6(and)-218.5(at)-225.8(steady)-225.2(state.)]TJ /F9 1 Tf 15.9677 0 TD -0.0121 Tc [(Th)-12.1(e)-213.2(m)-12.1(ed)-12.1(i)6.8(a)-12.1(n)]TJ -18.1984 -1.0528 TD 0 Tc [(va)15.1(lu)18.8(es)-321.8(of)-321.8(P)11.4(V)]TJ 7.97 0 0 7.97 361.247 433.304 Tm (20)Tj 9.963 0 0 9.963 372.416 433.304 Tm [(3)-330.8(h)-325.1(po)15.5(st)-318.1(fi)17.3(rs)18.4(t)-333.2(d)0(o)21.2(s)0(e)-321.8(a)0(n)15.1(d)-325.1(at)-323(st)17.7(ea)14.7(dy)-320.2(st)17.7(at)18.5(e)-331.2(a)0(r)19.2(e)]TJ -6.3336 -1.0471 TD [(pr)13.9(es)19.6(en)15.1(te)18.4(d)-427.6(i)0(n)-419.3(t)0(a)18.4(b)0(l)18.9(e)-428(2.)-427.9(The)-439.3(individua)-8.7(l)-435.6(data)-444.4(are)-437.2(show)-8.2(n)-433.3(i)0(n)]TJ 0 -1.0528 TD [(figur)-9.4(e)-331.2(2)0(.)-331.2(Three)-334.7(hours)-336.7(post)-331(firs)-9.8(t)-327.5(dose)-334.7(between)-337.2(zafir)-10.2(lukast)]TJ 0 -0.9958 TD [(80)-320.2(mg)-317.7(and)-315.7(placeb)-8.2(o)-313.7(the)-318.1(difference)-318(was)-315.1(statist)-12(ically)-319.8(signi-)]TJ 0 -1.0015 TD [(fican)-8.6(t)-316.1(\()0(p)]TJ /F8 1 Tf 3.3859 0 TD (=)Tj /F9 1 Tf 0.552 0 TD [(0.004\).)-319.1(However)24.2(,)-313.4(the)-318.1(difference)-312.3(betw)-9.8(een)-316.1(zafir-)]TJ -3.9379 -1.0015 TD [(lukas)-7.8(t)-498.2(2)0(0)-502.3(m)0(g)-499.7(and)-503.5(placebo)-504(was)-502.9(smaller)-506.2(\(p)]TJ /F8 1 Tf 17.9309 0 TD (=)Tj /F9 1 Tf 0.552 0 TD [(0.064\).)-506.9(At)]TJ -18.4829 -1.0015 TD [(stead)-8.2(y)-433.3(stat)-9.4(e)-433.7(a)0(t)-436.8(all)-439.9(time)-438.2(point)-8.6(s)-434.4(the)-437.6(median)-443.4(PV)]TJ 7.97 0 0 7.97 499.635 372.529 Tm (20)Tj 9.963 0 0 9.963 511.88 372.529 Tm [(of)-435.6(the)]TJ -20.3323 -0.9958 TD [(zafir)-10.2(lukas)-7.8(t)-447(8)0(0)-456.8(m)0(g)-454.2(group)-455(was)-457.4(consistent)-12.3(ly)]TJ /F8 1 Tf 17.7545 0 TD (>)Tj /F9 1 Tf 0.5577 0 TD [(60)-451.1(L)]TJ /F7 1 Tf 2.0543 0.1992 TD (.)Tj /F9 1 Tf 0.2731 -0.1992 TD (min)Tj 7.472 0 0 6.641 530.305 367.03 Tm (-1)Tj 9.963 0 0 9.963 309.316 352.63 Tm [(whi)-8.6(lst)-315.5(the)-318.1(median)-323.9(of)-316.1(the)-318.1(placebo)-321.9(group)-318.4(was)-315.1(consi)-7.8(stently)]TJ 0 -1.0015 TD [(betw)-9.8(een)-367.3(40)-365.7(L)]TJ /F7 1 Tf 5.6507 0.1992 TD (.)Tj /F9 1 Tf 0.2675 -0.1992 TD (min)Tj 7.472 0 0 6.641 383.698 347.074 Tm (-1)Tj 9.963 0 0 9.963 393.505 342.652 Tm 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[(Af)15.7(te)12.8(r)-201.5(r)0(e)19.2(p)0(e)15.1(a)0(t)18.4(e)0(d)-195.4(d)0(o)21.2(s)0(a)14(g)0(e)20.8(s)-201.1(ov)15.5(er)-197(5)-199.9(d)0(a)15.1(y)0(s)-190.5(t)0(h)18.9(e)-206(au)20.8(th)13.2(or)19.6(s)-201.1(f)0(o)13.9(u)0(n)21.2(d)-205.6(3)-199.9(h)]TJ -1.0015 -1.0527 TD [(af)13.5(te)18.4(r)-315.3(t)0(h)18.9(e)-314.2(la)12.8(st)-306.7(do)21.2(se)-310.4(a)-314.2(l)0(e)18.5(s)0(s)-305.5(p)0(r)13.9(o)0(n)21.2(o)0(u)15.5(n)0(c)20.8(e)0(d)-309.2(e)0(f)30.6(f)0(e)13.5(c)0(t)-305.9(w)0(h)17.3(i)0(c)18.4(h)-313.7(di)13.2(d)-313.7(n)0(o)21.2(t)]TJ T* [(re)13.5(ac)20.4(h)-444.6(s)0(t)17.7(a)0(t)18.4(i)0(s)17.7(t)0(i)16.5(c)0(a)14.7(l)-441.3(si)17.7(gn)15.5(i)13.9(f)0(i)11.6(c)0(a)20.4(n)0(c)15.1(e)0(.)-434(T)12.2(ho)15.5(ug)21.2(h)-444.6(t)0(h)18.9(e)0(s)13.9(e)-439.3(ob)15.5(se)19.6(rv)19.6(at)12.8(io)18.8(ns)]TJ T* [(we)16.9(re)-271(st)17.7(at)18.4(is)17.7(ti)16.5(ca)20.4(ll)16.5(y)-273.9(s)0(t)17.7(a)0(b)15.1(l)0(e)-266.1(w)0(i)14.9(t)0(h)18.9(i)0(n)-265.7(t)0(h)18.8(e)-274.3(gr)14(ou)21.2(p)-273.9(o)0(f)-270.6(1)0(9)-263.3(a)0(s)19.6(t)0(h)13.2(m)0(a)17.7(t)0(i)16.5(c)0(s)19.6(,)]TJ T* [(in)13.2(di)18.9(vi)18.9(du)15.5(al)-237.6(di)18.9(f)20.4(f)0(e)19.2(r)0(e)13.5(n)0(c)20.8(e)0(s)-236.4(w)0(e)11.2(r)0(e)-236.8(r)0(e)19.2(m)0(a)17.7(r)0(k)13.9(a)0(b)20.8(l)0(e)18.4(,)-245.1(in)13.2(di)18.9(ca)20.4(ti)16.5(ng)-234.8(an)-240.9(in)18.9(di)18.8(-)]TJ 0 -1.0471 TD [(vi)13.2(du)21.2(al)-175(fa)13.5(ct)18.4(or)-173.8(de)15.1(t)13.9(e)0(r)13.5(m)0(i)15.7(n)0(i)18.9(n)0(g)-172.2(t)0(h)13.2(e)-183.3(ai)18.5(rw)15.7(ay)-172.6(re)19.2(sp)14.3(on)21.2(se)-179.5(t)13.9(o)-188.6(th)18.8(e)-183.3(c)0(y)20.8(s)0(L)101.3(T)]TJ 7.472 0 0 6.641 532.743 414.765 Tm (1)Tj 9.963 0 0 9.963 309.316 405.978 Tm [(re)13.5(ce)20.4(pt)13.2(or)-424.2(an)15.1(ta)18.5(go)15.5(ni)18.9(st)-426.2(za)14.7(fi)17.3(rl)17.3(uk)21.2(as)13.9(t.)-424.6(Th)17.1(e)-439.3(i)0(n)18.8(t)0(e)18.4(r)0(p)13.9(r)0(e)19.2(t)0(a)18.4(t)0(i)16.5(o)0(n)-428.3(o)0(f)-429.9(t)0(h)18.9(e)]TJ 0 -1.0528 TD [(fi)17.3(nd)15.5(in)18.9(gs)-315.7(ne)15.1(ed)20.8(s)-326.3(d)0(i)18.9(s)0(c)19.6(u)0(s)14.4(s)0(i)17.7(o)0(n)-314.5(o)0(f)-316.1(v)0(a)20.8(r)0(i)17.3(o)0(u)15.5(s)-326.3(as)19.6(pe)15.1(ct)18.4(s,)-315.3(as)-316.1(fo)19.6(ll)16.5(ow)17.3(s.)]TJ 1.0015 -1.0527 TD [(Th)17.1(e)-268.6(a)0(u)20.8(t)0(h)13.2(o)0(r)19.6(s)-263.7(us)20(ed)-258(th)18.8(e)-268.6(m)0(e)17.7(t)0(h)18.9(o)0(d)-257.6(o)0(f)-253.5(i)0(s)17.7(o)0(c)15.1(a)0(p)20.8(n)0(i)13.2(c)-262.9(hy)15.5(pe)20.8(rv)14(en)20.8(ti)16.5(la)18.4(-)]TJ -1.0015 -1.0527 TD [(ti)16.5(on)-371.4(of)-367.3(co)20.8(ld)-368.1(ai)18.5(r)-377.9(t)0(o)-368.1(a)0(s)13.9(s)0(e)19.6(s)0(s)-368.1(a)0(i)18.4(r)0(w)15.7(a)0(y)-366.1(r)0(e)13.5(s)0(p)20(o)0(n)15.5(s)0(i)17.7(v)0(e)20.8(n)0(e)15.1(s)0(s)18.8(.)-376(Ai)14.9(rw)15.7(ay)]TJ 0 -1.0471 TD [(re)13.5(sp)20(on)15.5(se)-253.5(fo)13.9(ll)16.5(ow)17.3(in)18.9(g)-262.5(e)0(x)15.1(e)0(r)19.2(c)0(i)18.4(s)0(e)-259.2(a)0(n)15.1(d)-262.5(hy)15.5(pe)20.8(rv)14(en)20.8(ti)16.5(la)18.4(ti)16.5(on)-257.6(pr)19.6(ov)15.5(id)18.9(es)]TJ 0 -1.0527 TD [(a)-240.2(s)0(i)17.7(m)0(i)15.7(l)0(a)18.4(r)-241.4(de)15.1(gr)19.6(ee)-230(of)-230.7(ai)18.5(rw)15.7(ay)-229.6(ob)15.5(st)17.7(ru)19.6(ct)12.8(io)18.8(n)-239.8(p)0(r)19.6(o)0(v)15.5(i)0(d)18.9(e)0(d)-229.5(v)0(e)15.1(n)0(t)18.8(i)0(l)16.5(a)0(t)18.5(i)0(o)18.8(n)]TJ T* [(ra)13.5(te)18.4(,)-489.8(t)0(e)12.8(m)0(p)18.1(e)0(r)19.2(a)0(t)18.4(u)0(r)13.9(e)-490.6(an)15.1(d)-490.2(w)0(a)16.9(t)0(e)12.8(r)-491.7(co)20.8(nt)13.2(en)20.8(t)-492.5(o)0(f)-486.8(i)0(n)18.8(s)0(p)20(i)0(r)17.3(e)0(d)-485.6(a)0(i)18.5(r)-497.4(ar)19.2(e)]TJ T* [(ma)12(tc)18.4(he)20.8(d)-296.7([)0(2)19.6(1].)-299.4(This)-306.7(method)-312.1(has)-305.5(been)-305.5(used)-306.2(by)-308.8(the)-306.7(authors)]TJ T* [([15,)-277.4(16])-271.3(a)-6.9(n)0(d)-269(other)-270(groups)-274.8(in)-271.4(severa)-8.6(l)-270.6(d)-6.5(if)11.6(ferent)-278.4(studi)-9.8(es)-270.6([17,)]TJ T* [(22,)-337.7(23].)-334.3(Isocap)-8.2(nic)-335.1(hyperve)-7.7(ntilati)-12(on)-331.6(as)-333.2(used)-340.4(in)-334(this)-333.4(study)]TJ T* [(offers)-181.7(the)-187.2(advant)-7.8(age)-185.2(of)-185.2(const)-7.8(ructing)-188.5(a)-183.3(dose-r)-9.4(espons)-7.4(e)-183.3(curve)]TJ 0 -1.0471 TD [(rathe)-8.6(r)-144.6(than)-142.4(meas)-8.2(uring)-144.4(airflow)-148.5(obstr)-9(uction)-146.3(after)-146.8(a)-143.4(single)-147.5(test.)]TJ 0 -1.0528 TD [(Thi)-8.8(s)-178.4(offers)-176(the)-181.5(possibil)-9.9(ity)-177.8(of)-185.2(calculati)-12.3(ng)-177.9(provoca)-7.7(tive)-184.6(venti-)]TJ T* [(latio)-11.4(n)-217(\(PV\))-225.6(rates)-226(necess)-8.2(ary)-226.2(to)-220.2(decreas)-9.7(e)]TJ /F3 1 Tf 15.3759 0 TD (e.g.)Tj /F9 1 Tf 1.6616 0 TD (FEV)Tj 7.97 0 0 7.97 497.764 269.745 Tm (1)Tj 9.963 0 0 9.963 503.943 269.745 Tm [(by)-223.5(10)-217.8(or)]TJ -19.5357 -1.0528 TD [(20%)-488.4(from)-487.4(basel)-8.2(ine)-483.1(sim)-9(ilar)-487.8(to)-481.9(those)-485.8(met)-8.2(hods)-487.9(used)-482.7(for)]TJ T* [(asses)-8.2(smen)-7.8(t)-344.6(o)0(f)-350.2(the)-352.2(respon)-7.8(se)-350.2(to)-351(broncho)-7.3(constrictor)-356.5(agents)]TJ T* [(like)-190.3(histamine)-189.9(or)-179.5(met)-8.2(hachol)-7.8(ine.)-181.9(In)-185.2(addition)-190.1(reprod)-8.2(ucibility)]TJ T* [(of)-293.3(PV)80.7(-values)-295.8(is)-283.9(a)-6.9(cceptable)-292.5([15,)-294.5(24].)-288.8(Therefor)-10.1(e,)-286.1(sim)-9(ilar)-288.7(to)]TJ 0 -1.0471 TD [(other)-304.1(groups)-7.4(,)-302(the)-306.7(a)-6.9(uthors)-311.3(used)-306.3(this)-310.6(technique)-314.4(to)-305.5(sim)-9(ulate)]TJ 0 -1.0528 TD [(exe)-8.8(rcise-ind)-11.1(uced)-242.9(broncho)-7.3(constrict)-11.9(ion.)-238.4(The)-245.8(author)-9(s)-235.3(analy-)]TJ T* [(sed)-328.3(the)-318.1(d)-6.5(ata)-318.5(in)-322.6(term)-10.6(s)-320.6(o)0(f)-321.8(both)-324.1(PV)]TJ 7.97 0 0 7.97 441.468 196.384 Tm (10)Tj 9.963 0 0 9.963 452.579 196.384 Tm [(and)-321.4(PV)]TJ 7.97 0 0 7.97 482.797 196.384 Tm (20)Tj 9.963 0 0 9.963 493.909 196.384 Tm [(in)-322.6(order)-326.1(to)]TJ -18.5284 -1.0528 TD [(circu)-8.6(mvent)-544.7(the)-545.7(difficulties)-544.1(associ)-10.1(ated)-546.8(with)-541(b)-6.5(oth)-539.6(para-)]TJ T* [(met)-8.2(ers.)-290.4(The)-291.3(analys)-9(is)-289.6(of)-287.7(PV)]TJ 7.97 0 0 7.97 417.6 175.408 Tm (20)Tj 9.963 0 0 9.963 428.372 175.408 Tm [(was)-292.3(hampe)-7.8(red)-294.5(by)-286.1(censor)-8.2(ed)]TJ -11.9502 -1.0527 TD [(values)-9(,)-324.7(wher)-9(eas)-328.7(that)-332.6(of)-327.5(PV)]TJ 7.97 0 0 7.97 418.11 164.92 Tm (10)Tj 9.963 0 0 9.963 429.279 164.92 Tm [(was)-332.2(affected)-326.3(by)-325.9(the)-329.4(higher)]TJ -12.0412 -1.0528 TD [(varia)-8.6(bility)-270.2(of)-264.9(this)-270.8(parameter)39.7(.)-262.1(For)-264.9(examp)-7.8(le,)-266.5(subje)-7.8(ct)-266.1(No.)-261.9(1)27.7(1)]TJ T* [(show)-8.2(ed)-218.2(a)-223.1(variation)-227(from)-225.6(8\26160)-225(L)]TJ /F7 1 Tf 12.6273 0.2049 TD (.)Tj /F9 1 Tf 0.2731 -0.2049 TD (min)Tj 7.472 0 0 6.641 453.203 148.422 Tm (-1)Tj 9.963 0 0 9.963 459.383 143.943 Tm [(,)-216.6(i)0(n)-220.2(contr)-8.2(ast)-222.5(to,)]TJ /F3 1 Tf 6.0491 0 TD (e.g.)Tj /F9 1 Tf 1.4397 0 TD (,)Tj -22.5516 -1.0471 TD [(subje)-7.8(ct)-260.4(No.)-267.6(7)-256.8(whos)-8.2(e)-257.2(P)0(V)]TJ 7.97 0 0 7.97 405.354 133.512 Tm (10)Tj 9.963 0 0 9.963 415.899 133.512 Tm [(varie)-8.6(d)-256.8(betw)-9.8(een)-259.2(21\26126)-265.6(L)]TJ /F7 1 Tf 9.6682 0.1992 TD (.)Tj /F9 1 Tf 0.2731 -0.1992 TD (min)Tj 7.472 0 0 6.641 530.362 137.934 Tm (-1)Tj 9.963 0 0 9.963 309.316 123.024 Tm [(on)-172.3(five)-172.5(occasi)-9.4(ons)-168.5(under)-176.5(placebo)-174(\(fig.)-174(3\).)-168.5(Des)-7.8(pite)-173.3(these)-173.2(dif)10.8(f-)]TJ 0 -1.0528 TD [(erences)-9.7(,)-336.1(the)-335.1(resul)-9.4(ts)-335.2(were)-339.4(similar)-343.2(for)-335.5(both)-335.5(param)-9.4(eters.)]TJ ET 1 i 58.28 253.757 227.168 -0.51 re f 58.28 227.849 227.168 -0.454 re f 58.28 126.255 227.168 -0.51 re f BT /F2 1 Tf 8.966 0 0 8.966 58.28 295.994 Tm [(Table)-331.9(3.)-336.7(\261)-333.2(Mean)-596.5(values)-590.8(of)-596(provocative)-598.4(ventilation)-594.8(rate)]TJ 0 -1.0559 TD (\(L)Tj /F7 1 Tf 0.8852 0.2213 TD (.)Tj /F2 1 Tf 0.2719 -0.2213 TD (min)Tj 6.725 0 0 5.977 83.055 290.494 Tm (-1)Tj 8.966 0 0 8.966 89.008 286.526 Tm [(\))-210.8(t)0(o)-216.6(reduce)-215.2(forced)-214.3(expiratory)-217.3(volume)-213.6(in)-216.4(one)-209.2(second)]TJ -3.427 -1.0559 TD [(by)-225.2(10%)-230.3(and)-221.9(\(95%)-226.1(confidence)-228.2(intervals\))-228.8(after)-226.6(first)-226.9(dose)-227.7(and)]TJ T* [(3,)-545.4(8,)-551.7(12,)-543.4(24)-552.6(h)-548.2(after)-542.7(last)-548.1(dose)-550.1(for)-547.5(80)-546.3(mg)-549.8(and)-544.3(20)-552.6(mg)]TJ T* (zafirlukast)Tj /F9 1 Tf 0 -1.7072 TD [(T)28.6(iming)-332.9(of)-335.1(cold)]TJ 0 -1.0559 TD [(air)-336.7(challenge)]TJ 8.0807 1.0559 TD (Zafirlukast)Tj -0.0569 -1.0559 TD [(80)-334.1(mg)]TJ /F3 1 Tf 2.9338 0 TD (b.d.)Tj /F9 1 Tf 3.4713 1.0559 TD (Zafirlukast)Tj -0.0569 -1.0559 TD [(20)-334.1(mg)]TJ /F3 1 Tf 2.9402 0 TD (b.d.)Tj /F9 1 Tf 3.8127 1.0559 TD (Placebo)Tj -21.1248 -3.054 TD [(3)-334.6(h)-328.3(post)]TJ 0.6639 -1.0559 TD [(first)-340.5(dose)]TJ 8.7003 1.0559 TD (39.9)Tj -1.6945 -1.0559 TD (\(30.6\26149.2\)*)Tj 8.0491 1.0559 TD (32.9)Tj -1.4479 -1.0559 TD 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m 248.616 267.36 l 250.921 252.985 m 248.616 252.985 l 250.921 245.485 m 248.616 245.485 l 250.921 238.86 m 248.616 238.86 l 250.921 224.86 m 248.616 224.86 l 250.921 217.61 m 248.616 217.61 l 372.963 210.985 m 248.616 210.985 l 250.921 196.485 m 248.616 196.485 l 250.921 189.36 m 248.616 189.36 l 250.921 182.36 m 248.616 182.36 l 373.133 175.321 m 248.616 175.321 l 250.921 203.36 m 246.341 203.36 l 250.921 232.235 m 246.341 232.235 l 250.921 260.235 m 246.341 260.235 l 250.921 288.485 m 246.341 288.485 l S BT 10 0 0 10 235.466 284.965 Tm /GS4 gs (80)Tj 0 -2.85 TD (60)Tj 0 -2.825 TD (40)Tj 0 -2.8625 TD (20)Tj 0.45 -2.8 TD (0)Tj ET 3.864 M [2 2 ]0 d /GS3 gs 373.587 224.892 m 250.691 224.892 l S BT /F17 1 Tf 6 0 0 6 274.938 226.057 Tm /GS4 gs (l)Tj 12.6523 -2.5629 TD (n)Tj -16.0542 6.2548 TD (l)Tj 7.7025 -0.5473 TD (l)Tj 8.3314 -6.2912 TD (l)Tj -4.0005 2.9886 TD (l)Tj 0.0203 0.9318 TD (n)Tj -4.4299 3.7888 TD (n)Tj -4.206 -3.9597 TD (n)Tj -3.4053 -5.5081 TD (n)Tj ET 3.864 M []0 d /GS3 gs 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[(Aller)31.3(gy)-333.9(Clin)-336.2(Immunol)]TJ /F9 1 Tf 9.1113 0 TD [(1986;)-328.6(78:)-336(379\261387.)]TJ -11.6278 -1.1128 TD [(25.)-1266.5(Accolate)-230.7(Product)-232.1(Monograph.)-233.7(March)-232.6(1996,)-234.8(Macclesfield,)]TJ 2.5165 -1.1128 TD [(England,)-333.8(Zeneca)-328.3(Pharmacouticals.)]TJ -2.5165 -1.1128 TD [(26.)-1266.5(A)]TJ 2.7125 0.2213 TD (\310)Tj 0.5185 -0.2213 TD [(delroth)-375(E,)-372.6(Inman)-373.1(MD,)-372.6(Summers)-373.7(E,)-372.6(Pace)-368.9(D,)-372.4(Modi)-374.1(M,)]TJ -0.7145 -1.1065 TD (O)Tj /F10 1 Tf 0.7145 0 TD (')Tj /F9 1 Tf 0.2213 0 TD [(Byrne)-666.8(PM.)-665.1(Prolonged)-661(protection)-672.8(against)-665.8(exercise-)]TJ -0.9358 -1.1128 TD [(induced)-731.8(bronchoconstriction)-742(by)-732.5(the)-740.4(leukotriene)-735.3(D)]TJ 6.725 0 0 5.977 279.156 402.066 Tm (4)Tj 8.966 0 0 8.966 282.501 403.54 Tm (-)Tj -22.4906 -1.1128 TD [(receptor)-454.8(antagonist)-451.7(cinalukast.)]TJ /F3 1 Tf 12.9114 0 TD [(J)-454.5(Aller)31.3(gy)-454(Clin)-450.1(Immunol)]TJ /F9 1 Tf -12.9114 -1.1128 TD [(1997;)-328.6(99:)-336(210\261215.)]TJ 25.4813 43.3372 TD [(27.)-1266.5(Hofstra)-257.9(WB,)-252.5(Sterk)-252.1(PJ,)-254.6(Neijens)-258.2(HJ,)-253(van)-257.5(der)-252.1(W)70.8(eij)-255.9(AM,)-252.5(van)]TJ 2.5165 -1.1128 TD [(Zoest)-326.8(JGCM,)-333.2(Duiverman)-332.3(EJ.)-329(T)60.2(w)0(o)-331.1(weeks)-330.3(treatment)-333.5(with)]TJ T* [(zafirlukast)-497.2(\(Accolate)]TJ 6.725 0 0 5.977 407.962 756.227 Tm 0.0001 Tc (TM)Tj 8.966 0 0 8.966 417.997 752.201 Tm 0 Tc [(\),)-490.2(sodium)-501.9(cromoglycate)-493.8(or)-499.5(pla-)]TJ -9.6045 -1.1065 TD [(cebo)-155.6(on)-150.7(exercise-induced)-162.8(bronchoconstriction)-160.3(in)-153.1(asthmatic)]TJ 0 -1.1128 TD (adolescents.)Tj /F3 1 Tf 5.0141 0 TD [(Am)-208.1(J)-207.9(Respir)-201(Crit)-211(Car)33.6(e)-207.9(Med)]TJ /F9 1 Tf 10.8881 0 TD [(1997;)-202.2(155:)-209(A665.)]TJ -18.4186 -1.1128 TD [(28.)-1266.5(Fischer)-492.3(AR,)-490.4(Rosenber)10.3(g)-486.4(MA,)-492.7(Roth)-485.6(M,)-489.9(Loper)-488.5(M,)-489.9(Jun-)]TJ 2.5165 -1.1065 TD [(gerwirth)-416.7(S,)-418.3(Israel)-413(E.)-416.9(Effec)10.2(t)-419.2(o)0(f)-410.9(a)-416.6(novel)-416.9(5-)-417.3(lipoxygenase)]TJ 0 -1.1128 TD [(activating)-655(protein)-659.5(inhibitor)25.7(,)-654.2(B)0(A)81.5(Y)0(x)-653.6(1005,)-652.1(on)-656.6(asthma)]TJ T* [(induced)-333.5(by)-334.1(cold)-335.2(air)55.3(.)]TJ /F3 1 Tf 8.4158 0 TD (Thorax)Tj /F9 1 Tf 3.2057 0 TD [(1997;)-335(52:)-329.6(1074\2611077.)]TJ -14.138 -1.1128 TD [(29.)-1266.5(W)70.8(enzel)-226.8(SE,)-225.3(Larsen)-223.4(GL,)-230(Johnston)-222(K,)-227(V)123.6(oelkel)-228.9(NF)75(,)-230.5(W)77.1(estcott)]TJ 2.5165 -1.1065 TD [(JY)123(.)-331.7(Elevated)-332.3(levels)-331.2(of)-328.7(leukotriene)-336.9(C)]TJ 6.725 0 0 5.977 462.557 671.017 Tm (4)Tj 8.966 0 0 8.966 468.907 672.548 Tm [(in)-330.2(bronchoalveolar)]TJ -15.2825 -1.1128 TD [(lavage)-403.3(fluid)-401.5(from)-406.5(atopic)-399.6(asthmatics)-410.3(after)-399.7(endobronchial)]TJ T* [(aller)9.9(gen)-358.7(challenge.)]TJ /F3 1 Tf 7.9226 0 TD [(Am)-359.9(Rev)-355.6(Respir)-365.4(Dis)]TJ /F9 1 Tf 8.1945 0 TD [(1990,)-354.9(142:)-360.7(1)32.1(12\261)]TJ -16.1171 -1.1128 TD [(1)32.1(19.)]TJ -2.5165 -1.1065 TD [(30.)-1266.5(W)70.8(enzel)-492.3(SE,)-484.5(W)70.8(estcott)-491.2(JY)123(,)-489.8(Larsen)-495.3(GL.)-489.2(Bronchoalveolar)]TJ 2.5165 -1.1128 TD [(lavage)-567.7(fluid)-572.3(mediator)-565.8(levels)-571.5(5)-568.6(minutes)-566.8(after)-570.4(allergen)]TJ T* [(challenge)-340.7(in)-342.8(atopic)-342.7(subjects)-344.1(with)-341.2(asthma:)-345.2(relationship)-346.6(to)]TJ T* [(the)-436.9(development)-436.6(of)-436.2(late)-438.6(asthmatic)-441.2(responses.)]TJ /F3 1 Tf 19.0699 0 TD [(J)-435.6(Aller)24.9(gy)]TJ -19.0699 -1.1065 TD [(Clin)-336.2(Immunol)]TJ /F9 1 Tf 5.9056 0 TD [(1991;)-328.6(87:)-336(540\261548.)]TJ -8.4221 -1.1128 TD 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[(as)-252.9(a)-258.5(marker)-259.5(of)-252.9(nocturnal)-259.9(asthma.)]TJ /F3 1 Tf 13.1959 0 TD [(Am)-252.4(Rev)-260.8(Respir)]TJ -16.9264 -1.1128 TD (Dis)Tj /F9 1 Tf 1.7072 0 TD [(1992;)-334.9(145:)-329.1(A16.)]TJ -4.2237 -1.1065 TD [(33.)-1266.5(T)60.2(aylor)-392.6(IK,)-391.8(W)32.8(illings)-392.9(R,)-392.8(T)66.6(aylor)-392.6(GW)80.6(,)-394.9(Fuller)-393.1(R)52.7(W)83.4(.)-388.6(Urinary)]TJ 2.5165 -1.1128 TD [(leukotriene)-444.4(E)]TJ 6.725 0 0 5.977 381.09 511.653 Tm (4)Tj 8.966 0 0 8.966 388.46 513.127 Tm [(excretion)-443.1(in)-437.7(exercise)-442.2(induced)-447.3(asthma.)]TJ /F3 1 Tf 16.0728 0 TD (J)Tj -22.3831 -1.1128 TD [(Appl)-332.6(Physiol)]TJ /F9 1 Tf 5.5073 0 TD [(1992;)-334.9(73:)-336(743\261748.)]TJ -8.0238 -1.1128 TD [(34.)-1266.5(Smith)-407.4(CM,)-399.3(Christie)-408.1(PE,)-408.6(Hawksworth)-407.4(RJ,)-399.8(Thien)-407.8(F)71.5(,)-401.3(Lee)]TJ 2.5165 -1.1065 TD [(TH.)-577.7(Urinary)-585.5(leukotriene)-583.5(E)]TJ 6.725 0 0 5.977 434.381 481.72 Tm (4)Tj 8.966 0 0 8.966 442.942 483.25 Tm [(levels)-584.2(after)-576.7(allergen)-576.4(and)]TJ -12.3866 -1.1128 TD [(exercise)-410.5(challenge)-410.3(in)-406.1(bronchial)-411.7(asthma.)]TJ /F3 1 Tf 16.6166 0 TD [(Am)-410.5(Rev)-412.5(Respir)]TJ -16.6166 -1.1128 TD (Dis)Tj /F9 1 Tf 1.7072 0 TD [(1991;)-334.9(144:)-329.1(141)26.8(1\2611413.)]TJ -4.2237 -1.1065 TD [(35.)-1266.5(Broide)-725.6(DH,)-723(Eisman)-720.1(S,)-721.8(Ramsdell)-728.8(JW)82.7(,)-717.4(Ferguson)-710.9(P)103.1(,)]TJ 2.5165 -1.1128 TD [(Schwartz)-575.9(LB,)-572.8(W)77.1(asserman)-575.9(SI.)-570.5(Airway)-575.7(levels)-577.8(of)-569(mast)]TJ T* [(cell-derived)-482.6(mediators)-478(in)-475.6(exercise-induced)-478.9(asthma.)]TJ /F3 1 Tf 21.4979 0 TD (Am)Tj -21.4979 -1.1128 TD [(Rev)-330.3(Respir)-340.1(Dis)]TJ /F9 1 Tf 6.4367 0 TD [(1990;)-328.6(141:)-335.5(563\261568.)]TJ -8.9532 -1.1065 TD [(36.)-1266.5(W)70.8(a)0(y)-397.1(W)83.4(,)-401.3(Sasagawa)-402.7(M,)-395.1(T)60.2(akemoto)-398.6(A,)]TJ /F3 1 Tf 17.7864 0 TD [(et)-399.5(al)]TJ /F9 1 Tf 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