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[(le)18.4(ss)-225.8(ab)15.1(le)-226.2(to)-225.8(cl)18.5(ea)14.7(r)-235.7(s)0(e)19.6(c)0(r)13.5(e)0(t)18.4(i)0(o)18.9(n)0(s)-230.3(d)0(u)21.2(e)-234.5(to)-231.5(a)-234.5(l)0(a)18.4(c)0(k)-229.6(o)0(f)-225.1(c)0(i)18.4(l)0(i)16.5(a)-234.5(an)15.1(d)-234.1(a)-234.5(la)18.4(ck)]TJ 0 -1.0528 TD [(of)-412.8(hi)18.9(gh)-411.2(ga)15.1(s)-423.1(v)0(e)20.8(l)0(o)18.9(c)0(i)12.8(t)0(y)-407.9(g)0(e)15.1(n)0(e)15.1(r)0(a)19.2(t)0(e)18.4(d)-421.9(du)15.5(ri)17.3(ng)-411.3(co)20.8(ug)15.5(h.)-410.9(No)17.3(rm)16.5(al)18.4(ly)75.8(,)]TJ T* [(th)18.9(is)-261.2(is)-255.5(no)15.5(t)-270.6(a)-262.9(si)17.7(gn)15.5(if)17.3(ic)18.4(an)15.1(t)-264.9(i)0(s)17.7(s)0(u)14.4(e)0(,)-257.6(b)0(u)21.2(t)-270.6(in)-260(as)19.6(th)18.9(ma)-261.2(an)15.1(d)-268.2(o)0(t)18.9(h)0(e)20.8(r)-269.8(ob)15.5(s-)]TJ 0 -1.0471 TD [(tr)17.3(uc)15.1(ti)22.2(ve)-428.7(l)13.9(u)0(n)15.5(g)-433.3(di)18.9(se)19.6(as)13.9(es)-424.2(w)12.4(h)0(e)15.1(r)0(e)-424.6(s)0(m)16.9(a)0(l)18.4(l)-435.6(ai)18.4(rw)15.7(ay)-423(in)18.9(fl)17.3(am)17.7(ma)17.7(ti)16.5(on)]TJ 0 -1.0528 TD [(an)15.1(d)-376.3(g)0(o)15.5(b)0(l)18.9(e)0(t)-374.2(c)0(e)14.7(l)13.9(l)-384.4(m)0(e)17.7(t)0(a)18.4(p)0(l)13.2(a)0(s)19.6(i)0(a)-374.2(o)0(c)20.8(c)0(u)15.1(r)0(s)-374.2([)0(1)48.1(1)0(,)-382.4(12],)-391.2(these)-395.2(facto)-8.6(rs)]TJ 0 -1.0471 TD [(becom)-7.8(e)-365.4(magni)-9.7(fied.)-366.3(In)-367.3(addit)-9(ion,)-369.2(M)]TJ 6.974 0 0 6.974 198.085 227.622 Tm 0.0001 Tc (ICHEL)Tj /F4 1 Tf 9.963 0 0 9.963 222.123 227.622 Tm 0 Tc [(et)-368.5(al.)]TJ /F8 1 Tf 2.464 0 TD [([13])-370.4(have)]TJ -18.9097 -1.0528 TD [(shown)-367.4(that)-361(poll)-7.8(en)-360.4(particles)-370.8(reach)-365.1(the)-363.6(small)-366.1(airways)-373.7(and)]TJ 0 -1.0471 TD [(alveol)-10.1(i,)-248.2(which)-249.5(may)-250.5(furt)-8.6(her)-249(incre)-8.6(ase)-249(the)-249.8(infl)-9.4(ammator)-10.7(y)-245.5(res-)]TJ 0 -1.0527 TD [(ponse)-352.5(in)-351(the)-357.9(atopic)-351.6(asthm)-10.9(atic)-350.1(p)-6.5(atient)-354(if)-352.6(clear)-9(ance)-351.4(mech-)]TJ 0 -1.0471 TD [(anisms)-246.2(in)-237.2(this)-242.3(part)-240.7(of)-242.1(the)-238.4(lung)-244.4(are)-238(not)-238(ade)-8.8(quate.)-240.7(Given)-243.8(the)]TJ 0 -1.0527 TD [(small)-491.3(radius)-488.2(of)-486.8(curvature)-491.7(and)-486.4(high)-483.4(compl)-9.7(iance)-485.4(of)-486.8(the)]TJ 0 -1.0471 TD [(small)-383.2(airways)-379.4(as)-378.7(demon)-7.4(strated)-383.6(by)-371.4(M)]TJ 6.974 0 0 6.974 209.14 164.863 Tm 0.0001 Tc [(AR)42.8(TIN)]TJ 9.963 0 0 9.963 233.688 164.863 Tm 0 Tc [(and)-378.3(P)]TJ 6.974 0 0 6.974 257.272 164.863 Tm 0.0001 Tc (ROCTOR)Tj 9.963 0 0 9.963 58.28 154.375 Tm 0 Tc [([14])-575.3(these)-571.6(facto)-8.6(rs)-567.7(can)-572.2(lead)-575.3(to)-573(instabilit)-12.1(y)-569.8(and)-566.1(airw)-11.4(ay)]TJ 0 -1.0528 TD [(closu)-7.8(re)-179.9(at)-175(low)-185(lung)-181.8(volumes.)-183.6(In)-179.5(this)-185.4(setting,)-185.2(surfactant)-188.7(may)]TJ 0 -1.0471 TD [(confer)-276(stabili)-10.8(ty)-265.7(by)-269(p)-6.5(rotecting)-278.2(against)-273.9(excess)-8.2(ive)-272.5(change)-273.3(in)]TJ 0 -1.0528 TD [(radii)-363.4(with)-364.6(changes)-366.2(in)-362.4(volume.)-363.7(This)-363.6(possi)-8.6(bility)-361.2(was)-366.3(sug-)]TJ 0 -1.0471 TD [(geste)-8.2(d)-279.6(b)0(y)-286.1(M)]TJ 6.974 0 0 6.974 107.943 112.535 Tm 0.0001 Tc [(ACK)-11.4(LEM)]TJ 9.963 0 0 9.963 140.088 112.535 Tm 0 Tc [(and)-287.2(M)]TJ 6.974 0 0 6.974 166.054 112.535 Tm 0.0001 Tc (EAD)Tj 9.963 0 0 9.963 183.118 112.535 Tm 0 Tc [([1])-290(and)-281.5(demon)-7.4(strated)-292.5(in)-282.7(a)]TJ 12.6672 66.1583 TD [(subseq)-7.4(uent)-182.2(study)-178.1(in)-180.3(cats)-183.8([12].)-177.3(In)-179.5(asthma,)-183.2(surfa)-8.6(ctant)-180.1(may)-182.3(be)]TJ 0 -1.0471 TD [(repla)-8.6(ced)-367.3(by)-365.7(infl)-9.4(ammator)-10.7(y)-365(exudat)-7.8(e)-365.4(o)0(r)-367.3(mucus,)-373.1(thus)-365.1(rend-)]TJ 0 -1.0528 TD [(ering)-167.5(the)-170.1(small)-167(airways)-174.6(prone)-165.1(to)-163.2(obstr)-9(uction)-169.1(and)-162(closu)-7.8(re.)-163.2(In)]TJ T* [(fact,)-281.4(surfa)-8.6(ctant)-276.8(dysfun)-7.4(ction)-276.4(has)-277(been)-277(described)-280.7(in)-277.1(asthma)]TJ 0 -1.0471 TD [([15,)-220.5(16].)-214.8(If)-221(the)-215.6(stabili)-10.8(ty)-214.5(of)-213.7(the)-215.6(pe)-7.6(ripheral)-219.7(airways)-225.8(were)-219.9(lost)]TJ 0 -1.0527 TD [(due)-258.8(to)-254.3(incre)-8.6(ased)-255.4(secret)-11(ions)-257(and/or)-259.3(surfa)-8.6(ctant)-259.8(dysfun)-7.4(ction,)]TJ 0 -1.0471 TD [(these)-440.7(events)-441.4(could)-439.1(lead)-438.7(to)-436.4(narrow)-12.1(ing)-437.2(of)-435.6(the)-437.6(peripheral)]TJ 0 -1.0527 TD [(airw)-11.4(ays,)-459.5(airway)-468.5(closu)-7.8(re,)-464.8(higher)-464.2(lung)-466.4(volumes)-467.7(and)-463.6(gas)]TJ 0 -1.0471 TD [(trapp)-8.2(ing.)]TJ 1.0015 -1.0527 TD [(In)-429.9(ad)15.1(di)18.9(ti)16.5(on)-428.3(to)-430.7(th)18.9(e)-439.3(f)0(a)19.2(c)0(t)12.8(o)0(r)19.6(s)-440.1(di)18.9(sc)19.6(us)14.4(se)19.6(d)-438.9(a)0(b)20.8(o)0(v)15.5(e)0(,)-428.3(t)0(h)18.8(e)-439.3(ef)24.9(fe)19.2(c-)]TJ -1.0015 -1.0471 TD [(ti)16.5(ve)15.1(ne)20.8(ss)-260(of)-259.2(co)15.1(ug)15.5(h)-268.2(a)0(n)20.8(d)-268.2(se)19.6(cr)13.5(et)18.5(io)18.8(n)-268.2(c)0(l)18.4(e)0(a)14.7(r)0(a)19.2(n)0(c)15.1(e)-268.6(al)18.4(so)-258.8(de)15.1(pe)20.8(nd)15.5(s)-269.4(o)0(n)]TJ 0 -1.0528 TD [(th)13.2(e)-382.4(e)0(q)15.1(u)0(a)20.8(l)-384.4(pr)19.6(es)13.9(su)20(re)-379.1(po)21.2(in)18.9(t)-384.4(\()0(E)15.5(P)0(P)17.1(\))0(.)-378.3(T)12.2(he)-377.5(E)12.2(P)0(P)-375.5(i)0(s)-380.7(t)13.9(he)-377.5(po)15.5(in)18.8(t)-384.4(o)0(r)]TJ 0 -1.0471 TD [(po)15.5(in)18.9(ts)-477.4(al)18.5(on)15.5(g)-484.5(t)13.9(he)-479.9(ai)18.5(rw)15.7(ay)-474.3(wh)17.3(er)19.2(e)-484.9(a)0(t)-476.6(m)0(a)17.7(x)0(i)13.2(m)0(u)18.1(m)-487.6(ex)20.8(pi)18.9(ra)13.5(to)18.9(ry)]TJ 0 -1.0527 TD [(fl)17.3(ow)74.2(,)-279.2(t)0(h)18.9(e)-280(pr)13.9(es)19.6(su)20(re)-276.7(at)-271.8(th)18.9(e)-280(i)0(n)18.8(n)0(e)15.1(r)-281.2(wa)16.9(ll)-273.7(of)-270.6(th)18.9(e)-285.7(a)0(i)18.5(r)0(w)15.7(a)0(y)20.8(s)-280.8(is)-272.6(eq)15.1(ua)20.8(l)]TJ 0 -1.0471 TD [(to)-362.4(th)18.9(e)-371.1(p)0(l)18.9(e)0(u)15.1(r)0(a)19.2(l)-373(pr)19.6(es)13.9(su)20(re)19.2(.)-370.3(T)0(h)17.1(e)-371.1(EP)17.9(P)-369.9(d)0(i)18.9(v)0(i)18.9(d)0(e)15.1(s)-371.8(th)18.9(e)-371.1(a)0(i)18.5(r)0(w)15.7(a)0(y)-360.4(i)0(n)18.8(t)0(o)]TJ 0 -1.0527 TD [(up)15.5(st)17.7(re)19.2(am)-329.4(se)13.9(gm)18.1(en)20.8(ts)-329.5(be)15.1(tw)20.6(ee)14.7(n)-336.5(t)0(h)18.9(e)-336.9(al)18.5(ve)15.1(ol)18.9(i)-338.9(a)0(n)20.8(d)-336.5(th)18.8(e)-336.9(E)0(P)17.9(P)108.1(,)-330.4(a)0(n)15.1(d)]TJ T* [(do)15.5(wn)17.3(st)17.7(re)19.2(am)-278.2(se)13.9(gm)18.1(en)15.1(ts)-272.6(be)15.1(tw)14.9(ee)20.4(n)-285.3(t)0(h)13.2(e)-285.7(E)12.2(P)0(P)-278.8(a)0(n)15.1(d)-285.3(ai)18.5(rw)15.7(ay)-275.1(op)15.5(en)20.8(-)]TJ 0 -1.0471 TD [(in)13.2(g)-564.1(\()0(m)16.5(o)0(u)21.2(t)0(h)18.8(\))-565.7([2)19.6(].)-577.5(By)-575.3(exami)-10.1(ning)-574.5(expir)-8.2(atory)-577.3(flow)-580(after)]TJ 0 -1.0527 TD 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-0.0164 Tc [(T)-16.4(h)0.7(e)-376.1(q)-16.4(u)4.8(e)-16.4(st)-16.4(i)5.8(o)-16.4(n)-365.1(o)-16.4(f)-366.6(w)-16.4(he)-16.4(th)-16.4(er)-371.6(t)-16.4(h)-3.2(e)-370.4(p)-16.4(ar)-16.4(en)-16.4(ch)-16.4(y)4.8(m)-16.4(a)-368.6(e)-16.4(x)4.4(h)-16.4(ib)-16.4(it)-16.4(s)-362.9(t)-16.4(ru)-16.4(e)]TJ -1.0015 -1.0755 TD 0 Tc [(co)15.1(nt)18.9(ra)19.2(ct)18.5(il)16.5(e)-473.5(r)0(e)19.2(s)0(p)14.4(o)0(n)21.2(s)0(e)13.9(s)-468.6(or)-464.1(wh)17.3(et)18.4(he)15.1(r)-474.7(t)0(h)18.9(e)0(y)-462.9(a)0(r)19.2(e)-473.5(ju)18.9(st)-466(a)-473.5(c)0(o)20.8(n)0(s)20(e)0(-)]TJ 0 -1.0698 TD [(qu)15.5(en)20.8(ce)-315.3(of)-310.4(ai)18.5(rw)15.7(ay)-314.9(cl)18.5(os)20(ur)14(e)-319.8(a)0(n)15.1(d)0(/)18.9(o)0(r)-310.4(e)0(x)15.1(t)0(r)17.3(a)0(v)20.8(a)0(s)13.9(c)0(u)20.8(l)0(a)12.8(r)-321(lu)18.9(ng)-314.5(w)12.4(a)0(t)12.8(e)0(r)]TJ 0 -1.0755 TD -0.0158 Tc [(h)-15.8(a)-0.7(s)-285.2(b)-15.8(ee)-15.8(n)-273.8(e)-15.8(xp)-15.8(lo)-15.8(re)-15.8(d)-273.8(b)-15.8(y)-279.1(F)]TJ 6.974 0 0 6.974 149.726 376.157 Tm 0.0001 Tc [(RE)18.2(DB)18.4(ER)18.2(G)]TJ /F4 1 Tf 9.963 0 0 9.963 184.479 376.157 Tm 0 Tc [(et)-260.4(al)13.2(.)]TJ /F8 1 Tf 2.2421 0 TD [([3)13.9(2].)-271(Using)-290.2(isolated)]TJ -14.9092 -1.0755 TD [(parench)-8.2(ymal)-378.9(strips)-383.2(from)-379.3(male)-379.3(guinea)-377.7(pigs,)-382.6(F)]TJ 6.974 0 0 6.974 242.192 365.442 Tm 0.0001 Tc (REDBERG)Tj /F4 1 Tf 9.963 0 0 9.963 278.362 365.442 Tm 0 Tc (et)Tj -22.0907 -1.0755 TD (al.)Tj /F8 1 Tf 1.434 0 TD [([32])-416(d)-6.5(emonstrated)-424.3(that)-417.9(the)-414.8(parench)-8.2(yma)-415.6(can)-418.5(expres)-8.2(s)]TJ -1.434 -1.0755 TD [(diver)-8.2(se)-355.9(respon)-7.8(ses)-363.6(to)-356.7(severa)-8.6(l)-356(a)-6.9(gonists)-359.6(such)-363.2(as)-361.6(histami)-11.5(ne,)]TJ T* [(prosta)-10.1(glandin)-260.9(D)]TJ 7.472 0 0 6.641 121.89 331.653 Tm (2)Tj 9.963 0 0 9.963 125.631 333.298 Tm [(,)-256.5(leukot)-9.7(riene)-264.7(C)]TJ 7.472 0 0 6.641 184.309 331.653 Tm (4)Tj 9.963 0 0 9.963 188.05 333.298 Tm [(,)-262.1(methachol)-10.3(ine,)-261.5(and)-264.5(sub-)]TJ 12.1721 43.9993 TD [(stanc)-8.2(e)-291.4(P)102.4(.)-290.6(The)-291.3(respon)-7.8(ses)-289.6(to)-294.1(these)-298.4(agonists)-298.2(varied)-293.9(in)-294.1(inten-)]TJ 0 -1.0471 TD [(sit)-8.2(y)-461.7(but)-459.9(wer)-8.2(e)-456.4(presen)-8.2(t)-464.1(and)-463.6(signifi)-9.6(cant.)-461.9(The)-6.8(se)-458.4(respon)-7.8(ses)]TJ 0 -1.0528 TD [(sugges)-7.4(t)-333.2(that)-338.3(the)-335.1(parench)-8.1(yma)-335.9(exhibi)-9.7(ts)-329.5(contr)-8.2(actile)-337.3(respon)-7.8(-)]TJ 0 -1.0471 TD [(ses)-221.3(probably)-221(due)-213.2(to)-214.5(the)-221.3(presence)-221.1(of)-213.7(smoo)-7.4(th)-214.5(musc)-7.8(le,)-215.2(which)]TJ 0 -1.0528 TD [(may)-347.3(further)-343(contr)-8.2(ibute)-344.7(to)-339.7(the)-340.8(physi)-7.4(ological)-344.1(respon)-7.8(ses)-340.8(of)]TJ 0 -1.0471 TD [(the)-340.8(distal)-337.7(airways.)]TJ 1.0015 -1.0528 TD [(Wh)14.4(et)18.4(he)15.1(r)-434.8(t)0(h)18.9(e)-433.7(si)17.7(te)-431.1(of)-424.2(th)18.8(e)-433.7(c)0(o)15.1(n)0(t)18.9(r)0(a)13.5(c)0(t)18.5(i)0(l)16.5(e)-433.7(re)19.2(sp)14.4(on)21.2(se)-429.9(is)-426.2(at)-425.4(th)18.9(e)]TJ -1.0015 -1.0471 TD [(al)12.8(ve)20.8(ol)18.9(ar)-418.9(le)18.4(ve)15.1(l)-424.2(i)0(s)-414.8(c)0(o)15.1(n)0(t)18.9(r)0(o)19.6(v)0(e)15.1(r)0(s)18.4(i)0(a)18.4(l)0(.)-418.9(P)11.4(ot)18.9(en)15.1(ti)16.5(al)-414(me)12(ch)20.8(an)15.1(is)17.7(ms)-415.6(in)18.8(-)]TJ 0 -1.0527 TD [(cl)12.8(ud)21.2(e)-308.5(c)0(o)20.8(n)0(t)18.8(r)0(a)13.5(c)0(t)18.4(i)0(o)18.9(n)-302.4(of)-299(my)18.1(of)13.9(ib)18.8(ro)19.6(bl)18.9(as)13.9(ts)17.7(,)-302(c)0(o)15.1(n)0(t)18.9(r)0(a)19.2(c)0(t)12.8(i)13.9(le)-300.2(in)18.9(te)18.4(rs)18.4(ti)16.5(ti)16.5(al)]TJ T* 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TD [([38])-427.3(evalua)-8.2(ted)-420.5(subpl)-7.4(eural)-429.7(parench)-8.1(ymal)-424.4(strips)]TJ -4.2736 -1.0471 TD [(from)-436.2(human)-7.4(s)-428.7(t)0(o)-430.7(determin)-10.7(e)-428(dynam)-7.4(ic)-425.4(meas)-8.2(ures)-433(of)-429.9(resis-)]TJ 0 -1.0527 TD [(tance,)-349.2(elast)-10.6(ance)-345.7(and)-344.1(hysteresi)-10.7(vity)60.5(.)-341.8(Hys)-7.4(teresivi)-11.1(ty)64.4(,)-341.8(defin)-8.2(ed)]TJ 0 -1.0471 TD [(by)-263.3(F)]TJ 6.974 0 0 6.974 327.401 604.29 Tm 0.0001 Tc (REDBERG)Tj 9.963 0 0 9.963 362.438 604.29 Tm 0 Tc [(and)-264.5(S)]TJ 6.974 0 0 6.974 384.888 604.29 Tm 0.0001 Tc [(T)75.7(AMENOV)-12.2(IC)]TJ 9.963 0 0 9.963 428.542 604.29 Tm 0 Tc [([39],)-268.4(is)-261.2(a)-257.3(param)-9.4(eter)-263.9(used)-260.7(in)]TJ -11.9672 -1.0528 TD [(the)-443.3(assessmen)-10.3(t)-441.3(o)0(f)-435.6(lung)-443.6(tissue)-438.9(be)-7.6(haviour)24.4(,)-432.9(o)0(n)-7.2(e)-433.6(in)-442.1(which)]TJ 0 -1.0471 TD [(ene)-8.8(rgy)-197.4(diss)-7.8(ipation)-217.8(and)-213.2(storage)-216.2(are)-215.2(linked.)-215(Hys)-7.4(teresevit)-12.3(y)-211.3(i)0(s)]TJ 0 -1.0527 TD [(a)-154.8(funct)-8.2(ion)-158.3(of)-151.1(tis)-8.2(sue)-151.8(visca)-8.2(nce)-156.7(and)-156.3(lung)-159.1(elastance)-162.8(and)-156.3(is)-153.1(mod-)]TJ 0 -1.0471 TD [(ulat)-8.2(ed)-144.2(b)-6.5(y)-143(the)-147.3(c)-6.9(ontractile)-156.5(state)-152.8(of)-145.4(contr)-8.2(actile)-155.2(cells)-147.1(dist)-9(ributed)]TJ 0 -1.0528 TD [(throu)-7.8(ghout)-433(parench)-8.1(ymal)-435.8(tissue.)-439.3(Hysteres)-11.5(evity)-435.8(has)-430.7(been)]TJ 0 -1.0471 TD [(show)-8.2(n)-188.6(t)0(o)-191.7(incre)-8.6(ase)-192.1(with)-193.8(the)-192.9(adminis)-9.2(tration)-196.6(of)-190.9(meth)-9(acholine)]TJ 0 -1.0527 TD [(in)-282.8(a)-285.7(rabbit)-284.5(model)-288.6(described)-292.1(above)-283.5(by)-280.4(R)]TJ 6.974 0 0 6.974 466.809 531.042 Tm 0.0001 Tc [(OME)-12.1(RO)]TJ /F4 1 Tf 9.963 0 0 9.963 494.702 531.042 Tm 0 Tc [(et)-283.1(al.)]TJ /F8 1 Tf 2.2933 0 TD ([21].)Tj -20.9014 -1.0471 TD (D)Tj 6.974 0 0 6.974 316.516 520.611 Tm 0.0001 Tc (OLHNIKOFF)Tj /F4 1 Tf 9.963 0 0 9.963 358.186 520.611 Tm 0 Tc [(et)-243.3(al.)]TJ /F8 1 Tf 2.2136 0 TD [([38])-250.9(revealed)-250.7(that)-241.5(sti)-8.2(mulati)-9.6(on)-240.5(of)-242.1(human)]TJ -7.1189 -1.0528 TD [(lung)-272.9(parench)-8.1(ymal)-276.4(strips)-275.1(with)-273.5(acetylchol)-10.7(ine)-272.5(resulted)-276.2(in)-271.4(an)]TJ 0 -1.0471 TD [(incre)-8.6(ase)-209.1(in)-203.1(tension,)-211.2(resistanc)-11.1(e,)-206.4(elastance)-214(and)-207.6(hysteresi)-10.7(vity)60.5(.)]TJ 0 -1.0527 TD [(The)-484.8(respon)-7.8(se)-486.8(between)-485.2(stri)-10.6(ps)-480.7(was)-485.8(simil)-9.6(ar)30.6(,)-478.4(and)-486.4(did)-482.7(not)]TJ 0 -1.0471 TD [(dep)-8.4(end)-224.6(on)-229.2(the)-227(numbe)-7.4(r)-224.3(o)0(f)-225.1(smal)-10.2(l)-225.1(airways)-231.5(presen)-8.2(t)-225.1(withi)-9.2(n)-222.7(the)]TJ 0 -1.0528 TD [(strip)-11.4(s.)-212.9(The)-6.8(y)-217(also)-217.6(evalua)-8.2(ted)-221.3(the)-221.3(presen)-8.2(ce)-218.6(of)-213.7(smoo)-7.4(th)-220.2(muscle)]TJ 0 -1.0471 TD [(acti)-8.6(n)-217(b)0(y)-217.8(immunoh)-8.3(istochem)-10.3(istry)-221.9(and)-218.9(found)-216(acti)-8.6(n)-217(positivity)]TJ 0 -1.0528 TD [(in)-390.9(the)-392(smal)-10.2(l)-390.1(airways,)-396.9(alveolar)-394.9(duc)-8.4(ts)-386.4(and)-395.3(alveolar)-394.9(walls.)]TJ 0 -1.0471 TD [(Thu)-6.4(s,)-252.7(these)-252.9(data)-256.6(are)-255.1(consistent)-262.6(with)-256.4(other)-252.9(studies)-257.6([18,)-254.7(32])]TJ 0 -1.0527 TD [(but)-260.7(these)-258.6(investig)-9.2(ators)-254.1(took)-261.5(the)-255.5(additional)-262.7(step)-257.4(of)-253.5(sugges)-7.4(-)]TJ 0 -1.0471 TD [(ting)-389.1(that)-383.8(the)-386.3(contracti)-11.1(le)-379.9(elem)-9.4(ents)-382.6(are)-386(at)-385.6(the)-380.7(level)-390.7(of)-378.7(the)]TJ 0 -1.0527 TD [(alveol)-10.1(ar)-333.6(wal)-9(l.)]TJ /F4 1 Tf 0 -2.5607 TD [(Hum)-10.2(an)-331.6(studies)]TJ /F8 1 Tf 1.0015 -1.6503 TD [(St)14(ud)21.2(ie)12.8(s)-320.6(e)0(v)15.1(a)0(l)18.4(u)0(a)15.1(t)0(i)22.2(n)0(g)-320.2(t)0(h)18.8(e)-325.5(fu)19.6(nc)15.1(ti)22.2(on)-320.2(of)-316.1(th)18.8(e)-325.5(d)0(i)18.9(s)0(t)17.7(a)0(l)-317.3(a)0(i)18.5(r)0(w)15.7(a)0(y)20.8(s)-326.3(in)]TJ -1.0015 -1.0471 TD [(hu)15.5(ma)17.7(ns)-219(ra)19.2(ng)15.5(e)-223.1(f)0(r)12.4(o)0(m)-215.2(t)0(h)18.9(e)-228.8(no)21.2(ni)13.2(nv)21.2(as)13.9(iv)18.8(e)-223.1(e)0(v)15.1(a)0(l)18.4(u)0(a)15.1(t)0(i)16.5(o)0(n)-212.1(o)0(f)-219.4(d)0(y)15.5(n)0(a)20.8(m)0(i)15.7(c)]TJ 0 -1.0528 TD [(co)15.1(mp)18.1(li)16.5(an)15.1(ce)-372.2(an)15.1(d)-387.7(a)0(i)18.5(r)0(w)15.7(a)0(y)-371.8(h)0(y)15.5(s)0(t)17.7(e)0(r)19.2(e)0(s)13.9(i)0(s)-375(t)0(o)-379.5(d)0(i)18.9(r)0(e)19.2(c)0(t)-379.9(m)0(e)17.7(a)0(s)19.6(u)0(r)14(e)0(m)17.7(e)0(n)20.8(t)]TJ 0 -1.0471 TD [(of)-458.4(pe)20.8(ri)17.3(ph)15.5(er)19.2(al)-459.6(ai)18.4(rw)15.7(ay)20.8(s)-462.9(r)0(e)13.5(s)0(i)17.7(s)0(t)17.7(a)0(n)20.8(c)0(e)]TJ /F4 1 Tf 13.4069 0 TD 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[(ma)17.7(ti)16.5(c)-268.6(a)0(i)18.5(r)0(w)15.7(a)0(y)83.4(,)-267.8(in)-254.3(th)18.9(at)-260.4(th)18.9(e)-262.9(f)0(o)13.9(r)0(c)19.2(e)-262.9(fl)11.6(uc)20.8(tu)18.9(at)18.4(io)13.2(ns)-253.1(cr)13.5(ea)20.4(te)18.4(d)-268.2(b)0(y)-257.6(t)0(i)22.2(d)0(a)15.1(l)]TJ T* [(br)19.6(ea)14.7(th)18.9(in)18.9(g)-410.5(a)0(r)19.2(e)-405.2(su)14.4(bj)18.9(ec)20.4(t)-407.2(t)0(o)-396.6(f)0(a)13.5(c)0(t)18.5(o)0(r)19.6(s)-406(th)13.2(at)-397(le)18.4(ss)18.9(en)-400.3(pe)20.8(ri)17.3(br)13.9(on)21.2(ch)15.1(ia)18.4(l)]TJ 0 -1.0641 TD [(di)18.9(st)17.7(en)15.1(di)18.9(ng)-337.3(st)17.7(re)13.5(ss)18.9(,)-347.5(s)0(u)20(c)0(h)-343.4(a)0(s)-338.9(t)0(h)18.9(i)0(c)18.4(k)0(e)15.1(n)0(i)18.9(n)0(g)-337.3(o)0(f)-338.9(p)0(e)15.1(r)0(i)17.3(b)0(r)19.6(o)0(n)15.5(c)0(h)20.8(i)0(a)12.8(l)-344.6(ad)15.1(-)]TJ 0 -1.0698 TD [(ve)15.1(nt)18.9(it)16.5(ia)18.4(,)-364.6(l)0(o)18.8(s)0(s)-362.4(o)0(f)-355.9(e)0(l)18.5(a)0(s)13.9(t)0(i)16.5(c)-365.4(re)19.2(co)15.1(il)16.5(,)-364.6(b)0(r)14(e)0(a)20.4(t)0(h)18.9(i)0(n)13.2(g)-365(at)-357.1(lo)13.2(w)-363.2(l)0(u)13.2(n)0(g)-354.3(v)0(o)15.5(l)0(-)]TJ T* [(um)18.1(es)-270.6(or)-270.6(fa)19.2(il)16.5(ur)19.6(e)-280(t)0(o)-265.7(t)0(a)12.8(k)0(e)-263.7(d)0(e)15.1(e)0(p)-269.4(b)0(r)19.6(e)0(a)14.7(t)0(h)18.9(s)-275.1([7)13.9(0,)-274.3(71].)-294.5(If)-289.2(any)-287.2(or)-287.7(all)]TJ 0 -1.0641 TD [(of)-259.2(these)-264.3(facto)-8.6(rs)-260.4(are)-260.8(presen)-8.2(t,)-259.6(the)-261.2(musc)-7.8(le)-260.4(would)-266.2(stretch)-264.1(less)]TJ 0 -1.0698 TD [(with)-358.9(each)-357.1(breat)-8.6(h,)-354(and)-355.5(becom)-7.8(e)-354(progre)-8.2(ssively)-360(stiffer)-352.2(such)]TJ T* [(that)-298.4(physi)-7.4(ological)-304.3(forces)-300(acti)-8.6(ng)-291.7(on)-297.4(the)-301(muscle)-302.3(would)-300.3(be-)]TJ T* [(come)-234.6(insufficient)-234.4(to)-237.2(stretch)-235.6(the)-238.4(muscle)-239.7(appreciably)51.9(.)-233.7(Bron-)]TJ 0 -1.0641 TD [(chial)-225.6(hyperr)-8.2(espons)-7.4(iveness)-227.2(may)-222.1(be)-223.9(due)-224.6(to)-220.2(the)-227(failure)-224.7(of)-225.1(the)]TJ 0 -1.0698 TD [(underl)-9(ying)-335.5(pertu)-8.2(rbed)-335.1(equil)-9(ibrium)-338.4(to)-334(sust)-7.8(ain)-335.1(itself.)]TJ 1.0015 -1.0528 TD [(Fu)16.3(rt)17.3(he)20.8(rm)16.5(or)13.9(e,)-240.6(th)18.9(e)-251.6(p)0(r)19.6(o)0(b)15.5(l)0(e)18.4(m)-248.6(in)-242.9(as)19.6(th)18.9(ma)-244.1(ma)17.7(y)-251.2(n)0(o)21.2(t)-253.5(be)-240.9(th)18.8(at)-237.6(th)13.2(e)]TJ -1.0015 -1.0641 TD [(mu)18.1(sc)13.9(le)-226.2(is)-227(t)13.9(o)0(o)-229.2(s)0(t)17.7(r)0(o)19.6(n)0(g)15.5(,)-233.7(bu)21.2(t)-236.5(r)0(a)13.5(t)13.9(he)15.1(r)-235.7(t)0(o)18.9(o)-234.1(fa)13.5(st)17.7(.)-233.7(M)0(u)19.3(s)0(c)13.9(l)13.9(e)-240.2(t)13.9(h)0(a)15.1(t)-236.5(cy)20.8(cl)12.8(es)]TJ 0 -1.0698 TD [(qu)15.5(ic)18.4(kl)18.9(y)73.2(,)]TJ /F4 1 Tf 3.2664 0 TD [(i.)19.2(e.)]TJ /F8 1 Tf 1.343 0 TD [(cr)19.2(ea)14.7(te)18.4(s)-161.3(c)0(r)13.5(o)0(s)20(s)0(-)18.4(b)0(r)13.9(i)0(d)18.9(g)0(e)15.1(s)-161.3(qu)15.5(i)13.9(c)0(k)15.1(l)0(y)81.4(,)-165.4(ma)17.7(y)-165.8(b)0(e)-155.6(l)13.9(es)13.9(s)-161.3(l)0(i)16.5(k)0(e)15.1(l)0(y)]TJ -4.6093 -1.0698 TD [(to)-163.2(be)-161.3(pe)20.8(rt)11.6(ur)19.6(be)20.8(d)-171.5(b)0(y)-160.9(t)0(i)16.5(d)0(a)15.1(l)-168.2(br)13.9(ea)20.4(th)13.2(i)13.9(n)0(g)15.5(,)-171.1(as)-162.5(it)-159.9(ca)14.7(n)-171.5(r)0(e)19.2(a)0(t)18.4(t)0(a)18.4(c)0(h)-167(a)0(n)20.8(d)-171.5(co)15.1(n-)]TJ T* [(tr)17.3(ib)18.9(ut)18.9(e)-251.6(o)0(n)15.5(c)0(e)-241.3(a)0(g)15.1(a)0(i)18.5(n)-251.2(to)-242.9(ac)14.7(t)13.9(i)0(v)13.2(e)-251.6(fo)19.6(rc)19.2(e)-251.6(a)0(n)15.1(d)-251.2(st)17.7(if)28.6(fn)13.9(es)19.6(s.)-241.3(Co)16.5(mb)18.1(in)18.9(in)13.2(g)]TJ 0 -1.0641 TD [(al)18.4(l)-316.1(t)0(h)18.9(e)0(s)19.6(e)-314.2(fa)13.5(ct)18.5(or)19.6(s,)-309.6(t)13.9(h)0(i)13.2(s)-314.9(hy)21.2(po)15.5(th)18.9(es)19.6(is)-306.7(su)20(gg)15.5(es)19.6(ts)-306.7(th)18.9(at)-305.9(as)13.9(th)18.8(ma)-306.7(is)-306.7(a)]TJ 0 -1.0698 TD [(pr)19.6(oc)15.1(es)19.6(s)-280.8(t)0(h)18.9(a)0(t)-271.8(r)0(e)19.2(s)0(u)20(l)0(t)16.5(s)-280.8(in)-265.7(in)13.2(fl)17.3(am)17.7(ma)17.7(ti)16.5(on)-269(dr)19.6(iv)13.2(en)-269.4(re)19.2(mo)18.1(de)15.1(ll)16.5(in)18.8(g)-279.6(o)0(f)]TJ T* [(ai)18.4(rw)15.7(ay)-172.7(co)15.1(nn)21.2(ec)14.7(ti)16.5(ve)-172.7(ti)16.5(ss)18.9(ue)15.1(s)-178.4(a)0(n)15.1(d)-182.9(mo)18.1(di)18.9(fi)17.3(ca)14.7(ti)16.5(on)-172.2(of)-173.8(th)18.9(e)-183.3(p)0(r)19.6(o)0(c)15.1(e)0(s)19.6(s)0(e)13.9(s)]TJ 0 -1.0641 TD [(th)18.9(at)-317.3(re)19.2(gu)15.5(la)18.4(te)-317.3(cr)19.2(os)14.4(s)-320.6(b)0(r)13.9(i)13.9(d)0(g)15.5(e)-325.5(cy)20.8(cl)12.8(in)18.9(g)-325.1(r)0(a)19.2(t)0(e)18.4(s)-326.3([6)19.6(8,)-314.1(71)15.5(,)-324.7(7)0(2)21.2(])0(.)]TJ 1.0015 -1.0528 TD [(T)69.1(o)-336.5(fu)13.9(rt)17.3(he)20.8(r)-343.8(e)0(x)20.8(p)0(l)13.2(o)0(r)19.6(e)-342.6(th)18.9(e)-342.6(a)0(i)18.4(r)0(w)15.7(a)0(y)20.8(-)0(p)13.9(a)0(r)19.2(e)0(n)15.1(c)0(h)20.8(y)0(m)18.1(a)0(l)-334.4(i)0(n)18.9(t)0(e)12.8(r)0(a)19.2(c)0(t)18.4(i)0(o)18.9(n)0(,)]TJ -1.0015 -1.0698 TD [(an)-178.3(il)16.5(lu)18.9(st)17.7(ra)13.5(t)13.9(i)0(v)13.2(e)-183.3(st)17.7(ud)15.5(y)-188.6(w)0(a)16.9(s)-184.1(pe)15.1(rf)18(or)14(me)17.7(d)-188.6(b)0(y)-177.9(K)]TJ 6.974 0 0 6.974 213.109 293.442 Tm 0.0001 Tc [(AMI)23(NS)18.2(KY)]TJ /F4 1 Tf 9.963 0 0 9.963 246.161 293.442 Tm 0 Tc [(et)-175(al)13.2(.)]TJ /F8 1 Tf 2.0714 0 TD [([4)13.9(8].)]TJ -20.9298 -1.0641 TD [(They)-252.3(show)-8.2(ed)-252.3(that)-252.9(hyperpn)-7.3(oea)-253.5(caused)-257.4(signifi)-9.6(cant)-256.6(changes)]TJ 0 -1.0698 TD [(in)-447.8(the)-448.9(airway)-457.2(parench)-8.2(ymal)-452.8(interacti)-13.5(on.)-445.8(The)-6.8(y)-444.6(meas)-8.2(ured)]TJ T* [(speci)-8.2(fic)-171.7(condu)-9.9(ctance,)-179.7(static)-178.7(complianc)-10.3(e,)-172.3(lung)-176.2(volum)-9.3(es)-173.8(and)]TJ T* [(M/P)-261.9(ratio)-10.6(s)-258(before)-264.7(and)-264.5(after)-260.6(5)-262.5(min)-263.9(of)-259.2(hyperpn)-7.3(oea)-264.9(in)-260(seven)]TJ 0 -1.0641 TD [(asthmati)-12.7(cs)-469.7(and)-475(six)-472.5(no)-7.2(rmal)-477.2(controls)-475([48].)-478.9(Hype)-7.4(rapnoea)]TJ 0 -1.0698 TD [(caused)-200.5(a)-200.3(fall)-197.6(in)-197.4(speci)-8.2(fic)-194.5(cond)-9.1(uctance)-202.8(and)-196.2(an)-195.4(incre)-8.6(ase)-197.8(in)-197.4(the)]TJ T* [(M/P)-193.6(rati)-9.8(o)-188.6(though)-7(t)-196.6(t)0(o)-191.7(b)0(e)-195.4(due)-196.2(to)-191.7(large)-185(airw)-11.4(ay)-189.7(smoo)-7.4(th)-191.7(musc)-7.8(le)]TJ 0 -1.0641 TD [(contr)-8.2(action,)-317.8(hyperpn)-7.3(oea)-310.4(in)-311.2(asthm)-10.9(atics)-312.2(also)-314.3(caused)-320(an)-309.2(in-)]TJ 0 -1.0698 TD [(crease)-230.9(in)-225.8(resi)-8.6(dual)-227.8(volum)-9.3(e)-223.1(and)-230.3(pressure)-234.4(volume)-232.4(hysteresi)-10.7(s,)]TJ T* [(indica)-10.1(tive)-173.2(o)-6.5(f)-173.1(changes)-184.1(in)-174.6(parench)-8.2(ymal)-179.7(lung)-176.2(mecha)-8.2(nics.)-178.1(The)]TJ T* [(incre)-8.6(ase)-317.3(in)-322.6(residual)-321.7(volum)-9.3(e)-319.8(may)-318.8(be)-320.6(seconda)-7.7(ry)-316.1(to)-316.9(a)-6.9(irway)]TJ 0 -1.0641 TD [(closu)-7.8(re,)-151.9(as)-151.1(demon)-7.4(strated)-156(by)-149.5(G)]TJ 6.974 0 0 6.974 173.82 165.77 Tm 0.0001 Tc (UNST)Tj /F4 1 Tf 9.963 0 0 9.963 192.586 165.77 Tm 0 Tc [(et)-152.3(al.)]TJ /F8 1 Tf 2.0315 0 TD [([73].)-148.9(The)-6.8(y)-148.7(show)-8.2(ed)]TJ -15.5124 -1.0698 TD [(that)-173.2(after)-169.5(maxi)-9(mal)-167.6(b)-6.5(ronchoc)-7.7(onstriction)-174.7(by)-172.2(methachol)-10.3(ine)-170.1(in)]TJ T* [(excis)-8.2(ed)-138.5(dog)-138.9(lobes,)-139.1(a)-6.9(irway)-143(closure)-142.2(occurr)-8.6(ed)-138.5(at)-140.9(transpulm)-12.3(on-)]TJ T* [(ary)-140.9(press)-8.2(ures)-137.1(of)-139.7(7.5\26110)-140.8(cmH)]TJ 7.472 0 0 6.641 167.924 132.151 Tm 0 Tw (2)Tj 9.963 0 0 9.963 171.666 133.795 Tm [(O.)-136(The)-143.4(forces)-140.6(of)-139.7(parench)-8.2(ymal)]TJ -11.3811 -1.0641 TD [(interdepend)-16(ence)-493.7(were)-498.8(not)-494.1(sufficient)-492.3(to)-493.3(prevent)-499.5(airw)-11.4(ay)]TJ 0 -1.0698 TD [(closu)-7.8(re.)]TJ 26.1993 66.1583 TD [(Fu)16.3(rt)17.3(he)15.1(rm)16.5(or)19.6(e,)-280.4(re)13.5(sp)20(on)15.5(se)-276.3(to)-282.7(br)19.6(on)15.5(ch)15.1(od)21.2(il)16.5(at)18.4(or)13.9(s)-286.5(c)0(a)14.7(n)-285.3(al)12.8(so)-275.9(sh)14.3(ed)]TJ -1.0015 -1.0471 TD [(li)16.5(gh)15.5(t)-264.9(o)0(n)-263.3(t)0(h)18.9(e)-268.6(co)15.1(nt)18.9(ri)17.3(bu)21.2(ti)16.5(on)-257.6(of)-264.9(ai)18.4(rw)15.7(ay)20.8(s)-269.4(a)0(n)15.1(d)-268.2(pa)20.8(re)13.5(nc)20.8(hy)15.5(ma)17.7(l)-270.6(h)0(y)21.2(s)0(-)]TJ 0 -1.0528 TD [(te)12.8(re)19.2(si)17.7(s)-383.2(i)0(n)-373.8(a)0(s)19.6(t)0(h)18.9(m)0(a)-375([)0(4)13.9(2)0(,)-382.4(44].)-391.2(W)]TJ 6.974 0 0 6.974 427.748 750.727 Tm 0.0001 Tc (ANG)Tj /F4 1 Tf 9.963 0 0 9.963 446.74 750.727 Tm 0 Tc [(et)-391.3(al.)]TJ /F8 1 Tf 2.5095 0 TD [([44])-398.9(deter)-8.6(mined)]TJ -16.3034 -1.0527 TD [(maxi)-9(mal)-338.3(and)-332.7(partial)-344.9(flow)-335.3(volum)-9.3(e)-331.2(loops)-337.4(before)-338.6(and)-338.4(after)]TJ 0 -1.0471 TD [(progre)-8.2(ssiv)-7.8(e)-228.8(doses)-228.5(of)-230.7(albut)-9(erol)-229.4(\(180\2615,0)-7.3(40)]TJ /F7 1 Tf 16.844 0 TD (m)Tj /F8 1 Tf 0.5747 0 TD [(g,)-228.8(cumul)-9.7(ative)]TJ -17.4188 -1.0527 TD 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[(and)-236(small)-235.2(airw)-11.4(ays)-231.5(compo)-7.4(sed)-231.5(of)-236.4(greater)-239.7(numbers)-239.3(of)-230.8(CD8+)]TJ 0 -1.0527 TD [(than)-165.2(CD4+)-160.2(cells,)-164.6(normal)-165.7(proportion)-9.9(s)-155.6(o)0(f)-156.8(macr)-8.6(ophages)-166.7(and)-156.3(a)]TJ 0 -1.0471 TD [(signi)-9.8(ficant)-336.1(numbe)-7.4(r)-332.4(o)0(f)-327.5(a)-6.9(ctivated)-338.8(eosinophil)-10.7(s)-332(compared)-336.4(to)]TJ 0 -1.0527 TD [(hist)-9(orical)-216.6(asthma)-211.3(co)-7.6(ntrol)-209.3(subje)-7.8(cts.)-211.5(Some)-216.4(compa)-7.8(risons)-210.1(be)-7.6(t-)]TJ 0 -1.0471 TD [(ween)-349.2(proxi)-7.8(mal)-349.7(and)-344.1(dist)-9(al)-345.7(airways)-351(wer)-8.2(e)-342.6(perfor)-9.8(med,)-347.6(with)]TJ 0 -1.0528 TD [(great)-8.6(er)-350.7(numbe)-7.4(rs)-351.4(of)-344.6(macr)-8.6(ophages)-354.5(and)-349.8(eosin)-7.8(ophils)-352(appre-)]TJ T* [(ciat)-8.6(ed)-201.1(in)-208.8(the)-204.3(proxi)-7.8(mal)-207.4(as)-202.3(compa)-7.8(red)-209.2(to)-203.1(distal)-206.8(tis)-8.2(sue.)-203.4(Simi)-10.2(lar)]TJ 0 -1.0471 TD [(to)-248.6(the)-249.8(study)-252.1(by)-251.9(C)]TJ 6.974 0 0 6.974 377.064 478.715 Tm 0.0001 Tc (ARROLL)Tj /F4 1 Tf 9.963 0 0 9.963 407.282 478.715 Tm 0 Tc [(et)-249(al.)]TJ /F8 1 Tf 2.225 0 TD [([90])-250.9(the)-249.8(numbe)-7.4(rs)-249(of)-247.8(T)80.5(-cells)]TJ -12.0583 -1.0528 TD [(wer)-8.2(e)-171.9(also)-172.1(great)-8.6(er)-168.6(in)-174.6(the)-175.8(proximal)-175.3(a)-6.9(irways,)-173.8(but)-175.4(did)-175.4(not)-169.7(reach)]TJ 0 -1.0471 TD [(stat)-9.4(istical)-341.2(signifi)-9.6(cance.)]TJ 1.0015 -1.0528 TD [(In)-492.5(su)20(pp)15.5(or)19.6(t)-498.2(o)0(f)-486.8(s)0(i)17.7(g)0(n)15.5(i)13.9(fi)11.6(ca)20.4(nt)-487.6(di)18.8(st)17.7(al)-488(ai)12.8(rw)21.4(ay)-491.3(in)18.9(fl)17.3(am)17.7(ma)12(ti)22.2(on)15.5(,)]TJ -1.0015 -1.0471 TD (H)Tj 6.974 0 0 6.974 316.403 436.875 Tm 0.0001 Tc [(AM)17.9(ID)]TJ /F4 1 Tf 9.963 0 0 9.963 337.323 436.875 Tm 0 Tc [(et)-254.7(al)18.9(.)]TJ /F8 1 Tf 2.225 0 TD [([9)19.6(2])-264.9(evalua)-8.2(ted)-278.2(inflammati)-14.5(on)-274.7(in)-271.4(the)-272.5(large)-270.4(and)]TJ -5.0361 -1.0527 TD [(smal)-10.2(l)-441.3(airways)-447.7(from)-447.6(asthm)-10.9(atics)-448.8(and)-440.9(nonast)-8.6(hmatics)-447.7(who)]TJ 0 -1.0471 TD [(und)-8(erwent)-411.6(thora)-8.2(cic)-409.5(surgery)-408.5(for)-415.2(treatmen)-11.1(t)-407.2(o)0(f)-412.8(pulmonary)]TJ 0 -1.0527 TD [(carci)-9(noma.)-257.4(Six)-254.3(subjects)-258.7(were)-254.1(studie)-10.9(d)-245.5(i)0(n)-254.3(the)-255.5(asthma)-256.8(group)]TJ 0 -1.0471 TD [(and)-236(10)-229.1(in)-237.2(the)-232.7(nonast)-8.5(hma)-233.5(group.)-233.4(The)-234.4(mean)-234.6(cigar)-8.6(ette)-236.2(use)-231.5(in)]TJ 0 -1.0528 TD [(pac)-8.8(k-years)-448.7(was)-446(40.8\21331.9)-448.8(and)-446.6(41.9\21326.8,)-449.2(respec)-8.6(tively)56.2(.)]TJ T* [(Ai)-7.8(rways)]TJ /F7 1 Tf 3.6533 0 TD (>)Tj /F8 1 Tf 0.8422 0 TD (and)Tj /F7 1 Tf 1.7356 0 TD (<)Tj /F8 1 Tf 0.552 0 TD [(2)-291(m)0(m)-292.3(i)0(n)-294.1(diam)-9(eter)-292.4(wer)-8.2(e)-291.4(evalua)-8.2(ted)-295.3(for)-295.7(T)86.2(-)]TJ -6.7831 -1.0471 TD [(cell)-8.6(s,)-366.5(total)-369.9(eosinophil)-10.7(s)-360.5(using)-371.6(a)-365.4(major)-369.8(basic)-372.4(protein)-370.6(anti-)]TJ 0 -1.0527 TD [(bod)-8(y)61.8(,)-495.5(activated)-505(eosin)-7.8(ophil)-8.6(s)-497(using)-502.5(EG2)-499.7(antibody)57(,)-501.1(mast)]TJ 0 -1.0471 TD [(cell)-8.6(s)-309.2(using)-320.4(the)-312.4(antib)-9(ody)-309.6(direc)-8.6(ted)-312.4(agains)-9(t)-310.4(trypt)-10.2(ase)-311.6(\(AA1\))-9.2(,)]TJ 0 -1.0527 TD [(neu)-8.4(trophils)-602.2(using)-604.9(anti-neut)-10.7(rophil)-602.7(elastase)-606.7(and)-600.2(macro-)]TJ 0 -1.0471 TD [(pha)-8.4(ges)-333.9(using)-337.4(the)-335.1(CD68)-341.8(antibody)57(.)]TJ 1.0015 -1.0528 TD [(In)-310.4(ai)18.4(rw)15.7(ay)15.1(s)]TJ /F7 1 Tf 4.4671 0 TD (<)Tj /F8 1 Tf 0.5406 0 TD [(2)-313.7(m)0(m)-309.4(i)0(n)-311.2(d)0(i)18.9(a)0(m)17.7(e)0(t)18.5(e)0(r)47.7(,)-313.4(th)13.2(e)-314.2(n)0(u)21.2(m)0(b)12.4(e)0(r)19.2(s)-314.9(of)-304.7(T)91.9(-)0(c)13.5(e)0(l)18.5(l)0(s)17.7(,)]TJ -6.0092 -1.0471 TD [(to)13.2(ta)18.4(l)-282(e)0(o)15.1(s)0(i)17.7(n)0(o)15.5(p)0(h)21.2(i)0(l)16.5(s)-286.5(an)20.8(d)-285.3(a)0(c)14.7(t)0(i)16.5(v)0(a)20.8(t)0(e)12.8(d)-285.3(eo)20.8(si)17.7(no)15.5(ph)21.2(il)16.5(s)-286.5(w)0(e)16.9(r)0(e)-276.7(g)0(r)13.9(e)0(a)20.4(t)0(e)18.4(r)-286.9(in)]TJ 0 -1.0528 TD [(as)13.9(th)18.9(ma)17.7(ti)16.5(cs)-270.6(as)-270.6(co)20.8(mp)18.1(ar)13.5(ed)-269.4(t)13.9(o)-279.6(co)15.1(nt)18.9(ro)19.6(l)-276.3(s)0(u)14.3(b)0(j)18.9(e)0(c)14.7(t)0(s)17.7(.)-273.5(Th)17.1(e)-280(s)0(a)19.6(m)0(e)-272.5(r)0(e)19.2(s)0(-)]TJ 0 -1.0471 TD [(ul)13.2(ts)-113.2(we)16.9(re)-117.3(sh)20(ow)17.3(n)-126(f)0(o)13.9(r)-121.9(ai)18.4(rw)15.7(ay)15.1(s)]TJ /F7 1 Tf 10.6243 0 TD (>)Tj /F8 1 Tf 0.5463 0 TD 0.1131 Tc [(2)-7.2(m)113.1(m)-8.5(i)113.1(nd)113.1(i)126.3(a)113.1(m)130.8(e)113.1(t)131.6(e)113.1(r)-4.2(i)113.1(na)113.1(d)128.2(d)113.1(i)132(t)113.1(i)129.6(o)113.1(nt)113.1(o)]TJ -11.1706 -1.0528 TD 0 Tc [(in)13.2(cr)19.2(ea)14.7(se)19.6(d)-228.4(m)0(a)17.7(s)0(t)-221.3(c)0(e)20.4(l)0(l)16.5(s)-229.6(\(f)18(ig)18.8(.)-228(6\).)-231.1(In)-236.4(contr)-8.2(ast)-239.6(to)-237.2(the)-238.4(autops)-8.5(y)-239.8(stu-)]TJ T* [(dies,)-235(when)-229.3(the)-227(large)-224.8(and)-230.3(small)-229.6(airways)-237.2(were)-231.3(compa)-7.8(red)-226.2(d)-6.5(i)0(-)]TJ 0 -1.0471 TD [(rectl)-11(y)61.8(,)-410.1(there)-418.3(wer)-8.2(e)-410.9(great)-8.6(er)-413.2(numbe)-7.4(rs)-414(of)-418.5(activated)-419.7(\(E)-7.2(G2+\))]TJ 0 -1.0528 TD [(eosin)-7.8(ophil)-8.6(s)-229.6(i)0(n)-231.5(the)-232.7(small)-235.2(airways)-237.2(as)-230.7(compa)-7.8(red)-231.9(to)-231.5(the)-232.7(larger)]TJ 0 -1.0471 TD [(airw)-11.4(ays)-208.7(\(fig.)-213.9(6\).)-208.4(When)-209.5(the)-215.6(subjects)-213.2(using)-212.2(inhal)-9(ed)-206.8(corticos-)]TJ 0 -1.0528 TD [(teroi)-10.6(ds)-253.1(were)-259.8(exclud)-7.8(ed)-252.3(and)-258.8(the)-255.5(data)-256.6(reanal)-9.8(ysed,)-255.4(the)-255.5(resul)-9.4(ts)]TJ 0 -1.0471 TD [(wer)-8.2(e)-257.2(sti)-8.2(ll)-256.7(signi)-9.8(ficant.)-268.2(These)-260.3(findi)-10.2(ngs)-259.6(sugges)-7.4(t)-259.2(that)-264.3(patien)-10.2(ts)]TJ 0 -1.0527 TD [(wi)-7.8(th)-254.3(chroni)-9(c)-251.6(asthm)-10.9(a)-257.2(may)-256.2(exhibit)-263.3(signifi)-9.6(cant)-256.6(distal)-263.7(airway)]TJ 0 -1.0471 TD [(infl)-9.4(ammati)-10.7(on)-331.6(regard)-8.6(less)-338.3(of)-333.2(inhal)-9(ed)-332(corti)-10.6(costeroid)-339.6(use.)]TJ 1.0015 -1.0527 TD [(Fu)16.3(rt)17.3(he)15.1(r)-298.3(s)0(t)17.7(u)0(d)21.2(i)0(e)12.8(s)-297.9(by)-286.1(K)]TJ 6.974 0 0 6.974 400.422 175.294 Tm 0.0001 Tc [(RA)18.4(FT)]TJ /F4 1 Tf 9.963 0 0 9.963 420.094 175.294 Tm 0 Tc [(et)-288.8(al)13.2(.)]TJ /F8 1 Tf 2.299 0 TD [([8)19.6(0,)-297.1(82])-311.2(and)-310(W)]TJ 6.974 0 0 6.974 504.453 175.294 Tm 0.0001 Tc (ENZEL)Tj /F4 1 Tf 9.963 0 0 9.963 529.398 175.294 Tm 0 Tc (et)Tj -22.0907 -1.0471 TD (al.)Tj /F8 1 Tf 1.434 0 TD [([81])-410.3(in)-413.6(moderate)-418.5(asthmati)-12.7(cs,)-407.5(and)-412.4(severe)-412.6(asthm)-10.9(atics,)]TJ -1.434 -1.0527 TD [(respec)-8.6(tive)-8.2(ly)-527.4(support)-528.3(these)-531.7(studies.)-536.8(However)24.2(,)-523.9(the)-528.6(lung)]TJ 0 -1.0471 TD [(parench)-8.2(yma)-347.3(and)-338.4(large)-333(airw)-11.4(ays)-339.6(were)-345.1(evalua)-8.2(ted.)-341.2(K)]TJ 6.974 0 0 6.974 509.102 143.943 Tm 0.0001 Tc (RAFT)Tj /F4 1 Tf 9.963 0 0 9.963 529.398 143.943 Tm 0 Tc (et)Tj -22.0907 -1.0527 TD (al.)Tj /F8 1 Tf 1.3487 0 TD [([80,)-334.3(82])-328.2(perfor)-9.8(med)-330.2(transbronch)-10.3(ial)-331.8(and)-327.1(e)-6.9(ndobron)-6.9(chial)]TJ -1.3487 -1.0528 TD [(biops)-7.4(ies)-336.3(in)-328.3(subje)-7.8(cts)-336.3(with)-336.1(and)-332.7(without)-340.8(signifi)-9.6(cant)-330.6(noctur-)]TJ 0 -1.0471 TD [(nal)-437.6(worseni)-9.1(ng)-434(of)-435.6(asthma)-438.9(at)-431.1(1)-6.5(6:00)-432.2(h)-433.3(and)-435.2(04:00)-438.7(h.)-433.6(The)]TJ ET 0 0 0 1 K 0 J 0 j 0.49 w 2.613 M []0 d 1 i 102.605 770.104 m 102.605 642.544 l 102.863 769.916 m 100.177 769.916 l 102.863 727.295 m 100.177 727.295 l 102.863 684.651 m 100.177 684.651 l 102.863 642.767 m 100.177 642.767 l S BT /F28 1 Tf 9.8 0 0 9.8 87.616 638.104 Tm 0 0 0 1 k (0.0)Tj -0.4309 4.2547 TD (0.04)Tj 0 4.3438 TD (0.08)Tj 0 4.3165 TD (0.10)Tj ET 107.695 690.06 m 124.362 690.06 l 124.362 641.537 l 107.695 641.537 l 107.695 690.06 l S q 127.54 708.854 16.668 -67.35 re W* n 0.353 w 138.62 628.799 m 89.478 677.94 l 141.364 631.543 m 92.222 680.684 l 144.108 634.287 m 94.966 683.429 l 146.852 637.031 m 97.71 686.173 l 149.596 639.775 m 100.455 688.917 l 152.34 642.519 m 103.199 691.661 l 155.084 645.263 m 105.943 694.405 l 157.829 648.008 m 108.687 697.149 l 160.573 650.752 m 111.431 699.893 l 163.317 653.496 m 114.175 702.637 l 166.061 656.24 m 116.919 705.382 l 168.805 658.984 m 119.663 708.126 l 171.549 661.728 m 122.408 710.87 l 174.293 664.472 m 125.152 713.614 l 177.037 667.216 m 127.896 716.358 l 179.782 669.961 m 130.64 719.102 l 182.526 672.705 m 133.384 721.846 l 185.27 675.449 m 136.128 724.59 l S Q 127.54 708.854 16.668 -67.35 re S q 146.895 715.959 16.668 -74.454 re W* n BT /T9 1 Tf 3.528 0 0 3.528 146.848 641.469 Tm (aaaaa)Tj 0 1 TD (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj 0 -21 TD (bbbbb)Tj 0 1 TD (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj ET Q 146.895 715.959 16.668 -74.454 re 195.404 721.349 m 212.072 721.349 l 212.072 641.545 l 195.404 641.545 l 195.404 721.349 l S q 215.249 742.909 16.668 -101.365 re W* n 0.353 w 226.325 622.316 m 153.66 694.981 l 229.069 625.06 m 156.404 697.725 l 231.813 627.804 m 159.148 700.469 l 234.558 630.548 m 161.893 703.213 l 237.302 633.292 m 164.637 705.957 l 240.046 636.036 m 167.381 708.701 l 242.79 638.78 m 170.125 711.445 l 245.534 641.524 m 172.869 714.189 l 248.278 644.269 m 175.613 716.933 l 251.022 647.013 m 178.357 719.678 l 253.766 649.757 m 181.101 722.422 l 256.511 652.501 m 183.846 725.166 l 259.255 655.245 m 186.59 727.91 l 261.999 657.989 m 189.334 730.654 l 264.743 660.733 m 192.078 733.398 l 267.487 663.477 m 194.822 736.142 l 270.231 666.221 m 197.566 738.886 l 272.975 668.966 m 200.31 741.631 l 275.719 671.71 m 203.054 744.375 l 278.464 674.454 m 205.799 747.119 l 281.208 677.198 m 208.543 749.863 l 283.952 679.942 m 211.287 752.607 l 286.696 682.686 m 214.031 755.351 l 289.44 685.43 m 216.775 758.095 l 292.184 688.174 m 219.519 760.839 l 294.928 690.919 m 222.263 763.584 l 297.672 693.663 m 225.007 766.328 l S Q 215.249 742.909 16.668 -101.365 re S q 234.604 739.479 16.668 -97.974 re W* n BT /T10 1 Tf 3.528 0 0 3.528 234.553 641.469 Tm (aaaaa)Tj 0 1 TD (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj 0 -27 TD (bbbbb)Tj 0 1 TD (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj ET Q 234.604 739.479 16.668 -97.974 re 112.595 699.054 m 119.21 699.054 l 132.199 715.714 m 138.814 715.714 l 152.035 720.124 m 158.65 720.124 l 200.636 742.419 m 207.252 742.419 l 220.394 765.694 m 227.009 765.694 l 239.569 755.159 m 246.184 755.159 l 242.819 739.545 m 242.819 755.136 l 223.668 743.024 m 223.668 765.646 l 203.797 721.373 m 203.797 742.304 l 155.163 716.082 m 155.163 720.124 l 135.563 708.915 m 135.563 715.776 l 115.841 690.112 m 115.841 698.993 l S BT /F26 1 Tf 9.8 0 0 9.8 113.575 704.817 Tm (*)Tj 2.8501 2.5751 TD (*)Tj /F28 1 Tf -7.43 4.0822 TD (a\))Tj ET 102.605 616.832 m 102.605 489.272 l 102.863 616.644 m 100.177 616.644 l 102.863 575.134 m 100.177 575.134 l 102.863 532.49 m 100.177 532.49 l 102.863 489.495 m 100.177 489.495 l S BT 9.8 0 0 9.8 83.394 527.772 Tm (0.25)Tj 0 4.3297 TD (0.35)Tj 0 4.2035 TD (0.45)Tj ET 107.695 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682.639 Tm (1)Tj 8.966 0 0 8.966 428.258 682.639 Tm [(;)-330.7(significant)-340.7(posi-)]TJ -2.2762 -1.0559 TD [(tive)-337.6(correlation)-337.9(between)-330.2(alveolar)]TJ T* [(tissue)-332.7(CD4+)-336(and)-333.4(EG2+)-334.8(cells)]TJ -38.652 -1.2266 TD (H)Tj 6.276 0 0 6.276 67.691 652.705 Tm 0.0001 Tc (AMID)Tj 8.966 0 0 8.966 87.307 652.705 Tm 0 Tc ([92])Tj 7.0437 0.1707 TD (airways)Tj /F7 1 Tf 3.4081 0 TD (>)Tj /F8 1 Tf 0.5501 0 TD [(2)-334.6(m)0(m)-331.5(and)]TJ /F7 1 Tf 4.4766 0 TD (<)Tj /F8 1 Tf 0.5564 0 TD [(2)-328.3(m)0(m)-2335.9(N)0(F)75(A)-331.6(and)-333.4(control)-337.1(subjects)-337.7(under-)]TJ 4.7042 -1.0559 TD [(going)-328.6(thoracic)-336.1(surgery)]TJ 15.0106 1.0559 TD [(increased)-334.2(CD3+,)-338.9(EG2+)-328.4(MBP+)]TJ 0 -1.0559 TD [(and)-333.4(AA1+)-334.6(cells)-338.1(in)-330.2(air)-336.7(asthmatics)]TJ T* [(compared)-333.2(to)-336.5(control)-337(subjects)-331.4(in)]TJ T* (airways)Tj /F7 1 Tf 3.4081 0 TD (>)Tj /F8 1 Tf 0.5501 0 TD [(2)-334.6(mm;)-333.4(increased)]TJ 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[(th)18.9(ro)13.9(ug)21.2(h)-313.7(t)0(h)13.2(e)-314.2(us)20(e)-319.8(o)0(f)-304.7(B)0(A)18.3(L)-317.9(em)17.7(pl)13.2(oy)21.2(in)18.9(g)-319.4(a)-314.2(do)21.2(ub)15.5(le)18.4(-l)17.3(um)18.1(en)-309.2(ca)14.7(th)18.9(-)]TJ 0 -1.0641 TD [(et)18.4(er)-401.9(te)12.8(ch)20.8(ni)18.9(qu)15.5(e)-410.9([)0(9)19.6(3)0(])-412.8(o)0(r)-424.2(throu)-7.8(gh)-416.9(e)-6.9(valuation)-430.2(of)-418.5(initial)-433.1(and)]TJ T* [(subseq)-7.4(uent)-279(BAL)-276.8(aliq)-8.2(uots)-274.1([94\26199])-8.5(.)-273.5(W)26.5(ith)-274.5(the)-278.2(latter)-281.6(techni)-10.1(-)]TJ T* [(que,)-242.1(it)-233.9(is)-238.4(not)-243.7(entirely)-243.3(clear)-242.3(wher)-9(e)-234.5(i)0(n)-237.2(the)-238.4(a)-6.9(irway)-239.7(the)-238.4(samp)-7.8(le)]TJ T* [(originate)-10.7(d,)-308.4(but)-306.3(it)-307.9(can)-310.4(shed)-311.9(light)-306.9(on)-308.8(the)-312.4(presence)-312.1(of)-310.4(distal)]TJ T* [(inflamm)-12.7(ation)-339(in)-334(asthma.)-342.5(V)]TJ 6.974 0 0 6.974 165.827 176.145 Tm 0.0001 Tc (AN)Tj 9.963 0 0 9.963 179.206 176.145 Tm 0 Tc (V)Tj 6.974 0 0 6.974 186.35 176.145 Tm 0.0001 Tc (YVE)Tj /F4 1 Tf 9.963 0 0 9.963 203.924 176.145 Tm 0 Tc [(et)-334.4(a)-6.5(l)0(.)]TJ /F8 1 Tf 2.4014 0 TD [([94])-336.3(evalua)-8.2(ted)]TJ -17.0204 -1.0641 TD [(this)-253.7(technique)-257.5(by)-246.2(nami)-9(ng)-246.2(the)-249.8(first)-257.6(50)-246.2(mL)-253.5(aliquot)-251.9(of)-247.8(sali)-9.4(ne)]TJ T* [(the)-392("bro)-7.6(nchial)-397.1(sample")-397.1(and)-395.3(the)-392(subseq)-7.4(uent)-392.8(four)-393.2(50)-394.2(mL)]TJ T* [(aliquo)-9.7(ts)-403.4(the)-409.1("alveola)-9.3(r)-406.4(samp)-7.8(le")-406.4(in)-407.9(contr)-8.2(ol)-407.9(and)-406.7(asthmati)-12.7(c)]TJ T* [(subje)-7.8(cts.)-365.2(The)-6.8(y)-365(noted)-370.8(that)-366.7(the)-369.3(alveol)-10.1(ar)-367.7(sample)-370.6(contai)-10.1(ned)]TJ T* [(signifi)-9.6(cantly)-232.1(more)-224.4(cell)-8.6(s)-223.9(than)-227.8(the)-227(bronchi)-9.7(al)-220.6(samp)-7.8(le.)-226.6(W)26.5(ithin)]TJ T* [(the)-306.7(asthmati)-12.7(c)-302.8(group,)-307.4(the)-306.7(bronchial)-309.9(samp)-7.8(le)-305.9(contained)-308.7(sig-)]TJ 25.1977 66.1583 TD [(nifi)-9.4(cantly)-311.7(great)-8.6(er)-305.1(percent)-10.5(ages)-312.3(of)-304.7(neutr)-8.2(ophils,)-312.5(eosin)-7.8(ophils)]TJ 0 -1.0471 TD [(and)-344.1(epitheli)-10.7(al)-340.1(cells,)-341(whi)-8.6(le)-340.1(the)-340.8(alveolar)-349.4(sample)-342.1(co)-7.6(ntained)]TJ 0 -1.0528 TD [(signi)-9.8(ficantly)-596.1(great)-8.6(er)-589.7(percent)-10.5(ages)-591.2(of)-589.3(macr)-8.6(ophages)-593.5(and)]TJ 0 -1.0471 TD [(lym)-7.8(phocyt)-7.4(es.)-276.6(Using)-284.5(the)-283.9(scoring)-284.1(system)-286(of)-282(Aas)-281([100],)-280.5(the)]TJ 0 -1.0528 TD [(inves)-7.8(tigators)-460.3(reported)-456.3(a)-450.7(signific)-10.7(ant)-448.9(correlati)-12.7(on)-451.1(between)]TJ 0 -1.0471 TD [(alveol)-10.1(ar)30.6(,)-313.4(not)-312(b)-6.5(ronchial)-320.6(eosinophil)-10.7(s,)-309.6(and)-315.7(the)-318.1(score)-314.7(of)-316.1(Aas)]TJ 0 -1.0528 TD [([100].)-257.8(Althoug)-8.3(h)-245.5(weak)-7.8(,)-250.8(i)0(t)-245.3(was)-252.5(stro)-8.2(nger)-249.7(than)-256.2(that)-252.9(seen)-249.7(with)]TJ 0 -1.0471 TD [(the)-244.1(bronchi)-9.7(al)-243.3(sample)-245.4(eosin)-7.8(ophils)-243.8(\(r)]TJ /F7 1 Tf 13.902 0 TD (=)Tj /F8 1 Tf 0.552 0 TD [(0.25,)-242.1(p)]TJ /F7 1 Tf 2.7428 0 TD (=)Tj /F8 1 Tf 0.5577 0 TD [(0.024)-242.4(and)-241.7(r)]TJ /F7 1 Tf 4.4955 0 TD (=)Tj /F8 1 Tf -22.2501 -1.0527 TD [(0.38)-8.4(,)-444.2(p)]TJ /F7 1 Tf 2.9534 0 TD (=)Tj /F8 1 Tf 0.5577 0 TD [(0.0006)-448.1(for)-455(bronchi)-9.7(al)-448.2(and)-452.3(alveolar)-457.5(eosin)-7.8(ophils,)]TJ -3.5111 -1.0527 TD [(respec)-8.6(tive)-8.2(ly\).)-257(The)-6.8(se)-259.2(studies)-263.3(can)-259.2(be)-258(useful)-10.1(,)-256.5(but)-260.7(the)-261.2(precise)]TJ 0 -1.0471 TD [(compa)-7.8(rtm)-9.4(ent)-335.1(sampled)-342.9(may)-335.9(vary)-335.1(from)-339.4(pa)-7.6(tient)-335.7(to)-334(pati)-8.2(ent.)]TJ /F6 1 Tf 2.2535 -2.6632 TD [(Imaging)-340.5(studie)-8.6(s)-332(t)0(o)-338.9(evaluat)-8.9(e)-331.2(the)-339.2(distal)-341.4(lung)]TJ /F8 1 Tf -1.2519 -1.5478 TD [(Im)10.8(ag)20.8(in)18.9(g)-308.1(t)13.9(he)-297.8(lu)18.9(ng)-297.4(to)-294.1(de)20.8(te)12.8(ct)-294.5(ai)18.5(r)-304(t)0(r)17.3(a)0(p)15.1(p)0(i)18.9(n)0(g)-291.7(a)0(n)15.1(d)-302.4(ai)18.5(rw)15.7(ay)-297.8(cl)18.5(o-)]TJ -1.0015 -1.0471 TD [(su)14.4(re)-470.2(ha)20.8(s)-480(b)0(e)20.8(e)0(n)-474.3(u)0(s)20(e)0(d)-468.6(a)0(s)-469.7(a)-479.2(no)21.2(n-)13.9(in)18.8(va)20.8(si)12(ve)-468.6(ma)17.7(rk)19.6(er)-470.2(of)-469.8(sm)16.9(al)18.5(l)]TJ 0 -1.0527 TD [(ai)12.8(rw)15.7(ay)20.8(s)-263.7(f)0(u)13.9(n)0(c)20.8(t)0(i)16.5(o)0(n)-257.6(i)13.9(n)-268.2(a)0(s)19.6(t)0(h)18.8(m)0(a)-261.2([)0(1)19.6(0)0(1)15.5(\261109].)-278.9(One)-274.1(met)-8.2(hod)-275.4(is)]TJ /F4 1 Tf 21.5899 0 TD (via)Tj /F8 1 Tf -21.5899 -1.0471 TD [(high)-608.6(resoluti)-10.7(on)-599(compu)-7.4(ted)-602.6(tom)-7.8(ography)-604.8(\(HRCT)-11.5(\))-599.9(scan.)]TJ 0 -1.0527 TD [(Se)-6.8(veral)-412.6(studi)-9.8(es)-412.8(have)-413.6(been)-413.6(publi)-8.6(shed)-414.4(in)-413.6(this)-413(area)-415.6([101\261)]TJ T* [(106)-8(].)-270.2(N)]TJ 6.974 0 0 6.974 339.931 572.768 Tm 0.0001 Tc (EWMAN)Tj /F4 1 Tf 9.963 0 0 9.963 369.638 572.768 Tm 0 Tc [(et)-271.8(al.)]TJ /F8 1 Tf 2.2762 0 TD [([101])-280.2(used)-272.1(the)-278.2(pixel)-276.4(index,)-280.1(in)-277.1(which)]TJ -8.331 -1.0471 TD [(the)-272.5(percent)-10.5(age)-270.6(of)-264.9(pixel)-9(s)]TJ /F7 1 Tf 9.7593 0 TD (<)Tj /F8 1 Tf 0.5577 0 TD [(-900)-266.4(Houn)-7(sfeld)-271.2(unit)-7.8(s)-263.7(i)0(s)-272.6(used)-266.4(to)]TJ -10.317 -1.0528 TD [(asses)-8.2(s)-303.6(the)-301(degree)-309(of)-304.7(air)-302.6(trapping)-308.8(in)-299.8(asthm)-10.9(atics)-306.5(at)-300.2(end)-304.3(ex-)]TJ 0 -1.0471 TD [(pirat)-10.6(ion.)-295.3(As)-291.2(HRCT)-299.4(density)-296.2(of)-293.3(norm)-7.8(al)-294.5(lung)-290(is)-295.3(-700\261)-295.6(-800)]TJ 0 -1.0528 TD [(on)-490.9(inspirat)-10.7(ion,)-483.1(the)-488.8(pixel)-492.7(index)-490.3(descri)-10.6(bes)-487.6(areas)-491.5(of)-486.8(low)]TJ 0 -1.0471 TD [(atte)-8.6(nuation)-482.8(thought)-476.7(to)-476.2(be)-479.9(consistent)-484.6(with)-478.4(air)-479(trapping.)]TJ 0 -1.0527 TD [(The)-6.8(se)-344.6(inves)-7.8(tigators)-352.2(found)-346.8(that)-349.6(the)-346.5(pixel)-344.7(index)-348(at)-345.7(a)-348.3(level)]TJ 0 -1.0471 TD [(imm)-11(ediately)-321.8(superior)-326.2(to)-311.2(the)-318.1(diaphr)-9(agm)-318.8(was)-320.8(signifi)-9.6(cantly)]TJ 0 -1.0528 TD [(higher)-276.4(in)-265.7(asthmatics)-277.6(as)-264.9(compa)-7.8(red)-266.1(to)-265.7(c)-6.9(ontrol)-267(subje)-7.8(cts,)-268.4(and)]TJ 0 -1.0471 TD [(was)-275.3(there)-8.6(fore)-268.4(consi)-7.8(stent)-271.9(wi)-7.8(th)-265.7(incre)-8.6(ased)-272.5(air)-274.1(trapping.)-275(This)]TJ 0 -1.0528 TD [(index)-353.7(posit)-9.8(ively)-350.4(correl)-11(ated)-353.4(with)-353.2(the)-352.2(residua)-11.3(l)-344.6(volum)-9.3(e)-348.3(\()0(r)]TJ /F7 1 Tf 22.2501 0 TD (=)Tj /F8 1 Tf -22.2501 -1.0471 TD [(0.63)-8.4(,)-398.7(p)]TJ /F7 1 Tf 2.9079 0 TD (<)Tj /F8 1 Tf 0.5577 0 TD [(0.006\))-404.1(a)-6.9(n)0(d)-399.9(neg)-8.4(atively)-411.6(with)-404.4(the)-409.1(FEV)]TJ 7.97 0 0 7.97 493.455 457.738 Tm (1)Tj 9.963 0 0 9.963 501.449 457.738 Tm (\(r)Tj /F7 1 Tf 0.6487 0 TD (=)Tj /F8 1 Tf 0.5406 0 TD (-0.65,)Tj -20.4746 -1.0527 TD (p)Tj /F7 1 Tf 0.5008 0 TD (<)Tj /F8 1 Tf 0.5577 0 TD [(0.004\))-677.3(and)-679.9(forced)-680.1(vital)-682.8(capacity)-684(\(FVC\))-680.7(\(r)]TJ /F7 1 Tf 18.8755 0 TD (=)Tj /F8 1 Tf 0.5406 0 TD (-0.58,)Tj -20.4746 -1.0471 TD (p)Tj /F7 1 Tf 0.5008 0 TD (<)Tj /F8 1 Tf 0.5577 0 TD (0.02\).)Tj -0.0569 -1.0527 TD [(Th)17.1(es)14(e)-268.6(d)0(a)20.8(t)0(a)-260.4(w)0(e)16.9(r)0(e)-259.6(c)0(o)20.8(n)0(f)13.9(i)0(r)17.3(m)0(e)17.7(d)-268.2(by)-257.6(C)]TJ 6.974 0 0 6.974 446.967 426.331 Tm 0.0001 Tc [(AR)18.4(R)]TJ /F4 1 Tf 9.963 0 0 9.963 463.805 426.331 Tm 0 Tc [(et)-260.4(al)18.9(.)]TJ /F8 1 Tf 2.2364 0 TD [([1)14(04)21.2(],)-281.6(where)]TJ -17.7431 -1.0471 TD [(pati)-8.2(ents)-223.3(with)-222.3(severe)-224.8(asthma)-222.7(underw)-10.5(ent)-221.3(HRCT)-157.1(scanni)-9(ng)-217.8(to)]TJ 0 -1.0528 TD [(deter)-8.6(mine)-350.4(air)-348.1(trapp)-8.2(ing.)-346.5(Instead)-352.7(of)-344.6(using)-348.8(the)-346.5(pixel)-350.4(index,)]TJ 0 -1.0471 TD [(they)-358.7(quantifie)-10.7(d)-347.9(the)-357.9(area)-353(wher)-9(e)-348.3(air)-353.8(trapp)-8.2(ing)-351.8(was)-354.9(presen)-8.2(t.)]TJ 0 -1.0527 TD [(The)-6.8(y)-410.5(defined)-414.2(air)-416.4(trapp)-8.2(ing)-408.7(as)-412.8(decreas)-9.7(ed)-411.7(attenu)-10.2(ation)-413(and)]TJ 0 -1.0471 TD [(fail)-9.8(ure)-254.7(to)-254.3(reduce)-263.5(in)-254.3(volum)-9.3(e)-251.6(w)0(i)-7.8(t)0(h)-254.3(a)0(n)-252.3(associ)-10.1(ated)-256.6(incre)-8.6(ase)-254.7(in)]TJ 0 -1.0528 TD [(pulm)-8.6(onary)-603.3(vascul)-9(ar)-601(mark)-8.2(ings.)-604.5(The)-604.3(severe)-606.1(asthm)-10.9(atics)]TJ 0 -1.0471 TD [(\(FE)-7.2(V)]TJ 7.97 0 0 7.97 331.257 353.14 Tm (1)Tj 9.963 0 0 9.963 340.724 353.14 Tm [(56.6\2134.1%)-553.6(predi)-8.2(cted\))-554.9(exhibited)-555.4(a)-553.2(signifi)-9.6(cantly)]TJ -3.1526 -1.0528 TD [(great)-8.6(er)-253.9(area)-256.2(of)-253.5(air)-251.4(trapp)-8.2(ing)-249.4(as)-253.5(compa)-7.8(red)-254.7(to)-254.3(historical)-259.7(non-)]TJ 0 -1.0471 TD [(asthm)-10.9(a)-228.8(contr)-8.2(ol)-231.5(subjects)-236(\(75.9\2132%)]TJ /F4 1 Tf 13.6744 0 TD (versus)Tj /F8 1 Tf 2.7599 0 TD [(44.6)-8.4(\2131.0%\))-234.6(and)]TJ -16.4343 -1.0528 TD [(a)-297.1(neg)-8.4(ative)-299.6(correlati)-12.7(on)-297.4(with)-302(the)-301(FEV)]TJ 7.97 0 0 7.97 452.92 321.732 Tm (1)Tj 9.963 0 0 9.963 459.836 321.732 Tm (\(r)Tj /F7 1 Tf 0.643 0 TD (=)Tj /F8 1 Tf 0.5463 0 TD [(-0.60,)-301.3(p)]TJ /F7 1 Tf 3.1241 0 TD (<)Tj /F8 1 Tf 0.552 0 TD (0.001\).)Tj -19.9738 -1.0471 TD [(Des)-7.8(pite)-224.5(the)-227(limitati)-12.6(on)-217.8(o)-6.5(f)-218.6(the)-227(use)-225.8(of)-219.4(hist)-9(orical)-228(controls,)-230.7(this)]TJ 0 -1.0527 TD [(study)-297.6(suppor)-7.4(ts)-289.6(the)-295.3(hypothesis)-299.7(that)-292.7(air)-291.2(trapp)-8.2(ing)-294.9(by)-286.1(HRC)-10(T)]TJ 0 -1.0471 TD [(is)-295.3(incre)-8.6(ased)-301(in)-294.1(asthma)-302.3(and)-292.9(correl)-11(ated)-296.5(with)-296.3(lung)-301.3(function.)]TJ 1.0015 -1.0528 TD (K)Tj 6.974 0 0 6.974 326.381 279.893 Tm [(IN)15.7(G)]TJ 9.963 0 0 9.963 341.688 279.893 Tm [(an)20.8(d)-313.8(c)0(o)20.8(w)0(o)17.3(r)0(k)13.9(e)0(r)19.2(s)-309.2([1)13.9(07)21.2(,)-324.7(108])-323.3(expanded)-326(these)-326.9(obser-)]TJ -3.2493 -1.0471 TD [(tion)-7.8(s)-502.7(b)0(y)-502.3(empl)-9(oying)-507(single)-506(photon)-507.7(emi)-8.2(ssion)-503.7(compu)-7.4(ted)]TJ 0 -1.0527 TD [(tom)-7.8(ography)-217.9(\(SP)-8(ECT\))-216.8(and)-218.9(inhaled)-221.5(T)63.4(echnegas)-8.9(,)-216.6(a)0(n)-212.5(ultrafin)-11.2(e)]TJ 0 -1.0471 TD [(aeroso)-8.2(l)-270.6(o)0(f)-264.9(c)0(a)-8(rbon)-266.4(parti)-10.6(cles)-269.2(labelled)-276.2(with)]TJ 7.472 0 0 6.641 470.948 252.964 Tm (99m)Tj 9.963 0 0 9.963 484.157 248.542 Tm [(T)57.7(c)-268.6(to)-265.7(inves)-7.8(ti-)]TJ -17.5497 -1.0528 TD [(gate)-393.2(airway)-388.9(closu)-7.8(re.)-385.2(SPEC)-10.3(T)-317.9(scanni)-9(ng)-388.5(offers)-380.8(the)-386.3(advan-)]TJ T* [(tage)-649.3(of)-646.2(a)-644.2(three)-645.9(dimen)-9.7(sional)-648.3(image,)-647.9(thus)-644(potent)-9.8(ially)]TJ 0 -1.0471 TD [(avo)-8.4(iding)-315.9(any)-315.7(overl)-8.2(ap)-314.9(in)-316.9(stru)-8.2(ctures)-317.8(whic)-9.8(h)-313.8(can)-316.1(occur)-319.2(with)]TJ 0 -1.0527 TD [(HRC)-10(T)74.8(.)-284.9(These)-283.1(inves)-7.8(tiga)-8.2(tors)-281.4(defin)-8.2(ed)-280.8(airw)-11.4(ay)-280.8(closu)-7.8(re)-282.4(as)-282(the)]TJ 0 -1.0471 TD [(percent)-10.5(age)-281.9(of)-282(T)63.4(echnegas)-287.7(free)-285.9(lung)-284.3(volume.)-284(They)-280.7(compa)-7.8(-)]TJ 0 -1.0527 TD [(red)-231.9(this)-230.9(value)-234.6(to)-231.5(closing)-233.6(volume)-232.4(meas)-8.2(ured)]TJ /F4 1 Tf 16.8611 0 TD (via)Tj /F8 1 Tf 1.434 0 TD [(a)-228.8(modi)-8.6(fica-)]TJ -18.2951 -1.0471 TD [(tion)-332.2(of)-321.8(the)-329.4(single)-329.6(breath)-328(nitr)-9.4(ogen)-322.1(was)-7.8(hout)-324.1(test)-328.1(de)-7.6(scribed)]TJ 0 -1.0528 TD [(by)-269(B)]TJ 6.974 0 0 6.974 328.592 164.806 Tm 0.0001 Tc (UIST)Tj /F4 1 Tf 9.963 0 0 9.963 345.713 164.806 Tm 0 Tc [(et)-266.1(al.)]TJ /F8 1 Tf 2.2592 0 TD [([1)31(10].)-266(Closi)-8.8(ng)-263.3(capacity)-268.6(was)-269.6(defined)-266.2(as)-264.9(the)]TJ -5.9125 -1.0471 TD [(sum)-308.2(of)-299(the)-306.7(closing)-307.6(volume)-306.4(and)-304.3(residual)-310.4(volume.)-306.8(In)-304.7(asth-)]TJ 0 -1.0528 TD [(mat)-8.2(ics,)-382.2(the)-380.7(distributio)-11.7(n)-376.3(o)0(f)-378.7(airway)-383.2(closu)-7.8(re)-379.1(was)-383.4(predomi-)]TJ 0 -1.0471 TD [(natel)-9.4(y)-211.3(basal)-8.2(,)-216.6(but)-215.2(only)-216(correl)-11(ated)-216.8(with)-216.6(closi)-10.2(ng)-212.1(capaci)-8.6(ty)58.7(,)-210.9(but)]TJ 0 -1.0528 TD [(only)-443.6(in)-436.4(contr)-8.2(ol)-436.4(subje)-7.8(cts)-438.8(\(r)]TJ /F7 1 Tf 10.9429 0 TD (=)Tj /F8 1 Tf 0.552 0 TD [(0.86,)-441.2(p)]TJ /F7 1 Tf 2.942 0 TD (<)Tj /F8 1 Tf 0.552 0 TD [(0.01\).)-443.6(In)-435.6(asthm)-10.9(atic)]TJ -14.9889 -1.0471 TD [(subje)-7.8(cts,)-433.4(airway)-434.4(closu)-7.8(re)-430.3(was)-428.9(meas)-8.2(ured)-431.8(by)-428.3(the)-431.9(SPECT/)]TJ ET 0 0 0 1 K 0 J 0 j 0.5 w 3.864 M []0 d /GS3 gs 1 i 103.428 770.131 m 103.428 648.255 l 103.692 769.939 m 100.951 769.939 l 103.692 728.716 m 100.951 728.716 l 103.692 687.253 m 100.951 687.253 l 103.692 648.255 m 100.951 648.255 l S BT /F18 1 Tf 10 0 0 10 94.734 644.631 Tm 0 0 0 1 k /GS4 gs (0)Tj -0.8969 12.1567 TD (600)Tj 0 -4.125 TD (400)Tj 0 -4.1625 TD (200)Tj -2 8.6875 TD (a\))Tj 0 10 -10 0 81.293 673.046 Tm (Positive cells\341mm)Tj 0 8 -8 0 78.459 736.376 Tm (-2)Tj /F20 1 Tf 6 0 0 6 121.017 741.496 Tm (l)Tj 0 -1.3334 TD (l)Tj 0 -2.2481 TD (l)Tj 0 -3.2559 TD (l)Tj 6.7869 -6.5307 TD (l)Tj 0 1.4264 TD (l)Tj 0 1.2403 TD (l)Tj 6.7597 -1.597 TD (l)Tj 0 -0.8836 TD (l)Tj 0 -0.8683 TD (l)Tj 0 -0.9613 TD (l)Tj 6.7732 6.2481 TD 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[(five)-445.6(subjects.)-446.9(After)-446.2(the)-437.6(admi)-9(nistration)-447.1(of)-441.3(subcut)-8.6(aneous)]TJ 0 -1.0755 TD [(terbu)-8.2(taline,)-564.9(s)]TJ /F4 1 Tf 5.4231 0 TD (G)Tj /F8 1 Tf 7.97 0 0 7.97 119.452 144.567 Tm (aw)Tj 9.963 0 0 9.963 134.249 144.567 Tm [(and)-560.4(peak)-561.5(expir)-8.2(atory)-565.9(flow)-562.9(incre)-8.6(ased)]TJ /F11 1 Tf -7.6253 -1.0698 TD ($)Tj /F8 1 Tf 0.8365 0 TD [(25%)-357.5(in)-356.7(10)-354.3(subje)-7.8(cts,)-353.8(rati)-9.8(o)]TJ /F4 1 Tf 10.6186 0 TD (V)Tj /F9 1 Tf 0.6032 0 TD (')Tj /F8 1 Tf 7.97 0 0 7.97 180.624 133.909 Tm 0.0001 Tc (max)Tj 9.963 0 0 9.963 194.173 133.909 Tm 0 Tc [(50)-354.3(incre)-8.6(ased)]TJ /F11 1 Tf 5.4459 0 TD ($)Tj /F8 1 Tf 0.8365 0 TD [(0.10)-355.5(in)]TJ -19.9226 -1.0755 TD [(10)-325.9(subje)-7.8(cts,)-331(and)-327.1(radio)-8.2(aeroso)-8.2(l)-327.5(and)-327.1(xenon)-328.6(ima)-8.2(ges)-328.2(show)-8.2(ed)]TJ 0 -1.0698 TD [(improvem)-11.1(ent)-227(in)-225.8(1)27.7(1)-222.7(and)-224.6(eight)-230.9(subjects,)-230.7(respec)-8.6(tively)56.2(.)-222.3(The)-6.8(se)]TJ 25.1977 45.0065 TD [(findi)-10.2(ngs)-748.9(are)-750.2(consi)-7.8(stent)-755.6(with)-751.5(the)-750.5(acti)-8.6(on)-747(of)-748.6(inhal)-9(ed)]TJ 0 -1.0471 TD [(terbu)-8.2(taline)-314.1(main)-9(ly)-305.5(on)-308.8(large)-304.5(airways)-316.8(and)-310(of)-304.7(subcut)-8.5(aneous)]TJ 0 -1.0528 TD [(terbu)-8.2(taline)-268.6(on)-257.6(both)-267.2(lar)10.4(ge)-263.7(and)-264.5(small)-263.7(airways.)-271.7(Althoug)-8.3(h)-256.8(re-)]TJ 0 -1.0471 TD [(duc)-8.4(ed)-212.5(centr)-8.6(al)-214.9(radio)-8.2(aeroso)-8.2(l)-213.7(dep)-8.4(osition)-218.5(correl)-11(ated)-216.8(wel)-9(l)-213.7(with)]TJ 0 -1.0527 TD [(phy)-8(siologic)-9.1(al)-294.5(eviden)-7.8(ce)-292.6(of)-299(lar)10.4(ge)-297.8(airway)-303.5(dilatation,)-305.2(impro-)]TJ 0 -1.0471 TD [(vemen)-7.8(t)-287.7(i)0(n)-288.4(xenon)-288.7(distrib)-9.6(ution)-293.1(and)-287.2(washout)-292.1(could)-291.1(be)-286.5(attr)-9.8(i-)]TJ 0 -1.0528 TD [(buted)-342.3(to)-334(dilatatio)-13.9(n)-330.8(o)0(f)-333.2(e)-6.9(ither)-334.9(large)-333(and/or)-339(small)-337.7(airway)-13.3(s.)]TJ /F6 1 Tf 2.1738 -2.5095 TD [(The)-336.7(dista)-8.2(l)-333.2(lung)-339.6(in)-333.2(asthm)-8.2(a:)-333.2(is)-335.1(it)-341.3(important?)]TJ /F8 1 Tf -1.1723 -1.5478 TD [(Th)17.1(e)-319.8(f)0(i)17.3(n)0(d)21.2(i)0(n)13.2(g)-313.8(of)-310.4(di)18.9(st)17.7(al)-311.6(ai)18.5(rw)15.7(ay)-303.5(in)13.2(fl)17.3(am)17.7(ma)17.7(ti)16.5(on)-308.8(in)-305.5(as)13.9(th)18.9(ma)-306.7(is)]TJ -1.0015 -1.0527 TD [(si)17.7(gn)15.5(if)17.3(ic)18.4(an)15.1(t,)-373.4(as)-373(it)-370.5(is)-375(cu)15.1(rr)18(en)15.1(tl)22.2(y)-382(n)0(o)15.5(t)-384.4(cl)18.5(ea)20.4(r)-383.6(i)0(f)-375.4(i)0(n)18.9(h)0(a)15.1(l)0(e)18.4(d)-382(co)15.1(rt)17.3(ic)18.4(o-)]TJ 0 -1.0471 TD [(st)17.7(er)13.5(oi)18.9(ds)20(,)-341.8(t)0(h)18.9(e)-342.6(ma)17.7(in)18.9(st)17.7(ay)-332(of)-333.2(as)13.9(th)18.9(ma)-329.4(th)13.2(er)19.2(ap)15.1(y)73.2(,)-341.8(ef)30.6(fe)19.2(ct)12.8(iv)18.9(el)18.4(y)-342.2(t)0(r)17.3(e)0(a)20.4(t)]TJ 0 -1.0527 TD [(th)13.2(is)-494.5(co)20.8(mp)18.1(ar)13.5(tm)15.7(en)20.8(t)-503.9(o)0(f)-498.2(t)0(h)18.8(e)-501.9(lu)18.9(ng)15.5(.)-501.2(I)0(t)-494.9(h)0(a)15.1(s)-502.7(be)15.1(en)-491.3(sh)20(ow)11.6(n)-501.5(t)0(h)18.9(a)0(t)]TJ 0 -1.0471 TD [(tr)17.3(ea)14.7(tm)15.7(en)20.8(t,)-276.7(wi)14.9(th)-277.1(in)18.9(ha)15.1(le)18.4(d)-285.3(c)0(o)15.1(r)0(t)17.3(i)0(c)18.4(o)0(s)20(t)0(e)12.8(r)0(o)19.6(i)0(d)18.9(s)-286.5(do)15.5(es)-276.3(no)21.2(t)-287.7(n)0(o)15.5(r)0(m)16.5(a)0(l)18.4(i)0(z)18.4(e)]TJ 0 -1.0528 TD [(hy)15.5(pe)15.1(rr)18(es)19.6(po)15.5(ns)20(iv)18.8(en)15.1(es)19.6(s)-206.8([)0(1)48.1(1)0(3)15.5(])0(.)-219(I)0(n)-213.7(add)-8.4(ition,)-221.9(a)-217.4(study)-217.9(by)-217.8(E)]TJ 6.974 0 0 6.974 512.731 405.411 Tm 0.0001 Tc (SMAIL-)Tj -29.1684 -1.4958 TD [(POU)-11.6(R)]TJ /F4 1 Tf 9.963 0 0 9.963 332.107 394.979 Tm 0 Tc [(et)-425.4(al.)]TJ /F8 1 Tf 2.5721 0 TD [([1)25.3(14])-425(investig)-9.1(ated)-427.3(the)-420.5(d)-6.5(epositio)-9.1(n)-421.9(pattern)-427.9(of)]TJ -4.8597 -1.0527 TD [(flut)-9.4(icasone)-334.5(propionate)-333.5(in)-328.3(perip)-8.2(heral)-333(and)-327.1(centr)-8.6(al)-328.7(lung)-329.8(tis-)]TJ 0 -1.0471 TD [(sue)-459.1(obtaine)-10.9(d)-450.3(from)-458.9(asthm)-10.9(atics)-460.1(undergoing)-450.2(thora)-8.2(cic)-455(sur-)]TJ 0 -1.0528 TD [(gery)57.5(.)-546.7(Their)-547.2(study)-553.7(revealed)-552.3(signifi)-9.6(cantly)-550.8(greater)-552.7(tissue)]TJ 0 -1.0471 TD [(con)-8.4(centratio)-11.1(n)-643.8(o)0(f)-634.8(fluticas)-11.2(one)-645.7(in)-646.9(the)-642.4(c)-6.9(entral)-649.1(tissue)-649.5(as)]TJ 0 -1.0528 TD [(compa)-7.8(red)-328.7(to)-328.3(the)-329.4(pe)-7.6(ripheral)-333.5(tissue.)-331.2(One)-331(potent)-9.7(ial)-331.8(method)]TJ 0 -1.0471 TD [(to)-413.6(address)-414.2(this)-407.3(issu)-7.8(e)-405.2(i)0(s)-409.1(b)0(y)-411.3(altering)-414(the)-409.1(p)-6.5(ropellant)-10.7(s,)-406.4(and)]TJ 0 -1.0528 TD [(hen)-8.4(ce)-275.5(the)-272.5(parti)-10.6(cle)-278.6(size)-274.9(which)-283.7(may)-273.3(alte)-8.6(r)-275.5(medicati)-11.9(on)-274.7(deliv-)]TJ 0 -1.0471 TD [(ery)58.3(.)-330.4(L)]TJ 6.974 0 0 6.974 333.071 311.301 Tm 0.0001 Tc [(EAC)-11.6(H)]TJ /F4 1 Tf 9.963 0 0 9.963 355.294 311.301 Tm 0 Tc [(et)-328.7(al.)]TJ /F8 1 Tf 2.39 0 TD [([1)31(15])-333.9(have)-328.2(show)-8.2(n)-330.8(that)-332.6(beclometh)-10.3(asone)]TJ -7.0051 -1.0527 TD [(in)-328.3(h)-6.5(ydrofluoroa)-10.3(lkane)-331.4(\(HF)66.9(A\))-331.4(propellant)-335.8(reached)-332.9(the)-335.1(peri-)]TJ 0 -1.0471 TD [(phe)-8.4(ral)-353.8(airways)-368.1(more)-355.3(effectively)-361.8(than)-358.7(beclometh)-10.3(asone)-358.6(in)]TJ 0 -1.0528 TD [(chlor)-8.2(inate)-9.4(d)-478.8(fluorocarbo)-10.7(n)-478.8(p)-6.5(ropellant)-488.7(\(CFC\).)-488.3(These)-482.3(data)]TJ 0 -1.0471 TD [(must)-248.8(be)-246.6(interpret)-12.3(ed)-240.9(wi)-7.8(th)-242.9(caution,)-250.3(as)-242.1(label)-9.4(ling)-246.8(particles)-251.3(for)]TJ 0 -1.0527 TD [(visua)-7.8(lization)-340.8(can)-338.8(alter)-341(the)-335.1(distrib)-9.6(ution)-338.6(proper)-8.2(ties.)]TJ 1.0015 -1.0471 TD [(Ev)17.1(al)12.8(ua)20.8(ti)16.5(on)-519.4(of)-515.3(ph)15.5(ys)20(io)18.9(lo)13.2(gi)18.9(ca)20.4(l)-526.7(a)0(n)15.1(d)-524.3(pa)15.1(th)18.9(ol)18.9(og)15.5(ic)18.4(al)-516.5(st)17.7(ud)15.5(ie)18.4(s)]TJ -1.0015 -1.0528 TD [(su)14.4(gg)21.2(es)14(t)-333.2(t)0(h)18.9(a)0(t)-323(t)0(h)18.9(e)-336.9(di)18.9(st)17.7(al)-323(lu)18.9(ng)-325.9(un)21.2(it)16.5(s,)-326.7(i)13.9(n)0(c)15.1(l)0(u)18.9(d)0(i)18.9(n)0(g)-325.9(t)0(h)18.9(e)-331.2(sm)11.2(al)18.5(l)-333.2(a)0(i)18.5(r)20.4(-)]TJ T* [(wa)16.9(ys)-418.1(\()]TJ /F7 1 Tf 2.7542 0 TD (<)Tj /F8 1 Tf 0.5463 0 TD [(2)-421.9(m)0(m)14.9(\))-429.2(an)20.8(d)-427.6(l)0(u)18.9(n)0(g)-416.9(p)0(a)20.8(r)0(e)13.5(n)0(c)20.8(h)0(y)15.5(m)0(a)17.7(,)-427.2(pa)20.8(rt)17.3(ic)18.4(ip)13.2(at)18.5(e)-422.3(i)0(n)-419.3(t)0(h)18.9(e)]TJ -3.3005 -1.0471 TD [(pa)15.1(th)18.8(og)15.5(en)20.8(es)13.9(is)-443.3(of)-441.3(as)13.9(th)18.9(ma)17.7(.)-455.6(H)12.4(ow)17.3(ev)15.1(er)47.7(,)-449.9(t)0(h)18.9(e)-456.4(ch)20.8(al)12.8(l)13.9(e)0(n)15.1(g)0(e)-445.8(l)0(i)16.5(e)0(s)-441.3(i)0(n)]TJ 0 -1.0527 TD [(im)15.7(pr)13.9(ov)21.2(in)18.8(g)-273.9(t)0(h)18.9(e)-268.6(ab)15.1(il)22.2(it)16.5(y)-273.9(t)13.9(o)-273.9(a)0(s)19.6(s)0(e)19.6(s)0(s)-265.7(t)13.9(he)15.1(ir)-261.6(st)17.7(ru)19.6(ct)12.8(ur)19.6(e)-268.6(a)0(n)15.1(d)-268.2(fu)19.6(nc)15.1(ti)16.5(on)]TJ 0 -1.0471 TD [(no)15.5(ni)18.9(nv)15.5(as)19.6(iv)18.8(el)12.8(y)73.2(.)-558.1(Ph)16.3(ys)20(io)13.2(lo)18.9(gi)18.9(ca)14.7(l)-560.8(s)0(t)17.7(u)0(d)15.5(i)13.9(es)-555.1(of)-555.1(lu)18.9(ng)-553.5(hy)21.2(st)17.7(er)13.5(es)19.6(is)]TJ 0 -1.0527 TD [(re)13.5(ve)20.8(al)-470.9(im)15.7(po)21.2(rt)17.3(an)15.1(t)-475.5(r)0(e)19.2(l)0(a)18.4(t)0(i)16.5(o)0(n)15.5(s)0(h)20(i)0(p)18.9(s)-480(be)20.8(tw)14.9(ee)20.4(n)-478.8(t)0(h)18.9(e)-479.2(ai)18.5(rw)15.7(ay)20.8(s)-474.3(a)0(n)15.1(d)]TJ 0 -1.0471 TD [(pa)15.1(re)19.2(nc)15.1(hy)21.2(ma)12(,)-205.2(a)0(n)15.1(d)-205.6(po)15.5(te)18.4(nt)18.9(ia)18.4(ll)16.5(y)-211.3(p)0(r)19.6(o)0(v)15.5(i)0(d)18.8(e)-206(a)-211.7(w)12.4(ay)-201.1(to)-203.1(as)19.6(se)19.6(ss)-203.1(wh)17.3(ic)18.4(h)]TJ 0 -1.0528 TD [(co)15.1(mp)18.1(ar)13.5(tm)21.4(en)15.1(t)-333.2(o)0(f)-327.5(t)0(h)18.9(e)-331.2(lu)13.2(ng)-320.2(is)-329.5(co)20.8(nt)18.9(ri)17.3(bu)15.5(ti)16.5(ng)-320.2(th)13.2(e)-331.2(m)0(o)18.1(s)0(t)-329.5(s)0(i)17.7(g)0(n)21.2(i)0(f)17.3(i)0(-)]TJ 0 -1.0471 TD [(ca)14.7(nt)18.9(ly)-351(in)-351(a)-365.4(g)0(i)18.9(v)0(e)20.8(n)-365(as)19.6(th)18.8(ma)17.7(ti)16.5(c.)-354.4(Ho)17.3(we)16.9(ve)20.8(r)37.5(,)-358.9(th)18.8(e)-365.4(p)0(r)19.6(e)0(c)14.7(i)13.9(se)-355.9(si)17.7(te)-351.4(of)]TJ 0 -1.0528 TD [(ob)15.5(st)17.7(ru)19.6(ct)12.8(io)18.8(n)-273.9(i)0(s)-266.9(s)0(t)17.7(i)0(l)16.5(l)-276.3(co)15.1(nt)18.9(ro)19.6(ve)15.1(rs)18.4(ia)18.4(l)-276.3(i)0(n)-271.4(t)0(h)18.8(e)0(s)19.6(e)-280(st)17.7(ud)21.2(ie)12.8(s.)-264.1(Br)14.9(on)21.2(ch)15.1(o-)]TJ 0 -1.0471 TD [(sc)13.9(op)21.2(ic)-243.3(me)17.7(as)19.6(ur)14(em)17.7(en)15.1(t)13.9(s)-252.3(of)-236.4(pe)15.1(ri)17.3(ph)21.2(er)13.5(al)-237.6(re)13.5(si)17.7(st)17.7(an)20.8(ce)-241.3(of)31(fe)13.5(r)-247.1(a)-251.6(di)18.9(re)19.2(ct)]TJ 0 -1.0528 TD [(bu)15.5(t)-327.5(s)0(t)17.7(i)0(l)16.5(l)-327.5(in)18.8(va)15.1(si)17.7(ve)-314.9(me)17.7(th)13.2(od)-314.5(to)-316.9(ev)15.1(al)18.4(ua)15.1(te)-317.3(th)18.9(is)-318.1(co)15.1(mp)18.1(ar)19.2(tm)15.7(en)15.1(t)-327.5(o)0(f)]TJ 0 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[(14.)-1266.5(Martin)-369.9(HB,)-370.3(Proctor)-372.1(DF)75(.)-369.6(Pressure-volume)-372.8(measurements)]TJ 2.5165 -1.1128 TD [(on)-327.8(dog)-333.6(bronchi.)]TJ /F4 1 Tf 6.7782 0 TD [(J)-334.4(Appl)-332.6(Physiol)]TJ /F8 1 Tf 6.2787 0 TD [(1967;)-334.9(13:)-329.7(337\261343.)]TJ -15.5733 -1.1128 TD [(15.)-1266.5(Hohlfeld)-264(JM,)-263(Ahlf)-270.2(K,)-264.9(Enhorning)-261.5(G,)]TJ /F4 1 Tf 17.0845 0 TD [(et)-266.7(al)]TJ /F8 1 Tf 1.7451 0 TD [(.)-262.2(Dysfunction)-269.9(of)]TJ -16.3131 -1.1128 TD [(pulmonary)-303.9(surfactant)-311.9(in)-311.2(asthmatics)-309.1(after)-311.1(segmental)-312.4(aller-)]TJ 0 -1.1065 TD [(gen)-402.9(challenge.)]TJ /F4 1 Tf 6.285 0 TD [(Am)-404.1(J)-410.3(Respir)-403.3(Crit)-407(Car)27.2(e)-403.9(Med)]TJ /F8 1 Tf 12.0831 0 TD [(1999;)-410.8(159:)]TJ -18.3681 -1.1128 TD (1803\2611809.)Tj -2.5165 -1.1128 TD [(16.)-1266.5(van)-301.8(de)-302.3(Graaf)-305.7(EA,)-305.8(Jansen)-302.4(HM,)-303(Lutter)-309.4(R,)]TJ /F4 1 Tf 18.9498 0 TD [(et)-304.6(al)]TJ /F8 1 Tf 1.7767 0 TD [(.)-306.4(Surfactant)]TJ -18.21 -1.1065 TD [(protein)-216.9(A)-211.5(i)0(n)-216.4(bronchoalveolar)-219.4(lavage)-220(fluid.)]TJ /F4 1 Tf 16.7115 0 TD [(J)-220.6(Lab)-212(Clin)-216.1(Med)]TJ /F8 1 Tf -16.7115 -1.1128 TD [(1992;)-328.6(120:)-335.5(252\261263.)]TJ -2.5165 -1.1128 TD [(17.)-1266.5(Despas)-583.9(PJ,)-577(Leroux)-582.9(M,)-584.8(Macklem)-582.4(PT)68.5(.)-578.3(Site)-589.1(of)-581.7(airway)]TJ 2.5165 -1.1128 TD [(obstruction)-300.6(in)-298.6(asthma)-299.1(as)-303.5(determined)-305.3(by)-296.2(measuring)-304.9(maxi-)]TJ 0 -1.1065 TD [(mal)-540(expiratory)-544.9(flow)-542.1(breathing)-544.5(air)-545.4(and)-542(helium-oxygen)]TJ 0 -1.1128 TD (mixture.)Tj /F4 1 Tf 3.6546 0 TD [(J)-328.1(Clin)-336.2(Invest)]TJ /F8 1 Tf 5.4946 0 TD [(1972;)-334.9(51:)-336(3235\2613243.)]TJ -11.6658 -1.1128 TD [(18.)-1266.5(Ludwig)-278(MS,)-279.4(Romero)-282.5(PV)125.6(,)-281.1(Bates)-283.5(JH.)-284.6(A)-281(comparison)-279.1(of)-284.5(the)]TJ 2.5165 -1.1128 TD [(dose-response)-314.3(behavior)-308.6(of)-316.1(canine)-308.5(airways)-313.6(and)-314.4(parenchy-)]TJ 0 -1.1065 TD (ma.)Tj /F4 1 Tf 1.7894 0 TD [(J)-334.4(Appl)-332.6(Physiol)]TJ /F8 1 Tf 6.2786 0 TD [(1989;)-334.9(67:)-329.7(1220\2611225.)]TJ -10.5846 -1.1128 TD [(19.)-1266.5(Ludwig)-360.2(MS,)-361.6(Bellofiore)-368.6(S,)-361.4(Shore)-363.5(SA,)-364.2(Drazen)-360.9(JM,)-364.2(Fred-)]TJ 2.5165 -1.1128 TD [(ber)13.4(g)-397.9(JJ.)-402.6(Dynamics)-402.5(of)-398.3(the)-399(collateral)-402.8(pathways)-400.7(of)-398.3(canine)]TJ 0 -1.1065 TD [(lungs)-412(after)-418.6(flow)-421.9(interruption.)]TJ /F4 1 Tf 12.336 0 TD [(J)-416.6(Appl)-414.8(Physiol)]TJ /F8 1 Tf 6.5252 0 TD [(1989;)-417.1(67:)]TJ -18.8612 -1.1128 TD (1213\2611219.)Tj 25.4813 73.5671 TD [(20.)-1266.5(Romero)-219.2(PV)125.6(,)-211.6(Ludwig)-214.8(MS.)-216.1(Maximal)-218.3(methacholine-induced)]TJ 2.5165 -1.1191 TD [(constriction)-346.6(in)-349.1(rabbit)-343.9(lung:)-343.7(interactions)-352.7(between)-342.9(airways)]TJ 0 -1.1128 TD [(and)-333.4(tissue?)]TJ /F4 1 Tf 4.7928 0 TD [(J)-328.1(Appl)-338.9(Physiol)]TJ /F8 1 Tf 6.2787 0 TD [(1991;)-328.6(70:)-336(1044\2611050.)]TJ -13.5879 -1.1128 TD [(21.)-1266.5(Romero)-358.4(PV)125.6(,)-357(Robatto)-359.8(FM,)-355.2(Simard)-360.9(S,)-355.1(Ludwig)-360.2(MS.)-355.2(Lung)]TJ 2.5165 -1.1128 TD [(tissue)-326.3(behavior)-321.3(during)-322.8(methacholine)-324.5(challenge)-321.7(in)-323.8(rabbits)]TJ /F4 1 Tf 0 -1.1192 TD [(in)-330.2(vivo)]TJ /F8 1 Tf 2.7505 0 TD (.)Tj /F4 1 Tf 0.5817 0 TD [(J)-334.4(Appl)-332.6(Physiol)]TJ /F8 1 Tf 6.2787 0 TD [(1992;)-334.9(73:)-329.7(207\261212.)]TJ -12.1273 -1.1128 TD [(22.)-1266.5(Nagase)-323.2(T)72.9(,)-319.1(Ito)-324.3(T)72.9(,)-319.1(Y)92(anai)-322.4(M,)-319.2(Martin)-325.6(JG,)-322.5(Ludwig)-322.3(MS.)-317.3(Res-)]TJ 2.5165 -1.1128 TD [(ponsiveness)-303.4(of)-297.1(and)-301.8(interactions)-302.1(between)-304.9(airways)-301(and)-295.4(tis-)]TJ 0 -1.1192 TD [(sue)-429.4(in)-437.7(guinea)-435.2(pigs)-431.5(during)-430.3(induced)-434.6(constriction.)]TJ /F4 1 Tf 20.0752 0 TD [(J)-435.6(Appl)]TJ -20.0752 -1.1128 TD (Physiol)Tj /F8 1 Tf 3.3006 0 TD [(1993;)-334.9(74:)-329.6(2848\2612854.)]TJ -5.8171 -1.1128 TD [(23.)-1266.5(McNamara)-318(JJ,)-314.1(Castile)-312.5(RG,)-313.4(Ludwig)-315.9(MS,)-311(Glass)-315.1(GM,)-315.7(Ing-)]TJ 2.5165 -1.1191 TD [(ram)-216.1(RH)-215.7(Jr)49.4(.,)-214.5(Fredberg)-211(JJ.)-212.9(Heterogeneous)-221.6(regional)-222.5(behavior)]TJ 0 -1.1128 TD [(during)-259.5(forced)-257.7(expiration)-261.8(before)-257.7(and)-257.5(after)-266.9(histamine)-258.1(inhal-)]TJ 0 -1.1192 TD [(ation)-337.1(in)-330.2(dogs.)]TJ /F4 1 Tf 5.8803 0 TD [(J)-334.4(Appl)-332.6(Physiol)]TJ /F8 1 Tf 6.285 0 TD [(1994;)-328.6(76:)-336(356\261360.)]TJ -14.6818 -1.1065 TD [(24.)-1266.5(Fredberg)-400.7(JJ,)-402.6(Keefe)-412(DH,)-406.8(Glass)-410(GM,)-404.2(Castile)-413.7(RG,)-401.9(Frantz)]TJ 2.5165 -1.1192 TD [(IDD.)-464.2(Alveolar)-472.4(pressure)-467.7(nonhomogeneity)-466.9(during)-461.9(small-)]TJ 0 -1.1128 TD [(amplitude)-636.3(high-frequency)-636.1(oscillation.)]TJ /F4 1 Tf 16.2752 0 TD [(J)-631.6(Appl)-636.1(Physiol)]TJ /F8 1 Tf -16.2752 -1.1191 TD [(1984;)-334.9(57:)-329.6(788\261800.)]TJ -2.5165 -1.1128 TD [(25.)-1266.5(Bachofen)-342.4(H.)-334.5(Lung)-336.6(tissue)-345.3(resistance)-337.2(and)-339.7(pulmonary)-341.8(hys-)]TJ 2.5165 -1.1128 TD (teresis.)Tj /F4 1 Tf 3.0919 0 TD [(J)-334.4(Appl)-332.6(Physiol)]TJ /F8 1 Tf 6.2786 0 TD [(1968;)-335(24:)-336(296\261301.)]TJ -11.8871 -1.1128 TD [(26.)-1266.5(Hahn)-266.6(HL,)-261.6(W)70.8(atson)-266.4(A,)-264.9(W)32.8(ilson)-262.7(AG,)-267.7(Pride)-264.7(NB.)-269.1(Influence)-264.6(of)]TJ 2.5165 -1.1128 TD [(bronchomotor)-328.6(tone)-328.9(on)-327.8(airway)-325.6(dimensions)-332.5(and)-327.1(resistance)]TJ 0 -1.1192 TD [(in)-292.2(excised)-290.2(dog)-289.3(lungs.)]TJ /F4 1 Tf 8.8015 0 TD [(J)-290.1(Appl)-288.4(Physiol)]TJ /F8 1 Tf 6.1459 0 TD [(1980;)-290.7(49:)-291.7(270\261278.)]TJ -17.4639 -1.1128 TD [(27.)-1266.5(Hildebrandt)-220.3(J.)-218.6(Dynamic)-218.5(properties)-223.6(of)-214.9(air-filled)-215.5(excised)-220.6(cat)]TJ 2.5165 -1.1128 TD [(lung)-297.5(determined)-299(by)-302.5(liquid)-295(plethysmograph.)]TJ /F4 1 Tf 17.6599 0 TD [(J)-302.8(Appl)-294.7(Phys-)]TJ -17.6599 -1.1192 TD (iol)Tj /F8 1 Tf 1.3721 0 TD [(1969;)-334.9(27:)-336(246\261250.)]TJ -3.8886 -1.1065 TD [(28.)-1266.5(Ludwig)-315.9(MS,)-311(Dreshaj)-313.6(I,)-313.2(Solway)-317.1(J,)-313.4(Meuoz)-313.8(A,)-309.2(Ingram)-316.7(RH)]TJ 2.5165 -1.1192 TD [(Jr)49.4(.)-319.1(Partitioning)-327.6(of)-322.4(pulmonary)-322.9(resistance)-324.6(during)-322.8(constrict-)]TJ T* [(ion)-317(in)-317.5(the)-323.1(dog:)-316.5(ef)12.9(fects)-324(of)-316.1(volume)-323.4(history)59.9(.)]TJ /F4 1 Tf 16.9011 0 TD [(J)-321.8(Appl)-320(Physiol)]TJ /F8 1 Tf -16.9011 -1.1128 TD [(1987;)-334.9(62:)-329.6(807\261815.)]TJ -2.5165 -1.1128 TD [(29.)-1266.5(Fredberg)-280.5(JJ,)-295.1(Ingram)-291.4(RH)-291.5(Jr)49.4(.,)-290.4(Castile)-293.6(RG,)-288.1(Glass)-296.1(GM,)-290.4(Dra-)]TJ 2.5165 -1.1128 TD [(zen)-465.9(JM.)-471.7(Nonhomogeneity)-470.2(of)-467.9(lung)-468.3(response)-466.7(to)-469.3(inhaled)]TJ 0 -1.1192 TD [(histamine)-258.1(assessed)-265.6(with)-259(alveolar)-260.2(capsules.)]TJ /F4 1 Tf 17.0213 0 TD [(J)-258.5(Appl)-263.1(Physiol)]TJ /F8 1 Tf -17.0213 -1.1128 TD [(1985;)-334.9(58:)-329.6(1914\2611922.)]TJ -2.5165 -1.1128 TD [(30.)-1266.5(McNamara)-235.8(JJ,)-231.9(Castile)-230.3(RG,)-231.2(Glass)-232.9(GM,)-233.5(Fredberg)-223.6(JJ.)-231.9(Heter-)]TJ 2.5165 -1.1192 TD [(ogeneous)-262.2(lung)-265.9(emptying)-267.9(during)-265.9(forced)-270.3(expiration.)]TJ /F4 1 Tf 20.2396 0 TD [(J)-271.2(Appl)]TJ -20.2396 -1.1128 TD (Physiol)Tj /F8 1 Tf 3.3006 0 TD [(1987;)-334.9(63:)-329.6(1648\2611657.)]TJ -5.8171 -1.1128 TD [(31.)-1266.5(Gil)-272.1(J,)-269.2(Bachofen)-266.5(H,)-271.3(Gehr)-267.6(P)103.1(,)-268.5(W)70.8(eibel)-273.7(ER.)-269.3(Alveolar)-270.1(volume-)]TJ 2.5165 -1.1128 TD [(surface)-213.9(area)-213.2(relation)-212.2(in)-210(air-)-204.4(and)-213.2(saline-filled)-216.4(lungs)-209.7(fixed)-215.6(by)]TJ 0 -1.1192 TD [(vascular)-334.9(perfusion.)]TJ /F4 1 Tf 7.9479 0 TD [(J)-328.1(Appl)-338.9(Physiol)]TJ /F8 1 Tf 6.2787 0 TD [(1979;)-328.6(47:)-336(990\2611001.)]TJ -16.7431 -1.1128 TD [(32.)-1266.5(Fredberg)-261.5(JJ,)-269.8(Bunk)-274.6(D,)-271.3(Ingenito)-273.3(E,)-271.5(Shore)-268.7(SA.)-275.7(T)34.9(issue)-273.9(resis-)]TJ 2.5165 -1.1128 TD [(tance)-239.4(and)-238.5(the)-234.6(contractile)-244.3(state)-243.2(of)-233.9(lung)-240.6(parenchyma.)]TJ /F4 1 Tf 20.2713 0 TD [(J)-239.5(Appl)]TJ -20.2713 -1.1192 TD (Physiol)Tj /F8 1 Tf 3.3006 0 TD [(1993;)-334.9(74:)-329.6(1387\2611397.)]TJ -5.8171 -1.1065 TD [(33.)-1266.5(Kapanci)-210.1(Y)123.6(,)-211.6(Assimacopoulos)-214.6(A,)-214.4(Irle)-210.7(C,)-215.8(Zwahlen)-213.8(A,)-208(Gabbi-)]TJ 2.5165 -1.1192 TD [(ani)-765.7(G.)-764.4("Contractile)-772.6(interstitial)-771(cells")-773(in)-766.5(pulmonary)]TJ T* [(alveolar)-525.8(septa:)-527.2(a)-524.1(possible)-527.6(regulator)-526.5(of)-531.1(ventilation-per)7.1(-)]TJ 0 -1.1128 TD [(fusion)-273.4(ratio?)-274.1(Ultrastructural,)-279.4(immunofluorescence,)-276.1(and)]TJ /F4 1 Tf 22.048 0 TD (in)Tj -22.048 -1.1192 TD [(vitr)27.9(o)]TJ /F8 1 Tf 2.1624 0 TD (studies.)Tj /F4 1 Tf 3.3385 0 TD [(J)-328.1(Cell)-336(Biol)]TJ /F8 1 Tf 4.7232 0 TD [(1974;)-334.9(60:)-336(375\261392.)]TJ -12.7407 -1.1065 TD [(34.)-1266.5(Fukui)-327.2(M,)-325.6(Y)92(asui)-330.1(H,)-321.8(W)70.8(atanabe)-326.7(K,)]TJ /F4 1 Tf 15.9717 0 TD [(et)-329.9(al)]TJ /F8 1 Tf 1.8084 0 TD [(.)-325.4(Hypoxic)-324.3(contrac-)]TJ -15.2635 -1.1192 TD [(tion)-401.1(of)-404.6(contractile)-408.6(interstitial)-410.6(cells)-407.6(isolated)-408.5(from)-406.5(bovine)]TJ 0 -1.1128 TD (lung.)Tj /F4 1 Tf 2.3521 0 TD [(Am)-334.6(J)-334.4(Physiol)]TJ /F8 1 Tf 5.7286 0 TD [(1996;)-334.9(270:)-329.1(L962\261L972.)]TJ -10.5972 -1.1128 TD [(35.)-1266.5(Ludwig)-429.7(MS.)-431.1(Role)-434.8(of)-429.9(lung)-430.3(parenchyma.)]TJ /F4 1 Tf 19.443 0 TD (In)Tj /F8 1 Tf 0.822 0 TD [(:)-431.8(Barnes)-433.3(PJ,)]TJ -17.7484 -1.1192 TD [(Grunstein)-492.3(MM,)-490.1(Leff)-477.4(AR,)-490.4(W)77.1(oolcock)-491.6(AJ,)-486.9(eds.)]TJ /F4 1 Tf 19.5884 0 TD (Asthma)Tj /F8 1 Tf 2.9844 0 TD (.)Tj -22.5728 -1.1128 TD [(Philadelphia:)-338.3(Lippincott-Raven,)-335.2(1997;)-334.9(1319\2611334.)]TJ -2.5165 -1.1128 TD [(36.)-1266.5(T)60.2(epper)-269.8(RS,)-270.7(Shen)-274.5(X,)-271.3(Bakan)-267.3(E,)-271.5(Gunst)-276.2(SJ.)-267.2(Maximal)-275.2(airway)]TJ 2.5165 -1.1128 TD 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/F4 1 Tf 20.5495 0 TD [(Am)-511.6(J)]TJ -20.5495 -1.1128 TD [(Respir)-333.8(Crit)-337.4(Car)33.6(e)-334.4(Med)]TJ /F8 1 Tf 9.2251 0 TD [(1998;)-334.9(158:)-335.5(1607\2611612.)]TJ -11.7416 -1.1128 TD [(39.)-1266.5(Fredberg)-242.6(JJ,)-257.2(Stamenovic)-252.3(D.)-252.3(On)-255.2(the)-253.6(imperfect)-256.2(elasticity)-260.2(of)]TJ 2.5165 -1.1128 TD [(lung)-335.5(tissue.)]TJ /F4 1 Tf 4.9382 0 TD [(J)-328.1(Appl)-338.9(Physiol)]TJ /F8 1 Tf 6.2787 0 TD [(1989;)-328.6(67:)-336(2408\2612419.)]TJ -13.7334 -1.1128 TD [(40.)-1266.5(W)70.8(oolcock)-624.3(AJ,)-626(V)47.8(incent)-627.2(NJ,)-626(Macklem)-633(PT)74.8(.)-628.9(Frequency)]TJ 23.3379 76.3934 TD (1415)Tj 7.472 0 0 7.472 246.671 797.499 Tm 0.0001 Tc [(DIST)71.7(AL)-339.5(LUNG)-337.4(AND)-334.5(ASTHMA)]TJ ET endstream endobj 91 0 obj << /ProcSet [/PDF /Text ] /Font << /F4 7 0 R /F6 9 0 R /F8 11 0 R >> /ExtGState << /GS2 12 0 R >> >> endobj 93 0 obj << /Length 19024 >> stream BT /F8 1 Tf 8.966 0 0 8.966 80.844 772.157 Tm 0 g /GS2 gs 0 Tc [(dependence)-417.4(compliance)-424.3(as)-423.6(a)-422.9(test)-421(for)-424(obstruction)-420.8(in)-425(the)]TJ 0 -1.1191 TD [(small)-333.8(airways.)]TJ /F4 1 Tf 6.1206 0 TD [(J)-334.4(Clin)-336.2(Invest)]TJ /F8 1 Tf 5.5009 0 TD [(1969;)-328.6(48:)-336(1097\2611)34.7(106.)]TJ -14.138 -1.1065 TD [(41.)-1266.5(Burns)-421.6(CB,)-428.6(T)66.6(aylor)-430.5(WR,)-423.2(Ingram)-430.5(RH)-424.3(Jr)49.4(.)-426.5(E)0(f)15.5(fects)-431.5(of)-423.6(deep)]TJ 2.5165 -1.1192 TD [(inhalation)-471.9(in)-475.6(asthma:)-471.7(relative)-477.6(airway)-477.4(and)-472.5(parenchymal)]TJ 0 -1.1128 TD (hysteresis.)Tj /F4 1 Tf 4.4766 0 TD [(J)-334.4(Appl)-332.6(Physiol)]TJ /F8 1 Tf 6.2786 0 TD [(1985;)-334.9(59:)-329.7(1590\2611596.)]TJ -13.2718 -1.1128 TD [(42.)-1266.5(Ingram)-291.4(RH)-291.5(Jr)55.8(.)-293.8(Physiological)-293.1(assessment)-294.1(of)-290.8(inflammation)]TJ 2.5165 -1.1192 TD [(in)-349.1(the)-354.7(peripheral)-355(lung)-354.4(of)-354(asthmatic)-359(patients.)]TJ /F4 1 Tf 18.1404 0 TD (Lung)Tj /F8 1 Tf 2.409 0 TD (1990;)Tj -20.5495 -1.1128 TD [(168:)-329.1(237\261247.)]TJ -2.5165 -1.1128 TD [(43.)-1266.5(Pride)-365.9(NB,)-364(Ingram)-367.3(RH)-367.4(Jr)55.8(.,)-366.2(Lim)-366.6(TK.)-362.8(Interaction)-369.5(between)]TJ 2.5165 -1.1128 TD [(parenchyma)-325.6(and)-333.4(airways)-326.3(in)-330.2(chronic)-334.4(obstructive)-332(pulmon-)]TJ 0 -1.1192 TD [(ary)-264.8(disease)-266.1(and)-263.8(in)-266.9(asthma.)]TJ /F4 1 Tf 10.692 0 TD [(Am)-265(Rev)-267.1(Respir)-264.2(Dis)]TJ /F8 1 Tf 7.8214 0 TD [(1991;)-265.4(143:)]TJ -18.5135 -1.1191 TD (1446\2611449.)Tj -2.5165 -1.1065 TD [(44.)-1266.5(W)77.1(ang)-409.2(YT)70.1(,)-407.6(Thompson)-407.1(LM,)-410.7(Ingenito)-412.4(EP)106.4(,)-413.9(Ingram)-411.5(RH)-405.4(Jr)49.4(.)]TJ 2.5165 -1.1191 TD [(Ef)15.5(fects)-229.2(of)-227.6(increasing)-228.8(doses)-220.9(of)-227.6(beta-agonists)-224.5(on)-226.6(airway)-224.4(and)]TJ 0 -1.1128 TD [(parenchymal)-390.7(hysteresis.)]TJ /F4 1 Tf 10.0408 0 TD [(J)-391.3(Appl)-389.5(Physiol)]TJ /F8 1 Tf 6.4557 0 TD [(1990;)-391.9(68:)-386.6(363\261)]TJ -16.4965 -1.1192 TD (368.)Tj -2.5165 -1.1128 TD [(45.)-1266.5(W)77.1(agner)-712.5(EM,)-701.6(Liu)-712.5(MC,)-702.8(W)70.8(einmann)-708.4(GG,)-710.3(Permutt)-710.6(S,)]TJ 2.5165 -1.1128 TD [(Bleecker)-439.3(ER.)-440(Peripheral)-442.1(lung)-443(resistance)-438.4(in)-444(normal)-438.2(and)]TJ 0 -1.1192 TD [(asthmatic)-352.7(subjects.)]TJ /F4 1 Tf 7.9163 0 TD [(Am)-347.2(Rev)-355.6(Respir)-352.7(Dis)]TJ /F8 1 Tf 8.1566 0 TD [(1990;)-353.9(141:)-348.1(584\261)]TJ -16.0728 -1.1128 TD (588.)Tj -2.5165 -1.1128 TD [(46.)-1266.5(W)77.1(agner)-434.2(EM,)-423.4(Bleecker)-433(ER,)-427.4(Permutt)-432.3(S,)-430.9(Liu)-428(MC.)-430.9(Direct)]TJ 2.5165 -1.1128 TD [(assessment)-249.8(of)-252.9(small)-258(airways)-256.7(reactivity)-251.3(in)-254.3(human)-252(subjects.)]TJ /F4 1 Tf 0 -1.1192 TD [(Am)-328.2(J)-334.4(Respir)-333.8(Crit)-337.4(Car)27.2(e)-328.1(Med)]TJ /F8 1 Tf 11.6468 0 TD [(1998;)-334.9(157:)-335.5(447\261452.)]TJ -14.1633 -1.1128 TD [(47.)-1266.5(Kaminsky)-440.7(DA,)-451.1(Irvin)-444.4(CG,)-446.2(Gurka)-444.1(DA,)]TJ /F4 1 Tf 18.6652 0 TD [(et)-443.7(al)]TJ /F8 1 Tf 1.9222 0 TD [(.)-445.5(Peripheral)]TJ -18.0709 -1.1128 TD [(airways)-465.4(responsiveness)-468.2(to)-463(cool,)-464.6(dry)-461(air)-469.5(in)-463(normal)-463.5(and)]TJ 0 -1.1192 TD [(asthmatic)-308.4(individuals.)]TJ /F4 1 Tf 9.0481 0 TD [(Am)-309.3(J)-309.1(Respir)-308.5(Crit)-305.8(Car)27.2(e)-309.1(Med)]TJ /F8 1 Tf 11.5014 0 TD (1995;)Tj -20.5495 -1.1128 TD [(152:)-329.1(1784\2611790.)]TJ -2.5165 -1.1128 TD [(48.)-1266.5(Kaminsky)-206.8(DA,)-210.8(W)70.8(enzel)-214.1(SE,)-206.3(Carcano)-216.4(C,)-209.4(Gurka)-210.1(D,)-208(Feldsien)]TJ 2.5165 -1.1192 TD [(Q,)-340.8(Irvin)-343.2(CG.)-345(Hyperpnoea-induced)-345(changes)-344.7(in)-342.8(parenchy-)]TJ 0 -1.1128 TD [(mal)-249.1(lung)-253.3(mechanics)-252.9(in)-254.3(normal)-254.9(subjects)-255.5(and)-251.2(in)-248(asthmatics.)]TJ /F4 1 Tf 0 -1.1192 TD [(Am)-328.2(J)-334.4(Respir)-333.8(Crit)-337.4(Car)27.2(e)-328.1(Med)]TJ /F8 1 Tf 11.6468 0 TD [(1997;)-334.9(155:)-335.5(1260\2611266.)]TJ -14.1633 -1.1065 TD [(49.)-1266.5(Berman)-225.3(AR,)-218.5(Liu)-225.7(MC,)-222.3(W)70.8(agner)-225.6(EM,)-221(Proud)-224.6(D.)-220.7(Dissociation)]TJ 2.5165 -1.1192 TD [(of)-392(bradykin-induced)-396.2(plasma)-394(exudation)-391.7(and)-396.6(reactivity)-396.7(in)]TJ 0 -1.1128 TD [(the)-259.9(peripheral)-266.5(airways.)]TJ /F4 1 Tf 9.3136 0 TD [(Am)-265(J)-264.8(Respir)-264.2(Crit)-261.6(Car)27.2(e)-264.8(Med)]TJ /F8 1 Tf 11.2358 0 TD (1996;)Tj -20.5495 -1.1192 TD [(154:)-329.1(418\261423.)]TJ -2.5165 -1.1128 TD [(50.)-1266.5(Y)98.4(anai)-347.7(M,)-350.8(Sekizawa)-347(K,)-347.1(Ohrui)-345.5(T)72.9(,)-350.7(Sasaki)-346.4(H,)-347.1(T)66.6(akishima)-351.1(T)72.9(.)]TJ 2.5165 -1.1128 TD [(Site)-412.1(of)-410.9(airway)-414.1(obstruction)-420.8(in)-412.4(pulmonary)-411.4(disease:)-419.7(direct)]TJ 0 -1.1192 TD [(measurement)-393.8(of)-398.3(intrabronchial)-395.6(pressure.)]TJ /F4 1 Tf 16.7494 0 TD [(J)-391.3(Appl)-395.9(Physiol)]TJ /F8 1 Tf -16.7494 -1.1128 TD [(1992;)-328.6(72:)-336(1016\2611023.)]TJ -2.5165 -1.1128 TD [(51.)-1266.5(Froeb)-319.2(HF)75(,)-319.1(Mead)-320.7(J.)-319.7(Relative)-323.3(hysteresis)-326.2(of)-316.1(the)-323.1(dead)-320(space)]TJ 2.5165 -1.1192 TD [(and)-327(lung)]TJ /F4 1 Tf 3.8696 0 TD [(in)-336.5(vivo)]TJ /F8 1 Tf 2.7505 0 TD 0 Tw (.)Tj /F4 1 Tf 0.5817 0 TD [(J)-334.4(Appl)-332.6(Physiol)]TJ /F8 1 Tf 6.2787 0 TD [(1968;)-334.9(25:)-336(244\261248.)]TJ -15.997 -1.1065 TD [(52.)-1266.5(Sasaki)-295.8(H,)-296.6(Hoppin)-293.5(FG)-298.1(Jr)49.4(.)-293.8(Hysteresis)-297.9(of)-297.1(contracted)-303.2(airway)]TJ 2.5165 -1.1192 TD [(smooth)-331.2(muscle.)]TJ /F4 1 Tf 6.6391 0 TD [(J)-334.4(Appl)-332.6(Physiol)]TJ /F8 1 Tf 6.2787 0 TD [(1979;)-334.9(47:)-336(1251\2611262.)]TJ -15.4342 -1.1065 TD [(53.)-1266.5(Pichurko)-320.1(BM,)-317.1(Ingram)-316.7(RH)-323.2(Jr)49.4(.)-319.1(Effec)10.2(ts)-318.7(of)-322.4(airway)-319.3(tone)-316.3(and)]TJ 2.5165 -1.1192 TD [(volume)-310.8(history)-313.2(on)-315.1(maximal)-314.3(expiratory)-317.3(flow)-314.4(in)-311.2(asthma.)]TJ /F4 1 Tf 22.3768 0 TD (J)Tj -22.3768 -1.1192 TD [(Appl)-332.6(Physiol)]TJ /F8 1 Tf 5.5073 0 TD [(1987;)-334.9(62:)-329.6(1)32.1(133\2611)27.8(140.)]TJ -8.0238 -1.1065 TD [(54.)-1266.5(Lim)-139(TK,)-141.4(Pride)-144.6(NB,)-142.7(Ingram)-146(RH)-139.8(Jr)49.4(.)-142(Effects)-137.8(of)-139.1(volume)-146.4(history)]TJ 2.5165 -1.1192 TD [(during)-297.5(spontaneous)-302.2(and)-295.4(acutely)-304(induced)-295.5(airflow)-303.4(obstruc-)]TJ 0 -1.1128 TD [(tion)-318.9(in)-323.9(asthma.)]TJ /F4 1 Tf 6.3292 0 TD [(Am)-321.9(Rev)-324(Respir)-327.4(Dis)]TJ /F8 1 Tf 8.0491 0 TD [(1987;)-328.6(135:)-322.8(591\261596.)]TJ -16.8948 -1.1128 TD [(55.)-1266.5(Pliss)-445.8(LB,)-452.7(Ingenito)-450.4(EP)100.1(,)-445.5(Ingram)-455.8(RH)-449.6(Jr)49.4(.)-445.5(Responsiveness,)]TJ 2.5165 -1.1192 TD [(inflammation,)-314.1(and)-314.4(effects)-311.1(of)-316.1(deep)-313.7(breaths)-316.7(on)-315.1(obstruction)]TJ 0 -1.1128 TD [(in)-330.2(mild)-333.4(asthma.)]TJ /F4 1 Tf 6.6327 0 TD [(J)-328.1(Appl)-338.9(Physiol)]TJ /F8 1 Tf 6.2786 0 TD [(1989;)-328.6(66:)-336(2298\2612304.)]TJ -15.4279 -1.1128 TD [(56.)-1266.5(Fredberg)-413.3(JJ.)-421.6(Airway)-430.3(smooth)-426(muscle)-425.6(in)-425(asthma:)-427.4(flirting)]TJ 2.5165 -1.1128 TD [(with)-334.8(disaster)53.3(.)]TJ /F4 1 Tf 5.6337 0 TD [(Eur)-331.9(Respir)-333.8(J)]TJ /F8 1 Tf 5.5073 0 TD [(1998;)-328.6(12:)-336(1252\2611256.)]TJ -13.6575 -1.1128 TD [(57.)-1266.5(Fredberg)-299.5(JJ,)-307.8(Inouye)-313.8(DS,)-307.3(Mijailovich)-316.4(SM,)-311(Butler)-310.7(JP)102.4(.)-312.7(Per-)]TJ 2.5165 -1.1192 TD [(turbed)-354.2(equilibrium)-360.6(of)-360.4(myosin)-356.5(binding)-361.6(in)-355.5(airway)-363.5(smooth)]TJ 0 -1.1128 TD [(muscle)-210.6(and)-206.9(its)-206.8(implications)-217.1(in)-210(bronchospasm.)]TJ /F4 1 Tf 18.0582 0 TD [(Am)-208.1(J)-207.9(Respir)]TJ -18.0582 -1.1191 TD [(Crit)-331.1(Car)27.2(e)-334.4(Med)]TJ /F8 1 Tf 6.3103 0 TD [(1999;)-328.6(159:)-335.5(959\261967.)]TJ -8.8268 -1.1065 TD [(58.)-1266.5(Fredberg)-381.7(JJ,)-390(Inouye)-389.7(D,)-391.4(Miller)-391.2(B,)]TJ /F4 1 Tf 16.5407 0 TD [(et)-393.2(al)]TJ /F8 1 Tf 1.8653 0 TD [(.)-394.9(Airway)-392.4(smooth)]TJ -15.8895 -1.1192 TD [(muscle,)-295.7(tidal)-301.6(stretches,)-302.9(and)-295.4(dynamically)-299.9(determined)-299(con-)]TJ T* [(tractile)-442(states.)]TJ /F4 1 Tf 6.0321 0 TD [(Am)-442.1(J)-441.9(Respir)-441.3(Crit)-444.9(Car)27.2(e)-441.9(Med)]TJ /F8 1 Tf 12.3044 0 TD [(1997;)-442.4(156:)]TJ -18.3364 -1.1128 TD (1752\2611759.)Tj -2.5165 -1.1128 TD [(59.)-1266.5(Fish)-246.7(JE,)-246.8(Ankin)-249.7(Mg,)-249.2(Kelly)-251.9(JF)70.8(,)-249.5(Peterman)-252(VI.)-252.7(Regulation)-252.9(of)]TJ 2.5165 -1.1128 TD [(bronchomotor)-480.4(tone)-487(by)-485.9(lung)-480.9(inflation)-492.6(in)-481.9(asthmatic)-485.5(and)]TJ 0 -1.1192 TD [(nonasthmatic)-521.9(subjects.)]TJ /F4 1 Tf 9.7626 0 TD [(J)-517.8(Appl)-528.6(Phyiol:)-523.9(Respir)-523.4(Envir)27.3(on)]TJ -9.7626 -1.1128 TD [(Exer)35.7(cise)-336.2(Physiol)]TJ /F8 1 Tf 6.9931 0 TD [(1981;)-334.9(50:)-336(1079\2611086.)]TJ -9.5097 -1.1128 TD [(60.)-1266.5(W)77.1(oolcock)-238.6(AJ,)-234(Salome)-233.3(CM,)-241.2(Y)98.4(a)0(n)-239(K)0(.)-233.3(The)-235.7(slope)-234.8(of)-233.9(the)-234.6(dose-)]TJ 30.5144 73.5671 TD [(response)-258.1(curve)-257.2(to)-254.3(histamine)-258.1(in)-254.3(asthmatic)-264.2(and)-251.2(normal)-261.2(sub-)]TJ 0 -1.1191 TD (jects.)Tj /F4 1 Tf 2.3837 0 TD [(Am)-334.6(Rev)-330.3(Respir)-340.1(Dis)]TJ /F8 1 Tf 8.0933 0 TD [(1984;)-328.6(130:)-335.5(71\26175.)]TJ -12.9936 -1.1065 TD [(61.)-1266.5(Skloot)-506.1(G,)-505.2(Permutt)-508.2(S,)-500.5(T)60.2(ogias)-506.6(A.)-505.2(Airway)-506.2(hyperrespon-)]TJ 2.5165 -1.1192 TD [(siveness)-323.9(in)-330.2(asthma:)-326.3(a)-321.8(problem)-330.2(of)-322.4(limited)-330.1(smooth)-324.9(muscle)]TJ 0 -1.1128 TD [(relaxation)-267.9(with)-258.9(inspiration.)]TJ /F4 1 Tf 10.9702 0 TD [(J)-264.8(Clin)-260.4(Invest)]TJ /F8 1 Tf 5.286 0 TD [(1995;)-259.1(96:)-266.4(2393\261)]TJ -16.2562 -1.1192 TD (2403.)Tj -2.5165 -1.1128 TD [(62.)-1266.5(Jef)12.2(fery)-391.7(PK.)-395.8(Comparative)-391.7(morphology)-392.1(of)-392(the)-392.7(airways)-389.5(in)]TJ 2.5165 -1.1128 TD [(asthma)-292.8(and)-295.4(chronic)-296.5(obstructive)-294.1(pulmonary)-297.6(disease.)]TJ /F4 1 Tf 20.7644 0 TD [(Am)-296.6(J)]TJ -20.7644 -1.1192 TD [(Respir)-333.8(Crit)-337.4(Car)33.6(e)-334.4(Med)]TJ /F8 1 Tf 9.2251 0 TD [(1994;)-334.9(150:)-335.5(S6\261S13.)]TJ -11.7416 -1.1065 TD [(63.)-1266.5(Lambert)-289.2(RK,)-281.8(W)26.5(iggs)-286.1(BR,)-283.2(Kuwano)-287.8(K,)-283.9(Hogg)-285.8(JC,)-286(Pare)-287.9(PD.)]TJ 2.5165 -1.1192 TD [(Functional)-278.4(significance)-286.8(of)-278.2(increased)-277.3(airway)-281.3(smooth)-280.6(mus-)]TJ 0 -1.1128 TD [(cle)-247(in)-241.7(asthma)-248.5(and)-244.9(COPD.)]TJ /F4 1 Tf 10.2811 0 TD [(J)-239.6(Appl)-250.4(Physiol)]TJ /F8 1 Tf 6.0131 0 TD [(1993;)-240.1(74:)-247.5(2771\261)]TJ -16.2941 -1.1192 TD (2781.)Tj -2.5165 -1.1128 TD [(64.)-1266.5(James)-311.1(AL,)-318.5(Pare)-313.2(PD,)-313.6(Hogg)-311.1(JC.)-311.3(The)-317.9(mechanics)-316.1(of)-309.8(airway)]TJ 2.5165 -1.1128 TD [(narrowing)-236.7(in)-241.7(asthma.)]TJ /F4 1 Tf 8.6055 0 TD [(Am)-233.4(Rev)-235.5(Respir)-238.9(Dis)]TJ /F8 1 Tf 7.7013 0 TD [(1989;)-233.8(139:)-240.6(242\261)]TJ -16.3068 -1.1192 TD (246.)Tj -2.5165 -1.1065 TD [(65.)-1266.5(Brown)-272(RH,)-269.1(Zerhouni)-274.4(EA,)-274.2(Mitzner)-274.3(W)83.4(.)-268.5(Airway)-278.5(edema)-270.5(po-)]TJ 2.5165 -1.1192 TD [(tentiates)-587.2(airway)-578.5(readtivity)58.3(.)]TJ /F4 1 Tf 11.6784 0 TD [(J)-581(Appl)-579.2(Physiol)]TJ /F8 1 Tf 7.0184 0 TD [(1995;)-581.5(79:)]TJ -18.6968 -1.1128 TD (1242\2611248.)Tj -2.5165 -1.1128 TD [(66.)-1266.5(Bramley)-448.5(AM,)-448.5(Thomson)-445.6(RJ,)-450.4(Roberts)-448.1(CR,)-447.6(Schellenber)8.5(g)]TJ 2.5165 -1.1192 TD [(RR.)-245.3(Hypothesis:)-240.9(excessive)-245.9(bronchoconstriction)-248.9(in)-241.6(asthma)]TJ 0 -1.1128 TD [(is)-306.1(due)-301.8(to)-304.9(decreased)-306.3(airway)-306.6(elastance.)]TJ /F4 1 Tf 15.1307 0 TD [(Eur)-300.3(Respir)-308.5(J)]TJ /F8 1 Tf 5.4187 0 TD (1994;)Tj -20.5495 -1.1192 TD [(7:)-330.2(337\261341.)]TJ -2.5165 -1.1065 TD [(67.)-1266.5(Bai)-321.5(TR.)-326.2(Abnormalities)-325.9(in)-323.9(airway)-325.6(smooth)-318.5(muscle)-324.4(in)-323.9(fatal)]TJ 2.5165 -1.1192 TD [(asthma:)-269.4(a)-271.2(comparison)-272.7(between)-273.3(trachea)-270.8(and)-270.1(bronchus.)]TJ /F4 1 Tf 21.4979 0 TD (Am)Tj -21.4979 -1.1128 TD [(Rev)-330.3(Respir)-340.1(Dis)]TJ /F8 1 Tf 6.4367 0 TD [(1991;)-328.6(143:)-335.5(441\261443.)]TJ -8.9532 -1.1128 TD [(68.)-1266.5(Fan)-243.4(T)72.9(,)-249.5(Y)92(ang)-244.9(M,)-249.7(Halayko)-248.2(A,)-246(Mohapatra)-251.7(SS,)-245.6(Stephens)-244.2(NL.)]TJ 2.5165 -1.1192 TD [(Airway)-449.3(responsiveness)-449.2(in)-450.3(two)-446.8(inbred)-449(strains)-446.9(of)-448.9(mouse)]TJ 0 -1.1128 TD [(disparate)-374.7(in)-368.1(IgE)-376(and)-365(IL-4)-376.4(production.)]TJ /F4 1 Tf 15.7188 0 TD [(Am)-372.5(J)-372.3(Respir)-371.7(Cell)]TJ -15.7188 -1.1192 TD [(Molec)-335(Biol)]TJ /F8 1 Tf 4.7801 0 TD [(1997;)-334.9(17:)-329.7(156\261163.)]TJ -7.2966 -1.1065 TD [(69.)-1266.5(Kamm)-333.6(KE,)-331.1(Stull)-332(JT)72.2(.)-331.7(Myosin)-330(phosphorylation,)-333.1(force)-334.1(and)]TJ 2.5165 -1.1192 TD [(maximal)-263.7(shortening)-267.2(velocity)-261.9(in)-266.9(neurally)-266.8(stimulated)-266.3(trach-)]TJ T* [(eal)-234.4(smooth)-230(muscle.)]TJ /F4 1 Tf 7.8151 0 TD [(Am)-233.4(J)-226.9(Physiol)]TJ /F8 1 Tf 5.4187 0 TD [(1985;)-233.8(249:)-228(C238\261C247.)]TJ -15.7504 -1.1065 TD [(70.)-1266.5(Macklem)-215.7(PT)74.8(.)-217.9(A)-211.5(theoretical)-218.9(analysis)-217.6(of)-214.9(the)-215.6(effect)-209.2(of)-214.9(airway)]TJ 2.5165 -1.1192 TD [(smooth)-381.8(muscle)-381.3(load)-379.5(on)-378.4(airway)-382.5(narrowing.)]TJ /F4 1 Tf 17.7168 0 TD [(Am)-378.8(J)-385(Respir)]TJ -17.7168 -1.1128 TD [(Crit)-337.4(Car)33.6(e)-334.4(Med)]TJ /F8 1 Tf 6.3103 0 TD [(1996;)-334.9(153:)-329.1(83\26189.)]TJ -8.8268 -1.1128 TD [(71.)-1266.5(Moreno)-289.2(R,)-285.3(Hogg)-292.1(JC,)-286(Pare)-294.2(PD.)-288.3(Mechanics)-289.6(of)-290.8(airway)-287.7(nar-)]TJ 2.5165 -1.1192 TD (rowing.)Tj /F4 1 Tf 3.3954 0 TD [(Am)-334.6(Rev)-330.3(Respir)-333.8(Dis)]TJ /F8 1 Tf 8.087 0 TD [(1986;)-334.9(1986:)-335(1)32.1(171\2611)34.2(180.)]TJ -13.9989 -1.1065 TD [(72.)-1266.5(Macklem)-361.1(PT)74.8(.)-363.3(The)-355.8(mechanics)-366.7(of)-360.4(breathing.)]TJ /F4 1 Tf 20.2713 0 TD [(Am)-366.2(J)-359.7(Respir)]TJ -17.7547 -1.1192 TD [(Crit)-337.4(Car)33.6(e)-334.4(Med)]TJ /F8 1 Tf 6.3103 0 TD [(1998;)-334.9(157:)-329.1(S88\261S94.)]TJ -8.8268 -1.1128 TD [(73.)-1266.5(Gunst)-510.2(SJ,)-507.5(W)70.8(arner)-504.8(DO,)-514.3(W)32.8(ilson)-509.3(T)72.9(A)0(,)-511.5(Hyatt)-504.8(RE.)-509.6(Paren-)]TJ 2.5165 -1.1128 TD [(chymal)-386.4(interdependence)-388.7(and)-390.3(airway)-382.5(response)-390.8(to)-387.1(metha-)]TJ 0 -1.1192 TD [(choline)-392.8(in)-387.1(excised)-391.4(dog)-390.5(lobes.)]TJ /F4 1 Tf 12.4435 0 TD [(J)-391.3(Appl)-389.5(Physiol)]TJ /F8 1 Tf 6.443 0 TD [(1988;)-391.8(65:)]TJ -18.8865 -1.1128 TD (2490\2612497.)Tj -2.5165 -1.1128 TD [(74.)-1266.5(Crimi)-509.3(E,)-499.1(Spanevello)-509.7(A,)-498.9(Neri)-510.2(M,)-502.6(Ind)-505.3(PW)85.3(,)-502.4(Rossi)-506.4(GA,)]TJ 2.5165 -1.1128 TD [(Brusasco)-420.8(V)123.6(.)-413.9(Dissociation)-419.6(between)-418.7(airway)-420.5(inflammation)]TJ 0 -1.1191 TD [(and)-282.8(airway)-281.3(hyperresponsiveness)-289.3(in)-279.6(aller)9.9(gic)-285.2(asthma.)]TJ /F4 1 Tf 20.7771 0 TD [(Am)-284(J)]TJ -20.7771 -1.1128 TD [(Respir)-333.8(Crit)-337.4(Car)33.6(e)-334.4(Med)]TJ /F8 1 Tf 9.2251 0 TD [(1998;)-334.9(157:)-335.5(4\2619.)]TJ -11.7416 -1.1128 TD [(75.)-1266.5(Sekizawa)-258.5(K,)-264.9(Y)92(anai)-259.1(M,)-256(Shimizu)-267(Y)130(,)-262.2(Saske)-262.3(H,)-258.6(T)60.2(akishima)-262.5(T)72.9(.)]TJ 2.5165 -1.1192 TD [(Serial)-323.3(distribution)-330.4(of)-322.4(bronchoconstriction)-331.1(in)-323.9(normal)-324.4(sub-)]TJ 0 -1.1128 TD (jects.)Tj /F4 1 Tf 2.3837 0 TD [(Am)-334.6(Rev)-330.3(Respir)-340.1(Dis)]TJ /F8 1 Tf 8.0933 0 TD [(1988;)-328.6(137:)-335.5(1312\2611316.)]TJ -12.9936 -1.1128 TD [(76.)-1266.5(White)-241.5(JP)102.4(,)-243.2(Mills)-240.4(J,)-243.9(Eiser)-245.5(NM.)-239.8(Comparison)-246.1(of)-246.5(the)-240.9(effects)-235.2(of)]TJ 2.5165 -1.1128 TD [(histamine,)-482.3(H1-)-477(and)-472.5(H2-receptor)-482.8(agonists)-477.1(on)-479.5(lar)11(ge)-479.3(and)]TJ 0 -1.1192 TD [(small)-498.2(airways)-503.3(in)-500.9(normal)-501.4(and)-497.8(asthmatic)-504.5(subjects)-502.1(\(pub-)]TJ 0 -1.1128 TD [(lished)-243(erratum)-248.8(appears)-244.5(in)]TJ /F4 1 Tf 10.1862 0 TD [(Br)-243.9(J)-245.9(Dis)-245.6(Chest)]TJ /F8 1 Tf 6.0321 0 TD [(1987;)-246.4(81:)-241.1(3201\).)]TJ /F4 1 Tf -16.2183 -1.1192 TD [(Br)-332.5(J)-334.4(Dis)-334.1(Chest)]TJ /F8 1 Tf 6.3925 0 TD [(1987;)-334.9(81:)-329.7(155\261169.)]TJ -8.909 -1.1128 TD [(77.)-1266.5(Antic)-226.6(R,)-222.1(Macklem)-228.3(PT)68.5(.)-224.2(The)-223(influence)-228.1(of)-227.6(clinical)-226.1(factors)-229.1(on)]TJ 2.5165 -1.1128 TD [(site)-326.2(of)-322.4(airway)-325.6(obstruction)-325.9(in)-323.9(asthma.)]TJ /F4 1 Tf 15.0928 0 TD [(Am)-321.9(Rev)-324(Respir)-327.4(Dis)]TJ /F8 1 Tf -15.0928 -1.1192 TD [(1976;)-334.9(1)32.1(14:)-329.7(851\261859.)]TJ -2.5165 -1.1065 TD [(78.)-1266.5(Sekizawa)-391.3(K,)-385.1(Sasaki)-390.7(H,)-391.4(Shimizu)-387.1(Y)123.6(,)-388.6(T)60.2(akishima)-389(T)72.9(.)-388.6(Dose-)]TJ 2.5165 -1.1191 TD [(response)-365.5(ef)12.9(fects)-368.3(of)-360.4(methacholine)-368.7(in)-361.8(normal)-362.3(and)-365(in)-361.8(asth-)]TJ 0 -1.1128 TD [(matic)-402(subjects.)-403.9(Relationship)-407.2(between)-399.8(the)-405.3(site)-402.1(of)-398.3(airway)]TJ 0 -1.1192 TD [(response)-542.6(and)-542(overall)-545.5(airway)-546.9(hyperresponsiveness.)]TJ /F4 1 Tf 21.4979 0 TD (Am)Tj -21.4979 -1.1128 TD [(Rev)-330.3(Respir)-340.1(Dis)]TJ /F8 1 Tf 6.4367 0 TD [(1986;)-328.6(133:)-335.5(593\261599.)]TJ -8.9532 -1.1128 TD [(79.)-1266.5(Langley)-318(F)71.5(,)-319.1(Even)-323.7(P)109.4(,)-319.1(Duroux)-323.7(P)103.1(,)-319.1(Nicolas)-321.4(RL,)-319.9(Cumming)-323.4(G.)]TJ 2.5165 -1.1192 TD [(V)104.7(entilatory)-371.7(consequences)-368.2(of)-366.7(unilateral)-371.4(pulmonary)-373.5(artery)]TJ 0 -1.1128 TD (occlusion.)Tj /F4 1 Tf 4.3818 0 TD (Inserm)Tj /F8 1 Tf 3.0856 0 TD [(1975;)-334.9(51:)-329.7(209\261212.)]TJ -37.9817 76.3934 TD (1416)Tj 7.472 0 0 7.472 279.723 797.499 Tm 0.0001 Tc [(M.)-329.2(KRAFT)]TJ ET endstream endobj 94 0 obj << /ProcSet [/PDF /Text ] /Font << /F4 7 0 R /F8 11 0 R >> /ExtGState << /GS2 12 0 R >> >> endobj 96 0 obj << /Length 18452 >> stream BT /F8 1 Tf 8.966 0 0 8.966 58.28 772.157 Tm 0 g /GS2 gs 0 Tc [(80.)-1266.5(Kraft)-219.8(M,)-218.1(Djukanovic)-223.8(R,)-215.8(W)26.5(ilson)-218.4(S,)-216(Holgate)-225.3(ST)74.8(,)-217.9(Martin)-224.4(RJ.)]TJ 2.5165 -1.1191 TD [(Alveolar)-257.4(tissue)-256.8(inflammation)-254.3(in)-254.3(asthma.)]TJ /F4 1 Tf 16.1171 0 TD [(Am)-258.7(J)-252.2(Respir)-257.9(Crit)]TJ -16.1171 -1.1128 TD [(Car)33.6(e)-334.4(Med)]TJ /F8 1 Tf 4.3818 0 TD [(1996;)-334.9(154:)-329.1(1505\2611510.)]TJ -6.8983 -1.1128 TD [(81.)-1266.5(W)77.1(enzel)-397.5(SE,)-396(Szefler)-397(SJ,)-393.7(Leung)-399.1(DY)127.2(,)-394.9(Sloan)-396.5(SI,)-393.5(Rex)-395(MD,)]TJ 2.5165 -1.1128 TD [(Martin)-395.2(RJ.)-393.5(Bronchoscopic)-394(evaluation)-393.4(of)-392(severe)-396.8(asthma.)]TJ 0 -1.1192 TD [(Persistent)-288(inflammation)-292.2(associated)-292(with)-284.2(high)-291.2(dose)-283.5(gluco-)]TJ 0 -1.1128 TD (corticoids.)Tj /F4 1 Tf 4.4703 0 TD [(Am)-334.6(J)-334.4(Respir)-327.4(Crit)-337.4(Car)33.6(e)-334.4(Med)]TJ /F8 1 Tf 11.6468 0 TD [(1997;)-328.6(156:)-329.1(737\261)]TJ -16.1171 -1.1192 TD (743.)Tj -2.5165 -1.1128 TD [(82.)-1266.5(Kraft)-219.8(M,)-218.1(Djukanovic)-223.8(R,)-215.8(W)26.5(ilson)-218.4(S,)-216(Holgate)-225.3(ST)74.8(,)-217.9(Martin)-224.4(RJ.)]TJ 2.5165 -1.1128 TD [(L)53.9(ymphocyte)-309(and)-314.4(eosinophil)-312.8(influx)-312.5(into)-312.6(alveolar)-317.1(tissue)-313.7(in)]TJ 0 -1.1192 TD [(nocturnal)-259.9(asthma.)]TJ /F4 1 Tf 7.3093 0 TD [(Am)-258.7(J)-258.5(Respir)-257.9(Crit)-261.6(Car)27.2(e)-258.5(Med)]TJ /F8 1 Tf 11.2105 0 TD [(1999;)-259.1(159:)]TJ -18.5198 -1.1128 TD (228\261234.)Tj -2.5165 -1.1128 TD [(83.)-1266.5(Kuwano)-389(K,)-397.7(Bosken)-394.6(CH,)-395.6(Pare)-395.4(PD,)-389.5(Bai)-397.4(TR,)-395.8(W)32.8(iggs)-393.6(BR,)]TJ 2.5165 -1.1128 TD [(Hogg)-450.2(JC.)-456.7(Small)-451.4(airways)-459.1(dimensions)-452.6(in)-456.6(asthma)-457.2(and)-453.5(in)]TJ 0 -1.1192 TD [(chronic)-441.9(obstructive)-452.2(pulmonary)-443(disease.)]TJ /F4 1 Tf 16.5407 0 TD [(Am)-448.4(Rev)-444.1(Respir)]TJ -16.5407 -1.1128 TD (Dis)Tj /F8 1 Tf 1.7072 0 TD [(1993;)-328.6(148:)-335.5(1220\2611225.)]TJ -4.2237 -1.1128 TD [(84.)-1266.5(Carroll)-311.1(N,)-309.2(Elliot)-313.5(J,)-307.1(Morton)-310.8(A,)-309.2(James)-317.4(A.)-309.2(The)-305.2(structure)-319(of)]TJ 2.5165 -1.1191 TD [(lar)11(ge)-295.9(and)-295.4(small)-295.9(airways)-301(in)-292.2(nonfatal)-298.4(and)-295.4(fatal)-299.9(asthma.)]TJ /F4 1 Tf 21.4979 0 TD (Am)Tj -21.4979 -1.1128 TD [(Rev)-330.3(Respir)-333.8(Dis)]TJ /F8 1 Tf 6.4304 0 TD [(1993;)-334.9(147:)-335.5(405\261410.)]TJ -8.9469 -1.1128 TD [(85.)-1266.5(Carroll)-279.5(NG,)-280.4(Cooke)-280.1(C,)-285.3(James)-279.5(AL.)-280.6(Bronchial)-283.6(blood)-284.4(vessel)]TJ 2.5165 -1.1128 TD [(dimensions)-281.9(in)-285.9(asthma.)]TJ /F4 1 Tf 9.1872 0 TD [(Am)-290.3(J)-283.8(Respir)-283.2(Crit)-286.8(Car)33.6(e)-283.8(Med)]TJ /F8 1 Tf 11.3623 0 TD (1997;)Tj -20.5495 -1.1192 TD [(155:)-329.1(689\261695.)]TJ -2.5165 -1.1128 TD [(86.)-1266.5(Macklem)-222(PT)74.8(.)-224.2(Bronchial)-226.7(hyporesponsiveness.)]TJ /F4 1 Tf 20.5811 0 TD (Chest)Tj /F8 1 Tf 2.4849 0 TD (1987;)Tj -20.5495 -1.1128 TD [(91:)-329.6(189S\261191S.)]TJ -2.5165 -1.1128 TD [(87.)-1266.5(W)32.8(iggs)-317.7(BR,)-321.1(Moreno)-314.5(R,)-323.3(Hogg)-317.4(JC,)-317.6(Hilliam)-320.8(C,)-316.9(Pare)-319.5(PD.)-319.9(A)]TJ 2.5165 -1.1128 TD [(model)-494.7(of)-499.5(the)-500.1(mechanics)-505.8(of)-499.5(airway)-502.6(narrowing.)]TJ /F4 1 Tf 20.0057 0 TD [(J)-498.8(Appl)]TJ -20.0057 -1.1191 TD (Physiol)Tj /F8 1 Tf 3.3006 0 TD [(1990;)-328.6(69:)-336(849\261860.)]TJ -5.8171 -1.1128 TD [(88.)-1266.5(W)32.8(iggs)-311.4(BR,)-314.8(Hrousis)-321.6(CA,)-313.4(Drazen)-316.7(JM,)-313.6(Kamm)-314.6(RD.)-313.4(On)-318.4(the)]TJ 2.5165 -1.1128 TD [(mechanism)-362.5(of)-360.4(mucosal)-368.1(folding)-362.6(in)-361.8(normal)-362.3(and)-365(asthmatic)]TJ 0 -1.1192 TD (airways.)Tj /F4 1 Tf 3.6546 0 TD [(J)-328.1(Appl)-338.9(Physiol)]TJ /F8 1 Tf 6.2787 0 TD [(1997;)-328.6(83:)-336(1814\2611821.)]TJ -12.4498 -1.1065 TD [(89.)-1266.5(Carroll)-228.9(N,)-227(Carello)-227.7(S,)-222.3(Cooke)-229.6(C,)-228.4(James)-222.6(A.)-227(Airway)-228(structure)]TJ 2.5165 -1.1192 TD [(and)-447.2(inflammatory)-455.2(cells)-451.9(in)-450.3(fatal)-451.7(attacks)-450.6(of)-448.9(asthma.)]TJ /F4 1 Tf 21.3272 0 TD (Eur)Tj -21.3272 -1.1192 TD [(Respir)-333.8(J)]TJ /F8 1 Tf 3.6863 0 TD [(1996;)-328.6(9:)-336.5(709\261715.)]TJ -6.2028 -1.1065 TD [(90.)-1266.5(Carroll)-260.5(N,)-252.3(Cooke)-261.2(C,)-260(James)-254.2(A.)-258.6(The)-261(distribution)-260.9(of)-252.9(eosino-)]TJ 2.5165 -1.1192 TD 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[(asthmatics)-416.6(investigated)-414.9(by)-410(bronchoalveolar)-421.8(lavage.)-412.5(The)]TJ 0 -1.1192 TD [(ef)12.9(fects)-551.6(of)-556.4(antiasthmatic)-551.2(treatment)-561.1(with)-549.8(budesonide)-554.4(or)]TJ 0 -1.1128 TD (terbutaline.)Tj /F4 1 Tf 4.7991 0 TD [(Am)-334.6(Rev)-330.3(Respir)-333.8(Dis)]TJ /F8 1 Tf 8.087 0 TD [(1990;)-334.9(142:)-335.5(91\26199.)]TJ -15.4026 -1.1128 TD [(99.)-1266.5(Kelly)-308.8(CA,)-313.4(Kotre)-313.7(CJ,)-311.3(W)77.1(ard)-315.4(C,)-310.6(Hendrick)-311.9(DJ,)-309.9(W)70.8(alters)-313.2(EH.)]TJ 30.5144 73.5671 TD [(Anatomical)-392.2(distribution)-393.7(of)-385.7(bronchoalveolar)-390.1(lavage)-390.7(fluid)]TJ 0 -1.1191 TD [(as)-480.5(assessed)-480.6(by)-479.5(digital)-480(subtraction)-483.8(radiography)58.7(.)]TJ /F4 1 Tf 19.9425 0 TD (Thorax)Tj /F8 1 Tf -19.9425 -1.1128 TD [(1987;)-334.9(42:)-329.6(624\261628.)]TJ -2.5165 -1.1128 TD [(100.)-766.4(Aas)-483.3(K.)-486.2(Heterogeneity)-484.4(of)-486.8(bronchial)-481.2(asthma.)-485.4(Sub-popu-)]TJ 2.5165 -1.1128 TD [(lations)-225.9(or)-227.6(diff)10.4(erent)-228(stages)-228.9(of)-221.3(the)-228.3(disease.)]TJ /F4 1 Tf 15.9527 0 TD [(Aller)24.9(gy)]TJ /F8 1 Tf 3.0982 0 TD [(1981;)-227.5(36:)]TJ -19.0509 -1.1192 TD (3\26114.)Tj -2.5165 -1.1065 TD [(101.)-766.4(Newman)-555(KB,)-560(L)53.9(ynch)-554.2(DA,)-558.6(Newman)-555(LS,)-554(Ellegood)-560.4(D,)]TJ 2.5165 -1.1192 TD [(Newell)-273.4(JD)-269.1(Jr)49.4(.)-268.5(Quantitative)-274(computed)-271.6(tomography)-271.8(detects)]TJ 0 -1.1128 TD [(air)-336.7(trapping)-330.2(due)-333.4(to)-336.5(asthma.)]TJ /F4 1 Tf 11.2548 0 TD (Chest)Tj /F8 1 Tf 2.5924 0 TD [(1994;)-334.9(106:)-335.5(105\261109.)]TJ -16.3637 -1.1128 TD [(102.)-766.4(Kinsella)-291.6(M,)-287.6(Muller)-294(NL,)-293.2(Staples)-291.4(C,)-285.3(V)98.4(edal)-290.7(S,)-285.5(Chan-Y)89.1(eung)]TJ 2.5165 -1.1192 TD [(M.)-471(Hyperinflation)-481.4(in)-475.6(asthma)-476.2(and)-472.5(emphysema.)-476.8(Assess-)]TJ 0 -1.1128 TD [(ment)-343.4(by)-340.4(pulmonary)-341.8(function)-342.9(testing)-346(and)-339.7(computed)-341.2(tom-)]TJ T* [(ography)59.7(.)]TJ /F4 1 Tf 3.7811 0 TD (Chest)Tj /F8 1 Tf 2.5924 0 TD [(1988;)-334.9(94:)-329.7(286\261289.)]TJ -8.89 -1.1128 TD [(103.)-766.4(Kondoh)-291.1(Y)123.6(,)-293.8(T)66.6(aniguchi)-297.4(H,)-290.2(Y)92(okoyama)-288.7(S,)-291.8(T)60.2(aki)-291.5(F)71.5(,)-293.8(T)66.6(akagi)-296.6(K,)]TJ 2.5165 -1.1191 TD [(Satake)-389.3(T)72.9(.)-388.6(Emphysematous)-390.6(change)-388.3(in)-393.4(chronic)-391.3(asthma)-387.6(in)]TJ 0 -1.1128 TD [(relation)-401.9(to)-399.7(cigarette)-401(smoking.)-396.8(Assessment)-405.1(by)-397.3(computed)]TJ 0 -1.1192 TD [(tomography)63.3(.)]TJ /F4 1 Tf 5.3239 0 TD (Chest)Tj /F8 1 Tf 2.5924 0 TD [(1990;)-328.6(97:)-336(845\261849.)]TJ -10.4328 -1.1065 TD [(104.)-766.4(Carr)-276.3(DH,)-274(Hibon)-275(S,)-272.9(Rubens)-274.5(M,)-275(Chung)-267.7(KF)68.7(.)-274.8(Peripheral)-277.7(air)11(-)]TJ 2.5165 -1.1191 TD [(ways)-343.7(obstruction)-351.2(on)-346.8(high-resolution)-352.5(computed)-347.5(tomogra-)]TJ 0 -1.1128 TD [(phy)-232.4(in)-241.7(chronic)-239.6(severe)-232.4(asthma.)]TJ /F4 1 Tf 11.9882 0 TD [(Respir)-238.9(Med)]TJ /F8 1 Tf 4.8181 0 TD [(1998;)-233.8(92:)-241.1(448\261)]TJ -16.8063 -1.1192 TD (453.)Tj -2.5165 -1.1065 TD [(105.)-766.4(Paganin)-414.3(F)71.5(,)-407.6(T)28.6(russard)-411.5(V)123.6(,)-413.9(Seneterre)-414.7(E,)]TJ /F4 1 Tf 17.7547 0 TD [(et)-418.5(al)]TJ /F8 1 Tf 1.8906 0 TD [(.)-413.9(Chest)-416.5(radio-)]TJ -17.1288 -1.1191 TD [(graphy)-307.5(and)-308.1(high)-303.9(resolution)-313.8(computed)-309.5(tomography)-303.4(of)-309.8(the)]TJ 0 -1.1128 TD [(lungs)-393.1(in)-393.4(asthma.)]TJ /F4 1 Tf 7.1575 0 TD [(Am)-397.8(Rev)-393.5(Respir)-390.7(Dis)]TJ /F8 1 Tf 8.3336 0 TD [(1992;)-391.8(146:)-398.7(1084\261)]TJ -15.4911 -1.1192 TD (1087.)Tj -2.5165 -1.1128 TD [(106.)-766.4(L)53.9(ynch)-427.7(DA,)-432.1(Newell)-431.5(JD,)-430(T)60.2(schomper)-429.5(BA,)]TJ /F4 1 Tf 19.4999 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