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[(percent)-10.5(age)-367.3(of)-367.3(the)-369.3(airway)-371.8(wall)-370.7(area)-370.1(occupi)-7.8(ed)-366.1(by)-365.7(smoo)-7.4(th)]TJ 0 -1.0641 TD [(musc)-7.8(le)-311.6(in)-305.5(centr)-8.6(al)-311.6(and)-310(perip)-8.2(heral)-310.2(airw)-11.4(ays)-311.2(was)-309.4(2.6)-309.2(and)-315.7(14)]TJ 0 -1.0698 TD [(in)-328.3(adults)-329.6(and)-327.1(2.8)-326.3(and)-327.1(10)-325.9(in)-328.3(children,)-332.3(respec)-8.6(tive)-8.2(ly)64.4(.)-324.7(The)-6.8(se)]TJ 0 -1.0641 TD [(values)-390.2(for)-386.7(centr)-8.6(al)-385.6(airways)-390.8(are)-391.7(similar)-388.7(to)-390.9(those)-389.1(found)-386.7(in)]TJ 0 -1.0698 TD [(other)-338.2(studies:)-340.4(H)]TJ 6.974 0 0 6.974 122.457 303.874 Tm 0.0001 Tc (ALE)Tj /F4 1 Tf 9.963 0 0 9.963 139.238 303.874 Tm 0 Tc [(et)-328.7(al.)]TJ /F7 1 Tf 2.39 0 TD [([1)25.3(1])-327.5(2.)-6.8(5%,)-328.6(D)]TJ 6.974 0 0 6.974 216.113 303.874 Tm 0.0001 Tc (UNNILL)Tj /F4 1 Tf 9.963 0 0 9.963 245.14 303.874 Tm 0 Tc [(et)-334.4(al.)]TJ /F7 1 Tf 2.3957 0 TD ([12])Tj -21.1518 -1.0641 TD [(4.5%)-386.3(\(range)-389.8(2\2611)26.2(1%\),)-387.9(and)-384(T)]TJ 6.974 0 0 6.974 172.857 293.272 Tm 0.0001 Tc [(AKIZA)64.3(W)107.9(A)]TJ 9.963 0 0 9.963 208.516 293.272 Tm 0 Tc [(and)-384(T)]TJ 6.974 0 0 6.974 232.724 293.272 Tm 0.0001 Tc (HURLBECK)Tj 9.963 0 0 9.963 273.997 293.272 Tm 0 Tc ([6])Tj -21.6525 -1.0698 TD [(2.5%.)-369.6(S)]TJ 6.974 0 0 6.974 90.595 282.614 Tm 0.0001 Tc [(OBONY)99.6(A)]TJ 9.963 0 0 9.963 123.25 282.614 Tm 0 Tc [([13])-364.7(found)-369.6(a)-359.7(sim)-9(ilar)-368.3(trend)-366.7(in)-362.4(relat)-11(ion)-363.2(to)]TJ -6.5214 -1.0641 TD [(airway)-360.4(size)-360.2(even)-356.7(when)-360.2(comparing)-361.9(lobar)-361(with)-358.9(segmental)]TJ 0 -1.0698 TD [(airways.)-345.7(S)]TJ 6.974 0 0 6.974 100.29 261.354 Tm 0.0001 Tc [(AETT)67.1(A)]TJ /F4 1 Tf 9.963 0 0 9.963 125.858 261.354 Tm 0 Tc [(et)-334.4(al.)]TJ /F7 1 Tf 2.4014 0 TD [([14])-342(studied)-341.7(small)-343.4(airways)-345.3(with)-341.8(a)]TJ -9.1845 -1.0641 TD 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[(dividing)-314.8(it)-307.9(by)-303.1(the)-306.7(lengt)-9(h)-302.4(o)-6.5(f)-304(the)-306.7(basem)-9(ent)-306.7(mem)-9(brane)-307.8(\(the)]TJ T* [(perimete)-11.1(r)-332.4(o)0(f)-327.5(the)-329.4(airwa)-12.5(y\))-327.5(since)-332.6(this)-333.4(is)-329.5(indepe)-7.8(ndent)-331(of)-333.2(the)]TJ 0 -1.0641 TD [(degree)-274.8(of)-270.6(airway)-275.1(smooth)-273.1(musc)-7.8(le)-266.1(contr)-8.2(action)-271.9(and)-270.2(lung)-272.9(in-)]TJ 25.1977 51.3117 TD [(flat)-9.8(ion)-238([18,)-243.3(19].)-237.6(Exp)-6.4(ressing)-245.4(the)-238.4(amoun)-7.4(t)-236.5(o)0(f)-242.1(smooth)-244.6(muscle)]TJ 0 -1.0527 TD [(in)-299.8(this)-304.9(way)61.7(,)-302(a)0(s)-299(mean)-302.9(thickness)-305(in)-299.8(relation)-305.9(to)-299.8(airway)-309.2(peri-)]TJ 0 -1.0471 TD [(met)-8.2(er)30.6(,)-330.4(allows)-333.5(a)-325.5(ready)-336.3(compa)-7.8(rison)-333.3(between)-337.2(studies.)-331.9(As)-331(a)]TJ 0 -1.0527 TD 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[(pl)13.2(et)18.4(el)18.5(y)-456(b)0(e)20.8(l)0(o)18.8(w)-454.3(th)13.2(e)-450.7(l)0(e)18.5(v)0(e)15.1(l)-452.7(of)-447(th)18.8(e)-456.4(t)0(r)17.3(a)0(c)20.4(h)0(e)15.1(a)-450.7(\(f)12.4(ig)18.9(.)-449.9(1\).)-458.7(General)]TJ 0 -1.0527 TD [(descri)-10.6(ptions)-260.9(of)-264.9(airway)-263.7(smoo)-7.4(th)-260(muscle)-262.5([1])-261.6(have)-259.9(sugges)-7.4(ted)]TJ 0 -1.0471 TD [(that)-321.2(its)-315.5(orien)-8.2(tation)-319.4(is)-318.1(transverse)-324.1(in)-316.9(the)-318.1(trach)-8.6(ea)-315.3(and)-315.7(that)-321.2(it)]TJ 0 -1.0528 TD [(form)-9.4(s)-252.3(a)-257.2(heli)-8.2(cal)-255.9(or)-247.8(geodesi)-9.7(c)-251.6(p)-6.5(attern)-262.1(around)-257(the)-261.2(centr)-8.6(al)-254.7(and)]TJ T* [(perip)-8.2(heral)-298.8(airw)-11.4(ays.)-294.5(The)-297(a)-6.9(ngle)-296.1(of)-299(orientatio)-13.9(n)-291(may)-301.8(depend)]TJ 0 -1.0471 TD [(upo)-8(n)-217(the)-227(degree)-223.6(of)-225.1(inflation)-228.9(of)-225.1(the)-221.3(lung,)-222.1(being)-228.5(more)-224.4(open-)]TJ 0 -1.0528 TD [(mesh)-7.8(ed)-280.8(at)-283.1(full)-288.2(inflation)-291.5([1],)-284.7(which)-283.7(tends)-286.6(to)-282.7(maxi)-9(mize)-282.5(the)]TJ 0 -1.0471 TD [(ang)-8.4(le)-300.2(of)-299(orien)-8.2(tation.)-308.4(However)24.2(,)-302(there)-304.5(are)-300.6(few)-304.1(qua)-8.4(ntitative)]TJ 0 -1.0528 TD [(studi)-9.8(es.)-350.6(E)]TJ 6.974 0 0 6.974 348.831 373.323 Tm 0.0001 Tc (BINA)Tj /F4 1 Tf 9.963 0 0 9.963 369.241 373.323 Tm 0 Tc [(et)-357.1(al.)]TJ /F7 1 Tf 2.4356 0 TD [([10])-359.1(estimat)-11.9(ed)-349.1(that)-355.3(the)-357.9(angle)-354.1(o)-6.5(f)-349.5(or-)]TJ -8.4505 -1.0471 TD [(ient)-8.2(ation)-248(was)-241.1(smal)-10.2(l,)-242.5(consistent)-251.3(with)-245.1(a)-245.9(circular)-248.6(orien)-8.2(tation,)]TJ 0 -1.0528 TD [(in)-248.6(the)-249.8(centr)-8.6(al)-249(airways)-254.2(and)-247.4(approxi)-9.7(mately)-252.3(30)]TJ /F9 1 Tf 17.3903 0 TD (8)Tj /F7 1 Tf 0.6316 0 TD [(in)-248.6(the)-249.8(mem-)]TJ -18.022 -1.0471 TD [(branous)-270.3(bronchi)-9.7(oles)-268.8(of)-259.2(lungs)-269.2(at)-266.1(full)-265.5(inflati)-11.2(on.)-263.7(In)-264.9(a)-262.9(careful)]TJ 0 -1.0528 TD [(study)-229.3(using)]TJ /F4 1 Tf 4.7687 0 TD [(en)-229.6(face)]TJ /F7 1 Tf 3.0388 0 TD [(sectionin)-10.3(g)-222.7(and)-230.3(orientati)-13.1(ng)-223.5(the)-227(airways)]TJ -7.8074 -1.0471 TD [(by)-217.8(means)-219.5(of)-213.7(their)-215.4(o)-6.5(w)0(n)-210.3(longi)-8.6(tudinal)-217.7(bundle)-7.4(s,)-212.9(L)]TJ 6.974 0 0 6.974 489.997 321.052 Tm 0.0001 Tc (EI)Tj /F4 1 Tf 9.963 0 0 9.963 498.557 321.052 Tm 0 Tc [(et)-214.9(al.)]TJ /F7 1 Tf 2.1567 0 TD ([20])Tj -21.1518 -1.0528 TD [(meas)-8.2(ured)-295.3(the)-295.3(angle)-297.2(between)-297.4(the)-295.3(long)-295.7(axes)-295.3(of)-293.3(the)-295.3(smooth)]TJ 0 -1.0471 TD [(musc)-7.8(le)-260.4(nuclei)-266.2(and)-264.5(the)-261.2(transverse)-267.2(plane)-268.8(of)-259.2(the)-261.2(airway)55(.)-262.2(I)0(n)-259.2(a)]TJ 0 -1.0527 TD 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[(Th)17.1(er)19.2(ef)13.5(or)19.6(e,)-320.2(ai)18.4(rw)15.7(ay)-320.6(sm)16.9(oo)21.2(th)-322.6(m)13.2(u)0(s)14.4(c)0(l)18.4(e)-325.5(is)-323.8(pr)19.6(es)19.6(en)15.1(t)-327.5(a)0(n)15.1(d)-325.1(ac)20.4(ti)16.5(ve)]TJ -1.0015 -1.0527 TD [(in)-220.2(th)13.2(e)-228.8(n)0(o)21.2(r)0(m)16.5(a)0(l)-226.2(f)0(o)19.6(e)0(t)18.5(a)0(l)-226.2(l)0(u)18.9(n)0(g)21.2(,)-233.7(en)20.8(ci)18.4(rc)13.5(le)18.4(s)-229.6(t)0(h)18.9(e)-234.5(en)20.8(ti)16.5(re)-225.5(ai)18.4(rw)15.7(ay)-218.2(be)15.1(lo)18.8(w)]TJ 0 -1.0471 TD [(th)18.9(e)-365.4(l)0(e)12.8(v)0(e)20.8(l)-367.3(of)-355.9(th)13.2(e)-365.4(m)0(a)17.7(i)0(n)-356.7(b)0(r)13.9(o)0(n)21.2(c)0(h)15.1(u)0(s)20(,)-364.6(in)-362.4(ro)19.6(ug)21.2(hl)13.2(y)-365(a)-365.4(ci)18.4(rc)13.5(ul)18.9(ar)-356.3(or)25.3(-)]TJ 0 -1.0528 TD [(ie)18.4(nt)18.9(at)12.8(io)18.9(n,)-257.2(ex)20.8(ce)14.7(pt)-254.3(at)-260.4(hi)18.9(gh)-257.6(lu)18.9(ng)-257.6(vo)15.5(l)13.9(u)0(m)12.4(e)0(s)19.6(,)-267.8(oc)20.8(cu)15.1(pi)18.9(es)-259.2(re)19.2(la)18.4(ti)16.5(ve)15.1(ly)]TJ 0 -1.0471 TD [(mo)18.1(re)-458.8(of)-452.7(th)18.9(e)-467.8(a)0(i)18.4(r)0(w)15.7(a)0(y)-451.5(w)0(a)11.2(l)13.9(l)-469.8(i)13.9(n)-467.4(t)0(h)18.9(e)-462.1(pe)15.1(ri)17.3(ph)15.5(er)19.2(al)-453.9(ai)18.4(rw)15.7(ay)15.1(s)-462.9(a)0(n)15.1(d)]TJ 0 -1.0527 TD [(in)18.9(cr)13.5(ea)20.4(se)13.9(s)-480(i)13.9(n)-484.5(a)0(b)20.8(s)0(o)14.3(l)0(u)18.9(t)0(e)-470.9(v)0(o)21.2(l)0(u)13.2(m)0(e)-471.7(f)0(r)18(o)0(m)-471.3(i)0(n)18.9(f)0(a)13.5(n)0(c)20.8(y)-478.8(up)-473.8(to)-470.5(ea)14.7(rl)17.3(y)]TJ 0 -1.0471 TD [(ad)15.1(ul)18.9(th)18.9(oo)15.5(d)-319.4(w)0(i)14.9(t)0(h)-316.9(l)0(i)16.5(t)0(t)16.5(l)13.9(e)-325.5(c)0(h)15.1(a)0(n)20.8(g)0(e)-314.9(t)0(h)13.2(e)0(r)19.2(e)0(a)14.7(f)0(t)17.3(e)0(r)70.5(.)]TJ /F6 1 Tf 4.2565 -2.5323 TD [(Ai)-7.8(rway)-337.4(smooth)-339(muscl)-9.4(e)-331.2(i)0(n)-338.9(disease)]TJ /F4 1 Tf -4.2565 -2.2535 TD [(Asthm)-9.7(a)]TJ /F7 1 Tf 1.0015 -1.6503 TD [(In)-230.7(19)15.5(22)15.5(,)-239.4(H)]TJ 6.974 0 0 6.974 110.324 498.331 Tm 0.0001 Tc [(UB)18.4(ER)]TJ 9.963 0 0 9.963 131.074 498.331 Tm 0 Tc [(an)15.1(d)-239.8(K)]TJ 6.974 0 0 6.974 154.715 498.331 Tm 0.0001 Tc [(OE)21.5(SSL)25.4(ER)]TJ 9.963 0 0 9.963 186.746 498.331 Tm 0 Tc [([2)19.6(5])-247.8(compared)-256.7(cross)-258.6(sec-)]TJ -12.8948 -1.0471 TD [(tions)-339.8(of)-333.2(large)-333(and)-332.7(smal)-10.2(l)-333.2(airways)-345.3(stained)-342.2(with)-336.1(haema)-8.2(tox-)]TJ 0 -1.0528 TD [(ylin)-309.4(and)-310(eosin)-309.4(from)-311(six)-313.2(patients)-311.2(who)-313.5(had)-304.3(died)-313.1(of)-304.7(asthm)-10.9(a)]TJ 0 -1.0471 TD [(with)-375.9(seven)-370(cases)-377.3(without)-374.9(asthm)-10.9(a)-365.4(who)-376.1(had)-372.6(died)-370(of)-373(non-)]TJ 0 -1.0527 TD [(respirato)-11.1(ry)-304.7(causes)-8.2(.)-307.7(They)-303.5(atte)-8.6(mpted)-311.3(to)-305.5(overcome)-313.7(some)-309.4(of)]TJ 0 -1.0471 TD [(the)-283.9(facto)-8.6(rs)-283.2(confoun)-7.3(ding)-284.3(meas)-8.2(urement)-292.1(and)-281.5(compa)-7.8(rison)-287.8(of)]TJ 0 -1.0527 TD [(airway)-451.5(smooth)-443.8(musc)-7.8(le)-442.5(area)-449.7(in)-442.1(different)-438.3(subje)-7.8(cts.)-444.8(The)-6.8(y)]TJ 0 -1.0471 TD [(norm)-7.8(alized)-505.6(the)-500.2(area)-500.9(of)-503.9(smooth)-506.4(muscle)-501.5(by)-502.3(relating)-505(its)]TJ 0 -1.0528 TD [(thickn)-9.7(ess)-232.7(to)-237.2(the)-238.4(exter)-8.6(nal)-232.7(diam)-9(eter)-241.1(of)-236.4(the)-232.7(airw)-11.4(ay)-235.2(and)-236(noted)]TJ 0 -1.0471 TD [(that)-412.2(folding)-415.7(of)-412.8(the)-409.1(epit)-8.2(helial)-410.9(layer)25.5(,)-410.1(eviden)-7.8(ce)-412.1(of)-407.1(smoo)-7.4(th)]TJ 0 -1.0527 TD [(musc)-7.8(le)-379.9(contr)-8.2(action,)-386.1(show)-8.2(ed)-383.2(no)-377.1(syst)-7.8(ematic)-389.3(variation)-392(be-)]TJ 0 -1.0471 TD [(tween)-221.5(the)-209.9(tw)-7.8(o)-211.3(groups)-217.9(of)-213.7(subje)-7.8(cts,)-211.5(that)-218.8(airways)-220.1(of)-213.7(the)-215.6(same)]TJ 0 -1.0528 TD [(size)-320.4(in)-316.9(the)-318.1(same)-321.2(indi)-7.8(vidual)-322.7(showed)-323.1(marked)-323.1(variation)-10.7(s)-314.9(i)0(n)]TJ 0 -1.0471 TD [(structure)-11.1(s)-360.5(and)-361.2(that)-361(these)-366.7(varia)-8.6(tions)-362.6(were)-362.2(simil)-9.6(ar)-362(in)-356.7(thei)-8.2(r)]TJ 0 -1.0527 TD [(two)-389.9(groups)-7.4(.)-387.3(The)-6.8(y)-387.7(acknowledg)-9.5(ed)-388.9(that)-395.2(dif)10.8(ference)-10.1(s)-388.9(i)0(n)-390.9(the)]TJ 0 -1.0471 TD [(numbe)-7.4(rs)-311.6(o)-6.5(f)-309.7(meas)-8.2(urem)-8.2(ents)-314.3(obtai)-9(nable)-314.3(from)-322.4(dif)10.8(ferent)-323.9(per-)]TJ 0 -1.0528 TD [(sons)-278.6(might)-279.2(unequal)-8.5(ly)-277.1(weight)-281.1(the)-278.2(results.)-282.3(They)-275(found)-278.6(that)]TJ 25.1977 44.2326 TD [(the)-301(thick)-9(ness)-296.1(of)-299(the)-301(muscle)-302.3(layer)-298.8(in)-299.8(patients)-305.5(with)-302(asthma)]TJ 0 -1.0698 TD [(was)-263.9(mark)-8.2(edly)-261.9(incre)-8.6(ased)-261.1(\(fig.)-265.1(2\))-259.2(in)-260(all)-263.5(airway)-263.7(sizes)-265.5(except)]TJ 0 -1.0641 TD [(for)-415.2(airways)-419.3(with)-415.8(an)-411.7(outside)-415.7(diameter)-420.8(of)]TJ /F14 1 Tf 16.9408 0 TD 0 Tw (<)Tj /F7 1 Tf 0.5577 0 TD [(1\2612)-412(mm)-411.8(and)]TJ -17.4984 -1.0698 TD [(specul)-9(ated)-342(regard)-8.6(ing)-334.7(the)-340.8(relative)-346.1(contribut)-10.3(ions)-336.7(of)-338.9(hyper-)]TJ T* [(troph)-7.8(y)-336.5(and)-332.7(hyperpl)-9.7(asia.)]TJ 1.0015 -1.0471 TD [(T)69.1(w)0(o)-250.1(s)0(t)17.7(u)0(d)15.5(i)0(e)18.4(s)-263.7(ha)20.8(ve)-252.3(sy)20(st)17.7(em)12(at)18.5(ic)18.5(al)18.5(ly)-254.3(ex)20.8(am)12(i)13.9(n)0(e)15.1(d)-262.5(w)12.4(h)0(e)15.1(t)0(h)18.9(e)0(r)-253.9(t)0(h)18.8(e)0(-)]TJ -1.0015 -1.0698 TD [(re)-276.7(is)-272.6(hy)15.5(pe)20.8(rp)13.9(la)18.4(si)17.7(a)-285.7(o)0(r)-270.6(h)0(y)15.5(p)0(e)20.8(r)0(t)17.3(r)0(o)13.9(p)0(h)21.2(y)-285.3(of)-270.6(ai)12.8(rw)15.7(ay)-269.4(sm)16.9(oo)15.5(th)-271.4(mu)12.4(sc)19.6(le)]TJ 0 -1.0641 TD [(in)-425(pa)20.8(ti)16.5(en)20.8(ts)-420.5(wi)14.9(th)-419.3(as)14(th)18.8(ma)17.7(.)-427.2(H)]TJ 6.974 0 0 6.974 418.167 697.379 Tm 0.0001 Tc [(EAR)29(D)]TJ 9.963 0 0 9.963 441.184 697.379 Tm 0 Tc [(an)20.8(d)-427.6(H)]TJ 6.974 0 0 6.974 466.639 697.379 Tm 0.0001 Tc [(OS)18.2(SA)18.2(IN)]TJ 9.963 0 0 9.963 495.609 697.379 Tm 0 Tc [([2)14(6])-429.9(point)]TJ -18.6991 -1.0698 TD [(cou)-8.4(nted)-216.4(all)-218(musc)-7.8(le)-220.6(in)-214.5(seria)-9.8(l)-213.7(transv)-10.2(erse)-217.2(sections)-224.6(\(10)]TJ /F14 1 Tf 20.0933 0 TD (m)Tj /F7 1 Tf 0.5747 0 TD [(m\))-216.8(of)]TJ -20.6681 -1.0698 TD [(poste)-7.8(rior)-350.1(basal)-349.6(bronchu)-7.3(s)-343.4(i)0(n)-345.3(cases)-348.9(of)-333.2(fatal)-346.7(asthm)-10.9(a.)-343(Using)]TJ 0 -1.0641 TD [(the)-357.9(mean)-359.8(o)-6.5(f)-355.2(two)-355.7(meas)-8.2(uremen)-10.1(ts,)-352.6(they)-358.7(found)-363.9(a)-354(three)-8.6(-fold)]TJ 0 -1.0698 TD [(difference)-392(between)-394.1(contr)-8.2(ol)-385.2(cases)-394.4(\(mean)-390.6(0.50)-389.6(mm)]TJ 7.472 0 0 6.641 511.313 659.225 Tm (2)Tj 9.963 0 0 9.963 515.055 654.803 Tm [(\))-389.3(and)]TJ -20.651 -1.0698 TD [(cases)-371.6(of)-367.3(asthm)-10.9(a)-365.4(\(1.54)-369.2(mm)]TJ 7.472 0 0 6.641 416.92 648.567 Tm (2)Tj 9.963 0 0 9.963 420.661 644.145 Tm [(\))-366.6(with)-370.3(littl)-10(e)-365.4(overlap)-374.3(between)]TJ -11.1762 -1.0641 TD [(the)-318.1(tw)-7.8(o)-313.8(groups)-7.4(.)-313.4(Hyperplas)-11.1(ia)-317.3(was)-315.1(show)-8.2(n)-313.7(b)0(y)-314.5(a)0(n)-314.9(incre)-8.6(ased)]TJ 0 -1.0698 TD [(numbe)-7.4(r)-634(o)0(f)-629.1(smoo)-7.4(th)-635.6(muscle)-638.1(cell)-634.6(nuclei)-636.1(in)-629.9(asthm)-10.9(atics)]TJ T* [(\(2,047\))-343.9(compa)-7.8(red)-334.3(with)-341.8(control)-336.5(cases)-343.2(\(717\).)]TJ 1.0015 -1.0471 TD (E)Tj 6.974 0 0 6.974 325.247 601.795 Tm 0.0001 Tc [(BIN)23.4(A)]TJ /F4 1 Tf 9.963 0 0 9.963 345.713 601.795 Tm 0 Tc [(et)-362.8(al)13.2(.)]TJ /F7 1 Tf 2.4469 0 TD [([2)19.6(7])-373(studi)-9.8(ed)-383.2(lungs)-383(from)-390.7(16)-382.8(patien)-10.2(ts)-380.7(with)]TJ -6.1003 -1.0698 TD [(bronchi)-9.7(al)-482.3(asthma)-484.4(and)-475(c)-6.9(ompared)-483.2(them)-481.3(with)-484.1(20)-479.5(control)]TJ T* [(cases.)-286.6(The)-280(mean)-280.2(thickn)-9.7(ess)-278.2(of)-276.3(smoo)-7.4(th)-277.1(musc)-7.8(le)-277.5(was)-281(plotted)]TJ 0 -1.0641 TD [(aga)-8.8(inst)-492.7(airway)-497(radiu)-8.2(s)-491.3(o)0(n)-490.9(a)-490.6(logar)-8.2(ithmic)-499(scale)-492.3(and)-497.8(was)]TJ 0 -1.0698 TD [(incre)-8.6(ased)-409.1(in)-402.2(all)-411.5(airway)-411.6(size)-405.8(groups)-411.4(in)-402.2(cases)-411.4(of)-407.2(asthma,)]TJ T* [(compa)-7.8(red)-300.2(with)-302(control)-302.3(cases.)-298(Furthe)-8.2(r)-298.3(analysis)-304.3(of)-293.3(the)-301(dis-)]TJ 0 -1.0641 TD [(tri)-8.6(bution)-413.4(of)-412.8(musc)-7.8(ular)-417.2(thickening)-419.6(in)-413.6(the)-414.8(asthm)-10.9(atic)-412.7(cases)]TJ 0 -1.0698 TD [(sugges)-7.4(ted)-522.9(that)-520.4(two)-520.8(distinct)-529.4(subgrou)-8.1(ps)-514.9(exist)-10.2(ed,)-514.5(one)-520.5(in)]TJ T* [(whi)-8.6(ch)-320.6(musc)-7.8(le)-323(hypert)-9(rophy)-324.1(was)-326.5(presen)-8.2(t)-321.8(only)-329.8(in)-322.6(the)-323.7(large)]TJ 0 -1.0641 TD [(airw)-11.4(ays)-214.4(\(which)-217.8(they)-216.4(called)-221.1(type)-210.7(I)-212.9(c)-6.9(ases\),)-213.8(and)-218.9(one)-213.2(in)-214.5(which)]TJ 0 -1.0698 TD [(musc)-7.8(le)-334.4(hypertrophy)-338.7(was)-337.9(present)-335.7(both)-335.5(in)-328.3(large)-327.3(and)-332.8(small)]TJ T* [(airw)-11.4(ays)-345.3(\(type)-349.6(II)-346.2(cases\).)-345.9(The)-348.2(same)-349.6(group)-346.8([28])-347.7(report)-10.6(ed)-343.4(a)]TJ 0 -1.0641 TD [(more)-275.7(detai)-9.4(led)-272.5(study)-274.8(compa)-7.8(ring)-274.5(airways)-277(from)-276.8(five)-274.9(control)]TJ 0 -1.0698 TD [(cases)-348.8(with)-341.8(those)-343.5(from)-345.1(10)-343(asthmati)-12.7(cs,)-339.2(class)-9.4(ified)-340.6(eith)-8.2(er)-339.3(as)]TJ T* [(type)-261.9(I)-258.4(\(mus)-9(cle)-261.6(thickening)-266(in)-260(centr)-8.6(al)-260.4(bronchi)-260.1(only\))-263.9(or)-259.2(type)]TJ 0 -1.0641 TD [(II)-488.4(\(muscle)-486.8(thic)-8.2(kening)-485.4(along)-490.3(the)-483.1(entire)-489.8(bronchial)-492(tree\).)]TJ 0 -1.0698 TD [(The)-6.8(y)-512.9(used)-511.1(a)-513.3(three)-8.6(-dimensi)-11.5(onal)-512.3(samp)-7.8(ling)-514.3(techniq)-10.9(ue)-508.4(in)]TJ T* [(whi)-8.6(ch)-417.3(tracings)-424.2(of)-424.2(individua)-8.7(l)-418.6(smooth)-421(musc)-7.8(le)-419.7(cells)-426(from)]TJ 0 -1.0641 TD [(100)-8(\261200)-390(seri)-8.6(al)-391.3(airway)-394.6(secti)-10.6(ons)-390.4(\(3)]TJ /F14 1 Tf 14.2947 0 TD (m)Tj /F7 1 Tf 0.5747 0 TD [(m\))-393.2(wer)-8.2(e)-388.1(stack)-8.2(ed)-388.9(to)]TJ -14.8694 -1.0698 TD 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Tc (UNNILL)Tj /F4 1 Tf 9.963 0 0 9.963 264.132 646.129 Tm 0 Tc [(et)-408.3(al.)]TJ /F7 1 Tf -20.6624 -1.0527 TD [([12])-330.6(point)-327.2(counte)-7.8(d)-319.4(the)-329.4(amoun)-7.4(t)-321.8(o)0(f)-327.5(smoo)-7.4(th)-322.6(musc)-7.8(le)-323(in)-328.3(car-)]TJ 0 -1.0471 TD [(tilagin)-9.6(ous)-407.5(airways.)-419.7(They)-411.6(defined)-414.2(their)-408.9(cases)-417.1(of)-407.2(chroni)-9(c)]TJ 0 -1.0527 TD [(bronchi)-9.7(tis)-275.7(as)-276.3(those)-280.9(wi)-7.8(th)-277.1(usual)-275.2(c)-6.9(ough)-276.2(and)-275.8(sputu)-7.4(m)-277.1(without)]TJ T* [(emphy)-7.4(sema)-8.2(,)-347.5(alth)-8.2(ough)-350.2(all)-354.6(o)-6.5(f)-349.5(their)-357.7(cases)-354.5(ha)-7.6(d)-347.9(a)-354(history)-360(of)]TJ 0 -1.0471 TD [("chro)-8.8(nic)-448.9(airflow)-455.8(obstr)-9(uction".)-457.7(In)-447(subje)-7.8(cts)-450.1(with)-455.6(chroni)-9(c)]TJ 0 -1.0527 TD [(bronchi)-9.7(tis)-486.2(defined)-488.1(in)-487.6(this)-487(way)61.7(,)-484.1(airway)-491.3(smoo)-7.4(th)-481.9(musc)-7.8(le)]TJ 0 -1.0471 TD [(occupi)-7.8(ed)-462.9(5.8%)-466(of)-464.1(the)-466(airw)-11.4(ay)-462.9(wall,)-467.8(simil)-9.6(ar)-464.5(to)-464.8(the)-466(per-)]TJ 0 -1.0527 TD [(centag)-8.2(e)-262.9(seen)-266.8(in)-265.7(subjects)-270.1(with)-267.8(emphy)-7.4(sema)-264.3(\(5.5%\))-271.5(and)-264.5(not)]TJ 0 -1.0471 TD [(signifi)-9.6(cantly)-351.6(different)-347.3(from)-356.5(that)-349.7(in)-351(contr)-8.2(ol)-345.3(cases)-354.5(\(4.6%\))-9.7(,)]TJ 0 -1.0527 TD [(but)-511.1(less)-514.7(than)-518(that)-514.7(found)-511.9(in)-516.1(cases)-513.9(of)-509.6(asthm)-10.9(a)-507.6(\()0(1)25.3(1.9%\).)]TJ 0 -1.0471 TD (M)Tj 6.974 0 0 6.974 67.124 531.042 Tm 0.0001 Tc (ULLEN)Tj /F4 1 Tf 9.963 0 0 9.963 94.224 531.042 Tm 0 Tc [(et)-448.2(al.)]TJ /F7 1 Tf 2.6177 0 TD [([42])-450.1(studied)-449.9(smal)-10.2(l)-441.3(and)-446.6(large)-441.1(airways)-453.4(in)]TJ -6.2255 -1.0527 TD [(patien)-10.1(ts)-466(with)-472.7(chroni)-9(c)-467.8(bronchi)-9.7(tis)-469.2(who)-472.8(had)-469.3(norm)-7.8(al)-470.9(lung)]TJ 0 -1.0471 TD [(funct)-8.2(ion.)-477.4(The)-6.8(y)-478.8(found)-483.4(that)-480.5(the)-483.1(relat)-11(ive)-477.4(area)-483.9(of)-481.1(smoo)-7.4(th)]TJ 0 -1.0528 TD [(musc)-7.8(le)-283.2(increased)-286.8(tow)-8.6(ards)-279.4(the)-283.9(perip)-8.2(heral)-287.4(airways)-288.4(in)-282.7(cases)]TJ 0 -1.0471 TD [(and)-344.1(control)-342.1(subje)-7.8(cts)-342(\(see)-348.1(above\))-342.7(with)-347.5(no)-337.3(signifi)-9.6(cant)-342(dif-)]TJ 0 -1.0527 TD [(ference)-10.1(s)-457.2(betw)-9.8(een)-458.3(the)-466(groups)-462.6(for)-460.7(a)-6.9(n)0(y)-456.8(airway)-468.5(size.)-463.1(The)]TJ T* [(overal)-9.4(l)-452.7(mean)-456.6(for)-455(chronic)-459.7(bronchiti)-10.3(s)-451.5(was)-451.7(2.4%)-460.3(and)-452.3(for)]TJ 0 -1.0471 TD [(contr)-8.2(ols)-222.1(was)-224.1(2.0%.)-227.3(V)103.4(ery)-220.5(littl)-10(e)-223.1(inflammati)-14.5(on)-217.8(of)-225.1(the)-221.3(smoo)-7.4(th)]TJ 0 -1.0528 TD [(musc)-7.8(le)-516.5(was)-520(observ)-7.8(ed.)-514.5(N)]TJ 6.974 0 0 6.974 162.482 447.307 Tm 0.0001 Tc (AGAI)Tj /F4 1 Tf 9.963 0 0 9.963 184.932 447.307 Tm 0 Tc [(et)-516.5(al.)]TJ /F7 1 Tf 2.7656 0 TD [([43])-518.4(studied)-523.8(lung)]TJ -15.4783 -1.0471 TD [(speci)-8.2(mens)-485.8(from)-493.1(cases)-485.4(wi)-7.8(th)-481.9(moder)-9(ate-to-se)-11.5(vere)-489.2(airflow)]TJ 0 -1.0527 TD [(obstru)-9.7(ction)-293.5(\(mean)-293.9(FEV)]TJ 7.97 0 0 7.97 151.88 426.387 Tm (1)Tj 9.963 0 0 9.963 158.683 426.387 Tm [(of)-293.3(31%)-289.2(pred\))-297.6(from)-293.9(the)-289.6(Nationa)-9.1(l)]TJ -10.078 -1.0471 TD [(Institu)-9.6(te)-323(of)-327.5(Health)-332.8(Intermi)-11.1(ttent)-324.3(Po)-6.4(sitive)-326.3(Pressu)-8.2(re)-327.9(Breath-)]TJ 0 -1.0527 TD [(ing)-414.4(T)29.3(rial.)-414.2(Compar)-8.7(ed)-411.7(with)-415.8(controls,)-418.5(the)-409.1(cases)-417.1(had)-412.4(more)]TJ 0 -1.0471 TD [(emphy)-7.4(sema)-8.2(,)-245.1(narrow)-12.1(er)-253.9(bronchioles)-11.1(,)-250.8(decreas)-9.7(ed)-252.3(amounts)-257.2(of)]TJ 0 -1.0528 TD [(cartilage)-11.5(,)-387.3(a)0(n)-383.2(enlarged)-386.9(mucous)-390.6(gland)-387.9(area)-387.1(an)-7.6(d)-382(incre)-8.6(ased)]TJ 0 -1.0471 TD [(scores)-299.6(for)-295.7(infl)-9.4(ammati)-10.7(on.)-292.1(The)-6.8(y)-291(found)-301.3(that)-292.7(there)-304.5(tended)-298(to)]TJ 0 -1.0528 TD [(be)-240.9(more)-241.5(smoo)-7.4(th)-242.9(muscle)-245.4(in)-237.2(the)-244.1(younger)-246.3(subje)-7.8(cts,)-240(alth)-8.2(ough)]TJ 0 -1.0471 TD [(this)-401.7(was)-406.2(nonsi)-7.4(gnificant)-10.7(.)-398.7(The)-405.2(calculated)-409.4(volum)-9.3(e)-399.5(propor-)]TJ 0 -1.0527 TD [(tion)-343.6(of)-338.9(smoo)-7.4(th)-339.7(musc)-7.8(le)-340.1(in)-339.7(centr)-8.6(al)-340.1(and)-344.1(periphe)-10.1(ral)-342.4(airways)]TJ T* [(was)-451.7(4.6)-445.8(and)-452.2(8.5%)-448.9(in)-447.8(the)-448.9(COPD)-453(patients,)-453.8(signi)-9.8(ficantly)]TJ 0 -1.0471 TD [(great)-8.6(er)-584(than)-586.3(the)-585.5(2.8)-588(and)-583.1(5.8%)-591.2(in)-584.3(the)-585.5(contr)-8.2(ol)-584.3(cases.)]TJ 0 -1.0528 TD (M)Tj 6.974 0 0 6.974 67.124 311.301 Tm 0.0001 Tc [(A)100.3(TSUBA)]TJ 9.963 0 0 9.963 96.775 311.301 Tm 0 Tc [(and)-258.8(T)]TJ 6.974 0 0 6.974 119.735 311.301 Tm 0.0001 Tc (HURLBECK)Tj 9.963 0 0 9.963 159.761 311.301 Tm 0 Tc [([44])-262.3(found)-261.5(that)-8.2(,)-256.5(i)0(n)-260(pati)-8.2(ents)-263.1(with)]TJ -10.1861 -1.0471 TD [(bronchi)-9.7(tis,)-230.6(the)-227(relat)-11(ive)-227(area)-233.5(of)-230.7(smoo)-7.4(th)-225.8(musc)-7.8(le)-226.2(in)-231.5(large)-224.8(and)]TJ 0 -1.0528 TD [(small)-349.1(airways)-351(was)-343.6(3.3)-343.3(and)-344.1(9.5%)-346.5(respec)-8.6(tively)56.2(,)-341.8(compa)-7.8(red)]TJ 0 -1.0471 TD [(with)-336.1(2)-6.5(.)0(6)-331.2(and)-338.4(14%)-334.7(in)-334(norm)-7.8(al)-334.4(subje)-7.8(cts.)]TJ 1.0015 -1.0528 TD [(A)-363.2(n)0(u)21.2(m)0(b)12.4(e)0(r)-350.6(o)0(f)-350.2(s)0(t)17.7(u)0(d)15.5(i)0(e)18.4(s)-360.5([1)13.9(5,)-348.3(17)15.5(,)-358.9(4)0(5)21.2(])-366.6(fr)18(om)-351.8(th)18.9(e)-359.7(V)109.1(an)20.8(co)15.1(uv)21.2(er)]TJ -1.0015 -1.0471 TD [(gr)19.6(ou)15.5(p)-484.5(h)0(a)20.8(v)0(e)-479.9(s)0(y)20(s)0(t)17.7(e)0(m)17.7(a)0(t)12.8(i)0(c)18.4(a)0(l)18.4(l)0(y)-476.2(e)0(x)20.8(a)0(m)12(i)0(n)18.9(e)0(d)-474.2(t)0(h)18.9(e)-484.9(di)13.2(me)17.7(ns)20(io)18.9(ns)-480.7(of)]TJ 0 -1.0528 TD [(la)18.4(r)20.4(g)0(e)-377.5(a)0(n)15.1(d)-382(sm)16.9(al)18.4(l)-390.1(a)0(i)18.4(r)0(w)15.7(a)0(y)20.8(s)-383.2(fr)12.4(om)-374.6(sm)16.9(ok)15.5(er)19.2(s)-383.2(w)0(i)14.9(t)0(h)-373.8(a)0(n)15.1(d)-382(wi)14.9(th)18.9(ou)15.5(t)]TJ 0 -1.0471 TD [(ai)18.4(rf)18(lo)13.2(w)-220.9(o)0(b)21.2(s)0(t)17.7(r)0(u)13.9(c)0(t)18.4(i)0(o)18.8(n)-222.7(an)15.1(d)-217(f)0(r)12.4(o)0(m)-209.5(c)0(a)14.7(s)0(e)19.6(s)-223.9(of)-213.7(as)19.6(th)18.9(ma)17.7(.)-222.3(T)0(h)17.1(e)0(y)-212.5(p)0(l)18.9(o)0(t)18.9(t)0(e)12.8(d)]TJ 0 -1.0527 TD [(th)18.9(e)-319.8(s)0(q)20(u)0(a)15.1(r)0(e)-310.8(r)0(o)19.6(o)0(t)-311.2(o)0(f)-310.4(t)0(h)18.9(e)-319.8(ai)18.4(rw)15.7(ay)-309.2(sm)11.2(oo)21.2(th)-311.2(mu)18.1(sc)13.9(l)13.9(e)-319.8(ar)13.5(ea)-309.6(ag)20.8(ai)12.8(ns)20(t)]TJ 0 -1.0471 TD [(ai)18.4(rw)15.7(ay)-252.3(si)17.7(ze)14.7(,)-262.1(d)0(e)20.8(f)0(i)17.3(n)0(e)15.1(d)-262.5(by)-251.9(th)18.9(e)-262.9(b)0(a)20.8(s)0(e)13.9(m)0(e)17.7(n)0(t)-254.3(m)0(e)17.7(m)0(b)18.1(r)0(a)13.5(n)0(e)-252.3(p)0(e)20.8(r)0(i)17.3(m)0(e)12(t)0(e)18.4(r)]TJ 0 -1.0528 TD [(se)19.6(en)-514.1(on)-513.7(tr)17.3(an)15.1(sv)20(er)13.5(se)-515.3(se)19.6(ct)18.5(io)18.9(ns)14.4(.)-523.9(T)12.2(he)-514.1(co)15.1(ns)20(ta)18.4(nt)-516.1(an)15.1(d)-518.6(t)0(h)18.9(e)-524.7(co)15.1(-)]TJ T* [(ef)24.9(fi)17.3(ci)18.5(en)20.8(t)-287.7(f)0(o)13.9(r)-286.9(th)18.9(e)-291.4(l)0(i)22.2(n)0(e)15.1(a)0(r)-282.4(e)0(q)20.8(u)0(a)15.1(t)0(i)16.5(o)0(n)-274.7(g)0(i)18.9(v)0(e)-280.8(t)0(h)18.9(e)-291.4(ov)21.2(er)13.5(al)18.4(l)-287.7(d)0(i)18.9(f)20.4(fe)13.5(re)19.2(nc)15.1(e)]TJ 0 -1.0471 TD [(be)15.1(tw)20.6(ee)14.7(n)-382(c)0(a)14.7(s)0(e)-373(g)0(r)19.6(o)0(u)15.5(p)0(s)-372.6(a)0(n)15.1(d)-382(th)13.2(e)-382.4(d)0(e)20.8(g)0(r)14(e)0(e)-372.2(t)0(o)-379.5(w)12.4(hi)13.2(ch)-371.8(th)18.9(ey)-377.5(va)15.1(ry)]TJ 0 -1.0527 TD [(ac)14.7(co)20.8(rd)13.9(i)13.9(n)0(g)-263.3(t)13.9(o)-268.2(a)0(i)18.5(r)0(w)15.7(a)0(y)-258(s)0(i)17.7(z)0(e)14.7(.)-267.8(B)]TJ 6.974 0 0 6.974 164.92 175.294 Tm 0.0001 Tc [(OSK)20.9(EN)]TJ /F4 1 Tf 9.963 0 0 9.963 190.488 175.294 Tm 0 Tc [(et)-260.4(al)18.9(.)]TJ /F7 1 Tf 2.2364 0 TD [([4)19.6(5])-270.6(compared)-285.2(the)]TJ -15.5067 -1.0471 TD [(dimen)-9.7(sions)-327.2(of)-327.5(smal)-10.2(l)-327.5(airways)-333.9(\()]TJ /F14 1 Tf 12.2005 0 TD (<)Tj /F7 1 Tf 0.552 0 TD [(2)-325.1(m)0(m)-332.2(diameter)-11.1(\))-326.7(from)-333.7(30)]TJ -12.7525 -1.0527 TD [(smok)-7.4(ers)-312.8(without)-323.7(airflow)-319.2(obstr)-9(uction)-317(\(45)-316.9(pack-yr)-9.3(s,)-309.6(FEV)]TJ 7.97 0 0 7.97 281.48 154.375 Tm (1)Tj 9.963 0 0 9.963 58.28 143.943 Tm [(77%)-528.2(pred\))-525.2(wi)-7.8(th)-521.8(those)-531.3(from)-527.2(30)-525.1(smok)-7.4(ers)-523.3(with)-529.6(airflow)]TJ T* [(obstru)-9.7(ction)-259.4(\(70)-265.7(pack-yr)-9.3(s,)-258.4(FEV)]TJ 7.97 0 0 7.97 178.923 133.455 Tm (1)Tj 9.963 0 0 9.963 185.499 133.455 Tm [(55%)-260.7(pred\).)-263.9(The)-6.8(y)-256.8(show)-8.2(ed)]TJ -12.7696 -1.0471 TD [(that)-406.6(the)-403.4(airway)-411.6(walls)-406.7(were)-407.7(thicker)-410.8(in)-402.2(subjects)-406.7(wi)-7.8(th)-402.3(ob-)]TJ 0 -1.0528 TD [(structio)-10.7(n.)-439.3(Althoug)-8.3(h)-433.2(the)-443.2(percentag)-12.5(e)-433.7(o)0(f)-441.3(the)-437.6(inner)-440.7(airw)-11.4(ay)]TJ 25.1977 66.1583 TD 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[(be)-303.5(ex)15.1(pe)20.8(ct)18.4(ed)-303.5(to)-305.5(be)-303.5(gr)19.6(ea)14.7(te)18.4(r)-315.3(i)13.9(n)-313.8(t)0(h)18.9(e)-314.2(sm)16.9(al)18.4(le)12.8(r)-309.7(a)0(i)18.5(r)0(w)15.7(a)0(y)15.1(s)0(.)-303.9(O)12.4(ne)-303.5(an)15.1(-)]TJ 0 -1.0528 TD [(al)18.4(ys)14.4(is)-357.9(su)20(gg)15.5(es)19.6(ts)-357.9(th)18.9(at)-357.1(an)-360.4(in)18.9(cr)19.2(ea)14.7(se)-355.9(in)-356.7(th)13.2(e)-365.4(a)0(m)17.7(o)0(u)15.5(n)0(t)-356.7(o)0(f)-355.9(m)0(u)18.1(s)0(c)14(l)0(e)]TJ 0 -1.0471 TD [(wi)14.9(ll)-433.1(ha)15.1(ve)-434.4(th)18.9(e)-445(g)0(r)13.9(e)0(a)20.4(t)0(e)18.4(s)0(t)-437.6(e)0(f)24.9(f)0(e)19.2(c)0(t)18.4(s)-445.8(on)-434(ma)12(xi)18.9(ma)17.7(l)-447(n)0(a)20.8(r)0(r)18(o)0(w)11.6(i)13.9(ng)-439.7(in)]TJ 0 -1.0528 TD [(as)19.6(th)13.2(ma)17.7(,)-324.7(e)0(s)19.6(p)0(e)15.1(c)0(i)18.4(a)0(l)18.4(l)0(y)-316.9(i)0(n)-311.2(s)0(m)16.9(a)0(l)12.8(l)-321.8(ai)18.4(rw)15.7(ay)15.1(s)-320.6([)0(6)13.9(0].)]TJ 1.0015 -1.0471 TD [(Th)17.1(re)19.2(e)-297.1(i)0(m)15.7(p)0(o)21.2(r)0(t)17.3(a)0(n)15.1(t)-293.4(po)21.2(in)18.9(ts)-289.6(ar)19.2(is)17.7(e)-291.4(f)0(r)18(o)0(m)-289.2(t)0(h)18.9(e)0(s)19.6(e)-297.1(st)17.7(ud)21.2(ie)12.8(s.)-281.2(F)11.4(i)0(r)17.3(s)0(t)17.7(l)0(y)75.8(,)]TJ -1.0015 -1.0528 TD [(it)-285.1(is)-283.9(as)19.6(su)20(me)12(d)-291(t)0(h)18.9(a)0(t)-283.1(s)0(m)16.9(o)0(o)15.5(t)0(h)-282.7(m)0(u)18.1(s)0(c)19.6(l)0(e)-283.1(i)0(s)-283.9(m)0(a)12(x)0(i)18.9(m)0(a)17.7(l)0(l)16.5(y)-291(st)17.7(im)15.7(ul)18.9(at)18.4(ed)]TJ T* [(du)15.5(ri)17.3(ng)]TJ /F4 1 Tf 3.0046 0 TD [(in)-442.1(vi)18.4(vo)]TJ /F7 1 Tf 3.2834 0 TD [(in)13.2(ha)20.8(la)18.4(ti)16.5(on)15.5(al)-442.5(ch)15.1(al)18.4(le)18.4(ng)15.5(e.)-445.4(Th)17.1(is)-443.3(is)-449(ye)20.8(t)-458.4(t)0(o)-442.1(b)0(e)]TJ -6.2881 -1.0471 TD [(pr)19.6(ov)15.5(en)15.1(.)-449.9(S)11.4(ec)14.7(on)21.2(d,)-445(i)13.9(t)-452.7(is)-443.3(as)13.9(su)20(me)17.7(d)-450.3(t)0(h)18.9(a)0(t)-448.2(t)13.9(he)-445.8(fo)19.6(rc)13.5(e-)19.2(ge)15.1(ne)20.8(ra)19.2(ti)16.5(ng)]TJ 0 -1.0528 TD [(pr)19.6(op)15.5(er)19.2(ti)16.5(es)-196.6(of)-196.6(th)18.9(e)-206(s)0(m)16.9(o)0(o)15.5(t)0(h)-197.4(m)0(u)18.1(s)0(c)19.6(l)0(e)-197.8(a)0(r)13.5(e)-200.3(no)15.5(t)-202.3(c)0(h)15.1(a)0(n)15.1(g)0(e)20.8(d)-205.6(in)-197.4(as)19.6(th)18.9(ma)12(.)]TJ 0 -1.0471 TD [(Th)17.1(er)19.2(e)-376.7(a)0(r)19.2(e)-376.7(co)15.1(nf)19.6(li)16.5(ct)18.5(in)18.9(g)]TJ /F4 1 Tf 8.7578 0 TD [(in)-362.4(vi)12.8(tr)51.8(o)]TJ /F7 1 Tf 3.3062 0 TD [(da)20.8(ta)12.8(,)-370.3(a)0(s)-367.3(s)0(h)20(o)0(w)17.3(n)-376.3(ab)15.1(ov)21.2(e,)-365.7(an)15.1(d)]TJ -12.064 -1.0527 TD [(sm)16.9(oo)15.5(th)-351(mu)18.1(sc)19.6(le)-357.1(un)21.2(de)15.1(r)20.4(g)0(o)15.5(i)0(n)18.9(g)-359.3(hy)15.5(pe)20.8(rp)13.9(la)18.4(si)17.7(a)-359.7(m)0(a)17.7(y)-365(be)-349.1(ph)15.5(en)20.8(ot)18.9(y-)]TJ 0 -1.0471 TD [(pi)18.9(ca)14.7(ll)16.5(y)-319.4(a)0(n)15.1(d)-319.4(fu)19.6(nc)15.1(ti)16.5(on)21.2(al)18.5(ly)-316.9(al)18.4(te)18.4(re)13.5(d.)-308.4(Fi)14(na)20.8(ll)16.5(y)73.2(,)-324.7(de)20.8(sp)14.4(i)13.9(t)0(e)-317.3(a)0(l)18.4(l)-321.8(of)-310.4(th)13.2(e)]TJ 0 -1.0527 TD [(ab)15.1(ov)21.2(e)-228.8(c)0(o)15.1(n)0(c)15.1(e)0(r)19.2(n)0(s)20(,)-233.7(it)-222.5(mu)18.1(st)-221.3(be)-223.9(re)19.2(me)17.7(mb)18.1(er)13.5(ed)-218.2(th)13.2(at)-220.6(th)18.9(e)-234.5(c)0(l)18.4(i)0(n)18.8(i)0(c)18.4(a)0(l)18.4(,)]TJ /F4 1 Tf 22.0395 0 TD (in)Tj -22.0395 -1.0471 TD [(vi)18.4(vo)]TJ /F7 1 Tf 1.6104 0 TD (,)Tj /F4 1 Tf 0.5463 0 TD [(in)-294.1(vi)18.5(tr)46.1(o)]TJ /F7 1 Tf 3.1639 0 TD [(an)20.8(d)-302.4(m)0(o)18.1(d)0(e)15.1(l)0(l)16.5(i)13.9(ng)-291.7(ev)15.1(id)18.9(en)15.1(ce)-292.6(al)18.4(l)-299.1(d)0(e)15.1(m)0(o)18.1(n)0(s)14.4(t)13.9(ra)13.5(te)-294.5(t)13.9(h)0(a)15.1(t)]TJ -5.3207 -1.0527 TD [(at)-453.9(le)18.4(as)13.9(t)-464.1(s)0(o)20(m)0(e)-454.6(s)0(m)16.9(o)0(o)15.5(t)0(h)-453.5(m)0(u)18.1(s)0(c)13.9(l)13.9(e)-467.8(sh)20(or)19.6(te)12.8(ni)18.9(ng)-451.1(mu)12.4(st)-454.7(oc)20.8(cu)15.1(r)-463.3(t)0(o)]TJ 0 -1.0471 TD [(pr)19.6(od)15.5(uc)15.1(e)-439.3(t)13.9(he)-434.4(ex)20.8(ce)14.7(ss)18.9(iv)18.9(e)-439.3(a)0(i)12.8(r)0(w)15.7(a)0(y)-428.7(n)0(a)20.8(r)0(r)12.4(o)0(w)17.3(i)0(n)18.9(g)-438.9(th)18.9(at)-431.1(is)-431.9(se)19.6(en)-434.4(in)]TJ 0 -1.0527 TD [(as)19.6(th)13.2(ma)17.7(.)-250.8(I)0(t)-244.5(s)0(e)19.6(e)0(m)17.7(s)-252.3(un)15.5(li)16.5(ke)20.8(ly)-242.9(th)18.9(at)-243.3(th)18.9(e)-251.6(t)0(h)13.2(i)0(c)18.4(k)0(e)20.8(n)0(i)13.2(n)0(g)-240.5(o)0(f)-242.1(t)0(h)18.9(e)-251.6(ai)18.5(rw)15.7(ay)]TJ T* [(wa)16.9(ll)16.5(,)-296.3(i)0(n)18.9(c)0(r)13.5(e)0(a)20.4(s)0(e)13.9(d)-296.7(th)18.9(ic)18.4(kn)15.5(es)19.6(s)-297.9(o)0(f)-287.7(t)0(h)18.9(e)-302.8(sm)16.9(oo)21.2(th)-288.4(mu)18.1(sc)13.9(le)18.4(,)-296.3(i)0(n)18.9(c)0(r)13.5(e)0(a)20.4(s)0(e)13.9(d)]TJ 0 -1.0471 TD [(nu)15.5(mb)18.1(er)19.2(s)-223.9(o)0(f)-219.4(b)0(l)18.9(o)0(o)15.5(d)-222.7(ve)15.1(ss)18.9(el)18.4(s)-223.9([)0(5)13.9(8)0(])-225.1(o)0(r)-236.4(incre)-8.6(ased)-238.4(luminal)-243.6(mucus)]TJ 25.1977 66.1583 TD [([54])-262.3(will,)-264.9(by)-257.6(themselv)-10.3(es)-259.2(or)-259.2(even)-259.9(in)-254.3(combi)-9.7(nation,)-260.5(resul)-9.4(t)-253.5(i)0(n)]TJ 0 -1.0471 TD [(exc)-8.8(essive)-482.5(airway)-485.6(narrow)-12.1(ing)-477(in)-481.9(the)-483.1(absence)-486.2(of)-481.1(smooth)]TJ 0 -1.0528 TD [(musc)-7.8(le)-334.4(short)-9(ening.)]TJ /F6 1 Tf 0.5804 -3.2322 TD [(Rel)-9(ationship)-342.1(of)-333.2(airw)-9.8(ay)-331.6(smoot)-9(h)-335.7(muscle)-340.6(and)-336.5(airway)]TJ 7.9611 -1.0471 TD [(infl)-8.6(ammation)]TJ /F7 1 Tf -7.54 -1.5478 TD [(Th)17.1(e)-268.6(o)0(t)18.9(h)0(e)15.1(r)-264.1(ch)20.8(ar)13.5(ac)20.4(te)18.4(ri)17.3(st)17.7(ic)-260.4(of)-253.5(ai)18.5(rw)15.7(ay)-258(di)18.9(se)14(as)19.6(es)-253.5(is)-255.5(in)13.2(fl)17.3(am)17.7(ma)17.7(-)]TJ -1.0015 -1.0527 TD [(ti)16.5(on)15.5(.)-216.6(I)0(n)-208(c)0(h)20.8(r)0(o)13.9(n)0(i)18.9(c)-217.4(ob)21.2(st)17.7(ru)13.9(ct)18.5(iv)18.9(e)-217.4(p)0(u)15.5(l)0(m)15.7(o)0(n)21.2(a)0(r)13.5(y)-217(di)18.9(se)19.6(as)19.6(e)-217.4(t)0(h)13.2(i)0(s)-204.3(c)0(o)15.1(n)0(s)20(i)0(s)17.7(t)0(s)]TJ T* [(pr)13.9(ed)20.8(om)12.4(in)18.8(an)20.8(tl)16.5(y)-245.5(o)0(f)-230.7(l)0(y)13.2(m)13.2(p)0(h)15.5(o)0(c)15.1(y)0(t)18.9(e)0(s)-230.7(a)0(n)15.1(d)-239.8(ne)15.1(ut)18.9(ro)13.9(ph)21.2(il)16.5(s)-241([)0(6)14(1)0(])-242.1(and)-253.1(in)]TJ 0 -1.0471 TD [(asthm)-10.9(a)-462.1(predom)-9.7(inant)-9(ly)-464.8(of)-464.1(lym)-7.8(phocyt)-7.4(es)-464.1(and)-469.3(eosin)-7.8(ophils)]TJ 0 -1.0527 TD [([34,)-237.6(62],)-231.9(alth)-8.2(ough)-230.7(the)-238.4(relative)-238(numbe)-7.4(rs)-231.9(of)-236.4(neutrophil)-11.1(s)-229.6(and)]TJ 0 -1.0471 TD [(eosin)-7.8(ophil)-8.6(s)-332(may)-341.6(vary)-340.8(in)-339.7(both)-341.2(condition)-8.7(s)-337.7([62,)-340(63].)-340(How-)]TJ 0 -1.0527 TD [(eve)-8.8(r)31.8(,)-245.1(these)-252.9(inflammato)-12.1(ry)-247.8(cells)-249.6(may)-250.5(be)-246.6(less)-247.2(imp)-7.8(ortan)-8.2(t)-242.2(than)]TJ 0 -1.0471 TD [(mast)-232.1(cell)-8.6(s)-223.9(i)0(n)-225.8(deter)-8.6(mining)-228.7(airwa)-12.5(y)-222.7(smoo)-7.4(th)-225.8(muscle)-234(function.)]TJ 0 -1.0527 TD [(It)-284.3(has)-282.7(recently)-286.8(been)-282.7(shown)-282.1(that)-287.1(mast)-283.3(cells)-283.7(are)-283.5(more)-281.3(com-)]TJ 0 -1.0471 TD [(mon)-324.1(in)-322.6(smoo)-7.4(th)-322.6(muscle)-325.1(that)-326.9(is)-323.8(sensitized)-331.3(to)-322.6(allergen)-315.3([64])]TJ 0 -1.0527 TD [(and)-338.4(preliminary)-341.3(wor)-7.8(k)-330.8(show)-8.2(s)-332(that,)-333(in)-334(asthmati)-12.7(c)-331.2(and)-332.7(non-)]TJ 0 -1.0471 TD [(asthm)-10.9(atic)-361.4(tissue,)-365.3(mast)-363(cells)-363.4(are)-363.2(the)-357.9(predom)-9.7(inant)-361.8(inflam-)]TJ 0 -1.0527 TD [(mat)-8.2(ory)-373.8(cell)-378.5(in)-373.8(airway)-377.5(smoo)-7.4(th)-373.8(muscle)-376.3([65].)-376.5(The)-376.7(relative)]TJ 0 -1.0471 TD [(imp)-7.8(ortanc)-9.4(e)-251.6(o)0(f)-253.5(the)-255.5(relea)-9(se)-253.5(of)-259.2(inflamm)-12.7(atory)-258.6(cytokines,)-258.7(me-)]TJ 0 -1.0527 TD [(diat)-8.2(ors)-306.7(and)-304.3(grow)-8.6(th)-305.5(factors)-308.8(from)-311(these)-309.8(and)-310(other)-309.8(cells)-306.5(are)]TJ 0 -1.0471 TD [(yet)-340.8(to)-334(be)-332(d)-6.5(etermine)-11.1(d.)]TJ /F6 1 Tf 8.966 0 0 8.966 402.349 519.987 Tm [(Refer)11.6(ences)]TJ /F7 1 Tf 8.468 0 0 8.468 309.316 507.061 Tm [(1.)-1914.5(Macklin)-503.5(CC.)-500(The)-500.9(musculature)-500.8(of)-503.5(the)-500.1(bronchi)-499(and)-504.4(lungs.)]TJ /F4 1 Tf 2.6645 -1.0645 TD [(Physiol)-334.4(Rev)]TJ /F7 1 Tf 5.1148 0 TD [(1929;)-334.2(9:)-334.6(1\26160.)]TJ -7.7793 -1.0578 TD [(2.)-1914.5(Reisseisen)-340.1(FD.)-334.4(Uber)-332.6(den)-337.1(Bau)-331.7(der)-334.3(Lungen.)-330.7(Berlin,)-337.7(1822.)]TJ T* [(3.)-1914.5(Grancher)-136.2(J.)-134.9(Maladies)-134.6(de)-134.1(l)]TJ /F9 1 Tf 12.3452 0 TD (')Tj /F7 1 Tf 0.2142 0 TD [(appareil)-140.8(respiratoire.)]TJ /F4 1 Tf 8.1743 0 TD (In)Tj /F7 1 Tf 0.8235 0 TD [(:)-131.7(T)28.2(uberculose)]TJ -18.8927 -1.0578 TD [(et)-123.1(auscultation.)-135.4(Lecons)-122.8(cliniques)-133.1(recueilles)-131.2(par)-126.8(le)-129.8(Dr)-124.9(L.)-123.4(Faisans.)]TJ T* [(Paris,)-334.6(1890.)]TJ -2.6645 -1.0578 TD [(4.)-1914.5(Miller)-364.4(WSW)82.9(.)-359.2(The)-360.3(musculature)-366.9(of)-356.3(the)-359.5(finer)-364.9(divisions)-363.1(of)-363(the)]TJ 2.6645 -1.0578 TD [(bronchial)-347.7(tree)-348.2(and)-343.8(it)]TJ /F9 1 Tf 8.2212 0 TD (')Tj /F7 1 Tf 0.2209 0 TD [(s)-344.7(relation)-348(to)-341.3(certain)-352.9(pathological)-344.1(cond-)]TJ -8.4421 -1.0645 TD (itions.)Tj /F4 1 Tf 2.7783 0 TD [(Am)-338.3(Rev)-329.5(T)49.9(uber)]TJ /F7 1 Tf 6.1257 0 TD [(1921;)-334.2(5:)-334.6(689\261704.)]TJ -11.5686 -1.0578 TD [(5.)-1914.5(von)-374.5(Hayek)-380.4(H.)-384.3(The)-373.7(Human)-382.1(Lung.)-377.4(Hafner)-383.7(Publishing)-378.9(Com-)]TJ 2.6645 -1.0578 TD [(pany)-332.5(Inc.,)-336.4(New)-336.2(Y)95.4(ork,)-335.9(1960;)-334.2(pp.)-329.9(139\261144.)]TJ -2.6645 -1.0578 TD [(6.)-1914.5(T)61.7(akizawa)-285.3(T)75.1(,)-285.6(Thurlbeck)-288.1(WM.)-284.5(Muscle)-286(and)-283.5(mucous)-282(gland)-283.4(size)]TJ 2.6645 -1.0578 TD [(in)-502(the)-500.1(major)-506(bronchi)-505.7(of)-503.5(patients)-505.9(with)-504.8(chronic)-501.8(bronchitis,)]TJ T* [(asthma,)-331.7(and)-337.1(asthmatic)-334.4(bronchitis.)]TJ /F4 1 Tf 13.8046 0 TD [(Am)-331.6(Rev)-336.2(Respir)-331.1(Dis)]TJ /F7 1 Tf 8.0873 0 TD (1971;)Tj -21.8919 -1.0645 TD [(104:)-332.1(331\261336.)]TJ -2.6645 -1.0578 TD [(7.)-1914.5(Matsuba)-274.7(K,)-270.5(Thurlb)-8.6(eck)-272.9(WM.)-271.1(A)-272.8(morphometric)-279.8(study)-275.1(of)-269.2(bron-)]TJ 2.6645 -1.0578 TD [(chial)-348.8(and)-350.5(bronchiolar)-355.8(walls)-350.1(in)-348(children.)]TJ /F4 1 Tf 16.3554 0 TD [(Am)-351.7(Rev)-349.6(Respir)-351.2(Dis)]TJ /F7 1 Tf -16.3554 -1.0578 TD [(1972;)-334.2(105:)-332.1(908\261913.)]TJ -2.6645 -1.0578 TD [(8.)-1914.5(Hislop)-389.6(AA,)-389.3(Haworth)-384.4(SG.)-388(Airway)-389(size)-392.4(and)-383.9(structure)-393(in)-388.2(the)]TJ 2.6645 -1.0578 TD [(normal)-441.2(foetal)-435.1(and)-437.5(infant)-439.1(lung)-439.2(and)-430.8(the)-439.9(effect)-426(of)-436.6(premature)]TJ T* [(delivery)-338.9(and)-330.4(artificial)-336.8(ventilation.)]TJ /F4 1 Tf 13.798 0 TD [(Am)-338.3(Rev)-329.5(Respir)-337.8(Dis)]TJ /F7 1 Tf 8.094 0 TD (1989;)Tj -21.8919 -1.0645 TD 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[(34.)-1414.5(Carroll)-486.6(NG,)-483(Lehman)-487.6(E,)-478.2(Barret)-491.6(J,)-483(Morton)-484.1(AR,)-481.5(Cooke)-489.9(C,)]TJ 2.6645 -1.0578 TD [(James)-324.1(AL.)-329.3(V)102.1(ariability)-330.1(of)-329.5(airway)-328.5(structure)-332.7(and)-323.7(inflammation)]TJ T* [(in)-281.1(normal)-280.5(subjects)-290.5(and)-276.8(in)-287.8(cases)-282.2(of)-282.6(nonfatal)-285.3(and)-283.5(fatal)-285.8(asthma.)]TJ /F4 1 Tf 0 -1.0645 TD [(Path)-328.5(Res)-334.7(Pract)]TJ /F7 1 Tf 6.4939 0 TD [(1996;)-334.2(192:)-338.8(238\261248.)]TJ -9.1585 -1.0578 TD [(35.)-1414.5(James)-237(AL,)-242.2(Lougheed)-239.5(D,)-237(Pearce-Pinto)-246(G,)-243.7(R)30(yan)-236.7(G,)-237(Musk)-240.5(A)68.6(W)86.8(.)]TJ 2.6645 -1.0578 TD [(Maximal)-300.4(airway)-308.5(narrowing)-302.5(in)-301.2(a)-306.1(general)-303.7(population.)]TJ /F4 1 Tf 21.0551 0 TD [(Am)-304.8(Rev)]TJ -21.0551 -1.0578 TD [(Respir)-331.1(Dis)]TJ /F7 1 Tf 4.6194 0 TD [(1992;)-334.2(146:)-338.8(895\261899.)]TJ -7.2839 -1.0578 TD [(36.)-1414.5(Lenart)-536.3(E.)-531.8(Beobachtungen)-537.3(u)]TJ 13.972 -0.0201 TD 0 Tw (\310)Tj 0.4017 0.0201 TD [(ber)-535.2(das)-539.1(V)102.1(erhalten)-535.8(der)-521.8(glatten)]TJ -11.7092 -1.0578 TD [(Muskulatur)-371.5(der)-374.5(kleineren)-377.2(Luftwege)-376(bei)-372.9(verschiedenen)-376.4(Erk-)]TJ 0 -1.0645 TD (rankungen.)Tj /F4 1 Tf 4.5926 0 TD [(Zentralbl)-151.9(allg)-147(Path)-147.8(path)-144.6(Anat)]TJ /F7 1 Tf 11.4816 0 TD [(1923\2611924;)-150.4(34:)-142.6(202.)]TJ -18.7387 -1.0578 TD [(37.)-1414.5(Leibow)-244.6(AA,)-248.7(Loring)-249.6(WE,)-250.8(Felton)-249.2(WL.)-244.1(The)-246.5(musculature)-253.1(of)-249.1(the)]TJ 2.6645 -1.0578 TD [(lungs)-322(in)-321.2(chronic)-327.7(pulmonary)-326.9(disease.)]TJ /F4 1 Tf 14.916 0 TD [(Am)-324.9(J)-326.2(Pathol)]TJ /F7 1 Tf 5.3759 0 TD [(1953;)-327.5(29:)]TJ -20.2919 -1.0578 TD (885\261912.)Tj -2.6645 -1.0578 TD [(38.)-1414.5(Sobonya)-213.1(RE,)-220.6(Kleinerman)-226(J.)-215.2(Morphometric)-225(studies)-218.7(of)-222.4(bronchi)]TJ 2.6645 -1.0578 TD [(in)-307.8(young)-311.7(smokers.)]TJ /F4 1 Tf 7.7459 0 TD [(Am)-311.5(Rev)-309.5(Respir)-317.7(Dis)]TJ /F7 1 Tf 8.0003 0 TD [(1972;)-314.1(105:)-305.3(768\261775.)]TJ -18.4107 -1.0578 TD [(39.)-1414.5(Niewoehner)-222(DE,)-222.1(Kleinerman)-232.7(J,)-221.9(Rice)-225.1(DB.)-220.4(Pathologic)-229.2(changes)]TJ 2.6645 -1.0645 TD [(in)-254.3(the)-259.1(peripheral)-262.7(airways)-258.2(of)-255.8(young)-258.2(cigarette)-261.8(smokers.)]TJ /F4 1 Tf 21.3631 0 TD [(N)-257.9(Engl)]TJ -21.3631 -1.0578 TD [(J)-332.9(Med)]TJ /F7 1 Tf 2.8587 0 TD [(1974;)-334.2(291:)-338.8(755\261758.)]TJ -5.5232 -1.0578 TD [(40.)-1414.5(Hossain)-413.4(S,)-416.4(Heard)-411.1(BE.)-414.7(Hyperplasia)-418.9(of)-416.5(bronchial)-414.6(muscle)-414.4(in)]TJ 2.6645 -1.0578 TD [(chronic)-334.4(bronchitis.)]TJ /F4 1 Tf 7.8396 0 TD [(J)-332.9(Pathol)]TJ /F7 1 Tf 3.7491 0 TD [(1970;)-334.2(101:)-338.8(171\261184.)]TJ -14.2532 -1.0578 TD [(41.)-1414.5(Macleod)-216(LJ,)-207(Heard)-217(BE.)-213.9(Area)-214.9(of)-215.7(muscle)-220.2(in)-207.4(tracheal)-223.9(sections)-216.8(in)]TJ 2.6645 -1.0578 TD [(chronic)-501.8(bronchitis,)-508.9(measured)-503.2(by)-506.3(point-counting.)]TJ /F4 1 Tf 20.5731 0 TD [(J)-500.3(Pathol)]TJ /F7 1 Tf -20.5731 -1.0645 TD [(1968;)-334.2(97:)-330(157\261161.)]TJ -2.6645 -1.0578 TD [(42.)-1414.5(Mullen)-458.5(JBM,)-465(W)26.5(right)-461(JL,)-461.4(W)26.5(iggs)-460.5(BR,)-466.5(Pare)-461.2(PD,)-468.3(Hogg)-459.8(JC.)]TJ 32.309 76.2335 TD [(Reassessment)-818.9(of)-811.5(inflammation)-822.9(of)-811.5(airways)-820.5(in)-816.7(chronic)]TJ 0 -1.0578 TD (bronchitis.)Tj /F4 1 Tf 4.5391 0 TD (BMJ)Tj /F7 1 Tf 2.2026 0 TD [(1985;)-334.2(291:)-332.1(1235\2611239.)]TJ -9.4062 -1.0578 TD [(43.)-1414.5(Nagai)-309.1(A,)-304(W)73.4(est)-300.5(WW)79.8(,)-305.7(Paul)-302.9(JL,)-307.4(Thurlbeck)-301.5(WM.)-311.3(The)-300(National)]TJ 2.6645 -1.0578 TD [(Institutes)-407.7(of)-396.4(Healt)-10.2(h)-397.1(intermittent)-408.1(positive-pressure)-407.7(breathing)]TJ T* [(trial:)-89(pathology)-93.3(studies.)]TJ /F4 1 Tf 9.0848 0 TD [(Am)-90.6(Rev)-88.5(Respir)-90.1(Dis)]TJ /F7 1 Tf 7.1099 0 TD [(1985;)-86.5(132:)-91.1(937\261945.)]TJ -18.8592 -1.0578 TD [(44.)-1414.5(Matsuba)-288.1(K,)-283.9(Thurlbeck)-281.4(WM.)-284.5(Disease)-285(of)-289.3(the)-279.2(small)-291.4(airways)-285(in)]TJ 2.6645 -1.0578 TD [(chronic)-307.6(bronchitis.)]TJ /F4 1 Tf 7.786 0 TD [(Am)-304.8(Rev)-302.8(Respir)-304.3(Dis)]TJ /F7 1 Tf 7.9735 0 TD [(1973;)-307.4(107:)-305.3(552\261558.)]TJ -18.424 -1.0645 TD [(45.)-1414.5(Bosken)-252.2(CH,)-247.2(Hards)-255.6(J,)-248.7(Gatter)-250.6(K,)-250.4(Hogg)-252.3(JC.)-252.1(Characterization)-256.1(of)]TJ 2.6645 -1.0578 TD [(the)-372.9(inflammatory)-382.6(reaction)-381.8(in)-374.8(the)-372.9(peripheral)-383.2(airways)-372(of)-376.3(cig-)]TJ T* [(arette)-344.2(smokers)-342.8(using)-335.4(immunocyto)-10.6(chemistry)61.7(.)]TJ /F4 1 Tf 18.096 0 TD [(Am)-338.3(Rev)-342.9(Respir)]TJ -18.096 -1.0578 TD (Dis)Tj /F7 1 Tf 1.7072 0 TD [(1992;)-334.2(145:)-332.1(91)29.3(1\261917.)]TJ -4.3717 -1.0578 TD [(46.)-1414.5(Elliot)-386.7(J,)-382.6(V)55.2(ullermin)-389.9(P)103.4(,)-379.3(Carroll)-386.2(N,)-384.3(James)-384.3(A,)-377.6(Robinson)-389.9(P)103.4(.)-379.3(In-)]TJ 2.6645 -1.0578 TD [(creased)-385.6(airway)-382.1(smooth)-382.1(muscle)-380.9(in)-381.5(sudden)-378(infant)-385.5(death)-379.9(syn-)]TJ 0 -1.0645 TD (drome.)Tj /F4 1 Tf 3.1131 0 TD [(Am)-338.3(J)-332.9(Respir)-331.1(Crit)-337(Car)31.3(e)-332.9(Med)]TJ /F7 1 Tf 11.6556 0 TD [(1998;)-334.2(158:)-332.1(802\261806.)]TJ -17.4332 -1.0578 TD [(47.)-1414.5(Armour)-315.7(CL,)-314.3(Lazar)-313.6(NM,)-316(Schellenberg)-307.4(RR.)-312.6(A)-313(comparison)-319.5(of)]TJ /F4 1 Tf 2.6645 -1.0578 TD [(in)-240.9(vivo)]TJ /F7 1 Tf 2.8988 0 TD (and)Tj /F4 1 Tf 1.6737 0 TD [(in)-240.9(vitr)29.8(o)]TJ /F7 1 Tf 3.0863 0 TD [(human)-238.6(airway)-248.2(reactivity)-243.5(to)-240.9(histamine.)]TJ /F4 1 Tf 15.1771 0 TD (Am)Tj -22.8359 -1.0578 TD [(Rev)-336.2(Respir)-331.1(Dis)]TJ /F7 1 Tf 6.4337 0 TD [(1984;)-334.2(129:)-338.8(907\261910.)]TJ -9.0982 -1.0578 TD [(48.)-1414.5(Cerrina)-239.3(J,)-242(Le)-237.7(Roy)-242(Ladurie)-237.1(M,)-237.4(Labat)-242.4(C,)-242.2(Raf)12.5(festin)-239.4(B,)-242.2(Bayol)-237.9(A,)]TJ 2.6645 -1.0578 TD [(Brink)-319.4(C.)-309.1(Comparison)-324.9(of)-309.4(human)-318.9(bronchial)-320.9(muscle)-314(responses)]TJ T* [(to)-327.9(histamine)]TJ /F4 1 Tf 5.2688 0 TD [(in)-321.2(vivo)]TJ /F7 1 Tf 3.0662 0 TD [(with)-330.7(histamine)-331.7(and)-323.7(isoproterenol)-330(agon-)]TJ -8.335 -1.0645 TD (ists)Tj /F4 1 Tf 1.6469 0 TD [(in)-334.6(vitr)29.8(o)]TJ /F7 1 Tf 2.939 0 TD (.)Tj /F4 1 Tf 0.5824 0 TD [(Am)-331.6(Rev)-336.2(Respir)-331.1(Dis)]TJ /F7 1 Tf 8.094 0 TD [(1986;)-334.2(134:)-332.1(57\26161.)]TJ -15.9269 -1.0578 TD [(49.)-1414.5(V)48.5(incenc)-378(KS,)-381.3(Black)-387.9(JL,)-381.1(Y)95.4(a)0(n)-381.8(K)0(,)-384.3(Armour)-382.6(CL,)-381.3(Donnelly)-388.7(PD,)]TJ 2.6645 -1.0578 TD [(W)73.4(oolocock)-258.9(AJ.)-260.4(Comparison)-257.9(of)]TJ /F4 1 Tf 12.5661 0 TD [(in)-261(vivo)]TJ /F7 1 Tf 2.9323 0 TD (and)Tj /F4 1 Tf 1.6938 0 TD [(in)-254.3(vitr)29.8(o)]TJ /F7 1 Tf 3.1131 0 TD (responses)Tj -20.3053 -1.0578 TD [(to)-415(histamine)-412(in)-415(human)-412.7(airways.)]TJ /F4 1 Tf 13.4766 0 TD [(Am)-418.6(Rev)-409.9(Respir)-418.2(Dis)]TJ /F7 1 Tf 8.4153 0 TD (1983;)Tj -21.8919 -1.0578 TD [(128:)-332.1(875\261879.)]TJ -2.6645 -1.0578 TD [(50.)-1414.5(de)-422(Jongste)-417.1(JC,)-419.5(Mows)-424.1(H,)-417.8(Bonta)-425.3(IL,)-417.3(Kerrebijn)-428.2(KF)71.7(.)-419.5(Human)]TJ 2.6645 -1.0645 TD [(asthmatic)-321(airway)-315.2(responses)]TJ /F4 1 Tf 11.2673 0 TD [(in)-314.5(vitr)29.8(o)]TJ /F7 1 Tf 2.9189 0 TD (.)Tj /F4 1 Tf 0.5624 0 TD [(Eur)-311.9(J)-319.5(Respir)-317.7(Dis)]TJ /F7 1 Tf 7.1433 0 TD (1987;)Tj -21.8919 -1.0578 TD [(70:)-336.7(23\26129.)]TJ -2.6645 -1.0578 TD [(51.)-1414.5(Goldie)-230.5(RG,)-227.1(Spina)-231.4(D,)-230.3(Henry)-227.6(PJ,)-225.6(Lubich)-228.3(KM,)-229(Patterson)-236.6(JW)83.5(.)]TJ /F4 1 Tf 26.0025 0 TD (In)Tj -23.338 -1.0578 TD [(vitr)29.8(o)]TJ /F7 1 Tf 2.611 0 TD [(responsiveness)-778.3(of)-771.3(human)-780.9(asthmatic)-776.3(bronchus)-781.1(to)]TJ -2.611 -1.0578 TD [(carbachol,)-368.5(histamine,)]TJ /F14 1 Tf 8.9175 0 TD (b)Tj /F7 1 Tf 0.5557 0 TD [(-adrenoceptor)-367(agonist)-371.5(and)-363.8(theophyl-)]TJ -9.4731 -1.0578 TD (line.)Tj /F4 1 Tf 2.062 0 TD [(Br)-336.5(J)-332.9(Clin)-335.8(Pharmacol)]TJ /F7 1 Tf 8.884 0 TD [(1986;)-334.2(22:)-336.7(669\261676.)]TJ -13.6105 -1.0578 TD [(52.)-1414.5(Moreno)-598.3(RH,)-602(Hogg)-600.4(JC,)-593.6(Pare)-601.8(PD.)-602.2(Mechanics)-599(of)-604(airway)]TJ 2.6645 -1.0645 TD (narrowing.)Tj /F4 1 Tf 4.6529 0 TD [(Am)-338.3(Rev)-336.2(Respir)-331.1(Dis)]TJ /F7 1 Tf 8.094 0 TD [(1986;)-334.2(133:)-338.8(1)31.4(171\2611)29.7(180.)]TJ -15.4114 -1.0578 TD [(53.)-1414.5(Macklem)-441.4(PT)71.5(.)-439.6(Bronchial)-442.7(hyperresponsiveness.)]TJ /F4 1 Tf 21.8585 0 TD (Chest)Tj /F7 1 Tf 2.698 0 TD (1985;)Tj -21.8919 -1.0578 TD [(87:)-336.7(158S\261159S.)]TJ -2.6645 -1.0578 TD [(54.)-1414.5(James)-250.4(AL,)-255.6(Carroll)-252.3(NC.)-253.9(Theoretic)-253.1(effects)-248.6(of)-249.1(mucus)-253.2(gland)-249.9(dis-)]TJ 2.6645 -1.0578 TD [(charge)-165.3(on)-171.6(airway)-181.3(resistance)-176.9(in)-174(asthma.)]TJ /F4 1 Tf 15.0633 0 TD (Chest)Tj /F7 1 Tf 2.4369 0 TD [(1995;)-173.5(107:)-178.1(1)31.4(10S.)]TJ -20.1647 -1.0578 TD [(55.)-1414.5(W)33.2(iggs)-467.2(BR,)-459.9(Bosken)-459.7(C,)-463.1(Pare)-461.2(PD,)-461.6(James)-464.7(AL,)-463.2(Hogg)-459.8(JC.)-466.4(A)]TJ 2.6645 -1.0645 TD [(model)-341.4(of)-342.9(airway)-341.9(narrowing)-342.7(in)-341.3(asthma)-340.7(and)-343.8(in)-334.6(chronic)-347.8(obstr-)]TJ 0 -1.0578 TD [(uctive)-444.6(pulmonary)-447.4(disease.)]TJ /F4 1 Tf 11.1468 0 TD [(Am)-445.4(Rev)-443.4(Respir)-444.9(Dis)]TJ /F7 1 Tf 8.5292 0 TD [(1992;)-441.3(145:)]TJ -19.676 -1.0578 TD (1251\2611258.)Tj -2.6645 -1.0578 TD [(56.)-1414.5(Pare)-293.8(PD,)-294.2(W)33.2(iggs)-293.1(BR,)-292.5(James)-297.3(AL,)-295.8(Hogg)-292.5(JC,)-292.3(Y)95.4(aegashi)-294.2(H,)-297.3(Pare)]TJ 2.6645 -1.0578 TD [(PD.)-260.7(The)-266.5(comparative)-268.1(mechanics)-265.5(and)-263.4(morphology)-266(of)-262.5(airways)]TJ T* [(in)-287.8(asthma)-287.2(and)-283.5(in)-287.8(chronic)-287.5(obstructive)-295.2(pulmonary)-286.7(disease.)]TJ /F4 1 Tf 22.8359 0 TD (Am)Tj -22.8359 -1.0645 TD [(Rev)-336.2(Respir)-331.1(Dis)]TJ /F7 1 Tf 6.4337 0 TD [(1991;)-334.2(143:)-338.8(1)31.4(182\2611)29.7(189.)]TJ -9.0982 -1.0578 TD [(57.)-1414.5(Bates)-395.8(JHT)73.5(,)-392.7(Martin)-402.2(JG.)-394.3(A)-393.3(theoretical)-395.6(study)-395.6(of)-396.4(the)-393(effect)-385.9(of)]TJ 2.6645 -1.0578 TD [(airway)-308.5(smooth)-315.2(muscle)-307.3(orientation)-316.4(on)-305.5(bronchoconstriction.)]TJ /F4 1 Tf 23.7263 0 TD (J)Tj -23.7263 -1.0578 TD [(Appl)-335.2(Physiol)]TJ /F7 1 Tf 5.5098 0 TD [(1990;)-334.2(69:)-336.7(995\2611001.)]TJ -8.1743 -1.0578 TD [(58.)-1414.5(Carroll)-453.2(NG,)-449.6(Cooke)-443(C,)-449.7(James)-451.3(AL.)-449.8(Bronchial)-449.4(blood)-448(vessel)]TJ 2.6645 -1.0578 TD [(dimensions)-216(in)-214.1(asthma.)]TJ /F4 1 Tf 8.9777 0 TD [(Am)-217.8(J)-212.4(Respir)-210.6(Crit)-216.5(Car)31.3(e)-212.4(Med)]TJ /F7 1 Tf 10.9326 0 TD [(1997;)-207(155:)]TJ -19.9103 -1.0578 TD (689\261695.)Tj -2.6645 -1.0645 TD [(59.)-1414.5(James)-391(AL,)-382.8(Carroll)-392.9(NG.)-389.3(The)-380.4(patholo)-8.8(gy)-385.8(of)-376.3(fatal)-386.2(asthma.)]TJ /F4 1 Tf 25.7348 0 TD (In)Tj /F7 1 Tf 0.8235 0 TD (:)Tj -23.8937 -1.0578 TD [(Holgate)-402.7(ST)71.5(,)-406.1(Busse)-405.2(WT)74.9(,)-399.4(eds.)-402.9(Inflammator)-13.8(y)-397.1(Mechanisms)-409.9(in)]TJ T* [(Asthma.)-338.6(New)-329.5(Y)88.7(ork,)-335.9(Marcel)-331.6(Dekker)-339.5(Inc.,)-336.4(1998;)-334.2(pp.)-329.9(1\26126.)]TJ -2.6645 -1.0578 TD [(60.)-1414.5(Lambert)-435.7(RK,)-434.6(W)26.5(iggs)-433.7(BR,)-433.1(Kuwano)-436.2(K,)-431.2(Hogg)-433.1(JC,)-439.6(Pare)-434.4(PD.)]TJ 2.6645 -1.0578 TD [(Functional)-369.8(significance)-369.7(of)-363(increased)-365.4(airway)-368.7(smooth)-362(muscle)]TJ T* [(in)-294.5(asthma)-300.6(and)-296.9(COPD.)]TJ /F4 1 Tf 9.1049 0 TD [(J)-292.7(Appl)-301.7(Physiol)]TJ /F7 1 Tf 6.1726 0 TD [(1993;)-294(74:)-296.5(2771\2612781.)]TJ -17.942 -1.0645 TD [(61.)-1414.5(Saetta)-321.7(M.)-311(Central)-324.8(airways)-318.4(inflammation)-320.8(in)-321.2(the)-312.7(development)]TJ 2.6645 -1.0578 TD [(of)-336.2(COPD.)]TJ /F4 1 Tf 4.3985 0 TD [(Eur)-331.9(Respir)-331.1(Rev)]TJ /F7 1 Tf 6.5475 0 TD [(1997;)-334.2(7:)-334.6(109\2611)29.7(10.)]TJ -13.6105 -1.0578 TD [(62.)-1414.5(Carroll)-299.2(NG,)-295.6(Carello)-298(S,)-295.9(Cooke)-295.7(C,)-295.7(James)-297.3(A.)-290.6(Airway)-301.9(structure)]TJ 2.6645 -1.0578 TD [(and)-263.4(inflammatory)-268.8(cells)-262.9(in)-261(fatal)-265.7(attacks)-263.1(of)-262.5(asthma.)]TJ /F4 1 Tf 19.8299 0 TD [(Eur)-258.3(Respir)]TJ -19.8299 -1.0578 TD (J)Tj /F7 1 Tf 0.7699 0 TD [(1996;)-334.2(9:)-334.6(709\261715.)]TJ -3.4344 -1.0578 TD [(63.)-1414.5(Saetta)-696.6(M,)-699.3(Di)-692.4(Stefano)-697.5(A,)-699(Maestrelli)-696.5(P)103.5(,)]TJ /F4 1 Tf 20.7337 0 TD [(et)-698.9(al)]TJ /F7 1 Tf 2.1758 0 TD [(.)-694(Airway)]TJ -20.245 -1.0578 TD [(eosinophilia)-342.5(in)-334.6(chronic)-341.1(bronchitis)-337.2(during)-340.2(exacerbations.)]TJ /F4 1 Tf 22.8359 0 TD (Am)Tj -22.8359 -1.0645 TD [(J)-332.9(Respir)-337.8(Crit)-337(Car)31.3(e)-332.9(Med)]TJ /F7 1 Tf 10.002 0 TD [(1994;)-334.2(150:)-332.1(1646\2611652.)]TJ -12.6665 -1.0578 TD [(64.)-1414.5(Ammit)-281.5(AJ,)-280.5(Bekir)-275.3(SS,)-279.5(Johnson)-278.1(PR,)-279.3(Hughes)-280.5(JM,)-274.1(Armour)-282.2(CL,)]TJ 2.6645 -1.0578 TD [(Black)-441.5(JL.)-441.3(Mast)-439.7(cell)-447.1(numbers)-442(are)-444.2(increased)-445.7(in)-435.1(the)-446.6(smooth)]TJ T* [(muscle)-414.4(of)-409.8(human)-412.7(sensitised)-418.7(isolated)-412.2(bronchi.)]TJ /F4 1 Tf 18.9931 0 TD [(Am)-411.9(J)-413.2(Respir)]TJ -18.9931 -1.0578 TD [(Crit)-337(Car)31.3(e)-332.9(Med)]TJ /F7 1 Tf 6.3132 0 TD [(1997;)-334.2(155:)-332.1(1)31.4(123\2611)29.7(129.)]TJ -8.9777 -1.0578 TD [(65.)-1414.5(James)-451.3(AL,)-449.8(Carroll)-453.2(NG.)-449.6(Mast)-453.1(cells)-450.4(and)-444.2(neutrophils)-453.1(in)-455.1(the)]TJ 2.6645 -1.0645 TD [(airway)-408.9(wall)-400.4(in)-408.3(asthma.)]TJ /F4 1 Tf 9.8213 0 TD [(Am)-398.5(J)-406.5(Respir)-404.8(Crit)-404(Car)31.3(e)-406.5(Med)]TJ /F7 1 Tf 12.0707 0 TD (1998;)Tj -21.8919 -1.0578 TD [(157:)-332.1(A873.)]TJ 8.966 0 0 8.966 523.049 797.499 Tm (789)Tj 7.472 0 0 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