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283.6346 Tm [(Tc-SC)-425(particle)]TJ ET 313.058 710.135 239.131 .22681 re f 313.058 576.737 239.131 .22681 re f 313.058 681.222 239.131 .22675 re f BT /F11 1 Tf 8.9663 0 0 8.9663 360.5101 725.7825 Tm (Table)Tj /F5 1 Tf 3.0603 0 TD (1.)Tj /F11 1 Tf 1.2519 0 TD [(Summary)-335.9(of)-330(Subject)-338(Age)]TJ -2.7821 -1.1128 TD [(and)-331.7(Lung)-336.1(Function)-333.7(by)-334.1(Site)]TJ /F8 1 Tf -1.9791 -2.0423 TD [(No.)-332.4(of)-336.3(subjects/)]TJ 1.7894 -1.1128 TD (gender)Tj 7.2397 1.1128 TD [(Age)-331.8(mean)]TJ .588 -1.1128 TD (\(range\))Tj 6.3735 1.1128 TD [(FEV1)-332.2(%)-335.3(pred)]TJ .1518 -1.1128 TD [(mean)-334.6(\(range\))]TJ /F5 1 Tf -20.9857 -2.0929 TD [()-2543.4(21M)-6896.1(25)-327.8(\(1841\))-2546.6(101)-327.3(\(83138\))]TJ 4.8434 -1.1128 TD [(9F)-7781.1(27)-327.8(\(2237\))-2546.6(111)-327.3(\(93132\))]TJ T* [(All)-7501.1(26)-327.8(\(1841\))-2546.6(104)-327.3(\(83138\))]TJ -4.8434 -1.4416 TD [(JHU)-2929.4(6M)-7396.1(29)-327.8(\(2337\))-3046.2(97)-327.8(\(82115\))]TJ 4.8434 -1.1128 TD [(4F)-7781.1(21)-327.8(\(1824\))-2546.6(107)-327.3(\(101117\))]TJ T* [(All)-7501.1(26)-327.8(\(1837\))-2546.6(101)-327.3(\(82117\))]TJ -4.8434 -1.4416 TD [(Pitt)-3325.4(4M)-7396.1(21)-327.8(\(2022\))-3046.2(99)-327.8(\(90117\))]TJ 4.8434 -1.1128 TD [(6F)-7781.1(25)-327.8(\(2237\))-3046.2(99)-327.8(\(81126\))]TJ 0 -1.1065 TD [(All)-7501.1(24)-327.8(\(2034\))-3046.2(99)-327.8(\(81126\))]TJ 7.9702 0 0 7.9702 321.0519 564.9447 Tm [(FEV1,)-328(forced)-330.1(expiratory)-321.3(volume)-329.1(in)-327.8(1)-168.6(sec.)]TJ ET q 1 i 313.625 258.066 m 551.565 258.066 l 551.565 113.839 l 313.625 113.839 l W n q 238.023 0 0 144.227 313.625 113.839 cm /Im1 Do Q Q BT /F10 1 Tf 8.9663 0 0 8.9663 313.0582 97.1149 Tm [(FIG.)-349.5(1.)]TJ /F5 1 Tf 4.1099 0 TD [(Radioaerosol)-346(inhalation)-351.8(setup:)-342.4(Devilbiss)-348.5(646)-346.3(nebu-)]TJ -4.1099 -1.1128 TD [(lizer)-260.1(\(NEB\))-259.8(and)-252.5(Spira)-256.5(Electro2)-262.1(Inhalation)-255.6(Dosimeter)-260.5(\(SPIRA\).)]TJ 0 -1.1065 TD 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8.9663 0 0 8.9663 69.9023 79.2 Tm [(Xe)-699.6(equilibrium)-700.4(lung)-695.6(image:)-703.4(\(1\))-696(a)-701.4(rectangular)-702(region)]TJ -1.1318 -1.2203 TD [(around)-541.9(the)-534.9(entire)-539(right)-537.3(lung)-537.5(\(along)-532.6(the)-541.2(edges)-533.3(of)-540.7(an)-534(iso-)]TJ 0 -1.2267 TD [(contour)-352.2(of)-344.7(15%)-348.4(peak)-346.6(activity\))-347.5(and)-341(\(2\))-348.2(a)-347.3(C)-341.6(ROI)-350.8(that)-345.3(was)-343.9(po-)]TJ 28.0042 41.2507 TD [(sitioned)-397.3(and)-391.6(centered)-392.2(on)-391.9(the)-395.8(interior)-394.4(boundary)-398.9(of)-388.9(the)-395.8(lung)]TJ 0 -1.2266 TD [(that)-427.5(included)-434.3(approximately)-434.1(25%)-424.3(of)-433.2(the)-433.7(area)-429.6(of)-426.9(the)-433.7(whole)]TJ 0 -1.2203 TD [(lung)-341.5(ROI.)]TJ 6.7246 0 0 5.9768 350.0219 409.1526 Tm (\(3\))Tj 8.9663 0 0 8.9663 360.8503 405.1841 Tm [(The)-341.4(P)-342.8(region)-343.5(was)-343.9(the)-345.2(area)-347.4(lying)-341.8(between)-344.7(the)-345.2(C)]TJ -5.5768 -1.2203 TD [(and)-303.1(whole)-302.1(lung)-303.5(outline.)-302.4(We)-302.4(then)-304.3(calculated)-306.6(the)-307.3(ratio)-304.2(of)-300.4(C)-303.7(t)0(o)]TJ 0 -1.2266 TD [(P)-406(counts)-413.2(from)-412.5(the)-408.4(initial)-409.5(particle)-413(deposition)-414.1(scan,)-404.8(\(C/P\)Tc,)]TJ 0 -1.2203 TD [(and)-454.8(normalized)-449.7(this)-457.6(ratio)-455.9(by)-451.4(dividing)-455.1(by)-451.4(the)-452.7(C/P)-453.5(for)-452.9(the)]TJ T* [(xenon)-334.1(scan,)-335.2(\(C/P\)Xe;)]TJ 8.0933 -2.5861 TD (\(C)Tj /F13 1 Tf 1.0306 0 TD (=)Tj /F5 1 Tf .4995 0 TD (P\)Tc)Tj /F13 1 Tf 1.9601 0 TD (=)Tj /F5 1 Tf .4995 0 TD (\(C)Tj /F13 1 Tf 1.0306 0 TD (=)Tj /F5 1 Tf .4995 0 TD (P\)Xe)Tj /F6 1 Tf 2.2193 0 TD ()Tj /F5 1 Tf .9358 0 TD (C)Tj /F13 1 Tf .7082 0 TD (=)Tj /F5 1 Tf .4995 0 TD [(P)-6950.2(\(1\))]TJ -16.8632 -2.251 TD [(This)-295.8(normalization)-298.4(was)-299.6(done)-299.9(to)-294.1(account)-303.2(for)-294.8(the)-300.9(difference)]TJ -1.1128 -1.2203 TD [(in)-449.5(relative)-457.2(lung)-455.3(areas)-456.2(and)-448.5(thickness)-459.6(between)-458.5(the)-452.7(C)-455.4(and)-448.5(P)]TJ T* (regions.)Tj 6.7246 0 0 5.9768 341.9149 300.0755 Tm (\(14\))Tj 8.9663 0 0 8.9663 356.4849 296.107 Tm [(The)-392(C/P)-383.9(ratio)-392.7(provides)-386.4(an)-388.6(index)-391.4(of)-388.9(relative)-394(de-)]TJ -5.0899 -1.2266 TD [(position)-246.8(between)-243.5(the)-244(two)-245.1(regions)-243.6(that)-244.1(can)-242.5(be)-244.6(used)-245.8(to)-243.5(relate)-244.3(to)]TJ 0 -1.2203 TD (MCC,)Tj /F8 1 Tf 2.8769 0 TD (i.e)Tj /F5 1 Tf .9042 0 TD [(.,)-277.7(as)-272.7(a)-271.4(covariate)-278.3(to)-275.1(consider)-279.5(in)-272.5(MCC)-277.3(analysis.)-278.7(A)-273.3(C/P)]TJ -3.7811 -1.2203 TD [(of)-528(1.0)-526.7(reects)-529.4(equal)-527.2(deposition)-534.2(in)-525.4(each)-526.9(region.)-529.8(However,)]TJ T* [(because)-479.9(the)-484.3(C)-480.7(region)-482.6(outlines)-490.5(both)-478.9(airways)-484.8(and)-480.1(lung)-480.6(pa-)]TJ 0 -1.2266 TD [(renchyma)-374.9(surrounding)-380(these)-384.3(airways,)-373.9(a)-372.6(C/P)-377.6(of)-376.3(about)-381.6(1)-372.6(re-)]TJ 0 -1.2203 TD [(ects)-307.5(primarily)-305.7(deposition)-312.9(in)-304.1(the)-307.3(pulmonary)-311.8(airspaces)-309.9(distal)]TJ T* [(to)-376.3(anatomic)-379.1(dead)-378.5(space.)-383.7(Increases)-380.5(in)-380(C/P)-377.6(to)-382.6(values)-379.4(greater)]TJ 0 -1.2266 TD [(than)-335.5(1)-328.3(reect)-338.4(an)-331.7(increased)-339.3(bronchial)-336.7(airway)-331.8(deposition.)]TJ 1.1128 -1.2203 TD [(The)-297.1(whole)-308.4(lung)-297.2(ROI)-306.6(of)-300.4(the)-300.9(right)-303.4(lung)-303.5(\(Fig.)-306.6(2\))-297.2(was)-306(used)-302.8(to)]TJ -1.1128 -1.2203 TD [(determine,)-415.9(by)-407.2(computer)-420.7(analysis,)-411.5(the)-414.7(whole)-409.6(lung)-417.4(retention)]TJ 0 -1.2266 TD [(\(decay)-322.7(and)-328.4(background)-320.4(corrected\))-328.9(as)-323.3(a)-328.3(fraction)-326.3(of)-325.7(the)-326.2(initial)]TJ 0 -1.2203 TD [(counts)-406.9(in)-405.3(the)-408.4(right)-410.9(lung,)-407.6(over)-408.8(the)-402.1(94-min)-408.6(clearance)-409.7(period.)]TJ T* [(Fractional)-421.8(retention)-425.5(at)-423.6(10-min)-421.3(intervals)-424.1(throughout)-425.8(the)-421.1(pe-)]TJ 0 -1.2266 TD [(riod)-332.5(was)-337.6(determined)-340.1(using)-342.8(the)-332.5(sum)-341.7(of)-338.4(two)-333.7(2-min)-339.6(images)-335(at)]TJ 0 -1.2203 TD [(each)-514.2(time)-507.3(point,)]TJ /F8 1 Tf 8.0175 0 TD (e.g)Tj /F5 1 Tf 1.1381 0 TD [(.,)-511.7(retention)-514(at)-512.1(60)-169.7(min)-510.3(was)-508.3(determined)]TJ -9.1556 -1.2203 TD [(from)-273.4(the)-275.6(sum)-278.4(of)-275.1(the)-275.6(6062-)-269.9(and)-277.8(6264-min)-274.4(images.)-274.7(Similarly,)]TJ T* [(R24)-332(was)-331.2(calculated.)]TJ /F12 1 Tf 0 -2.7821 TD [(Statistical)-336.1(methods)]TJ /F5 1 Tf 1.1128 -1.8336 TD [(An)-327.3(overall)-326.8(signicance)-330.4(level)-330.1(of)]TJ /F8 1 Tf 14.0432 0 TD (p)Tj /F9 1 Tf .6702 0 TD ()Tj /F5 1 Tf .7145 0 TD [(0.05)-330.2(was)-324.9(considered)-332.9(to)]TJ -16.5407 -1.2203 TD [(be)-358.4(signicant.)-366.2(All)-362.5(values)-360.4(are)-360.5(expressed)-363.6(as)-361.2(the)-364.2(mean)-360.8(\()]TJ /F9 1 Tf 24.084 0 TD ()Tj /F5 1 Tf .7145 0 TD (SD\).)Tj ET q 1 i 311.527 732.245 m 549.184 732.245 l 549.184 495.779 l 311.527 495.779 l W n q 237.657 0 0 236.466 311.527 495.779 cm /Im2 Do Q Q BT /F10 1 Tf 8.9663 0 0 8.9663 310.8472 478.9983 Tm [(FIG.)-260.9(2.)]TJ /F5 1 Tf 6.7246 0 0 5.9768 346.9038 482.9668 Tm (133)Tj 8.9663 0 0 8.9663 356.9952 478.9983 Tm [(Xe)-263.4(equilibrium)-257.8(and)-265.1(initial)]TJ 6.7246 0 0 5.9768 460.2896 482.9668 Tm (99m)Tj 8.9663 0 0 8.9663 472.8755 478.9983 Tm [(Tc-SC)-267(aerosol)-263.4(scans)]TJ -18.0709 -1.1128 TD [(with)-255.6(whole)-257.8(lung)-259.3(and)-258.8(central)-259.7(ROI)-256(for)-263.2(a)-252.4(male)-259.8(\()]TJ /F8 1 Tf 19.639 0 TD (top)Tj /F5 1 Tf 1.2583 0 TD [(\))-259.7(\(C/P)]TJ /F9 1 Tf 2.9781 0 TD (=)Tj /F5 1 Tf .7208 0 TD (1.53\))Tj -24.5961 -1.1065 TD [(and)-334.7(female)-336(\()]TJ /F8 1 Tf 5.5831 0 TD (bottom)Tj /F5 1 Tf 2.7441 0 TD [(\))-335.6(\(C/P)]TJ /F9 1 Tf 3.054 0 TD (=)Tj /F5 1 Tf .7208 0 TD [(1.54\))-330.7(subject)-340.5(at)-328.8(.)]TJ /F3 1 Tf -40.1062 32.4112 TD [(MUCOCILIARY)-339.2(AND)-337.2(COUGH)-337(CLEARANCE)-334.5(METHODS)-27497.5(159)]TJ ET endstream endobj 59 0 obj <>stream AdobedC        s!1AQa"q2B#R3b$r%C4Scs5D'6Tdt& EFVU(eufv7GWgw8HXhx)9IYiy*:JZjz??OuS5Nj9rֵUAws|\S5Nj9sTS5NjKG ?'TS;8 q_Iʈ0R(ё/U;eU1ƼdE! |B< GJcl~BՆ54KQ!@LPBNDSG7 Po _Ocke$S%_jDdS6lٳf͏R)ˉ4QIiRN@d6xo8ďA6lٳf͛6lKGc 39˿?,M͛5aҳ?a1RM|q M u+ڰqPXZ*گAr:~}@~?dс|qX¤lT1<{cJCZIur&e kVܩ+f͛6lٳg ]j?͞]x|gnlؽ&Bjq^M5CT4ٽ찣0n cqV v" O:Df{iesn$Uhǥsp:xM.8mHI8QC)ᜒxJH;&w,E =rFdE> Ob\#4㴝:Sh1'gY@S`re&{SB~nVl+S]#"f͖roCX.]BHv~ Jw!"v+1Vlٳf͛=8_Qz6ywse"3ɹbcdfq1GvQn- k%aPn#8E)p42p r|FPzPN8;+F9 JZw"U8`μӢ܎\Q_pV-#㈚PP1땛6J4?8_Ȧlٳe`P9M2QG8UT;NUA卑E9D*$V !2 S=3ef͛6lٳ.o@.o>XFy76lQYEi]: XVFƒ.8Q鉰P]GR2tIUF{B8`H1ABC)ە:c*)!W<04_T!$${G=ޙiw,ZYxwJ 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[(reproducible)-342.9(between)-351(sites)-341.6(with)-344.1(the)-345.2(use)-344(of)-344.7(the)-345.2(Spira)-338.7(dosim-)]TJ 0 -1.2203 TD [(eter,)-408.5(which)-415.9(provides)-411.7(a)-404.2(ow)-412.1(signal)-414(feedback)-409.2(for)-408.6(subjects)-417.7(to)]TJ T* [(monitor.)-374.5(This)-378(breathing)-380.1(pattern)-378.8(was)-375.5(chosen)-383.1(because)-378.7(it)-377.1(pro-)]TJ 0 -1.2266 TD [(duced)-310(sufcient)-309.9(inspiratory)-312.6(ow)-310.9(rates)-311.7(to)-306.7(allow)-308.2(impaction)-314.9(of)]TJ 0 -1.2203 TD [(particles)-547(in)-550.7(the)-547.5(large)-545.5(bronchial)-551.7(airways)-548.1(with)-546.5(a)-543.3(relatively)]TJ T* [(small)-492.3(TV)-492.7(\(less)-493.4(than)-499.9(500)-162.9(mL\))-494.2(to)-496.4(minimize)-495.4(penetration)-495.9(and)]TJ 0 -1.2266 TD [(deposition)-401.4(of)-401.6(particles)-401.6(in)-405.3(the)-402.1(alveolar)-402.2(region.)-397(Nevertheless,)]TJ 0 -1.2203 TD [(the)-351.5(mean)-354.5(R24)-357.3(of)-351(about)-356.3(0.6)-349.7(for)-358(all)-354.3(sites)-354.3(suggests)-355.9(that)-351.6(a)-353.6(large)]TJ T* [(proportion)-329.6(of)-332(alveolar)-326.3(deposition)-331.9(still)-334.9(occurs)-327.2(for)-332.7(the)-326.2(particle)]TJ T* [(size/inhalation)-517.2(pattern)-517.9(used)-511.4(in)-512.8(these)-517.1(studies.)-519.6(Further)-516.8(de-)]TJ 0 -1.2266 TD [(velopment)-426.9(of)-420.6(methods)-425.7(should)-420(consider)-424.9(optimizing)-424.7(particle)]TJ 0 -1.2203 TD [(size/inhalation)-453.9(maneuvers)-447(to)-452.2(allow)-447.3(for)-452.9(an)-445.5(improved)-452.2()55(sig-)]TJ T* [(nal)54.9()-330.7(from)-336.6(the)-338.9(bronchial)-330.4(airways.)]TJ 6.7246 0 0 5.9768 440.9007 466.7527 Tm (\(15\))Tj 8.9663 0 0 8.9663 320.8251 451.7857 Tm [(As)-603.4(a)-612.8(metric)-608.5(for)-610.9(comparing)-606.9(our)-611.8(retention)-608.9(versus)-612.3(time)]TJ -1.1128 -1.2203 TD [(curves)-496.5(in)-493.8(this)-495.6(report,)-502(we)-494.7(have)-496.7(used)-492.4(the)-496.9(AUC)-496.2(or)-496.7(average)]TJ T* [(retention)-514(over)-516.3(the)-509.6(90-min)-516.1(period)-510.8(of)-515.4(observation)-512.7(\(AUC90\))]TJ 0 -1.2266 TD (\()Tj /F8 1 Tf .3225 0 TD (i.e)Tj /F5 1 Tf .9042 0 TD [(.,)-606.5(average)-611.7(of)-610.2(the)-610.8(10-min)-611(retention)-615.2(values)-607(from)-608.5(10)-612.3(to)]TJ -1.2266 -1.2203 TD [(90)-163.4(min,)-279.3(respectively\).)-290.3(There)-278.8(has)-282.4(not)-278.5(been)-285.8(a)-277.7(single)-281.6(method)-285.3(for)]TJ T* [(analyzing)-489.1(retention)-495.1(versus)-492.2(time)-488.3(curves)-496.5(in)-487.5(the)-490.6(literature.)]TJ 6.7246 0 0 5.9768 542.2109 400.9889 Tm (\(2\))Tj 8.9663 0 0 8.9663 310.8472 386.0219 Tm [(Approaches)-396.7(have)-395.6(ranged)-390.3(from)-393.5(reporting)-402.9(retentions)-395.2(at)-392(a)-391.5(gi-)]TJ T* [(ven)-238(time)-235.4(point)-239.2(to)-237.2(multiexponential)-241.3(ts)-238.7(of)-237.2(the)-237.7(retention)-242.1(versus)]TJ T* [(time)-235.4(data.)-239.4(Once)-239.6(an)-243.2(intervention)-243.5(occurs,)]TJ /F8 1 Tf 17.2995 0 TD (e.g)Tj /F5 1 Tf 1.1381 0 TD [(.,)-233.5(in)-240.9(our)-238.8(case)-240.3(CC)-240.6(or)]TJ -18.4376 -1.2203 TD [(with)-369.4(therapies,)]TJ 6.7246 0 0 5.9768 370.3747 357.1653 Tm (\(5,6\))Tj 8.9663 0 0 8.9663 386.4755 353.1967 Tm [(it)-377.1(becomes)-371.9(more)-374(difcult)-375.1(to)-376.3(attribute)-371.2(ex-)]TJ -8.4348 -1.2266 TD [(ponential)-416.2(decay)-410.8(to)-407.9(these)-416(data.)-410.1(Exponential)-421.4(ts)-409.5(of)-414.2(retention)]TJ 0 -1.2203 TD [(versus)-277.2(time)-273.4(data)-274.4(may)-273.4(also)-279(be)-276.2(better)-271.4(than)-278.6(linear)-276.1(ts)-276.7(over)-276(very)]TJ T* [(long)-273.3(observation)-278.8(periods.)-274.7(Figure)-279.9(7)-271.4(shows)-276(that,)-278.6(for)-275.8(the)-275.6(period)]TJ 0 -1.2266 TD [(of)-262.5(MCC)-258.4(observation)-266.1(in)-259.8(our)-257.7(study)-263.5(prior)-262(to)-262.5(cough)-264.1(intervention)]TJ 0 -1.2203 TD [(\(60)-163.9(min\),)-336.7(there)-333.1(is)-327.3(no)-334.9(difference)-333(between)-332.1(a)-334.6(single)-332.2(exponential)]TJ T* [(versus)-429(a)-435.8(linear)-427.9(t)-433.4(of)-433.2(the)-433.7(data)-426.1(and)-435.9(the)-427.4(slopes)-433.8(\(either)-438.3(expo-)]TJ 0 -1.2266 TD [(nential)-266.6(or)-269(linear)-269.8(in)-272.5(percent)-270.6(clearance/time)-275(is)-264.1(similar)-268.9(between)]TJ 0 -1.2203 TD [(the)-376.8(two)-371.6(ts\),)]TJ /F8 1 Tf 6.0953 0 TD (e.g)Tj /F5 1 Tf 1.1381 0 TD [(.,)-372.6(0.23)-374.5(and)-372.6(0.21%/min,)-373.9(respectively,)-378.4(for)-377(the)]TJ -7.2334 -1.2203 TD [()-311.4(data)-318.6(in)-316.7(Figure)-311.5(3.)-318.6(For)-311.4(retention)-318(versus)-321.5(time)-311.3(data)-318.6(where)]TJ T* [(the)-414.7(time)-412.5(points)-417.5(are)-411.1(equally)-415(separated,)]TJ /F8 1 Tf 17.6093 0 TD (e.g)Tj /F5 1 Tf 1.1318 0 TD [(.,)-410.5(every)-416.6(10)-169.7(min)-409.1(in)]TJ -18.7411 -1.2266 TD [(our)-321(case,)-319.1(the)-319.9(average)-320.8(of)-319.4(the)-319.9(retentions)-325.6(over)-320.3(that)-320(period)-321.1(\()]TJ /F8 1 Tf 25.0324 0 TD (e.g)Tj /F5 1 Tf 1.1318 0 TD (.,)Tj -26.1642 -1.2203 TD [(1060)-162(min)-308(for)-313.8(AUC60\),)-308.9(or)-307(AUC,)-309.4(provides)-310.5(a)-309.3(similar)-306.9(metric)-311.3(to)]TJ T* [(the)-364.2(slope)-369.3(for)-364.3(linear)-364.6(t)-363.9(through)-370.6(the)-364.2(retention)-368.6(values.)-369.7(For)-362(ex-)]TJ 0 -1.2267 TD [(ample,)-270.3(the)-275.6(AUC60)-273.9(\(Table)-270.1(2\))-271.9(for)-275.8()-273.4(is)-270.4(0.92)-273.3(\(associated)-270.3(with)]TJ 0 -1.2203 TD [(the)-617.1(mean)-613.7(retention)-621.5(at)-619.6(the)-617.1(midpoint)-616.3(of)-616.6(the)-617.1(time)-614.8(points,)]TJ T* [(35)-163.4(min\).)-475.8(To)-473.7(obtain)-475.7(an)-470.8(average)-472.6(%/min)-470.7(cleared,)-476.6(one)-473.9(would)]TJ 0 -1.2266 TD [(divide)-310.9(100)-308.4(*)-310.5(\()0(1)-309.8()-303(0.92\))-311.7(by)-306(the)-313.6(average)-314.5(time)-305(point)-315(of)-306.8(the)-313.6(data,)]TJ 0 -1.2203 TD [(in)-405.3(this)-407(case)-411(35)-169.7(min,)-405.8(to)-407.9(get)-409.5(0.23%/min)-402.6(\(similar)-408.5(to)-414.2(the)-408.4(linear)]TJ T* [(and)-303.1(exponential)-310.8(slopes)-307.4(discussed)-304.9(above\).)-307.9(In)-302.7(other)-310.7(words,)-303.2(all)]TJ 0 -1.2266 TD [(these)-428.6(metrics)-432.7(provide)-429.3(similar)-427(characterization)-439.1(of)-426.9(the)-427.4(reten-)]TJ 0 -1.2203 TD [(tion)-339(versus)-334.1(time)-336.6(data)-337.6(over)-332.9(our)-339.9(period)-333.7(of)-338.4(observation.)-338.6(In)-334.3(the)]TJ T* [(interest)-344.8(of)-344.7(simplicity,)-343.9(we)-343(propose)-339(to)-344.7(take)-345.7(the)-338.9(average)-346.1(of)-338.4(the)]TJ T* [(10-min)-256.9(retention)-267.4(values)-265.6(over)-257(the)-263(period)-264.2(of)-262.5(observation)-259.8(\(AUC)]TJ 0 -1.2266 TD [(analysis\))-472.2(for)-471.8(data)-476.7(with)-470.6(equally)-478.2(spaced)-472.3(retention)-476.1(values)-474.2(in)]TJ 0 -1.2203 TD [(time.)-434.3(For)-431.5(different)-441.8(data)-432.5(sets,)]TJ /F8 1 Tf 13.3919 0 TD (e.g)Tj /F5 1 Tf 1.1381 0 TD [(.,)-429.5(uneven)-438.6(time)-437.7(intervals)-436.7(or)]TJ -14.53 -1.2203 TD [(longer)-318.2(periods)-316.1(of)-313.1(observation,)-319.6(linear)-320.4(or)-313.3(exponential)-317.1(ts)-320.9(may)]TJ 0 -1.2267 TD [(be)-333.1(more)-336.1(appropriate.)]TJ ET q 1 i 60.321 732.189 m 298.261 732.189 l 298.261 587.962 l 60.321 587.962 l W n q 238.023 0 0 144.227 60.321 587.962 cm /Im5 Do Q Q BT /F10 1 Tf 8.9663 0 0 8.9663 59.7543 571.2377 Tm [(FIG.)-551.8(5.)]TJ /F5 1 Tf 4.3122 0 TD [(Average)-556.7(retention)-558.3(at)-550.1(each)-552.2(time)-551.6(point)-555.3(for)-554(males)]TJ -4.3122 -1.1128 TD (\()Tj /F8 1 Tf .3225 0 TD (n)Tj /F9 1 Tf .7208 0 TD (=)Tj /F5 1 Tf .7208 0 TD [(31\))-246.1(vs.)-251.6(females)-255.1(\()]TJ /F8 1 Tf 6.9552 0 TD (n)Tj /F9 1 Tf .7145 0 TD (=)Tj /F5 1 Tf .7208 0 TD [(19\))-252.4([mean)-247.4(C/P)]TJ /F9 1 Tf 6.6327 0 TD (=)Tj /F5 1 Tf .7208 0 TD [(1.76)-248(\()-82.7(M)0(\))-252.2(vs.)-251.6(1.73)-248(\(F\)].)]TJ ET q 1 i 60.321 373.549 m 298.261 373.549 l 298.261 84.302 l 60.321 84.302 l W n q 238.023 0 0 289.247 60.321 84.302 cm /Im6 Do Q Q BT /F10 1 Tf 8.9663 0 0 8.9663 59.7543 67.4645 Tm [(FIG.)-267.3(6.)-1001.5(\(A\))]TJ /F5 1 Tf 5.7096 0 TD [(R)14.7(e)0(p)17.7(e)12.8(a)13.1(t)-259.7(m)15.1(e)0(a)19.6(s)0(u)22.6(r)0(e)18.4(s)-254.2(o)16.2(f)-259.7(AU)22.5(C)12.5(9)13.1(0)-258.7(i)15.4(n)]TJ /F8 1 Tf 13.1769 0 TD (n)Tj /F9 1 Tf .7082 0 TD (=)Tj /F5 1 Tf .7082 0 TD -.0129 Tc [(16)-265.3(at)-272.6(U)-12.9(N)11(C.)]TJ /F10 1 Tf 5.0773 0 TD -.0122 Tc [(\(B)-12.2(\))]TJ /F5 1 Tf -25.3802 -1.1065 TD 0 Tc [(Re)21.2(pe)17.7(a)13.1(t)-322.9(me)21.5(as)18.1(ur)23.2(e)12.7(s)-323.8(of)-313.1(2)13.1(4)0(-)19(h)0(r)-313.9(r)0(e)24.7(t)0(e)18.6(n)0(t)21.4(i)0(o)19(n)-319.5(\(R)20.6(24)19.9(\))-322.9(i)0(n)]TJ /F8 1 Tf 19.3165 0 TD (n)Tj /F9 1 Tf .7082 0 TD (=)Tj /F5 1 Tf .7082 0 TD [(1)13.1(6)-322(at)-316.1(UN)23.9(C)12.5(.)]TJ /F3 1 Tf -20.7328 77.1964 TD [(MUCOCILIARY)-339.2(AND)-337.2(COUGH)-337(CLEARANCE)-334.5(METHODS)-27497.5(161)]TJ ET endstream endobj 78 0 obj <>stream AdobedC       - s!1AQa"q2B#R3b$r%C4Scs5D'6Tdt& EFVU(eufv7GWgw8HXhx)9IYiy*:JZjz?Nlٳf_Iֿ7Ϟr]FsOey\[L592pO#Mq7#Mq7#Mq N,|۝;ȑŞ^nt؞5U϶w_F6?^o_F6?^o_F6?^o_F6?^i_j5;2TˈQGuEYME0WכWכWכWכWכWכWכWכWכWכWכWכWכWכWכWכWכWכWכWכWכWכWכWכWכWכWכWכWכWכWכWכWכWכWכWכWכWכW׃?̓BmiSÖC$P\̈́vFui>(ć%>eΌ$%ؘٰՋbđt14-+,/ǎԦpݳi-%˧Yᱹq)ٳ峧˾:ט/ٳ:p܈'ĿΙ+͛<JXD ^D 9ķwhݠ[ Ĵ#њfO|͛6lٳf͛6lٳf͛6lٲ;O\}EI,ٳf͜HOΉ6յK'K/X21ĥnvZbyT|eIZYF蒳*4#:r$xF*8'i^۳f͐$W@ f͛ ^Kɥ4lٲQy{3OfN<2$re* F"jN KLPKmk&O\r>Zt΁6lٳf͛6lٳf͛6G|k2E6lٳ>Q7Y3f¿4z~\Դ+VRG_:g9ףMky)}x Z Xqv⭽HΩegoeeogl-HaOB-6#2Ar䈊 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[(trolled)-488.1(coughing)-490.5(into)-484.4(a)-486.4(study)-484.8(design)-489.8(may)-482(depend)-484.8(on)-486.7(the)]TJ 0 -1.2266 TD [(patient)-603(group)-598.6(and/or)-600.4(the)-598.1(therapeutic)-604.2(intervention)-603.9(to)-603.9(be)]TJ 0 -1.2203 TD (studied.)Tj 6.7246 0 0 5.9768 344.8629 554.3998 Tm (\(2\))Tj 8.9663 0 0 8.9663 355.8613 550.4313 Tm [(Postintervention)-382.2(measures)-374.6(of)-376.3(baseline)-369.6(MCC)-372.2(may)]TJ -4.7738 -1.2203 TD [(also)-418.1(be)-409(important)-414.4(\()]TJ /F8 1 Tf 8.713 0 TD (e.g)Tj /F5 1 Tf 1.1381 0 TD [(.,)-410.5(beyond)-409.9(90)-169.7(min)-409.1(in)-411.6(our)-415.8(case\))-411.5(for)-408.6(un-)]TJ -9.8511 -1.2266 TD [(derstanding)-243.9(the)-244(effect)-240.8(of)-237.2(the)-237.7(intervention.)-246.4(However,)-242.5(it)-237.9(should)]TJ 0 -1.2203 TD [(also)-247.4(be)-238.3(recognized)-244(that)-244.1(postintervention)-249.4(MCC)-239.4(may)-241.8(be)-238.3(slower)]TJ T* [(simply)-245.7(because)-246(the)-244(signal)-243.3(\(tracer\))-241.8(has)-244.5(been)-241.6(removed)-244.8(from)-241.8(the)]TJ T* [(fastest)-408.1(clearing)-400(airways)-402.6(by)-400.9(the)-402.1(end)-398.3(of)-401.6(the)-402.1(intervention,)]TJ /F8 1 Tf 25.2664 0 TD (i.e)Tj /F5 1 Tf .9042 0 TD (.,)Tj -26.1705 -1.2266 TD [(not)-379.7(that)-370.6(the)-376.8(intervention)-376.3(has)-370.9(resulted)-376.9(in)-373.6(a)-366.2(slowing)-374.7(of)-376.3(MCC)]TJ 0 -1.2203 TD [(post)-341(intervention.)]TJ 1.1128 -1.2203 TD [(We)-302.4(observed)-303.6(signicantly)-308(faster)-305.9(clearance)-302.2(through)-307.4(90)-169.7(min)]TJ -1.1128 -1.2266 TD [(in)-380(females)-381.6(versus)-384.7(males)-374.9(in)-380(our)-377.9(combined)-380.6(data)-381.9(set.)-377.7(Further-)]TJ 0 -1.2203 TD [(more,)-326.3(this)-324.8(nding)-330.6(was)-324.9(not)-322.8(dependent)-330.5(on)-322.3(gender)-327.5(differences)]TJ T* [(in)-329.4(regional)-333.9(deposition,)]TJ /F8 1 Tf 10.3 0 TD (i.e)Tj /F5 1 Tf .9042 0 TD [(.,)-328.3(there)-333.1(were)-330.9(no)-328.6(differences)-334.3(in)-329.4(C/P)]TJ -11.2042 -1.2266 TD [(ratio)-354.7(or)-351.2(R24)-351(between)-357.4(the)-351.5(two)-352.6(groups.)-356.3(This)-352.7(nding)-355.8(suggests)]TJ 0 -1.2203 TD [(that)-402.2(gender)-403.3(distribution)-407.9(should)-401.1(be)-396.3(considered)-402.5(in)-398.9(study)-402.6(de-)]TJ T* [(sign)-417.3(and)-410.6(data)-413.5(analysis)-408.5(when)-413(comparing)-417.2(an)-407.6(intervention)-420.5(at)]TJ 0 -1.2266 TD [(one,)-375.7(or)-376.5(several)-372.3(sites,)-376.2(in)-373.6(future)-377.3(clinical)-376(studies)-371.3(of)-376.3(MCC.)-375.1(Our)]TJ 0 -1.2203 TD [(observed)-487(differences)-486.1(in)-481.1(gender)-479.2(are)-480.6(similar)-483.9(to)-477.5(those)-488.4(previ-)]TJ T* [(ously)-500.3(reported)-502(by)-495.7(others.)-498.3(Svartengren)]TJ /F8 1 Tf 18.0077 0 TD [(et)-500.7(al)]TJ /F5 1 Tf 1.9158 0 TD (.)Tj 6.7246 0 0 5.9768 493.9085 368.107 Tm (\(18\))Tj 8.9663 0 0 8.9663 509.4424 364.1385 Tm [(reported)-502(a)]TJ -21.9026 -1.2203 TD [(higher)-337.8(percent)-333.8(retention)-337(\()]TJ /F8 1 Tf 11.337 0 TD (i.e)Tj /F5 1 Tf .9105 0 TD [(.,)-328.3(slower)-332.3(MCC\))-334.7(in)-329.4(healthy)-337.1(males)]TJ -12.2475 -1.2266 TD (\(41)Tj /F9 1 Tf 1.4922 0 TD ()Tj /F5 1 Tf .7208 0 TD [(23%\))-254(versus)-251.9(females)-261.4(\(26)]TJ /F9 1 Tf 10.5782 0 TD ()Tj /F5 1 Tf .7208 0 TD [(17%\))-254(2)-163.9(h)0(r)-257(after)-254(inhalation)-257(of)-256.2(6-)]TJ /F7 1 Tf -13.5121 -1.2203 TD (l)Tj /F5 1 Tf .5564 0 TD [(m)-313.7(particles,)-322.3(and)-322(Garrard)]TJ /F8 1 Tf 11.2738 0 TD [(et)-323.6(al)]TJ /F5 1 Tf 1.7388 0 TD (.)Tj 6.7246 0 0 5.9768 436.9322 335.2251 Tm (\(19\))Tj 8.9663 0 0 8.9663 450.8786 331.2566 Tm [(reported)-318.6(slower)-319.7(proximal)]TJ -15.371 -1.2203 TD [(clearance)-390.7(in)-380(nine)-383.3(men)-380.2(compared)-383.5(with)-388.4(four)-378.3(women.)-387.6(On)-379.5(the)]TJ 0 -1.2266 TD [(other)-291.8(hand,)-290.4(Yeates)]TJ /F8 1 Tf 8.498 0 TD [(et)-292(al)]TJ /F5 1 Tf 1.7072 0 TD (.)Tj 6.7246 0 0 5.9768 406.8282 313.3416 Tm (\(20\))Tj 8.9663 0 0 8.9663 420.4912 309.3164 Tm [(reported)-287(no)-290.7(difference)-295.1(in)-291.4(tracheal)]TJ -11.9819 -1.2203 TD [(transport)-320.5(rates)-318(in)-316.7(32)-315.2(healthy)-318.1(men)-317(versus)-321.5(10)-315.2(healthy)-318.1(women,)]TJ T* [(and)-379(Hasani)]TJ /F8 1 Tf 5.5199 0 TD [(et)-374.2(al)]TJ /F5 1 Tf 1.7894 0 TD (.)Tj 6.7246 0 0 5.9768 380.8629 291.4015 Tm (\(21\))Tj 8.9663 0 0 8.9663 395.2629 287.433 Tm [(also)-380.2(found)-371.4(no)-379.2(gender)-371.7(difference)-383.6(in)-373.6(tra-)]TJ -9.1682 -1.2266 TD [(cheobronchial)-329.4(MCC)-315.3(\()]TJ /F8 1 Tf 9.4591 0 TD (i.e)Tj /F5 1 Tf .9042 0 TD [(.,)-322(corrected)-322.1(for)-320.1(24-hr)-319.7(retentions\))-319.8(over)]TJ -10.3633 -1.2203 TD [(a)-347.3(6-hr)-351.8(period.)-349.3(The)-347.7(explanation)-348.3(for)-351.7(our)-346.3(observed)-347.9(gender)-352.7(dif-)]TJ T* [(ferences)-460.1(in)-455.8(MCC)-454.4(is)-453.8(unknown.)-459.5(However,)-457.5(our)-453.8(data)-457.7(suggest)]TJ T* [(that)-282(the)-275.6(gender)-270.5(difference)-282.4(might)-274.9(be)-276.2(most)-274(evident)-276.5(in)-272.5(the)-275.6(early)]TJ 0 -1.2266 TD [(period)-485.5(of)-483.8(observation)-481.1(post)-486.5(deposition)-483.6(of)-477.5(the)-484.3(radioaerosol,)]TJ 0 -1.2203 TD [(which)-434.9(involves)-439.6(clearance)-435(from)-431.5(the)-433.7(most)-438.4(proximal)-434.8(bronchi.)]TJ T* [(Compared)-283.2(with)-280.9(adult)-279.8(males,)-276.6(females)-280.4(likely)-278.6(contain)-277.9(proximal)]TJ 0 -1.2267 TD [(bronchi)-732(with)-729.8(shorter)-730.1(pathway)-731.1(lengths)]TJ 6.7246 0 0 5.9768 478.2046 203.7543 Tm (\(2224\))Tj 8.9663 0 0 8.9663 505.8707 199.729 Tm [(and)-726.7(conse-)]TJ -21.5042 -1.2203 TD [(quently)-346.3(shorter)-344.4(times)-344.2(required)-348.6(for)-345.4(particle)-343.4(transit)-344.5(and)-341(clear-)]TJ T* [(ance.)-352.8(These)-355.3(airway)-350.7(path)-352.5(lengths)-351.5(may)-349.3(not)-354.4(correlate)-354.5(with)-350.5(the)]TJ 0 -1.2266 TD [(patients)-505(height,)-504.9(because)-498.9(we)-494.7(observed)-505.9(no)-499.3(relationship)-503.9(be-)]TJ 0 -1.2203 TD [(tween)-340.4(AUC90)-330.8(and)-334.7(subject)-340.5(height)-331.2(in)-335.7(this)-337.5(study.)]TJ 1.1128 -1.2203 TD [(Repeat)-289.9(measures)-279.8(at)-284.5(the)-288.3()-279.8(site)-283.4(provide)-290.2(paired)-279.9(standard)]TJ -1.1128 -1.2266 TD [(deviation)-383.6(data)-381.9(that)-383.2(should)-382.1(be)-377.4(useful)-387.3(for)-377(calculating)-384.5(sample)]TJ 0 -1.2203 TD [(sizes)-460.8(in)-462.2(crossover)-458.4(studies)-466.1(of)-458.5(MCC/CC)-457.7(associated)-459.5(with)-457.9(an)]TJ T* [(intervention.)-474(For)-469.5(example,)-468.4(to)-464.8(show)-470.7(a)-461.1(decrease)-471.4(of)-464.8(0.065)-468.9(in)]TJ T* [(AUC90)-286.5([)]TJ /F8 1 Tf 3.857 0 TD (i.e)Tj /F5 1 Tf .9042 0 TD [(.,)-284(an)-281.1(improvement)-286.1(of)-287.8(50%)-278.9(in)-285.1(MCC/CC)-280.7(associated)]TJ -4.7612 -1.2266 TD [(with)-318.8(an)-319(intervention)-319.4(over)-320.3(the)-313.6(mean)-316.5(AUC90)-318.1(of)-313.1(0.87)-317.6(\()]TJ /F8 1 Tf 23.1988 0 TD (i.e)Tj /F5 1 Tf .9042 0 TD [(.,)-315.7(0.13)]TJ -24.1029 -1.2203 TD [(clearance\))-397.5(for)-389.6(this)-388.1(group)-390(of)-395.3(subjects],)-389.4(an)-388.6(N)-392(o)0(f)-388.9(1)0(5)-391(would)-391.7(be)]TJ T* [(required)-456.1(for)-452.9(a)-454.8(two-sided)-452.4(paired)-450.6(analysis)-452.8(with)]TJ /F7 1 Tf 21.4094 0 TD (a)Tj /F9 1 Tf .6639 0 TD (=)Tj /F5 1 Tf .7208 0 TD [(0.05)-450.4(and)]TJ -22.7941 -1.2267 TD (power)Tj /F9 1 Tf 2.9907 0 TD (=)Tj /F5 1 Tf .7208 0 TD [(0.80.)-472.3(Previous)-479.6(studies)-478.8(at)-480.5()-475.8(in)-474.8(healthy)-476.2(subjects)]TJ ET q 1 i 62.929 732.189 m 300.132 732.189 l 300.132 570.784 l 62.929 570.784 l W n q 237.528 0 0 161.405 62.929 570.784 cm /Im7 Do Q Q BT /F10 1 Tf 8.9663 0 0 8.9663 62.022 554.0597 Tm [(FIG.)-830(7.)]TJ /F5 1 Tf 4.5904 0 TD [(Comparison)-835.1(of)-825.2(linear)-832.5(\(data)-831.3(expressed)-837.8(as)-829.1(%)]TJ -4.5904 -1.1128 TD (cleared)Tj /F9 1 Tf 3.3132 0 TD (=)Tj /F5 1 Tf .7208 0 TD [(100)-276.7(*)-278.9([)0(1)-278.2()-284(Ret\(t\)]\))-285.2(vs.)-276.9(exponential)-285.5(\(data)-281.2(expressed)-287.7(as)]TJ -4.034 -1.1128 TD [(%)-450.6(cleared)]TJ /F9 1 Tf 4.5968 0 TD (=)Tj /F5 1 Tf .7208 0 TD [(100)-453.8(*)-449.6([Ln)-455.3(\(Ret\(t\)\)]\))-463.1(t)-452.4(for)-452.9()-456.8(mean)-449.3(data)-451.4(in)]TJ -5.3176 -1.1128 TD [(Figure)-336.8(3.)-331.2(R2)]TJ /F9 1 Tf 5.5831 0 TD (=)Tj /F5 1 Tf .7208 0 TD [(0.99)-330.2(for)-332.7(both)-339.8(regressions.)]TJ /F3 1 Tf -6.3039 25.1525 TD (162)Tj 46.3849 0 TD [(BENNETT)-338(ET)-338.7(AL.)]TJ ET endstream endobj 84 0 obj <>stream AdobedC       Q s!1AQa"q2B#R3b$r%C4Scs5D'6Tdt& EFVU(eufv7GWgw8HXhx)9IYiy*:JZjz?Nl?:|d<1Q_2ivpSoN\>6 qY5Y2Y~M>N;PG;{7v^B\OJ.-ݶmKO[Gi,W HgDնHZZ[Ekk 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0 -1.2266 TD [(low)-456.9(signal)-458.3(to)-458.5(background)-459.6(at)-455.2(these)-460.2(time)-456.7(points,)-458.4(we)-456.8(would)]TJ 0 -1.2203 TD [(expect)-325.5(the)-319.9(repeat)-318(measures)-324(to)-319.4(be)-314.1(more)-323.4(variable)-315.3(with)-318.8(greater)]TJ T* [(differences)-384.9(in)-373.6(actual)-376.7()55(24-hr)-378.5(times)52.2()-374.9(post)-379(deposition)-382.4(between)]TJ T* [(the)-326.2(repeat)-318(measures.)-320.6(Among)-325.7(the)-319.9(16)-315.2(repeat)-324.3(measures)-324(of)-319.4(R24,)]TJ 0 -1.2266 TD [(10)-308.8(subjects)-316.5(had)-309.4(differences)-309(of)-313.1(less)-309.6(than)-310.3(90)-169.7(min)-308(between)-313.1(their)]TJ 0 -1.2203 TD [()55(24-hr)-448.1(times)52.2()-450.8(a)13.1(nd)-423.7(t)12.2(h)0(e)-426.9(o)0(t)22.1(h)0(e)22(r)-437(si)20.4(x)-432.1(h)0(a)22.4(d)-433(a)-435.8(d)0(i)18.8(f)12.2(f)12.2(e)0(r)18.4(e)12.8(nc)22.6(e)-436.2(o)0(f)-426.9(g)14.6(re)18.4(a)13.1(t)0(e)18.6(r)]TJ T* [(th)15.1(a)13.1(n)-654.6(20)19.9(0)-157.6(m)15.1(in)18.4(.)-660.5(I)16.9(nt)15.1(e)12.8(r)0(e)18.4(s)0(t)23.5(i)0(n)18.4(g)14.6(ly)23.7(,)-660.5(t)12.2(he)-648.2(va)18.7(ri)21.1(a)13.1(b)0(i)23.7(l)0(i)18.2(t)12.2(y)-655.7(o)0(f)-648.2(r)0(e)18.4(p)0(e)24(a)0(t)-651.2(R)0(2)21.6(4)]TJ 0 -1.2266 TD [(me)21.5(as)18.1(ur)23.2(e)12.7(s)-368(wa)24.2(s)-361.7(n)0(o)-353.9(d)0(i)18.8(f)12.2(fe)18.6(re)24.7(nt)-357.9(b)14.6(e)0(t)18.6(w)0(e)23.8(e)0(n)-357.4(t)12.2(he)22(se)-355.3(t)12.2(w)0(o)-352.2(g)0(r)20.2(o)0(u)21.2(p)0(s)-356.8(\()12.2(me)21.5(a)13.1(n)]TJ /F14 1 Tf 0 -1.2203 TD (D)Tj /F5 1 Tf .6576 0 TD [(R2)21.5(4)]TJ /F9 1 Tf 1.802 0 TD (=)Tj /F5 1 Tf .7082 0 TD [(0)13.1(.)0(0)22.9(9)-347.3(fo)15.7(r)-348.5(t)12.2(ho)19.1(se)-342.6(wi)20.1(t)12.2(h)-351.1(le)21.9(ss)-337.7(th)15.1(a)13.1(n)-351.1(9)13.1(0)13.1(-)0(m)20.9(i)0(n)-342(d)0(i)18.8(f)12.2(f)12.2(e)0(r)18.4(e)12.8(nc)22.6(e)-354(v)0(e)18.3(r)0(s)23.3(u)0(s)]TJ /F14 1 Tf -3.1678 -1.2203 TD (D)Tj /F5 1 Tf .6576 0 TD [(R2)21.5(4)]TJ /F9 1 Tf 1.802 0 TD (=)Tj /F5 1 Tf .7082 0 TD [(0)13.1(.)0(0)22.9(6)-309.3(f)12.2(o)0(r)-300.6(t)12.2(ho)19.1(se)-298.4(wi)20.1(t)12.2(h)-313.2(g)14.6(r)0(e)18.4(a)13.1(t)12.2(e)0(r)-304.1(t)12.2(ha)22.4(n)-313.2(2)13.1(0)13.1(0)0(-)-297.2(m)0(i)17.9(n)-306.9(di)18.8(f)12.2(f)12.2(e)0(r)18.4(e)12.8(nc)16.3(e)-309.7(i)15.4(n)]TJ -3.1678 -1.2266 TD [()61.3()0(2)23.9(4)13.1(-)-341.9(h)0(r)-332.9(t)0(i)21.3(m)0(e)21.5()61.3(\))22.9(.)-338(T)0(h)18.9(e)-341.3(fa)19(c)13.4(t)-341.9(th)15.1(a)13.1(t)-341.9(t)12.2(h)0(o)19.1(s)0(e)-330(w)0(i)20.1(t)12.2(h)-344.8(g)14.6(re)18.4(a)13.1(t)0(e)18.6(r)-342.1(di)25.1(ff)18(e)12.7(r)0(e)18.4(n)0(c)22.6(e)0(s)-336.3(i)15.4(n)]TJ 0 -1.2203 TD [(th)15.1(e)-379.3(t)0(i)21.3(m)0(e)-376.8(a)13.1(ss)16.3(o)16.2(c)0(i)16.2(a)13.1(t)12.2(e)0(d)-375.9(w)0(i)20.1(t)12.2(h)-382.8(t)0(h)21.4(e)0(i)21.9(r)-386.4(re)18.4(pe)24(at)-373(R2)21.5(4)-385.2(m)0(e)21.5(a)13.1(su)16.3(re)24.7(s)-387(w)0(e)23.8(r)0(e)-373.6(n)0(o)]TJ T* [(mo)18.6(re)-240.9(va)18.7(ri)21.1(a)13.1(b)0(l)23.7(e)-259.1(\()12.2(s)0(i)20.4(m)0(i)24.2(l)0(a)22.2(r)-259.9(a)13.1(b)14.6(so)21.2(lu)20.4(te)-247(di)25.1(ff)18(e)12.7(r)0(e)18.4(n)0(c)22.6(e)0(\))-247(t)12.2(ha)22.4(n)-256.3(t)0(h)21.4(o)0(s)21.2(e)-259.1(c)13.4(l)0(o)19(s)0(e)24.1(r)-259.9(i)15.4(n)]TJ T* [(ti)21.3(me)-256.7(wo)20.9(ul)20.4(d)-262.2(s)0(u)22.6(g)0(g)22.8(e)0(s)17.8(t)-259.7(th)15.1(a)13.1(t)-266(t)12.2(h)0(e)-256.2(l)15.4(os)21.2(s)-266.9(o)0(f)-256.2(s)0(i)20.4(g)14.6(na)22.4(l)-262.8(a)0(s)18.1(s)0(o)21.2(c)13.4(ia)22.3(te)18.6(d)-262.2(w)0(i)20.1(t)12.2(h)-268.9(l)15.4(ow)]TJ 0 -1.2266 TD [(in)18.4(it)21.3(ia)22.2(l)-389.2(c)13.4(ou)21.2(nt)21.4(s)-387(a)0(n)16.1(d)-382.4(is)20.4(ot)22.1(op)21.2(e)-391.9(d)0(e)22.4(c)13.4(ay)-377(is)-377.9(no)19.1(t)-386.2(p)0(r)23.2(i)0(m)17.9(a)13.1(ri)21.1(ly)-374.7(re)18.4(sp)22.6(on)19.1(si)20.4(b)14.6(l)0(e)]TJ 0 -1.2203 TD [(fo)15.7(r)-316.8(t)0(h)15.1(e)-322.4(i)15.4(n)0(t)21.4(e)0(r)18.4(s)0(u)22.6(b)0(j)22.3(e)0(c)19.8(t)-322.9(va)18.7(ri)27.4(ab)21.4(il)18.2(i)15.4(t)0(y)-314.7(w)0(e)-311.3(s)0(e)17.8(e)-322.4(i)15.4(n)-325.9(R)14.7(2)0(4)-315.2(\()12.2(Fi)23.7(g.)-310.8(6B)22.8(\).)]TJ /F3 1 Tf 0 -3.054 TD (Conclusions)Tj /F5 1 Tf 1.1128 -1.8336 TD [(Using)-500.9(standardized)-497.4(methods,)-498.2(we)-494.7(found)-497.9(that)-497(MCC)-498.6(and)]TJ -1.1128 -1.2266 TD [(MCC/CC)-394.5(were)-394.1(similar)-395.4(in)-392.6(healthy)-394(adult)-399.9(subjects)-392.4(studied)-398.3(at)]TJ 0 -1.2203 TD [(three)-364.8(different)-359.6(sites.)-363.5(In)-359.6(addition,)-357.2(clearance)-365.4(was)-356.5(signicantly)]TJ T* [(faster)-293.2(in)-291.4(females)-293(than)-291.3(males)-286.4(over)-295(the)-288.3(60-)-290.3(and)-290.4(90-min)-288.5(periods)]TJ 0 -1.2266 TD [(post)-379(deposition)-382.4(of)-370(radioaerosol,)-383.3(suggesting)-378.6(a)-372.6(gender)-378(differ-)]TJ 0 -1.2203 TD [(ence)-470.4(in)-468.5(large)-469.6(airway)-470.9(clearance.)-469.5(The)-467.9(standardized)-472.1(protocol)]TJ T* [(used)-599.9(here)-591.9(may)-595.8(prove)-593.5(benecial)-598.2(in)-588.6(multicenter)-604.4(trials)-590.8(for)]TJ T* [(testing)-253.8(new)-245.2(therapies)-250.3(that)-244.1(are)-246.7(designed)-246.1(to)-249.8(improve)-246.8(MCC)-245.7(and)]TJ 0 -1.2266 TD [(MCC/CC,)-321.5(allowing)-319.5(more)-323.4(subjects)-322.8(to)-319.4(be)-320.5(studied)-322.4(in)-316.7(a)-322(shorter)]TJ 0 -1.2203 TD [(period)-359(of)-351(time,)-352.1(and)-353.7(thus)-360.6(bringing)-350.3(new)-352.7(therapies)-357.8(to)-357.3(patients)]TJ T* [(more)-399.3(rapidly.)-404.7(Toward)-396.3(that)-402.2(end,)-394.9(multisite)-403.7(comparisons)-405.5(and)]TJ 0 -1.2267 TD [(repeatability)-375.3(for)-364.3(MCC/CC)-369.2(in)-367.3(patients)-370.3(with)-369.4(airways)-371(disease)]TJ 28.0042 74.5598 TD [(should)-533.8(also)-531.9(be)-535.4(determined.)-532.8(Further)-535.7(improvements)-540.3(to)-534.4(the)]TJ 0 -1.2203 TD [(methodology)-417(described)-426(here)-414.9(may)-418.8(provide)-423(greater)-416.6(differen-)]TJ 0 -1.2266 TD [(tiation)-412(between)-407.9(airway)-407.6(versus)-410(alveolar)-408.5(deposition)-414.1(of)-407.9(parti-)]TJ 0 -1.2203 TD [(cles,)-354.7(thereby)-354.6(enhancing)-355.3(the)-351.5(MCC/CC)-356.6(signal)-350.8(and)-353.7(leading)-358.7(to)]TJ T* [(greater)-334.4(sensitivity)-338.8(for)-332.7(assessing)-338.5(therapeutic)-338.7(effects.)]TJ /F3 1 Tf 0 -2.3332 TD (Acknowledgments)Tj /F5 1 Tf 1.1128 -1.8336 TD [(This)-390.6(study)-389.9(was)-394.5(funded)-390.5(by)-388.2(a)-391.5(grant)-394.2(from)-393.5(the)-389.5(CF)-390.3(Founda-)]TJ -1.1128 -1.2266 TD [(tion.)-639(We)-643.9(gratefully)-644.3(acknowledge)-641.4(the)-642.4(statistical)-645.2(input)-648.7(of)]TJ 0 -1.2203 TD [(Hongtao)-418(Zhang)-413.3(and)-416.9(Haibo)-414.9(Zhou,)-419.3(PhD,)-420.1(and)-410.6(for)-421.3(the)-414.7(mixed)]TJ T* [(model)-335.6(analysis)-332.7(of)-332(MCC)-334.3(data.)]TJ /F3 1 Tf 0 -2.3142 TD [(Author)-332.4(Disclosure)-336.7(Statement)]TJ /F5 1 Tf 1.1128 -1.8336 TD [(The)-328.8(authors)-338.3(declare)-334.6(that)-339(no)-334.9(conicts)-335.5(of)-332(interest)-338.5(exist.)]TJ /F3 1 Tf -1.1128 -2.2193 TD (References)Tj /F5 1 Tf 8.4682 0 0 8.4682 315.0424 538.5258 Tm [(1.)-501.9(Wanner)-647.1(A,)-640.3(Salathe)-646.3(M,)-640.7(and)-640.4(ORiordan)-642(TG:)-642.2(Mucociliary)]TJ 1.2519 -1.2318 TD [(clearance)-323.7(in)-325.3(the)-325.1(airways)-322.3(\(State)-324.3(of)-322(the)-318.4(Art\).)-327.7(Am)-323.3(J)-320.7(Respir)-324.2(Crit)]TJ 0 -1.2385 TD [(Care)-335.7(Med.)-338.6(1996;154:18681902.)]TJ -1.2519 -1.2318 TD [(2.)-501.9(Bennett)-314(WD,)-303.1(Daviskas)-307.8(E,)-304.2(Hasani)-310(A,)-305.6(Mortensen)-313.3(J,)-305(Fleming)-308.7(J,)]TJ 1.2519 -1.2385 TD [(and)-386(Scheuch)-384.4(G:)-375.8(Mucociliary)-385.3(and)-386(cough)-377.9(clearance)-384(as)-382.8(a)-383.7(bio-)]TJ 0 -1.2318 TD [(marker)-436.8(for)-432.4(therapeutic)-441.6(development.)-436.4(J)-434.5(Aerosol)-434.1(Med)-434.6(Pulm)]TJ 0 -1.2385 TD [(Drug)-337.8(Deliv.)-333.7(2010;23:261272.)]TJ -1.2519 -1.2318 TD [(3.)-501.9(Donaldson)-625.8(SH,)-624(Bennett)-621.9(WD,)-624.4(Zeman)-621.2(KL,)-617.2(Knowles)-623.1(MK,)]TJ 1.2519 -1.2385 TD [(Tarran)-629(R,)-623.8(and)-627(Boucher)-631.1(RC:)-625.5(Mucus)-632.5(clearance)-631.7(and)-620.3(lung)]TJ 0 -1.2318 TD [(function)-417.1(in)-405.6(cystic)-413.7(brosis)-413.5(with)-408.8(hypertonic)-411.9(saline.)-412(N)-409.8(Engl)-407.8(J)]TJ 0 -1.2385 TD [(Med.)-338.6(2006;354:241250.)]TJ -1.2519 -1.2318 TD [(4.)-501.9(Robinson)-391.4(M,)-386.3(Regnis)-392.4(JA,)-385.3(Bailey)-386.9(DL,)-391.1(King)-387.6(M,)-386.3(Bautovich)-388.2(GJ,)]TJ 1.2519 -1.2385 TD [(and)-519.9(Bye)-518.3(PTP:)-524.1(Effect)-524.3(of)-516.1(hypertonic)-525.7(saline,)-525.9(amiloride,)-521.6(and)]TJ 0 -1.2318 TD [(cough)-471.6(on)-467(mucociliary)-474(clearance)-471(in)-465.9(patients)-469.2(with)-469.1(cystic)-473.9(-)]TJ 0 -1.2385 TD [(brosis.)-339(Am)-336.7(J)-334.1(Respir)-337.6(Crit)-332.5(Care)-335.7(Med.)-331.9(1996;153:1503150)-7(9.)]TJ -1.2519 -1.2318 TD [(5.)-501.9(Daviskas)-341.2(E,)-331(Anderson)-338.3(SD,)-334.5(Eberl)-341.1(S,)-334.6(and)-332.4(Young)-336.4(IH:)-335.7(Effect)-336.8(of)]TJ 1.2519 -1.2385 TD [(increasing)-296(doses)-299.9(of)-295.2(mannitol)-293.8(on)-292.9(mucus)-292.8(clearance)-296.9(in)-298.5(patients)]TJ 0 -1.2318 TD [(with)-335.2(bronchiectasis.)-345.2(Eur)-332.7(Respir)-337.6(J.)-338.5(2008;31:765772.)]TJ -1.2519 -1.2385 TD [(6.)-501.9(Daviskas)-281(E,)-270.7(Anderson)-278(SD,)-274.3(Eberl)-280.8(S,)-274.4(and)-272.2(Young)-276.1(IH:)-275.4(Benecial)]TJ 1.2519 -1.2318 TD [(effect)-526.4(of)-522.8(inhaled)-524.7(mannitol)-521.4(and)-519.9(cough)-525.2(in)-519.4(asthmatics)-527.4(with)]TJ 0 -1.2385 TD [(mucociliary)-340.1(dysfunction.)-342.4(Respir)-337.6(Med.)-331.9(2010;104:16451653.)]TJ -1.2519 -1.2318 TD [(7.)-501.9(Agnew)-326.5(JE,)-316.9(Bateman)-323.2(JRM,)-322.2(Watts)-325.5(M,)-319.3(Paramanda)-320.2(V,)-324.1(Pavia)-322.3(D,)]TJ 1.2519 -1.2385 TD [(and)-406.1(Clarke)-406.5(SW:)-405.8(The)-404.6(importance)-408.6(of)-409(aerosol)-409.6(penetration)-412.2(for)]TJ 0 -1.2318 TD [(lung)-338.5(mucociliary)-333.4(clearance)-343.8(studies.)-332.1(Chest.)-343.6(1981;80:843846.)]TJ -1.2519 -1.2385 TD [(8.)-501.9(Ilowite)-328.6(JS,)-320.6(Smaldone)-325.4(GC,)-323.9(Perry)-328.4(RJ,)-321.9(Bennett)-327.4(WD,)-323.2(and)-325.7(Foster)]TJ 1.2519 -1.2318 TD [(WM:)-417.3(Relationship)-425.2(between)-420.9(tracheobronchial)-426.7(particle)-421.8(clear-)]TJ 0 -1.2385 TD 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