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[(sw)16.1(it)16.5(ch)20.8(in)13.2(g)-370.7(t)0(h)18.9(e)-376.7(im)15.7(mu)18.1(ne)-366.1(sy)20(st)17.7(em)-369.3(aw)16.9(ay)-366.1(fr)18(om)-363.2(de)15.1(ve)20.8(lo)13.2(pi)18.9(ng)-365.7(al)18.4(-)]TJ 0 -1.0527 TD [(le)18.4(r)20.4(g)0(i)13.2(c)-285.7(re)19.2(ac)14.7(ti)16.5(on)21.2(s,)-281.2(mo)18.1(st)17.7(ly)-282.7(ba)20.8(se)13.9(d)-285.3(o)0(n)-280.4(s)0(t)17.7(u)0(d)21.2(i)0(e)18.4(s)-292.2(in)18.9(to)-277.1(th)18.9(e)-291.4(r)0(e)19.2(l)0(a)18.4(t)0(i)16.5(o)0(n)15.5(s)]TJ 0 -1.0471 TD [(be)15.1(tw)20.6(ee)14.7(n)-199.9(a)0(t)18.4(o)0(p)15.5(y)-199.9(an)15.1(d)-199.9(f)0(a)19.2(m)0(i)15.7(l)0(y)-191.7(s)0(i)17.7(z)0(e)14.7(,)-199.6(bi)18.9(rt)17.3(h)-205.6(o)0(r)19.6(d)0(e)15.1(r)43.2(,)-205.2(n)0(u)21.2(m)0(b)18.1(e)0(r)-197(o)0(f)-190.9(o)0(l)18.9(d)0(e)15.1(r)]TJ 0 -1.0528 TD [(si)17.7(bl)18.9(in)18.9(gs)-514.9(an)15.1(d)-524.3(d)0(a)20.8(y)-524.3(ca)14.7(re)-515.7(us)20(e)-524.7([)0(7)19.6(\261)0(1)26.9(1].)-532.7(The)-536(study)-536.6(by)-536.4(V)]TJ 6.974 0 0 6.974 275.414 510.123 Tm 0.0001 Tc (ON)Tj 9.963 0 0 9.963 58.28 499.691 Tm 0 Tc 0 Tw (M)Tj 6.974 0 0 6.974 67.124 499.691 Tm 0.0001 Tc (UTIUS)Tj /F5 1 Tf 9.963 0 0 9.963 90.595 499.691 Tm 0 Tc [(et)-311.6(al.)]TJ /F4 1 Tf 2.3502 0 TD [([4])-318.5(finds)-316.3(an)-309.2(inver)-8.2(se)-310.4(relat)-11(ionship)-318.6(with)-313.3(early)]TJ -5.5938 -1.0527 TD [(infec)-8.6(tions)-231.7(only)-233.1(in)-231.5(the)-227(smal)-10.2(l)-225.1(subgro)-7.4(up)-229.2(o)-6.5(f)-224.3(asthm)-10.9(atics,)-232.9(and)-230.3(it)]TJ 0 -1.0471 TD [(seem)-8.2(s)-531.2(that)-537.4(the)-534.3("hyg)-6(iene)-535.5(hypoth)-7(esis")-535.5(must)-539(be)-531.2(view)-9.8(ed)]TJ 0 -1.0528 TD [(critical)-12.7(ly)-413.6(on)-411.3(the)-420.5(basis)-418.7(of)-412.8(these)-417.9(new)-416.3(data.)-416.3(Al)-7.8(though)-416.7(the)]TJ 0 -1.0471 TD [(asses)-8.2(sment)-625.5(of)-623.4(e)-6.9(arly)-622(infec)-8.6(tion)-7.8(s)-622.2(was)-622.4(admi)-9(ttedly)-626.7(retr)-9(o-)]TJ 0 -1.0528 TD [(spect)-8.2(ive)-363.6(and)-361.2(indirect)-368.5(in)-362.4(this)-367.5(study)60.9(,)-358.9(i)0(t)-364.8(i)0(s)-363.6(still)-361.7(more)-366.7(direc)-8.6(t)]TJ 0 -1.0471 TD [(than)-261.9(assum)-9.7(ptions)-266.6(about)-262.7(exposur)-8.5(e)-257.2(t)0(o)-260(infec)-8.6(tion)-263.9(based)-267.6(upon)]TJ 0 -1.0527 TD [(family)-498.2(size,)-491.5(birth)-493.9(order)26.7(,)]TJ /F5 1 Tf 10.4877 0 TD (etc.)Tj /F4 1 Tf 1.8893 0 TD [(As)-490.3(a)-484.9(resul)-9.4(t)-486.8(more)-497.6(weight)]TJ -12.3769 -1.0471 TD [(would)-266.2(be)-263.7(placed)-264.2(on)-263.3(studies)-263.3(that)-264.3(have)-265.6(looked)-263.4(at)-266.1(infection)-10.7(s)]TJ 0 -1.0527 TD [(\(more)-10.6(\))-406.4(direc)-8.6(tly)-411.1(than)-409.9(proxy)-415.1(variables)-419.7(which)-414.6(may)-409.9(be)-411.7(as-)]TJ 0 -1.0471 TD [(socia)-8.2(ted)-443.3(with)-449.9(a)-445(whole)-448.7(range)-450.1(of)-441.3(other)-452.1(factors)-451.1(that)-446.4(may)]TJ 0 -1.0528 TD [(actual)-10.6(ly)-254.3(explai)-10.1(n)-256.8(the)-255.5(relat)-11(ionship)-261.7(between)-263.2(fami)-10.6(ly)-254.3(size,)]TJ /F5 1 Tf 21.4022 0 TD (etc.)Tj /F4 1 Tf -21.4022 -1.0471 TD [(and)-463.6(atopy)56(.)-461.3(T)57.7(wo)-460.7(more)-469.1(recent)-470.7(publicati)-11.5(ons)-464.4(suppor)-7.4(t)-458.4(this)-9(.)]TJ 0 -1.0528 TD [(Another)-497.3(study)-491.1(from)-493.1(form)-9.4(er)-487.2(East)-489.2(Ger)-8.2(many)-490.3([12])-495.6(found)]TJ 0 -1.0471 TD [(more)-355.3(alle)-8.6(rgic)-343.2(mani)-9(festatio)-11.1(ns)-349.8(and)-355.5(atopy)-359.4(in)-351(chil)-8.2(dren)-352.2(from)]TJ 0 -1.0527 TD [(small)-332(fami)-10.6(lies)-328.1(who)-330.6(had)-332.7(been)-328.2(sent)-331.4(to)-328.3(day)-327.1(ca)-8(re)-327.9(before)-332.9(the)]TJ T* [(age)-236.4(of)-242.1(1)-234.1(y)0(r)-236.4(than)-239.2(in)-237.2(chil)-8.2(dren)-238.4(who)-239.5(had)-236(been)-237.2(sent)-240.3(to)-237.2(day)-241.7(care)]TJ 0 -1.0471 TD [(after)-402.8(the)-403.4(age)-401.4(of)-401.5(2)-399.1(yrs,)-403.8(a)-399.5(finding)-404.3(which)-403.2(is)-403.4(seemingl)-10.3(y)-399.1(i)0(n)]TJ 0 -1.0527 TD [(coheren)-8.2(ce)-264.1(wi)-7.8(th)-265.7(the)-261.2("hyg)-6(iene)-268(hypoth)-7(esis",)-268.4(as)-264.9(day)-270.2(care)-267.6(use)]TJ 0 -1.0471 TD [(is)-454.7(known)-457.3(to)-453.5(be)-451.5(associated)-460.2(wi)-7.8(th)-453.5(exposur)-8.5(e)-450.7(t)0(o)-453.5(infectiou)-10.7(s)]TJ 0 -1.0527 TD [(agents)-287.8([12].)-285.5(However)24.2(,)-279.2(skin)-285.5(prick)-287(and)-281.5(radio)-8.2(allergosorbent)]TJ 0 -1.0471 TD [(test)-265.5(resul)-9.4(ts)-261.2(in)-265.7(children)-269.3(from)-271.2(lar)10.4(g)-6.5(e)-262.9(families)-270.4(were)-265.5(sim)-9(ilar)-265.9(to)]TJ 0 -1.0527 TD [(those)-406.1(in)-407.9(child)-9(ren)-402.6(from)-413.4(small)-406(fami)-10.6(lies,)-408.1(even)-407.9(in)-402.2(the)-409.1(sub-)]TJ 0 -1.0471 TD [(group)-284.2(that)-281.4(went)-282.9(into)-281(day)-275.8(care)-284.7(later)45.9(.)-279.2(A)-277.8(study)-280.5(from)-282.5(the)-283.9(UK)]TJ 0 -1.0528 TD [([13];)-322.4(found)-324.1(little)-324.2(associ)-10.1(ation)-322(between)-325.8(asthma)-325.1(and)-321.4(family)]TJ 0 -1.0471 TD [(size,)-292.3(and)-287.2(any)-287.2(associa)-11.3(tion)-286.7(presen)-8.2(t)-287.7(was)-286.7(related)-291.7(to)-288.4(the)-289.6(num-)]TJ 0 -1.0528 TD [(ber)-271.7(of)-270.6(younger)-274.8(rathe)-8.6(r)-269.8(than)-273.3(older)-270(sibl)-9(ings.)-274.5(If,)-266.9(in)-271.4(the)-272.5(end,)-270.5(it)]TJ 0 -1.0471 TD [(is)-363.6(asthm)-10.9(a)-359.7(that)-366.7(ca)-8(uses)-364.3(more)-366.7(concern)-372.3(than)-370(atopy)-365.1(as)-367.3(such,)]TJ 0 -1.0527 TD [(then)-364.3(this)-361.8(is)-357.9(anothe)-7.8(r)-360.9(finding)-364.5(that)-361(shoul)-7.4(d)-359.3(result)-365.3(in)-356.7(a)-359.7(more)]TJ 0 -1.0471 TD [(careful)-382(consi)-7.8(derat)-8.6(ion)-374.6(of)-378.7(the)-375(effect)-369.9(of)-378.7(infec)-8.6(tions)-379.7(early)-378.5(in)]TJ 0 -1.0528 TD [(life)-510.6(on)-508(the)-505.8(develo)-7.8(pment)-510.5(of)-509.6(asthma.)-513.3(Unfortu)-9.1(nately)52.4(,)-501.2(all)]TJ 25.1977 58.8004 TD [(three)-537.8(recent)-539(studies)-536.4(were)-532.9(retrospect)-12.3(ive,)-534.7(and)-531.9(relied)-535.3(on)]TJ 0 -1.0584 TD [(proxy)-568.8(variables)-567.6(for)-563.2(meas)-8.2(uring)-565.5(exposur)-8.5(e)-558.8(t)0(o)-561.6(infec)-8.6(tions)]TJ T* [(rathe)-8.6(r)-309.7(than)-307.4(on)-308.8(direc)-8.6(t)-310.4(assessmen)-10.3(ts.)-307.1(More)-314.3(defin)-8.2(ite)-309.1(answers)]TJ T* [(wi)-7.8(ll)-245.3(hopeful)-9.7(ly)-242.9(be)-252.3(provided)-249.5(by)-246.2(the)-249.8(prospe)-7.8(ctive)-248.4(studi)-9.8(es)-247.8(that)]TJ T* [(are)-340.4(now)-336.3(being)-336.7(conduc)-11.1(ted)-335.1(througho)-10.1(ut)-334(Europe)-340.7([14].)]TJ /F8 1 Tf 8.966 0 0 8.966 402.349 687.628 Tm [(Refer)11.6(ences)]TJ /F4 1 Tf -10.3759 -2.2826 TD [(1.)-1766.5(Stein)-519.1(R)52.7(T)72.9(,)-521.4(Holberg)-515(CJ,)-520(Mor)12.5(gan)-523.1(WJ,)]TJ /F5 1 Tf 18.3111 0 TD [(et)-519.6(al)]TJ /F4 1 Tf 1.998 0 TD [(.)-521.4(Peak)-514.6(flow)]TJ -17.7927 -1.1191 TD [(variability)56.4(,)-565.7(methacholine)-571(responsiveness)-569.3(and)-567.3(atopy)-568.7(as)]TJ T* [(markers)-399.3(for)-405.1(detecting)-400.2(different)-394.6(wheezing)-399.3(phenotypes)-402.7(in)]TJ T* (childhood.)Tj /F5 1 Tf 4.5588 0 TD (Thorax)Tj /F4 1 Tf 3.212 0 TD [(1997;)-328.6(52:)-336(946\261952.)]TJ -10.2874 -1.1128 TD [(2.)-1766.5(Martinez)-393.7(FD,)-389.5(Stern)-391.2(DA,)-387.9(W)26.5(right)-388.9(AL,)-388(T)60.2(aussig)-393.5(LM,)-385.4(Hal-)]TJ 2.5165 -1.1255 TD [(onen)-402.4(M.)-407.7(Association)-405.1(of)-410.9(nonwheezing)-404(lower)-408.5(respiratory)]TJ 0 -1.1192 TD [(tract)-426.4(illnesses)-429.3(in)-431.3(early)-424(life)-427.1(with)-429.7(persistently)-429.9(diminished)]TJ T* [(serum)-336.4(IgE)-331.7(levels.)]TJ /F5 1 Tf 7.3915 0 TD (Thorax)Tj /F4 1 Tf 3.212 0 TD [(1995;)-328.6(50:)-336(1067\2611072.)]TJ -13.12 -1.1128 TD [(3.)-1766.5(Christie)-528.2(GL,)-527.1(Helms)-524.5(PJ,)-526.5(Ross)-523.5(SJ,)]TJ /F5 1 Tf 17.2552 0 TD [(et)-525.9(al)]TJ /F4 1 Tf 2.0044 0 TD [(.)-521.4(Outcome)-528.3(for)]TJ -16.7431 -1.1191 TD [(children)-228.8(of)-221.3(parents)-228.1(with)-227.3(atopic)-222.6(asthma)-229.6(and)-225.9(transient)-225.6(child-)]TJ T* [(hood)-333.1(wheezy)-334.7(bronchitis.)]TJ /F5 1 Tf 10.2368 0 TD (Thorax)Tj /F4 1 Tf 3.2057 0 TD [(1997;)-334.9(52:)-336(953\261957.)]TJ -15.959 -1.1128 TD [(4.)-1766.5(V)123.6(o)0(n)-511.2(Mutius)-515.7(E,)-511.7(Illi)-518.2(S,)-506.8(Hirsch)-516.7(T)72.9(,)-515.1(Leupold)-514.2(W)83.4(,)-508.8(Keil)-518(U,)]TJ 2.5165 -1.1192 TD [(W)70.8(eiland)-500.8(S.)-500.5(Cross-sectional)-502.2(study)-506.9(on)-498.5(the)-500.1(frequency)-502.5(of)]TJ 0 -1.1255 TD 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