From: Subject: NEJM -- Mucus Clearance and Lung Function in Cystic Fibrosis with Hypertonic Saline Date: Sat, 19 Apr 2008 08:06:14 +0200 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0000_01C8A1F4.3CC0F570" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.3198 This is a multi-part message in MIME format. ------=_NextPart_000_0000_01C8A1F4.3CC0F570 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: http://content.nejm.org/cgi/content/abstract/354/3/241 NEJM -- Mucus Clearance and Lung Function in Cystic = Fibrosis with Hypertonic Saline
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Mucus=20 Clearance and Lung Function in Cystic Fibrosis with Hypertonic=20 Saline
Scott H. Donaldson, M.D., William D. Bennett, = Ph.D.,=20 Kirby L. Zeman, Ph.D., Michael R. Knowles, M.D., Robert Tarran, Ph.D., = and=20 Richard C. Boucher, M.D.

 
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3D" by=20 Ratjen,=20 = F.
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ABSTRACT

Background Abnormal = homeostasis of the=20 volume of airway surface liquid in patients with cystic = fibrosis is=20 thought to produce defects in mucus clearance and airway = defense.=20 Through osmotic forces, hypertonic saline may increase the = volume of=20 airway surface liquid, restore mucus clearance, and improve = lung=20 function.

Methods A total of 24 patients with cystic fibrosis were = randomly=20 assigned to receive treatment with inhaled hypertonic saline = (5=20 ml of 7 percent sodium chloride) four times daily with or = without=20 pretreatment with amiloride. Mucus clearance and lung = function were=20 measured during 14-day baseline and treatment periods. =

Results Long-term inhalation of hypertonic saline without=20 pretreatment with amiloride (i.e., with placebo pretreatment) = resulted in a sustained (3D≥=208 hours) increase = in 1-hour=20 rates of mucus clearance, as compared with those with = amiloride=20 pretreatment (14.0=B12.0 vs. 7.0=B11.5 percent, respectively; = P=3D0.02) and=20 increased 24-hour rates of mucus clearance over baseline.=20 Furthermore, inhalation of hypertonic saline with placebo = improved=20 the forced expiratory volume in one second (FEV1) = between=20 the baseline period and the treatment period (mean = difference, 6.62=20 percent; 95 percent confidence interval, 1.6 to 11.7; = P=3D0.02),=20 whereas hypertonic saline with amiloride did not improve=20 FEV1 (mean difference, 2.9 percent; 95 percent = confidence=20 interval, =962.2 to 8.0; P=3D0.23). Forced vital capacity = (FVC), the=20 forced expiratory flow between 25 and 75 percent of FVC=20 (FEF25=9675), and respiratory symptoms also = significantly=20 improved in patients treated with hypertonic saline and = placebo,=20 whereas the residual volume as a proportion of total lung = capacity=20 (RV:TLC) did not change in either group. A comparison of the = changes=20 in lung function in the two groups showed no significant=20 difference. In vitro data suggested that sustained hydration = of=20 airway surfaces was responsible for the sustained improvement = in=20 mucus clearance, whereas inhibition of osmotically driven = water=20 transport by amiloride accounted for the observed loss of = clinical=20 benefit.

Conclusions In patients with cystic fibrosis, inhalation = of=20 hypertonic saline produced a sustained acceleration of mucus=20 clearance and improved lung function. This treatment may = protect=20 the lung from insults that reduce mucus clearance and produce = lung disease.


Source=20 Information

From the University of North Carolina at Chapel Hill = Cystic=20 Fibrosis Research and Treatment Center (S.H.D., W.D.B., M.R.K., R.T., = R.C.B.)=20 and the Center for Environmental Medicine, Asthma and Lung Biology = (W.D.B.,=20 K.L.Z.) =97 both in Chapel Hill.

Drs. = Donaldson and=20 Bennett contributed equally to this article.

Address reprint requests to Dr. Donaldson at 6019 = Thurston=20 Bowles Bldg., CB# 7248, University of North Carolina at Chapel Hill = Research and=20 Treatment Center, Chapel Hill, NC 27599, or at scott_donaldson{at}med.unc.edu .

Full Text of = this=20 Article


Related Letters:=20

Hypertonic= Saline=20 for Cystic Fibrosis
Aziz I., Kastelik J. A., Zarogiannis = S.,=20 Hatzoglou C., Gourgoulianis K., Kuver R., Lee S. P., Bye P. T.P., Elkins = M. R.,=20 Donaldson S. H., Tarran R., Boucher R. C., Ratjen F.
Extract<= /A> | Full = Text | PDF =  
N=20 Engl J Med 2006; 354:1848-1851, Apr 27, 2006. Correspondence =

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i;G = 1C(){9(s.1C)s.1C(M,1v);9(s.1Z)E.1j.1F("5I",[i,s])}G = 1l(){9(s.1l)s.1l(i,1v);9(s.1Z)E.1j.1F("6t",[i,s]);9(s.1Z&&!--E.5b)E.1j.1F= ("5K")}},5r:G(s,a,b,e){9(s.3U)s.3U(a,b,e);9(s.1Z)E.1j.1F("5J",[a,s,e])},5= b:0,6S:G(r){2a{I!r.1v&&9n.9l=3D=3D"54:"||(r.1v>=3D6N&&r.1v<9j)||r.1v=3D=3D= 6M||E.V.1N&&r.1v=3D=3DW}29(e){}I P},6R:G(a,c){2a{H b=3Da.5s("6P-5x");I = a.1v=3D=3D6M||b=3D=3DE.49[c]||E.V.1N&&a.1v=3D=3DW}29(e){}I = P},6Q:G(r,b){H c=3Dr.5s("9i-O");H = d=3Db=3D=3D"6K"||!b&&c&&c.1g("6K")>=3D0;H = a=3Dd?r.9g:r.40;9(d&&a.2V.37=3D=3D"5k")6G"5k";9(b=3D=3D"1J")E.5f(a);9(b=3D= =3D"45")a=3D3w("("+a+")");I a},3a:G(a){H = s=3D[];9(a.1c=3D=3D1B||a.4c)E.N(a,G(){s.1a(3f(6.2H)+"=3D"+3f(6.1Q))});J = L(H j 1i = a)9(a[j]&&a[j].1c=3D=3D1B)E.N(a[j],G(){s.1a(3f(j)+"=3D"+3f(6))});J = s.1a(3f(j)+"=3D"+3f(a[j]));I = s.66("&").1p(/%20/g,"+")}});E.1b.1k({1A:G(b,a){I = b?6.1U({1H:"1A",2N:"1A",1r:"1A"},b,a):6.1E(":1P").N(G(){6.R.19=3D6.3h?6.3= h:"";9(E.17(6,"19")=3D=3D"2s")6.R.19=3D"2Z"}).2D()},1z:G(b,a){I = 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    • ' + '
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' + '

I am a:

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  • ' + '
    • ' + '
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    • ' + '
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', =09 '

 ' +=20 ' 

' + '

' +=20 'Thanks for participating in this survey.

' + '
 
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'); if (typeof(CM8MultiShow) !=3D "undefined") CM8MultiShow(F, I); }; if (! window.CM8InternalFSF) { window.CM8InternalFSF =3D true; document.write(""); } ------=_NextPart_000_0000_01C8A1F4.3CC0F570 Content-Type: application/octet-stream Content-Transfer-Encoding: quoted-printable Content-Location: http://survey.nejm.org/scripts/survey.js function invite(inviteurl,frmWidth,frmHeight,svyName,expire) { //******************************************************************** // Display invitation if specific cookie not found and set cookie // Parameters // inviteurl: URL of invite form // frmWidth & frmHeight: dimensions of invitation window // svyName: Name of the specific survey // expire: Number of days before cookie expires //=20 // Created by Chris Miceli 2/25/2004 //******************************************************************** // define variables var theCookie =3D document.cookie; var today =3D new Date(); var expDate =3D new Date(); // Check if user has visited page before if (theCookie.indexOf(svyName) =3D=3D -1) { =20 expDate =3D whenIs(today, expire); expDate =3D expDate.toGMTString(); document.cookie =3D svyName + "; path=3D/; expires=3D" + expDate + = ";"; window.open(inviteurl, "", "toolbar=3Dno,status=3Dno,width=3D" + = frmWidth + ",height=3D" + frmHeight + ",top=3D150,left=3D50"); //window.open(surveyurl, "", = "toolbar=3Dno,status=3Dno,width=3D270,height=3D220,top=3D150,left=3D50");= } } function invite(inviteurl,frmWidth,frmHeight,svyName,expire,path) { //******************************************************************** // Display invitation if specific cookie not found and set cookie // Parameters // inviteurl: URL of invite form // frmWidth & frmHeight: dimensions of invitation window // svyName: Name of the specific survey // expire: Number of days before cookie expires // path: cookie path //=20 // Created by Chris Miceli 2/25/2004 //******************************************************************** // define variables var theCookie =3D document.cookie; var today =3D new Date(); var expDate =3D new Date(); // Check if user has visited page before if (readCookie(svyName) =3D=3D null) { =09 createCookie(svyName, svyName, expire); window.open(inviteurl, "", "toolbar=3Dno,status=3Dno,width=3D" + = frmWidth + ",height=3D" + frmHeight + ",top=3D150,left=3D50"); } } function whenIs(anyDate, n){ //-- Returns the date that is n days from any date. var newDate =3D new Date(); newDate.setTime(anyDate.getTime()+(n*1000*60*60*24)); return newDate; } //******************************************************************** // Display invitation if specific cookie not found and set cookie // Parameters // Display invitation every nthe hit on page, every 5th customer or = every 163rd customer. =20 // Created by SFungafat , Modified RKumar June 2004 //******************************************************************** function intercept(surveyurl) { // define variables var cookie_ls =3D document.cookie; var date_ls =3D new Date(); var S =3D new Date(); // if not yet sampled if (cookie_ls.indexOf("NEJM062004WEB") =3D=3D -1) { rnd.today=3Dnew Date(); rnd.seed=3Drnd.today.getTime(); =20 function whenIs(anyDate, n){ //-- Returns the date that is n days from any date. var newDate =3D new Date(); = newDate.setTime(anyDate.getTime()+(n*1000*60*60*24)); return newDate; } function rnd() { rnd.seed =3D (rnd.seed*9301+49297) % 233280; return rnd.seed/(233280.0); }; function rand(number) { return Math.ceil(rnd()*number); }; =20 sample=3Drand(5); // for the sample grab 1 in 5 if (sample=3D=3D5) { S =3D whenIs(date_ls, 3); S =3D S.toGMTString(); document.cookie =3D "NEJM062004WEB; path=3D/; expires=3D" + = S + ";"; window.open(surveyurl, "", = "toolbar=3Dno,status=3Dno,width=3D600,height=3D300,top=3D150,left=3D50") } } } //************************************************ // Set pop-up cookie based on country and IP type // Parameters // country: two character country code // instFlag: NEJM Institution, 1=3DTrue, 0=3DFalse // ** Use ISO 3166 standard 2-letter country codes ** //************************************************ function intlSurvey(country, instFlag) { var validCtys =3D "JP"; if (cookiesAreEnabled()) { country =3D country.toUpperCase() =09 // Invite only displayed for valid countries if (country.indexOf(validCtys) > -1) { if (instFlag =3D=3D 1) { //Set cookie one day for NEJM Institutions = invite('http://survey.nejm.org/NEJMJPN/popup.aspx',510,260,'NEJMESINST',1= , 'nejm.org'); } else { //60 days for all others = invite('http://survey.nejm.org/NEJMJPN/popup.aspx',510,260,'NEJMESNONINST= ',45, 'nejm.org'); } =09 } } } //************************************************ // Set pop-up cookie based on country.=20 // Parameters // userCty: Country user from // validCty: Country or countries to test against // inviteurl: URL of invite form // svyName: Name of the specific survey // expire: Number of days before cookie expires // frmWidth & frmHeight: dimensions of invitation window //************************************************ function surveyByCty(userCty, validCty, inviteurl, svyName, expire, = frmWidth, frmHeight) { if (cookiesAreEnabled()) { userCty =3D userCty.toUpperCase() validCty =3D validCty.toUpperCase() =09 // Invite only displayed for valid countries if (userCty.indexOf(validCty) > -1) { //Display invite invite(inviteurl, frmWidth, frmHeight, svyName, expire); } } } // Checks if cookies are enabled in browser. function cookiesAreEnabled() { setCookie( "foo", "bar" ); if ( getCookie( "foo" ) ) { deleteCookie( "foo" ); return true; } else { return false; } } function setCookie( name, value, expires, path, domain, secure ) { document.cookie =3D name + "=3D" + escape (value) + ( ( expires ) ? "; expires=3D" + expires : "" ) + ( ( path ) ? "; path=3D" + path : "" ) + ( ( domain ) ? "; domain=3D" + domain : "" ) + ( ( secure ) ? "; secure" : "" ); } function getCookie( name ) { var arg =3D name + "=3D"; var alen =3D arg.length; var clen =3D document.cookie.length; var i =3D 0; while ( i < clen ) { var j =3D i + alen; if ( document.cookie.substring(i, j) =3D=3D arg ) return = getCookieVal(j); i =3D document.cookie.indexOf( " ", i ) + 1; if ( i =3D=3D 0 ) break; } return null; } /** * Helper function for getCookie() */ function getCookieVal( offset ) { var endstr =3D document.cookie.indexOf ( ";", offset ); if ( endstr =3D=3D -1 ) endstr =3D document.cookie.length; return unescape( document.cookie.substring( offset, endstr ) ); } function deleteCookie( name, path, domain ) { if ( getCookie( name ) ) { document.cookie =3D name + "=3D" + ( ( path ) ? "; path=3D" + path : "" ) + ( ( domain ) ? "; domain=3D" + domain : "" ) + "; expires=3DThu, 01-Jan-70 00:00:01 GMT"; } } function createCookie(name, value, days) { if (days) { var date =3D new Date; date.setTime(date.getTime() + days * 24 * 60 * 60 * 1000); var expires =3D "; expires=3D" + date.toGMTString(); } else { var expires =3D ""; } document.cookie =3D name + "=3D" + value + expires + "; path=3D/" } function readCookie(name) { var nameEQ =3D name + "=3D"; var ca =3D document.cookie.split(";"); for (var i =3D 0; i < ca.length; i++) { var c =3D ca[i]; while (c.charAt(0) =3D=3D " ") { c =3D c.substring(1, c.length); } if (c.indexOf(nameEQ) =3D=3D 0) { return c.substring(nameEQ.length, c.length); } } return null; } ------=_NextPart_000_0000_01C8A1F4.3CC0F570--