Effect of continued treatment with pirfenidone following clinically meaningful declines in forced vital capacity: analysis of data from three phase 3 trials in patients with idiopathic pulmonary fibrosis
Identifieur interne : 003268 ( Ncbi/Checkpoint ); précédent : 003267; suivant : 003269Effect of continued treatment with pirfenidone following clinically meaningful declines in forced vital capacity: analysis of data from three phase 3 trials in patients with idiopathic pulmonary fibrosis
Auteurs : Steven D. Nathan [États-Unis] ; Carlo Albera [Italie] ; Williamson Z. Bradford [États-Unis] ; Ulrich Costabel ; Roland M. Du Bois [Royaume-Uni] ; Elizabeth A. Fagan [États-Unis] ; Robert S. Fishman [États-Unis] ; Ian Glaspole ; Marilyn K. Glassberg ; Kenneth F. Glasscock [États-Unis] ; Talmadge E. King [États-Unis] ; Lisa Lancaster ; David J. Lederer [États-Unis] ; Zhengning Lin [États-Unis] ; Carlos A. Pereira [Brésil] ; Jeffrey J. Swigris [États-Unis] ; Dominique Valeyre [France] ; Paul W. Noble ; Athol U. Wells [Royaume-Uni]Source :
- Thorax [ 0040-6376 ] ; 2016.
Descripteurs français
- KwdFr :
- Anti-inflammatoires non stéroïdiens (usage thérapeutique), Capacité vitale (), Estimation de Kaplan-Meier, Fibrose pulmonaire idiopathique (mortalité), Fibrose pulmonaire idiopathique (traitement médicamenteux), Humains, Plan de recherche, Pyridones (usage thérapeutique), Relation dose-effet des médicaments, Résultat thérapeutique, Survie sans rechute, Évolution de la maladie.
- MESH :
- mortalité : Fibrose pulmonaire idiopathique.
- traitement médicamenteux : Fibrose pulmonaire idiopathique.
- usage thérapeutique : Anti-inflammatoires non stéroïdiens, Pyridones.
- Capacité vitale, Estimation de Kaplan-Meier, Humains, Plan de recherche, Relation dose-effet des médicaments, Résultat thérapeutique, Survie sans rechute, Évolution de la maladie.
English descriptors
- KwdEn :
- Anti-Inflammatory Agents, Non-Steroidal (therapeutic use), Disease Progression, Disease-Free Survival, Dose-Response Relationship, Drug, Humans, Idiopathic Pulmonary Fibrosis (drug therapy), Idiopathic Pulmonary Fibrosis (mortality), Kaplan-Meier Estimate, Pyridones (therapeutic use), Research Design, Treatment Outcome, Vital Capacity (drug effects).
- MESH :
- chemical , therapeutic use : Anti-Inflammatory Agents, Non-Steroidal, Pyridones.
- drug effects : Vital Capacity.
- drug therapy : Idiopathic Pulmonary Fibrosis.
- mortality : Idiopathic Pulmonary Fibrosis.
- Disease Progression, Disease-Free Survival, Dose-Response Relationship, Drug, Humans, Kaplan-Meier Estimate, Research Design, Treatment Outcome.
Abstract
The assessment of treatment response in idiopathic pulmonary fibrosis (IPF) is complicated by the variable clinical course. We examined the variability in the rate of disease progression and evaluated the effect of continued treatment with pirfenidone in patients who experienced meaningful progression during treatment.
The source population included patients enrolled in the ASCEND and CAPACITY trials (N=1247). Pearson's correlation coefficients were used to characterise the relationship between changes in FVC during consecutive 6-month intervals in the placebo population. Outcomes following a ≥10% decline in FVC were evaluated by comparing the proportion of patients in the pirfenidone and placebo groups who experienced a ≥10% decline in FVC or death during the subsequent 6 months.
A weak negative correlation was observed between FVC changes during consecutive intervals in the placebo population (coefficient, −0.146, p<0.001), indicating substantial variability. Thirty-four (5.5%) and 68 (10.9%) patients in the pirfenidone and placebo groups, respectively, experienced a ≥10% decline in FVC by month 6. During the subsequent 6 months, fewer patients in the pirfenidone group compared with placebo experienced a ≥10% decline in FVC or death (5.9% vs 27.9%; relative difference, 78.9%). There was one (2.9%) death in the pirfenidone group and 14 (20.6%) deaths in the placebo group (relative difference, 85.7%).
Longitudinal FVC data from patients with IPF showed substantial intrasubject variability, underscoring the inability to reliably assess therapeutic response using serial FVC trends. In patients who progressed during treatment, continued treatment with pirfenidone resulted in a lower risk of subsequent FVC decline or death.
NCT01366209, NCT00287729, NCT00287716.
Url:
DOI: 10.1136/thoraxjnl-2015-207011
PubMed: 26968970
PubMed Central: 4862066
Affiliations:
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Nathan</name><affiliation wicri:level="1"><nlm:aff id="af1"><institution>Inova Fairfax Hospital, Heart and Lung Transplant Center</institution>,<addr-line>Falls Church, Virginia</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Albera, Carlo" sort="Albera, Carlo" uniqKey="Albera C" first="Carlo" last="Albera">Carlo Albera</name><affiliation wicri:level="1"><nlm:aff id="af2"><addr-line>Department of Clinical and Biological Sciences</addr-line>,<institution>University of Turin</institution>,<addr-line>Turin</addr-line>,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bradford, Williamson Z" sort="Bradford, Williamson Z" uniqKey="Bradford W" first="Williamson Z" last="Bradford">Williamson Z. Bradford</name><affiliation wicri:level="1"><nlm:aff id="af3"><institution>InterMune Inc.</institution>,<addr-line>Brisbane, California</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Costabel, Ulrich" sort="Costabel, Ulrich" uniqKey="Costabel U" first="Ulrich" last="Costabel">Ulrich Costabel</name><affiliation><nlm:aff id="af4"><addr-line>Department of Pneumology/Allergy</addr-line>,<institution>Ruhrlandklinik</institution>,<addr-line>Essen</addr-line>,<institution>Germany</institution></nlm:aff></affiliation></author><author><name sortKey="Du Bois, Roland M" sort="Du Bois, Roland M" uniqKey="Du Bois R" first="Roland M" last="Du Bois">Roland M. Du Bois</name><affiliation wicri:level="1"><nlm:aff id="af5"><institution>Imperial College</institution>,<addr-line>London</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Fagan, Elizabeth A" sort="Fagan, Elizabeth A" uniqKey="Fagan E" first="Elizabeth A" last="Fagan">Elizabeth A. Fagan</name><affiliation wicri:level="1"><nlm:aff id="af3"><institution>InterMune Inc.</institution>,<addr-line>Brisbane, California</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Fishman, Robert S" sort="Fishman, Robert S" uniqKey="Fishman R" first="Robert S" last="Fishman">Robert S. Fishman</name><affiliation wicri:level="1"><nlm:aff id="af3"><institution>InterMune Inc.</institution>,<addr-line>Brisbane, California</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Glaspole, Ian" sort="Glaspole, Ian" uniqKey="Glaspole I" first="Ian" last="Glaspole">Ian Glaspole</name><affiliation><nlm:aff id="af6"><institution>Alfred Hospital and Monash University</institution>,<addr-line>Melbourne</addr-line>,<institution>Australia</institution></nlm:aff></affiliation></author><author><name sortKey="Glassberg, Marilyn K" sort="Glassberg, Marilyn K" uniqKey="Glassberg M" first="Marilyn K" last="Glassberg">Marilyn K. Glassberg</name><affiliation><nlm:aff id="af7"><institution>University of Miami Miller School of Medicine</institution>,<addr-line>Miami, Florida</addr-line>,<institution>USA</institution></nlm:aff></affiliation></author><author><name sortKey="Glasscock, Kenneth F" sort="Glasscock, Kenneth F" uniqKey="Glasscock K" first="Kenneth F" last="Glasscock">Kenneth F. Glasscock</name><affiliation wicri:level="1"><nlm:aff id="af3"><institution>InterMune Inc.</institution>,<addr-line>Brisbane, California</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="King, Talmadge E" sort="King, Talmadge E" uniqKey="King T" first="Talmadge E" last="King">Talmadge E. King</name><affiliation wicri:level="1"><nlm:aff id="af8"><institution>University of California</institution>,<addr-line>San Francisco, California</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lancaster, Lisa" sort="Lancaster, Lisa" uniqKey="Lancaster L" first="Lisa" last="Lancaster">Lisa Lancaster</name><affiliation><nlm:aff id="af9"><institution>Vanderbilt University Medical Center</institution>,<addr-line>Nashville, Tennessee</addr-line>,<institution>USA</institution></nlm:aff></affiliation></author><author><name sortKey="Lederer, David J" sort="Lederer, David J" uniqKey="Lederer D" first="David J" last="Lederer">David J. Lederer</name><affiliation wicri:level="1"><nlm:aff id="af10"><institution>Columbia University Medical Center</institution>,<addr-line>New York, New York</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lin, Zhengning" sort="Lin, Zhengning" uniqKey="Lin Z" first="Zhengning" last="Lin">Zhengning Lin</name><affiliation wicri:level="1"><nlm:aff id="af3"><institution>InterMune Inc.</institution>,<addr-line>Brisbane, California</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Pereira, Carlos A" sort="Pereira, Carlos A" uniqKey="Pereira C" first="Carlos A" last="Pereira">Carlos A. Pereira</name><affiliation wicri:level="1"><nlm:aff id="af11"><institution>Paulista School of Medicine, Federal University of São Paulo</institution>,<addr-line>São Paulo</addr-line>,<country>Brazil</country></nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Swigris, Jeffrey J" sort="Swigris, Jeffrey J" uniqKey="Swigris J" first="Jeffrey J" last="Swigris">Jeffrey J. Swigris</name><affiliation wicri:level="1"><nlm:aff id="af12"><addr-line>Interstitial Lung Disease Program</addr-line>,<institution>National Jewish Health</institution>,<addr-line>Denver, Colorado</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Valeyre, Dominique" sort="Valeyre, Dominique" uniqKey="Valeyre D" first="Dominique" last="Valeyre">Dominique Valeyre</name><affiliation wicri:level="1"><nlm:aff id="af13"><institution>Assistance Publique-Hôpitaux de Paris, Avicenne University Hospital</institution>,<addr-line>Bobigny</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Noble, Paul W" sort="Noble, Paul W" uniqKey="Noble P" first="Paul W" last="Noble">Paul W. Noble</name><affiliation><nlm:aff id="af14"><institution>Cedars Sinai Medical Center</institution>,<addr-line>Los Angeles, California</addr-line>,<institution>USA</institution></nlm:aff></affiliation></author><author><name sortKey="Wells, Athol U" sort="Wells, Athol U" uniqKey="Wells A" first="Athol U" last="Wells">Athol U. Wells</name><affiliation wicri:level="1"><nlm:aff id="af15"><institution>Royal Brompton Hospital</institution>,<addr-line>London</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Thorax</title><idno type="ISSN">0040-6376</idno><idno type="eISSN">1468-3296</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Anti-Inflammatory Agents, Non-Steroidal (therapeutic use)</term><term>Disease Progression</term><term>Disease-Free Survival</term><term>Dose-Response Relationship, Drug</term><term>Humans</term><term>Idiopathic Pulmonary Fibrosis (drug therapy)</term><term>Idiopathic Pulmonary Fibrosis (mortality)</term><term>Kaplan-Meier Estimate</term><term>Pyridones (therapeutic use)</term><term>Research Design</term><term>Treatment Outcome</term><term>Vital Capacity (drug effects)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Anti-inflammatoires non stéroïdiens (usage thérapeutique)</term><term>Capacité vitale ()</term><term>Estimation de Kaplan-Meier</term><term>Fibrose pulmonaire idiopathique (mortalité)</term><term>Fibrose pulmonaire idiopathique (traitement médicamenteux)</term><term>Humains</term><term>Plan de recherche</term><term>Pyridones (usage thérapeutique)</term><term>Relation dose-effet des médicaments</term><term>Résultat thérapeutique</term><term>Survie sans rechute</term><term>Évolution de la maladie</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Anti-Inflammatory Agents, Non-Steroidal</term><term>Pyridones</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Vital Capacity</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Idiopathic Pulmonary Fibrosis</term></keywords><keywords scheme="MESH" qualifier="mortality" xml:lang="en"><term>Idiopathic Pulmonary Fibrosis</term></keywords><keywords scheme="MESH" qualifier="mortalité" xml:lang="fr"><term>Fibrose pulmonaire idiopathique</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Fibrose pulmonaire idiopathique</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Anti-inflammatoires non stéroïdiens</term><term>Pyridones</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Disease Progression</term><term>Disease-Free Survival</term><term>Dose-Response Relationship, Drug</term><term>Humans</term><term>Kaplan-Meier Estimate</term><term>Research Design</term><term>Treatment Outcome</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Capacité vitale</term><term>Estimation de Kaplan-Meier</term><term>Humains</term><term>Plan de recherche</term><term>Relation dose-effet des médicaments</term><term>Résultat thérapeutique</term><term>Survie sans rechute</term><term>Évolution de la maladie</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>The assessment of treatment response in idiopathic pulmonary fibrosis (IPF) is complicated by the variable clinical course. We examined the variability in the rate of disease progression and evaluated the effect of continued treatment with pirfenidone in patients who experienced meaningful progression during treatment.</p></sec><sec><title>Methods</title><p>The source population included patients enrolled in the ASCEND and CAPACITY trials (N=1247). Pearson's correlation coefficients were used to characterise the relationship between changes in FVC during consecutive 6-month intervals in the placebo population. Outcomes following a ≥10% decline in FVC were evaluated by comparing the proportion of patients in the pirfenidone and placebo groups who experienced a ≥10% decline in FVC or death during the subsequent 6 months.</p></sec><sec><title>Results</title><p>A weak negative correlation was observed between FVC changes during consecutive intervals in the placebo population (coefficient, −0.146, p<0.001), indicating substantial variability. Thirty-four (5.5%) and 68 (10.9%) patients in the pirfenidone and placebo groups, respectively, experienced a ≥10% decline in FVC by month 6. During the subsequent 6 months, fewer patients in the pirfenidone group compared with placebo experienced a ≥10% decline in FVC or death (5.9% vs 27.9%; relative difference, 78.9%). There was one (2.9%) death in the pirfenidone group and 14 (20.6%) deaths in the placebo group (relative difference, 85.7%).</p></sec><sec><title>Conclusions</title><p>Longitudinal FVC data from patients with IPF showed substantial intrasubject variability, underscoring the inability to reliably assess therapeutic response using serial FVC trends. In patients who progressed during treatment, continued treatment with pirfenidone resulted in a lower risk of subsequent FVC decline or death.</p></sec><sec><title>Trial registration numbers</title><p>NCT01366209, NCT00287729, NCT00287716.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Raghu, G" uniqKey="Raghu G">G Raghu</name></author><author><name sortKey="Collard, Hr" uniqKey="Collard H">HR Collard</name></author><author><name sortKey="Egan, Jj" uniqKey="Egan J">JJ Egan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Noble, Pw" uniqKey="Noble P">PW Noble</name></author><author><name sortKey="Albera, C" uniqKey="Albera C">C Albera</name></author><author><name sortKey="Bradford, Wz" uniqKey="Bradford W">WZ Bradford</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="King, Te" uniqKey="King T">TE King</name></author><author><name sortKey="Bradford, Wz" uniqKey="Bradford W">WZ Bradford</name></author><author><name sortKey="Castro Bernardini, S" uniqKey="Castro Bernardini S">S Castro-Bernardini</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Richeldi, L" uniqKey="Richeldi L">L Richeldi</name></author><author><name sortKey="Du Bois, Rm" uniqKey="Du Bois R">RM du Bois</name></author><author><name sortKey="Raghu, G" uniqKey="Raghu G">G Raghu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Du Bois, Rm" uniqKey="Du Bois R">RM du Bois</name></author><author><name sortKey="Weycker, D" uniqKey="Weycker D">D Weycker</name></author><author><name sortKey="Albera, C" uniqKey="Albera C">C Albera</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Collard, Hr" uniqKey="Collard H">HR Collard</name></author><author><name sortKey="King, Te" uniqKey="King T">TE King</name></author><author><name sortKey="Bartelson, Bb" uniqKey="Bartelson B">BB Bartelson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Flaherty, Kr" uniqKey="Flaherty K">KR Flaherty</name></author><author><name sortKey="Mumford, Ja" uniqKey="Mumford J">JA Mumford</name></author><author><name sortKey="Murray, S" uniqKey="Murray S">S Murray</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jegal, Y" uniqKey="Jegal Y">Y Jegal</name></author><author><name sortKey="Kim, Ds" uniqKey="Kim D">DS Kim</name></author><author><name sortKey="Shim, Ts" uniqKey="Shim T">TS Shim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zappala, Cj" uniqKey="Zappala C">CJ Zappala</name></author><author><name sortKey="Latsi, Pi" uniqKey="Latsi P">PI Latsi</name></author><author><name sortKey="Nicholson, Ag" uniqKey="Nicholson A">AG Nicholson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Du Bois, Rm" uniqKey="Du Bois R">RM du Bois</name></author><author><name sortKey="Weycker, D" uniqKey="Weycker D">D Weycker</name></author><author><name sortKey="Albera, C" uniqKey="Albera C">C Albera</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Richeldi, L" uniqKey="Richeldi L">L Richeldi</name></author><author><name sortKey="Ryerson, Cj" uniqKey="Ryerson C">CJ Ryerson</name></author><author><name sortKey="Lee, Js" uniqKey="Lee J">JS Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Martinez, Fj" uniqKey="Martinez F">FJ Martinez</name></author><author><name sortKey="Safrin, S" uniqKey="Safrin S">S Safrin</name></author><author><name sortKey="Weycker, D" uniqKey="Weycker D">D Weycker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cohen, J" uniqKey="Cohen J">J Cohen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schmidt, Sl" uniqKey="Schmidt S">SL Schmidt</name></author><author><name sortKey="Tayob, N" uniqKey="Tayob N">N Tayob</name></author><author><name sortKey="Han, Mk" uniqKey="Han M">MK Han</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wuyts, Wa" uniqKey="Wuyts W">WA Wuyts</name></author><author><name sortKey="Antoniou, Km" uniqKey="Antoniou K">KM Antoniou</name></author><author><name sortKey="Borensztajn, K" uniqKey="Borensztajn K">K Borensztajn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Richeldi, L" uniqKey="Richeldi L">L Richeldi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Du Bois, Rm" uniqKey="Du Bois R">RM du Bois</name></author><author><name sortKey="Nathan, Sd" uniqKey="Nathan S">SD Nathan</name></author><author><name sortKey="Richeldi, L" uniqKey="Richeldi L">L Richeldi</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Brésil</li><li>France</li><li>Italie</li><li>Royaume-Uni</li><li>États-Unis</li></country></list><tree><noCountry><name sortKey="Costabel, Ulrich" sort="Costabel, Ulrich" uniqKey="Costabel U" first="Ulrich" last="Costabel">Ulrich Costabel</name><name sortKey="Glaspole, Ian" sort="Glaspole, Ian" uniqKey="Glaspole I" first="Ian" last="Glaspole">Ian Glaspole</name><name sortKey="Glassberg, Marilyn K" sort="Glassberg, Marilyn K" uniqKey="Glassberg M" first="Marilyn K" last="Glassberg">Marilyn K. Glassberg</name><name sortKey="Lancaster, Lisa" sort="Lancaster, Lisa" uniqKey="Lancaster L" first="Lisa" last="Lancaster">Lisa Lancaster</name><name sortKey="Noble, Paul W" sort="Noble, Paul W" uniqKey="Noble P" first="Paul W" last="Noble">Paul W. Noble</name></noCountry><country name="États-Unis"><noRegion><name sortKey="Nathan, Steven D" sort="Nathan, Steven D" uniqKey="Nathan S" first="Steven D" last="Nathan">Steven D. Nathan</name></noRegion><name sortKey="Bradford, Williamson Z" sort="Bradford, Williamson Z" uniqKey="Bradford W" first="Williamson Z" last="Bradford">Williamson Z. Bradford</name><name sortKey="Fagan, Elizabeth A" sort="Fagan, Elizabeth A" uniqKey="Fagan E" first="Elizabeth A" last="Fagan">Elizabeth A. Fagan</name><name sortKey="Fishman, Robert S" sort="Fishman, Robert S" uniqKey="Fishman R" first="Robert S" last="Fishman">Robert S. Fishman</name><name sortKey="Glasscock, Kenneth F" sort="Glasscock, Kenneth F" uniqKey="Glasscock K" first="Kenneth F" last="Glasscock">Kenneth F. Glasscock</name><name sortKey="King, Talmadge E" sort="King, Talmadge E" uniqKey="King T" first="Talmadge E" last="King">Talmadge E. King</name><name sortKey="Lederer, David J" sort="Lederer, David J" uniqKey="Lederer D" first="David J" last="Lederer">David J. Lederer</name><name sortKey="Lin, Zhengning" sort="Lin, Zhengning" uniqKey="Lin Z" first="Zhengning" last="Lin">Zhengning Lin</name><name sortKey="Swigris, Jeffrey J" sort="Swigris, Jeffrey J" uniqKey="Swigris J" first="Jeffrey J" last="Swigris">Jeffrey J. Swigris</name></country><country name="Italie"><noRegion><name sortKey="Albera, Carlo" sort="Albera, Carlo" uniqKey="Albera C" first="Carlo" last="Albera">Carlo Albera</name></noRegion></country><country name="Royaume-Uni"><noRegion><name sortKey="Du Bois, Roland M" sort="Du Bois, Roland M" uniqKey="Du Bois R" first="Roland M" last="Du Bois">Roland M. Du Bois</name></noRegion><name sortKey="Wells, Athol U" sort="Wells, Athol U" uniqKey="Wells A" first="Athol U" last="Wells">Athol U. Wells</name></country><country name="Brésil"><noRegion><name sortKey="Pereira, Carlos A" sort="Pereira, Carlos A" uniqKey="Pereira C" first="Carlos A" last="Pereira">Carlos A. Pereira</name></noRegion></country><country name="France"><noRegion><name sortKey="Valeyre, Dominique" sort="Valeyre, Dominique" uniqKey="Valeyre D" first="Dominique" last="Valeyre">Dominique Valeyre</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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