Description
Humana Molecular Basis of Pulmonary Disease Insights from Rare Lung Disorders by Francis X. McCormack, Ralph J. Panos, Bruce C. Trapnell
Dr. SharonRounds,theeditorforthisserieswhoinvitedustowriteabookonrare lungdiseases,developedtheideaafterattendingthe2004Lymphangioleiomyomatosis (LAM)Foundationannualresearchmeeting. Shewasakeynotespeakeratthatevent (duringhertenureasthepresidentoftheAmericanThoracicSociety)andwasw- nesstothepowerofpatientadvocacyandthemission-basedscienti ceffortthathad broughtthisrarediseaseofwomenfromobscuritytoclinicaltrialswithtargetedmol- ulartherapiesinunderadecade. Theprogressinpulmonaryalveolarproteinosis(PAP), pulmonaryalveolarmicrolithiasis(PAM),inheriteddisordersofsurfactantmetabolism, and pulmonary arterial hypertension, to name a few, has been no less astounding. Advanceshavecomefromthemostsurprisingdirections;fruit iesforLAM,gen- ically engineered mice made for other purposes for PAP, and groundbreaking hi- densitySNP(single-nucleotidepolymorphism)analysesdoneonahandfuloffamilies forPAM._x000D_Inmanycases,insightsintobiologygainedfromrarediseaseshaveinformed researchapproachesandtreatmentstrategiesformorecommondiseases;forexample, knowledgegainedfromthestudyofPAPabouttheroleofGM-CSFinthelunghas sparkedinterestintheuseofantiGM-CSFapproachestocontrolbothpulmonaryand extrapulmonaryin ammationinavarietyofdiseases. The ndingthatinterstitiallung diseasedevelopsinfamilieswithcytotoxicmutationsinsurfactantproteinC(SP-C), agenewhichisexpressedonlyinalveolartypecells,hasunderscoredtheimportance oftheintegrityofthealveolarepitheliuminthepathogenesisofparenchymal brosis. Opportunitiestoapproachlungdiseasepathogenesisfromthevantagepointofap- marymoleculardefectaregiftsfromnaturethatareuniquelyabundantamongtherare lungdisorders. WesalutetheNIHandtheNationalCenterforResearchResourcesfortheirvisionin facilitatingthetranslationofbasicresearchadvancesinrarelungdiseasesintoclinical realitythroughtheRareLungDiseaseConsortium,anetworkof13USandinter- tionalsitesthatiscurrentlyconductingclinicaltrialsandstudiesinLAM,alphaone antitrypsin de ciency, pediatric interstitial lung disease, and PAP._x000D_It has been a rare privilegetoworkonsuchfascinatingdiseaseswithsuchcapableinvestigatorsfromall overtheworldoverthepast6years. v vi Preface Theformatforthisvolumeisunique. Mostchaptershavebeenauthoredbyacli- cianandabasicscientistwhoareexpertinthediseasetopicandunderlyingmolecular defect,respectively. Theirchargewastofocusonthegeneticbasisandmolecularpat- genesisofdisease,animalmodels,clinicalfeatures,diagnosticapproach,conventional managementandtreatment,andfuturetherapeutictargetsanddirections. Theintentwas nottoprovideabroadoverview,butrathertoshedlightonthemolecularmechanisms thatevoketheclinicalpresentationandengendertreatmentstrategiesforeachdisease. Wehopethatthisapproachwillproveusefulforpulmonarycliniciansandscientists alike. Wethankourwives,Holly,Jean,andVicky,fortheirsupportandindulgencewith latenightemailsandwork- lledweekends,Dr. Roundsfortheinvitationtowritethe book,andalloftheauthorswhocontributed. FrancisMcCormack,MD RalphPanos,MD BruceTrapnell,MD Contents Preface...v Contributors...ix 1 AClinicalApproachtoRareLungDiseases...1 RalphJ. Panos 2 ClinicalTrialsforRareLungDiseases...31 JeffreyKrischer 3 IdiopathicandFamilialPulmonaryArterialHypertension ...39 JeanM._x000D_Elwing,GailH. Deutsch,WilliamC. Nichols, andTimothyD. LeCras 4 Lymphangioleiomyomatosis...85 ElizabethP. HenskeandFrancisX. McCormack 5 AutoimmunePulmonaryAlveolarProteinosis...111 BruceC. Trapnell,KohNakata,andYoshikazuInoue 6 MutationsinSurfactantProteinCandInterstitialLungDisease ...133 RalphJ. PanosandJamesP. Bridges 7 HereditaryHaemorrhagicTelangiectasia ...167 ClaireShovlinandS. PaulOh 8 Hermansky-Dr. SharonRounds,theeditorforthisserieswhoinvitedustowriteabookonrare lungdiseases,developedtheideaafterattendingthe2004Lymphangioleiomyomatosis (LAM)Foundationannualresearchmeeting. Shewasakeynotespeakeratthatevent (duringhertenureasthepresidentoftheAmericanThoracicSociety)andwasw- nesstothepowerofpatientadvocacyandthemission-basedscienti ceffortthathad broughtthisrarediseaseofwomenfromobscuritytoclinicaltrialswithtargetedmol- ulartherapiesinunderadecade. Theprogressinpulmonaryalveolarproteinosis(PAP), pulmonaryalveolarmicrolithiasis(PAM),inheriteddisordersofsurfactantmetabolism, and pulmonary arterial hypertension, to name a few, has been no less astounding._x000D_Advanceshavecomefromthemostsurprisingdirections;fruit iesforLAM,gen- ically engineered mice made for other purposes for PAP, and groundbreaking hi- densitySNP(single-nucleotidepolymorphism)analysesdoneonahandfuloffamilies forPAM. Inmanycases,insightsintobiologygainedfromrarediseaseshaveinformed researchapproachesandtreatmentstrategiesformorecommondiseases;forexample, knowledgegainedfromthestudyofPAPabouttheroleofGM-CSFinthelunghas sparkedinterestintheuseofantiGM-CSFapproachestocontrolbothpulmonaryand extrapulmonaryin ammationinavarietyofdiseases. The ndingthatinterstitiallung diseasedevelopsinfamilieswithcytotoxicmutationsinsurfactantproteinC(SP-C), agenewhichisexpressedonlyinalveolartypecells,hasunderscoredtheimportance oftheintegrityofthealveolarepitheliuminthepathogenesisofparenchymal brosis. Opportunitiestoapproachlungdiseasepathogenesisfromthevantagepointofap- marymoleculardefectaregiftsfromnaturethatareuniquelyabundantamongtherare lungdisorders._x000D_WesalutetheNIHandtheNationalCenterforResearchResourcesfortheirvisionin facilitatingthetranslationofbasicresearchadvancesinrarelungdiseasesintoclinical realitythroughtheRareLungDiseaseConsortium,anetworkof13USandinter- tionalsitesthatiscurrentlyconductingclinicaltrialsandstudiesinLAM,alphaone antitrypsin de ciency, pediatric interstitial lung disease, and PAP. It has been a rare privilegetoworkonsuchfascinatingdiseaseswithsuchcapableinvestigatorsfromall overtheworldoverthepast6years. v vi Preface Theformatforthisvolumeisunique. Mostchaptershavebeenauthoredbyacli- cianandabasicscientistwhoareexpertinthediseasetopicandunderlyingmolecular defect,respectively. Theirchargewastofocusonthegeneticbasisandmolecularpat- genesisofdisease,animalmodels,clinicalfeatures,diagnosticapproach,conventional managementandtreatment,andfuturetherapeutictargetsanddirections. Theintentwas nottoprovideabroadoverview,butrathertoshedlightonthemolecularmechanisms thatevoketheclinicalpresentationandengendertreatmentstrategiesforeachdisease. Wehopethatthisapproachwillproveusefulforpulmonarycliniciansandscientists alike._x000D_Wethankourwives,Holly,Jean,andVicky,fortheirsupportandindulgencewith latenightemailsandwork- lledweekends,Dr. Roundsfortheinvitationtowritethe book,andalloftheauthorswhocontributed. FrancisMcCormack,MD RalphPanos,MD BruceTrapnell,MD Contents Preface...v Contributors...ix 1 AClinicalApproachtoRareLungDiseases...1 RalphJ. Panos 2 ClinicalTrialsforRareLungDiseases...31 JeffreyKrischer 3 IdiopathicandFamilialPulmonaryArterialHypertension ...39 JeanM. Elwing,GailH. Deutsch,WilliamC. Nichols, andTimothyD. LeCras 4 Lymphangioleiomyomatosis...85 ElizabethP. HenskeandFrancisX. McCormack 5 AutoimmunePulmonaryAlveolarProteinosis...111 BruceC. Trapnell,KohNakata,andYoshikazuInoue 6 MutationsinSurfactantProteinCandInterstitialLungDisease ...133 RalphJ. PanosandJamesP. Bridges 7 HereditaryHaemorrhagicTelangiectasia ...167 ClaireShovlinandS. PaulOh 8 Hermansky-Dr. SharonRounds,theeditorforthisserieswhoinvitedustowriteabookonrare lungdiseases,developedtheideaafterattendingthe2004Lymphangioleiomyomatosis (LAM)Foundationannualresearchmeeting._x000D_Shewasakeynotespeakeratthatevent (duringhertenureasthepresidentoftheAmericanThoracicSociety)andwasw- nesstothepowerofpatientadvocacyandthemission-basedscienti ceffortthathad broughtthisrarediseaseofwomenfromobscuritytoclinicaltrialswithtargetedmol- ulartherapiesinunderadecade. Theprogressinpulmonaryalveolarproteinosis(PAP), pulmonaryalveolarmicrolithiasis(PAM),inheriteddisordersofsurfactantmetabolism, and pulmonary arterial hypertension, to name a few, has been no less astounding. Advanceshavecomefromthemostsurprisingdirections;fruit iesforLAM,gen- ically engineered mice made for other purposes for PAP, and groundbreaking hi- densitySNP(single-nucleotidepolymorphism)analysesdoneonahandfuloffamilies forPAM. Inmanycases,insightsintobiologygainedfromrarediseaseshaveinformed researchapproachesandtreatmentstrategiesformorecommondiseases;forexample, knowledgegainedfromthestudyofPAPabouttheroleofGM-CSFinthelunghas sparkedinterestintheuseofantiGM-CSFapproachestocontrolbothpulmonaryand extrapulmonaryin ammationinavarietyofdiseases._x000D_The ndingthatinterstitiallung diseasedevelopsinfamilieswithcytotoxicmutationsinsurfactantproteinC(SP-C), agenewhichisexpressedonlyinalveolartypecells,hasunderscoredtheimportance oftheintegrityofthealveolarepitheliuminthepathogenesisofparenchymal brosis. Opportunitiestoapproachlungdiseasepathogenesisfromthevantagepointofap- marymoleculardefectaregiftsfromnaturethatareuniquelyabundantamongtherare lungdisorders. WesalutetheNIHandtheNationalCenterforResearchResourcesfortheirvisionin facilitatingthetranslationofbasicresearchadvancesinrarelungdiseasesintoclinical realitythroughtheRareLungDiseaseConsortium,anetworkof13USandinter- tionalsitesthatiscurrentlyconductingclinicaltrialsandstudiesinLAM,alphaone antitrypsin de ciency, pediatric interstitial lung disease, and PAP. It has been a rare privilegetoworkonsuchfascinatingdiseaseswithsuchcapableinvestigatorsfromall overtheworldoverthepast6years. v vi Preface Theformatforthisvolumeisunique. Mostchaptershavebeenauthoredbyacli- cianandabasicscientistwhoareexpertinthediseasetopicandunderlyingmolecular defect,respectively._x000D_Theirchargewastofocusonthegeneticbasisandmolecularpat- genesisofdisease,animalmodels,clinicalfeatures,diagnosticapproach,conventional managementandtreatment,andfuturetherapeutictargetsanddirections. Theintentwas nottoprovideabroadoverview,butrathertoshedlightonthemolecularmechanisms thatevoketheclinicalpresentationandengendertreatmentstrategiesforeachdisease. Wehopethatthisapproachwillproveusefulforpulmonarycliniciansandscientists alike. Wethankourwives,Holly,Jean,andVicky,fortheirsupportandindulgencewith latenightemailsandwork- lledweekends,Dr. Roundsfortheinvitationtowritethe book,andalloftheauthorswhocontributed. FrancisMcCormack,MD RalphPanos,MD BruceTrapnell,MD Contents Preface...v Contributors...ix 1 AClinicalApproachtoRareLungDiseases...1 RalphJ. Panos 2 ClinicalTrialsforRareLungDiseases...31 JeffreyKrischer 3 IdiopathicandFamilialPulmonaryArterialHypertension ...39 JeanM. Elwing,GailH. Deutsch,WilliamC. Nichols, andTimothyD. LeCras 4 Lymphangioleiomyomatosis...85 ElizabethP. HenskeandFrancisX. McCormack 5 AutoimmunePulmonaryAlveolarProteinosis...111 BruceC. Trapnell,KohNakata,andYoshikazuInoue 6 MutationsinSurfactantProteinCandInterstitialLungDisease ...133 RalphJ._x000D_PanosandJamesP. Bridges 7 HereditaryHaemorrhagicTelangiectasia ...167 ClaireShovlinandS. PaulOh 8 Hermansky-PudlakSyndrome...189 LisaR. YoungandWilliamA. Gahl 9 Alpha-1AntitrypsinDe ciency ...209 CharlieStrangeandSabinaJanciauskiene vii viii Contents 10 TheMarfanSyndrome ...225 AmareshNathandEnidR. Neptune 11 SurfactantDe ciencyDisorders:SP-BandABCA3...247 LawrenceM. Nogee 12 PulmonaryCapillaryHemangiomatosis ...267 EdwardD. Chan,KathrynChmura,andAndrewSullivan 13 Anti-glomerularBasementDisease:Goodpasture'sSyndrome...275 GangadharTaduri,RaghuKalluri,andRalphJ. Panos 14 PrimaryCiliaryDyskinesia...293 MichaelR. Knowles,HildaMetjian,MargaretW. Leigh, andMaimoonaA. Zariwala 15 PulmonaryAlveolarMicrolithiasis...325 KoichiHagiwara,TakeshiJohkoh,andTeruoTachibana 16 CysticFibrosis...339 AndreM. Cantin 17 PulmonaryLangerhans'CellHistiocytosis-Advances intheUnderstandingofaTrueDendriticCellLungDisease...369 RobertVassallo 18 Sarcoidosis...389 RalphJ. PanosandAndrewP. Fontenot 19 SclerodermaLungDisease...409 BrentW. Kinder SubjectIndex...421 Contributors JamesP. Bridges,PhD, DepartmentofNeonatologyinPulmonaryBiology,Children's HospitalMedicalCenter,Cincinnati,OH AndreM._x000D_Cantin,MD, Department of Medicine, University of Sherbrooke, Sherbrooke,QC,Canada EdwardD. Chan,MD, DepartmentofInternalMedicine,NationalJewishMedicaland ResearchCenter,Denver,CO KathrynChmura,BA, Department of Medicine, University of Colorado School of Medicine,Denver,CO GailH._x000D_show more Table of contents : - _x000D_
Chapter 1. A Clinical Approach to Rare Lung Diseases _x000D_
Ralph Panos, M.D._x000D_
_x000D_
Chapter 2. Clinical Trials for Rare Lung Diseases_x000D_
Jeffrey Krischer, Ph.D._x000D_
_x000D_
Chapter 3. Idiopathic and Familial Pulmonary Arterial Hypertension_x000D_
Jean M. Elwing, M.D., Gail Deutsch, M.D., William C. Nichols, Ph.D., and Timothy LeCras, Ph.D., _x000D_
_x000D_
Chapter 4. Lymphangioleiomyomatosis_x000D_
Francis X. McCormack, M.D, and Elizabeth P. Henske, M.D., Ph.D._x000D_
_x000D_
Chapter 5. Autoimmune Pulmonary Alveolar Proteinosis _x000D_
Bruce Trapnell, M.D., Koh Nakata, M.D., Ph.D., and Yoshikazu Inoue, M.D., Ph.D._x000D_
_x000D_
Chapter 6. Mutations in Surfactant Protein C and Interstitial Lung Disease_x000D_
James P. Bridges, Ph. D. and Ralph Panos, M.D._x000D_
_x000D_
Chapter 7. Hereditary Hemorrhagic Telangiectasia_x000D_
Claire Shovlin, M.D and S. Paul Oh, Ph.D. _x000D_
_x000D_
Chapter 8. Hermansky Pudlak Syndrome_x000D_
Lisa Young, M.D. and Bill Gahl, M.D., Ph.D._x000D_
_x000D_
Chapter 9. Alpha One Antitrypsin Deficiency_x000D_
Charlie Strange, M.D. and Sabrina Janciauskiene, Ph.D. _x000D_
Chapter 10. The Marfan Syndrome_x000D_
Amaresh Nath, M.D and Enid Neptune, M.D._x000D_
_x000D_
Chapter 11. Surfactant Deficiency Disorders SP-B and ABCA3_x000D_
Larry Nogee, M.D._x000D_
_x000D_
Chapter 12. Pulmonary Capillary Hemangiomatosis _x000D_
Edward D. Chan, M.D., Kathryn Chmura, B.A, and Andrew Sullivan, M.D._x000D_
_x000D_
Chapter 13. Goodpasture's Syndrome_x000D_
Gangadar Taduri, M.D., D.M., Raghu Kalluri, Ph.D., and Ralph P. Panos, M.D. _x000D_
_x000D_
Chapter 14. Primary Ciliary Diskinesia _x000D_
Michael R. Knowles, M.D., Hilda Morillas, M.D., Margaret W. Leigh, M.D., Maimoona Zariwala, Ph.D._x000D_
_x000D_
Chapter 15. Pulmonary Alveolar Microlithiasis_x000D_
Koichi Hagiwara, MD, Takeshi Jokoh, M.D., Teruo Tachibana, MD _x000D_
Chapter 16. Cystic Fibrosis _x000D_
Andre Cantin, M.D._x000D_
_x000D_
Chapter 17. Pulmonary Langerhan's CellHistiocytosis _x000D_
Robert Vassallo, M.D._x000D_
_x000D_
Chapter 18. Sarcoidosis_x000D_
Ralph Panos, M.D. and Andrew Fontenot, M.D._x000D_
_x000D_
Chapter 19. Scleroderma Lung Disease_x000D_
Brent Kinder, M.D._x000D_