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36 Collard PulmonaryFibrosis - UCSF CME€¦ · OH: retired school teacher, woodworker ... AJRCCM...
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Pulmonary FibrosisPulmonary FibrosisCase StudiesCase Studies
Harold R Collard, MDHarold R Collard, MDAssistant Professor of MedicineAssistant Professor of Medicine
Interstitial Lung Disease ProgramInterstitial Lung Disease ProgramUniversity of California San FranciscoUniversity of California San Francisco
Mr. H.Mr. H.
62 year old man62 year old manDry coughDry coughSlowly progressive Slowly progressive dyspneadyspnea on exertionon exertionExercise limitationExercise limitationDry Dry inspiratoryinspiratory cracklescracklesClubbingClubbing
QuestionsQuestions
What do I do with this patient?What do I do with this patient?DiagnosisDiagnosisPrognosisPrognosisManagementManagement
Pharmacologic therapyPharmacologic therapyNonNon--pharmacologic therapypharmacologic therapyTransplantationTransplantation
Normal LungNormal Lung
Pulmonary FibrosisPulmonary Fibrosis Mechanisms of fibrosisMechanisms of fibrosis
MMP/TIMP
TGFβInflammation
Clinical ClassificationClinical ClassificationPulmonary Fibrosis
Exposure-related:- Occupational- Environmental- Avocational- Medication
Idiopathic interstitial
pneumonia (IIP)
Connective tissue disease:- Scleroderma- Rheum. arthritis- Sjogrens- UCTD
Other:- Sarcoidosis- Vasculitis/Diffuse alveolar
hemorrhage (DAH)- Langherhans cell histiocytosis
(LCH)- Lymphagioleiomyomatosis
(LAM)- Pulmonary alveolar
proteinosis (PAP)- Eosinophilic pneumonias- Neurofibromatosis- Inherited disorders- Chronic aspiration- Inflammatory bowel disease
Idiopathic pulmonary
fibrosis (IPF)
Desquamative interstitial pneumonia (DIP)
Acute interstitial pneumonia (AIP)
Nonspecific interstitial pneumonia (NSIP)
Respiratory bronchiolitis interstitial lung dis. (RBILD)
Cryptogenic organizing pneumonia (COP)
Lymphocytic interstitial pneumonia (LIP)
DonDon’’t stop with t stop with ““pulmonary fibrosispulmonary fibrosis””
Reasons for a specific diagnosis:Reasons for a specific diagnosis:
Many forms are treatableMany forms are treatableTreatments depend on diagnosisTreatments depend on diagnosisPrognosis variesPrognosis variesClinical trial eligibility requirementsClinical trial eligibility requirements
Diagnostic AlgorithmDiagnostic AlgorithmSuspected PF
HRCTDetailed history + PFTs/Labs +
Smoking historyOcc/Env history
Autoimmune ROSFamily history
SpirometryLung volumes/DLCO
ANA, RF
HighHigh--resolution CT (HRCT)resolution CT (HRCT)
11--1.5 mm 1.5 mm collimationcollimation
Images taken every Images taken every 10 mm10 mm
Supine, prone and Supine, prone and expiratory imagesexpiratory images
Diagnostic AlgorithmDiagnostic AlgorithmSuspected PF
HRCTDetailed history +
Non-diagnosticDiagnostic
Lung biopsy
1. IPF2. Sarcoidosis3. CV-ILD4. Hypersensitivity
pneumonitis5. Rare disease
(LAM, PAP)
PFTs/Labs +
Smoking historyOcc/Env history
Autoimmune ROSFamily history
SpirometryLung volumes/DLCO
ANA, RF
Case 1Case 1
Case 1Case 160 year old man60 year old manShortness of breath for one yearShortness of breath for one yearOccasional nonproductive coughOccasional nonproductive cough
PMH: PMH: atrialatrial fibrillation, GERDfibrillation, GERDMeds: Meds: metoprololmetoprolol, , omeprazoleomeprazoleSH: h/o tobacco, quit 10 years agoSH: h/o tobacco, quit 10 years agoOH: retired school teacher, woodworkerOH: retired school teacher, woodworker
Case 1Case 1
Physical examinationPhysical examinationDesaturatesDesaturates to 86% with walkingto 86% with walkingBibasilar Bibasilar inspiratoryinspiratory cracklescracklesIrregularly irregular, no murmurIrregularly irregular, no murmurDigital clubbing, no edema, rashesDigital clubbing, no edema, rashes
Pulmonary function testsPulmonary function testsFVC 65% predicted, FEV1/FVC 0.85FVC 65% predicted, FEV1/FVC 0.85TLC 70% predictedTLC 70% predictedDLCO 32% predictedDLCO 32% predicted
Case 1: HRCTCase 1: HRCT Case 1: HRCTCase 1: HRCT
Case 1: HRCTCase 1: HRCT Diagnosis?Diagnosis?
A) A) SarcoidosisSarcoidosisB) Hypersensitivity B) Hypersensitivity pneumonitispneumonitisC) Idiopathic Pulmonary FibrosisC) Idiopathic Pulmonary FibrosisD) Cryptogenic Organizing PneumoniaD) Cryptogenic Organizing PneumoniaE) Connective Tissue Related ILDE) Connective Tissue Related ILDF) Requires more informationF) Requires more information
Diagnosis?Diagnosis?
A B C D E F
17% 17% 17%17%17%17%A) A) SarcoidosisSarcoidosisB) Hypersensitivity B) Hypersensitivity pneumonitispneumonitisC) Idiopathic Pulmonary C) Idiopathic Pulmonary FibrosisFibrosisD) Cryptogenic D) Cryptogenic Organizing PneumoniaOrganizing PneumoniaE) Connective Tissue E) Connective Tissue Related ILDRelated ILDF) Requires more F) Requires more informationinformation
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IPF: HRCT diagnosisIPF: HRCT diagnosis
Clinical ClassificationClinical ClassificationPulmonary Fibrosis
Exposure-related:- Occupational- Environmental- Avocational- Medication
Idiopathic interstitial
pneumonia (IIP)
Connective tissue disease:- Scleroderma- Rheum. arthritis- Sjogrens- UCTD
Other:- Sarcoidosis- Vasculitis/Diffuse alveolar
hemorrhage (DAH)- Langherhans cell histiocytosis
(LCH)- Lymphagioleiomyomatosis
(LAM)- Pulmonary alveolar
proteinosis (PAP)- Eosinophilic pneumonias- Neurofibromatosis- Inherited disorders- Chronic aspiration- Inflammatory bowel disease
Idiopathic pulmonary
fibrosis (IPF)
Desquamative interstitial pneumonia (DIP)
Acute interstitial pneumonia (AIP)
Nonspecific interstitial pneumonia (NSIP)
Respiratory bronchiolitis interstitial lung dis. (RBILD)
Cryptogenic organizing pneumonia (COP)
Lymphocytic interstitial pneumonia (LIP)
SurvivalSurvival
Median survival for IPF is 2Median survival for IPF is 2--3 years3 yearsOthers betterOthers better
BjorakerBjoraker. American Journal of Respiratory and Critical Care Medicine 199. American Journal of Respiratory and Critical Care Medicine 1998;v157:p199 8;v157:p199
IPF
IPF: Published DefinitionIPF: Published Definition
““A specific form of chronic A specific form of chronic fibrosingfibrosing interstitial interstitial pneumonia limited to the lung and associated pneumonia limited to the lung and associated with the with the histologichistologic appearance of usual appearance of usual interstitial pneumonia on surgical lung biopsy.interstitial pneumonia on surgical lung biopsy.””
AJRCCM 2000;161:646AJRCCM 2000;161:646
Usual Interstitial PneumoniaUsual Interstitial Pneumonia
Conventional therapyConventional therapy
Ineffective (and often harmful)Ineffective (and often harmful)
Collard Chest 2004;125:2169Collard Chest 2004;125:2169
p = 0.58
Corticosteroids
Adding Adding AcetylcysteineAcetylcysteine
Demedts NEJM 2005;353:2229
PREDNISONE AND AZATHIOPRINE PLUS
ACETYLCYSTEINE(80)
PREDNISONE AND AZATHIOPRINE
ALONE (75)
182 subjects
12 months
Change in FVC and DLCO
P/A/NP/A
P/A/NP/A
Novel therapiesNovel therapies
Interferon Interferon γγ 1b1bPirfenidonePirfenidoneBosentanBosentanEtanerceptEtanercept
TreatmentTreatment
Enroll in a clinical trialEnroll in a clinical trialConsider therapy:Consider therapy:
prednisone/prednisone/azathioprine/acetylcysteineazathioprine/acetylcysteinePulmonary rehabilitationPulmonary rehabilitationLung transplantation evaluationLung transplantation evaluation
Case 2Case 2
Case 2Case 250 year old woman 50 year old woman Progressive cough and dyspnea over 6 Progressive cough and dyspnea over 6 months months
PMH: PMH: ““arthritisarthritis””Meds: ibuprofen as neededMeds: ibuprofen as neededSH: former smoker, quit 1 year agoSH: former smoker, quit 1 year agoOH: Clerical work, OH: Clerical work, ““dusty officedusty office””
Case 2Case 2
Physical examinationPhysical examinationNo No desaturationdesaturation with walkingwith walkingScattered expiratory wheezesScattered expiratory wheezesRegular rate, rhythmRegular rate, rhythmNo clubbing, edemaNo clubbing, edema
Pulmonary function testsPulmonary function testsFVC 75% predicted, FEV1/FVC 68%FVC 75% predicted, FEV1/FVC 68%TLC 75% predictedTLC 75% predictedDLCO 65% predictedDLCO 65% predicted
Case 2: HRCTCase 2: HRCT
Case 2: HRCTCase 2: HRCT Case 2: HRCTCase 2: HRCT
Case 2: HRCTCase 2: HRCT Diagnosis?Diagnosis?
A) A) SarcoidosisSarcoidosisB) Hypersensitivity B) Hypersensitivity pneumonitispneumonitisC) Idiopathic Pulmonary FibrosisC) Idiopathic Pulmonary FibrosisD) Cryptogenic Organizing PneumoniaD) Cryptogenic Organizing PneumoniaE) Connective Tissue Related ILDE) Connective Tissue Related ILDF) Requires more informationF) Requires more information
Diagnosis?Diagnosis?
A B C D E F
17% 17% 17%17%17%17%A) A) SarcoidosisSarcoidosisB) Hypersensitivity B) Hypersensitivity pneumonitispneumonitisC) Idiopathic Pulmonary C) Idiopathic Pulmonary FibrosisFibrosisD) Cryptogenic D) Cryptogenic Organizing PneumoniaOrganizing PneumoniaE) Connective Tissue E) Connective Tissue Related ILDRelated ILDF) Requires more F) Requires more informationinformation
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Surgical Lung BiopsySurgical Lung BiopsyVATS is preferred VATS is preferred approachapproach
Requires single Requires single lung ventilationlung ventilation
Several disparate Several disparate biopsies takenbiopsies taken
Surgical PathologySurgical Pathology Surgical PathologySurgical Pathology
Diagnosis?Diagnosis?
A) A) SarcoidosisSarcoidosisB) Hypersensitivity B) Hypersensitivity pneumonitispneumonitisC) Idiopathic Pulmonary FibrosisC) Idiopathic Pulmonary FibrosisD) Cryptogenic Organizing PneumoniaD) Cryptogenic Organizing PneumoniaE) Connective Tissue Related ILDE) Connective Tissue Related ILDF) Requires more informationF) Requires more information
Diagnosis?Diagnosis?
A B C D E F
17% 17% 17%17%17%17%A) A) SarcoidosisSarcoidosisB) Hypersensitivity B) Hypersensitivity pneumonitispneumonitisC) Idiopathic Pulmonary C) Idiopathic Pulmonary FibrosisFibrosisD) Cryptogenic D) Cryptogenic Organizing PneumoniaOrganizing PneumoniaE) Connective Tissue E) Connective Tissue Related ILDRelated ILDF) Requires more F) Requires more informationinformation
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Clinical ClassificationClinical ClassificationPulmonary Fibrosis
Exposure-related:- Occupational- Environmental- Avocational- Medication
Idiopathic interstitial
pneumonia (IIP)
Connective tissue disease:- Scleroderma- Rheum. arthritis- Sjogrens- UCTD
Other:- Sarcoidosis- Vasculitis/Diffuse alveolar
hemorrhage (DAH)- Langherhans cell histiocytosis
(LCH)- Lymphagioleiomyomatosis
(LAM)- Pulmonary alveolar
proteinosis (PAP)- Eosinophilic pneumonias- Neurofibromatosis- Inherited disorders- Chronic aspiration- Inflammatory bowel disease
Idiopathic pulmonary
fibrosis (IPF)
Desquamative interstitial pneumonia (DIP)
Acute interstitial pneumonia (AIP)
Nonspecific interstitial pneumonia (NSIP)
Respiratory bronchiolitis interstitial lung dis. (RBILD)
Cryptogenic organizing pneumonia (COP)
Lymphocytic interstitial pneumonia (LIP)
ExposureExposure--related ILDrelated ILD
Inorganic agents (= pneumoconiosis)Inorganic agents (= pneumoconiosis)asbestosisasbestosissilicosissilicosis
Organic agents (= hypersensitivity Organic agents (= hypersensitivity pneumonitis)pneumonitis)
Fungal spores (water damage, moldy hay)Fungal spores (water damage, moldy hay)Animal proteins (birds!)Animal proteins (birds!)
MedicationsMedicationsAmiodaroneAmiodarone, , NitrofurantoinNitrofurantoin, , MethotrexateMethotrexate
Hypersensitivity Hypersensitivity PneumonitisPneumonitis Case 2: Expiratory imagesCase 2: Expiratory images
Case 2: Expiratory imagesCase 2: Expiratory images TreatmentTreatment
Removal from antigenRemoval from antigenImmunosuppressionImmunosuppression
CorticosteroidsCorticosteroidsAzathioprineAzathioprine
Pulmonary rehabilitationPulmonary rehabilitationLung transplantation evaluationLung transplantation evaluation
Case 3Case 3
Case 3Case 340 year old man 40 year old man PersistantPersistant cough and cough and dyspneadyspnea over 6 over 6 months months
PMH: asthmaPMH: asthmaMeds: Meds: albuterolalbuterol MDIMDISH: active smokerSH: active smokerOH: Machinist for aerospace companyOH: Machinist for aerospace company
Case 3Case 3
Physical examinationPhysical examinationNo No desaturationdesaturation with walkingwith walkingScattered cracklesScattered cracklesSkin nodules at site of Skin nodules at site of tatootatooNo clubbing, edemaNo clubbing, edema
Pulmonary function testsPulmonary function testsFVC 80% predicted, FEV1/FVC 75%FVC 80% predicted, FEV1/FVC 75%TLC 70% predictedTLC 70% predictedDLCO 55% predictedDLCO 55% predicted
Case 3: HRCTCase 3: HRCT
Diagnosis?Diagnosis?
A) A) SarcoidosisSarcoidosisB) Hypersensitivity B) Hypersensitivity pneumonitispneumonitisC) Idiopathic Pulmonary FibrosisC) Idiopathic Pulmonary FibrosisD) Cryptogenic Organizing PneumoniaD) Cryptogenic Organizing PneumoniaE) Connective Tissue Related ILDE) Connective Tissue Related ILDF) Requires more informationF) Requires more information
Diagnosis?Diagnosis?
A B C D E F
17% 17% 17%17%17%17%
A) A) SarcoidosisSarcoidosisB) Hypersensitivity B) Hypersensitivity pneumonitispneumonitisC) Idiopathic Pulmonary C) Idiopathic Pulmonary FibrosisFibrosisD) Cryptogenic D) Cryptogenic Organizing PneumoniaOrganizing PneumoniaE) Connective Tissue E) Connective Tissue Related ILDRelated ILDF) Requires more F) Requires more informationinformation
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SarcoidosisSarcoidosisIdiopathic disease affecting all organ systemsIdiopathic disease affecting all organ systems
Baughman. AJR
CC
M 2001;164:1885
Surgical PathologySurgical Pathology
Surgical PathologySurgical Pathology Radiographic StageRadiographic Stage
Stage 1 Stage 2
Stage 4Stage 3
##
##
##
#
TreatmentTreatment
Stage 1 disease: often no therapyStage 1 disease: often no therapyStage 2Stage 2--3 disease:3 disease:
PrednisonePrednisoneMethotrexateMethotrexateHydroxychloroquineHydroxychloroquineAzathioprineAzathioprineInfliximabInfliximab
Stage 4 disease: transplantationStage 4 disease: transplantation