2023
Circulating Mitochondrial DNA Is Associated With High Levels of Fatigue in Two Independent Sarcoidosis Cohorts
Fiorini V, Hu B, Sun Y, Yu S, McGovern J, Gandhi S, Woo S, Turcotte-Foster S, Pivarnik T, Khan Z, Adams T, Herzog E, Kaminski N, Gulati M, Ryu C. Circulating Mitochondrial DNA Is Associated With High Levels of Fatigue in Two Independent Sarcoidosis Cohorts. CHEST Journal 2023, 165: 1174-1185. PMID: 37977267, PMCID: PMC11110677, DOI: 10.1016/j.chest.2023.11.020.Peer-Reviewed Original ResearchPatient-related outcome measuresToll-like receptor 9Fatigue Assessment ScalePlasma mtDNA concentrationsTLR9 activationSarcoidosis patientsMtDNA concentrationsMulti-organ sarcoidosisCommon chief complaintInnate immune activationNovel therapeutic strategiesDomains of fatigueSevere clinical phenotypePsychobiologic mechanismsSarcoidosis cohortScadding stageCorticosteroid useCytokine levelsExtrapulmonary diseaseProspective cohortFAS scoresPulmonary fibrosisChief complaintImmune activationPatient population
2022
Disparities in Lung Transplant among Patients with Idiopathic Pulmonary Fibrosis: An Analysis of the IPF-PRO Registry
Swaminathan A, Hellkamp A, Neely M, Bender S, Paoletti L, White E, Palmer S, Whelan T, Dilling D, Baker A, Beegle S, Belperio J, Condos R, Cordova F, Culver D, Fitzgerald J, Flaherty K, Gibson K, Gulati M, Guntupalli K, Gupta N, Case A, Hotchkin D, Huie T, Kaner R, Kim H, Lancaster L, Lasky J, Lee D, Liesching T, Lipchik R, Lobo J, Luckhardt T, Mageto Y, Menon P, Morrison L, Namen A, Oldham J, Paul T, Zhang D, Porteous M, Raj R, Ramaswamy M, Russell T, Sachs P, Safdar Z, Shafazand S, Siddiqi A, Sigal B, Strek M, Suliman S, Tabak J, Walia R. Disparities in Lung Transplant among Patients with Idiopathic Pulmonary Fibrosis: An Analysis of the IPF-PRO Registry. Annals Of The American Thoracic Society 2022, 19: 981-990. PMID: 35073248, PMCID: PMC9169123, DOI: 10.1513/annalsats.202105-589oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisMedian ZIP code incomeZip code incomeLung transplant programsLung transplantProspective outcomes registryClinical characteristicsOutcomes RegistryPulmonary fibrosisTransplant programsSocial determinantsLung transplant centersDisease severity measuresIPF-PRO RegistryLikelihood of deathYears of ageLung transplantationPrespecified covariatesU.S. registriesDifferential associationsTransplant centersTransplant eligibilityClinical trialsTherapeutic modalitiesPatientsCorrection to: Association of Circulating Proteins with Death or Lung Transplant in Patients with Idiopathic Pulmonary Fibrosis in the IPF-PRO Registry Cohort
Todd JL, Neely ML, Overton R, Mulder H, Roman J, Lasky JA, de Andrade JA, Gulati M, Huang H, Leonard TB, Hesslinger C, Noth I, Belperio JA, Flaherty KR, Palmer SM. Correction to: Association of Circulating Proteins with Death or Lung Transplant in Patients with Idiopathic Pulmonary Fibrosis in the IPF-PRO Registry Cohort. Lung 2022, 200: 19-19. PMID: 35166906, PMCID: PMC8881254, DOI: 10.1007/s00408-022-00516-3.Peer-Reviewed Original ResearchAssociation of Circulating Proteins with Death or Lung Transplant in Patients with Idiopathic Pulmonary Fibrosis in the IPF-PRO Registry Cohort
Todd JL, Neely ML, Overton R, Mulder H, Roman J, Lasky JA, de Andrade JA, Gulati M, Huang H, Leonard TB, Hesslinger C, Noth I, Belperio JA, Flaherty KR, Palmer SM. Association of Circulating Proteins with Death or Lung Transplant in Patients with Idiopathic Pulmonary Fibrosis in the IPF-PRO Registry Cohort. Lung 2022, 200: 11-18. PMID: 35066606, PMCID: PMC8881240, DOI: 10.1007/s00408-021-00505-y.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisLung transplantRespiratory deathsPulmonary fibrosisClinical measuresOptimism-corrected C-indexRisk of mortalityVariable clinical courseIPF-PRO RegistryRegistry cohortComposite outcomeClinical courseMultivariable analysisUnivariable analysisPatient outcomesC-indexCirculating proteinFatal diseaseTransplantPatientsDeathFibrosisOutcomesAssociationRegistry
2021
Delphi Consensus Recommendations on Management of Dosing, Adverse Events, and Comorbidities in the Treatment of Idiopathic Pulmonary Fibrosis with Nintedanib
Rahaghi F, Belperio JA, Fitzgerald J, Gulati M, Hallowell R, Highland KB, Huie TJ, Kim HJ, Kolb M, Lasky JA, Southern BD, Swigris JJ, de Andrade JA. Delphi Consensus Recommendations on Management of Dosing, Adverse Events, and Comorbidities in the Treatment of Idiopathic Pulmonary Fibrosis with Nintedanib. Clinical Medicine Insights Circulatory Respiratory And Pulmonary Medicine 2021, 15: 11795484211006050. PMID: 33854398, PMCID: PMC8013629, DOI: 10.1177/11795484211006050.Peer-Reviewed Original ResearchIdiopathic pulmonary fibrosisConsensus recommendationsAdverse eventsPulmonary fibrosisPrescribing informationManagement of comorbiditiesManagement of patientsAdverse event managementClinical trial dataEvidence-based literatureReal-world evidenceCytochrome P450 3A4Delphi consensus recommendationsConcomitant medicationsLiver dysfunctionTolerability issuesConcomitant administrationGastrointestinal effectsDisease progressionNintedanibComorbiditiesAppropriate managementTrial dataPatientsP450 3A4
2020
The Pulmonary Fibrosis Foundation Patient Registry. Rationale, Design, and Methods.
Wang BR, Edwards R, Freiheit EA, Ma Y, Burg C, de Andrade J, Lancaster L, Lindell K, Nathan SD, Raghu G, Gibson K, Gulati M, Mason W, Noth I, Schmidt B, Spino C, Staszak S, Stauffer J, Wolters PJ, Cosgrove GP, Flaherty KR. The Pulmonary Fibrosis Foundation Patient Registry. Rationale, Design, and Methods. Annals Of The American Thoracic Society 2020, 17: 1620-1628. PMID: 32776789, DOI: 10.1513/annalsats.202001-035sd.Peer-Reviewed Original ResearchConceptsInterstitial lung diseasePatient RegistryClinician accessLarge multicenter registryMean diffusing capacityPositive smoking historyPercent of patientsIdiopathic pulmonary fibrosisTime of enrollmentIndividuals 18 yearsMulticenter registrySmoking historyPulmonary fibrosisSupplemental oxygenVital capacityLung diseaseMean agePatient populationAntifibrotic therapyApplicable biomarkersClinical informationDiffusing capacityPatientsClinical sitesRegistryAntifibrotic Drug Use in Patients with Idiopathic Pulmonary Fibrosis. Data from the IPF-PRO Registry
Salisbury M, Conoscenti C, Culver D, Yow E, Neely M, Bender S, Hartmann N, Palmer S, Leonard T, Baker A, Beegle S, Belperio J, Condos R, Cordova F, Culver D, Dilling D, Fitzgerald J, Flaherty K, Gibson K, Gulati M, Guntupalli K, Gupta N, Case A, Hotchkin D, Huie T, Kaner R, Kim H, Lancaster L, Lasky J, Lee D, Liesching T, Lipchik R, Lobo J, Luckhardt (formerly Joao de Andrade) T, Mageto Y, Malik N, Menon P, Morrison L, Namen A, Oldham J, Paul T, Podolanczuk A, Porteous M, Raj R, Ramaswamy M, Russell T, Sachs P, Safdar Z, Shafazand S, Siddiqi A, Sigal B, Strek M, Suliman S, Tabak J, Walia R, Whelan T. Antifibrotic Drug Use in Patients with Idiopathic Pulmonary Fibrosis. Data from the IPF-PRO Registry. Annals Of The American Thoracic Society 2020, 17: 1413-1423. PMID: 32574517, PMCID: PMC7640723, DOI: 10.1513/annalsats.201912-880oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisIPF-PRO RegistrySelf-rated healthAntifibrotic medicationsEnrollment windowPulmonary fibrosisDiagnosis of IPFVital capacity percentageMajority of patientsWorse self-rated healthInterstitial lung diseaseProspective outcomes registryGreater disease severityEligible patientsU.S. registriesCarbon monoxide percentageLung biopsyPatient characteristicsMedication useOutcomes RegistrySleep apneaLung diseaseDefinite diagnosisClinical trialsFamily historyAssociations between Patient-reported Outcomes and Death or Lung transplant in IPF: Data from the IPF-PRO Registry
Case AH, Hellkamp AS, Neely ML, Bender S, Dilling DF, Gulati M, Hotchkin DL, Huie TJ, Lancaster L, Snyder LD, Conoscenti CS, Palmer S. Associations between Patient-reported Outcomes and Death or Lung transplant in IPF: Data from the IPF-PRO Registry. Annals Of The American Thoracic Society 2020, 0: 699-705. PMID: 32040340, PMCID: PMC7258421, DOI: 10.1513/annalsats.201906-437oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPatient-reported outcomesLung transplantClinical variablesSt. George's Respiratory Questionnaire total scoreSGRQ activity scoreUnderwent lung transplantClinical risk factorsPredictors of mortalityHealth-related qualityQuestionnaire total scoreIPF-PRO RegistryProspective outcomes registrySGRQ symptomsComposite outcomeExercise capacityActivity scoreOutcomes RegistryPulmonary fibrosisRisk factorsPhysical activityPatientsUnivariable modelsTransplantWorse scores
2019
Peripheral blood proteomic profiling of idiopathic pulmonary fibrosis biomarkers in the multicentre IPF-PRO Registry
Todd JL, Neely ML, Overton R, Durham K, Gulati M, Huang H, Roman J, Newby LK, Flaherty KR, Vinisko R, Liu Y, Roy J, Schmid R, Strobel B, Hesslinger C, Leonard TB, Noth I, Belperio JA, Palmer SM. Peripheral blood proteomic profiling of idiopathic pulmonary fibrosis biomarkers in the multicentre IPF-PRO Registry. Respiratory Research 2019, 20: 227. PMID: 31640794, PMCID: PMC6805665, DOI: 10.1186/s12931-019-1190-z.Peer-Reviewed Original ResearchConceptsDisease severity measuresIPF-PRO RegistryProtein expressionLung diseaseC motif chemokine ligand 17Disease severitySeverity measuresBackgroundIdiopathic pulmonary fibrosisProgressive lung diseaseChemokine ligand 17Differential protein expressionVon Willebrand factorPulmonary fibrosisImmune activationPermeability-increasing proteinFibrosis biomarkersMultivariable modelHaemostatic responseLigand 17Control statusGlycoprotein thrombospondin-1IPFBiomarker candidatesThrombospondin-1Protein CPatient Registries in Idiopathic Pulmonary Fibrosis
Culver DA, Behr J, Belperio JA, Corte TJ, de Andrade JA, Flaherty KR, Gulati M, Huie TJ, Lancaster LH, Roman J, Ryerson CJ, Kim HJ. Patient Registries in Idiopathic Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2019, 200: 160-167. PMID: 31034241, PMCID: PMC6635784, DOI: 10.1164/rccm.201902-0431ci.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisPatient RegistryPrecision medicine approachQuality of lifeThousands of patientsClinical characteristicsRegistry databasePatient populationLarge registriesDisease progressionClinical trialsPatient profilesRare diseasePatientsRegistryDisease severityMedicine approachFibrosisDiseaseAnalysis of biospecimensBroad spectrumCurrent practiceComorbiditiesLongitudinal dataPredictors of death or lung transplant after a diagnosis of idiopathic pulmonary fibrosis: insights from the IPF-PRO Registry
Snyder L, Neely ML, Hellkamp AS, O’Brien E, de Andrade J, Conoscenti CS, Leonard T, Bender S, Gulati M, Culver DA, Kaner RJ, Palmer S, Kim HJ. Predictors of death or lung transplant after a diagnosis of idiopathic pulmonary fibrosis: insights from the IPF-PRO Registry. Respiratory Research 2019, 20: 105. PMID: 31142314, PMCID: PMC6542049, DOI: 10.1186/s12931-019-1043-9.Peer-Reviewed Original ResearchConceptsRisk of deathLung transplantIPF-PRO RegistryPatient characteristicsDisease severityPulmonary fibrosisUS registryOxygen useBackgroundIdiopathic pulmonary fibrosisPredictors of deathIdiopathic pulmonary fibrosisVariable clinical courseAnalysis cohortLower FVCProgressive diseaseClinical courseLow DLCOMultivariable analysisMortality outcomesVital capacityMonth 30Diffusion capacityPatientsTransplantHigh mortality
2018
Predictors of death or transplant in patients with idiopathic pulmonary fibrosis in the IPF-PRO Registry
Snyder L, Neely M, Hellkamp A, O'Brien E, Flaherty K, De Andrade J, Conoscenti C, Leonard T, Bender S, Gulati M, Culver D, Kaner R, Palmer S, Kim H. Predictors of death or transplant in patients with idiopathic pulmonary fibrosis in the IPF-PRO Registry. 2018, pa2196. DOI: 10.1183/13993003.congress-2018.pa2196.Peer-Reviewed Original Research
2017
Antifibrotic role of vascular endothelial growth factor in pulmonary fibrosis
Murray LA, Habiel DM, Hohmann M, Camelo A, Shang H, Zhou Y, Coelho AL, Peng X, Gulati M, Crestani B, Sleeman MA, Mustelin T, Moore MW, Ryu C, Osafo-Addo AD, Elias JA, Lee CG, Hu B, Herazo-Maya JD, Knight DA, Hogaboam CM, Herzog EL. Antifibrotic role of vascular endothelial growth factor in pulmonary fibrosis. JCI Insight 2017, 2: e92192. PMID: 28814671, PMCID: PMC5621899, DOI: 10.1172/jci.insight.92192.Peer-Reviewed Original ResearchIdiopathic pulmonary fibrosisPulmonary fibrosisEndothelial cell-derived mediatorsThrombospondin-1Chronic progressive declineIntratracheal bleomycin challengeVEGF transgenic miceCell-derived mediatorsLung-specific overexpressionVascular endothelial growth factorEpithelial cell injuryLevels of VEGFAssociation of VEGFEndothelial growth factorImpaired restitutionBleomycin challengeIPF pathogenesisLung functionEpithelial wound closureLung fibrosisAntifibrotic roleHealthy controlsPreclinical modelsProgressive phenotypeCell injuryExtracellular Mitochondrial DNA Is Generated by Fibroblasts and Predicts Death in Idiopathic Pulmonary Fibrosis
Ryu C, Sun H, Gulati M, Herazo-Maya J, Chen Y, Osafo-Addo A, Brandsdorfer C, Winkler J, Blaul C, Faunce J, Pan H, Woolard T, Tzouvelekis A, Antin-Ozerkis DE, Puchalski JT, Slade M, Gonzalez AL, Bogenhagen DF, Kirillov V, Feghali-Bostwick C, Gibson K, Lindell K, Herzog RI, Dela Cruz CS, Mehal W, Kaminski N, Herzog EL, Trujillo G. Extracellular Mitochondrial DNA Is Generated by Fibroblasts and Predicts Death in Idiopathic Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2017, 196: 1571-1581. PMID: 28783377, PMCID: PMC5754440, DOI: 10.1164/rccm.201612-2480oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisNormal human lung fibroblastsExtracellular mitochondrial DNABronchoalveolar lavageIPF fibroblastsPulmonary fibrosisInnate immune ligandsEvent-free survivalSmooth muscle actin expressionMtDNA concentrationsSmooth muscle actin-expressing myofibroblastsGrowth factor-β1Muscle actin expressionHuman lung fibroblastsTGF-β1 stimulationExtracellular mtDNAIPF cohortClinical outcomesControl subjectsDisease progressionGlycolytic reprogrammingSoluble mediatorsTGF-β1Factor-β1Immune ligands
2016
Validation of the prognostic value of MMP‐7 in idiopathic pulmonary fibrosis
Tzouvelekis A, Herazo‐Maya J, Slade M, Chu J, Deiuliis G, Ryu C, Li Q, Sakamoto K, Ibarra G, Pan H, Gulati M, Antin‐Ozerkis D, Herzog EL, Kaminski N. Validation of the prognostic value of MMP‐7 in idiopathic pulmonary fibrosis. Respirology 2016, 22: 486-493. PMID: 27761978, PMCID: PMC5352520, DOI: 10.1111/resp.12920.Peer-Reviewed Original ResearchConceptsTransplant-free survivalIdiopathic pulmonary fibrosisMMP-7 concentrationsMatrix metalloproteinase-7IPF patientsCause mortalityPulmonary fibrosisHealthy controlsMultivariate Cox proportional hazards modelCox proportional hazards modelPulmonary function parametersVariable clinical courseBaseline pulmonary function parametersProportional hazards modelIPF biomarkersProgressive diseaseClinical coursePoor prognosisPrognostic valueVital capacityIndependent biomarkerLung capacityPrognostic thresholdPlasma concentrationsMortality riskPlexin C1 deficiency permits synaptotagmin 7–mediated macrophage migration and enhances mammalian lung fibrosis
Peng X, Moore M, Mathur A, Zhou Y, Sun H, Gan Y, Herazo‐Maya J, Kaminski N, Hu X, Pan H, Ryu C, Osafo‐Addo A, Homer RJ, Feghali‐Bostwick C, Fares W, Gulati M, Hu B, Lee C, Elias JA, Herzog EL. Plexin C1 deficiency permits synaptotagmin 7–mediated macrophage migration and enhances mammalian lung fibrosis. The FASEB Journal 2016, 30: 4056-4070. PMID: 27609773, PMCID: PMC5102121, DOI: 10.1096/fj.201600373r.Peer-Reviewed Original ResearchConceptsLung fibrosisPlexin C1Macrophage migrationPulmonary fibrosisBone marrow-derived cellsSynaptotagmin-7Idiopathic pulmonary fibrosisInterstitial lung diseaseMarrow-derived cellsTGF-β1 overexpressionFatal conditionLung diseaseMonocyte migrationUnrecognized observationCollagen accumulationFibrosisMice showBoyden chamberGenetic deletionLungMouse macrophagesSemaphorin receptorsMacrophagesC1s deficiencyDeficiencyNetrin‐1 Regulates Fibrocyte Accumulation in the Decellularized Fibrotic Sclerodermatous Lung Microenvironment and in Bleomycin‐Induced Pulmonary Fibrosis
Sun H, Zhu Y, Pan H, Chen X, Balestrini JL, Lam TT, Kanyo JE, Eichmann A, Gulati M, Fares WH, Bai H, Feghali-Bostwick CA, Gan Y, Peng X, Moore MW, White ES, Sava P, Gonzalez AL, Cheng Y, Niklason LE, Herzog EL. Netrin‐1 Regulates Fibrocyte Accumulation in the Decellularized Fibrotic Sclerodermatous Lung Microenvironment and in Bleomycin‐Induced Pulmonary Fibrosis. Arthritis & Rheumatology 2016, 68: 1251-1261. PMID: 26749424, PMCID: PMC5547894, DOI: 10.1002/art.39575.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibiotics, AntineoplasticAntibodies, NeutralizingBiomechanical PhenomenaBleomycinCase-Control StudiesCell DifferentiationCollagenCollagen Type ICollagen Type I, alpha 1 ChainFibrosisFlow CytometryFluorescent Antibody TechniqueHeterozygoteHumansLeukocyte Common AntigensLeukocytes, MononuclearLungLung Diseases, InterstitialMiceMice, KnockoutMicroscopy, Electron, ScanningNerve Growth FactorsNetrin-1ProteomicsPulmonary FibrosisReverse Transcriptase Polymerase Chain ReactionScleroderma, SystemicTissue ScaffoldsTumor Suppressor ProteinsConceptsSSc-related interstitial lung diseaseInterstitial lung diseaseFibrocyte accumulationNetrin-1Lung extracellular matrixPulmonary fibrosisLung scaffoldsBleomycin-Induced Pulmonary FibrosisPeripheral blood mononuclear cellsBlood mononuclear cellsHealthy control subjectsNovel therapeutic targetSystemic sclerosisExtracellular matrixLung fibrosisLung diseaseMononuclear cellsControl subjectsLung microenvironmentHealthy controlsScleroderma patientsAberrant anatomyLung matrixPatientsTherapeutic target
2015
Chitinase 3–like–1 and its receptors in Hermansky-Pudlak syndrome–associated lung disease
Zhou Y, He CH, Herzog EL, Peng X, Lee CM, Nguyen TH, Gulati M, Gochuico BR, Gahl WA, Slade ML, Lee CG, Elias JA. Chitinase 3–like–1 and its receptors in Hermansky-Pudlak syndrome–associated lung disease. Journal Of Clinical Investigation 2015, 125: 3178-3192. PMID: 26121745, PMCID: PMC4563747, DOI: 10.1172/jci79792.Peer-Reviewed Original ResearchMeSH KeywordsAdipokinesAdultAnimalsApoptosisBiomarkersChitinase-3-Like Protein 1Disease Models, AnimalFemaleGlycoproteinsHermanski-Pudlak SyndromeHumansInterleukin-13 Receptor alpha2 SubunitLectinsMaleMiceMice, KnockoutPulmonary FibrosisReceptors, ImmunologicReceptors, ProstaglandinRespiratory MucosaConceptsHermansky-Pudlak syndromePulmonary fibrosisChitinase 3Pulmonary fibrosis progressionFibroproliferative repairCHI3L1 levelsFibrosis progressionLung diseaseHPS-4HPS patientsIL-13Rα2Effector functionsReceptor CRTH2Epithelial apoptosisFibrosisProtective roleDisease severityPotential biomarkersCHI3L1Major causeHPS-1Abnormal localizationPatientsCell deathSeverityAsbestosis and environmental causes of usual interstitial pneumonia
Gulati M, Redlich CA. Asbestosis and environmental causes of usual interstitial pneumonia. Current Opinion In Pulmonary Medicine 2015, 21: 193-200. PMID: 25621562, PMCID: PMC4472384, DOI: 10.1097/mcp.0000000000000144.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisUsual interstitial pneumoniaInterstitial pneumoniaDevelopment of IPFUsual interstitial pneumonia patternRecent epidemiologic investigationsEnvironmental exposuresFibrotic lung diseaseInterstitial pneumonia patternExposure-disease relationshipsIPF patientsPneumonia patternClinical courseIPF diagnosisPulmonary fibrosisHistopathologic patternLung diseaseAsbestos exposureRadiographic changesOverall burdenAsbestosis patientsClinical challengeEpidemiologic studiesCase controlAgricultural exposures
2014
Chitinase 3–Like 1 Suppresses Injury and Promotes Fibroproliferative Responses in Mammalian Lung Fibrosis
Zhou Y, Peng H, Sun H, Peng X, Tang C, Gan Y, Chen X, Mathur A, Hu B, Slade MD, Montgomery RR, Shaw AC, Homer RJ, White ES, Lee CM, Moore MW, Gulati M, Lee CG, Elias JA, Herzog EL. Chitinase 3–Like 1 Suppresses Injury and Promotes Fibroproliferative Responses in Mammalian Lung Fibrosis. Science Translational Medicine 2014, 6: 240ra76. PMID: 24920662, PMCID: PMC4340473, DOI: 10.1126/scitranslmed.3007096.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisCHI3L1 levelsChitinase 3Lungs of patientsAlternative macrophage activationLevel of apoptosisAcute exacerbationFibroproliferative repairLung transplantationDisease exacerbationInjury phaseAmbulatory patientsEpithelial injuryPulmonary fibrosisIPF populationLung fibrosisMacrophage accumulationCHI3L1 expressionFibrotic phaseDisease progressionProfibrotic roleFibroproliferative responseMacrophage activationMyofibroblast transformationProtective role