2023
Learnings from clinical trials in patients with connective tissue disease-associated interstitial lung disease
Higuero Sevilla J, Memon A, Hinchcliff M. Learnings from clinical trials in patients with connective tissue disease-associated interstitial lung disease. Arthritis Research & Therapy 2023, 25: 118. PMID: 37422652, PMCID: PMC10329300, DOI: 10.1186/s13075-023-03090-y.Peer-Reviewed Original ResearchConceptsConnective tissue disease-associated interstitial lung diseaseInterstitial lung diseaseTreatment of patientsMycophenolate mofetilSSc-ILDLung diseaseClinical trialsScleroderma Lung Study IIPatient-reported outcome instrumentsIdiopathic inflammatory myositisClinical trial resultsInflammatory myositisIntravenous cyclophosphamideOral cyclophosphamideSubcutaneous tocilizumabGood tolerabilityLung functionSystemic sclerosisTreatment armamentariumRheumatoid arthritisPatient outcomesSimilar efficacyOutcome instrumentsPatientsUS Food
2022
Circulating CTRP9 Is Associated With Severity of Systemic Sclerosis–Associated Interstitial Lung Disease
Yang MM, Balmert LC, Marangoni RG, Carns M, Hinchcliff M, Korman BD, Varga J. Circulating CTRP9 Is Associated With Severity of Systemic Sclerosis–Associated Interstitial Lung Disease. Arthritis Care & Research 2022, 75: 152-157. PMID: 34251759, PMCID: PMC9233895, DOI: 10.1002/acr.24749.Peer-Reviewed Original ResearchConceptsC1q/tumor necrosis factor-related protein 9Interstitial lung diseaseSystemic sclerosisLung diseaseLung functionSystemic Sclerosis-Associated Interstitial Lung DiseaseSSc-associated interstitial lung diseasePulmonary function test dataLatent trajectory analysisVital capacity percentWorse lung functionPrimary outcome measureWorse pulmonary functionCause of morbidityRetrospective longitudinal studyAdipose tissue metabolismCross-sectional analysisAdipokine homeostasisDisease stabilityPulmonary functionSSc patientsSerum levelsPatient RegistryPredictive markerCapacity percent
2021
Esophageal Dilation and Other Clinical Factors Associated With Pulmonary Function Decline in Patients With Systemic Sclerosis
Showalter K, Hoffmann A, Richardson C, Aaby D, Lee J, Dematte J, Agrawal R, Savas H, Wu X, Chang RW, Hinchcliff M. Esophageal Dilation and Other Clinical Factors Associated With Pulmonary Function Decline in Patients With Systemic Sclerosis. The Journal Of Rheumatology 2021, 48: 1830-1838. PMID: 34266985, PMCID: PMC8985598, DOI: 10.3899/jrheum.210533.Peer-Reviewed Original ResearchConceptsRadiographic interstitial lung diseaseInterstitial lung diseasePulmonary function testsSystemic sclerosisEsophageal dilationPulmonary function declineFVC declineClinical factorsEsophageal diameterFunction declineScl-70 positivitySSc-ILD patientsSubanalysis of patientsScl-70Function testsPrognostic implicationsVital capacityLung diseaseStudy criteriaI autoantibodiesRisk factorsPFT declineDiffusion capacityPatientsLinear mixed effects modelsA review and roadmap of the skin, lung and gut microbiota in systemic sclerosis
Teaw S, Hinchcliff M, Cheng M. A review and roadmap of the skin, lung and gut microbiota in systemic sclerosis. Rheumatology 2021, 60: 5498-5508. PMID: 33734316, PMCID: PMC8643452, DOI: 10.1093/rheumatology/keab262.Peer-Reviewed Original ResearchLarge‐Scale Characterization of Systemic Sclerosis Serum Protein Profile: Comparison to Peripheral Blood Cell Transcriptome and Correlations With Skin/Lung Fibrosis
Bellocchi C, Ying J, Goldmuntz EA, Keyes‐Elstein L, Varga J, Hinchcliff ME, Lyons MA, McSweeney P, Furst DE, Nash R, Crofford LJ, Welch B, Goldin JG, Pinckney A, Mayes MD, Sullivan KM, Assassi S. Large‐Scale Characterization of Systemic Sclerosis Serum Protein Profile: Comparison to Peripheral Blood Cell Transcriptome and Correlations With Skin/Lung Fibrosis. Arthritis & Rheumatology 2021, 73: 660-670. PMID: 33131208, PMCID: PMC8005427, DOI: 10.1002/art.41570.Peer-Reviewed Original ResearchConceptsDiffuse cutaneous systemic sclerosisInterstitial lung diseaseSerum protein profilesHealthy control subjectsControl subjectsSex-matched healthy control subjectsRodnan skin thickness scoreSevere interstitial lung diseaseCutaneous systemic sclerosisMean disease durationDiffuse cutaneous SScWhole blood gene expression profilingSkin thickness scoreBlood gene expression profilingPeripheral blood cellsCancer antigen 15Epidermal growth factor receptorSoluble epidermal growth factor receptorSerum proteinsGrowth factor receptorDisease activityDisease durationSystemic sclerosisCutaneous SScImmunosuppressive agents
2020
Performance Characteristics of Pulmonary Function Tests for the Detection of Interstitial Lung Disease in Adults With Early Diffuse Cutaneous Systemic Sclerosis
Bernstein EJ, Jaafar S, Assassi S, Domsic RT, Frech TM, Gordon JK, Broderick RJ, Hant FN, Hinchcliff ME, Shah AA, Shanmugam VK, Steen VD, Khanna D. Performance Characteristics of Pulmonary Function Tests for the Detection of Interstitial Lung Disease in Adults With Early Diffuse Cutaneous Systemic Sclerosis. Arthritis & Rheumatology 2020, 72: 1892-1896. PMID: 32583956, PMCID: PMC7722107, DOI: 10.1002/art.41415.Peer-Reviewed Original ResearchConceptsDetection of ILDPulmonary function testsInterstitial lung diseaseDiffuse cutaneous SScEarly diffuse cutaneous systemic sclerosisDiffuse cutaneous systemic sclerosisNegative predictive valueCutaneous systemic sclerosisSystemic sclerosisFunction testsLung diseaseDevelopment of ILDDiagnosis of ILDEarly diffuse cutaneous SScRadiographic interstitial lung diseaseInadequate screening toolsEarly systemic sclerosisRetrospective cohort studyCause of deathProspective registrySSc cohortCohort studyVital capacityHRCT imagingHigh risk
2018
Performance of Forced Vital Capacity and Lung Diffusion Cutpoints for Associated Radiographic Interstitial Lung Disease in Systemic Sclerosis
Showalter K, Hoffmann A, Rouleau G, Aaby D, Lee J, Richardson C, Dematte J, Agrawal R, Chang RW, Hinchcliff M. Performance of Forced Vital Capacity and Lung Diffusion Cutpoints for Associated Radiographic Interstitial Lung Disease in Systemic Sclerosis. The Journal Of Rheumatology 2018, 45: 1572-1576. PMID: 30275265, PMCID: PMC6214765, DOI: 10.3899/jrheum.171362.Peer-Reviewed Original ResearchConceptsScl-70 autoantibodiesPulmonary function testsNegative predictive valueInterstitial lung diseaseSSc-ILDVital capacityLung diseaseSystemic sclerosis-associated interstitial lung diseaseRadiographic interstitial lung diseaseHigh negative predictive valueReceiver-operating characteristic curveForced Vital CapacityILD evaluationChest HRCTSystemic sclerosisFunction testsTomography scanAmerican CollegeFVCDLCOPatientsAutoantibodiesPredictive valueSSc criteriaThoracic radiologistsThe novel adipokine C1q-TNF related protein 9 (CTRP9) is elevated in systemic sclerosis-associated interstitial lung disease.
Korman B, Alejo R, Sudhakar D, Hinchcliff M, Agrawal R, Varga J, Marangoni RG. The novel adipokine C1q-TNF related protein 9 (CTRP9) is elevated in systemic sclerosis-associated interstitial lung disease. Clinical And Experimental Rheumatology 2018, 36 Suppl 113: 184-185. PMID: 30183591, PMCID: PMC7389309.Peer-Reviewed Original Research
2017
Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span
Misharin AV, Morales-Nebreda L, Reyfman PA, Cuda CM, Walter JM, McQuattie-Pimentel AC, Chen CI, Anekalla KR, Joshi N, Williams KJN, Abdala-Valencia H, Yacoub TJ, Chi M, Chiu S, Gonzalez-Gonzalez FJ, Gates K, Lam AP, Nicholson TT, Homan PJ, Soberanes S, Dominguez S, Morgan VK, Saber R, Shaffer A, Hinchcliff M, Marshall SA, Bharat A, Berdnikovs S, Bhorade SM, Bartom ET, Morimoto RI, Balch WE, Sznajder JI, Chandel NS, Mutlu GM, Jain M, Gottardi CJ, Singer BD, Ridge KM, Bagheri N, Shilatifard A, Budinger GRS, Perlman H. Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span. Journal Of Experimental Medicine 2017, 214: 2387-2404. PMID: 28694385, PMCID: PMC5551573, DOI: 10.1084/jem.20162152.Peer-Reviewed Original ResearchConceptsMonocyte-derived alveolar macrophagesTissue-resident alveolar macrophagesAlveolar macrophage differentiationMacrophage differentiationTissue-resident macrophagesProfibrotic genesHuman homologueTranscriptomic profilingGenetic deletionAlveolar macrophagesGenesFlow-sorted cellsResolution of fibrosisLife spanDifferentiationHuman alveolar macrophagesSpecific genetic deletionMacrophagesRelative importanceHomologuesA novel multi-network approach reveals tissue-specific cellular modulators of fibrosis in systemic sclerosis
Taroni JN, Greene CS, Martyanov V, Wood TA, Christmann RB, Farber HW, Lafyatis RA, Denton CP, Hinchcliff ME, Pioli PA, Mahoney JM, Whitfield ML. A novel multi-network approach reveals tissue-specific cellular modulators of fibrosis in systemic sclerosis. Genome Medicine 2017, 9: 27. PMID: 28330499, PMCID: PMC5363043, DOI: 10.1186/s13073-017-0417-1.Peer-Reviewed Original ResearchConceptsDisease-associated signaturesFunctional genomic networksGene expression signaturesPulmonary fibrosisAutoimmune diseasesDisease processMulti-organ autoimmune diseaseDistinct underlying pathologyPro-fibrotic macrophagesInternal organ involvementPulmonary arterial hypertensionExpression signaturesSkin of patientsInnate immune systemWilcoxon rank sum testGenomic networksRank sum testBackgroundSystemic sclerosisArterial hypertensionOrgan involvementSystemic sclerosisUnderlying pathologyLung microenvironmentSkin fibrosisFibrotic genes
2016
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial
Tashkin DP, Roth MD, Clements PJ, Furst DE, Khanna D, Kleerup EC, Goldin J, Arriola E, Volkmann ER, Kafaja S, Silver R, Steen V, Strange C, Wise R, Wigley F, Mayes M, Riley DJ, Hussain S, Assassi S, Hsu VM, Patel B, Phillips K, Martinez F, Golden J, Connolly MK, Varga J, Dematte J, Hinchcliff ME, Fischer A, Swigris J, Meehan R, Theodore A, Simms R, Volkov S, Schraufnagel DE, Scholand MB, Frech T, Molitor JA, Highland K, Read CA, Fritzler MJ, Kim GHJ, Tseng CH, Elashoff RM, Investigators S. Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial. The Lancet Respiratory Medicine 2016, 4: 708-719. PMID: 27469583, PMCID: PMC5014629, DOI: 10.1016/s2213-2600(16)30152-7.Peer-Reviewed Original ResearchConceptsInterstitial lung diseaseMycophenolate mofetilParallel-group trialLung diseaseOral cyclophosphamidePrimary endpointCyclophosphamide groupGroup trialsPrimary analysisProgressive interstitial lung diseaseMycophenolate mofetil groupUS medical centersTreatment of sclerodermaProgression of sclerodermaPotential clinical effectivenessModified intentionProgressive sclerodermaStudy drugGood tolerabilityHRCT studiesLung functionPulmonary functionTreat analysisTreatment failureVital capacityTenascin-C drives persistence of organ fibrosis
Bhattacharyya S, Wang W, Morales-Nebreda L, Feng G, Wu M, Zhou X, Lafyatis R, Lee J, Hinchcliff M, Feghali-Bostwick C, Lakota K, Budinger GR, Raparia K, Tamaki Z, Varga J. Tenascin-C drives persistence of organ fibrosis. Nature Communications 2016, 7: 11703. PMID: 27256716, PMCID: PMC4895803, DOI: 10.1038/ncomms11703.Peer-Reviewed Original ResearchConceptsSystemic sclerosisToll-like receptorsOrgan fibrosisFibrosis resolutionPathogenesis of SScTreatment of SScLevels of tenascinEndogenous danger signalsSSc skin biopsy samplesSkin biopsy samplesMechanism of actionLung fibrosisPathogenic roleTLR activatorsMouse modelBiopsy samplesFibroblast activationDanger signalsMyofibroblast transformationFibrosisSSc fibroblastsCollagen gene expressionSkin fibroblastsAmplification loopTenascin
2015
Serum Amyloid A Is a Marker for Pulmonary Involvement in Systemic Sclerosis
Lakota K, Carns M, Podlusky S, Mrak-Poljsak K, Hinchcliff M, Lee J, Tomsic M, Sodin-Semrl S, Varga J. Serum Amyloid A Is a Marker for Pulmonary Involvement in Systemic Sclerosis. PLOS ONE 2015, 10: e0110820. PMID: 25629975, PMCID: PMC4321755, DOI: 10.1371/journal.pone.0110820.Peer-Reviewed Original ResearchConceptsSerum amyloid ASystemic sclerosisPulmonary involvementSSc patientsAmyloid AAcute phase protein serum amyloid AEarly diffuse cutaneous systemic sclerosisEffect of SAAInflammatory marker serum amyloid ALevels of SAAElevated serum amyloid AFrequent interstitial lung diseaseDiffuse cutaneous systemic sclerosisLung fibroblastsRecombinant serum amyloid APatient-reported outcome measuresDiffuse cutaneous involvementCutaneous systemic sclerosisEarly-stage diseaseMarkers of inflammationInterstitial lung diseaseNormal lung fibroblastsDose-dependent stimulationHuman pulmonary fibroblastsCutaneous involvement
2014
Antinuclear antibody-negative systemic sclerosis
Salazar GA, Assassi S, Wigley F, Hummers L, Varga J, Hinchcliff M, Khanna D, Schiopu E, Phillips K, Furst DE, Steen V, Baron M, Hudson M, Taillefer SS, Pope J, Jones N, Docherty P, Khalidi NA, Robinson D, Simms RW, Silver RM, Frech TM, Fessler BJ, Molitor JA, Fritzler MJ, Segal BM, Al-Kassab F, Perry M, Yang J, Zamanian S, Reveille JD, Arnett FC, Pedroza C, Mayes MD. Antinuclear antibody-negative systemic sclerosis. Seminars In Arthritis And Rheumatism 2014, 44: 680-686. PMID: 25578738, PMCID: PMC4447614, DOI: 10.1016/j.semarthrit.2014.11.006.Peer-Reviewed Original ResearchConceptsANA-negative groupANA-negative patientsPulmonary arterial hypertensionAntinuclear antibodiesSSc patientsDiffuse cutaneous involvementLower gastrointestinal involvementNegative antinuclear antibodyRight heart catheterizationScleroderma Family RegistrySSc-related antibodiesRodnan skin scoreSystemic sclerosis patientsANA-positive patientsRenal crisisVasculopathic manifestationsCause mortalityCutaneous involvementGastrointestinal involvementArterial hypertensionChart reviewClinical characteristicsHeart catheterizationMale patientsSkin scorePulmonary hypertension and interstitial lung disease within PHAROS: impact of extent of fibrosis and pulmonary physiology on cardiac haemodynamic parameters.
Fischer A, Swigris J, Bolster M, Chung L, Csuka M, Domsic R, Frech T, Hinchcliff M, Hsu V, Hummers L, Gomberg-Maitland M, Mathai S, Simms R, Steen V. Pulmonary hypertension and interstitial lung disease within PHAROS: impact of extent of fibrosis and pulmonary physiology on cardiac haemodynamic parameters. Clinical And Experimental Rheumatology 2014, 32: s-109-14. PMID: 25372796.Peer-Reviewed Original ResearchConceptsSeverity of ILDHaemodynamic parametersNew York Heart Association functional class IIFunctional class IILeft heart diseasePulmonary vascular diseasePulmonary function testingInterstitial lung diseaseImpact of extentMajority of subjectsHRCT evidenceILD extentILD severityPH-ILDSSc-ILDPulmonary hypertensionBaseline characteristicsHaemodynamic profileCutaneous SScHRCT scansFunction testingLung diseaseVascular diseaseHeart diseasePulmonary physiology
2012
The Pulmonary Fibrosis-Associated MUC5B Promoter Polymorphism Does Not Influence the Development of Interstitial Pneumonia in Systemic Sclerosis
Peljto AL, Steele MP, Fingerlin TE, Hinchcliff ME, Murphy E, Podlusky S, Carns M, Schwarz M, Varga J, Schwartz DA. The Pulmonary Fibrosis-Associated MUC5B Promoter Polymorphism Does Not Influence the Development of Interstitial Pneumonia in Systemic Sclerosis. CHEST Journal 2012, 142: 1584-1588. PMID: 22576636, PMCID: PMC3515031, DOI: 10.1378/chest.12-0110.Peer-Reviewed Original ResearchConceptsInterstitial pneumoniaSystemic sclerosisPromoter polymorphismDistinct genetic risk factorsMUC5B Promoter PolymorphismUnaffected control subjectsGenetic risk factorsReticular infiltratesLung involvementControl subjectsRisk factorsIP diagnosisSporadic formsSecondary analysisFVCPneumoniaSclerosisCommon variantsConservative definitionPhenotypic heterogeneitySubjectsMinor allele frequencyPolymorphismAllele frequenciesAssociation