2024
Gene expression meta-analysis reveals aging and cellular senescence signatures in scleroderma-associated interstitial lung disease
Yang M, Lee S, Neely J, Hinchcliff M, Wolters P, Sirota M. Gene expression meta-analysis reveals aging and cellular senescence signatures in scleroderma-associated interstitial lung disease. Frontiers In Immunology 2024, 15: 1326922. PMID: 38348044, PMCID: PMC10859856, DOI: 10.3389/fimmu.2024.1326922.Peer-Reviewed Original ResearchConceptsScleroderma-associated interstitial lung diseaseSSc-ILDInterstitial lung diseaseLung tissueGene expression meta-analysisPulmonary fibrosisLung diseaseSenescence signatureDegree of skin involvementIdiopathic pulmonary fibrosisTelomere lengthType II alveolar cellsCellular senescence signaturesCellular senescenceIndependent of ageSkin involvementSSc skinExpression meta-analysisHealthy controlsAssociated with degreeAlveolar cellsLungMeta-analysisAging genesFibrosis
2023
Clinical Phenotypes of Patients With Systemic Sclerosis With Distinct Molecular Signatures in Skin
Yang M, Goh V, Lee J, Espinoza M, Yuan Y, Carns M, Aren K, Chung L, Khanna D, McMahan ZH, Agrawal R, Nelson L, Shah SJ, Whitfield ML, Hinchcliff M. Clinical Phenotypes of Patients With Systemic Sclerosis With Distinct Molecular Signatures in Skin. Arthritis Care & Research 2023, 75: 1469-1480. PMID: 35997480, PMCID: PMC9947190, DOI: 10.1002/acr.24998.Peer-Reviewed Original ResearchConceptsRadiographic interstitial lung diseaseInterstitial lung diseaseHigher mRSSSSc patientsSerum autoantibodiesClinical phenotypeHealthy participantsScl-70 antibodyPresent multicenter studySimilar disease durationSystemic sclerosis patientsDistinct clinical phenotypesSkin gene expressionValuable clinical informationDcSSc patientsDisease durationIdentifies patientsSystemic sclerosisSclerosis patientsMulticenter studyLung diseaseSkin fibrosisSimilar prevalenceClinical dataMultivariable modelingLearnings 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 FoodCorrection: Learnings from clinical trials in patients with connective tissue disease‑associated interstitial lung disease
Higuero Sevilla J, Memon A, Hinchcliff M. Correction: Learnings from clinical trials in patients with connective tissue disease‑associated interstitial lung disease. Arthritis Research & Therapy 2023, 25: 132. PMID: 37501068, PMCID: PMC10373245, DOI: 10.1186/s13075-023-03123-6.Peer-Reviewed Original Research
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 modelsClinical characteristics, visceral involvement, and mortality in at-risk or early diffuse systemic sclerosis: a longitudinal analysis of an observational prospective multicenter US cohort
Jaafar S, Lescoat A, Huang S, Gordon J, Hinchcliff M, Shah AA, Assassi S, Domsic R, Bernstein EJ, Steen V, Elliott S, Hant F, Castelino FV, Shanmugam VK, Correia C, Varga J, Nagaraja V, Roofeh D, Frech T, Khanna D. Clinical characteristics, visceral involvement, and mortality in at-risk or early diffuse systemic sclerosis: a longitudinal analysis of an observational prospective multicenter US cohort. Arthritis Research & Therapy 2021, 23: 170. PMID: 34127049, PMCID: PMC8201684, DOI: 10.1186/s13075-021-02548-1.Peer-Reviewed Original ResearchConceptsDiffuse cutaneous systemic sclerosisInterstitial lung diseaseImmunosuppressive therapyProgression of skinCardiac involvementSystemic sclerosisUS cohortAnti-RNA polymerase III antibodiesProgressive interstitial lung diseaseEarly diffuse systemic sclerosisMean HAQ-DIMulticenter prospective cohortMulticenter US cohortVital capacity declineMedian disease durationCurrent immunosuppressive therapiesCutaneous systemic sclerosisInternal organ involvementPolymerase III antibodiesDiffuse systemic sclerosisLimited cutaneous SScHigh case fatalityLongitudinal analysisBaseline mRSHAQ-DIPredictive Significance of Serum Interferon‐Inducible Protein Score for Response to Treatment in Systemic Sclerosis–Related Interstitial Lung Disease
Assassi S, Li N, Volkmann ER, Mayes MD, Rünger D, Ying J, Roth MD, Hinchcliff M, Khanna D, Frech T, Clements PJ, Furst DE, Goldin J, Bernstein EJ, Castelino FV, Domsic RT, Gordon JK, Hant FN, Shah AA, Shanmugam VK, Steen VD, Elashoff RM, Tashkin DP. Predictive Significance of Serum Interferon‐Inducible Protein Score for Response to Treatment in Systemic Sclerosis–Related Interstitial Lung Disease. Arthritis & Rheumatology 2021, 73: 1005-1013. PMID: 33350170, PMCID: PMC8169525, DOI: 10.1002/art.41627.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBeta 2-MicroglobulinChemokine CCL19Chemokine CCL8Chemokine CXCL10Chemokine CXCL9CyclophosphamideFemaleHumansImmunosuppressive AgentsLung Diseases, InterstitialMaleMethotrexateMiddle AgedMycophenolic AcidObservational Studies as TopicPrognosisRandomized Controlled Trials as TopicReceptors, Tumor Necrosis Factor, Type IIScleroderma, SystemicVital CapacityConceptsInterstitial lung diseaseMycophenolate mofetilPredictive significanceCYC armILD courseMMF armSSc-ILDSystemic sclerosisLung diseaseHigh baseline C-reactive protein levelsTumor necrosis factor receptor type IIBaseline C-reactive protein levelsScleroderma Lung Study IIC-reactive protein levelsGood responseVital capacity percentChemotactic protein-2Receptor type IIActive immunosuppressionClinical predictorsCRP levelsObservational cohortProtein scoreActive treatmentTreatment armsLarge‐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 riskRegulator combinations identify systemic sclerosis patients with more severe disease
Wang Y, Franks JM, Yang M, Toledo DM, Wood TA, Hinchcliff M, Whitfield ML. Regulator combinations identify systemic sclerosis patients with more severe disease. JCI Insight 2020, 5: e137567. PMID: 32721949, PMCID: PMC7526449, DOI: 10.1172/jci.insight.137567.Peer-Reviewed Original ResearchConceptsInterstitial lung diseaseSystemic sclerosisActivity scoreSevere diseaseSevere interstitial lung diseaseSubsets of SScVital capacity declineRodnan skin scoreSubgroup of patientsSystemic sclerosis patientsHeterogeneous autoimmune disorderInternal organ dysfunctionGene expression subsetsSkin gene expressionActivation of regulatorsIntrinsic subsetOrgan dysfunctionSclerosis patientsSkin scoreAutoantibody productionClinical outcomesAutoimmune disordersClinical variablesLung diseaseSkin fibrosisCurrent and Potential New Targets in Systemic Sclerosis Therapy: a New Hope
Hinchcliff M, O’Reilly S. Current and Potential New Targets in Systemic Sclerosis Therapy: a New Hope. Current Rheumatology Reports 2020, 22: 42. PMID: 32562016, PMCID: PMC7305248, DOI: 10.1007/s11926-020-00918-3.Peer-Reviewed Original ResearchConceptsSkin fibrosisNew targetsSSc interstitial lung diseaseAutoimmune connective tissue diseaseSystemic sclerosis therapyConnective tissue diseaseInterstitial lung diseaseCurrent ongoing trialsNew therapeutic targetsActivation of fibroblastsPotential new targetsReviewSystemic sclerosisSclerosis therapyOngoing trialsTissue diseaseLung diseaseClinical trialsTherapeutic targetRate of declineDisease pathogenesisPhase IIIPhase IIFibrosisNew hopeDisease
2019
Connective Tissue Disease–Associated Interstitial Lung Disease Evaluation and Management
Antin-Ozerkis D, Hinchcliff M. Connective Tissue Disease–Associated Interstitial Lung Disease Evaluation and Management. Clinics In Chest Medicine 2019, 40: 617-636. PMID: 31376896, DOI: 10.1016/j.ccm.2019.05.008.Peer-Reviewed Original ResearchConceptsNonpharmacologic management strategiesMainstay of therapyConnective tissue diseaseInterstitial lung diseaseRate of progressionDisease activityTherapy initiationTissue diseaseRadiographic findingsLung diseaseDrug toxicityDisease severityDisease evaluationMultidisciplinary approachPatientsDiseaseImportant contributorImmunosuppressionMorbidityTherapyInfectionMainstayMortalityProgressionTrials
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 ResearchConceptsSystemic sclerosis-associated interstitial lung diseaseInterstitial lung diseaseLung diseaseC1q-TNFProtein 9The Scleroderma Patient-Centered Intervention Network Cohort: baseline clinical features and comparison with other large scleroderma cohorts
Dougherty DH, Kwakkenbos L, Carrier ME, Salazar G, Assassi S, Baron M, Bartlett SJ, Furst DE, Gottesman K, van den Hoogen F, Malcarne VL, Mouthon L, Nielson WR, Poiraudeau S, Sauvé M, Boire G, Bruns A, Chung L, Denton C, Dunne JV, Fortin P, Frech T, Gill A, Gordon J, Herrick AL, Hinchcliff M, Hudson M, Johnson SR, Jones N, Kafaja S, Larché M, Manning J, Pope J, Spiera R, Steen V, Sutton E, Thorne C, Wilcox P, Thombs BD, Mayes MD, Albert A, Arsenault G, Bissonette L, Boutron I, Carreira P, Maia A, Dagenais P, Domsic R, El-Baalbaki G, Ells C, van den Ende C, Fligelstone K, Fortune C, Godard D, Gyger G, Harel D, Ikic A, Impens A, Jang Y, Artur Jose de B, Kennedy A, Khalidi N, Korman B, Leite C, Liang P, Marra C, Masetto A, Nielsen K, Portales A, Riggs R, Reyna T, Roux S, Schouffoer A, Steele R, Suarez-Almazor M, Varga J, Welling J, Wigley F, Wong-Rieger D, Cumin J, Delisle V, Fedoruk C, Fox R, Gholizadeh S, Jewett L, Levis B, Mills S, Pepin M, Persmann J, Turner K. The Scleroderma Patient-Centered Intervention Network Cohort: baseline clinical features and comparison with other large scleroderma cohorts. Rheumatology 2018, 57: 1623-1631. PMID: 29868924, DOI: 10.1093/rheumatology/key139.Peer-Reviewed Original ResearchConceptsIntervention Network CohortSPIN CohortSSc cohortAntibody frequencyCanadian Scleroderma Research Group cohortBaseline clinical featuresEuropean Scleroderma TrialsLarge SSc cohortPatient-reported outcome dataSSc renal crisisInterstitial lung diseasePatient-reported outcomesWeb-based cohortRenal crisisScleroderma cohortDcSSc patientsScleroderma TrialsOrgan involvementWhite patientsClinical featuresHigher proportionLung diseaseScleroderma patientsHigh prevalenceOutcome data
2016
Molecular Stratification by Gene Expression as a Paradigm for Precision Medicine in Systemic Sclerosis
Hinchcliff M, Whitfield M. Molecular Stratification by Gene Expression as a Paradigm for Precision Medicine in Systemic Sclerosis. 2016, 657-670. DOI: 10.1007/978-3-319-31407-5_49.Peer-Reviewed Original ResearchSystemic sclerosisPatient subsetsProgressive interstitial lung diseaseDiffuse cutaneous systemic sclerosisAppropriate patient subsetsScleroderma renal crisisCutaneous systemic sclerosisInvestigator-initiated trialPulmonary arterial hypertensionSubset of patientsDifferent patient subsetsInterstitial lung diseaseDifferent pathophysiological processesMolecular pathwaysPrecision medicineGene expression subsetsT lymphocyte activationUninvolved skin samplesInflammatory subsetRenal crisisSSc complicationsArterial hypertensionMycophenolate mofetilClinical improvementOrgan involvementMycophenolate 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 capacityComment on “Esophageal dilatation and interstitial lung disease in systemic sclerosis: A cross-sectional study”
Hoffmann A, Lee J, Ma M, Agrawal R, Chang RW, Richardson C, Hinchcliff M, Showalter K. Comment on “Esophageal dilatation and interstitial lung disease in systemic sclerosis: A cross-sectional study”. Seminars In Arthritis And Rheumatism 2016, 46: e11-e12. PMID: 27312382, PMCID: PMC6701947, DOI: 10.1016/j.semarthrit.2016.04.006.Peer-Reviewed Original ResearchEsophageal dilatation and interstitial lung disease in systemic sclerosis: A cross-sectional study
Richardson C, Agrawal R, Lee J, Almagor O, Nelson R, Varga J, Cuttica MJ, Dematte J, Chang RW, Hinchcliff ME. Esophageal dilatation and interstitial lung disease in systemic sclerosis: A cross-sectional study. Seminars In Arthritis And Rheumatism 2016, 46: 109-114. PMID: 27033049, PMCID: PMC5500283, DOI: 10.1016/j.semarthrit.2016.02.004.Peer-Reviewed Original ResearchConceptsRadiographic interstitial lung diseaseSSc interstitial lung diseaseInterstitial lung diseaseSystemic sclerosisCross-sectional studyEsophageal diameterEsophageal dilatationLung diseaseProgression of ILDSSc disease subtypesPulmonary function testsRodnan skin scoreErythrocyte sedimentation rateSecondary outcome variablesBody mass indexGround-glass opacitiesProton pump inhibitorsLow lung volumesSemi-quantitative scoreRegistry patientsDisease durationLow DLCOSkin scoreMedication useSerum autoantibodies