2022
Severe asthma and death in a worker using methylene diphenyl diisocyanate MDI asthma death
Wisnewski AV, Cooney R, Hodgson M, Giese K, Liu J, Redlich CA. Severe asthma and death in a worker using methylene diphenyl diisocyanate MDI asthma death. American Journal Of Industrial Medicine 2022, 65: 166-172. PMID: 35028957, PMCID: PMC8846433, DOI: 10.1002/ajim.23323.Peer-Reviewed Case Reports and Technical NotesConceptsCause of deathMedical recordsDiisocyanate asthmaSevere asthmaSerum IgEParaffin-embedded lung tissue sectionsWorkers' medical recordsSmooth muscle hypertrophyTotal serum IgEHallmark of asthmaSevere asthma attacksBasement membrane thickeningLung tissue sectionsPost-mortem findingsEnzyme-linked immunosorbent assayPotential chemical exposuresInflamed airwaysMucus pluggingOccupational asthmaPulmonary embolismTotal IgEAsthma deathsAsthma attacksLung pathologyAutopsy findings
2021
Mechanisms, Genetics, and Pathophysiology
Maestrelli P, Wisnewski A, Carlsten C, Munoz X, Tsui H, Vanoirbeek J, Malo J, Bernstein D. Mechanisms, Genetics, and Pathophysiology. 2021, 35-54. DOI: 10.1201/9781003000624-4.Peer-Reviewed Original ResearchOccupational asthmaAirway inflammationDevelopment of OASensitizer-induced occupational asthmaType of OAChemical respiratory allergyIgE-dependent hypersensitivityIrritant-induced asthmaIgE-mediated mechanismNeutrophilic airway inflammationIgE-mediated responsesWork-related symptomsPossible pathogenic mechanismsPathways of inflammationStimulation of cholinergicPathophysiology of diseaseHMW agentsInflammatory markersAirflow limitationBronchial hyperresponsivenessImmunologic sensitizationSensory nervesSensitized subjectsIgE antibodiesLMW agents
2020
Molecular Characterization and Experimental Utility of Monoclonal Antibodies with Specificity for Aliphatic Di- and Polyisocyanates
Wisnewski AV, Liu J. Molecular Characterization and Experimental Utility of Monoclonal Antibodies with Specificity for Aliphatic Di- and Polyisocyanates. Monoclonal Antibodies In Immunodiagnosis And Immunotherapy 2020, 39: 66-73. PMID: 32302507, PMCID: PMC7310211, DOI: 10.1089/mab.2020.0006.Peer-Reviewed Original ResearchConceptsBALB/c miceMonoclonal antibodiesOccupational asthmaC miceSerologic detectionDifferent carrier proteinsNew mAbsEpitope specificityUseful research reagentsDisease preventionImmune recognitionStable hybridomasWestern blotAlbumin adductsMouse skinMAbsSurveillance approachSurveillance effortsAntibodiesMolecular determinantsHybridomasAliphatic diComplementary determining regionsMolecular characterizationResearch reagents
2019
LC-UV-MS and MS/MS Characterize Glutathione Reactivity with Different Isomers (2,2' and 2,4' vs. 4,4') of Methylene Diphenyl-Diisocyanate.
Wisnewski AV, Liu J, Nassar AF. LC-UV-MS and MS/MS Characterize Glutathione Reactivity with Different Isomers (2,2' and 2,4' vs. 4,4') of Methylene Diphenyl-Diisocyanate. EC Pharmacology And Toxicology 2019, 7: 205-219. PMID: 31143884, PMCID: PMC6536005.Peer-Reviewed Original Research
2017
Reaction products of hexamethylene diisocyanate vapors with “self” molecules in the airways of rabbits exposed via tracheostomy
Wisnewski AV, Kanyo J, Asher J, Goodrich JA, Barnett G, Patrylak L, Liu J, Redlich CA, Nassar AF. Reaction products of hexamethylene diisocyanate vapors with “self” molecules in the airways of rabbits exposed via tracheostomy. Xenobiotica 2017, 48: 488-497. PMID: 28489470, PMCID: PMC5863241, DOI: 10.1080/00498254.2017.1329569.Peer-Reviewed Original ResearchConceptsCollision-induced dissociation (CID) fragmentation patternsReaction productsLower airwaysChemical reactivityLow molecular weight fractionWeight fractionHigh molecular weight fractionAliphatic diisocyanateMolecular weight fractionFragmentation patternsHexamethylenediisocyanateLC-MSHDI vaporAirways of rabbitsBronchoalveolar lavage fluidRabbit bronchoalveolar lavage fluidMoleculesDiisocyanate vaporsMs. 4Albumin. 5Occupational asthmaReactivityBAL fluidAsthma pathogenesisLavage fluid
2016
The influence of diisocyanate antigen preparation methodology on monoclonal and serum antibody recognition
Hagerman LM, Law BF, Bledsoe TA, Hettick JM, Kashon ML, Lemons AR, Wisnewski AV, Siegel PD. The influence of diisocyanate antigen preparation methodology on monoclonal and serum antibody recognition. Journal Of Occupational And Environmental Hygiene 2016, 13: 829-839. PMID: 27124286, PMCID: PMC5016257, DOI: 10.1080/15459624.2016.1183013.Peer-Reviewed Original ResearchConceptsOccupational asthmaDifferent conjugatesPolyclonal antibody responsePanel of antigensSpecific antibody clonesHuman serumMDI conjugationPolyclonal serum antibodiesSpecific IgEAntibody responseSerum antibodiesSerologic detectionStandard antigenMonoclonal antibodiesAntibody clonesAntibodiesAsthmaSignificant differencesAntigenSerumMAbsAntibody recognitionAntigenicityMinimal differencesConjugates
2015
Immunochemical detection of the occupational allergen, methylene diphenyl diisocyanate (MDI), in situ
Wisnewski AV, Liu J. Immunochemical detection of the occupational allergen, methylene diphenyl diisocyanate (MDI), in situ. Journal Of Immunological Methods 2015, 429: 60-65. PMID: 26690039, PMCID: PMC4753098, DOI: 10.1016/j.jim.2015.12.008.Peer-Reviewed Original ResearchConceptsKeyhole limpet hemocyaninFreund's adjuvantDiisocyanate-induced asthmaComplete Freund's adjuvantIncomplete Freund's adjuvantLung tissue sectionsFormalin-fixed paraffinOccupational asthmaLower airwaysBooster injectionOccupational allergensAirway cellsAlveolar macrophagesLimpet hemocyaninAdjuvantHealth effectsTissue distributionTissue samplesTissue sectionsAsthmaDot blot analysisFurther studiesImmunochemical studiesBlot analysisEpithelial regionsGlutathione Reaction Products with a Chemical Allergen, Methylene-diphenyl Diisocyanate, Stimulate Alternative Macrophage Activation and Eosinophilic Airway Inflammation
Wisnewski AV, Liu J, Colangelo CM. Glutathione Reaction Products with a Chemical Allergen, Methylene-diphenyl Diisocyanate, Stimulate Alternative Macrophage Activation and Eosinophilic Airway Inflammation. Chemical Research In Toxicology 2015, 28: 729-737. PMID: 25635619, PMCID: PMC4667722, DOI: 10.1021/tx5005002.Peer-Reviewed Original ResearchConceptsEosinophilic inflammatory responseAlternative macrophage activationInflammatory responseChemical allergensMacrophage activationAirway eosinophil numbersEosinophilic airway inflammationInnate immune responseGreater inflammatory responseAirway levelsMDI conjugationAirway inflammationOccupational asthmaIL-12MDI exposureAsthma pathogenesisEosinophil numbersNaïve miceAirway fluidRespiratory tractImmune responseMucus productionSkin exposureMDI conjugatesVivo evidence
2014
Inception cohort study of workers exposed to toluene diisocyanate at a polyurethane foam factory: Initial one‐year follow‐up
Gui W, Wisnewski AV, Neamtiu I, Gurzau E, Sparer JA, Stowe MH, Liu J, Slade MD, Rusu OA, Redlich CA. Inception cohort study of workers exposed to toluene diisocyanate at a polyurethane foam factory: Initial one‐year follow‐up. American Journal Of Industrial Medicine 2014, 57: 1207-1215. PMID: 25266741, PMCID: PMC4198484, DOI: 10.1002/ajim.22385.Peer-Reviewed Original ResearchMeSH KeywordsAdultAir Pollutants, OccupationalAirway ObstructionAsthma, OccupationalFemaleFollow-Up StudiesForced Expiratory VolumeHumansImmunoglobulin EImmunoglobulin GLost to Follow-UpMaleMiddle AgedOccupational ExposurePolyurethanesPrevalenceProspective StudiesTime FactorsToluene 2,4-DiisocyanateVital CapacityYoung AdultConceptsAsthma symptomsIsocyanate asthmaInception cohort studyHealth effectsCurrent asthma symptomsTDI levelsFirst yearFurther longitudinal evaluationAirflow obstructionCohort studyInception cohortOccupational asthmaTDI exposureRespiratory healthSkin exposureLongitudinal evaluationAsthmaOne-yearPersonal samplingSymptomsRiskExposureFindingsFEV1Spirometry
2013
Molecular determinants of humoral immune specificity for the occupational allergen, methylene diphenyl diisocyanate
Wisnewski AV, Liu J. Molecular determinants of humoral immune specificity for the occupational allergen, methylene diphenyl diisocyanate. Molecular Immunology 2013, 54: 233-237. PMID: 23295252, PMCID: PMC3563841, DOI: 10.1016/j.molimm.2012.11.017.Peer-Reviewed Original ResearchConceptsEpitope specificityAutologous serum proteinsLow molecular weight chemicalsOccupational asthmaOccupational allergensMolecular determinantsDisease pathogenesisSecreting clonesCDR3 regionWestern blotGene usageMonoclonal antibodiesMajor causeWeight chemicalsIgG1 mAbGermline gene usageHuman albuminImmune specificityMAbsSerum proteinsELISADiagnostic reagentsUseful diagnostic reagentHybridomasSomatic hypermutation
2011
Pathogenesis and Disease Mechanisms of Occupational Asthma
Lummus ZL, Wisnewski AV, Bernstein DI. Pathogenesis and Disease Mechanisms of Occupational Asthma. Immunology And Allergy Clinics Of North America 2011, 31: 699-716. PMID: 21978852, PMCID: PMC4683932, DOI: 10.1016/j.iac.2011.07.008.Peer-Reviewed Original ResearchConceptsOccupational asthmaWork-related lung diseaseMultifactorial pathogenetic mechanismsGenetic susceptibility factorsNonimmunologic mechanismsLung diseaseClinical managementInflammatory processPathogenetic mechanismsSusceptibility factorsDisease mechanismsCommon formAsthmaDiseasePatientsPathogenesisImmune sensitization to methylene diphenyl diisocyanate (MDI) resulting from skin exposure: albumin as a carrier protein connecting skin exposure to subsequent respiratory responses
Wisnewski AV, Xu L, Robinson E, Liu J, Redlich CA, Herrick CA. Immune sensitization to methylene diphenyl diisocyanate (MDI) resulting from skin exposure: albumin as a carrier protein connecting skin exposure to subsequent respiratory responses. Journal Of Occupational Medicine And Toxicology 2011, 6: 6. PMID: 21414210, PMCID: PMC3068988, DOI: 10.1186/1745-6673-6-6.Peer-Reviewed Original ResearchRespiratory tract inflammationImmune sensitizationSkin exposureMDI conjugationBronchoalveolar lavageInflammatory responseRespiratory tract exposureAirway inflammatory responseAcetone/olive oilSubsequent immune responseSpecific antibody productionDisease prevention effortsAlbumin conjugatesOccupational asthmaSerum levelsMDI exposureAsthma pathogenesisSerum IgGIntranasal deliveryImmune responseImmune sensitivityMurine modelPathogenic mechanismsInflammationAntibody production
2010
Pro/Con debate: is occupational asthma induced by isocyanates an immunoglobulin E‐mediated disease?
Wisnewski AV, Jones M. Pro/Con debate: is occupational asthma induced by isocyanates an immunoglobulin E‐mediated disease? Clinical & Experimental Allergy 2010, 40: 1155-1162. PMID: 20545707, PMCID: PMC3121887, DOI: 10.1111/j.1365-2222.2010.03550.x.Peer-Reviewed Original ResearchConceptsAllergen-specific IgEOccupational asthmaIsocyanate asthmaPro/Con DebateScreening/surveillanceCause of asthmaIgE-mediated diseasesHypersensitive individualsLow molecular weight chemicalsEnvironmental AsthmaAllergic asthmaBronchial hyperreactivityHypersensitivity disordersCommon causeAsthmaPathogenic mechanismsIgEChronic exposureCon debateImportant mediatorDiagnostic testsWeight chemicalsDiseaseHypersensitivityPrevention
2008
Human innate immune responses to hexamethylene diisocyanate (HDI) and HDI–albumin conjugates
Wisnewski AV, Liu Q, Liu J, Redlich CA. Human innate immune responses to hexamethylene diisocyanate (HDI) and HDI–albumin conjugates. Clinical & Experimental Allergy 2008, 38: 957-967. PMID: 18498542, PMCID: PMC3131007, DOI: 10.1111/j.1365-2222.2008.02982.x.Peer-Reviewed Original ResearchMeSH KeywordsAdipokinesAdministration, InhalationAlbuminsAntigens, CDBlotting, WesternCells, CulturedChemokine CCL2Chitinase-3-Like Protein 1ChitinasesCyanatesEnzyme-Linked Immunosorbent AssayGene ExpressionGlycoproteinsHumansImmunity, InnateIntramolecular OxidoreductasesIsocyanatesLectinsLeukocytes, MononuclearLysosomesMacrophage Migration-Inhibitory FactorsMicroscopy, FluorescenceOligonucleotide Array Sequence AnalysisPolymerase Chain ReactionPolymorphism, GeneticProteinsRNAConceptsPeripheral blood mononuclear cellsInnate immune responseImmune responsePercentage of PBMCHuman peripheral blood mononuclear cellsFlow cytometrySystemic innate immune responseExposure-dependent decreaseMonocyte/macrophage traffickingHuman innate immune responseProtein expressionSpecific inhalation challengeBlood mononuclear cellsAdaptive immune responsesLow-density lipoproteinPattern recognition receptorsInhalation challengeOccupational asthmaClinical spectrumControl antigenMononuclear cellsHDI exposureSerum concentrationsAdaptive immunityGene/protein expression
2007
Developments in laboratory diagnostics for isocyanate asthma
Wisnewski AV. Developments in laboratory diagnostics for isocyanate asthma. Current Opinion In Allergy And Clinical Immunology 2007, 7: 138-145. PMID: 17351466, PMCID: PMC3131002, DOI: 10.1097/aci.0b013e3280895d22.Peer-Reviewed Original ResearchConceptsIsocyanate asthmaSpecific inhalation challengeCause of asthmaEnzyme-linked immunosorbentBiomarkers of exposureGold standard testInhalation challengeOccupational asthmaAsthma pathogenesisRisk factorsSpecialized centersAsthmaWorkplace exposuresAsthma diagnosticsEfficient laboratory testsHuman IgELaboratory testsClinical diagnosisContemporary laboratory testsLaboratory diagnosticsSubset of workersIgEDisease developmentExposureCause
2004
Isocyanate vapor-induced antigenicity of human albumin
Wisnewski AV, Stowe MH, Cartier A, Liu Q, Liu J, Chen L, Redlich CA. Isocyanate vapor-induced antigenicity of human albumin. Journal Of Allergy And Clinical Immunology 2004, 113: 1178-1184. PMID: 15208602, DOI: 10.1016/j.jaci.2004.03.009.Peer-Reviewed Original ResearchConceptsHDI exposureHuman albuminAuto body shop workersHDI vaporHuman immune systemOccupational asthmaHumoral armSpecific IgEIgG titersHealthy workersImmune responseSerology studiesHuman airwaysImmune systemSignificant associationAntigenic formsShop workersAlbumin conjugatesAsthmaticsAsthmaIgEAntigenicityParallel studyAlbuminSignificant changes
2003
Human γ/δ T-cell proliferation and IFN-γ production induced by hexamethylene diisocyanate
Wisnewski AV, Herrick CA, Liu Q, Chen L, Bottomly K, Redlich CA. Human γ/δ T-cell proliferation and IFN-γ production induced by hexamethylene diisocyanate. Journal Of Allergy And Clinical Immunology 2003, 112: 538-546. PMID: 13679813, DOI: 10.1016/s0091-6749(03)01865-7.Peer-Reviewed Original ResearchConceptsGamma/delta T cellsDelta T cellsHuman immune responseT cellsT cell receptorImmune responseAlpha/beta T cell receptorBeta T cell receptorHuman airway epithelial cellsIFN-γ productionGamma/deltaT cell proliferationAirway epithelial cellsHuman T cell lineT cell linesHuman T cellsCell typesOccupational asthmaCytokine productionPeripheral bloodIL-13IL-5Antigen-mediated selectionAntigen leadIFN-gammaDifferential roles for CD4 and CD8 T cells after diisocyanate sensitization: Genetic control of TH2-induced lung inflammation
Herrick CA, Das J, Xu L, Wisnewski AV, Redlich CA, Bottomly K. Differential roles for CD4 and CD8 T cells after diisocyanate sensitization: Genetic control of TH2-induced lung inflammation. Journal Of Allergy And Clinical Immunology 2003, 111: 1087-1094. PMID: 12743574, DOI: 10.1067/mai.2003.1413.Peer-Reviewed Original ResearchConceptsContact hypersensitivityT cellsAirway eosinophiliaAirway inflammationBALB/c miceDiisocyanate-induced asthmaCD8 T cellsLung inflammatory responseMajor effector cellsIL-13 productionMeans of inhalationNovel mouse modelEpicutaneous exposureAtopic asthmaLung inflammationMucus hypersecretionOccupational asthmaEpicutaneous sensitizationEffector cellsCytokine productionC miceIL-5Serum antibodiesInflammatory responseC57BL/10 mice
2002
Diisocyanate‐exposed auto body shop workers: A one‐year follow‐up
Redlich CA, Stowe MH, Coren BA, Wisnewski AV, Holm CT, Cullen MR. Diisocyanate‐exposed auto body shop workers: A one‐year follow‐up. American Journal Of Industrial Medicine 2002, 42: 511-518. PMID: 12439874, DOI: 10.1002/ajim.10143.Peer-Reviewed Original ResearchConceptsHealthy worker effectAuto body shop workersWorker effectHexamethylene diisocyanate exposureHistory of asthmaLower asthma prevalenceCross-sectional studyDiisocyanate exposureOccupational asthmaAsthma prevalenceImmunologic responseLow prevalenceAsthmaOne-yearHigh job turnover ratesShop workersEpisodic exposureSignificant differencesAuto body shopsPrevalenceEffect of HDISignificant changesExposureSymptomsIgGA novel mouse model of diisocyanate-induced asthma showing allergic-type inflammation in the lung after inhaled antigen challenge
Herrick CA, Xu L, Wisnewski AV, Das J, Redlich CA, Bottomly K. A novel mouse model of diisocyanate-induced asthma showing allergic-type inflammation in the lung after inhaled antigen challenge. Journal Of Allergy And Clinical Immunology 2002, 109: 873-878. PMID: 11994714, DOI: 10.1067/mai.2002.123533.Peer-Reviewed Original ResearchConceptsDiisocyanate-induced asthmaNovel mouse modelLung inflammationMouse modelAirway eosinophiliaAntigen challengeHuman asthmaAntigen-induced lung inflammationBALB/c miceAllergic-type inflammationLung inflammatory cellsCytokine-deficient miceVigorous inflammatory responsePrevious mouse modelsAtopic asthmaMucus hypersecretionOccupational asthmaContact hypersensitivityInflammatory cellsC miceInflammatory responseType cytokinesIFN-gammaAsthmaHuman diseases