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RESEARCH PRODUCT
Lung microenvironments and disease progression in fibrotic hypersensitivity pneumonitis
Arno VanstapelVincent GeudensAnnelore SacreasJames C. HoggWim A. WuytsAnke Van HerckErik VerbekenLaurens J. De SadeleerJohn E. McdonoughMaximilian AckermannNaftali KaminskiDominique ScholsJonas C. SchuppStephanie EveraertsCeline AelbrechtTinne GoosManon MahieuTillie-louise HackettTim S. NawrotAnabelle DecottigniesSandra ClaesJohny VerschakelenDries S. MartensXiting YanBart M. VanaudenaerdeStijn E. VerledenStijn E. Verledensubject
AdultGenetic MarkersMalePulmonary and Respiratory MedicinePathologymedicine.medical_specialtyExtrinsic Allergic Alveolitisextrinsic allergic alveolitisCritical Care and Intensive Care MedicineSeverity of Illness IndexTranscriptome03 medical and health sciences0302 clinical medicineFibrosisPulmonary fibrosisMedicineHumansLungAged030304 developmental biology0303 health sciencesLungmedicine.diagnostic_testpulmonary fibrosisbusiness.industryGene Expression ProfilingInterstitial lung diseaseReproducibility of ResultsOriginal ArticlesMiddle Agedrespiratory systemmedicine.diseaseFibrosisIdiopathic Pulmonary Fibrosis3. Good healthrespiratory tract diseasesmedicine.anatomical_structureBronchoalveolar lavage030228 respiratory systemCase-Control StudiesDisease ProgressionLinear ModelsFemaleHuman medicineTranscriptomebusinesstranscriptomeHypersensitivity pneumonitisAlveolitis Extrinsic Allergicdescription
Rationale: Fibrotic hypersensitivity pneumonitis (fHP) is an interstitial lung disease caused by sensitization to an inhaled allergen. Objectives: To identify the molecular determinants associated with progression of fibrosis. Methods: Nine fHP explant lungs and six unused donor lungs (as controls) were systematically sampled (4 samples/lung). According to microcomputed tomography measures, fHP cores were clustered into mild, moderate, and severe fibrosis groups. Gene expression profiles were assessed using weighted gene co-expression network analysis, xCell, gene ontology, and structure enrichment analysis. Gene expression of the prevailing molecular traits was also compared with idiopathic pulmonary fibrosis (IPF). The explant lung findings were evaluated in separate clinical fHP cohorts using tissue, BAL samples, and computed tomography scans. Measurements and Main Results: We found six molecular traits that associated with differential lung involvement. In fHP, extracellular matrix and antigen presentation/sensitization transcriptomic signatures characterized lung zones with only mild structural and histological changes, whereas signatures involved in honeycombing and B cells dominated the transcriptome in the most severely affected lung zones. With increasing disease severity, endothelial function was progressively lost, and progressive disruption in normal cellular homeostatic processes emerged. All six were also found in IPF, with largely similar associations with disease microenvironments. The molecular traits correlated with in vivo disease behavior in a separate clinical fHP cohort. Conclusions: We identified six molecular traits that characterize the morphological progression of fHP and associate with in vivo clinical behavior. Comparing IPF with fHP, the transcriptome landscape was determined considerably by local disease extent rather than by diagnosis alone. ispartof: AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE vol:205 issue:1 pages:60-+ ispartof: location:United States status: published
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2022-01-01 | American journal of respiratory and critical care medicine |