Positive fungal quantitative PCR and Th17 cytokine detection in bronchoalveolar lavage fluids: Complementary biomarkers of hypersensitivity pneumonitis?

Bellanger, Anne‐Pauline; Gbaguidi‐Haore, Houssein; Gondoin, Anne; Pallandre, Jean-René; Vacheyrou, Mallory; Valot, Benoı̂t; Soumagne, Thibaud; Reboux, Gabriel; Dalphin, Jean‐Charles; Millon, Laurence

doi:10.1016/j.jim.2016.04.008

Cited by 10 publications

(7 citation statements)

References 27 publications

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“…A systematic search of the literature identified 1,500 potentially relevant articles. The full text of 340 articles was reviewed, and 84 observational studies were selected to inform the guideline committee ( 12 , 105 , 176 – 255 ). Most studies enrolled patients with known HP or other types of ILD, performed BAL with lymphocyte cellular analysis, and compared the percentage of lymphocytes among patients with different conditions.…”

Section: Diagnostic Interventionsmentioning

confidence: 99%

Diagnosis of Hypersensitivity Pneumonitis in Adults: An Official ATS/JRS/ALAT Clinical Practice Guideline

Raghu¹,

Rémy‐Jardin²,

Ryerson³

et al. 2020

Am J Respir Crit Care Med

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684

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Background: This guideline addresses the diagnosis of hypersensitivity pneumonitis (HP). It represents a collaborative effort among the American Thoracic Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax. Methods: Systematic reviews were performed for six questions. The evidence was discussed, and then recommendations were formulated by a multidisciplinary committee of experts in the field of interstitial lung disease and HP using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Results: The guideline committee defined HP, and clinical, radiographic, and pathological features were described. HP was classified into nonfibrotic and fibrotic phenotypes. There was limited evidence that was directly applicable to all questions. The need for a thorough history and a validated questionnaire to identify potential exposures was agreed on. Serum IgG testing against potential antigens associated with HP was suggested to identify potential exposures. For patients with nonfibrotic HP, a recommendation was made in favor of obtaining bronchoalveolar lavage (BAL) fluid for lymphocyte cellular analysis, and suggestions for transbronchial lung biopsy and surgical lung biopsy were also made. For patients with fibrotic HP, suggestions were made in favor of obtaining BAL for lymphocyte cellular analysis, transbronchial lung cryobiopsy, and surgical lung biopsy. Diagnostic criteria were established, and a diagnostic algorithm was created by expert consensus. Knowledge gaps were identified as future research directions. Conclusions: The guideline committee developed a systematic approach to the diagnosis of HP. The approach should be reevaluated as new evidence accumulates.

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Section: Diagnostic Interventionsmentioning

confidence: 99%

Diagnosis of Hypersensitivity Pneumonitis in Adults: An Official ATS/JRS/ALAT Clinical Practice Guideline

Raghu¹,

Rémy‐Jardin²,

Ryerson³

et al. 2020

Am J Respir Crit Care Med

Self Cite

675

684

View full text Add to dashboard Cite

show abstract

“…Despite this fact, many currently available in vitro models of pulmonary fibrosis rely on a single stimulus 65 . To mimic a pro‐fibrotic milieu in vitro, we designed a novel cocktail (IPF‐RC) containing nine IPF‐relevant cytokines and assessed its effect on differentiating iPSC‐derived distal lung epithelial progenitor cells 35‐43 . As we primarily aimed to investigate the effect of a fibrosis‐relevant environment on progenitors of the alveolar epithelium, IPF‐RC stimulation was initiated by day 35 of the protocol, following induction of SFTPC expression, which constitutes a specific feature of alveolar epithelial progenitors in fetal human lungs 66‐68 …”

Section: Discussionmentioning

confidence: 99%

“…Building on previous efforts to derive alveolar epithelium from hPSCs, we first aimed to develop a novel model system that allows human ATII‐like differentiation from iPSCs in 2D air‐liquid interface (ALI) culture to mimic the physiological environment of the lung epithelium. We next aimed to apply this model to studying alveolar epithelial dysfunction in IPF by exposing iPSC‐derived alveolar epithelial progenitor cells to an IPF‐relevant cocktail (IPF‐RC), based on upregulated cytokines found in IPF patient bronchoalveolar lavage or sputum 35‐43 …”

Section: Introductionmentioning

confidence: 99%

Recapitulating idiopathic pulmonary fibrosis related alveolar epithelial dysfunction in a human iPSC‐derived air‐liquid interface model

Schruf

Schroeder

et al. 2020

FASEB j.

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Idiopathic pulmonary fibrosis (IPF) is a fatal disease of unknown cause that is characterized by progressive fibrotic lung remodeling. An abnormal emergence of airway epithelial‐like cells within the alveolar compartments of the lung, herein termed bronchiolization, is often observed in IPF. However, the origin of this dysfunctional distal lung epithelium remains unknown due to a lack of suitable human model systems. In this study, we established a human induced pluripotent stem cell (iPSC)‐derived air‐liquid interface (ALI) model of alveolar epithelial type II (ATII)‐like cell differentiation that allows us to investigate alveolar epithelial progenitor cell differentiation in vitro. We treated this system with an IPF‐relevant cocktail (IPF‐RC) to mimic the pro‐fibrotic cytokine milieu present in IPF lungs. Stimulation with IPF‐RC during differentiation increases secretion of IPF biomarkers and RNA sequencing (RNA‐seq) of these cultures reveals significant overlap with human IPF patient data. IPF‐RC treatment further impairs ATII differentiation by driving a shift toward an airway epithelial‐like expression signature, providing evidence that a pro‐fibrotic cytokine environment can influence the proximo‐distal differentiation pattern of human lung epithelial cells. In conclusion, we show for the first time, the establishment of a human model system that recapitulates aspects of IPF‐associated bronchiolization of the lung epithelium in vitro.

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“…Building on previous efforts to derive alveolar epithelium from hPSCs, we aimed to develop a novel model system that allows human ATII-like differentiation from induced 6 pluripotent stem cells (iPSCs) in 2D air-liquid interface (ALI) culture. We next aimed to apply this model to studying alveolar epithelial dysfunction in IPF by exposing iPSC-derived alveolar epithelial progenitor cells to an IPF-relevant cocktail (IPF-RC), based on upregulated cytokines found in IPF patient bronchoalveolar lavage or sputum (38)(39)(40)(41)(42)(43)(44)(45)(46).…”

Section: Introductionmentioning

confidence: 99%

“…Despite this fact, many currently available in vitro models of pulmonary fibrosis rely on a single stimulus (59). To mimic a profibrotic milieu in vitro, we designed a novel cocktail (IPF-RC) containing nine IPF-relevant cytokines and assessed its effect on differentiating iPSC-derived distal lung epithelial progenitor cells (38)(39)(40)(41)(42)(43)(44)(45)(46). As we primarily aimed to investigate the effect of a fibrosis-relevant environment on progenitors of the alveolar epithelium, IPF-RC stimulation was initiated by day 35 of the protocol, following induction of SFTPC expression, which constitutes a specific feature of alveolar epithelial progenitors in fetal human lungs (60)(61)(62).…”

mentioning

confidence: 99%

Recapitulating idiopathic pulmonary fibrosis related alveolar epithelial dysfunction in an iPSC-derived air-liquid interface model

Schruf

Schroeder

et al. 2019

Preprint

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An abnormal emergence of airway epithelial-like cells within the alveolar compartments of the lung, herein termed bronchiolization, is a process often observed in patients suffering from idiopathic pulmonary fibrosis (IPF), a fatal disease characterized by progressive fibrotic lung remodeling. However, the origin of this dysfunctional epithelium remains unknown.In this study, we aimed to investigate the effects of a pro-fibrotic milieu, similar to that found in an IPF lung, on human alveolar epithelial progenitor cell differentiation. We developed an induced pluripotent stem cell (iPSC)-derived air-liquid interface (ALI) model of alveolar type II (ATII)-like cell differentiation and stimulated it with an IPF-relevant cocktail (IPF-RC), composed of cytokines previously reported to be elevated in IPF lungs. iPSC-derived cultures express ATII markers and contain lamellar body-like structures. Stimulation with IPF-RC during the last two weeks of differentiation increases secretion of IPF biomarkers. Transcriptome analysis of IPF-RC treated cultures reveals significant overlap with human IPF data and enrichment of transcripts associated with extracellular matrix organization. IPF-RC stimulation further impairs ATII differentiation by driving a shift towards an airway epithelial-like expression signature.In conclusion, we show for the first time, the establishment of a human model system that recapitulates aspects of IPF-associated bronchiolization in vitro. Our findings reveal how aberrant alveolar epithelial progenitor cell differentiation in a pro-fibrotic environment could contribute to alveolar bronchiolization in the distal IPF lung.SOURCE OF SUPPORTThe research was funded by Boehringer Ingelheim Pharma GmbH & Co. KG.

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Positive fungal quantitative PCR and Th17 cytokine detection in bronchoalveolar lavage fluids: Complementary biomarkers of hypersensitivity pneumonitis?

Cited by 10 publications

References 27 publications

Diagnosis of Hypersensitivity Pneumonitis in Adults: An Official ATS/JRS/ALAT Clinical Practice Guideline

Diagnosis of Hypersensitivity Pneumonitis in Adults: An Official ATS/JRS/ALAT Clinical Practice Guideline

Recapitulating idiopathic pulmonary fibrosis related alveolar epithelial dysfunction in a human iPSC‐derived air‐liquid interface model

Recapitulating idiopathic pulmonary fibrosis related alveolar epithelial dysfunction in an iPSC-derived air-liquid interface model

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