An epithelial biomarker signature for idiopathic pulmonary fibrosis: an analysis from the multicentre PROFILE cohort study

Maher, Toby M.; Oballa, Eunice; Simpson, Juliet K.; Porte, Joanne; Habgood, Anthony; Fahy, William A; Flynn, AA; Molyneaux, Philip L.; Braybrooke, Rebecca; Divyateja, Hrushikesh; Parfrey, Helen; Rassl, Doris M.; Russell, Anne-Marie; Saini, Gauri; Renzoni, Elisabetta A.; Duggan, Anne-Marie; Hubbard, Richard; Wells, Adrian; Lukey, Pauline T.; Marshall, Richard P.; Jenkins, R Gisli

doi:10.1016/s2213-2600(17)30430-7

Cited by 205 publications

(181 citation statements)

References 33 publications

(46 reference statements)

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“…The Prospective Observation of Fibrosis in Lung Clinical Endpoints (PROFILE) Central England (NCT01134822) study is a longitudinal observational clinical trial that has been described previously [19, 20]. Age was grouped at 65 or under, 66-79, 80 or over; comorbidities were grouped as none, 1-2, 3 or more.…”

Section: Methodsmentioning

confidence: 99%

Patient reported distress can aid clinical decision making in idiopathic pulmonary fibrosis: analysis of the PROFILE cohort

Stewart

McKeever

Braybrooke

et al. 2018

Preprint

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Idiopathic pulmonary fibrosis is a progressive and fatal interstitial lung disease. We aimed to determine if patient response to a palliative assessment survey could predict disease progression or death.We undertook a cross-sectional study in a UK clinical cohort of incident cases. Rasch-based methodology provided a disease distress value from an abridged 11 item model of the original 45 item survey. Distress values were compared with measures of lung function. Disease progression or mortality alone was predicted at twelve months from survey completion, with risk of death assessed at three, six and twelve months.Disease distress values were negatively correlated with lung function (r=-0.275 percent predicted DLCO). Expected survey scores computed from distress values could distinguish disease progression, 8.8 (p=0.004), and people who died, 10.2 (p=0.002), from those who did not progress, 6.9. Actual survey scores predicted disease progression and mortality with an area under the curve of 0.60 and 0.64, respectively. Each point increment in actual score increased risk of twelve-month mortality by 10%, almost 43% of people scoring above 18 did not survive beyond 105 days.We define a short questionnaire that can score disease distress and predict prognosis, assisting clinical decision making in progressive fibrosis.

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Section: Methodsmentioning

confidence: 99%

Patient reported distress can aid clinical decision making in idiopathic pulmonary fibrosis: analysis of the PROFILE cohort

Stewart

McKeever

Braybrooke

et al. 2018

Preprint

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“…The difficulty in predicting disease behaviour and response to treatment across ILD entities has driven the search for improved prognostic tools. Matrix metalloproteinase 7 (MMP7) has perhaps been the most studied single serum marker in IPF . Tzouvelekis et al .…”

Section: Interstitial Lung Diseasementioning

confidence: 99%

Year in review 2017: Interstitial lung disease, pulmonary vascular disease and sleep

et al. 2018

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“…Analysis of the culture medium in IPF-RC treated cells showed increased MMP-7 and MMP-10, both of which are elevated in IPF patient BAL and serum, and RNA-seq analysis revealed an enrichment of transcripts involved in extracellular matrix organization, indicating an induction of IPF-relevant processes (63)(64)(65). Furthermore, a comparison of transcriptional changes in IPF-RC treated iPSC-derived cultures and human IPF patient lungs revealed a significant overlap of upand down-regulated transcripts (48).…”

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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An epithelial biomarker signature for idiopathic pulmonary fibrosis: an analysis from the multicentre PROFILE cohort study

Abstract: GlaxoSmithKline R&D and the UK Medical Research Council.

Cited by 205 publications

References 33 publications

Patient reported distress can aid clinical decision making in idiopathic pulmonary fibrosis: analysis of the PROFILE cohort

Patient reported distress can aid clinical decision making in idiopathic pulmonary fibrosis: analysis of the PROFILE cohort

Year in review 2017: Interstitial lung disease, pulmonary vascular disease and sleep

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

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