Evidence map›Paper›PMID 35672770›Full record

ArticleRespiratory research2022

Digital quantification of p16-positive foci in fibrotic interstitial lung disease is associated with a phenotype of idiopathic pulmonary fibrosis with reduced survival.

Jonathan Keow, Matthew J Cecchini, Nathashi Jayawardena, Maurizio Zompatori, Mariamma G Joseph, Marco Mura

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Respiratory research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.4field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Current oncology (Toronto, Ont.) · 2026
    Article
  3. Multi-omics to study chronic respiratory diseases and viral infections.European respiratory review : an official journal of the European Respiratory Society · 2026
    Review
  4. Review
  5. Targeting MLL1/WDR5-Mediated Epigenetic Regulation Mitigates Peritoneal Fibrosis by Reducing p16FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  6. Article
  7. ModulatingAging · 2024
    Article
  8. Review
  9. Article
  10. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 2 countries.

Jonathan KeowDepartment of Pathology and Laboratory Medicine, Western University, London, ON, Canada.
Matthew J CecchiniDepartment of Pathology and Laboratory Medicine, Western University, London, ON, Canada.
Nathashi JayawardenaInterstitial Lung Disease Research Laboratory, Lawson Research Institute, Western University, London, ON, Canada.
Maurizio ZompatoriMultiMedica Group, I.R.C.C.S. San Giuseppe Hospital, Milan, Italy.
Mariamma G JosephDepartment of Pathology and Laboratory Medicine, Western University, London, ON, Canada.
Marco MuraInterstitial Lung Disease Research Laboratory, Lawson Research Institute, Western University, London, ON, Canada. marco.mura@lhsc.on.ca.ORCID http://orcid.org/0000-0002-2159-7083
Western University · CAMultiMedica · IT

Funding

Academic Medical Organization of Southwestern Ontario INN19-006lawson health research institute Fall 2018 Internal Research Fund (IRF)
6 · The paper itself

Abstract

backgroundIdiopathic pulmonary fibrosis (IPF) is associated with increased expression of cyclin-dependent kinase inhibitors such as p16 and p21, and subsequent induction of cell cycle arrest, cellular senescence, and pro-fibrotic gene expression. We sought to link p16-expression with a diagnosis of IPF or other fibrotic interstitial lung diseases (ILDs), radiographic pattern, senescent foci-specific gene expression, antifibrotic therapy response, and lung transplant (LTx)-free survival.

methodsEighty-six cases of fibrosing ILD were identified with surgical lung biopsy. Immunohistochemistry for p16 was performed on sections with the most active fibrosis. p16-positive foci (loose collection of p16-positive fibroblasts with overlying p16-positive epithelium) were identified on digital slides and quantified. Cases were scored as p16-low (≤ 2.1 foci per 100 mm

resultsThe presence of p16-positive foci was specific for the diagnosis of IPF, where 50% of cases expressed any level of p16 and 26% were p16-high. There was no relationship between radiographic pattern and p16 expression. However, there was increased expression of cyclin-dependent kinase inhibitors, collagens and matrix remodeling genes within p16-positive foci, and cases with high p16 expression had shorter LTx-free survival. On the other hand, antifibrotic therapy was significantly protective. DSP demonstrated that fibroblastic foci exhibit transcriptional features clearly distinct from that of normal-looking and even fibrotic areas.

conclusionsWe demonstrated the potential clinical applicability of a standardized quantification of p16-positive fibroblastic foci. This method identifies an IPF phenotype associated with foci-specific upregulation of senescence-associated and matrix remodeling gene expression. While these patients have reduced LTx-free survival, good response to antifibrotic therapies was observed in those who were treated.

Indexed as

Idiopathic Pulmonary FibrosisLung Diseases, InterstitialCyclin-Dependent KinasesFibrosisHumansLungPhenotypeCyclin-Dependent KinasesIdiopathic pulmonary fibrosisInterstitial lung diseaseSenescenceUsual interstitial pneumonia

Identifiers

PMID35672770
PMCPMC9175499
OpenAlexW4281688910

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.