Usual interstitial pneumonia in asbestos‐exposed cohorts – concurrent idiopathic pulmonary fibrosis or atypical asbestosis?

Attanoos, Richard; Alchami, Fouad; Pooley, F. D.; Gibbs, A R

doi:10.1111/his.12951

Cited by 23 publications

(15 citation statements)

References 29 publications

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“…We also know that many risk factors for IPF are also known to change DNA methylation patterns, such as, cigarette smoke exposure [187,236], aging [34, 236,237], asbestos exposure [236,238,239], male gender [237,240], relatedness [237,241] and ethnicity [242,243].…”

Section: Chapter III Dna Methylation Of the Muc5b Promoter In Ipf Intmentioning

confidence: 99%

Regulation of MUC5B Expression in Idiopathic Pulmonary Fibrosis

Helling

Gerber

Kadiyala

et al. 2017

Am J Respir Cell Mol Biol

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Idiopathic pulmonary fibrosis (IPF) is the most common and the most aggressive fibrosing interstitial lung disease (ILD). Despite recent promising clinical trials, IPF remains incurable and largely untreatable. Genetic studies have identified several risk loci for both sporadic and familial forms of IPF. A single variant upstream of MUC5B is predicted to account for more than 30% of all IPF risk. This variant, rs35705950, is associated with expression of MUC5B in healthy lung tissue. However, the mechanism underlying the relationship between rs35705950 and MUC5B expression remains unclear.The first goal of my thesis research was to determine whether rs35705950 is also a risk factor for other forms of ILD. Genomic DNA from individuals with IPF, HP, COPD, iNSIP, and RB-ILD was obtained and genotyped for the common MUC5B promoter variant. In these populations the risk allele was associated with IPF and iNSIP which suggested a potential shared disease mechanism. Additionally, I showed that in the IPF and control populations rs35705950 is associated with lung MUC5B expression.The second goal of my thesis research was to investigate MUC5B promoter DNA methylation which has previously been shown to play a role in MUC5B expression.Methylation analysis of the 4KB region upstream of MUC5B identified two differentially methylated regions (DMRs) associated with IPF, one DMR associated with MUC5B iv expression, and one DMR associated with rs35705950. The IPF, MUC5B expression, and rs35705950 associated DMRs are all differentially methylated at a cluster of 11 CpG motifs. overlapping DMR, including the motif disrupted by rs35705950. These findings suggest that DNA methylation may play a role in MUC5B gene regulation and IPF risk.Next, I used cross species analysis to identify highly conserved domains within the overlapping DMR. Evolutionary conservation indicated selective pressures to maintain sequences overtime and suggests biological importance. The overlapping DMR contains a highly conserved binding motif for FOXA2, a transcription factor. Further analysis using ChIP-qPCR, reporter constructs, and siRNA, established a role for FOXA2 in regulation of MUC5B expression in lung tissue. Additionally, siRNA knock down identified 3 other transcription factors which are associated with MUC5B expression; STAT3, HOXA9 and ZBTB7A. These transcriptional regulators provide insight into possible therapeutic intervention for MUC5B dysregulation and IPF.The form and content of this abstract are approved. I recommend its publication.

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Section: Chapter III Dna Methylation Of the Muc5b Promoter In Ipf Intmentioning

confidence: 99%

Regulation of MUC5B Expression in Idiopathic Pulmonary Fibrosis

Helling

Gerber

Kadiyala

et al. 2017

Am J Respir Cell Mol Biol

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“…Differentiation should include above all those disease entities which can be associated with a radiographic or histopathological pattern of UIP. First and foremost, differentiation should pertain to chronic hypersensitivity pneumonitis (cHP) [61], ILD in the course of CTD (CTD-ILD) (especially in the course of rheumatoid arthritis, RA) [62], pneumoconioses (especially asbestosis) [63] or drug-induced changes [22]. Table 7 presents the basic features of other diseases facilitating such differentiation.…”

Section: Differential Diagnosismentioning

confidence: 99%

Guidelines of the Polish Respiratory Society for Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis

Piotrowski

Bestry²,

Białas

et al. 2020

Advances in Respiratory Medicine

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“…To determine whether UIP pattern fibrosis is seen in asbestosis Attanoos et al studied the occurrence of UIP pattern fibrosis in four asbestos cohorts (17-year period, >25000 persons) systematically referred following post-mortem [11]. Out of 233 subjects 210 had degrees of interstitial fibrosis with a Nonspecific Interstitial Pneumonia (NSIP) pattern and 3 showed UIP pattern fibrosis.…”

Section: Asbestosis and Other Interstitial Lung Diseasesmentioning

confidence: 99%

Non-neoplastic asbestos-related respiratory diseases: what relationship with other lung diseases?

Sartorelli¹,

Bianchi²,

Paolucci³

2017

Pulm Crit Care Med

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Non-neoplastic asbestos-related respiratory diseases in practice are represented by asbestosis and pleural plaques. Clinical features and architectural tissue abnormalities of asbestosis do not differ from those of other causes of interstitial fibrosis which allows a confident diagnosis without a history of significant exposure to asbestos. But the relationship between non-neoplastic asbestos-related diseases and other lung diseases is not only represented by the need for differential diagnosis. developing lung diseases not classified as Asbestos-Related Diseases.The article reviews the existing relationship between non-neoplastic asbestos-related respiratory diseases and interstitial lung diseases, lung function and risk of pleuropulmonary neoplastic diseases.

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Usual interstitial pneumonia in asbestos‐exposed cohorts – concurrent idiopathic pulmonary fibrosis or atypical asbestosis?

Cited by 23 publications

References 29 publications

Regulation of MUC5B Expression in Idiopathic Pulmonary Fibrosis

Regulation of MUC5B Expression in Idiopathic Pulmonary Fibrosis

Guidelines of the Polish Respiratory Society for Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis

Non-neoplastic asbestos-related respiratory diseases: what relationship with other lung diseases?

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