Development and Progression of Radiologic Abnormalities in Individuals at Risk for Familial Interstitial Lung Disease

Salisbury, M.L.; Hewlett, J.C.; Ding, Guixiao; Markin, Cheryl; Douglas, Keith; Mason, Wendi R.; Guttentag, Adam; Phillips, John A.; Cogan, Joy D.; Reiss, Sara; Mitchell, Daphne B.; Wu, Pingsheng; Young, Lisa R.; Lancaster, Lisa; Loyd, James E.; Humphries, Stephen; Lynch, David A.; Kropski, Jonathan A.; Blackwell, Timothy S.

doi:10.1164/rccm.201909-1834oc

Cited by 77 publications

(82 citation statements)

References 36 publications

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“…Longitudinal studies have demonstrated that while in most of individuals these abnormalities persist without progression, in 20-40% of the cases imaging abnormalities are progressive which is usually associated to an increased decline in pulmonary function and increased rate of mortality [1,8,42]. Moreover, in a recent 5-years longitudinal study, that included a high-risk population of asymptomatic first-degree relatives of patients with familial interstitial pneumonia, it was found that the majority of individuals with early/mild ILA at the time of enrollment had evidence of progression to an interstitial lung disease [43]. All these studies support the notion that screening for ILA might eventually provide a tool for the early identification of an ILD, including IPF which is the most aggressive of them [44,45].…”

Section: Discussionmentioning

confidence: 99%

Circulating microRNA Signature Associated to Interstitial Lung Abnormalities in Respiratory Asymptomatic Subjects

Ortiz‐Quintero

Buendía-Roldán

Ramírez‐Salazar

et al. 2020

Cells

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Interstitial lung abnormalities (ILA) are observed in around 9% of older respiratory asymptomatic subjects, mainly smokers. Evidence suggests that ILA may precede the development of interstitial lung diseases and may evolve to progressive fibrosis. Identifying biomarkers of this subclinical status is relevant for early diagnosis and to predict outcome. We aimed to identify circulating microRNAs (miRNAs) associated to ILA in a cohort of respiratory asymptomatic subjects older than 60 years. We identified 81 subjects with ILA from our Lung-Aging Program in Mexico City (n = 826). We randomly selected 112 subjects without ILA (Ctrl) from the same cohort. Using polymerase chain reaction PCR-Array technology (24 ILA and 24 Ctrl, screening cohort) and reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) (57 ILA and 88 Ctr, independent validation cohort) we identified seven up-regulated miRNAs in serum of ILA compared to Ctrl (miR-193a-5p, p < 0.0001; miR-502-3p, p < 0.0001; miR-200c-3p, p = 0.003; miR-16-5p, p = 0.003; miR-21-5p, p = 0.002; miR-126-3p, p = 0.004 and miR-34a-5p, p < 0.005). Pathways regulated by these miRNAs include transforming growth factor beta (TGF-β), Wnt, mammalian target of rapamycin (mTOR), Insulin, mitogen-activated protein kinase (MAPK) signaling, and senescence. Receiver operator characteristic (ROC) curve analysis indicated that miR-193a-5p (area under the curve AUC: 0.75) and miR-502-3p (AUC 0.71) have acceptable diagnostic value. This is the first identification of circulating miRNAs associated to ILA in respiratory asymptomatic subjects, providing potential non-invasive biomarkers and molecular targets to better understand the pathogenic mechanisms associated to ILA.

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Section: Discussionmentioning

confidence: 99%

Circulating microRNA Signature Associated to Interstitial Lung Abnormalities in Respiratory Asymptomatic Subjects

Ortiz‐Quintero

Buendía-Roldán

Ramírez‐Salazar

et al. 2020

Cells

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“…Furthermore, demographic differences were observed in relation to ever-smoking with lower rates in ILA than would be expected in IPF, with less than 50% of those with observed with ILA describing themselves as ever-smokers. However, the risk of having ILA compared with no ILA was only lower in male ever-smokers in one study (9). Therefore, it might be possible that ILAs are precursor lesions in those with additional risk factors such as male sex, ever-smoking history, MUC5B polymorphism, and short telomeres.…”

Section: Yonis H Mortaza S Baboi L Mercatmentioning

confidence: 87%

“…It is well-recognized that patients present after years of increasing symptoms (1). However, it seems unlikely that the study by Salisbury and colleagues was revealing undiagnosed disease because only 4% had extensive ILA and there was little functional difference between patients with or without ILA, with near-normal lung function in the small number of patients with available data (9). However, in contrast, 18% of people in the study by Hunninghake and colleagues had changes sufficiently extensive to merit the label of an ILD even though they had a fairly well-preserved FVC, although a substantially reduced DL CO , and a number required treatment with an antifibrotic (10).…”

Section: Yonis H Mortaza S Baboi L Mercatmentioning

confidence: 96%

“…1230-1239) and Hunninghake and colleagues (pp. 1240-1248) provide data that help inform the answers to these two crucial questions (9,10). Both these studies use computed tomography scanning to "screen" unaffected first-degree relatives of patients with familial pulmonary fibrosis (FPF), and the study by Hunninghake and colleagues also screens first-degree relatives of patients with sporadic IPF.…”

Section: Yonis H Mortaza S Baboi L Mercatmentioning

confidence: 99%

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Three Steps to Cure Pulmonary Fibrosis. Step 1: The Runaway Train or Groundhog Day?

Jenkins

2020

Am J Respir Crit Care Med

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“…Animal studies clearly show that herpes virus-associated changes occur prior to onset of clinical features and in some cases that early treatment provides more greater benefit than later (81). For this reason, it will be all the more important to identify and diagnose people in the early stages of PF and to conduct trials at this time, rather than at symptomatic presentation, which is likely to represent a more treatment-resistant "end-stage" situation (11,121,122).…”

Section: Diagnosis Of Significant Herpes Virus Infectionmentioning

confidence: 99%

The Role of Herpes Viruses in Pulmonary Fibrosis

Duckworth

Longhurst

Paxton³

et al. 2021

Front. Med.

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Pulmonary fibrosis (PF) is a serious lung disease which can result from known genetic or environmental exposures but is more commonly idiopathic (IPF). In familial PF (FPF), the majority of identified causal genes play key roles in the maintenance of telomeres, the protective end structures of chromosomes. Recent evidence suggests that short telomeres may also be implicated causally in a significant proportion of idiopathic cases. The possible involvement of herpes viruses in PF disease incidence and progression has been examined for many years, with some studies showing strong, statistically significant associations and others reporting no involvement. Evidence is thus polarized and remains inconclusive. Here we review the reported involvement of herpes viruses in PF in both animals and humans and present a summary of the evidence to date. We also present several possible mechanisms of action of the different herpes viruses in PF pathogenesis, including potential contributions to telomere attrition and cellular senescence. Evidence for antiviral treatment in PF is very limited but suggests a potential benefit. Further work is required to definitely answer the question of whether herpes viruses impact PF disease onset and progression and to enable the possible use of targeted antiviral treatments to improve clinical outcomes.

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Development and Progression of Radiologic Abnormalities in Individuals at Risk for Familial Interstitial Lung Disease

Cited by 77 publications

References 36 publications

Circulating microRNA Signature Associated to Interstitial Lung Abnormalities in Respiratory Asymptomatic Subjects

Circulating microRNA Signature Associated to Interstitial Lung Abnormalities in Respiratory Asymptomatic Subjects

Three Steps to Cure Pulmonary Fibrosis. Step 1: The Runaway Train or Groundhog Day?

The Role of Herpes Viruses in Pulmonary Fibrosis

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