Natural History of Pulmonary Fibrosis in Two Subjects With the Same Telomerase Mutation

El–Chemaly, Souheil; Ziegler, Shira G.; Calado, Rodrigo T.; Wilson, Kirkland; Wu, Hui-Ping; Haughey, Mary; Peterson, Nathan R.; Young, Neal S.; Gahl, William A.; Moss, Joel; Gochuico, Bernadette R.

doi:10.1378/chest.10-2048

Cited by 41 publications

(32 citation statements)

References 17 publications

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“…Age-related changes in cellular function may play roles in IPF (21). Several mutations (mutations in surfactant proteins, gel-forming mucin, and telomerase) suggest a genetic predisposition (22)(23)(24), and inflammation and fibroblast and epithelial cell dysfunction are possible pathogenic changes in IPF.…”

Section: Discussionmentioning

confidence: 99%

Relationship between survival and age in patients with idiopathic pulmonary fibrosis

Koo

Uh²,

Kim

et al. 2016

J. Thorac. Dis.

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Background: There is a debate that older patients with idiopathic pulmonary fibrosis (IPF) have a worse prognosis. We evaluated whether age affects the survival of patients with IPF. Methods:The Korean Interstitial Lung Disease (ILD) Research Group conducted a national survey to evaluate the clinical, physiological, radiological, and survival characteristics of patients with IPF. A total of 1,663 patients with IPF were stratified into three groups according to age: (I) <60 years (n=309); (II) 60-69 years (n=613); and (III) ≥70 years (n=741).Results: The 1-, 3-and 5-year observed survival rates were 83.0%, 62.6%, and 49.2% in the total population, respectively. The 1-, 3-, and 5-year relative survival rates were 85.7%, 69.1%, and 58.0% in all patients, respectively. The observed survival rate of the group ≥70 years of age was significantly lower than those of the other groups (P<0.001). In contrast, no significant difference in relative survival rate was detected among the three age groups. Compared with patients less than 60 years of age, patients with above 70 years of age had not increased risk of worse relative survival [P=0.252; hazard ratio (HR), 1.11; 95% confidence interval (CI), 0.76-1.64]. Conclusions:The prognosis of patients above 70 years of age with IPF was not different to that of patients less than 60 years of age, using relative survival rate. Age may not affect survival in patients with IPF.

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Section: Discussionmentioning

confidence: 99%

Relationship between survival and age in patients with idiopathic pulmonary fibrosis

Koo

Uh²,

Kim

et al. 2016

J. Thorac. Dis.

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“…Estimates of the allelic frequency of this mutation range from 0.6% in an ethnically diverse population 19 to 2.5% in a white population. 2 In vitro analyses have previously demonstrated that heterozygosity in the Ala 1062 Th r variant of TERT does not result in signifi cant decrease in telomerase activity. 3 In contrast, another study has demonstrated that the Ala 1062 Th r variant of TERT can result in a decrease in telomerase enzymatic activity via haploinsuffi ciency.…”

Section: Discussionmentioning

confidence: 99%

Short Telomeres, Telomeropathy, and Subclinical Extrapulmonary Organ Damage in Patients With Interstitial Lung Disease

George

Rosas

Cui

et al. 2015

Chest

Self Cite

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“…Telomere-mediated organ failure typically has a protracted course, especially in adults who may have subclinical disease for many years before becoming symptomatic (67). In some cases, for example with an offending insult such as an infection or an exposure to drug toxicities, acute declines can be sustained.…”

Section: Telomere Biology and Its Role In Advancing Clinical Paradigmsmentioning

confidence: 99%

Telomeres and age-related disease: how telomere biology informs clinical paradigms

2013

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Telomere length shortens with age and predicts the onset of replicative senescence. Recently, short telomeres have been linked to the etiology of degenerative diseases such as idiopathic pulmonary fibrosis, bone marrow failure, and cryptogenic liver cirrhosis. These disorders have recognizable clinical manifestations, and the telomere defect explains their genetics and informs the approach to their treatment. Here, I review how telomere biology has become intimately connected to clinical paradigms both for understanding pathophysiology and for individualizing therapy decisions. I also critically examine nuances of interpreting telomere length measurement in clinical studies.Understanding basic biological mechanisms holds the potential to advance clinical paradigms. The emerging impact of telomerase and telomere biology in medicine provides a clear example of this promise. Research in this area was initially sparked by fundamental questions about how genomes are protected at chromosome ends, and focused on curiosity-driven questions in maize, yeast, and protozoa (1). These highly conserved molecular mechanisms have now led to unforeseen benefits for understanding idiopathic disease and have opened a new area of translational research. Here I review the trajectory of the evolving role of telomere biology in clinical paradigms and highlight how it has become central to understanding the pathophysiology of age-dependent disorders as well as for informing new approaches to their treatment.

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Natural History of Pulmonary Fibrosis in Two Subjects With the Same Telomerase Mutation

Cited by 41 publications

References 17 publications

Relationship between survival and age in patients with idiopathic pulmonary fibrosis

Relationship between survival and age in patients with idiopathic pulmonary fibrosis

Short Telomeres, Telomeropathy, and Subclinical Extrapulmonary Organ Damage in Patients With Interstitial Lung Disease

Telomeres and age-related disease: how telomere biology informs clinical paradigms

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