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Age, family aggregation, haematological abnormalities predict telomere shortening in IPF patients

25 Jan 2019
The secret to living forever? first successful gene therapy to reverse ageing

Patients with sporadic idiopathic pulmonary fibrosis (IPF) aged <60 years and who have nonspecific immunological or haematological abnormalities are at increased risk of telomere shortening, as well as present a poorer prognosis, according to a study.

“[I]dentification of telomere shortening in pulmonary fibrosis is important in predicting patient outcome,” researchers said. “Our study determines a probability pretest model for telomere shortening that detects IPF patients with higher risk and, therefore, that most benefit from genetic study.”

Family aggregation, age of <60 years, and presence of nonspecific immunological or haematological abnormalities all predicted a greater risk of telomere shortening. [Respirology 2019;24:146-153]

Of the patients, 66.6 percent younger than 60 years with telomere shortening succumbed to death or needed lung transplantation, independent of functional impairment at diagnosis. On the other hand, the negative impact of telomere shortening on outcome was not significant in those older than 60 years.

“Our most important finding was the different ratio of shortened telomeres depending on the clinical phenotype,” researchers said. “Thus, although the overall probability of telomere shortening was 25 percent, in those patients younger than 60 years of age who presented some nonspecific immunological and haematological abnormalities, the probability was almost 100 percent.”

Furthermore, suspicion regarding the negative impact of telomere shortening on outcome might grow with the presence of identified blood or immunological abnormalities even in IPF patients older than 60 years, the age group at which most of them are diagnoses, they added. [Am J Respir Crit Care Med 2011;183:788-824]

The strongest independent predictive factor for telomere shortening is family aggregation, but age is another strong predictor based on evidence from previous studies on telomere mutations in familial pulmonary fibrosis. [Am J Respir Crit Care Med 2005;172:1146-1152; Rev Mal Respir 2015;32:413-434; Eur Respir J 2016;48:1710-1720; Eur Respir J 2016;48:1721-1731]

Retrospective cohort studies found an association between telomere shortening and worse survival outcomes. Newton and colleagues reported a survival rate of 2–3 years in the analysis of telomere-related gene mutation from 64 families, but the mean age for those mutation carriers was 58 years. [Eur Respir J 2016;48:1710-1720; Eur Respir J 2014;44:178-187; Respirology 2015;20:947-952]

“The results from our prospective cohort highlight that the prognosis associated with telomere shortening depends in part on the age of disease onset, suggesting that the sooner the lung fibrotic process develops the faster the lung ageing and disease progression occur,” researchers said.

“Several hypotheses could explain this observation, including genetic anticipation and higher cell turnover in younger patients with the same gene defect,” they added.

The present study involved consecutive Spanish patients, followed up for 3 years. Results found in Spanish sporadic IPF were validated using DNA blood samples from a Mexican cohort. Prior to treatment, researchers measured telomere length through quantitative polymerase chain reaction and Southern blot. They evaluated the outcome according to mortality or need for lung transplantation. Statistical analysis was performed using a multivariate regression logistic model.

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Most Read Articles
10 Jan 2021
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Dr. Hsu Li Yang, Dr. Tan Thuan Tong, Dr. Andrea Kwa, 08 Jan 2021
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