ABSTRACT
Background and objective
The abnormal shortening of telomeres is a mechanism linking ageing to idiopathic pulmonary fibrosis (IPF) that could be useful in the clinical setting. The objective ...of this study was to identify the IPF patients with higher risk for telomere shortening and to investigate the outcome implications.
Methods
Consecutive Spanish patients were included at diagnosis and followed up for 3 years. DNA blood samples from a Mexican cohort were used to validate the results found in Spanish sporadic IPF. Prior to treatment, telomere length was measured through quantitative polymerase chain reaction (qPCR) and Southern blot. Outcome was assessed according to mortality or need for lung transplantation. A multivariate regression logistic model was used for statistical analysis.
Results
Family aggregation, age of <60 years and the presence of non‐specific immunological or haematological abnormalities were associated with a higher probability of telomere shortening. Overall, 66.6% of patients younger than 60 years with telomere shortening died or required lung transplantation, independent of functional impairment at diagnosis. By contrast, in patients older than 60 years with telomere shortening, the negative impact of telomere shortening in outcome was not significant.
Conclusion
Our data indicate that young sporadic IPF patients (<60 years) with some non‐specific immunological or haematological abnormalities had higher risk of telomere shortening, and furthermore, they presented a poorer prognosis.
The study establishes predictive factors for telomere shortening in idiopathic pulmonary fibrosis (IPF) and demonstrates clinical implications in pulmonary fibrosis. Sporadic IPF patients younger than 60 years and/or presenting non‐specific immunological or haematological abnormalities were at higher risk of telomere shortening. A poor prognosis is more frequently associated with a young disease onset.
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The soluble receptor for advanced glycation end-products (sRAGE) has been suggested that it acts as a decoy for capturing advanced glycation end-products (AGEs) and inhibits the activation of the ...oxidative stress and apoptotic pathways. Lung AGEs/sRAGE is increased in idiopathic pulmonary fibrosis (IPF). The objective of the study was to evaluate the AGEs and sRAGE levels in serum as a potential biomarker in IPF.
Serum samples were collected from adult patients: 62 IPF, 22 chronic hypersensitivity pneumonitis (cHP), 20 fibrotic non-specific interstitial pneumonia (fNSIP); and 12 healthy controls. In addition, 23 IPF patients were re-evaluated after 3-year follow-up period. Epidemiological and clinical features were recorded: age, sex, smoking habits, and lung function. AGEs and sRAGE were evaluated by ELISA, and the results were correlated with pulmonary functional test values.
IPF and cHP groups presented a significant increase of AGE/sRAGE serum concentration compared with fNSIP patients. Moreover, an inverse correlation between AGEs and sRAGE levels were found in IPF, and serum sRAGE at diagnosis correlated with FVC and DLCO values. Additionally, changes in serum AGEs and sRAGE correlated with % change of FVC, DLCO and TLC during the follow-up. sRAGE levels below 428.25 pg/ml evolved poor survival rates.
These findings demonstrate that the increase of AGE/sRAGE ratio is higher in IPF, although the levels were close to cHP. AGE/sRAGE increase correlates with respiratory functional progression. Furthermore, the concentration of sRAGE in blood stream at diagnosis and follow-up could be considered as a potential prognostic biomarker.
ABSTRACT
Background and objective
The relationship between IPF development and environmental factors has not been completely elucidated. Analysing geographic regions of idiopathic pulmonary fibrosis ...(IPF) cases could help identify those areas with higher aggregation and investigate potential triggers. We hypothesize that cross‐analysing location of IPF cases and areas of consistently high air pollution concentration could lead to recognition of environmental risk factors for IPF development.
Methods
This retrospective study analysed epidemiological and clinical data from 503 patients registered in the Observatory IPF.cat from January 2017 to June 2019. Incident and prevalent IPF cases from the Catalan region of Spain were graphed based on their postal address. We generated maps of the most relevant air pollutant PM2.5 from the last 10 years using data from the CALIOPE air quality forecast system and observational data.
Results
In 2018, the prevalence of IPF differed across provinces; from 8.1 cases per 100 000 habitants in Barcelona to 2.0 cases per 100 000 in Girona. The ratio of IPF was higher in some areas. Mapping PM2.5 levels illustrated that certain areas with more industry, traffic and shipping maintained markedly higher PM2.5 concentrations. Most of these locations correlated with higher aggregation of IPF cases. Compared with other risk factors, PM2.5 exposure was the most frequent.
Conclusion
In this retrospective study, prevalence of IPF is higher in areas of elevated PM2.5 concentration. Prospective studies with targeted pollution mapping need to be done in specific geographies to compile a broader profile of environmental factors involved in the development of pulmonary fibrosis.
This study identifies geographic regions of notable air pollution, juxtaposed over locations with higher prevalence of idiopathic pulmonary fibrosis (IPF). Certain areas with elevated air pollutants may be deserving greater analysis for screening of IPF and optimizing early identification. Prospective studies are required for evaluating air pollution as an IPF risk factor.
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Telomeres are nucleoprotein structures present at the terminal region of the chromosomes. Mutations in genes coding for proteins involved in telomere maintenance are causative of a number of ...disorders known as telomeropathies. The genetic origin of these diseases is heterogeneous and has not been determined for a significant proportion of patients.
This article describes the genetic characterization of a cohort of patients. Telomere length was determined by Southern blot and quantitative PCR. Nucleotide variants were analyzed either by high-resolution melting analysis and Sanger sequencing of selected exons or by massive sequencing of a panel of genes.
Forty-seven patients with telomere length below the 10% of normal population, affected with three telomeropathies: dyskeratosis congenita (4), aplastic anemia (22) or pulmonary fibrosis (21) were analyzed. Eighteen of these patients presented known pathogenic or novel possibly pathogenic variants in the telomere-related genes TERT, TERC, RTEL1, CTC1 and ACD. In addition, the analyses of a panel of 188 genes related to haematological disorders indicated that a relevant proportion of the patients (up to 35%) presented rare variants in genes related to DNA repair or in genes coding for proteins involved in the resolution of complex DNA structures, that participate in telomere replication. Mutations in some of these genes are causative of several syndromes previously associated to telomere shortening.
Novel variants in telomere, DNA repair and replication genes are described that might indicate the contribution of variants in these genes to the development of telomeropathies. Patients carrying variants in telomere-related genes presented worse evolution after diagnosis than the rest of patients analyzed.
Multidisciplinary team (MDT) diagnosis of interstitial lung disease (ILD) has been proposed as a gold standard, but there are no formal recommendations for MDT process or composition and limited ...knowledge regarding prevalence in routine practice. We performed a systematic evaluation of ILD diagnostic practice across a range of healthcare settings around the world. Electronic questionnaires were distributed across all global regions
society and collaborators networks. Responses from 457 unique centres across 64 countries were included in the analysis. Of the 350 (76.6%) centres holding formal meetings, the majority held face-to-face MDT meetings (80%), for a minimum of 30 min (93%), and discussed diagnosis (96.9%) and patient management (94.9%) at the meetings. Compared with non-academic and academic non-ILD centres, ILD academic centres reported a higher ILD caseload, held more formal MDT meetings, and were more likely to include histopathology and rheumatology specialists in their diagnostic team. Of the centres holding MDT meetings, 5.5% routinely discussed all new cases at such meetings. An MDT approach to ILD diagnosis is consistently interpreted and widely implemented across a range of routine care settings around the world. This observation will inform future ILD diagnostic agreement studies and diagnostic pathway recommendations.
BackgroundNon-invasive biomarkers for the assessment of disease severity in idiopathic pulmonary fibrosis (IPF) are urgently needed. Calprotectin belongs to the S-100 proteins produced by ...neutrophils, which likely contribute to IPF pathogenesis. Calprotectin is a well-established biomarker in inflammatory bowel diseases. In this cross-sectional study, we aimed to establish the potential role of calprotectin as a biomarker in IPF. Specifically, we hypothesised that patients with IPF have higher serum calprotectin levels compared with healthy controls, and that calprotectin levels are associated with disease severity.MethodsBlood samples were obtained from healthy volunteers (n=26) and from two independent IPF cohorts (derivation cohort n=26, validation cohort n=66). Serum calprotectin levels were measured with a commercial kit adapted for that purpose and compared between healthy controls and patients with IPF. Clinical parameters, including forced vital capacity, diffusing capacity for carbon monoxide (DLCO) and the Composite Physiologic Index (CPI), were correlated with calprotectin serum levels.ResultsThe IPF derivation cohort showed increased serum calprotectin levels compared with healthy controls (2.47±1.67 vs 0.97±0.53 µg/mL, p<0.001). In addition, serum calprotectin levels correlated with DLCO% predicted (r=−0.53, p=0.007) and with CPI (r=0.66, p=0.007). These findings were confirmed in an independent IPF validation cohort.ConclusionSerum calprotectin levels are significantly increased in patients with IPF compared with healthy controls and correlate with DLCO and CPI. Calprotectin might be a potential new biomarker for disease severity in IPF.
Cross-analysis of clinical and pollution factors could help calculate the risk of fibrotic interstitial lung disease (ILD) development and progression. The intent of this study is to build a body of ...knowledge around early detection and diagnosis of lung disease, harnessing new data sets generated for other purposes. We cross-referenced exposure levels to particulate matter 2.5 (PM2.5) with telomere length of a cohort of 280 patients with fibrotic ILD to weigh impact and associations. There was no linear correlation between PM2.5 and telomere length in our data sets, as the value of the correlation coefficient was 0.08. This exploratory study offers additional insights into methodologies for investigating the development and prognosis of pulmonary fibrosis.
Pulmonary fibrosis (PF) and its most common form, idiopathic pulmonary fibrosis (IPF), are chronic, progressive diseases resulting in increasing loss of lung function and impaired quality of life and ...survival. The aim of this joint expert and patient statement was to highlight the most pressing common unmet needs of patients with PF/IPF, putting forward recommendations to improve the quality of life and health outcomes throughout the patient journey.
Two online surveys for patients and healthcare professionals (HCPs) were conducted by the European Idiopathic Pulmonary Fibrosis and Related Disorders Federation (EU-IPFF) in 14 European countries.
The surveys were answered by 286 patients and 69 HCPs, including physicians and nurses. Delays in diagnosis and timely access to interstitial lung disease specialists and pharmacological treatment have been identified as important gaps in care. Additionally, patients and HCPs reported that a greater focus on symptom-centred management, adequate information, trial information and increasing awareness of PF/IPF is required.
The surveys offer important insights into the current unmet needs of PF/IPF patients. Interventions at different points of the care pathway are needed to improve patient experience.
Introduction:
Fibrotic interstitial lung diseases (ILDs) are the first indication for lung transplantation (LT). Telomere dysfunction has been associated with poor post-transplant outcomes. The aim ...of the study was to evaluate the morbi-mortality and quality of life in fibrotic ILDs after lung transplant depending on telomere biology.
Methods:
Fibrotic ILD patients that underwent lung transplant were allocated to two arms; with or without telomere dysfunction at diagnosis based on the telomere length and telomerase related gene mutations revealed by whole-exome sequencing. Post-transplant evaluation included: (1) short and long-term mortality and complications and (2) quality of life.
Results:
Fifty-five percent of patients that underwent LT carried rare coding mutations in telomerase-related genes. Patients with telomere shortening more frequently needed extracorporeal circulation and presented a higher rate of early post-transplant hematological complications, longer stay in the intensive care unit (ICU), and a higher number of long-term hospital admissions. However, post-transplant 1-year survival was higher than 80% regardless of telomere dysfunction, with improvement in the quality of life and oxygen therapy withdrawal.
Conclusions:
Post-transplant morbidity is higher in patients with telomere dysfunction and differs according to elapsed time from transplantation. However, lung transplant improves survival and quality of life and the associated complications are manageable.
Idiopathic pulmonary fibrosis (IPF) prognosis is heterogeneous despite antifibrotic treatment. Cluster analysis has proven to be a useful tool in identifying interstitial lung disease phenotypes, ...which has yet to be performed in IPF. The aim of this study is to identify phenotypes of IPF with different prognoses and requirements.
Observational retrospective study including 136 IPF patients receiving antifibrotic treatment between 2012 and 2018. Six patients were excluded due to follow-up in other centres. Cluster analysis of 30 variables was performed using approximate singular value-based tensor decomposition method and comparative statistical analysis.
The cluster analysis identified three different groups of patients according to disease behaviour and clinical features, including mortality, lung transplant and progression-free survival time after 3-year follow-up. Cluster 1 (n=60) was significantly associated (p=0.02) with higher mortality. Diagnostic delay was the most relevant characteristic of this cluster, as 48% of patients had ≥2 years from first respiratory symptoms to antifibrotic treatment initiation. Cluster 2 (n=22) had the longest progression-free survival time and was correlated to subclinical patients evaluated in the context of incidental findings or familial screening. Cluster 3 (n=48) showed the highest percentage of disease progression without cluster 1 mortality, with metabolic syndrome and cardiovascular comorbidities as the main characteristics.
This cluster analysis of IPF patients suggests that diagnostic and treatment delay are the most significant factors associated with mortality, while IPF progression was more related to metabolic syndrome and cardiovascular comorbidities.
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