scholarly journals Telomere length and genetic variant associations with interstitial lung disease progression and survival

2019 ◽  
Vol 53 (4) ◽  
pp. 1801641 ◽  
Author(s):  
Chad A. Newton ◽  
Justin M. Oldham ◽  
Brett Ley ◽  
Vikram Anand ◽  
Ayodeji Adegunsoye ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Function ◽  
Lung Disease ◽  
Disease Progression ◽  
Telomere Length ◽  
Hazard Ratio ◽  
Lung Function Decline ◽  
Free Survival ◽  
Genomic Markers ◽  
Observational Cohort

Leukocyte telomere length (LTL), MUC5B rs35705950 and TOLLIP rs5743890 have been associated with idiopathic pulmonary fibrosis (IPF).In this observational cohort study, we assessed the associations between these genomic markers and outcomes of survival and rate of disease progression in patients with interstitial pneumonia with autoimmune features (IPAF, n=250) and connective tissue disease-associated interstitial lung disease (CTD-ILD, n=248). IPF (n=499) was used as a comparator.The LTL of IPAF and CTD-ILD patients (mean age-adjusted log-transformed T/S of −0.05±0.29 and −0.04±0.25, respectively) is longer than that of IPF patients (−0.17±0.32). For IPAF patients, LTL <10th percentile is associated with faster lung function decline compared to LTL ≥10th percentile (−6.43% per year versus −0.86% per year; p<0.0001) and worse transplant-free survival (hazard ratio 2.97, 95% CI 1.70–5.20; p=0.00014). The MUC5B rs35705950 minor allele frequency (MAF) is greater for IPAF patients (23.2, 95% CI 18.8–28.2; p<0.0001) than controls and is associated with worse transplant-free IPAF survival (hazard ratio 1.92, 95% CI 1.18–3.13; p=0.0091). Rheumatoid arthritis (RA)-associated ILD (RA-ILD) has a shorter LTL than non-RA CTD-ILD (−0.14±0.27 versus −0.01±0.23; p=0.00055) and higher MUC5B MAF (34.6, 95% CI 24.4–46.3 versus 14.1, 95% CI 9.8–20.0; p=0.00025). Neither LTL nor MUC5B are associated with transplant-free CTD-ILD survival.LTL and MUC5B MAF have different associations with lung function progression and survival for IPAF and CTD-ILD.

scholarly journals A cluster-based analysis evaluating the impact of comorbidities in fibrotic interstitial lung disease

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Alyson W. Wong ◽  
Tae Yoon Lee ◽  
Kerri A. Johannson ◽  
Deborah Assayag ◽  
Julie Morisset ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Function ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Disease Progression ◽  
Rapid Decline ◽  
Agglomerative Clustering ◽  
Lung Function Decline ◽  
Obstructive Sleep ◽  
The Impact

Abstract Background Comorbidities are frequent and have been associated with poor quality of life, increased hospitalizations, and mortality in patients with interstitial lung disease (ILD). However, it is unclear how comorbidities lead to these negative outcomes and whether they could influence ILD disease progression. The goal of this study was to identify clusters of patients based on similar comorbidity profiles and to determine whether these clusters were associated with rate of lung function decline and/or mortality. Methods Patients with a major fibrotic ILD (idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis, connective tissue disease-associated ILD, and unclassifiable ILD) from the CAnadian REgistry for Pulmonary Fibrosis (CARE-PF) were included. Hierarchical agglomerative clustering of comorbidities, age, sex, and smoking pack-years was conducted for each ILD subtype to identify combinations of these features that frequently occurred together in patients. The association between clusters and change in lung function over time was determined using linear mixed effects modeling, with adjustment for age, sex, and smoking pack-years. Kaplan Meier curves were used to assess differences in survival between the clusters. Results Discrete clusters were identified within each fibrotic ILD. In IPF, males with obstructive sleep apnea (OSA) had more rapid decline in FVC %-predicted (− 11.9% per year [95% CI − 15.3, − 8.5]) compared to females without any comorbidities (− 8.1% per year [95% CI − 13.6, − 2.7]; p = 0.03). Females without comorbidities also had significantly longer survival compared to all other IPF clusters. There were no significant differences in rate of lung function decline or survival between clusters in the other fibrotic ILD subtypes. Conclusions The combination of male sex and OSA may portend worse outcomes in IPF. Further research is required to elucidate the interplay between sex and comorbidities in ILD, as well as the role of OSA in ILD disease progression.

scholarly journals Impact of Lung Function Decline on Time to Hospitalisation Events in Systemic Sclerosis-associated Interstitial Lung Disease (SSc-ILD): a Joint Model Analysis

2021 ◽  
Author(s):  
Michael Kreuter ◽  
Francesco Del Galdo ◽  
Corinna Miede ◽  
Dinesh Khanna ◽  
Wim A. Wuyts ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Function ◽  
Lung Disease ◽  
Fold Increase ◽  
Phase Iii ◽  
Lung Function Decline ◽  
Related Hospitalisation ◽  
The Relationship ◽  
Increase In Risk

Abstract Background: Interstitial lung disease (ILD) is a common organ manifestation in systemic sclerosis (SSc) and is the leading cause of death in patients with SSc. A decline in forced vital capacity (FVC) is an indicator of ILD progression and is associated with mortality in patients with SSc-associated ILD (SSc-ILD). However, the relationship between FVC decline and hospitalisation events in patients with SSc-ILD is largely unknown. The objective of this post-hoc analysis was to investigate the relationship between FVC decline and clinically important hospitalisation endpoints.Methods: We used data from SENSCIS®, a Phase III trial investigating the efficacy and safety of nintedanib in patients with SSc-ILD. Joint models for longitudinal and time-to-event data were used to assess the association between rate of decline in FVC% predicted and hospitalisation-related endpoints (including time to first all-cause hospitalisation or death; time to first SSc-related hospitalisation or death; and time to first admission to an emergency room [ER] or admission to hospital followed by admission to intensive care unit [ICU] or death) during the treatment period, over 52 weeks in patients with SSc-ILD.Results: There was a statistically significant association between FVC decline and the risk of all-cause (n=78) and SSc-related (n=42) hospitalisations or death (both P<0.0001). A decrease of 3% in FVC corresponded to a 1.43-fold increase in risk of all-cause hospitalisation or death (95% confidence interval [CI] 1.24, 1.65) and a 1.48-fold increase in risk of SSc-related hospitalisation or death (95% CI 1.23, 1.77). No statistically significant association was observed between FVC decline and admission to ER or to hospital followed by admission to ICU or death (n=75; P=0.15). The estimated slope difference for nintedanib versus placebo in the longitudinal sub-model was consistent with the primary analysis in SENSCIS®.Conclusions: The association of lung function decline with an increased risk of hospitalisation suggests that slowing FVC decline in patients with SSc-ILD may prevent hospitalisations. Our findings also provide evidence that FVC decline may serve as a surrogate endpoint for clinically relevant hospitalisation-associated endpoints.Trial registration: Clinialtrials.gov, NCT02597933. Registered 8 October 2015, https://clinicaltrials.gov/ct2/show/study/NCT02597933.

scholarly journals Circulating fibrocytes are not disease-specific prognosticators in idiopathic pulmonary fibrosis

2021 ◽  
pp. 2100172
Author(s):  
Iain D. Stewart ◽  
Henry Nanji ◽  
Grazziela Figueredo ◽  
William A. Fahy ◽  
Toby M. Maher ◽  
...  
Keyword(s):  
Lung Function ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Disease Progression ◽  
Hazard Ratio ◽  
Mortality Data ◽  
Prospective Clinical Study ◽  
Lung Function Decline ◽  
Mixed Effect ◽  
Circulating Fibrocytes

ObjectiveCirculating fibrocytes are elevated in idiopathic pulmonary fibrosis, but the relationship between fibrocyte level with lung function decline and outcomes is lacking replication in prospective clinical study. We aim to validate the utility of circulating fibrocyte levels as a prognostic biomarker in idiopathic pulmonary fibrosis.MethodsWe tested associations between circulating fibrocyte levels, mortality, disease progression and longitudinal lung function in a well-defined prospective observational study of pulmonary fibrosis (PROFILE; NCT01134822). A subset of recruited participants had blood samples processed for fibrocyte measurement, with flow cytometry based on CD45 and collagen-I gating. Associations were tested using univariable and multivariable generalised linear models. Mortality data were subsequently combined with an independent cohort in a mixed-effect multilevel analysis.ResultsIn 102 participants with idiopathic pulmonary fibrosis, a previously defined mortality risk threshold of 5% circulating fibrocytes was not reproducible. An empirically defined cutpoint of 2.22% was associated with a greater risk of overall mortality in adjusted analysis (Hazard Ratio 2.24 95% CI 1.06-4.72). A 2.5 fold greater risk of mortality was supported in a pooled analysis with a historic cohort for a larger sample of 162 participants with idiopathic pulmonary fibrosis (Hazard Ratio 2.49 95% CI 2.41-2.56). We found no association of fibrocytes with lung function or disease progression.ConclusionsIn a large sample of circulating fibrocytes from people with idiopathic pulmonary fibrosis, levels of 2.22% or above were associated with greater mortality, but not with disease related decline in lung function.

scholarly journals Functional Progression in Patients with Interstitial Lung Disease Resulted Positive to Antisynthetase Antibodies: A Multicenter, Retrospective Analysis

2020 ◽  
Vol 9 (9) ◽  
pp. 3033
Author(s):  
Giulia Dei ◽  
Paola Rebora ◽  
Martina Catalano ◽  
Marco Sebastiani ◽  
Paola Faverio ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Function ◽  
Lung Disease ◽  
Demographic Data ◽  
Real Life ◽  
Lung Function Decline ◽  
Main Determinant ◽  
Life Study ◽  
Antisynthetase Antibodies

Antisynthetase syndrome (ASSD) is a rare autoimmune disease characterized by serologic positivity for antisynthetase antibodies. Anti-Jo1 is the most frequent, followed by anti PL-7, anti PL-12, anti EJ, and anti OJ antibodies. The lung is the most frequently affected organ, usually manifesting with an interstitial lung disease (ILD), which is considered the main determinant of prognosis. Some evidences suggest that non-anti-Jo-1 antibodies may be associated with more severe lung involvement and possibly with poorer outcomes, while other authors do not highlight differences between anti-Jo1 and other antisynthetase antibodies. In a multicenter, retrospective, “real life” study, we compared lung function tests (LFTs) progression in patients with ILD associated with anti-Jo1 and non-anti-Jo1 anti-synthetase antibodies to assess differences in lung function decline between these two groups. Therefore, we analyzed a population of 57 patients (56% anti-Jo1 positive), referred to the outpatient Clinic of four referral Centers in Italy (Modena, Monza, Siena, and Trieste) from 2008 to 2019, with a median follow-up of 36 months. At diagnosis, patients showed a mild ventilatory impairment and experienced an improvement of respiratory function during treatment. We did not observe statistically significant differences in LFTs at baseline or during follow-up between the two groups. Moreover, there were no differences in demographic data, respiratory symptoms onset (acute vs. chronic), extrapulmonary involvement, treatment (steroid and/or another immunosuppressant), or oxygen supplementation. Our study highlights the absence of differences in pulmonary functional progression between patients positive to anti-Jo-1 vs. non anti-Jo-1 antibodies, suggesting that the type of autoantibody detected in the framework of ASSD does not affect lung function decline.

scholarly journals Natural history of systemic sclerosis–related interstitial lung disease: How to identify a progressive fibrosing phenotype

2019 ◽  
Vol 5 (2_suppl) ◽  
pp. 31-40 ◽  
Author(s):  
Elizabeth R Volkmann
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Function ◽  
Natural History ◽  
Lung Disease ◽  
Disease Progression ◽  
Rapid Progression ◽  
History Of ◽  
Rate Of Decline ◽  
Patients Experience

The natural history of interstitial lung disease in patients with systemic sclerosis is highly variable. Historical observational studies have demonstrated that the greatest decline in lung function in systemic sclerosis occurs early in the course of the disease; however, not all patients experience a decline in lung function even in the absence of treatment. Furthermore, among patients who do experience a decline in lung function, the rate of decline can be either rapid or slow. The most common clinical phenotypes of systemic sclerosis–related interstitial lung disease are, therefore, as follows: (1) rapid progressors, (2) gradual progressors, (3) stabilizers, and (4) improvers. This review summarizes the features of systemic sclerosis–related interstitial lung disease patients who are more likely to experience rapid progression of interstitial lung disease, as well as those who are more likely not to experience interstitial lung disease progression. Understanding the clinical, biological, and radiographic factors that consistently predict interstitial lung disease–related outcomes in systemic sclerosis is central to our ability to recognize those patients who are at heightened risk for interstitial lung disease progression. With new options available for treating patients with systemic sclerosis–related interstitial lung disease, it is more important than ever to accurately identify patients who may derive the most benefit from aggressive systemic sclerosis–related interstitial lung disease therapy. Early therapeutic intervention in patients with this progressive fibrosing phenotype may ultimately improve morbidity and mortality outcomes in patients with systemic sclerosis–related interstitial lung disease.

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