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Inoue Y, Kaner RJ, Guiot J, et al., 2020, Diagnostic and prognostic biomarkers for chronic fibrosing interstitial lung diseases with a progressive phenotype, Chest, Vol: 158, Pages: 646-659, ISSN: 0012-3692
Biomarkers have the potential to become central to the clinical evaluation and monitoring of patients with chronic fibrosing interstitial lung diseases with a progressive phenotype. Here we summarize the current understanding of putative serum, bronchoalveolar lavage fluid and genetic biomarkers in this setting, according to their hypothesized pathobiologic mechanisms: evidence of epithelial cell dysfunction (eg, Krebs von den Lungen-6 antigen), fibroblast proliferation and extracellular matrix production/turnover (eg, matrix metalloproteinase-1), or immune dysregulation (eg, CC chemokine ligand 18). While most of the available data comes from idiopathic pulmonary fibrosis, the prototypic progressive fibrosing interstitial lung disease, there are data available in the broader patient population of chronic fibrosing interstitial lung diseases. While a number of these biomarkers show promise, none have been validated. In this review article, we assess both the status of proposed biomarkers for chronic fibrosing lung diseases with a progressive phenotype in predicting disease risk or predisposition, diagnosis, prognosis and treatment response, and provide a direct comparison between idiopathic pulmonary fibrosis and other chronic fibrotic interstitial lung diseases. We also reflect on the current clinical usefulness and future direction of research for biomarkers in the setting of chronic fibrosing interstitial lung diseases with a progressive phenotype.
Hoffmann-Vold A-M, Allanore Y, Bendstrup E, et al., 2020, The need for a holistic approach for SSc-ILD - achievements and ambiguity in a devastating disease, Respiratory Research, Vol: 21, ISSN: 1465-9921
Systemic sclerosis (SSc) is a multi-organ autoimmune disease with complex interactions between immune-mediated inflammatory processes and vascular pathology leading to small vessel obliteration, promoting uncontrolled fibrosis of skin and internal organs. Interstitial lung disease (ILD) is a common but highly variable manifestation of SSc and is associated with high morbidity and mortality. Treatment approaches have focused on immunosuppressive therapies, which have shown some efficacy on lung function. Recently, a large phase 3 trial showed that treatment with nintedanib was associated with a reduction in lung function decline. None of the conducted randomized clinical trials have so far shown convincing efficacy on other outcome measures including quality of life determined by patient reported outcomes. Little evidence is available for non-pharmacological treatment and supportive care specifically for SSc-ILD patients, including pulmonary rehabilitation, supplemental oxygen, symptom relief and adequate information. Improved management of SSc-ILD patients based on a holistic approach is necessary to support patients in maintaining as much quality of life as possible throughout the disease course and to improve long-term outcomes.
Bonifazi M, Sverzellati N, Negri E, et al., 2020, Pleuroparenchymal fibroelastosis in systemic sclerosis: prevalence and prognostic impact, EUROPEAN RESPIRATORY JOURNAL, Vol: 56, ISSN: 0903-1936
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- Citations: 27
Maher T, Distler O, Azuma A, et al., 2020, Effects of Nintedanib in Patients With Systemic Sclerosis-associated ILD (SSc-ILD) and Differing FVC at Baseline: The SENSCIS Trial, 74th Annual Meeting of the Canadian-Rheumatology-Association, Publisher: J RHEUMATOL PUBL CO, Pages: 1085-1085, ISSN: 0315-162X
Highland K, Distler O, Kuwana M, et al., 2020, Efficacy and Safety of Nintedanib in Patients with Systemic Sclerosis-Associated Interstitial Lung Disease by Use of Mycophenolate at Baseline: Subgroup Analysis of the SENSCIS Trial, 74th Annual Meeting of the Canadian-Rheumatology-Association, Publisher: J RHEUMATOL PUBL CO, Pages: 1085-1086, ISSN: 0315-162X
Leavy O, Allen R, Oldham J, et al., 2020, Genome-Wide SNP-by-rs35705950 Interaction Analysis of Susceptibility to Idiopathic Pulmonary Fibrosis, 48th European Mathematical Genetics Meeting (EMGM), Publisher: KARGER, Pages: 215-215, ISSN: 0001-5652
Kraven L, Allen R, Taylor A, et al., 2020, A Genome-Wide Association Study of the Age-of-Onset of Idiopathic Pulmonary Fibrosis Using Time-to-Event Analysis Methods, 48th European Mathematical Genetics Meeting (EMGM), Publisher: KARGER, Pages: 214-214, ISSN: 0001-5652
Olson AL, Maher TM, Acciai V, et al., 2020, Healthcare Resources Utilization and Costs of Patients with Non-IPF Progressive Fibrosing Interstitial Lung Disease Based on Insurance Claims in the USA, ADVANCES IN THERAPY, Vol: 37, Pages: 3292-3298, ISSN: 0741-238X
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- Citations: 15
Maher TM, 2020, Chronic hypersensitivity pneumonitis; an enigmatic and frequently fatal disease, EUROPEAN RESPIRATORY REVIEW, Vol: 29, ISSN: 0905-9180
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- Citations: 3
Spagnolo P, Bonella F, Ryerson CJ, et al., 2020, Shedding light on developmental drugs for idiopathic pulmonary fibrosis, Expert Opinion on Investigational Drugs, Vol: 29, Pages: 797-808, ISSN: 1354-3784
INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is an age-related disease of unknown cause. The disease is characterized by relentless scarring of the lung parenchyma resulting in respiratory failure and death. Two antifibrotic drugs (pirfenidone and nintedanib) are approved for the treatment of IPF worldwide, but they do not offer a cure and are associated with tolerability issues. Owing to its high unmet medical need, IPF is an area of dynamic research activity. AREAS COVERED: There is a growing portfolio of novel therapies that target different pathways involved in the complex pathogenesis of IPF. In this review, we discuss the mechanisms of action and available data for compounds in the most advanced stages of clinical development. We searched PubMed for articles on this topic published from 1 January 2000, to 6 June 2020. EXPERT OPINION: The approval of pirfenidone and nintedanib has fueled IPF drug discovery and development. New drugs are likely to reach the clinic in the near future. However, numerous challenges remain; the lack of animal models that reproduce the complexity of human disease and the poor translation of preclinical and early-phase positive effects to late stage clinical trials must be tackled.
Kouranos V, Ward S, Kokosi MA, et al., 2020, Mixed ventilatory defects in pulmonary sarcoidosis: prevalence and clinical features., Chest, Vol: 158, Pages: 2007-2014, ISSN: 0012-3692
BACKGROUND: In cohort studies of pulmonary sarcoidosis, abnormal ventilatory patterns have generally been sub-divided into restrictive and obstructive defects. Mixed ventilatory defects have been largely overlooked in pulmonary sarcoidosis as total lung capacity (TLC) has seldom been taken into account in historical series. RESEARCH QUESTION: We evaluated the prevalence of mixed disease in pulmonary sarcoidosis and its clinical associations. STUDY DESIGN: and Methods: In patients with pulmonary sarcoidosis (n=1110), mixed defects were defined using ATS/ERS criteria. Clinical data, pulmonary function variables and vital status were abstracted from clinical records. Chest radiographs were evaluated independently by two experienced radiologists. RESULTS: The prevalence of a mixed ventilatory defect was 10.4% in the whole cohort, rising to 25.9% in patients with airflow obstruction. When compared to isolated airflow obstruction, mixed defects were associated with lower DLco levels (50.7 ± 16.3 versus 70.8 ± 18.1, p<0.0001), a higher prevalence of chest radiographic stage IV disease (63.5% versus 38.3%, p<0.0001), and higher mortality (HR 2.36; 95% CI 1.34, 4.15; p=0.003). These findings were reproduced in all patient sub-group analyses, including patients with a histologic diagnosis, a clinical diagnosis, incident disease and prevalent disease. INTERPRETATION: Mixed disease is present in approximately 25% of pulmonary sarcoidosis patients with airflow obstruction and is associated with lower DLco levels, a higher prevalence of stage IV disease and higher mortality than seen in a pure obstructive defect. These observations identify a distinct phenotype associated with a mixed ventilatory defect, justifying future studies of its clinical and pathogenetic significance.
Barnes H, Morisset J, Molyneaux P, et al., 2020, A systematically derived exposure assessment instrument for Chronic Hypersensitivity Pneumonitis, Chest, Vol: 157, Pages: 1506-1512, ISSN: 0012-3692
BACKGROUND: Chronic hypersensitivity pneumonitis (CHP) is an immune mediated interstitial lung disease, caused by inhalational exposure to environmental antigens, resulting in parenchymal fibrosis. By definition, a diagnosis of CHP assumes a history of antigen exposure, but only half of all patients eventually diagnosed with CHP will have a causative antigen identified. Individual clinician variation in eliciting a history of antigen exposure may affect the frequency and confidence of CHP diagnosis. METHODS: A list of potential causative exposures were derived from a systematic review of the literature. A Delphi method was applied to an international panel of ILD experts, to obtain consensus regarding technique for the elicitation of exposure to antigens relevant to a diagnosis of CHP. The consensus threshold was set at 80% agreement, and median ≤ 2, IQR = 0 on a five-point Likert scale (1: strongly agree, 2: tend to agree, 3: neither agree nor disagree, 4: disagree, 5: strongly disagree). RESULTS: In two rounds, 36/40 experts participated. Experts agreed on 18 exposure items to ask every patient with suspected CHP. Themes included CHP inducing exposures, features that contribute to an exposure's relevance, and quantification of a relevant exposure. Based on the results from the literature review and Delphi process, a CHP exposure assessment instrument was derived. Using cognitive interviews, the instrument was revised by ILD patients for readability and usability. CONCLUSIONS: This Delphi survey provides items that ILD experts agree are important to ask in all patients presenting with suspected CHP and provides basis for a systematically derived CHP exposure assessment instrument. Clinical utility of this exposure assessment instrument may be affected by different local prevalence patterns of exposures. Ongoing research is required to clinically validate these items and consider their impact in more geographically diverse settings.
Hoffmann-Vold A-M, Maher TM, Distler O, 2020, European consensus statements for interstitial lung disease in systemic sclerosis – Authors' reply, The Lancet Rheumatology, Vol: 2, Pages: e319-e320, ISSN: 2665-9913
Spagnolo P, Balestro E, Aliberti S, et al., 2020, Pulmonary fibrosis secondary to COVID-19: a call to arms?, The Lancet Respiratory Medicine, ISSN: 2213-2600
Kreuter M, Maher TM, 2020, Treatment of acute exacerbation of IPF - A call to arms., American Journal of Respiratory and Critical Care Medicine, Vol: 201, Pages: 1030-1031, ISSN: 1073-449X
Wells AU, Flaherty KR, Brown KK, et al., 2020, Nintedanib in patients with progressive fibrosing interstitial lung diseases-subgroup analyses by interstitial lung disease diagnosis in the INBUILD trial: a randomised, double-blind, placebo-controlled, parallel-group trial, LANCET RESPIRATORY MEDICINE, Vol: 8, Pages: 453-460, ISSN: 2213-2600
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- Citations: 257
Gayle A, Schoof N, Alves M, et al., 2020, Healthcare resource utilization among patients in England with systemic sclerosis-associated interstitial lung disease: a retrospective database analysis., Advances in Therapy, Vol: 37, Pages: 2460-2476, ISSN: 0741-238X
INTRODUCTION: Systemic sclerosis-associated interstitial lung disease (SSc-ILD) places a substantial burden on patients and healthcare systems. The objectives of this study were to describe clinical characteristics and assess healthcare resource utilization and costs of patients with SSc-ILD in England, compared with patients with non-pulmonary organ involvement related to SSc (SSc-OOI). METHODS: This population-based retrospective study used data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics. Data were extracted from medical records dated January 1, 2005 to March 31, 2016. Patients with SSc were identified and placed in subgroups based on organ involvement: SSc-ILD, SSc-OOI, and both (SSc-ILD-OOI). Patients with SSc-ILD-OOI were included in both the SSc-ILD and SSc-OOI subgroups. All-cause healthcare costs, excluding medication costs, were calculated to 2016 British pounds sterling (£). RESULTS: This study included 675 patients with SSc: 174 (26%) had neither ILD nor other organ involvement (OOI); 127 (19%) had SSc-ILD; 477 (71%) had SSc-OOI; 103 (15%) had SSc-ILD-OOI. Age-weighted median [interquartile range (IQR)] annual healthcare costs per patient were: £1496 (£664-£2817) in SSc only; £6375 (£3451-£15,041) in SSc-ILD; £4084 (£1454-£10,105) in SSc-OOI; £6632 (£4023-£17,009) in SSc-ILD-OOI. In multivariate analysis, older age at diagnosis, diagnosis of anemia, and number of comorbid diseases were associated with higher yearly healthcare costs. CONCLUSION: The annual healthcare cost for patients with SSc-ILD is substantial, and higher than that of patients with SSc-OOI or SSc only. These results quantify the economic burden of SSc-ILD in a real-world setting, and highlight the need for treatment of this disease.
Invernizzi R, Barnett J, Rawal B, et al., 2020, Bacterial burden in the lower airways predicts disease progression in idiopathic pulmonary fibrosis and is independent of radiological disease extent, European Respiratory Journal, Vol: 55, Pages: 1-9, ISSN: 0903-1936
Increasing bacterial burden in the lower airways of patients with idiopathic pulmonary fibrosis confers an increased risk of disease progression and mortality. However, it remains unclear whether this increased bacterial burden directly influences progression of fibrosis or simply reflects the magnitude of the underlying disease extent or severity.We prospectively recruited 193 patients who underwent bronchoscopy and received a multidisciplinary diagnosis of idiopathic pulmonary fibrosis. Quantification of the total bacterial burden in bronchoalveolar lavage fluid was performed by 16S rRNA gene qPCR. Imaging was independently evaluated by two readers assigning quantitative scores for extent, severity and topography of radiographic changes and relationship of these features with bacterial burden was assessed.Increased bacterial burden significantly associated with disease progression (hazard ratio 2.1; 95% confidence interval 1.287–3.474; p=0.0028). Multivariate stepwise regression demonstrated no relationship between bacterial burden and radiological features or extent of disease. When specifically considering patients with definite or probable usual interstitial pneumonia there was no difference in bacterial burden between these two groups. Despite a postulated association between pleuroparenchymal fibroelastosis and clinical infection, there was no relationship between either the presence or extent of pleuroparenchymal fibroelastosis and bacterial burden.We demonstrate that bacterial burden in the lower airways is not simply secondary to the extent of the underlying architectural destruction of the lung parenchyma seen in idiopathic pulmonary fibrosis. The independent nature of this association supports a relationship with the underlying pathogenic mechanisms and highlights the urgent need for functional studies.
Stock CJW, De Lauretis A, Visca D, et al., 2020, Defining genetic risk factors for scleroderma-associated interstitial lung disease : IRF5 and STAT4 gene variants are associated with scleroderma while STAT4 is protective against scleroderma-associated interstitial lung disease, Clinical Rheumatology, Vol: 39, Pages: 1173-1179, ISSN: 0770-3198
Although several genetic associations with scleroderma (SSc) are defined, very little is known on genetic susceptibility to SSc-associated interstitial lung disease (SSc-ILD). A number of common polymorphisms have been associated with SSc-ILD, but most have not been replicated in separate populations. Four SNPs in IRF5, and one in each of STAT4, CD226 and IRAK1, selected as having been previously the most consistently associated with SSc-ILD, were genotyped in 612 SSc patients, of European descent, of whom 394 had ILD. The control population (n = 503) comprised individuals of European descent from the 1000 Genomes Project. After Bonferroni correction, two of the IRF5 SNPs, rs2004640 (OR (95% CI)1.30 (1.10-1.54), pcorr = 0.015) and rs10488631 (OR 1.48 (1.14-1.92), pcorr = 0.022), and the STAT4 SNP rs7574865 (OR 1.43 (1.18-1.73), pcorr = 0.0015) were significantly associated with SSc compared with controls. However, none of the SNPs were significantly different between patients with SSc-ILD and controls. Two SNPs in IRF5, rs10488631 (OR 1.72 (1.24-2.39), pcorr = 0.0098), and rs2004640 (OR 1.39 (1.11-1.75), pcorr = 0.03), showed a significant difference in allele frequency between controls and patients without ILD, as did STAT4 rs7574865 (OR 1.86 (1.45-2.38), pcorr = 6.6 × 10-6). A significant difference between SSc with and without ILD was only observed for STAT4 rs7574865, being less frequent in patients with ILD (OR 0.66 (0.51-0.85), pcorr = 0.0084). In conclusion, IRF5 rs2004640 and rs10488631, and STAT4 rs7574865 were significantly associated with SSc as a whole. Only STAT4 rs7574865 showed a significant difference in allele frequency in SSc-ILD, with the T allele being protective against ILD.Key points• We confirm the associations of the IRF5 SNPs rs2004640 and rs10488631, and the STAT4 SNP rs7574865, with SSc as a whole.&b
Kreuter M, Polke M, Walsh SLF, et al., 2020, Acute exacerbation of idiopathic pulmonary fibrosis: international survey and call for harmonisation, EUROPEAN RESPIRATORY JOURNAL, Vol: 55, ISSN: 0903-1936
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- Citations: 41
Lukey PT, Coello C, Gunn R, et al., 2020, Clinical quantification of the integrin αvβ6 by [18F]FB-A20FMDV2 positron emission tomography in healthy and fibrotic human lung (PETAL Study), European Journal of Nuclear Medicine and Molecular Imaging, Vol: 47, Pages: 967-979, ISSN: 0340-6997
PURPOSE: The RGD-integrin, αvβ6, plays a role in the pathogenesis of pulmonary fibrosis through activation of transforming growth factor beta (TGFβ). This study sought to quantify expression of αvβ6 in the lungs of healthy humans and subjects with pulmonary fibrosis using the αvβ6-selective [18F]FB-A20FMDV2 PET ligand. METHODS: [18F]FB-A20FMDV2 PET/CT scans were performed in healthy subjects and those with fibrotic lung disease. Standard uptake values (SUV) and volume of distribution (VT) were used to quantify αvβ6 expression. In subjects with fibrotic lung disease, qualitative assessment of the relationship between αvβ6 expression and the distribution of fibrosis on high resolution computed tomography was conducted. RESULTS: A total of 15 participants (6 healthy, 7 with idiopathic pulmonary fibrosis (IPF) and 2 with connective tissue disease (CTD) associated PF) were enrolled. VT and SUV of [18F]FB-A20FMDV2 were increased in the lungs of subjects with pulmonary fibrosis (PF) compared with healthy subjects. Geometric mean VT (95% CI) was 0.88 (0.60, 1.29) mL/cm3 for healthy subjects, and 1.40 (1.22, 1.61) mL/cm3 for subjects with IPF; and SUV was 0.54 (0.36, 0.81) g/mL for healthy subjects and 1.03 (0.86, 1.22) g/mL for subjects with IPF. The IPF/healthy VT ratio (geometric mean, (95% CI of ratio)) was 1.59 (1.09, 2.32) (probability ratio > 1 = 0.988)) and the SUV ratio was 1.91 (1.27, 2.87) (probability ratio > 1 = 0.996). Increased uptake of [18F]FB-A20FMDV2 in PF was predominantly confined to fibrotic areas. [18F]FB-A20FMDV2 measurements were reproducible at an interval of 2 weeks. [18F]FB-A20FMDV2 was safe and well tolerated. CONCLUSIONS: Lung uptake of [18F]FB-A20FMDV2, a measure of expression of the integrin αvβ6, was markedly increased in subjects with PF compared with healthy subjects.
Maher TM, Simpson JK, Porter JC, et al., 2020, A positron emission tomography imaging study to confirm target engagement in the lungs of patients with idiopathic pulmonary fibrosis following a single dose of a novel inhaled αvβ6 integrin inhibitor, Respiratory Research, Vol: 21, ISSN: 1465-9921
BackgroundIdiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease with poor prognosis and a significant unmet medical need. This study evaluated the safety, pharmacokinetics (PK) and target engagement in the lungs, of GSK3008348, a novel inhaled alpha-v beta-6 (αvβ6) integrin inhibitor, in participants with IPF.MethodsThis was a phase 1b, randomised, double-blind (sponsor unblind) study, conducted in the UK (two clinical sites, one imaging unit) between June 2017 and July 2018 (NCT03069989). Participants with a definite or probable diagnosis of IPF received a single nebulised dose of 1000 mcg GSK3008348 or placebo (ratio 5:2) in two dosing periods. In period 1, safety and PK assessments were performed up to 24 h post-dose; in period 2, after a 7-day to 28-day washout, participants underwent a total of three positron emission tomography (PET) scans: baseline, Day 1 (~ 30 min post-dosing) and Day 2 (~ 24 h post-dosing), using a radiolabelled αvβ6-specific ligand, [18F]FB-A20FMDV2. The primary endpoint was whole lung volume of distribution (VT), not corrected for air volume, at ~ 30 min post-dose compared with pre-dose. The study success criterion, determined using Bayesian analysis, was a posterior probability (true % reduction in VT > 0%) of ≥80%.ResultsEight participants with IPF were enrolled and seven completed the study. Adjusted posterior median reduction in uncorrected VT at ~ 30 min after GSK3008348 inhalation was 20% (95% CrI: − 9 to 42%). The posterior probability that the true % reduction in VT > 0% was 93%. GSK3008348 was well tolerated with no reports of serious adverse events or clinically significant abnormalities that were attributable to study treatment. PK was successfully characterised showing rapid absorption followed by a multiphasic elimination.ConclusionsThis study demonstrated engagement of th
Distler O, Assassi S, Cottin V, et al., 2020, Predictors of progression in systemic sclerosis patients with interstitial lung disease, European Respiratory Journal, Vol: 55, ISSN: 0903-1936
Systemic sclerosis (SSc) is a systemic autoimmune disease affecting multiple organ systems, including the lungs. Interstitial lung disease (ILD) is the leading cause of death in SSc.There are no valid biomarkers to predict the occurrence of SSc-ILD, although auto-antibodies against anti-topoisomerase I and several inflammatory markers are candidate biomarkers that need further evaluation. Chest auscultation, presence of shortness of breath and pulmonary function testing are important diagnostic tools, but lack sensitivity to detect early ILD. Baseline screening with high-resolution computed tomography (HRCT) is therefore necessary to confirm an SSc-ILD diagnosis. Once diagnosed with SSc-ILD, patients' clinical courses are variable and difficult to predict, though certain patient characteristics and biomarkers are associated with disease progression. It is important to monitor patients with SSc-ILD for signs of disease progression, though there is no consensus about which diagnostic tools to use or how often monitoring should occur. In this article, we review methods used to define and predict disease progression in SSc-ILD.There is no valid definition of SSc-ILD disease progression, but we suggest that either a decline in forced vital capacity (FVC) from baseline of ≥10%, or an FVC decline of 5-9% in association with a decline in diffusing capacity of carbon monoxide of ≥15% represents progression. An increase in the radiographic extent of ILD on HRCT imaging would also signify progression. A time period of 1-2 years is generally used for this definition, but a decline over a longer time period may also reflect clinically relevant disease progression.
Allen RJ, Guillen-Guio B, Oldham JM, et al., 2020, Genome-wide association study of susceptibility to idiopathic pulmonary fibrosis, American Journal of Respiratory and Critical Care Medicine, Vol: 201, Pages: 564-574, ISSN: 1073-449X
Rationale: Idiopathic pulmonary fibrosis (IPF) is a complex lung disease characterised by scarring of the lung that is believed to result from an atypical response to injury of the epithelium. Genome-wide association studies have reported signals of association implicating multiple pathways including host defence, telomere maintenance, signalling and cell-cell adhesion. Objectives: To improve our understanding of factors that increase IPF susceptibility by identifying previously unreported genetic associations. Methods and measurements: We conducted genome-wide analyses across three independent studies and meta-analysed these results to generate the largest genome-wide association study of IPF to date (2,668 IPF cases and 8,591 controls). We performed replication in two independent studies (1,456 IPF cases and 11,874 controls) and functional analyses (including statistical fine-mapping, investigations into gene expression and testing for enrichment of IPF susceptibility signals in regulatory regions) to determine putatively causal genes. Polygenic risk scores were used to assess the collective effect of variants not reported as associated with IPF. Main results: We identified and replicated three new genome-wide significant (P<5×10−8) signals of association with IPF susceptibility (associated with altered gene expression of KIF15, MAD1L1 and DEPTOR) and confirmed associations at 11 previously reported loci. Polygenic risk score analyses showed that the combined effect of many thousands of as-yet unreported IPF susceptibility variants contribute to IPF susceptibility. Conclusions: The observation that decreased DEPTOR expression associates with increased susceptibility to IPF, supports recent studies demonstrating the importance of mTOR signalling in lung fibrosis. New signals of association implicating KIF15 and MAD1L1 suggest a possible role of mitotic spindle-assembly genes in IPF susceptibility.
Prasse A, Maher TM, Distler O, et al., 2020, Effects of nintedanib in patients with systemic sclerosis-associated ILD (SSc-ILD) and differing FVC at baseline: the SENSCIS Trial, Publisher: GEORG THIEME VERLAG KG, Pages: S57-S57, ISSN: 0934-8387
Kreuter M, Highland KB, Kuwana M, et al., 2020, Dose adjustments in the SENSCIS Trial of nintedanib in patients with systemic sclerosis-associated ILD (SSc-ILD), Publisher: GEORG THIEME VERLAG KG, Pages: S55-S56, ISSN: 0934-8387
Wiewrodt R, Raghu G, Distler O, et al., 2020, Effects of nintedanib in patients with systemic sclerosis-associated ILD (SSc-ILD) and differing extents of lung fibrosis: the SENSCIS trial, Publisher: GEORG THIEME VERLAG KG, Pages: S58-S59, ISSN: 0934-8387
Kreuter M, Highland KB, Azuma A, et al., 2020, Changes in FVC in the SENSCIS Trial of nintedanib in patients with systemic sclerosis-associated ILD (SSc-ILD), Publisher: GEORG THIEME VERLAG KG, Pages: S56-S57, ISSN: 0934-8387
Prasse A, Distler O, Highland KB, et al., 2020, Nintedanib in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD): the SENSCIS trial, Publisher: GEORG THIEME VERLAG KG, Pages: S57-S58, ISSN: 0934-8387
Pfeifer M, Maher TM, Stowasser S, et al., 2020, Effect of nintedanib on biomarkers of extracellular matrix (ECM) turnover and FVC decline in patients with IPF: results from the INMARK study, Publisher: GEORG THIEME VERLAG KG, Pages: S103-S104, ISSN: 0934-8387
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