Publications
772 results found
Myall KJ, West AG, Martinovic JL, et al., 2023, Nocturnal hypoxemia associates with symptom progression and mortality in patients with progressive fibrotic interstitial lung disease., Chest, Pages: 1-34, ISSN: 0012-3692
BACKGROUND: Obstructive sleep apnea (OSA) and nocturnal hypoxemia (NH) are common in patients with fibrotic interstitial lung disease (F-ILD), but their relationship with disease outcomes remains unclear. RESEARCH QUESTIONS: What is the relationship between NH and OSA and clinical outcomes in patients with F-ILD? STUDY DESIGN AND METHODS: Prospective observational cohort study of patients with F-ILD and without daytime hypoxemia. Subjects underwent home sleep study at baseline and were followed up for at least one year or until death. NH was defined as ≥ 10% of sleep with SpO2 <90%. OSA was defined as an apnea-hypopnea index of ≥ 15/hour. RESULTS: Among 102 (male 74.5%; age 73.0 ± 8.7 years; FVC 2.74 ± 0.78L; 91.1% idiopathic pulmonary fibrosis) participants, 20 (19.6%) demonstrated prolonged nocturnal hypoxemia (NH), and 32 (31.4%) had obstructive sleep apnea (OSA). There were no significant differences between those with and without NH or OSA at baseline. Despite this, nocturnal hypoxemia was associated with a more rapid decline in both quality of life as measured by the King's Brief Interstitial Lung Disease questionnaire (change -11.3 ± 5.3 points in the NH group vs -6.7 ± 6.5 in those without NH, p=0.005) and higher all-cause mortality at one year (HR 8.21; 95% CI 2.40-28.1, p<0.001). No statistically significant difference was seen between the groups in annualised change in measures of pulmonary function testing. INTERPRETATION: Prolonged NH but not OSA is associated with worsening disease-related quality of life and increased mortality in patients with F-ILD.
Maher TM, Ford P, Brown KK, et al., 2023, Ziritaxestat, a novel autotaxin inhibitor, and lung function in idiopathic pulmonary fibrosis, JAMA: Journal of the American Medical Association, Vol: 329, Pages: 1567-1578, ISSN: 0098-7484
Importance There is a major need for effective, well-tolerated treatments for idiopathic pulmonary fibrosis (IPF).Objective To assess the efficacy and safety of the autotaxin inhibitor ziritaxestat in patients with IPF.Design, Setting, and Participants The 2 identically designed, phase 3, randomized clinical trials, ISABELA 1 and ISABELA 2, were conducted in Africa, Asia-Pacific region, Europe, Latin America, the Middle East, and North America (26 countries). A total of 1306 patients with IPF were randomized (525 patients at 106 sites in ISABELA 1 and 781 patients at 121 sites in ISABELA 2). Enrollment began in November 2018 in both trials and follow-up was completed early due to study termination on April 12, 2021, for ISABELA 1 and on March 30, 2021, for ISABELA 2.Interventions Patients were randomized 1:1:1 to receive 600 mg of oral ziritaxestat, 200 mg of ziritaxestat, or placebo once daily in addition to local standard of care (pirfenidone, nintedanib, or neither) for at least 52 weeks.Main Outcomes and Measures The primary outcome was the annual rate of decline for forced vital capacity (FVC) at week 52. The key secondary outcomes were disease progression, time to first respiratory-related hospitalization, and change from baseline in St George’s Respiratory Questionnaire total score (range, 0 to 100; higher scores indicate poorer health-related quality of life).Results At the time of study termination, 525 patients were randomized in ISABELA 1 and 781 patients in ISABELA 2 (mean age: 70.0 [SD, 7.2] years in ISABELA 1 and 69.8 [SD, 7.1] years in ISABELA 2; male: 82.4% and 81.2%, respectively). The trials were terminated early after an independent data and safety monitoring committee concluded that the benefit to risk profile of ziritaxestat no longer supported their continuation. Ziritaxestat did not improve the annual rate of FVC decline vs placebo in either study. In ISABELA 1, the least-squares mean annual rate of FVC decline was –124.6 mL
Roofeh D, Brown KK, Kazerooni EA, et al., 2023, Systemic sclerosis associated interstitial lung disease: a conceptual framework for subclinical, clinical and progressive disease, RHEUMATOLOGY, Vol: 62, Pages: 1877-1886, ISSN: 1462-0324
Jones S, Flewett M, Flewett R, et al., 2023, Clinical trial simulations in pulmonary fibrosis: patient-focused insights and adaptations, ERJ OPEN RESEARCH, Vol: 9
Huang Y, Oldham J, Ma S, et al., 2023, Machine Learning of Plasma Proteomics for Differential Diagnosis of Interstitial Lung Disease, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Maher TM, Brown KK, Cunningham S, et al., 2023, Estimating the Effect of Nintedanib on Forced Vital Capacity in Children and Adolescents With Fibrosing Interstitial Lung Disease: Extrapolation Using a Bayesian Borrowing Approach, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Kirov KR, Thillai M, Ruggiero A, et al., 2023, Automated Image Analysis of Vascular and Fibrotic Lung Volumes Shows Association With IPF Mortality, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Maher TM, Avram C, Bortey E, et al., 2023, Efficacy of Oral Nalbuphine Extended Release in Patients With Idiopathic-Pulmonary-Fibrosis-related Chronic Cough: A Phase 2 Study, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Kulkarni T, Santiaguel J, Aul R, et al., 2023, Safety and Tolerability of LYT-100 (Deupirfenidone) in Post-Acute Sequelae of SARS-CoV-2 (PASC) "Long COVID" Patients Presenting With Respiratory Complications, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Corte TJ, Cottin V, Glassberg MK, et al., 2023, BMS-986278, an Oral Lysophosphatidic Acid Receptor 1 (LPA1) Antagonist, for Patients With Idiopathic Pulmonary Fibrosis: Results From a Phase 2 Randomized Trial, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Maher TM, Avram C, Bortey E, et al., 2023, The Effect of Oral Nalbuphine Extended Release on Patient-reported Outcome Measures in Patients With Idiopathic-Pulmonary-Fibrosis-related Chronic Cough, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Batta R, Maher TM, Ganslandt C, et al., 2023, An Updated Interim Analysis of the Air Trial; an Open-label, Single-arm, 36-week, Phase 2 Trial of an Angiotensin Type 2 Receptor Agonist, C21, in Individuals With IPF, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Kirov KR, Thillai M, Ruggiero A, et al., 2023, The Addition of Imaging Improves Mortality Prediction in IPF, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Noth I, Maher TM, Bonella F, et al., 2023, Circulating Biomarkers in Patients With Progressive Pulmonary Fibrosis: Data From the INBUILD Trial, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Maher TM, Jenkins RG, Bonella F, et al., 2023, Effects of Nintedanib on Circulating Biomarkers in Patients With Progressive Pulmonary Fibrosis: Subgroup Analyses of the INBUILD Trial, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Myall KJ, West A, Martinovic JL, et al., 2023, Nocturnal Hypoxemia Is Associated With Increased Risk of Disease Progression and All-cause Mortality at One and Two Year Follow Up in Patients With Fibrotic Interstitial Lung Disease, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Denton CP, Goh NS, Humphries SM, et al., 2023, Extent of fibrosis and lung function decline in patients with systemic sclerosis and interstitial lung disease: data from the SENSCIS trial, Rheumatology, Vol: 62, Pages: 1870-1876, ISSN: 1462-0324
OBJECTIVE: To assess associations between the extent of fibrotic interstitial lung disease (ILD) and forced vital capacity (FVC) at baseline and change in FVC over 52 weeks in patients with systemic sclerosis-associated ILD (SSc-ILD) in the SENSCIS trial. METHODS: We used generalised additive models, which involve few assumptions and allow for interaction between non-linear effects, to assess associations between the extent of fibrotic ILD on high-resolution computed tomography (HRCT), and the interplay of extent of fibrotic ILD on HRCT and FVC % predicted, at baseline and FVC decline over 52 weeks. RESULTS: In the placebo group (n = 288), there was weak evidence of a modest association between a greater extent of fibrotic ILD at baseline and a greater decline in FVC % predicted at week 52 (r: -0.09 [95% CI -0.2, 0.03]). Higher values of both the extent of fibrotic ILD and FVC % predicted at baseline tended to be associated with greater decline in FVC % predicted at week 52. In the nintedanib group (n = 288), there was no evidence of an association between the extent of fibrotic ILD at baseline and decline in FVC % predicted at week 52 (r: 0.01 [95% CI: -0.11, 0.12]) or between the interplay of extent of fibrotic ILD and FVC % predicted at baseline and decline in FVC % predicted at week 52. CONCLUSION: Data from the SENSCIS trial suggest that patients with SSc-ILD are at risk of ILD progression and benefit from nintedanib largely irrespective of their extent of fibrotic ILD at baseline. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02597933.
van der Vis JJ, Prasse A, Renzoni EA, et al., 2023, MUC5B rs35705950 minor allele associates with older age and better survival in idiopathic pulmonary fibrosis, Respirology, Vol: 28, Pages: 455-464, ISSN: 1323-7799
Background and Objective:The minor T-allele of the MUC5B promoter polymorphism rs35705950 is strongly associated with idiopathic pulmonary fibrosis (IPF). However, conflicting results have been reported on the relationship between the MUC5B minor allele and survival and it is unknown whether a specific subgroup of IPF patients might benefit from MUC5B minor allele carriage. We investigated the association between MUC5B rs35705950, survival and patient characteristics in a real-world population of European IPF patients.Methods:In this retrospective study, 1751 patients with IPF from 8 European centres were included. MUC5B rs35705950 genotype, demographics, clinical characteristics at diagnosis and survival data were analysed.Results:In a multi-variate Cox proportional hazard model the MUC5B minor allele was a significant independent predictor of survival when adjusted for age, sex, high resolution computed tomography pattern, smoking behaviour and pulmonary function tests in IPF. MUC5B minor allele carriers were significantly older at diagnosis (p = 0.001). The percentage of MUC5B minor allele carriers increased significantly with age from 44% in patients aged <56 year, to 63% in patients aged >75. In IPF patients aged <56, the MUC5B minor allele was not associated with survival. In IPF patients aged ≥56, survival was significantly better for MUC5B minor allele carriers (45 months [CI: 42–49]) compared to non-carriers (29 months [CI: 26–33]; p = 4 × 10−12).Conclusion:MUC5B minor allele carriage associates with a better median transplant-free survival of 16 months in the European IPF population aged over 56 years. MUC5B genotype status might aid disease prognostication in clinical management of IPF patients.
Reynolds CJ, Del Greco M F, Allen RJ, et al., 2023, The causal relationship between gastro-esophageal reflux disease and idiopathic pulmonary fibrosis: A bidirectional two-sample Mendelian randomization study., Eur Respir J
BACKGROUND: Gastro-esophageal reflux disease (GERD) is associated with idiopathic pulmonary fibrosis (IPF) in observational studies. It is not known if this association arises because GERD causes IPF, or IPF causes GERD, or because of confounding by factors, such as smoking, associated with both GERD and IPF. We used bidirectional Mendelian randomisation (MR), where genetic variants are used as instrumental variables to address issues of confounding and reverse causation, to examine how, if at all, GERD and IPF are causally related. METHODS AND RESULTS: A bidirectional two-sample MR was performed to estimate the causal effect of GERD on IPF risk, and of IPF on GERD risk, using genetic data from the largest GERD (78 707 cases and 288 734 controls) and IPF (4125 cases and 20 464 controls) genome-wide association meta-analyses currently available. GERD increased the risk of IPF, with an odds ratio (OR) of 1.6 (95% Confidence Interval, CI: 1.04-2.49; p=0.032). There was no evidence of a causal effect of IPF on the risk of GERD, with an OR of 0.999 (95%CI: 0.997-1.000; p=0.245). CONCLUSION: We found that GERD increases the risk of IPF, but found no evidence that IPF increases the risk of GERD. GERD should be considered in future studies of IPF risk, and interest in it as a potential therapeutic target should be renewed. The mechanisms underlying the effect of GERD on IPF should also be investigated.
Kolb M, Crestani B, Maher TM, 2023, Phosphodiesterase 4B inhibition: a potential novel strategy for treating pulmonary fibrosis, European Respiratory Review, Vol: 32, Pages: 1-13, ISSN: 0905-9180
Patients with interstitial lung disease can develop a progressive fibrosing phenotype characterised by an irreversible, progressive decline in lung function despite treatment. Current therapies slow, but do not reverse or stop, disease progression and are associated with side-effects that can cause treatment delay or discontinuation. Most crucially, mortality remains high. There is an unmet need for more efficacious and better-tolerated and -targeted treatments for pulmonary fibrosis. Pan-phosphodiesterase 4 (PDE4) inhibitors have been investigated in respiratory conditions. However, the use of oral inhibitors can be complicated due to class-related systemic adverse events, including diarrhoea and headaches. The PDE4B subtype, which has an important role in inflammation and fibrosis, has been identified in the lungs. Preferentially targeting PDE4B has the potential to drive anti-inflammatory and antifibrotic effects via a subsequent increase in cAMP, but with improved tolerability. Phase I and II trials of a novel PDE4B inhibitor in patients with idiopathic pulmonary fibrosis have shown promising results, stabilising pulmonary function measured by change in forced vital capacity from baseline, while maintaining an acceptable safety profile. Further research into the efficacy and safety of PDE4B inhibitors in larger patient populations and for a longer treatment period is needed.
Kreuter M, Bendstrup E, Jouneau S, et al., 2023, Weight loss and outcomes in subjects with progressive pulmonary fibrosis: data from the INBUILD trial, Respiratory Research, Vol: 24, Pages: 1-9, ISSN: 1465-9921
BACKGROUND: Lower body mass index (BMI) and weight loss have been associated with worse outcomes in some studies in patients with pulmonary fibrosis. We analyzed outcomes in subgroups by BMI at baseline and associations between weight change and outcomes in subjects with progressive pulmonary fibrosis (PPF) in the INBUILD trial. METHODS: Subjects with PPF other than idiopathic pulmonary fibrosis were randomized to receive nintedanib or placebo. In subgroups by BMI at baseline (< 25, ≥ 25 to < 30, ≥ 30 kg/m2), we analyzed the rate of decline in FVC (mL/year) over 52 weeks and time-to-event endpoints indicating disease progression over the whole trial. We used a joint modelling approach to assess associations between change in weight and the time-to-event endpoints. RESULTS: Among 662 subjects, 28.4%, 36.6% and 35.0% had BMI < 25, ≥ 25 to < 30 and ≥ 30 kg/m2, respectively. The rate of decline in FVC over 52 weeks was numerically greater in subjects with baseline BMI < 25 than ≥ 25 to < 30 or ≥ 30 kg/m2 (nintedanib: - 123.4, - 83.3, - 46.9 mL/year, respectively; placebo: - 229.5; - 176.9; - 171.2 mL/year, respectively). No heterogeneity was detected in the effect of nintedanib on reducing the rate of FVC decline among these subgroups (interaction p = 0.83). In the placebo group, in subjects with baseline BMI < 25, ≥ 25 to < 30 and ≥ 30 kg/m2, respectively, 24.5%, 21.4% and 14.0% of subjects had an acute exacerbation or died, and 60.2%, 54.5% and 50.4% of subjects had ILD progression (absolute decline in FVC % predicted ≥ 10%) or died over the whole trial. The proportions of subjects with these events were simi
Strambu IR, Seemayer CA, Fagard LM-CA, et al., 2023, GLPG1205 for idiopathic pulmonary fibrosis: a phase 2 randomised placebo-controlled trial, EUROPEAN RESPIRATORY JOURNAL, Vol: 61, ISSN: 0903-1936
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Kreuter M, Hoffmann-Vold A-M, Matucci-Cerinic M, et al., 2023, Impact of lung function and baseline clinical characteristics on patient-reported outcome measures in systemic sclerosis-associated interstitial lung disease, Rheumatology, Vol: 62, Pages: S143-S153, ISSN: 1462-0324
OBJECTIVE: The SENSCIS® trial demonstrated a significant reduction of lung function decline in patients with systemic sclerosis (SSc)-associated interstitial lung disease (SSc-ILD) treated with nintedanib, but no significant effect on health-related quality of life (HRQoL). To assess whether SSc/SSc-ILD severity and large changes in lung function correlate with HRQoL, a post-hoc analysis of SENSCIS®, aggregating treatment arms, was undertaken. METHODS: Patient-reported outcome (PRO) measures (St. George's Respiratory Questionnaire [SGRQ], Functional Assessment of Chronic Illness Therapy [FACIT]-Dyspnoea, and Health Assessment Questionnaire-Disability Index [HAQ-DI], incorporating the Scleroderma Health Assessment Questionnaire visual analogue scale [SHAQ VAS]) at baseline and week 52 were assessed for associations to SSc-ILD severity. RESULTS: At baseline and at week 52, forced vital capacity (FVC) <70% predicted was associated with worse PRO measure scores compared with FVC ≥70% predicted (week 52: SGRQ 45.1 vs 34.0 [p< 0.0001]; FACIT-Dyspnoea 48.9 vs 44.5 [p< 0.0001]; HAQ-DI 0.7 vs 0.6 [p< 0.0228]; SHAQ VAS breathing problems 3.6 vs 2.6 [p< 0.0001]). Patients with diffuse cutaneous SSc and other characteristics associated with SSc-ILD severity had worse PRO measure scores. Patients requiring oxygen or with >30% fibrosis on high-resolution computed tomography at baseline demonstrated worse PRO measure scores at week 52. After 1 year, patients with a major (>10%) improvement/worsening in FVC demonstrated corresponding improvement/worsening in SGRQ and other PRO measures, significant for the SGRQ symptom domain (p< 0.001). CONCLUSION: Severe SSc-ILD and major deteriorations in lung function have important impacts on HRQoL. Treatments that slow lung function decline and prevent severe SSc-ILD are important to preserve HRQoL. TRIAL REGISTRATION: clinicaltrials.gov, www.clinicaltrials.gov, NCT02597933.
Khanna D, Maher TM, Volkmann ER, et al., 2023, Effect of nintedanib in patients with systemic sclerosis-associated interstitial lung disease and risk factors for rapid progression, RMD OPEN, Vol: 9, ISSN: 2056-5933
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Peljto AL, Blumhagen RZ, Walts AD, et al., 2023, Idiopathic pulmonary fibrosis is associated with common genetic variants and limited rare variants, American Journal of Respiratory and Critical Care Medicine, Vol: 207, Pages: 1194-1202, ISSN: 1073-449X
Rationale: Idiopathic pulmonary fibrosis is a rare, irreversible, and progressive disease of the lungs. Common genetic variants, in addition to non-genetic factors, have been consistently associated with IPF. Rare variants identified by candidate gene, family-based, and exome studies have also been reported to associate with IPF. However, the extent to which rare variants genome-wide may contribute to the risk of IPF remains unknown. Objectives: We used whole-genome sequencing to investigate the role of rare variants, genome-wide, on IPF risk. Methods: As part of the Trans-Omics for Precision Medicine Program, we sequenced 2,180 cases of IPF. Association testing focused on the aggregated effect of rare variants (minor allele frequency ≤0.01) within genes or regions. We also identified individual variants that are influential within genes and estimated the heritability of IPF based on rare and common variants. Measurements and Main Results: Rare variants in both TERT and RTEL1 were significantly associated with IPF. A single rare variant in each of the TERT and RTEL1 genes was found to consistently influence the aggregated test statistics. There was no significant evidence of association with other previously reported rare variants. The SNP-heritability of IPF was estimated to be 32% (s.e. 3%). Conclusions: Rare variants within the TERT and RTEL1 genes and well-established common variants have the largest contribution to IPF risk overall. Efforts in risk profiling or development of therapies for IPF that focus on TERT, RTEL1, common variants, and environmental risk factors are likely to have the largest impact on this complex disease.
Maher TM, Tudor VA, Saunders P, et al., 2023, Rituximab versus intravenous cyclophosphamide in patients with connective tissue disease-associated interstitial lung disease in the UK (RECITAL): a double-blind, double-dummy, randomised, controlled, phase 2b trial, The Lancet Respiratory Medicine, Vol: 11, Pages: 45-54, ISSN: 2213-2600
BACKGROUND: Rituximab is often used as rescue therapy in interstitial lung disease (ILD) associated with connective tissue disease (CTD), but has not been studied in clinical trials. This study aimed to assess whether rituximab is superior to cyclophosphamide as a treatment for severe or progressive CTD associated ILD. METHODS: We conducted a randomised, double-blind, double-dummy, phase 2b trial to assess the superiority of rituximab compared with cyclophosphamide. Patients aged 18-80 years with severe or progressive ILD related to scleroderma, idiopathic inflammatory myositis, or mixed CTD, recruited across 11 specialist ILD or rheumatology centres in the UK, were randomly assigned (1:1) to receive rituximab (1000 mg at weeks 0 and 2 intravenously) or cyclophosphamide (600 mg/m2 body surface area every 4 weeks intravenously for six doses). The primary endpoint was rate of change in forced vital capacity (FVC) at 24 weeks compared with baseline, analysed using a mixed-effects model with random intercepts, adjusted for baseline FVC and CTD type. Prespecified secondary endpoints reported in this Article were change in FVC at 48 weeks versus baseline; changes from baseline in 6 min walk distance, diffusing capacity of the lung for carbon monoxide (DLCO), physician-assessed global disease activity (GDA) score, and quality-of-life scores on the St George's Respiratory Questionnaire (SGRQ), King's Brief Interstitial Lung Disease (KBILD) questionnaire, and European Quality of Life Five-Dimension (EQ-5D) questionnaire at 24 and 48 weeks; overall survival, progression-free survival, and time to treatment failure; and corticosteroid use. All endpoints were analysed in the modified intention-to-treat population, which comprised all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov (NCT01862926). FINDINGS: Between Dec 1, 2014, and March 31, 2020, we screened 145 participants, of whom 101 participants were randomly allocated
Solomon JJ, Danoff SK, Woodhead FA, et al., 2023, Safety, tolerability, and efficacy of pirfenidone in patients with rheumatoid arthritis-associated interstitial lung disease: a randomised, double-blind, placebo-controlled, phase 2 study, LANCET RESPIRATORY MEDICINE, Vol: 11, Pages: 87-96, ISSN: 2213-2600
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Allen RJ, Oldham JM, Jenkins DA, et al., 2023, Longitudinal lung function and gas transfer in individuals with idiopathic pulmonary fibrosis: a genome-wide association study, The Lancet Respiratory Medicine, Vol: 11, Pages: 65-73, ISSN: 2213-2600
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an incurable lung disease characterised by progressive scarring leading to alveolar stiffness, reduced lung capacity, and impeded gas transfer. We aimed to identify genetic variants associated with declining lung capacity or declining gas transfer after diagnosis of IPF. METHODS: We did a genome-wide meta-analysis of longitudinal measures of forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO) in individuals diagnosed with IPF. Individuals were recruited to three studies between June, 1996, and August, 2017, from across centres in the US, UK, and Spain. Suggestively significant variants were investigated further in an additional independent study (CleanUP-IPF). All four studies diagnosed cases following American Thoracic Society/European Respiratory Society guidelines. Variants were defined as significantly associated if they had a meta-analysis p<5 × 10-8 when meta-analysing across all discovery and follow-up studies, had consistent direction of effects across all four studies, and were nominally significant (p<0·05) in each study. FINDINGS: 1329 individuals with a total of 5216 measures were included in the FVC analysis. 975 individuals with a total of 3361 measures were included in the DLCO analysis. For the discovery genome-wide analyses, 7 611 174 genetic variants were included in the FVC analysis and 7 536 843 in the DLCO analysis. One variant (rs115982800) located in an antisense RNA gene for protein kinase N2 (PKN2) showed a genome-wide significant association with FVC decline (-140 mL/year per risk allele [95% CI -180 to -100]; p=9·14 × 10-12). INTERPRETATION: Our analysis identifies a genetic variant associated with disease progression, which might highlight a new biological mechanism for IPF. We found that PKN2, a Rho and Rac effector protein, is the most likely gene of interest fro
Wijsenbeek MS, Moor CC, Johannson KA, et al., 2023, Home monitoring in interstitial lung diseases, The Lancet Respiratory Medicine, Vol: 11, Pages: 97-110, ISSN: 2213-2600
The widespread use of smartphones and the internet has enabled self-monitoring and more hybrid-care models. The COVID-19 pandemic has further accelerated remote monitoring, including in the heterogenous and often vulnerable group of patients with interstitial lung diseases (ILDs). Home monitoring in ILD has the potential to improve access to specialist care, reduce the burden on health-care systems, improve quality of life for patients, identify acute and chronic disease worsening, guide treatment decisions, and simplify clinical trials. Home spirometry has been used in ILD for several years and studies with other devices (such as pulse oximeters, activity trackers, and cough monitors) have emerged. At the same time, challenges have surfaced, including technical, analytical, and implementational issues. In this Series paper, we provide an overview of experiences with home monitoring in ILD, address the challenges and limitations for both care and research, and provide future perspectives. VIDEO ABSTRACT.
Richeldi L, Azuma A, Cottin V, et al., 2022, Plain language summary: Clinical study of BI 1015550 as a potential treatment for idiopathic pulmonary fibrosis, JOURNAL OF COMPARATIVE EFFECTIVENESS RESEARCH, ISSN: 2042-6305
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