Roland M. du Bois

Bio: Roland M. du Bois is an academic researcher from Imperial College London. The author has contributed to research in topics: Idiopathic pulmonary fibrosis & Pulmonary fibrosis. The author has an hindex of 74, co-authored 181 publications receiving 25722 citations. Previous affiliations of Roland M. du Bois include Monash University & Mayo Clinic.

Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis

Abstract: Background Nintedanib (formerly known as BIBF 1120) is an intracellular inhibitor that targets multiple tyrosine kinases. A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis. Methods We conducted two replicate 52-week, randomized, double-blind, phase 3 trials (INPULSIS-1 and INPULSIS-2) to evaluate the efficacy and safety of 150 mg of nintedanib twice daily as compared with placebo in patients with idiopathic pulmonary fibrosis. The primary end point was the annual rate of decline in forced vital capacity (FVC). Key secondary end points were the time to the first acute exacerbation and the change from baseline in the total score on the St. George’s Respiratory Questionnaire, both assessed over a 52-week period. Results A total of 1066 patients were randomly assigned in a 3:2 ratio to receive nintedanib or placebo. The adjusted annual rate of change in FVC was −114.7 ml with nintedanib versus −239.9 ml with placebo (difference, 125.3 ml; 95% confidence interval [CI], 77.7 to 172.8; P<0.001) in INPULSIS-1 and −113.6 ml with nintedanib versus −207.3 ml with placebo (difference, 93.7 ml; 95% CI, 44.8 to 142.7; P<0.001) in INPULSIS-2. In INPULSIS-1, there was no significant difference between the nintedanib and placebo groups in the time to the first acute exacerbation (hazard ratio with nintedanib, 1.15; 95% CI, 0.54 to 2.42; P = 0.67); in INPULSIS-2, there was a significant benefit with nintedanib versus placebo (hazard ratio, 0.38; 95% CI, 0.19 to 0.77; P = 0.005). The most frequent adverse event in the nintedanib groups was diarrhea, with rates of 61.5% and 18.6% in the nintedanib and placebo groups, respectively, in INPULSIS-1 and 63.2% and 18.3% in the two groups, respectively, in INPULSIS-2. Conclusions In patients with idiopathic pulmonary fibrosis, nintedanib reduced the decline in FVC, which is consistent with a slowing of disease progression; nintedanib was frequently associated with diarrhea, which led to discontinuation of the study medication in less than 5% of patients. (Funded by Boehringer Ingelheim; INPULSIS-1 and INPULSIS-2 ClinicalTrials.gov numbers, NCT01335464 and NCT01335477.)

A common MUC5B promoter polymorphism and pulmonary fibrosis

Abstract: A b s t r ac t Background The mutations that have been implicated in pulmonary fibrosis account for only a small proportion of the population risk Methods Using a genomewide linkage scan, we detected linkage between idiopathic interstitial pneumonia and a 34-Mb region of chromosome 11p15 in 82 families We then evaluated genetic variation in this region in gel-forming mucin genes expressed in the lung among 83 subjects with familial interstitial pneumonia, 492 subjects with idiopathic pulmonary fibrosis, and 322 controls MUC5B expression was assessed in lung tissue Results Linkage and fine mapping were used to identify a region of interest on the p-terminus of chromosome 11 that included gel-forming mucin genes The minor-allele of the single-nucleotide polymorphism (SNP) rs35705950, located 3 kb upstream of the MUC5B transcription start site, was present at a frequency of 34% among subjects with familial interstitial pneumonia, 38% among subjects with idiopathic pulmonary fibrosis, and 9% among controls (allelic association with familial interstitial pneumonia, P = 12×10 − 15 ; allelic association with idiopathic pulmonary fibrosis, P = 25×10 − 37 ) The odds ratios for disease among subjects who were heterozygous and those who were homozygous for the minor allele of this SNP were 68 (95% confidence interval [CI], 39 to 120) and 208 (95% CI, 38 to 1137), respectively, for familial interstitial pneumonia and 90 (95% CI, 62 to 131) and 218 (95% CI, 51 to 935), respectively, for idiopathic pulmonary fibrosis MUC5B expression in the lung was 141 times as high in subjects who had idiopathic pulmonary fibrosis as in those who did not (P<0001) The variant allele of rs35705950 was associated with up-regulation in MUC5B expression in the lung in unaffected subjects (expression was 374 times as high as in unaffected subjects homozygous for the wild-type allele, P<0001) MUC5B protein was expressed in lesions of idiopathic pulmonary fibrosis Conclusions A common polymorphism in the promoter of MUC5B is associated with familial interstitial pneumonia and idiopathic pulmonary fibrosis Our findings suggest that dysregulated MUC5B expression in the lung may be involved in the pathogenesis of pulmonary fibrosis (Funded by the National Heart, Lung, and Blood Institute and others)

Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis.

Abstract: In patients with idiopathic pulmonary fibrosis, BIBF 1120 at a dose of 150 mg twice daily, as compared with placebo, was associated with a trend toward a reduction in the decline in lung function, with fewer acute exacerbations and preserved quality of life. (Funded by Boehringer Ingelheim; ClinicalTrials.gov number, NCT00514683.)

Interstitial lung disease in systemic sclerosis: a simple staging system.

Abstract: Rationale: In interstitial lung disease complicating systemic sclerosis (SSc-ILD), the optimal prognostic use of baseline pulmonary function tests (PFTs) and high-resolution computed tomography (HRCT) is uncertain.Objectives: To construct a readily applicable prognostic algorithm in SSc-ILD, integrating PFTs and HRCT.Methods: The prognostic value of baseline PFT and HRCT variables was quantified in patients with SSc-ILD (n = 215) against survival and serial PFT data.Measurements and Main Results: Increasingly extensive disease on HRCT was a powerful predictor of mortality (P < 0.0005), with an optimal extent threshold of 20%. In patients with HRCT extent of 10–30% (termed indeterminate disease), an FVC threshold of 70% was an adequate prognostic substitute. On the basis of these observations, SSc-ILD was staged as limited disease (minimal disease on HRCT or, in indeterminate cases, FVC ⩾ 70%) or extensive disease (severe disease on HRCT or, in indeterminate cases, FVC < 70%). This system (hazards ratio [H...

An Official ATS/ERS/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-Based Guidelines for Diagnosis and Management

Abstract: This document is an international evidence-based guideline on the diagnosis and management of idiopathic pulmonary fibrosis, and is a collaborative effort of the American Thoracic Society, the European Respiratory Society, the Japanese Respiratory Society, and the Latin American Thoracic Association. It represents the current state of knowledge regarding idiopathic pulmonary fibrosis (IPF), and contains sections on definition and epidemiology, risk factors, diagnosis, natural history, staging and prognosis, treatment, and monitoring disease course. For the diagnosis and treatment sections, pragmatic GRADE evidence-based methodology was applied in a question-based format. For each diagnosis and treatment question, the committee graded the quality of the evidence available (high, moderate, low, or very low), and made a recommendation (yes or no, strong or weak). Recommendations were based on majority vote. It is emphasized that clinicians must spend adequate time with patients to discuss patients' values and preferences and decide on the appropriate course of action.

Interpretative strategies for lung function tests

Abstract: SERIES “ATS/ERS TASK FORCE: STANDARDISATION OF LUNG FUNCTION TESTING” Edited by V. Brusasco, R. Crapo and G. Viegi Number 5 in this Series This section is written to provide guidance in interpreting pulmonary function tests (PFTs) to medical directors of hospital-based laboratories that perform PFTs, and physicians who are responsible for interpreting the results of PFTs most commonly ordered for clinical purposes. Specifically, this section addresses the interpretation of spirometry, bronchodilator response, carbon monoxide diffusing capacity ( D L,CO) and lung volumes. The sources of variation in lung function testing and technical aspects of spirometry, lung volume measurements and D L,CO measurement have been considered in other documents published in this series of Task Force reports 1–4 and in the American Thoracic Society (ATS) interpretative strategies document 5. An interpretation begins with a review and comment on test quality. Tests that are less than optimal may still contain useful information, but interpreters should identify the problems and the direction and magnitude of the potential errors. Omitting the quality review and relying only on numerical results for clinical decision making is a common mistake, which is more easily made by those who are dependent upon computer interpretations. Once quality has been assured, the next steps involve a series of comparisons 6 that include comparisons of test results with reference values based on healthy subjects 5, comparisons with known disease or abnormal physiological patterns ( i.e. obstruction and restriction), and comparisons with self, a rather formal term for evaluating change in an individual patient. A final step in the lung function report is to answer the clinical question that prompted the test. Poor choices made during these preparatory steps increase the risk of misclassification, i.e. a falsely negative or falsely positive interpretation for a lung function abnormality or a change …

Complex networks orchestrate epithelial–mesenchymal transitions

Abstract: Epithelial-mesenchymal transition is an indispensable mechanism during morphogenesis, as without mesenchymal cells, tissues and organs will never be formed. However, epithelial-cell plasticity, coupled to the transient or permanent formation of mesenchyme, goes far beyond the problem of cell-lineage segregation. Understanding how mesenchymal cells arise from an epithelial default status will also have a strong impact in unravelling the mechanisms that control fibrosis and cancer progression.

American thoracic society/European respiratory society international multidisciplinary consensus classification of the idiopathic interstitial pneumonias

Abstract: Executive Summary Objectives Participants Evidence Validation Key Messages Introduction Rationale for a Change in the Approach to Classification of Idiopathic Interstitial Pneumonias Development of a New Classification of Idiopathic Interstitial Pneumonia Current Classification of IIP New ATS/ERS Classification Principles Guiding the Assessment of Patients with Idiopathic Interstitial Pneumonias The Diagnostic Process Is Dynamic Clinical Evaluation Radiological Evaluation Role of Surgical Lung Biopsy Unclassifiable Interstitial Pneumonia Bronchoalveolar Lavage Fluid Evaluation Idiopathic Pulmonary Fibrosis Clinical Features Radiologic Features Histologic Features IPF: Areas of Uncertainty Nonspecific Interstitial Pneumonia Clinical Features Radiologic Features Histologic Features NSIP: Areas of Uncertainty Cryptogenic Organizing Pneumonia Clinical Features Radiologic Features Histologic Features COP: Areas of Uncertainty Acute Interstitial Pneumonia Clinical Features Radiologic Features Histologic Features AIP: Areas of Uncertainty Respiratory Bronchiolitis-Associated Interstitial Lung Disease Clinical Features Radiologic Features Histologic Features RB-ILD: Areas of Uncertainty Desquamative Interstitial Pneumonia Clinical Features Radiologic Features Histologic Features DIP: Areas of Uncertainty Lymphoid Interstitial Pneumonia Clinical Features Radiologic Features Histologic Features LIP: Areas of Uncertainty References Appendix

Fleischner Society: Glossary of Terms for Thoracic Imaging

Abstract: Members of the Fleischner Society compiled a glossary of terms for thoracic imaging that replaces previous glossaries published in 1984 and 1996 for thoracic radiography and computed tomography (CT), respectively. The need to update the previous versions came from the recognition that new words have emerged, others have become obsolete, and the meaning of some terms has changed. Brief descriptions of some diseases are included, and pictorial examples (chest radiographs and CT scans) are provided for the majority of terms.