Resumen: Idiopathic pulmonary fibrosis (IPF) has a variable clinical course, which ranges from being asymptomatic to progressive respiratory failure. The purpose of this study was to evaluate the novel clinical parameters of IPF patients who receive an anti-fibrotic agent. Materials and Methods: From January 2011 to January 2021, we identified 39 IPF patients at Okinawa Chubu Hospital. Clinical information was obtained, such as laboratory data, pulmonary function test (PFT) results, and chest images,  including of soft tissue thickness and the high-resolution computed tomography (HRCT) pattern at diagnosis. Results: The mean age was 72.9 ± 7.0 (53-85); 27 patients were men and 12 were women. The mean body mass index was 25.1 ± 3.9 (17.3-35). Twenty-four were active smokers and the median number of packs per year was 20. Regarding laboratory findings, mean white blood cell (WBC), lactate dehydrogenase (LDH), and Krebs Von den Lungen-6 (KL-6) values were 7816 ± 1859, 248 ± 47,and 1615 ±  1503, respectively. In PFT, the mean percent predicted FVC, percent predicted total lung capacity, percent predicted functional residual capacity (FRC), and percent predicted diffusion capacity of the lung for carbon monoxide (DLco) were 66.8 ± 14.9%, 71.8 ±  13.7%, 65 ± 39.6%, and 64.6 ± 27.9%, respectively. In chest radiological findings, soft tissue thickness at the right 9 thrib was 26.4 ± 8.8mm. Regarding chest HRCT patterns, 15 showed the definite usual interstitial pneumonia (UIP) pattern, 16 showed the  probable UIP pattern, and eight showed the indeterminate for UIP pattern. In the treatment, 24 patients received pirfenidone and 15 patients took nintedanib. The mean observation period was 38.6 ± 30.6 months and 24 patients died. The median survival time was 32.4 months(0.9-142.5). Multivariate analysis adjusted for age showed that both soft tissue thickness [Hazard ratio (HR): 0.912,95% confidence interval (CI): 0.859-0.979, p-value: 0.009] and percent FRC [HR: 0.980,95% CI: 0.967-0.992, p-value: 0.002]  were robust predictors of IPF mortality. Conclusions: In IPF patients treated with anti-fibroticagents, both soft tissue thickness at the right 9th rib shown on the chest radiograph and %FRC can be novel predictors of IPF mortality.

Resumen: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease that requires ongoing care and is associated with considerable socio economic burden. We evaluated the IPF care path way from symptom recognition to treatment. We describe the  impact of IPF on health care resource use (HCRU), quality of life (QoL) and work impairment, and report differences in patient and physician perspectives using real-world data from France, Germany, Japan and the United States.

Quantitative, point-in-time data were collected as part of the Adelphi IPF II Disease Specific Programme™. Physician-reported data (patient demographics, medical history, diagnoses, treatment) were matched to patient-reported data (HCRU,QoL,work impairment). HCRU was measured as physician visits and hospitalizations. QoL and work impairment were measured using the EuroQol-5 Dimensions (EQ-5D) and Work Productivity and Activity Impairment questionnaires.

Overall, 244 physicians reported data on 1249 patients, 739 of whom self-reported data. Diagnostic delays of 0.8 (Germany) to 2.0 (Japan) years after symptom onset were reported; treatment initiation was further delayed. In all countries, patients more often  reported symptoms in the survey than did their physicians. On average, patients under went 7-10 clinical tests before diagnosis. Antifibrotic use increased from 57% (2016) to 69% (2019); only 50% of patients with moderate/severe IPF were satisfied with their treatment. The 12-month hospitalization rates were 24% (Japan) to 64% (United States). Patients reported low QoL (mean EQ-5D visual analogue scale: 61.7/100).

Patients with IPF experience considerable diagnostic and treatment delays. More effective therapies and management are needed to reduce the disease burden.

Resumen: The efficacy of nintedanib in progressive fibrosing interstitial lung diseases (ILDs) was demonstrated in the randomised, double-blind, placebo-controlled INBUILD trial. This subgroup analysis evaluated the efficacy and safety of nintedanib in the  Japanese population. Patients with progressive fibrosing ILDs (evaluated by physicians within 24 months of screening) were randomised (1:1) to twice-daily 150-mg nintedanib or placebo; treatment continued until the last patient completed 52 weeks. The  primary end point was the annual rate of decline in forced vital capacity (FVC) over 52 weeks. Time-to-first acute ILD exacerbation or death and time-to-death upuntil the last patient had completed the week 52 visit were evaluated. This subgroup analysis included 108 Japanese patients.

The adjusted annual rates of FVC decline (mL/year) over 52 weeks for Japanese patients were -148.31 (nintedanib) and -240.36 (placebo), adjusted difference: 92.05 (95% CI: -10.69-194.80) and for non-Japanese patients were -67.41 (nintedanib) and -177.65  (placebo), adjusted difference: 110.24 (95% CI: 64.97-155.52). No heterogeneity in treatment effect between Japanese and non-Japanese subgroups was observed (treatment-by-subgroup interaction, p=0.75). The risks of "acute exacerbation or death"  (hazard ratio, 0.30 [95% CI: 0.10-0.91])and mortality (hazard ratio, 0.54 [95% CI: 0.14-2.11]) in Japanese patients were numerically lower for nintedanib than placebo. There were no new or unexpected safety findings.

In Japanese patients, nintedanib slowed ILD progression, evidenced by a reduction in the annual rate of decline in FVC vs placebo. The efficacy and safety of nintedanibin Japanese patients were consistent with the overall INBUILD population. CLINICALTRIALS.GOV: NCT02999178 (21-Dec-2016).

Resumen: Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with limited therapeutic options. Current evidence suggests that IPF may be initiated by repeated epithelial injuries in the distal lung, which are followed by abnormal wound healing  responses that occur be cause of intrinsic and extrinsic factors. Mechanisms contributing to chronic damage of the alveolar epithelium in IPF include dysregulated cellular processes such as apoptosis, senescence, abnormal activation of the develop mental  pathways, aging, and genetic mutations. Therefore, targeting the regenerative capacity of the lung epithelium is an attractive approach in the development of novel therapies for IPF. Endogenous lung regeneration is a complex process involving coordinated cross-talk among multiple cell types and reestablishment of anormal extracellular matrix environment. This review will describe the current knowledge of reparative epithelial progenitor cells in the alveolar region of the lung and discuss potential  novel therapeutic approaches for IPF, focusing on endogenous alveolar repair.

Resumen: The interstitial pneumonias comprise a diverse group of diseases that are typically defined by their cause (either idiopathic or non-idiopathic) and their distinct histopathological features, for which radiology, in the form of high-resolution CT, is  often used as a surrogate. One trend, fuelled by the failure of conventional therapies in a subset of patients and the broad-spectrum use of antifibrotic therapies, has been the focus on the progressive fibrosing phenotype of interstitial lung  disease. The histological pattern, known as usual interstitial pneumonia, is the archetype of progressive fibrosis. However, it is clear that progressive fibrosis is not exclusive to this histological entity. Techniques including immunohistochemistry and single-cell RNA sequencing are providing pathogenetic insights and, if integrated with traditional histopathology, are likely to have an effect on the pathological classification of interstitial lung disease. This review, which focuses on the histopathology of  interstitial lung disease and its relationship with progressive fibrosis, asks the question: is it all about usual interstitial pneumonia?

Resumen: Numerous clinical and research investigations conducted during the last two decades have implicated excessive oxidative stress caused by high levels of reactive oxygen species (ROS) in the development of the severe and frequently  progressive fibrotic process in Systemic Sclerosis (SSc). The role of excessive oxidative stress in SSc pathogenesis has been supported by the demonstration of increased levels of numerous biomarkers, indicative of cellular and molecular oxidative  damage in serum, plasma, and other biological fluids from SSc patients, and by the demonstration of elevated production of ROS by various cell types involved in the SSc fibrotic process. However, the precise mechanisms mediating oxidative stress  development in SSc and its pathogenetic effects have not been fully elucidated. The participation of the NADPH oxidase NOX4, has been suggested and experimentally supported by the demonstration that SSc dermal fibroblasts display constitutively increased  NOX4 expression and that reduction or abrogation of NOX4 effects decreased ROS production and the expression of genes encoding fibrotic proteins. Furthermore, NOX4-stimulated ROS production may be involved in the development of certain endothelial and  vascular abnormalities and may even participate in the generation of SSc-specific autoantibodies. Collectively, these observations suggest NOX4 as a novel therapeutic target for SSc.

Resumen: Rapidly progressive interstitial lung disease (RP-ILD) is a fatal complication of dermatomyositis (DM) and clinically amyopathic DM (CADM). The objective of this study was to evaluate risk markers associated with RP-ILD incidence in patients with  DM/CADM and to develop a RP-ILD risk prediction (RRP) model. The clinical records of 229 patients with DM/CADM from Peking University People's Hospital, and 97patients from four other independent clinical centers were retrospectively reviewed.  Univariate and multivariate logistic regression analyses were performed to identify independent risk factors associated with later RP-ILD incidence to build a risks core model. The concordance index (C-index) and calibration curve were calculated to evaluate  the predictive accuracy of the RRP model. A multi parametric RRP model was established based on weighted clinical features, including fever (yes, 5; no, 0), periungual erythema (yes, 6; no, 0), elevated CRP (yes, 5; no, 0), anti-MDA5 antibody (positive, 8; negative, 0),and anti-Ro-52 antibody (positive, 6; negative, 0). Patients were divided into three risk groups according to the RRP total score: low, 0-9; medium, 10-19; high, 20-30. The C-index and calibration curve of the RRP model showed a promising predictive accuracy on the incidence of RP-ILD. The RRP model might promisingly predict the incidence of RP-ILD in DM/CADM patients to guide early individual treatment and further improve the prognosis of DM/CADM patients.

Resumen: Rapidly progressive interstitial lung disease (RP-ILD) is a fatal complication of dermatomyositis (DM) and clinically amyopathic DM (CADM). The objective of this study was to evaluate risk markers associated with RP-ILD incidence in patients with  DM/CADM and to developa RP-ILD risk prediction (RRP) model. The clinical records of 229 patients with DM/CADM from Peking University People's Hospital, and 97 patients from four other independent clinical centers were retrospectively reviewed.  Univariate and multivariate logistic regression analyses were performed to identify independent risk factors associated with later RP-ILD incidence to build a risks core model. The concordance index (C-index) and calibration curve were calculated to evaluate  the predictive accuracy of the RRP model. A multiparametric RRP model was established based on weighted clinical features, including fever (yes, 5; no, 0), periungual erythema (yes, 6; no, 0), elevated CRP (yes, 5; no, 0), anti-MDA5 antibody (positive, 8; negative, 0), and anti-Ro-52 antibody (positive, 6; negative, 0). Patients were divided into three risk groups according to the RRP total score: low, 0-9; medium, 10-19; high, 20-30. The C-index and calibration curve of the RRP model showed a promising predictive accuracy on the incidence of RP-ILD. The RRP model might promisingly predict the incidence of RP-ILD in DM/CADM patients to guide early individual treatment and further improve the prognosis of DM/CADM patients.

Resumen: In Spain, the prevalence of different rheumatic diseasesis known mainly through the EPISER studies coordinated by the Spanish Society of Rheumatology and based on surveys in a population sample. The aim of our study is to describe the prevalence  in 2016 of different rheumatic diseases in the population residing in Baix Empordà according to health care coding records.

Observational, descriptive and cross-sectional study carried out on the population attended from 2016-2017 in Serveis de Salut Integrats del Baix Empordà, an organizational service that includes all the health care facilities in the Baix Empordà area with a  unique information system. Patients ≥ 20 years of age were selected and the ICD9-CM coding of all their health care contacts was analysed according to 11 entities and 28 diseases. The entities were: polyarthritis, spondyloarthritis, microcrystalline arthritis,  osteoarthritis, soft tissue rheumatism, fibromyalgia, chronic spinal pain, osteoporosis, connective tissue diseases, vasculitis and others. The studied population was assigned to the categories: “with rheumatic disease”, “possible rheumatic disease” and “without rheumatic disease”.

In total, 71,785 patients were distributed as: 36.2% “with rheumatic disease (n=25,990); 6.1% with “possible rheumatic disease” (n=4,406) and 57.7% “without rheumatic disease” (n=41,389). The group “with rheumatic disease” showed a predominance of  women (59.8% vs. 44.9%) and older age (59.1±17.7 vs. 45.1±16.2; P <.001) compared to the group “without rheumatic disease”. The presence of rheumatic disease increased progressively with age, being maximum in the group between 55-75 years.

36.2% of our population has some type of rheumatic disease. The estimated prevalence of some rheumatic diseases in the Baix Empordà population is partially consistent with that estimated by the EPISER 2016 study. Rheumatic disease affects women in a  greater proportion and is more frequent in patients over 45 years of age.