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Introduction: Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible and frequently fatal disease. Currently there are national and multinational registries in Europe, United States, Australia and China to better understand the magnitude of the problem and the characteristics of the IPF patients. However, there are no national or regional registries in Latin America, so the objective of this study was to carry out a Latin American registry that would allow the identification of IPF patients in our region., Methodology: A system consisting of 3 levels of control was designed, ensuring that patients met the diagnostic criteria for IPF according to international guidelines ATS/ERS/ALAT/JRS 2011. Demographic, clinical, serological, functional, tomographic, histological and treatment variables were recorded through a digital platform., Results: 761 IPF patients from 14 Latin American countries were included for analysis, 74.7% were male, with a mean age of 71.9+8.3 years. In general there was a long period of symptoms before definitive diagnosis (median 1 year). In functional tests, an average reduction of FVC (70.9%) and DLCO (53.7%) was detected. 72% received at least one antifibrotic drug (pirfenidone or nintedanib) and 11.2% of the patients had an acute exacerbation, of which 38 (45.2%) died from this cause., Conclusions: Like other registries, we found that there is difficulty in the recognition and excessive delay in the diagnosis of IPF in Latin America. Most of the patients in REFIPI received antifibrotics; these were well tolerated and associated with fewer adverse events than those reported in clinical trials., (Copyright © 2022 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible and usually lethal lung disease of unknown etiology. Once considered as a relatively homogeneous, slowly progressive disease, is now recognized that the clinical behavior shows substantial heterogeneity, including an accelerated variant, and the presence of acute exacerbations. In addition, since IPF largely affects individuals over 60 years of age, the patients are at increased risk of several comorbidities that in turn have a remarkable clinical impact on the disease and increases mortality rate. Among others, combined pulmonary fibrosis and emphysema, secondary pulmonary arterial hypertension, lung cancer, and cardiovascular diseases are frequently associated with IPF and impact survival. For these reasons clinical phenotypes and comorbidities should be timely identified and managed. The aim of this review is to describe the common pulmonary and extra-pulmonary comorbidities in IPF, as well as the putative mechanisms involved., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Idiopathic pulmonary fibrosis (IPF) is a devastating disease of unknown etiology. The pathogenic mechanisms are unclear, but evidence indicates that aberrantly activated alveolar epithelial cells secrete a variety of mediators which induce the migration, proliferation and activation of fibroblasts and finally the excessive accumulation of extracellular matrix with the consequent destruction of the lung parenchyma. CC16 (approved symbol SCGB1A1), a putative anti-inflammatory protein produced by "club" cells in the distal airways, has not been evaluated in IPF lungs. In this study, we determined the serum and bronchoalveolar lavage (BAL) levels as well as the lung cell localization of this protein. Also, we explored the usefulness of serum levels of CC16 for the differential diagnosis of IPF (n = 85), compared with non-IPF interstitial lung diseases [chronic hypersensitivity pneumonitis (cHP; n = 85) and connective tissue diseases (CTD-ILD; n = 85)]. CC16 was significantly increased in serum and BAL fluids of IPF patients and was found not only in club cells but also in alveolar epithelial cells. When compared with non-IPF patients and controls, serum levels were significantly increased (p<0.0001). Sensitivity and specificity for CC16 (cut-off 41ng/mL) were 24% and 90%, positive predictive value 56% and negative predictive value 69%. These findings demonstrate that CC16 is upregulated in IPF patients suggesting that may participate in its pathogenesis. Although higher than the serum levels of non-IPF patients it shows modest sensitivity to be useful as a potential biomarker for the differential diagnosis., Competing Interests: The authors have declared that no competing interests exist.

Background and Objective: Studies of autoimmunity and anti-citrullinated protein antibodies (ACPA) in idiopathic pulmonary fibrosis (IPF) have been confined to investigations of anti-cyclic citrullinated peptide (anti-CCP) antibodies which utilize synthetic peptides as surrogate markers for in vivo citrullinated antigens. We studied immune activation by analysing the prevalence of in vivo anti-modified protein antibodies (AMPA) in IPF., Methods: We included patients with incident and prevalent IPF (N = 120), sex and smoking-matched healthy controls (HC) (N = 120) and patients with RA (N = 104). Serum (median time: 11 months [Q1-Q3: 1-28 months] from diagnosis) was analysed for presence of antibodies towards native and posttranslational modified (citrullinated [Cit, N = 25]; acetylated [Acet, N = 4] and homocitrullinated [Carb, N = 1]) peptides derived from tenascin (TNC, N = 9), fibrinogen (Fib, N = 11), filaggrin (Fil, N = 5), histone (N = 8), cathelicidin (LL37, N = 4) and vimentin (N = 5) using a custom-made peptide microarray., Results: AMPA were more frequent and in increased levels in IPF than in HC (44% vs. 27%, p < 0.01), but less than in RA (44% vs. 79%, p < 0.01). We specifically observed AMPA in IPF towards certain citrullinated, acetylated and carbamylated peptides versus HC: tenascin (Cit (2033) -TNC 2025-2040 ; Cit (2197) -TNC 2177-2200 ; Cit (2198) -TNC 2177-2200 ) , fibrinogen (Cit (38,42) -Fibα 36-50 ; Cit (72) -Fibβ 60-74 ) and filaggrin (Acet-Fil 307-324 , Carb-Fil 307-324 ). No differences in survival (p = 0.13) or disease progression (p = 0.19) between individuals with or without AMPA was observed in IPF. However, patients with incident IPF had better survival if AMPA were present (p = 0.009)., Conclusion: A significant proportion of IPF patients present with specific AMPA in serum. Our results suggest autoimmunity as a possible characteristic for a subgroup of IPF that may affect disease outcome., (© 2023 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Background: It has been suggested that the presence of emphysema modifies the outcome of patients with idiopathic pulmonary fibrosis (IPF). In this article we compare clinical features, smoking history, pulmonary function, estimated systolic pulmonary artery pressure (eSPAP), and mortality in IPF with emphysema vs IPF without emphysematous changes., Methods: A cohort of 110 IPF patients was evaluated. Clinical data were collected from clinical charts. High-resolution CT (HRCT) scans were examined by an expert blinded to clinical data, and patients were classified into the following two groups: patients with IPF with emphysema; and patients with IPF without emphysema. The Kaplan-Meier method, log-rank test, and Cox regression model were used for statistical analyses., Results: The prevalence of emphysema in the IPF cohort was 28% (31 of 110 patients). IPF with emphysema was significantly associated with male gender (odds ratio [OR], 18; 95% confidence interval [CI], 2.7 to 773.7; p = 0.0003), and smoking (OR, 3.8; 95% CI, 1.36 to 11.6; p = 0.004). Patients with IPF and emphysema had a higher mean (+/- SD) decrease in oxygen saturation during rest and exercise (16.3 +/- 6.7% vs 13.5 +/- 4.6%, respectively; p = 0.04), a higher mean fibrosis HRCT scan score (1.75 +/- 0.36 vs 1.55 +/- 0.38, respectively; p = 0.015), a higher eSPAP (82 +/- 20 vs 57 +/- 15 mm Hg, respectively; p < 0.0001), and lower median survival time (25 vs 34 months, respectively; p = 0.01) than patients with IPF without emphysema. The Cox regression model showed that the two most important variables associated with mortality were FVC < 50% predicted (hazard ratio [HR], 2.6; 95% CI, 1.19 to 5.68; p = 0.016) and eSPAP >or= 75 mm Hg (HR, 2.25; 95% CI, 1.12 to 4.54; p = 0.022)., Conclusions: IPF patients with emphysema exhibited higher mortality compared with those with IPF without emphysema. This dire prognosis seems to be at least partially associated with the development of severe pulmonary arterial hypertension.

Objective: Several software-based quantitative computed tomography (CT) analysis methods have been developed for assessing emphysema and interstitial lung disease. Although the texture classification method appeared to be more successful than the other methods, the software programs are not commercially available, to our knowledge. Therefore, this study aimed to investigate the usefulness of a commercially available software program for quantitative CT analyses., Methods: This prospective cohort study included 80 patients with chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF)., Results: The percentage of low attenuation volume and high attenuation volume had high sensitivity and high specificity for detecting emphysema and pulmonary fibrosis, respectively. The percentage of diseased lung volume (DLV%) was significantly correlated with the lung diffusion capacity for carbon monoxide in all patients with COPD and IPF patients., Conclusions: The quantitative CT analysis may improve the precision of the assessment of DLV%, which itself could be a useful tool in predicting lung diffusion capacity in patients with the clinical diagnosis of COPD or IPF., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Cigarette smoking and occupational exposures each have been reported to increase the risk of idiopathic pulmonary fibrosis (IPF), a disease previously considered of unknown origin. We investigated the risk of IPF mortality associated with combined smoking and occupational exposures., Methods: A registry study of Swedish construction workers (N = 389,132), linked baseline smoking and occupational data with registry data on cause of death and hospital care diagnoses. Occupation was classified by the likelihood of exposure to vapors, gases, dusts, or fumes using a job-exposure matrix. Those likely exposed to asbestos or silica were excluded from the analysis. Age-adjusted relative risks [RRs] were calculated using Poisson regression. Follow-up observation began at age 40 and ended at age 89., Results: Heavy smokers at baseline who were exposed to inorganic dusts during their working life had an increased risk of IPF mortality (RR 1.70; 95% confidence interval [CI] 1.11-2.60), while there was no statistically increased risk in the other exposure groups. There were dose-response relationships between smoking at baseline and IPF mortality among both unexposed and dust exposed workers, with similar risk for dust exposed and unexposed, except among baseline heavy smokers, where workers exposed to inorganic dust manifested the highest risk (RR 4.22; 95% CI 2.69-6.60). Excluding workers with chronic obstructive pulmonary disease or emphysema did not affect the results substantively., Conclusion: A clear dose-response relationship was seen between smoking at baseline and IPF, supporting a causal relationship. Occupational exposure to inorganic dusts, excluding silica and asbestos, was associated with increased risk of IPF in baseline heavy current smokers., (© 2021 The Authors. American Journal of Industrial Medicine Published by Wiley Periodicals LLC.)

Background: Volumetric high-resolution computed tomography (HRCT) of the chest has recently replaced incremental CT in the diagnostic workup of idiopathic pulmonary fibrosis (IPF). Concomitantly, visual and quantitative scores have been proposed for disease extent assessment to ameliorate disease management., Purpose: To compare the performance of density histograms (mean lung attenuation, skewness, and kurtosis) and visual scores, along with lung function correlations, in IPF patients submitted to incremental or volumetric thorax HRCT., Material and Methods: Clinical data and CT scans of 89 newly diagnosed and therapy-naive IPF patients were retrospectively evaluated., Results: Forty-six incremental and 43 volumetric CT scans were reviewed. No differences of density histograms and visual scores estimates were found by comparing two HRCT techniques, with an optimal inter-operator agreement (concordance correlation coefficient >0.90 in all instances). Single-breath diffusing lung capacity for carbon monoxide (DLCO sb ) was inversely related with the Best score (r = -00.416; p = 0.014), the Kazerooni fibrosis extent (r = -0.481; p = 0.004) and the mean lung attenuation (r = -0.382; p = 0.026), while a positive correlation was observed with skewness (r = 0.583; p = 0.001) and kurtosis (r = 0.543; p = 0.001) in the incremental HRCT sub-group. Similarly, in the volumetric CT sub-cohort, DLCO sb was significantly associated with skewness (r = 0.581; p = 0.007) and kurtosis (r = 0.549; p = 0.018). Correlations with visual scores were not confirmed. Forced vital capacity significantly related to all density indices independently on HRCT technique., Conclusions: Density histograms and visual scores similarly perform in incremental and volumetric HRCT. Density quantification displays an optimal reproducibility and proves to be superior to visual scoring as more strongly correlated with lung function.

Introduction and Objective: Pulmonary hypertension (PH) complicating idiopathic pulmonary fibrosis (IPF) is challenging to diagnose given inaccuracy of transthoracic echocardiogram (TTE) measurements. However, it has significant prognostic implications and is therefore important to accurately identify., Methods: We conducted a cross-sectional study of patients with IPF who underwent RHC as part of their evaluation. A variety of commonly available noninvasive variables were evaluated for their ability to predict pulmonary arterial pressure in a linear regression model, including the traditionally used right ventricular systolic pressure (RVSP) estimated from TTE., Results: There were 105 eligible patients identified from January 2006 to July 2016. The average age was 62.7 ± 7.7 years, 35 had RHC proven PH and 43% ultimately underwent lung transplantation. A linear model including three terms: RVSP (ANOVA P < .01), the ratio of FVC/DLCO from PFTs (P = .05) and pulmonary artery to aorta diameter ratio from CT (P < .01) was found to predict the mean pulmonary artery pressure more reliably than RVSP alone (R 2 .39 vs .29, P < .05), with a lower rate of incorrect classification of PH status in these individuals (27.6 vs 35.2%, P = .05) and high negative predictive value (87.2%)., Conclusion: If used in conjunction with RVSP from TTE, parameters from PFTs and the CT scan more accurately predict the presence or absence of PH than any of the variables in isolation. Using these in concert may allow greater discrimination in deciding which patients to subject to diagnostic right heart catheterization., (© 2019 John Wiley & Sons Ltd.)

Rationale: Fibrotic hypersensitivity pneumonitis (FHP) is a debilitating interstitial lung disease driven by incompletely understood immune mechanisms. Objectives: To elucidate immune aberrations in FHP in single-cell resolution. Methods: Single-cell 5′ RNA sequencing was conducted on peripheral blood mononuclear cells and BAL cells obtained from 45 patients with FHP, 63 patients with idiopathic pulmonary fibrosis (IPF), 4 patients with nonfibrotic hypersensitivity pneumonitis, and 36 healthy control subjects in the United States and Mexico. Analyses included differential gene expression (Seurat), TF (transcription factor) activity imputation (DoRothEA-VIPER), and trajectory analyses (Monocle3 and Velocyto-scVelo-CellRank). Measurements and Main Results: Overall, 501,534 peripheral blood mononuclear cells from 110 patients and control subjects and 88,336 BAL cells from 19 patients were profiled. Compared with control samples, FHP has elevated classical monocytes (adjusted-P = 2.5 × 10−3) and is enriched in CCL3hi/CCL4hi and S100Ahi classical monocytes (adjusted-P < 2.2 × 10−16). Trajectory analyses demonstrate that S100Ahi classical monocytes differentiate into SPP1hi lung macrophages associated with fibrosis. Compared with both control subjects and IPF, cells from patients with FHP are significantly enriched in GZMhi cytotoxic T cells. These cells exhibit TF activities indicative of TGFβ and TNFα and NFκB pathways. These results are publicly available at . Conclusions: Single-cell transcriptomics of patients with FHP uncovered novel immune perturbations, including previously undescribed increases in GZMhi cytotoxic CD4+ and CD8+ T cells—reflecting this disease's unique inflammatory T cell–driven nature—as well as increased S100Ahi and CCL3hi/CCL4hi classical monocytes also observed in IPF. Both cell populations may guide the development of new biomarkers and therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background: The presence of the rs35705950 variant in the MUC5B gene promoter is a critical genetic risk factor in idiopathic pulmonary fibrosis (IPF). It has been associated with usual interstitial pneumonia (UIP) in several interstitial lung diseases (ILDs). In antisynthetase syndrome (ASSD), most high-resolution computed tomography (HRCT) patterns are inflammatory, but up to 13% have UIP, leading to a worse prognosis. Methods: This single-center study included 60 patients with ASSD-ILD. We investigated whether carrying the MUC5B rs35705950 promoter variant was associated with UIP. To estimate the strength of the association between the genotype of the MUC5B rs35705950 promoter variant and the fibrotic pattern we used the odds ratio (cOR), and to assess the effect of confounding variables (age, evolution time, and sex), we performed a logistic regression to obtained the adjusted odds ratio (aOR). Results: The GT genotype of the MUC5B rs35705950 promoter variant is associated with up to a 4-fold increased risk of UIP (cOR 5.0, 95% CI 1.13–22.10), and the effect was even maintained after adjusting for potentially confounding variables such as sex, age, and time to progression (aOR 5.2, 95% CI 1.04–25.89). Conclusions: our study supports the role of MUC5B rs35705950 in ASSD-ILD with UIP. It reinforces that this polymorphism in our population could have a similar genetic basis to that already described in other ILDs that present predominantly fibrotic patterns. [ABSTRACT FROM AUTHOR]

Background: No single pulmonary function test captures the functional effect of emphysema in idiopathic pulmonary fibrosis (IPF). Without experienced radiologists, other methods are needed to determine emphysema extent. Here, we report the development and validation of a formula to predict emphysema extent in patients with IPF and emphysema. Methods: The development cohort included 76 patients with combined IPF and emphysema at the Royal Brompton Hospital, London, United Kingdom. The formula was derived using stepwise regression to generate the weighted combination of pulmonary function data that fitted best with emphysema extent on high-resolution computed tomography. Test cohorts included patients from two clinical trials (n = 455 [n = 174 with emphysema]; NCT00047645, NCT00075998) and a real-world cohort from the Royal Brompton Hospital (n = 191 [n = 110 with emphysema]). The formula is only applicable for patients with IPF and concomitant emphysema and accordingly was not used to detect the presence or absence of emphysema. Results: The formula was: predicted emphysema extent = 12.67 + (0.92 x percent predicted forced vital capacity) – (0.65 x percent predicted forced expiratory volume in 1 second) – (0.52 x percent predicted carbon monoxide diffusing capacity). A significant relationship between the formula and observed emphysema extent was found in both cohorts (R2 = 0.25, P < 0.0001; R2 = 0.47, P < 0.0001, respectively). In both, the formula better predicted observed emphysema extent versus individual pulmonary function tests. A 15% emphysema extent threshold, calculated using the formula, identified a significant difference in absolute changes from baseline in forced vital capacity at Week 48 in patients with baseline-predicted emphysema extent < 15% versus ≥ 15% (P = 0.0105). Conclusion: The formula, designed for use in patients with IPF and emphysema, demonstrated enhanced ability to predict emphysema extent versus individual pulmonary function tests. Trial registration: NCT00047645; NCT00075998. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) due to interstitial lung disease (ILD), a commonly encountered complication of fibrotic ILDs, is associated with significant morbidity and mortality. Until recently, the studies of pulmonary vasodilator therapy in PH‐ILD have been largely disappointing, with some even demonstrating the potential for harm. This paper is part of a series of Consensus Statements from the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative for Group 3 Pulmonary Hypertension, with prior publications covering pathogenesis, prevalence, clinical features, phenotyping, clinical trials, and impact of PH‐ILD. It offers a comprehensive review of and a holistic approach to treatment of PH‐ILD, including the management of underlying interstitial lung diseases, importance of treating the comorbidities, emphasis on importance of exercise and palliation of dyspnea, and review of the most up‐to‐date guidelines for referral for potential lung transplant work up. It also summarizes the prior, ongoing, and possibly future studies in treatment of the vascular derangement of this morbid condition. [ABSTRACT FROM AUTHOR]

Usual Interstitial Pneumonia (UIP) is characterized by progression of lung parenchyma that may be observed in various autoimmune rheumatic diseases (ARDs), including rheumatoid arthritis and connective tissue diseases. From a diagnostic point of view, a UIP pattern related to ARDs may display imaging and pathological features able to distinguish it from that related to IPF, such as the "straight-edge" sign at HRCT and lymphoplasmacytic infiltrates at histologic specimens. Multidisciplinary approach (MDD), involving at least pulmonologist, rheumatologist and radiologist, is fundamental in the differential diagnosis process, but MDD is also required in the evaluation of severity, progression and response to treatment, that is based on the combination of changes in symptoms, pulmonary function trends, and, in selected patients, serial CT evaluation. Differently from IPF, in patients with ARDs both functional evaluation and patient-reported outcomes may be affected by systemic involvement and comorbidities, including musculoskeletal manifestations of disease. Finally, in regards to pharmacological treatment, immunosuppressants have been considered the cornerstone of therapy, despite the lack of solid evidence in most cases; recently, antifibrotic drugs were also proposed for the treatment of progressive fibrosing ILDs other than IPF. In ARD-ILD, the therapeutic choice should balance the need for the control of systemic and lung involvements with the risk of adverse events from multi-morbidities and -therapies. Purpose of this review is to summarize the definition, the radiological and morphological features of the UIP pattern in ARDs, together with risk factors, diagnostic criteria, prognostic evaluation, monitoring and management approaches of the UIP-ARDs. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) is a common complication of chronic lung diseases, particularly in chronic obstructive pulmonary disease (COPD) and interstitial lung diseases (ILD) and especially in advanced disease. It is associated with greater mortality and worse clinical course. Given the high prevalence of some respiratory disorders and because lung parenchymal abnormalities might be present in other PH groups, the appropriate diagnosis of PH associated with respiratory disease represents a clinical challenge. Patients with chronic lung disease presenting symptoms that exceed those expected by the pulmonary disease should be further evaluated by echocardiography. Confirmatory right heart catheterization is indicated in candidates to surgical treatments, suspected severe PH potentially amenable with targeted therapy, and, in general, in those conditions where the result of the hemodynamic assessment will determine treatment options. The treatment of choice for these patients who are hypoxemic is long-term oxygen therapy and pulmonary rehabilitation to improve symptoms. Lung transplant is the only curative therapy and can be considered in appropriate cases. Conventional vasodilators or drugs approved for pulmonary arterial hypertension (PAH) are not recommended in patients with mild-to-moderate PH because they may impair gas exchange and their lack of efficacy shown in randomized controlled trials. Patients with severe PH (as defined by pulmonary vascular resistance >5 Wood units) should be referred to a center with expertise in PH and lung diseases and ideally included in randomized controlled trials. Targeted PAH therapy might be considered in this subset of patients, with careful monitoring of gas exchange. In patients with ILD, inhaled treprostinil has been shown to improve functional ability and to delay clinical worsening. [ABSTRACT FROM AUTHOR]

Background: Idiopathic pulmonary fibrosis (IPF) is one of the most aggressive forms of interstitial lung diseases (ILDs), marked by an ongoing, chronic fibrotic process within the lung tissue. IPF leads to an irreversible deterioration of lung function, ultimately resulting in an increased mortality rate. Therefore, the focus has shifted towards the biomarkers that might contribute to the early diagnosis, risk assessment, prognosis, and tracking of the treatment progress, including those associated with epithelial injury. Methods: We conducted this review through a systematic search of the relevant literature using established databases such as PubMed, Scopus, and Web of Science. Selected articles were assessed, with data extracted and synthesized to provide an overview of the current understanding of the existing biomarkers for IPF. Results: Signs of epithelial cell damage hold promise as relevant biomarkers for IPF, consequently offering valuable support in its clinical care. Their global and standardized utilization remains limited due to a lack of comprehensive information of their implications in IPF. Conclusions: Recognizing the aggressive nature of IPF among interstitial lung diseases and its profound impact on lung function and mortality, the exploration of biomarkers becomes pivotal for early diagnosis, risk assessment, prognostic evaluation, and therapy monitoring. [ABSTRACT FROM AUTHOR]

Interstitial lung disease and airway disease (AD) are often complicated with rheumatoid arthritis (RA) and have a poor prognosis. Several studies reported genetic associations with interstitial lung disease in RA. However, few genetic studies have examined the susceptibility to AD in RA patients. Here, we investigated whether single nucleotide variants susceptible to idiopathic pulmonary fibrosis might be associated with interstitial lung disease or AD in Japanese RA patients. Genotyping of rs2736100 [C/A] in TERT and rs1278769 [G/A] in ATP11A was conducted in 98 RA patients with usual interstitial pneumonia, 120 with nonspecific interstitial pneumonia (NSIP), 227 with AD, and 422 without chronic lung disease using TaqMan assays. An association with AD in RA was found for rs2736100 (p = 0.0043, Pc = 0.0129, odds ratio [OR] 1.40, 95% confidence interval [CI] 1.11–1.77). ATP11A rs1278769 was significantly associated with NSIP in older RA patients (>65 years, p = 0.0010, OR 2.15, 95% CI 1.35–3.40). This study first reported an association of rs2736100 with AD in RA patients and ATP11A rs1278769 with NSIP in older RA patients. [ABSTRACT FROM AUTHOR]

Background: Among present reports, the T/G allelic variation at the rs2609255 locus of the family sequence similarity gene 13A (FAM13A) was considerable associated with susceptibility to interstitial lung diseases (ILDs). In this study, we summarized relevant studies and applied a meta‐analysis to explore whether the polymorphism of rs2609255 site of the FAM13A gene can be utilized to predict susceptibility to idiopathic pulmonary fibrosis (IPF) patients or rheumatoid arthritis‐associated interstitial lung disease (RA‐ILD) or silicosis patients in different populations for the first time. Methods: We compared the frequency of G allele on rs2609255 site of FAM13A between the control subjects and IPF or RA‐ILD or silicosis patients from different races by using meta‐analysis. Nine studies were involved in this meta‐analysis, including five IPF studies, two RA‐ILD studies, and two silicosis studies, and containing 14 subgroups. We conducted separate meta‐analyses for different races. Results: In all individuals, a substantial link between the G allele of the FAM13A rs2609255 polymorphism and IPF (OR: 1.47, 95% CI: 1.33–1.63, p < 0.00001) was indicated. After dividing by ethnicity, the G allele was illustrated to be considerable correlation with IPF in Asian (OR: 2.63, 95% CI: 1.81–3.81, p < 0.00001) and with RA‐ILD individuals (OR: 3.27, 95% CI: 1.26–8.49, p = 0.01). Conversely, there was no correlation with the G allele and IPF in European individuals (OR: 1.27, 95% CI: 0.89–1.83, p = 0.13) or silicosis in Chinese individuals (OR: 1.20, 95% CI: 0.99–1.46, p = 0.07). Conclusion: This is the first meta‐analysis that provides evidence that the rs2609255 of FAM13A might increase susceptibility to RA‐ILD, and IPF especially in Asian but not in European individuals, and not be correlated with silicosis in Chinese individuals, which indicated the differences in susceptibility to disease by race were noteworthy. [ABSTRACT FROM AUTHOR]

Background and Objective: Little is known about the association between ambient air pollution and idiopathic pulmonary fibrosis (IPF) in areas with lower levels of exposure. We aimed to investigate the impact of air pollution on lung function and rapid progression of IPF in Australia. Methods: Participants were recruited from the Australian IPF Registry (n = 570). The impact of air pollution on changes in lung function was assessed using linear mixed models and Cox regression was used to investigate the association with rapid progression. Results: Median (25th–75th percentiles) annual fine particulate matter (<2.5 μm, PM2.5) and nitrogen dioxide (NO2) were 6.8 (5.7, 7.9) μg/m3 and 6.7 (4.9, 8.2) ppb, respectively. Compared to living more than 100 m from a major road, living within 100 m was associated with a 1.3% predicted/year (95% confidence interval [CI] −2.4 to −0.3) faster annual decline in diffusing capacity of the lungs for carbon monoxide (DLco). Each interquartile range (IQR) of 2.2 μg/m3 increase in PM2.5 was associated with a 0.9% predicted/year (95% CI −1.6 to −0.3) faster annual decline in DLco, while there was no association observed with NO2. There was also no association between air pollution and rapid progression of IPF. Conclusion: Living near a major road and increased PM2.5 were both associated with an increased rate of annual decline in DLco. This study adds to the evidence supporting the negative effects of air pollution on lung function decline in people with IPF living at low‐level concentrations of exposure. [ABSTRACT FROM AUTHOR]

Both lung carcinoma and idiopathic pulmonary fibrosis (IPF) have an adverse prognosis, and the co-existence of both diseases is not uncommon. We introduce a clinical case involving a patient diagnosed with concurrent occurrences of lung adenocarcinoma and IPF. The patient underwent a therapeutic regimen comprising the administration of docetaxel in conjunction with nintedanib. This treatment approach was followed by the sustained utilization of maintenance nintedanib over an extended duration, leading to substantial enhancements in the patient’s quality of life. Furthermore, we discuss the few therapeutic options concerning this clinical challenge and possible future therapeutic options. [ABSTRACT FROM AUTHOR]

Background: Biomarkers have been proposed as tools to aid in the identification and prognostication of interstitial lung disease (ILD) in rheumatoid arthritis (RA). We performed a systematic review of studies evaluating peripheral blood biomarkers and their association with RA‐ILD and its prognosis. Methods: Medline, Embase, the Cochrane Library, and Scopus were queried for relevant studies, with the final search update on July 12, 2021. We included studies evaluating peripheral blood biomarkers for the identification and/or prognostication of RA‐ILD, extracting the performance of individual biomarkers for identifying RA‐ILD, and predicting prognosis. Modified versions of the Quality Assessment of Diagnostic Accuracy Studies 2 and the Quality in Prognosis Studies tools were used for quality assessment. Results: Seventy studies met eligibility criteria. Study and patient characteristics, analytical methods, strength and consistency of associations, and study quality were heterogeneous. A total of 92 biomarkers were positively associated and 12 were negatively associated with RA‐ILD among patients with RA in one or more report. Only a small number of biomarkers were evaluated in multiple cohorts using adjusted analyses. Biomarkers most strongly associated with RA‐ILD overlapped with those identified for idiopathic pulmonary fibrosis. Few prognostic biomarkers of RA‐ILD were identified. Conclusion: Several peripheral blood biomarkers are associated with the presence of RA‐ILD, but few have been assessed in multivariable models, have been externally validated, have discriminated RA‐ILD from other lung disease, or have prognosticated the disease course. High‐quality studies investigating and validating peripheral biomarkers in RA‐ILD are needed before they can be employed in clinical care. [ABSTRACT FROM AUTHOR]

Background: Tripartite motif (TRIM) family genes get involved in the pathogenesis and development of various biological processes; however, the prognostic value of TRIM genes for idiopathic pulmonary fibrosis (IPF) needs to be explored. Methods: We acquired gene expression based on bronchoalveolar lavage (BAL) cells and clinical data of three independent IPF cohorts in the GSE70866 dataset from the Gene expression omnibus (GEO) database. Differentially expressed TRIM genes (DETGs) between IPF patients and healthy donors were identified and used to establish a risk signature by univariate and multivariate Cox regression analysis in the training cohort. The risk signature was further validated in other IPF cohorts, and compared with previously published signatures. Moreover, we performed functional enrichment analysis to explore the potential mechanisms. Eventually, the quantitative real time PCR was conducted to validate the expressions of the key genes in BAL from 12 IPF patients and 12 non-IPF controls from our institution. Results: We identified 4 DETGs including TRIM7, MEFV, TRIM45 and TRIM47 significantly associated with overall survival (OS) of IPF patients (P < 0.05). A multiple stepwise Cox regression analysis was performed to construct a 4-TRIM-gene prognostic signature. We categorized IPF patients into one low-risk group and the other high-risk group as per the average risk value of the TRIM prognostic signature in the training and validation cohorts. The IPF individuals in the low-risk group demonstrated an obvious OS advantage compared with the high-risk one (P < 0.01). The time-dependent receiver operating characteristic approach facilitated the verification of the predictive value of the TRIM prognostic signature in the training and validation cohorts, compared with other published signatures. A further investigation of immune cells and IPF survival displayed that higher proportion of resting memory CD4+ T cells and resting mast cells harbored OS advantage over lower proportion, however lower proportion of neutrophils, activated dendritic cells and activated NK cells indicated worse prognosis. Conclusion: The TRIM family genes are significant for the prognosis of IPF and our signature could serve as a robust model to predict OS. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to assess clinical and imaging features of rheumatoid arthritis (RA) associated with interstitial lung disease (ILD), (RA-ILD) group, in comparison to RA without ILD (RA-C) and to identify the associated factors to ILD. Methods: This was a retrospective comparative study (from June 2015 to March 2022) including RA patients aged =18 years. The RA-C control group was matched according to age (±2 years), gender, and RA duration (±2 years). General data, RA characteristics, ILD features, and treatment modalities were recorded. Statistical analysis was performed to determine the predictive factors of ILD. Results: A total of 104 patients were included (52 RA-ILD and 52 RA-C); sex ratio was 0.36. Mean age was 66.3±11 years (RA-ILD) versus 65.6±10.8 years (RA-C) (p=0.72). In comparison to RA-C, RA-ILD patients were significantly higher smokers (p=0.01) and physically inactive (p=0.01). Regarding RA features, RA-ILD patients have significantly increased positive anti-citrullinated peptide antibody (ACPA) (p=0.01), ACPA rate (p<0.001), erosive disease (p<0.001), and disease activity score (p<0.001). Mean time to ILD diagnosis was 5.85±7.16 years. Chest high-resolution computed tomography (HRCT) patterns of disease were identified: nonspecific interstitial pneumonia (NSIP) (28.8%), usual interstitial pneumonia (UIP) (17.3%), organizing pneumonia (OP) (25%), acute interstitial pneumonia (13.5%), and respiratory bronchiolitis (3.8%). Multivariate analysis identified smoking, high baseline DAS28 (disease activity score 28) and ACPA positivity as predictive factors of ILD. Conclusion: Our results confirmed the reported associated factors of ILD in RA (smoking, higher disease activity, ACPA positivity). Thus, we need to target the modifiable factors by supporting and educating RA patients to quit smoking and intensify disease modifying anti-rheumatoid drugs (DMARD) to reach remission. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant activation of the alveolar epithelium, the expansion of the fibroblast population, and the accumulation of extracellular matrix. Global gene expression of human lung fibroblasts stimulated with TGFβ-1, a strong fibrotic mediator revealed the overexpression of ZNF365, a zinc finger protein implicated in cell cycle control and telomere stabilization. We evaluated the expression and localization of ZNF365 in IPF lungs and in the fibrotic response induced by bleomycin in WT and deficient mice of the orthologous gene Zfp365. In IPF, ZNF365 was overexpressed and localized in fibroblasts/myofibroblasts and alveolar epithelium. Bleomycin-induced lung fibrosis showed an upregulation of Zfp365 localized in lung epithelium and stromal cell populations. Zfp365 KO mice developed a significantly higher fibrotic response compared with WT mice by morphology and hydroxyproline content. Silencing ZNF365 in human lung fibroblasts and alveolar epithelial cells induced a significant reduction of growth rate and increased senescence markers, including Senescence Associated β Galactosidase activity, p53, p21, and the histone variant γH2AX. Our findings demonstrate that ZNF365 is upregulated in IPF and experimental lung fibrosis and suggest a protective role since its absence increases experimental lung fibrosis mechanistically associated with the induction of cell senescence. [ABSTRACT FROM AUTHOR]

Aim: Combined pulmonary fibrosis and emphysema (CPFE) and idiopathic pulmonary fibrosis (IPF) have been discussed intensively in recent years as two different entities. We aimed to compare the clinical, functional and respiratory parameters, clinical course and mortality rates of patients with CPFE and IPF. Materials and Methods: 36 patients with a diagnosis of CPFE and 40 IPF who applied between September 2013 and February 2019 were retrospectively included in the study. Demographic data, comorbidities, pulmonary function parameters, mortality, systolic pulmonary artery pressures(sPAP) recorded. Results: In the CPFE patient group, the ratio of male patients (p=0.02), smoking history (p=0.00), frequency of acute exacerbation (p=0.001) were found to be significantly higher, SF-36 total score (p=0.000) were significantly lower than IPF group. While FVC% (p=0.00), FEV1% (p=0.049) and TLC% (p=0.002) were significantly higher in the CPFE group than IPF group, TLCO% (p=0.002) and FEV1/FVC (p=0.00) was lower. Pulmonary hypertension (PH) was 40% in CPFE and 37% in IPF and no significant difference was found between them (p=0.806). Those who received long-term oxygen therapy (LTOT) were more common in the CPFE group (p=0.04). In CPFE patients; the percentage of those who treated with bronchodilator, antifibrotic, systemic corticosteroid was respectively 52.7%, 36.1%, 5.6%. Mortality from any cause was 9(25%) in CPFE and 8(20%) in IPF, and there was no significant difference between the two groups (p=0.601). Conclusion: It was observed that lung volumes were preserved and gas exchange of the lung was significantly decreased in patients with CPFE. Compared to IPF, the quality of life was lower and acute exacerbation was more common in CPFE. The frequency of PH and mortality were similar in both groups. Male gender and smoking history were important risk factors for CPFE patients. There is a need for multicenter studies reporting the clinical features, prognosis, and mortality of CPFE. [ABSTRACT FROM AUTHOR]

Purpose: To assess the impact of concomitant emphysema on outcomes in patients with idiopathic pulmonary fibrosis (IPF). Methods: The IPF-PRO Registry is a US registry of patients with IPF. The presence of combined pulmonary fibrosis and emphysema (CPFE) at enrollment was determined by investigators' review of an HRCT scan. Associations between emphysema and clinical outcomes were analyzed using Cox proportional hazards models. Results: Of 934 patients, 119 (12.7%) had CPFE. Compared with patients with IPF alone, patients with CPFE were older (median 72 vs 70 years); higher proportions were current/former smokers (88.2% vs 63.7%), used oxygen with activity (49.6% vs 31.9%) or at rest (30.8% vs 18.4%), had congestive heart failure (13.6% vs 4.8%) and had prior respiratory hospitalization (25.0% vs 16.7%); they had higher FVC (median 71.8 vs 69.4% predicted) and lower DLco (median 35.3 vs 43.6% predicted). In patients with CPFE and IPF alone, respectively, at 1 year, rates of death or lung transplant were 17.5% (95% CI: 11.7, 25.8) and 11.2% (9.2, 13.6) and rates of hospitalization were 21.6% (14.6, 29.6) and 20.6% (17.9, 23.5). There were no significant associations between emphysema and any outcome after adjustment for baseline variables. No baseline variable predicted outcomes better in IPF alone than in CPFE. Conclusion: Approximately 13% of patients in the IPF-PRO Registry had CPFE. Physiologic characteristics and comorbidities of patients with CPFE differed from those of patients with IPF alone, but the presence of emphysema did not drive outcomes after adjustment for baseline covariates. Trial registration: ClinicalTrials.gov, NCT01915511; registered August 5, 2013. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to assess clinical and imaging features of rheumatoid arthritis (RA) associated with interstitial lung disease (ILD), (RA-ILD) group, in comparison to RA without ILD (RA-C) and to identify the associated factors to ILD. Methods: This was a retrospective comparative study (from June 2015 to March 2022) including RA patients aged ≥18 years. The RA-C control group was matched according to age (±2 years), gender, and RA duration (±2 years). General data, RA characteristics, ILD features, and treatment modalities were recorded. Statistical analysis was performed to determine the predictive factors of ILD. Results: A total of 104 patients were included (52 RA-ILD and 52 RA-C); sex ratio was 0.36. Mean age was 66.3±11 years (RA-ILD) versus 65.6±10.8 years (RA-C) (p=0.72). In comparison to RA-C, RA-ILD patients were significantly higher smokers (p=0.01) and physically inactive (p=0.01). Regarding RA features, RA-ILD patients have significantly increased positive anti-citrullinated peptide antibody (ACPA) (p=0.01), ACPA rate (p<0.001), erosive disease (p<0.001), and disease activity score (p<0.001). Mean time to ILD diagnosis was 5.85±7.16 years. Chest high-resolution computed tomography (HRCT) patterns of disease were identified: nonspecific interstitial pneumonia (NSIP) (28.8%), usual interstitial pneumonia (UIP) (17.3%), organizing pneumonia (OP) (25%), acute interstitial pneumonia (13.5%), and respiratory bronchiolitis (3.8%). Multivariate analysis identified smoking, high baseline DAS28 (disease activity score 28) and ACPA positivity as predictive factors of ILD. Conclusion: Our results confirmed the reported associated factors of ILD in RA (smoking, higher disease activity, ACPA positivity). Thus, we need to target the modifiable factors by supporting and educating RA patients to quit smoking and intensify disease modifying anti-rheumatoid drugs (DMARD) to reach remission. [ABSTRACT FROM AUTHOR]

Background: Multiple studies have revealed that idiopathic pulmonary fibrosis (IPF) patients are more at risk for cardiovascular diseases and that many IPF patients receive cardiovascular medications like statins, angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), and anticoagulants. Existing studies have reported divergent findings on the link between cardiovascular medications and fibrotic disease processes. The aim of this study is to synthesize the evidence on the efficacy of cardiovascular medications in IPF. Methods: We searched studies reporting the effect of cardiovascular medications on IPF in the PubMed, Embase, Web of Science, Cochrane Library, and two Chinese databases (China National Knowledge Infrastructure database and China Wanfang database). We calculated survival data, forced vital capacity (FVC) decline, and IPF-related mortality to assess the efficacy of cardiovascular medications in IPF. We also estimated statistical heterogeneity by using I2 and Cochran Q tests, and publication bias was evaluated by risk of bias tools ROBINS-I. Results: A total of 12 studies were included in the analysis. The included studies had moderate-to-serious risk of bias. Statin use was associated with a reduction in mortality (hazard ratio (HR), 0.89; 95% CI 0.83–0.97). Meta-analysis did not demonstrate any significant relationship between statin use and the FVC decline (HR, 0.86; 95% CI 0.73–1.02), ACEI/ARB use, and survival data (HR, 0.92; 95% CI 0.73–1.15) as well as anticoagulant use and survival data (HR, 1.16; 95% CI 0.62–2.19). Conclusion: Our study suggested that there is a consistent relationship between statin therapy and survival data in IPF population. However, there is currently insufficient evidence to conclude the effect of ACEI, ARB, and anticoagulant therapy on IPF population especially to the disease-related outcomes in IPF. [ABSTRACT FROM AUTHOR]

Background: Interstitial lung disease (ILD) is a common and potentially life-threatening complication for rheumatoid arthritis (RA) patients. However, there is a lack of clear prognostic factors in rheumatoid arthritis-associated interstitial lung disease (RA-ILD) patients. The purpose of this study was to complete a systematic review and meta-analysis of the factors associated with mortality in RA-ILD patients.Methods: Medline, EMBASE and the Cochrane Library were searched up to September 1, 2020. The Newcastle-Ottawa Scale (NOS) was applied to assess the methodological quality of the eligible studies. Study characteristics and magnitude of effect sizes were extracted. Then, pooled hazard ratios (HRs) with the corresponding 95% confidence intervals (CIs) and pooled risk ratios (RRs) with 95% CIs were calculated to assess the factors associated with mortality in RA-ILD.Results: Twenty-three of 3463 articles were eligible, and ten factors associated with mortality for RA-ILD were evaluated in the meta-analysis. Older age (HRs = 1.04, 95% CI 1.03-1.05), male sex (HRs = 1.44, 95% CI 1.21-1.73), having a smoking history (HRs = 1.42, 95% CI 1.03-1.96), lower diffusing capacity of the lung for carbon monoxide (DLCO)% predicted (HRs = 0.98, 95% CI 0.97-1.00), forced vital capacity (FVC)% predicted (HRs = 0.99, 95% CI 0.98-1.00), composite physiological index (CPI) (HRs = 1.04, 95% CI 1.02-1.06), usual interstitial pneumonia (UIP) pattern on HRCT (HRs = 1.88, 95% CI 1.14-3.10 and RRs = 1.90, 95% CI 1.50-2.39), emphysema presence (HRs = 2.31, 95% CI 1.58-3.39), and acute exacerbation of ILD (HRs = 2.70, 95% CI 1.67-4.36) were associated with increased mortality in RA-ILD, whereas rheumatoid factor (RF) positive status was not associated.Conclusions: Through this systematic review and meta-analysis, we found that older age, male sex, smoking history, higher CPI, lower DLCO% predicted, lower FVC% predicted, UIP pattern on HRCT, emphysema presence and acute exacerbation of ILD were associated with an increased risk of mortality in RA-ILD. [ABSTRACT FROM AUTHOR]

The month of September is Pulmonary Fibrosis Awareness Month. In this context, we would like to highlight the concept of progressive pulmonary fibrosis, a common denominator/phenotype of many interstitial lung diseases other than idiopathic pulmonary fibrosis, leading to clinical deterioration, decreased quality of life, and high mortality. [ABSTRACT FROM AUTHOR]

Interstitial lung disease (ILD) represents a frequent extra-articular manifestation of rheumatoid arthritis (RA) deeply impacting both quality of life and overall prognosis. Areas covered: A literature search was performed including PubMed, Embase, Scopus, and Web of Science. Many retrospective studies investigated the possible risk factors for RA-related ILD (RA-ILD), aiming to identify patients at risk. Among them, males, smokers, positivity of anti-citrullinated peptide antibodies have been associated with RA-ILD, such as some genetic haplotypes. Usual interstitial pneumonia is the histologic and radiologic pattern most frequently observed, followed by nonspecific interstitial pneumonia. Since lung involvement can represent the RA onset, an early differential diagnosis with idiopathic interstitial pneumonia can be difficult or sometimes impossible. High-resolution computed tomography represents the gold standard for ILD diagnosis, while multidisciplinary discussion should be required to assess disease staging, severity and progression. Expert opinion: Management of RA-ILD patients is challenging due to the lack of evidence-based data regarding both assessment and treatment. Moreover, the high variability of clinical presentation and evolution makes it difficult to establish the correct therapeutic strategy. Currently, multidisciplinary approach, including at least rheumatologists, pulmonologists, and radiologists, is desirable to define therapy and follow-up strategies. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disorder with an estimated median survival time of 3-5 years after diagnosis. This condition occurs primarily in elderly subjects, and epidemiological studies suggest that the main risk factors, ageing and exposure to cigarette smoke, are associated with both pulmonary and extrapulmonary comorbidities (defined as the occurrence of two or more disorders in a single individual). Ageing and senescence, through interactions with environmental factors, may contribute to the pathogenesis of IPF by various mechanisms, causing lung epithelium damage and increasing the resistance of myofibroblasts to apoptosis, eventually resulting in extracellular matrix accumulation and pulmonary fibrosis. As a paradigm, syndromes featuring short telomeres represent archetypal premature ageing syndromes and are often associated with pulmonary fibrosis. The pathophysiological features induced by ageing and senescence in patients with IPF may translate to pulmonary and extrapulmonary features, including emphysema, pulmonary hypertension, lung cancer, coronary artery disease, gastro-oesophageal reflux, diabetes mellitus and many other chronic diseases, which may lead to substantial negative consequences in terms of various outcome parameters in IPF. Therefore, the careful diagnosis and treatment of comorbidities may represent an outstanding chance to improve quality of life and survival, and it is necessary to contemplate all possible management options for IPF, including early identification and treatment of comorbidities. [ABSTRACT FROM AUTHOR]

Background: The different types of pulmonary fibrosis are a subgroup of the interstitial lung diseases (ILDs). They are associated with a chronic and often progressive course. Methods: This review is based on pertinent publications retrieved by a selective search in the EMBASE and PubMed databases, with an emphasis on articles published from 2000 to 2020. Results: The most common type of pulmonary fibrosis is idiopathic pulmonary fibrosis (IPF). Among other relevant types, the most important ones are fibrosing hypersensitivity pneumonitis (fHP) and ILDs associated with systemic diseases, all of which are rare and generally carry a poor prognosis. The essential prerequisite to accurate diagnosis is aninterdisciplinary approach, taking account of the clinical, histological, and radiological aspects. The main complications of pulmonary fibrosis are acute exacerbations and pulmonary hypertension; comorbidities are also of prognostic relevance. Treatment of pulmonary fibrosis depends on the subtype and clinical behavior. For IPF, antifibrotic therapy is indicated; fHP, on the other hand, is mainly treated by antigen avoidance and immune modulation. The predominant mode of treatment for systemic disease-associated pulmonary fibrosis is immune suppression. Antifibrotic agents can also be useful in the treatment of other types of progressivepulmonary fibrosis besides IPF. Conclusion: The differential diagnosis of pulmonary fibrosis, though complex, is clinically essential, as different types of pulmonary fibrosis are treated differently. [ABSTRACT FROM AUTHOR]

Background: The antifibrotic drugs nintedanib and pirfenidone are used for the treatment of idiopathic pulmonary fibrosis (IPF). We analysed the association of common profibrotic polymorphisms in MUC5B (mucin 5B, rs35705950) and DSP (desmoplakin, rs2076295) on antifibrotic treatment outcomes in IPF. Methods: MUC5B rs35705950 and DSP rs2076295 were assessed in IPF patients (n = 210, 139 men/71 women) from the Czech EMPIRE registry and age- or sex-matched healthy individuals (n = 205, 125 men/80 women). Genetic data were collated with overall survival (OS), acute exacerbation episodes, worsening lung function and antifibrotic treatment. Results: We confirmed overexpression of the MUC5B rs35705950*T allele (55.2% versus 20.9%, p < 0.001) and the DSP rs2076295*G allele (80.4% versus 68.3%, p < 0.001) in IPF compared with controls. On antifibrotic drugs, lower mortability was observed in IPF patients with DSP G* allele (p = 0.016) and MUC5B T* allele (p = 0.079). Carriers of the DSP rs2076295*G allele benefitted from nintedanib treatment compared with TT genotype by a longer OS [hazard ratio (HR) = 7.99; 95% confidence interval (CI) = 1.56–40.90; p = 0.013] and a slower decline in lung function (HR = 8.51; 95% CI = 1.68–43.14; p = 0.010). Patients with a TT genotype (rs2076295) benefitted from treatment with pirfenidone by prolonged OS (p = 0.040; HR = 0.35; 95% CI = 0.13–0.95) compared with nintedanib treatment. Both associations were confirmed by cross-validation analysis. After stratifying by MUC5B rs35705950*T allele carriage, no difference in treatment outcome was observed for nintedanib or pirfenidone (p = 0.784). In the multivariate model, smoking, age, forced vital capacity (FVC) and DLCO (diffuse lung capacity) at the IPF diagnosis were associated with survival. Conclusion: Our real-world study showed that IPF patients with MUC5B T* allele or DSP G* allele profit from antifibrotic treatment by lower mortability. Moreover, carriers of the DSP rs2076295*G allele benefit from treatment with nintedanib, and TT genotype from treatment with pirfenidone. MUC5B rs35705950 did not impact the outcome of treatment with either nintedanib or pirfenidone. Our single-registry pilot study should be confirmed with an independent patient cohort. [ABSTRACT FROM AUTHOR]

Background: Interstitial lung disease (ILD) is a complex and heterogeneous group of acute and chronic lung diseases of several known and unknown causes. While clinical practice guidelines (CPG) for idiopathic pulmonary fibrosis (IPF) have been recently updated, CPG for ILD other than IPF are needed. Methods: A working group of multidisciplinary clinicians familiar with clinical management of ILD (pulmonologists, radiologist, pathologist, and rheumatologist) and three epidemiologists selected by the leaderships of Indian Chest Society and National College of Chest Physicians, India, posed questions to address the clinically relevant situation. A systematic search was performed on PubMed, Embase, and Cochrane databases. A modified GRADE approach was used to grade the evidence. The working group discussed the evidence and reached a consensus of opinions for each question following face-to-face discussions. Results: Statements have been made for each specific question and the grade of evidence has been provided after performing a systematic review of literature. For most of the questions addressed, the available evidence was insufficient and of low to very low quality. The consensus of the opinions of the working group has been presented as statements for the questions and not as an evidence-based CPG for the management of ILD. Conclusion: This document provides the guidelines made by consensus of opinions among experts following discussion of systematic review of evidence pertaining to the specific questions for management of ILD other than IPF. It is hoped that this document will help the clinician understand the accumulated evidence and help better management of idiopathic and nonidiopathic interstitial pneumonias. [ABSTRACT FROM AUTHOR]

Background: Previous analyses of combined pulmonary fibrosis and emphysema (CPFE) cohorts have provided conflicting data on the survival of patients with CPFE. Therefore, the aim of this study was to investigate the clinical prognosis of acute exacerbations (AE) of CPFE.Methods: We retrospectively reviewed the medical records of patients who had been treated at the Shinshu University Hospital (Matsumoto, Japan) between 2003 and 2017. We identified 21 patients with AE of CPFE and 41 patients with AE of idiopathic pulmonary fibrosis (IPF) and estimated their prognoses using the Kaplan-Meier method.Results: Treatment content and respiratory management were not significantly different between the two groups before and after exacerbation. At the time of AE, the median serum Krebs von den Lungen-6 level was significantly lower in the CPFE group (Krebs von den Lungen-6: 966 U/μL; white blood cell count: 8810 /μL) than that in the IPF group (Krebs von den Lungen-6: 2130 U/μL, p < 0.001; white blood cells: 10809/μL, p = 0.0096). The baseline Gender-Age-Physiology scores were not significantly different between the two groups (CPFE, 4.5 points; IPF, 4.7 points; p = 0.58). Kaplan-Meier curves revealed that the survival time after AE for patients with CPFE was longer than that for patients with IPF (p < 0.001, log-rank test).Conclusions: Survival prognoses after AE were significantly better for patients with CPFE than that for those with IPF. Our findings may improve the medical treatment and respiratory management of patients with AE-CPFE. [ABSTRACT FROM AUTHOR]

Nonspecific interstitial pneumonia (NSIP) is a complex disorder commonly associated with other conditions such as connective tissue diseases (CTDs) and environmental exposures. Although idiopathic NSIP has been recognized as a separate clinical entity, recent studies have suggested that a proportion of these cases have autoimmune features suggestive of underlying CTDs. The diagnosis of NSIP usually carries a better prognosis compared with idiopathic pulmonary fibrosis but has an unpredictable natural history. Its pathogenesis is thought to be an inflammatory-driven process involving multiple pathways, including a genetic predisposition. The lack of specific clinical features often makes the diagnosis of NSIP difficult. The huge variability of radiological and histological features seen in NSIP adds to the complexity of achieving an accurate diagnosis of NSIP and a multidisciplinary approach is often required. There is a lack of consensus on the optimal management strategy of NSIP. Early clarification of the goals of therapy and close monitoring for the progression of disease is important across the spectrum of NSIP irrespective of its etiology. Although immunosuppressive and immunomodulatory agents are commonly used for severe and progressive disease, the therapeutic landscape of NSIP is constantly evolving as the role of newer agents such as antifibrotic therapies is being explored. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) represents a condition included in the heterogeneous group of interstitial lung diseases without known causes. The recent ATS/ERS/JRS/ALAT guidelines and the white paper published by the Fleischner Society have well-defined diagnosis and management of idiopathic pulmonary fibrosis. Idiopathic pulmonary fibrosis management is complex because it is also influenced by several co-morbidities and complications. The new frontier in idiopathic pulmonary fibrosis is represented by the effort to understand the complex mechanism of the pathogenesis and progression of disease in order to predict several consequences and co-morbidities. In our review, we tried to distinguish co-morbidities from complications of idiopathic pulmonary fibrosis. In each complication, we have reviewed the existing literature and we have emphasized the complex pathobiological pathway which links the progression of idiopathic pulmonary fibrosis to the development of the complication itself. For every co-morbidity, we tried to identify share common risk factors which explain the coexistence of idiopathic pulmonary fibrosis with its co-morbidities. We then analyzed high-resolution computed tomography (CT) aspects of co-morbidities and complications of idiopathic pulmonary fibrosis that the radiologist should be aware of. In this review, we focused on the role of high-resolution CT imaging in the evaluation of co-morbidities and complications in idiopathic pulmonary fibrosis because their early diagnosis and treatment could change the prognosis in patients with idiopathic pulmonary fibrosis. We have also pointed out that in some cases the final combined quantitative CT tools and conventional visual CT score would allow to get an accurate analysis and quantification of disease progression, co-morbidities, and complications of idiopathic pulmonary fibrosis in order to improve staging systems in idiopathic pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Background: Combined pulmonary fibrosis and emphysema (CPFE) is a syndrome characterized by the coexistence of upper lobe emphysema and lower lobe fibrosis. However, whether CPFE has a higher or lower mortality than idiopathic pulmonary fibrosis (IPF) alone is still not clear. In this study we conducted a meta-analysis to assess the survival rate (SR) of CPFE versus IPF alone in clinical trials. Methods: We performed a systematic search of PubMed, Embase, and the Cochrane Central Register of Controlled Trials for trials published prior to 31 March 2018. Extracts from the literature were analyzed with Review Manager version 5.3. Results: Thirteen eligible trials were included in this analysis (involving 1710 participants). Overall, the pooled results revealed that no statistically significant difference was detected in the 1-year [relative risk (RR) = 0.98, 95% confidence interval (CI): 0.94–1.03, p = 0.47], 3-year (RR = 0.83, 95% CI: 0.68–1.01, p = 0.06), and 5-year (RR = 0.80, 95% CI: 0.59–1.07, p = 0.14) SRs of CPFE versus IPF alone. Conclusions: CPFE exhibits a very poor prognosis, similar to IPF alone. Additional studies are needed to provide more convincing data to investigate the natural history and outcome of patients with CPFE in comparison to IPF. The reviews of this paper are available via the supplemental material section. [ABSTRACT FROM AUTHOR]

Objectives: Interstitial lung disease (ILD) is a common extra-muscular manifestation of anti-synthetase syndrome (ASS) and the main cause of morbidity and mortality in patients with ASS. Data on prognostic factors in these patients are lacking.Methods: A total of 69 patients with ILD and positivity for at least one of the following autoantibodies were included: anti-Jo-1, anti-PL7, anti-PL12, and anti-EJ. Relevant clinical characteristics were registered. According to the changes in the extent of abnormalities at the follow-up on high-resolution computed tomography (HRCT), three groups were defined: the regression, stability, and deterioration groups. Univariate analysis was performed to evaluate possible prognostic factors and multivariate analysis by logistic regression was then applied to determine the independent prognostic factors in ASS-ILD.Results: The cohort comprised 69 patients positive for anti-synthetase antibodies, i.e., 30 for anti-Jo-1, 16 for anti-EJ, 13 for anti-PL7, and 10 for anti-PL12. The mean length of follow-up was 15 months. Sex, age at diagnosis, fever at presentation, and counts of CD3+CD4+ cells were significantly different among the three groups. According to the multivariate analysis, fever at presentation, lower counts of CD3+CD4+ cells, and a pattern of usual interstitial pneumonia were the three independent risk factors for poor outcomes of ASS-ILD.Conclusions: At the onset of ASS, some clinical features and HRCT pattern of ILD may suggest an unfavorable outcome of lung involvement on HRCT, even with routine therapy. These factors may contribute to the high long-term mortality of ASS.Key Points: • Evaluation of lung involvement on HRCT is important in the follow-up of patients with interstitial lung disease related to anti-synthetase syndrome (ASS-ILD). • The interstitial lung disease related to ASS responds to the treatment variably. • Some clinical and imaging characteristics are associated with poor prognosis in patients with ASS-ILD, including fever at diagnosis, a lower serum CD3 + /CD4 + level, and a UIP pattern. [ABSTRACT FROM AUTHOR]

Background and objective: This study evaluated whether patients with combined pulmonary fibrosis and emphysema (CPFE) have an increased likelihood of pulmonary hypertension (PHT) when compared with idiopathic pulmonary fibrosis (IPF) patients without emphysema. Methods: Two consecutive IPF populations having undergone transthoracic echocardiography were examined (n = 223 and n = 162). Emphysema and interstitial lung disease (ILD) extent were quantified visually; ILD extent was also quantified by a software tool, CALIPER. Echocardiographic criteria categorized PHT risk. Results: The prevalence of an increased PHT likelihood was 29% and 31% in each CPFE cohort. Survival at 12 months was 60% across both CPFE cohorts with no significantly worsened outcome identified when compared with IPF patients without emphysema. Using logistic regression models in both cohorts, total computed tomography (CT) disease extent (ILD and emphysema) predicted the likelihood of PHT. After adjustment for total disease extent, CPFE had no stronger association with PHT likelihood than IPF patients without emphysema. Conclusion: Our findings indicate that the reported association between CPFE and PHT is explained by the summed baseline CT extents of ILD and emphysema. Once baseline severity is taken into account, CPFE is not selectively associated with a malignant microvascular phenotype, when compared with IPF patients without emphysema. [ABSTRACT FROM AUTHOR]

Summary: Introduction: Prognostic factors of idiopathic pulmonary fibrosis (IPF) currently recognized include changes in vital capacity and radiologic findings. However, most of the prognostic studies in IPF are based on clinical studies with preselected IPF populations. Therefore, we decided to analyze the factors influencing IPF prognosis based on the real‐practice data from our IPF registry. Methods: Data of 514 subjects consecutively entered since 2012 into Czech EMPIRE IPF registry were analyzed. Results: Median age of our patient cohort was 67 years (50–82). Median overall survival (OS) of the cohort was 63.1 months. The clinical course of IPF according to FVC (forced vital capacity) changes was stabilized in 32.8% of patients (29.7% according to DLCO [diffuse lung capacity] changes), slowly progressive in 39.5% (45%), rapidly progressive in 23.5% (20.7%); and 1.7% patients had at least one acute exacerbation during follow‐up. Deterioration in FVC of ≥10% at month 12 and in DLCO of ≥15% at months 12, 18, and 24 influenced the OS significantly. The fast progressors defined by the DLCO decline rate had higher risk of death compared to those defined by the FVC change over time. In multivariate analysis, age ≥70 years, interstitial HRCT scores ≥3, and change in DLCO of ≥15% at month 12 were confirmed as factors negatively influencing OS. Conclusions: DLCO changes over time were shown as a better predictor of mortality compared with FVC changes in our study. In our opinion it is necessary to implement the DLCO analysis into clinical trials and routine practice. [ABSTRACT FROM AUTHOR]

Background: The prevalence of chronic kidney disease (CKD) increases with age as with idiopathic pulmonary fibrosis (IPF). Objectives: We assessed the prevalence of CKD (stages 3-5) and investigated the relationship of CKD to clinical features and outcomes in patients with IPF. Methods: This study comprised 123 patients with IPF; 61 subjects with chronic obstructive pulmonary disease (COPD), which was reportedly associated with CKD, were also enrolled as a disease control. CKD (stages 3-5) was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m². Results: Thirty-seven patients (30%) with IPF and 14 controls (23%) with COPD were diagnosed with CKD, and these frequencies were not significantly different. The patients with IPF and CKD were older (p < 0.01) and had a higher frequency of hypertension (p = 0.048) and ischemic heart disease (p = 0.02) than those with IPF but without CKD. Furthermore, the diffusing capacity of the lung for carbon monoxide (DLCO) and the 6-min walking distance in the patients with CKD were significantly lower (40.0 ± 13.2 vs. 45.9 ± 14.4%, p = 0.04, and 416 ± 129 vs. 474 ± 84 m, p = 0.01, respectively) than in the patients without CKD. The outcome of the patients with CKD showed significantly worse survival compared with the patients without CKD (p = 0.04). Moreover, eGFR remained an independent predictor of survival after adjusting for age and pulmonary function data. Conclusion: A substantial percentage of IPF patients have CKD. CKD with a low eGFR was associated with decreased survival in IPF. [ABSTRACT FROM AUTHOR]

Background: Chronic hypersensitivity pneumonitis (CHP) has a variable disease course. Computer analysis of CT features was used to identify a subset of CHP patients with an outcome similar to patients with idiopathic pulmonary fibrosis (IPF).Methods: Consecutive patients with a multi-disciplinary team diagnosis of CHP (n = 116) had pulmonary function tests (FEV1, FVC, DLco, Kco, and a composite physiologic index [CPI]) and CT variables predictive of mortality evaluated by analysing visual and computer-based (CALIPER) parenchymal features: total interstitial lung disease (ILD) extent, honeycombing, reticular pattern, ground glass opacities, pulmonary vessel volume (PVV), emphysema, and traction bronchiectasis. Mean survival was compared between both CHP and IPF patients (n = 185).Results: In CHP, visual/CALIPER measures of reticular pattern, honeycombing, visual traction bronchiectasis, and CALIPER ILD extent were predictive of mortality (p < 0 · 05) on univariate analysis. PVV was strongly predictive of mortality on univariate (p < 0 · 0001) and multivariate analysis independent of age, gender and disease severity (represented by the CPI [p < 0 · 01]). CHP patients with a PVV threshold >6 · 5% of the lung had a mean survival (35 · 3 ± 6 · 1 months; n = 20/116 [17%]) and rate of disease progression that closely matched IPF patients (38 · 4 ± 2 · 2 months; n = 185).Conclusions: Pulmonary vessel volume can identify CHP patients at risk of aggressive disease and a poor IPF-like prognosis. [ABSTRACT FROM AUTHOR]

Aims To evaluate pulmonary vasculopathy in an autopsy series of patients with combined pulmonary fibrosis and emphysema ( CPFE), and compare these findings with those of patients with idiopathic pulmonary fibrosis ( IPF) alone and emphysema alone. Methods and results We retrospectively analysed the clinical, radiological and pathological features of 26 patients with CPFE, 11 with IPF, and 23 with emphysema. We evaluated pulmonary vascular, venous-venular and arteriolar tissue changes in the fibrotic, emphysematous and relatively unaffected (preserved) areas by using the Heath-Edwards scoring system. We found moderate-to-severe vasculopathy in the CPFE group, but no significant differences in the fibrotic and emphysematous areas among the three groups. However, in the preserved area, the grading was significantly different among the three groups ( P < 0.001), and vasculopathy in the CPFE group was the most severe. Although venous-venular and arteriolar changes in almost all fibrotic and emphysematous areas in the three groups showed no significant differences, there were significant differences in venous-venular ( P = 0.004) and arteriolar ( P < 0.001) changes in the preserved area among the three groups, which were most prevalent in the CPFE group. In the CPFE group, venous-venular changes and vasculopathy by Heath-Edwards grading were highest in the fibrotic area and lowest in the preserved area. Conclusions These results imply that pulmonary vasculopathy in patients with CPFE could occur in the whole lung tissue. This may explain the tendency for it to lead to the development of pulmonary hypertension in CPFE cases. [ABSTRACT FROM AUTHOR]

Background: The prognosis of combined cases of pulmonary fibrosis and emphysema is unresolved partially because radiological differentiation between usual interstitial pneumonia and nonspecific interstitial pneumonia is difficult in coexisting emphysema cases. Objective:The purpose of this study was to clarify the clinical impact of emphysema on the survival of patients with idiopathic pulmonary fibrosis (IPF). Methods: One hundred and seven patients with interstitial lung diseases were diagnosed by surgical lung biopsies between 2006 and 2012, and 47 patients were diagnosed with IPF through multidisciplinary discussion. Emphysema on high-resolution computed tomography scans was evaluated semiquantitatively by visual scoring. Results: Eight out of the 47 IPF patients showed a higher emphysema score (>3) and were diagnosed to have IPF-emphysema. The median survival time of patients with IPF-emphysema (1,734 days) from the initial diagnosis was significantly shorter than that of patients with IPF alone (2,229 days) by Kaplan-Meier analysis (p = 0.007, log-rank test). Univariate Cox proportional hazard regression analyses revealed that a higher total emphysema score (>3.0) was a significantly poor prognostic factor in addition to Krebs von den Lungen-6, surfactant pro-tein-D, arterial oxygen tension, percent forced vital capacity, and percent diffusing capacity of carbon monoxide (%DLCO). Multivariate Cox proportional hazard regression analyses with the stepwise method showed that higher total emphysema score (>3) and %DLCO were significantly poor prognostic factors. Conclusions: The prognosis of IPF-emphysema was significantly worse than that of IPF alone. [ABSTRACT FROM AUTHOR]

Combined pulmonary fibrosis and emphysema is a relatively newly defined entity, which has been deeply studied in the recent years. Despite the wide numbers of papers on this topic, there are still several open questions about pathogenesis, epidemiology, natural history and prognosis. The diagnosis could be assessed only after HRCT scan as functional tests often result in an underestimation of this syndrome. What radiologists need to know about this syndrome consists in the heterogeneity of appearances: emphysema is mainly paraseptal and fibrotic pattern could be variable, including the variant of airspace enlargement with fibrosis which needs to be differentiated from honeycombing. A special attention must be paid on complications which could worsen the prognosis, such as pulmonary hypertension and lung cancer. Further studies are needed to address if the type of fibrotic pattern as well as fibrosis CT index could be considered as prognostic factors. Thus, the role of radiologists in the management of these patients is crucial as it involves diagnosis, detection of complications and could possible concerns the identification of patients at higher risk. [ABSTRACT FROM AUTHOR]