Aging (Albany NY). 2021 Jul 30;13(undefined). doi: 10.18632/aging.203335. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) mainly occurs in elderly people over the age of sixty. IPF pathogenesis is associated with alveolar epithelial cells (AECs) senescence. Activation of PI3K/AKT signaling induced by insulin-like growth factor 1 (IGF1) participates in AEC senescence and IPF by releasing CTGF, TGF-β1, and MMP9. Our previous study demonstrated that core fucosylation (CF) modification, catalyzed by a specific core fucosyltransferase (FUT8) can regulate the activation of multiple signaling pathways, and inhibiting CF can alleviate pulmonary fibrosis in mice induced by bleomycin. However, whether CF is involved in IGF1-mediated AEC senescence in IPF remains unclear. In this study, we found that the IGF1/PI3K/AKT signaling pathway was activated in IPF lung tissue. Meanwhile, CF was present in senescent AECs. We also showed that IGF1 could induce AECs senescence with enhanced CF in vivo and in vitro. Inhibiting CF alleviated AECs senescence and pulmonary fibrosis induced by IGF1. In addition, activation of IGF1/PI3K/AKT signaling depends on CF. In conclusion, this study confirmed that CF is an important target regulating the IGF1 signaling pathway in AEC senescence and IPF, which might be a candidate target to treat IPF in the future.

PMID:34329195 | DOI:10.18632/aging.203335

Ann Am Thorac Soc. 2021 Aug;18(8):1285-1286. doi: 10.1513/AnnalsATS.202105-536ED.

NO ABSTRACT

PMID:34328404 | DOI:10.1513/AnnalsATS.202105-536ED

Histopathology. 2021 Jul 30. doi: 10.1111/his.14530. Online ahead of print.

ABSTRACT

Telomere biology disorders (TBD), including dyskeratosis congenita (DC), are a group of accelerated aging diseases caused by mutations in genes encoding factors involved in telomere maintenance. Hepatic involvement affects 10-40% of TBD patients with nodular regenerative hyperplasia (NRH) and cirrhosis being the most common hepatic manifestations, both of which can result in portal hypertension (1-3). Lung involvement includes interstitial lung disease (ILD) such as idiopathic pulmonary fibrosis (IPF) and hepatopulmonary syndrome (HPS) which can be associated with portal hypertension. Vascular complications in TBD include pulmonary arteriovenous malformations, gastrointestinal telangiectasias and exudative vitreoretinopathy.

PMID:34327718 | DOI:10.1111/his.14530

Sci Rep. 2021 Jul 29;11(1):15502. doi: 10.1038/s41598-021-94907-w.

ABSTRACT

Several biomarkers for detecting pulmonary hypertension (PH) have been reported. However, these biomarkers are deemed insufficient to detect PH in its early stages. We evaluated the utility of serum angiopoietin (ANGP), a glycoprotein related to angiogenesis, as a diagnostic and prognostic biomarker of PH. Patients with PH who underwent right-heart catheterization, were retrospectively studied. Serum concentrations of ANGP-1 and ANGP-2 were measured using an enzyme-linked immunosorbent assay in patients with PH (n = 32), those with idiopathic pulmonary fibrosis (IPF) without PH (as a disease control, n = 75), and age-matched healthy controls (HC, n = 60). Nineteen patients (59.4%) with PH had World Health Organization group 3 PH. Serum ANGP-2 concentration, but not ANGP-1, in patients with PH was significantly higher compared with that in HC (p = 0.025) and in patients with IPF without PH (p = 0.008). Serum ANGP-2 concentration in patients with PH positively and significantly correlated with N-terminal pro-B-type natriuretic peptide (r = 0.769, p < 0.001), right ventricular diameter on echocardiography (r = 0.565, p = 0.035), and mean pulmonary arterial pressure (r = 0.449, p = 0.032) and pulmonary vascular resistance (r = 0.451, p = 0.031) on right-heart catheterization. ANGP-1 and ANGP-2 were expressed on lung vascular endothelial cells, as shown by immunohistochemistry. Patients with PH with higher ANGP-2 concentration (≥ 2.48 ng/mL) had significantly worse survival (p = 0.022). Higher ANGP-2 concentration was a significant worse prognostic factor (hazard ratio = 6.063, p = 0.037), while serum ANGP-1 concentration was not. In conclusion, serum ANGP-2 may be a useful diagnostic and prognostic biomarker in patients with PH, especially in patients with group 3 PH.

PMID:34326408 | DOI:10.1038/s41598-021-94907-w

Eur Respir J. 2021 Jul 29:2101531. doi: 10.1183/13993003.01531-2021. Online ahead of print.

NO ABSTRACT

PMID:34326190 | DOI:10.1183/13993003.01531-2021

BMJ Open Respir Res. 2021 Jul;8(1):e000889. doi: 10.1136/bmjresp-2021-000889.

ABSTRACT

BACKGROUND: Acute exacerbation (AE) has been reported to herald a poor prognosis in idiopathic pulmonary fibrosis and is now thought to do so in idiopathic interstitial pneumonias (IIPs). However, the pathophysiology of AE-IIPs is not sufficiently understood. In our previously reported SETUP trial, we found better survival in patients with AE-IIPs treated with corticosteroids and thrombomodulin than in those treated with corticosteroids alone. In that study, we collected serum samples to evaluate changes in cytokine levels and retrospectively examined the prognostic significance and pathophysiological role of serum cytokines in patients with AE-IIPs.

METHODS: This study included 28 patients from the SETUP trial for whom serial serum samples had been prospectively obtained. AE-IIPs were diagnosed using the Japanese Respiratory Society criteria. All patients were treated with intravenous thrombomodulin and corticosteroids from 2014 to 2016. Serum levels of 27 cytokines were measured using Bio-Plex. The high-resolution CT pattern at the time of diagnosis of AE was classified as diffuse or non-diffuse.

RESULTS: Univariate analysis revealed that higher serum levels of interleukin (IL)-2, IL-7, IL-9, IL-12, IL13, basic fibroblast growth factor, granulocyte-macrophage colony-stimulating factor, interferon-γ inducible protein-10, platelet-derived growth factor and regulated on activation, normal T cell expressed and secreted (RANTES) at AE were significant predictors of 90-day survival. The HRCT pattern was also a significant clinical predictor of 90-day survival. Multivariate analysis with stepwise selection identified a higher serum RANTES level at AE to be a significant predictor of 90-day survival, including after adjustment for HRCT pattern. Multivariate analysis with stepwise selection suggested that a marked increase in the serum IL-10 level on day 8 could predict 90-day mortality.

CONCLUSIONS: A higher serum RANTES level at AE the time of diagnosis predicted a good survival outcome, and an elevated serum IL-10 level on day 8 predicted a poor survival outcome.

TRIAL REGISTRATION NUMBER: UMIN000014969.

PMID:34326155 | DOI:10.1136/bmjresp-2021-000889

Chin Med. 2021 Jul 28;16(1):66. doi: 10.1186/s13020-021-00474-7.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a serious chronic disease of the respiratory system, but its current treatment has certain shortcomings and adverse effects. In this study, we evaluate the antifibrotic activity of pterostilbene (PTE) using an in vitro IPF model induced by transforming growth factor (TGF)-β1.

METHODS: A549 and alveolar epithelial cells (AECs) were incubated with 10 ng/ml TGF-β1 to induce lung fibroblast activation. Then, 30 μmol/L of PTE was used to treat these cells. The epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) accumulation, and autophagy in cells were evaluated by western blot. Apoptosis was validated by flow cytometry analysis and western blot. Transcriptome high-throughput sequencing was performed on A549 cells incubated with TGF-β1 alone or TGF-β1 and PTE (TGF-β1 + PTE), and differentially expressed genes in PTE-treated cells were identified. The acid sensing ion channel subunit 2 (ASIC2) overexpression plasmid was used to rescue the protein levels of ASIC2 in A549 and AECs.

RESULTS: TGF-β1 caused EMT and ECM accumulation, and blocked the autophagy and apoptosis of A549 and AECs. Most importantly, 30 μmol/L of PTE inhibited pulmonary fibrosis induced by TGF-β1. Compared with TGF-β1, PTE inhibited EMT and ECM accumulation and rescued cell apoptosis and autophagy. The results of transcriptome high-throughput sequencing revealed that PTE greatly reduced the protein level of ASIC2. Compared with the TGF-β1 + PTE group, the transfection of ASIC2 overexpression plasmid stimulated the EMT and ECM accumulation and inhibited apoptosis and autophagy, suggesting that PTE inhibited pulmonary fibrosis by downregulating ASIC2.

CONCLUSIONS: This study suggests that PTE and ASIC2 inhibitors may have potential as IPF treatments in the future.

PMID:34321072 | DOI:10.1186/s13020-021-00474-7

Int Immunol. 2021 Jul 28:dxab048. doi: 10.1093/intimm/dxab048. Online ahead of print.

ABSTRACT

Regulation of messenger RNA (mRNA) decay plays a crucial role in the control of gene expression. Canonical mRNA decay pathways are initiated by deadenylation and decapping, and are followed by exonucleolytic degradation. However, recent studies revealed that endoribonucleolytic cleavage also mediates mRNA decay, and both exoribonucleolytic and endoribonucleolytic decay pathways are important for the regulation of immune responses. Regnase-1 functions as an endoribonuclease to control immunity by damping mRNAs. Particularly, Regnase-1 controls cytokines and other inflammatory mediators by recognizing their mRNAs via stem-loop structures present in the 3' untranslated regions. Regnase-1 was found to be critical for human inflammatory diseases such as ulcerative colitis and idiopathic pulmonary fibrosis. Furthermore, a set of Regnase-1-related RNases contribute to immune regulation as well as antiviral host defense. In this review, we provide an overview of recent findings as to immune-related RNA-binding proteins (RBPs) with an emphasis on stem-loop-mediated mRNA decay via Regnase-1 and related RNases and discuss how the function of these RBPs is regulated and contributes to inflammatory disorders.

PMID:34320195 | DOI:10.1093/intimm/dxab048

J Mater Chem B. 2021 Jul 28. doi: 10.1039/d1tb01307f. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a devastating and fatal interstitial lung disease due to various challenges in diagnosis and treatment. Due to its complicated pathogenesis and difficulty in early diagnosis, there is no effective cure. Cyclooxygenase-2 (COX-2) is inextricably associated with pulmonary fibrosis. The abnormal level of COX-2 leads to extremely exacerbated pulmonary fibrosis. Therefore, we reported a near-infrared fluorescent probe Cy-COX to detect the fluctuation of COX-2 levels during pulmonary fibrosis and explain its important protective effect. The probe Cy-COX showed a significant enhancement of fluorescence signal to COX-2 with excellent selectivity and sensitivity. In order to clarify the relationship between COX-2 and pulmonary fibrosis, we used the probe Cy-COX to detect COX-2 fluctuation in organisms with pulmonary fibrosis. The results showed that the COX-2 level increased in the early stage and decreased in the late stage with the aggravation of pulmonary fibrosis. Furthermore, up-regulation of COX-2 levels can effectively alleviate the severity of pulmonary fibrosis. Therefore, Cy-COX is a fast and convenient imaging tool with great potential to predict the early stage of pulmonary fibrosis and evaluate the therapeutic effects.

PMID:34320042 | DOI:10.1039/d1tb01307f

JMIR Res Protoc. 2021 Jun 11. doi: 10.2196/28873. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic Lung disorders like Chronic obstructive pulmonary disease (COPD) and Idiopathic pulmonary fibrosis (IPF) are characterised by exacerbations which are a significant problem: unpleasant for patients, and sometimes severe enough to cause hospital admission (and therefore National Health Service (NHS) pressures) and death. Reducing the impact of exacerbations is very important. Moreover, due to the coronavirus disease (COVID-19) pandemic, the vulnerable populations with these disorders are at high risk and hence their routine care cannot be done properly. Remote monitoring offers a low cost and safe solution of gaining visibility into the health of people in their daily life. Thus, remote monitoring of patients in their daily lives using mobile and wearable devices could be useful especially in high vulnerability groups. A scenario we consider here is to monitor patients and detect disease exacerbation and progression and investigate the opportunity of detecting exacerbations in real time with a future goal of real time intervention.

OBJECTIVE: The primary objective is to assess the feasibility and acceptability of remote monitoring using wearable and mobile phones in patients with pulmonary diseases. The aims will be evaluated over these areas: Participant acceptability, drop-out rates and interpretation of data, Detection of clinically important events such as exacerbations and disease progression, Quantification of symptoms (physical and mental health), Impact of disease on mood and wellbeing/Quality-of-Life(QoL) and The trajectory-tracking of main outcome variables, symptom fluctuations and order. The secondary objective of this study is to provide power calculations for a larger longitudinal follow-up study. Power calculations will be centered around understanding the number of exacerbations according to sample size and duration.

METHODS: Participants will be recruited from 2 NHS sites in 3 different cohorts - COPD, IPF and Post hospitalised Covid. A total of 60 participants will be recruited, 20 in each cohort. Data collection will be done remotely using the RADAR-Base (Remote Assessment of Disease And Relapse) mHealth (mobile health) platform for different devices - Garmin wearable devices, smart spirometers, mobile app questionnaires, surveys and finger pulse oximeters. Passive data collected includes wearable derived continuous heart rate, oxygen saturation (SpO2), respiration rate, activity, and sleep. Active data collected includes disease-specific Patient Reported Outcome Measures (PROMs), mental health questionnaires and symptoms tracking to track disease trajectory in addition to speech sampling, spirometry and finger Pulse Oximetry. Analyses are intended to assess the feasibility of RADAR-Base for lung disorder remote monitoring (include quality of data, cross-section of passive and active data, data completeness, the usability of the system, acceptability of the system). Where adequate data is collected, we will attempt to explore disease trajectory, patient stratification and identification of acute clinically interesting events such as exacerbations. A key part of this study is understanding the potential of real-time data collection, here we will simulate an intervention using the Exacerbation Rating Scale (ERS) to acquire responses at-time-of-event to assess the performance of a model for exacerbation identification from passive data collected.

RESULTS: RALPMH study provides a unique opportunity to assess the use of remote monitoring in the study of lung disorders. The study is set to be started in mid-June 2021. The data collection apparatus, questionnaires and wearable integrations have been set up and tested by clinical teams as of 24th April 2021. While waiting for ethics approval, real-time exacerbation identification models are currently being constructed. The models will be pre-trained daily on previous days data but the inference will be run in real-time (with inputs from the wearable sensor data collected which is real-time) to acquire responses at-time-of-event to assess the performance of a model.

CONCLUSIONS: Remote Assessment of Lung Disease and Impact on Physical and Mental Health (RALPMH) will provide a reference infrastructure for the use of wearable data for monitoring lung diseases. Specifically information regarding the feasibility and acceptability of remote monitoring and the potential of real-time remote data collection and analysis in the context of chronic lung disorders. Moreover, it provides a unique standpoint to look into the specifics of novel coronavirus without burdensome interventions. It will help plan and inform decisions in any future studies that make use of remote monitoring in the area of Respiratory health.

CLINICALTRIAL: Isrctn.com ISRCTN16275601, https://www.isrctn.com/ISRCTN16275601.

PMID:34319235 | DOI:10.2196/28873

JACC Case Rep. 2020 Jun 17;2(6):938-942. doi: 10.1016/j.jaccas.2020.03.037. eCollection 2020 Jun.

ABSTRACT

As a rare complication after lung transplant, cardiac constriction should not be missed. Physical exam, echocardiography, and catheterization are essential for diagnosis A 65-year-old man with previous coronary artery disease and idiopathic pulmonary fibrosis underwent bilateral lung transplant and subsequently presented for progressive dyspnea and volume overload. Cardiac imaging and cardiac catheterization confirmed constriction, and complete pericardiectomy was performed. The patient had rapid resolution of heart failure symptoms. Pericardial constriction is a rare complication following lung transplant, and we provide a review of the literature and discussion of potential contributing factors. (Level of Difficulty: Intermediate.).

PMID:34317386 | PMC:PMC8302063 | DOI:10.1016/j.jaccas.2020.03.037

Nat Commun. 2021 Jul 27;12(1):4566. doi: 10.1038/s41467-021-24853-8.

ABSTRACT

The airway epithelium serves as the interface between the host and external environment. In many chronic lung diseases, the airway is the site of substantial remodeling after injury. While, idiopathic pulmonary fibrosis (IPF) has traditionally been considered a disease of the alveolus and lung matrix, the dominant environmental (cigarette smoking) and genetic (gain of function MUC5B promoter variant) risk factor primarily affect the distal airway epithelium. Moreover, airway-specific pathogenic features of IPF include bronchiolization of the distal airspace with abnormal airway cell-types and honeycomb cystic terminal airway-like structures with concurrent loss of terminal bronchioles in regions of minimal fibrosis. However, the pathogenic role of the airway epithelium in IPF is unknown. Combining biophysical, genetic, and signaling analyses of primary airway epithelial cells, we demonstrate that healthy and IPF airway epithelia are biophysically distinct, identifying pathologic activation of the ERBB-YAP axis as a specific and modifiable driver of prolongation of the unjammed-to-jammed transition in IPF epithelia. Furthermore, we demonstrate that this biophysical state and signaling axis correlates with epithelial-driven activation of the underlying mesenchyme. Our data illustrate the active mechanisms regulating airway epithelial-driven fibrosis and identify targets to modulate disease progression.

PMID:34315881 | DOI:10.1038/s41467-021-24853-8

Eur J Med Chem. 2021 Jul 20;224:113714. doi: 10.1016/j.ejmech.2021.113714. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a lethal disease with limited therapeutic options and a particularly poor prognosis. Matrix metalloproteinases (MMPs), promising targets for the treatment of IPF, have been identified as playing a pivotal role in IPF. Although the pathological processes of MMPs and IPF have been verified, there are no MMP inhibitors for the treatment of IPF in the clinic. In this review, we will present the latest developments in MMP inhibitors, including pharmacophores, binding modes, selectivity and optimization strategies. In addition, we will also discuss the future development direction of MMP inhibitors based on emerging tools and techniques.

PMID:34315043 | DOI:10.1016/j.ejmech.2021.113714

Ann Am Thorac Soc. 2021 Jul 27. doi: 10.1513/AnnalsATS.202103-295OC. Online ahead of print.

ABSTRACT

RATIONALE: The development of novel therapies for idiopathic pulmonary fibrosis (IPF) has brought increased attention to the population burden of disease. However, little is known about the epidemiology of IPF among United States Veterans.

OBJECTIVES: This study examines temporal trends in incidence and prevalence, patient characteristics, and risk factors associated with IPF among a national cohort of United States Veterans.

METHODS: We used data from Veterans Health Administration (VHA) electronic health record system to describe the incidence, prevalence, and geographic distribution of IPF between January 2010 and December 2019. We evaluated patient characteristics associated with IPF using multivariate logistic regression.

RESULTS: Among 10.7 million Veterans who received care from the VHA between 2010 and 2019, 139,116 (1.26%) were diagnosed with IPF. Using a narrow case definition of IPF, the prevalence increased from 276 cases per 100,000 in 2010 to 725 cases per 100,000 in 2019. The annual incidence increased from 73 cases per 100,000 person-years in 2010 to 210 cases per 100,000 person-years in 2019. Higher absolute incidence and prevalence rates were noted when a broader case definition of IPF was used. Risk factors associated with IPF among Veterans included older age, White race, tobacco use, and rural residence. After accounting for interactions, the average marginal difference in IPF prevalence between males and female sex was small. There was significant geographic heterogeneity of disease across the U.S.

CONCLUSIONS: This study is the first comprehensive epidemiologic analysis of IPF among the U.S. Veteran population. The incidence and prevalence of IPF among Veterans has increased over the past decade. The effect of sex on risk of IPF was attenuated once accounting for other risk factors. The geographic distribution of disease is heterogenous across the U.S with rural residence associated with a higher odds of IPF. The reason for these trends deserves further study.

PMID:34314645 | DOI:10.1513/AnnalsATS.202103-295OC

PLoS One. 2021 Jul 27;16(7):e0255365. doi: 10.1371/journal.pone.0255365. eCollection 2021.

ABSTRACT

BACKGROUND: Interstitial lung diseases (ILDs) are chronic, parenchymal lung diseases with a variable clinical course and a poor prognosis. Within various clinical courses, acute exacerbation (AE) is a devastating condition with significant morbidity and high mortality. The aim of this study was to investigate the role of interleukin-6 (IL-6) to predict AE and prognosis in patients with ILD.

METHODS: Eighty-three patients who were diagnosed with ILD from 2016 to 2019 at the Haeundae Paik Hospital, Busan, South Korea, were included and their clinical data were retrospectively analyzed.

RESULTS: The median follow-up period was 20 months. The mean age was 68.1 years and 65.1% of the patients were men with 60.2% of patients being ever-smokers. Among ILDs, idiopathic pulmonary fibrosis was the most common disease (68.7%), followed by connective tissue disease-associated ILD (14.5%), cryptogenic organizing pneumonia (9.6%), and nonspecific interstitial pneumonia (6.0%). The serum levels of IL-6 were measured at diagnosis with ILD and sequentially at follow-up visits. During the follow-ups, 15 (18.1%) patients experienced an acute exacerbation (AE) of ILD and among them, four (26.7%) patients died. In the multivariable analysis, high levels of IL-6 (OR 1.014, 95% CI: 1.001-1.027, p = 0.036) along with lower baseline saturations of peripheral oxygen (SpO2) were independent risk factors for AE. In the receiver operating characteristic curve analysis, the area under the curve was 0.815 (p < 0.001) and the optimal cut-off value of serum IL-6 to predict AE was 25.20 pg/mL with a sensitivity of 66.7% and specificity of 80.6%. In the multivariable Cox analysis, a high level of serum IL-6 (HR 1.007, 95% CI: 1.001-1.014, p = 0.018) was only an independent risk factor for mortality in ILD patients.

CONCLUSIONS: In our study, a high level of serum IL-6 is a useful biomarker to predict AE and poor prognosis in patients with ILD.

PMID:34314462 | DOI:10.1371/journal.pone.0255365

Radiology. 2021 Jul 27:204149. doi: 10.1148/radiol.2021204149. Online ahead of print.

ABSTRACT

Background Recent studies demonstrate that antifibrotic drugs previously reserved for idiopathic pulmonary fibrosis (IPF) may slow progression in other interstitial lung diseases (ILDs), creating an urgent need for tools that can sensitively assess disease activity, progression, and therapy response across ILDs. Hyperpolarized xenon 129 (129Xe) MRI and spectroscopy have provided noninvasive measurements of regional gas-exchange abnormalities in IPF. Purpose To assess gas exchange function using 129Xe MRI in a group of study participants with nonspecific interstitial pneumonia (NSIP) compared with healthy control participants. Materials and Methods In this prospective study, participants with NSIP and healthy control participants were enrolled between November 2017 and February 2020 and underwent 129Xe MRI and spectroscopy. Quantitative imaging provided three-dimensional maps of ventilation, interstitial barrier uptake, and transfer into the red blood cell (RBC) compartment. Spectroscopy provided parameters of the static RBC and barrier uptake compartments, as well as cardiogenic oscillations in RBC signal amplitude and chemical shift. Differences between NSIP and healthy control participants were assessed using the Wilcoxon rank-sum test. Results Thirty-six participants with NSIP (mean age, 57 years ± 11 [standard deviation]; 27 women) and 15 healthy control participants (mean age, 39 years ± 18; two women) were evaluated. Participants with NSIP had no difference in ventilation compared with healthy control participants (median, 4.4% [first quartile, 1.5%; third quartile, 8.7%] vs 6.0% [first quartile, 2.8%; third quartile, 6.9%]; P = .91), but they had a higher barrier uptake (median, 6.2% [first quartile, 1.8%; third quartile, 23.9%] vs 0.53% [first quartile, 0.33%; third quartile, 2.9%]; P = .003) and an increased RBC transfer defect (median, 20.6% [first quartile, 11.6%; third quartile, 27.8%] vs 2.8% [first quartile, 2.3%; third quartile, 4.9%]; P < .001). NSIP participants also had a reduced ratio of RBC-to-barrier peaks (median, 0.24 [first quartile, 0.19; third quartile, 0.31] vs 0.57 [first quartile, 0.52; third quartile, 0.67]; P < .001) and a reduced RBC chemical shift (median, 217.5 ppm [first quartile, 217.0 ppm; third quartile, 218.0 ppm] vs 218.2 ppm [first quartile, 217.9 ppm; third quartile, 218.6 ppm]; P = .001). Conclusion Participants with nonspecific interstitial pneumonia had increased barrier uptake and decreased red blood cell (RBC) transfer compared with healthy controls measured using xenon 129 gas-exchange MRI and reduced RBC-to-barrier ratio and RBC chemical shift measured using spectroscopy. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Wild in this issue.

PMID:34313473 | DOI:10.1148/radiol.2021204149

Sci Rep. 2021 Jul 26;11(1):15145. doi: 10.1038/s41598-021-94655-x.

ABSTRACT

Most epidemiologic studies of patients with idiopathic pulmonary fibrosis (IPF) have been conducted in North America and Europe. Moreover, there are limited data concerning the cause of death and cause-specific mortality rate of IPF patients in population-based studies. We analyzed information from the Korean National Health Insurance Service database from 2006 to 2016. Patients with a diagnosis code of IPF were extracted from the database and we included those who satisfied the narrow definition of IPF diagnosis. Age- and sex-matched controls were randomly selected at a case-to-control rate of 1:3. We included 42,777 patients newly diagnosed with IPF during the study period. Their mean age was 64.6 years, and 65.4% were male. The age-standardized mortality rates were 85.66 (95% confidence interval [CI] 84.45-86.89) per 1000 person-years. The survival rates of IPF patients 1, 2, 3, 5, and 10 years after IPF diagnosis were 84.5%, 77.4%, 71.9%, 62.9%, and 48.4%, respectively. The standardized mortality ratio of IPF patients compared to that of the normal population was 4.66. The leading cause of death in IPF patients was respiratory causes, followed by cancer. Patients with IPF in Korea showed significantly higher mortality compared to the general population.

PMID:34312485 | DOI:10.1038/s41598-021-94655-x

Respir Investig. 2021 Jul 23:S2212-5345(21)00118-0. doi: 10.1016/j.resinv.2021.06.009. Online ahead of print.

ABSTRACT

Idiopathic pulmonary hemosiderosis (IPH) is a rare immunological disease with a genetic predisposition. It is characterized by recurrent episodes of diffuse alveolar hemorrhage (DAH). Timely use of immunosuppressive medications has significantly improved overall outcomes, including mortality. Still, uncontrolled and frequent episodes of DAH can eventually cause pulmonary fibrosis, leading to end-stage lung disease (ESLD). The objective of the present project was to scrutinize the literature and summarize the demographic, clinical, radiological, and histopathological features, as well as the overall outcomes, in this patient population following lung transplant. The Medline database was searched using the PubMed platform. Articles published in English between 1960 and 2020 were included in the search. Different search terms were used to identify all patients who underwent lung transplantation to manage ESLD due to IPH. Only four cases of lung transplantation have been reported in the literature in patients with IPH. All but one of these underwent deceased donor lung transplant; recurrence was reported in two of these patients and suspected in the third. One patient received living donor lung transplant and had no recurrence during a five-year follow-up. Patients with IPH should not be excluded from lung transplantation because the disease may not recur in all patients, and even when it does recur it can be promptly treated by increasing immunosuppression.

PMID:34312096 | DOI:10.1016/j.resinv.2021.06.009

Evid Based Complement Alternat Med. 2021 Jul 7;2021:8634705. doi: 10.1155/2021/8634705. eCollection 2021.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic respiratory disease with high incidence, morbidity, and mortality rates. Jinshui Huanxian formula (JHF) is an empirical formula that targets the pathogenesis of lung-kidney qi deficiency and phlegm-blood stasis in pulmonary fibrosis (PF). The purpose of this study was to explore JHF's potential pharmacological mechanisms in IPF therapy using network intersection analysis. JHF's primary active components and corresponding target genes were predicted using various databases. Two sets of IPF disease genes were obtained from the DisGeNET and GEO databases and two sets of IPF drug targets were collected. The disease and drug target genes were analyzed. The JHF target genes that intersected with IPF's differentially expressed genes were identified to predict JHF's targets of action in IPF. The functions and pathways of predicted targets acting on IPF were analyzed using the DAVID and KEGG pathway databases. Finally, the resulting drug target mechanisms were validated in a rat model of PF. The initial analyses identified 494 active compounds and 1,304 corresponding targets for JHF. The intersection analysis revealed four common genes for the JHF targets, IPF disease, and anti-IPF drugs in the KEGG database. Furthermore, these genes were targeted by several JHF compounds. Seventy-two JHF targets were closely related to IPF, which suggests that they are therapeutically relevant. Target screening revealed that they regulate IPF through 18 pathways. The targets' molecular functions included regulation of oxidoreductase activity, kinase regulator activity, phosphotransferase activity, and transmembrane receptor protein kinase activity. In vivo experiments showed that JHF alleviated the degree of PF, including decreases in collagen deposition and epithelial-mesenchymal transition. This study systematically explored JHF's mechanisms to identify the specific target pathways involved in IPF. The generated pharmacological network, paired with in vivo validation, elucidates the potential roles and mechanisms of JHF in IPF therapy.

PMID:34306156 | PMC:PMC8279870 | DOI:10.1155/2021/8634705

J Clin Endocrinol Metab. 2021 Jul 24:dgab553. doi: 10.1210/clinem/dgab553. Online ahead of print.

ABSTRACT

CONTEXT: Diabetes mellitus (DM) is a systemic disease characterized by chronic hyperglycemia associated with inflammation and oxidative stress, and the lung may be a target organ of diabetic microvascular damage. Several studies have indicated a positive association between idiopathic pulmonary fibrosis (IPF) and diabetes with controversial findings.

OBJECTIVE: Primary outcomes were to compare the prevalence of DM among individuals with IPF to non-IPF controls, and the prevalence of IPF among individuals with DM to non-DM controls.

DATA SOURCES: PubMed, EMBASE and the Cochrane Library.

STUDY SELECTION: Studies contained sufficient data to calculate the prevalence of DM among individuals with and without IPF, or the prevalence of IPF among individuals with and without DM.

DATA EXTRACTION: Two investigators independently identified eligible studies and extracted data. Pooled odds ratio (OR) with 95% CIs was the summary effect measure.

DATA SYNTHESIS: Eighteen studies including 26,410,623 individuals met eligibility criteria, of which 16 recruited people with IPF and 2 recruited people with DM. The OR of DM in IPF subjects was 1.54 (95% CI: 1.30-1.84; P<0.001) compared to that in non-IPF controls. However, compared with that in non-DM patients, the risk of IPF in DM patients was not found to be significantly reduced (OR: 0.89, 95% CI: 0.64-1.25; P=0.497).

CONCLUSION: This meta-analysis suggests that people with IPF have 1.54 times increased odds of diabetes compared to non-IPF controls, while whether patients with DM have an increased risk of IPF is still controversial. Further large, prospective cohort studies investigating the prevalence of IPF in diabetic patients are warranted.

PMID:34302736 | DOI:10.1210/clinem/dgab553