Am J Respir Cell Mol Biol. 2023 Mar 30. doi: 10.1165/rcmb.2023-0096ED. Online ahead of print.

NO ABSTRACT

PMID:36996473 | DOI:10.1165/rcmb.2023-0096ED

Epigenetics. 2023 Dec;18(1):2195305. doi: 10.1080/15592294.2023.2195305.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with an unclear pathogenesis. This study aimed to elucidate the function and potential mechanisms of TUG1 in IPF progression. Cell viability and migration were detected by CCK-8 and transwell assays. Autophagy, fibrosis, or EMT-related proteins were measured by Western blotting. Pro-inflammatory cytokine levels were assessed by ELISA kits. The subcellular localization of TUG1 was observed by FISH assay. RIP assay detected the interaction between TUG1 and CDC27. TUG1 and CDC27 was up-regulated in TGF-β1-induced RLE-6TN cells. TUG1 depletion suppressed pulmonary fibrosis via attenuating inflammation, EMT, inducing autophagy and inactivating PI3K/Akt/mTOR pathway in vitro and in vivo. TUG1 knockdown prevented CDC27 expression. TUG1 silencing ameliorated pulmonary fibrosis by reducing CDC27 expression and inhibiting PI3K/Akt/mTOR pathway.

PMID:36994860 | DOI:10.1080/15592294.2023.2195305

Zhonghua Jie He He Hu Xi Za Zhi. 2023 Apr 12;46(4):388-395. doi: 10.3760/cma.j.cn112147-20220914-00758.

ABSTRACT

Objective: To evaluate the protective effect of anti-idiopathic pulmonary fibrosis (IPF) marketed drug Pirfenidone and its clinical drug Sufenidone (SC1011) against lung injury in a mouse tuberculosis model. Methods: C57BL/6 mouse model of tuberculosis was established. A total of 75 C57BL/6 mice were infected with 1×107 CFU/ml H37Rv suspension by aerosol and randomly divided into untreated (n=9) group, isoniazid+rifampicin+pyrazinamide (HRZ) group (n=22), PFD+HRZ group (n=22), and SC1011+HRZ group (n=22). C57BL/6 mice were infected with H37Rv by aerosol for 6 weeks and then treated. Seven mice in each treatment group were weighed, sacrificed, dissected and observed for lung and spleen lesions at 4 and 8 weeks of treatment. HE staining and Masson staining were used to assess degree of lung injury and fibrosis, respectively. ELISA was used to assess the IFN-γ/TNF-α content in the serum of mice in each treatment group after 4 weeks of treatment. Hydroxyproline (HYP) content in lung tissue was measured by alkaline hydrolysis; meanwhile, CFU counts were used to assess the bacterial load in the lung and spleen of mice in each treatment group and the recurrence of spleen and lung tissue after 12 weeks of drug withdrawal. Results: At 8 weeks, the HYP content in the lung tissue was (630±58), (635±17), and (840±70) μg/mg in the PFD+HRZ, SC1011+HRZ, and HRZ treatment group, respectively (P<0.05).At 8 weeks, the proportion of Masson staining blue-stained area, that was, positive area, in lung tissue was 16.65%±1.82%, 10.01%±2.16%, and 21.36%±3.21%, respectively (F=27.11, P<0.001).The lung injury scores by HE staining at 8 weeks were (5.00±0.50), (5.00±0.47), and (6.89±0.99) points, respectively (F=19.81, P<0.001).The results of 4-week ELISA showed that the levels of TNF-α and IFN-γ in the serum of the SC1011+HRZ-treated group were lower than those of the HRZ-treated group (all P<0.05).The degree of lung injury and fibrosis in PFD+HRZ and SC1011+HRZ treatment groups were lower than those in HRZ treatment group (all P<0.001). The number of viable bacteria in the lung tissue of mice treated with PFD+HRZ, SC1011+HRZ, and HRZ for 4 weeks was lower than that of mice untreated [(1.82±0.10), (1.91±0.05), (1.79±0.17) vs. (5.27±0.07) lg(CFU+1)/ml, all P<0.05)]. And the aseptic transformation of the spleen of mice was achieved in each treatment group at 8 weeks of administration. After 12 weeks of drug withdrawal, the recurrence of lung infection in the SC1011+HRZ treatment group was 3/7 lower than 5/7 in the HRZ treatment group (P>0.05); the recurrence of spleen infection in the SC1011+HRZ treatment group was 1/7 lower than 5/7 in the HRZ treatment group (P>0.05).Pulmonary infection recurred more frequently in PFD+HRZ 6/7 versus HRZ 5/7 (P>0.05). Conclusions: PFD/SC1011, when combined with HRZ, reduced lung injury and reduced secondary fibrosis in pulmonary tuberculosis in C57BL/6 mice. SC1011 combined with HRZ has no significant short-term therapeutic effect on MTB, but may reduce its recurrence rate in long-term treatment, especially in reducing the recurrence rate of mouse spleen.

PMID:36990703 | DOI:10.3760/cma.j.cn112147-20220914-00758

Life (Basel). 2023 Feb 21;13(3):599. doi: 10.3390/life13030599.

ABSTRACT

Interstitial lung disease is an umbrella term that encompasses a spectrum of parenchymal lung pathologies affecting the gas exchanging part of the lung. While many of these disease entities are not fibrotic in nature, a number can lead to pulmonary fibrosis which may or may not progress over time. Idiopathic pulmonary fibrosis is the prototypical, progressive fibrotic interstitial lung disease, which can lead to worsening hypoxemic respiratory failure and mortality within a number of years from the time of diagnosis. The importance of an accurate and timely diagnosis of interstitial lung diseases, which is needed to inform prognosis and guide clinical management, cannot be overemphasized. Developing a consensus diagnosis requires the incorporation of a variety of factors by a multidisciplinary team, which then may or may not determine a need for tissue sampling. Clinical management can be challenging given the heterogeneity of disease behavior and the paucity of controlled trials to guide decision making. This review addresses current paradigms and recent updates in the diagnosis and pharmacologic management of these fibrotic interstitial lung diseases.

PMID:36983755 | DOI:10.3390/life13030599

Diagnostics (Basel). 2023 Mar 18;13(6):1166. doi: 10.3390/diagnostics13061166.

ABSTRACT

BACKGROUND: We have previously shown that SHP2 downregulation may predispose fibroblasts to differentiate into myofibroblasts and proposed a role for SHP2 downregulation in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Recent data have shown that SHP2 localizes to the mitochondrial intercristae, and its overexpression enhances mitochondrial metabolism leading to oxidative stress and senescence.

OBJECTIVE: To determine the effect of SHP2 on fibrotic responses.

METHODS AND RESULTS: Primary mouse lung fibroblasts derived from mice carrying a conditional knock-in mutation (D61G/+), rendering the SHP2 catalytic domain constitutively active, had reduced proliferation (1.6-fold, p < 0.05), migration (2-fold, p < 0.05), as well as reduced responsiveness of TGFB-1 induced fibroblasts-to-myofibroblasts differentiation, compared to wild-type ones. Electron microscope analysis revealed that SHP2 D61G/+ mouse lung fibroblasts were characterized by mitochondrial abnormalities, including swollen mitochondria with disrupted electron-lucent cristae and an increased number of autophagosomes compared to wild-type ones. SHP2 D61G/+ MLFs exhibited increased protein levels of autophagy markers, including LC3B-II and p-62, evidence that was confirmed by immunofluorescence analysis. Mitochondrial function analysis revealed that stable (genotype D61G/+) overexpression of SHP2 led to impaired mitochondrial function, as assessed by decreased mitochondrial membrane potential (1.29-fold, p < 0.05), coupling efficiency (1.82 fold, p < 0.05), oxygen consumption rate (1.9-fold, p < 0.05), and increased reactive oxygen species production both at baseline (1.75-fold, p < 0.05) and following H2O2 stimulation (1.63-fold, p < 0.05) compared to wild-type ones (SHP2+/+). SHP2 D61G/+ mouse lung fibroblasts showed enhanced AMPK activity, as well as decreased activation of the mTORC1 signaling pathway, potentially leading to ineffective mitochondrial metabolism and increased autophagy.

CONCLUSIONS: SHP2 attenuates fibrotic responses in fibroblast cell lines through negative regulation of mitochondrial metabolism and induction of autophagy. SHP2 activation may represent a promising therapeutic strategy for patients with fibrotic lung diseases.

PMID:36980473 | DOI:10.3390/diagnostics13061166

Diagnostics (Basel). 2023 Mar 15;13(6):1109. doi: 10.3390/diagnostics13061109.

ABSTRACT

The six-minute-walking test (6MWT) is an easy-to-perform, cheap and valuable tool to assess the physical performance of patients. It has been used as one of the endpoints in many clinical trials investigating treatment efficacy in pulmonary arterial hypertension and idiopathic pulmonary fibrosis. However, the utility of 6MWT in patients diagnosed with hypersensitivity pneumonitis (HP) is still under investigation. The aim of the present retrospective study was to assess the value of different 6MWT parameters, including the newly developed distance-desaturation index (DDI), to evaluate immunomodulatory treatment outcomes in HP patients.

METHODS: 6MWT parameters (distance, initial saturation, final saturation, desaturation, distance-saturation product (DSP), and DDI) were analyzed at baseline and after 3 to 6 months of treatment with corticosteroids alone or in combination with azathioprine.

RESULTS: 91 consecutive HP patients diagnosed and treated in a single pulmonary unit from 2005 to 2017 entered the study. There were 44 (48%) males and 52 (57%) patients with fibrotic HP (fHP). Sixty-three patients (69%) responded to treatment (responders) and 28 (31%) did not respond (non-responders). In the responders group, all parameters assessed during 6MWT significantly improved, whereas in non-responders, they worsened. Medians (95% CI) of best indices were post-treatment DDI/baseline DDI-1.67 (1.85-3.63) in responders versus 0.88 (0.7-1.73) in non-responders (p = 0.0001) and change in walking distance-51 m (36-72 m) in responders, versus 10.5 m (-61.2-27.9) in non-responders (p = 0.0056). The area under the curve (AUC) of receiver operating characteristics (ROC) for post-treatment DDI/baseline DDI was 0.74 and the optimal cut-off was 1.075, with 71% of specificity and 71% of sensitivity.

CONCLUSIONS: 6MWT may be used as a tool to assess and monitor the response to immunomodulatory therapy in HP patients, especially if indices incorporating both distance and desaturation are used. Based on the present study results, we recommend 6MWD and DDI use, in addition to FVC and TL,co, to monitor treatment efficacy in patients with interstitial lung diseases.

PMID:36980416 | DOI:10.3390/diagnostics13061109

Am J Hosp Palliat Care. 2023 Mar 28:10499091231167879. doi: 10.1177/10499091231167879. Online ahead of print.

ABSTRACT

Objective: to examine the validity of a novel dyspnea scale, Edmonton Dyspnea Inventory in idiopathic pulmonary fibrosis (IPF). Methods: Edmonton Dyspnea Inventory (EDI), is a clinical instrument to measure dyspnea severity with activities of daily living, exercise and rest using a numeric rating scale (0 -10). Consecutive IPF patients (2012-2018) with baseline MRC and EDI were included. To validate EDI, psychometric analysis was conducted. Correlations between EDI, MRC and lung function were examined. Group-based trajectory modeling was used to group patients based on dyspnea severity. Net Reclassification Improvement (NRI) was calculated to assess the improvement in 1-year mortality prediction by adding trajectory groups to MRC grade. Results: 100 consecutive IPF patients were identified; mean age 73 years (SD = 9) and 65% males; 73% were in MRC grades ≥3. Item analysis showed all 8 EDI components have excellent discrimination power with ability to differentiate patients with varying dyspnea severity. EDI has good internal consistency (Cronbach α = .92). Exploratory factor analysis showed a one-factor solution with loadings from .66 to .89 suggesting 8 EDI components measured essentially one dimension of dyspnea. All EDI components were correlated with MRC and some with lung function. Modeling data identified three EDI dyspnea severity groups with differing mortality (P = .009). The addition of EDI dyspnea severity groups to the MRC score improved 1-year mortality prediction (NRI = .66; 95% CI, .18-1.14). Conclusions: EDI is a valid dyspnea instrument, correlated with MRC and lung function. It can categorize IPF patients into 3 dyspnea severity groups associated with increased mortality. Key Message: We describe the development of a novel scale, Edmonton Dyspnea Inventory, that facilitates measurement of dyspnea severity in the context of daily activities in patients with IPF. The results indicate that the new instrument is valid and correlated to MRC. It identifies 3 categories of severity not recognized by MRC with impact on mortality. Knowledge of dyspnea severity can help triage patients and assign appropriate therapies.

PMID:36977656 | DOI:10.1177/10499091231167879

Am J Physiol Lung Cell Mol Physiol. 2023 Mar 28. doi: 10.1152/ajplung.00229.2022. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a rare interstitial lung disease with a poor prognosis. Chronic micro-injuries, mainly caused by environmental factors to an aging alveolar epithelium, would lead to the aberrant differentiation and accumulation of aberrant mesenchymal cells with a contractile phenotype, known as fibrosis-associated myofibroblasts, which trigger abnormal extracellular matrix accumulation and fibrosis. The origin of those pathological myofibroblasts in pulmonary fibrosis is not fully understood to date. Lineage tracing methods using mouse models have opened new avenues for studying cell fate in a pathological context. This review aims to present a non-exhaustive list of different potential sources of those harmful myofibroblasts during lung fibrosis, based on these in vivo approaches, and considering the normal and fibrotic lung cellular atlas recently established by single-cell RNA sequencing.

PMID:36976924 | DOI:10.1152/ajplung.00229.2022

Sarcoidosis Vasc Diffuse Lung Dis. 2023 Mar 28;40(1):e2023003. doi: 10.36141/svdld.v40i1.11460.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with elevated mortality. Delay in diagnosis lead to worse outcomes. Guidelines developed at academic medical centers are difficult to replicate in the community.

OBJECTIVES: Our primary objective was to ascertain consistency with the 2011 IPF guidelines. Our secondary objective was to conduct an interdisciplinary review to ascertain whether the evidence supported the original diagnosis of IPF or not.

METHODS: We asked permission from pulmonologists to review records of patients diagnosed with IPF after 2011. We collected physician demographics and training data; patient demographics, clinical and diagnostic/management data. The clinical data and available images were reviewed by the interdisciplinary review panel.

RESULTS: 26 practicing pulmonologists located in the Southeast of the United States consented to participate. Mean age was 48, 70% were male and all had current certification. We reviewed data from 96 patients. The mean age was 71.4 and most were male. Only 23% had the recommended screening for a connective tissue disease and 42.6% were screened for exercise-induced hypoxemia. Among patients with available images for review (n=66), only 50% had a high-resolution CT scan. 22% of patients underwent a surgical biopsy and in only 33% of the cases three lobes were sampled. No patient had documentation that a multidisciplinary discussion occurred. In 20% of the cases with available images, the evidence supported an alternative diagnosis. 56% of eligible candidates were ever started on anti-fibrotics.

CONCLUSIONS: Our findings suggest that consistency with the IPF guidelines is low in non-academic settings.

PMID:36975060 | DOI:10.36141/svdld.v40i1.11460

Vasa. 2023 Mar 28. doi: 10.1024/0301-1526/a001068. Online ahead of print.

ABSTRACT

Background: Interstitial lung diseases (ILD) are a heterogenous group of diseases, which have pulmonary fibrosis, restrictive lung disease, and decreased diffusion capacity as a common final path. Premature death frequently results not from ILD itself but from comorbidities. Peripheral artery disease (PAD) is a common comorbid disease in different chronic lung diseases. The focus of the present study is to clarify the prevalence of PAD in ILD. Patients and methods: A total of 97 patients with ILD and 30 controls were included in the study. Patients with ILD were subdivided into two groups according to the progression of pulmonary fibrosis: progressive fibrosing and non-progressive fibrosing ILD (PF-ILD and nPF-ILD, respectively). All participants underwent standard angiological and pneumological diagnostic procedures including six-minute walking test, measurement of ankle-brachial-index, and colour-coded duplex sonography. Results: We observed no relevant differences in the baseline characteristics except age. Both, PF-ILD and nPF-ILD patients, presented with a highly increased incidence of atherosclerotic lesions compared to the control group (p<0.001). PAD was present in all patients with PF-ILD and in 73% of patients with nPF-ILD. These results were confirmed by age-adjusted regression analyses. Conclusions: The present results indicate that ILD is an independent risk factor for atherosclerosis. Patients with PF-ILD are more severely affected than nPF-ILD patients with age as a confounding variable. Atherogenesis in ILD may be mediated by increased cardiovascular risk, systemic inflammation and chronic hypoxemia.

PMID:36974466 | DOI:10.1024/0301-1526/a001068

Respirol Case Rep. 2023 Mar 24;11(4):e01118. doi: 10.1002/rcr2.1118. eCollection 2023 Apr.

ABSTRACT

We report a patient with advanced idiopathic pulmonary fibrosis (IPF), who in a single presentation experienced three complications of the disease: an acute exacerbation, spontaneous pneumomediastinum, and platypnoea-orthodeoxia syndrome. Despite there being no definitive evidence-based treatment for an acute exacerbation, we report a marked improvement with high-dose steroids. This case also highlights the importance in IPF patients of considering pneumomediastinum as a cause of non-cardiac chest pain, as well as platypnoea-orthodeoxia in those with positional dyspnoea.

PMID:36970298 | PMC:PMC10037082 | DOI:10.1002/rcr2.1118

Acta Pharm Sin B. 2023 Mar;13(3):1110-1127. doi: 10.1016/j.apsb.2022.10.006. Epub 2022 Oct 12.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with unclear etiology and limited treatment options. The median survival time for IPF patients is approximately 2-3 years and there is no effective intervention to treat IPF other than lung transplantation. As important components of lung tissue, endothelial cells (ECs) are associated with pulmonary diseases. However, the role of endothelial dysfunction in pulmonary fibrosis (PF) is incompletely understood. Sphingosine-1-phosphate receptor 1 (S1PR1) is a G protein-coupled receptor highly expressed in lung ECs. Its expression is markedly reduced in patients with IPF. Herein, we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin (BLM) challenge. Selective activation of S1PR1 with an S1PR1 agonist, IMMH002, exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier. These results suggest that S1PR1 might be a promising drug target for IPF therapy.

PMID:36970190 | PMC:PMC10031262 | DOI:10.1016/j.apsb.2022.10.006

Front Pharmacol. 2023 Mar 9;14:1127219. doi: 10.3389/fphar.2023.1127219. eCollection 2023.

ABSTRACT

Introduction: Cryptotanshinone(CTS), a compound derived from the root of Salvia miltiorrhiza, has been linked to various of diseases, particularly pulmonary fibrosis. In the current study, we investigated the benefit of CTS on Sprague-Dawley (SD) rats induced by bleomycin (BLM) and established high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) methods to compare pharmacokinetics and tissue distribution in subsequent normal and modulated SD rats. Methods: The therapeutic effect of CTS on BLM-induced SD rats was evaluated using histopathology, lung function and hydroxyproline content measurement, revealing that CTS significantly improved SD rats induced by BLM. Additionally, a simple, rapid, sensitive and specific HPLC-MS/MS method was developed to determine the pharmacokinetics of various components in rat plasma. Results: Pharmacokinetic studies indicated that CTS was slowly absorbed by oral administration and had low bioavailability and a slow clearance rate. The elimination of pulmonary fibrosis in 28-day rats was slowed down, and the area under the curve was increased compared to the control group. Long-term oral administration of CTS did not accumulate in vivo, but the clearance was slowed down, and the steady-state blood concentration was increased. The tissue distribution study revealed that CTS exposure in the lungs and liver. Discussion: The lung CTS exposure was significantly higher in the model group than in the control group, suggesting that the pathological changes of pulmonary fibrosis were conducive to the lung exposure of CTS and served as the target organ of CTS.

PMID:36969870 | PMC:PMC10034131 | DOI:10.3389/fphar.2023.1127219

Front Public Health. 2023 Mar 10;11:1135162. doi: 10.3389/fpubh.2023.1135162. eCollection 2023.

ABSTRACT

INTRODUCTION: Air pollution has a significant impact on the morbidity and mortality of various respiratory diseases. However, this has not been widely studied in diffuse interstitial lung diseases, specifically in idiopathic pulmonary fibrosis.

OBJECTIVE: In this study we aimed to assess the relationship between four major air pollutants individually [carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), and nitrogen oxides (NOx)] and the development of chronic respiratory failure, hospitalization due to respiratory causes and mortality in patients with idiopathic pulmonary fibrosis.

METHODS: We conducted an exploratory retrospective panel study from 2011 to 2020 in 69 patients with idiopathic pulmonary fibrosis from the pulmonary medicine department of a tertiary hospital. Based on their geocoded residential address, levels of each pollutant were estimated 1, 3, 6, 12, and 36 months prior to each event (chronic respiratory failure, hospital admission and mortality). Data was collected from the air quality monitoring stations of the Community of Madrid located <3.5 km (2.2 miles) from each patient's home.

RESULTS: The increase in average values of CO [OR 1.62 (1.11-2.36) and OR 1.84 (1.1-3.06)], NO2 [OR 1.64 (1.01-2.66)], and NOx [OR 1.11 (1-1.23) and OR 1.19 (1.03-1.38)] were significantly associated with the probability of developing chronic respiratory failure in different periods. In addition, the averages of NO2, O3, and NOx were significantly associated with the probability of hospital admissions due to respiratory causes and mortality in these patients.

CONCLUSION: Air pollution is associated with an increase in the probability of developing chronic respiratory failure, hospitalization due to respiratory causes and mortality in patients with idiopathic pulmonary fibrosis.

PMID:36969686 | PMC:PMC10036896 | DOI:10.3389/fpubh.2023.1135162

Ann Thorac Med. 2023 Jan-Mar;18(1):45-51. doi: 10.4103/atm.atm_206_22. Epub 2023 Jan 25.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive age-related lung disease causing relentless fibrosis of the lung parenchyma. Currently, pirfenidone and nintedanib are the two antifibrotic drugs, approved for the treatment of IPF. Both are shown to slow progression by preserving lung functions from rapid decline compared to a placebo. We are reporting a real-life patient experience using these two antifibrotic medications (AFMs) in our tertiary care hospital.

METHODS: A retrospective cohort study was conducted for all IPF cases diagnosed in multidisciplinary meetings between 2015 and 2020 at KAMC, Riyadh (Saudi Arabia). We are reporting patients' demographics, lung function, survival, tolerance, side effects, or death in patients taking AFMs.

RESULTS: A total of 81 cases were identified. The majority of patients aged 67 years (68%) were men with a median age of 68 years. Late presentation, severe disease, and definite usual interstitial pneumonia patterns were reported in 60% of our patients. The average number of hospital admissions before starting treatment was 1 (range: 0-3) in the nintedanib group and 1.4 (range: 1.2-5) in the pirfenidone group. There was an increase in the number of hospital admissions in the group started on pirfenidone 1.7 (range: 1.9-8) compared to nintedanib 0.5 (range: 0-3), P = 0.001. The observed mortality outcome in this cohort was 4 (11%) and 12 (27%) for nintedanib and pirfenidone, respectively. The predominant side effects were gastrointestinal symptoms for both the groups 18 (22%).

CONCLUSIONS: Pirfenidone and nintedanib are the available approved antifibrotic agents used for many years to treat IPF patients. Real-life data showed better tolerability than reported in the West, good compliance, and a manageable side effect profile in this group of elderly and severe IPF patients.

PMID:36968327 | PMC:PMC10034822 | DOI:10.4103/atm.atm_206_22

Vet Radiol Ultrasound. 2023 Mar 26. doi: 10.1111/vru.13230. Online ahead of print.

ABSTRACT

A dog was evaluated for right pelvic limb lameness. Computed tomography and magnetic resonance imaging revealed an irregular, contrast-enhancing mass extending along the proximolateral right tibia, involving the long digital extensor tendon (LDET) ± cranial tibialis muscle. Pulmonary nodules, nonspecific hepatomegaly, and splenic nodules were also present. The primary differential diagnosis was soft tissue neoplasia. Surgical biopsy with histopathology revealed benign, chronic inflammation, and fibrosis. Idiopathic synovial inflammation should be included as a differential diagnosis for dogs with this combination of clinical and imaging characteristics.

PMID:36967518 | DOI:10.1111/vru.13230

Intern Emerg Med. 2023 Mar 25. doi: 10.1007/s11739-023-03219-6. Online ahead of print.

ABSTRACT

During the last decade, the CHA2DS2-VASc score has been used for stratifying the mortality risk in both atrial fibrillation (AF) and non-AF patients. However, no previous study considered this score as a prognostic indicator in non-AF patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF). All consecutive non-AF patients with mild-to-moderate IPF, diagnosed between January 2016 and December 2018 at our Institution, entered this study. All patients underwent physical examination, blood tests, spirometry, high-resolution computed tomography and transthoracic echocardiography. CHA2DS2-VASc score, Gender-Age-Physiology (GAP) index and Charlson Comorbidity Index (CCI) were determined in all patients. Primary endpoint was all-cause mortality, while the secondary endpoint was the composite of all-cause mortality and rehospitalizations for all causes over mid-term follow-up. 103 consecutive IPF patients (70.7 ± 7.3 yrs, 79.6% males) were retrospectively analyzed. At the basal evaluation, CHA2DS2-VASc score, GAP index and CCI were 3.7 ± 1.6, 3.6 ± 1.2 and 5.5 ± 2.3, respectively. Mean follow-up was 3.5 ± 1.3 yrs. During the follow-up period, 29 patients died and 43 were re-hospitalized (44.2% due to cardiopulmonary causes). On multivariate Cox regression analysis, CHA2DS2-VASc score (HR 2.15, 95% CI 1.59-2.91) and left ventricular ejection fraction (LVEF) (HR 0.91, 95% CI 0.86-0.97) were independently associated with all-cause mortality in IPF patients. CHA2DS2-VASc score (HR 1.66, 95% CI 1.39-1.99) and LVEF (HR 0.94, 95% CI 0.90-0.98) also predicted the secondary endpoint in the same study group. CHA2DS2-VASc score > 4 was the optimal cut-off for predicting both outcomes. At mid-term follow-up, a CHA2DS2-VASc score > 4 predicts an increased risk of all-cause mortality and rehospitalizations for all causes in non-AF patients with mild-to-moderate IPF.

PMID:36966265 | DOI:10.1007/s11739-023-03219-6

Inflammopharmacology. 2023 Mar 25. doi: 10.1007/s10787-023-01193-1. Online ahead of print.

ABSTRACT

The "Thalidomide tragedy" is a landmark in the history of the pharmaceutical industry. Despite limited clinical trials, there is a continuous effort to investigate thalidomide as a drug for cancer and inflammatory diseases such as rheumatoid arthritis, lepromatous leprosy, and COVID-19. This review focuses on the possibilities of targeting inflammation by repurposing thalidomide for the treatment of idiopathic pulmonary fibrosis (IPF). Articles were searched from the Scopus database, sorted, and selected articles were reviewed. The content includes the proven mechanisms of action of thalidomide relevant to IPF. Inflammation, oxidative stress, and epigenetic mechanisms are major pathogenic factors in IPF. Transforming growth factor-β (TGF-β) is the major biomarker of IPF. Thalidomide is an effective anti-inflammatory drug in inhibiting TGF-β, interleukins (IL-6 and IL-1β), and tumour necrosis factor-α (TNF-α). Thalidomide binds cereblon, a process that is involved in the proposed mechanism in specific cancers such as breast cancer, colon cancer, multiple myeloma, and lung cancer. Cereblon is involved in activating AMP-activated protein kinase (AMPK)-TGF-β/Smad signalling, thereby attenuating fibrosis. The past few years have witnessed an improvement in the identification of biomarkers and diagnostic technologies in respiratory diseases, partly because of the COVID-19 pandemic. Hence, investment in clinical trials with a systematic plan can help repurpose thalidomide for pulmonary fibrosis.

PMID:36966238 | DOI:10.1007/s10787-023-01193-1

Expert Rev Respir Med. 2023 Mar 25. doi: 10.1080/17476348.2023.2196015. Online ahead of print.

ABSTRACT

INTRODUCTION: Cell therapy has emerged as an alternative option for chronic lung diseases with the highest rates of morbidity and mortality rates worldwide.

AREAS COVERED: This review addresses the definition of mesenchymal stromal cells (MSCs), their properties, mechanisms of action, as well as preclinical and clinical studies that have used cell therapy in chronic lung diseases such as asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, pulmonary arterial hypertension, and silicosis. Ongoing clinical trials are also presented.

EXPERT OPINION: Experimental evidence has shown that MSCs have immunomodulatory and regenerative properties that could rescue impaired lung function and histoarchitecture. Their beneficial effects have been mainly associated with their ability to communicate with target cells through the secretion of soluble mediators and extracellular vesicles or even through transfer of organelles (e.g. mitochondria). MSC-derived conditioned medium, extracellular vesicles and mitochondria induce beneficial effects in selected scenarios. The initial results in clinical trials were modest compared with the experimental results, therefore researchers were encouraged to move from bedside back to bench to develop new strategies able to potentiate the effects of MSCs.

PMID:36964742 | DOI:10.1080/17476348.2023.2196015

Sci Rep. 2023 Mar 23;13(1):4788. doi: 10.1038/s41598-023-30870-y.

ABSTRACT

Absorption-based clinical computed tomography (CT) is the current imaging method of choice in the diagnosis of lung diseases. Many pulmonary diseases are affecting microscopic structures of the lung, such as terminal bronchi, alveolar spaces, sublobular blood vessels or the pulmonary interstitial tissue. As spatial resolution in CT is limited by the clinically acceptable applied X-ray dose, a comprehensive diagnosis of conditions such as interstitial lung disease, idiopathic pulmonary fibrosis or the characterization of small pulmonary nodules is limited and may require additional validation by invasive lung biopsies. Propagation-based imaging (PBI) is a phase sensitive X-ray imaging technique capable of reaching high spatial resolutions at relatively low applied radiation dose levels. In this publication, we present technical refinements of PBI for the characterization of different artificial lung pathologies, mimicking clinically relevant patterns in ventilated fresh porcine lungs in a human-scale chest phantom. The combination of a very large propagation distance of 10.7 m and a photon counting detector with [Formula: see text] pixel size enabled high resolution PBI CT with significantly improved dose efficiency, measured by thermoluminescence detectors. Image quality was directly compared with state-of-the-art clinical CT. PBI with increased propagation distance was found to provide improved image quality at the same or even lower X-ray dose levels than clinical CT. By combining PBI with iodine k-edge subtraction imaging we further demonstrate that, the high quality of the calculated iodine concentration maps might be a potential tool for the analysis of lung perfusion in great detail. Our results indicate PBI to be of great value for accurate diagnosis of lung disease in patients as it allows to depict pathological lesions non-invasively at high resolution in 3D. This will especially benefit patients at high risk of complications from invasive lung biopsies such as in the setting of suspected idiopathic pulmonary fibrosis (IPF).

PMID:36959233 | DOI:10.1038/s41598-023-30870-y