scholarly journals Transcriptomic Regulation of Lung Lavage Cells from Pulmonary Fibrosis Patients under the Inhibition of PI3K

2021 ◽  
Vol 7 (2) ◽  
pp. 1-8
Author(s):  
Mengqiao Wang ◽  

Pneumoconiosis refers to a series of lung diseases caused by inhalation of mineral dust and the main pathological characteristics are chronic lung inflammation and progressive pulmonary fibrosis

2021 ◽  
Vol 10 (11) ◽  
pp. 2285
Author(s):  
John N. Shumar ◽  
Abhimanyu Chandel ◽  
Christopher S. King

Progressive fibrosing interstitial lung disease (PF-ILD) describes a phenotypic subset of interstitial lung diseases characterized by progressive, intractable lung fibrosis. PF-ILD is separate from, but has radiographic, histopathologic, and clinical similarities to idiopathic pulmonary fibrosis. Two antifibrotic medications, nintedanib and pirfenidone, have been approved for use in patients with idiopathic pulmonary fibrosis. Recently completed randomized controlled trials have demonstrated the clinical efficacy of antifibrotic therapy in patients with PF-ILD. The validation of efficacy of antifibrotic therapy in PF-ILD has changed the treatment landscape for all of the fibrotic lung diseases, providing a new treatment pathway and opening the door for combined antifibrotic and immunosuppressant drug therapy to address both the fibrotic and inflammatory components of ILD characterized by mixed pathophysiologic pathways.


2021 ◽  
Author(s):  
Mengmeng Xu ◽  
Xiaohui Wang ◽  
Lu Xu ◽  
Hai Zhang ◽  
Chenfei Li ◽  
...  

2021 ◽  
pp. 2004507
Author(s):  
Moisés Selman ◽  
Annie Pardo

Interstitial lung diseases (ILD) comprise a large and heterogeneous group of disorders of known and unknown etiology characterised by diffuse damage of the lung parenchyma. In the past years, it has become evident that patients with different types of ILD are at risk of developing progressive pulmonary fibrosis known as pulmonary fibrosing ILD (PF-ILD). This is a phenotype behaving similar to idiopathic pulmonary fibrosis, the archetypical example of progressive fibrosis. PF-ILD is not a distinct clinical entity but describes a group of ILD with a similar clinical behavior. This phenotype may occur in diseases displaying distinct etiologies and different biopathology during their initiation and development. Importantly, these entities may have the potential for improvement or stabilisation prior to entering in the progressive fibrosing phase. The crucial questions are (1) why a subset of patients develops a progressive and irreversible fibrotic phenotype even with appropriate treatment, and (2) what the pathogenic mechanisms driving progression possibly are. We here provide a framework highlighting putative mechanisms underlying progression, including genetic susceptibility, aging, epigenetics, the structural fibrotic distortion, the aberrant composition and stiffness of the extracellular matrix, and the emergence of distinct profibrotic cell subsets. Understanding the cellular and molecular mechanisms behind PF-ILD will provide the basis for identifying risk factors and appropriate therapeutical strategies.


2018 ◽  
Vol 27 (150) ◽  
pp. 180077 ◽  
Author(s):  
Amy L. Olson ◽  
Alex H. Gifford ◽  
Naohiko Inase ◽  
Evans R. Fernández Pérez ◽  
Takafumi Suda

The availability of epidemiological data relating to interstitial lung diseases (ILDs) has increased over recent years, but information on the prevalence and incidence of ILDs of different aetiologies remains limited. Despite global distribution, the proportion of patients who develop a progressive phenotype across different ILDs is not well known. Disease behaviour is well documented in idiopathic pulmonary fibrosis but idiosyncratic in other ILDs that may present a progressive fibrosing phenotype. Possible reasons may include the heterogeneous nature of the aetiology, the complexity of diagnosis (and subsequent documentation of cases) and the methods employed to retrospectively analyse patient databases. This review presents a broad overview of the epidemiological data available for ILDs that may present a progressive-fibrosing phenotype, collectively and stratified according to clinical classification. We also note where further data are needed in comparison to the well-studied IPF indication.


Life ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1092
Author(s):  
Sikandar Ali ◽  
Ali Hussain ◽  
Satyabrata Aich ◽  
Moo Suk Park ◽  
Man Pyo Chung ◽  
...  

Idiopathic pulmonary fibrosis, which is one of the lung diseases, is quite rare but fatal in nature. The disease is progressive, and detection of severity takes a long time as well as being quite tedious. With the advent of intelligent machine learning techniques, and also the effectiveness of these techniques, it was possible to detect many lung diseases. So, in this paper, we have proposed a model that could be able to detect the severity of IPF at the early stage so that fatal situations can be controlled. For the development of this model, we used the IPF dataset of the Korean interstitial lung disease cohort data. First, we preprocessed the data while applying different preprocessing techniques and selected 26 highly relevant features from a total of 502 features for 2424 subjects. Second, we split the data into 80% training and 20% testing sets and applied oversampling on the training dataset. Third, we trained three state-of-the-art machine learning models and combined the results to develop a new soft voting ensemble-based model for the prediction of severity of IPF disease in patients with this chronic lung disease. Hyperparameter tuning was also performed to get the optimal performance of the model. Fourth, the performance of the proposed model was evaluated by calculating the accuracy, AUC, confusion matrix, precision, recall, and F1-score. Lastly, our proposed soft voting ensemble-based model achieved the accuracy of 0.7100, precision 0.6400, recall 0.7100, and F1-scores 0.6600. This proposed model will help the doctors, IPF patients, and physicians to diagnose the severity of the IPF disease in its early stages and assist them to take proactive measures to overcome this disease by enabling the doctors to take necessary decisions pertaining to the treatment of IPF disease.


2021 ◽  
Vol 12 ◽  
Author(s):  
Duncan C. Humphries ◽  
Ross Mills ◽  
Ross Dobie ◽  
Neil C. Henderson ◽  
Tariq Sethi ◽  
...  

Rationale: Galectin-3 (Gal-3) is an immune regulator and an important driver of fibrosis in chronic lung injury, however, its role in acute lung injury (ALI) remains unknown. Previous work has shown that global deletion of galectin-3 reduces collagen deposition in a bleomycin-induced pulmonary fibrosis model (MacKinnon et al., Am. J. Respir. Crit. Care Med., 2012, 185, 537–46). An inhaled Gal-3 inhibitor, GB0139, is undergoing Phase II clinical development for idiopathic pulmonary fibrosis (IPF). This work aims to elucidate the role of Gal-3 in the myeloid and mesenchymal compartment on the development of acute and chronic lung injury.Methods:LgalS3fl/fl mice were generated and crossed with mice expressing the myeloid (LysM) and mesenchymal (Pdgfrb) cre drivers to yield LysM-cre+/-/LgalS3fl/fl and Pdgfrb-cre+/-/LgalS3fl/fl mice. The response to acute (bleomycin or LPS) or chronic (bleomycin) lung injury was compared to globally deficient Gal-3−/− mice.Results: Myeloid depletion of Gal-3 led to a significant reduction in Gal-3 expression in alveolar macrophages and neutrophils and a reduction in neutrophil recruitment into the interstitium but not into the alveolar space. The reduction in interstitial neutrophils corelated with decreased levels of pulmonary inflammation following acute bleomycin and LPS administration. In addition, myeloid deletion decreased Gal-3 levels in bronchoalveolar lavage (BAL) and reduced lung fibrosis induced by chronic bleomycin. In contrast, no differences in BAL Gal-3 levels or fibrosis were observed in Pdgfrb-cre+/-/LgalS3fl/flmice.Conclusions: Myeloid cell derived Galectin-3 drives acute and chronic lung inflammation and supports direct targeting of galectin-3 as an attractive new therapy for lung inflammation.


Chest Imaging ◽  
2019 ◽  
pp. 453-457
Author(s):  
Cylen Javidan-Nejad

Idiopathic pulmonary fibrosis (IPF) represents one of the most common chronic interstitial lung diseases. Usual interstitial pneumonia (UIP) is the pathologic diagnosis of IPF and can be diagnosed when honeycombing is present with a basilar and peripheral predominance and findings not typical of UIP are absent. In the current era, when a diagnosis of UIP is made with confidence on HRCT, biopsy can be avoided. Yet, one must be familiar with mimics of UIP/IPF (most notably pulmonary edema superimposed on emphysema) to avoid confusion misdiagnosis. Radiologists must also be familiar with potential complications of UIP including progression, infection, accelerated fibrosis (which can be lethal) and primary lung cancer (which has an increased incidence in UIP).


Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 938 ◽  
Author(s):  
Soo Jung Cho ◽  
Kyoung Sook Hong ◽  
Ji Hun Jeong ◽  
Mihye Lee ◽  
Augustine M. K. Choi ◽  
...  

Idiopathic pulmonary fibrosis (IPF) has been linked to chronic lung inflammation. Drosha ribonuclease III (DROSHA), a class 2 ribonuclease III enzyme, plays a key role in microRNA (miRNA) biogenesis. However, the mechanisms by which DROSHA affects the lung inflammation during idiopathic pulmonary fibrosis (IPF) remain unclear. Here, we demonstrate that DROSHA regulates the absent in melanoma 2 (AIM2) inflammasome activation during idiopathic pulmonary fibrosis (IPF). Both DROSHA and AIM2 protein expression were elevated in alveolar macrophages of patients with IPF. We also found that DROSHA and AIM2 protein expression were increased in alveolar macrophages of lung tissues in a mouse model of bleomycin-induced pulmonary fibrosis. DROSHA deficiency suppressed AIM2 inflammasome-dependent caspase-1 activation and interleukin (IL)-1β and IL-18 secretion in primary mouse alveolar macrophages and bone marrow-derived macrophages (BMDMs). Transduction of microRNA (miRNA) increased the formation of the adaptor apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) specks, which is required for AIM2 inflammasome activation in BMDMs. Our results suggest that DROSHA promotes AIM2 inflammasome activation-dependent lung inflammation during IPF.


2020 ◽  
Vol 6 (4) ◽  
pp. 00479-2020
Author(s):  
Jesper Rømhild Davidsen ◽  
Lars Christian Lund ◽  
Christian B. Laursen ◽  
Jesper Hallas ◽  
Daniel Pilsgaard Henriksen

BackgroundIdiopathic pulmonary fibrosis (IPF) is a well-characterised interstitial lung disease. Typically, IPF diagnosis is delayed due to nonspecific symptoms, but can also be delayed due to treatment attempts on false indication or due to treatment targeting common comorbidities. This observational study aimed to assess the dynamics in the medication and diagnosis patterns in the period before and after an IPF diagnosis.MethodsWe identified all Danish patients with IPF between 2002 and 2017. We evaluated new and ongoing drug treatments and incident diagnoses 36 months before and 12 months after an IPF diagnosis by use of Danish nationwide registries. To aid interpretation, 10 random controls were recruited for each case.ResultsA total of 650 IPF patients were identified (median age 73 years (interquartile range 65–78), 70.3% males). Prior to the IPF diagnosis, the most prevalent diagnoses were dyspnoea and non-IPF interstitial lung diseases. For drug use, IPF patients had higher initiation rates for antibiotics, oral corticosteroids and mucolytics. In terms of drug volume, IPF patients used more respiratory drugs, antibiotics, immunosuppressants, corticosteroids, proton pump inhibitors, benzodiazepines and opium alkaloids within the 6 months preceding their IPF diagnosis, compared to the controls. Overall drug use decreased after an IPF diagnosis, mainly due to a reduced glucocorticoid and cardiovascular drug use.ConclusionAmong IPF patients, an increased drug use was observed for diagnoses with symptoms overlapping those of IPF, particularly this was observed during the last 6 months before an IPF diagnosis. This emphasises the need for an increased IPF awareness.


2020 ◽  
Vol 17 ◽  
pp. 147997312095842
Author(s):  
Elisabetta Balestro ◽  
Gioele Castelli ◽  
Nicol Bernardinello ◽  
Elisabetta Cocconcelli ◽  
Davide Biondini ◽  
...  

Idiopathic pulmonary fibrosis presents a progressive and heterogeneous functional decline. CA 19-9 has been proposed as biomarker to predict disease course, but its role remains unclear. We assessed CA 19-9 levels and clinical data in end-stage ILD patients (48 IPF and 20 non-IPF ILD) evaluated for lung transplant, to correlate these levels with functional decline. Patients were categorized based on their rate of functional decline as slow (n = 20; ΔFVC%pred ≤ 10%/year) or rapid progressors (n = 28; ΔFVC%pred ≥ 10%/year). Nearly half of the entire patients (n = 32; 47%) had CA 19-9 levels ≥37kU/L. CA 19-9 levels in IPF were not different from non-IPF ILD populations, however, the latter group had a median CA 19-9 level above the normal cut-off value of 37 KU/l (60 [17–247] kU/L). Among IPF patients, CA 19-9 was higher in slow than in rapid progressors with a trend toward significance (33vs17kU/L; p = 0.055). In the whole population, CA19-9 levels were inversely related with ΔFVC/year (r = −0.261; p = 0.03), this correlation remained in IPF patients, particularly in rapid progressors (r = −0.51; p = 0.005), but not in non. Moreover, IPF rapid progressors with normal CA 19-9 levels showed the greater ΔFVC/year compared to those with abnormal CA 19-9 (0.95 vs. 0.65 L/year; p = 0.03). In patients with end-stage ILD, CA 19-9 may represent a marker of disease severity, whereas its level is inversely correlated with functional decline, particularly among IPF rapid progressors.


Sign in / Sign up

Export Citation Format

Share Document