Idiopathic Fibrosis Research Articles

Epidemiology of Dupuytren’s and Sociodemographic Factors Related to it Among Chronic Diabetic Patients

Background: Dupuytren’s disease(DD) is characterized by progressive idiopathic fibrosis of the hand palm and the formation of nodules & contractures. Its prevalence ranges from 3 to 42% worldwide. Aim: To assess Dupuytren’s disease’s prevalence, severity and its association with different demographic factors. Study design: Analytical, Cross-sectional study done using Non-probability convenient sampling. Method: This study was conducted on 424 diabetic patients of age between 40 and 80. A questionnaire was used to assess different sociodemographic factors among them. Tubiana classification & tabletop test was used to assess the severity of the disease. Chi-square test was applied to find out the p-value for the association between variables. Results: About 9% of total participants were affected by DD. Most of the affected people were in the nodular stage or stage 1.There was a significant relationship found between DD and different factors like age group (p=<0.01),Family history of DD(p=<0.01), and previous hand injury (p=<0.01) Practical implication: This study provides us the baseline risk factors leading to the disease for better future interventions. Treatments gets easier when we reach the cause. Because nowadays the widely available treatment is surgical excision which is not a good option for everyone. Also there is a dearth of research on this emerging hand disability caused by diabetes that’s why this research is being conducted Conclusions: The results showed high prevalence of DD in diabetic patients with old age, positive family history of DD disease and previous hand injury. Therapeutic studies are required for the betterment of society and to prevent the disease from causing disability. Keywords: Contractures, Dupuytren’s disease, Dupuytren’s nodules, diabetes, personal factors, Family history.

Differences in lung and lobe volumes between supine and upright computed tomography in patients with idiopathic lung fibrosis

No clinical study has compared lung or lobe volumes on computed tomography (CT) between the supine and standing positions in patients with idiopathic lung fibrosis (IPF). This study aimed to compare lung and lobe volumes between the supine and standing positions and evaluate the correlations between the supine/standing lung volumes on CT and pulmonary function in patients with IPF. Twenty-three patients with IPF underwent a pulmonary function test and both low-dose conventional (supine position) and upright CT (standing position) during inspiration breath-holds. The volumes of the total lungs and lobes were larger in the standing than in the supine position in patients with IPF (all p < 0.05). Spearman's correlation coefficients between total lung volumes on chest CT in supine/standing positions and vital capacity (VC) or forced VC (FVC) were 0.61/0.79 or 0.64/0.80, respectively. CT-based volumes on upright CT were better correlated with VC and FVC than those on supine CT. Lung and lobe volumes in the standing position may be useful biomarkers to assess disease severity or therapeutic effect in patients with IPF.

Symptomatic Bradycardia in a Young Adult After Camping.

Scenario: An 18-year-old man with no significant medical history arrived at the emergency department via ambulance after a sudden syncopal episode of unknown cause. He had just returned from camping a few days prior. At the time of the episode, the patient was performing chores and his mother found him down and disoriented. En route to the hospital, emergency medical services reported a heart rate of 48/min and a blood pressure of 72/33 mm Hg; he was treated with a 500-mL saline bolus. During examination, he recalled the event and stated that he had felt dizzy so he had lain down. At this time, he reported no shortness of breath, chest pain, nausea, vomiting, changes in vision or hearing, or headache. Vital signs upon his arrival at the emergency department were recorded as heart rate 67/min, blood pressure 97/64 mm Hg, body temperature 38 °C (100.7 °F), respiratory rate 18/min, and oxygen saturation (via pulse oximetry) 98% on room air. A 12-lead electrocardiogram (ECG) was obtained after a bradycardic telemetry alarm. The rhythm strip of the 12-lead ECG is shown here.Mobitz II second-degree atrioventricular block at a heart rate of 60/min with bundle branch block (BBB) and a prolonged QTc interval.Atrioventricular (AV) block occurs when the electrical impulses traveling from the sinoatrial (SA) node through the AV node are impaired. The physiological reason for AV blocks is that gap junctions, protein channels that transfer electrical impulses between cells, are scarce in and around the AV node. The scarcity of gap junctions delays electrical conduction to allow the atria enough time to empty blood into the ventricles, but when this delay becomes excessive, it can cause symptoms. There are 3 types of AV block: first-degree AV block implies slowed conduction; second-degree AV block implies partial conduction from the SA node through the AV node; and third-degree AV block implies complete block of conduction from the SA node through the AV node. The rhythm above has a regularly irregular pattern with partial conduction exhibited by every third P wave lacking an associated QRS complex, consistent with second-degree AV block.Second-degree AV blocks are subdivided into Mobitz type I (Wenckebach) and Mobitz type II. Mobitz type I is characterized as progressive lengthening of the conduction time through the AV node until an electrical impulse is completely blocked, appearing on the ECG as progressive lengthening of the PR interval until a P wave appears without an associated QRS complex. Mobitz type I is typically caused by drugs, electrolyte imbalances, or myocarditis. In contrast, Mobitz type II is characterized as a consistent conduction time through the AV node, and a blocked electrical impulse typically in a predictable pattern (every second beat, third beat, etc). On the ECG, Mobitz type II is characterized as a fixed PR interval with a P wave that appears without an associated QRS complex. Mobitz type II is typically caused by idiopathic fibrosis of the conduction system, inflammatory conditions such as rheumatic fever and Lyme disease, and infiltrative myocardial disease.On this strip, the PR interval is fixed at 162 ms and every third P wave is blocked, which is consistent with second-degree AV block (Mobitz II). A BBB (evidenced by the prolonged QRS duration of 138 ms) and a prolonged corrected QT interval (480 ms) also are apparent. The BBB is presumably a left BBB, owing to the broad, monophasic R wave in lead V5.This young adult with no significant medical history had a new onset of unexplained second-degree AV block (Mobitz II), a left BBB, and a prolonged QTc, all of which were confirmed on the 12-lead ECG. Given his recent camping trip, Lyme disease was suspected and later confirmed. Lyme disease is caused by a spirochete (Borrelia burgdorferi), which can infect the myocardium and induce an inflammatory reponse of the transmural and conductive tissues. Notably, AV blocks are the most common cardiac manifestation of Lyme disease; 98% of adults with cardiac manifestations of Lyme disease will develop first-degree AV block, and up to 50% of those patients may transition to a third-degree AV block.In this case, the problem did not advance beyond second-degree AV block (Mobitz II) and the arrhythmia was intermittent. From a nursing standpoint, important actions include preparing for temporary pacing and diligent cardiac monitoring. In this case, the heart block resolved after treatment with antibiotics.

Vitamin D status in chimpanzees in human care: a Europe wide study

While vitamin D deficiency is a public health concern in humans, comparatively little is known about vitamin D levels in non-human primates. Vitamin D plays a crucial role in overall health and its deficiency is associated with a range of disorders, including cardiovascular disease, which is a leading cause of death in great apes. Serum samples (n = 245) from chimpanzees (Pan troglodytes) housed at 32 European zoos were measured for 25-hydroxyvitamin D2, 25-hydroxyvitamin D3 and total 25-hydroxyvitamin D (25-OHD) using liquid chromatography and tandem mass spectrometry. Of these samples, 33.1% indicated inadequate vitamin D status, using the human reference interval (25-OHD < 50 nmol/L). The season of the year, health status of the animal, and the provision of daily outdoor access had a significant effect on vitamin D status. This is the first large-scale study on vitamin D status of non-human great apes in human care. Inadequate 25-OHD serum concentrations are widespread in the chimpanzee population in Europe and could be a risk factor for the development of idiopathic myocardial fibrosis, a major cause of mortality in this species, as well as other diseases. A review of husbandry and nutrition practices is recommended to ensure optimal vitamin D supply for these endangered animals.

Neumonías intersticiales idiopáticas

Idiopathic interstitial fibrosis has nonspecific, insidious clinical symptoms; it is the most common interstitial disease and has the worse known prognosis, with a survival without treatment of two to five years. In 2018, scientific societies updated the diagnostic criteria; the presence of a usual interstitial pneumonia pattern on an HRCT scan and/or a lung biopsy are decisive for establishing a diagnosis. Among idiopathic interstitial pneumonias, the most common is pulmonary fibrosis, but there are other less common entities such as nonspecific interstitial pneumonia (NSIP), respiratory bronchiolitis-associated diffuse interstitial lung disease (RB-DILD), and desquamative interstitial pneumonia (DIP); the latter two are related to tobacco use. There are also those which present in acute or subacute forms, such as cryptogenic organizing pneumonia (COP) and acute interstitial pneumonia (AIP). Lastly, there are the least common forms, such as lymphoid interstitial pneumonia (LIP) and idiopathic pleuroparenchymal fibroelastosis (IPPFE).

Identification of the effects of COVID-19 on patients with pulmonary fibrosis and lung cancer: a bioinformatics analysis and literature review.

Coronavirus disease 2019 (COVID-19) poses a serious threat to human health and life. The effective prevention and treatment of COVID-19 complications have become crucial to saving patients’ lives. During the phase of mass spread of the epidemic, a large number of patients with pulmonary fibrosis and lung cancers were inevitably infected with the SARS-CoV-2 virus. Lung cancers have the highest tumor morbidity and mortality rates worldwide, and pulmonary fibrosis itself is one of the complications of COVID-19. Idiopathic lung fibrosis (IPF) and various lung cancers (primary and metastatic) become risk factors for complications of COVID-19 and significantly increase mortality in patients. Therefore, we applied bioinformatics and systems biology approaches to identify molecular biomarkers and common pathways in COVID-19, IPF, colorectal cancer (CRC) lung metastasis, SCLC and NSCLC. We identified 79 DEGs between COVID-19, IPF, CRC lung metastasis, SCLC and NSCLC. Meanwhile, based on the transcriptome features of DSigDB and common DEGs, we identified 10 drug candidates. In this study, 79 DEGs are the common core genes of the 5 diseases. The 10 drugs were found to have positive effects in treating COVID-19 and lung cancer, potentially reducing the risk of pulmonary fibrosis.

Dynamically upregulated mast cell CPA3 patterns in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis.

BackgroundThe mast cell-specific metalloprotease CPA3 has been given important roles in lung tissue homeostasis and disease pathogenesis. However, the dynamics and spatial distribution of mast cell CPA3 expression in lung diseases remain unknown.MethodsUsing a histology-based approach for quantitative spatial decoding of mRNA and protein single cell, this study investigates the dynamics of CPA3 expression across mast cells residing in lungs from control subjects and patients with severe chronic obstructive pulmonary disease (COPD) or idiopathic lung fibrosis (IPF).ResultsMast cells in COPD lungs had an anatomically widespread increase of CPA3 mRNA (bronchioles p < 0.001, pulmonary vessels p < 0.01, and alveolar parenchyma p < 0.01) compared to controls, while granule-stored CPA3 protein was unaltered. IPF lungs had a significant upregulation of both mast cell density, CPA3 mRNA (p < 0.001) and protein (p < 0.05), in the fibrotic alveolar tissue. Spatial expression maps revealed altered mast cell mRNA/protein quotients in lung areas subjected to disease-relevant histopathological alterations. Elevated CPA3 mRNA also correlated to lung tissue eosinophils, CD3 T cells, and declined lung function. Single-cell RNA sequencing of bronchial mast cells confirmed CPA3 as a top expressed gene with potential links to both inflammatory and protective markers.ConclusionThis study shows that lung tissue mast cell populations in COPD and IPF lungs have spatially complex and markedly upregulated CPA3 expression profiles that correlate with immunopathological alterations and lung function. Given the proposed roles of CPA3 in tissue homeostasis, remodeling, and inflammation, these alterations are likely to have clinical consequences.

FREQUENCY OF PULMONARY HYPERTENSION USING ECHOCARDIOGRAPHY IN PATIENTS OF IDIOPATHIC PULMONARY FIBROSIS AT A TERTIARY CARE HOSPITAL

Objective: To determine the frequency of pulmonary hypertension among patients with idiopathic pulmonary fibrosis using echocardiography, presenting to the Pulmonology Department of a tertiary care hospital. Methodology: This cross-sectional study was conducted on a sample size of 130 patients (aged 50-80 years) with idiopathic pulmonary fibrosis presented to the Department of Pulmonology, Jinnah Hospital Lahore from September 2018 to March 2019. Mean pulmonary artery pressure (mPAP) 25 mmHg at rest was regarded to be pulmonary hypertension, whilst mPAP of 25–40 mmHg at rest was deemed to be moderate pulmonary hyper­tension, and mPAP &gt;40 mmHg at rest was considered to be a serious disease. Data was analyzed using SPSS v.17.0. Numerical variables were summarized as mean and standard deviation. Chi-square test was used as a test of significance and a p-value &lt; 0.05 was considered as significant. Results: Mean age was 64.5+8.7 years with 67 (51.5%) male and 63 (48.5%) female. The mean duration of the disease since diagnosis of Idiopathic Pulmonary Fibrosis was 13.6+6.4 months. After doing echocardiography, pulmonary hypertension was found in 19 (14.6%) patients with moderate pulmonary hypertension in 14 (10.7%) while 5 (3.8%) had severe disease. Mean mPAP was 19.2+9.2 mmHg (mPAP 10-50 mmHg). Conclusion: Pulmonary Hypertension is not an uncommon finding in patients with Idiopathic Interstitial Fibrosis. Prevalence of pulmonary hypertension had no association with the finding of this study. Moreover, no association of age, sex, or duration of disease with the prevalence of pulmonary hypertension was seen.

Co-achievement of enhanced absorption and elongated retention of insoluble drug in lungs for inhalation therapy of pulmonary fibrosis

The unique composite particles consisting of γ-cyclodextrin metal-organic framework (MOF) (0.5–3 μm of geometric particle size) and 18 β-Glycyrrhetinic acid (GA) were developed as dry powder inhaler (DPI) to alleviate idiopathic lung fibrosis (IPF), which possessed the property of biphasic release in vivo and vitro. In vitro release, the burst release of almost 55% emerged before 2 min and the continued release maintained till 120 h. This specifical phenomenon might be attributed to the structure of MOF containing a pair of γ-CD and cavity. Compared to GA raw material group, the AUC0-t and Cmax of GA@MOF inhalation were enhanced about 3.8 times and 21.4 times, respectively. Furthermore, the absorption time prolonged by 8 h which elongated retention of GA in lungs. Evident by the 92% deposition of GA in the lung based on its biodistribution result, it made sense to expect a locally direct effect on IPF via inhalation

A rare case of disseminated pulmonary ossification associated with fibrotic lung disease

Abstract Disseminated pulmonary ossification (DPO) is a rare disease characterised by diffuse calcification/ossification of lung parenchyma. Most of the cases are idiopathic, while rest of the cause may have underlying cause like lung congestion, lung injury, lung amyloidosis and interstitial lung disease (ILD). We present a rare case of 58-year-old women with progressive dyspnoea and dry cough. On CT, there were extensive confluent nodular and linear calcification of bilateral lung parenchyma associated with lung fibrosis. Imaging findings lead to diagnosis of DPO associated with idiopathic lung fibrosis. Development of such calcification in ILD is very unusual, therefore knowledge of imaging features of DPO is very crucial for its diagnosis.

Novel pyridine and pyrimidine derivatives as promising anticancer agents: A review

Pyridines and pyrimidines are the class of heterocyclic nitrogenous compounds having plethora of applications in anticancer drug development. These synthetic sources serve as the potent class of compounds in treatment of breast cancer, myeloid leukemia, pancreatic cancer, liver cancer and idiopathic respiratory fibrosis etc. The present review enumerates the results of studies published during past three years (2019–2021) on pyridine and pyrimidine analogues with their respective anticancer properties characterized in vitro or through in silico studies and illustrates their potential in development of anticancer agents. Recent advances on pyridine and pyrimidine analogues mentioned in this review add to the appealing opportunities for cancer therapy.

Cell-Surface Programmed Death Ligand-1 Expression Identifies a Sub-Population of Distal Epithelial Cells Enriched in Idiopathic Pulmonary Fibrosis.

Idiopathic lung fibrosis (IPF) is a fatal lung disease characterized by chronic epithelial injury and exhausted repair capacity of the alveolar compartment, associated with the expansion of cells with intermediate alveolar epithelial cell (AT2) characteristics. Using SftpcCreERT2/+: tdTomatoflox/flox mice, we previously identified a lung population of quiescent injury-activated alveolar epithelial progenitors (IAAPs), marked by low expression of the AT2 lineage trace marker tdTomato (Tomlow) and characterized by high levels of Pd-l1 (Cd274) expression. This led us to hypothesize that a population with similar properties exists in the human lung. To that end, we used flow cytometry to characterize the CD274 cell-surface expression in lung epithelial cells isolated from donor and end-stage IPF lungs. The identity and functional behavior of these cells were further characterized by qPCR analysis, in vitro organoid formation, and ex vivo precision-cut lung slices (PCLSs). Our analysis led to the identification of a population of CD274pos cells expressing intermediate levels of SFTPC, which was expanded in IPF lungs. While donor CD274pos cells initiated clone formation, they did not expand significantly in 3D organoids in AT2-supportive conditions. However, an increased number of CD274pos cells was found in cultured PCLS. In conclusion, we demonstrate that, similar to IAAPs in the mouse lung, a population of CD274-expressing cells exists in the normal human lung, and this population is expanded in the IPF lung and in an ex vivo PCLS assay, suggestive of progenitor cell behavior. CD274 function in these cells as a checkpoint inhibitor may be crucial for their progenitor function, suggesting that CD274 inhibition, unless specifically targeted, might further injure the already precarious lung epithelial compartment in IPF.

Mechanical Circulatory Support in Lung Transplant Recipients: Early and Long-Term Survival

<h3>Purpose</h3> Lung transplantation can be performed off-pump with sequential one-lung ventilation or with mechanical circulatory support (MCS) either by using a cardiopulmonary bypass or veno-venous / veno-arterial extracorporeal membrane oxygenation. Furthermore, MCS might be necessary throughout postoperative course for improving pulmonary function. Here we aimed to investigate early and long-term survival of lung recipients, who are temporarily in need for mechanical circulatory support during lung transplantation and / or after and additionally who did not receive any mechanical circulatory support. <h3>Methods</h3> We performed a retrospective review of patients who underwent lung transplantation at our center between January 2009 and July 2021. We compared 100 days survival as well as five-year survival of lung transplant recipients, who received mechanical circulatory support intra- and postoperatively (group 1, n=14) vs. no mechanical circulatory support (group 2, n=14) or just intraoperatively (group 3, n=69). Survival depicted as Kaplan-Meier-Curves. <h3>Results</h3> Recipients treated with mechanical circulatory support intra- and postoperatively after lung transplantation (n=14), presented with pulmonary artery hypertension (n=5), pulmonary veno-occlusive disease (n=1), idiopathic fibrosis (n=2), Sarcoidosis (n=1) and chronic obstructive pulmonary disease (n=5). 100 days after initial lung transplantation 4 out of 14 patients were alive. Early survival between group 1 and 2 was 38.5% vs. 85.7% (p=0.0073) and as compared to group 3 38.5% vs 90.9% (p<0.0001). Five-year survival was 33.3% in patient group 1 compared to 67.3% in group 3 (p<0.0001) as well as 33.3% vs 64.3% when compared to patient group 2 (p=0.0262). Survival between group 2 and 3 did not differ significantly. <h3>Conclusion</h3> Here we report clearly that patients after lung transplantation who needed intra- and postoperatively mechanical circulatory support have a significantly reduced early as well as long-term survival compared to recipients without any need of mechanical circulatory support or only intraoperatively. Early and long-term survival of lung recipients treated with circulatory support only intraoperatively did not differ when compared to patients without any use of support.

Syringic and ascorbic acids prevent NDMA-induced pulmonary fibrogenesis, inflammation, apoptosis, and oxidative stress through the regulation of PI3K-Akt/PKB-mTOR-PTEN signaling pathway

Idiopathic lung fibrosis (ILF) is a severe and life threatening lung disorder that is characterized by scarring of lung tissue, leading to thickening and stiffening of affected areas. This study looked at the role played by PI3K-Akt/PKB-mToR signaling pathway in the pathogenesis of N-Nitrosodimethylamine (NDMA)-induced lung fibrotic injury, and the effects of syringic acid (SYR) and ascorbic acid (ASC) treatments in male Wistar rats. Pulmonary fibrosis was induced by intraperitoneal injection of 10 mg/kg NDMA once daily, thrice (consecutively) a week for four weeks, and this condition was treated daily with SYR (50 mg/kg) and ASC (100 mg/kg) acids orally for four weeks. Fibrogenesis, following NDMA administration was marked by a significant increase in collagen-1 and α-SMA levels, while oxidative stress was marked by a significant decrease in GSH level, GST, GPx, CAT, and SOD activities. Also, NDMA significantly increased lung Bax, p53, caspase-3, TNF-α, IL-1β, NFkB, and decreased Bcl-2, mdm2, cyclin D1 and Nrf-2 levels. Looking at the PI3K-Akt-mTOR signaling pathway, NDMA administration significantly activated lung PI3K, Akt, and mTOR, and deactivated PTEN, FoxO1 and TSC2. Treatments with SYR and ASC significantly reduced oxidative stress by restoring the antioxidant systems via Nrf2 activation, decreased the levels of inflammatory markers through inhibition of NFkB, downregulated p53, Bax, and caspase-3 via up-regulation of mdm2 and cyclin D1. SYR and ASC also regulated the PI3K-Akt-mTOR signaling pathway via the deactivation of PI3K, Akt, and mTOR, and up-regulation of PTEN, FoxO1 and TSC2. Overall, SYR and ASC modulate the PI3K-Akt-mTOR signaling pathway via inhibition of oxidative stress, inflammation and apoptosis in NDMA-induced lung fibrosis.

Efficacy of Qingfei oral liquid for idiopathic pulmonary fibrosis in rats and related network pharmacology study.

To investigate the therapeutic effect and mechanism of Qingfei oral liquid in idiopathic pulmonary fibrosis. Seventy-two male SD rats were divided into control group, model group, pirofenidone group and Qingfei group with 18 animals in each group. The idiopathic pulmonary fibrosis was induced in last three groups by intratracheal injection of bleomycin; pirofenidone group was given oral administration of pirofenidone b.i.d for 21 d, and Qingfei group was given Qingfei oral liquid 3.6 mL/kg q.d for Lung tissues were obtained for HE staining, Masson staining and transforming growth factor (TGF)-β immunohistochemical staining. Superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) were detected in tissue homogenates. The BATMAN-TCM database was used to retrieve the chemical components and their corresponding targets of Qingfei oral solution by network pharmacology method, and then the component-target-disease network diagram was constructed. Finally, the pathway enrichment analysis was carried out to explore the molecular mechanism of Qingfei oral liquid against idiopathic fibrosis. Histopathology results showed that Qingfei oral liquid had a similar relieving effect on pulmonary fibrosis as the positive drug pirfenidone; TGF-β secretion had a significant reduction in lung tissues of Qingfei group; and Qingfei oral liquid had better regulatory effect on SOD, MDA and GSH than pirfenidone. The results of component-target-disease network and pathway enrichment analysis showed that the related molecular pathways were concentrated in inflammation, extracellular matrix and cytokines. Qingfei oral liquid has a good therapeutic effect on idiopathic pulmonary fibrosis in rats via regulation of inflammation, extracellular matrix and cytokines.

Efficacy of N-acetylcysteine on idiopathic or postinfective non-cystic fibrosis bronchiectasis: a systematic review and meta-analysis protocol

IntroductionNon-cystic fibrosis (non-CF) bronchiectasis is a chronic pulmonary disorder that causes destruction and permanent dilatation of the airways, resulting in excessive sputum production, repeated infection and inflammation. A need for...

Immunoglobulin G4-associated disease in pulmonology

A brief review and description of two clinical cases of an IgG4-related disease are presented, one with lung and salivary glands involvement, the other with lung involve-ment associated with post-COVID changes and diagnosed clinically as a neoplasm. Verification of an IgG4-associat-ed disease, which is c haracterized by stereotypical clinical manifestations that make differential diagnosis difficult, became possible due to the histological and immunohis-tochemical study of biopsy and surgical specimen of the salivary glands and lungs. Diagnostic criteria developed by Japanese authors in 2019 were used. Literature review and own observations made it possible to assume an IgG4-associated disease affecting the lungs and salivary glands a real-life, but rarely diagnosed form of idiopath-ic fibrosis of various organs, primarily pneumofibrosis. In the IgG4-associated disease the main diagnostical meth-ods with high specificity are histological and immunohis-tochemical ones with antibodies to CD138, IgG, IgG4, and morphometry. They allow to detect massive infiltration of tissue with lymphocytes, eosinophils, and plasma cells expressing IgG4, in combination with obliterating phle-bitis

Corticosteroid Resistant Pulmonary Fibrosis: Pathophysiology and Management

Pulmonary fibrosis is a disease of the lower respiratory system. It might be as Idiopathic fibrosis which is obscure reason for disease or might be as an optional impact from different causes, for example, the environmental causes, for example, toxins and smoking, some connective tissue illnesses., infection diseases, for example, tuberculosis (TB) and corona virus, a few medications, for example, bleomycin, methotrexate, and radiation treatment. Glucocorticoid are used for treating inflammatory and immune diseases, like asthma, but interstitial lung disease, cystic fibrosis, and chronic obstructive pulmonary disease (COPD) at some stage, may become resistant to corticosteroid treatment. Glucocorticoids inhibit inflammation by many mechanisms. The oxidative stress leads to significantly decrease in activity and expression of Histone deacetylase 2 (HDAC-2) which causes resistant to the action of glucocorticoid. However, the dissociated glucocorticoids have been developed to decrease side effects, the dissociated glucocorticoid receptor agonists (DIGRAs) are a class of experimental drugs designed to share many of the desirable anti-inflammatory, immunosuppressive, or anticancer properties of classical glucocorticoid drugs with fewer side effects, but it is so difficult to dissociate anti-inflammatory effects from adverse effects. Patients with glucocorticoid resistance must use alternative anti-inflammatory treatments as well as drugs that may reverse the molecular mechanism of glucocorticoid resistant. Objective: This paper is to review the corticosteroid resistant pulmonary fibrosis and how overcome this resistance.&#x0D; The data was collected from December 2020 to September 2021.

The tyrosine-kinase inhibitor Nintedanib ameliorates autosomal-dominant polycystic kidney disease

Autosomal-dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease and is characterized by progressive growth of fluid-filled cysts. Growth factors binding to receptor tyrosine kinases (RTKs) stimulate cell proliferation and cyst growth in PKD. Nintedanib, a triple RTK inhibitor, targets the vascular endothelial growth-factor receptor (VEGFR), platelet-derived growth-factor receptor (PDGFR), and fibroblast growth-factor receptor (FGFR), and is an approved drug for the treatment of non-small-cell lung carcinoma and idiopathic lung fibrosis. To determine if RTK inhibition using nintedanib can slow ADPKD progression, we tested its effect on human ADPKD renal cyst epithelial cells and myofibroblasts in vitro, and on Pkd1f/fPkhd1Cre and Pkd1RC/RC, orthologous mouse models of ADPKD. Nintedanib significantly inhibited cell proliferation and in vitro cyst growth of human ADPKD renal cyst epithelial cells, and cell viability and migration of human ADPKD renal myofibroblasts. Consistently, nintedanib treatment significantly reduced kidney-to-body-weight ratio, renal cystic index, cystic epithelial cell proliferation, and blood-urea nitrogen levels in both the Pkd1f/fPkhd1Cre and Pkd1RC/RC mice. There was a corresponding reduction in ERK, AKT, STAT3, and mTOR activity and expression of proproliferative factors, including Yes-associated protein (YAP), c-Myc, and Cyclin D1. Nintedanib treatment significantly reduced fibrosis in Pkd1RC/RC mice, but did not affect renal fibrosis in Pkd1f/fPkhd1Cre mice. Overall, these results suggest that nintedanib may be repurposed to effectively slow cyst growth in ADPKD.

A Pilot Study to Estimate the Impact of High Matrix Image Reconstruction on Chest Computed Tomography

Objectives:The objectives of the study were to estimate the impact of high matrix image reconstruction on chest computed tomography (CT) compared to standard image reconstruction.Material and Methods:This retrospective study included patients with interstitial or parenchymal lung disease, airway disease, and pulmonary nodules who underwent chest CT. Chest CT images were reconstructed using high matrix (1024 × 1024) or standard matrix (512 × 512), with all other parameters matched. Two radiologists, blinded to reconstruction technique, independently examined each lung, viewing image sets side by side and rating the conspicuity of imaging findings using a 5-point relative conspicuity scale. The presence of pulmonary nodules and confidence in classification of internal attenuation was also graded. Overall image quality and subjective noise/artifacts were assessed.Results:Thirty-four patients with 68 lungs were evaluated. Relative conspicuity scores were significantly higher using high matrix image reconstruction for all imaging findings indicative of idiopathic lung fibrosis (peripheral airway visualization, interlobular septal thickening, intralobular reticular opacity, and end-stage fibrotic change; P ≤ 0.001) along with emphysema, mosaic attenuation, and fourth order bronchi for both readers (P ≤ 0.001). High matrix reconstruction did not improve confidence in the presence or classification of internal nodule attenuation for either reader. Overall image quality was increased but not subjective noise/artifacts with high matrix image reconstruction for both readers (P < 0.001).Conclusion:High matrix image reconstruction significantly improves the conspicuity of imaging findings reflecting interstitial lung disease and may be useful for diagnosis or treatment response assessment.