Lung Disorders Research Articles

Norisoboldine exerts antiallergic effects on IgE/ovalbumin-induced allergic asthma and attenuates FcεRI-mediated mast cell activation.

Allergic asthma is an inflammatory lung disorder, and mast cells play crucial roles in the development of this allergic disease. Norisoboldine (NOR), the major isoquinoline alkaloid present in Radix Linderae, has received considerable attention because it has anti-inflammatory effects. Herein, the aim of this study was to explore the antiallergic effects of NOR on allergic asthma in mice and mast cell activation. In a murine model of ovalbumin (OVA)-induced allergic asthma, oral administration at 5mg/kg body weight (BW) of NOR produced strong reductions in serum OVA-specific immunoglobulin E (IgE) levels, airway hyperresponsiveness, and bronchoalveolar lavage fluid (BALF) eosinophilia, while an increase in CD4+Foxp3+ T cells of the spleen was detected. Histological studies demonstrated that NOR treatment significantly ameliorated the progression of airway inflammation including the recruitment of inflammatory cells and mucus production by decreasing levels of histamine, prostaglandin D2 (PGD2), interleukin (IL)-4, IL-5, IL-6, and IL-13 in BALF. Furthermore, our results revealed that NOR (3∼30μM) dose-dependently reduced expression of the high-affinity receptor for IgE (FcεRI) and the production of PGD2 and inflammatory cytokines (IL-4, IL-6, IL-13, and TNF-α), and also decreased degranulation of bone marrow-derived mast cells (BMMCs) activated by IgE/OVA. In addition, a similar suppressive effect on BMMC activation was observed by inhibition of the FcεRI-mediated c-Jun N-terminal kinase (JNK) signaling pathway using SP600125, a selective JNK inhibitor. Collectively, these results suggest that NOR may have therapeutic potential for allergic asthma at least in part through regulating the degranulation and the release of mediators by mast cells.

Association of A1AT genetic polymorphism and NSCLC: a case- control study in Egyptian population

BackgroundLung cancer mortality is higher than other forms of cancer. Genetic tendencies in cancer patients have long been known. Given the link between A1ATD and numerous lung disorders, it is worth investigating if this genetic trait is linked to a higher risk of developing LC, as the lung is the most afflicted organ in individuals with severe A1ATD. This study is intended to investigate the possible association between AAT rs17580 and rs8004738 gene polymorphisms and susceptibility to non-small cell lung cancer for early prediction in Egyptians.MethodsA case–control study was performed on 124 NSCLC cases and 124 healthy controls from 2021 to 2022 in the oncology center of Mansoura University. Peripheral blood was used to obtain genomic DNA. ARMS-PCR was used to genotype SNPs and other chemical parameters. Windows SPSS Statistics was used to review, encode, and tabulate the acquired data.ResultsA molecular study for A1AT rs17580 and rs8004738 genotypes showed that NSCLC cases were significantly associated with a higher proportion of mutant S (T) and mutant Z (A) alleles (p = 0.042, 0.041, respectively). Different A1AT genotypes (MS, MZ, SS, SZ, and ZZ) showed no significant association with NSCLC or NLR.ConclusionS and Z alleles might have significant impacts on NSCLC risk and can be useful for detecting and protecting individuals who may be vulnerable to carcinogens. Further research with larger sample sizes is needed to confirm the current findings.

Abnormal Respiratory Sound Identification Using Audio-Spectrogram Vision Transformer.

Respiratory disease, the third leading cause of deaths globally, is considered a high-priority ailment requiring significant research on identification and treatment. Stethoscope-recorded lung sounds and artificial intelligence-powered devices have been used to identify lung disorders and aid specialists in making accurate diagnoses. In this study, audio-spectrogram vision transformer (AS-ViT), a new approach for identifying abnormal respiration sounds, was developed. The sounds of the lungs are converted into visual representations called spectrograms using a technique called short-time Fourier transform (STFT). These images are then analyzed using a model called vision transformer to identify different types of respiratory sounds. The classification was carried out using the ICBHI 2017 database, which includes various types of lung sounds with different frequencies, noise levels, and backgrounds. The proposed AS-ViT method was evaluated using three metrics and achieved 79.1% and 59.8% for 60:40 split ratio and 86.4% and 69.3% for 80:20 split ratio in terms of unweighted average recall and overall scores respectively for respiratory sound detection, surpassing previous state-of-the-art results.

Recent advances in nanoparticle applications in respiratory disorders: a review.

Various nanoparticles are used in the discovery of new nanomedicine to overcome the shortages of conventional drugs. Therefore, this article presents a comprehensive and up-to-date review of the effects of nanoparticle-based drugs in the treatment of respiratory disorders, including both basic and clinical studies. Databases, including PubMed, Web of Knowledge, and Scopus, were searched until the end of August 2022 regarding the effect of nanoparticles on respiratory diseases. As a new tool, nanomedicine offered promising applications for the treatment of pulmonary diseases. The basic composition and intrinsic characteristics of nanomaterials showed their effectiveness in treating pulmonary diseases. The efficiency of different nanomedicines has been demonstrated in experimental animal models of asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis (PF), lung cancer, lung infection, and other lung disorders, confirming their function in the improvement of respiratory disorders. Various types of nanomaterials, such as carbon nanotubes, dendrimers, polymeric nanomaterials, liposomes, quantum dots, and metal and metal oxide nanoparticles, have demonstrated therapeutic effects on respiratory disorders, which may lead to new possible remedies for various respiratory illnesses that could increase drug efficacy and decrease side effects.

HDAC inhibition regulates oxidative stress in CD4+Thelper cells of chronic obstructive pulmonary disease and non-small cell lung cancer patients via mitochondrial transcription factor a (mtTFA) modulating NF-κB/HIF1α axis

Histone deacetylases (HDACs) play a crucial role in the epigenetic regulation of gene expression by remodelling chromatin. Isoenzymes of the HDAC family exhibit aberrant regulation in a wide variety of cancers as well as several inflammatory lung disorders like chronic obstructive pulmonary disease (COPD). Inhibition of HDACs is a potential therapeutic strategy that could be used to reverse epigenetic modification. Trichostatin A (TSA), a powerful histone deacetylase (HDAC) inhibitor, has anti-cancer effects in numerous cancer types. However, it is not yet apparent how HDAC inhibitors affect human non-small cell lung cancer cells (NSCLC) and COPD. This study aims to investigate TSA's role in restoring mitochondrial dysfunction and its effect on hypoxia and inflammation in CD4+T cells obtained from patients with COPD and lung cancer. As a result of treatment with TSA, there is a reduction in the expression of inflammatory cytokines and a decreased enrichment of transcriptional factors associated with inflammation at VEGFA gene loci. We have seen a substantial decrease in the expression of NF-κB and HIF1α, which are the critical mediators of inflammation and hypoxia, respectively. Following TSA treatment, mtTFA expression was increased, facilitating patients with COPD and NSCLC in the recovery of their dysfunctional mitochondria. Furthermore, we have discovered that TSA treatment in patients with COPD and NSCLC may lead to immunoprotective ness by inducing Th1ness. Our finding gives a new insight into the existing body of knowledge regarding TSA-based therapeutic methods and highlights the necessity of epigenetic therapy for these devastating lung disorders.

Current mechanisms in the pathogenesis of lung fibrosis

Pulmonary fibrosis is a diverse group of lung disorders defined by varying degrees of fibrosis and inflammation in the pulmonary parenchyma. While it may be caused by a known disease, e.g., autoimmune or connective tissue disorder, drugs, hypersensitivity to inhaled organic antigens, or sarcoidosis, it also occurs to be idiopathic. When we examine the pathogenesis of lung fibrosis, we see that cellular aging plays a major role. Lung fibroblasts play an active role in the regeneration process. However, despite all the information, the pathogenesis of lung fibrosis is not clearly understood. It is not yet clear how senescent cells in the lung mingle and cause fibrosis. The pathogenesis of lung fibrosis will be understood more clearly following future studies.

Beyond Visual Interpretation: Quantitative Analysis and Artificial Intelligence in Interstitial Lung Disease Diagnosis "Expanding Horizons in Radiology".

Diffuse lung disorders (DLDs) and interstitial lung diseases (ILDs) are pathological conditions affecting the lung parenchyma and interstitial network. There are approximately 200 different entities within this category. Radiologists play an increasingly important role in diagnosing and monitoring ILDs, as they can provide non-invasive, rapid, and repeatable assessments using high-resolution computed tomography (HRCT). HRCT offers a detailed view of the lung parenchyma, resembling a low-magnification anatomical preparation from a histological perspective. The intrinsic contrast provided by air in HRCT enables the identification of even the subtlest morphological changes in the lung tissue. By interpreting the findings observed on HRCT, radiologists can make a differential diagnosis and provide a pattern diagnosis in collaboration with the clinical and functional data. The use of quantitative software and artificial intelligence (AI) further enhances the analysis of ILDs, providing an objective and comprehensive evaluation. The integration of "meta-data" such as demographics, laboratory, genomic, metabolomic, and proteomic data through AI could lead to a more comprehensive clinical and instrumental profiling beyond the human eye's capabilities.

Regulatory Cues in Pulmonary Fibrosis-With Emphasis on the AIM2 Inflammasome.

Pulmonary fibrosis (PF) is a chronic lung disorder characterized by the presence of scarred and thickened lung tissues. Although the Food and Drug Administration approved two antifibrotic drugs, pirfenidone, and nintedanib, that are currently utilized for treating idiopathic PF (IPF), the clinical therapeutic efficacy remains unsatisfactory. It is crucial to develop new drugs or treatment schemes that combine pirfenidone or nintedanib to achieve more effective outcomes for PF patients. Understanding the complex mechanisms underlying PF could potentially facilitate drug discovery. Previous studies have found that the activation of inflammasomes, including nucleotide-binding and oligomerization domain (NOD)-like receptor protein (NLRP)1, NLRP3, NOD-like receptor C4, and absent in melanoma (AIM)2, contributes to lung inflammation and fibrosis. This article aims to summarize the cellular and molecular regulatory cues that contribute to PF with a particular emphasis on the role of AIM2 inflammasome in mediating pathophysiologic events during PF development. The insights gained from this research may pave the way for the development of more effective strategies for the prevention and treatment of PF.

Achalasia Subtype Differences Based on Respiratory Symptoms and Radiographic Findings.

Three subtypes of achalasia have been defined using esophageal manometry. Several studies have reported that symptoms are experienced differently among men and women, regardless of subtype. All subtypes could have some impact on the appearance of respiratory symptoms and lung complications due to compression of the trachea or aspiration of undigested food. The aim of this research was to analyze the differences in respiratory symptoms and radiographic presentation of lung pathology depending on the diameter and achalasia types. One or more respiratory symptoms were reported in 48% of 114 patients, and all of them had two or more gastrointestinal symptoms. The symptom score (SS) is statistically significant for the prediction of subtype 1 (area under the curve = 0.318; p < 0.001, cut-off score of 6.5 had 95.2% sensitivity) and subtype 2 (area under the curve = 0.626; p = 0.020, cut-off score of 7.5 had 93.1% sensitivity). The most common type was subtype 2 (50.8%), and although only 14 patients had subtype 3, they had the largest esophageal diameter (mean 5.8 cm). The difference in esophageal diameter was significant between subtype 1 and 3 (p = 0.011), subtype 2 and subtype 3 (p = 0.011). Nine patients (6%) had mega-esophagus (four patients in type 1, three in type 2 and two in type 3). More than half of all patients (51.7%) had at least one parenchymal lung change on CT scan. Recurrent micro-aspirations led to changes in the structure of the airways and lung parenchyma such as ground glass (GGO) and nodular changes (12%) and fibrosis (14.5%), and they had higher esophageal diameters (p < 0.001). Patients with chronic lung CT changes had significantly higher esophageal diameter than with acute changes (p < 0.001). Awareness of the association of achalasia and lung disorders is important in early diagnosis and treatment. More than half (57.5%) of patients with achalasia had some clinical and/or structural pulmonary abnormalities. All three subtypes had similar respiratory symptoms, meaning they cannot be used to predict the subtype of achalasia; on the contrary, SS can predict the first two subtypes. A higher diameter of the esophagus is associated with chronic structural lung changes. Although unexpected, the pathological radiological findings and diameter were significantly different in subtype 3 patients, but those parameters cannot lead us to a specified subtype.

Macrophage-based delivery of anti-fibrotic proteins alleviates bleomycin-induced pulmonary fibrosis in mice.

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterized by chronic, progressive, and fibrotic lung injury. Although remarkable progress has been made toward understanding the pathogenesis of PF, finding more effective treatments for this fatal disease remains a challenge. In this study, we describe an innovative macrophage-based approach to deliver anti-fibrotic protein to the lung and inhibit PF in a mouse model of bleomycin (BLM)-induced lung injury. We engineered macrophages to continuously secrete three types of proteins: interleukin-10, which prevents inflammation; TGFRcFc, a soluble truncated TGF-βR2 that blocks TGF-β; and CD147, which induces matrix metalloproteinases (MMPs) and causes collagen degradation. Infusing these engineered macrophages into the lungs of BLM-induced PF mouse models in an optimal pattern significantly ameliorated PF in mice. Specifically, the most effective therapeutic outcome was achieved by infusing IL-10-secreting macrophages on day 1, followed by TGFRcFc-secreting macrophages on day 7 and CD147-secreting macrophages on day 14 into the same mice after BLM treatment. Our data suggest that macrophage-based delivery of anti-fibrotic proteins to the lungs is a promising therapy for fibrotic lung disorders.

Comprehensive biomarker analysis of patients with idiopathic pulmonary fibrosis and interstitial lung disease with healthy individuals.

Interstitial lung diseases (ILDs) are a group of diffuse parenchymal lung disorders that can be idiopathic [idiopathic pulmonary fibrosis (IPF)] or associated with other diseases and are characterized by varying degrees of inflammation and fibrosis with poor prognosis. Several indicators are essential in diagnosing these individuals and differentiating between IPF and ILD. The study involved 44 IPF patients, 22 ILD (non-IPF) patients, and 24 healthy people. We aimed to compare ILD (non-IPF) and IPF patient groups with each other and with healthy people in terms of interleukin (IL)-1, tumor necrosis factor-alpha (TNF-α), matrix metalloproteinase (MMP)-1, MMP-7, galectin (Gal)-3, IL-6, Krebs von den Lungen-6 (KL-6), total antioxidant status (TAS), total oxidant status (TOS), pyruvate kinase (PK), complete blood count (CBC), ferritin, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) features. Furthermore, it was intended to assess the patient groups in terms of visual semi-quantitative score (VSQS) (IPF alone), respiratory function tests (RFT), and 6-minute walk test (6MWT), also potential correlations between these tests and the previously indicated parameters. MMP-1, MMP-7, Gal-3, IL-6, KL-6, forced vital capacity (FVC), % FVC, forced expiratory volume in 1 second (FEV1), % FEV1, TAS, TOS, and PK values significantly elevated in IPF and ILD. Weight, IL-1, MMP-1, MMP-7, Gal-3, IL-6, KL-6, % FVC, FEV1, % FEV1, eosinophil count, and % red blood cell distribution width (RDW) values differed between IPF and ILD. VSQS, 6MWT, and PK were substantially linked with MMP-1, MMP-7, Gal-3, IL-6, and KL-6 in IPF. The factors investigated can be helpful in the diagnosis and distinction of IPF and ILD. In addition to focusing on the inflammatory environment in IPF and ILD patients, oxidant and antioxidant interactions must be studied.

Evaluation of lung adverse events with nivolumab using the spontaneous reporting system in Japan

This study was conducted to examine times to onset, incidence rates, and outcomes of nivolumab-induced lung adverse events (AEs), using the Japanese Adverse Drug Event Report database. We analysed data for the period between April 2004 and March 2021. Data on lung AEs were extracted, and relative risks of AEs were estimated using the reporting odds ratio. We analysed 5,273,115 reports and found 18,721 reports of nivolumab-related AEs, including 3084 lung AEs. Signals were detected for nine lung AEs: interstitial lung disease; pneumonitis; lung disorder; organising pneumonia; pleural effusion; pneumonia aspiration; pneumonia bacterial; radiation pneumonitis; and infectious pleural effusion. Among these, interstitial lung disease was the most frequently reported (68.7%) and included some fatal cases. A histogram of median times to onset showed AEs occurring from 34 to 79 days after the first dose, but some cases occurred even more than one year after starting administration. In conclusion, we focused on lung AEs caused by nivolumab as post-marketing AEs. Some cases could potentially involve serious outcomes, particularly in interstitial lung disease. Patients should be monitored for signs of the development of these AEs not only at the start of administration, but also over an extended time.

0447 Study of PAP response and compliance in patients with ILD and OSA: A case-control single center cohort

Abstract Introduction Interstitial lung disease (ILD) is a heterogenous group of parenchymal lung disorders with multiple etiologies. ILD often affects the quality of life and survival of patients. OSA is commonly diagnosed among ILD patients with reported prevalences of 50-90%, and a prevalence of moderate to severe OSA as high as 65%. There is also concern that patients with ILD may be less tolerant of PAP therapies. We aim to identify differences in PAP treatment response and adherence in patients with ILD and OSA compared with a group of matched OSA controls. Methods A retrospective cohort analysis was conducted on patients ≥ 18 years-old that were evaluated at Mayo Clinic Center for Sleep Medicine between July 2012 to June 2022. Inclusion criteria were patients with a diagnosis of ILD per ATS criteria also diagnosed with OSA by HSAT or PSG. Control OSA patients were matched to ILD/OSA patients by age, BMI, and AHI ranges. Exclusion criteria included comorbid conditions of asthma or COPD. Patients with early non-adherence to CPAP or those who didn't have sleep follow up were also excluded. Follow-up sleep visits were assessed to determine CPAP adherence, change in PAP pressure, addition of oxygen, and change in Epworth sleepiness scale. Results We compared 51 patients with ILD/OSA and 51 OSA matched-controls. Twenty-five ILD/OSA patients were diagnosed by PSG and 26 by HSAT. Median treatment follow-up for the ILD group was 7 months (IQR of 3 to 18 months). Baseline characteristics, including oxygen desaturation index (ODI), oxygen saturation, time spent below 89% during overnight oximetry, and baseline Epworth scale, were similar between ILD/OSA and non-ILD OSA patients. Importantly, there was no statistically significant difference in PAP adherence, median PAP levels, PAP pressure change, residual AHI, or change in Epworth after treatment Conclusion There was no significant difference in baseline OSA characteristics, treatment response, and PAP adherence in ILD patients with OSA compared with matched non-ILD OSA controls. Outcome assessment may be limited by sample size and the shorter follow-up period. Future studies should include longer-term follow-up with a larger ILD cohort to assess the impact of ILD progression on PAP adherence over time. Support (if any)

Severe Neonatal Interstitial Lung Disease Caused by a Rare Surfactant Protein C Mutation.

Childhood interstitial lung disease (chILD) is a collective term for a group of rare lung disorders of heterogeneous origin. Surfactant dysfunction disorders are a cause of chILD with onset during the neonatal period and infancy. Clinical signs of tachypnea and hypoxemia are nonspecific and usually caused by common conditions like lower respiratory tract infections. We report on a full-term male newborn who was readmitted to the hospital at 7 days of age with marked tachypnea and poor feeding during the respiratory syncytial virus season. After exclusion of infection and other, more common congenital disorders, chILD was diagnosed using chest computed tomography and genetic analysis. A likely pathogenic heterozygous variant of SFTPC (c.163C>T, L55F) was detected by whole exome sequencing. The patient received supplemental oxygen and noninvasive respiratory support and was treated with intravenous methylprednisolone pulses and hydroxychloroquine. Despite the treatment, his respiratory situation deteriorated continuously, leading to several hospitalizations and continuous escalation of noninvasive ventilatory support. At 6 months of age, the patient was listed for lung transplant and transplanted successfully aged 7 months.

TMT proteomics analysis reveals the mechanism of bleomycin-induced pulmonary fibrosis and effects of Ginseng honeysuckle superfine powdered tea

BackgroundPulmonary fibrosis (PF) is a chronic and potentially fatal lung disease and disorder. Although the active ingredients of ginseng honeysuckle superfine powdered tea (GHSPT) have been proven to have anti-inflammatory and antioxidant effects, the mechanism of GHSPT on PF remains unclear. The present study was to explore the underlying mechanism of GHSPT in treating PF based on proteomics and network pharmacology analysis and to confirm it in vivo.Materials and methodsWe used intratracheal instillation of bleomycin to induce the PF mouse model and GHSPT (640 mg/kg) intragastrically administrated to PF mice for 21 days. The lung tissues were harvested for TMT-based proteomics. The UPLC-Q-Exactive MS/MS analyze the serum migrant compounds of GHSPT in the PF mice. Moreover, components of GHSPT were harvested from the pharmacology database of the TCMSP system. PF-related targets were retrieved using NCBI and GeneCards databases.ResultsOur results showed that GHSPT significantly alleviated PF mice. Proteomics analysis showed that 525 proteins had significantly changed in the lung of untreated PF mice. Among them, 19 differential proteins were back-regulated to normal levels after GHSPT therapy. Moreover, 25 compounds originating from GHSPT were identified in the serum sample. Network analysis showed 159 active ingredients and 92 drug targets against PF. The signaling pathways include apoptosis, ferroptosis, cytokine-cytokine receptor, P53, and PI3K-Akt signaling pathway.ConclusionThe evidence suggests that GHSPT might play an effective role in the treatment of PF by multi-target interventions against multiple signaling pathways.

Rev-erbα agonists suppresses TGFβ1-induced fibroblast-to-myofibroblast transition and pro-fibrotic phenotype in human lung fibroblasts

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by excessive scarring of the lungs that can lead to respiratory failure and death. Lungs of patients with IPF demonstrate excessive deposition of extracellular matrix (ECM) and an increased presence of pro-fibrotic mediators such as transforming growth factor-beta 1 (TGFβ1), which is a major driver of fibroblast-to-myofibroblast transition (FMT). Current literature supports that circadian clock dysfunction plays an essential role in the pathophysiology of various chronic inflammatory lung diseases such as asthma, chronic obstructive pulmonary disease, and IPF. The circadian clock transcription factor Rev-erbα is encoded by Nr1d1 that regulates daily rhythms of gene expression linked to immunity, inflammation, and metabolism. However, investigations into the potential roles of Rev-erbα in TGFβ-induced FMT and ECM accumulation are limited. In this study, we utilized several novel small molecule Rev-erbα agonists (GSK41122, SR9009, and SR9011) and a Rev-erbα antagonist (SR8278) to determine the roles of Rev-erbα in regulating TGFβ1-induced FMT and pro-fibrotic phenotypes in human lung fibroblasts. WI-38 cells were either pre-treated/co-treated with or without Rev-erbα agonist/antagonist along with TGFβ1. After 48 h, the following parameters were evaluated: secretion of COL1A1 (Slot-Blot analysis) and IL-6 (ELISA) into condition media, expressions of α-smooth muscle actin (αSMA: immunostaining and confocal microscopy), and pro-fibrotic proteins (αSMA and COL1A1 by immunoblotting), as well as gene expression of pro-fibrotic targets (qRT-PCR: Acta2, Fn1, and Col1a1). Results revealed that Rev-erbα agonists inhibited TGFβ1-induced FMT (αSMA and COL1A1), and ECM production (reduced gene expression of Acta2, Fn1, and Col1a1), and decreased pro-inflammatory cytokine IL-6 release. The Rev-erbα antagonist promoted TGFβ1-induced pro-fibrotic phenotypes. These findings support the potential of novel circadian clock-based therapeutics, such as Rev-erbα agonist, for the treatment and management of fibrotic lung diseases and disorders.

Nintedanib reduces corticosteroid resistance pulmonary fibrosis induced by bleomycin in mice by increasing the expression of β3 and β6 integrins

Background: Pulmonary fibrosis is a progressive lung disorder that occurs by lung injury and scarring of the lung tissue. This injury makes the lung thickened and stiff causing difficulty to breathe. Corticosteroid resistance pulmonary fibrosis is a major health problem. Bleomycin is an anti-cancer agent, it induces pulmonary fibrosis resistance to corticosteroid therapy, this study aimed to determine the effectiveness of nintedanib (NIN) a tyrosine kinase inhibitor on corticosteroid resistance pulmonary fibrosis induced by bleomycin in mice. Methods: Sixty albino male adult mice were used in this study. The mice were divided into five groups (n=12) at random. control group, the BLM group received a single dose of bleomycin (BLM); 2U/kg by endotracheal instillation, the BLM+MP group received bleomycin and methylprednisolone (MP) 10mg/kg/day by gastric gavage, BLM+NIN group received BLM and NIN, 60mg/kg/day by gastric gavage and the combined treatment group received BLM, NIN, and MP. All groups were sacrificed after the last dose of treatment on day 7 (acute stage) and day 28 (chronic stage). The lung tissues were obtained for biochemical analysis, gene expression, and histopathological examination at the end of the experiment. Results: After 7 days of treatments, BLM+NIN and BLM + NIN + MP groups showed a significant (P&lt;0.05) decrease in the contents of interleukin-2, interleukin-4, interferon-gamma, tumor necrosis factor-alpha, Malondialdehyde with an increase in the glutathione content in lung tissue compared to MP group. Also, they showed a significant decrease in the lung water content compared to the BLM group treated with MP. After 28 days, both NIN groups showed a significant reduction in hydroxyproline, and transforming growth factor beta (β) contents in the lung tissues compared to the MP group, and they showed a positive effect on the expression of β3 and β6 integrins compared to the negative effect of the MP group. Upon histopathology examination, the BLM+NIN group and BLM + NIN + MP groups showed significant improvement compared to the MP group by hematoxylin and eosin (H and E) and Masson’s trichrome stains. Immunohistochemical staining revealed negative BCL-2 expression in the cytoplasm of bronchiolar epithelium in BLM+NIN and BLM + NIN + MP groups after 7 and 28 days of treatment. Morphometric studies of lung tissue showed significant improvement in pathological changes induced by BLM in the BLM+NIN group and BLM + NIN + MP groups. Conclusion: Altogether, our data indicate that NIN overcame corticosteroid resistance pulmonary fibrosis induced by bleomycin in mice mainly by decreasing TGF-β and improving the expression of β3 and β6 integrins.

Telemedicine Management of COPD: Advancements in Chronic Disease Treatment and Implications for Medical Education

Social determinants of health are non-medical, social and economic factors that influence health. The practice of telemedicine enables physicians to virtually connect patients with healthcare resources. Throughout the COVID-19 pandemic, healthcare providers have increasingly utilized telemedicine as a method to provide appropriate care to patients with chronic diseases, including Chronic Obstructive Pulmonary Disease (COPD). COPD is a progressive obstructive lung disorder which is substantially impacted by social determinants of health including access to healthcare. The successful utilization of telemedicine in the care of patients with chronic diseases, including COPD, highlights its emerging importance in healthcare. However, many Canadian medical schools have yet to implement a formalized telemedicine curriculum, and most Canadian students do not feel adequately prepared for virtual healthcare delivery. Here, we outline the utilization of telemedicine in COPD management and advocate for the rapid introduction of a formalized telemedicine curriculum at the undergraduate and postgraduate levels.

Chronic pulmonary aspergillosis after post-tuberculosis lung disorders misdiagnosed as tuberculosis, acquiring more attention: Case series and literature review

Background: Chronic Pulmonary Aspergillosis (CPA) is a destructive pulmonary disease caused by a fungal infection, a frequent complication

Histologic Analysis of Idiopathic Pulmonary Fibrosis by Morphometric and Fractal Analysis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disorder, ultimately leading to respiratory failure and death. Despite great research advances in understanding the mechanisms underlying the disease, its diagnosis, and its treatment, IPF still remains idiopathic without known biological or histological markers able to predict disease progression or response to treatment. The histologic hallmark of IPF is usual interstitial pneumonia (UIP), with its intricate architectural distortion and temporal inhomogeneity. We hypothesize that normal lung alveolar architecture can be compared to fractals, such as the Pythagoras tree with its fractal dimension (Df), and every pathological insult, distorting the normal lung structure, could result in Df variations. In this study, we aimed to assess the UIP histologic fractal dimension in relationship to other morphometric parameters in newly diagnosed IPF patients and its possible role in the prognostic stratification of the disease. Clinical data and lung tissue specimens were obtained from twelve patients with IPF, twelve patients with non-specific interstitial pneumonia (NSIP), and age-matched "healthy" control lung tissue from patients undergoing lung surgery for other causes. Histology and histomorphometry were performed to evaluate Df and lacunarity measures, using the box counting method on the FracLac ImageJ plugin. The results showed that Df was significantly higher in IPF patients compared to controls and fibrotic NSIP patients, indicating greater architectural distortion in IPF. Additionally, high Df values were associated with higher fibroblastic foci density and worse prognostic outcomes in IPF, suggesting that Df may serve as a potential novel prognostic marker for IPF. The scalability of Df measurements was demonstrated through repeated measurements on smaller portions from the same surgical biopsies, which were selected to mimic a cryobiopsy. Our study provides further evidence to support the use of fractal morphometry as a tool for quantifying and determining lung tissue remodeling in IPF, and we demonstrated a significant correlation between histological and radiological Df in UIP pattern, as well as a significant association between Df and FF density. Furthermore, our study demonstrates the scalability and self-similarity of Df measurements across different biopsy types, including surgical and smaller specimens.