Chronic Lung Disorders Research Articles

Transcriptomic and Epigenetic Profiling of Fibroblasts in Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF), a devastating, fibroproliferative, chronic lung disorder, is associated with expansion of fibroblasts/myofibroblasts, which leads to excessive production and deposition of extracellular matrix. IPF is typically clinically identified as end-stage lung disease, after fibrotic processes are well-established and advanced. Fibroblasts have been shown to be critically important in the development and progression of IPF. We hypothesize that differential chromatin access can drive genetic differences in IPF fibroblasts relative to healthy fibroblasts. To this end, we performed assay of transposase-accessible chromatin sequencing to identify differentially accessible regions within the genomes of fibroblasts from healthy and IPF lungs. Multiple motifs were identified to be enriched in IPF fibroblasts compared with healthy fibroblasts, including binding motifs for TWIST1 and FOXA1. RNA sequencing identified 93 genes that could be annotated to differentially accessible regions. Pathway analysis of the annotated genes identified cellular adhesion, cytoskeletal anchoring, and cell differentiation as important biological processes. In addition, single nucleotide polymorphism analysis showed that linkage disequilibrium blocks of IPF risk single nucleotide polymorphisms with IPF-accessible regions that have been identified to be located in genes that are important in IPF, including MUC5B, TERT, and TOLLIP. Validation studies in isolated lung tissue confirmed increased expression for TWIST1 and FOXA1 in addition to revealing SHANK2 and CSPR2 as novel targets. Thus, modulation of differential chromatin access may be an important mechanism in the pathogenesis of lung fibrosis.

Comparative analysis of the bronchoalveolar microbiome in Portuguese patients with different chronic lung disorders

The lung is inhabited by a diverse microbiome that originates from the oropharynx by a mechanism of micro-aspiration. Its bacterial biomass is usually low; however, this condition shifts in lung cancer (LC), chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). These chronic lung disorders (CLD) may coexist in the same patient as comorbidities and share common risk factors, among which the microbiome is included. We characterized the microbiome of 106 bronchoalveolar lavages. Samples were initially subdivided into cancer and non-cancer and high-throughput sequenced for the 16S rRNA gene. Additionally, we used a cohort of 25 CLD patients where crossed comorbidities were excluded. Firmicutes, Proteobacteria and Bacteroidetes were the most prevalent phyla independently of the analyzed group. Streptococcus and Prevotella were associated with LC and Haemophilus was enhanced in COPD versus ILD. Although no significant discrepancies in microbial diversity were observed between cancer and non-cancer samples, statistical tests suggested a gradient across CLD where COPD and ILD displayed the highest and lowest alpha diversities, respectively. Moreover, COPD and ILD were separated in two clusters by the unweighted UniFrac distance (P value = 0.0068). Our results support the association of Streptoccocus and Prevotella with LC and of Haemophilus with COPD, and advocate for specific CLD signatures.

Investigating the Role of NHE1 in the Regulation of Changes in Cellular Functions Related to the Development of Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis is a chronic lung disorder characterized by the thickening, stiffening, and scaring of tissue within the lungs. Affected individuals develop shortness of breath and the progressive reduction of respiratory function. Fibrosis ultimately results in low blood flow and hypoxia in the tissue, a microenvironment which is closely associated with the upregulation of the sodium-hydrogen exchanger isoform 1 (NHE1). NHE1 is a ubiquitously expressed protein that exchanges one extracellular Na+ for one intracellular H+. This regulates intracellular pH and cell progression through the cell cycle. When NHE1 is upregulated it supports increased cell proliferation and migration, indicating that it may play a vital role in the behavior of fibroblasts in the development of idiopathic pulmonary fibrosis. We hypothesized that inhibition of NHE1 activation would decrease cell progression towards a fibrotic phenotype in lung fibroblasts. For this assessment, we compared differences in cellular behavior in three cell lines to evaluate the role of NHE1 in these processes. LL29 cells are human fibroblasts derived from a patient diagnosed with idiopathic pulmonary fibrosis; WI-38 cells which are derived from healthy lung tissue; and PSN cells, which are derived from Chinese hamster lung fibroblasts and express only human NHE1.Transforming growth factor beta 1 (TGF-b1), Lysophosphatidic Acid (LPA) and Serotonin (5-hydroxytryptamine) were evaluated for their ability to alter cell proliferation, stress fiber formation, and myofibroblast differentiation in all three cell lines. TGF-b1 is a cytokine that is a growth factor implicated in the pathogenesis of pulmonary fibrosis and is involved in differentiation, proliferation, and matrix production of fibroblasts. Serotonin (5-HT) is a signaling molecule that binds to G-protein coupled receptors supporting the increase in TGF-b1 and its effects in cells. This hormone is involved in wound healing and stimulating inflammation. LPA is a lipid signaling molecule that plays a role in mediating inflammation and activating TGF-b1 signaling. All experiments were performed in the presence and absence of Ethylisopropylamiloride (EIPA), a potent inhibitor of NHE1, to evaluate the role of NHE1 in fibrotic transformation. In PSN cells, stimulation with 10 µM LPA increased stress fiber formation over 2-fold and this stimulation was absent in cells treated with 10 µM EIPA indicating a role for NHE1 in the regulation of stress fiber formation and related cellular processes.

EVs from BALF—Mediators of Inflammation and Potential Biomarkers in Lung Diseases

Extracellular vesicles (EVs) have been identified as key messengers of intracellular communication in health and disease, including the lung. EVs that can be found in bronchoalveolar lavage fluid (BALF) are released by multiple cells of the airways including bronchial epithelial cells, endothelial cells, alveolar macrophages, and other immune cells, and they have been shown to mediate proinflammatory signals in many inflammatory lung diseases. They transfer complex molecular cargo, including proteins, cytokines, lipids, and nucleic acids such as microRNA, between structural cells such as pulmonary epithelial cells and innate immune cells such as alveolar macrophages, shaping mutually their functions and affecting the alveolar microenvironment homeostasis. Here, we discuss this distinct molecular cargo of BALF-EVs in the context of inducing and propagating inflammatory responses in particular acute and chronic lung disorders. We present different identified cellular interactions in the inflammatory lung via EVs and their role in lung pathogenesis. We also summarize the latest studies on the potential use of BALF-EVs as diagnostic and prognostic biomarkers of lung diseases, especially of lung cancer.

A Review of Placenta and Umbilical Cord-Derived Stem Cells and the Immunomodulatory Basis of Their Therapeutic Potential in Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is a devastating lung disorder of preterm infants as a result of an aberrant reparative response following exposures to various antenatal and postnatal insults. Despite sophisticated medical treatment in this modern era, the incidence of BPD remains unabated. The current strategies to prevent and treat BPD have met with limited success. The emergence of stem cell therapy may be a potential breakthrough in mitigating this complex chronic lung disorder. Over the last two decades, the human placenta and umbilical cord have gained increasing attention as a highly potential source of stem cells. Placenta-derived stem cells (PDSCs) and umbilical cord-derived stem cells (UCDSCs) display several advantages such as immune tolerance and are generally devoid of ethical constraints, in addition to their stemness qualities. They possess the characteristics of both embryonic and mesenchymal stromal/stem cells. Recently, there are many preclinical studies investigating the use of these cells as therapeutic agents in neonatal disease models for clinical applications. In this review, we describe the preclinical and clinical studies using PDSCs and UCDSCs as treatment in animal models of BPD. The source of these stem cells, routes of administration, and effects on immunomodulation, inflammation and regeneration in the injured lung are also discussed. Lastly, a brief description summarized the completed and ongoing clinical trials using PDSCs and UCDSCs as therapeutic agents in preventing or treating BPD. Due to the complexity of BPD, the development of a safe and efficient therapeutic agent remains a major challenge to both clinicians and researchers.

Does bronchial asthma influences dental health of the diseased children?

Background/Aim. Asthma is a chronic inflammatory lung disorder. The effect of asthma drugs on oral health is still the subject of debate among researchers in dentistry. The aim of this study was t o e valuate dental status in asthmatic children and evaluate the possible effect of drugs treating asthma on dental health. Methods. Study participants were divided into two groups: the asthma (AG) and the non-asthma (NAG) group. Based on the symptoms of asthma and the possibility for effective control of the disease, the AG group was divided into two subgroups. The oral examination of the teeth was per-formed using a probe and mouth mirror under artificial light in accordance with the recommendations of the World Health Organization. Saliva analysis was carried out by the GC Saliva-Check Buffer, according to the manufacturer's instructions. Results. The study included 136 children aged 6 to 16 years (10.5 ? 3.3). The mean of decayed, missing, and filled teeth (dmft/DMFT) of the children in the AG group (6.0 ? 4.0/3.3 ? 4.4) was higher than in the NAG group (4.8 ? 4.4/2.5 ? 3.4), but significant differences were not observed between the groups. Salivary pH values were found to be similar in both groups, but the quantity and buffering capacity of the stimulated saliva were found to be significantly lower in the AG group (p < 0.001 and p < 0.05, respectively). Conclusion. Although the prevalence of dental caries in the AG group was similar to that of the NAG group in this study, decreased quantity and buffering capacity of the stimulated saliva in the A G group may contribute to higher values of dental caries in asthmatic children in the future.

The Effect of Gas Smelling among Fuel Stations Employees in Qassim Region

Benzene is a carcinogenic compound used in industrial manufacturing. Benzene exposure is associated with a multiplicity of clinical conditions ranging from hematologic diseases to chronic lung disorders. Respiratory system is affected more than the other system because the benzene is highly volatile and inhaled deeply into respiratory airway reaching the alveoli where gas exchange takes place. This study aims to show the effect of benzene on respiratory system of fuel station employees and its role in causing respiratory problems. The design of the study is an experimental study to evaluate the effect of benzene inhalation on the lung tissue by detecting cytological change among Fuel stations employees in Qassim region. The sputum sample was obtained from male stations employees in Qassim region and stained with Papanicolaou stain. The fuel station employees were suffering from dyspnea, nasal irritation and sore throat. In total 15 sputum samples collected are subdivided into three groups: group number one is those not exposed to benzene; the second group is exposed for 2 - 4 years. However, group number three is exposed for more than 4 years. Long-term exposure to benzene leads to cytological change and reduces immunity that is indicated by the present of neutrophil cells (pus) and other inflammatory features.

Pulmonary Tuberculosis; A Dominant Etiology of Pulmonary Hypertension in Endemic Areas

Background: Many patients with chronic lung disorders like infections, COPD, ILD, OSA & Thrombo-embolism, present with dyspnea, not showing adequate improvement by conventional treatment. Most of these were diagnosed as pulmonary hypertension by further multidisciplinary work-up. Such patients show reduced life expectancy due to late diagnosis and insufficient treatment. Many TB patients often remain undiagnosed in this context. The understanding of etiology and risk factors is essential for a high index of suspicion. Objective: To explore the etiology of Pulmonary Hypertension in chronic respiratory patients. Study Design: A Retrospective Observational Study. Settings: Male pulmonology ward, Gulab Devi Chest Hospital, Lahore Pakistan. Duration: 37 months from January 2014 to February 2017. Methodology: 231, consecutive cases, having Age >14 years with clinical and radiological suspicion of pulmonary hypertension were included. Patients having Age >90 years and <14years, not willing for further investigations were excluded. Detailed history, physical examination, radiological, hematological, bacteriological biochemical and immunologic findings were recorded. PH was diagnosed by ECG, Echocardiography, CT-Angiography. HRCT thorax & PFTs, were employed to recognize the underlying lung disorders. Risk factors were identified. Data tabulated, analyzed statistically and conclusions were drawn. Results: 69/231 (29.87%) cases with active and 76/231(32.90%) with old-treated TB, 50(21.64%) COPD, 10(4.32%) pneumonia, 5(2.16%) CLD, six bronchiectasis and three cases of chest deformities were diagnosed PH. Cigarette smoking, DM and obesity were major risk factors. Conclusion: Pulmonary Tuberculosis can be the dominant etiology of PH in high prevalence populations.

A concise review of telomere and telomerase-related genetic markers in fibrotic lung diseases

Fibrotic lung diseases are a heterogeneous group of diffuse parenchymal lung diseases caused by various factors. Pulmonary fibrosis is one of the common pathological changes of advanced fibrotic lung diseases. Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic lung disorder with unknown etiology. IPF mainly affects the elderly that is considered as an aging related disease. Telomeres are specialized structures at the ends of chromosomes. Telomere shortening results in cellular senescence or apoptosis. Telomerase is a ribonucleoprotein complex that maintains telomere length and genome stability. The telomere shortening and mutations in telomere-related genes are associated with incidence and prognosis of pulmonary fibrosis. Here, a concise review of telomere and telomerase-related genomic markers in IPF and other fibrotic lung diseases is written.

Sophoricoside from Sophora japonica ameliorates allergic asthma by preventing mast cell activation and CD4+ T cell differentiation in ovalbumin-induced mice

Asthma is a chronic inflammatory lung disorder with continuously increasing prevalence worldwide. Novel strategies are needed to prevent or improve asthma. The aim of this study was to investigate the effects of sophoricoside from Sophora japonica on allergic asthma. The mature seeds of S. japonica contain a large amount of sophoricoside. Sophoricoside reduced allergic and asthmatic symptoms by suppressing airway inflammation and antibody-antigen reaction in mouse models. In particular, sophoricoside suppressed immune cell recruitment into the airway lumens of the lungs and production of pro-inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) of ovalbumin (OVA)-induced mice. It also decreased the amounts of histamine and arachidonic acid metabolites released in OVA-induced mice and antibody-antigen stimulated mast cells. In addition, sophoricoside decreased differentiation of naïve CD4+ T cells into T helper type 1 (Th1), Th2, and Th17 cells. Overall, we demonstrated that sophoricoside improved allergic asthma by suppressing mast cell activation and CD4+ T cell differentiation.

Interplay between aging, lung inflammation/remodeling, and fibronectin EDA in lung cancer progression

ABSTRACT Lung cancer remains the leading cause of cancer death in the United States. Since most lung cancers occur in aged individuals with chronic lung disorders characterized by inflammation and/or fibrosis, we hypothesized that aging and tissue inflammation/remodeling act in concert to promote lung cancer progression. To test this, we engaged in studies using young and aged C57BL/6 mice in conjunction with bleomycin treatment in a syngeneic model of lung cancer. Wildtype young (3 months) and aged (9 months) C57BL/6 mice were injected with Lewis Lung Carcinoma (LLC) cells at day 14 after injection with phosphate-buffered saline or bleomycin. Untreated aged mice were found to develop more lung metastases than young mice. Bleomycin induced weight loss and lung inflammation/remodeling in both young and aged mice, and it increased the number of lung metastases in aged lungs, but not in young lungs. Since aged lungs show alterations in the expression of fibronectin EDA, we repeated studies in aged WT and aged FN EDA KO mice. In the absence of tissue remodeling/inflammation, WT and FN EDA KO mice developed the same number of metastases when injected with LLC cells. However, the increase in lung metastasis due to bleomycin treatment was abolished in FN EDA KO mice, but only in aged and injured lungs. Together, these studies show increased lung cancer metastasis in aging animals and point to the influence of FN EDA and injury in this process.

Riparin II potentials the effect of ephedrine on inflammation and remodelling in the airway of rats suffering from asthma by regulating transforming growth factor-β/Smad3 signalling pathway

Asthma is a chronic obstructive lung disorder involving hyperresponsive lung tissue. This study evaluated the protective effects of riparin II against asthma and determined the synergistic effects of riparin II with ephedrine in treatment of asthma. Asthma was induced by intraperitoneal injection of Al(OH)3 (100 mg) with ovalbumin 1 mg/kg and subsequent exposure to 2% ovalbumin aerosol for 1 week. All animals were treated with riparin II 50 mg/kg and ephedrine 25 mg/kg alone and in combination for the duration of the study. Interleukin levels were assessed in the serum and bronchoalveolar lavage fluid (BALF) of asthmatic rats, while inflammatory cell infiltration was determined in the lungs. Airway remodelling was determined by assessing the lung tissue expression levels of transforming growth factor beta 1 (TGF-β1), Smad, and collagen I in asthmatic rats. There were lower levels of cytokines in the serum and BALF in riparin II-treated rats than in negative control rats. Moreover, inflammatory cell and IgE levels were reduced while interferon level was enhanced in the lungs of riparin II-treated rats, compared to negative control rats. These data reveal that treatment with riparin II ameliorates the altered expression of TGF-β1, Smad, and collagen I in lung tissue of asthmatic rats. In conclusion, riparin II treatment alone and in combination with ephedrine ameliorated the hyperresponsiveness of lung tissue due to reductions in airway remodelling and inflammation in asthmatic rats.

Hsa_circ_0044226 knockdown attenuates progression of pulmonary fibrosis by inhibiting CDC27.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disorder. Here, we performed a bioinformatics analysis using the GSE102660 dataset from the Gene Expression Omnibus database to identify differentially expressed circRNAs (DEcircRNAs) in tissues from IPF patients and healthy controls. The results identified 45 DEcircRNAs, among which expression of hsa_circ_0044226 was markedly higher in lung tissues from IPF patients than from healthy controls. Knocking down hsa_circ_0044226 expression using a targeted shRNA inhibited TGF-β1-induced fibrosis in RLE-6TN cells and in a bleomycin-induced mouse model of IPA. The diminished TGF-β1-induced fibrosis was associated with upregulated expression of E-cadherin and downregulated expression of α-SMA, collagen III and fibronectin 1, as well as with reduced expression of CDC27, suggesting inhibition of epithelial-to-mesenchymal transition (EMT). All of those effects were reversed by overexpression of CDC27. This suggests CDC27 overexpression abolishes the antifibrotic effect of hsa_circ_0044226 knockdown through activation of EMT. Furthermore, hsa_circ_0044226 knockdown decreased the expression of CDC27 in BLM-induced pulmonary fibrosis mouse model. Collectively then, these findings indicate that downregulation of hsa_circ_0044226 attenuates pulmonary fibrosis in vitro and in vivo by inhibiting CDC27, which in turn suppresses EMT. This suggests hsa_circ_0044226 may be a useful therapeutic target for the treatment of IPF.

An experimental mouse model of lung fibrosis

Pulmonary fibrosis is a pathologic chronic lung disorder characterized by the deposition of extracellular matrix and damage to lung architecture. Models of pulmonary fibrosis were developed in several animal species. However, murine models are more common due to their low costs, availability and well characterized immune systems. Indeed, these murine models play an important role in understanding the biology of the diseases, deciphering the cellular and molecular mechanisms mediating pulmonary pathobiology and to explore novel therapeutic approaches. Although the majority of these models mimic certain characteristics of human idiopathic pulmonary fibrosis, most of them do not mimic other features especially those related to the progressive and irreversible nature of this disease. The present protocol describes the induction of a pulmonary fibrosis model in mice with bleomycin, which is a risk factor for human lung fibrosis. Specifically, we described the methodology of intratracheal instillation of bleomycin as well as the assessment methods of pulmonary fibrosis either histopathologically based on Ashcroft grading score or by quantitatively based on biochemical biomarkers. Moreover, we proposed a detailed readout that can determine the degree of lung injury in bronchoalveolar lavage fluids. We described different cellular and molecular markers such as by total protein concentration, total cell count, immune cell differential count, and the expression of pro-inflammatory mediators. We present this model as a reference for studies on the pulmonary fibrosis.

NHE1 activity is required for profibrotic agonist activation of cytoskeleton remodeling in lung fibrosis

Idiopathic pulmonary fibrosis (IPF) is an untreatable chronic lung disorder that is characterized by an accumulation of fibroblasts and scarring tissue due to aberrant tissue remodeling. The lung tissue loses flexibility as the disease upsurges and the affected patient’s alveolar architecture is destroyed. This leads to a disruption of gas exchange, eventual respiratory failure, and death. Sodium hydrogen exchanger isoform 1 (NHE1) is a membrane bound protein that moderates cellular pH, supports cell migration, and regulates cell behavior. NHE1 has also been found to impact the pathophysiology of cancer. Considering that a myriad of signaling pathways that activate tumor cells are also involved in profibrotic activity of fibroblasts and myofibroblasts, the purpose of this study was to investigate if NHE1 exacerbates IPF and if inhibiting NHE1 would decrease the advancing fibrosis. We measured one of the indicators of progressing fibrosis, the remodeling of skeletal proteins, through the formation of actin stress fibers. Actin stress fibers have an important role in cell migration and contractility in fibroblasts. To stimulate this formation, cells were treated with three agonists that increase fibrotic activity: transforming growth factor ‐ β(TGF‐β), serotonin (5HT), and lysophosphatidic acid (LPA) in the presence and absence of ethyl‐isopropyl amiloride (EIPA). LPA induced stress fibers 43.94+/−4.4 percent over the control, and both TGF‐βand 5HT also stimulated the formation of stress fibers by 32.08+/−2.1 and 39.1+/−4.2 percent over the control, non‐treated cells. In each case, addition of EIPA blocked agonist‐induced stress fiber formation, indicating that all three profibrotic factors require NHE1 activity for cytoskeletal remodeling. Interestingly, we also observed that stimulation in any combination of agonists had seemed to block stress fiber formation in comparison to the control. An initial interpretation indicates that the agonists negatively regulate the others in stimulating stress fiber formation. The role of each agonist in fibroblasts isolated from fibrotic patients and control, non‐diseased tissue are presented. Myofibroblasts are a specialized cell type that contribute to fibrosis. The role of NHE1 in TGF‐βinduced fibroblast‐myofibroblast differentiation is also determined. The marker for myofibroblast differentiation, α‐smooth muscle actin (α‐SMA) was measured with and without EIPA to determine the role of NHE1 in advancing disease. Finally, the role of NHE1 in myofibroblasts was investigated with EIPA and stress fiber changes with agonists. This work highlights for the first time that NHE1 has a role supporting profibrotic factors and may be a novel target or adjuvant to fight IPF.

Investigating the Role of NHE1 in Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis is a chronic lung disorder characterized by thickening, stiffening and scaring of tissue within the lungs. Affected individuals develop shortness of breath and progressive reduced respiratory function. In order to be able to analyze this process two cell lines will be compared throughout the project. The first being LL29 cells which are human fibroblasts that were derived from a patient with idiopathic pulmonary fibrosis. In comparison to those cells will be further investigation of WI‐38 cells which are derived from normal lung tissue. In fibroblast cells, TGF‐b1, LPA, and 5HT will be investigated to differentiate between the two cell lines through analysis of their proliferation, stress fiber formation, collagen contraction and myofibroblast differentiation. Transforming growth factor beta 1 (TGF‐b1) is a cytokine that is a growth factor implicated in the pathogenesis of pulmonary fibrosis and is involved in differentiation, proliferation and matrix production of fibroblasts. Serotonin (5‐HT) is a signaling molecule that that functions through a G‐protein coupled receptors that support the increase of TGF‐b1 and the development of the fibrotic phenotype. This hormone is involved in wound healing and stimulating inflammation. LPA is a bioactive lipid signaling molecule that plays a role in mediating inflammation and activating TGF‐b1 signaling. Fibrosis ultimately results in low blood flow and hypoxia in the tissue, a microenvironment in which is closely associated with the upregulation of the sodium‐hydrogen exchanger isoform 1 (NHE1). NHE1 is a ubiquitously expressed protein that exchanges one extracellular Na+ for one intracellular H+. This regulates intracellular pH and cell progression through the cell cycle. When NHE1 is upregulated it supports increased cell proliferation and migration, indicating that it may play a vital role in the behavior of fibroblasts in idiopathic pulmonary fibrosis. Here we evaluate NHE1‐dependent changes in cell proliferation, stress fiber formation, α‐smooth muscle actin expression and collagen contraction.

Lactoferrin infant feeding trial_Canada (LIFT_Canada): protocol for a randomized trial of adding lactoferrin to feeds of very-low-birth-weight preterm infants

BackgroundIn Canada alone, almost 3000 VLBW infants are born and treated annually with almost 1200 going onto death or survival with severe brain injury, chronic lung disorders, aggressive retinopathy of prematurity, late-onset sepsis, or significant necrotizing enterocolitis. Lactoferrin is an antimicrobial, antioxidant, anti-inflammatory iron-carrying, bifidogenic glycoprotein found in all vertebrates and in mammalian milk, leukocytes and exocrine secretions. Lactoferrin aids in creating an environment for growth of beneficial bacteria in the gut, thus reducing colonization with pathogenic bacteria. It is hypothesized that oral bovine lactoferrin (bLF), through its antimicrobial, antioxidant and anti-inflammatory properties, will reduce the rate of mortality or major morbidity in very low birth weight preterm infants.MethodLactoferrin Infant Feeding Trial_Canada (LIFT_Canada) is a multi-centre, double-masked, randomized controlled trial with the aim to enroll 500 infants whose data will be combined with the data of the 1542 infants enrolled from Lactoferrin Infant Feeding Trial_Australia/New Zealand (LIFT_ANZ) in a pooled intention-to-treat analysis. Eligible infants will be randomized and allocated to one of two treatment groups: 1) a daily dose of 200 mg/kg bLF in breast/donor human milk or formula milk until 34 weeks corrected gestation or for a minimum of 2 weeks, whichever is longer, or until discharge home or transfer, if earlier; 2) no bLF with daily feeds. The primary outcome will be determined at 36 weeks corrected gestation for the presence of neonatal morbidity and at discharge for survival and treated retinopathy of prematurity. The duration of the trial is expected to be 36 months.DiscussionCurrently, there continues to be no clear answer related to the benefit of bLF in reducing mortality or any or all of the significant neonatal morbidities in very low birth weight infants. LIFT_Canada is designed with the hope that the pooled results from Australia, New Zealand, and Canada may help to clarify the situation.Trial registrationClinical Trials.Gov, Identifier: NCT03367013, Registered December 8, 2017.

Ayurveda Management of Emphysema of the Lungs

Chronic lung disorders are occurring commonly in Indian population. Altered food habits, faulty life style, smoking, air pollution has resulted in increase in pulmonary disorders. Among these, Chronic Bronchial Asthma, COPD, Bronchiectasis and Emphysema of the lung have been increased. Any patient of Bronchial Asthma who are not treated properly or in chronic course lead to emphysema in the end. Patients of emphysema will have barrel shaped or pigeon shaped chest and increased resonant note on percussion. These patients will have thick and productive sputum on expectoration. In Ayurveda respiratory diseases occur due to involvement of Pranavaha Srotas where cough, breathing difficulties, disturbed respiratory pattern occurs . Ayurveda medicines has positive role in the management of Emphysema of the lung. Formulations like Poornachandrodaya rasa, Hiranyagarbha pottali, Malla sindoora, Tala sindhoora, Rasamanikya, Siddha makaradwaja, Kanakasava, Somasava, Vasakarista, Taleesadi choorna and Sitopaladi choorna are commonly used in the management of Emphysema. These formulations are having the ingredients with actions like immunomodulatory, antiinfective, anti-bacterial, krimighna, bronchodilator, expectorant, rasayana, ojaskara, vayasthapana and mucolytic action.The present paper highlights about the role of Ayurveda medicines in the management of Emphysema of the lungs.

Recent Advances in Molecular Basis of Lung Aging and Its Associated Diseases.

Aging is often viewed as a progressive decline in fitness due to cumulative deleterious alterations of biological functions in the living system. Recently, our understanding of the molecular mechanisms underlying aging biology has significantly advanced. Interestingly, many of the pivotal molecular features of aging biology are also found to contribute to the pathogenesis of chronic lung disorders such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis, for which advanced age is the most crucial risk factor. Thus, an enhanced understanding of how molecular features of aging biology are intertwined with the pathobiology of these aging-related lung disorders has paramount significance and may provide an opportunity for the development of novel therapeutics for these major unmet medical needs. To serve the purpose of integrating molecular understanding of aging biology with pulmonary medicine, in this review, recent findings obtained from the studies of aging-associated lung disorders are summarized and interpreted through the perspective of molecular biology of aging.

THE PROTECTIVE EFFECT OF THE CARTHMUS TINCTORIUS LEAVES EXTRACTON METHOTREXATE-INDUCED PULMONARY FIBROSIS IN RATS

Objective: Pulmonary fibrosis (PF) is an irreversible and untreatable human disease encompasses a large group of chronic lung disorders associated with excessive remodeling, scarring, and fibrosis.
 The current work was designed to study the harmful effects of methotrexate (MTX) administration on the lung and the possible protective role of Carthmus tinctorius leaves extract. The animals were utilized in this study.
 Methods: A total of 40 male healthy adult Wistar albino rats with anaverage body weight of 200±25 g, were divided into four groups (10 animals each). G1: control group, G2: MTX group, G3: Carthamus tinctorius (CT), group G4:MTX+Carthamus tinctorius(CT). CT was administered orally at a dose of (40 mg/kg/day) for 4 w to G3 and G4. The (CT) group were performed to explore any toxic effect of the (CT) extract on the lung. Rats of G2 and G4 administered 4 mg/kg dose of MTX orally for 28 d. Rats of G1 were intraperitoneally (i. p) administered with normal saline 0.5 ml ∕ day for four weeks (4wk) to serveas control. The animals were weighed at the beginning, though, and at the end of experiments.
 Results: The study showed that the relative lung weight was significantly increased at (P˂0.01) in MTX-treated animals in comparison to the control group. A combination of CT extract with MTX revealed significant decrease (P<0.01) in the lung relative weight in comparison to MTX group. Histopathological examination revealed that lung injury was less severe in group 3 and 4compared to group 2. The results indicated that CT significantly decreased collagen deposition, hydroxyproline content, and ameliorated pathological changes.
 Conclusion: The study has clearly identified the importance protective role of CT extract on pulmonary fibrosis induced by methoxerate. We recommended CT as one of therapeutic strategy to amelioratethe lung fibrosis associated with methotrexate therapy.