Destruction Of Lung Parenchyma Research Articles

Lipolysis engages CD36 to promote ZBP1-mediated necroptosis-impairing lung regeneration in COPD

Lung parenchyma destruction represents a severe condition commonly found in chronic obstructive pulmonary disease (COPD), a leading cause of morbidity and mortality worldwide. Promoting lung regeneration is crucial for achieving clinical improvement. However, no therapeutic drugs are approved to improve the regeneration capacity due to incomplete understanding of the underlying pathogenic mechanisms. Here, we identify a positive feedback loop formed between adipose triglyceride lipase (ATGL)-mediated lipolysis and overexpression of CD36 specific to lung epithelial cells, contributing to disease progression. Genetic deletion of CD36 in lung epithelial cells and pharmacological inhibition of either ATGL or CD36 effectively reduce COPD pathogenesis and promote lung regeneration in mice. Mechanistically, disruption of the ATGL-CD36 loop rescues Z-DNA binding protein 1 (ZBP1)-induced cell necroptosis and restores WNT/β-catenin signaling. Thus, we uncover a crosstalk between lipolysis and lung epithelial cells, suggesting the regenerative potential for therapeutic intervention by targeting the ATGL-CD36-ZBP1 axis in COPD.

Mechanism of cigarette smoke in promoting small airway remodeling in mice via STAT 3 / PINK 1-Parkin / EMT

BackgroundAirway remodeling is an important pathological of airflow limitation in chronic obstructive pulmonary disease (COPD).However,its mechanism still needs to be further clarify. MethodsAnimals:Healthy male C57BL/6 mice aged 4–6 weeks were randomly divided into control group and cigarette smoke(CS)group. Mice in the CS group were placed in a homemade glass fumigator, 5 cigarettes/time, 40 min/time, 4 times/day, 5 days/week, for 24 weeks. Mice in the control group were placed in a normal air environment.Cells:BEAS-2B cells were stimulated with 0.1%cigarette smoke extract(CSE).HE staining, immunohistochemical staining and Masson staining were used to observe the pathological of lung tissues, transmission electron microscopy was used to observe the structural of mitochondria in bronchial epithelial cells.Western blotting was used to detect the expression of STAT3,transforming growth factor-β1(TGF-β1),microtubule-associated protein 1A/1B-light chain3(LC3),PINK1,Parkin,E-cadherin,zonula occludens1(ZO-1),vimentin and snail family transcriptional inhibitor1 (Snail1),and MitoSOX Red was used to detect mitochondrial reactive oxygen species(mtROS). ResultsCS exposure causes lung parenchymal destruction and airway remodeling in mice.Compared to the control group,the expression of p-STAT3,TGF-β1 and EMT in the whole lung homogenate of the CS group was increased.Mitochondrial architecture disruption in bronchial epithelial cells of CS mice, with impaired PINK1-Parkin-dependent mitophagy.In vitro experiments showed that CSE exposure led to STAT3 activation, increased TGF-β1,EMT and enhanced PINK1-Parkin-mediated mitophagy.STAT3 inhibition reversed TGF-β1 upregulation induced by CSE and improved CSE-induced EMT and mitophagy.Inhibition of mitophagy improves EMT induced by CSE. Inhibition of mitophagy reduces STAT3-induced EMT. ConclusionCS activates the STAT3,and activated STAT3 promotes EMT in bronchial epithelial cells by enhancing PINK1-Parkin-mediated mitophagy and TGF-β1 signaling.Moreover, activated STAT3 can promote EMT directly.This may be one of the mechanisms by which CS causes small airway remodeling in COPD.

Lung Hyperinflation as Treatable Trait in Chronic Obstructive Pulmonary Disease: A Narrative Review.

Lung hyperinflation (LH) is a common clinical feature in patients with chronic obstructive pulmonary disease (COPD). It results from a combination of reduced elastic lung recoil as a consequence of irreversible destruction of lung parenchyma and expiratory airflow limitation. LH is an important determinant of morbidity and mortality in COPD, partially independent of the degree of airflow limitation. Therefore, reducing LH has become a major target in the treatment of COPD over the last decades. Advances were made in the diagnostics of LH and several effective interventions became available. Moreover, there is increasing evidence suggesting that LH is not only an isolated feature in COPD but rather part of a distinct clinical phenotype that may require a more integrated management. This narrative review focuses on the pathophysiology and adverse consequences of LH, the assessment of LH with lung function measurements and imaging techniques and highlights LH as a treatable trait in COPD. Finally, several suggestions regarding future studies in this field are made.

The correlation between smoking cumulative dose based on Brinkman Index with peak expiratory flow rate.

Indonesia is the country with the highest prevalence of smokers above 15 years old according to WHO, with a percentage of 76.2%. Smoking-induced lung damage is characterized by inflammation, leading to the destruction of lung parenchyma and airway obstruction, ultimately worsening lung function parameters. This study aims to find correlation between cumulative dose of smoking based on Brinkman index (BI) with Peak Expiratory Flow Rate (PEFR). This is a cross-sectional correlative study conducted on January-March 2020. Data were collected through history taking and PEFR measured with a peak flowmeter by taking the average of three peak flowmeter measurements, each separated by a 2-min interval. Inclusion criteria include male active smokers, aged 30 to 40 years, who have had a smoking history for at least 1 year. Exclusion criteria are as follows: uses e-cigarretes for smoking, has a history of chronic lung diseases such as tuberculosis, pneumonia, post-COVID-19 syndrome, asthma, and has not smoked in the last 28 days. A total of 48 male smokers are included in this study. The mean age of participants was 35.91 years, with a history of smoking of 18.12 years, and 12.5 cigarettes smoked daily. Patients included in this study had BI classified as mild (47.91%), moderate (47.91%), and severe (4.16%). PEFR in patients was classified into green (10.41%), yellow (83.33%), and red (6.25%). Analysis showed significant negative correlation between BI and PEFR (r = -0.721; p < 0.001) suggesting that increasing Brinkman Index may lead to a decrease in PEFR. Higher BI correlates with a decrease in PEFR. PEFR may prove to be useful in early detection of reduced pulmonary function. Further trials conducted on larger sample sizes and evaluating other lung function parameters are recommended.

A 32-Year-Old Female with Incidentally Detected Multifocal Cystic Pulmonary Lesions on Chest Computed Tomography

Lymphangioleiomyomatosis (LAM) is a rare condition that exclusively affects women and is characterized by lung parenchymal destruction and the formation of cysts due to infiltration by LAM cells. It can also impact the lymphatic system, leading to the development of fluid-filled cystic structures and abdominal involvement, including renal angiomyolipomas (AML) or lymphangioleiomyoma. LAM can occur sporadically or be associated with tuberous sclerosis complex. Common symptoms include respiratory issues such as dyspnea, pneumothorax, chylothorax, along with other manifestations like renal AML and lymphatic involvement. The diagnosis of LAM relies on a combination of clinical, radiological, and laboratory findings, and treatment options vary depending on symptoms and patient status, with mTOR inhibitors being considered as a treatment option. This case outlines the diagnostic journey and clinical course of a 32-year-old female patient with LAM.

“Miliary lung parenchymal opacities” as presenting feature of metastatic papillary type of thyroid malignancy: It’s not tuberculosis always!

Pulmonary tuberculosis (TB) is the most common cause of mortality and morbidity in South East Asia due to infective causes and tops the list of all infectious etiologies in India. Radiological presentations in pulmonary TB are diverse with the most common in them, which are nodules, consolidation, cavitation, and lung parenchymal destruction with or without collapse and consolidation. In this case report, a 31-year-old female presented with constitutional symptoms with miliary opacities in chest X-ray without microbiological evidence for TB in smear microscopy or nucleic acid amplification tests. She was treated as a case of miliary TB with antituberculosis treatment (ATT) on two occasions in the past 2 years as an “X-ray-positive case” on the basis of symptoms and chest radiology findings. She was never shown any clinical and radiological response in the past 1½ years in spite of satisfactory ATT adherence and compliance. After retrospective analysis of this case at our center, we have documented worsening of radiological findings and chest high-resolution computed tomography conformed miliary nodules and not typical miliary mottling favoring TB. We have noted right thyroid enlargement with a nodule in contrast tomography of neck. Fine-needle aspiration cytology confirmed as papillary carcinoma of the thyroid. We have confirmed this case as miliary metastasis due to primary thyroid malignancy. Miliary metastasis should be considered in cases with atypical radiological and clinical presentations with negative microbiological workup. No empirical ATT should be offered in the era of highly sensitive nucleic acid amplification tests and the term “X-ray-positive with negative microbiological tests” should be phased out.

Pharmacotherapy and pulmonary fibrosis risk after SARS-CoV-2 infection: a prospective nationwide cohort study in the United States

Pulmonary fibrosis is characterized by lung parenchymal destruction and can increase morbidity and mortality. Pulmonary fibrosis commonly occurs following hospitalization for SARS-CoV-2 infection. As there are medications that modify pulmonary fibrosis risk, we investigated whether distinct pharmacotherapies (amiodarone, cancer chemotherapy, corticosteroids, and rituximab) are associated with differences in post-COVID-19 pulmonary fibrosis incidence. We used the National COVID-19 Cohort Collaboration (N3C) Data Enclave, which aggregates and harmonizes COVID-19 data across the United States, to assess pulmonary fibrosis incidence documented at least 60 days after COVID-19 diagnosis among adults hospitalized between January 1st, 2020 and July 6th, 2022 without pre-existing pulmonary fibrosis. We used propensity scores to match pre-COVID-19 drug-exposed and unexposed cohorts (1:1) based on covariates with known influence on pulmonary fibrosis incidence, and estimated the association of drug exposure with risk for post-COVID-19 pulmonary fibrosis. Sensitivity analyses considered pulmonary fibrosis incidence documented at least 30- or 90-days post-hospitalization and pulmonary fibrosis incidence in the COVID-19-negative N3C population. Among 5,923,394 patients with COVID-19, we analyzed 452,951 hospitalized adults, among whom pulmonary fibrosis incidence was 1.1 per 100-person-years. 277,984 hospitalized adults with COVID-19 were included in our primary analysis, among whom all drug exposed cohorts were well-matched to unexposed cohorts (standardized mean differences <0.1). The post-COVID-19 pulmonary fibrosis incidence rate ratio (IRR) was 2.5 (95% CI 1.2-5.1, P=0.01) for rituximab, 1.6 (95% CI 1.3-2.0, P<0.0001) for chemotherapy, and 1.2 (95% CI 1.0-1.3, P=0.02) for corticosteroids. Amiodarone exposure had no significant association with post-COVID-19 pulmonary fibrosis (IRR=0.8, 95% CI 0.6-1.1, P=0.24). In sensitivity analyses, pre-COVID-19 corticosteroid use was not consistently associated with post-COVID-19 pulmonary fibrosis. In the COVID-19 negative hospitalized population (n=1,240,461), pulmonary fibrosis incidence was lower overall (0.6 per 100-person-years) and for patients exposed to all four drugs. Recent rituximab or cancer chemotherapy before COVID-19 infection in hospitalized patients is associated with increased risk for post-COVID-19 pulmonary fibrosis. The analyses described in this publication were conducted with data or tools accessed through the NCATS N3C Data Enclave https://covid.cd2h.org and N3C Attribution & Publication Policy v1.2-2020-08-25b supported by NIHK23HL146942, NIHK08HL150291, NIHK23HL148387, NIHUL1TR002389, NCATSU24 TR002306, and a SECURED grant from the Walder Foundation/Center for Healthcare Delivery Science and Innovation, University of Chicago. WFP received a grant from the Greenwall Foundation. This research was possible because of the patients whose information is included within the data and the organizations (https://ncats.nih.gov/n3c/resources/data-contribution/data-transfer-agreement-signatories) and scientists who have contributed to the on-going development of this community resource (https://doi.org/10.1093/jamia/ocaa196).

IMAGING IN MASSIVE PULMONARY HAEMORRHAGE: A RARE COMPLICATION AFTER SEVERE TRAUMA.

Trauma is one of the most common causes of mortality and morbidity in young adults worldwide. A blunt force to the chest causes pulmonary contusion (PC), which is dened as destruction of lung parenchyma. Massive pulmonary haemorrhage (MPH) is caused by pulmonary vascular injury after severe trauma. It is a rare form of pulmonary contusion that is associated with signicant mortality if not recognised early and treated promptly. Here is a case series on the imaging appearance of MPH.

Pulmonary hypertension associated with lung disease

Pulmonary hypertension (PH) is amultifactorial pulmonary vascular disease. PH associated with pre-existing lung disease is common and classified as group3 in the clinical classification. Patients with chronic obstructive or interstitial lung disease are most likely to develop PH, with up to 20% of patients showing signs of PH. Distinguishing between the symptoms of the underlying lung disease and concomitant PH can be difficult. Clinical assessment, lung function tests, laboratory tests, and echocardiography can be helpful. The hemodynamic definition of PH has recently been changed. PH associated with lung disease is apre-capillary form by definition. A special sub-stratification in group3 is the differentiation of hemodynamic severity. Severe PH in group3 is defined as apulmonary vascular resistance (PVR) greater than 5Wood units (WU). This pulmonary vascular phenotype is characterized by rather mild to moderate impairment of lung function or lung parenchymal destruction but with severe pulmonary vascular disease or right heart strain. Currently, there are no specific PH medications approved for group3. However, the use of specific PH medications for the pulmonary vascular phenotype is being discussed in studies or on acase-by-case basis, while in patients with aPVR below 5WU treatment focuses on the underlying disease.

Pharmacology and Emerging Therapies for Group 3 Pulmonary Hypertension Due to Chronic Lung Disease.

Pulmonary hypertension (PH) frequently complicates chronic lung disease and is associated with high morbidity and poor outcomes. Individuals with interstitial lung disease and chronic obstructive pulmonary disease develop PH due to structural changes associated with the destruction of lung parenchyma and vasculature with concurrent vasoconstriction and pulmonary vascular remodeling similar to what is observed in idiopathic pulmonary arterial hypertension (PAH). Treatment for PH due to chronic lung disease is largely supportive and therapies specific to PAH have had minimal success in this population with exception of the recently FDA-approved inhaled prostacyclin analogue treprostinil. Given the significant disease burden of PH due to chronic lung diseases and its associated mortality, a great need exists for improved understanding of molecular mechanisms leading to vascular remodeling in this population. This review will discuss the current understanding of pathophysiology and emerging therapeutic targets and potential pharmaceuticals.

Post-TB bronchiectasis: from pathogenesis to rehabilitation

The destruction of lung parenchyma caused by TB can result in pulmonary sequelae that are classified as bronchiectasis due to traction (radiological sequelae), and bronchiectasis persisting with an inflammatory bronchial component and opportunistic bronchial infection. There is a lack of studies that comprehensively analyse whether post-TB bronchiectasis differs in clinical, prognostic or therapeutic aspects from bronchiectasis arising from other aetiologies. However, it has been noted that post-TB bronchiectasis tends to appear more frequently in the upper lung lobes. In many countries, TB is the most frequent known cause of bronchiectasis, but there is currently no targeted management of bronchiectasis due to TB as opposed to other aetiologies. It is imperative to first prevent TB, and when that fails to provide early diagnosis and adequate treatment for TB disease. In addition, efforts should be made to limit additional lung insults such as tobacco use and provide management of post TB bronchiectasis to minimise further pulmonary sequelae. The objective of this minireview was to provide an update on post-TB bronchiectasis, its definition, epidemiological data, pathophysiology, and clinical, diagnosis and therapeutic aspects.

Effects of photobiomodulation as an adjunctive treatment in chronic obstructive pulmonary disease: a narrative review.

Chronic obstructive pulmonary disease (COPD) is a disease characterized by chronic airway inflammation and remodeling and lung parenchymal inflammation and destruction, which result in many pulmonary and extrapulmonary manifestations. The anti-inflammatory effect of photobiomodulation (PBM) has been reported in previous studies. This review was conducted to evaluate the direct effect of PBM on lung inflammation in COPD. The other effects of PBM on modulation of peripheral and respiratory muscle metabolism and angiogenesis in lung tissues were also discussed. The databases of PubMed, Cochrane Library, and Google Scholar were searched to find the relevant studies. Keywords included PBM and related terms, COPD-related signs, and lung inflammation. A total of 12 articles were selected and reviewed in this study. Based on the present review, PBM is helpful in reducing lung inflammation through decreasing the inflammatory cytokines and chemokines at multiple levels and increasing anti-inflammatory cytokines. In addition, PBM also improves both peripheral and respiratory muscle metabolism and promote angiogenesis. This review demonstrated that PBM is a promising adjunctive treatment modality for COPD management which merits further validation.

The novel TAK1 inhibitor handelin inhibits NF-κB and AP-1 activity to alleviate elastase-induced emphysema in mice

Emphysema, one of the two major components of chronic obstructive pulmonary disease (COPD), is driven by aberrant inflammatory responses and associated with irreversible lung parenchymal destruction. As effective therapy for preventing or treating COPD/emphysema is yet unavailable, development of molecular targets and therapeutic agents for COPD/emphysema is required. We identified handelin-a guaianolide dimer of sesquiterpene lactones- from a chemical library of 431 natural products as it exhibited potent inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) and reactive oxygen species (ROS) production, LPS-induced activation of nuclear factor κB (NF-κB), mitogen-activated protein kinase (MAPK)/AP-1, and expression of proinflammatory mediators in macrophage cells. In silico docking and biochemical studies enabled the identification of the ATP-binding pocket of transforming growth factor beta-activated kinase 1 (TAK1), a kinase upstream of NF-κB and MAPK/AP-1 pathways, as a molecular target for handelin. Moreover, oral administration of handelin (10mg/kg) suppressed elastase-induced development of emphysematous phenotypes, including lung function disturbance, airspace enlargement, and increases in the level of neutrophils and CD8+ T cells in lung tissues, without overt toxicity. Consistent with in vitro results, analyses of lung tissues revealed that treatment with handelin suppressed elastase-induced NF-κB and AP-1 activation in the lungs, followed by downregulation of their targets including interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and matrix metalloproteinase 9 (MMP9). These findings suggest that handelin, as a TAK1 inhibitor, effectively prevents development of emphysema in an elastase-induced mouse model by inhibiting a proinflammatory mediators mediated by NF-κB and AP-1.

Comparison of Respiratory Proprioceptive Neuromuscular Facilitation and Segmental Breathing on Pulmonary functions, Dyspnoea and Exercise Tolerance in COPD Patients: A Comparative Study

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is a preventable and treatable disease marked by airflow limitation, destruction of lung parenchyma and other associated respiratory symptoms (e.g., dyspnoea and coughing). Pathological changes and symptoms do not appear altogether, symptoms may not appear but pathological changes are likely to be present. Segmental breathing and Proprioceptive Neuromuscular Facilitation (PNF) techniques are both effective techniques in improving pulmonary functions in COPD patients. Aim: To compare PNF and Segmental breathing with respect to pulmonary functions to relieve dyspnoea and improve exercise capacity in COPD patients. Materials and Methods: This was a comparative study conducted from July 2020 to June 2021 at Department of Physiotherapy, SGT University, Gurugram, Haryana, India. On 30 in-patient aged between 40-60 years with Forced Expiratory Volume in 1st second/Forced Vital Capacity (FEV1/ FVC) &lt; 0.7, hospitalised clinically stable patients . Out of these, 15 were allocated in the segmental breathing group and another 15 participants were allocated into the respiratory PNF group through the sealed envelope. The session was of 10-15 minutes under the protocol of 18-20 repetitions of each technique in segmental breathing and respiratory PNF in either respective group. The dyspnoea was assessed by Modified Borg Scale, pulmonary functions was done with spirometry, followed by the 6-Minute Walk Test (6-MWT). The data was statistically analysed using Statistical Package for Social Sciences(SPSS) version 24.0. Paired t-test was used to compare the means of measurements within the groups. The independent t-test was used to compare the means of all the variables between the groups. Results: Both of these techniques improved SpO2 (change in mean from 81.27 to 86.20 and 82.13 to 90.67 in segmental and PNF group, respectively) and relieve dyspnoea post-exertion (8.33 to 6.60 and 8.0 to 5.67 in segmental and PNF groups) within 1-week of intervention (p &lt; 0.01). There was improvement seen in pulmonary functions (FEV1 from 0.87 to 0.95 and 0.78 to 1.02 in segmental and PNF groups) and exercise tolerance (6- Minute Walk Test (MWT) from 149.47 to 204.80 and 151.77 to 242.20 in segmental and PNF groups) as well. And out of both, respiratory PNF is more efficient in improving pulmonary function, dyspnoea and exercise tolerance in a week (p&lt;0.01) which makes the master improvement and pulmonary rehabilitation can proceed with further advancement. Conclusion: Segmental breathing and respiratory PNF are effective techniques for patients with COPD admitted to hospital whose modified Borg’s dyspnoea score is higher even at rest and intolerant to physical exercise and peripheral capillary oxygen saturation is lower than 88%.

Transforming Growth Factor-β1 Regulates Peroxisomal Genes/Proteins via Smad Signaling in Idiopathic Pulmonary Fibrosis Fibroblasts and Transgenic Mouse Models

Idiopathic pulmonary fibrosis (IPF) is a chronic human disease with persistent destruction of lung parenchyma. Transforming growth factor-β1 (TGF-β1) signaling plays a pivotal role in the initiation and pathogenesis of IPF. As shown herein, TGF-β1 signaling down-regulated not only peroxisome biogenesis but also the metabolism of these organelles in human IPF fibroblasts. Invitro cell culture observations in human fibroblasts and human lung tissue indicated that peroxisomal biogenesis and metabolic proteins were significantly down-regulated in the lung of 1-month-old transgenic mice expressing a constitutively active TGF-β type I receptor kinase (ALK5). The peroxisome biogenesis protein peroxisomal membrane protein Pex13p (PEX13p) as well as the peroxisomal lipid metabolic enzyme peroxisomal acyl-coenzyme A oxidase 1 (ACOX1) and antioxidative enzyme catalase were highly up-regulated in TGF-β type II receptor and Smad3 knockout mice. This study reports a novel mechanism of peroxisome biogenesis and metabolic regulation via TGF-β1-Smad signaling: interaction of the Smad3 transcription factor with the PEX13 gene in chromatin immunoprecipitation-on-chip assay as well as in a bleomycin-induced pulmonary fibrosis model applied to TGF-β type II receptor knockout mice. Taken together, data from this study suggest that TGF-β1 participates in regulation of peroxisomal biogenesis and metabolism via Smad-dependent signaling, opening up novel strategies for the development of therapeutic approaches to inhibit progression of pulmonary fibrosis patients with IPF.

PULMONARY LIMITED SERONEGATIVE GRANULOMATOSIS WITH POLYANGIITIS VASCULITIS

PULMONARY LIMITED SERONEGATIVE GRANULOMATOSIS WITH POLYANGIITIS VASCULITIS

Gene-gene and gene-environment interactions of the inflammatory gene variants in the development of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease that is characterized by partly reversible airflow limitation, chronic inflammation, fibrosis of small airways, and destruction of lung parenchyma. We aimed to assess the association of the inflammatory gene loci singly and in combinations with COPD in smokers and non-smokers in ethnic Tatar from Russia to evaluate the gene-gene and gene-environment interactions in COPD development. Eleven loci of inflammatory genes, including IL19, IL20, IL24, PPBP, IL4, IL4RA, С5, FAS, FASLG, and TGFb1, were genotyped in 484 smoking COPD patients, 517 healthy smokers, 117 non-smoking COPD patients, and 100 healthy non-smokers. Significant associations with COPD in smokers were identified for IL19 (rs2243193), IL4 (rs2243250), IL4 (rs2070874), and PPBP (rs352010). In non-smokers, associations were established for IL24 (rs291107), IL4 (rs2070874), and PPBP (rs352010). Associations of inflammatory genes loci IL19 (rs2243193), IL4 (rs2070874), TGFb1 (rs1800469), PPBP (rs352010), and FASLG (rs763110) and smoking index were determined. Associations of FAS (rs1800682), FASLG (rs763110), IL4 (rs2243250), IL4RA (rs1805010), and PPBP (rs352010) loci with pulmonary function variables were observed. The results of gene-gene interactions analysis showed distinctive patterns of association of inflammatory gene loci with COPD in groups stratified by smoking status. The combination of A allele of IL19 (rs2243193), C allele of IL4 (rs2243250), and T allele of PPBP (rs352010) was the main component of the majority of protective gene-gene combination associated with COPD in smokers. The highest risk of COPD was conferred by TT genotype of PPBP (rs352010) in combination with A allele of FAS (rs1800682). While in non-smokers, the most commonly featured was IL24 (rs291107) C allele in protective patterns and IL24 (rs291107) T allele in predisposing combinations. The highest risk of COPD in non-smokers was detected in a gene-gene combination consisting of A allele of IL12RB2 (rs3762317) together with G allele of IL12A (rs2243115), C allele of IL4 (rs2070874), and A allele of IL4RA (rs1805010).

Blocking P2X purinoceptor 4 signalling alleviates cigarette smoke induced pulmonary inflammation.

BackgroundChronic obstructive pulmonary disease (COPD) is associated with elevated ATP levels in the extracellular space. Once released, ATP serves as danger signal modulating immune responses by activating purinergic receptors. Accordingly, purinergic signalling has been implicated in respiratory inflammation associated with cigarette smoke exposure. However, the role of P2X4-signalling has not been fully elucidated yet. MethodsHere, we analysed the P2X4 mRNA expression in COPD patients as well as cigarette smoke-exposed mice. Furthermore, P2X4-signalling was blocked by either using a specific antagonist or genetic depletion of P2rx4 in mice applied to an acute and prolonged model of cigarette smoke exposure. Finally, we inhibited P2X4-signalling in macrophages derived from THP-1 before stimulation with cigarette smoke extract.ResultsCOPD patients exhibited an increased P2X4 mRNA expression in cells isolated from the bronchoalveolar lavage fluid and peripheral mononuclear cells. Similarly, P2rx4 expression was elevated in lung tissue of mice exposed to cigarette smoke. Blocking P2X4-signalling in mice alleviated cigarette smoke induced airway inflammation as well as lung parenchyma destruction. Additionally, human macrophages derived from THP-1 cells released reduced concentrations of proinflammatory cytokines in response to cigarette smoke extract stimulation when P2X4 was inhibited.ConclusionTaken together, we provide evidence that P2X4-signalling promotes innate immunity in the immunopathologic responses induced by cigarette smoke exposure.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12931-022-02072-z.

Effect of Crocin From Saffron (Crocus sativus L.) Supplementation on Oxidant/Antioxidant Markers, Exercise Capacity, and Pulmonary Function Tests in COPD Patients: A Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Chronic obstructive pulmonary disease (COPD) is a progressive and chronic respiratory disorder characterized by reversible airflow limitation and lung parenchyma destruction. The main feature of COPD is inflammation and disturbance of the oxidant/antioxidant balance in the airways. The therapeutic use of herbal supplements with antioxidant and anti-inflammatory properties seems to be very useful in the medical management of patients with COPD. Method: COPD patients were divided into placebo and intervention groups (each group n = 23) in a clinical trial study. The intervention group received crocin supplementation (30 mg/day for 12 weeks), and the control group received a placebo. Pre- and after the intervention, pulmonary function tests (PFTs), exercise capacity (using a 6-min walking distance test (6MWD)), and serum levels of total oxidant status (TOS), total antioxidant capacity (TAOC), and NF-kB were assessed using the ELISA test. Results: Intervention with crocin for 12 weeks in COPD patients decreased serum levels of TOS and NF-κB as well as increased TAOC. In addition, the results of the 6MWD test reveal an improvement in patients’ exercise capacity. Conclusion: Crocin supplementation appears to effectively establish oxidant/antioxidant balance and improve inflammatory conditions in patients with COPD.

COMPUTED TOMOGRAPHY FEATURES OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE&#x0D; ASSOCIATED WITH LUNG CANCER

Relevance: Chronic obstructive pulmonary disease (COPD) associated with lung cancer is common in smoking patients. Computed tomography (CT) is vital in detecting lung cancer, assessing regional lung parenchymal destruction, and airway remodeling in COPD.&#x0D; ДИАГНОСТИКА&#x0D; 40 Онкология и радиология Казахстана, №1 (63) 2022&#x0D; The study aimed to determine the CT features of COPD associated with lung cancer.&#x0D; Methods: This retrospective study included chest CT exams of 56 patients over the age of 40, with a smoking history of 10 years and more and&#x0D; with suspected COPD. 46.43% of patients had CT signs of lung cancer associated with COPD.&#x0D; Results: Barrel-shaped chest (19.23%), saber-sheath trachea (7.69%), and bronchiectasis (15.38%) were less common in patients with lung&#x0D; cancer. Paraseptal and centrilobular emphysema were diagnosed in 96.15%, bullae – 73.33%. Bronchial narrowing of the lumen and wall thickening were identified for all lobar bronchus, segmental bronchus, and subsegmental bronchus.&#x0D; Conclusion: Paraseptal and centrilobular emphysema and bullae in the upper lobes of lungs were predominant CT features in patients with&#x0D; COPD associated with lung cancer. Lumen narrowing and wall thickening of lobar bronchus, segmental bronchus, and subsegmental bronchus&#x0D; were also revealed.