Following endobronchial examination, a young mine supervisor was treated with antibiotics for a pulmonary nontuberculous mycobacterial infection for approximately 1 year. However, a review of the ...radiological findings, which had not been previously assessed, revealed a different possibility. Accordingly, pulmonary resection was performed, enabling histopathological analysis, which showed numerous yeast-like fungi. Given the history of a stay in the southwestern United States for 2 months in 2009, 8 years previously, coccidioidomycosis was strongly suspected and the diagnosis was subsequently confirmed by serology and polymerase chain reaction testing of the excised specimen. Here, we report an educational case emphasizing the importance of meticulous medical history-taking and awareness of endemic mycoses in other countries in the context of globalization.
•Ozone therapy seems to have an immunological role within SARS-CoV-2 regimens, because of the modulation of cytokines and interferons, including the induction of gamma interferon.•Ozone exerts ...antiviral activity through the inhibition of viral replication and direct inactivation of viruses.•Ozone is an antiviral drug enhancer and is not an alternative to antiviral drugs.•The routes of ozone administration are direct intravenous, major autohaemotherapy and extravascular blood oxygenation-ozonation.•Combined treatment with involving ozone and antivirals demonstrated a reduction in inflammation and lung damage.
The main objective of this narrative review is to describe the available evidence on the possible antiviral activity of ozone in patients with COVID-19 and its therapeutic applicability through hospital protocols. Amongst different possible therapies for SARS-CoV-2 pneumonia, ozone therapy seems to have an immunological role because of the modulation of cytokines and interferons, including the induction of gamma interferon. Some data suggest the possible role of ozone therapy in SARS, either as a monotherapy or, more realistically, as an adjunct to standard treatment regimens; therefore, there is increasing interest in the role of ozone therapy in COVID-19 treatment
The PubMed and Scopus databases and the Italian Scientific Society of Oxygen Ozone Therapy website were used to identify articles focused on ozone therapy. The search was limited to articles published from January 2011 to July 2020. Of 280 articles found on ozone therapy, 13 were selected and narratively reviewed. Ozone exerts antiviral activity through the inhibition of viral replication and direct inactivation of viruses. Ozone is an antiviral drug enhancer and is not an alternative to antiviral drugs. Combined treatment with involving ozone and antivirals demonstrated a reduction in inflammation and lung damage. The routes of ozone administration are direct intravenous, major autohaemotherapy and extravascular blood oxygenation-ozonation.
Systemic ozone therapy seems useful in controlling inflammation, stimulating immunity and as antiviral activity and providing protection from acute coronary syndromes and ischaemia reperfusion damage, thus suggesting a new methodology of immune therapy. Systemic ozone therapy in combination with antivirals in COVID-19-positive patients may be justified, helpful and synergic.
The chemokine receptors CXCR1/2 and their ligand CXCL8 are essential for the activation and trafficking of inflammatory mediators as well as tumor progression and metastasis. The CXCL8-CXCR1/2 ...signaling axis is involved in the pathogenesis of several diseases including chronic obstructive pulmonary diseases (COPD), asthma, cystic fibrosis and cancer. Interaction between CXCL8 secreted by select cancer cells and CXCR1/2 in the tumor microenvironment is critical for cancer progression and metastasis. The CXCL8-CXCR1/2 axis may play an important role in tumor progression and metastasis by regulating cancer stem cell (CSC) proliferation and self-renewal. During the past two decades, several small-molecule CXCR1/2 inhibitors, CXCL8 releasing inhibitors, and neutralizing antibodies against CXCL8 and CXCR1/2 have been reported. As single agents, such inhibitors are expected to be efficacious in various inflammatory diseases. Several preclinical studies suggest that combination of CXCR1/2 inhibitors along with other targeted therapies, chemotherapies, and immunotherapy may be effective in treating select cancers. Currently, several of these inhibitors are in advanced clinical trials for COPD, asthma, and metastatic breast cancer. In this review, we provide a comprehensive analysis of the role of the CXCL8-CXCR1/2 axis and select genes co-expressed in this pathway in disease progression. We also discuss the latest progress in developing small-molecule drugs targeting this pathway.
Chronic obstructive pulmonary disease (COPD) is one of the most severe respiratory diseases and can be diagnosed by several clinical modalities such as spirometric measures, lung function tests, ...parametric response mapping, wheezing events of lung sounds (LSs), etc. Since LSs are related to the respiratory irregularities caused by pulmonary illnesses, examining them is more effective for identifying respiratory issues. In this letter, we propose a visibility graph (VG)-based adjacency matrix representation of LS in conjunction with a residual deep neural network (ResNet) for accurate detection of COPD, namely, the VGAResNet. The proposed framework comprises four stages: preprocessing, visibility graph creation, adjacency matrix (AdjM) generation, and lastly, classification of these AdjMs using the ResNet architecture. The proposed framework is extensively evaluated using the publicly available LS database and outperforms the existing noteworthy research works by achieving the highest performance rates of 95.13%, 96.33%, and 94.37% for accuracy, sensitivity, and specificity, respectively.
Generic inhalers are often perceived as inferior to their branded counterparts; however, they are safe and effective if they can meet the regulatory requirements. The approach to assess ...bioequivalence (BE) in oral dosage form products is not sufficient to address the complexities of inhalational products (e.g., patient-device interface); hence, more considerations are needed and caution should be applied in determining BE of inhaled compounds. Areas covered: This review outlines the evaluation process for generic inhalers, explores the regulatory approaches in BE assessment, and highlights the considerations and challenges in the current in vitro and in vivo approaches (lung deposition, pharmacokinetic, pharmacodynamic/clinical studies, and patient-device interface) for establishing BE of inhaled compounds. Expert opinion: The ultimate goals in this field are to establish uniformity in the regulatory approaches to speed the drug submission process in different regions, clear physicians' misconception of generic inhalers, and have meaningful clinical endpoints such as improvement in patient quality of life when compared to placebo and brand name drugs. As inhalational drugs become more common for other indications such as antibiotics, the technologies developed for inhaled compounds in the treatment of chronic pulmonary diseases may be extrapolated to these other agents.
•We found long-term low-dose PM2.5 exposure could enhance proliferation, migration and invasion of BEAS-2B cells.•We found PM2.5 could stimulate the excretion of exosomes from BEAS-2B cells.•We ...explored the effects of PM2.5 on gene expression and exosomal miRNA expression profiles of BEAS-2B cells.•We constructed DE-Exo-MiRs-DEGs networks which might contribute to the PM2.5 induced-invasive BEAS-2B phenotype.
Epidemiological studies have established the correlations between PM2.5 and a wide variety of pulmonary diseases. However, their underlying pathogeneses have not been clearly elucidated yet. In the present study, the epithelial-mesenchymal transition (EMT) phenotype with enhanced proliferation and migration activity of human pulmonary epithelial cell line BEAS-2B was observed after exposure to low dose PM2.5 exposure (50 μg/ml) for 30 passages. Then, epithelial cells derived-exosomal micro-RNA (miRNA) and intracellular total RNA were extracted, and the differentially expressed exosomal miRNAs (DE-Exo-MiRs) as well as differentially expressed protein coding genes (DEGs) were identified by RNA sequencing (RNA-seq) and transcriptome analysis. We found that chronic PM2.5 exposure stimulated the release of pulmonary epithelium derived exosomes. 45 DE-Exo-MiRs including 32 novelly predicted miRNAs and 843 DEGs between PM2.5 exposed group and the normal control were detected. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that DEGs were significantly enriched in extracellular matrix organization, focal adhesion and cancer related terms. Besides, the enrichment analyses on 7774 mRNA targets of 27 DE-Exo-MiRs predicted by MiRanda software also revealed the potential regulatory role of exosomal miRNAs in pathways in cancer, Wingless/Integrated (Wnt) signaling pathway, focal adhesion related genes and other multiple pathogenic pathways. Moreover, the interactive exosomal miRNA-mRNA pair networks were constructed using Cytoscape software. Our results provided a novel basis for a better understanding of the mechanisms of chronic PM2.5 exposure induced pulmonary disorders including pulmonary fibrosis and cancer, in which exosomal miRNAs (Exo-MiRs) potentially functions by dynamically regulating gene expressions.
Vitamin D is customarily involved in maintaining bone and calcium homeostasis. However, contemporary studies have identified the implication of vitamin D in several cellular processes including ...cellular proliferation, differentiation, wound healing, repair and regulatory systems inclusive of host defence, immunity, and inflammation. Multiple studies have indicated corelations between low serum levels of vitamin D, perturbed pulmonary functions and enhanced incidences of inflammatory diseases. Almost all of the pulmonary diseases including acute lung injury, cystic fibrosis, asthma, COPD, Pneumonia and Tuberculosis, all are inflammatory in nature. Studies have displayed strong inter-relations with vitamin D deficiency and progression of lung disorders; however, the underlying mechanism is still unknown. Vitamin D has emerged to possess inhibiting effects on pulmonary inflammation while exaggerating innate immune defenses by strongly influencing functions of inflammatory cells including dendritic cells, monocyte/macrophages, T cells, and B cells along with structural epithelial cells. This review dissects the effects of vitamin D on the inflammatory cells and their therapeutic relevance in pulmonary diseases. Although, the data obtained is very limited and needs further corroboration but presents an exciting area of further research. This is because of its ease of supplementation and development of personalized medicine which could lead us to an effective adjunct and cost-effective method of therapeutic modality for highly fatal pulmonary diseases.
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Providing an overview on Mycoplasma pneumoniae-related extra-pulmonary diseases (MpEPDs) in children, who represent the preferred target population by those complications, and discussing the main ...pathogenic mechanisms implicated or potentially involved.
Recent evidences supported the fact that M. pneumoniae is more than an extra-cellular pathogen colonizing epithelial cells of the respiratory tract. It is able to penetrate the cell membrane of host cells and to invade the respiratory mucosa, leading to pronounced inflammatory responses and also spreading outside the respiratory system, to some extent. Thus, direct and indirect (immune-mediated) mechanisms have been described in M. pneumoniae infections, but the latter ones have been mainly implicated in MpEPDs, as reviewed here. Recently, interesting insights have been provided, especially as concern neurologic complications, and new potential mechanisms of disease have been emerging for autoimmunity.
The awareness of the occurrence of MpEPDs, showing very variable clinical expressions, could promote a correct diagnosis and an appropriate treatment. The knowledge of disease mechanisms in MpEPDs is largely incomplete, but recent advances from clinical studies and murine models might promote and direct future research.
선행 연구에서 동맥경화와 폐기능이상과 연관성이 있었다. 맥압은 동맥경화의중요한 예측이지만 아직까지 폐기능이상과 맥압의 연관성은 불분명하다. 따라서, 본 연구는 대한민국 비흡연 성인을 대상으로 맥압과 폐기능장애(예측 강제 폐활량, 예측 강제 날숨량 1초율)의 관련성을 알아보고자 실시하였다. 본 연구는 2013년부터 2015년까지 3년간의 대한민국 ...국민건강영양조사자료에서 비흡연 성인(6,857명)을 대상으로 실시하였다. 본 연구의 주요 결과는 맥압과 폐기능장애에 대한 관련 변수를 보정한 후의 결과에서, 정상 맥압(pulse pressure, PP≤60 mmHg)에 비하여 고맥압(PP＞60 mmHg; 1.337 95% confidence interval (CI), 1.049∼1.703)에서 제한성 폐질환(restrictive pulmonary disease, RPD; the predicted FVC＜80.0% with FEV 1 /FVC≥70.0%)의 교차비(odds ratio, OR)가 유의하게 높았다. 추가적으로, 정상맥압에 비하여 고맥압(1.339 95% CI, 1.093∼1.642)에서 폐쇄성 폐질 환(obstructive pulmonary disease, OPD; FEV 1 /FVC＜70.0%)의 교차비가 유의하게 높았다. 결론적으로, 대한민국 비흡연 성인에서 제한성 폐질환 및 폐쇄성 폐질환은 고맥압과 유의한 관계가 있었다.
According to previous studies, an impaired pulmonary function is associated with arterial stiffness (AS). The pulse pressure (PP) is an important predictor of AS, but the association of an impaired pulmonary function with the PP is unclear. Therefore, this study assessed the associations between the PP and the predicted forced vital capacity (predicted FVC) and predicted forced expiratory volume in one second (predicted FEV1) in Korean non-smoking adults. The data obtained from 6,857 adults during the 2013∼2015 Korean National Health and Nutrition Examination Survey were analyzed. After adjusting for the related variables, the ORs of restrictive pulmonary disease (RPD, the predicted FVC＜80.0% with FEV 1 /FVC≥70.0%) using the normal PP group (PP≤60 mmHg) as a reference group was significant for the high PP group (PP＞60 mmHg; 1.337 95% confidence interval (CI), 1.049∼1.703). In addition, the ORs of obstructive pulmonary disease (OPD, FEV 1 /FVC＜70.0%) using the normal PP group as a reference group were significant for the high PP group (1.339 95% CI, 1.093∼1.642). In conclusion, a high PP is positively associated with both RPD and OPD in Korean non-smoking adults.
Copyright Ⓒ 2020 The Korean Society for Clinical Laboratory Science. All rights reserved.
COPD patients are prone to acute infectious exacerbations that impair their quality of life and hamper prognosis. The purpose of the present study was to investigate the in situ IFN-β response in the ...lungs of stable COPD and non-COPD patients. Lung samples from 70 subjects (9 control never smokers, 19 control smokers without COPD, 21 patients with moderate COPD and 21 patients with very severe COPD) were studied for the expression of IFN-β, its main transcription factor, IRF-7, and two products of its autocrine function, namely RIG-I and MDA-5, by immunohistochemical techniques and quantitative real-time PCR. IFN-β, IRF-7, RIG-I and MDA-5 were widely detected in most lung cell types. In epithelial tissues and alveolar macrophages, IFN-β and IRF-7 labeling scores were decreased up to 65% and 74%, respectively, for COPD patients, paralleling an analogous reduction (43% and 65%, respectively) in the amount of their lung mRNA. Moreover, this decreased production of IFN-β in COPD patients correlated with a similar decrease in the expression of RIG-I and MDA-5, two essential members of the innate immune system. Our study indicates that most lung cells from stable COPD patients show a constitutive decreased expression of IFN-β, IRF-7, RIG-I and MDA-5, suggesting that this deficiency is the main cause of their acute viral exacerbations.
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